An official American Thoracic Society clinical practice guideline: the clinical utility of bronchoalveolar lavage cellular analysis in interstitial lung disease.

BACKGROUND: The clinical utility of bronchoalveolar lavage fluid (BAL) cell analysis for the diagnosis and management of patients with interstitial lung disease (ILD) has been a subject of debate and controversy. The American Thoracic Society (ATS) sponsored a committee of international experts to examine all relevant literature on BAL in ILD and provide recommendations concerning the use of BAL in the diagnosis and management of patients with suspected ILD. PURPOSE: To provide recommendations for (1) the performance and processing of BAL and (2) the interpretation of BAL nucleated immune cell patterns and other BAL characteristics in patients with suspected ILD. METHODS: A pragmatic systematic review was performed to identify unique citations related to BAL in patients with ILD that were published between 1970 and 2006. The search was updated during the guideline development process to include published literature through March 2011. This is the evidence upon which the committee's conclusions and recommendations are based. RESULTS: Recommendations for the performance and processing of BAL, as well as the interpretation of BAL findings, were formulated by the committee. CONCLUSIONS: When used in conjunction with comprehensive clinical information and adequate thoracic imaging such as high-resolution computed tomography of the thorax, BAL cell patterns and other characteristics frequently provide useful information for the diagnostic evaluation of patients with suspected ILD.

Comparison of atopic and nonatopic children with chronic cough: bronchoalveolar lavage cell profile.

Chronic cough is a common complaint in children and its relationship with asthma is controversial. The aim of the present study was to determine the pattern of airway inflammation in atopic and nonatopic children with chronic cough, and to investigate whether atopy is a predictive factor for eosinophilic inflammation in cough. Bronchoalveolar lavage (BAL; three aliquots of 1 ml/kg saline) was performed in the right middle lobe of 24 (11 atopic and 13 nonatopic) children with persistent cough (8 females, 16 males), mean age 4.7 years (range: 1-11). Atopy was defined as an elevated total serum IgE or a positive RAST test. Both atopic and nonatopic children with persistent cough had an increase in total cells/ml in BAL (atopic: median 39 x 10(4), range: 20-123; nonatopic: median 22 x 10(4), range: 17-132) compared to nonatopic controls (median 11 x 10(4), range 9-30). The increases were mainly in neutrophils (atopic: median 17%, range 2.5-88.5%; nonatopic: median 6%, range 1.0-55.0%) compared to controls (median 1.55%, range 0.5-7.0%; atopics vs. controls, P < 0.005). There were no significant increases in eosinophils, lymphocytes, epithelial cells, or mast cells. Eosinophils were elevated in only 5/11 atopic and none of the nonatopic children. The increased percentage of neutrophils in the BAL fluid of atopic and nonatopic children with persistent cough could be due to an underlying inflammatory process driving the cough, or even conceivably, due to the effect of coughing itself. In this highly selected series, the absence of eosinophilic inflammation in the majority suggests that most would be predicted not to respond to inhaled corticosteroid therapy. This study underscores the need to be cautious about treating coughing children with inhaled corticosteroids, even in the context of a tertiary referral practice.

SmokeHaz: Systematic Reviews and Meta-analyses of the Effects of Smoking on Respiratory Health.

BACKGROUND: Smoking tobacco increases the risk of respiratory disease in adults and children, but communicating the magnitude of these effects in a scientific manner that is accessible and usable by the public and policymakers presents a challenge. We have therefore summarized scientific data on the impact of smoking on respiratory diseases to provide the content for a unique resource, SmokeHaz. METHODS: We conducted systematic reviews and meta-analyses of longitudinal studies (published to 2013) identified from electronic databases, gray literature, and experts. Random effect meta-analyses were used to pool the findings. RESULTS: We included 216 articles. Among adult smokers, we confirmed substantially increased risks of lung cancer (risk ratio (RR), 10.92; 95% CI, 8.28-14.40; 34 studies), COPD (RR, 4.01; 95% CI, 3.18-5.05; 22 studies), and asthma (RR, 1.61; 95% CI, 1.07-2.42; eight studies). Exposure to passive smoke significantly increased the risk of lung cancer in adult nonsmokers and increased the risks of asthma, wheeze, lower respiratory infections, and reduced lung function in children. Smoking significantly increased the risk of sleep apnea and asthma exacerbations in adult and pregnant populations, and active and passive smoking increased the risk of tuberculosis. CONCLUSIONS: These findings have been translated into easily digestible content and published on the SmokeHaz website.

Airway eosinophilia in children with severe asthma: predictive values of noninvasive tests.

RATIONALE: Children with severe asthma experience persistent symptoms despite maximal conventional treatment. Fraction of exhaled nitric oxide (Fe(NO)) and sputum eosinophils are used as markers of airway inflammation to guide treatment with steroids, but no data are available on how reliable they are in predicting airway eosinophilia assessed bronchoscopically in these children. OBJECTIVES: To determine how Fe(NO) and sputum eosinophils predict airway eosinophilia measured in both bronchoalveolar lavage (BAL) and endobronchial biopsy. METHODS: Twenty-seven children with moderate to severe persistent asthma attempted measurement of Fe(NO) and sputum eosinophils, followed by bronchoscopy, BAL, and endobronchial biopsy within 24 h. MAIN RESULTS: Significant correlations were found between eosinophils in sputum and both BAL eosinophils (n = 20, r = 0.45, p = 0.045) and Fe(NO) (n = 23, r = 0.42, p = 0.049). The relationship between Fe(NO) and BAL eosinophils was also significant with a stronger correlation (n = 24, r = 0.54, p = 0.006). The positive predictive value (PPV) for increased sputum eosinophil percentage (> 2.5%) to detect elevated eosinophils in BAL (> 1.19%) was 75%; the negative predictive value (NPV) was 63%. All patients with both increased sputum eosinophils and an elevated Fe(NO) value (> 23 ppb) had elevated eosinophils in BAL (PPV, 100%); the NPV of these two markers was 65%. Eight of nine patients without any sputum eosinophils had normal subepithelial eosinophil numbers (< 1.2%; NPV, 89%). However, the PPV of any sputum eosinophils for increased subepithelial eosinophilia was only 36.4%. CONCLUSIONS: There was moderate agreement between both Fe(NO) and sputum eosinophils and BAL eosinophils. There was good NPV, but only poor PPV for these markers for mucosal eosinophilia.

From birds to humans: new concepts on airways relative to alveolar surfactant.

Pulmonary surfactant is a surface-active mixture of phospholipids and specific proteins that lines the epithelial surfaces of mammalian lungs. In the alveoli, its main function is to reduce surface tension to ensure that these structures can remain open during respiratory cycles of contraction and expansion. However, surfactant is also present in the conducting airways, even though they are relatively rigid and do not need a system capable of rapidly lowering surface tension in response to compression. This has raised the question whether there is a difference in composition and function between airway and alveolar surfactant. Interest in this question has been stimulated further by the recognition that surfactant also has important functions in the immune defenses of the respiratory tract. In this review, we describe differences that have been reported between human airway and alveolar surfactant. In addition, we draw parallels between human airway surfactant and surfactant from the lungs of birds. The latter are tubular and rigid and do not undergo cycles of contraction and expansion, thus more resembling the human conducting airways than alveoli. Using this as a model, we propose a new hypothesis to explain structural and functional differences between human airway and alveolar surfactant. We suggest that the molecular composition of surfactant is adapted to differences in the architecture of pulmonary surfaces and to the dynamics of surface area changes during respiration.

Histopathologic subsets of fibrosing alveolitis in patients with systemic sclerosis and their relationship to outcome.

Fibrosing alveolitis associated with systemic sclerosis (FASSc) has a better prognosis than idiopathic pulmonary fibrosis. In view of recent reports that idiopathic nonspecific interstitial pneumonia (NSIP) has a better prognosis than idiopathic usual interstitial pneumonia (UIP), we classified histologic appearances of surgical lung biopsies performed in 80 patients with FASSc. NSIP (n = 62, 77.5%), subcategorized as cellular NSIP (n = 15) and fibrotic NSIP (n = 47) was much more prevalent than UIP (n = 6), end-stage lung disease (ESL, n = 6), or other patterns (n = 6). There were 25 deaths (NSIP 16/62, 26%; UIP/ESL 6/12, 50%). Five-year survival differed little between NSIP (91%) and UIP/ESL (82%); mortality was associated with lower initial carbon monoxide diffusing capacity (DL(CO)) and FVC levels (p = 0.004 and p = 0.007, respectively). Survival and serial FVC and DL(CO) trends did not differ between cellular and fibrotic NSIP. Increased mortality in NSIP was associated with lower initial DL(CO) levels (p = 0.04), higher BAL eosinophil levels (p = 0.03), and deterioration in DL(CO) levels during the next 3 years (p < 0.005). We conclude that NSIP is the histopathologic pattern in most patients with FASSc. However, outcome is linked more strongly to disease severity at presentation and serial DL(CO) trends than to histopathologic findings.