The burden of nonsmoker COPD was considerable. Older age, male sex, lower BMI, self-reported asthma, and self-reported tuberculosis were risk factors for nonsmoker COPD and there were differences between nonsmoker and smoker COPD in terms of sex, comorbidities, and HRQoL.

Background Diagnostic cutoff points for sarcopenia in chest computed tomography (CT) have not been established although CT is widely used for investigating skeletal muscles. This study aimed to determine reference values for sarcopenia of thoracic skeletal muscles acquired from chest CT scans and to analyse variables related to sarcopenia using the cutoff values determined in a general Asian population. Methods We retrospectively reviewed chest CT scans of 4470 participants (mean age 54.8 ± 9.9 years, 65.8% male) performed at a check‐up centre in South Korea (January 2016–August 2017). To determine cutoffs, 335 participants aged 19–39 years (mean age 35.2 ± 3.6 years, 75.2% male) were selected as the healthy and younger reference group, and 4135 participants aged ≥40 years (mean age 56.4 ± 8.4 years, 65.1% male) were selected as the study group. We measured the following: cross‐sectional area (CSA) of the pectoralis, intercostalis, paraspinal, serratus, and latissimus muscles at the 4th vertebral region (T4CSA); T4CSA divided by height2 (T4MI); pectoralis muscle area (PMCSA); and PMCSA divided by height2 (PMI) at the 4th vertebral region. Sarcopenia cutoff was defined as sex‐specific values of less than −2 SD below the mean from the reference group. Results In the reference group, T4CSA, T4MI, PMCSA, and PMI cutoffs for sarcopenia were 100.06cm2, 33.69cm2/m2, 29.00cm2, and 10.17cm2/m2 in male, and 66.93cm2, 26.01cm2/m2, 18.29cm2, and 7.31cm2/m2 in female, respectively. The prevalence of sarcopenia in the study group measured with T4CSA, T4MI, PMCSA and PMI cutoffs were 11.4%, 8.7%, 8.5%, and 10.1%, respectively. Correlations were observed between appendicular skeletal mass divided by height2 measured by bioelectrical impedance analysis (BIA) and T4CSA (r = 0.82; P < 0.001)/T4MI (r = 0.68; P < 0.001), and ASM/height2 measured by BIA and PMCSA (r = 0.72; P < 0.001)/PMI (r = 0.63; P < 0.001). In the multivariate logistic regression models, sarcopenia defined by T4CSA/T4MI were related to age [odds ratio (95% confidence interval), P‐values: 1.09 (1.07–1.11), <0.001/1.05 (1.04–1.07), <0.001] and diabetes [1.60 (1.14–2.25), 0.007/1.47 (1.01–2.14), 0.043]. Sarcopenia defined by PMCSA/PMI were related to age [1.09 (1.08–1.10), <0.001/1.05 (1.03–1.06), <0.001], male sex [0.23 (0.18–0.30), <0.001/0.47 (0.32–0.71), <0.001], diabetes [2.30 (1.73–3.05), <0.001/1.63 (1.15–2.32), 0.007], history of cancer [2.51 (1.78–3.55), <0.001/1.61 (1.04–2.48), 0.033], and sufficient physical activity [0.67 (0.50–0.89), 0.007/0.74 (0.56–0.99), 0.042]. Conclusions The reference cutoff values of a general population reported here will enable sex‐specific standardization of thoracic muscle mass quantification and sarcopenia assessment.

Dysfunction of mitochondrial metabolism is implicated in cellular injury and cell death. While mitochondrial dysfunction is associated with lung injury by lung inflammation, the mechanism by which the impairment of mitochondrial ATP synthesis regulates necroptosis during acute lung injury (ALI) by lung inflammation is unclear. Here, we showed that the impairment of mitochondrial ATP synthesis induces receptor interacting serine/threonine kinase 3 (RIPK3)-dependent necroptosis during lung injury by lung inflammation. We found that the impairment of mitochondrial ATP synthesis by oligomycin, an inhibitor of ATP synthase, resulted in increased lung injury and RIPK3 levels in lung tissues during lung inflammation by LPS in mice. The elevated RIPK3 and RIPK3 phosphorylation levels by oligomycin resulted in high mixed lineage kinase domain-like (MLKL) phosphorylation, the terminal molecule in necroptotic cell death pathway, in lung epithelial cells during lung inflammation. Moreover, the levels of protein in bronchoalveolar lavage fluid (BALF) were increased by the activation of necroptosis via oligomycin during lung inflammation. Furthermore, the levels of ATP5A, a catalytic subunit of the mitochondrial ATP synthase complex for ATP synthesis, were reduced in lung epithelial cells of lung tissues from patients with acute respiratory distress syndrome (ARDS), the most severe form of ALI. The levels of RIPK3, RIPK3 phosphorylation and MLKL phosphorylation were elevated in lung epithelial cells in patients with ARDS. Our results suggest that the impairment of mitochondrial ATP synthesis induces RIPK3-dependent necroptosis in lung epithelial cells during lung injury by lung inflammation.