Towards Treatable Traits for Pulmonary Fibrosis

Abstract

Interstitial lung diseases (ILD) are a heterogeneous group of disorders, of which many have the potential to lead to progressive pulmonary fibrosis. A distinction is usually made between primarily inflammatory ILD and primarily fibrotic ILD. As recent studies show that anti-fibrotic drugs can be beneficial in patients with primarily inflammatory ILD that is characterized by progressive pulmonary fibrosis, treatment decisions have become more complicated. In this perspective, we propose that the ‘treatable trait’ concept, which is based on the recognition of relevant exposures, various treatable phenotypes (disease manifestations) or endotypes (shared molecular mechanisms) within a group of diseases, can be applied to progressive pulmonary fibrosis. These targets for medical intervention can be identified through validated biomarkers and are not necessarily related to specific diagnostic labels. Proposed treatable traits are: cigarette smoking, occupational, allergen or drug exposures, excessive (profibrotic) auto- or alloimmunity, progressive pulmonary fibrosis, pulmonary hypertension, obstructive sleep apnea, tuberculosis, exercise intolerance, exertional hypoxia, and anxiety and depression. There are also several potential traits that have not been associated with relevant outcomes or for which no effective treatment is available at present: air pollution, mechanical stress, viral infections, bacterial burden in the lungs, surfactant-related pulmonary fibrosis, telomere-related pulmonary fibrosis, the rs35705950 MUC5B promoter polymorphism, acute exacerbations, gastro-esophageal reflux, dyspnea, and nocturnal hypoxia. The ‘treatable traits’ concept can be applied in new clinical trials for patients with progressive pulmonary fibrosis and could be used for developing new treatment strategies.

The challenge of tobacco and nicotine use among women

“…ILDs are a heterogeneous group of lung disorders; several may lead to progressive pulmonary fibrosis 37 . There is a higher ILD prevalence in women related to connective tissue diseases and hypersensitivity pneumonitis (HP); home environmental antigens are mostly responsible for this gender-difference.…”

“…There is a higher ILD prevalence in women related to connective tissue diseases and hypersensitivity pneumonitis (HP); home environmental antigens are mostly responsible for this gender-difference. Because they can have extremely aggressive behavior, treatable traits for ILDs have been proposed 37 . Smoking is definitely one of them, being linked to more severe HP, worse survival in idiopathic pulmonary fibrosis, and other progressive ILDs.…”