Association of antinuclear antibody seropositivity with inhaled environmental exposures in patients with interstitial lung disease

Background Interstitial lung diseases (ILDs) are diffuse parenchymal lung disorders that cause substantial morbidity and mortality. In patients with ILD, elevated antinuclear antibody (ANA) titres may be a sign of an autoimmune process. Inhalational exposures contribute to ILD pathogenesis and affect prognosis and may trigger autoimmune disease. The association of inhalational exposures with ANA sempositivity in ILD patients is unknown. Methods This was a retrospective cohort study of adult ILD patients from five centres in the United States. Exposures to tobacco, inhaled organic antigens and inhaled inorganic particles were extracted from medical records. A multivariable logistic regression model was used to analyse the effects of confounders including age, ILD diagnosis, gender and exposure type on ANA seropositivity. Results Among 1265 patients with ILD, there were more ANA-seropositive (58.6%, n=741) than ANA-scronegative patients (41.4%, n=524). ANA-seropositive patients had lower total lung capacity (69% versus 75%, p<0.001) and forced vital capacity (64% versus 70%, p<0.001) than patients who were ANA-seronegative. Among patients with tobacco exposure, 61.4% (n=449) were ANA-positive compared to 54. 7% (n=292) of those without tobacco exposure. In multivariable analysis, tobacco exposure remained independently associated with increased ANA seropositivity (OR 1.38, 95% CI 1.12-1.71). This significant difference was similarly demonstrated among patients with and without a history of inorganic exposures (OR 1.52, 95% CI 1.12-2.07). Conclusion Patients with ILD and inhalational exposure had significantly higher prevalence of ANA-sempositivity than those without reported exposures across ILD diagnoses. Environmental and occupational exposures should be systematically reviewed in patients with ILD, particularly those with ANA-seropositivity.