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The epidemiological patterns of incident chronic obstructive pulmonary disease (COPD) and lung adenocarcinoma are changing, with an increasing fraction of disease occurring in patients who are never-smokers or were not exposed to traditional risk factors. However, causative mechanism(s) are obscure. Overactivity of Src family kinases (SFKs) and myeloid cell–dependent inflammatory lung epithelial and endothelial damage are independent candidate mechanisms, but their pathogenic convergence has not been demonstrated. Here we present a novel preclinical model in which an activating mutation in Lyn, a nonreceptor SFK that is expressed in immune cells, epithelium, and endothelium—all strongly implicated in the pathogenesis of COPD—causes spontaneous inflammation, early-onset progressive emphysema, and lung adenocarcinoma. Surprisingly, even though activated macrophages, elastolytic enzymes, and proinflammatory cytokines were prominent, bone marrow chimeras formally demonstrated that myeloid cells were not disease initiators. Rather, lung disease arose from aberrant epithelial cell proliferation and differentiation, microvascular lesions within an activated endothelial microcirculation, and amplified EGFR (epidermal growth factor receptor) expression. In human bioinformatics analyses, LYN expression was increased in patients with COPD and was correlated with increased EGFR expression, a known lung oncogenic pathway, and LYN was linked to COPD. Our study shows that a singular molecular defect causes a spontaneous COPD-like immunopathology and lung adenocarcinoma. Furthermore, we identify Lyn and, by implication, its associated signaling pathways as new therapeutic targets for COPD and cancer. Moreover, our work may inform the development of molecular risk screening and intervention methods for disease susceptibility, progression, and prevention of these increasingly prevalent conditions.

While recent studies have indicated a potential link between incense burning and respiratory diseases, there is a lack of data specifically focused on diabetic patients. To explore the relationship between indoor incense burning and impaired lung function among Chinese individuals with diabetes, a comprehensive cross-sectional study was undertaken, enrolling 431 adults diagnosed with diabetes. Information on incense burning and characteristics was collected using a structured questionnaire. The outcome of the study, impaired lung function, was assessed using spirometry. Multivariable logistic regression models were employed. In the fully adjusted model, participants exposed to indoor incense burning exhibited 130% higher odds of impaired lung function compared to those not exposed, as indicated by an odds ratio (OR) of 2.3 (95% confidence interval [CI]: 0.97, 5.16; P  = 0.05). Notably, this association was statistically significant only in men (OR = 3.39; 95%CI: 1.07, 9.82; P  = 0.03). Our study has elucidated an association between exposure to indoor incense burning and impaired lung function in individuals with diabetes, independently of demographic factors. These findings underscore the importance of considering indoor environmental factors, such as incense burning, in the comprehensive management and care of diabetic individuals.

Whether sleep-disordered breathing (SDB) severity and diminished lung function act synergistically to heighten the risk of adverse health outcomes remains a topic of significant debate. The current study sought to determine whether the association between lower lung function and mortality would be stronger in those with increasing severity of SDB in a community-based cohort of middle-aged and older adults. Full montage home sleep testing and spirometry data were analyzed on 6,173 participants of the Sleep Heart Health Study. Proportional hazards models were used to calculate risk for all-cause mortality, with FEV and apnea-hypopnea index (AHI) as the primary exposure indicators along with several potential confounders. All-cause mortality rate was 26.9 per 1,000 person-years in those with SDB (AHI ≥5 events/h) and 18.2 per 1,000 person-years in those without (AHI <5 events/h). For every 200-ml decrease in FEV , all-cause mortality increased by 11.0% in those without SDB (hazard ratio, 1.11; 95% confidence interval, 1.08-1.13). In contrast, for every 200-ml decrease in FEV , all-cause mortality increased by only 6.0% in participants with SDB (hazard ratio, 1.06; 95% confidence interval, 1.04-1.09). Additionally, the incremental influence of lung function on all-cause mortality was less with increasing severity of SDB (P value for interaction between AHI and FEV , 0.004). Lung function was associated with risk for all-cause mortality. The incremental contribution of lung function to mortality diminishes with increasing severity of SDB.

Background Early detection and prevention of cardiometabolic risk factors in an increasingly aging society are a global public health concern. Maintaining adequate lung function is important for healthy aging. Few studies exist on lung function impairment and decline in primary healthcare settings, especially among rural adults with cardiometabolic risks. This study aimed to explore the prevalence of impaired lung function and its association with cardiometabolic risks among rural adults. Methods A community-based, cross-sectional study was conducted between March and December 2019 in western coastal Yunlin County, Taiwan. The lung function test was measured by spirometry, based on the American Thoracic Society recommendations. Three lung function parameters were obstructive lung impairment, restrictive lung impairment, and mixed lung impairment. Restrictive, obstructive, and mixed type lung function was categorized as impaired. Cardiometabolic risk factors and metabolic syndrome were based on the national standard and include five abnormal biomarkers, including abdominal obesity, blood pressure, fasting plasma glucose, triglycerides, and decreased high-density cholesterol levels. Results The median age of the 1653 (92.9%) participants with complete data was 66 years (interquartile range: 55 to 75 years). The prevalence of impaired lung function was 37%, including 31.7% restrictive, 2.5% obstructive, and 2.7% mixed type. Adults with impaired lung function (86% restrictive type) engaged more in smoking and betel nut chewing, ate fewer vegetables and fruit, and drank less water compared to the normal lung function group. After adjusting for potential confounding variables, multivariate logistic regression analysis showed that cardiometabolic risk factors were independently associated with restrictive lung impairment, while cigarette smoking (OR = 2.27, 95% CI = 1.14–4.53) and betel nut chewing (OR = 2.33, 95% CI = 1.09–5.01) were significantly associated with the obstructive type of lung impairment. Conclusions A high prevalence of restrictive lung impairment, cardiometabolic risks, and unhealthy lifestyles among rural adults were found in this study. For adults with cardiometabolic risks in rural areas, initiating lifestyle modifications with culture-tailored programs to improve lung function should be an important issue for clinicians and primary healthcare providers.

Background Predicted postoperative forced expiratory volume in 1 s (ppoFEV1) and expected transfer factor for CO (TLCO) values < 30–35% are often considered to be a contraindication for anatomical lung resection in patients with lung cancer. Based on our prior positive experience in lung volume reduction surgery (LVRS), we retrospectively analyzed all patients with impaired pulmonary function undergoing anatomical minimally-invasive lung resection, either for LVRS or treatment of non-small cell lung cancer (NSCLC) at our institute. Methods From August 2016 to April 2021, n = 42 consecutive anatomical lung resections were performed in patients with poor lung function (< 35% ppoFEV1). We retrospectively searched our records and investigated the patients’ pre- and postoperative conditions and their outcome. Results We included 16 patients (9 males, age 68.4 ± 8.9 years old) scheduled for lung cancer surgery. The procedures were performed via uniportal video assisted thoracoscopic surgery (VATS; n = 10, 62.5%, including one non-intubated VATS) or via thoracotomy (n = 6, 37.5%) and included lobectomy (9 patients, 55.3%) or (multiple) segmentectomy. Resected parenchyma as described by total number of removed segments was 3.9 ± 1.6 segments. Preoperative FEV1 was 35.1 ± 7.2%, with an expected ppoFEV1 28.1 ± 5.9%. Measured postoperative FEV1 was 39 ± 8.7% (p < 0.001). Postoperative complications included persistent air leak (PAL) in 7 patients (43.8%), atelectasis in 3 (18.8%), pleural effusion in 4 (25%), pneumonia in 1 (6.3%), and empyema in one (6.3%), patients. No patient required continuous O2 therapy or died. Conclusions Even in severely impaired lung function, anatomical resection appears to be feasible with reasonable morbidity and mortality. Highlight box Key findings Surgical indications for anatomical lung resection might be now expanded and include a larger number of patients with limited lung capacity previously considered unresectable. What is known and what is new? In the aging society, the number of lung cancer patients with low lung function patients is increasing. In our retrospective study, the result of anatomical lung resection for patients with low lung function was acceptable. What is the implication, and what should change now? Our result may expand the operative indication related to lung function and increase the radical resection possibility in elderly patients, a large group of lung cancer patients.

(1) Background: Reduced lung function in early adulthood is associated with future risks to health outcomes that have not been fully explored by gender. We investigated gender-specific relationships between lung function and extrapulmonary variables, assessing their potential as screening markers for respiratory dysfunction in young adults. (2) Methods: The participants were 151 medical students. Clinical data, handgrip strength (HS); body composition parameters such as skeletal muscle mass index (SMI), whole-body phase angle (WBPhA), and bone mineral content (BMC); and pulmonary function variables, vital capacity (VC), forced VC (FVC), and forced expiratory volume in one second (FEV1), were measured. (3) Results: FEV1 was significantly correlated with BMI, SMI, WBPhA, BMC, and both left and right HS (p < 0.0001, respectively) across all participants. According to gender, FEV1 had the strongest positive association with left HS in males (p < 0.0001) and BMC in females (p < 0.0001). The area under the curve for detecting the bottom quartile of FEV1 was 0.705 (cut-off 41.0 kg, sensitivity 91%) for left HS in males and 0.742 (cut-off 2.11 kg, sensitivity 81%) for BMC in females. (4) Conclusions: Gender-specific relationships between intrapulmonary and extrapulmonary factors such as left HS and BMC could be useful for screening suspected respiratory dysfunction in early adulthood.

Background The long‐term implications of COVID‐19 attract global attention in the post‐COVID‐19 pandemic era. Impaired lung function is the main sequelae in adults' survivors of SARS‐CoV‐2 infection. Methods and Results The plasma proteomic pattern provides novel evidence on multiple biological domains relevant to monitoring lung function and targeting the clinical application in adults with acute respiratory distress syndrome (ARDS) secondary to SARS‐CoV‐2 infection (SARS‐CoV‐2‐ARDS). Preliminary studies support the evidence of pulmonary function tests (PFT) and computed tomography (CT) scan as routine follow‐up tools. Combining the early fibrotic indicators and D‐dimer levels could prove the validity and reliability of the proactive management of lung function assessment during the long‐term recovery in SARS‐CoV‐2 infection. Conclusion In summary, protocolized PFT and CT scan and effective biomarkers for early fibrotic changes should be applied to clinical practice during the long follow‐up in patients with severe COVID‐19.

Background Symptom-based questionnaires can be a cost effective tool enabling identification and diagnosis of patients with respiratory illnesses in resource limited setting. This study aimed to determine the correlation of respiratory symptoms and spirometric lung patterns and validity of ATS respiratory questionnaire in a rural community setting. Methods This cross sectional survey was conducted between January – March 2009 on a sample of 200 adults selected from two villages of district Khairpur, Sindh, Pakistan. A modified version of the American thoracic society division of lung disease questionnaire was used to record the presence of respiratory symptoms. Predicted lung volumes i.e. forced vital capacity (FVC), forced expiratory volume in one second (FEV1) and their ratio (FEV 1 /FVC) were recorded using portable spirometer. Results In the study sample there were 91 (45.5%) males and 109 (54.5%) females with overall mean age of 34 years (±11.69). Predominant respiratory symptom was phlegm (19%) followed by cough (17.5%), wheeze (14%) and dyspnea (10.5%). Prevalence of physician diagnosed and self-reported asthma was 5.5% and 9.5% respectively. Frequency of obstructive pattern on spirometry was 28.72% and that of restrictive pattern was 19.68%. After adjustment for age, gender, socioeconomic status, spoken dialect, education, smoking status, height, weight and arsenic in drinking water, FVC was significantly reduced for phlegm (OR 3.01; 95% CI: 1.14 – 7.94), wheeze (OR 7.22; 95% CI: 2.52 – 20.67) and shortness of breath (OR 4.91; 95% CI: 1.57 – 15.36); and FEV 1 was significantly reduced for cough (OR 2.69; 95% CI: 1.12 – 6.43), phlegm (OR 3.01; 95% CI: 1.26 – 7.16) and wheeze (OR 10.77; 95% CI: 3.45 – 33.6). Presence of respiratory symptoms was significantly associated with restrictive and/or obstructive patterns after controlling for confounders. Similar findings were observed through linear regression where respiratory symptoms were found to be significantly associated with decrements in lung volumes. Specificity and positive predictive values were found to be higher for all the symptoms compared to sensitivity and negative predictive values. Conclusion Symptoms based respiratory questionnaires are a valuable tool for screening of respiratory symptoms in resource poor, rural community setting.

Background TP53 gene mutations can lead to the expression of a dysfunctional protein that in turn may enable genetically unstable cells to survive and change into malignant cells. Mutant p53 accumulates early in cells and can precociously induce circulating anti-p53 antibodies (p53Abs); in fact, p53 overexpression has been observed in pre-neoplastic lesions, such as bronchial dysplasia, and p53Abs have been found in patients with Chronic Obstructive Pulmonary Disease, before the diagnosis of lung and other tobacco-related tumors. Methods A large prospective study was carried out, enrolling non-smokers, ex-smokers and smokers with or without the impairment of lung function, to analyze the incidence of serum p53Abs and the correlation with clinicopathologic features, in particular smoking habits and impairment of lung function, in order to investigate their possible role as early markers of the onset of lung cancer or other cancers. The p53Ab levels were evaluated by a specific ELISA in 675 subjects. Results Data showed that significant levels of serum p53Abs were present in 35 subjects (5.2%); no difference was observed in the presence of p53Abs with regard to age and gender, while p53Abs correlated with the number of cigarettes smoked per day and packs-year. Furthermore, serum p53Abs were associated with the worst lung function impairment. The median p53Ab level in positive subjects was 3.5 units/ml (range 1.2 to 65.3 units/ml). Only fifteen positive subjects participated in the follow-up, again resulting positive for serum p53Abs, and no evidence of cancer was found in these patients. Conclusion The presence of serum p53Abs was found to be associated with smoking level and lung function impairment, both risk factors of cancer development. However, in our study we have not observed the occurrence of lung cancer or other cancers in the follow-up of positive subjects, therefore we cannot directly correlate the presence of serum p53Abs with cancer risk.

Background Preserved Ratio Impaired Spirometry (PRISm) is defined as FEV1/FVC ≥ 70% and FEV1 < 80%pred by pulmonary function test (PFT). It has highly prevalence and is associated with increased respiratory symptoms, systemic inflammation, and mortality. However, there are few radiological studies related to PRISm. The purpose of this study was to investigate the quantitative high-resolution computed tomography (HRCT) characteristics of PRISm and to evaluate the correlation between quantitative HRCT parameters and pulmonary function parameters, with the goal of establishing a nomogram model for predicting PRISm based on quantitative HRCT. Methods A prospective and continuous study was performed in 488 respiratory outpatients from February 2020 to February 2021. All patients underwent both deep inspiratory and expiratory CT examinations, and received pulmonary function test (PFT) within 1 month. According to the exclusion criteria and Global Initiative for Chronic Obstructive Lung Disease (GOLD) classification standard, 94 cases of normal pulmonary function, 51 cases of PRISm and 48 cases of mild to moderate chronic obstructive lung disease (COPD) were included in the study. The lung parenchyma, parametric response mapping (PRM), airway and vessel parameters were measured by automatic segmentation software (Aview). One-way analysis of variance (ANOVA) was used to compare the differences in clinical features, pulmonary function parameters and quantitative CT parameters. Spearman rank correlation analysis was used to evaluate the correlation between CT quantitative index and pulmonary function parameters. The predictors were obtained by binary logistics regression analysis respectively in normal and PRISm as well as PRISm and mild to moderate COPD, and the nomogram model was established. Results There were significant differences in pulmonary function parameters among the three groups (P < 0.001). The differences in pulmonary parenchyma parameters such as emphysema index (EI), pixel indices-1 (PI-1) and PI-15 were mainly between mild to moderate COPD and the other two groups. The differences of airway parameters and pulmonary vascular parameters were mainly between normal and the other two groups, but were not found between PRISm and mild to moderate COPD. Especially there were significant differences in mean lung density (MLD) and the percent of normal in PRM (PRM Normal ) among the three groups. Most of the pulmonary quantitative CT parameters had mild to moderate correlation with pulmonary function parameters. The predictors of the nomogram model using binary logistics regression analysis to distinguish normal from PRISm were smoking, MLD, the percent of functional small airways disease (fSAD) in PRM (PRM fSAD ) and Lumen area. It had a good goodness of fit (χ 2  = 0.31, P < 0.001) with the area under curve (AUC) value of 0.786. The predictor of distinguishing PRISm from mild to moderate COPD were PRM Emph (P < 0.001, AUC = 0.852). Conclusions PRISm was significantly different from subjects with normal pulmonary function in small airway and vessel lesions, which was more inclined to mild to moderate COPD, but there was no increase in pulmonary parenchymal attenuation. The nomogram based on quantitative HRCT parameters has good predictive value and provide more objective evidence for the early screening of PRISm.