Lung最新文献

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.

Purpose: In aging populations, the Global Initiative for Obstructive Lung Disease (GOLD) spirometry threshold may misclassify normal spirometry as airflow limitation. The Global Lung Initiative (GLI) method provides age-adjusted criteria. We investigated how the use of GOLD or GLI thresholds in an algorithm affects the classification of elderly smokers into COPD risk phenotypes.

Methods: Using a modified COPDGene algorithm, including exposure, symptoms, and abnormal spirometry, 200 smokers aged 60 years and older were classified into 4 mutually exclusive phenotypes: Phenotype A (no symptoms, normal spirometry; reference), Phenotype B (symptoms, normal spirometry; possible COPD), Phenotype C (no symptoms, abnormal spirometry; possible COPD), and Phenotype D (symptoms, abnormal spirometry; probable COPD). Abnormal spirometry was defined according to the GOLD or GLI criteria. A comparison was made between the GOLD- and GLI-defined phenotypes.

Results: Using GLI criteria/cut-offs, 18.5% (n = 37) had phenotype A (no COPD), 42% (n = 84) had phenotype B (possible COPD), 7.5% (n = 15) had phenotype C (possible COPD), and 32% (n = 64) had phenotype D (probable COPD). Using GOLD criteria cut-offs, 14.5% (n-29) had phenotype A (no COPD); 31% (n = 62) had phenotype B, 11.5% (n = 23) had phenotype C (probable COPD), and 43% (n = 86) had phenotype D (probable COPD). Eight smokers with GOLD phenotype C were reclassified as GLI phenotype A, while 22 with GOLD phenotype D were reclassified as GLI phenotype B. Smokers identified as ‟probable COPD" by GOLD alone (potential false positives) had better spirometry results than those identified as ‟probable COPD" by both GOLD and GLI.

Conclusion: The use of the GOLD threshold in an algorithm resulted in older smokers being classified into more severe COPD risk phenotypes compared to the GLI threshold. This suggests that GOLD may misclassify smokers with less affected phenotypes as having respiratory impairment, potentially leading to unnecessary and harmful treatments.

Background: Free fatty acids (FFAs) are established risk factors for various cardiovascular and metabolic disorders. Elevated FFAs can trigger inflammatory response, which may be associated with the occurrence of acute respiratory distress syndrome (ARDS) in cardiac surgery. In this prospective study, we aimed to investigate the association between circulating FFA and the incidence of ARDS, as well as the length of ICU stay, in patients undergoing off-pump coronary artery bypass grafting (CABG).

Methods: We conducted a single-center, prospective, observational study among patients undergoing off-pump CABG. The primary endpoint was the occurrence of ARDS within 6 days after off-pump CABG. Serum FFA were measured at baseline and 24 h post-procedure, and the difference (Δ-FFA) was calculated.

Results: A total of 180 patients were included in the primary analysis. The median FFA was 2.3 mmol/L (quartile 1 [Q1]-Q3, 1.4-3.2) at baseline and 1.5 mmol/L (Q1-Q3, 0.9-2.3) 24 h after CABG, with a Δ-FFA of 0.6 mmol/L (Q1-Q3, -0.1 to 1.6). Patients with elevated Δ-FFA levels had a significantly higher ARDS occurrence (55.6% vs. 22.2%; P < 0.001). Elevated Δ-FFA after off-pump CABG correlated with a significantly lower PaO₂/FiO₂ ratio, prolonged mechanical ventilation, and extended length of ICU stay. The area under the curve (AUC) of Δ-FFA for predicting ARDS (AUC, 0.758; 95% confidence interval, 0.686-0.831) significantly exceeded the AUC of postoperative FFA (AUC, 0.708; 95% CI 0.628-0.788; P < 0.001).

Conclusions: Elevated Δ-FFA levels correlated with ARDS following off-pump CABG. Monitoring FFA may assist in identifying high-risk patients for ARDS, facilitating timely interventions to improve clinical outcomes.

Purpose: Air trapping, often attested in humans by elevated residual volume (RV) and ratio of RV on total lung capacity (RV/TLC), is frequently observed in asthma. Confirming these alterations in experimental asthma would be important for translational purposes. Herein, lung volumes were investigated in a mouse model of pulmonary allergic inflammation.

Methods: Eight- to 10-week-old male C57BL/6 and BALB/c mice were exposed once daily to intranasal house dust mite (HDM) for 10 consecutive days. All readouts were measured 24 h after the last exposure. Lung volumes were assessed with the flexiVent using a new automated method consisting of degassing the lungs followed by a full-range pressure-volume maneuver. The weight and the volume of the lungs were also measured ex vivo and a lobe was further processed for histological analyses.

Results: HDM exposure led to tissue infiltration with inflammatory cells, goblet cell hyperplasia, thickening of the airway epithelium, and elevated ex vivo lung weight and volume. It also decreased TLC and vital capacity but without affecting RV and RV/TLC. These observations were similar between the two mouse strains.

Conclusion: Alterations of lung volumes in a murine model of pulmonary allergic inflammation are inconsistent with observations made in human asthma. These discrepancies reflect the different means whereby lung volumes are measured between species. The invasive method used herein enables RV to be measured more precisely and without the confounding effect of air trapping, suggesting that changes in RV and RV/TLC using this method in mice should be interpreted differently than in humans.

Purpose: Lung transplantation (LTx) is a potential intervention for end-stage COVID-19 lung disease. Current literature is sparse regarding the outcomes of LTx for COVID-19 related acute respiratory distress syndrome (ARDS) and pulmonary fibrosis (PF). This study aims to characterize outcomes and patterns of LTx for COVID-19 related lung disease throughout the pandemic.

Methods: Patients who underwent LTx during the pandemic for COVID-19 related lung disease were retrospectively identified using the UNOS registry. Demographics, as well as outcomes measures and nationwide patterns of care were collected and analyzed.

Results: A total of 510 adult cases of LTx for COVID-19 (259 ARDS, 251 PF) were compared to 4,031 without COVID-19 (3,994 PF, 37 ARDS). Patients who received LTx for COVID-19 ARDS did not differ in 2-year survival when compared to those with COVID-19 PF (81.9% vs 77.2%, p = 0.4428). Compared to non-COVID-19 etiologies, COVID-19 ARDS patients had higher rates of stroke (2.3% vs 0%, p = 0.0005), lower rates of graft failure (12.8% vs 36.1%, p = 0.0003) and post-transplant ECMO (29.6% vs 41.7%, p = 0.0002), and improved 2-year survival following LTx (81.9% vs 61.7%, p = 0.0064). No difference in 2-year survival following LTx was observed between patients with COVID-19 and non-COVID-19 PF (77.2% vs 71.8%, p = 0.34). Rates of LTx spiked with variant emergence and declined with rounds of vaccination.

Conclusion: Our results are consistent with early reports of survival outcomes following LTx for COVID-19 ARDS and PF while providing an increased layer of granularity. LTx may be considered as a safe and effective intervention for COVID-19 lung disease.