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Biological sex, gender and race are important considerations in patients with interstitial lung diseases (ILD).Do patient's sex assigned at birth and race influence ILD treatment initiation?Patients with ILD from three longitudinal prospective registries were compared in this observational study. ILD-related medications included antifibrotics and immunomodulating medications. Race was dichotomized as "White" vs non-White". Time to treatment initiation was determined from the date of initial ILD registry visit to the date of first medication initiation. Proportions of treated patients were compared between groups using Chi2 test. Cox proportional analysis was used to determine how sex and race was associated with time to treatment initiation stratified by ILD diagnosis.A total of 4572 patients were included across all cohorts. The proportion of men who received treatment was higher than for women in the Canadian cohort (47 vs 40%, p,0.001), and the proportion of White patients who received treatment was also higher compared to non-Whites (46 vs 36%, p0.001). In contrast, the proportion of treated men in the Chicago cohort was lower compared to women (56 vs 64%, p=0.005), and that of White patients was lower compared to non-Whites (56 vs 69%, p0.001). No sex- or race-based differences in proportions of patients treated were found in the Australasian cohort. White race was significantly associated with earlier treatment initiation compared to non-White patients across diagnoses in the Canadian cohort, while the opposite association was found in the Australasian cohort.Sex- and racial-based differences exist in the initiation of ILD treatment, with variability across different cohorts in different countries. Reasons for these differences need to be further explored in future studies.

SummaryBackgroundPulmonary rehabilitation improves outcomes in patients with interstitial lung disease (ILD), however it is unclear whether these effects are long lasting and which patients benefit most.MethodsPatients with ILD were recruited into this prospective cohort study from three pulmonary rehabilitation programs. Patients completed functional assessments (6-minute walk distance (6MWD), and 4-meter walk time) and surveys (quality of life, dyspnea, depression, and physical activity) before rehabilitation, after rehabilitation, and at six months. Changes from baseline were compared using a paired t-test. Independent predictors of change in 6MWD and quality of life were determined using multivariate analysis.ResultsFifty-four patients were recruited (22 with idiopathic pulmonary fibrosis), 50 patients (93%) completed the rehabilitation program, and 39 returned for six-month follow-up. 6MWD improved 57.6 m immediately after rehabilitation (95% confidence interval (CI) 40.2–75.1 m, p

Transforming growth factor-beta-1 (TGF-beta1) is secreted by cells in a latent form (L-TGF-beta1) noncovalently bound to a latency-associated peptide. Activated alveolar macrophages obtained from rat lungs after bleomycin-induced pulmonary injury released increased amounts of active TGF-beta1 as well as plasmin, a protease, and thrombospondin-1 (TSP-1), a trimeric glycoprotein. Previously we had demonstrated that plasmin was critical to the activation of L-TGF- beta1. In the present study we demonstrated that TSP-1 is also important for the activation of L-TGF- beta1 because the activation can be inhibited by anti-TSP-1 monoclonal antibody. Proteins obtained from alveolar macrophage cell lysates immunoprecipitated with antibodies specific for TSP-1 were identified on immunoblots as LAP and TGF-beta1, indicating that TSP-1/L-TGF-beta1 complexes are present on alveolar macrophages. However, in the presence of plasmin both latency-associated peptide and TGF-beta1 were decreased in the same cell lysates, indicating that L-TGF-beta1 associated with TSP-1 is released by plasmin. Using immunofluorescence and antibodies to TGF-beta1 and CD36, a receptor for TSP-1, there was colocalization of TGF-beta1 with CD36. Because TSP-1 but not TGF-beta1 is a natural ligand for CD36, these findings suggest that the L-TGF-beta1 in a complex with TSP-1 localizes to the macrophage cell surface when TSP-1 interacts with its receptor, CD36. Furthermore, the association of TSP-1/L-TGF-beta1 complex with CD36 is necessary to the activation of L-TGF-beta1 because antibodies to CD36 prevent the colocalization of TGF-beta1 with CD36 as observed by immunofluorescence and inhibit activation of the L-TGF-beta1 by explanted alveolar macrophages. These findings suggest that activation of L-TGF-beta1 by plasmin occurs at the cell surface of activated alveolar macrophages and requires a TSP-1/CD36 interaction.