Lower respiratory tract abnormalities in rheumatoid interstitial lung disease. Potential role of neutrophils in lung injury.
Although the etiology of rheumatoid interstitial lung disease (RILD) remains unknown, bronchoalveolar lavage (BAL) has been useful in studying potentially pathogenic mechanisms in this disorder. Previous investigations in patients with rheumatoid arthritis (RA) and RILD revealed abnormal BAL T-lymphocyte subpopulations and a significant elevation in BAL neutrophils. Because neutrophils have been implicated as important effector cells in inflammatory disorders such as ARDS and idiopathic pulmonary fibrosis, we evaluated BAL fluid in patients with RA for neutrophil chemotactic and activating properties and for evidence of neutrophil activation. The BAL fluid from patients with RILD contained significant neutrophil chemotactic activity derived from both lipid and nonlipid components. Evidence for neutrophil stimulation in the lower respiratory tract of patients with RILD was suggested by elevations in both myeloperoxidase activity and immunologically determined levels of human neutrophil elastase in BAL fluid. Free uninhibited elastolytic activity, however, was not demonstrated, suggesting that adequate protease inhibitor levels were present to inhibit active elastase activity. In addition to elevated myeloperoxidase activity, a potential role for neutrophil-derived oxidant injury was indirectly suggested by the enhanced release of superoxide anion (O2-) from resting normal human blood neutrophils challenged with concentrated BAL fluid from patients with RA and interstitial lung disease. Significant correlations were found between physiologic parameters and the percentage of BAL neutrophils, as well as levels of neutrophil-derived mediators. For example, levels of human neutrophil elastase were strongly correlated with diminished diffusion capacity (r = -0.73, p less than 0.001) and reduced forced vital capacity (r = -0.63, p less than 0.006).(ABSTRACT TRUNCATED AT 250 WORDS)
Garcia
J G
JG
Division of Pulmonary Medicine, Albany Medical College, New York.
James
H L
HL
Zinkgraf
S
S
Perlman
M B
MB
Keogh
B A
BA
D001172:Arthritis, Rheumatoid / Q000150:complications* / Q000503:physiopathology; D001992:Bronchoalveolar Lavage Fluid / Q000032:analysis / Q000166:cytology; D002634:Chemotaxis, Leukocyte; D002908:Chronic Disease; D006801:Humans; D007958:Leukocyte Count; D009504:Neutrophils / Q000502:physiology*; D010196:Pancreatic Elastase / Q000378:metabolism; D009195:Peroxidase / Q000378:metabolism; D011446:Prospective Studies; D011658:Pulmonary Fibrosis / Q000175:diagnosis / Q000209:etiology* / Q000503:physiopathology; D012137:Respiratory System / Q000503:physiopathology*; D013481:Superoxides / Q000378:metabolism
D013481:Superoxides; D009195:Peroxidase; D010196:Pancreatic Elastase