Characterization of the lower respiratory tract inflammation of nonsmoking individuals with interstitial lung disease associated with chronic inhalation of inorganic dusts

Our plain-English summary of Characterization of the lower respiratory tract inflammation of nonsmoking individuals with interstitial lung disease associated with chronic inhalation of inorganic dusts, by W.N. Rom, P.B. Bitterman, S.I. Rennard, et al (The American Review of Respiratory Disease, 1987).

The study

• Authors: W.N. Rom, P.B. Bitterman, S.I. Rennard, A. Cantin, R.G. Crystal
• Journal: The American Review of Respiratory Disease
• Published: 1987;136(6):1429-34
• Cited by: 214 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. 000349).

Abstract

The pneumoconioses, interstitial lung disorders resulting from the inhalation of inorganic dusts, are associated with chronic inflammatory processes in the lower respiratory tract. To characterize these inflammatory processes in relation to the pathogenesis of these disorders, we studied 39 nonsmoking individuals with long-term occupational exposures to inorganic dust and functional evidence of interstitial disease (asbestosis, n = 18; coal workers' pneumoconiosis, n = 15; silicosis, n = 6). In all 3 disorders, the inflammation was dominated by alveolar macrophages. Because a common feature of these interstitial lung diseases is concurrent injury and fibrosis of alveolar walls, we assessed whether these alveolar macrophages were spontaneously releasing mediators capable of giving rise to these changes. Alveolar macrophages from the study population were spontaneously releasing increased amounts of superoxide anion and hydrogen peroxide (both p less than 0.01 compared to normals), oxidants capable of injuring lung parenchymal cells. The alveolar macrophages were also spontaneously releasing significantly increased amounts of fibronectin and alveolar macrophage-derived growth factor (both p less than 0.01 compared to normals), mediators that act synergistically to signal fibroblast replication. Taken together, these findings define a major role for the alveolar macrophage in mediating the alveolar wall injury and fibrosis that characterize the common pneumoconioses and suggest that the alveolar macrophage is an important "target" for developing strategies designed to prevent loss of lung function in these individuals.

In plain English

The authors studied inflammation in 39 men with interstitial lung disease from long-term workplace dust: 18 with asbestosis, 15 with coal workers' pneumoconiosis and 6 with silicosis. All were lifelong nonsmokers or had not smoked within 5 years. Using gallium-67 lung scans and bronchoalveolar lavage (lung washing), they compared them with normal individuals. All dust-exposed men had positive gallium scans, and alveolar macrophages were the main cell recovered, as in normals. On average, the men's macrophages released 2- to 3-fold more of the oxidants superoxide and hydrogen peroxide. This was significant for asbestosis and silicosis, not coal workers' pneumoconiosis. They also released more fibronectin (6.2 ± 1.6 versus 1.1 ± 0.7 ng per million cells per hour) and macrophage-derived growth factor (97 ± 25 versus 0 units per million cells, per hour, though a figure caption says per 4 hours). Gallium scans, macrophage and neutrophil proportions, oxidant release and mediator release did not differ significantly among the three disease groups. The authors proposed that these macrophages may help cause lung injury and scarring. Only a prospective, long-term study could prove this, they added.

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 laboratory comparison study: gallium-67 lung scans and bronchoalveolar lavage in dust-exposed patients, with macrophage mediator release compared against groups of normal individuals
• Who was studied: 39 nonsmoking men (lifelong nonsmokers or no smoking within 5 years) with interstitial lung disease from occupational dust exposure: 18 with asbestosis, 15 with coal workers' pneumoconiosis (all from underground Appalachian coal mines) and 6 with silicosis. Separate groups of mostly young nonsmoking normal individuals served as comparisons for each test. The place and dates of the study are not stated beyond the authors' affiliation (National Heart, Lung, and Blood Institute, Bethesda, Maryland).
• Exposure: High-level chronic occupational exposure to asbestos, coal or silica. Asbestos jobs were graded by intensity, from asbestos insulator down to bystander exposure. Fiber types were not specified. All men in the asbestosis group also had pleural changes consistent with chronic asbestos exposure.
• Main results:
  • All dust-exposed individuals had a positive gallium-67 lung scan. The scan index was significantly higher than in normals for each disorder (p less than 0.01) and did not differ among the 3 disorders (asbestosis group 168 ± 16 units; normals 25 ± 7).
  • Alveolar macrophages were the dominant cell recovered by lavage (asbestosis group 76 ± 4%). Their proportion was similar to normals and similar among the 3 diseases.
  • Neutrophil proportions were increased in the dust-exposed group (3.3 ± 0.6% versus 1.7 ± 0.2%, p less than 0.01), with no difference among the 3 disorders (p greater than 0.1). The authors noted that neutrophils were still a very small proportion of the cells.
  • On average, cells from the dust-exposed group spontaneously released 2- to 3-fold more superoxide anion and hydrogen peroxide than normals (both p less than 0.01).
  • The oxidant differences from normals were significant for asbestosis and silicosis (p less than 0.05).
  • For coal workers' pneumoconiosis, oxidant release was higher than normal but not statistically significant.
  • Oxidant release did not differ among the 3 disorders (p greater than 0.1).
  • Dust-exposed macrophages released 6.2 ± 1.6 ng fibronectin per 10^6 cells-hr, compared with 1.1 ± 0.7 for normals (p less than 0.01). The difference was significant in each of the 3 groups, with no differences among the groups (p greater than 0.1).
  • Release of alveolar macrophage-derived growth factor was 97 ± 25 units per 10^6 cells-hr in the dust-exposed group, compared with 0 in normals (p less than 0.001). The Figure 3 caption gives the unit as per 10^6 cells per 4 hours. The difference was significant for each group (p less than 0.01), with no differences among the 3 groups (p greater than 0.1).
  • To check for effects of age and sex, the authors evaluated 9 older individuals (mean age 47) and found no significant differences in lavage parameters compared with the younger normal nonsmokers.
• The authors' conclusion: In their summary, the authors stated that the findings define a major role for the alveolar macrophage in the alveolar wall injury and fibrosis of the common pneumoconioses. In the discussion, they described it as a reasonable hypothesis that the activated macrophages may be playing a role in disease development, and suggested that it may be possible to design therapies that suppress these processes.
• Limitations the authors state:
  • The authors stated that the hypothesis that activated macrophages cause these diseases can only be proved by a prospective, long-term study.
  • The authors noted that cells other than activated macrophages may contribute to a positive gallium-67 scan.

Topics

Medical terms in this study, explained in our Lexicon: Inflammation, Interstitial Lung Disease, Interstitial, Occupational Exposure, Pneumoconiosis, Silicosis, Alveolar Macrophage, Fibrosis.

Related studies

• Relationship of inflammatory cell cytokines to disease severity in individuals with occupational inorganic dust exposure — W.N. Rom (1991)
• The effect of cigarette smoking on the detection of small radiographic opacities in inorganic dust diseases — P.D. Blanc, G. Gamsu (1988)
• Inhibition of lung injury, inflammation, and interstitial pulmonary fibrosis by polyethylene glycol-conjugated catalase in a rapid inhalation model of asbestosis — B.T. Mossman, J.P. Marsh, et al. (1990)
• The pathobiology of asbestos-induced lung disease: a proposed role for macrophage-derived growth factors — J.A. Lasky, J.C. Bonner, et al. (1991)
• Role of oxidants in interstitial lung diseases: pneumoconioses, constrictive bronchiolitis, and chronic tropical pulmonary eosinophilia — W.N. Rom (2011)
• Accumulation of mixed mineral dusts in the lungs of rats during chronic inhalation exposure — C.H. McMillan, A.D. Jones, et al. (1989)

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