Chest. 2009;136(2):327-328. doi:10.1378/chest.09-0601

At the 2008 Annual Meeting of the American College of Chest Physicians, I was asked to debate the usefulness of endobronchial ultrasound (EBUS) with fine-needle aspiration (FNA) compared to standard blind transbronchial needle aspiration (TBNA) for evaluating mediastinal adenopathy. I was given the pro EBUS-FNA position. I thought I was awarded the easier assignment. My opponent had the problematic task of defending a technology with a spotty track record at best. I felt that I mounted a vigorous assault on TBNA based on clinical data when it was available, and clinical logic when it was not. At the end of the debate, like all who are passionate in what they believe, I clearly thought that the weight of the evidence heavily favored EBUS. The moderator asked for the audience to settle the score via a show of hands. With > 150 people in attendance, only three hands arose on behalf of EBUS-FNA. After crawling back to my hotel to digest this stunning defeat, I again reviewed the literature on this topic and tried to determine whether I was truly wrong or had failed to adequately articulate my position. Perhaps in writing this editorial I can better convey the case for EBUS.

Chest. 2009;136(2):329-330. doi:10.1378/chest.09-0808

It is now well established that COPD is a chronic inflammatory condition with significant extrapulmonary manifestations.1 In patients with mild-to-moderate COPD, the leading cause of morbidity and mortality is cardiovascular disease. In the Lung Health Study,2 which examined nearly 6,000 smokers whose FEV1 was between 55% and 90% predicted, cardiovascular diseases were the leading cause of hospitalization, accounting for nearly 50% of all hospital admissions, and the second leading cause of mortality, accounting for a quarter of all deaths. Subsequent studies3 have confirmed that, on average, patients with COPD have two to three times the risk of hospitalization for cardiovascular conditions (including ischemic heart disease, stroke, and heart failure) compared to those patients without COPD. However, in more severe stages of disease (Global Initiative for Chronic Obstructive Lung Disease [GOLD] stages 3 and 4), the clinical relevance of cardiovascular disease is less certain. The conventional wisdom is that in these groups of patients “lung failure” is the predominant driver of morbidity and mortality, and that other “comorbidities,” including cardiovascular disease, play less important roles. This notion is supported by large-scale COPD studies such as that by Celli et al,4 which reported that 61% of patients with predominantly GOLD 3 and 4 stage disease died from respiratory failure; whereas, only 14% died from myocardial ischemia.4 In a more recent study, the Towards a Revolution in COPD Health (or TORCH) investigators5 demonstrated that 35% of predominantly GOLD 3 and 4 patients died from respiratory failure; whereas only 10% died of a clear cut cardiovascular event such as myocardial ischemia, heart failure, or stroke. Although the Towards a Revolution in COPD Health study5 and other studies2,4,6 went to extreme measures to ensure the accuracy of the reporting of the underlying causes of death, there were nevertheless some important limitations. In most cases, investigators relied on death certificates or medical records of events that led to the patient's demise for attributing causality. However, even with detailed documentation, assigning a cause of mortality based on these sources can be problematic and fraught with significant misclassification errors.7 Autopsies, on the other hand, are less susceptible to this type of error and are a more accurate means of attributing causality. However, previous autopsy studies8 of patients dying with COPD have produced heterogeneous results owing largely to selection bias of cases included in each of the series. This is not surprising given that only a very select (and biased) sample of cases go on to autopsies.8

Chest. 2009;136(2):330-333. doi:10.1378/chest.09-0848

Idiopathic pulmonary fibrosis (IPF) is an irreversible, fatal lung disease. Although the etiology of IPF is unknown, it is currently believed to occur as a result of repeated insults to the lungs over a period of years in individuals with occult, genetically determined, predisposing factors. Symptoms leading to diagnosis typically manifest in patients > 50 years old. Following diagnosis of IPF by surgical lung biopsy, the median survival is 2.8 years.1 While lung transplantation may improve survival for some patients, this option is appropriate for only a minority of patients with this debilitating disease.

Chest. 2009;136(2):333-335. doi:10.1378/chest.09-0785

The article by Velayati and colleagues1 in this issue of CHEST (see page 420) describes cases of extensively drug-resistant (XDR) tuberculosis (TB) in Iran. The authors describe a pattern of resistance that they term “total drug resistance” (or TDR) to signal resistance of Mycobacterium tuberculosis isolates to essentially all antibiotics known to have activity against mycobacteria. Their report highlights several issues that need to be urgently addressed if progress is to be made in containing and reversing the spread of severely multidrug-resistant (MDR)-TB.

Chest. 2009;136(2):335-338. doi:10.1378/chest.09-0637

In this issue of CHEST (see page 426), Levin et al1 describe their experience with an infection control program aimed at technicians employing portable radiology equipment in the ICU setting. These investigators showed that an intervention aimed at improving infection control measures using an alcohol hand rub and changing gloves before and after each contact with the patient or radiology equipment significantly reduced colonization of the radiology equipment with Gram-negative bacteria (reduction 39 to 0%; p < 0.001). Additionally, these authors demonstrated that Acinetobacter baumannii colonization of portable radiology equipment, originating from a patient, occurred during the observation period. Of equal clinical importance was the finding that the infection control program deteriorated significantly during a third observation period conducted 5 months after completion of the intervention period. This deterioration was related to a decrease in compliance with the measures contained within the infection control program. This study highlights the importance of monitoring practice improvement changes following the intervention phase where the involvement and compliance of the participants is generally at its highest level. The high level of compliance during the intervention phase is usually due to the knowledge that individuals' compliance with the intervention and clinical outcomes are being prospectively monitored.

Second Opinion

Chest. 2009;136(2):339. doi:10.1378/chest.136.2.339
Topics: stress , health care
Chest. 2009;136(2):339. doi:10.1378/chest.136.2.339


Chest. 2009;136(2):340-346. doi:10.1378/chest.08-2768

Background:  Endobronchial ultrasound (EBUS)-guided transbronchial needle aspiration (TBNA) of mediastinal lymph nodes has been found to be more accurate than standard TBNA in the setting of malignancy. In patients with suspected sarcoidosis, the smaller ultrasound needle may yield inadequate material to make a histologic diagnosis of granulomatous inflammation. The aim of this study was to compare the diagnostic yield of EBUS-guided TBNA to TBNA performed with a standard 19-gauge needle in patients with mediastinal adenopathy and a clinical suspicion of sarcoidosis.

Methods:  A randomized controlled trial was performed in a university medical center, enrolling 50 patients (of 61 screened, 2 declined, and 9 did not meet entry criteria) with hilar and/or mediastinal adenopathy and a clinical suspicion of sarcoidosis. Twenty-four patients were randomized to undergo EBUS-guided TBNA and 26 to undergo TBNA using a standard 19-gauge needle.

Results:  The primary outcome measure of diagnostic yield was 53.8% vs 83.3% in favor of the EBUS-guided TBNA group, an absolute increase of 29.5% (p < 0.05; 95% confidence interval [CI], 8.6 to 55.4%). After blinded research pathology review, diagnostic yield was 73.1% vs 95.8%, in favor of the EBUS-guided TBNA group, an absolute increase of 22.7% (p = 0.05; 95% CI, 1.9 to 42.2%). Sensitivity and specificity were 60.9% and 100%, respectively, in the standard TBNA group, and 83.3% and 100%, respectively, in the EBUS-guided TBNA group (absolute increase in sensitivity, 22.5%; p = 0.085; 95% CI, 3.2 to 44.9%).

Conclusions:  The diagnostic yield of EBUS-guided TBNA is superior to TBNA using a standard 19-gauge needle for sampling of mediastinal lymph nodes in patients with a clinical suspicion of sarcoidosis.

Trial registration:  ClinicalTrials.gov Identifier: NCT00373555

Chest. 2009;136(2):347-354. doi:10.1378/chest.08-2924

Background:  Anticholinergic premedication is commonly used during flexible bronchoscopy, although the benefits are unproven and potential risks exist.

Methods:  We studied 1,000 patients undergoing diagnostic flexible bronchoscopy to investigate the efficacy and safety of atropine and glycopyrrolate. Patients received atropine (0.01 mg/kg; n = 339), glycopyrrolate (0.005 mg/kg; n = 336), or placebo (2 mL of normal saline solution; n = 325) IM before bronchoscopy in a randomized, double-blind fashion. Bronchoscopist- and patient-reported secretions, cough and patient discomfort, oxygen desaturation, procedure time, and procedure-related adverse events were compared among the groups.

Results:  After adjusting for covariates, glycopyrrolate (p = 0.02), but not atropine (p = 0.064), was associated with reduced bronchoscopist-reported airway secretions. Neither drug was independently associated with patient-reported airway secretions or with bronchoscopist- or patient-reported cough or discomfort. Neither drug was independently associated with oxygen desaturation. Atropine was associated with a longer procedure time (p = 0.042). Rise in heart rate and BP was significantly greater with anticholinergics, particularly atropine, compared with placebo.

Conclusions:  Anticholinergic premedication may reduce airway secretions during flexible bronchoscopy but is not associated with any significant reduction in cough, patient discomfort, oxygen desaturation, or procedure time and is associated with greater hemodynamic fluctuations. Routine anticholinergic premedication may be unnecessary or even harmful during flexible bronchoscopy.

Chest. 2009;136(2):355-360. doi:10.1378/chest.08-2389

Background:  Prolonged pulmonary air leaks are a significant source of frustration for patients and physicians. When conventional therapy fails, an alternative to prolonged chest tube drainage or surgery is needed. Bronchoscopic blockage of a bronchus can be performed with the hope of accelerating closure of the air leak by reducing the flow of air through the leak. To our knowledge, this article presents the largest series of patients with prolonged air leaks treated with an endobronchial valve.

Methods:  With Internal Review Board approval, endobronchial valves were compassionately placed using flexible bronchoscopy in patients with prolonged air leaks at 17 international sites.

Results:  Between December 2002 and January 2007, 40 patients (15 women; mean age ± SD, 60 ± 14 years) were treated with one to nine endobronchial valves per patient. The air leaks had recurrent spontaneous pneumothorax (n = 21), postoperative (n = 7), iatrogenic (n = 6), first-time spontaneous pneumothorax (n = 4), bronchoscopic lung volume reduction (n = 1), and trauma (n = 1) etiologies. Nineteen patients (47.5%) had a complete resolution of the air leak, 18 (45%) had a reduction, 2 had no change, and 1 had no reported outcome. The mean time from valve insertion to chest tube removal was 21 days (median, 7.5 days; interquartile range [IQR], 3 to 29 days) and from valve procedure to hospital discharge was 19 ± 28 days (median, 11 days; IQR, 4 to 27 days).

Conclusions:  Use of endobronchial valves is an effective, nonsurgical, minimally invasive intervention for patients with prolonged pulmonary air leaks.

Chest. 2009;136(2):361-368. doi:10.1378/chest.08-2448

Study objectives:  To analyze and compare radiologic lung expansion after talc pleurodesis performed either by videothoracoscopy or chest tube and correlate it with clinical outcome. Secondary end points evaluated were as follows: clinical efficacy; quality of life; safety; and survival.

Methods:  Prospective randomized study that included 60 patients (45 women, 15 men; mean age, 55.2 years) with recurrent malignant pleural effusion between January 2005 and January 2008. They were randomized into the following two groups: video-assisted thoracic surgery (VATS) talc poudrage; and talc slurry (TS) administered through a chest tube. Lung expansion was evaluated through chest CT scans obtained 0, 1, 3 and 6 months after pleurodesis. Complications, drainage time, hospital stay, and quality of life (Medical Outcomes Study 36-item short form and World Health Organization quality-of-life questionnaires) were also analyzed.

Results:  There were no significant differences in preprocedure clinical and pathologic variables between groups. The immediate total (ie, > 90%) lung expansion was observed in 27 patients (45%) and was more frequent in the VATS group (60% vs 30%, respectively; p = 0.027). During follow-up, 71% of the patients showed unaltered or improved lung expansion and 9 patients (15%) needed new pleural procedures (VATS group, 5 recurrences; TS group, 4 recurrences; p = 0.999). No differences were found between groups regarding quality of life, complications, drainage time, hospital stay, and survival. Immediate lung expansion did not correlate with radiologic recurrence, clinical recurrence, or complications (p = 0.60, 0.15, and 0.20, respectively).

Conclusion:  Immediate partial lung expansion was a frequent finding and was more frequent after TS. Nonetheless, no correlation between immediate lung expansion and clinical outcome was found in this study.

Trial registration:  ClinicalTrials.gov Identifier: NTC00789087

Chest. 2009;136(2):369-375. doi:10.1378/chest.08-2237

Background:  Photodynamic therapy (PDT) is considered a useful and minimally invasive modality for treating centrally located early lung cancer. To date, there has been limited information on the long-term outcome of patients treated with PDT, especially those who are medically operable.

Methods:  Beginning in 1994, patients with roentgenographically occult bronchogenic squamous cell carcinoma (ROSCC) who met our criteria underwent PDT at Tohoku University Hospital and were followed up through 2006. Our criteria were as follows: (1) ROSCC without distant metastasis; (2) medically operable by means of lobectomy or further resection; (3) longitudinal tumor length of ≤ 10 mm; and (4) superficial bronchoscopic tumor findings.

Results:  A total of 48 patients with ROSCC underwent PDT. The complete response (CR) rate was 94% (45 of 48 of patients). Nine patients (20%) had local recurrence after CR. A total of 11 deaths was observed, with 6 resulting from multiple primary lung cancer and only 1 from the original ROSCC. The 5-year and 10-year overall survival rates for all 48 patients were 81% and 71%, respectively. The Cox proportional hazard model showed that only metachronous multiple primary lung cancer was an independent poor prognostic factor.

Conclusions:  PDT is thought to be a first-line modality for patients who have ROSCC with a tumor length of ≤ 10 mm, even if the tumor is medically operable. Most local recurrence can be cured by active therapy such as surgery, radiotherapy, or PDT. Multiple primary lung cancer subsequent to PDT is an important issue from the viewpoint of survival.

Original Research: COPD

Chest. 2009;136(2):376-380. doi:10.1378/chest.08-2918

Background:  Mortality from COPD is increasing worldwide, but detailed causes of death are rarely assessed, particularly in low-income countries.

Methods:  In a retrospective study, we reviewed the autopsy reports and medical records of deceased patients admitted to the hospital for severe exacerbation of COPD, from January 2005 to December 2007, at the Institute for Pulmonary Diseases of Vojvodina, Serbia.

Results:  Forty-three patients with a hospital admission diagnosis of COPD exacerbation underwent autopsy; all had died within 24 h of admission to the hospital. Twenty-three patients (54%) had a long COPD history (> 10 years), and 19 patients (44%) had more than one hospitalization in the last year of life. The median age at death was 70 years (interquartile range, 65 to 75 years), and male sex was predominant (n = 31; 72%). The main (primary) causes of death were reported as cardiac failure (n = 16; 37.2%), pneumonia (n = 12; 27.9%), and pulmonary thromboembolism (PTE) (n = 9; 20.9%). Respiratory failure due to a progression of COPD was the primary cause of death in six patients (14%). Most patients had more then one comorbid disease (n = 33; 77%), and the most frequent comorbid disease was chronic heart failure (n = 25; 58%).

Conclusions:  Autopsy results suggest that common contributing causes of early death in patients hospitalized with severe COPD exacerbation are concomitant complications, as follows: cardiac failure, pneumonia, and PTE. Quality improvement interventions should focus on recognizing and treating these conditions at the time of hospital admission.

Chest. 2009;136(2):381-386. doi:10.1378/chest.09-0421

Background:  FEV1 is used for the classification of disease severity and is a good predictor of COPD mortality. However, it is a poor predictor of clinical symptoms, exercise tolerance, and response to bronchodilators in COPD. Progressive reduction in inspiratory capacity (IC) during exercise reflects dynamic hyperinflation and is a good predictor of decreased exercise ability as well as increased exertional dyspnea. In animal models of COPD, N-acetylcysteine (NAC), an antioxidant/mucous modifier, has been shown to modify small airways, which mainly causes lung hyperinflation.

Objective:  Our goal was to examine the effect of 1,200 mg/d of NAC on lung hyperinflation at rest and after exercise in patients with moderate-to-severe COPD.

Methods:  This was a randomized, double-blind, cross-over study that included 24 eligible patients > 40 years of age with a diagnosis of COPD, a FEV1 < 70% of predicted, FEV1/FVC ratio < 0.70, and a functional residual capacity > 120% of predicted normal. Patients were randomized to placebo treatment or NAC treatment twice daily for 6 weeks. This was followed by a 2-week washout period, and then patients were crossed over to alternate therapy for an additional 6 weeks. Evaluation was performed after each 6 weeks of each treatment.

Results:  IC and FVC were higher especially after exercise after NAC treatment compared with placebo treatment. In addition, the relationship of residual volume to total lung capacity was reduced in a similar pattern. Furthermore, endurance time was longer after NAC treatment compared with placebo treatment.

Conclusions:  NAC treatment of patients with stable, moderate-to-severe COPD has a beneficial effect on physical performance, probably due to a reduction in air trapping.

Trial registration:  Clinicaltrials.gov Identifier: NCT00476736

Chest. 2009;136(2):387-395. doi:10.1378/chest.09-0165

Background:  Current guidelines on pulmonary rehabilitation (PR) recommend upper extremity exercise training (UEET) in patients with COPD. However, the literature still questions the effectiveness of systematic UEET in this population. We studied the effects of 15 sessions of unsupported UEET on functional exercise capacity, the ability to perform activities of daily living (ADL), and symptoms perceived during activities involving arms in patients with COPD.

Methods:  We conducted a randomized trial that consisted of 3 weeks of inpatient PR, comparing the short-term effects of unsupported UEET plus PR (intervention group) to those of PR alone (control group). A change in the 6-min ring test (6MRT) was the primary outcome; the ADL field test (four shuttle stations), the dyspnea score as assessed by the Medical Research Council scale, the London Chest Activity of Daily Living scale (LCADL), and the distance walked in 6 min served as secondary outcomes of the study. At the 6-month follow-up, we repeated the 6MRT and the LCADL.

Results:  Fifty patients with COPD were randomly assigned to the two groups and completed the study. At the end of the study period, patients in the intervention group improved in the 6MRT and ADL field test compared with those patients in the control group (p = 0.018 and p = 0.010, respectively) with reduced perception of fatigue (p ≤ 0.006). At the 6-month follow-up, 6MRT (p = 0.001) and LCADL (p = 0.039) scores were still significantly better in the intervention group compared with the control group.

Conclusions:  Our trial corroborates the effectiveness of unsupported UEET in specifically improving functional exercise capacity of patients with COPD. Moreover, it also provides evidence that this training modality may ameliorate and maintain the patients' autonomy over and above standard PR.

Trial registration:  ClinicalTrials.gov Identifier: NCT00825032

Chest. 2009;136(2):396-404. doi:10.1378/chest.08-2858

Background:  CT scan measures of emphysema and airway disease have been correlated with lung function in cohorts of subjects with a range of COPD severity. The contribution of CT scan-assessed airway disease to objective measures of lung function and respiratory symptoms such as dyspnea in severe emphysema is less clear.

Methods:  Using data from 338 subjects in the National Emphysema Treatment Trial (NETT) Genetics Ancillary Study, densitometric measures of emphysema using a threshold of −950 Hounsfield units (%LAA-950) and airway wall phenotypes of the wall thickness (WT) and the square root of wall area (SRWA) of a 10-mm luminal perimeter airway were calculated for each subject. Linear regression analysis was performed for outcome variables FEV1 and percent predicted value of FEV1 with CT scan measures of emphysema and airway disease.

Results:  In univariate analysis, there were significant negative correlations between %LAA-950 and both the WT (r = −0.28, p = 0.0001) and SRWA (r = −0.19, p = 0.0008). Airway wall thickness was weakly but significantly correlated with postbronchodilator FEV1% predicted (R = −0.12, p = 0.02). Multivariate analysis showed significant associations between either WT or SRWA (β = −5.2, p = 0.009; β = −2.6, p = 0.008, respectively) and %LAA-950 (β = −10.6, p = 0.03) with the postbronchodilator FEV1% predicted. Male subjects exhibited significantly thicker airway wall phenotypes (p = 0.007 for WT and p = 0.0006 for SRWA).

Conclusions:  Airway disease and emphysema detected by CT scanning are inversely related in patients with severe COPD. Airway wall phenotypes were influenced by gender and associated with lung function in subjects with severe emphysema.

Chest. 2009;136(2):405-411. doi:10.1378/chest.08-2304

Background:  Asthma and COPD are characterized by substantial racial disparities in morbidity and mortality. We hypothesized that because African-American patients with these conditions experience greater mortality and morbidity than their white counterparts, they would use more health-care resources when no difference in health insurance exists.

Methods:  A retrospective, population-based cohort study was conducted using Maryland Medicaid Managed Care patient encounter data. We compared health services utilization and cost outcomes in both African-American and white patients with COPD, asthma, or coexisting COPD and asthma.

Results:  The study population consisted of 9,131 patients with COPD, asthma, or both conditions. Of the total population, 52% were African American (n = 4,723), and 44% were white (n = 4,021); all other races were combined into the “unknown race” category to account for the remaining 4% (n = 387). After controlling for age, gender, cohort allocation, and comorbidities, we found that African-American adults with COPD, asthma, or coexisting COPD and asthma actually used fewer medical services and accounted for lower medical costs than white adults.

Conclusions:  Lower health services utilization and medical costs among African-American patients with COPD and asthma may provide a possible explanation for the racial disparities in outcomes of patients with these conditions.

Chest. 2009;136(2):412-419. doi:10.1378/chest.08-2739

Background:  Although pulmonary hypertension commonly complicates COPD, the functional consequences of increased pulmonary artery pressures in patients with this condition remain poorly defined.

Methods:  We conducted a cross-sectional analysis of a cohort of 362 patients with severe COPD who were evaluated for lung transplantation. Patients with pulmonary hemodynamics measured by cardiac catheterization and available 6-min walk test results were included. The association of mean pulmonary artery pressure (mPAP) with pulmonary function, echocardiographic variables, and 6-min walk distance was assessed.

Results:  The prevalence of pulmonary hypertension (mPAP, > 25 mm Hg; pulmonary artery occlusion pressure [PAOP], < 16 mm Hg) was 23% (95% confidence interval, 19 to 27%). In bivariate analysis, higher mPAP was associated with lower FVC and FEV1, higher Pco2 and lower Po2 in arterial blood, and more right heart dysfunction. Multivariate analysis demonstrated that higher mPAP was associated with shorter distance walked in 6 min, even after adjustment for age, gender, race, height, weight, FEV1, and PAOP (−11 m for every 5 mm Hg rise in mPAP; 95% confidence interval, −21 to −0.7; p = 0.04).

Conclusions:  Higher pulmonary artery pressures are associated with reduced exercise function in patients with severe COPD, even after controlling for demographics, anthropomorphics, severity of airflow obstruction, and PAOP. Whether treatments aimed at lowering pulmonary artery pressures may improve clinical outcomes in COPD, however, remains unknown.

Original Research: TUBERCULOSIS

Chest. 2009;136(2):420-425. doi:10.1378/chest.08-2427

Background:  The study documented the emergence of new forms of resistant bacilli (totally drug-resistant [TDR] or super extensively drug-resistant [XDR] tuberculosis [TB] strains) among patients with multidrug-resistant TB (MDR-TB).

Methods:  Susceptibility testing against first- and second-line drugs was performed on isolated Mycobacterium tuberculosis strains. Subsequently, the strains identified as XDR or TDR M tuberculosis were subjected to spoligotyping and variable numbers of tandem repeats (VNTR).

Results:  Of 146 MDR-TB strains, 8 XDR isolates (5.4%) and 15 TDR isolates (10.3%) were identified. The remaining strains were either susceptible (67%) or had other resistant patterns (20%). Overall, the median of treatments and drugs previously received by MDR-TB patients was two courses of therapy of 15 months' duration with five drugs (isoniazid [INH], rifampicin [RF], streptomycin, ethambutol, and pyrazinamide). The median of in vitro drug resistance for all studied cases was INH and RF. The XDR or TDR strains were collected from both immigrants (Afghan, 30.4%; Azerbaijani, 8.6%; Iraqi, 4.3%) and Iranian (56.5%) MDR-TB cases. In such cases, the smear and cultures remained positive after 18 months of medium treatment with second-line drugs (ethionamide, para-aminosalicylic acid, cycloserine, ofloxacin, amikacin, and ciprofloxacin). Spoligotyping revealed Haarlem (39.1%), Beijing (21.7%), EAI (21.7%), and CAS (17.3%) superfamilies of M tuberculosis. These superfamilies had different VNTR profiles, which eliminated the recent transmission among MDR-TB cases.

Conclusions:  The isolation of TDR strains from MDR-TB patients from different regional countries is alarming and underlines the possible dissemination of such strains in Asian countries. Now the next question is how one should control and treat such cases.


Chest. 2009;136(2):426-432. doi:10.1378/chest.09-0049

Background:  Approximately 15% of nosocomial infections in the ICU result from spread of bacteria on caregivers' hands. The routine chest radiograph provides an unexamined opportunity for bacterial spread: close contact with each patient and sequential examination of ICU patients. This study examined infection control procedures performed during routine chest radiographs, assessed whether resistant bacteria were transferred to the radiograph machine, and determined whether improved infection control practices by radiograph technicians could reduce bacterial transfer.

Methods:  Radiograph technicians were observed performing chest radiographs on all ICU patients. Culture specimens were taken from the radiograph machine. An educational intervention directed at technicians was instituted, and its effect on infection control and machine contamination was measured.

Results:  Surveillance of 173, 113, and 120 chest radiographs during observation, intervention, and follow-up periods was performed. Adequate infection control was practiced during the performance of 2 of 173 observation period radiographs (1%), 48 of 113 intervention period radiographs (42%; p < 0.001), and 12 of 120 follow-up period radiographs (10%; (p < 0.001) [follow-up vs intervention and observation periods]. Radiograph machine surface culture samples yielded resistant Gram-negative bacteria on 12 of 30 occasions (39%), 0 of 29 occasions, and 7 of 14 occasions (50%), respectively, for the observation, intervention, and follow-up periods (p < 0.001).

Conclusion:  Multiresistant bacteria are frequently transferred from patients to the radiograph machine in the presence of poor infection control practices, and may be a source of cross-infection/colonization. Improved infection control practices decrease the occurrence of resistant organisms on the radiograph equipment. Radiograph technicians should be included in efforts to improve infection control measures.

Chest. 2009;136(2):433-439. doi:10.1378/chest.09-0706

Background:  Poor oral hygiene is associated with respiratory pathogen colonization and secondary lung infection. The impact of adding electric toothbrushing to oral care in order to reduce ventilator-associated pneumonia (VAP) incidence is unknown.

Methods:  The study design was a prospective, simple-blind, randomized trial of adult patients intubated for > 48 h. Controlling for exposure to antibiotic treatment, patients were randomized to oral care every 8 h with 0.12% chlorhexidine digluconate (standard group) or standard oral care plus electric toothbrushing (toothbrush group). VAP was documented by quantitative respiratory cultures. Mechanical ventilation (MV) duration, hospital ICU length of stay (LOS), antibiotic use, and hospital ICU mortality were secondary end points.

Results:  The study was terminated after randomizing 147 patients (74 toothbrush group) in a scheduled interim analysis. The two groups were comparable at baseline. The toothbrush group and standard group had similar rates of suspected VAP (20.3% vs 24.7%; p = 0.55). After adjustment for severity of illness and admission diagnosis, the incidence of microbiologically documented VAP was also similar in the two groups (hazard ratio, 0.84; 95% confidence interval, 0.41 to 1.73). The groups did not differ significantly in mortality, antibiotic-free days, duration of MV, or hospital ICU LOS.

Conclusions:  Our findings suggest that the addition of electric toothbrushing to standard oral care with 0.12% chlorhexidine digluconate is not effective for the prevention of VAP.

Trial registration:  ClinicalTrials.gov Identifier: NCT00842478

Chest. 2009;136(2):440-447. doi:10.1378/chest.08-1634

Background:  Stress ulcer prophylaxis (SUP) using ranitidine, a histamine H2 receptor antagonist, has been associated with an increased risk of ventilator-associated pneumonia. The proton pump inhibitor (PPI) pantoprazole is also commonly used for SUP. PPI use has been linked to an increased risk of community-acquired pneumonia. The objective of this study was to determine whether SUP with pantoprazole increases pneumonia risk compared with ranitidine in critically ill patients.

Methods:  The cardiothoracic surgery database at our institution was used to identify retrospectively all patients who had received SUP with pantoprazole or ranitidine, without crossover between agents. From January 1, 2004, to March 31, 2007, 887 patients were identified, with 53 patients excluded (pantoprazole, 30 patients; ranitidine, 23 patients). Our analysis compared the incidence of nosocomial pneumonia in 377 patients who received pantoprazole with 457 patients who received ranitidine.

Results:  Nosocomial pneumonia developed in 35 of the 377 patients (9.3%) who received pantoprazole, compared with 7 of the 457 patients (1.5%) who received ranitidine (odds ratio [OR], 6.6; 95% confidence interval [CI], 2.9 to 14.9). Twenty-three covariates were used to estimate the probability of receiving pantoprazole as measured by propensity score (C-index, 0.77). Using this score, pantoprazole and ranitidine patients were stratified according to their probability of receiving pantoprazole. After propensity adjusted, multivariable logistic regression, pantoprazole treatment was found to be an independent risk factor for nosocomial pneumonia (OR, 2.7; 95% CI, 1.1 to 6.7; p = 0.034).

Conclusion:  The use of pantoprazole for SUP was associated with a higher risk of nosocomial pneumonia compared with ranitidine. This relationship warrants further study in a randomized controlled trial.

Chest. 2009;136(2):448-456. doi:10.1378/chest.08-3018

Background:  Noninvasive positive-pressure ventilation (NPPV) modes are currently available on bilevel and ICU ventilators. However, little data comparing the performance of the NPPV modes on these ventilators are available.

Methods:  In an experimental bench study, the ability of nine ICU ventilators to function in the presence of leaks was compared with a bilevel ventilator using the IngMar ASL5000 lung simulator (IngMar Medical; Pittsburgh, PA) set at a compliance of 60 mL/cm H2O, an inspiratory resistance of 10 cm H2O/L/s, an expiratory resistance of 20 cm H2O/ L/s, and a respiratory rate of 15 breaths/min. All of the ventilators were set at 12 cm H2O pressure support and 5 cm H2O positive end-expiratory pressure. The data were collected at baseline and at three customized leaks.

Main results:  At baseline, all of the ventilators were able to deliver adequate tidal volumes, to maintain airway pressure, and to synchronize with the simulator, without missed efforts or auto-triggering. As the leak was increased, all of the ventilators (except the Vision [Respironics; Murrysville, PA] and Servo I [Maquet; Solna, Sweden]) needed adjustment of sensitivity or cycling criteria to maintain adequate ventilation, and some transitioned to backup ventilation. Significant differences in triggering and cycling were observed between the Servo I and the Vision ventilators.

Conclusions:  The Vision and Servo I were the only ventilators that required no adjustments as they adapted to increasing leaks. There were differences in performance between these two ventilators, although the clinical significance of these differences is unclear. Clinicians should be aware that in the presence of leaks, most ICU ventilators require adjustments to maintain an adequate tidal volume.

Chest. 2009;136(2):457-464. doi:10.1378/chest.09-0383

Background:  Vascular endothelial growth factor (VEGF) is postulated to have a role in ARDS. The functional VEGF + 936 polymorphic T allele is associated with an increased susceptibility to and severity of ARDS. The reasons for this are unclear. We hypothesized that the T allele would be associated with an alteration in the relation between epithelial lining fluid (ELF) and plasma VEGF levels as a potential explanation for its association with susceptibility to and severity of ARDS.

Methods:  Plasma and ELF VEGF protein levels were measured by enzyme-linked immunosorbent assay from 10 at-risk patients receiving mechanical ventilation and 16 ARDS patients with the T allele, as well as 18 at-risk patients receiving mechanical ventilation and 26 ARDS patients without the T allele (wild-type CC genotype).

Results:  The T allele was associated with a significantly lower mean ELF VEGF level in ARDS patients (2,090 ± 758 pg/mL vs 3,292 ± 865 pg/mL, p < 0.05) and mean ELF/plasma VEGF level ratio (13.7 ± 4.6 pg/mL vs 94.7 ± 51.2 pg/mL, p < 0.01). There was no relation between the T allele and plasma VEGF level, oxygenation, or acute physiology score in at-risk and ARDS patients. ELF VEGF levels were significantly higher than plasma levels in both cohorts except for at-risk patients without the T allele (wild-type CC genotype).

Conclusion:  The T allele is associated with a significant decrease in ELF levels and the ELF/plasma ratio in ARDS patients. This may explain the increased susceptibility and physiologic derangement in ARDS patients with the T allele. We speculate VEGF has a protective function in the lung. Further studies are necessary to clarify the underlying mechanisms.

Chest. 2009;136(2):465-470. doi:10.1378/chest.09-0085

Background:  Failure to wean from prolonged mechanical ventilation (MV) is common in long-term acute care hospitals (LTACHs), but the process of terminal withdrawal of MV in LTACHs is not well described. We compared terminal withdrawal of MV at an LTACH with that in a medical ICU (MICU).

Methods:  A retrospective medical chart review was done of all patients undergoing terminal withdrawal of MV in an LTACH (n = 30) and in a MICU (n = 74) over a 2-year period.

Results:  The decision to withdraw MV was more likely initiated by patient or family in the LTACH and by medical staff in the MICU (p < 0.0001). Social workers, pastoral care, and hospital administration were more likely to participate in the withdrawal process at the LTACH compared with the MICU (p < 0.05). Time from initiation of MV to orders for do not resuscitate, comfort measures only, or withdrawal of MV was significantly greater in the LTACH (weeks) compared with the MICU (days) (p < 0.05). The dose of benzodiazepines given during the final 24 h of life was greater in the MICU as compared with the LTACH (p < 0.05). Narcotic and benzodiazepine use in the hour before or after withdrawal of MV did not differ between the two groups. COPD and pneumonia were the most common causes of death among patients undergoing withdrawal of MV at the LTACH, as opposed to septic shock in the MICU (p < 0.05).

Conclusions:  Terminal withdrawal of MV in the LTACH differs from that in the MICU with regard to decision making, benzodiazepine use, and cause of death.

Chest. 2009;136(2):471-480. doi:10.1378/chest.08-2413

Background:  C-reactive protein (CRP) has been studied as a marker of systemic inflammation and outcome in a number of diseases, but little is known about its characteristics in ARDS. We sought to examine plasma levels of CRP in patients with ARDS and their relationship to outcome and measures of illness severity.

Methods:  We measured CRP levels in 177 patients within 48 h of disease onset and tested the association of protein level with 60-day mortality, 28-day daily organ dysfunction scores, and number of ventilator-free days.

Results:  We found that CRP levels were significantly lower in nonsurvivors when compared with survivors (p = 0.02). Mortality rate decreased with increasing CRP decile (p = 0.02). An increasing CRP level was associated with a significantly higher probability of survival at 60 days (p = 0.005). This difference persisted after adjustment for age and severity of illness in a multivariable model (p = 0.009). Multivariable models were also used to show that patients in the group with higher CRP levels had significantly lower organ dysfunction scores (p = 0.001) and more ventilator-free days (p = 0.02).

Conclusions:  Increasing plasma levels of CRP within 48 h of ARDS onset are associated with improved survival, lower organ failure scores, and fewer days of mechanical ventilation. These data appear to be contrary to the established view that CRP is solely a marker of systemic inflammation.

Original Research: SLEEP MEDICINE

Chest. 2009;136(2):481-489. doi:10.1378/chest.08-2747

Background:  It is not fully understood why habitual snoring frequently progresses to obstructive sleep apnea syndrome (OSAS). Vibrations per se may cause peripheral nerve lesions. Therefore, snoring vibrations could cause nervous lesions, leading to impaired reflex activation of dilating muscles at inspiration. In this study, the methodology for quantitative sensory testing in the oropharynx was developed, and the presence of sensory nerve lesions in patients with OSAS and snoring was evaluated.

Methods:  Vibration detection thresholds (VDTs) and/or cold detection thresholds (CDTs) were tested at the tonsillar pillars, tongue, lip, and finger in 23 nonsnoring individuals, 13 habitual snorers (apnea-hypopnea index [AHI] < 10), and 31 patients with OSAS (AHI > 20).

Results:  At tonsillar pillars, there were significant gender differences in both VDT and CDT, with women having lower thresholds. VDT showed no significant differences between any of the three groups when men only were tested. Two nonsnoring control subjects could not detect vibrations at all. When both genders were tested, there was significant difference only between nonsnorers and patients with OSAS (p = 0.003). CDT showed significant differences between nonsnorers and snorers (p = 0.001) and also between nonsnorers and patients with OSAS (p < 0.001), but not between snorers and patients with OSAS. CDT was easier to test than VDT with low variability in nonsnorers.

Conclusions:  CDT gave more discriminative results than VDT. Signs of sensory nervous lesions were present in the oropharynx of most patients with OSAS and some snorers, supporting the hypothesis of a progressive oropharyngeal nervous lesion. CDT testing could be a useful clinical method to evaluate the degree of oropharyngeal nervous lesions in patients who snore and in those with OSAS.

Chest. 2009;136(2):490-497. doi:10.1378/chest.08-2646

Introduction:  This French, multicenter, randomized double-blind controlled trial tested the hypothesis that pressure reduction during exhalation (C-Flex; Respironics; Murrysville, PA) would improve continuous positive airway pressure (CPAP) compliance, comfort, and quality of life.

Methods:  Two hundred eighteen newly diagnosed sleep apnea patients (seven centers; mean [± SD] age, 55 ± 11 years; mean body mass index, 31 ± 6 kg/m2; mean apnea-hypopnea index, 44 ± 21 events/h) were randomly assigned to receive 3 months of treatment with CPAP (108 patients) or C-Flex (110 patients). Objective compliance, generic quality-of-life questionnaire (SF-36) scores, disease-specific quality-of-life questionnaire (Grenoble Sleep Apnea Quality of Life [GrenobleSAQOL]) scores, and visual analog scales for CPAP comfort and side effects were determined at baseline and after 3 months. After 3 months, patients in the CPAP arm were moved to the C-Flex arm for 3 additional months (open study).

Results:  An intention-to-treat analysis demonstrated that there were no differences at 3 months between C-Flex and CPAP use in terms of compliance, the rate of side effects, and comfort. Low compliers receiving CPAP therapy (< 4 h of use) significantly improved this outcome during the open study (p = 0.04). There was a significant improvement in six of eight of the SF-36 domain scores and in all of the domains of the GrenobleSAQOL scores in both groups using either CPAP or C-Flex.

Conclusion:  In unselected sleep apnea patients, C-Flex was associated with similar outcomes to standard CPAP. Low compliers receiving CPAP therapy improved their adherence when moving to C-Flex.

Trial registration:  ISRCTN Register Identifier: 08065291

Original Research: ASTHMA

Chest. 2009;136(2):498-506. doi:10.1378/chest.08-3056

Background:  Definitive conclusions regarding the antiinflammatory effects of macrolide antibiotics for treatment of asthma are difficult to formulate since their beneficial effects may be related to their antimicrobial action. We hypothesized that azithromycin possesses distinct antiinflammatory properties and tested this assumption in a noninfectious mouse model of allergic asthma.

Methods:  To induce allergic airway inflammation, 7-week-old BALB/cJ mice underwent intraperitoneal ovalbumin sensitization on days 0 and 7 followed by an intranasal challenge on day 14. Mice were treated with azithromycin or phosphate-buffered saline (PBS) solution on days 13 through 16. On day 17, airway inflammation was assessed by quantifying leukocytes in the airway, expression of multiple inflammatory mediators in the BAL fluid, and mucous cell metaplasia. In a separate set of experiments, azithromycin or PBS solution treatment were initiated after the ovalbumin challenge. Each experiment was repeated 3 times (a total of 9 to 11 mice in each group).

Results:  Compared to treatment with PBS solution, azithromycin attenuated the ovalbumin-dependent airway inflammation. We observed a decrease in total leukocytes in the lung tissue and BAL fluid. In addition, azithromycin attenuated the expression of cytokines (eg, interleukin [IL]-13 and IL-5) and chemokines (eg, CCL2, CCL3, and CCL4) in the BAL fluid and abrogated the extent of mucous cell metaplasia. Similar antiinflammatory effects were observed when azithromycin treatment was initiated after the ovalbumin challenge.

Conclusion:  In this noninfectious mouse model of allergic asthma, azithromycin attenuated allergic airway inflammation. These findings demonstrate an antiinflammatory effect of azithromycin and suggest azithromycin may have beneficial effects in treating noninfectious airway inflammatory diseases, including asthma.

Chest. 2009;136(2):507-518. doi:10.1378/chest.08-2990

Background:  Churg-Strauss syndrome (CSS) is a rare systemic vasculitis associated with asthma, eosinophilia, sinusitis, and pulmonary infiltrates. CSS has been reported in association with asthma therapies.

Materials and methods:  The objective is to describe the characteristics of CSS in patients treated with the anti-IgE antibody omalizumab (Xolair; Genentech Inc; South San Francisco, CA). A retrospective review of available data to identify cases of CSS was performed using the Novartis Argus global drug safety database for omalizumab in asthma patients.

Results:  We identified 34 potential cases of CSS. Of these, 13 cases fulfilled at least four of the six criteria identified in the American College of Rheumatology classification criteria. Eight of the patients in these 13 definite or probable cases (62%) had CSS symptoms prior to receiving omalizumab or described symptom onset just after corticosteroid weaning. Six of the 13 patients (46%) were confirmed as having been treated with corticosteroids for what was perceived to be severe asthma; when corticosteroids were tapered in conjunction with omalizumab treatment, CSS symptoms appeared just after the tapering. There were 4 other cases of possible CSS, and the remaining 17 patients were judged to not have CSS.

Conclusions:  CSS may develop in patients receiving asthma medications who have an underlying eosinophilic disorder that is unmasked by the withdrawal of therapy with corticosteroids, or in patients who delay therapy in favor of other medications. Omalizumab treatment may unmask CSS due to the weaning of corticosteroids in some asthma patients or may delay corticosteroid treatment allowing for CSS to manifest.

Trial registration:  ClinicalTrials.gov Identifier: NCT00252135

Chest. 2009;136(2):519-525. doi:10.1378/chest.08-2741

Background:  Numerous studies have examined the relationship between the fractional concentration of exhaled nitric oxide (Feno) and airway hyperresponsiveness (AHR). Our objective was to determine the effects of age on the relationship between Feno and AHR in asthmatic children.

Methods:  AHR was examined in 267 asthmatic patients (age range, 5 to 20 years). A challenge test was performed using acetylcholine chloride (Ach). We determined the provocative concentration of Ach producing a 20% decrease in FEV1 from baseline (PC20). Feno was examined using the recommended online method before the Ach challenge test.

Results:  In children < 12 years of age (range, 5 to 11 years), decreasing AHR (PC20) was significantly related to higher Feno (r = −0.43; β = −0.28; p < 0.001). In adolescents ≥ 12 years of age (range, 12 to 20 years), decreasing PC20 was associated with peripheral airway obstruction (FEV1: r = 0.32; β = 5.5; p = 0.002; forced expiratory flow at 50% of the FVC: r = 0.24; β=8.4; p = 0.006; and forced expiratory flow at 25% of FVC: r = 0.28; β=11.4; p = 0.002). AHR and Feno were weakly related (r = −0.18; β = −0.14; p = 0.02).

Conclusions:  In children with asthma, AHR is associated with airway inflammation. AHR in children with asthma may consist of variable components mainly reflecting airway inflammation. In contrast, in adolescents with asthma, AHR is associated with airway structural changes and weakly with airway inflammation. AHR in adolescents with asthma may consist of chronic components mainly reflecting airway remodeling.

Original Research: SARCOIDOSIS

Chest. 2009;136(2):526-535. doi:10.1378/chest.08-1876

Background:  The best method to interpret the chest roentgenogram and its sensitivity to detect effect of treatment for sarcoidosis remains unclear. In a double-blind, randomized trial of infliximab for chronic pulmonary sarcoidosis, changes in serial chest roentgenograms were examined by radiologists, blinded to order or treatment.

Methods:  Chest roentgenograms were obtained at 0, 6, and 24 weeks of therapy with either placebo, 3 mg/kg infliximab, or 5 mg/kg infliximab. Films were reviewed in random order by two independent radiologists, unaware of treatment. The films were compared using two methods: the prespecified objective assessment, a scoring system previously proposed by Muers; and the post hoc assessment, a 5-point Likert scale global assessment between two films.

Results:  Of 138 patients enrolled in the study, chest roentgenograms for all studies were available on 130 patients. There was only fair agreement between the two radiologists in the original stage of the chest roentgenogram (weighted κ = 0.43; 95% confidence interval [CI], 0.32 to 0.54). For the Likert scale of global assessment of change, there was good agreement between the two readers (weighted κ = 0.61; 95% CI, 0.51 to 0.71). There was good correlation between the two readers for the various components of the Muers score, especially the reticulonodular (R) score (R = 0.578; p < 0.05). The initial R score was positively correlated with improvement in FVC with infliximab therapy (R = 0.239; p < 0.05).

Conclusion:  Global assessment and the Muers scoring system were associated with good agreement between two expert readers. Improvement in both scores correlated with improvement in FVC.

Trial registration:  ClinicalTrials.gov Identifier: NCT00073437


Chest. 2009;136(2):536-544. doi:10.1378/chest.08-1965

Objective:  This study assessed current health risks due to occupational exposure to coffee dust.

Methods:  We performed a cross-sectional study in a coffee haulage company (n = 24), a coffee silo (n = 19), and a decaffeinating company (n = 17). Cross-shift and cross-week case histories of these employees as well as lung function values were recorded. During the handling of green coffee, measurements of airborne dust were conducted.

Results:  The employees in these workplaces were mainly affected by erythematous and rhinoconjunctival symptoms. They occurred especially in subjects exposed to a high dust load (> 10 mg of inhalable dust per cubic meter of air; n = 28) [Pearson χ2 test, p = 0.020 and p = 0.023]. IgE antibodies to green coffee and castor beans were detected in 3 workers and 10 workers, respectively. The majority of them (two employees and six employees, respectively) had shown respiratory symptoms during the past 12 months. The preshift lung function values were below average but were not dependent on the level of the inhalable coffee dust exposure. Employees with a coffee dust load > 10 mg/m3 of air showed higher unspecific bronchial responsiveness more frequently than those with lower exposures.

Conclusion:  During the transshipment (especially during unloading) of green coffee, a high and clinically relevant exposure to irritative and sensitizing dust occurs. Therefore, efforts to reduce these dust exposures are generally recommended.


Chest. 2009;136(2):545-553. doi:10.1378/chest.08-1378

Background:  Smoking and obesity are leading global causes of death. The aim of the present study was to develop a test to detect early lung abnormalities caused by smoking and/or obesity and to elucidate the underlying mechanisms and major contributory factors.

Methods:  One hundred twenty-nine healthy adults, 20 to 40 years of age, with normal spirometry findings, were divided into the following five groups: 38 healthy subjects (15 female subjects); 46 smokers (5 female smokers); 18 overweight nonsmokers (2 female nonsmokers; normal body mass index [BMI], ≥ 25 kg/m2; range, 25.0 to 37.2 kg/m2); 19 overweight smokers (1 female smoker; BMI range, 25.2 to 33.5 kg/m2); and 8 ex-smokers (BMI range, 20.8 to 24.1 kg/m2). A modified pulse oximeter was employed for measuring the fall in pulse oximetric saturation caused by 20-s breath-holding (dSpo2) at resting end expiration in the sitting posture.

Results:  In healthy subjects, dSpo2 had no significant correlation with age (r2 = 0.009; p = 0.66). In smokers, dSpo2 correlated with both the number of pack-years (r2 = 0.590; p < 0.001) and closing volume (CV)/vital capacity (VC) ratio (r2 = 0.573; p < 0.001). In overweight nonsmokers, dSpo2 increased significantly with BMI alone (r2 = 0.667; p < 0.001). In overweight smokers, the largest increase in the mean dSpo2 was observed. Multiple linear regression analysis suggested that BMI and CV/VC are the two major contributing factors determining dSpo2 during breath-holding. In young former smokers, no significant increase in the mean dSpo2 was observed (p = 0.77) a mean (± SD) duration of 5.2 ± 2.9 years after the cessation of smoking. No significant difference in dSpo2 was observed between men and women.

Conclusions:  A new test that measures oxygen saturation during breath-holding reveals early lung abnormalities in subjects who either smoke or are overweight, especially if these factors are combined. Peripheral airway abnormalities and/or lung volume reduction may play roles in the greater desaturation.

Chest. 2009;136(2):554-560. doi:10.1378/chest.08-2798

Background:  Interrupter respiratory resistance (Rint) is useful in evaluating lung function in children who cannot perform the traditional lung function tests. However, available reference Rint values are confined to whites. Our aims were as follows: (1) to establish reference values in local preschool Chinese children, (2) to examine their relationship with demographic and anthropometric factors, and (3) to determine the 10-min and 6-week repeatability of Rint.

Methods:  Rint was measured in preschool children from randomly chosen local kindergartens, and the repeatability of Rint measurement was assessed in a subgroup of subjects 10 min and 6 weeks after the initial measurement.

Results:  Rint measurement was performed in 509 children between 4 and 6 years of age. Age, height, and weight significantly inversely correlated with Rint values. However, on multiple linear regression, height was the only variable that independently correlated with Rint. Repeat measurements obtained 10 min and 6 weeks after the initial reading in 45 children showed good agreement with little variability, and the interclass correlation coefficients for 10-min and 6-week measurements were 0.877 and 0.923, respectively.

Conclusion:  Rint reference centile curves for Chinese preschool children have been determined. Rint in preschool Chinese children has good short- and long-term repeatability.

Topics: chinese people


Chest. 2009;136(2):561-570. doi:10.1378/chest.08-1549

Background:  Considerable evidence indicates a key role for primary cilia of mammalian cells in mechanochemical sensing. Dysfunctions of primary cilia have been linked to the pathogenesis of several human diseases. However, cilia-related research has been limited to a few cell and tissue types; to our knowledge, no literature exists on primary cilia in airway smooth muscle (ASM). The aim of this study was to characterize primary cilia in human ASM.

Methods:  Primary cilia of human bronchial smooth muscle cells (HBSMCs) were examined using immunofluorescence confocal microscopy, and scanning and transmission electron microscopy. HBSMC migration and injury repair were examined by scratch-wound and epidermal growth factor (EGF)-induced migration assays.

Results:  Cross-sectional images of normal human bronchi revealed that primary cilia of HBSMCs within each ASM bundle aggregated at the same horizontal level, forming a “cilium layer.” Individual cilia of HBSMCs projected into extracellular matrix and exhibited varying degrees of deflection. Mechanochemical sensing molecules, polycystins, and α2-, α5-, and β1-integrins were enriched in cilia, as was EGF receptor, known to activate jointly with integrins during cell migration. Migration assays demonstrated a ciliary contribution to HBSMC migration and wound repair.

Conclusions:  The primary cilia of ASM cells exert a role in sensing and transducing extracellular mechanochemical signals and in ASM injury repair. Defects in ASM ciliary function could potentially affect airway wall maintenance and/or remodeling, possibly relating to the genesis of bronchiectasis in autosomal dominant polycystic kidney disease, a disease of ciliopathy.

Translating Basic Research Into Clinical Practice

Chest. 2009;136(2):571-577. doi:10.1378/chest.08-2943

Pulmonary alveolar proteinosis (PAP) is a rare disorder characterized by ineffective clearance of surfactant by alveolar macrophages. Through recent studies with genetically altered mice, the etiology of this idiopathic disease is becoming clearer. Functional deficiency of granulocyte-macrophage colony-stimulating factor (GM-CSF) appears to contribute to disease pathogenesis because mutant mice deficient in GM-CSF or its receptor spontaneously develop PAP. Recent human studies further suggest a connection between PAP and defective GM-CSF activity because inactivating anti–GM-CSF autoantibodies are observed in all patients with idiopathic PAP, and additional rare cases of PAP in children have been accompanied by genetic defects in the α chain of the GM-CSF receptor. In patients and mouse models of PAP, deficient GM-CSF activity appears to result in defective alveolar macrophages that are unable to maintain pulmonary surfactant homeostasis and display defective phagocytic and antigen-presenting capabilities. The most recent studies also suggest that neutrophil dysfunction additionally contributes to the increased susceptibility to lung infections seen in PAP. Because the phenotypic and immunologic abnormalities of PAP in mouse models can be corrected by GM-CSF reconstituting therapies, early clinical trials are underway utilizing administration of GM-CSF to potentially treat human PAP. The development of novel treatment approaches for PAP represents a dramatic illustration in pulmonary medicine of the “bench-to-bedside” process, in which basic scientists, translational researchers, and clinicians have joined together to rapidly take advantage of the unexpected observations frequently made in the modern molecular biology research laboratory.

Special Feature

Chest. 2009;136(2):578-582. doi:10.1378/chest.08-2730

Tuberculosis, only a few decades ago, was believed to be under control and decreasing in incidence, in both developed and developing countries. A number of scientists and physicians have contributed to the understanding of tuberculosis and have been honored on postage stamps by several countries around the world. This article contains brief histories of these individuals and depictions of the postage stamps commemorating them for their contributions to the better understanding of the disease.

Topics: tuberculosis

Recent Advances in Chest Medicine

Chest. 2009;136(2):583-596. doi:10.1378/chest.08-1527

With vastly heterogeneous morphologic manifestations, sarcoidosis is one of the “great imitators” of medicine. Because there is no specific confirmatory test, the diagnosis rests on clinical acumen coupled with supportive information from tissue or blood evaluation and the exclusion of other diseases. The characteristic histologic pattern of noncaseating, epithelioid cell granulomas is not always present in skin lesions, which may be visually distinctive or diverse in appearance. As a result of their high incidence of respiratory disease, patients with sarcoidosis frequently seek care from pulmonologists who may become their primary health-care providers. Physicians who treat patients with sarcoidosis should be aware of the disease's diverse organ manifestations, but particularly those appearing on the skin because these can be disfiguring, have prognostic importance, and may not be readily diagnosed even by skin specialists. In this comprehensive review, we sought to illustrate this diversity and to update the diagnostic approach, histologic spectrum, and therapeutic strategies involved in cutaneous sarcoidosis.

Topics: sarcoidosis


Chest. 2009;136(2):597-603. doi:10.1378/chest.08-1260

To our knowledge, there are no specific and validated measures of quality of life (QoL) or degree of disability for pulmonary arterial hypertension (PAH). A review of the literature shows that, with the exception of one recently designed specifically for pulmonary hypertension, QoL questionnaires used in PAH studies are generic measures. These are selected because of shared symptoms that do not necessarily correlate well with functional or physiologic measures and have not been validated for applicability in PAH.

In this review, we present the available QoL tools for pulmonary artery hypertension and describe the need for more specific instruments that consider the physical and emotional implications of the diseases associated with PAH and the impact of various treatment options. We also discuss the impact of PAH on work ability and the need for provisions to address medical disability status and Social Security benefit status.

Chest. 2009;136(2):604-607. doi:10.1378/chest.09-1214

Despite 20 years of debate, several US Food and Drug Administration (FDA) hearings, black-box warnings, and many descriptive articles and metaanalyses, controversy regarding the safety of long-acting β-agonist (LABA) treatment in asthma patients continues. This has resulted in a recent call for another large and definitive safety study. This commentary focuses first on data provided in the metaanalysis recently undertaken by the FDA of safety outcomes among 60,954 individuals in 110 LABA trials, and second on the sample size that would be required for a new definitive study of LABA safety in the presence of mandatory treatment with an inhaled corticosteroid (ICS). A critical stratified analysis in the FDA report involving 15,192 individuals indicates that a LABA used with mandatory ICS therapy was not associated with an increased risk of asthma-related mortality, intubations, or exacerbations (risk difference [RD], 0.25 per 1,000 individuals; 95% confidence interval [CI], −1.69 to 2.18). Using the same stratified data to calculate the sample size required to prove or disprove an association between the use of LABA with mandatory ICS therapy and adverse outcomes, assuming the RD is exactly 0.25, and ignoring the 95% CI, which includes 0.0 or even a negative risk, such a study is both logistically and scientifically impossible. A new study is not practicable, nor is one needed in the light of current analyses of existing data. It is time to learn from the past, to rigorously avoid LABA monotherapy in asthma, and to use a LABA (when indicated) always in mandatory combination with appropriate doses of an ICS.

Topics in Practice Management

Chest. 2009;136(2):608-614. doi:10.1378/chest.08-2315

Spirometry is a useful test of pulmonary function and can be safely performed in a variety of clinical situations. Although the technique for performing the maneuver is straightforward, there are many sources of variability in results. Specific criteria must be met in order for the test to be considered valid. For the best results, proper instruction and coaching is essential, and patient understanding and effort must be maximized. Appropriate interpretation of spirometry requires several steps, including recognition and reporting of technically sound maneuvers, comparison to an appropriate reference population, and finally application of a well-developed interpretation scheme utilized in the context of patient symptoms and findings. Failure at any point along this path from performance to interpretation can yield misleading results that may ultimately poorly impact patient care. A clear understanding by the provider of proper coding and billing for spirometry is necessary to receive appropriate reimbursement from payers.

Topics: spirometry

Selected Reports

Chest. 2009;136(2):615-617. doi:10.1378/chest.08-0383

Background:  Cast bronchitis is a rare but potentially fatal condition caused by the accumulation of mucus in the bronchial tree usually secondary to infection, inflammation, or vascular stasis. Air leakage is an uncommon presentation of cast bronchitis. We report on three children with cast bronchitis who presented with acute air leakage as the main clinical feature.

Methods:  All three patients underwent bronchoscopic evaluation that led to a diagnosis and removal of bronchial casts.

Results:  Pathologic examination of casts from all three patients showed a mucoid substance with eosinophilic infiltration. The outcome for all patients was favorable.

Conclusions:  Acute respiratory failure presenting with wheezing and thoracic air leakage refractory to standard asthma therapy should raise suspicion of cast bronchitis, and urgent bronchoscopy should be performed.

Chest. 2009;136(2):617-620. doi:10.1378/chest.08-2641

Anatomic right-to-left shunt causes hypoxemia that can pose a diagnostic challenge to clinicians. Among the many possible causes of right-to-left shunt, persistent left-sided superior vena cava (PLSVC) with an “unroofed” coronary sinus represents an uncommon congenital anomaly in which detection by saline-contrast echocardiogram (bubble echo) or contrast-enhanced CT scan requires injection of contrast in the left arm. We present the case of an elderly man with hypoxemia on the basis of a right-to-left shunt accompanying a PLSVC with unroofed coronary sinus in whom the shunt escaped initial detection following a bubble echo with contrast injected into the right arm. This case reminds pulmonary clinicians, who are frequently called on to assess the cause of hypoxemia, that specifying a contrast injection into the left arm is required in the pursuit of this specific shunt-producing anomaly.


Chest. 2009;136(2):622-627. doi:10.1378/chest.08-2902

A 40-year-old woman presented to the pulmonary clinic with abnormal chest radiograph findings. She had longstanding primary Raynaud phenomenon, and 3 years prior to this presentation she had experienced transient, right knee inflammatory arthritis of unclear etiology. One month prior to the clinic visit, bilateral knee and wrist arthralgias developed with subjective fevers; the patient presented to her primary care doctor with these complaints. In retrospect, her 4-year-old son had experienced fevers and a rash, and had been subsequently diagnosed with Fifth disease. Her physician was concerned about sarcoidosis and obtained a chest radiograph. Based on these results, a chest CT scan was performed, and the patient was referred to the pulmonary clinic for further evaluation.

Topics: cyst , right lung , lung


Chest. 2009;136(2):628-632. doi:10.1378/chest.09-0080

A 50-year-old woman was admitted to the hospital for further workup of symptoms of progressive shortness of breath and lower extremity edema. Over the past 6 months leading up to her hospital admission, she became virtually incapacitated by shortness of breath. She also complained of weight gain and ankle swelling. Her exercise tolerance was reduced to walking several feet at a time. She received therapy with an inhaler and a short course of steroids with taper from her primary care doctor, but her condition did not improve.

Chest. 2009;136(2):634-638. doi:10.1378/chest.08-2962

A 61-year-old woman presented to her oncologist complaining of a 3-day history of fever, chills, fatigue, anorexia, and mild shortness of breath without cough or chest pain. She had recently received a diagnosis of invasive ductal carcinoma of the breast with liver metastases. She had completed her third cycle of palliative chemotherapy 3 weeks prior to presentation. Her chemotherapy regimen consisted of doxorubicin, cyclophosphamide, pegfilgrastim, dexamethasone (10 mg IV), and lorazepam. She also received oral dexamethasone, 4 mg twice daily for 3 days, after every cycle for nausea. Her medical history included hypertension, and she had recently quit smoking (40 pack-year smoking history). She denied contacts with sick persons, pets, travel, or history of malignancy among parents or siblings. She was admitted to the hospital and treated for community-acquired pneumonia without improvement. After 3 days, she required transfer to the ICU for worsening hypoxemia with persistent fever and leukocytosis.

Postgraduate Education Corner: MEDICAL WRITING TIP OF THE MONTH

Chest. 2009;136(2):639-642. doi:10.1378/chest.08-2620

MaryAnn Foote has done an excellent job of presenting a guide to writing up research results for publication.14 She has taken sections of a typical clinical trials research report one at a time and shown how it is done, focusing on CHEST requirements. Other very useful guides to scientific writing have also been published.517 The brief dissertation that follows is similar but presents in one document all elements of a research paper that may be either basic or clinical. It is also intended to be broadly applicable beyond CHEST. It does not address a variety of important associated issues such as who should be on the author list and in what position, which journal to submit to, or which ethical/conflict-of-interest issues to confront. At the outset, it must be recognized that there are literally thousands of scientific journals in existence. Each has its own list of instructions for authors that may to some extent conflict with, and therefore trump, the stereotypical approach of what now follows.


Chest. 2009;136(2):643. doi:10.1378/chest.09-0203

To do a mitzvah, it is not enough,
the rabbis say, to visit the sick
like God did with Miriam and Abraham.
To achieve even a sliver of righteousness,
it is said, one-sixtieth of a sufferer's
suffering must be relieved by deeds.
Sweep, the rabbis teach, chop wood,
fix food, wash, soothe, help the family,
reach out to hold the hand in pain.
This time I pick you up, you whom
I have known since we laughed
our way through the endless list
of eligibles. You sit inside to avoid
the sun. Thin as an afternoon shadow,
you are almost at the car before I
see you. A sigh escapes as you settle
in, whisper “Hi,” brush my cheek.
You struggle with the seat belt.
I reach over to help. My spine shoots
warnings of the mistake before your cool,
pale hand corrects me. “Feel like lunch
before?” I ask, practicing the art
of casual questions. “We'll see,”
is all you promise. Today it's bloods
for both. Is one strong enough for
another surgery? Is the other's count
good enough for donating and storing?
Long past adjusting to husbands, dogs,
and children, we have slipped across
a new border, stumbled into a new
language. We love neither doctors nor
needles. Waiting rooms provide no haven
for catching up. Suddenly, we are awash
in the precarious work of women getting
women through their fifties. One-sixtieth?
Old friends must struggle with new math.
“Put the top down,” you say. I pause,
worrying. Two-sixtieths? “Do it,” you
command, wanting to feel the breeze.
We laugh. Three-sixtieths? I push
the button. Six-sixtieths? We do not
know the fractions of the rabbis
of old. We just fight the odds. Sun
floods the car. For now, the mitzvah
is to refuse to begin letting go.

Chest. 2009;136(2):644. doi:10.1378/chest.09-0206

I couldn't talk to him,
Or rather he couldn't talk to me.
He was bound to tubes and wires
In the ICU and had no phone.
Distance separated us
As it always had and I communicated
With him through my mother
And sisters. He said
He didn't want
The women ganging up on him.
He was going to get dressed and go
To Foster's for fried chicken,
Blockage in his heart or not.
He was not a good patient and tried
To get up, my mother said,
Until the sedative calmed him.
He'd always been restless,
A doer, active with his hands
And mind, the fighter pilot
Who put his faith in skill
And training, not in luck.
Soon, all that would be over,
And he'd go home.
The tubes and wires would fall
Off him like leaves and then,
When he was bare as the hickory
In my neighbor's backyard,
We'd be able to talk.


Chest. 2009;136(2):645. doi:10.1378/chest.08-2644

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Chest. 2009;136(2):653. doi:
Chest. 2009;136(2):653. doi:
Chest. 2009;136(2):653. doi:10.1378/chest.136.2.653

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