Association between neutrophil concentration in bronchoalveolar lavage fluid and recent losses in diffusing capacity in men formerly exposed to asbestos

Our plain-English summary of Association between neutrophil concentration in bronchoalveolar lavage fluid and recent losses in diffusing capacity in men formerly exposed to asbestos, by M.R. Cullen, W.W. Merrill (Chest, 1992).

The study

• Authors: M.R. Cullen, W.W. Merrill
• Journal: Chest
• Published: 1992;102(3):682-7
• Cited by: 13 articles, as counted by NIH iCite
• Read it: PubMed · Publisher
• In J-M's library: Johns-Manville's company medical library held a copy (J-M no. 004884).

Abstract

It has been observed widely that some individuals exposed to asbestos will experience continued losses of lung function after asbestos exposure ceases. Unfortunately, there are few data on factors that determine clinical course, limiting the clinician's ability to determine prognosis in an individual case and restricting the possibility for testing or targeting any potential intervention to alter the course among the millions at risk. In an attempt to address this question, we studied a volunteer population of 50 such men from among a stable, heterogeneous population of asbestos-exposed workers who had been continuously followed in our occupational medicine clinics for up to 12 years (mean, 6.3 years); most had some clinical or roentgenographic sign of asbestos effect, pleural or parenchymal. Each subject was reexamined clinically, functionally, and roentgenographically. Asbestos and tobacco exposure histories were carefully reviewed with the subjects and quantified based on these reports and available data regarding the various work environments from which they came. Subsequently, each underwent a bronchoalveolar lavage to assess cellularity and levels of various proteins. The levels of risk factors, clinical findings, and biologic parameters from lavage were examined for their relationship to serial changes in lung function during the period over which they had been previously followed. Results of the study demonstrate that serial changes in lung function were not closely related to level or length of prior exposure, smoking behavior, chest roentgenographic findings, or lung volumes. Progressive loss of diffusing capacity for carbon monoxide (Dco) was significantly associated with two factors: level of neutrophil concentration in lavage fluid (0.043 +/- 0.016 ml/min/mm Hg/yr drop for each 0.1 x 10(4) neutrophils per milliliter, p = 0.02) and the level of Dco itself (0.17 +/- 0.07 ml/min/mm Hg/yr drop for each 10 percent decrease in percent Dco predicted, p = 0.01). The relationship with neutrophil concentration was statistically independent of the association with Dco itself and stronger; it persisted when loss of Dco was adjusted for baseline value. Lung volume changes were not associated with any predictor variables, alone or in combination. We conclude that the presence of neutrophils in bronchoalveolar lavage fluid is associated with recent disease progression that may have implications in studies of the mechanisms of asbestos-associated disease and in clinical treatment of patients at risk.

In plain English

This study examined 50 men formerly exposed to asbestos at work. All were Yale Occupational Medicine Program patients in Connecticut previously diagnosed with pulmonary asbestosis or asbestos-related nonmalignant pleural disease. They gave work and smoking histories and had chest X-rays. Of the 50, 49 completed breathing tests and 48 completed bronchoalveolar lavage, a procedure that washes fluid out of the lungs through a bronchoscope. The authors compared lavage results with earlier changes in lung function in the 32 men who had enough past clinic tests. Changes in lung function were not closely tied to exposure, smoking or X-ray findings. Faster loss of diffusing capacity, a measure of how well the lungs pass gas into the blood, was associated with a higher concentration of neutrophils, a type of white blood cell, in lavage fluid. Neutrophils explained about one fifth of the variation, and the link held after allowing for smoking and for diffusing capacity itself. The authors concluded that neutrophils in lavage fluid are associated with recent disease progression. They noted few men, possible measurement errors, and lavage done at the end rather than the start of follow-up.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Clinical study combining a one-time examination and bronchoalveolar lavage with a look back at each man's earlier lung function tests. The authors say they would ideally have done the lavage first and then followed the men forward in time.
• Who was studied: 50 male volunteers aged 37 to 74, recruited from over 1,000 patients of the Yale Occupational Medicine Program (New Haven, Connecticut) who had been previously diagnosed with pulmonary asbestosis or asbestos-related nonmalignant pleural disease and followed for up to 12 years. 49 completed resting lung function testing; one could not because of a laryngectomy. 48 completed lavage. 32 had at least three acceptable lung function tests (follow-up 29 to 139 months, average 63) and were used for the analysis of change over time.
• Exposure: Past occupational asbestos exposure in asbestos product manufacturing, ship-building, insulation, general construction trades and industrial maintenance. The article does not name fiber types. Dose was estimated on a relative 'insulator-year' scale: cumulative exposure ranged from 2.5 to 36 insulator-years, with a mean of 14.8. No subject had been significantly exposed after his first clinic visit.
• Main results:
  • Among the men with follow-up data, average losses of lung volumes were greater than 50 ml per year and the mean loss of diffusing capacity was over 0.5 ml/min/mm Hg per year. The authors describe each as two to three times the values predicted for healthy men of comparable age.
  • Simple correlations between the rates of lung function change (total lung capacity, forced vital capacity, diffusing capacity) and the main suspected risk factors were unrevealing.
  • The level of diffusing capacity at the time of study was the only lung function measure significantly related to its rate of change (r = 0.406). The rate of loss increased by 0.17 plus or minus 0.07 ml/min/mm Hg per year for each 10 percent drop in percent predicted diffusing capacity, p = 0.02.
  • Neutrophil concentration in lavage fluid (as its square root) explained one fifth of the variation in diffusing capacity loss (R2 = 0.20). The slope was a drop of 0.043 plus or minus 0.016 ml/min/mm Hg per year in diffusing capacity for each additional 0.1 x 10^4 neutrophils per milliliter of lavage fluid (p = 0.01).
  • Adding smoking (log pack-years or smoking group) to the analysis had virtually no impact on the neutrophil association. Within the separate smoking groups, the regression coefficients were similar: 0.008 in nonsmokers, 0.005 in 'smokers' and 0.010 in current smokers, against 0.007 overall. Because of small numbers, only the current smokers' regression approached significance (p less than 0.06).
  • When diffusing capacity and neutrophil concentration were analyzed together, neutrophil concentration remained significant (p less than 0.05) but diffusing capacity did not. Together the two explained 28.4 percent of the variation in diffusing capacity loss.
  • None of the proteins measured in lavage fluid was significantly associated with decline in lung function. Neutrophils and eosinophils showed no effect on changes in lung volumes.
  • Correlation between diffusing capacity loss and ILO X-ray grade was minimal (Spearman r = 0.19), as was its correlation with quantitative gallium scan results (Pearson r = 0.29, measured in a subset of 18 men).
  • Smoking markedly increased total cells recovered by lavage: on average 27.7 x 10^6 in nonsmokers, 36.7 x 10^6 in ex-smokers and 107.8 x 10^6 in active smokers. The difference among the groups was significant (p less than 0.002).
• The authors' conclusion: The authors concluded that neutrophils in bronchoalveolar lavage fluid are associated with recent disease progression. They added that this may have implications for studying the mechanisms of asbestos-associated disease and for clinical treatment of patients at risk.
• Limitations the authors state:
  • The study population was small: only 32 of the 50 men had enough acceptable lung function tests to be used in the analysis of disease progression.
  • Risks may have been misclassified, and the predictor and outcome variables may have been measured inaccurately.
  • The design was reversed from the ideal. Lavage was done at the end of follow-up rather than the start, so neutrophil levels and lung function decline may both have been misclassified. This limits how well the findings can predict future course.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Asbestosis.

Medical terms in this study, explained in our Lexicon: Bronchoalveolar Lavage (BAL), Diffusing Capacity (DLCO), Asbestos Exposure, Prognosis, Disease Progression.

Related studies

• Pulmonary elastic recoil and diffusing capacity in subjects with intermediate concentrations of alpha-1 antitrypsin — A.W. Musk, P.W. Robertson (1976)
• Reduced diffusing capacity as an isolated finding in asbestos- and silica-exposed workers — J.G. Garcia, D.E. Griffith, et al. (1990)
• Bronchoalveolar lavage fluid cellular profile in workers exposed to chrysotile asbestos — F.P. Kokkinis, D. Bouros, et al. (2011)
• Biphasic lung diffusing capacity: detection of early asbestos induced changes in lung function — Z. Dujić, J. Tocilj, et al. (1992)
• Lung diffusing capacity relates better to short-term progression on HRCT abnormalities than spirometry in mild asbestosis — C.R. Nogueira, L.M. Nápolis, et al. (2011)
• Single breath diffusing capacity in the industrial setting — B. Make, A. Miller, et al. (1982)

Browse more research in Chest, or return to medical research.