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Abstract: Slide Presentations

Chest. 2003;124(4_MeetingAbstracts):69S. doi:10.1378/chest.124.4_MeetingAbstracts.69S
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PURPOSE:  Empyema remains a significant cause of morbidity in children. This study was undertaken to evaluate the changes that have affected the outcome in children including the emergence of resistant organisms, the introduction of the pneumococcal conjugate vaccine, and earlier treatment with video assisted thoracoscopy (VATS).

METHODS:  A retrospective chart review was performed on all patients discharged with a diagnosis of empyema and community-acquired pneumonia over a ten-year period (1993-2002) at Texas Children’s Hospital in Houston, TX. Data collected included demographic information, clinical presentation, radiographic studies, laboratory data including culture results, and hospital course.

RESULTS:  Two hundred thirty charts were available for review. The mean age was 4.0±3.6 years. Of the pleural fluid cultures performed, 32% (69/219) were positive. An additional 27 patients had an etiology identified by blood culture. The first penicillin non-susceptible S. pneumoniae was identified in 1995, and the first methicillin-resistant S aureus (MRSA) was identified in 1998. Following the universal use of the pneumococcal conjugate vaccine three major changes have occurred (1999-2000 vs 2001-2002): (1) the number of patients admitted with empyema (per 10,000 admissions) has decreased from 23 to 11 (p=0.04); (2) the prevalence of S pneumoniae has decreased from 32% (28/87) to 9% (5/53) (p=0.001); and (3) S aureus has become the most common pathogen isolated (8% vs. 19%, p=0.05) with 70% of those being methicillin-resistant. The use of early VATS (<48 hours after admission) has significantly decreased the length of hospitalization (11.5±6.6d vs 15.4±8.8d, p=0.005) as well as length of fever (7.1±5.6d vs 9.4±5.5d, p=0.046)CONCLUSIONS: The microbiologic etiology of empyema has changed with an increasing incidence of S aureus and particularly of MRSA. The use of VATS for initial therapy of empyema results in decreased length of stay and length of fever.

CLINICAL IMPLICATIONS:  Initial antibiotic therapy in these patients should empirically cover MRSA. Early VATS is beneficial to patients and is now part of the standard therapy for patients with empyema admitted to our institution.

DISCLOSURE:  K.D. Schultz, None.

Topics: empyema
Chest. 2003;124(4_MeetingAbstracts):69S. doi:10.1378/chest.124.4_MeetingAbstracts.69S-a
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PURPOSE:  Several clinical asthma scores have been derived from combinations of physical findings in pediatric asthmatic patients. However, few scores have proven predictive value for asthma exacerbations. This study was designed to test the reproducibility and validity of one such score, the modified pulmonary index score (MPIS), and to assess its predictive value in children hospitalized for asthma.

METHODS:  In the MPIS, six categories are evaluated: oxygen saturation, accessory muscle use, inspiratory to expiratory flow ratio, degree of wheezing, heart rate, and respiratory rate. For each of these six measurements or observations, a score of 0-3 is assigned. To assess the reproducibility of the MPIS, thirty inpatients with status asthmaticus (median age 6.4 years, range 0.8-17 years) were examined by an attending physician, nurse, and respiratory therapist who were blinded to the other observers’ scores. To assess the validity of the MPIS as a scale of severity of illness in asthmatic patients, the score at admission was compared with selected outcomes in the same thirty patients.

RESULTS:  The MPIS is highly reproducible with a high degree of inter-rater reliability across caregiver groups (MD to RN: R=0.98, 95% CI>0.96; MD to RT: R=0.95, 95% CI>0.92; RN to RT: R=0.94, 95% CI>0.90). The admission MPIS positively correlated with ICU admission (p<0.01), days of continuous albuterol therapy (p<0.01), days of supplemental oxygen (p<0.01) and length of hospital stay (p<0.01).CONCLUSIONS: The MPIS is highly reproducible and a valid indicator of severity of illness in children with asthma.

CLINICAL IMPLICATIONS:  This is the first pediatric clinical asthma score demonstrated to be reproducible across three groups of health care professionals. The correlation between the MPIS and routinely measured clinical outcomes may make this score a useful tool for assessing the effects of therapeutic maneuvers for pediatric asthmatic patients.

DISCLOSURE:  C.L. Carroll, None.

Chest. 2003;124(4_MeetingAbstracts):69S. doi:10.1378/chest.124.4_MeetingAbstracts.69S-b
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PURPOSE:  The purpose of this presentation is to examine the utility of exhaled nitrous oxide (eNO) as a measure of asthma control.

METHODS:  The data presented here are baseline assessments from a prospective treatment study of children with moderate persistent asthma who by history were well controlled. On enrollment into the study we collected baseline data on the children’s medical history, conducted a brief physical examination and collected standard pulmonary function measures. Enrollment criteria were: between the ages of 8 to 14, moderate persistent but stable asthma, no respiratory tract infections or hospitalizations for the last two months, and no use of oral steroids for the previous 3 months.

RESULTS:  We present baseline data on 35 children in this ongoing study. Sixty percent of the children were male, their average age was 10.3 (SD=1.7). Two-thirds of the children were Caucasian, one third were Hispanic. At baseline their FVC% predicted was 104% (SD=12.4), FEV1 % predicted was 81.98% (SD 7.17), and FEV25-75% predicted was 88.26% (SD = 29.29). Forty-three percent had been admitted to a hospital at least once overnight for asthma, and 17% had been admitted to intensive care for asthma symptoms. Their average eNO was 9.98 (range 3.2 to 27.2, SD=6.30). eNO values significantly correlated only with recent cold, FEV1 and, by history, number of times admitted overnight to a hospital for asthma symptoms.CONCLUSIONS: In this sample of children with moderate persistent asthma, eNO did not correlate to asthma control as measured by pulmonary function, other than FEV1. eNO was also not correlated to physical exam findings or use of inhaled steroids.

CLINICAL IMPLICATIONS:  eNO may be useful as a broader screening tool for asthma control, rather than as a clinical indicator of asthma severity in children with moderate controlled asthma.

DISCLOSURE:  J. Mark, None.

Topics: nitric oxide , asthma
Chest. 2003;124(4_MeetingAbstracts):69S-c-72S. doi:10.1378/chest.124.4_MeetingAbstracts.69S-c
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PURPOSE:  Airway obstruction and atelectasis attributable to mucus plugging is a frequent complication in ventilated pediatric intensive care (PICU) patients due to a combination of thick viscous secretions and the small caliber of the airway. The abnormal viscoelastic properties of the secretions are due to the presence of highly polymerized polyionic DNA from the nuclei of degenerating polymorphonuclear leukocytes.Treatment of the atelectasis by conventional methods often fails and flexible bronchoscopy is technically difficult in this population. Recombinant human DNase (rhDNase, Pulmozyme) has been shown to reduce the viscosity of purulent bronchial secretion by fragmenting extracellular DNA. We present our experience with rhDNase in a ventilated pediatric population.

METHODS:  Retrospective chart review of all intubated and ventilated patients in the PICU treated with rhDNase for atelectasis (N=6). Conventional methods of treating atelectasis failed or were contra-indicated in these patients. All had atelectasis for over 48 hours. 2.5mg of rhDNase was instilled through the endotracheal tube via an in-line suction catheter every 12 hrs till resolution of atelectasis. Patients were positioned with the atelectatic side down. Outcome was monitored with serial chest radiographs.

RESULTS:  All six patients who met the inclusion criteria suffered varying degrees of atelectasis while on mechanical ventilation. All had complete resolution of atelectasis, documented by chest radiograph, with one to four doses of rhDNase. Table IRhDNase Patient CharacteristicsPatientAgeWeightDiagnosisDoses of rhDNaseAA4 mo3.8kgRSV(-) Bronchiolitis2TC17 mo12.5kgRSV (+) Bronchiolitis4DB2 yrs12.7kgAbdominal Trauma1CL3 yrs15kgHead Trauma4TP17 yrs32kgRetts Syndrome/Aspiration1CW2 yrs11.3kgCricoid Split/Subglottic Stenosis2and Figs.

CONCLUSION:  RhDNase is used in Europe and Canada for the treatment of atelectasis; there is consensus over the efficacy of a standatd 2.5mg dose. However, the optimal mode of administration is still debated. In our case series we demonstrate the effective use of instilled rather than nebulized rhDNase to treat atelectasis when administered as 2.5mg diluted in 5cc of normal saline, followed with manual breaths. The patient is positioned with the atelectatic side in the dependent position to improve delivery of the rhDNase.CLINICAL IMPLICATION: A therapeutic trial of rhDNase should be considered in the treatment of atelectasis in ventilated children before invasive bronchoscopy.

DISCLOSURE:  S.S. Da-Silva, None.

Chest. 2003;124(4_MeetingAbstracts):73S. doi:10.1378/chest.124.4_MeetingAbstracts.73S
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PURPOSE:  Palivizumab is frequently administered for respiratory synctial virus (RSV) prophylaxis to infants at high-risk. Our objective was to determine hospitalization rates and associated risk factors for RSV among infants who received palivizumab.

METHODS:  Data were prospectively gathered on all patients referred for palivizumab in a suburban pediatric pulmonary setting in Atlanta between 1999 and 2003. Data collected included hospitalization for RSV bronchiolitis, gender, gestational age, birthweight, single or multiple birth, number of siblings, smoker in household, daycare attendance, and type of insurance. Patients were seen by a pediatric pulmonologist or a supervised nurse practitioner or physician assistant and were treated for concurrent illnesses during the visits. Patients were reminded about risk factors for RSV infection at each visit.

RESULTS:  There were 3,520 patients who received palivizumab during the four-year period; 29 (0.8%) were hospitalized for RSV. The following relationships were found between potential risk factors and hospitalization for RSV: Hospitalization, n=29No Hospitalization, n=3491OR95% CIGestational age <35 weeks, [n (%)]27 (93.1)2811 (80.5)3.30.8 – 13.8Birthweight <2000 grams, [n (%)]24 (82.8)2361 (67.6)2.30.9 – 6.0Daycare, [n (%)]6 (21.4)366 (11.6)2.10.8 – 5.2Gender (male), [n (%)]19 (67.9)1899 (54.9)1.70.8 – 3.8Medicaid, [n (%)]9 (32.1)840 (24.6)1.50.7 – 3.2Smoker, [n (%)]5 (17.9)406 (12.9)1.50.6 – 3.9Number of siblings, [median (range)]1 (0-3)1 (0-7)0.90.6 – 1.3Multiple birth (2 or more), [n (%)]2 (7.1)1187 (34.3)0.10.1 – 0.6*

* Significant results

CONCLUSIONS: Patients who received palivizumab had a lower hospitalization rate due to RSV bronchiolitis than the hospitalization rate reported in the published IMpact study (0.8% versus 4.8%). This finding suggests that palivizumab has greater efficacy than previously determined. A comprehensive care model attending monthly to comorbidities, with monthly reminders on avoiding respiratory synctial virus exposure, may have contributed to the lower hospitalization rates. In the current study, those patients who were hospitalized trended toward having had a gestational age <35 weeks, a birthweight <2000 grams, attended daycare, male gender, insured by Medicaid, lived in a household with a smoker, and fewer siblings. Additionally, patients who were a multiple birth (i.e. twin, triplet, etc.) were significantly less likely to be hospitalized for RSV than patients who were a single birth.

CLINICAL IMPLICATIONS:  Palivizumab is highly effective in preventing RSV in a high-risk population, more so than previously recognized.

DISCLOSURE:  B.L. Lesnick, MedImmune, Grant monies.

Topics: palivizumab
Chest. 2003;124(4_MeetingAbstracts):73S. doi:10.1378/chest.124.4_MeetingAbstracts.73S-a
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PURPOSE:  To evaluate if obstructive sleep apnea syndrome (OSAS) is a mechanism of hypertension in obese patients.

METHODS:  Retrospective analysis of overnight polysomnography records of 90 pediatric patients aged 4.5 to 18.5 years. Obesity was expressed as BMIscore [body mass index (BMI) χ the 95th percentile BMI]. The severity of systolic and diastolic hypertension are expressed as SBPscore (systolic BP χ the 95th percentile systolic BP) and DBPscore (diastolic BP χ the 95th percentile diastolic BP).

RESULTS:  The incidence of hypertension (68%) and obesity (75%) was higher in patients with OSAS. Obese patients had a higher incidence of hypertension (70% vs. 9%), incidence of OSAS (54% vs. 29%), SBPscore (1.02±0.10 vs. 0.88±0.09), DBPscore (0.93±0.12 vs. 0.79±0.11), hypopnea index (HI) (3.83±6.20 vs. 0.89±1.54), and apnea-hypopnea index (AHI) (8.91±13.7 vs. 5.06±9.2) compared to non-obese patients (all p <0.05). In obese patients, SBPscore correlated with BMIscore (r = 0.33), Arousal Index (AI) (r = 0.32), and HI (r = 0.34). DBPscore correlated with BMIscore (r = 0.37), AI (r = 0.28), AHI (r = 0.4), and HI (r = 0.44). Multiple regression analysis was performed using BMIscore and log10-transformed HI, AHI, and AI as independent predictors. Log10HI (R2 = 7%) and BMIscore (R2 = 14%) were significant independent predictors of SBPscore. Log10HI (R2 = 18%) and BMIscore (R2 = 10%) were significant independent predictors of DBPscore. Obese hypertensive patients (n=39) had a significantly higher HI (4.8±6.9 vs. 1.58±3.17), AHI (10.5±15.2 vs. 5.24±8.85), and incidence of OSAS (64% vs. 29%) than the obese normotensive patients (n=17).CONCLUSIONS: Our findings are consistent with the hypothesis that OSAS is a mechanism of hypertension in obese pediatric patients.CLINICAL IMPLICATION: Hypertensive obese patients should be screened for OSAS.

DISCLOSURE:  R.M. Perkin, None.

Chest. 2003;124(4_MeetingAbstracts):73S. doi:10.1378/chest.124.4_MeetingAbstracts.73S-b
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PURPOSE:  Little data are available regarding the prevalence and characteristics of REM-OSA.We describe the prevalence and characteristics of REM-OSA.

METHODS:  We conducted a retrospective review of polysomnograms of patients diagnosed with obstructive sleep apnea at the Cleveland Clinic Foundation between July 1, 2000 and June 30, 2001. REM-OSA was defined as: overall apnea-hypopnea index (AHI) >5, REM-AHI >5, non REM-AHI (NREM-AHI) <5. We determined the prevalence and characteristics of REM-OSA. Correlation of REM-OSA with age, sex, body-mass index (BMI), Beck depression inventory (BDI), and Epworth sleepiness scale (ESS) was performed.

RESULTS:  1012 patients were diagnosed with OSA between July 1, 2000 and June 30, 2001. 104 patients satisfied our criteria for REM-OSA diagnosis (10.3%). The mean plus or minus standard deviation for the different characteristics were: age (47.6±13.4) years, BMI (33.3 ±7.8) Kg/m2, ESS (10.9±5.1), BDI (9.6±8.1), REM-AHI (28.8±15.2), NREM-AHI (3.2±1.3), AHI (7.4±2.2). The percentage of women in the REM-OSA group was 46.2 versus 27.9 in the OSA group (p value < 0.001). A weak correlation was found between REM-AHI and BMI (r= 0.4), but none was detected between REM-AHI and any of the other characteristics.CONCLUSIONS: REM-OSA represents a significant proportion of patients with OSA and appears to have a different gender predilection. It may represent a distinct subgroup with characteristics different from the ones established for OSA.

CLINICAL IMPLICATIONS:  REM-OSA with its different gender predilection may be a distinct subgroup of OSA. This may have therapeutic implications (continuous positive airway pressure therapy versus REM-suppressant medications).

DISCLOSURE:  G.S. Juvelekian, None.

Chest. 2003;124(4_MeetingAbstracts):74S. doi:10.1378/chest.124.4_MeetingAbstracts.74S
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PURPOSE:  Obstructive sleep apnea (OSA) can occur exclusively during rapid eye movement (REM) sleep, but its frequency and significance are unknown. Furthermore, REM sleep suppression is common in adults with sleep apnea and the total amount of REM sleep on the first night in the sleep laboratory is usually reduced. We intended to study the frequency of this entity and its effect on daytime hypersomnolence.

METHODS:  We retrospectively reviewed the Polysomnograms and the multiple sleep latency test (MSLT) of 140 consecutive patients diagnosed with OSA [apnea hypopnea index (AHI) ≥ 5]; The nonREM-AHI, the REM-AHI and the mean sleep latency (MSL) were noted for each patient. The combination of a nonREM-AHI ≤ 6 and a REM-AHI ≥ 15 was considered diagnostic of REM specific OSA. An MSL < 10 was considered to be indicative of significant daytime hypersomnolence. The MSL of the REM-specific OSA group was compared to the MSL of a non-REM specific OSA group (n=16) within the same range of AHI and Arousal Index (AI) using Chi Square Test.

RESULTS:  18 patients (12.8%) had exclusively REM-specific OSA. Their AHI ranged from 5 to 21 with a mean of 10.5±5.0. Ninety one patients (65%) had an MSLT. Eleven patients of these had REM-specific OSA. The mean MSL of the REM-specific OSA group and the matching group were 6.2±3.9 and 8.3±5.9 respectively. 91 % of the REM-specific OSA group and 56% of the matching group had an MSL < 10 (p=0.131).

CONCLUSION:  REM sleep-related OSA is found in about 13 % of patients with OSA. Almost all of these patients had significant daytime hypersomnolence. There was a trend for this group to have more daytime sleepiness than a group of patients with OSA of the same severity.

CLINICAL IMPLICATIONS:  Since some patients have OSA exclusively during REM sleep, the diagnosis of OSA should not be excluded unless the patient has REM sleep on the polysomnography.

DISCLOSURE:  Z.C. Boujaoude, None.

Chest. 2003;124(4_MeetingAbstracts):74S. doi:10.1378/chest.124.4_MeetingAbstracts.74S-a
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INTRODUCTION:  The aim of the study was to estimate the sympathetic activity in patients with obstructive sleep apnea (OSAS) and to evaluate the correlation between serum concentration of epinephrine and norepinephrine compared with body mass index and other constitual parameters. All patients underwent polysomnography. They were all classified as having OSA with AHI>10.

METHODS:  30 patients (27 M,3 F),aged 30-71(x= 50,96 ±9,90)were included in the study. In 5 cases hypertensive disorder were diagnosed. Based on body mass index (BMI) the obesity was found in 15 patients and overweight in 11 ones.The serum concentration of epinephrine, norepinephrine, urine acid, glucose and lipids level were measured in all patients.The HPLC methods(BIO- Rad Laboratories)were used to estimate the concentration of catecholamines.

RESULTS:  The middle serum concentration of epinephrine in hypertension group vs non hypertension group was 97.12±45.04 vs 57.25±26.56 pg/mL ( N:10-82pg/mL, x=27pg/mL vs 10-67 pg/ml x= 25pg/mL), and norepinephrine 625,26±147,81 vs 482.57±157.27pg/mL (N:41-773pg/mL x=288pg/mL vs 95-446 pg/mL x= 286pg/mL).There were observed positive correlation between epinephrine concenration(1)and norepinephrine(2) and body weigh (kg) (r1=0.44, r2=0.44), BMI (r1=0.44. r2=0.38) and waist/hips index (r2 = 0.38). The were also statistically significant correlation between catecholamines level and with uric acid concentration(r1=0.49, r2=0.77).CONCLUSIONS: We found the higher plasma catecholamines concentration in study group than in normal population, which is suggested a chronic elevation of sympathetic activity in OSAS. There were statistically significant correlation between serum catecholamines level and body weigh, BMI, waist/hips index and serum uric acid concentration.

CLINICAL IMPLICATIONS:  Elevated sympathetic activity may explain the increased cardiovascular morbidity associated with obstructive sleep apnoea.

DISCLOSURE:  R. Chazan, Medical University of Warsaw, University monies.

Chest. 2003;124(4_MeetingAbstracts):74S. doi:10.1378/chest.124.4_MeetingAbstracts.74S-b
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PURPOSE:  To study the awareness about sleep disordered breathing (SDB) among physicians under training (PUT) in medicine at a 600 bed tertiary care center.

METHODS:  A survey questionnaire with 9 questions pertaining to epidemiology, clinical features, and complications of SDB was administered to PUT. These physicians are expected to encounter and manage patients with SDB.

RESULTS:  The response rate was 61%. Following pertinent responses were obtained; 1) 61% of physicians do not record symptoms of SDB on initial encounter; 2) 19% thought that SDB is as commonly prevalent as asthma, while 41% were unaware of prevalence of SDB; 3) Only 11% said they would suspect SDB if the patient has had atleast 1 motor vehicle accident (MVA); 4) Majority (84%) were aware that polysomonography (PSG) is needed to diagnose SDB, and 77% said they could order the PSG; 5) Only 1/3 knew that SDB can occur in normal weight patients; 6) 1/3 said they do not need PSG to order continuous positive airway pressure (CPAP) therapy for SDB; 7) Only 36% ordered PSG to detect SDB.CONCLUSIONS: Majority of the PUT in a tertiary care center are unaware of the various clinical and epidemiological aspects of the SDB including its recognition and treatment. However, there was high awareness that PSG is needed to diagnose SDB and that they could order the appropriate test. A significant number of PUT did not recognize that SDB can occur in normal weight patients. Majority (89%) would not suspect SDB even if the patient has had one MVA. Some PUT said they do not need PSG to order CPAP for SDB.

CLINICAL IMPLICATIONS:  The low level of knowledge amongst PUT makes it imperative that high priority and more education hours need to be devoted towards educating physicians trainee about this common problem of SDB.

DISCLOSURE:  S. Sheel, None.

Chest. 2003;124(4_MeetingAbstracts):74S-c-75S. doi:10.1378/chest.124.4_MeetingAbstracts.74S-c
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PURPOSE:  Patients with obstructive sleep apnea (OSA) syndrome have a very high incidence of gastro-esophageal reflux disease (GERD). Previous studies have shown that one night of CPAP is efficacious in reducing the frequency of reflux events. The aim of this study was to assess the effect of one week of CPAP treatment on gastro-esophageal reflux in patients with objectively documented OSA and GERD.

METHODS:  Patients with suspected OSA and GERD based on clinical criteria were recruited. Polysomnography (PSG) and 24h continuous esophageal pH monitoring were performed. Patients with AHI > 20 events / hour and esophageal acid contact time of at least 6% were included. All patients had a CPAP titration to reduce the AHI < 10 events / hour. Patients were sent home on nasal CPAP for one week. Patients were re-evaluated after 7 nights of CPAP therapy. On the seventh night of CPAP treatment, repeat esophageal pH monitoring and PSG were performed.

RESULTS:  Twelve patients age (53±11) years with a BMI (33.4±5.4) completed the protocol with useable data. The mean AHI prior to treatment was 56.3 ± 31.5 and during CPAP treatment it was 4.1 ± 2.9. The mean CPAP treatment level was 8.2 ± 2.4 cmH2O. Sleep related acid contact pct (ACP) fell from 11.1 ± 8.8 to 7.2 ± 9.7 after CPAP (p < .05). The number of reflux events during sleep declined from 34.5 to 13.0 (P < .05). Arousal responses were not significantly altered.CONCLUSIONS: 1) Chronic CPAP use does significantly reduce episodes of reflux and ACP 2) Reduction in reflux events appears to be related to the decline in obstructive events, but acid contact time is reduced only by approximately 4%.

CLINICAL IMPLICATIONS:  A reduction in only 4% ACP is of questionable clinical significance.

DISCLOSURE:  M.M. Tawk, None.

Chest. 2003;124(4_MeetingAbstracts):75S. doi:10.1378/chest.124.4_MeetingAbstracts.75S
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PURPOSE:  Nothwithstanding regular use of nasal continuous positive airway pressure (nCPAP), some patients with obstructive sleep apnea (OSA) experience residual excessive sleepiness. In double-blind studies, modafinil, a novel wake-promoting agent, significantly improves wakefulness in patients with OSA who regularly use nCPAP. This 12-month open-label extension study evaluated long-term treatment with modafinil for residual excessive sleepiness in patients with OSA who were using nCPAP.

METHODS:  Eligible patients from a 12-week, randomized, double-blind, placebo-controlled study were enrolled in a 12-month, open-label extension trial. Modafinil was administered at either 200 mg/day, 300 mg/day, or 400 mg/day (adjusted clinically). Efficacy assessments included the epworth sleepiness scale (ESS) every three months, and the Functional Outcomes of Sleep Questionnaire (FOSQ) at Month 12 (or final visit).

RESULTS:  266 patients entered the open-label period; 175 (66%) completed the study. Modafinil significantly improved self-reporting wakefulness (assessed by ESS), at all time points. Mean changes (±SD) in ESS scores from baseline (baseline score, 14.5±3.6) at Months 3, 6, 9, and 12 were −5.7±4.5, −5.3±4.4, −5.4±4.6, and −4.5±4.7, respectively (p<0.01). Modafinil significantly improved functional status, measured as the mean change from baseline to final visit in the total score on FOSQ (increased 14% from baseline; p<0.01). Long-term modafinil treatment was well tolerated. The most frequently reported adverse events (≥5%) were infection (11%), nervousness (9%), headache (9%), accidental injury (8%), sinusitis (7%), rhinitis (7%), depression and anxiety (6% each), and insomnia and dizziness (5% each); most were mild or moderate in severity.CONCLUSIONS: Modafinil increased self-reported wakefulness, improved functional status, and was well-tolerated during 12-months treatment in nCPAP compliant patients with OSA who experienced residual sleepiness.

CLINICAL IMPLICATIONS:  Modafinil is effective for long term use as a good adjunctive therapy to augment nCPAP to improve wakefulness and functional status in patients with OSA.

DISCLOSURE:  M. Hirshkowitz, None. Supported by Cephalon, Inc., West Chester, PA

Chest. 2003;124(4_MeetingAbstracts):75S. doi:10.1378/chest.124.4_MeetingAbstracts.75S-a
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PURPOSE:  To investigate the contribution of video-assisted thoracoscpoic surgery (VATS) as part of an aggressive approach to the diagnosis and treatment of patients presenting with solitary pulmonary nodules (SPNs).

METHODS:  A retrospective chart review was performed to evaluate the outcome of solitary pulmonary nodules recommended for VATS from January 2002 through January 2003. A SPN was defined as a lung parenchymal lesion measuring 3 cm or less and no tissue diagnosis prior to surgery. Standard VATS techniques were used under general anesthesia. A wedge resection was performed, yiedling a frozen section, the pathology of which determined proceeding to lobectomy vs termination of the procedure in cases of benign nodules or advanced disease.

RESULTS:  52 patients with a diagnosis of a solitary pulmonary nodule were recommended for VATS. 35 malignancies were diagnosed, constituting a 67 percent yeild of malignancy for SPNs. Two conversions were necessary due to nodule size and location in one patient and an inability to perform single-lung ventilation in the second patient. One complication, stable atrial fibrillation, occurred on post-operative day one in a patient who underwent VATS only. The most common benign lesion was a granuloma, which in 5 of 7 patients PET scanning was positive.CONCLUSIONS: VATS is a safe procedure, with a 100% diagnostic yield. When there is a high clinical suspicion based on a patient’s medical history, tobacco use, current medical condition and PET scan results, VATS biopsy yields a high rate of malignancy.

CLINICAL IMPLICATIONS:  VATS is an integral part of the armamentarium for definitive diagnosis and treatment of lung nodules. It allows early intervention in the SPN, which in our experience is often a malignancy. Further investigation of the confounding value of PET scanning in the subset of patients with granulomatous disease is warranted. Number of CasesNodule Size(mm)PET Scan +PET Scan −VATS only211390Benign151370Malignant61620VATS + lobectomy3119154Benign21801Malignant2919153

DISCLOSURE:  L.T. Withers, None.

Chest. 2003;124(4_MeetingAbstracts):75S. doi:10.1378/chest.124.4_MeetingAbstracts.75S-b
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PURPOSE:  To assess whether cervical mediastinoscopy is mandatory before radical resection of malignant pleural mesothelioma (MPM).

METHODS:  46 patients who underwent radical excision of MPM between August 1999 and April 2003 were prospectively followed. Pre operative contrast enhanced magnetic resonance imaging (CEMRI) stage, tumour stage, long axis of lymph nodes and presence of metastatic tumour were collected. Pre operative CEMRI stage was compared with histological stage to generate sensitivity and specificity for nodal staging. The long axis measurements of lymph nodes in 42 patients’ pathological specimens were compared with the presence of tumour.

RESULTS:  46 patients (6 women, 40 men, median age 58 years, range 41 – 70) underwent 3 radical pleurectomies and 43 extrapleural pneumonectomies. Comparison of the postoperative survival of N0/1 with N2 disease is shown in the table. Comparison of N0/1 and N2 patientsNodal StageN0/1N2n3412Age (years)median5761NSrange41 - 7041 - 68Post operative survival (days)median417135p=0.0395% confidence interval292 - 542103 - 167T stage (TMN classification)I20II226III103IV1362 negative lymph nodes were measured and had a mean long axis of 16.2 mm (median 15, range 4 - 47) compared to 19 positive lymph nodes whose mean long axis was 14.4 mm (median 12, range 7 - 30) [p=0.20].CEMRI was performed a median 16 days pre operatively (range 1 - 53). CEMRI sensitivity for nodal disease is (4/19) 21% and specificity (23/26) 88%.CONCLUSIONS: In MPM N2 disease is related to poor survival compared with N1/0 disease. Preoperative staging by CEMRI differentiates poorly between nodal stages. Pathological nodal involvement cannot be predicted from nodal dimensions.

CLINICAL IMPLICATIONS:  These data suggest all patients considered for radical resection of MPM should undergo cervical mediastinoscopy.

DISCLOSURE:  J. Pilling, None.

Chest. 2003;124(4_MeetingAbstracts):76S. doi:10.1378/chest.124.4_MeetingAbstracts.76S
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PURPOSE:  For patients undergoing lung resection, estimation of postoperative lung function utilizing chest X-ray planimetry (CXR-planimetry) may be as effective as more complicated radionuclide studies of pulmonary regional ventilation and perfusion (regional-V/Q).

METHODS:  We estimated postoperative FEV1 (ppo-FEV1) using CXR-planimetry and regional-V/Q for patients who had pulmonary function studies before and after lung resection between Jan 1, 2000 and Dec 31, 2002 at UT MD Anderson Cancer. The estimated values obtained by each method were compared with one another and with the actual values measured postoperatively. Pearson’s comparison and linear regression tests were used to analyze this data. Patients’ demographics, underlying diagnoses, and types of surgical interventions were also studied.

RESULTS:  Twenty patients (M=14, F=6) with a mean age of 61 yr (range 39 to 73) were evaluated. Fourteen patients had non-small cell lung cancers, 4 had mesotheliomas, and 2 had lung metastases from extrathoracic cancers. Surgery consisted of pneumectomy in 6 patients, lobectomy in 9, bilobectomy in 3, and segmental resection in 2. There was a strong association between values of ppo-FEV1 estimated by CXR-planimetry test and by regional-V/Q (r=0.989, p=0.00001). Both methods were also equally effective for predicting postoperative FEV1. We found a significant strong association between the results of FEV1 measured postoperatively with those estimated preoperatively by CXR-planimetry (r=0.828, p=0.00004) and by regional-V/Q (r=0.828, p=0.000001).

CONCLUSION:  Chest X-ray planimetry can be as effective as regional-V/Q for predicting postoperative lung function for patients undergoing lung resection.

CLINICAL IMPLICATIONS:  Chest X-ray planimetry can be used as a simple and inexpensive alternative for preoperative estimation of pulmonary function after lung resection.

DISCLOSURE:  Y.M. Ersoy, None.

Chest. 2003;124(4_MeetingAbstracts):76S. doi:10.1378/chest.124.4_MeetingAbstracts.76S-a
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PURPOSE:  Major thoracic surgery is associated with a 5-10% incidence of post-operative cardiac events. It has been shown to be difficult, based on clinical criteria alone, to determine the severity of cardiac disease. We hypothesized that routine stress testing would identify patients at increased risk for cardiac complications and would lead to subsequent interventions, ultimately improving outcomes.

METHODS:  In 1998, a prospective study of routine cardiac stress testing in all patients undergoing major thoracic surgery was instituted, regardless of cardiac symptoms. From July, 1998 to February, 2003, 344 patients underwent major pulmonary or esophageal resections. These included VATS lobectomies/segmentectomies (240), open lobectomies/pneumonectomies (79), and Ivor Lewis esophagectomies (25). Pre-operative stress testing consisted of pharmacologic thallium scintigraphy or dobutamine echocardiography. The patients with positive stress tests underwent further evaluations/interventions and were treated wth PA catheter monitoring and beta blockers. Our thoracic surgical database was reviewed for: pre-operative presentations, stress test results, interventions, intra-operative events, post-operative course, complications, and mortality.

RESULTS:  The overall mortality in the 344 patients was 7 (2.0%), with 2 (0.6%) cardiac events. 10 patients (2.9%) had an overtly positive stress test: 8 underwent cardiac catheterization, 3 of whom had placement of a coronary stent. In this group there was one MI and no mortality. In the remaining 334 (97.1%) with a negative stress test, there was one MI (0.3%) with subsequent death. All cardiac events occurred in patients with pulmonary resections.CONCLUSIONS: There is a relatively low rate of cardiac events in this series of major thoracic surgeries. This may be due to identification of high risk patients by routine stress testing and subsequent interventions and modifications of peri-operative care.

CLINICAL IMPLICATIONS:  The results of this study suggest that routine pre-operative stress testing defines which patients would benefit from further cardiac study and interventions. Further study and analysis is warranted.

DISCLOSURE:  N.M. Katz, None.

Chest. 2003;124(4_MeetingAbstracts):76S. doi:10.1378/chest.124.4_MeetingAbstracts.76S-b
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INTRODUCTION:  The VALR™ surgical system (Spiration Inc, Redmond, WA) has been successfully tested in several small and large animal models of emphysema for lung volume reduction surgery (LVRS). However the size and anatomy of animal lungs is different than human, requiring analysis on ex-vivo human lungs with emphysema (EVHLE).

PURPOSE:  To evaluate the VALR system sleeve sizes in EVHLE and determine: the amount of tissue captured with a single sleeve, the effectiveness of sealing after tissue resection and safety.

METHODS:  Fifteen complete sets of fresh EVHLE were used in these experiments. The VALR surgical system uses controlled vacuum to capture lung tissue into a silicone sleeve. When deployed, the sleeve produces compression and sealing facilitating LVRS. Three different sleeve sizes (15, 17.5 and 20mm diameter) were tested on the upper lobes. After deployment, each sleeve was secured with suture, and then the tissue captured within the sleeve was resected leaving a small band of material compressing the lung. The volume of tissue captured was visually estimated compared to the entire lobe. The lungs were then inflated and tested for air leaks underwater. The tissue captured by the sleeve was weighed.

RESULTS:  The average volume of upper lobe captured and reduced by the devices was 10-15, 25-30 and 35-40 percent by the 15, 17.5 and 20 mm sleeves, respectively. After tissue resection, no air leaks or tissue trauma were observed during lung inflation. By weight, 10±9, 30±7 and 41±10 grams of upper lobe were captured by the 15, 17.5 and 20 mm sleeves, respectively.CONCLUSIONS: In EVHLE, a single deployment of the VALR compression sleeves safely captured adequate amounts of tissue without apparent trauma or complications. There were no air leaks observed after tissue resection. A direct correlation was established between the size of the sleeve and the mass and volume of tissue reduced.

CLINICAL IMPLICATIONS:  The VALR surgical system may be adequate for clinical use.

DISCLOSURE:  L.E. Snyder, Spiration Inc, Shareholder, Industry, discussion of product research or unlabeled uses of product.

Chest. 2003;124(4_MeetingAbstracts):77S. doi:10.1378/chest.124.4_MeetingAbstracts.77S
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BACKGROUND:  Current modalities for imaging the lung and lower airway have relatively low resolution and have limitations in the ability to accurately characterize pleural, lung, or lower airway malignancies and other abnormalities. Optical Coherence Tomography (OCT) is a rapidly developing high resolution (near histologic level) imaging modality that has many potential advantages for early diagnosis. In order to assess the potential for OCT real-time imaging of pleural or peripheral lower airways, lungs in various states of inflation were imaged with OCT.

PURPOSE:  To evaluate the potential of OCT to provide accurate real-time high resolution imaging of the lung, pleura, and lower airway.

METHODS:  Freshly excised lungs were obtained from pigs and New Zealand White rabbits and imaged (inflated, deflated, and fluid filled) by OCT, using a prototype super-luminescent diode system constructed in our laboratory (10μm resolution and center wavelength of 1300nm). After OCT images were obtained, the samples were processed for standard H&E histology for comparison to OCT.

RESULTS:  The OCT imaging offered high resolution of the lung, and lower airway, with approximately 10 μm resolution, to depths of about 2 mm below the lung surface. The OCT images closely matched histological images, showing detailed structure including the pleura, alveoli, and respiratory bronchioles.

CONCLUSIONS:  OCT, using NIR interferometric methods to enable near histological level imaging with the potential for ‘optical biopsy’ capabilities, has demonstrated high-resolution imaging feasibility in excised lung and lower airway, both along pleural surface and in superficial lung tissue.

CLINICAL IMPLICATIONS:  This imaging modality can be adapted to potentially obtain in vivo real time imaging for minimally invasive diagnostic purposes. With further advances, OCT may provide an accurate in vivo method for early diagnosis of pulmonary abnormalities.

DISCLOSURE:  N. Mikhail-Hanna, TRDRP# 9RT-0094, Grant monies; Air Force D/F49620-00-10371, Grant monies.

Chest. 2003;124(4_MeetingAbstracts):77S. doi:10.1378/chest.124.4_MeetingAbstracts.77S-a
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BACKGROUND:  Solitary pulmonary nodules (SPN) can be visualized by endobronchial ultrasound (EBUS) in at least 75%. It has been described that by a complex analysis of different structural items the histology is suggested. In a preliminary study we demonstrated that computerized analysis might be a simple and reliable alternative method.

AIM OF STUDY:  In a prospective study on 50 SPN the distribution of grey scale signals on the EBUS-image were calculated by a computer program (“histogram”) and compared to the histological findings. By computer analysis of the greyscale distribution in EBUS-images of solitary pulmonary nodules the nature could be predicted in the majority of cases. The consistency of these data had to be confirmed by an independent study.

RESULTS:  EBUS images of SPN in 50 consecutive cases in Kumamoto (25 benign, 25 malignant) were sent to Heidelberg for computerised analysis of their internal structure without knowing the final histology. After decision for a benign or malignant nature according to the grey scale distribution the results were compared to the histology. In 46 of 50 cases (92%) the diagnosis by EBUS was correct. Two benign lesions (1 Cryptococcosis and 1 Aspergilloma, 2%) had a malignant appearance, whereas two small cell lung cancers (2%) appeared as inflammatory infiltrates.

CONCLUSION:  The study confirmed our primary assumption that computerized analysis of the EBUS image is a simple and reliable method to predict the histology of SPN and might be useful in decision for treatment of these

DISCLOSURE:  H.D. Becker, None.

Chest. 2003;124(4_MeetingAbstracts):77S. doi:10.1378/chest.124.4_MeetingAbstracts.77S-b
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PURPOSE:  OCT can obtain high-resolution, cross-sectional microimages of tissue potentially allowing for optical biopsy to substitute for conventional excisional biopsy. The purpose of the present study is to investigate the capability of OCT to image the microstructure of the normal and abnormal bronchial tissue.

METHODS:  Equipment: OCT system; the OCT system of this study has been produced by Light Lab Imaging (Boston, USA). Preclinical examination: the OCT system was used in seven resected lung specimens which had been signed the informed consent for the OCT study. The OCT catheter was inserted from biopsy channel of the bronchoscope and evaluation of bronchial lumen was performed. The catheter directs the OCT beam radially and scans a circumferential pattern to generate a transluminal image. We collected OCT images of normal bronchus, primary tumors (2 cases of centrally located) and alveoli. All the images were captured and marked to identify the source of OCT imaging for later correlation with histology.

RESULTS:  1) Normal bronchus; the bronchial mucosal layer appears homogenous in OCT image. Submucosal layer is relatively reflective due to the presence of extracellular matrix. A gap can be seen between the submucosa and smooth muscle layer and cartilage appears highly scattering below the muscle layer. 2) Alveoli; the uniform bronchial wall and the structure of alveoli containing air can be observed. 3) Bronchial tumor; nodular-infiltrative type squamous cell carcinoma is observed. The tumor is depicted by unevenly distributed high backscattering area and resultant loss of layer structure in the OCT image.CONCLUSIONS: Five layers were separately observed in normal bronchus by OCT image, as opposed to bronchial tumors which lacked a layered structure. OCT images were captured by OCT catheter probe inserted through the biopsy channel of bronchoscope, which was a good clinical simulation.

CLINICAL IMPLICATIONS:  OCT should revamp the present strategies for endoscopic early diagnosis. Optical biopsy using by OCT system is considered to be useful in follow up to dysplasia as well as evaluation of therapeutic outcome.

DISCLOSURE:  M. Tsuboi, None.

Chest. 2003;124(4_MeetingAbstracts):78S. doi:10.1378/chest.124.4_MeetingAbstracts.78S
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PURPOSE:  Flexible bronchoscopy (FB) in intubated patients on mechanical ventilation (MV) increases airway resistance. During FB, two ventilatory strategies are possible: maintaining tidal volume (TV) while maintaining baseline PaCO2 or allowing reduction of TV while permitting hypercapnea. Lawson (Chest 2000; 118:824-831) reported significant hyperinflation due to expiratory flow limitation with FB in an intubated lung model particularly with small endotracheal tubes. We studied end expiratory lung volume (EELV) during FB in intubated patients while limiting TV and permitting hypercapnea.

METHODS:  Changes in EELV were measured using respiratory inductance plethysmography (RIP). We studied 12 intubated patients on MV requiring bronchoscopy with calibrated RIP. Patients were sedated and paralyzed. MV settings: A/C, FIO2 1.0, pressure limit 60cm H2O, Peak Flow 60 Lpm ramp. TV, PEEP level, respiratory rate settings were constant. RIP, SaO2, cycling pressure, EKG, BP were measured continuously with pre/post bronchoscopy respiratory mechanics and ABG.

RESULTS:  On insertion of FB, there was pressure limiting with resultant marked decrease in TV. There was no increase in EELV in any patient during intubated bronchoscopy. There were multiple episodes of decrease in EELV that coincided with suctioning (max 1250cc decrement). In patients with diffuse lung disease, loss of EELV coincided with marked transient desaturation. Vital signs were stable. Respiratory mechanics were unchanged. PaO2/FIO2 ratio decreased 66+/-43 (mean+/-SD) and PaCO2 increased by 12+/-9mmHg (mean+/-SD) pre/post bronchoscopy.CONCLUSIONS: No elevation of EELV occurred during bronchoscopy in intubated patients. TV was reduced by peak pressure limit protecting the patient against hyperinflation though with consequent increase in PaCO2. Suctioning during bronchoscopy caused reduction of EELV.

CLINICAL IMPLICATIONS:  Increase in EELV during bronchoscopy in intubated patients does not occur when tidal volume is limited. Permissive hypercapnea during bronchoscopy appears to be well tolerated. Suctioning should be limited, especially in patients vulnerable to derecruitment effect. To reduce hyperinflation risk during FB, the approach of permissive hypercapnea is appropriate and may be especially applicable to patients who have small diameter ET tubes.

DISCLOSURE:  E. Shakespeare, None.

Chest. 2003;124(4_MeetingAbstracts):78S. doi:10.1378/chest.124.4_MeetingAbstracts.78S-a
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PURPOSE:  According to ATS statement of bronchoalveolar lavage in adults with pulmonary diseases (1990) about fluid instillation. It mentioned 2 different aspiration techniques (hand suction versus wall suction) that were used in the procedure. BAL fluid characteristics and volume will be affected by airway collapse and bronchial contamination from uncontrolled suction. Our aim was to investigate the differences between fluid from 2 methods.

METHODS:  Prospective randomized study in the adult patients underwent diagnostic bronchoscopy during October 2002-April 2003. When BAL procedures were performed, serial 4 separated 50-ml aliquots of saline were instilled and fluid was aspirated by hand suction into syringe (2 aliquots), followed by controlled wall suction (2 aliquots). The second aliquot from each method was selected. Recovered fluid volume measurement and cell analysis were done. Statistical analyses were 2-sample t-test and Wilcoxon signed rank test.

RESULTS:  Thirty patients were enrolled, and 60 fluid specimens were obtained. Diffused / localized lung disease ratio was 1/2. Between hand suction and wall suction methods, there was no significant difference in recovered fluid volume(23.93+/-8.66 ml vs. 21.36+/-9.68 ml, p > 0.283), the total cells count( median 3.55x 106 vs. 3.51x106cells, p > 0.959), percentage of alveolar macrophage (61.16+/-27.82 vs. 70.96+/-30.49, p > 0.198) and number of bronchial epithelium per 100 nucleated cells.

CONCLUSION:  There was no difference in volume and characteristics of the BAL fluid obtained from hand suction and wall suction.CLINICAL IMPLICATION: Both hand suction and wall suction with controlled pressure can be performed in BAL procedure without effect on the BAL fluid interpretation.

DISCLOSURE:  T. Kawamatawong, None.

Chest. 2003;124(4_MeetingAbstracts):78S. doi:10.1378/chest.124.4_MeetingAbstracts.78S-b
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PURPOSE:  Fiberoptic Bronchoscopy has been used to evaluate patients with suspected malignancy for many years. Specimen collection typically includes bronchial washings, bronchial brushings, and transbronchial biopsies. The goal of our study was to determine if there is an optimal order of specimen collection.

METHODS:  Patients referred for bronchoscopic evaluation of possible malignancy were stratified according to the presence or absence of an endobronchial abnormality. They were then prospectively randomized to one of three experimental arms: Wash/Brush/Biopsy, Brush/Wash/Biopsy, and Brush/Biopsy/Wash. Data recorded included patient demographics, lesion size and location, final diagnosis with method of determination, and complications.

RESULTS:  141 patients were randomized of which fifty-five patients had visible endobronchial lesions. Bronchoscopy yielded a diagnosis in 63% of patients without endobronchial lesions and in 82% of patients with visible lesions. There was no significant difference between the yield of the three sampling orders in the visible endobronchial lesion or non-visible lesion groups. In patients with no visible lesion, bronchial washing yielded a diagnosis of malignancy in 17%, bronchial brushing yielded a diagnosis in 34%, and transbronchial biopsy yielded a diagnosis in 24%. In patients with a visible lesion, bronchial washing yielded a diagnosis in 23%, mucosal biopsy yielded a diagnosis in 70%, and bronchial brushing yielded a diagnosis in 50% of patients. The diagnosis of a malignant lesion was never made solely on the basis of the cytologic evaluation of bronchial washing. Complications included two patients with bradycardia and hypotension, four patients with ventilatory insufficiency, and one patient with bronchospasm. There were no deaths in this study.CONCLUSIONS: Altering the sequence of sample collection does not alter the yield in patients undergoing fiberoptic bronchoscopy for suspected malignancy. Bronchial washing cytology is of minimal utility in patients with suspected malignancy.

CLINICAL IMPLICATIONS:  Bronchial washing cytology has relatively low yield in the diagnosis of malignancy and may not be necessary during bronchoscopy for patients with suspected malignancy.

DISCLOSURE:  V.J. Test, Scott, White, Sherwood, and Brindley Foundation, University monies.

Chest. 2003;124(4_MeetingAbstracts):78S-c-79S. doi:10.1378/chest.124.4_MeetingAbstracts.78S-c
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PURPOSE:  Linezolid, the first approved oxazolidinone, has activity against gram-positive bacteria, including strains resistant to other antibiotics. We report the adverse event (AE) profile during linezolid use in nosocomial pneumonia for the subset of patients with ventilator-associated pneumonia (VAP).

METHODS:  AE data were pooled for the subset of patients with VAP from 2 identical, randomized, double blind, IV studies comparing linezolid (LZD) and vancomycin (VAN) in patients with gram positive nosocomial pneumonia. The investigator recorded and rated AEs as serious or non-serious, with judgment on severity by standard definitions, and assessed the relationship of AEs to study medication.

RESULTS:  544 VAP patients were treated (282 LZD, 262 VAN). There were no significant differences between groups in the number of patients with at least one AE (82% vs 84%, respectively), drug-related AEs (14% vs 12%), discontinuation due to drug-related AEs (1.4% vs 1.5%), serious AEs (37% vs 38%), or deaths (16% vs 20%). AEs ≥5%, regardless of causality, in LZD vs VAN groups, respectively, were diarrhea (13.1% vs 11.1%), fever (5.7% vs 6.1%), pneumonia (6.0% vs 7.3%), respiratory failure (8.2% vs 5.0%), sepsis (7.4% vs 9.5%), urinary tract infection (8.2% vs 7.3%), and vomiting (5.3% vs 5.3%). Additional AEs ≥5% were pressure sore (5.3%), nausea (5.0%) and hypertension (5.0%) in the LZD group, and rash (7.3%) and hypotension (5.0%) in the VAN group. The only AE in ≥2% of patients that was considered drug-related was diarrhea (4.3% LZD vs 2.3% VAN, p=.20). The most common serious AEs (≥3%) were related to patients’ underlying disease: respiratory and multi-organ failure for LZD and sepsis, pneumonia and respiratory failure for VAN.CONCLUSIONS: IV LZD is generally well tolerated in patients with ventilator-associated pneumonia. The nature and frequency of AEs were comparable in the LZD and VAN groups and were influenced by the severity of patients’ underlying disease.

CLINICAL IMPLICATIONS:  Linezolid is a reasonable therapeutic option, with no increased risk of adverse events, in the treatment of patients with VAP.

DISCLOSURE:  G.J. Hooper, Pharmacia employee, Industry.

Chest. 2003;124(4_MeetingAbstracts):79S. doi:10.1378/chest.124.4_MeetingAbstracts.79S
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PURPOSE:  To assess the impact of frequent changes of antibiotics on the outcome of patients with Ventilator Associated Pneumonia (VAP)

METHODS:  Retrospective chart review of 56 patients with VAP, divided into four groups, based on the frequency of changes in antimicrobial regimens, excluding de-escalation and simplification of therapy. The Clinical pulmonary infection score (CPIS) was used for the evaluation of pneumonia severity.

RESULTS:  19 Patients had no change of initial antibiotic regimen (Group 0); 8 and 19 patients, respectively had one and two changes (Group 1 and 2); and 10 patients had three or more changes (Group 3). There were no differences between the four groups with regard to age, gender, underlying disease, length of hospital stay, and the CPIS at diagnosis. The duration of ICU stay and mechanical ventilation increased with the frequency of changes. The adequacy of the treatment did not significantly differ among groups, but the rate of initial inadequate therapy tended to decrease as the frequency of changes increased (Group 0: 12.7%; Group 1: 8.1%; Group 2: 6.9%; Group 3: 5.9%.) Changes were based on the results of cultures in 37.5%, 15.8% and 14.0% of Group 1, 2 and 3, respectively. On the other hand, changes were for more often for uncertain reasons as the frequency of changes increased: 1.25%, 23.7% and 37.2% in Groups 1, 2 and 3, respectively. The crude mortality of Group 0 (21.1%) and Group 1 (25.0%) were similar. However, compared to Group 0, the mortality of Group 2 (57.9%) and Group 3 (80.0%) were higher (p = 0.04 and 0.004, respectively).CONCLUSIONS: Frequent changes of antibiotics, often for uncertain reasons, were associated with increased mortality in patients with VAP.

CLINICAL IMPLICATIONS:  If initial therapy is inadequate, there will be no increased mortality if antibiotics are changed only once.

DISCLOSURE:  M. Kawabata, None.

Chest. 2003;124(4_MeetingAbstracts):79S. doi:10.1378/chest.124.4_MeetingAbstracts.79S-a
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PURPOSE:  Late onset ventilator associated pneumonia (VAP) caused by enteric gram negative bacteria has an attributable mortality ranging from 10-60%. This high mortality rate despite the use of multiple IV antibiotics has led to speculation regarding the inability of IV antibiotics to reach the lungs. Data regarding the use of aerosolized tobramycin (TOBI) in VAP is sparce.

METHODS:  We performed a retrospective analysis of a case controlled utilization study of TOBI in VAP caused by enteric gram negative bacteria (microbiologically documented). Trauma patients diagnosed with VAP (by quantitative microbiologic techniques) were pulled from our trauma registry database and a detailed chart review was performed. All patients received either 2 IV antibiotics (Control group-n=25) or 1 IV antibiotic and TOBI (Study group-n=24). Demographic and outcome data were collected and analyzed for statistical significance.

RESULTS:  Demographic data (gender, age, injury severity score (ISS), and APACHE-2 score at the time of diagnosis of VAP) were statistically comperable between the control and study groups (Table 1)

Demographic data

Male/Female ratioAgeISSAPACHE-2Control group n=2520/537 ± 1825.1 ± 9.523.7 ± 4.9Study group n=2417/744 ± 1922.8 ± 12.322.5 ± 5.6. Outcome data (ICU length of stay, ventilator days, and hospital length of stay) showed significant reductions. Overall survival to hosptal discharge was not signifcantly different (Table 2)

Outcome data

ICU Length of Stay (days)Ventilator daysHospital Length of Stay (days)Survival (%)Control group n=2516.0 ± 7.115.4 ± 6.521.8 ± 7.480Study group11.1 ± 5.49.9 ± 3.316.3 ± 5.491 n=24*p<0.05*p<0.05*p<0.05CONCLUSIONS: In clinically matched trauma patients with VAP caused by enteric gram negative bacteria the use of aerosolized tobramycin (TOBI) seems to improve clinical outcomes.

CLINICAL IMPLICATIONS:  TOBI may be a useful tool in the treatment of VAP caused by enteric gram negative bacteria.

DISCLOSURE:  A. Chendrasekhar, CHIRON, discussion of product research or unlabeled uses of product.

Chest. 2003;124(4_MeetingAbstracts):79S-b-80S. doi:10.1378/chest.124.4_MeetingAbstracts.79S-b
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PURPOSE:  We have substantial experience with suppression of bacterial growth in chronic lung disease by the use of colistin aerosol. VAP with highly resistant Gram negative organisms has become a major clinical problem in the last few years. We report here the results of our efforts to treat such infections with direct instillation of colistin solution in patients with artificial airways.

METHODS:  Retrospective chart review of 11 patients in our institution who had VAP with Gram negative bacilli resistant to all available systemic antibiotics. Patients were given colistin by direct instillation of 50 mg in 50 ml of saline via catheters passed through their endotracheal or tracheostomy tube, localized according to the distribution of pulmonary infiltrates. Roentgenographic, hemodynamic, microbiologic, hematologic and serum chemistry data before and after colistin instillation were recorded, as were vital signs, demographics and outcome. No antibiotic therapy other than local colistin was administered.

RESULTS:  Of the 11 patients who were treated with local instillation of colistin, 8 recovered and were discharged, while 3 died. All patients improved or completely resolved their pulmonary infiltrates after colistin instillation except one patient whose post-treatment chest x-ray was not conclusive due to fluid overload. Sputum cultures were sterilized in all 11 patients. Fever and systemic signs resolved in all patients. WBC count improved significantly in 8 patients. No toxicity was detected. The 3 deaths were unrelated to infection.

CONCLUSION:  Local instillation of colistin is an effective treatment for VAP caused by highly resistant Gram negative organisms.

CLINICAL IMPLICATIONS:  This treatment should be considered in severe pulmonary infections caused by highly resistant Gram negative organisms, especially when they occur in patients with artificial airways.

DISCLOSURE:  W.D. Marino, None.

Chest. 2003;124(4_MeetingAbstracts):80S. doi:10.1378/chest.124.4_MeetingAbstracts.80S
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PURPOSE:  Nosocomial pneumonia (NP) remains a significant challenge in the ICU. Most clinical trials in this area have focused on non-ventilated patients with hospital-acquired pneumonia. Few studies have included individuals with ventilator-associated pneumonia (VAP). We describe the results for patients with VAP participating in a recent randomized trial comparing levofloxacin (L) to imipenem/cilistatin (I).

METHODS:  In this multicenter, randomized, controlled trial, subjects with NP were treated with either L 750 mg q24 h or I 500 – 1000 mg q6-8h. Both combination therapy with additional anti-pseudomonal agents in cases of known or suspected P. aeruginosa and the use of vancomycin were permitted. Patients with VAP were defined as those receiving at least 48 hours of mechanical ventilation (MV) before developing pneumonia. Clinical success (either clinical cure or improvement) represented the primary endpoint. Mortality at follow-up evaluation (28-32 days post-therapy) served as a secondary endpoint.

RESULTS:  The entire NP cohort included 438 patients of which 222 (50.7%) had VAP. The most frequently isolated gram negative pathogens included: P. aeruginosa (n=36), E. coli (n=19), and K. pneumoniae (n=17). Patients treated with L (n=111) were comparable to those receiving I (n=111): mean age 52.2±20.9 yrs. for L vs 53.5±21.6 yrs. for I, (p=.65); mean APACHE II 14.8±5.2 with L vs. 15.1±5.4 for I, (p=.88). Neither duration of MV prior to developing VAP (8.0±7.3 days with L vs. 9.8±18.2 days with I, p=.31) nor need for vasopressors (17.1% with L vs. 12.6% with I, p=.35) differed based on initial antibiotic regimen. Outcome results are shown in the tableLIP-valueITT*, clinical success58.6%63.1%.49Clinically evaluable cohort#, success56.1%58.1%.82Mortality11.0%13.1%.68*

ITT – intention to treat;

#

Clinically evaluable – received at least 5 days of study therapy

below.CONCLUSIONS: L is as effective as I for the empiric treatment of VAP.

CLINICAL IMPLICATIONS:  Levofloxacin (750 mg q24h) represents an effective, once daily alternative for therapy in critically ill patients with VAP.

DISCLOSURE:  A.F. Shorr, OMP, Grant monies.

Chest. 2003;124(4_MeetingAbstracts):80S. doi:10.1378/chest.124.4_MeetingAbstracts.80S-a
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PURPOSE:  Tracheobronchitis (TCB) due to Herpes Simplex Virus (HSV) is thought to be uncommon as a lower respiratory pathogen. The literature mainly consists of small case series. To better define this syndrome, we identified and retrospectively reviewed charts of patients (pts) with HSV TCB at Hahnemann University Hospital (HUH).

METHODS:  The pathology and microbiology computer databases were queried for pts with HSV cytopathic effect (CPE) and for patients with HSV (+) cultures (cx) from bronchoscopy (BCS) specimens. The diagnosis of HSV TCB was made based on evidence of CPE typical of HSV from BCS samples.

RESULTS:  Twenty seven cases were identified over 7 yrs. Mean age was 63 yrs. 30% pts had prior history of HSV. 30% had other sites of active HSV. 37% used corticosteroids; 33% had cancer; 14% were undergoing chemotherapy. 20% had history of smoking. 44% pts had fever. 96% were intubated. 93% were short of breath and 56% had bronchospasm. All pts had other respiratory symptoms and abnormal BCS findings. The most common findings were bland nodules, erythema, exudate, ulcerations and edema. HSV was recovered in 19 cases; 1 pt had negative BCS HSV cx; 7 pts did not have cx performed. 85% received Acyclovir. Everyone recovered from TCB but the associated mortality was 48%.

CONCLUSION:  27 cases of HSV TCB were reviewed. Most pts did not have a prior history of HSV. Only half of pts were immunosupressed (e.g. steroids, cancer, chemotherapy). Nearly all pts were critically ill and intubated in intensive care. Bronchospasm, a commonly reported associated symptom, was seen in about half of pts. Nodules, erythema and exudate were the most common BCS findings. All pts recovered from TCB but many died from co-morbid conditions.

CLINICAL IMPLICATIONS:  HSV TCB should be considered in critically ill pts with unexplained respiratory symptoms and the above described BCS findings.

DISCLOSURE:  R.A. Promisloff, None.

Chest. 2003;124(4_MeetingAbstracts):80S. doi:10.1378/chest.124.4_MeetingAbstracts.80S-b
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PURPOSE:  Talc used for pleurodesis may elicit systemic effects due to the migration of small talc particles into the systemic circulation or the absorption of inflammatory mediators from the pleural space. The aim of this study was to compare the acute systemic inflammatory response produced by talc in doses considered effective (400 mg/kg) and ineffective (100 mg/kg) in producing pleurodesis in rabbits.

METHODS:  Groups of six rabbits were injected intrapleurally with talc 100 or 400 mg/kg and after 6, 24 and 48 hours samples of blood were assayed for leukocytes (WBC), neutrophil percent (%N), lactic dehydrogenase (LDH) and the inflammatory cytokines interleukin-8 (IL-8) and vascular endothelial growth factor (VEGF). Pre-injection blood samples were used as controls. Statistics: ANOVA.RESULTS: 6 hours24 hours48 hoursControlTL100TL400TL100TL400TL100TL400WBC5.1 ± 1.6*7.6 ± 2.19.7 ± 3.64.7 ± 1.36.8 ± 3.17.8 ± 2.99.0 ± 3.4%N53 ± 7*74 ± 977 ± 661 ± 544 ± 1#54 ± 630 ± 9#LDH217 ± 84499 ± 170677 ± 569336 ± 160359 ± 228227 ± 135206 ± 100IL-890 ± 31*890 ± 390620 ± 3801461 ± 610880 ± 5401410 ± 8701600 ± 440VEGF< 15*65 ± 3543 ± 1066 ± 4295 ± 92121 ± 56164 ± 142

WBC: *p< 0.05 TL400 6 and 48 hours vs control.

%N: *p< 0.001 TL100 and TL400 6h vs control; #p< 0.05 TL100 24 and 48 hours vs TL400.

LDH: NS.

IL-8 and VEGF: *p< 0.05 TL100 and TL400 at all times vs control.

CONCLUSIONS: Intrapleural talc elicited an acute systemic inflammatory response of a comparable degree with doses considered either ineffective or effective in producing pleurodesis. The WBC tended to increase more in the TL400 groups while the %N tended to increase more in the TL100 group. In both treatment groups, there were significant increases in the %N, LDH, IL-8 and VEGF at most time points.

CLINICAL IMPLICATIONS:  Side-effects reported with talc pleurodesis may be related to a systemic inflammatory response that is not dependent on the dose of talc instilled into the pleural cavity.SUPPORTED BY: FAPESP, CNPq.

DISCLOSURE:  E. Marchi, None.

Chest. 2003;124(4_MeetingAbstracts):81S. doi:10.1378/chest.124.4_MeetingAbstracts.81S
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PURPOSE:  Air in the pleural space is among the most common etiologies of eosinophilic pleural effusions (EPE). We have recently developed a mouse model of pneumothorax-induced pleural eosinophilia to examine the mechanisms of eosinophil accumulation in pleural tissues. In the present study we examined the significance of IL-5 and IL-13 in

METHODS:  Nine wild-type (wt), 6 IL-5 knockout and 4 IL-13 knockout C57/BL-6 mice where injected intrapleurally with 0.4 ml air. Mice were sacrificed 48 hours after the introduction of pneumothorax because, as we have previously shown, pleural eosinophilia peaks at this time point. Pleural lavage (PL) with 1 ml saline was performed immediately after death. Nucleated cell counts were measured with an automatic cell counter. Cytospins were made and stained with Wright-Giemsa stain for the differential cell count.

RESULTS:  The mean ± SEM PL eosinophil counts were: 1799±188/mm3 in the wt group, 215±53/mm3 in the IL-5 knockout group and 1544±626/mm3 in the IL-13 knockout group. The mean ± SEM PL eosinophil percentages were 33±3.6%, 4.8±1.1% and 26±4.9%, respectively. The PL eosinophil counts and percentages were significantly lower in the IL-5 knockout mice than in the wt (p<0.001, for both the counts and the percentages), or the IL-13 knockout mice (p=0.001, for the percentage and p=0.03 for the counts). However, the PL eosinophil counts and percentages did not differ significantly between wt and IL-13 knockout mice.

CONCLUSION:  IL-5 but not IL-13 is a crucial mediator of pneumothorax-associated pleural eosinophilia.

CLINICAL IMPLICATIONS:  Anti-IL-5 treatment may be useful in the treatment of persistent, symptomatic post-traumatic eosinophilic pleural effusions.

DISCLOSURE:  I.T. Kalomenidis, None.

Chest. 2003;124(4_MeetingAbstracts):81S. doi:10.1378/chest.124.1.159
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PURPOSE:  The presence of blood and/or air in the pleural cavity is thought to be the leading cause of eosinophilic pleural effusions (EPE). The frequency of malignancy among EPE is controversial. Moreover, since malignant pleural effusions (MPE) are frequently bloody, it is not clear whether the reason of pleural fluid eosinophilia in MPE is the presence of blood. In this study we hypothesized that malignancy is a common cause of EPE and that pleural fluid eosinophilia in MPE is frequently due to the presence of blood.

METHODS:  A data-base containing data from 1195 pleural effusions was searched for EPE, defined as the effusions that contained more than 10% eosinophils at the first thoracentesis, and MPE (again only at first thoracenesis).

RESULTS:  One hundred and seventy-two EPE were found. The most common etiology was heart surgery (68%), followed by malignancy (8.7%), parapneumonic (4.6%), heart failure (4.6%) and other diseases (4.1%). No etiology was found in 10% of the cases. We also identified 170 MPE; 13 of them were bloody, defined as those with at least 100,000 red blood cells/mm3. Three of the 13 bloody MPE (23%), and 12 of the 157 (7.6%) non-bloody MPE were EPE (Fisher’s exact test: p=0.093).

CONCLUSION:  Malignancy was the second most common cause of EPE. Although bloody MPE tended to be eosinophilic more frequently than the non-bloody MPE, 80% of the eosinophilic MPE were not bloody, suggesting that factors other than blood contribute to pleural fluid eosinophil accumulation in MPE.

CLINICAL IMPLICATIONS:  The presence of pleural fluid eosinophilia in a non-bloody pleural effusion does not rule out the diagnosis of malignancy.

DISCLOSURE:  I.T. Kalomenidis, None.

Chest. 2003;124(4_MeetingAbstracts):81S. doi:10.1378/chest.124.4_MeetingAbstracts.81S-b
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PURPOSE:  To assess the value of closed pleural method versus thoracoscopy in bacteriological diagnosis of tuberculous pleural effusions.

METHODS:  100ml of pleural fluid and 5 pleural biopsy specimens each obtained by closed Abrahams punch pleural biopsy followed by medical thoracoscopy in 50 consecutive cases of tuberculous pleural effusions were examined separately for mycobacterium tuberculosis by direct smear and culture.The specimens obtained by thoracoscopy were under vision from areas of interest.

RESULTS:  The positive smear and or culture for tuberculosis in pleural fluid and biopsy specimens obtained through Abrahams punch biopsy technique in tuberculous pleural effusions were 21 (42%) and 17 (34%) of cases respectively.In comparision specimens obtained through thoracoscopy yielded confirmation in 36 (72%) and 29 (58%) of cases respectively.

CONCLUSION:  The chance of obtaining mycobacterium containing pleural specimens in tuberculous pleural effusion is much higher with medical thoracoscopy as compared with closed pleural biopsy technique.CLINICAL IMPLICATION: Medical thoracoscopy is far superior to closed pleural method in obtaining pleural specimens for bacteriological confirmation of tuberculous pleural effusions.

DISCLOSURE:  M.B. Prasad, None.

Chest. 2003;124(4_MeetingAbstracts):81S. doi:10.1378/chest.124.4_MeetingAbstracts.81S-c
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PURPOSE:  To evaluate the clincopathologic features of pleural effusion in patients with lymphoproliferative disorders and to determine clinical variables that correlate with malignant pleural effusion and mortality in these patients.PATIENTS & METHODS: Medical records of 74 patients with lymphoproliferative disorders who were hospitalized on 79 occasions and underwent thoracentesis from 1993-2002 were reviewed. Their median age was 68 yrs (4-92) and M:F was 40:34. Fifty patients had non-Hodgkin lymphoma, 18 had CLL, and 6 had Hodgkin disease. Fifty-two patients had stage >= 3 disease and 37 had received prior chemotherapy. Of 79 cases, 32 had mediastinal/and or hilar lymphadenopathy and 22 had pulmonary infiltrates. Cytological examination was performed in all 79 specimens, whereas immunophenotyping and/or genetic study was done in 38 specimens. Fisher’ Exact test was carried out to determine clinical variables that correlated with malignant pleural effusion and hospital mortality.

RESULTS:  Of 79 cases of pleural effusion, 40 were bilateral and 72 were exudates. Forty-six effusions were diagnosed as malignant, 32 as reactive and 2 as empyema. Six were chylous effusion and 4 of them were malignant. Among the clinical variables examined for their correlation with malignant effusion, presence of secondary cancer and pleural fluid total nucleated cell count >1000/ul were significantly correlated with malignant effusion with a relative risk of malignant effusion of 1.59 (95% CI 1.67-2.17) and 1.53 (95% CI 1.02-2.29) respectively. Twenty of 74 patients died during their hospitalization. Presence of pleural fluid:serum LDH ratio >1, pneumonia, and secondary cancer significantly correlated with increased mortality with relative risk of death of 9 (95% CI 2.26-35.83), 3.54 (95% CI 1.68-7.45), and 3.12 (95% CI 1.60-6.00) respectively.CONCLUSIONS: Malignant effusion is a common cause of pleural effusion in patients with lymphoproliferative disorders. Secondary cancer and a high pleural fluid neucleated cell count correlated with presence of a malignant effusion, whereas a high pleural fluid to serum LDH ratio, pneumonia and secondary cancer correlated with increased hospital mortality.

CLINICAL IMPLICATIONS:  Pleural fluid examination can predict hospital mortality of patients with lymphoproliferative disorders.

DISCLOSURE:  A.K. Siddiqui, None.

Chest. 2003;124(4_MeetingAbstracts):82S. doi:10.1378/chest.124.4_MeetingAbstracts.82S
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PURPOSE:  Spontaneous pneumothorax still has controversial aspects. During the decade we observed in Romania a change in the proportion of etiological factors. The aim of our study is to establish how these changes and the modern diagnostic and surgical procedures affect the management of spontaneous pneumothorax.

METHODS:  We retrospectively analysed 245 consecutive patients with spontaneous pneumothorax treated in our clinic during the last 18 years. Data abstracted included patient′s demographics, medical history, clinical presentation, radiographic aspect, CT scans in some cases, surgical treatment and postoperative follow-up. We compared the results obtained between 1985 - 1994 with those obtained between 1995 - 2003.

RESULTS:  The average age was 47 years with a female/male ratio of 2/9. Tube thoracostomy was used in 80% of cases and in 19,5% of cases we performed major surgical treatment (thoracotomy, resection of blebs or other lesions and parietal pleurectomy). In two cases of repeated episodes of pneumothorax due to generalized bullous emphysema, with respiratory failure, we performed two-stage bilateral lung volume reduction surgery associated with electrocoagulation of the pulmonary parenchyma and diaphragm and parietal pleurectomy (no possibility to perform lung transplantation in Romania). In 4 cases with residual cavities we performed thoracopleuroplasties, own procedure. In very few cases (0,5%) we performed only simple needle-aspiration.CONCLUSIONS: During the last years we observed an important increase of secondary pneumothorax, due to the growing number of patients with tuberculosis. The proportion of patients with spontaneous pneumothorax as first sign of tuberculosis raised from 4,5% between 1985-1994 to 30,2% between 1995-2003. There are some rare causes of spontaneous pneumothorax (ruptured aspergiloma, pleuro-pericardial cyst, sequestration, hydatid cyst etc.), which are usually not taken into consideration; even if each of these lesions is extremely rare, together they account for a significant proportion.

CLINICAL IMPLICATIONS:  These results suggest the need of a more aggressive and differentiated treatment of spontaneous pneumothorax, with serious clinical, social and economic implications.

DISCLOSURE:  P.V. Botianu, None.

Chest. 2003;124(4_MeetingAbstracts):82S. doi:10.1378/chest.124.4_MeetingAbstracts.82S-a
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PURPOSE:  Routine clinical use of computed tomography (CT) has recently made detection of many small pulmonary nodules possible. There however have been no proven preoperative indicators on postoperative survival of patients with a small lung cancer. We therefore investigated prognostic determinants detected preoperatively on CT images in such patients.

METHODS:  Of 952 consecutive patients operated on for primary lung cancer, 167 patients with a proven adenocarcinoma 3 cm or less in diameter underwent complete removal of the primary tumor. We examined their CT scans to estimate tumor shadow disappearance rate (TDR) which was defined as the ratio of the tumor area of the mediastinal window to that of the lung window, reviewed the clinical records and evaluated their relation to prognosis.

RESULTS:  On univariate analyses, size of the tumor (p=0.0380), TDR (p=0.0018), and carcinoembryonic antigen (p=0.0001) and pathologic stage (p<0.0001), nodal involvement (p<0.0001), lymphatic invasion (p=0.0001), and vascular invasion (p=0.0017) were significantly associated with prognosis. Also, the outcomes of multivariable analyses for preoperative factors indicated that TDR (p=0.0340), and CEA (p=0.0047) are significant independent prognostic determinants. The 5-year survival was 48% in cases with a TDR of 0 to 25%, 87% in those with a TDR of 26 to 50%, 97% in those with a TDR of 51 to 75%, and 100% in those with a TDR of 76 to 100%. The incidence of lymphatic, vascular invasion, and nodal metastases was lower in patients with a higher TDR.CONCLUSIONS: Small-sized adenocarcinomas with a higher TDR showed less lymphatic, vascular vessel invasion or nodal involvement, and demonstrated longer survival, suggesting that TDR was associated with clinical-pathologic characteristics and tumor aggressiveness.

CLINICAL IMPLICATIONS:  Preoperative assessment of TDR may be useful to identify an appropriate candidate for a lesser pulmonary resection.

DISCLOSURE:  M. Okada, None.

Chest. 2003;124(4_MeetingAbstracts):82S. doi:10.1378/chest.124.4_MeetingAbstracts.82S-b
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PURPOSE:  Nonsmall cell lung cancer (NSCLC) is best treated by complete surgical resection, most commonly involving lobectomy or pneumonectomy. This study compared the late (> 1 year) effect of thoracotomy with lobectomy or pneumonectomy on patients younger than 70 years old verses those at or older than 70 years of age.

METHODS:  Retrospective review of 159 patients who from July 1996 to December 2001 underwent lobectomy (140) or pneumonectomy (19) for NSCLC at the Minneapolis VA Medical Center. 56 of 66 lobectomy and 5 of 8 pneumonectomy patients were alive > 1 year status-post surgery, and evaluated with pulmonary function testing and functional status assessment based on the Karnovsky score (KS). Results were compared between younger (n=35 lobectomy, 3 pneumonectomy) and older (n=21 lobectomy, 2 pneumonectomy) patients.

RESULTS:  Following lobectomy, functional vital capacity (FVC) decreased by 14% and 15%, with forced expiratory volume in one second (FEV1) decreased by 24% and 18% in younger and older patients, respectively. Functional status declined for 11 (31%) of the younger patients with KS drop from 10 (normal activity without limitation) to 7 (unable work, but able to care for self at home). Similarly, 6 (28%) older patients dropped from 9-10 to 7. Following pneumonectomy, results between age groups were nearly identical with an average reduction of 39% in FVC and 45% in FEV1, and average KS decreased from 9 preoperatively to 8 postoperatively.

CONCLUSION:  Elderly patients undergoing lobectomy or pneumonectomy for NSCLC have similar late recovery of pulmonary function and functional status compared to younger patients. Interestingly, the decrease in FEV1 does not directly correlate with a lower KS unless the FEV1 was < 1.0L/sec.

CLINICAL IMPLICATIONS:  Although, as expected, pneumonectomy has a greater overall impact on a patient than lobectomy, curative resection should not be denied a patient based on age alone.

DISCLOSURE:  R.F. Kelly, None.

Chest. 2003;124(4_MeetingAbstracts):82S-c-83S. doi:10.1378/chest.124.4_MeetingAbstracts.82S-c
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PURPOSE:  We retrospectively investigated the major complications after pulmonary resection following induction therapy for lung cancer.

METHODS:  From 1990 to 2002, 90 patients underwent pulmonary resection after induction therapy. The indications for induction therapy were N2 disease in 56, superior sulcus tumor in 8, involvement of great vessels in 7, small cell carcinoma in 6, chest wall invasion in 6, and miscellaneous in 7. Induction therapy consisted of 2 cycles of platinum-based chemotherapy concurrent with 40 Gy radiation.

RESULTS:  There was no postoperative death within 30 days. Major complications occurred in 15 patients. Eight patients experienced them during the same hospitalization as the surgery and 7 did after discharge. Major complications included radiation pneumonitis (n = 10), late bronchial stump dehiscence (n = 3), empyema without fistula (n = 1), and interstitial pneumonia (n = 1). Of the 10 patients who suffered from radiation pneumonitis 3 patients developed contralateral interstitial pneumonia and 2 patients developed bacterial pneumonia within radiation pneumonitis, which was refractory and resulted in empyema. Treatment-related death added up to 7 patients (7.8%), of whom 6 patients died after second admission.CONCLUSIONS: Major complications in relation to surgery following concurrent chemoradiotherapy can happen in the late postoperative phase, and thus, careful attention should be paid for these patients at an outpatient department. Radiation may play an important role in the development of late morbidity.

CLINICAL IMPLICATIONS:  Major complications in relation to surgery following concurrent chemoradiotherapy can happen in the late postoperative phase.

DISCLOSURE:  T. Sakamoto, None.

Chest. 2003;124(4_MeetingAbstracts):83S. doi:10.1378/chest.124.4_MeetingAbstracts.83S
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PURPOSE:  To compare the outcome of video assisted thorascopic (VATS) lung resection for non small cell lung cancer (NSCLC) with open surgery.

METHODS:  A retrospective case note review comparing patients who underwent VATS lung resection between April 1997 and February 2003 using standard techniques without rib spreading with patients who underwent lobectomy between April 1997 and December 1999. All operations were for early stage NSCLC (T1/2, N0/1). All operations were part of a single thoracic surgical practice. The preoperative respiratory function, histology, stage, intercostal drain time, hospital stay and follow up data were analysed.

RESULTS:  Video-assisted thoracoscopic resection was performed in 25 patients [11 male, median age 72 years (range 55–82)].They underwent 10 upper, 5 middle and 10 lower lobectomies. 102 patients underwent open lobectomy [66 male, median age 69 years (range 48–82)]. They underwent 67 upper, 1 middle and 34 lower lobectomies.21 of 25 VATS patients had N0 disease compared with 75 of 102 open resection patients. Kaplan-Meier analysis was performed for survival, disease free survival and local recurrence.

CONCLUSION:  VATS lobectomy has been used to extend resection to patients previously thought inoperable. The high local recurrence rate may be due to technical deficiencies of the operation or demonstrate a learning experience in our series. In our study there was a high rate of local recurrence there was no difference in overall survival.

CLINICAL IMPLICATIONS:  The high local recurrence rate after VATS resection for early stage NSCLC compared with open surgery calls into question its validity as an oncological operation Comparison of open and VATS lobectomies for early NSCLCOpen n=102VATS n=25SignificanceFEV1 Median (range)1.6L (0.68–3.6)1.8L (0.35–2.59)NSIntercostal Drainage Medain (range)5 days (1–55)3 days (1–30)NSHospital stay Median (range)7 days (2–41)6 days (3–31)p=0.04Hospital mortailty4 (3.9%)1 (4%)NSFollow up Median (range)53 months (37–71)39 months (1–70)Three year survival65%75%NSThree year disease Free survival57%50%NSLocal recurrence13 (12.7%)6 (24%)Three year free of Local recurrence86%61%p=0.05

DISCLOSURE:  J. Pilling, None.

Chest. 2003;124(4_MeetingAbstracts):83S. doi:10.1378/chest.124.4_MeetingAbstracts.83S-a
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PURPOSE:  The objective of this study is to establish whether it is possible to minimize the operative insult during lung lobectomies and pneumonectomies to such an extent that these operations can be safely performed as outpatient procedures.

METHODS:  Between January of 2000 and October of 2001, 50 consecutive patients with tumors of the lung and negative metastatic work-up underwent major lung resections. Thirty-two were females and 18 males with a mean age of 68 years (34 to 88) and 7 patients were older than 80 years of age. No patients were excluded on the bases of poor pulmonary function, large tumor size, need for an extended resection, need for reoperation, presence of comorbidities, nor advance age. The operation was performed through a minimally invasive approach, the analgesic method was multimodal, a portable chest drainage system was used, and the anesthetic management was adjusted to perform these operations as ambulatory procedures.

RESULTS:  There were 42 lobectomies, 2 bilobectomies, and 6 pnuemonectomies. The cumulative length of hospital stay (LOS) for the 50 patients was 50 days (mean LOS, 1 day). Forty-three patients (86%) met discharge criteria within 24 hours of admission, and 20 (40%) were managed as ambulatory procedures. One patient required readmission 7 days after surgery for deep vein thrombosis and expired due to a massive pulmonary embolism (2% mortality rate). There were 5 complications, none of which required readmission.CONCLUSIONS: This study suggests that by adjusting surgical and anesthetic techniques, ambulatory major lung resections are feasible and safe procedures. Further studies are needed to confirm our findings.

CLINICAL IMPLICATIONS:  The transformation of major lung resections into a purely ambulatory procedure may represent in itself a significant paradigm shift in thoracic surgery. In addition, it may extend the indications of these procedures to sicker and more compromised patients.

DISCLOSURE:  E.A. Tovar, None.

Chest. 2003;124(4_MeetingAbstracts):83S-b-84S. doi:10.1378/chest.124.4_MeetingAbstracts.83S-b
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PURPOSE:  Recent advances in video-assisted thoracoscopic surgery (VATS) have allowed this new surgical technique to be applied to a variety of thoracic diseases. The aim of this study is to clarify the usefulness and indication of the treatment for mediastinal tumors by VATS.PATIENTS AND METHODS: A total of 95 patients underwent resections of mediastinal tumors at our institute between 1993 and 2002. We retrospectively analyzed 37 patients who underwent the VATS procedure for mediastinal tumors. Our indications for VATS were location, size and presumed resectability of the mass without invasion to the adjacent organs on the basis of the preoperative assessment. Twenty-one females and sixteen males ranged in age from 16 to 77 years, with a mean of 52.9 years.

RESULTS:  VATS resections were performed by the unilateral thorax approach in all patients. The distribution of anatomical location was 26 anterior, 1 middle, and 10 posterior masses. The average operating time was 85 min (range, 35 to 155). Almost half of these resections were carried out for thymic disease, which included 13 thymomas and 6 thymic cysts. The other mediastinal tumors included 8 neurogenic tumors, 6 teratomas, and 4 bronchogenic cysts. In 33 patients (89.2%), the procedure was completed thoracoscopically. Conversion to thoracotomy was required in two patients due to control the hemorrhage from an intercostal vessel and in two patients due to severe adhesions between the pulmonary structure and the chest wall. Another complication was Horner’s syndrome in one patient. There were no operative or hospital deaths. The follow-up ranges 8 to 116 months and no recurrences have been discovered yet in any patient.CONCLUSIONS: This study showed that VATS was an acceptable method for the therapeutic extirpation of mediastinal tumors, particularly in selected patients and that our operative indication in this series was feasible.

CLINICAL IMPLICATIONS:  The decision on which approach to use in VATS procedures for mediastinal tumors requires careful assessment of the lesion’s location and proper port placement.

DISCLOSURE:  M. Takahama, None.

Chest. 2003;124(4_MeetingAbstracts):84S. doi:10.1378/chest.124.4_MeetingAbstracts.84S
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PURPOSE:  The purpose of this study is to determine whether patients with significant chronic obstructive pulmonary disease (COPD) had their wishes regarding end of life care discussed with them.

METHODS:  All pulmonary function tests (PFT) performed at a university hospital between year 2000 and 2002 were reviewed. Patients with a forced expiratory volume in 1 second (FEV1) less than 50% of predicted were included. Patients with a smoking history of less than 20 pack years, cancer, asthma, or less than 50 years of age were excluded. Data collected included age, sex, smoking history, and FEV1. Patients were then contacted for a phone interview. Patients who agreed to participate were asked a set of 8 questions.

RESULTS:  A total of 102 patients were contacted. 83 agreed to participate. The following tables summarize the results.Results shown are mean values, p/y=pack/years, % pred=percent predicted.69 patients (83%) have not had their wishes regarding end of life care or the use of mechanical ventilation (MV) discussed with them. Out of those, 51 (74%) believe that they should have been given the opportunity to discuss their wishes. The mean number of hospitalizations and office visits were 1 and 2.7 respectively within the 6 months prior to the phone interview. Out of the 12 subjects who had previous MV, 10 (83%) did not have prior discussion, and 6 (50%) do not want to be intubated again. 43 subjects (52%) did not have a pulmonologist.

CONCLUSION:  More than 80% of patients with moderate to severe COPD have not had their wishes regarding end of life care or the use of mechanical ventilation discussed with them. Half of the patients who had previous MV do not wish to have that experience again.CLINICAL IMPLICATION: End of life care should be an integral part of a comprehensive management plan of patients with moderate to severe COPD. This should improve patients satisfaction and autonomy. Age (years)Men (%)Women (%)Smoking (p/y)FEV1(%pred)64.528 (33.7)55 (66.3)54.50.76 (36.6)Do you know your Dx?(%)Do you know how severe(%)Did you discuss your wishes(%)Did you want to discuss wishe(%)H/O Mechanical Ventilation (%)Yes: 62 (74)Yes: 28 (45)Yes: 14 (17)Yes: 65 (78)Yes: 12 (14)No: 21 (26)No: 34 (55)No: 69 (83)No: 12 (14)No: 71 (86)

DISCLOSURE:  T. Dernaika, None.

Chest. 2003;124(4_MeetingAbstracts):84S. doi:10.1378/chest.124.4_MeetingAbstracts.84S-a
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PURPOSE:  Informed consent for invasive medical procedures is not routinely obtained (AJRCCM 2003; 167: A105). We examine patients’ perspectives regarding consent with three questions: 1. Do patients want to give informed consent for invasive medical procedures, 2. What frequency of complications do patients think should require consent, and 3. Do patients recall elements of the admission general consent-to-treat?

METHODS:  Adult patients admitted to a 325-bed hospital for acute medical or surgical problems were interviewed using a questionnaire. Responses were examined to determine differences based on age, gender, educational level and ethnicity.

RESULTS:  Two hundred sixty five patients (132 men and 133 women, ranging in age from 19 to 97 years; mean± SE=64.4± 1.0 years) participated in the study. The majority (58%) of patients wanted to consent for medical procedures. Amongst patients who felt that they should give consent, most felt that procedures with small or non-serious risks should not require written consent. For procedures with potentially serious risks in up to 1% of cases, 28% wanted to consent. This study also demonstrates that most (94% of) patients did not sign, did not read or did not recall properly the admission consent-to-treat.CONCLUSIONS: This study demonstrates that most, but not all, patients want to consent for procedures and they feel the general consent to treat is not adequate. There is a mismatch of patients’ expectations (and regulatory/legal standards) of consent and that being practiced “in the field.”

CLINICAL IMPLICATIONS:  Consensus is required to provide a clear binding standard for practitioners, based on ethical principles of respect of patient autonomy, while recognizing the very real logistics of patient care and the need that such standards not impede prompt and optimal medical therapies.

DISCLOSURE:  N. Thorevska, None.

Chest. 2003;124(4_MeetingAbstracts):84S. doi:10.1378/chest.124.4_MeetingAbstracts.84S-b
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BACKGROUND:  85% of hospitalized medical patients who receive CPR, do not leave the hospital alive( JAMA 1991; 265:1868-1871). Patients who survive CPR, are those with sudden unexpected cardiopulmonary arrest. However in patients with terminal disease and who are moribund despite maximal support, CPR has no benefit and may be burdensome. In such patients CPR is carried out beacause of lack of do not resuscitate (DNR) order.

PURPOSE:  We sought to identify the prevalence of medically futile CPR in two community hospital in Queens, NY and to identify the reasons for performing futile CPRs, i.e, provider unwillingness to discuss and/or patient/surrogate refusal to consent for DNR.

METHODS:  We retrospectively identified 58 patients who received CPR. Based on Pre CPR medical contions of patients, CPR was considered either Futile or beneficial. And this was compared with ultimate outcomeof CPR.

RESULTS:  Only one of 58 patients(1.7%) survivied to hospital discharge. Though 30 of 58 patients were moribund and CPR would not have benefited, providers discussed medical futility of CPR and DNR in only 11(35%).

CONCLUSIONS:  Medically futile CPR was mainly due to: 1) lack of awareness on the part of providers and their discomfort/unwillingness to discuss medical futility with family 2) Surrogate insistence on CPR though CPR was considered to be medically futile. 3) Physician unwillingness to withhold CPR unilaterally based on medical futility.

PRACTICE IMPLICATION:  Physician education of medical ethics and family conseling can help reduce futile CPR

DISCLOSURE:  V.P. Vasudevan, None.

Chest. 2003;124(4_MeetingAbstracts):84S-c-85S. doi:10.1378/chest.124.4_MeetingAbstracts.84S-c
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PURPOSE:  More than 90% of people in the US die in an institution, primarily in an acute care hospital, most often secondary to complications of a chronic illness. Many die suffering various aspects of “total pain” with its physical, emotional, social and spiritual components. Their caregivers are often equally burdened.

METHODS:  As part of a statewide initiative involving 40 hospitals, Hoag Memorial Hospital, a 400-bed not-for-profit acute care community hospital, developed and implemented a palliative medicine consult service (PMCS) from existing hospital and medical staff resources. Building on a clinical pathway of comfort care for dying patients (supportive care pathway [SCP]) in existence since 2000, an interdisciplinary team of physicians, social worker, nurses and chaplain received training in palliative care, developed a team approach to the care of the patient and initiated the service

RESULTS:  542 in-patients died in this community hospital in CY 2002; 76 died while on the SCP; another 20 were discharged to hospice and other care. This report reflects the experience of expanding the impact of this pathway by implementing a PMCS to address the needs of seriously-ill and/or dying patients admitted to the hospital. The steps taken in the development of this service, including identifying potential obstacles and how they were addressed will be presented. The experience of the first eight months of the operation of the PMCS will also be presented. Issues of team interaction, leadership support, staff in-service and marketing of the service will be discussed as a potential template for other hospitals.CONCLUSIONS: A PMCS can be developed and implemented in an acute care community hospital utilizing local resources.CLINCAL IMPLICATIONS: The suffering of inpatients with complex and life-threatening illnesses can be treated in a comprehensive manner utilizing an interdisciplinary team approach to palliative care.

DISCLOSURE:  P.A. Selecky, None.

Chest. 2003;124(4_MeetingAbstracts):85S. doi:10.1378/chest.124.4_MeetingAbstracts.85S
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PURPOSE:  A previous study demonstrated that medical students significantly improved their proficiency in identifying cardiac murmurs when they were monitored listening to 250 or 500 consecutive repetitions of four basic cardiac murmurs. This follow-up study was performed to determine if students could achieve similar results using serial repetitions of the same cardiac murmurs in unmonitored settings.

METHODS:  Twenty-nine second year medical students at an urban East Coast medical school were randomized to receive an audio CD containing 250 repetitions of four left-sided valvular lesions (AS, AR, MS, MR) in a consecutive or serial pattern. Students were instructed to listen to it one to two times in unmonitored sessions. Two tests of proficiency were given, a pretest and a final test, at which students were asked to identify the timing and the lesion in 10 recorded cardiac murmurs.

RESULTS:  Twenty-nine students were available for analysis at study completion. Sixteen students received a CD with consecutive repetitions (Group A) and thirteen received a CD with serial repetitions (Group B). In total, the twenty-nine students demonstrated a pretest score of 23.4 +/- 11.4% and a final test score of 83.1 +/- 16.5%. Group A demonstrated a pretest proficiency score (Mean +/- SD) of 21.3 +/-11.4% and a final test score of 84.4 +/- 14.6%. Group B demonstrated a pretest score of 26.2 +/- 10.4% and a final test score of 81.5 +/- 19.1%. Both Groups demonstrated a statistically significant rise in their scores compared to baseline (p<0.001), but no statistical difference was observed between each group (p>0.1).CONCLUSIONS: Medical students demonstrated dramatic improvement in identifying cardiac murmurs in an unmonitored setting using 250 repetitions of each murmur in both the serial and consecutive fashion.

CLINICAL IMPLICATIONS:  These results suggest that cardiac auscultation is, in part, a technical skill requiring repetition to be mastered. Also, the results suggest that the number of repetitions was more important than the pattern of repetitions.

DISCLOSURE:  C.S. Lacey, None.

Topics: heart murmur
Chest. 2003;124(4_MeetingAbstracts):85S. doi:10.1378/chest.124.4_MeetingAbstracts.85S-a
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PURPOSE:  We developed a lung sounds auscultation trainer (LSAT) and started using it in 2001. In 2002, we used it in OSCE. To evaluate the educational effects of the LSAT, we compared the outcome between the fifth year medical students in 2001 and those in 2002.

METHODS:  From June 2001 to March 2002, we used the LSAT for small group education among one hundred of the fifth year medical students. In the next school year, we opened our laboratory so that the fifth year students could study the LSAT by themselves for one month. Then, the LSAT was used for OSCE in May 2002. From June 2002 to April 2003, we used the LSAT again among eighty-four of the fifth year students who passed OSCE. The class consisted of ninety minutes training for the auscultation of lung sounds. At first, auscultation tests were performed. Namely, students listened to three cases of abnormal lung sounds on the LSAT through their stethoscopes. Next they answered questions corresponding to the portion and quality of the sounds. Then we explained the correct answers and how to differentiate lung sounds on the LSAT. Additionally, at the beginning and the end of the lecture, five degrees of self-assessments for the auscultation of the lung sounds were performed.

RESULTS:  The ratio of correct answers (students in 2001 vs. in 2002) of lung sounds were 36.9% vs. 37.2% for decrease or disappearance of lung sounds, 52.5% vs. 55.8% for coarse crackles, 34.1% vs. 60.5% for fine crackles, 69.2% vs. 70.8% for wheezes, 62.1% vs. 94.7% for rhonchi, and 22.2% vs. 32.6% for stridor. Self-assessment scores were significantly higher after the class than before, especially in stridor, both in 2001 and in 2002.

CONCLUSION:  The ratio of correct answers of lung sounds was higher among fifth year students in 2002 than those in 2001.

CLINICAL IMPLICATIONS:  The one-month self-training on the LSAT before the OSCE was extremely effective for the improvement of auscultation skills.

DISCLOSURE:  C. Yoshii, None.

Topics: auscultation , rales
Chest. 2003;124(4_MeetingAbstracts):85S-b-86S. doi:10.1378/chest.124.4_MeetingAbstracts.85S-b
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PURPOSE:  Home personal computer and internet use has expanded dramatically over the past decade. The Internet enables health care consumers to access information and supports a shift toward patient-centered care. Accordingly, the objective of this study was to determine the frequency of which Long Island residents use computers and the Internet in order gather information on health care.

METHODS:  This prospective study surveyed consecutive patients seen in a single practioner’s university-based office practice. Patients were administered computer and internet usage questionnaires.

RESULTS:  There were 80 patients, median age 68 years, 60% male. 35% had coronary disease, 15% had heart failure, 10% had atrial fibrillation and 10% had valvular disease. 45% of patients owned a personal computer at home. Of the 20% of patients who were employed, 75% used a computer at work. 30% used the internet a mean of 3.7x/week and 3.8hours/week. The most common uses were: email:30% and shopping 20%. Health care information was accessed by only 10% and was more frequent among males, patients who were married, and those who were employed. 39% of the patients who did not access health care information had a first degree relative who did it on their behalf. Overall, 45% of patients either primarily or by surrogate used the Internet to access health care information.CONCLUSIONS: Although aprroximately half of cardiovascular patients own personal computers at home and some use computers at work, only 10% of patients access use the Internet to access health care information. This low utilization rate is in part counterbalanced by involvement of first degree relatives who access information on the patient’s behalf.

CLINICAL IMPLICATIONS:  Web based strategies designed to target patients with cardiovascular disease need to consider surrogates who use Internet to access health care information. Further study is needed to characterize specific ways in which Internet is used to assist patients make decisions regarding health care.

DISCLOSURE:  J.M. Lazar, None.

Chest. 2003;124(4_MeetingAbstracts):86S. doi:10.1378/chest.124.4_MeetingAbstracts.86S
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PURPOSE:  This study was performed to evaluate the understanding of an increased alveolar-arterial oxygen gradient (Aa-gradient) among hospital-based health care professionals in an university-affiliated teaching hospital.

METHODS:  A common clinical scenario was chosen with a setting of “pure” oxygen inhalation (FiO2 of 1.0) and a “normal” arterial PO2 of 100 mm Hg with a pCO2 of 40 mm Hg. One hundred subjects, consisting of students, medical residents, fellows of different subspecialties, attendings, nurses and respiratory therapists, were interviewed. Evaluation with and without a personal digital assistant device (PDA)-based Aa-gradient program was performed (MedCalc 2001). A subgroup of twenty individuals was randomized with a coin toss. The study group was unbiased and had no prior knowledge of the study question. EpiInfo, version 6, Statcalc, was used for evaluation.

RESULTS:  Of the randomized 20 subjects, 10 out of 10 individuals had correct answers with the use of a PDA. Only 2 out of 10 subjects estimated an Aa-gradient of greater than 200 without prior PDA use (p = 0.0003, confidence interval 1.5-17.3). A scatter plot shows the estimated A-a gradient (AaDO2) and the level of education. The mean estimated Aa-gradient was 128 with a range of 0-500. Four subjects stated that they did not know the answer and 7 individuals were excluded because of prior knowledge of the study results.

CONCLUSION:  Appreciation of the large Aa-gradient in patients with a pO2 of 100 on FiO2 of 1.0 was not evident. Increased awareness is useful because an Aa-gradient of 563 is potentially fatal if adequate intervention is not undertaken. The PDA-based program significantly improved awareness of acute lung injury and acute respiratory distress syndrome.

CLINICAL IMPLICATIONS:  A real-time PDA-based Aa-gradient program increases the appreciation of acute lung injury and acute respiratory distress syndrome. This may change the aggressiveness of the diagnostic and therapeutic approach to critically ill patients.

DISCLOSURE:  S. Amanullah, None.

Chest. 2003;124(4_MeetingAbstracts):86S. doi:10.1378/chest.124.4_MeetingAbstracts.86S-a
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PURPOSE:  To investigate the acoustic characteristics of breath sounds that may be useful in the detection of pneumothorax (PTX) in an animal model.

METHODS:  Eight mongrel dogs under general anesthesia were endotracheally intubated and placed in the left lateral decubitus position. A ventilator delivered tidal volumes of 20 ml/kg at 12 cycles/minute. An electronic stethoscope (Labtron Electromax; Hauppauge, NY) measured the breath sounds in the right mid-clavicular line at the level of the third rib. Breath sounds were acquired in the control (non-PTX) and in an artificially created30% PTX state (confirmed with a thoracoscope), and recorded on a tape recorder (Portastudio 424; Teac Corp.; Japan) for 20 seconds during each test. Recorded sounds were digitized (at 4000 sample/sec) using a laptop computer (Latitude Xpi, P120D; Dell Computers; Dallas, TX) and analog-to-digital card (Card 500; National Instruments; Austin, TX). Digital signal processing software (Matlab; MathWorks; Natick, MA) were employed to calculate and analyze the breath sound spectra. Statistical analysis was performed using the Wilcoxon signed-rank test.

RESULTS:  Breath sound amplitudes decreased with pneumothorax in all animals (p<0.01, Figure). The amplitude drop was most pronounced for frequencies between 200-700 Hz.

CONCLUSION:  Pneumothorax decreased the amplitude of breath sounds detected electronically in an animal model. This effect varied with acoustic frequency (“pitch”), with the differences between control and the PTX state being most pronounced within the 200-700 Hz bandwidth. This is consistent with the clinical finding of decreased breath sounds with pneumothorax. Further studies are warranted in human patients.

CLINICAL IMPLICATIONS:  These findings may lead to the development of devices that can immediately detect pneumothoraces acoustically, facilitating prompt treatment. The accuracy, simplicity of use, portability, and low cost of such devices may make them attractive diagnostic modalities in emergency rooms, ambulances, and intensive care units.

DISCLOSURE:  H.A. Hassaballa, None.

Chest. 2003;124(4_MeetingAbstracts):86S-b-87S. doi:10.1378/chest.124.4_MeetingAbstracts.86S-b
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PURPOSE:  A 12-week, open-label study designed to examine whether switching to fluticasone propionate/salmeterol (FSC) 100/50mcg maintained control of airway inflammation in asthma patients previously treated with fluticasone propionate (FP) 220mcg BID or an equivalent dose of another inhaled corticosteroid (ICS).

METHODS:  52 patients (mean age 36.8 yrs) on moderate dose ICS (mean dose=498mcg/day) for ≥4 weeks participated. All patients underwent bronchoalveolar lavage (BAL) and biopsy before and 12-weeks after switching to FSC 100/50mcg BID. Eosinophil percentages and inflammatory mediators (GM-CSF, IL-8, ECP, tryptase) were evaluated on BAL specimens. Eosinophils and basement membrane thickness were quantified from biopsy specimens.

RESULTS:  Cell/MediatornBaseline on ICS (mean ± SE)Endpoint on FSC (mean ± SE)p Value*Bronchial mucosa eosinophils (cells/mm3)392715.5 ± 3593173.2 ± 7100.753BAL eosinophils (%)480.52 ± 0.140.84 ± 0.330.522Basement membrane thickness (microns)464.07 ± 0.163.97 ± 0.150.403GM-CSF (pg/mL)311.20 ± 0.182.40 ± 0.670.096IL-8 (pg/mL)3625.54 ± 5.0731.13 ± 7.370.370ECP (μg/mL)360.66 ± 0.252.45 ± 2.060.590Tryptase (μg/mL)460.15 ± 0.070.22 ± 0.090.438*

based upon Wilcoxon signed-rank tests

The switch to FSC was not associated with changes in BAL eosinophils, BAL inflammatory mediators or sub-epithelial collagen thickness on mucosal biopsies. In addition, the switch to FSC was associated with significant (p≤0.05) improvements in AM PEF, rescue albuterol use and asthma symptoms while FEV1 and PC20 were unchanged from baseline.

CONCLUSION:  In patients receiving moderate doses of ICS, FSC 100/50mcg BID enabled a >50% reduction in ICS dose without altering sub-epithelial collagen thickness, eosinophil numbers in BAL or mucosal biopsies, or BAL inflammatory mediators.

CLINICAL IMPLICATIONS:  Treatment with a low dose ICS and a long-acting beta-agonist appears as effective as higher dose ICS alone in controlling eosinophilic airway inflammation.

DISCLOSURE:  P.M. Dorinsky, Employee of GSK, Industry.

Chest. 2003;124(4_MeetingAbstracts):87S. doi:10.1378/chest.124.4_MeetingAbstracts.87S
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PURPOSE:  ICS are a common therapy for both asthma and COPD. While use of systemic corticosteroids can decrease BMD, the impact of long-term ICS use on BMD is uncertain.

METHODS:  A meta-analysis evaluating the impact of ICS therapy on BMD was performed. We searched MEDLINE and EMBASE databases and consulted with experts to identify published and unpublished literature reporting BMD among adult asthma and COPD patients using ICS and non-ICS using controls. Studies selected for review included at least one-year of follow-up. Two independent reviewers evaluated studies; data from those meeting specified inclusion criteria were abstracted. Random-effects meta-analysis was performed for all outcomes present in at least four included studies.

RESULTS:  A total of 266 studies were identified and reviewed; 14 (5.3%) met specified inclusion criteria for the meta-analysis. Sufficient data were available to perform meta-analysis on BMD measures for ICS-using patients; only one measure (lumbar BMD) was available among non-ICS using controls. Using current NAEPP definitions, the majority of studies (12 of 14) included patients receiving moderate to high doses of ICS. Mean changes in lumbar BMD were not significantly different from baseline or from controls (−0.02%) for patients with asthma (+0.13%) and COPD (−0.42%) following 1 to 4 years of treatment. Among ICS users, changes from baseline in femoral neck and major trochanter BMD (−0.17% and +1.46%, respectively) were not statistically significant. Non-significant changes from baseline in lumbar BMD of −0.20%, −0.39%, and −0.73% were observed with fluticasone, budesonide, and beclomethasone, respectively.CONCLUSIONS: Long-term use of ICS in patients with asthma or COPD was not associated with significant changes in BMD.

CLINICAL IMPLICATIONS:  Treatment with ICS at standard doses in patients with asthma or COPD does not have a clinically meaningful effect on BMD.

DISCLOSURE:  M.T. Halpern, GlaxoSmithKline, Grant monies.

Chest. 2003;124(4_MeetingAbstracts):87S. doi:10.1378/chest.124.4_MeetingAbstracts.87S-a
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PURPOSE:  To observe the effect of dexamethasone on airway remodeling and to explore significance of the balance between matrix metalloproteinase and tissue inhibitor of metalloproteinase.

METHODS:  Thirty male Wistar rats were randomly divided into asthmatic group (n=10), dexamethasone group (n=10) and control group (n=10). Lung tissues were sliced and stained with H.E. The following parameters that reflects thickness of airway wall were measured by image analysis system: bronchial basement membrane perimeter (Pbm), total bronchial wall area (WAt), inner wall area (WAi) and smooth muscle area (WAm). Expression levels of MMP-2 and TIMP-1 mRNA in the lungs were assessed by semiquantitative reverse transcription-polymerase chain reaction (RT-PCR).

RESULTS:  (1) WAt/Pbm,WAi/Pbm and WAm/Pbm in asthmatic group [(25.3±2.1)μm2/μm, (20.4±2.3)μm2/μm, (4.2±2.0)μm2/μm, respectively] were significantly higher than that in control group [(20.8±1.3)μm2/μm,(15.3±2.1)μm2/μm, (3.1±1.1)μm2/μm](p<0.01). The differences between control and dexamethasone group [(21.3±2.4)μm2/μm, (14.2±2.5)μm2/μm, (3.2±1.0)μm2/μm] were not statistically significant (p>0.05). (2) MMP-2 and TIMP-1mRNA levels in asthmatic group [(0.68±0.14), (0.56±0.10)] and dexamethasone group [(0.37±0.11), (0.31±0.10)] were significantly higher than that in control group [(0.14±0.03), (0.11±0.05)]. The differences between asthmatic group and dexamethasone group were also significant (p<0.01). (3) In control and dexamethasone group (r=0.67,0.58.p<0.05) but not in asthmatic group (r=0.24, p>0.05), there was a significantly positive correlation between MMP-2 and TIMP-1 mRNA.

CONCLUSION:  Dexamethasone could prevent airway remodeling by downregulating expression of MMP and TIMP and restoring the balance between MMP and TIMP.

CLINICAL IMPLICATIONS:  Selective MMP inhibitors may provide a novel strategy for treatment of asthma.

DISCLOSURE:  Y. Yuan, None.

Chest. 2003;124(4_MeetingAbstracts):87S-b-88S. doi:10.1378/chest.124.4_MeetingAbstracts.87S-b
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PURPOSE:  Recently, FSC was shown to permit a 60% reduction in the ICS dose while maintaining asthma control in patients requiring fluticasone propionate (FP) 250mcg BID for asthma stability. The purpose of this post-hoc analysis was to assess the impact of baseline asthma severity on the ICS-sparing properties of FSC.

METHODS:  Lung function, albuterol use and asthma symptom data from two, replicate, double-blind, 12-week, parallel group studies were evaluated for patients with baseline FEV1 ≥80% vs. <80% predicted at randomization.

RESULTS:  Data below represents change from baseline (SE) at the 12-week endpoint.

CONCLUSION:  FSC was an effective ICS-sparing agent regardless of baseline asthma severity, allowing the ICS dose to be reduced by 60% while improving overall asthma control.

CLINICAL IMPLICATIONS:  Treating the two main components of asthma (inflammation and smooth muscle dysfunction) with a low dose ICS and a long-acting β2-agonist is a more effective treatment strategy than a higher dose ICS alone. ParameterFEV1 ≥80% PredictedFEV1 <80% PredictedFSC n=284FP 250 n=273FSC n=288FP 250 n=279# Pts withdrawn*33473138Baseline FEV1 % predicted88.5 (0.41)88.1 (0.36)72.7 (0.27)72.8 (0.26)FEV1 (L) Baselline2.98 (0.04)2.98 (0.04)2.47 (0.03)2.48 (0.04) Change0.04 (0.01)−0.05 (0.02)0.09 (0.01)−0.01 (0.02)AM PEF (L/min) Baseline472.3 (8.2)468.9 (9.0)438.5 (7.5)421.4 (8.3) Change35.3 (3.9)18.7 (4.1)39.4 (3.9)19.8 (3.3)Albuterol use (puffs/24 hrs) Baseline0.75 (0.07)0.87 (0.08)0.97 (0.07)1.04 (0.08) Change−0.25 (0.06)−0.20 (0.07)−0.36 (0.08)−0.20 (0.07)% Symptom Free days Baseline46.2 (2.5)43.5 (2.6)38.4 (2.5)38.9 (2.3) Change11.7 (1.8)4.8 (1.8)11.0 (2.0)5.9 (1.8)*

due to worsening asthma;

p≤0.02 FSC vs. FP 250

DISCLOSURE:  P.M. Dorinsky, Employee of GSK, Industry.

Chest. 2003;124(4_MeetingAbstracts):88S. doi:10.1378/chest.124.4_MeetingAbstracts.88S
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PURPOSE:  This post-hoc analysis examined clinical markers of worsening asthma with FSC 100/50 BID versus FP 250 BID in patients who required FP 250 BID for asthma control.

METHODS:  Data from two replicate, double-blind, parallel group, equivalence studies were evaluated. Patients requiring FP 250 BID for asthma stability were randomized to FSC 100/50 or FP 250 BID for 12–24 weeks. For subjects who developed worsening asthma, patient-evaluated morning/evening PEF, albuterol use, and asthma symptom scores were analyzed for 14 days prior to the development of worsening asthma as defined by: ≥20% decrease in FEV1, ≥20% decrease in AM PEF on 3 consecutive days, or an asthma exacerbation.

RESULTS:  ParameterWeeks 1–12Weeks 13–24FSC 100/50 BID (n=572)FP 250 BID (n=552)FSC 100/50 BID (n=269)FP 250 BID (n=240)Worsening asthma*35 (6%)53(10%)17(6%)17 (7%) ≥20% decrease in FEV1162066 ≥20% decrease in AM PEF61755 Asthma141564 Exacerbation Investigator21212 Discretion*

Patients may have met more than one criterion for worsening asthma.

Fewer FSC vs FP patients developed worsening asthma and no patient in either group developed an exacerbation requiring hospitalization. The percentage of patients withdrawn due to worsening asthma based on FEV1 or AM PEF were comparable in both groups over the study period (63–65% in each group). The pattern of changes in PEF, albuterol use, and asthma symptoms was similar.CONCLUSIONS: Among patients requiring FP 250 BID for asthma stability, FSC was ICS-sparing allowing a 60% reduction in ICS dose while reducing the overall incidence of worsening asthma. The pattern of worsening asthma did not differ in patients treated with FSC versus higher dose FP alone.

CLINICAL IMPLICATIONS:  Though fewer FSC patients developed worsening asthma, the pattern of decline in clinical parameters preceding an exacerbation was similar for both groups, suggesting that both clinicians and patients can follow a standard action plan for detecting and treating exacerbations.

DISCLOSURE:  P.M. Dorinsky, I am an employee of GSK, Industry.

Chest. 2003;124(4_MeetingAbstracts):88S. doi:10.1378/chest.124.4_MeetingAbstracts.88S-a
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PURPOSE:  Inhaled corticosteroids (ICS) are the mainstay of asthma treatment, but are underprescribed and their effectiveness is compromised by low patient compliance. Current ICS are recommended for use 2 or more times per day, making compliance problematic. The current study assessed the compliance and efficacy of once-daily inhaled fluticasone propionate in Indian patients of Eastern Uttar Pradesh having moderate asthma.

METHODS:  The efficacy of inhaled fluticasone propionate (FP) at a dose of 500 μg and salmeterol 50 μg once a day was compared with fluticasone propionate 250 μg and salmeterol 50 μg twice a day in moderate asthma. A total of 280 asthmatics aged 16 to 45 years were randomized to receive either fluticasone with salmeterol once a day or FP with salmeterol twice a day for 3 months by accuhaler.During the study, the patients were recorded morning and evening peak expiratory flow (PEF), symptom score and use of rescue salbutamol. Pulmonary function parameters were measured at the beginning of the study after the first, fourth, eighth and twelve weeks.

RESULTS:  At the end of twelve weeks, in comparison with FP + salmeterol once a day resulted in higher FEV1/FVC (p=0.016) and lower diurnal variability of PEF (p=0.038). The number of puffs of rescue salbutamol was also significantly lower. Compliance at the end of therapy was 84% in once daily therapy as compared to 48% in twice a day treatment ( p<0.001).

CONCLUSION:  Using a once-daily fluticasone increases effectiveness of asthma treatment as compared to twice a day treatment.

CLINICAL IMPLICATIONS:  Once-daily fluticasone may be tried in patients having moderate asthma to improve compliance and to improve efficacy of asthma treatment.

DISCLOSURE:  S.K. Agarwal, None.

Chest. 2003;124(4_MeetingAbstracts):88S-b-89S. doi:10.1378/chest.124.4_MeetingAbstracts.88S-b
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PURPOSE:  Compounds that lead to a reversal of established pulmonary vascular disease might provide a cure for pulmonary arterial hypertension. The aim of this study was to examine the effect of simvastatin (2mg/kg/day) in rats with established pulmonary arterial hypertension (PAH).

METHODS:  Four weeks after pneumonectomy rats received monocrotaline 60mg/kg by intraperitoneal injection. Severe PAH develops 11 weeks after pneumonectomy (mean pulmonary artery pressure, mPAP = 42 vs. 17mmHg in normal rats). Rats were randomized to receive simvastatin or control solution by gavage from week 11.

RESULTS:  All rats that received control solution died at week 13. When rats with severe PAH received simvastatin (2 mg/kg/day, by gavage) from week 11, there was 100% survival, reversal of PAH at week 13 (mPAP = 36mmHg) and week 17 (mPAP = 24mmHg). Simvastatin therapy was associated with reduced right ventricular hypertrophy and reduced proliferation and increased apoptosis of pathological smooth muscle cells in the neointima and medial walls of pulmonary arteries. Longitudinal transcriptional profiling revealed that simvastatin downregulated inflammatory genes fos, jun, and TNF-α, and upregulated cell cycle inhibitor p27Kip1 and endothelial Nitric oxide synthase (eNOS).

CONCLUSION:  Simvastatin reverses monocrotaline-induced pulmonary arterial hypertension and confers a 100% survival advantage.

CLINICAL IMPLICATIONS:  Simvastatin is a candidate therapy for human pulmonary hypertension. Study of the effect of simvastatin in humans is indicated.

DISCLOSURE:  J.L. Faul, Merck, Grant monies. Speaker’s forum.

Chest. 2003;124(4_MeetingAbstracts):89S. doi:10.1378/chest.124.4_MeetingAbstracts.89S
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PURPOSE:  Maternal mortality is a known complication of pregnancy in PAH patients. Most maternal deaths occur during the immediate postpartum period. We present the successful clinical management of six pregnant women, including the delivery of six viable infants.

METHODS:  Six women were referred to the pulmonary hypertension clinic for management of moderate to severe PAH during their pregnancies. The underlying disease states included 1 with SLE/anticardiolipin antibody syndrome, 2 with PPH, 2 with PAH after corrected congenital heart disease, and 1 with stenosis of a bioprosthetic mitral valve with persistent PAH. Clinic visits occurred monthly until 28 weeks gestation, at which time weekly visits with echocardiographic imaging of the right heart was completed. The delivery date was dictated by any deterioration in right ventricular function. All physicans participating in the delivery were included in a pre-delivery planning meeting.

RESULTS:  The average age of the women was 25.1 (range 22–34) years. The average gestational time at delivery was 35 weeks (range 33 weeks + 3 days - 36 weeks + 4 days). Four deliveries were scheduled with epidural anesthesia, while 2 had scheduled C-sections with general anesthesia. Epoprostanol, nitric oxide, and dobutamine were utilized in their management. The average length of the hospital stay for the mothers was 5 days, while the average stay for the infants was 8 days. Three of the mothers developed right heart failure symptoms prior to delivery, but all six proceeded through the deliveries safely and successfully.CONCLUSIONS: Six consecutive pregnant women with PAH were successfully managed and delivered without adverse outcome to the mother or the baby. Weekly surveillance of right ventricular function beginning at week 28 was critical in scheduling the timing of delivery. We attributed the successful management and survival to this close monitoring and induction of delivery before term.

CLINICAL IMPLICATIONS:  Although pregnancy with PAH is extremely high risk, appropriate clinical and hemodynamic management, with close attention to right ventricular function can result in a successful outcome.

DISCLOSURE:  D.L. Zwicke, None.

Chest. 2003;124(4_MeetingAbstracts):89S. doi:10.1378/chest.124.4_MeetingAbstracts.89S-a
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PURPOSE:  We hypothesized that giving bosentan to patients with pulmonary arterial hypertension currently receiving epoprostenol, will allow systematic epoprostenol weaning with no decline in World Health Organization (WHO) functional class or exercise capacity, minimize medication side effects, and significantly reduce cost of therapy.

METHODS:  Five patients with primary pulmonary hypertension which were stable with continuous IV infusion of epoprostenol were initiated on 62.5 mg bid of bosentan; the dose was increased to 125 mg bid at Week 4. By Week 12, subjects were weaned down to a goal of at least 25% of epoprostenol dose at study entry. Patients were then admitted to hospital for complete epoprostenol discontinuation. Right-heart catheterization with epoprostenol challenge was performed four to six weeks after epoprostenol discontinuation, and echocardiograms were done at baseline and at 12 and 24 weeks. Exercise capacity was evaluated with monthly measurement of six-minute walk test (6MWT) up to Week 24. Laboratory assessments were carried out monthly.

RESULTS:  All patients were titrated to the 25% epoprostenol goal. One patient discontinued the study protocol before complete epoprostenol discontinuation due to significant elevations in alanine aminotransferase levels (>8 times upper limit of normal). The remaining four patients were successfully weaned off epoprostenol. Epoprostenol challenge during catheterization produced no further improvement in pulmonary pressures in any of the four patients. Echocardiography remained unchanged in all five patients. WHO functional class remained unchanged in four out of the five patients and improved from IV to III in one patient. Two of four patients experienced further increases in 6MWT at Week 24; the mean increase was +19.7±33.26% (mean baseline 6MWT was 384.5 ± 171.9 m). There were no significant adverse events observed in the four patients who completed the study.CONCLUSIONS: The use of bosentan in the down-titration and the eventual discontinuation of epoprostenol in patients with stable primary pulmonary hypertension are safe.

CLINICAL IMPLICATIONS:  Bosentan is as effective as epoprostenol in the management of stable pulmonary arterial hypertension.

DISCLOSURE:  Z. Bshouty, None.

Chest. 2003;124(4_MeetingAbstracts):89S. doi:10.1378/chest.124.4_MeetingAbstracts.89S-b
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PURPOSE:  Echocardiographic findings in pulmonary arterial hypertension (PAH) include enlargement, hypertrophy and decreased contraction of the right ventricle. Echocardiographic assessment of patients receiving long-term PAH treatment is limited.Treprostinil, a stable prostacyclin analog administered as a continuous subcutaneous infusion, diminished the symptoms of PAH in 12-week clinical efficacy studies. Echocardiography studies in PAH patients receiving long-term treprostinil treatment (beyond 3 months) may identify the effects of this compound on right ventricular performance.

METHODS:  Long-term efficacy was evaluated in a cohort of patients receiving treprostinil as primary therapy for moderate to severe PAH. Doses of treprostinil were adjusted during the study to reduce symptoms of PAH without producing intolerable adverse effects. Echocardiographic studies, 6-minute walk tests and WHO functional classification were performed pre-treatment and upon achievement of the optimal therapeutic dose.

RESULTS:  Ten patients (9 female/1 male) received subcutaneous treprostinil for an average duration of 17 months (range: 9–30 months). Mean age (±SD) was 55.0±13.0 years. Pretreatment WHO functional class was: class IV (n=5), class III (n=4) and class II (n=1). Right ventricular systolic pressure (RVSP) ranged from 64 to 110 mmHg (mean±SD, 81±15 mmHg). Right ventricular ejection fraction (RVEF) ranged from 10 to 35 percent (mean±SD, 27±9 percent). Baseline assessment of right ventricular hypertrophy (RVH) was moderate (n=6) to severe (n=4).The mean dose of treprostinil at the follow-up assessment was 29.8±10.6 ng/kg/min. Mean RVSP decreased from 81 mmHg to 60 mmHg (p<0.001). Mean RVEF increased from 27 percent to 41 percent (p<0.001). Follow-up assessment of RVH was mild (n=2) to moderate (n=8). All patients reported improved symptoms and had WHO functional class improvement. Exercise capacity improved with mean distance walked in six minutes increasing by 59 meters (p<0.05).CONCLUSIONS: Long-term treatment with treprostinil improves the echocardiographic manifestations of PAH as well as the clinical symptoms and exercise capacity.

CLINICAL IMPLICATIONS:  Subcutaneous treprostinil is a promising alternative to intravenous epoprostenol for the long-term treatment of patients with moderate to severe PAH.

DISCLOSURE:  D. Zwicke, United Therapeutics. Clinical Trials Grant

Chest. 2003;124(4_MeetingAbstracts):90S. doi:10.1378/chest.124.4_MeetingAbstracts.90S
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PURPOSE:  Patients with pulmonary arterial hypertension (PAH) can develop acute medical or surgical conditions requiring an urgent change in the treatment of their PAH. Both Flolan and Remodulin infusions have been shown to be efficacious for the relief of PAH symptoms. When monitoring of exact drug delivery is necessary, a subcutaneous depot of drug may not allow for optimal regulation of drug dosing. We report five PAH patients who required urgent transfer from subcutaneous infusions of Remodulin to intravenous Flolan.

METHODS:  Data was collected from five patients with PAH, including two abdominal transplant patients. All required urgent change of therapy from a subcutaneous to an intravenous delivery system for reasons listed in the tableSEXAGEPAH ETIOLOGYREMODULINTRANSITION REASONDOSEF36PPH3.25 yearsSepsis, low output52ngF40PPH45 daysTreatment Failure23ngF56Scleroderma3 yearsRight Heart Failure42ngF29Lupus4 monthsKidney Transplant40ngF52Hepato-pulmonary3.5 yearsLiver Transplant32ngbelow:All five patients had Remodulin discontinued for 2 hours, then intravenous Flolan was initiated at 50% of their previously stable Remodulin dose. Titration to 100% of the Remodulin dose equivalent was completed over the next 4–8 hours.

RESULTS:  All five patients promptly stabilized on the IV Flolan regimen. Only 1 patient required a reduction in the dosing schedule and remained at a lower dose due to headache and vomiting. The first three patients required dobutamine as adjunctive therapy during their transition secondary to clinical right heart failure present at the time of admission.

CONCLUSION:  Rapid transition from Remodulin, with an abdominal subcutaneous delivery system, to intavenous Flolan was accomplished without any sequelae in five patients, including two patients undergoing abdominal cadaveric organ transplantations.

CLINICAL IMPLICATIONS:  PAH patients at high risk for serious medical illnesses or on active transplant lists can be managed with Remodulin therapy, with a decreased risk for central line infection that is frequently encountered with Flolan therapy. When skin perfusion and drug absorption is in question or the abdominal surface is needed for surgery, rapid transition to intravenous Flolan therapy can be done rapidly and safely.

DISCLOSURE:  D.L. Zwicke, United Therapeutics, Grant monies.

Chest. 2003;124(4_MeetingAbstracts):90S. doi:10.1378/chest.124.4_MeetingAbstracts.90S-a
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PURPOSE:  Use of central venous catheters (CVC) impregnated with minocycline and rifampin reduces the density of bacterial growth on catheters and decreases the incidence of catheter-related bloodstream infections (CRBSI). Questions have been raised over the possibility that the use of these catheters will select for antibiotic resistant organisms. We hypothesized these catheters would not predispose to such resistance.

METHODS:  Catheter segments (1.0 cm) were placed on the surface of agar plates previously inoculated with bacterial suspensions such that a subconfluent lawn of colony growth would be apparent after 24 h incubation at 35°C in air. Test organisms included ATCC type strains of Staphylococcus aureus, Staphylococcus epidermidis, Enterococcus faecalis, Escherichia coli, and Pseudomonas aeruginosa. Zones of inhibition of colony growth surrounding catheters were measured at 24h intervals up to 7 days. Colonies on agar surfaces located at varying distances from catheter segments were examined for minocycline and rifampin resistance following various periods of exposure. In addition, selected colonies were subsequently exposed to minocycline or rifampin in broth and examined for selection of minocycline or rifampin resistance.

RESULTS:  Inhibitory zones of 14–47 mm were observed with S. aureus, S. epidermidis, E. faecalis, and E. coli. Growth of P. aeruginosa was not inhibited by CVC segments. Testing of colonies of the first four organisms at various distances from CVC segments after varying periods of exposure revealed only a single instance of the emergence of resistance (e.g. S. aureus versus rifampin). Recovery of resistant clones was enhanced with minocycline or rifampin broth selection; however, a direct link between CVC exposure and resistance induction was not statistically established.CONLUSIONS: These results suggest that exposure of Gram positive cocci to either rifampin or minocycline alone can lead to the development of resistance; however, the risk of developing resistance is low when bacteria are exposed to this antibiotic combination impregnated in CVC.

CLINICAL IMPLICATIONS:  The risk of the development of bacterial resistance to minocycline/rifampin impregnated catheters is low.

DISCLOSURE:  S.O. Heard, Cook Critical Care, Grant monies.

Chest. 2003;124(4_MeetingAbstracts):90S. doi:10.1378/chest.124.4_MeetingAbstracts.90S-b
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PURPOSE:  Despite the current definition of septic shock, patients with normal or high blood pressure may still display global tissue hypoxia. The following study evaluates early, goal-directed therapy (EGDT) in patients with severe sepsis in the absence of hypotension.

METHODS:  This is a post-hoc anlysis of patients presenting to an urban ED in severe sepsis and septic shock. Patients were included if they had SIRS critieria, lactic acidosis (> 4 mmol/liter), and mean arterial pressure (MAP) > 100 mm Hg. Patients were randomized to conventional care (inclusive of central venous pressure (CVP) monitoring) or EGDT. EGDT consisted of 6 hours of resuscitation to goals of CVP between 8–12, MAP between 65–90, and central venous oximetry (ScvO2) greater than 70%.

RESULTS:  There was no difference in mean MAP (116.0 mm Hg in the control and 117.6 mm Hg in the treatment group), and there was no difference in APACHE, MODS, and SAPS scores between groups. Forty-eight patients (23 in the control group and 25 in the EGDT group) were analyzed. The mortality was 60.9% in the control group compared to 20% in the EGDT group [p < 0.004]. The mean initial ScvO2 was 45 % and 44 % in the control and treatment groups respectively. At six hours, ScvO2 was higher in the EGDT (76% versus 59%), whereas the lactate and MODS score were reduced (p < 0.05). The EGDT group received more total intravenous fluids than the treatment group (p < 0.05) during the first six hours. At sixty days, mortality in the control (70%) and in the treament group (24%) remained significant (p=0.002).CONCLUSIONS: This study confirms that patients with severe sepsis accompanied by lactic acidosis may display global tissue hypoxia in the absence of hypotension. Early identification and goal-directed therapy of this subgroup leads to a reduction in morbidity and mortality.

CLINICAL IMPLICATIONS:  Application of early, goal-directed therapy to patients with global tissue hypoxia in the absence of hypotension can markedly reduce mortality.

DISCLOSURE:  M.W. Donnino, None.

Chest. 2003;124(4_MeetingAbstracts):91S. doi:10.1378/chest.124.4_MeetingAbstracts.91S
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PURPOSE:  We investigated the possible association between albumin administration and worse outcome in a large cohort of ICU patients.

METHODS:  All 3147 adult patients admitted to 198 European ICUs between May 1 and 15, 2002 were followed up until death, hospital discharge, or for 60 days. Patients were classified into those who received albumin at any time during their ICU stay and those who did not. Propensity score case-matching was performed with matched pairs examined for baseline characteristics and outcome.

RESULTS:  Three hundred fifty-four patients (11.2%) received albumin. On admission, patients who received albumin had a higher incidence of cancer and liver cirrhosis, were more commonly medical admissions, had higher SAPS II and SOFA scores, and had a higher incidence of sepsis syndromes. As expected, ICU and hospital mortality rates were higher in the albumin group (35.3 vs. 16.4, and 41.5 vs. 21.3%, p<0.001) than in other patients. In a Cox regression analysis with ICU mortality at 60 days as the dependent factor, albumin administration was an independent risk factor for death (relative hazard 1.4, 95% confidence interval 1.2–1.8, p<0.001) at 60 days. Moreover, in 343 propensity matched pairs, ICU and hospital mortality rates were higher in patients who received albumin than in those who did not (34.7 vs. 20.7 and 41.1 vs. 25.7%, p<0.001). Survival at 30 days was lower in the albumin group than in its matched group (Log Rank 6.9, p<0.001). Albumin administration was associated with a higher relative hazard of death at 60 days across all subgroups of age, SAPS II and fluid balance (relative hazard >1, p<0.01).CONCLUSIONS: In this observational study, albumin administration was associated with increased mortality.

CLINICAL IMPLICATIONS:  The use of albumin in critically ill patients may be associated with increased mortality and requires further evaluation by prospective randomized trials.

DISCLOSURE:  J. Vincent, None.

Topics: albumins
Chest. 2003;124(4_MeetingAbstracts):91S. doi:10.1378/chest.124.4_MeetingAbstracts.91S-a
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PURPOSE:  The objective of this study is to determine the combined impact of a scheduled antibiotic rotation for empiric coverage of gram negative nosocomial pneumonia followed by antibiotic de-escalation based upon culture results in critically injured trauma patients. We hypothesize that gram-negative resistance can be reduced by these interventions.

METHODS:  Sputum cultures in a dedicated TICU at a Level I Trauma Center for six months prior to beginning a scheduled rotation of empiric combination antibiotics served as a control period. An antibiotic rotation was initiated from 4/98 to 12/2000 in patients who met modified criteria of the 1995 American Thoracic Society Consensus Statement. Three antibiotic combinations were chosen based upon control period antibiogram: Amikacin/Imipenem, Amikacin/Zosyn, Amikacin/Levaquin. Antibiotic coverage was de-escalated based upon patient-specific culture results. A resistance index (RI) was calculated for each bacterial isolate. Length of stay (LOS), ICU days, revised trauma score (RTS), injury severity score (ISS) were analyzed using ANOVA and Bonferroni post-hoc test. Mortality was analyzed using a Fisher’s test. Results were significant if p<0.05.

RESULTS:  Gram-negative RI decreased significantly from 6.28 in the control period to 4.79 in the first six months and to a low of 3.89 in the fourth 6 month period. There were no significant differences between the groups RTS, ISS, length of stay, ICU days, or mortality rates.CONCLUSIONS: Rotation of empiric antibiotics combined with de-escalation reduces antibiotic resistance in gram negative pneumonia. Decreased resistance is maintained through multiple cycling periods.

CLINICAL IMPLICATIONS:  Nosocomial pneumonia carries an attributable mortality of 14–38%, with an annual cost of $5–10 billion annually. Interventions that can decrease resistance may be correlated with decreased mortality, resource utilization and may prevent the emergence of increasingly resistant bacterial organisms.

DISCLOSURE:  L.K. Browder, None.

Chest. 2003;124(4_MeetingAbstracts):91S. doi:10.1378/chest.124.5.1789
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PURPOSE:  Community acquired pneumonia (CAP) was reported in 35.6% of patients enrolled in a phase III trial of drotrecogin alfa (activated) in severe sepsis (PROWESS). 28 days following infusion, the relative risk reduction (RRR) in CAP was 27.8% (p = 0.015). We report in-hospital and 90-day survival for patients with CAP including Streptococcus pneumoniae.

METHODS:  CAP was defined as: (1) lung identified as primary site of infection as determined by a blinded clinical evaluation committee (CEC) (2) admission to hospital from home, and (3) receipt of study drug within 4 days of hospital admission. The CEC also adjudicated causative microorganism(s) responsible for severe sepsis in each patient. Mortality relative risk estimates with 95% confidence intervals (CIs) were calculated for each subgroup.

RESULTS:  In the overall PROWESS population, treatment with drotrecogin alfa (activated) yielded a 19.4% adjusted RRR in all-cause mortality at day 28, p=0.005. Of the 602 patients with any CAP, 46% received placebo and 54% received drotrecogin alfa (activated). Hospital mortality for CAP was 27.0% for drotrecogin alfa (activated) and 35.4% for placebo, an absolute risk reduction of 8.4% and a RRR of 23.8% (relative risk = 0.762, 95% CI = 0.598 – 0.971). At 90 days, mortality for CAP was 33.8% for drotrecogin alfa (activated) and 39.5% for placebo (RRR = 14.4%, relative risk = 0.856, 95% CI = 0.688 – 1.065). Of the 157 patients with CAP due to S. pneumoniae, 52% received placebo and 48% received drotrecogin alfa (activated). In the S. pneumoniae subgroup, hospital and 90-day mortality rates for drotrecogin alfa (activated) were 26.4% and 31.8% and for placebo 37.5% and 38.8%, respectively. RRR for patients with S. pneumoniae was 29.6% in hospital and 17.9% at 90 days.CONCLUSIONS: The survival benefit associated with drotrecogin alfa (activated) is maintained 28 to 90 days after treatment for any CAP including S. pneumoniae.CLINICAL IMPLICATION: A long-term survival benefit in CAP from drotrecogin alfa (activated) was similar to the overall PROWESS trial.

DISCLOSURE:  R.G. Wunderink, Eli Lilly and Company, Discussion of product research or unlabeled uses of Product.

Chest. 2003;124(4_MeetingAbstracts):91S-c-92S. doi:10.1378/chest.124.4_MeetingAbstracts.91S-c
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PURPOSE:  Treatment with drotrecogin alfa (activated) [DrotAA] and standard supportive care in a phase 3 clinical trial conducted at 164 sites in 11 countries was found to be associated with a significant mortality reduction and favorable benefit-risk profile compared to placebo and standard supportive care in adult patients with severe sepsis (PROWESS; DrotAA n = 850; placebo n = 840). We now report baseline characteristics and mortality from a global, single-arm, open-label trial of DrotAA in adult patients with severe sepsis conducted at 400 sites in 25 countries (ENHANCE, n=2378).

METHODS:  Inclusion and exclusion criteria were virtually identical to PROWESS. All-cause mortality was assessed at study day 28. Patients eligible for participation had known or suspected infection, 3 or 4 of the criteria defining the systemic inflammatory response syndrome, and 1 or more acute (<48 hr duration) organ dysfunctions. Patients at high risk for bleeding were excluded from participation.

RESULTS:  VariableENHANCE (DrotAA) (N = 2378)PROWESS (DrotAA) (n = 850)PROWESS (Placebo) (n = 840)Baseline CharacteristicsAge (years; mean (SD))59 (17)60 (17)61(16)Males (%)585658APACHE II (mean (SD))22.0 (7.4)24.6 (7.6)25.0 (7.8)Acute Physiology Score (mean (SD))18.6 (7.1)20.2 (7.1)20.5 (7.1)Organ Dysfunctions (mean (SD))2.7 (1.1)2.4 (1.1)2.4 (1.1)≥2 Organ Dysfunctions (%)84.374.675.9≥3 Organ Dysfunctions (%)54.642.843.4Ventilator Support (%)82.073.377.6Vasopressor Support (%)73.771.875.528-Day MortalityOverall (%)25.324.730.8Only countries in both studies* (%)23.4 (n=1478)24.7 (n=814)31.7 (n=805)*

Results for countries in common to both ENHANCE and PROWESS

CONCLUSIONS: DrotAA patients in ENHANCE tended to have lower APACHE scores but more organ dysfunctions at baseline compared with placebo patients in PROWESS. Overall mortality was similar for DrotAA-treated patients in ENHANCE and PROWESS and lower than for patients receiving placebo. These data indicate that the treatment effect associated with DrotAA remains robust despite the increase in number of countries and investigative sites participating in clinical studies.

CLINICAL IMPLICATIONS:  An increase in survival can be expected with the use of drotrecogin alfa (activated) in adult patients with severe sepsis.

DISCLOSURE:  A.P. Wheeler, None. Eli Lilly and Company (Indianapolis, IN) provided support for this research.

Chest. 2003;124(4_MeetingAbstracts):92S. doi:10.1378/chest.124.4_MeetingAbstracts.92S
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PURPOSE:  Aspiration pneumonia in familial dysautonomia (FD) patients is common and causes increased secretions. Hypotonia, poorly coordinated breathing, and spine curvature impede effective clearance of secretions and increase risk for chronic lung disease. Chest physiotherapy (CPT) has inherent complications due to concomitant labile blood pressures and gastroesophageal reflux. High-frequency chest wall oscillation (HFCWO) therapy (administered via an inflatable vest) creates airflow within the lungs that loosens and mobilizes secretions cephalad. Although HFCWO is used in a variety of patients, outcomes in FD have not been reported. We hypothesized that HFCWO therapy would reduce respiratory problems and medical interventions and improve lung function.

METHODS:  Fifteen FD patients (age range 11–33 y) were enrolled in a one-year clinical trial of HFCWO therapy. Two subjects withdrew after 3 and 6 months, respectively. Retrospective chart review of 12 months prior to entry provided baseline data regarding respiratory illnesses, medications, doctor visits, hospitalizations, and absenteeism. Daily logs provided prospective data. Evaluations were performed at one, 3, 6, 9, and 12 months for pulse oximetry, spirometry and log review.

RESULTS:  In the first month >=85% compliance was achieved by 87% of 15 subjects contrasted with 50% of 13 subjects by study completion. Mean oxygen saturation improved by one month (93.5±3.3% vs. 96.8±1.6%, p =0.005) and was sustained at exit evaluation (97.9±0.7%). Mean FVC was the pulmonary function measure with sustained improvement from 3 months to exit (p<0.05). When retrospective and prospective data were compared, all measured health outcomes improved significantly including pneumonias (p=0.0156), hospitalizations (p=0.0161), antibiotic courses (p=0.0005), antibiotic days (p=0.0002), doctor visits (p=0.0005), and absenteeism (p=0.0002).

CONCLUSION:  In this study of FD patients, HFCWO effected significant improvements in all measured health outcomes and oxygen saturation; FVC was the pulmonary function measure with sustained improvement.CLINICAL IMPLICATION: HFCWO is beneficial for FD patients with lung disease.

DISCLOSURE:  A.A. Chaikin, Advanced Respiratory, Grant monies,, Industry,, Discussion of product research or unlabeled uses of Product.

Chest. 2003;124(4_MeetingAbstracts):92S. doi:10.1378/chest.124.4_MeetingAbstracts.92S-a
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PURPOSE:  Water activities play an important role in the rehabilitation of spinal cord injury patients. Immersion in water reduces the vital capacity of normal individuals. Our objective was to compare the effect of immersion on pulmonary function of tetraplegic patients to normal individuals under controlled conditions.

METHODS:  23 otherwise well tetraplegic subjects were compared to a control group of 11 similar healthy subjects before and during 15 minutes of isothermal immersion in water to shoulders level.

RESULTS:  Immersion increased the forced vital capacity of tetraplegic patients an average of 18.4%+/-18.7 above basal measurements whereas that of the control group worsened %= -8.8%+/-4.4). Among the tetraplegic patients the lower the pre immersion χ( vital capacity the greater the percentage of improvement following immersion (r= -0,79, CI95% -0,91 to -0,56; P<0,0001). No relationship was found between time since, or level of, cervical cord injury and the degree of improvement.

CONCLUSION:  Under strictly controlled experimental conditions the pulmonary function of a group of tetraplegic patients was seen to improve during isothermic shoulder level immersion compared to a control group.

CLINICAL IMPLICATIONS:  Aquatic activities pose no apparent functional risk to tetraplegics and may improve pulmonary rehabilitation.

DISCLOSURE:  T.A. Horan, None.

Chest. 2003;124(4_MeetingAbstracts):92S-b-93S. doi:10.1378/chest.124.4_MeetingAbstracts.92S-b
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PURPOSE:  Increased resting airway tone and airway hyper responsiveness have been described in patients with cervical spinal cord injury. These conditions are attributed to unopposed cholinergic bronchoconstrictor activity from loss of sympathetic innervation of the airway. Previous studies were spirometry based. Plethysmographic assessment of baseline airway resistance has not been previously reported. Our objective was to determine the resting airway caliber in a population of spinal cord injury patients and to better define the participation of cholinergic innervation in this condition.

METHODS:  We studied 18 tetraplegic patients and 24 healthy control subjects by measuring airway conductance, before and after inhaled ipratropium bromide.

RESULTS:  The average baseline airway specific conductance was less in tetraplegic patients than control group, 0.25and 0.50cm H2O/L/s/L (P =0.001), respectively. All patients had improved post bronchodilator specific conductance greater than 35% whereas only half of the controls exhibited improvement (P less than 0.05). The percent variation for tetraplegics increased an average 235% versus only 31% for controls (P<0.001).CONCLUSIONS: Cervical spinal cord injury patients have a reduced baseline airway specific conductance compared to controls.

CLINICAL IMPLICATIONS:  Marked improvement in conductance occurs after an inhaled anticholinergic drug in tetraplegic patients.

DISCLOSURE:  T.A. Horan, None.

Chest. 2003;124(4_MeetingAbstracts):93S. doi:10.1378/chest.124.4_MeetingAbstracts.93S
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PURPOSE:  To determine the effect of body posture on the flow rates, flow-volume loop (FVL) configuration and upper airway obstruction (UAO) indices (FEV1/PEF, FEF50/FIF50) before and after thyroid surgery for goiter.

METHODS:  FVLs were measured in four different body postures (sit, supine, left and right recumbent posture) using a spirometer according to ATS standards in 21 consecutive patients before and after thyroid surgery. Flow rates were derived from the envelope FVL. Visual analysis of the FVL was performed to detect flattening of the FVL. UAO indices and flow rates were compared in the different body postures using repeated measures analysis and Bonferroni post-hoc testing when appropiate.

RESULTS:  21 patients, 3 men and 18 woman, performed spirometry before and after surgery. Mean age was 49.5 years (range 24–82). Mean body mass index was 26.4 (±SD 4.7). All flow rates decreased significantly in the recumbent postures. Two patients had flattening of the sitting expiratory FVL preoperatively. One normalised, in the other it was postoperatively more ponounced (unilateral vocal cord paralysis). In 3 patients expiratory flattening in the recumbent postures disappeared postoperatively. In one, flattening in the supine and right lateral expiratory FVL persisted postoperatively only in the supine posture. In another, flattening in all four postures persisted only in the sitting and left supine posture. In one obese patient (BMI 28.5) the expiratory recumbent FVLs did not change at all. In 3 patients flattening of the inspiratory FVLs normalised after surgery. The UAO indices did not change significantly with posture, except for the FEF50/FIF50 which preoperatively was significantly lower on the left side compared to the supine posture (p= 0.012).CONCLUSIONS: Performing FVL testing in the supine body postures increases the likelehood of detecting a functional, variable UAO, nor revealed in the sitting posture.

CLINICAL IMPLICATIONS:  Earlier detection of functional UAO due do tracheal compression by the thyroid gland may be achieved by assessing the FVL in different body postures.

DISCLOSURE:  M. Meysman, None.

Chest. 2003;124(4_MeetingAbstracts):93S. doi:10.1378/chest.124.4_MeetingAbstracts.93S-a
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PURPOSE:  Vapotherm is a novel oxygen delivery system capable of flow rates of 40 l/min. Unlike non-rebreather (NRB) systems, Vapotherm uses a nasal canula, allowing patients to talk and eat while receiving high-flow oxygen. We sought to compare the efficacy of NRB masks and Vapotherm at increasing arterial oxygen levels.

METHODS:  We conducted a prospective, randomized trial comparing Vapotherm to NRB masks in patients with advanced lung disease. All patients were clinically stable at time of enrollment. After obtaining a baseline, room air blood gas (ABG) subjects were randomly assigned to receive oxygen with either Vapotherm or through a NRB mask. The Vapotherm was set to 40 l/min for oxygen delivery while the NRB was calibrated to deliver 100% oxygen. After 60 minutes of the first intervention a second ABG was obtained. Prior to crossing over to the alternative system, patients breathed room air for an additional 60 minutes. An ABG was obtained after this washout period to document return to baseline values. The primary study endpoint was the arterial oxygen tension with each intervention.

RESULTS:  The study cohort included 14 male patients (mean age 60 ± 5.2 years, 12 with COPD and 2 with idiopathic pulmonary fibrosis). The mean baseline room air oxygen tension was 68.9±6.6 mmHg. With the NRB the mean arterial oxygen level increased to 389.1±82.9 mmHg (p<0.0001 vs. baseline) and with Vapotherm the level measured 375.1±69.4 mmHg (p<0.0001 vs. baseline). The difference between oxygen levels while breathing through the NRB mask and the Vapotherm device were not statistically significant (p=0.62). Neither the pCO2 nor the arterial pH appeared altered by either delivery mechanism.CONCLUSIONS: Vapotherm is as effective as a NRB mask at delivering high-flow oxygen.

CLINICAL IMPLICATIONS:  Since Vapotherm appears to provide oxygen as efficaciously as a NRB mask and better tolerated than a NRB mask, broader use of Vapotherm is warranted.

DISCLOSURE:  M.L. Guerrero, None.

Topics: oxygen delivery
Chest. 2003;124(4_MeetingAbstracts):93S. doi:10.1378/chest.124.4_MeetingAbstracts.93S-b
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BACKGROUND:  Police officers are allowed, by law, to request screening samples of breath for alcohol at the roadside. If a person, without reasonable excuse, does not adequately perform the required breath test, there is a mandatory loss of driving license for one year and a fine. Although the breath testing devices in common use in Canada require minimum flow rates and effort, they have not been widely tested on individuals with respiratory disease. Moreover, because some individuals who perhaps would be found guilty of a breath testing related offence have falsely used respiratory disease as their excuse, little credibility has been given to individuals with severe lung disease who may truly be unable to provide adequate samples of breath.

OBJECTIVES:  To determine if patients with respiratory disease can provide adequate breath samples to meet the requirements of alcohol breath test machines; to determine whether the ability to provide a breath sample is related to pulmonary function values.

DESIGN:  Prospective clinical evaluation.

SETTING:  Pulmonary function laboratory at a university hospital.

PATIENTS:  One hundred fifty undifferentiated patients referred for pulmonary function testing by their primary care physician.

METHODS:  Following informed consent and receiving proper instruction, patients provided a maximum of three breath samples into each of two alcohol breath testing devices (Dräger Alcotest® 7410 Breath Alcohol Monitor; Alcohol Countermeasure Systems Alcolmeter S-L2 Portable Breath Analysis System). The ability to provide adequate samples of breath into each device was recorded. Patients then performed pulmonary function tests.

RESULTS:  48.7% and 19.3% of the participants failed to activate the Alcolmeter S-L2 and Alcotest 7410 breath testing devices, respectively. 18.7% of the participants could not activate either device. Some PFT values were significantly different between those that could provide adequate samples of breath and those that could not.

CONCLUSIONS:  These data suggest that the Alcotest 7410 may be a more suitable alcohol breath testing device to use than the Alcolmeter S-L2.

DISCLOSURE:  A.R. Mc Ivor, Nova Scotia Lung Association Legacy Grant, Grant monies.

Chest. 2003;124(4_MeetingAbstracts):93S-c-94S. doi:10.1378/chest.124.4_MeetingAbstracts.93S-c
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RATIONALE:  There are 2 million asthma related emergency department events (ED) each year in the US. Under recognition and under treatment may be associated with this high rate. This study describes patterns of asthma care before and after asthma ED.

METHODS:  Retrospective observational study utilizing the PharMetrics Integrated Outcomes Database containing medical and pharmacy claims of ≥ 20 managed care plans. Patients with an asthma ED visit (primary ICD-9 493.xx) during 2001 were identified. Patients excluded with ≥ 1 asthma-related ED or hospitalization 1 year prior to the index ED. Asthma related pharmacy and medical claims were studied in the 12 months prior to and 2 months after the ED.

RESULTS:  12,636 patients were identified. Twelve months prior to the index ED, patients used short-acting beta-agonist (SABA) and inhaled corticosteroid (ICS) at a 3:1 ratio. A total of 24.5% had ≥ 1 ICS claim (mean claims, 0.7/yr) and 53.5% had ≥ 1 SABA claim (2.2/yr), while 29.9% had ≥ 1 oral corticosteroid (OCS) claim (0.59/yr). Also, 93.6% had ≥ 1 office visit in the year prior but only 11.2% had ≥ 1 spirometry test. ICS claims increased 2.4 fold while OCS increased 6.8 fold the month immediately after the ED, returning to pre event levels 2 months after. Only 13.2% of patients not on ICS prior to the event received an ICS within 2 months after the event.

CONCLUSION:  ICS containing treatments reduce exacerbations and ED visits. This study demonstrates that patients at risk for ED are not frequently assessed with spirometry and use 3 times more SABA than ICS. In addition, nearly 75% of patients were not receiving an ICS containing medication 1 year prior to the ED and the ED visits did not result in a substantial increase in the percent of patients using ICS.

CLINCIAL IMPLICATIONS:  The use of ICS and spirometry is underutilized in asthmatics at risk for a ED. Emphasis should be on improving asthma care, especially post ED discharge

DISCLOSURE:  D.A. Stempel, Received monies from GlaxoSmithKline, Industry.

Chest. 2003;124(4_MeetingAbstracts):94S. doi:10.1378/chest.124.4_MeetingAbstracts.94S
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PURPOSE:  To investigate the prevalence of gastroesophageal reflux (GER) among adult asthmatics and to study the effect of omeprazole therapy on the outcome of asthma in asthmatics with GER

METHODS:  In this double blind, placebo-controlled crossover study, 100 asthma patients meeting the criteria of the American Thoracic Society were enrolled. Ambulatory pH monitoring was done to find the prevalence of GER and the patients who were found to have GER were randomized to receive omeprazole 40 mg qd, or placebo for 8 weeks. After a 2 week washout period, the patients were crossed over to the other treatment. Spirometry was performed at baseline and immediately after both treatment periods. Peak expiratory flow rates (PEFR) and the pulmonary and gastric symptoms were recorded daily in a diary.

RESULTS:  Significant GER was found in 58% of the study group. There was significant reduction in mean weekly daytime asthma symptom score (13.68±2.37 to 11.65±1.79, p<0.05) as well as night-time asthma symptom score (13.52±1.65 to 10.56±1.51, p<0.01) after omeprazole therapy. Based on the symptom scores, 40% of the patients were regarded as responders to omeprazole treatment. There was significant improvement in PEFR (70.15±10.12 to 81.39±12.56, p<0.01) but no improvement in FEV1 (72.11±29.16 to 73.44±30.81, p=0.14) after omeprazole treatment.CONCLUSIONS: Asthmatics have high prevalence of GER. Antireflux treatment improves asthma symptoms as well as PEFR in asthmatics with GER.

CLINICAL IMPLICATIONS:  GER may contribute to asthma symptoms in some asthmatics. Antireflux therapy may have a beneficial effect on asthma outcome in these patients.

DISCLOSURE:  B. Sharma, None.

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    Print ISSN: 0012-3692
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