Abstract: Late-Breaking Science

Chest. 2005;128(4_MeetingAbstracts):496S. doi:10.1378/chest.128.4_MeetingAbstracts.496S

PURPOSE:  BREATHE-5 was the first placebo-controlled trial to investigate the effects of bosentan (Tracleer®) in patients with Eisenmenger physiology (EP). EP is characterized by the development of pulmonary arterial hypertension (PAH) and consequent intracardiac right to left shunt and hypoxemia in patients with pre-existing congenital heart disease. EP has been regarded as not amenable to conventional treatments or surgery. Theoretically, some treatments may worsen the shunt and increase hypoxemia. Since EP is associated with increased endothelin expression, it has been hypothesized that patients may benefit from endothelin antagonism.

METHODS:  BREATHE-5 was a multi-center, randomized, double-blind, placebo-controlled study evaluating the effect of the dual endothelin receptor antagonist, bosentan on oxygen saturation (main primary objective, non-inferiority) and hemodynamics (second primary objective, superiority) in patients with WHO functional class III. Secondary objectives included exercise capacity, safety, and tolerability.

RESULTS:  Fifty-four patients were randomized 2:1 to bosentan (n = 37) or placebo (n = 17). Baseline characteristics, including mean oxygen saturation (SpO2), mean pulmonary vascular resistance, indexed (PVRi) and 6-minute walk distance (6MWD), were comparable in both groups. After 16 weeks the treatment effect on SpO2 was 1.0% (95% CI = > -5, non-inferiority margin), demonstrating that bosentan did not worsen oxygen saturation. As this primary safety endpoint was reached, efficacy analyses were conducted. In comparison with placebo, PVRi was significantly reduced (treatment effect - 472 dyn.sec.cm-5; p=0.04) and exercise capacity, measured by the 6MWD was significantly increased (treatment effect + 34m; p=0.02). Four patients discontinued due to adverse events, two (5.4%) in the bosentan group and two (11.8%) in the placebo group. The bosentan safety profile was comparable to that observed in previous clinical trials in PAH.

CONCLUSION:  In this first placebo-controlled trial in patients with EP, bosentan was well tolerated and improved exercise capacity and hemodynamics, without compromising peripheral oxygen saturation.

CLINICAL IMPLICATIONS:  Bosentan may be an important new treatment option for patients with EP, a disease with poor prognosis.

DISCLOSURE:  Nazzareno Galiè, None.

Chest. 2005;128(4_MeetingAbstracts):496S. doi:10.1378/chest.128.4_MeetingAbstracts.496S-a

PURPOSE:  IPF is a fatal disease with no approved treatment. Tumor necrosis factor-a (TNF-a) is implicated in the pathogenesis of IPF. Efficacy and safety of etanercept, a fully human soluble TNF-a receptor, were evaluated in IPF patients.

METHODS:  Eighty-seven patients with well-defined IPF who had evidence of disease progression participated in a prospective, randomized, double-blind, placebo controlled, parallel-group, multicenter trial (≪26>48 weeks). Patients received etanercept (25 mg subcutaneous) or placebo twice weekly. Those with severe disease (forced vital capacity predicted <45% or diffusing capacity of lung for carbon monoxide, corrected for hemoglobin predicted <25% or partial pressure of arterial oxygen <55mmHg and oxygen saturation <88% on room air (at rest) were excluded. Concomitant treatment with corticosteroids or other therapies for IPF was not allowed. Using an ANCOVA model to calculate differences between treatment groups, the three primary endpoints, FVC% predicted, DLCOC% predicted, and alveolar to arterial O2 difference P(A-aO2) difference (at rest), were analyzed as change from baseline to Week 48. Fisher’s exact test was used to compare rate of combined endpoint death or disease p! rogression between treatment groups.

RESULTS:  No significant difference in baseline demographics or disease status was noted. Number of men/women was 59/28, mean age was 65.2 years, length of prior diagnosis was 13.6 months, and FVC % predicted was 63.4. At 48 weeks, no significant differences between treatment groups in primary and secondary endpoints were observed (Table). In a post hoc analysis, the frequency of patients who died or had disease progression (=>10% decline in FVC [L]) at the last visit, up to 14 days after last dose was 15/45 (33.3%) and 22/40 (55.0%) in etanercept and placebo groups (p=0.052). There was no significant difference in incidence or type of adverse events, serious adverse events, infections, or serious infections between treatment groups.

CONCLUSION:  Although no statistical difference was found between treatment groups in predefined primary endpoints, etanercept therapy resulted in a trend toward reduced disease progression by several measures in these patients with progressive IPF.

DISCLOSURE:  Drs. Raghu, Lasky, Costabel, Brown, Cottin, du Bois, Thomeer, and Utz have received research grants in this Wyeth sponsored trial. Dr. McDermott is an employee of Wyeth.

Chest. 2005;128(4_MeetingAbstracts):496S-b-497S. doi:10.1378/chest.128.4_MeetingAbstracts.496S-b

PURPOSE:  Bronchoscopic lung volume reduction (BLVR) using bioactive agents to remodel damaged lung tissue has reduced lung volume in a sheep model of emphysema. This abstract reports preliminary findings using this approach to treat advanced heterogeneous emphysema in humans.

METHODS:  A two-stage study involving 6 subjects was conducted at 2 medical centers to assess safety. Stage 1 subjects received subtherapeutic treatment at 2 subsegmental sites in a single lung. Stage 2 subjects received treatment at 4 subsegmental sites in a single lung. Safety was assessed as the number of serious adverse events associated with treatment in Stage 1 and 2 subjects.

RESULTS:  There were no serious adverse events associated with initial BLVR treatment in either stage of the study. All subjects were discharged from the hospital on post-treatment Day 1. Two-month follow-up in Stage 2 subjects demonstrated improvements in pre- and post-bronchodilator FEV1 (+11% & +6%) and FVC (+20% & +12%), a reduction in RV (10%), improvement in 6 MWD (+35%), and a reduction in MRC dyspnea (3.3 to 2). These trends did not reach statistical significance. Two of the Stage 1 subjects have had subsequent retreatment at 2 sites. There were no early adverse events after retreatment; studies of therapeutic response are pending.

CONCLUSION:  BLVR using tissue remodeling appears to be safe in subjects with advanced emphysema. Suggestion of efficacy after treatment at 4 sites is apparent at 2-month follow-up.

CLINICAL IMPLICATIONS:  Additional follow-up is needed to assess long-term safety and durability of response. These results warrant further cautious clinical trials.

DISCLOSURE:  George Richard Washko MD, None.

Chest. 2005;128(4_MeetingAbstracts):497S. doi:10.1378/chest.128.4_MeetingAbstracts.497S

PURPOSE:  To investigate the safety and feasibility of Carbon Dioxide (CO2) laser transmission through the OmniGuide Photonic Bandgap Fiber (OPBF) for treatment of airway obstruction.

METHODS:  Experiments using discarded human lung tumor tissue were carried out to determine the therapeutic dose for effective tumor destruction. Laser bronchoscopy was performed on 20 sheep to examine the safety and feasibility of the proposed treatment algorithm (dosages 3W to 10W). Animals were euthanized at 1 week and 4 weeks for pathological examination.

RESULTS:  A dose response with the maximal thermal effect at the highest dose was observed. Microscopically, the maximal depth of penetration (0.5mm) was obtained only with the high dose at the shortest distance (10W, 5mm). The thermal effect to non-targeted tissue was minimal. Animal experiments demonstrated ease in maneuverability and flexibility of the procedure. Distal airways were easily accessible with the fiber. Tissue damage was highly localized and visible, facilitating a very high degree of control over penetration, ablation and cutting. No laser-related complications were observed. Application of maximal dosage (10 Watts) did not result in perforation, bleeding or other injuries. Four incidents of mild bleeding were easily and immediately controlled with laser shots at the high dosage setting.

CONCLUSION:  The CO2 laser delivered through the OPBF can supply an effective dose for tumor destruction. The same dosages can be applied via flexible bronchoscopy safely in airways of live animals. Depth of penetration can be controlled by altering output power or distance from the target tissue. In no case was the penetration deeper than the superficial cartilage.

CLINICAL IMPLICATIONS:  This is the first reported CO2 laser delivery through a standard flexible bronchoscope for ablative therapy in the distal airways. CO2 laser transmission through the OPBF may potentially provide a more controllable and precise modality for treatment of benign and malignant airway lesions. This precision is likely to make laser therapy safer and applicable to more lesions. Moreover, potential exists for superficial mucosal ablation of carcinoma in-situ.

DISCLOSURE:  Raphael Bueno, None.

Abstract: Poster Presentations

Chest. 2005;128(4_MeetingAbstracts):225S. doi:10.1378/chest.128.4_MeetingAbstracts.225S

PURPOSE:  Clinical and basic studies have suggested that interleukin 2 (IL-2) plays an important role for the development of pulmonary edema. However, its precise mechanism is still undetermined. For the resolution of pulmonary edema, alveolar fluid clearance is essential, and this clearance is known to be dependent of ion transport ability of alveolar epithelial cells. In this study, we determined the effects of IL-2 on alveolar fluid clearance.

METHODS:  Isotonic 5% albumin solutions with pharmacological treatments were instilled into the distal airways in the isolated rat lungs. The lungs were inflated with 100% oxygen at 8cm H2O and placed in a humid incubator at 37°C. Alveolar fluid clearance was estimated by the progressive increase in the albumin concentration over 1h.

RESULTS:  Seven male S-D rats were used in each group. IL-2 stimulation caused dose-dependent increase in alveolar fluid clearance (Control, IL-2 (50U/ml), IL-2 (5000U/ml), vs. IL-2 (10000U/ml): 15.8±1.8%, 15.3±1.5%, 21.8±1.0%, vs. 24.6±1.7: P<0.05). Terbutaline (β adrenergic receptor agonist) caused significant increase in alveolar fluid clearance (27.8±1.1%), and this increase was inhibited by propranolol (β adrenergic receptor blocker). In contrast, propronolol did not inhibit the IL-2 stimulation.

CONCLUSION:  This study indicates that IL-2 increases alveolar fluid clearance in the isolated rat lungs. Because the stimulatory effect by IL-2 is not inhibited by propranolol, IL-2 may increase alveolar fluid clearance via non-β adrenergic receptor mediated pathway.

CLINICAL IMPLICATIONS:  Intravenous administration of IL-2 has been shown to cause pulmonary edema. However, our results suggest that IL-2 stimulates transalveolar fluid transport for clearance of excess edema fluid. This study was supported by Grant for Promoted Research from Kanazawa Medical University (S2003-8).

DISCLOSURE:  Makoto Sugita, None.

Chest. 2005;128(4_MeetingAbstracts):225S. doi:10.1378/chest.128.4_MeetingAbstracts.225S-a

PURPOSE:  Acute respiratory distress syndrome (ARDS) is a serious form of acute lung injury (ALI), and has a high mortality of 30-50%. Understanding of ALI at molecular level may provide insights and lead to new therapies. PTX3 is a newly identified acute-phase protein, which can be induced from a variety of tissue cells on pro-inflammatory stimulations, such as LPS, IL1β and TNFα. In this study we sought to define the PTX3 expression patterns in multiple ALI models in rats and its relationship with the lung injury.

METHODS:  Rats were randomized to receive hemorrhagic (HS) or endotoxic shock (LPS) followed by resuscitation, or sham operation. Then the animals were subjected to either high (HV) or low (LV) volume ventilation for 4 hours. Blood gas, lung elastance, and wet/dry ratio were measured. PTX3, IL1β, and TNFα were assayed by quantitative real time PCR and ELISA. Distribution of PTX3 in the lung tissue was determined by immunohistochemistry.

RESULTS:  After 4 hours of mechanical ventilation, the PTX3 expression in both mRNA and protein levels in the lung tissues were significantly enhanced by HS, or LPS, which is further increased by HV. In fact, HV alone also increased PTX3 expression significantly. In contrast, the serum level of PTX3 was found no obviously increase by HV and HS, but only slightly enhanced by LPS. Immunohistochemistry showed a profound positive staining of PTX3 on the epithelial layer of alveolar walls, indicating a major local response of PTX3 during ALI. The local PTX3 expression was well correlated with IL-1β and TNFα. Furthermore, the PTX3 expression was highly correlated with changes in wet/dry lung ratios, elastance, and PaO2, respectively (p < 0.0001).

CONCLUSION:  PTX3 is an important inflammatory mediator whose expression can be increased by the inflammatory responses in the pathogenesis of ALI.

CLINICAL IMPLICATIONS:  PTX3 might serve as a sensitive biomarker for local inflammatory responses during ALI.

DISCLOSURE:  Daisuke Okutani, None.

Chest. 2005;128(4_MeetingAbstracts):225S. doi:10.1378/chest.128.4_MeetingAbstracts.225S-b

PURPOSE:  Two previous studies showed that ARDS patients fed an enteral diet containing EPA+GLA and elevated antioxidants (Oxepa) had significantly increased oxygenation, and improved clinical outcomes. We investigated the potential benefits of the same diet in patients with ARDS in addition to Multiple Organ Dysfunction (MOD) which correlates strongly with the risk of intensive care unit (ICU) mortality.

METHODS:  We enrolled 16 ICU patients with ARDS (as defined by the American-European Consensus Conference) as a prospective, multicenter, double-blind, randomized controlled trial. Patients meeting entry criteria were randomized and continuously tube-fed EPA+GLA or an isonitrogenous, isocaloric standard diet at a minimum caloric delivery of 90% of basal energy expenditure for at least 4 days.

RESULTS:  Ventilator settings were recorded and arterial blood gases were measured, at baseline and study days 4 and 7 to enable calculation of PaO2/FIO2, a marker for gas exchange and part of the Modified Lung Injury Score (LIS). Significant improvements in oxygenation (PaO2/FIO2) from baseline to study day 4 with lower ventilation variables (FIO2, positive end-expiratory pressure, and minute ventilation) occurred in patients with higher APACHE scoring at enrollment who were fed EPA+GLA compared with controls (p<.01). In addition, patients fed EPA+GLA had a decrease in their APACHE score 4 days after initiation of the enteral nutrition with decreased in length of stay in the intensive care unit (12.8 vs. 17.5 days; p = .016) compared with controls. Over all, patients fed EPA+GLA had a significant decrease in MOD score at 28 days after initiation of their tube feeding (p<.05).

CONCLUSION:  This preliminary report support the previously reported benefits of EPA+GLA diet on gas exchange, and length of ICU stay. In addition, patients fed EPA+GLA had reduction of their APACHE score within 4days of initiating of the enteral nutrition with decreased MOD scores 28 days after initiation of their tube feeding.

CLINICAL IMPLICATIONS:  Enteral nutrition of ARDS patients with EPA+GLA diet can improve their gas exchange, in addition to decrease length of ICU stay and 28 days mortality.

DISCLOSURE:  Elamin Elamin, None.

Chest. 2005;128(4_MeetingAbstracts):225S-c-226S. doi:10.1378/chest.128.4_MeetingAbstracts.225S-c

PURPOSE:  The primary purpose of this study was to determine the effects of different positive end-expiratory pressure in the lung protective strategy on ventilation-perfusion distribution measured by the multiple inert gas elimination technique.

METHODS:  All patients were on pressure-controlled mode with the inspiratory pressure, FiO2 and PEEP adjusted to provide a tidal volume of 6-8 ml/kg, an oxygen saturation > 90% and a plateau pressure ≤ 35 cm H2O. Six levels of PEEP were studied in an incremental manner: 0 cmH2O (ZEEP), PLIP-4, -1, +2, +5, +8 cmH2O. All physiological parameters were measured at the end of each 30-min PEEP trial. If the patient showed signs of hemodynamic instability or desaturation to < 88% during trials at lower PEEP, that trial was terminated and PEEP was increased to the next higher level.

RESULTS:  Eleven patients were ventilated with low tidal volume and PEEP from 0 to 8 cmH2O above the lower inflection point pressure. These patients had a large intrapulmonary shunt and dead space with an additional mode at the high ventilation-perfusion regions. Intrapulmonary shunt and dead space improved with increasing positive end-expiratory pressure up to 2-5 cmH2O above the lower inflection point pressure. Higher positive end-expiratory pressure increased dead space without further reduction in intrapulmonary shunt.

CONCLUSION:  The dispersion of ventilation and perfusion also followed a similar trend. Other endpoints commonly used for titrating positive end-expiratory pressure, such as oxygenation, alveolar recruitment and lung compliance, all increased with increasing positive end-expiratory pressure while hemodynamic parameters were unaffected. Thus based on ventilation-perfusion matching, positive end-expiratory pressure of 2-5 cmH2O above the lower inflection point pressure appears optimalduring protective lung ventilation.

CLINICAL IMPLICATIONS:  We determined PEEP effects during protective lung ventilation using ventilation-perfusion (VA/Q) distribution as an endpoint.This method of adjusting PEEP was used because it has been shown that the recruiting potential of lung tissues with PEEP varied significantly among individual ARDS patients. Our goal was to determine if there was a PEEP level that gave the most optimal VA/Q distribution.

DISCLOSURE:  Chin-Pyng Wu, None.

Chest. 2005;128(4_MeetingAbstracts):226S. doi:10.1378/chest.128.4_MeetingAbstracts.226S

PURPOSE:  Non Invasive Positive Pressure Ventilation (NIPPV) is the accepted initial treatment for exacerbation of chronic obstructive lung disease and cardiogenic pulmonary edema. Its role in Acute Lung Injury (ALI) is controversial. We sought to assess the outcome of ALI initially treated with NIPPV and to identify specific risk factors for NIPPV failure in this patient population.

METHODS:  In this observational cohort study,consecutive patients with ALI initially treated with NIPPV were identified. ALI was defined according to standard American European Consensus Conference Definition. Patients with do not resuscitate orders were excluded. NIPPV failure was defined as the need to intubation or death while on NIPPV. Data on demographics, APACHE III scores, degree of hypoxemia (PaO2/FIO2), presence of shock, sepsis, aspiration, transfusion, metabolic acidosis, time to intubation, as well as NIPPV parameters (tidal volume, minute volume, inspiratory and expiratory pressure) were recorded. Univariate and multivariate regression analysis was performed to identify risk factors for NIPPV failure.

RESULTS:  79 patients met the inclusion criteria. 23 were excluded because of do not resuscitate order and 2 denied research authorization. 34 of the remaining 54 patients (62.9%) had a primary diagnosis of pneumonia. 38 (70.3%) patients failed NIPPV, including all 19 patients with shock. ALI patients successfully treated with NIPPV had lower Apache-3 scores (55.5 vs 81.5; p=0.004), were less likely to have metabolic acidosis (base deficit: 0.52 vs -4.01; p=0.017) and severe hypoxemia (PaO2/FIO2: 147 vs 112; p=0.020). Multivariate logistic regression analysis identified higher base deficit (p= 0.04) and lower PaO2/FIO2 ratio (p=0.008) but not APACHE III scores (p=0.105) as significant predictors of NIPPV failure. In patients who failed NIPPV the observed mortality was higher than APACHE predicted mortality (68.4% vs 38.6 %).

CONCLUSION:  The presence of septic shock, low PaO2/FIO2 ratio and metabolic acidosis in patients with Acute Lung Injury predicts failure of NIPPV .

CLINICAL IMPLICATIONS:  NIPPV should not be used in patients with Acute Lung Injury who have shock, metabolic acidosis or profound hypoxemia.

DISCLOSURE:  Sameer Rana, None.

Chest. 2005;128(4_MeetingAbstracts):226S. doi:10.1378/chest.128.4_MeetingAbstracts.226S-a

PURPOSE:  Mechanical ventilation (MV) with low tidal volumes (Vt: 8-6 cc/kg of IBW) has become a standard of care for patients with ARDS since mid-2000 (NEJM 2000, 342: 1301). To analyze MV setting’s habits for ARDS patients by Quebec ICU physicians, before and after the ARDS network report.

METHODS:  i) files of 71 ARDS patients from 5 Quebec ICUs studied from January 2000 to March 2002, ii) 2 groups arbitrarily defined to compare the period up to 6 months (i.e November 2000) following the ARDS network report, with the period after this landmark.Outcomes primary: the change of Vt over-time between the groups, secondary: mortality, number of days without organ failure, PEEP level, respiratory rate, PaCO2 .

RESULTS:  21/71 patients were enrolled before the landmark and 50/71 after the landmark. Vt normalized to real or IBWs were reduced after Nov 2000 (7.8 +/- 0.2 vs 6.8 +/- 0.1 p<0.0001 and 9.3 +/- 0.2 vs 8.1 +/- 0.1 p<0.0001 respectively). There was no significant difference of mortality between the two groups (48% vs 36%, NS). PEEP (10.6 +/- 0.4 vs 13.9 +/- 0.2 p=0.02), respiratory rate (20 +/- 1.2 vs 29 +/- 0.6 p<0.0001), PaCO2 (47 +/- 1.4 vs 50 +/- 0.7 p=0.02) significantly changed. A trend towards higher number of days without organ dysfunction was found after November 2000 (all organs: 14.8 vs 20.5; p=0.08, renal: 19.5 vs 24.4; p=0.06, cardiovascular: 15.4 vs 22.4; p=0.07, hepatic 18.8 vs 22.4, p=0.2, coagulation; 18.4 vs 24.1; p=0.07).

CONCLUSION:  Knowledge translation regarding on ventilation setting of ARDS patients has moved nearer standard practice in Quebec ICUs after the 2000 ARDS Net release. Morbidity was affected in this small cohort of patients.

CLINICAL IMPLICATIONS:  Standard practice regarding on mechanical ventilation of ARDS patients has changed with time following the ARDS Net release, with trends toward lower secondary organ dysfunction rate.


Chest. 2005;128(4_MeetingAbstracts):226S-b-227S. doi:10.1378/chest.128.4_MeetingAbstracts.226S-b

PURPOSE:  Mechanical ventilation (NCMV) using extra-tracheal continuous gas insufflation (ETCGI) and nitric oxide (NO) has been used for patients with ALI(1).The purpose of this preliminary study was to compare the conventional mechanical ventilation (CMV) through lung protective ventilation versus the effect of ETCGI using NO mixture, on oxygenation and ventilation parameters in patients with ARDS and refractory hypoxemia.

METHODS:  Five patients (four women) with severe systemic inflammatory response syndrome, multiple organ system failure (ApacheII:26,88,5±2,99) and ARDS (LIS:3,75±0,3) with refractory hipoxemia (PaO2/FiO2:52,06±2,14 torr and SatO2:65,2±4,20 cmH2O) were studies. The sequential ventilatory support protocol was: 1.Protocol CMV: Initial PRVC:Pressure regulated volume control or PCV: Pressure controlled ventilation to 6,28±0,38 ml/kg tidal volume (protective ventilation), optimizing best Peep (17,4±1,81 cmH2O) and NO. 2.Protocol NCMV: Subsequently changes ventilation mode to PRVC or PCV, with Peep (2,4±0,54 cmH2O), ETCGI (9,0±2,64 liters/minute) and Nitric Oxide (3,92±0,83 ppm). The tidal volume, finaly was: 11,97±1,89 ml/kg and the volume minute was 15654±3050 ml/minute (range:12400-19600). The peak pressure (PIP) values in ETCGI mode, were obtained through tracheal level monitoring. All patients, the informed consent was obtained, less in two patients that was obtained differed.

RESULTS:  See table: t-Student for comparative samples (95% CI).

CONCLUSION:  1.- NO+ETCGI optimal application appears to improve oxygenation and ventilation substantially. 2.- All patients survived the refractory hypoxemia. 3.-One patient died due to refractory septic shock, after a new episode of sepsis. 4.- No high levels of NO2 (<1,0 ppm). 5.- No barotrauma episodes, in spite use high tidal volume (two patients development barotrauma previous and were treated with NO+ETCGI without ventilatory problems). REFERENCE: 1.Herrero S, Varon J, Fromm RE. “Nitric Oxide and Extratracheal continuous gas flow in the acute respiratory distress syndrome. Crit Care Med. December 2004. Vol. 32, No. 12 (Suppl.) P400.

CLINICAL IMPLICATIONS:  1.- In life-threatening ARDS with refractory hypoxemia, it is possible to maintain an adequate PaO2 with the application of NO and ETCGi (considered as ”rescue treatment“) 2.- ETCGi can be performed even in presence of previous barotrauma.

DISCLOSURE:  Santiago Herrero, None.

Chest. 2005;128(4_MeetingAbstracts):227S. doi:10.1378/chest.128.4_MeetingAbstracts.227S

PURPOSE:  Mechanical ventilation as a life-sustaining procedure is a benefit to medicine and usually safe for the patient. When performed over extended periods, it is known to cause lung injury. Various methods of assessing lung injury have been utilized. An objective measure, lactate dehydrogenase (LDH) isozyme profiles, changed significantly after ventilation in lung-healthy rats. Human studies using LDH 4/5 ratio in bronchoalveolar lavage (BAL) have assisted in diagnosing pulmonary infection. We hypothesized that BAL LDH isozymes would relate to lung changes induced by mechanical ventilation.

METHODS:  With IRB approval and individual signed consent, 30 patients with healthy lungs undergoing elective surgery were enrolled in a prospective non-randomized trial to determine levels of LDH isozymes in BAL fluid, and to correlate these levels to time on mechanical ventilation. Bronchoscopy was performed and a BAL was obtained at intubation. After surgery a second BAL was done in the contralateral lung. Total LDH and LDH isozymes were measured by protein electrophoresis on BAL concentrates. Using pre-surgical BAL LDH isozymes as individual baseline, change in each LDH isozyme as a function of time on mechanical ventilation was plotted.

RESULTS:  Mechanical ventilation averaged 2 hr 20 minutes (range: 15-509 minutes). All 5 LDH isozymes increased in the post-surgical BAL, isozyme 4 significantly so (p=0.05). Ventilator time was compared with the change in each LDH isozyme; no statistical significance was found.

CONCLUSION:  This study demonstrated an elevated LDH isoenzyme 4 in BAL fluid during surgical mechanical ventilation with an average time of approximately 2 hours. LDH isozyme measurements, which have historically emphasized cardiac and skeletal muscle metabolism, showed that isozyme 4 is usually remarkably stable, with exercise and training affecting the other isozymes.

CLINICAL IMPLICATIONS:  The significant increase in BAL isozyme 4 in the present study suggests a potential target for investigating lung injury in patients who are subjected to prolonged mechanical ventilation.

DISCLOSURE:  Gregory Howell, University grant monies We work for the University of Missouri-Kansas City. The study was funded by the University.

Chest. 2005;128(4_MeetingAbstracts):227S. doi:10.1378/chest.128.4_MeetingAbstracts.227S-a

PURPOSE:  High frequency oscillation (HFO) is increasingly used to support adults with ARDS. Little data are available to guide the transition to conventional mechanical ventilation (CMV); commonly this occurs when mean airway pressure has been weaned below 24 cmH2O. This study aimed to identify predictive factors for successful transition from HFO to CMV.

METHODS:  Retrospective chart review of all patients receiving HFO in our institutions from 2000 to 2005. Data are presented as mean ± SD. Student’s t-test was used for comparisons.

RESULTS:  117 patients received HFO, with a mean age 50.9 ± 18.8 years. We excluded from analysis patients who died on HFO (n=10), or who were transitioned for withdrawal of care (n=25) or other reasons (e.g. hemodynamic compromise or deterioration on HFO, n=17). The remaining 65 patients were transitioned to CMV with a view to weaning. Of these, 24 (37%) died a mean of 19.1 ± 24.1 days after transition (“non-survivors”) and 41 (63%) survived to discharge (“survivors”). Comparing non-survivors with survivors, no differences were noted in illness severity when HFO was initiated (APACHE II 19.1 ± 6.8 and 21.1 ± 8.3, p=0.20; PaO2/FiO2 ratio 105 ± 43.3 and 120 ± 74.0, p=0.49; oxygenation index 32.1 ± 13.6 and 34.4 ± 16.4, p=0.39). At the time of transition to CMV, no difference was noted between non-survivors and survivors in mean airway pressure (23.6 ± 2.6 cmH2O and 24.6 ± 3.9 cmH2O, p=0.062) or ventilator frequency (4.90 ± 1.59 Hz and 4.93 ± 1.84 Hz, p=0.43). However, non-survivors had significantly worse oxygenation at transition than survivors (PaO2/FiO2 ratio 191 ± 74.3 and 224 ± 72.3, p<0.05; OI 14.4 ± 6.1 and 12.0 ± 3.3, p<0.05).

CONCLUSION:  Despite similar severity of illness and oxygenation at initiation of HFO, patients who did not survive following successful transition to CMV demonstrated worse oxygenation parameters at the time of transition.

CLINICAL IMPLICATIONS:  These finding may suggest a role for oxygenation indices in the decision to transition from HFO to CMV.

DISCLOSURE:  Satomi Shiota, Consultant fee, speaker bureau, advisory committee, etc. Speakers fees

Chest. 2005;128(4_MeetingAbstracts):227S. doi:10.1378/chest.128.4_MeetingAbstracts.227S-b

PURPOSE:  Previous work has shown that inducible nitric oxide synthase (iNOS) derived from inflammatory cells plays a particularly important role in the development of high-protein pulmonary edema and increased oxidative stress in sepsis-induced acute lung injury (ALI). Interestingly, iNOS-/- animals show increased pulmonary polymorphonuclear leukocyte (PMN) infiltration despite decreased lung injury. The purpose of this study was to test the hypothesis that iNOS reduces pulmonary production of CXC chemokines and increases surface expression of adhesion molecules on PMN.

METHODS:  Experiments were performed using iNOS+/+ and iNOS-/- C57BL/6 mice. Sepsis was induced via cecal ligation and perforation (CLP), the lungs were removed and homogenized for analysis of the CXC chemokine macrophage inflammatory protein-2 (MIP-2). Alveolar macrophages (AM) were cultured, stimulated with LPS+IFN-γ and the culture medium was analyzed for MIP-2 production. Surface expression of CD11b and CD62L was measured via flow cytometry in bone marrow PMN after LPS+IFN-γ stimulation.

RESULTS:  MIP-2 levels in lung homogenate were increased in septic mice vs control and were significantly lower in septic iNOS+/+ vs iNOS-/- mice (35.8±12.3 vs 67.4±14.2 ng/mL). AM MIP-2 production increased following LPS+IFN-γ stimulation but there was no difference between iNOS+/+ and iNOS-/- AM. Bone marrow PMN stimulated with LPS+IFN-γ showed increased expression of CD11b and decreased expression of CD62L vs control but there was no difference between iNOS+/+ and iNOS+/+ PMN.

CONCLUSION:  iNOS inhibits septic pulmonary, but not AM production of MIP-2. PMN iNOS has no apparent effect septic PMN surface expression of CD11b and CD62L on PMN.

CLINICAL IMPLICATIONS:  A better understanding of the mechanisms by which iNOS affects PMN infiltration and sequestration may lead to new therapeutic options for patients with ALI.

DISCLOSURE:  Cedrin Law, None.

Chest. 2005;128(4_MeetingAbstracts):227S-c-228S. doi:10.1378/chest.128.4_MeetingAbstracts.227S-c

PURPOSE:  Use of lower tidal volumes (VT) is recommended for patients suffering from ALI/ARDS. We previously reported on a simple ’intervention’ aiming at lowering VT in our institution (goal: VT 6-8 ml/kg): this intervention existed of feedback and education on the use of lower VT, during which special attention was paid to the importance of closely adjusting VT to predicted body weight (PBW) in stead of actual bodyweight (Wolthuis, Intensive Care Med 2005).

METHODS:  To determine the longstanding effects of the above-mentioned intervention, we (a) compared data on VT-settings of mechanically ventilated patients before feedback and education (June 2003, N = 30) with VT-settings 15 months later (September 2004, N = 103); in addition, we (b) collected data on VT-settings of patients recruited in two consecutive randomized controlled ALI/ARDS- trials: the first trial was performed in 10-month period before the intervention (March 2002 –December 2002, N = 12), the second was performed in a 10-month period after the intervention (July 2003 –May 2004, N = 8). Statistical analysis: Mann-Whitney U test. P-value < 0.05 was considered to represent a significant difference.

RESULTS:  (a) Before intervention, VT was 9.6 ± 1.8 ml/kg PBW; VT declined shortly after the intervention (8.0 ± 1.8 ml/kg PBW), and remained low (7.8 ± 1.3 ml/kg PBW) 15 months after the intervention. (b) VT in the second randomized controlled trial was significantly lower as compared with VT in the first study on ALI/ARDS-patients: while in the majority of patients in the first study VT was > 10 ml/kg at all times, in the second study almost all VT were between 6 and 8 ml/kg.

CONCLUSION:  Feedback and education caused a sustained decline in VT in mechanically ventilated patients in our institution.

CLINICAL IMPLICATIONS:  These results possibly underscore the importance of the use of PBW, instead of actual bodyweight, to adjust VT.

DISCLOSURE:  Marcus Schultz, None.

Chest. 2005;128(4_MeetingAbstracts):228S. doi:10.1378/chest.128.4_MeetingAbstracts.228S

PURPOSE:  Current practice employs low tidal volumes (Vt) in the ventilation of patients with ARDS. Studies supporting this approach also suggest that plateau alveolar pressures (Pplat) associated with such tidal volumes (25 cmH2O) are much lower than Pplat values (<35 cmH2O) previously demonstrated to be safe. These studies assume that Pplat during mechanical ventilation remains constant. We have observed fluctuating airway pressures during positive pressure ventilation of patients with ARDS. The “snapshot” measurements of mechanics in the above studies could thus misrepresent the actual Pplat, explaining the studies’ discrepancies. We have measured serial pulmonary mechanics and pressures during short periods of ventilation of patients with ARDS in order to evaluate this possibility.

METHODS:  In each of 20 patients using mechanical ventilation for ARDS, clinical and ventilator data were extracted from the chart. Subsequently compliance, airway resistance (Raw), peak airway pressure (Ppeak) and Pplat were measured every 30 minutes for 6 hours. These measurements were performed in the absence of any spontaneous breathing effort or change in ventilator settings. Mean values and the range of values of each parameter were measured in each patient.

RESULTS:  7 males and 13 females, aged 72+/-17 years were studied. All utilized volume ventilation with a Vt of 9+/-2.6ml/kg and inspired oxygen concentration of 48+/-21%. Compliance was 32+/-10ml/cm with an intraindividual variation of 12+/-6ml/cm. Raw was 18+/-6.6l/s/cm with a variation of 12+/-6.6l/s/cm. Pplat was 23.8+/-8.9cmH2O with ranges of values from 5 to 18 cmH2O. Ppeak was 32 +/-11cmH2O with ranges from 7 to 17.

CONCLUSION:  There is substantial short term variation in airway and alveolar pressures during mechanical ventilation of lungs with ARDS. This may expose such lungs to barotrauma if initial ventilator settings cause alveolar pressures at the high end of the safe pressure range, since these pressures may be exceeded during continued mechanical ventilation.

CLINICAL IMPLICATIONS:  When optimizing ventilation and lung expansion of patients with ARDS, Pplat should be monitored serially to prevent exposure of the lung to traumatic pressures.

DISCLOSURE:  William Marino, None.

Chest. 2005;128(4_MeetingAbstracts):228S. doi:10.1378/chest.128.4_MeetingAbstracts.228S-a

PURPOSE:  Obstructive sleep apnea (OSA) adversely affects ventricular function, increasing the incidence of nocturnal death of cardiac origin and contributing to the pathogenesis of congestive heart failure. The large swings in intrathoracic pressure caused by airway occlusion increase cardiac transmural pressure, decrease preload, and increase afterload, augmenting metabolic demand at the same time as arterial oxygen content decreases. We hypothesized that repeated inspiratory occlusions, mimicking OSA, cause myocardial dysfunction and injury.

METHODS:  We subjected anesthetized male Sprague-Dawley rats to 3 h of repeated airway occlusion (30 s occlusion every 2 min); results were compared to sham rats.

RESULTS:  Following occlusions, left ventricular function decreased; the peak rates of pressure generation (+dP/dt) and relaxation (-dP/dt) fell from 7820 ± 271 (SEM) to 6310 ± 623 and from -8851 ± 502 to -7121 ± 381 mmHg/s (p < 0.05), respectively. Myofibril proteins were isolated from the left ventricle for determination of Ca2+-activated myosin ATPase activity. Compared to shams, inspiratory occlusion significantly reduced maximum (97 ± 5 vs. 137 ± 9, p < 0.01) and minimum (35 ± 6 vs. 76 ± 9 nmol/min/mg, p < 0.01) ATPase activity. We detected release of cTnT into the blood in 4 of 9 occluded rats but none of the shams.

CONCLUSION:  These results demonstrate for the first time that repeated inspiratory occlusions acutely impair left ventricular contractility, reduce ATPase activity of myofibril proteins, and, in some rats, cause myocardial necrosis. The mechanism(s) underlying the decrease in ATPase activity is unknown but probably reflects a post-translational modification(s) to one or more myofibril proteins.

CLINICAL IMPLICATIONS:  Collectively, these results may account for the acute pathological effects of OSA.

DISCLOSURE:  Colleen Lynch, None.

Chest. 2005;128(4_MeetingAbstracts):228S-b-229S. doi:10.1378/chest.128.4_MeetingAbstracts.228S-b

PURPOSE:  To evaluate a new measure of EEG synchrony or stability using fundamental frequency analysis provided by Morpheus in subjects with severe obstructive sleep apnea (OSA) adequately treated with CPAP using a split night protocol.

METHODS:  A total of 27 adults were selected with a primary diagnosis of obstructive sleep apnea and who were treated with CPAP during their initial study. Each individual had a baseline and treatment period. Only those individuals with a respiratory disturbance index (RDI) < 10 episodes per hour and oxygen saturation greater than 85% during the ideal CPAP titration period were selected. When there was more than one CPAP level that this occurred, the multiple levels were included. Fundamental frequency values below 4 Hz are believed to represent increased EEG synchrony. The percentage of fundamental frequency below 4 Hz was calculated during the baseline period and ideal CPAP titration period (total sleep time).

RESULTS:  Means with standard deviations are reported. There were 24 males (ages 25-77) and 3 females (ages 46-52). Body mass index was 35(7); Epworth Sleepiness Scale 12(5), and SleepMed Insomnia Index 16(8). Low oxygen saturation at baseline was 81%(6); oxygen saturation at ideal CPAP level 91%(2); RDI at baseline 71(26); and RDI at ideal CPAP level 3(3). Fundamental frequency under 4Hz during the baseline period was 12%(13) and at the ideal CPAP pressure 31%(13). Independent t-tests comparing % of fundamental frequency below 4Hz at the baseline period with the ideal CPAP period were significant p<0.001.

CONCLUSION:  Early intervention with CPAP in OSA improves sleep quality. Automated analysis that calculates modal frequency of adaptive segmentation and fuzzy logic segments in sleep EEG demonstrates EEG synchrony that is believed to reflect improvement in sleep quality.

CLINICAL IMPLICATIONS:  Enhanced resolution by automated analysis offers improved efficiencies, reproducibility, and insights into sleep states and processes.

DISCLOSURE:  Richard Bogan, Shareholder SleepMed Inc.

Chest. 2005;128(4_MeetingAbstracts):229S. doi:10.1378/chest.128.4_MeetingAbstracts.229S

PURPOSE:  The standard diagnostic test of OSA, i.e. overnight polysomnography (PSG), is complex and difficult to perform outside the sleep laboratory. However, the value of electrophysiological and respiratory monitoring has not been assessed critically in unattended settings. In this study we evaluated whether full PSG is necessary to establish a diagnosis of OSA in unattended studies.

METHODS:  Full unattended PSG studies were conducted in the home place (25 tetraplegic patients)or in the hospital (25 surgical patients studied preoperatively)using a standard montage. Installation of the biosensors was performed by a trained sleep technician. Recording was initiated at a preset time and all signals stored on a digital storage media (Flash card) and subsequently downloaded to a desktop computer for analysis. No overnight monitoring was possible. The PSGs were first scored using standard criterions by one of 3 trained sleep technicians and an apnea/hypopnea index (AHI) calculated as the number of respiratory events per hour of sleep as determined by sleep staging. The analysis was then repeated on a separate day and in a blind fashion using respiratory variables only (i.e. without EEG and EMG signals) and a respiratory disturbance index (RDI) calculated as the number of respiratory events per hour of recording time.

RESULTS:  Sleep efficiency was 77.1±13.8%. Recording time exceeded sleep time by 117±79 minutes (p<.03) but RDI (20.5±21.3) was not ≥significantly different from AHI (22.9±24.2; p=.116). Both were highly correlated (r2=.82). Using a AHI diagnostic cutoff value ≥15 events/h, the diagnostic sensitivity and specificity of RDI were both 86%. If a RDI cutoff value of ≥10 events/h was adopted instead, sensitivity would be 100%.

CONCLUSION:  Because of frequent arousal, the Rechtschaffen and Kales method for scoring sleep markedly underestimate sleep time as well as the number of respiratory events. We conclude that bioelectric signals are not necessary for the diagnosis of OSA.

CLINICAL IMPLICATIONS:  Because PSGs are much simpler to perform without bioelectric signals, this simplified approach should improve access to and cost/benefit of diagnosis and treatment of OSA.

DISCLOSURE:  Pierre Mayer, None.

Chest. 2005;128(4_MeetingAbstracts):229S. doi:10.1378/chest.128.4_MeetingAbstracts.229S-a

PURPOSE:  The objective was to evaluate the clinical prevalence of nasal breathing mode, the most frequent one, and the presence of nasal obstruction. The obstruction sites (naso and oropharynx) and frequency in the oral-breathing mode and mixed-breathing mode were also evaluated.

METHODS:  The study design was transversal, analyzing 145 consecutive healthy patients enrolled at UERJ Faculty of Dentistry, without any previous history of smoking or respiratory disease. They were classified by clinical examination in 3 groups according their mode of breathing: nasal-breathing, oral-breathing, mixed-breathing (turns nasal or oral mode). Their respiratory airflow were measured by the Forced Oscillation Technique (FOT), Oscilab-version 2.0, from nose and from mouth at a frequency of 5 Hz, to determine the obstruction in naso and oropharynx.

RESULTS:  The Fisher exact test was used, with significant association between breathing mode and the obstruction level (p = 0,003). The oral-breathing occurred when there were obstruction (p=0,001) in nasopharynx (33.33%), and/or oropharynx (44.44%). The nasal and mixed mode were more frequent with the obstruction absence (68.54% and 53.19%, respectively).

CONCLUSION:  The breathing pattern had positive correlation with the obstruction site. The nasal and the mixed-breathing, may occur with some obstruction degree. The naso or oropharynx obstruction contributed significantly to oral-breathing mode.

CLINICAL IMPLICATIONS:  In the literature review, there wasn’t any reference about quantitative or qualitative methods to verify the relationship between the type of breathing and obstruction. This technique could testify this correlation significantly.

DISCLOSURE:  Florence Sekito, None.

Evaluation of the Clinical Concepts of Normal Breathing, Types of Breathing and the Obstruction in Nasopharynx and Oropharynx

Frequency%Nasal-BreathingOral-BreathingMixed-BreathingTotalNo obstructionn61 68.54%111.11%25 53.19%87Nasopharynx obstructionn1516.85%4 44.44%817.02%27Oropharynx obstructionn66.74%3 33.33%1021.28%19Naso and Oropharynx obstructionn77.87%111.11%48. 51%12Total89947145

Chest. 2005;128(4_MeetingAbstracts):229S-b-230S. doi:10.1378/chest.128.4_MeetingAbstracts.229S-b

PURPOSE:  To know prevalence estimates for key symptoms and features that can indicate the presence of obstructive sleep apnea(OSA) in Indian population.

METHODS:  Single centre cross sectional study done from August 2003 to July 2004 in consecutive apparently healthy attendants of 25-64 years age group coming to outdoor of Department of Pulmonary Medicine, King George’s Medical University, Lucknow, India. We recorded data on a pre-designed proforma and took interview on the basis of pre-tested Berlin Questionnaire with some relevant modifications.

RESULTS:  Out of 816 subjects approached, 702 responded. Out of 702, 452(64.4%)were males. Mean age was 42.7 ± 10.4 years; mean neck circumference was 13.6 ± 1.2 inch, mean BMI was 23.8 ± 4.2 kg/m2. 31.1%(218/702) were snorers. The loud snorers were17.4%, and 60.5% of them were at high risk for OSA. Among snorers 22.9% bothered other people and 46.0% of them were at high risk for OSA. Out of 702, 6.0% had morning tiredness or sleepy awakening (≥ 3-4 times /wk) and 52.4% of them were at high risk for OSA, 5.1% had wake time tiredness and 61.1% of them were at high risk for OSA. Out of 702, 45.3% either did not know to drive or never needed driving and only 54.7 % used to drive. Among persons who use to drive 2.1% had drowsiness behind the wheel (≥ 3-4 times/wk) and 75% of them were at high risk for OSA. Out of 702, 13.0% were obese and 19.8% of them were at high risk for OSA. Overall there were 3.7% (26/702) were at high risk for OSA(qualified for 2 or more category symptoms of Berlin questionnaire) .

CONCLUSION:  Obstructive sleep apnea is a common disease and there is high demand of its awareness, evaluation, diagnosis and management in countries like India.

CLINICAL IMPLICATIONS:  There is need of relevant modification of Berlin Questionnaire for countries like India as half of our population either do not know to drive ored not to drive.

DISCLOSURE:  Rajendra Prasad, University grant monies Received no grants; Grant monies (from sources other than industry) Nil; Grant monies (from industry related sources) Nil

Chest. 2005;128(4_MeetingAbstracts):230S. doi:10.1378/chest.128.4_MeetingAbstracts.230S

PURPOSE:  The main purpose of this study is to estimate the prevalence of sleep related breathing disorders in patients with sarcoidosis by using Sleep Apnea/Sleep Disorders Questionnaire (SA/SDQ) and Epworth Sleepiness Scale (ESS).

METHODS:  70 consecutive patients with diagnosis of biopsy proven sarcoidosis seen at the sarcoid clinic were screened for sleep related breathing disorders using SA/SDQ and ESS. The SA/SDQ consists of 8 questions and 4 other items related to weight, smoking status, age, and body mass index, which are calculated to generate a raw score. Total scores range from 0-60. To suspect sleep apnea, cutoffs of 32 for women and 36 for men were used as a criteria for sleep study referral.

RESULTS:  70 patients with sarcoidosis completed the questionnaires. There were 42 females and 28 males with a mean age of 48 ± 10 years. 34% of pateints were African American. Mean duration of diagnosis was 78 months. 60% of patients had 2 or more organs involved. Approximately 2/3rd of patients were actively treated with steroids or other immunosupressive agents (mean prednisone dose was 7 mg/day). 39 patients had positive questionnaires (25 with positive SA/SDQ while 14 with positive ESS). Considering the reported 81% specificity of SA/SDQ for sleep apnea in general population, 39% of patients will most likely have sleep apnae syndrome by polysomnography.

CONCLUSION:  The prevalence of sleep apnea syndrome in patients with sarcoidosis is significantly high. In this study, we persented our experience with SA/SDQ as a screening instrument for sleep disordered breathing in a sample of patients with sarcoidosis.

CLINICAL IMPLICATIONS:  Screening tools such as the SA/SDQ are gaining increasing importance because of high prevalence of sleep disordered breathing in chronic diseases and the high cost of polysomnography. Sleep disordered breathing is highly prevalent in our sarcoid population and SA/SDQ may be a useful test in identifying patients at risk for sleep apnea syndrome.

DISCLOSURE:  Majid Mughal, None.

Chest. 2005;128(4_MeetingAbstracts):230S. doi:10.1378/chest.128.4_MeetingAbstracts.230S-a

PURPOSE:  Nasal flow sensors are utilized for diagnosis of sleep apnea syndrome (SAS). Discomfort and fluctuation in sensitivity caused by body movements are problems when patients wear nasal flow sensors during polysomnography (PSG) tests. The aim of this study was to clarify the accuracy of non-restrictive sensing system for diagnosing SAS using three-dimensional Fiber-Grating (FG) sensors.

METHODS:  Twenty patients with SAS were enrolled in the study [M:F=19:1, age 50.0±26 years old, BMI 26.2kg/m2, apnea-hypopnea index (AHI): 25.6]. Three-dimensional FG measurement and PSG tests were conducted simultaneously. AHI determined by using pressure flow, and the movement of thoracic and abdominal walls during PSG were compared to those by FG sensors in the supine and lateral positions.

RESULTS:  AHI determined by FG sensors and PSG tests were well correlated (r=0.973, P<0.0001; supine position: r=0.974, P<0.0001, lateral position: r=0.965, P<0.0001, respectively). All twenty patients underwent these tests with no trouble and good compliance.

CONCLUSION:  The accuracy of non-restrictive sensing system for diagnosing SAS was clarified.

CLINICAL IMPLICATIONS:  Since the non-restrictive system using FG sensors is more comfortable and convenient for making diagnosis of SAS than the conventional one, it may be widely introduced.

DISCLOSURE:  Hisashi Takaya, None.

Chest. 2005;128(4_MeetingAbstracts):230S. doi:10.1378/chest.128.4_MeetingAbstracts.230S-b

PURPOSE:  The purpose of this study is to compare the incidence of possible obstructive sleep apnea syndrome (OSAS) in patients with acute myocardial infarction (AMI) and normal coronary angiography to the incidence of possible OSAS in patients with MI and abnormal coronary angiography.

METHODS:  All patients admitted to a university hospital with the diagnosis of AMI were evaluated. AMI was defined as having 2 out of 3 criteria: Chest pain, ST elevation of > 1 mm in two contiguous leads, or elevated cardiac enzymes. Patients who underwent coronary angiography were included in the study. The subjects were asked a set of questions. The questions were scored from 1 to 3. The questions addressed the following: Epworth sleepiness scale (ESS). ESS>10 (score 1), ESS>18 (score 2), snoring (score 1), witnessed apneas (score 3), falling asleep in inappropriate situations (score 2), unrefreshed sleep (score 1), and history of OSA diagnosed by NPSG. The subjects were then classified into five classes. Class I highly unlikely to have OSA (score ≤ 1), class II unlikely to have OSA (score 2), class III likely to have OSA (score 3), class IV highly likely to have OSA (score ≥3), and class V definite OSA (OSA diagnosed by nocturnal polysomnography (NPSG)). The subjects were divided into two groups. Group I included patients with normal coronaries, whereas group II included patients with abnormal coronaries on angiography.

RESULTS:  A total of 55 patients were included in the final data analysis. 22 subject in group I, and 33 in group II.The results are summarized in the following table.

CONCLUSION:  The incidence of possible OSAS was significantly higher in patients with AMI and normal coronaries compared to patients with AMI and abnormal coronaries on angiography. 28.5% compared to 6% p value 0.035.

CLINICAL IMPLICATIONS:  Patients with AMI and normal coronary angiography should be investigated for the possibility of OSAS. Those found to have high likelihood of having OSAS should be sent for NPSG and adequate treatment offered.

DISCLOSURE:  Michael Chalhoub, None.Age (years)BMI (Kg/m2)Male (%)Female (%)Class III/IV (%)Group1 n=2257.1±13.139.6±10415928.6Group 2 n=3366.2±11.831.1±869316P valueNSNS0.0290.0290.035

Results are mean+standard deviations unless otherwise specified. BMI= Body Mass Index.

Chest. 2005;128(4_MeetingAbstracts):231S. doi:10.1378/chest.128.4_MeetingAbstracts.231S

PURPOSE:  Patients with obstructive sleep apnea (OSA) report excessive daytime sleepiness and attention impairment. This study assesses the impact of continuous positive airway pressures (CPAP) treatment of attention deficit.

METHODS:  We studied 41 adult patients who presented at a nationally accredited sleep center for evaluation of OSA. Severity of OSA is evaluated using the Epworth Sleepiness Scale (ESS) a self report questionnaire designed to assess daytime sleepiness on a scale of 0 to 24; and by the respiratory disturbance index (RDI) measured during their sleep study. Attention impairment was evaluated using the adult self-report scale (ASRS) symptom checklist, a validated scale assessing attention impairment on a scale of 0 to 36. A score of 17 or greater indicates possible or probable attention deficit. Patients completed both questionnaires at baseline and following CPAP treatment; the RDI was measured during their baseline sleep study and during a subsequent CPAP titration study.

RESULTS:  The average baseline score on ESS was 11.6 (4.2) and 2.7 (3.3) at 3 months post-treatment (t=11.8,p<.0001). The average RDI on the baseline PSG was 29.9 (16.8) and 2.2 (3.6) on the subsequent CPAP study (t=10.5,p<.0001). The ASRS score was 16 (8) at baseline and 11 (8) at 3 months post-treatment (t=6.0,p<.0001). Of 41 patients at baseline, 19 demonstrated an ASRS score of 17 or greater; at 3 months post-treatment, 11 showed an ASRS that had decreased to the normal range, while 8 did not. These patients were subsequently diagnosed with ADD due to a comorbid psychological or neuromuscular diagnosis, hearing or reading deficit, or memory or executive function impairment. Most suffered from concurrent insomnia and non-restorative sleep.

CONCLUSION:  This study demonstrated a high comorbidity between ADD and OSA. Forty-six percent showed significant attention impairment at baseline; with treatments, 58% reported substantial improvement, but 42% reported persistent serious attention deficit, and required further evaluation and treatment.

CLINICAL IMPLICATIONS:  OSA is a significant factor contributing to ADD. In patients with persisting deficits after CPAP treatment, further evaluation and treatment is required.

DISCLOSURE:  Clifford Risk, None.

Chest. 2005;128(4_MeetingAbstracts):231S. doi:10.1378/chest.128.4_MeetingAbstracts.231S-a

PURPOSE:  OSA occurs in non-obese patients,but they may exhibit different characteristics than obese patients with OSA. To elucidate this point,we investigated several physiological and clinical parameters among non-obese and obese OSA patients.

METHODS:  Of 254 patients referred to sleep clinic,we identified 102 patients with OSA(Apnea Hypopnea Index≥5). We classified OSA patients with Body Mass Index(BMI)<30 as non-obese and those with a BMI≥30 as obese. We conducted a retrospective evaluation that included demographic,physiological and clinical data and compared the non obese and obese groups. For statistical comparisons, continuous variables were analyzed by student’s t-test and categorical variables by chi-square. Fisher’s exact test was used for analysis when a variable contained less than 5 observations.

RESULTS:  Of 102 patients with OSA,17(16.7%)were non-obese and 85(83.3%)were obese. The groups of non-obese and obese OSA patients differed significantly in four parameters. Mean AHI was 13.5 in the non-obese group and 27.6 in the obese group(P= 0.03). Non-obese patients were older(average age 57.1 years compared to 48.3 years among obese patients)(t-test,p= 0.01);used more sedatives(usage of one or more sedatives by 52.9% in non-obese group compared to 24.7% in the obese group)(Chi-square,p= 0.02);and,exhibited less upper airway narrowing(23.5% of the non-obese group compared to 55.1% in the obese group)(Chi-square,p= 0.02). Only one non-obese patient(5.9%) was younger than 50,compared to 48 patients(56%)in the obese group(Chi-square,p<0.0001). There were no significant differences between non-obese and obese OSA patients in gender,family history of OSA,facial malformations,adenoid or tonsillar enlargement,smoking,co-morbid conditions and use of narcotics.

CONCLUSION:  In our study,about 1 in 5 patients with OSA was non-obese,suggesting OSA is not limited to obese persons. Non-obese persons differed from obese persons in several important characteristics. We report for the first time that excess use of sedatives occurred in non-obese OSA patients compared to obese patients.

CLINICAL IMPLICATIONS:  OSA is milder in non-obese patients and is unlikely in non-obese patients who are less than 50 years old.

DISCLOSURE:  Ammar Ghanem, None.

Chest. 2005;128(4_MeetingAbstracts):231S. doi:10.1378/chest.128.4_MeetingAbstracts.231S-b

PURPOSE:  Obesity is epidemic in the United States and is a major cause of morbidity and mortality. In addition to obstructive sleep apnea, obesity is associated with obesity hypoventilation syndrome (OHS), characterized by daytime hypercapnia. OHS is associated with significant morbidity and mortality. In order to initiate therapy with non invasive positive pressure ventilation (NIPPV), a sleep study is required. We perrformed a study to determine the prevalence of daytime hypercapnia in morbidly obese patients referred for evaluation of dyspnea and to evaluate if body mass index or pulmonary function test help distinguish simple obesity from OHS.

METHODS:  All subjects who underwent pulmonary function test (PFT) at our institution from January 2003 to December 2004 were screened. Inclusion criteria was a BMI ≥ 35 kg/m2, ≤ 20 pack years history of smoking, an FEV1 > 50%, an FEV1 / FVC >70, and absence of neuromuscular disorder. Simple Obesity (SO) was defined as a BMI ≥ 35 kg/m2 in the absence of daytime hypercapnea. OHS was defined as a BMI ≥ 35 Kg/m2 and daytime hypercapnia (arterial PaCO2 ≥ 45 mm Hg). Data on subjects age, gender, height, weight, smoking history, pulmonary function tests (PFT’s), arterial blood gas (ABG), polysomnography and use of NIPPV were collected by chart review.

RESULTS:  1904 PFT’s were performed during the study period. 122 patients met the inclusion criteria. Seventy six (62%) patients had complete PFT’s and an ABG available for review. Twelve (16%) subjects had daytime hypercapnia.

CONCLUSION:  OHS is common in morbidly obese patients. Clinical parameters such as BMI and pulmonary function test do not help distinguish OHS from SO. Arterial blood gas measurements are necessary to establish a diagnosis of OHS.

CLINICAL IMPLICATIONS:  Morbidly obese individuals with unexplained dyspnea should have arterial blood gas measurements to exclude daytime hypercapnia. Polysomnography should be considered in patients with daytime hypercapnia to determine the presence of sleep disordered breathing and to initiate noninvasive positive pressure ventilation.

DISCLOSURE:  Farooq Sattar, None.

Chest. 2005;128(4_MeetingAbstracts):231S-c-232S. doi:10.1378/chest.128.4_MeetingAbstracts.231S-c

PURPOSE:  We evaluated the efficacy of an abbreviated sleep questionnaire, desgined to recognize sleep disordered breathing (SDB)in a cohort of patients assigned to a VA heart failure clinic.

METHODS:  A 6 point data set consisting of (1)Excessive Daytime Sleepiness,(2) Snoring, (3)Observed Apneas,(4) Non-restorative sleep, (5)BMI, (6)and Neck Circumference were collected. Each positive response was given one point. BMI>30 and Neck Circumference>17.5 in were given one point each. Scores of 3 or more points were placed in the high probability category and were assigned high priority for SDB evaluation. Two or less point scores were assigned to the Low probability. All were scheduled for Attended Polysomnography.

RESULTS:  Of the 40 heart failure clinic patients evaluated 25 had scores of 3 or more points on the screening questionnaire. 15 patients had 2 or less points and were referred to the VA sleep clinic for confirmatory examination. Four of those 15 patients were referred for polysomnography while the remainder were felt unlikely to have significant SDB. All high probablity patients were scheduled for polyomnography. Sleep Disordered Breathing was identified in 70 per cent of those patients.

CONCLUSION:  The 6 point screening questionnaire appeared to delineate a higher risk group for sleep disordered breathing in this cohort of patients with known heart failure. Less than 30 per cent of the low probability cohort were ultimately studied.

CLINICAL IMPLICATIONS:  SDB is present in approximately 50 percent of patients with known stable CHF. A short simplified 6 point data set appeared to be sensitive in selecting patients with a high probability for SDB. Use of the questionnaire should identify patients at risk for SDB earlier, and could prioritize their early evaluation and should result in earlier treatment.

DISCLOSURE:  John Roehrs, None.Variable (mean ± SD)Simple Obesity (n=64)Obesity Hypoventilation Syndrome (n=12)Age54.2±12.952.5±13.4Body mass index (kg/m2) Pulmonary Function (% predicted) FEV-1 FVC FEV-1/FVC TLC ERV DLCO43.5±9.348.3±10.2    FEV-181±1677±15    FVC82±1577∓15    FEV-1/FVC80±581±5    TLC88±1287±13    ERV48±3737±21    DLCO85±2285±14Arterial blood gases    pH7.41±0.037.39±0.02*    PaO276±969±12*    PaCO239.5±348.4±6.6*Polysomnogram n (%)20 (31)1 (8)    Apnea-hypopnea index ≥ 5 (n)131*

p-value < 0.05

Chest. 2005;128(4_MeetingAbstracts):232S. doi:10.1378/chest.128.4_MeetingAbstracts.232S

PURPOSE:  OSA is a relatively common condition with a prevalence of 5%. Significant reduction in QOL is the major complication OSA.Continuous positive airway pressure (CPAP) titrated to eliminate Apnea and Hypoapnea significantly improve quality of life. Previous study indicates there is no correlation between QOL and severity of sleep apnea. There are various physical and polysomnographic finding that associated with the decrease in health related QOL in this cohort study. The purpose of this study is to evaluate the impact of polysomnographic features and physical characteristics to health related QOL in a patient with OSA.

METHODS:  The Study was conducted in sleep laboratory of Kings County medical center, Brooklyn, New York. We studied 34 adult (22 male and 12 female) patients with mean age of 45 (19-72), a body mass index (BMI) of 41.99 and diagnosis of OSA (apnea-hypoapnea index more than 5). Patients with major medical and psychiatric illness were excluded. Baseline physical and polysomnographic characteristics were obtained. The health related QOL was assessed by administering medical outcomes short-form ( MOS SF-36), a 36-item questionnaire that summarizes health related QOL using eight subscales and two summary scores. The results were analyzed using Pearson correlation statistics.

RESULTS:  The was significant negative correlation between BMI and SF-36 physical score ( p<0.001). Subclass analysis also showed significant correlation between BMI and all components. There was also positive correlation between sleep efficiency and physical functioning and mental health. It is of note that there was no significant correlation between apnea-hypoanea index (AHI), arousal index, nocturnal oxygen desaturation (NOD) and the SF-36 physical and mental health scores.

CONCLUSION:  AHI factor that define OSA may not determine the severity of disease outcome with respect to health related QOL.The study showed the significant impact of obesity on QOL in patients with OSA.

CLINICAL IMPLICATIONS:  weight reduction measures should aggressively be incorporated in management of OSA to improve their QOL. The positive association in sleep efficiency and QOL may indicate possible mechanism of improvement of QOL with CPAP.

DISCLOSURE:  Asegid Kebede, None.

Chest. 2005;128(4_MeetingAbstracts):232S. doi:10.1378/chest.128.4_MeetingAbstracts.232S-a

PURPOSE:  Active heated humidification improves the side-effects of CPAP therapy for patients with sleep-breathing disorder (SAS) in the upper airways.In a cool ambience temperature, however, condensation will form and the patients feel disturbed in their sleep.The object of this study was to examine the effects of condensation on sleep quality during continuous CPAP. Furthermore, a comparison of sleep quality achieved with an active heating breathing tube versus conventional heated humidification was intended to be gained in a prospectively random study.

METHODS:  19 patients with a first diagnosis of obstructive sleep apnoea syndrome, median age 55.2 (+/- 10.4) years, median BMI 32.8 (+/- 6.3) kg/m2 and median ESS score 10.8 (+/- 5.0) were treated with CPAP (HC 602, Fisher & Paykel) with conventional heated humidification (integrated humidifier and tube heater turned off, humidification via HC100, temperature 32°C) and on another night with an active heated breathing tube (level 8, heating humidifier 32°C) in the sleep lab.

RESULTS:  The results of the poysomnography data.

CONCLUSION:  If condensation forms in the CPAP tubing system, sleep quality is considerably reduced. This can be eliminated almost entirely by a heated breathing tube.

CLINICAL IMPLICATIONS:  We suggest that patients needing active heated humidification during CPAP, who wish to sleep in a cold bedroom ambience, should use a system with a heated breathing tube.

DISCLOSURE:  Georg Nilius, Grant monies (from industry related sources) The study was fianced by gift from fisher and Paykel healthcare

Chest. 2005;128(4_MeetingAbstracts):232S-b-233S. doi:10.1378/chest.128.4_MeetingAbstracts.232S-b

PURPOSE:  Nasal symptoms are a common side effect of CPAP therapy. Although most patients experience self-limiting nasal congestion, at least 10% complain of persistent nasal problems to some degree after 6 months of therapy. Nasal symptoms can be treated in a variety of ways (inhaled nasal steroids, antihistamines, topical saline sprays and heated humidification); there is limited trial data of their effectiveness. The ideal and best treatment is heated humidification. Unfortunately heated humidification is expensive and many patients cannot afford this treatment. Nasal sesame oil (“Nozoil™”) has been shown to be superior to Normal Saline when used in patients with nasal symptoms associated with dry winter months in the northern hemisphere. The aim of the study was to assess the effect of “Nozoil™” on nasal symptoms and objective compliance.

METHODS:  Randomised, single-blinded, cross-over trial of subjects with obstructive sleep apnoea on CPAP with nasal symptoms, recruited from a tertiary referral Sleep Disorders Centre. Subjects were assessed with visual analogue scales of nasal symptoms, anterior rhinomanometry, and objective compliance at enrolment and at the end of each 2 week intervention period. Patients were randomised to normal saline (NS) or “Nozoil™” for 2 weeks then crossed over for a further 2 weeks.

RESULTS:  17 subjects have completed the protocol. Compliance significantly improved on “Nozoil™” from baseline (5.50±2.05 hours/day improving to 6.50±1.35, p=0.007) and also when compared to NS (6.50±1.35 vs. 5.97±1.55, p=0.002). There was no statistically significant difference with nasal resistance between the baseline and intervention measurements. Significant subjective improvements in nasal crustiness (p<0.05), nasal and sinus discomfort on CPAP (p<0.001) and CPAP tolerance (p<0.001) were seen with the use of “Nozoil™”. Subjects also reported “Nozoil™” was superior to NS in making it easier to breathe through the nose (p<0.001).

CONCLUSION:  The use of “Nozoil™” in subjects with nasal side effects with CPAP results in improvements in objective compliance with CPAP and subjective improvement in nasal symptoms.

CLINICAL IMPLICATIONS:  “Nozoil™” is a potential alternative treatment for patients with nasal symptoms on CPAP.

DISCLOSURE:  John Feenstra, None.

Chest. 2005;128(4_MeetingAbstracts):233S. doi:10.1378/chest.128.4_MeetingAbstracts.233S

PURPOSE:  CPAP is the established treatment of moderate/severe OSA. The parameters capable to influence the level of effective CPAP in these patients are yet unknown. Previous predictive equations for CPAP (hereafter called eCPAP) included body mass index (BMI), neck circumference (NC) and baseline apnea-hypopnea index (AHI. None of these equations included arousal index (AI) or desaturation index (DI).

METHODS:  Fifty consecutive patients (20 females and 30 males) with moderate/severe OSA, who underwent a split-night or a CPAP titration polysomnographic study in our Sleep Center, were retrospectively analyzed. We used multiple regression analysis to compute a predictive equation of the effective level of CPAP and we analyzed the correlation between eCPAP and the prescribed CPAP (pCPAP).

RESULTS:  The derived predictive equation for pCPAP was: pCPAP = 6.8 + 0.001AHI + 0.10BMI - 0.08NC + 0.06AI - 1.14DI (p<0.0001, R2=0.45, SD=2.0). The mean pCPAP was 10 (±2.6 SD); the mean eCPAP was 8 (±2.3 SD); mean difference was 2 cmH2O. The mean difference was slightly smaller in split-night vs. titration studies (2.0 vs. 2.6), in males vs. females (2.0 vs. 2.8), and in severe OSA vs. moderate OSA (2.0 vs. 3.0) cmH2O. The derived equation is distinct from previously published equations, which estimated eCPAP. There was a weak correlation between pCPAP and eCPAP [R2=0.48, p<0.0001]. This could be explained by the fact that our CPAP prescription protocol takes into account not only normalization of AHI, but also near-normalization of AI and DI.

CONCLUSION:  We determined an equation for pCPAP based on several clinical parameters. The correlation between eCPAP and the pCPAP was weak, warranting new studies to explore the lack of correlation and the role of additional predictive parameters.

CLINICAL IMPLICATIONS:  This is a pilot phase of a larger study for derivation and validation of the best predictive equation for effective CPAP in OSA. The predictive value of OSA severity parameters such as AHI, AI, DI, and body habitus characteristics such as NC and BMI will be evaluated extensively in the main study.

DISCLOSURE:  Octavian Ioachimescu, None.

Chest. 2005;128(4_MeetingAbstracts):233S. doi:10.1378/chest.128.4_MeetingAbstracts.233S-a

PURPOSE:  Patients with chronic fatigue syndrome (CFS), as defined by Centers of Disease Control criteria, often have a potentially treatable sleep disorder. However, even when obstructive sleep apnea (OSA) is identified in these patients, improvement with treatment is not predictable. We sought to determine whether any parameters of the diagnostic or titration sleep study were associated with improvement in symptoms of CFS after a subsequent trial of home CPAP.

METHODS:  We reviewed the clinical and polysomnographic (PSG) findings of 78 patients with CFS. Thirty-nine (50%) were found to have OSA and underwent a CPAP titration night. Thirty-seven pts subsequently agreed to a therapeutic CPAP trial lasting up to 6 months. They then rated their CFS symptoms as “improved” or “not-improved”.

RESULTS:  In the diagnostic PSG, patients with CFS who reported improvement to later CPAP had a higher mean arousal index 67.6 (70.1) vs. 26.1 (12.1) in those who did not improve (p = 0.037). The following table compares several PSG variables in patients who improved with the CPAP trial compared with those who did not. Each value represents the change between the diagnostic and CPAP titration nights (mean and standard deviation).

CONCLUSION:  Patients with CFS and OSA are more likely to improve with CPAP if they have higher arousal indices in the diagnostic PSG and show improved sleep efficiency during CPAP titration. Changes in REM latency and stage 1 and 2 sleep may also predict improvement.

CLINICAL IMPLICATIONS:  The above mentioned PSG variables may be clinically useful in predicting which patients with CFS and OSA are more likely to improve with CPAP use.

DISCLOSURE:  Marcel Baltzan, None.Diagnostic vs. TitrationImprovement with CPAPNo Improvement with CPAPp ValueChange in Sleep Efficiency (%)13.1 (27.8)−9.6 (14.2)0.010Change in Latency to REM-sleep (min)−40.8 (108)48.9 (75.8)0.023Change in Stage 1 Sleep (%)−4.8 (8.9)2.9 (12.1)0.050Change in Stage 2 Sleep (%)5.0 (10.3)−7.5 (18.2).0.023Change in Apnea-hypopnea index (per hour)−21.7 (50.7)3.3 (19.5)0.094

Chest. 2005;128(4_MeetingAbstracts):233S-b-234S. doi:10.1378/chest.128.4_MeetingAbstracts.233S-b

PURPOSE:  CPAP is the cornerstone treatment for OSAS, yet its compliance was unsatisfactory. Attempt is made to look at the factors associated with compliance.

METHODS:  A retrospective study evaluating CPAP compliance in a group of newly diagnosed OSAS Chinese patients in a regional hospital over a 6-month period (August 2003 - February 2004). Objective and self-reported compliance was obtained 6 months after commencing CPAP. Acceptable compliance was defined as CPAP usage for at least 4 hours/day in at least 70% of the night. Suboptimal treatment was defined as either refusal of CPAP treatment or unsatisfactory CPAP compliance. Newly diagnosed patients are invited to attend a specialty-nurse conducted educational session on OSAS before physician assessment.

RESULTS:  One hundred and six subjects were diagnosed to have OSAS. Only 58 patients (54.7%) accepted CPAP treatment. Fifty patients (86.2%) fulfilled the criteria of acceptable compliance (mean5.9±1.3 hours/day) and 8 had unsatisfactory compliance (mean 3.0±1.7 hours/day). Attendance of the education class (p=0.007) and number of side effects experienced by patients (p=0.007) were independent predictors of satisfactory compliance. Fifty-six (52.8%) either declined or failed to comply to CPAP satisfactorily. There were no significant differences in age, sex distribution, presenting symptoms, degree of sleepiness, level of CPAP pressure, and type of side effects experienced between the 2 groups. Univariate analysis suggested associations of optimal treatment with greater body weight (p<0.05) and body mass index (p< 0.01), higher respiratory disturbance index (p< 0.05), higher desaturation index (p<0.01), higher arousal index (p< 0.05), having hypertension (p< 0.01), attendance of an education session (p< 0.001). Using logistic regression, CPAP education was the only independent predictor of both good acceptance and compliance (p< 0.001).

CONCLUSION:  CPAP acceptance rate was fair (54.7%). A single educational session could improve CPAP acceptance and compliance in newly diagnosed OSAS patients.

CLINICAL IMPLICATIONS:  Since augmented CPAP education has not been shown to offer additional benefits (Hui DSC et al. Chest 2000), basic education appears a cost-effective intervention in improving acceptance and compliance rate.

DISCLOSURE:  Maggie Lit, None.

Chest. 2005;128(4_MeetingAbstracts):234S. doi:10.1378/chest.128.4_MeetingAbstracts.234S

PURPOSE:  To evaluate the effects of successful uvulopalatopharyngoplasty (UPPP) on cardiopulmonary exercise testing (CPET) in patients with obstructive sleep apnea syndrome (OSAS).

METHODS:  25 subjects with moderately severe or severe OSAS who desired UPPP were enrolled. All patients had an overnight sleep study and CPET before and 3 months after LAUP. Patients were divided into 2 groups based on the success (group I) or failure (group II) of UPPP to improve their sleep apnea.

RESULTS:  The results showed that successful UPPP in group I was followed by improvement in right ventricular ejection fraction, maximal work rate (WRmax), VO2max/kg, anaerobic threshold, oxygen pulse and a lower breathing reserve. CPET results were unchanged after UPPP in group II subjects.

CONCLUSION:  Patients with OSAS before UPPP had abnormal CPET as reflected by low VO2peak/kg, WRmax, anaerobic threshold and oxygen pulse. All of these variables improved after UPPP that successfully ameliorated OSAS.

CLINICAL IMPLICATIONS:  Patients with OSAS before UPPP had abnormal CPET. CPET improved after UPPP that successfully ameliorated OSAS.

DISCLOSURE:  Ching Lin, None.

Chest. 2005;128(4_MeetingAbstracts):234S. doi:10.1378/chest.128.4_MeetingAbstracts.234S-a

PURPOSE:  Oral appliance therapy (OAT) is an alternative therapy for obstructive sleep apnea (OSA). It is most often recommended for patients who have mild OSA, or who have moderate-severe OSA and are unwilling or unable to comply with continuous positive airway pressure. We sought to identify the subset of patients most likely to benefit from OAT.

METHODS:  Patients of a sleep disordered breathing dental clinic with nocturnal polysomnography date before OAT initiation and during OAT titration. The main outcome variable was success of OAT (post-treatment AHI<10/hr). Secondary outcome measures included average nocturnal oxygen saturation (SpO2) and subjective symptoms. Independent variables available for analysis included patient demographics (age, sex), body anthropomorphic measurements (body-mass index (BMI), neck circumference, canine classification, facial skeletal classification), sleep characteristics (apnea-hypopnea index, average nocturnal oxygen saturation), and intervention (type of oral appliance, posture change during PSG and overall). Comparisons of patients by treatment success were performed using Student’s t-tests and chi-squared tests.

RESULTS:  Twenty-nine patients were identified for analysis, with age 54.7±13.3years, 62.1% male, and BMI 30.1 kg/m2. Most patients (76%) had moderate to severe OSA (AHI>20/hr) at baseline. OAT resulted in total posture change of 6.5±3.1mm, with 66.8±32.7% reduction in AHI (p<0.001), 6.8±7.5% absolute increase in SpO2 (p<0.001), improvement of subjective symptoms of 86%, and overall success of 69.0%. In the bivariate analysis, patients with post-treatment success were no different by age, sex, anthropomorphic measurements, or intervention characteristics compared to patients with post-treatment failure, but had higher average baseline SpO2 (82.4% vs. 76.2%, p=0.061). SpO2 remained significantly different after therapy (89.1% vs. 82.1%, p<0.001).

CONCLUSION:  OAT improves AHI, SpO2, and subjective symptoms in most patients with OSA, regardless of severity. Baseline hypoxia may predict failure of OAT monotherapy.

CLINICAL IMPLICATIONS:  OAT may be appropriate for treatment of OSA patients without baseline hypoxemia. Further studies are needed to evaluate the role for OAT in adjuvant therapy with CPAP and to determine the degree of baseline oxygen saturation that will predict OAT success.

DISCLOSURE:  Vidya Krishnan, None.

Chest. 2005;128(4_MeetingAbstracts):234S. doi:10.1378/chest.128.4_MeetingAbstracts.234S-b

PURPOSE:  The purpose of this study is to evaluate the long-term effects of domiciliary bilevel noninvasive positive pressure ventilation (NPPV) on sleep apnea, cardiac function, sympathetic nervous activity and heart rate variability in stable congestive heart failure.

METHODS:  We examined 6 patients with stable congestive heart failure who completed 1 year of domiciliary NPPV with pulsed oxymeter, chest and abdominal wall motion sensor, nasal air flow sensor and electrocardiographic monitoring system (TEIJIN, Morpheus C) during sleep at night under a room air and NPPV before (Control; C) and after 1 month (1M), 4 month (4M) and 1 year (1Y) of NPPV. Urinary noradrenaline level at night and next morning mood index were also examined. Chest rentogenogram, electrocardiography, doppler echocardiography and serum noradrenaline level were measured befor and after 1M, 4M and 1Y of domiciliary NPPV.

RESULTS:  Apnea hypopnea index (/h) improved from 23 (C; Air) to 9 (C; NPPV), 9 (1M; NPPV), 10 (4M; NPPV) and 10 (1Y; NPPV). Centrl apnea index (/h) improved from 11 (C; Air) to 2 (C; NPPV), 2 (1M; NPPV), 3 (4M; NPPV) and 1 (1Y; NPPV). The left ventricular systolic dimension (mm) by echocardiography decreased from 50 (C) to 46 (1M), 43 (4M) and 43 (1Y). Percent fractional shortening (%) of the left ventricle increased from 21 (C) to 28 (1M), 29 (4M) and 32 (1Y), and the left ventricular ejection fraction (%) increased from 42 (C) to 51 (1M), 53 (4M) and 56 (1Y). Heart rate (bpm) decreased from 65 (C) to 59 (4M), and SDNN increased from 86 (C) to 98 (4M) and 108 (1Y). Serum noradrenaline level had decreased tendency in 1M and 1Y.

CONCLUSION:  The long-term domiciliary bilevel NPPV improved a sleep apnea, cardiac function, sympathetic nervous activity, heart rate and heart rate variability in patients with stable congestive heart failure.

CLINICAL IMPLICATIONS:  The long-term domiciliary bilevel NPPV might be a useful complementary therapy for stable congestive heart failure.

DISCLOSURE:  Hitoshi Koito, None.

Chest. 2005;128(4_MeetingAbstracts):234S-c-235S. doi:10.1378/chest.128.4_MeetingAbstracts.234S-c

PURPOSE:  Dyslipidemia has been reported to be common in subjects with obstructive sleep apnea (OSA), but this may be comorbid with obesity or visceral obesity which are highly prevalent in those with OSA. This prospective cohort study investigated the relationship of OSA to lipid profile in Chinese subjects.

METHODS:  Consecutive Chinese subjects of male sex, with no history of cardiovascular disease, diabetes mellitus, hyperlipidemia or significant chronic illness or medications, were recruited from our sleep laboratory. Their demographic and anthropometric data, fasting lipid profile (cholesterol, triglycerides, low density lipoprotein-cholesterol (LDL-cholesterol) & high density lipoprotein-cholesterol (HDL-cholesterol), apolipoproteins A1 & B (Apo A1 & B), and polysomnographic findings were collected. The relationships between apnea-hypoapnea index (AHI) and each lipid parameter were examined with multiple linear regression, adjusted for obesity (body mass index or waist circumference).

RESULTS:  98 subjects were recruited, aged between 21 and 65. OSA was defined as AHI≥5. 73 subjects had OSA. Significant linear relationships were present between AHI and waist circumference, body mass index (BMI), LDL-cholesterol, HDL-cholesterol, Apo B, LDL-cholesterol:HDL-cholesterol and Apo B:Apo A1 (all p<0.05). On multiple linear regression analysis, with lipid parameters as dependent variables, adjusted for BMI, AHI was associated with Apo B (p<0.05), total cholesterol:HDL-cholesterol (p< 0.01), LDL-cholesterol:HDL cholesterol (p< 0.05)and Apo B:Apo A1 (p<0.05).

CONCLUSION:  In this cohort of Chinese subjects, AHI was associated with apolipoprotein B, apolipoprotein and cholesterol fraction ratios, controlled for obesity.

CLINICAL IMPLICATIONS:  OSA may have an independent effect on adverse lipid profile, and thus confer independently to cardiovascular risks.

DISCLOSURE:  Jamie Lam, University grant monies This project was supported by the Hong Kong Research Grants Council, The University of Hong Kong, HKU7307/00M

Chest. 2005;128(4_MeetingAbstracts):235S. doi:10.1378/chest.128.4_MeetingAbstracts.235S

PURPOSE:  Currently, there are controversies about the relationship between OSA and subjective sleepiness. Recent study has shown the correlation between subjective sleep complaints and respiratory arousal. However, there is limited information on the relationship between subjective sleep perceptions and objective sleep parameters in different patient populations.

METHODS:  A retrospective study was performed in patients with obstructive sleep apnea. All patients completed post-test questionnaire after sleep study as part of our routine procedure. Any patients with significant neurological diseases, psychiatric disorder, central sleep apnea, severe periodic leg movements (PLMI>50) or incomplete records were excluded from the study.

RESULTS:  79 patients met the criteria for entry into analysis; 41 African American (B) and 38 Caucasian (W). The average age is 47.5±10.1 years and the mean apnea-hypopnea index (AHI) is 25.9±19.5 per hour. There was no difference between age, sex, BMI or AHI between two groups. The subjective feeling upon awakening (Question 15 (Q15); scale 1-6) correlated with the arousal index (r=0.27, P=0.019), AHI (r=0.3, P=0.008), and apnea-hypopnea related arousal (r=0.24, P=0.038). There is a tendency toward significant correlation between subjective sleep quality (Question 7 (Q7), scale 1-4) and arousal index (r=0.22, P=0.054) as well as between Q7 and AHI (r=0.22, P=0.056). The subgroup analysis revealed a significant correlation between Q15 and arousal index only in African American population (r=0.36, P=0.02 [B] versus r=0.17, P=NS [W]). However, Q15 correlated with AHI only with Caucasian population (r=0.20, P=NS [B] versus r=0.46 P<0.01 [W]).

CONCLUSION:  It is concluded that subjective perception from post-sleep questionnaire correlates significantly with severity of apnea and frequency of arousals especially respiratory arousals. The subjective perception correlates only with the frequency of arousals in African American population, while subjective perception of Caucasian population correlates directly with severity of apnea.

CLINICAL IMPLICATIONS:  It is speculated that other factors in addition to apnea may play a role in sleep disruption in African American population with sleep apnea. However, more studies are needed.

DISCLOSURE:  Cynthia Crowder, None.

Chest. 2005;128(4_MeetingAbstracts):235S. doi:10.1378/chest.128.4_MeetingAbstracts.235S-a

PURPOSE:  Obstructive sleep apnea (OSA) patients using CPAP (Continuous Positive Airway Pressure) are frequently prescribed BZRA(Benzodiazepine receptor agonist) hypnotics. However, no prior studies have evaluated the effect of BZRAs on the efficacy of CPAP. CPAP works as a pneumatic splint so upper airway muscle tone is much reduced. Therefore, further reduction in muscle tone by BZRAs should be minimal. For this reason, we hypothesize that Zolpidem (selective BZRA with greater hypnotic than muscle relaxant properties)should not cause a change in the level of required CPAP to maintain an open airway.

METHODS:  To test this hypothesis, we conducted a double blind placebo controlled cross-over study in patients with OSA currently being treated with CPAP. Patients were studied on three nights in the sleep laboratory over three consecutive weeks (one night per week). On night one, the pressure level required to prevent apnea, hypopnea, and snoring was determined (optimal pressure). On the second night and third nights, either Placebo or Zolpidem 10 mg was given and subjects slept on the CPAP level determined by first night (optimal pressure).

RESULTS:  For our initial four patients, there was no significant difference in Total Sleep Time (TST), REM sleep, AHI overall, or AHI NREM sleep (see table).

CONCLUSION:  Study of a limited number of OSA patients suggests Zolpidem 10 mg does not significantly increase the AHI in a patient treated with an appropriate level of CPAP. We plan to study at least 20 patients to confirm this preliminary result.

CLINICAL IMPLICATIONS:  If further study confirms our preliminary findings this would suggests Zolpidem can be used safely in OSA patients with insomnia who are on CPAP. This may improve tolerance of CPAP in these patients.

DISCLOSURE:  Prakash Patel, None.

Chest. 2005;128(4_MeetingAbstracts):236S. doi:10.1378/chest.128.4_MeetingAbstracts.236S

PURPOSE:  Patients with vocal cord dysfunction (VCD) have high medical utilization. This has been attributed to somatization, but may reflect a lack of understanding and recognition of the VCD disease process. The effect of laryngoscopic diagnosis of VCD on medical utilization has never been evaluated and results from this study will add insight into the benefit of laryngoscopy evaluation and treatment of VCD. Furthermore, the role of somatization in the pathogenesis of VCD may be better understood.

METHODS:  Subjects were obtained thru retrospective review of all laryngoscopies conducted in our clinic from January 2002 to March 2004. Patients with laryngoscopy confirmed VCD had their medical utilization evaluated. Inclusion required subjects to have evidence of medical utilization one year predating and one year postdating diagnosis and exclusion occurred if their diagnosis could not be confirmed by chart review. Medical utilization information for the preceding year and anteceding year were compiled from a computerized medical record. t-test analyses was utilized to compare differences between the group’s medical utilization before and after diagnosis of VCD. This study was approved by the Institutional Review Board.

RESULTS:  Forty three ambulatory patients with VCD with a mean age of 45 (range 21-81) yearsmet inclusion criteria. Total physician visits and primary care visits were found to reduce significantly after diagnosis of VCD. These patients were also found to have comparable frequency of hospitalizations, urgent care visits, and prescriptions.

CONCLUSION:  Total physician visits and primary care visits among ambulatory VCD patients are significantly reduced after diagnosis of VCD by laryngoscopic criteria.

CLINICAL IMPLICATIONS:  Aggressive diagnosis of ambulatory VCD patients has a significant impact on healthcare utilization.

DISCLOSURE:  Jeffrey Mikita, None.Health Care MeasureYear preceding VCD diagnosis n=43Year anteceding VCD diagnosis n=43pTotal Physician Visits7966030.049*Primary Care Visits2651370.0005*Urgent Care Visits77490.084Hospitalizations1250.068Total Prescriptions767767ns

Chest. 2005;128(4_MeetingAbstracts):236S. doi:10.1378/chest.128.6_suppl.582S

PURPOSE:  An elevated concentration of nitric oxide (NO) in alveolar ventilation indicates inflammatory stress within the lung. Trace-gas analysis using mass spectrometers (MS) have been used extensively within the atmospheric community with great success. We present here the first description of time-resolved NO measurement in breath using photoionization MS, providing new capabilities for the medical investigator, such as isotopic tracing.

METHODS:  For NO measurement, we use resonance enhanced multiphoton ionization (REMPI) coupled with a time-of-flight MS with a medium pressure laser ion source. A single male subject breathes NO-free air for several minutes, and then the exhaled breath is monitored for NO.

RESULTS:  The ability of REMPI to differentiate among three different isotopomers of NO is demonstrated, and then the concentration profile of NO in exhaled breath is measured. A similar time-dependence concentration is found as observed by previous techniques.

CONCLUSION:  This study presents MPLI-MS as a new technique available for the time-resolved measurement of NO in breath. The resulting system can be made portable and brought into the medical setting using newer-generation, broad-bandwidth lasers. When measuring NO via REMPI, we found a concentration profile in agreement with that of research groups using different techniques (chemiluminescence and LMRS). Sampling the breath from a person without respiratory ailments, we found a dead-space air NO concentration of 20 ppbV and an alveolar ventilation concentration of 5 ppbV. In contrast to the chemical-based technique chemiluminescence, MPLI-MS can also selectively measure isotopically-labeled NO, as demonstrated with REMPI of 14N16O, 15N16O and 14N18O. Further, MPLI-MS can be used to measure other biologically-significant molecules, such as the aldehydes. In forthcoming studies, we will explore the application of MPLI-MS for the measurement of other biologically-significant molecules.

CLINICAL IMPLICATIONS:  (1) ppbV mixing ratios of NO can be measured on a sub-second time scale, (2) other biologically significant gas molecules can be measured on a similar time scale and (3) since the technique operates optically as well as mass-resolved, isotopomers of NO are discernable, permitting the use of isotopic tracing.

DISCLOSURE:  Luke Short, None.

Chest. 2005;128(4_MeetingAbstracts):236S-b-237S. doi:10.1378/chest.128.4_MeetingAbstracts.236S-b

PURPOSE:  In bronchial asthma, airway wall remodeling may result in reduced airway distensibility. In this study, we assessed in asthmatic patients both the baseline airway caliber and distensibility by means of High Resolution Computed Tomography (HRCT).

METHODS:  We studied 7 patients (2 M, age range: 36-69 yrs) affected by chronic asthma (FEV1 range: 30-87 % of predicted; FEV1/VC range: 48-75 % of predicted) in stable clinical conditions and 6 healthy subjects (3 M, age range: 29-50 yrs), as a control group. In all subjects, HRCT scanning, obtained at suspended end-espiratory volume, was performed at rest and during ventilation with 6 and 12 cmH2O by nCPAP, both at baseline and after the inhalation of 200 mcg oxitropium bromide MDI.. External and lumen diameter (mm) of the right apical upper lobe bronchus were measured in all HRCT scans.

RESULTS:  Results (means±SD) are listed in the table.

CONCLUSION:  Our results showed that in asthmatic patients the airway distensibility, assessed by HRCT, could differ as compared to that of healthy controls.

CLINICAL IMPLICATIONS:  HRCT can provide useful information on airway distensibility.

DISCLOSURE:  Antonio Castagnaro, None.Asthmatics PatientsBaselineAfter OxitropiumAt rest6 cmH2O12 cmH2OAt rest6 cmH2O12 cmH2Oexternal Ø (mm)6.2±0.96.3±0.96.7±0.8*7.3±16.9±0.77.1±0.9lumen Ø (mm)3.3±0.73.5±0.63.8±0.6*4.4±0.63.8±0.44±0.4Healthy Controlsexternal Ø (mm)7.3±1.87.9±1.77.8±28±1.68±1.89±1.7lumen Ø (mm)4.0±1.64.8±1.6*4.7±1.7*5±1.55±1.4*6±1.6**

p< 0.05 vs at rest

Chest. 2005;128(4_MeetingAbstracts):237S. doi:10.1378/chest.128.4_MeetingAbstracts.237S

PURPOSE:  Nitric oxide in exhaled air (FENO) is a marker of airway inflammation in asthma. This study was undertaken to determine whether FENO increases as a result of stress.

METHODS:  This study was a prospective, unblinded study in an office setting. 20 adult asthmatics were recruited to participate. Subjects were initially put into a relaxed state using a progressive relaxation technique. They were then put into a stressful state by asking them to complete complicated mathematical problems.

RESULTS:  FENO was measured using standard techniques after relaxation and after stress. Pulse was monitored during the stressful intervention. FENO significantly increased after stress. Mean +/-Standard Deviation (SD) for baseline FENO was 2.9 +/- 2.1. After stress, mean +/- SD FENO rose to 3.1 +/- 2.1. This was significant by paired test. (p= 0.03).

CONCLUSION:  A stressful situation can cause an immediate increase in the inflammatory state of the airways in adult asthmatics, as measured by FENO.

CLINICAL IMPLICATIONS:  This study provides insight into the mechanism in which a psychological stress could lead to worsening asthma.

DISCLOSURE:  Jonathan Ilowite, None.

Chest. 2005;128(4_MeetingAbstracts):237S. doi:10.1378/chest.128.4_MeetingAbstracts.237S-a

PURPOSE:  Prolonged hormonal exposure has been linked to an increased severity of asthma among Caucasian women. Our aim is to determine if the same is true or are there differences in the severity of asthma among premenopausal(PREM) vs postmenopausal(PM)African American(AA)women.

METHODS:  We enrolled 37 women ages 18-82, who were admitted through the emergency department over a 2-year period with asthma exacerbation. In this retrospective chart review, asthma severity was defined by the National Heart Lung and Blood Institute guidelines. Menopause was defined as cessation of the menstrual cycle by natural or surgical means.Additionally, body mass index (BMI), age of onset of menarche and number of cigarette pack years (CPY) of smoking were recorded.

RESULTS:  Twenty (58.5%)of the women were PM, and 17 (41.5%)were PREM. The mean ages were 35+/-8.2 for PREM and 60+/-10 for PM women. There was no significant difference in population demographics except for CPY, that was statistically greater in PM women P=0.003. Multivariate analysis was used to control for BMI, CPY, number of pregnancies, highest educational level and onset of menarche. Eighty percent of PM and 55.8% of PREM women had a BMI >30, (40% of PM vs 29%of PREM had BMI’S > 40). P = 0.68 between the groups. Average onset of menarche in the PREM vs PM group was 11.2+/-2.8 and 13.4 +/-2.7, P = 0.9. Chi-Square test was used in the analysis of the asthma severity. Although there was a percentage trend to more severe asthma in the PM group, it was not statistically significant P = 0.189.

CONCLUSION:  Women in the PM group had shorter duration of hormonal exposure, however an increased severity of asthma. While not explained by population characteristics except CYP and BMI that were not statistically significant, nonetheless, severe obesity rather than hormonal changes may be the primary factor in asthma severity among PREM and PM AA women.

CLINICAL IMPLICATIONS:  Asthma severity in PREM vs PM AA women may need to be evaluated using different parameters. Further studies are required.

DISCLOSURE:  Reverly John, None.

Chest. 2005;128(4_MeetingAbstracts):237S. doi:10.1378/chest.128.4_MeetingAbstracts.237S-b

PURPOSE:  In this study, we aimed to analyze the effects of obesity to the severity of the disease, by investigating the correlation between body mass index (BMI) and characteristics of asthma in hospitalized asthma patients.

METHODS:  Characteristics of asthma related factors and BMI of patients analyzed retrospectively from the data obtained from the clinic files of 160 hospitalized patients (41male,119female, mean age 46.5±1.1years)who were followed in our department.Body mass index was calculated as body weight/height (kg/m2).Patients were divided and evaluated in three groups according to their BMI; Group1: BMI<22.5 thin, Group2: 22.5≤ BMI<30 normal or overweight,Group3: BMI≥30 obese.

RESULTS:  The mean BMI of the whole patients was 28.3±0.5, whilst the mean BMI of patients in Group 1 was 32.9±2.9,in Group 2 was 46.6 ± 1.6,and in Group 3 was 49.2 ± 1.5. The 20% of patients in Group 1, 47% of patients in Group2 and 33% of patients in Group3 were atopic The 33%of the asthmatic patients was also diagnosed to have allergic rhinites.The 8.4% of patients (n:13)had a history of childhood asthma (54% in Group1, 31% in Group2 and 15% in Group3).The percentage of patients with the history of childhood asthma was significantly higher in Group1 than in Group2 and Group 3.Although there was not any significant difference in the mean eosinophiles counts and mean serum ECP levels of patients, those values were lower in Group3 than in other groups.There was not any significant difference in mean outdoor and indoor allergen sensitivity scores of patients among groups. Mean medication score (number of controller drugs) of patients in Group1 was significantly lower than in Group2 and Group3.The lung function parameters of FEV1 and PEF were not significantly different among groups, but predicted value of FVC was significantly higher in Group1 than Group2 and Group3 .

CONCLUSION:  According these results we came to the conclusion that obesity was a severity factor in hospitalized asthmatic patients.

CLINICAL IMPLICATIONS:  Asthma outcomes was effected badly with increasing body weight in asthmatics.

DISCLOSURE:  Esra Uzaslan, None.

Chest. 2005;128(4_MeetingAbstracts):237S-c-238S. doi:10.1378/chest.128.4_MeetingAbstracts.237S-c

PURPOSE:  Chronic non allergenic Rhinosinusitis accounts for 1/3 of visits to physicians offices.In many of our asthmatics, cough is the presenting symptom. This study is to evaluate benefits of daily nasal steroids and HT1 blockers in decreasing severity of bronchial inflamation, improvement of disease control and quality of life.

METHODS:  Study is a retrospective observational based on Blue Shield Puerto Rico expenditures of all services and medications paid in 2004 for the population of this study and the control patients. The subject were 358 patients referred to center because of refractioness to management. Control population consisted of 12,070 asthmatics treated by the neumologists in the community. Inclussion criteria were: an age of 12-70 years, presence of Rhinosinusitis, cough as prominent symptons, severe airway obstruction shown by spirometry and low peak flow (PEF)readings, prior visits to emergency department and or hospital admissions in 2003.Upon entry patients received instructions in the use of PEF and logging, nasal steroids, inhaled bronchial medication, emergency albuterol inhalations.The use of daily nasal steroids was continous for 4 weeks.

RESULTS:  Asthma complex with Bronchial Obstruction decreased as evidenced by peak flow redings and controller medications and by dollars paid for them.The shift in cost occurs in favor use of nasal steroids and HT1 blockers .The emergency dept visits and admissions decreased to the lowest levels. In 2004 2 out of 176 ptswere admitted for 0.4% lower than in 2003that was 1 %.

CONCLUSION:  The study showed dramatical improvement in severity of airway obstructions and symptoms complex with 88% less hpspital admissions and a dramatic decrease in the use and cost of controller medications. Use of daily nasal steroids is of great benefit in the majority of patients.

CLINICAL IMPLICATIONS:  Daily nasal steroids and HT1 blockers should be part of the management of moderately severe and severe asthmatic. Study showed the benefit of this practice for patients and for the economy. This study may improved the asthma management.

DISCLOSURE:  Ramon Figueroa -Lebron, None.

Chest. 2005;128(4_MeetingAbstracts):238S. doi:10.1378/chest.128.4_MeetingAbstracts.238S

PURPOSE:  Little is known about the relationships between total IgE as a marker for Th2 phenotype, T cell production of interferon _ (IFN-_) and IL4 as markers of Th1 and Th2 phenotypes, respectively, and IL10 as a marker of immune regulation, in a population of racially diverse females categorized by history of asthma diagnosis.

METHODS:  We analyzed blood samples taken during pregnancy from the mothers of urban and suburban African American and Caucasian children in a geographically defined Detroit area birth cohort (WHEALS). Total IgE was measured using the Pharmacia CAP low range with a detection limit of 0.1 IU/ml. IFN-_, IL4 and IL10 production by PMA stimulated lymphocytes was detected by antibody staining and flow cytometry. Results are expressed as the percentage of CD4+ cells positive for these cytokines. Wilcoxon rank sum tests were used to compare mean IgE and mean IFN-_, IL4 and IL10 percentages by history of physician diagnosed asthma and race.

RESULTS:  Blood samples from 443 women were tested; 65% were African American and 21.0% had a history of asthma. Total IgE was higher in women with asthma (155.7 vs 71.2 IU/mL, p< .001) and higher in African American women vs Caucasian women with asthma (185.8 vs 114.7 IU/mL, p< .001). IFN-_ positive cells tended to be lower in women with an asthma history (8.0% vs 9.4%, p<0.065), and lower in African American vs Caucasian asthmatics (7.4% vs 9.2%, p<0.097). There were no differences in IL4 or IL10.

CONCLUSION:  Total IgE is higher in women with a history of asthma and African American women, while IFN-_ was lower, following the Th1-Th2 paradigm. NIAID.

CLINICAL IMPLICATIONS:  Total IgE is higher in women with a history of asthma and African American women, while IFN-_ was lower, following the Th1-Th2 paradigm. NIAID.

DISCLOSURE:  Christine Johnson, None.

Chest. 2005;128(4_MeetingAbstracts):238S. doi:10.1378/chest.128.4_MeetingAbstracts.238S-a

PURPOSE:  To identify demographic characteristics of patients with repeat Emergency Department (ED) attendance for asthma exacerbation.

METHODS:  Analysis of computer database records of all patients that were treated and discharged from the ED of a tertiary hospital over 6 months in year 2004 for asthma. Data analyzed included demographic characteristics such as age, sex, ethnicity and ED attendance in the past 40 days and past 24hrs for acute asthma.

RESULTS:  750 patients with Male: Female of 1:1 was seen at the ED for asthma exacerbation and 195 had previous attendances. Out of these 195 patients, 132 had past attendance within 40 days, 64 had past attendance within last 24 hrs and 1 had past attendance in the last 40 days and within last 24 hrs. The median age for our patients was 32 years (range 2 to 92 years). 42% of the patients were Chinese, 29% were Malays, 23% were Indians and 7% were of other ethnicity. Male patients had a significantly higher repeat ED attendance compared to female patients (34.3% vs 13.8%, p < 0.0001).There was also a significantly higher proportion of Malay patients with repeat attendance when compared to Chinese, Indians and other ethnicity (35.3% vs 23.3% vs 22.2% vs 16.4% respectively, p = 0.002).Patients of age 21 years and below were also found to have higher repeat attendance for asthma when compared to those above 21 years of age (39.3% vs 21.3%, p < 0.0001). Multivariate analysis showed that male sex (OR 3.03, p < 0.0001), Malay ethnicity (OR 2.30, p = 0.04) and age 21 years and below (OR 1.61, p = 0.015) were associated with increased risk of repeat ED attendance.

CONCLUSION:  Male sex, Malay ethnicity and young age of 21 years and below were associated with higher risk of repeat ED attendance in our asthmatic patients.

CLINICAL IMPLICATIONS:  Further studies should be conducted on this high risk group to identify factors which contribute to their frequent ED visits in order to optimise their asthma control.

DISCLOSURE:  Lee Lan Phoa, None.

Chest. 2005;128(4_MeetingAbstracts):238S. doi:10.1378/chest.128.4_MeetingAbstracts.238S-b

PURPOSE:  In this study we aimed to investigate the correlation between body mass index and characteristics of asthma in female asthmatic patients of our clinic.

METHODS:  Characteristics of asthma related factors and body mass index (BMI) analyzed from the data obtained out-patients files of 900 female patients, who were followed in our department between the years of 1992-2004.Patients were divided and evaluated in four groups according to their BMI; Group1: BMI<18.5 thin,Group2:18.5≤BMI<25 normal, Group3: 25≤BMI<30 overweight, Group4: BMI ≥30 obese.

RESULTS:  The number of patients in Group1 was 23, was 336 in Group 2, was 302 in Group3, and was 239 in Group4. The mean BMI of patients was 26.9±0.2. The mean age of patients was 37.4± 0.4 and the patients in Group4 was significantly older than patients in other groups. The 42.6% of patients were atopic and 50.9 % was also diagnosed to have allergic rhinites. The 53.8 % of patients in Group1, 72.9 % of patients in Group2, 63.5 % of patients in Group3, 58.2 % of patients in Group4 were atopic . The mean serum IgE levels of patients in Group4 was significantly lower than others. Although there was not any significant difference in the mean eosinophiles count of patients, those values were lower in Group4 than in other groups. The mean asthmatic years of patients in Group4 was significantly longer than others. The mean and predicted values of lung function parameters of Group4 were generally lower than other groups, especially the means FEV1 and FVC values was significantly lower in Group4 than Group1, Group2 and Group3. The mean medication score (number of controller drugs) of patients in Group4 was significantly higher than in patients of other groups.The hospitalization rate of patients in Group4 (19%) was significantly higher than patients in patients Group2 (9%) and Group3 (12) (p<0.05).

CONCLUSION:  In conclusion, obesity was a severity factor for asthmatic female patients.

CLINICAL IMPLICATIONS:  Asthma outcomes are effected badly due to obesity in females.

DISCLOSURE:  Esra Uzaslan, None.

Chest. 2005;128(4_MeetingAbstracts):238S-c-239S. doi:10.1378/chest.128.4_MeetingAbstracts.238S-c

PURPOSE:  There appear to be gender differences in the prevalence, morbidity and severity of asthma, with variations across the lifespan. Asthma is a chronic obstructive airway disease that occurrs more frequently in adult females. The objective of the survey was to determine whether respiratory therapy students (SRT) and registered respiratory therapists (RRT) who may deal with adult asthmatic patients are aware of the sex and gender differences that exist in this disease.

METHODS:  A survey was conducted with 175 subjects. Four different groups were surveyed: first-year, second-year, and third-year SRTs from the Michener Institute for Applied Health Sciences and RRTs from hospitals in Toronto.

RESULTS:  There was a 78% response rate. Out of all the respondents, 25.3% thought that asthma was the same in males and females, 24.7% thought that more males had asthma, 21.4% thought that more females had asthma, and 28.6% did not know. The second year SRTs and RRTs had the majority choosing males as having asthma more than females. The third year SRTs were the only group that identified women as having asthma more than males.

CONCLUSION:  Sex and gender differences of asthma in adulthood are still relatively new areas of research. SRTs and RRTs may not be aware of these differences, which may lead to misdiagnosis, and sub-optimal treatment and management plans for the female asthmatic population.

CLINICAL IMPLICATIONS:  More research in this area is needed. Updated school curricula should reflect emerging issues to provide the best treatment possible.

DISCLOSURE:  Wendy Lopez, None.

Chest. 2005;128(4_MeetingAbstracts):239S. doi:10.1378/chest.128.4_MeetingAbstracts.239S

PURPOSE:  Increased levels of fraction exhaled nitric oxide (FENO) have been found among individuals with atopic asthma and are believed to reflect on going airway inflammation. However, routine use of FENO in health care diagnosis and treatment is limited by the expense of the required equipment. Two offline methods are currently available for obtaining FENO namely, the American Thoracic Society (ATS) FENO 350cc/sec recommended method and the Dead Space Discard (DSD) FENO 50cc/sec kit method. However, there have not been published studies comparing the two techniques in the field. In the current study we sought to compare the FENO levels obtained by the ATS method and the DSD method and to investigate the utility of FENO levels in detecting inflammation is persons with diagnosed asthma.

METHODS:  Cross-sectional study. A convenient sample of 45 subjects ages 17 to 82 years, mean age 44.26 ± 16.71 years. There were 19 females and 26 males. Paired exhaled samples were collected from the subjects in triplicate using ATS and DSD techniques and analyzed offline using Sievers 280i Nitric Oxide Analyzer.

RESULTS:  Comparison of the two methods was performed using correlations, regression analysis and ANOVA. 33.3% had health care provider diagnosed asthma, 8.9% had other respiratory problems, the remainders were healthy individuals with no known respiratory conditions; 11.1% were current cigarette smokers. FENO levels obtained by DSD technique were consistently higher than those obtained by the ATS technique. The two techniques were highly correlated r= 0.691, p<0.000, 2df and r2 = 0.48.

CONCLUSION:  FENO levels obtained by the ATS and DSD technique are highly and positively correlated.

CLINICAL IMPLICATIONS:  The DSD technique is well suited for field studies when replicate samples are to be collected from many subjects. Furthermore, the smaller bags are more cost efficient and easier to transport than the high flow bags.

DISCLOSURE:  Jamson Lwebuga-Mukasa, None.

Chest. 2005;128(4_MeetingAbstracts):239S. doi:10.1378/chest.128.4_MeetingAbstracts.239S-a

PURPOSE:  Find out whether workplace exposures to coal mine dust contribute to the development of allergic diseases and if atopy in miners is more frequent than in general population. Atopy is an important risk factor for asthma. Latest epidemiological studies in Czech Republic estimate, that prevalence of allergic diseases in Czech population is 24 %, the prevalence of asthma 5 % and atopy 40-50 %.

METHODS:  In the cross-sectional study (2004/2005) we studied the frequency distribution of airway diseases(spirometry including non-specific bronchoprovocation test, if indicated, examination by physician), allergic disease in personal history (mucosal and cutaneous) and atopy (presence of specific IgE to common inhalation allergens in blood by Phadiatop) in 548 coal miners (mean age 49) and 315 subjects of control group (mean age 43). Controls where recruited from men, who have never been exposed to dust in their occupational environment. Subjects where divided into cohorts according to age and lengh of exposure; statistical analysis was by x-square testing using contingency tables.

RESULTS:  Atopy and allergic diseases after mean exposure to coal dust lasting 3 years, 14 years, and 29 years was 38 % and 22 %; 31 % and 26 %, and 17 % and 19 %, respectively. Atopy and allergic diseases in miners age 27-31 years, 32-40 years, and 54-65 years was 37 % and 25 %; 30 % and 23 %, and 22 % and 20 %, respectively. Controls ind the same age group had atopy and allergic diseases in 48 % and 51 %; 37 % and 40 %, and 22 % and 19 %, respectively. Statistical analysis has shown, no influence of either coal-mine dust or of smoking status on the prevalence of atopy, rhinitis and asthma. Prevalence of chronic bronchitis and COPD increased with age and exposure to coal-dust.

CONCLUSION:  Coal mining does not seem to represent a risk factor of atopy and respiratory allergic disorders.

CLINICAL IMPLICATIONS:  In occupational medical care atopy in miners should not represent contra-indication for mining occupation.

DISCLOSURE:  Zdenka Hajduková, None.

Chest. 2005;128(4_MeetingAbstracts):239S. doi:10.1378/chest.128.5.3156

PURPOSE:  We have shown previously that the allergic reaction does not change the beat frequency of nasal cilia (Europ. Respir. J., Vol. 22, Suppl. 45, 291s). Increasing allergen dose and length of exposure did not change this (CHEST, Vol. 124, Suppl. 4, 140s). It might be argued that significant components of the allergic reaction were lacking in our biopsy specimens.

METHODS:  We obtained surgical specimens during turbinate surgery. All patients (n = 17, 10M, 7F, age 35 ± 14) had allergic rhinitis (allergy testing and clinical history). From each specimen we obtained at least five biopsies with a bronchoscopy forceps. We processed these biopsies histologically and stained them with H.E. and Giemsa. The sections were 3 μ thick with a distance of 10 μ in between; we analyzed a total of 8 sections. We overlaid them with a grid (integration plate I, Zeiss) and counted hits over the different tissue structures. We also counted single cells (mast cells, eosinophils, and polymorphonuclear leukocytes attached to the vessel wall [marginating PMN]) and expressed them per total grid area.

RESULTS:  Tissue composition derived from percent hits over each structure was as follows: epithelium 20,65%, blood vessels 10,32%, connective tissue 55,59%, serous glands 10,34%, mucous glands 3,10%, mast cells 47/mm2, marginating PMN 210/mm2, eosinophils 13/mm2.

CONCLUSION:  We conclude that all tissue components of the allergic reaction were contained in even the smallest of our biopsy specimens. Similarly, isolated blood or tissue cells that are known to be involved in the allergic reaction were present in our specimens in sufficient numbers.

CLINICAL IMPLICATIONS:  We suggest that a full blown allergic response with mediator release and mucosecretion was possible in our specimens and must have taken place following allergen challenge. Equivalence of mediator release from specimens challenged in vivo and in vitro has been shown (Nakamura et al., J. Allergy Clin. Immunol. 2000;105:1146-52). Nevertheless ciliary beating was unchanged and thus appears to be remarkably resistant to effects of the allergic reaction.

DISCLOSURE:  Thorsten Stein, None.

Chest. 2005;128(4_MeetingAbstracts):239S-c-240S. doi:10.1378/chest.128.4_MeetingAbstracts.239S-c

PURPOSE:  About one-third of women with asthma (A) have an increase in asthma symptoms during in menstrual period. Patients affected by premenstrual asthma (PA) in comparison to asthmatic women without premenstrual asthma (WPA), generally have more sever symptoms and more frequently hospitalization. Hormonal fluctuations and changes during the menstrual cycle may be responsible for PA occurring. GSTT1, GSTM1 genes take part in detoxification and excretion of xenobiotics from organism, and also in metabolism of prostaglandins, leukotreine and sexual hormones. Allergy also is a major risk factor for asthma. To evaluate the role of GSTT1 and GSTM1 genotypes and allergy in susceptibility to PA, we conducted the given study.

METHODS:  We survey 74 asthmatic women, 9 (12.16%) with PA, average age 44.95±1.50 years and 65 (87.84%) WPA, average age 44.47±1.22 years. All subjects were interviewed using a special questionnaire, which allowed taking into account presence or absence of symptoms of asthma related to menstrual cycle and allergy. Allergy is also assessed by skin prick test. GSTT1 and GSTM1 genotypes were identified by multiplex polymerase chain reaction.

RESULTS:  We found that the frequency of GSTT1 functional allele in women with PA was 100% and in asthmatic women WPA was 68.96% (p=0.0001).The frequency of allergy in patients WPA was 83.07% and in women with PA was 44.45% (χ2 =4.37, P=0.027).

CONCLUSION:  We concluded that:1) The patients with PA have a significantly higher frequency of GSTT1 functional genotype as compared to those WPA.2) The frequency of allergy in patients WPA is significantly higher, then in cases with PA.

CLINICAL IMPLICATIONS:  The diagnosis of premenstrual asthma as one form of sever asthma in related to GSTM1 and GSTT1 genotypes in women.

DISCLOSURE:  Natalia Gorovenko, None.

Chest. 2005;128(4_MeetingAbstracts):240S. doi:10.1378/chest.128.4_MeetingAbstracts.240S

PURPOSE:  Provincial drug programs are increasingly listing pharmaceutical products with restrictions. This may be to ensure appropriate use of a drug or serve as a cost containment strategy to control the provincial formulary budget. To determine if physicians treat asthma patients who are beneficiaries of the provincial drug plan differently than patients who have private drug plan.

METHODS:  On-line market research was conducted using a structured questionnaire with 284 general practitioners (GPs) from across Canada. The sample was weighted by province. Physicians were provided scenario-based questions to determine their preferences for treating patients. They were presented with two scenarios for patients uncontrolled on moderate doses of inhaled corticosteroids (ICS), provincial plan beneficiary vs. private drug plan beneficiary. These asked whether they would increase the dose of ICS or add additional therapy.

RESULTS:  Physicians ranked asthma symptoms, treatment guidelines and insurance coverage (public versus private) as the three most important factors impacting drug therapy choice. Eighty percent of physicians (80%) reported that they ask patients about drug coverage (private vs. public) before making a prescribing decision. 37% of physicians reported that they would increase the dose of ICS for public versus 22% for privately insured patients uncontrolled on moderate doses of ICS. This trend remained consistent across the regions, however in Atlantic Canada there was no difference at 35%.For provincial drug plan patients, the majority reported adding a long acting beta agonist (LABA) via a separate inhaler vs. those with private drug plans where the physicians opted for a combination of ICS + LABA in one inhaler.

CONCLUSION:  Asthma treatment approaches differ for patients with public vs. private drug plans. Patients uncontrolled on ICS alone with public drug coverage, physicians continue to increase the dose of ICS, despite the fact that this approach is misaligned with current guideline recommendations.

CLINICAL IMPLICATIONS:  Patients with private drug coverage are treated more closely to national guidelines developed to improve outcomes. The market research used to prepare this document was performed by PSL Inc.,Toronto, Ontario, Canada.

DISCLOSURE:  Andrew Mc Ivor, None.

Chest. 2005;128(4_MeetingAbstracts):240S. doi:10.1378/chest.128.4_MeetingAbstracts.240S-a

PURPOSE:  To obtain current 2005 information to determine the unmet needs of Canadians with asthma.

METHODS:  Telephone survey of patients with physician diagnosed asthma was performed during March 2005 in Canada. The authors developed a study questionnaire and ethics approval was obtained. The telephone interview was performed by a prominent Canadian Market Research Firm. The sample was weighted to obtain a representative sample of adult patients with asthma in Canada with respect to age, gender and geographical location (10 Provinces and 1 Canadian Territory).

RESULTS:  997 patients with physician diagnosed asthma responded to the complete survey. Age ranges 18% (18-34 years old), 52% (35-54 years old), and 39% (55+ years old). 60% of the respondents were female. 10% of patients had been treated in the emergency room in the last year and 12% missed work or school; 97% of patients said that asthma effected their work or school performance over the previous year. 28% were experiencing daily daytime symptoms and 67% reported daytime symptoms at least weekly. 6% experienced nocturnal wakening from their asthma on a daily basis with 29% wakening at least once a week with asthma.Only 50% of the sample had objective tests of pulmonary function performed (peak flow/spirometry). 70% of patients stated that they had not had their inhaler technique checked. Only 15% had been referred for asthma education. Significant misconceptions of medications were identified including 39% of patients using short acting bronchodilators as their most often used “controller” medications and a further 11% were unsure as to which of their medications were “controller” medications.

CONCLUSION:  This March 2005, nationwide Canadian survey identifies significant asthma care gaps, patient and physician misconceptions around knowledge transfer of asthma guidelines to patient care. These have not reduced from previous surveys.

CLINICAL IMPLICATIONS:  Guideline groups should integrate methods of dissemination and implementation strategies to change practice, reduce care gaps and improve asthma outcomes.Funding via unrestricted grant from Novartis through the Asthma Society of Canada. Telephone survey conducted by Pollara Inc., Toronto, Canada.

DISCLOSURE:  Andrew Mc Ivor, None.

Chest. 2005;128(4_MeetingAbstracts):240S-b-241S. doi:10.1378/chest.128.4_MeetingAbstracts.240S-b

PURPOSE:  Asthma is a common chronic condition. Despite published guidelines for the diagnosis and treatment of asthma, the real medical practices for this condition vary among different care providers. The purpose of this study is to evaluate the current perceptions and practices of asthma among asthma specialists in Lebanon.

METHODS:  A cross sectional survey was conducted on asthma specialists in Lebanon in November 2004. The studied parameters included asthma diagnosis, follow-up, treatment, patient education, use of asthma guidelines, demographic characteristics of providers and their involvement in continuous medical education.

RESULTS:  Out of 125 practicing pulmonolgists and allergists registered in Lebanon, 70 filled out the questionnaire (56%). These were 20 females (29%) and 50 males (71%). The average age was 42.6+8.5 years. There were 55 pulmonolgists (78.5%), 5 allergists (7.1%) and 10 with double specialty in pulmonary and allergy (14.3%). 81.4% of responders performed spirometry on newly diagnosed subjects with asthma, while 74.3% monitored peak flows. The frequency of use of different treatment modalities for asthma was 94.1% for inhaled steroids, 95.4% for long acting beta-agonists (LABA), 60.6% for Leukotriene antagonists, 32.8% for theophylline, 25.8% for oral anti-histamines and 5.2% for cromolyn sodium. The inhaler technique is often monitored by 65.2% and sometimes by 24.6%, while peak flow diary is often reviewed by 29.9% and sometimes by 34.3%. About 87.9% of the responders indicated that they follow asthma practice guidelines, 84.6% of them reported using the GINA guidelines. Around 92.6% of asthma specialists in Lebanon attended continuous medical education (CME) program on asthma in the past year.

CONCLUSION:  This survey characterizes the pattern of asthma treatment by specialists in Lebanon. The overall performance of the responders meets the international guidelines.

CLINICAL IMPLICATIONS:  This study provides data for improving the performance of asthma treatment in Lebanon.

DISCLOSURE:  Hani Lababidi, None.

Chest. 2005;128(4_MeetingAbstracts):241S. doi:10.1378/chest.128.4_MeetingAbstracts.241S

PURPOSE:  The goal of this survey was to assess the knowledge, attitudes and beliefs of interns (students in internship year of medical faculty)about asthma and its management and to compare the correct response rate of interns with physicians in specialization training (PST) in teaching hospitals.

METHODS:  An asthma questionnaire including 33 items was applied to interns (n:209,40% female and 60 % male) and PST (n:202,49% female and 51% male)of Uludag Medical Faculty in July 2004.

RESULTS:  The 89% of interns believed that asthma can be cured, whilst 84 % of PST believed so(p>0.05).The 13% of interns thought that when acute asthma attacks resolved, the disease can be cured, whilst 15% of thought so (p>0.05).The 76% of interns believed that asthma runs in families whilst 53% of PST believed so (p<0.001).The 99% of interns and 97% of PST knew that animal feathers were one of the triggers of asthma ((p>0.05).The 76% of interns and 47% of PST knew that cockroach was one of the triggers of asthma (p<0.001). The 57% of interns and 46% of PST thought that nutritional conditions can trigger asthma (p<0.05).There was not any significant difference on correct response rate to questions on about asthma signs. The 97% of interns believed that asthmatics can be treated without hospitalization, whilst 96% of PST believed so (p>0.05).The 19% of interns and 18% of PST thought that asthma medication should be sold without prescription (p>0.05).The 9% of interns and 9% of PST believed that asthma medication was addictive (p>0.05). The 90% of interns and 85% of PST thought that inhaler (vaporizer) was a good treatment (p>0.05).The 64 % of interns and 61% of PST believed that asthma care was expensive (p>0.05).

CONCLUSION:  The interns knowledge about asthma was generally better than the PST, but by the time passing this compact knowledge may decrease as we observed in PST.

CLINICAL IMPLICATIONS:  Postgraduate education about asthma should be offered every physician whatever their specialization is, when planning to improve asthma outcomes in society.

DISCLOSURE:  Esra Uzaslan, None.

Chest. 2005;128(4_MeetingAbstracts):241S. doi:10.1378/chest.128.4_MeetingAbstracts.241S-a

PURPOSE:  To determine the knowledge, attitude and practice of hospital based physicians in the diagnosis, management and prevention of asthma.

METHODS:  The study was conducted in a tertiary government hospital involving physicians in practice of Family Medicine, Internal Medicine, Pediatrics and Pulmonary Medicine. A 31 point questionnaire was distributed consisting eight subject areas: assessment, asthma diagnosis, education, pathology, prevention, pharmacology, severity and therapy. The score for each of the subjects and the total score were calculated and grouped according to the level of training of the physicians and specialties. The mean score for each group of physicians were compared using the one way analysis of variance with level of significance set at p< 0.05 with 95% CI.

RESULTS:  A total of 144 (75.8%) physicians out of the 190 responded.The mean score is 45.8 +/- 13.4 (mean, SEM) performing best in asthma diagnosis and scored poorly in prevention of asthma triggers. The pulmonary fellows in training got the highest mean score (59.7 SEM 12.3). The physicians performed least in asthma assessment, education, prevention, severity classification and therapy. Significant differences were noted in physician understanding of the guidelines concerning:diagnosis(p= .001),pathology(p<.001), pharmacology (p < .001), severity (p < .001) and therapy(p< .001). Across different specialties,pulmonary specialists got the highest mean score (61.7 SEM 11.6).Significant differences in understanding of the guidelines were observed in asthma diagnosis (p < .001), assessment (p < .026), pathology (p < .001), pharmacology (p < .001), prevention (p <.001) and therapy (p < .001).

CONCLUSION:  The results of the study showed that there is a need for further improvement in the knowledge and understanding of the NHLBI Global Initiative for Asthma among physicians at the VMMC.Subject areas that should be emphasized in asthma guidelines dissemination are proper assessment, asthma education, prevention of asthma triggers, proper severity classification and choice of appropriate therapy.

CLINICAL IMPLICATIONS:  Proper diagnosis and management of asthma will reduce its fatal consequences. This can be achieved by ensuring physicians’ understanding of existing guidelines through continuing medical education.

DISCLOSURE:  Ogee Mer Panlaqui, None.

Chest. 2005;128(4_MeetingAbstracts):242S. doi:10.1378/chest.128.4_MeetingAbstracts.242S

PURPOSE:  The ATS has developed criteria suggesting that a significant post-bronchodilator FEV1 response is 200 ml and 12% improvement. To our knowledge, the ATS criteria never been validated versus the clinical diagnosis of asthma.

METHODS:  All spirometry tests done from Sept 1999 to Sept 2004 were analyzed for meeting the ATS criteria for FEV1 improvement There were a total of 1862 tests meeting the ATS FEV1 criteria with a total of 644 individual non-duplicate records. A total of 311 individual patient records were analyzed for staff respirologists.

RESULTS:  311 patients were found who met ATS FEV1 criteria and whose complete physician records were available. There were 170 men and 141 women with a median age of 62.8 years. Of the 311 patients meeting a 12% FEV1 change, there were 170 (54.7%) diagnosed by the staff respirologist with asthma. Of the 208 patients meeting a 15% FEV1 improvement, there were 120 (57.7%) diagnosed with asthma. Of the 98 patients meeting a 20% FEV1 improvement, there were 62 (63.3%) patients diagnosed by the staff respirologist with asthma. For the diagnosis of asthma versus not asthma, there was a statistically significant difference in the post-bronchodilator FEV1 % improvement with p=0.02 (CI 0.256-3.02). Of the 170 patients with asthma (for 12% FEV1 response), there was a mean improvement in FEV1 of 19.4% (SD 6.87), while the 140 not asthma patients had a mean improvement in FEV1 of 17.8% (SD 5.53).

CONCLUSION:  While the ATS FEV1 criteria are a help in asthma diagnosis, relying on spirometric criteria alone is inadequate in asthma diagnosis. Only 170 patients (54.7%) meeting ATS bronchodilator improvement criteria were felt to clinically have asthma.

CLINICAL IMPLICATIONS:  The diagnosis of asthma requires a clinical history and physical examination. Spirometry changes are helpful but the level of bronchodilator significance remains unclear.

DISCLOSURE:  John Gjevre, None.

Chest. 2005;128(4_MeetingAbstracts):242S. doi:10.1378/chest.128.4_MeetingAbstracts.242S-a

PURPOSE:  Current guideline criteria for mild asthma are based on symptomatology or rescue use which are quite broad, suggesting that they may not define a distinct group of patients. Furthermore, the results of a recent study suggested that patients with mild persistent asthma may not require regular maintenance treatment with an inhaled corticosteroid (ICS).1.

METHODS:  This analysis evaluated subjects (n=85) previously receiving short-acting beta2-agonists alone from two completed 12-wk trials in which subjects received placebo. Subjects were initially stratified by baseline PEF ≥80% or <80% predicted and further stratified by symptoms and/or albuterol use on ≤2 days/wk, 3-6 days/wk or 7 days/wk.

RESULTS:  For subjects with PEF ≥80% and symptoms/albuterol use on ≤2 days/wk, the majority of weeks (78%) were spent in the intermittent or mild categories. However, for subjects with PEF ≥80% and symptoms/albuterol use on 3-6 days/wk, subjects who could be guideline-classified as having mild persistent asthma, approximately 54% of weeks were spent in the moderate or severe categories. In addition, for subjects with PEF ≥80% and daily symptoms or albuterol use (i.e., the type of subject often recruited into mild asthma studies1), 77% of weeks were spent in the moderate category. Furthermore, when only those pts with PEF <80% and symptoms/albuterol use on ≤2 days/wk were considered, approximately 67% of weeks were spent in the moderate or severe categories.

CONCLUSION:  This analysis clearly demonstrates that asthma severity cannot be determined in many patients by discrete, point-in-time assessments of lung function, albuterol use or symptoms. More importantly, these observations suggest that the current classification system for persistent asthma needs to be re-evaluated as many patients who meet current guideline criteria for mild persistent asthma would appear to be more appropriately classified as having moderate or severe disease.

CLINICAL IMPLICATIONS:  Using current guidelines to define mild asthma may underestimate the true severity of the underlying disease. In light of recent publications, this underestimation may lead to inadequate therapy for patients with mild asthma. 1. Boushey, et al. NEJM 2005;352:1519-28.

DISCLOSURE:  Paul Dorinsky, Shareholder I am a GSK shareholder; Employee I am a GSK employee

Chest. 2005;128(4_MeetingAbstracts):242S. doi:10.1378/chest.128.4_MeetingAbstracts.242S-b

PURPOSE:  This study investigates the relationship between responses to a lung health questionnaire and measured pulmonary function using spirometry.

METHODS:  Community-based, cross-sectional study design using a convenient sample of adults. A total of 567 adults, ages from 18 to 86 years, mean age of 45 ± 15.48; 36.5% males and 63.5% females; 24.3% African American, 53.8% Caucasian, 14.6% Latino/Hispanic, and 5.5% of other race/ethnicity. Lung function was measured by spirometry; an 18-item questionnaire was administered to adults attending health fairs in Western New York State over a period of two years (2003-2005).

RESULTS:  Asthma prevalence was 19.6%. Persons who reported three or four symptoms, namely: wheeze, night cough, wheezing with exercise, and long-lasting colds, in the preceding 12 months had a lower percent predicted value for the forced expiratory volume in the first second (FEV1) (F=5.92, p=.015 and p=.001, respectively) than persons who did not report any symptoms of asthma. Persons who had health care utilization for asthma in the preceding 12 months had lower percent predicted FEV1 values (<75%) than persons who had not (p=.000, OR=3.62, CI=2.18-6.02). The same relationship was seen for mid-expiratory flow rate (MEFR 25/75) (p=.000, OR=2.62, CI=1.66-4.15). As the frequency of self-reported health care utilization increased, abnormal FEV1 measurements increased (B=-1.250, p=.001), and the ratio of FEV1 to the forced vital capacity (FEV1/FVC) decreased by -.131 standard deviations, S.E.=.001, p=.017.

CONCLUSION:  These results indicate that self-reported symptoms of asthma in thelung health questionnaire are associated with decreased pulmonary function and increased health care utilization.

CLINICAL IMPLICATIONS:  The results demonstrate that self-reported symptoms may be used as a cost-effective method for actual pulmonary function where spirometry is unavailable.

DISCLOSURE:  Jamson Lwebuga-Mukasa, None.

Chest. 2005;128(4_MeetingAbstracts):242S-c-243S. doi:10.1378/chest.128.6_suppl.575S-a

PURPOSE:  Current guidelines advocate stepping-down inhaled corticosteroid (ICS) therapy at 3-monthly intervals once asthma control has been achieved. Despite this, there are no data describing how widespread the practice of reducing ICS therapy is, especially in secondary care.

METHODS:  We assessed patients with asthma being followed up in a secondary care respiratory clinic for a minimum period of 6 months. Patients who were actively receiving or had received either oral or parenteral corticosteroids, or immunosuppressive therapy within a 12-month period were excluded. Patients were also required to be exacerbation-free during this period. A retrospective study was performed over the preceding 12 months in order to evaluate whether ICS therapy had been reduced or not following a prolonged period of stability.

RESULTS:  60 consecutive patients with asthma were assessed in clinic. 12 patients with mean age of 56 years and forced expiratory volume in 1 second of 1.97L (73% predicted) completed the study. The mean beclomethasone dipropionate (BDP) equivalent ICS daily dose was 1267μg and patients had either moderate (n = 6) or severe (n = 6) asthma. Only two patients had step-down in ICS therapy. One patient had a 33% reduction in ICS dose from an initial daily dose of BDP 1500μg, having had stable asthma for 11 months. The other patient had a 50% reduction in ICS dose from an initial daily dose of fluticasone propionate 1000μg, having had stable asthma for 8 months. The remaining 10 patients continued on the same dose of ICS despite having had stable asthma during the preceding 12 months. There were no significant differences in any outcomes according to whether patients had ICS therapy reduced or not.

CONCLUSION:  Our preliminary data have shown that stepping-down ICS therapy in patients with stable asthma is being poorly implemented.

CLINICAL IMPLICATIONS:  If this is reflective of practices throughout the United Kingdom, many patients with stable asthma may be exposed to unnecessary high doses of ICS.

DISCLOSURE:  Daniel Lee, None.

Chest. 2005;128(4_MeetingAbstracts):243S. doi:10.1378/chest.128.4_MeetingAbstracts.243S

PURPOSE:  Medical literature and government (Federal & State) reports that Hispanics suffer greater morbidity and mortality from asthma than the general population. This study compares the efficacy between a goal oriented management with the current NAEPP guidelines in this population since there is not a Spanish version of them and are inaccesible to patients.

METHODS:  A retrospective observational study based on expenditures paid by Blue Shield Puerto Rico for the years 2003-04 for services provided for the treatment of asthma. The services compared were office visits, ED admissions, ICU admissions, medications,readmissions and all diagnostic & therapeutic procedures per patient/year.Population was divided in two groups:A- 24,320 patients treated by 108 pneumologists with presumed knowledge of NAEPP guidelines in private offices.B- 1,094 patients treated by a team of a physician, therapist, nurse, and assistant. The management followed faithfully the Asthma Patient Bill of Rights (APBOR)Spanish version. Each person received a copy of the document.Patients were of low middle and middle class and Spanish was their principal language. On February Blue Shield provided the expenses paid for the previous year in U.S. dollars.

RESULTS:  Data showed huge differences between groups. The goal oriented had lowest expenses when compared to the standard therapy group saving $3 millions. No deaths in the goal oriented group and many in the standard group. Deaths occurred more at home or in route to hospital than in the ICU admissions. Readmissions were 20% within 15 days after discharge in the standard therapy group.There were no readmissions in the goal oriented group.

CONCLUSION:  Results were positive beyond expectations. No mortality and less morbidity in the goal oriented treatment group with great savings in resources. Current NAEPP guidelines are ignored by physicians creating inadequate prescriptions patterns and no patient education and support.

CLINICAL IMPLICATIONS:  A goal oriented management based on Spanish language guidelines (APBOR) generate commitment in patients, relatives, physicians with an unexpected positive outcome in Hispanics asthmatics.

DISCLOSURE:  Ramon Figueroa-Lebron, None.

Chest. 2005;128(4_MeetingAbstracts):243S. doi:10.1378/chest.128.4_MeetingAbstracts.243S-a

PURPOSE:  Asthma in older adults is under-diagnosed, under-treated, and the role of immunoglobulin E (IgE) in asthma is under-appreciated in this population . Therapy with omalizumab (OMA), an anti-IgE antibody, is indicated in patients with moderate to severe IgE-mediated asthma whose remain symptomatic despite inhaled corticosteroids. We conducted a pooled analysis of all double-blind placebo-controlled trials to evaluate the effect of OMA on asthma symptom score and rescue beta-agonist use in patients 50 years and older.

METHODS:  Data were combined from 5 randomized double blind placebo-controlled (PBO) trials of patients with moderate to severe IgE-mediated asthma; 4 were of 28 weeks and 1 was 32 weeks in duration. From the pooled study population comprised of 2236 patients, 601 were ≥ 50 years of age (296 OMA, 305 PBO). The change from baseline in mean total asthma symptom score [range 0 (symptom free) to 9], and in mean beta-agonist rescue puffs was assessed using an analysis of covariance. Least-squares mean treatment differences were calculated and 95% confidence intervals were constructed.

RESULTS:  The mean age of the older subgroup was 58 years; 61% were female; median IgE level was 132 IU/dl; mean percent predicted FEV1 64.6% ± 17.0%; baseline mean total asthma symptom score was 3.35 (OMA) and 3.40 (PBO), and baseline mean daily rescue beta-agonist use was 4.48 puffs (OMA) and 4.37 puffs (PBO). In this subpopulation, least-squares mean difference (OMA-PBO) for change from baseline in mean asthma symptom score was -0.26 (95% CI -0.51, -0.01; p=0.0411) and least-squares mean difference for change from baseline in rescue beta-agonist puffs was -0.47 (95% CI -0.92, -0.02; p=0.0414). The tolerability profile of OMA in the ≥ 50 year age subgroup was generally similar to that of the overall study population.

CONCLUSION:  Treatment with omalizumab significantly improved asthma symptoms and reduced beta-agonist use in older patients with moderate to severe persistent IgE-mediated asthma.

CLINICAL IMPLICATIONS:  IgE-mediated asthma is important to recognize and manage in older patients.

DISCLOSURE:  Robert Maykut, Employee I am an employee of Novartis Pharmaceuticals Corporation.

Chest. 2005;128(4_MeetingAbstracts):243S. doi:10.1378/chest.128.4_MeetingAbstracts.243S-b

PURPOSE:  To report on the continued experience with the use of omalizumab in patients with obstructive lung disease who may also have a comorbid asthmatic component mediated by IgE antibody.

METHODS:  All patients were drawn from the original pool of 250 patients in a pulmonary practice who had asthma or chronic bronchitis and qualifying levels of IgE (>30 IU/ml). Seventeen patients have been studied. Eleven completed 12 months of therapy (4 completed 4 to 9 months of therapy). Age range was 48 to 82 years. Nine were females. Fifteen have heavy primary or secondary cigarette exposure. Sixteen had positive skin tests to relevant indoor allergens. Baseline FEV1 was below 60% predicted in 11 patients. IgE ranged from 32 to 496 IU/ml. End points were reduction in number of acute exacerbations requiring hospitalizations or unscheduled office visits, reduction in inhaler use and improvement in dyspnea or cough indices. A 12 month baseline period was compared was compared with treatment intervals after the first month of omalizumab therapy.

RESULTS:  Comparing the year before therapy to the treatment period, the average monthly exacerbation rate decreased from 0.20 to 0.11. Comparing the month before therapy with the final treatment month, the average daily number of inhalations of asthma inhalers decreased from 13.5 to 7.4. The average daily Fletcher dyspnea score decreased from 1.35 to 0.53. The average daily cough severity scale decreased from 1.12 to 0.59. Of the six patients that were prednisone dependent at baseline the average daily prednisone requirement decreased from 37 to 10 mg.

CONCLUSION:  Continued experience with the use of omalizumab in patients with severe chronic obstructive lund disease confirms the initial impression of effectiveness. The role of IgE in these patients may be significant in disease severity. This pilot study suggests that further controlled studies in this group of patients would be warranted.

CLINICAL IMPLICATIONS:  A patient population with chronic obstructive lung disease should be screened for the use of omalizumab therapy. Skin test reactivity to indoor allergens was common.

DISCLOSURE:  Clifford Risk, None.

Chest. 2005;128(4_MeetingAbstracts):244S. doi:10.1378/chest.128.4_MeetingAbstracts.244S

PURPOSE:  Asthma continues to be a major health concern internationally despite improvements in treatment and the introduction of international asthma guidelines. Asthma education and action plans are essential to enhancing asthma knowledge, adherance, quality of life, and control of asthma and these form the basis for all treatment strategies recommended. There are over 90 Internet websites that provide asthma education. These sites did not provide interactive asthma management and the majority did not even meet acceptable educational standards. This study aimed to assess the impact of providing asthma management by a Certified Asthma Educator (CAE) to patients with asthma via the Internet.

METHODS:  The Virtual Asthma Clinic (VAC) was created to allow a CAE to communicate with patients, and assist patients with asthma management. Patients initially had spirometry testing, an asthma education session, and completed Asthma Quality of Life Questionnaire (AQLQ), symptoms questionnaire and SF-36. The site provided access to their personalized action plan, and asthma information. Data was compared between those who actively participated in the program and those who dropped-out.

RESULTS:  A total of 16 physicians referred 63 patients to the clinic. The active participants have taken part for a mean of 107.4 days (ongoing), while the dropouts participated for a mean of 140.6 days. The dropouts were younger (p<0.01) and both groups were predominantly female (60.5% active participants, 75.0% dropouts, NS). There were no differences in history of smoking. Participants had a mean of 41.4 hits to the website, compared to 14.8 for the dropouts (p<0.01). Participants were more likely to email the nurse (p<0.01), enter peak flow data (p<0.01), complete the weekly survey (p<0.05), the AQLQ (p<0.01), the SF-36 (p<0.01).

CONCLUSION:  Active participants in the VAC were older and while they were enrolled for fewer days, participated more actively.

CLINICAL IMPLICATIONS:  It is feasible to provide asthma management to patients online. Through this study we are able to identify a specific demographic of older patients who appear to participate more readily in the program than young adults.

DISCLOSURE:  Irvin Mayers, Grant monies (from sources other than industry) Capital Health Regional Telehealth, Alberta Health & Wellness; and The Alberta Strategy to Help Manage Asthma; Grant monies (from industry related sources) AstraZeneca Canada Inc.

Chest. 2005;128(4_MeetingAbstracts):244S. doi:10.1378/chest.128.4_MeetingAbstracts.244S-a

PURPOSE:  To determine the effects of additional nursing care in the treatment of asthma and COPD patients at a pulmonary outpatient clinic.

METHODS:  In a randomized, double blind clinical trial, 191 patients were allocated to an additional care (ACG) or control group (CG). Patients were masked for the trial objectives. Patients in the ACG group received an extra education program on individual basis provided by a pulmonary nurse. Between initial and final assessments was a six months interval.

RESULTS:  97 patients were randomized to the additional care group and 94 to the control group of which 157 finished the trial. Small albeit significant differences were found for the outcomes knowledge and exacerbation rate in favour of the additional care group. No differences were found for self-management scores, inhalation technique, health-related quality of life and satisfaction with provided care.

CONCLUSION:  for the outcomes knowledge and exacerbation rate patients in the additional care group had significant better results. No differences were found for the outcomes self-management scores, inhalation technique, health-related quality of life and satisfaction with provided care.

CLINICAL IMPLICATIONS:  additional care by a pulmonary nurse is easy to implement, provides patient tailored care, is easy accessible and might reduce the workload of the pulmonary physician. Since we found that some aspects were effective we conclude that it is worthwhile to consider providing additional nursing care to asthma and COPD patients in a pulmonary outpatient clinic.

DISCLOSURE:  Geert Rootmensen, None.

Primary outcomes: knowledge, self management, inhalation technique and exacerbation frequency incidences. Differerences between additional care (ACG) and control group (CG)

ACG (n=80)median#CG (n=77) median#p-valueknowledge*initial55 (33-73)55 (41-73)final64 (38-77)59 (45-70)change score5 (-5-14)0 (-5-9)0,02inhalation technique**initial78 (68-83)70 (63-80)final83 (68-90)72 (63-83)change score0 (-5-10)0 (-8-12)0,84self managementinitial36 (25-56)36 (25-48)final38 (25-63)38 (25-53)change score3 (-12-19)6 (-10-13)0,85exacerbation frequency?incidence rate1,463,650,40 (0,24-0,67)= exacerbation*?11%24%0,68 (0,49-0,94)

Chest. 2005;128(4_MeetingAbstracts):244S. doi:10.1378/chest.128.3.1891

PURPOSE:  To assess the utility of inhaled corticosteroids for the early management of acute exacerbations of asthma in the emergency room.

METHODS:  This randomized, double-blind, placebo-controlled study was conducted to evaluate the efficacy of high dose inhaled fluticasone with frequent beta-2-agonist therapy in patients of acute moderate exacerbations of asthma. Eighty patients between 15 and 45 years of age with acute moderate exacerbations of asthma were put on aerosolized 500 μg of fluticasone at half hourly intervals for three doses with metered dose inhaler and zero stat ‘V’ spacer. All patients received humidified oxygen and nebulized salbutamol (0.15 mg/kg in 3 ml saline) prior to fluticasone administration. The control group received placebo instead of inhaled fluticasone. Patients who had received corticosteroids in the preceding 72 h were excluded from the study. If there was an inadequate response or no response to treatment at the end of 2 hour, oxygen and salbutamol therapy were continued and given one dose of intravenous hydrocortisone and was started on an aminophylline infusion.

RESULTS:  Both fluticasone and control group showed a significant improvement in respiratory status at the end of 2 h. However, patients in the fluticasone group showed greater improvement in PEFR (P < 0.05) and significantly lower proportion of patients required oxygen improvement in PEFR (P < 0.01). The length of stay was significantly shorter in the fluticasone group than in the placebo group (P < 0.01).

CONCLUSION:  Aerosolized fluticasone therapy with MDI and spacer together with salbutamol in the treatment of acute exacerbations of asthma helped in early recovery and decreased hospital stay.

CLINICAL IMPLICATIONS:  Inhaled fluticasone may be given with MDI and spacer in the treatment of acute exacerbations of asthma.

DISCLOSURE:  Sudhir Agarwal, None.

Chest. 2005;128(4_MeetingAbstracts):245S. doi:10.1378/chest.128.4_MeetingAbstracts.245S

PURPOSE:  Zileuton Provided Significant Improvement in Pulmonary Function Compared to Placebo in Moderate and Severe Asthmatics.

METHODS:  This was a randomized, placebo-controlled, double-blind, parallel, multicenter study of the safety and efficacy of zileuton in patients with asthma. Asthma patients on no chronic asthma treatment other than inhaled beta-agonists were randomized to one of three treatment groups: zileuton, 600 mg QID, zileuton, 400 mg QID, or placebo for six months. Efficacy assessments included forced expiratory volume (FEV1) and peak expiratory flow rate (PEFR).In an exploratory secondary analysis, 231 asthma patients randomized to treatment were stratified by baseline (BL) percent predicted normal FEV1 into two subgroups: moderate (>60%-<80%; n=133) and severe (≤60%; n=98). Pulmonary function measurements were obtained on asthmatics on 600 mg zileuton and compared to placebo.

RESULTS:  Moderate and severe patients on zileuton experienced significant improvement in FEV1 and A.M. PEFR. This difference was demonstrated as early as 30 minutes post-dose and was sustained throughout the duration of the study. Improvements in P.M. PEFR were also demonstrated.

CONCLUSION:  Zileuton, 600 mg QID, provided rapid and sustained improvement in pulmonary function in moderate and severe asthmatic patients versus placebo.

CLINICAL IMPLICATIONS:  Zileuton, a 5-lipoyxgenase inhibitor approved for chronic asthma, may improve pulmonary function via its mechanism of action in moderate and severe asthmatics.

DISCLOSURE:  William Berger, None.Severity GroupDifference From Placebo in Mean Change From BL to Post-Dose in FEV1 (L)Difference From Placebo in Mean Change From BL in A.M. PEFR (L/Min)Month 3Month 630 Mins60 Mins120 Mins30 Mins60 Mins120 MinsDays 2-22Days 163-190Moderate0.19*0.26**0.16♦μ0.110.120.18♦μ17.76**11.47Severe0.35*0.30*0.28♦μ0.27♦μ0.33*0.32♦μ15.93*30.24***





p≤0.100; Mins=Minutes

Chest. 2005;128(4_MeetingAbstracts):245S. doi:10.1378/chest.128.6_suppl.594S

PURPOSE:  Zileuton Provided Clinically Relevant Reductions in the Need for Rescue Medication and Oral Corticosteroids Compared to Placebo in Moderate and Severe Asthmatics.

METHODS:  This was a previously published, randomized, placebo-controlled, double-blind, parallel, multi-center six-month study of the safety and efficacy of zileuton (400 or 600 mg QID) in 373 patients with asthma on no chronic asthma treatment other than beta-agonists (J Allergy Clin Immunol 1996; 98(5):859-71). Assessments included beta-agonist use, acute asthma exacerbations requiring alternative treatment or oral corticosteroids, and daily and nocturnal symptoms, as well as mean FEV1 and other pulmonary function tests.In an exploratory secondary analysis of patients in the high dose zileuton 600 mg QID group, patients were stratified by baseline (BL) percent predicted FEV1 into two subgroups of asthma severity: moderate (>60%-<80%) and severe (≤60%).

RESULTS:  Moderate and severe zileuton patients reported reduced daily number of occasions of beta-agonist use. Fewer zileuton patients experienced asthma exacerbations requiring alternative treatment and oral corticosteroid treatment. Improvements in daily and nocturnal symptoms were also reported. These differences were sustained throughout the six-month study.

CONCLUSION:  In severe asthmatic patients, Zileuton, 600 mg QID, provided significant improvement versus placebo in markers of asthma control including reductions in daily number of occasions of beta-agonist use, asthma exacerbations.

CLINICAL IMPLICATIONS:  Zileuton, a 5-lipoyxgenase inhibitor approved for the treatment of chronic asthma, may reduce the need for beta-agonists and oral corticosteroids and improve other markers of asthma control, especially in severe asthmatics.

DISCLOSURE:  Mark Liu, None.Severity GroupMean Change From BL to Days 163-190 in Beta-Agonist Use (Number of Occasions/Day)Patients With Exacerbations Requiring Alternative Treatment (%)Patients Requiring Oral Corticosteroids (%)ZileutonPlaceboZileutonPlaceboZileutonPlaceboModerate (n=133)-0.70-0.4013.6%+26.5%9.1%17.7%Severe (n=98)-0.85**+0.167.8%*23.4%5.9%**25.5%

Chest. 2005;128(4_MeetingAbstracts):245S. doi:10.1378/chest.128.4_MeetingAbstracts.245S-b

PURPOSE:  The aim of this study to evaluate the of post-treatment effects of Leukotriene Receptor Antagonists (LTRA) in persistent asthmatic patients who have been treated with inhaler steroid and LTRA, by investigating clinical and laboratory parameters before addition of LTRA, end of treatment with LTRA and at least three months after ending of LTRA treatment.

METHODS:  We retrospectively investigated clinical data of 19 asthmatic patients (16 females, 3 males, mean age 33.3±2.5 years) before LTRA treatment,last day of LTRA treatment and at least three months after ending of LTRA treatment and compared symptom score, medication score (number of controller drugs for asthma), total dose of inhaler steroid and lung function tests of patients for each visits.

RESULTS:  We found decreases in symptom score (p<0.01), medication score (p>0.05), total dose of inhaler steroid (p>0.05),and increases lung function tests (p>0.05) at the end of the treatment.When we evaluated same parameters at least three months after the ending of LTRA treament, we observed continuation of increases in FEV1 and PEF values (p>0.05) comparing to beginning and ending of treatment and also a significant decrease in total dose of inhaler steroid comparing to beginning of treatment (p<0.05).

CONCLUSION:  We come to the conclusion that in persistent asthmatic who use LTRA in addition to inhaler steroids,the improvement in lung function tests, symptom scores and medication scores are protected and the total dose of inhaler steroids needed for control of asthma is decreased,even 3 months after the ending of treatment.

CLINICAL IMPLICATIONS:  The post-treatment effects of LTRA continues three months after the discontinuation of the treatment in asthmatics.

DISCLOSURE:  Esra Uzaslan, None.BaselinePost-treatment3 months laterSymptom score1.3±0.80.5±0.60.9±0.8Medication score1.4±0.91.2±0.71.3±0.2Inhaled steroid dose (mcg)875±583695±391445±216FEV1 (L)2.62±0.92.66±0.92.75±0.8PEF (L/sec)5.68±1.76.27±1.86.77±1.8

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