In order to characterize intraluminal airway inflammation in subjects with chronic bronchitis, bronchoscopy and bronchoalveolar lavage were performed in 28 subjects with chronic bronchitis with fixed airway obstruction and, for comparison, 15 asymptomatic smokers and 25 normal nonsmoking volunteers. The chronic bronchitics had a cough productive of sputum on most days of the month for 6 months in the preceding 2 yr, had at least one exacerbation requiring medical intervention in each of the previous 2 yr, and had an FEV1 less than 76% of predicted without response to bronchodilator. During bronchoscopy the airways were assessed for visual evidence of inflammation by assigning them a score, the bronchitis index, that graded the airways according to the apparent severity of airway edema, erythema, friability, and secretions. Bronchoalveolar lavage was performed by sequentially instilling and retrieving with gentle suction five 20-ml aliquots of sterile normal saline into each of three separate lobes. The first aliquots, the "bronchial" sample, were pooled and processed separately from the final four aliquots, the "distal" sample. Cell counts, cell differentials, and albumin were determined for both the bronchial and distal samples. In order to correlate inflammation with clinical parameters, sputum was collected for 24 h prior to bronchoscopy; spirometry was performed just prior to bronchoscopy, and smoking histories were obtained. Visual inspection of the airways, as quantified by the bronchitis index, demonstrated significantly more evidence for inflammation in the chronic bronchitics than in either the asymptomatic smokers or the normal subjects. The bronchial sample lavage fluids from the chronic bronchitics tended to contain more cells (6.1 +/- 2.2 x 10(6) cells) than the bronchial sample fluids from the asymptomatic smokers (3.6 +/- 0.6 x 10(6) cells) or normal subjects (3.7 +/- 0.5 x 10(6) cells). Furthermore, the chronic bronchitics had a higher percentage of neutrophils in their bronchial lavage fluid (35.8 +/- 5.6%) than did either the asymptomatic smokers (20.7 +/- 2.6%, p = 0.0001) or the normal subjects (10.3 +/- 5.6%). The distal sample lavage fluid also recovered more neutrophils from both the chronic bronchitics (15.0 +/- 4.2%, p = 0.0012) and asymptomatic smokers (5.7 +/- 1.3%, p = 0.002) than from the normal subjects (2.8 +/- 0.4%). The chronic bronchitics were divided into two groups: those with low (less than 20%) and those with high (greater than 20%) bronchial sample neutrophils. Those with higher bronchial sample neutrophils had significantly more sputum production and lower FEV1, FEV1/FVC, and FEF25-75 than did the subjects with lower bronchial sample neutrophils.(ABSTRACT TRUNCATED AT 400 WORDS)
Bronchoalveolar lavage has been widely used to sample the lower respiratory tract. Most of the material recovered with this technique represents alveolar contents. A number of modifications have been suggested in order to obtain samples relatively enriched for bronchial material. In order to be able to use a standard technique for bronchoalveolar lavage to sample both airways and "routine" alveolar material, a simple modification of the technique as described by Reynolds and Newball was used: five sequential 20-ml aliquots were infused into the lower respiratory tract, and each aliquot was immediately aspirated. The return from the first aliquot was processed separately from the return from the subsequent four aliquots. These last four aliquots were pooled. Analysis of the first aliquot revealed it to be enriched for ciliated epithelial cells when compared with the subsequent aliquots. There were also differences in inflammatory cell composition with the bronchial sample containing relatively more neutrophils and relatively less lymphocytes. Aspiration during transoral bronchoscopy was documented by quantifying salivary amylase in the bronchial and alveolar lavage fluids. It was estimated, however, that the aspiration was not of quantitative significance in the vast majority of subjects studied. Finally, with the technique of fractional processing of bronchoalveolar lavage samples, it was possible to compare the protein concentrations in bronchial and alveolar lavages. Most prominent among the differences was a marked relative enrichment in the bronchial samples for immunoglobulin A. The technique of fractional processing of bronchoalveolar lavage samples provides a simple means to obtain samples enriched for bronchial and alveolar components. This should facilitate analysis of lower respiratory tract specimens in airway disease.
Although cough and sputum production may impact patients' well being and functioning in COPD and chronic bronchitis, there is no validated instrument for cough and sputum symptoms and their impact on patients' daily activities. To fill that gap, we developed and validated a specific, multilingual Cough and Sputum Assessment Questionnaire (CASA-Q) that evaluates clinical symptoms and their impact on patients with COPD or chronic bronchitis. In a three-country validation study (n=671), there was adequate internal consistency (Cronbach's alphas, 0.80-0.91) and test-retest reliability (correlation coefficients>0.70) for the CASA-Q. The cough impact and sputum impact domains correlated with the SGRQ impact domain and SGRQ total score, as did the cough impact domain with the SF-36 social functioning domain. The cough symptom and sputum symptom domains correlated with sputum wet weight (p<0.05; r=-0.56), but not with cough recordings. The mean CASA-Q cough symptom and sputum symptom domain scores indicated responsiveness towards both worse and improved symptoms, whereas the impact domains scored already in the upper third of the scale range, indicating the need for further improvement of its properties. Differences in the CASA-Q domain scores by smoking status (current vs. former smokers) were highest for cough symptoms and lowest for sputum impact. These data indicate that the CASA-Q may be a useful measure of cough and sputum production, and their impact in patients with COPD and/or chronic bronchitis. Further validation will need to assess the responsiveness of the CASA-Q to changes in symptoms.
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