Clinical relevance of cellular mediators of inflammation in workers exposed to asbestos

Our plain-English summary of Clinical relevance of cellular mediators of inflammation in workers exposed to asbestos, by D.A. Schwartz, J.R. Galvin, K.L. Frees, et al (The American Review of Respiratory Disease, 1993).

The study

• Authors: D.A. Schwartz, J.R. Galvin, K.L. Frees, C.S. Dayton, L.F. Burmeister, J.A. Merchant, G.W. Hunninghake
• Journal: The American Review of Respiratory Disease
• Published: 1993;148(1):68-74
• Cited by: 20 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

To identify the clinical relevance of cellular mediators of inflammation in workers exposed to asbestos, we investigated the relationship between inflammatory products primarily released by alveolar macrophages and the clinical expression of asbestos-induced interstitial fibrosis. Our study population consisted of 93 white men who had been occupationally exposed to asbestos and were on average 60 yr of age. Pulmonary function tests, chest radiographs, high-resolution CT scans, and bronchoalveolar lavage (BAL) were performed on almost all study subjects; 11 (11.8%) had restrictive lung function, 22 (23.7%) had abnormal gas exchange, 30 (32.3%) had interstitial fibrosis on chest x-ray, and 24 (25.8%) had interstitial changes on high-resolution CT scan. The cellular markers of parenchymal inflammation that we examined included fibronectin in BAL fluid and alveolar macrophage release of prostaglandin E2 (PGE2), interleukin-1 beta (IL-1 beta), and tumor necrosis factor (TNF-alpha) under unstimulated and endotoxin (LPS)-stimulated culture conditions. Significantly higher concentrations of fibronectin in BAL fluid were observed among those with restrictive lung function. In addition, higher concentrations of PGE2, released from cultured but otherwise unstimulated alveolar macrophages, were associated with restrictive lung function. However, the inverse relationship with PGE2 was observed among subjects with abnormal gas exchange. Interestingly, no consistent changes in these inflammatory mediators were observed in those with interstitial changes identified on either the chest radiograph or the high-resolution CT scan.(ABSTRACT TRUNCATED AT 250 WORDS)

In plain English

This study asked whether lung inflammation markers from bronchoalveolar lavage (rinsing part of the lung) were linked to lung function and imaging in 93 white men, average age 60. All had at least one year of direct occupational asbestos exposure. The researchers measured fibronectin in lavage fluid and three substances (PGE2, IL-1 beta, TNF-alpha) released by alveolar macrophages, lung immune cells, in culture. Eleven men (11.8%) had restrictive lung function, 22 (23.7%) had abnormal gas exchange, 30 (32.3%) had interstitial fibrosis on chest x-ray, and 24 (25.8%) had interstitial changes on high-resolution CT. Men with restrictive lung function had significantly higher fibronectin and higher PGE2 from unstimulated cells. Men with abnormal gas exchange showed the opposite PGE2 pattern. The authors reported IL-1 beta and TNF-alpha were not significantly related to lung function or imaging, though one table marks lower unstimulated TNF-alpha with abnormal gas exchange as significant. No marker changed consistently with x-ray or CT findings. The authors concluded that routine lavage gives too little information to stage asbestos-related lung disease. They suggested lavage may have missed the lung areas asbestosis affects most.

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 of a single group of asbestos-exposed workers. Lavage markers were compared with lung function and chest imaging using univariate comparisons and multivariate regression.
• Who was studied: 93 white men occupationally exposed to asbestos, average age 60 years. 17% had never smoked, 68% were former smokers and 15% were current smokers. Men with asbestos-related lung or pleural disease were preferentially invited, but exposed men without obvious disease were also included.
• Exposure: Occupational asbestos exposure for at least 1 year in a high-exposure setting (direct exposure). At least 20 years had passed since first exposure. Mean exposure duration was 32.8 years and mean time from first exposure to study entry was 36 years. Fiber types were not specified.
• Main results:
  • Of the 93 men, 11 (11.8%) had restrictive lung function, 22 (23.7%) had abnormal gas exchange, 30 (32.3%) had interstitial fibrosis on chest x-ray, and 24 (25.8%) had interstitial changes on high-resolution CT.
  • Men with restrictive lung function (n = 11) had significantly higher fibronectin in lavage fluid than men without it (n = 82): mean 276.1 (SD 456.1) versus 104.2 (SD 73.1). They also had higher PGE2 from unstimulated macrophages: mean 32.1 (SD 70.4) versus 7.7 (SD 18.1).
  • Among men with abnormal gas exchange, the PGE2 relationship was inverse. Unstimulated PGE2 averaged 6.1 (SD 14.6) in men with abnormal gas exchange (n = 22) versus 12.2 (SD 33.7) in men without it (n = 71).
  • The authors' text states that IL-1 beta and TNF-alpha released by macrophages, whether unstimulated or stimulated with endotoxin, were not significantly related to lung function or to x-ray or CT findings.
  • Table 5, however, marks unstimulated TNF-alpha as significantly lower (p 0.05 or less) in men with abnormal gas exchange (n = 22): mean 430.6 (SD 725.0) versus 716.0 (SD 1,089.6) in men without it (n = 71). This contradicts the text.
  • No consistent changes in the inflammatory markers were seen in men with interstitial changes on chest x-ray or high-resolution CT.
  • After controlling for age, smoking status and pack-years, decreased lung volume remained independently associated with higher fibronectin and higher PGE2 (data not presented). The markers showed no clear relationship with fibrosis on x-ray or CT.
• The authors' conclusion: The authors concluded that the routine approach to bronchoalveolar lavage does not provide enough information to stage patients with asbestos-induced lung disease. They suggested future research on CT-directed lavage.
• Limitations the authors state:
  • Most men had only mild to moderate interstitial fibrosis, which may have prevented the study from detecting a relationship with cytokine production.
  • Lavage was done in anterior lung segments (right middle lobe and lingula), while asbestosis most often affects posterior, lower segments. Lavage may therefore not have sampled the most affected lung.
  • Laboratory culture conditions may distort the properties of the lavaged cells.
  • Restrictive lung function was defined as residual volume or total lung capacity below 80% of predicted. The authors note that 10 to 15% of the normal population is expected to have a residual volume below 80% of predicted.

Topics

Medical terms in this study, explained in our Lexicon: Inflammation, Alveolar Macrophage, Interstitial Fibrosis, Pulmonary Function Test (PFT), Chest X-Ray, High-Resolution CT (HRCT), Bronchoalveolar Lavage (BAL), Restrictive Lung Disease.

Related studies

• Alveolar macrophage cytokine and growth factor production in a rat model of crocidolite-induced pulmonary inflammation and fibrosis — K.E. Driscoll, J.K. Maurer, et al. (1995)
• The clinical relevance of asbestos-induced pleural fibrosis — D.A. Schwartz (1991)
• The clinical utility and reliability of asbestos bodies in bronchoalveolar fluid — D.A. Schwartz, J.R. Galvin, et al. (1991)
• Relative release of interleukin-1 beta and interleukin-1 receptor antagonist by alveolar macrophages. A study in asbestos-induced lung disease, sarcoidosis, and idiopathic pulmonary fibrosis — J.N. Kline, D.A. Schwartz, et al. (1993)
• Mineral dusts directly induce epithelial and interstitial fibrogenic mediators and matrix components in the airway wall — J. Dai, B. Gilks, et al. (1998)
• Characterization of the lower respiratory tract inflammation of nonsmoking individuals with interstitial lung disease associated with chronic inhalation of inorganic dusts — W.N. Rom, P.B. Bitterman, et al. (1987)

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