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Purpose: Tripartite motif-containing protein 13 (TRIM13) directly or indirectly participates in autophagy and apoptosis. However, it remains unclear whether TRIM13 participates in chronic obstructive pulmonary disease (COPD) progression. This study aimed to reveal the molecular mechanisms through which TRIM13 regulates alveolar epithelial cell injury in COPD to provide new molecular targets for COPD treatment.

Methods: The TRIM13 expression levels were determined in clinical COPD patients and a rat emphysema model. A cigarette smoke-induced model of endoplasmic reticulum stress (ERS) and endoplasmic reticulum autophagy (ER-phagy) was developed using A549 cells, and the effects of TRIM13 gene overexpression/knockdown on ERS, ER-phagy, and cell apoptosis were assessed in these cells.

Results: TRIM13 expression was significantly decreased in the lung tissues of COPD patients and rats with emphysema. Moreover, the apoptosis level was significantly increased in the lung tissues of rats with emphysema. TRIM13 gene overexpression reduced the expression levels of ERS-related molecules (GRP78, GRP94, XBP-1, and eIF2a) in the COPD model; it also lowered the ER-phagy level, as evidenced by decreased number of autolysosomes observed by transmission electron microscopy, improved endoplasmic reticulum structure, reduced LC3-II/LC3-I and Beclin1 expression levels, and increased expression level of the autophagy inhibitory molecule Bcl-2. TRIM13 gene knockdown, however, led to opposite results.

Conclusion: TRIM13 expression attenuated alveolar epithelial cell injury in COPD by inhibiting ERS-induced ER-phagy.

Background: Asthma is associated with accelerated rate of FEV₁ decline.

Objective: To determine predictive factors associated with accelerated FEV₁ decline in adult asthma and evaluate sputum cytokines as potential biomarkers for airflow decline.

Methods: We recruited 125 asthmatics evaluated at the asthma clinic of Liège and reevaluated them at least 5 years later. Clinical, functional and inflammatory characteristics were compared between patients with accelerated decline (FEV₁ decline > 0.85% pred.y^-1) and others. Predictive factors were highlighted with linear regression analysis. Sputum EGF, VEGF, FGF, IL5, IL8, TGF-β, and IgE levels were measured in 58 of these patients at both visits by Human XL cytokine Luminex Performance assay and Elisa.

Results: Post-BD FEV₁ decline was 0.06 ± 2.44% pred.y^-1 in the overall population. Median (IQR) time between visits was 66 (62 - 86) months. The multivariable analysis showed that an increase in blood eosinophils over time (Δ BEC) (Reg. Coef. (95%CI): 0.002 (0.001 to 0.004), p = 0.005)) and onset of asthma (0.04 (0.003 to 0.07), p = 0.036) were independently associated with FEV₁ decline. IL8 levels measured at baseline were higher (499 (408-603) pg/ml, p = 0.0040) in patients with accelerated decline compared to others (143 (88-308) pg/ml).

Conclusion: In this study, we have confirmed that an increase in blood eosinophil counts over a follow-up of at least 5 years and later onset of asthma are associated with accelerated annual FEV₁ decline. Moreover, high sputum IL8 levels could be a risk factor for accelerated decline in asthma patients.

Purpose: In people with cystic fibrosis (pwCF), elexacaftor/tezacaftor/ivacaftor (ETI) therapy is associated with an average improvement in FEV₁ of 10-14%. However, a subset of individuals fails to achieve a clinically meaningful increase in spirometric indicators. In this study, we aimed to assess whether the lung clearance index (LCI_2.5), a more sensitive indicator of lung involvement, improves following ETI initiation in this population.

Methods: We conducted a prospective observational study in a specialized CF center in Italy. PwCF performed a spirometry and a multiple breath nitrogen washout test the day they initiated ETI therapy and after 6 and 12 months. They were grouped according to the 12-month change in FEV₁ into two groups: Individuals who experienced a change in FEV₁ ≥ a minimal clinically important difference (MCID) of 3% and those who did not. Mean changes in LCI_2.5 were estimated using generalized estimating equations.

Results: The study included 129 pwCF who initiated ETI at our center (Age Range: 12-36 years). In 20 subjects (15.5%), the FEV₁ change was < MCID. These individuals had better baseline pulmonary function than those with FEV₁ changes ≥ MCID (Median FEV₁: 102.5 vs 87.0%), with the majority (90%) having FEV₁ values ≥ 90%. Mean changes in LCI_2.5 at 12-month follow-up visit were - 1.44 units (95% CI: - 2.12; - 0.75) in individuals with changes in FEV₁ < MCID and - 2.64 units (95% CI: -3.05; -2.23) in those with values ≥ MCID.

Conclusion: LCI_2.5 is a useful measure to monitor the effectiveness of ETI in pwCF with normal spirometry and limited FEV₁ change following treatment initiation.

Purpose: To clarify the associations of climatic indices with chronic respiratory symptoms, with a final aim to approximate the effects of climate change on them.

Methods: An e-mail survey was directed to the members of the Finnish Pensioners` Federation. The mean 20-years' precipitation and temperature in each subjects' home municipality were obtained from the Finnish Meteorological Institute, separately for summer and winter. Adjusted multivariate models were utilized to investigate the associations of the climatic indices with chronic rhinosinusitis, chronic cough, wheezing with dyspnea, and sleep apnea.

Results: There were 6189 responders from 283 municipalities. Chronic rhinosinusitis and chronic cough were most prevalent in the southeastern regions of the country, where the precipitation counts were highest. In the multivariate models, winter precipitation in the home municipality increased the risks of chronic rhinosinusitis and chronic cough [adjusted OR 1.80 (1.30-2.51) per 100 mm, p < 0.001, and 1.57 (1.19-2.07) per 100 mm, p = 0.001, respectively]. Wheezing with dyspnea and sleep apnea were not associated with the climatic indices.

Conclusion: Chronic rhinosinusitis and chronic cough were associated with long-term winter precipitation. Given the anticipated increase in winter precipitation in Northern America and Northern Europe, the prevalences of chronic rhinosinusitis and chronic cough may increase there.

Purpose: Anxiety and depression are often underdiagnosed in patients with chronic obstructive pulmonary disease (COPD). This study aimed to develop and validate a screening tool for anxiety and depression in COPD patients.

Methods: Stable COPD patients were consecutively recruited from November 2021 to October 2023 and underwent a psychiatric interview to diagnose generalized anxiety disorder (GAD) and/or major depressive disorder (MDD) based on the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition. Patients were split into training and validation sets according to their recruitment time. We assessed known risk factors and used core items from the Patient Health Questionnaire Anxiety and Depression Scale (PHQ-ADS) to develop a prediction nomogram. Multivariable logistic regression with least absolute shrinkage and selection operator (LASSO) were used to construct the nomogram.

Results: Among the enrolled COPD patients (n = 329), 58 (25.6%) in the training cohort and 33 (32.4%) in the validation cohort were diagnosed with GAD and/or MDD. Three variables were identified in the prediction nomogram: COPD Assessment Test score and two core items from PHQ-ADS. The under the curve (AUC) value for the nomogram was 0.826 (95% CI: 0.755-0.897) and 0.855 (95% CI: 0.767-0.942) in the training and validation cohorts, respectively. The calibration curve was close to the diagonal. The discriminatory power of the screening nomogram was comparable to that of PHQ-ADS (AUC: 0.826 vs. 0.831, P = 0.832).

Conclusion: The new screening tool for GAD and MDD in COPD patients is concise and valid, with discriminatory power comparable to existing anxiety/depression screening questionnaires.

Purpose: Inhaled mannitol induces bronchoconstriction and cough. This study aimed to describe the cough response to mannitol among healthy adult subjects.

Methods: 125 healthy subjects (aged 18-82 years, 52% females, 50% skin prick test positive) underwent a mannitol test. The coughs were recorded both simultaneously and afterwards from video recordings by two researchers. Three indices were evaluated: The cumulative number of coughs per cumulative dose of mannitol (CDR), cumulative provocative dose of mannitol to cause at least 5 coughs, and the maximal number of coughs provoked by any single mannitol dose. The test was repeated in 26 subjects after 3-7 days.

Results: CDR showed the best repeatability with an intraclass correlation coefficient of 0.829. Gender was the only characteristics that associated with the cough response: The median CDR was 2.53 (interquartile range 0.45-7.01) coughs/100 mg among females and 0.787 (0.0-3.29) coughs/100 mg among males (p = 0.002). The interquartile range upper limits were defined as the cut-off limits for a normal response. The threshold for a statistically significant change in CDR was 6.26 coughs/100 mg. There was a close correlation between simultaneous- and video-assessed CDR (intraclass correlation coefficient 0.985).

Conclusion: Females cough more than males in response to mannitol. CDR is the most suitable index to describe the cough responsiveness. The repeatability of the response is good. Video recording of the coughs is not mandatory. The cut-off limits for a normal cough response to mannitol were provided.

Objectives: Examine the association of asthma, COPD, and Asthma-COPD overlap (ACO) on rates of lung cancer screening.

Methods: 2022 Behavior and Risk Factors Surveillance Survey was used for cross-sectional analysis of self-reported lung cancer screening prevalence in those with COPD, asthma, and ACO, with stratification by smoking status. Multivariate logistic regression was performed to assess the relationship between asthma, COPD, ACO and lung cancer screening status.

Results: 17.9% of eligible adults were up-to-date on lung cancer screening. Those with COPD and ACO had higher rates of ever undergoing lung cancer screening (50.8% and 47.5%) than those with asthma (26.4%) or neither condition (23%). Adults with COPD (adjusted odds ratios (aOR): 2.86, 95% CI 2.49-3.28) and ACO (aOR: 2.85, 95% CI 2.49-3.28) had increased odds of ever having lung cancer screening compared with those without either condition. Stratification by smoking status shows that individuals who formerly smoked had slightly higher odds of ever undergoing screening than individuals currently smoking.

Conclusion: Lung cancer screening rates have increased; however, it remains low. Adults with COPD and ACO are more likely to undergo lung cancer screening.

Purpose: Methotrexate (MTX)-induced pulmonary fibrosis is associated with high morbidity and mortality, with limited treatment options available. This study investigates whether disulfiram (DSF) can mitigate MTX-induced pulmonary fibrosis and explores the underlying mechanisms.

Methods: Eight-week-old male mice were divided into control, DSF, MTX, and MTX+DSF groups and treated for 8 weeks. Weight, food, and water intake were monitored. Post-treatment, lung tissues were analyzed using HE and Masson staining, and electron microscopy. Real-time qPCR and ELISA were employed to assess inflammatory markers such as IL-1β and TNF-α in lung tissues and serum. PCR, ELISA, and Western blot were used for fibrotic markers including Col1α1, α-SMA, and hydroxyproline. Type 2 alveolar epithelial cell line MLE12 cells were similarly grouped, followed by RNA sequencing and bioinformatics analysis to elucidate the mechanisms by which DSF exerts anti-MTX-induced pulmonary fibrosis effects. ELISA and Western blot were used to measure E-cadherin and α-SMA expression.

Results: DSF significantly reduced MTX-induced alveolar septal thickening, pulmonary fibrosis, and inflammatory cell infiltration. It also decreased the expression of inflammatory factors IL-1β and TNF-α, as well as the expression of Col1α1, α-SMA, and others. RNA-seq revealed that DSF induces changes in multiple signaling pathways associated with pulmonary fibrosis, particularly in extracellular matrix-related genes. ELISA and Western blot showed decreased E-cadherin and increased α-SMA in the MTX group, which was partially restored with DSF treatment.

Conclusion: DSF alleviates MTX-induced pulmonary fibrosis by reducing epithelial-mesenchymal transition (EMT) in type 2 alveolar epithelial cells. Disulfiram shows potential as a therapeutic agent for MTX-induced pulmonary fibrosis.

FOXM1, a key member of the FOX transcription factor family, maintains cell homeostasis by accurately controlling diverse biological processes, such as proliferation, cell cycle progression, differentiation, DNA damage repair, tissue homeostasis, angiogenesis, apoptosis, redox signaling, and drug resistance. In recent years, an increasing number of studies have focused on the role of FOXM1 in the occurrence of multiple diseases and various pathophysiological processes. In the field of pulmonary diseases, FOXM1 has a certain reparative effect by promoting cell proliferation, regulating cell cycle, antifibrosis, participating in inflammation regulation, and synergizing with other signaling pathways. On the basis of the repair properties of FOXM1, this review explores its therapeutic potential in acute lung injury/acute respiratory distress syndrome, asthma, chronic obstructive pulmonary disease, idiopathic pulmonary fibrosis, pulmonary arterial hypertension, lung cancer, and other lung diseases, with the goal of providing a new perspective for the analysis of FOXM1-related mechanism of action and the expansion of clinical treatment strategies.