Change in lung function in never‐smokers with non‐tuberculous mycobacterial lung disease

Background and Aim: Influenza is one of the major global health problems. Pneumonia secondary to influenza is the major cause of mortality from this. During the resolution of pneumonia, loss of lung function combined with fibrotic change can happen, however the mechanism is still unclear. Furthermore, little is known about the effect of smoking on influenza pneumonia. In this study, we evaluated the impact of smoke exposure on the pulmonary fibroblastic response after influenza infection. Methods: Male 10-11weeks C57BL/6J mice were used for experiments. After 2weeks of exposure to smoking (smoking group) or air (nonsmoking group), mice were infected with H1N1 influenza intranasally. The amount of collagen in right lung is analyzed with Sircol assay. TGFβ1 in bronchoalveolar fluid (BAL) were measured with ELISA. Primary fibroblasts were isolated from the lung of mice. Results: The amount of collagen in right lung increased after influenza infection, however the amount between the smoking and nonsmoking group were not different up to 15 days. Interestingly, collagen increased more in the smoking group, causing significant higher amount in compared to the non-smoking group on 30 days after infection (465.8 24.01ug vs. 295.4 23.4, P=0.036). Mean linear intercepts and lung volume were also increased in the smoking group compared to nonsmoking group. Active TGFβ1 levels in the BAL fluid increased in both groups after infection. The level was greater in non-smoking group at an early phase (day 6), but the level was greater in smoking mice at a later phase (day 24). In ex-vivo model, fibroblasts isolated from the smoking group infected with influenza showed rapid proliferation with increased expression of various growth factors and stress fibers. Conclusion: Smoking changes the fibroblastic process after influenza infection. It induced more fibrosis with a delayed increase in TGFβ1 and transformed characteristics of fibroblast.