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Influenza viruses can result in significant lung injury with significant morbidity and mortality. In this study, we evaluated the impact of cigarette smoke (CS) exposure on the pulmonary fibroblastic response after influenza infection. We used a murine model in which animals were exposed to CS or room air and subsequently infected with H1N1 influenza virus. Inflammatory and fibrotic responses were measured at different time points after influenza infection. Primary fibroblasts were isolated from the lungs of mice and their characteristics were evaluated. Exposure to CS significantly increased the amount of collagen in the lungs of mice infected with influenza virus compared with the nonsmoking group at 30 days after infection. Furthermore, the presence of fibroblast-specific protein–positive cells increased in the lungs of influenza-infected mice that were exposed to CS compared with the infection-alone group. The smoking group also showed delays in weight recovery and higher cell counts in BAL fluid after infection. Active transforming growth factor β1 levels in BAL fluid increased in both groups; however, CS-exposed mice had a later surge in active transforming growth factor β1 (Day 24). Ex vivo cultures of lung-derived fibroblasts from CS-exposed mice with influenza infection showed rapid proliferation, increased expression of α-smooth muscle actin–stained stress fibers, and higher expression of growth factors compared with fibroblasts from room air–exposed lungs after infection. These results suggest that CS exposure changes the fibroblastic potential, leading to increased fibrosis after influenza infection. [ABSTRACT FROM AUTHOR]

Rationale: We previously showed that the choice of levofloxacin or moxifloxacin for the treatment of patients with fluoroquinolone-sensitive multidrug-resistant tuberculosis (MDR-TB) did not affect sputum culture conversion at 3 months of treatment.Objectives: To compare final treatment outcomes between patients with MDR-TB randomized to levofloxacin or moxifloxacin.Methods: A total of 151 participants with MDR-TB who were included for the final analysis in our previous trial were followed through the end of treatment. Treatment outcomes were compared between 77 patients in the levofloxacin group and 74 in the moxifloxacin group, based on the 2008 World Health Organization definitions as well as 2013 revised definitions of treatment outcomes. In addition, the time to culture conversion was compared between the two groups.Measurements and Main Results: Treatment outcomes were not different between the two groups, based on 2008 World Health Organization definitions as well as 2013 definitions. With 2008 definitions, cure was achieved in 54 patients (70.1%) in the levofloxacin group and 54 (73.0%) in the moxifloxacin group (P = 0.72). Treatment success rates, including cure and treatment completed, were not different between the two groups (87.0 vs. 81.1%, P = 0.38). With 2013 definitions, cure rates (83.1 vs. 78.4%, P = 0.54) and treatment success rates (84.4 vs. 79.7%, P = 0.53) were also similar between the levofloxacin and moxifloxacin groups. Time to culture conversion was also not different between the two groups (27.0 vs. 45.0 d, P = 0.11 on liquid media; 17.0 vs. 42.0 d, P = 0.14 on solid media). Patients in the levofloxacin group had more adverse events than those in the moxifloxacin group (79.2 vs. 63.5%, P = 0.03), especially musculoskeletal ones (37.7 vs. 14.9%, P = 0.001).Conclusions: The choice of levofloxacin or moxifloxacin made no difference to the final treatment outcome among patients with fluoroquinolone-sensitive MDR-TB. Clinical trial registered with www.clinicalrials.gov (NCT01055145). [ABSTRACT FROM AUTHOR]