Chronic obstructive pulmonary disease (COPD) is commonly staged according to the percentage of predicted forced expiratory volume in 1 s (FEV₁% pred), but other methods have been proposed. In this study we compared the performance of seven staging methods in predicting outcomes.We retrospectively studied 296 COPD outpatients. For each patient the disease severity was staged by separately applying the following methods: the criteria proposed by the Global Initiative for Chronic Obstructive Lung Disease (GOLD), quartiles of FEV₁% pred and z-score of FEV₁, quartiles and specified cut-off points of the ratio of FEV₁over height squared ((FEV₁·Ht⁻²)_Aand (FEV₁·Ht⁻²)_B, respectively), and quartiles of the ratio of FEV₁over height cubed (FEV₁·Ht⁻³) and of FEV₁quotient (FEV₁Q). We evaluated the performance of these methods in predicting the risks of severe acute exacerbation and all-cause mortality.Overall, staging based on the reference-independent FEV₁Q performed best in predicting the risks of severe acute exacerbation (including frequent exacerbation) and mortality, followed by (FEV₁·Ht⁻²)_B. The performance of staging methods could also be influenced by the choice of cut-off values. Future work using large and ethnically diverse populations to refine and validate the cut-off values would enhance the prediction of outcomes.

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 (D_LCO) < 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 D_LCO). 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.

Background and objective: A multidimensional assessment of COPD was recommended by the Global Initiative for Chronic Obstructive Lung Disease (GOLD) in 2013 and revised in 2017. We examined the ability of the GOLD 2017 and the new 16 subgroup (1A–4D) classifications to predict clinical outcomes, including exacerbation and mortality, and compared them with the GOLD 2013 classifications. Methods: Patients with COPD were recruited from January 2006 to December 2017. The predictive abilities of grades 1–4 and groups A–D were examined through a logistic regression analysis with receiver operating curve estimations and area under the curve (AUC). Results: A total of 553 subjects with COPD were analyzed. The mortality rate was 48.6% during a median follow-up period of 5.2 years. Both the GOLD 2017 and the 2013 group A–D classifications had good predictive ability for total and severe exacerbations, for which the AUCs were 0.79 vs 0.77 and 0.79 vs 0.78, respectively. The AUCs for the GOLD 2017 groups A–D, grades 1–4, and the GOLD 2013 group A–D classifications were 0.70, 0.66, and 0.70 for all-cause mortality and 0.73, 0.71, and 0.74 for respiratory cause mortality, respectively. Combining the spirometric staging with the grouping for the GOLD 2017 subgroups (1A–4D), the all-cause mortality rate for group B and D patients was significantly increased from subgroups 1B–4B (27.7%, 50.6%, 53.3%, and 69.2%, respectively) and groups 1D–4D (55.0%, 68.8%, 82.1%, and 90.5%, respectively). The AUCs of subgroups (1A–4D) were 0.73 and 0.77 for all-cause and respiratory mortality, respectively; the new classification was determined more accurate than the GOLD 2017 for predicting mortality (P<0.0001). Conclusion: The GOLD 2017 classification performed well by identifying individuals at risk of exacerbation, but its predictive ability for mortality was poor among COPD patients. Combining the spirometric staging with the grouping increased the predictive ability for all-cause and respiratory mortality. Summary at a glance: We validate the ability of the GOLD 2017 and 16 subgroup (1A–4D) classifications to predict clinical outcome for COPD patients. The GOLD 2017 classification performed well by identifying individuals at risk of exacerbation, but its predictive ability for mortality was poor. The new 16 subgroup (1A–4D) classification combining the spirometric 1–4 staging and the A–D grouping increased the predictive ability for mortality and was better than the GOLD 2017 for predicting all-cause and respiratory mortality among COPD patients.

This study tests our hypothesis that patients with chronic obstructive pulmonary disease (COPD) have an increased risk of traumatic brain injury (TBI). In this nationwide retrospective cohort study, we used a subset of Taiwan's National Health Insurance Research Database, involving 1 million randomly selected beneficiaries. Patients with newly diagnosed COPD between 2000 and 2008 were identified. They were subgrouped as ‘COPD_AE+’ (if they had severe acute exacerbation of COPD during the follow-ups) or ‘COPD_AE−’ (if they had no acute exacerbation), and were frequency matched with randomly selected subjects without COPD (the ‘non-COPD’ group). Baseline differences were balanced by the inverse probability of treatment weighting based on the propensity score. For each patient, the risk of TBI during the subsequent 5 years was determined. The competing risk of death was controlled. We identified 3734 patients in ‘COPD_AE+’, and frequency matched them with 11,202 patients in ‘COPD_AE−’ and 11,202 subjects in ‘non-COPD’. Compared with those in ‘non-COPD’, patients in ‘COPD_AE+’ and ‘COPD_AE−’ had an increased risk of TBI: the adjusted HR for ‘COPD_AE+’ was 1.50, 95% CI 1.31 to 1.73, and that for ‘COPD_AE−’ was 1.21, 95% CI 1.09 to 1.34. The highest risk was observed in the ‘COPD_AE+’ group that aged <65 (the adjusted HR was 1.92; 95% CI 1.39 to 2.64). COPD has been linked to complications beyond the respiratory system. In this study we showed that COPD is associated with an increased risk of TBI.

Relapsing polychondritis (RP) is a rare autoimmune disorder, characterized by the inflammation of cartilaginous structures and proteoglycan‐rich tissues. Due to its rarity and the notoriously variable presentations, the diagnosis of RP could be challenging. We report an unusual case of RP with isolated tracheal involvement and very non‐specific symptoms of exertional dyspnoea and dry cough. The initial chest radiograph showed long‐segment narrowing of the trachea, and the computed tomography of the chest revealed thickened cartilaginous walls of the trachea, while the posterior membranous portion was spared. The tracheal narrowing was readily observed under bronchoscopy. The patient was treated with oral prednisolone. Although the subsequent course was transiently complicated by an episode of severePneumocystis jiroveciipneumonia with acute respiratory distress syndrome, the patient overall responded well to systemic corticosteroid therapy. No new symptoms developed during a two‐year follow‐up.

Lung cancer remains a formidable health challenge due to its high mortality and morbidity rates. Non-small cell lung cancer (NSCLC) constitutes approximately 85% of all lung cancer cases, with small cell lung cancer (SCLC) accounting for the remainder. Both NSCLC and SCLC cells express receptor tyrosine kinases, which may be overexpressed or mutated in lung cancer, leading to increased activation. The c-Met receptor tyrosine kinase, crucial for cell transformation and tumor growth, invasion, and metastasis, became the focus of our study. We used an E1B55KD-deleted, replication-selective oncolytic adenovirus (Ad.What), driven by the c-Met promoter, targeting lung cancer cells with c-Met overexpression, thus sparing normal cells. Previous studies have shown the enhanced antitumor efficacy of oncolytic adenoviruses when combined with chemotherapeutic agents. We explored combining rapamycin, a selective mTOR inhibitor with promising clinical trial outcomes for various cancers, with Ad.What. This combination increased infectivity by augmenting the expression of coxsackievirus and adenovirus receptors and αV integrin on cancer cells and induced autophagy. Our findings suggest that combining a c-Met promoter-driven oncolytic adenovirus with rapamycin could be an effective lung cancer treatment strategy, offering a targeted approach to exploit lung cancer cells’ vulnerabilities, potentially marking a significant advancement in managing this deadly disease.