Background Nintedanib is effective for treating idiopathic pulmonary fibrosis (IPF), but some patients may exhibit a suboptimal response and develop on-treatment acute exacerbation (AE-IPF), hepatic injury, or mortality. It remains unclear which patients are at risk for these adverse outcomes. Methods We analysed the demographic and clinical data, baseline plasma levels of Krebs von den Lungen-6 (KL-6) and surfactant protein A (SPA), and longitudinal clinical courses of a real-world cohort of IPF patients who received nintedanib ≥ 14 days between March 2017 and December 2020. Cox proportional-hazards regression, subdistribution hazards regression, and sensitivity analyses were performed to investigate the association between baseline predictors and AE-IPF, mortality, and nintedanib-related hepatic injury. The relationship between baseline predictors and pulmonary function decline was determined. Results Fifty-seven patients were included, of whom 24 (42%) developed hepatic injury, 20 (35%) had AE-IPF, and 16 (28%) died on-treatment. A baseline plasma KL-6 level ≥ 2.5 ng/mL, and diffusion capacity for carbon monoxide (DLCO) < 55% predicted, were associated with increased risk of hepatic injury (adjusted hazard ratio [aHR] was 3.46; 95% CI 1.13–10.60; p = 0.029 for KL-6, and 6.05; 95% CI 1.89–19.32; p = 0.002 for DLCO). Both factors also predicted severe and recurrent hepatic injury. Patients with baseline KL-6 ≥ 2.5 ng/mL also had a higher risk of AE-IPF (aHR 4.52; 95% CI 1.63–12.55; p = 0.004). For on-treatment mortality, baseline KL-6 ≥ 3.5 ng/mL and SPA ≥ 600 pg/mL were significant predictors (aHR 5.39; 95% CI 1.16–24.97; p = 0.031 for KL-6, and aHR 12.28; 95% CI 2.06–73.05; p = 0.006 for SPA). Results from subdistribution hazard regression and sensitivity analyses supported these findings. Patients with elevated baseline plasma KL-6 levels also exhibited a trend towards faster pulmonary function decline. Conclusions For patients with IPF who are receiving nintedanib, we have identified baseline predictors, in particular plasma KL-6 levels, for the risk of adverse outcomes. Patients with these predictors may require close monitoring for unfavourable responses during treatment. Our findings also support the prognostic role of molecular markers like KL-6 and may contribute to future formulation of more individualized therapeutic strategies for IPF.

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BackgroundSmoking behavior differs between the sexes. Weight control is one of the main reasons leading to tobacco abuse in women but not in men. Studies on the predictive factors of cessation failure between sexes are scarce. This study is aim to investigate whether there are sex differences in the effect of weight gain on smoking cessation rate.MethodsParticipants in the smoking-cessation program at a Medical Center in Taiwan between 2018 and 2019 were included. Details of age, sex, comorbidities, depression screening, nicotine dependence, body weight, and cessation medications of the participants were collected. The participants were classified based on their sex, and multivariable logistic regression analyses were conducted. Multivariable logistic regression analyses were performed for sensitivity analysis after stratifying the participants according to their weight loss (weight loss ≥ 1.5 kg and weight loss ≥ 3.0 kg).ResultsA total of 1,475 participants were included. The body-weight gain in women was associated with failed abstinence (adjusted odds ratio (OR): 3.10, 95% CI: 1.10–9.04). In contrast, body-weight gain in men was associated with successful 6-month prolonged abstinence (adjusted OR: 0.77, 95% CI: 0.61–0.98). The adjusted ORs for any body-weight loss, body-weight loss ≥1.5 kg, and body-weight loss ≥3.0 kg were 0.28 (95% CI: 0.09–0.88), 0.14 (95% CI: 0.03–0.55), and 0.03 (95% CI: 0.01–0.42), respectively.ConclusionBody-weight gain in women during a hospital-based smoking-cessation program is associated with abstinence failure. Further multicenter studies, including participants of different races and cultural backgrounds, are warranted.