Enhanced Lyn Activity Causes Severe, Progressive Emphysema and Lung Cancer.

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.

Association of impaired lung function with dementia, and brain magnetic resonance imaging indices: a large population-based longitudinal study.

OBJECTIVE: to examine the association between different patterns of impaired lung function with the incident risk of dementia and magnetic resonance imaging (MRI)-based brain structural features. METHODS: in UK Biobank, a total of 308,534 dementia-free participants with valid lung function measures (forced expiratory volume in 1 s [FEV1] and forced vital capacity [FVC]) were included. Association was assessed using Cox proportional hazards regression model. Furthermore, the association between impaired lung function and brain MRI biomarkers related to cognitive function was analysed among 30,159 participants. RESULTS: during a median follow-up of 12.6 years, 3,607 incident all-cause dementia cases were recorded. Restrictive impairment (hazard ratio [HR], 1.42; 95% confidence interval [CI], 1.27-1.60) and obstructive impairment (HR, 1.28; 95% CI, 1.15-1.42) were associated with higher risk of all-cause dementia. The restricted cubic splines indicated FEV1% predicted and FVC % predicted had reversed J-shaped associations with dementia. Participants with impaired lung function have higher risks of all-cause dementia across all apolipoprotein E (APOE) risk categories, whereas associations were stronger among those of low APOE risk (P for interaction = 0.034). In addition, restrictive and obstructive impairment were linked to lower total (ß: -0.075, SE: 0.021, Pfdr = 0.002; ß: -0.033, SE: 0.017, Pfdr = 0.069) and frontoparietal grey matter volumes, higher white matter hyperintensity, poorer white matter integrity, lower hippocampus (ß: -0.066, SE: 0.024, Pfdr = 0.017; ß: -0.051, SE: 0.019, Pfdr = 0.019) and other subcortical volumes. CONCLUSIONS: participants with restrictive and obstructive impairments had a higher risk of dementia. Brain MRI indices further supported adverse effects and provided insight into potential pathophysiology biomarkers.

Incense (bakhour) smoke exposure is associated with respiratory symptoms and impaired lung function among adults: A cross-sectional study in Eastern Province of Saudi Arabia.

Burning incense (bakhour) is a common cultural practice in Saudi Arabia. However, its health risk assessment has rarely been studied. This study aims to investigate the association between exposure to incense smoke on lung function impairments and respiratory symptoms among young adults in Saudi Arabia. A community-based cross-sectional study was designed with a representative study sample (N = 125) in the Eastern Province of Saudi Arabia. Study participants, exposed group (n = 45), working in bakhour shop and matched control (n = 80), no history of occupational exposure to bakhour smoke, were recruited randomly from the population registry. Socio-demographic and respiratory symptom information were collected through a questionnaire developed based on European Community Respiratory Health Survey II (ECRHS II). Lung function measurements were conducted using a field spirometer. The overall prevalence of wheezing or whistling was 16.8%, with a higher prevalence in exposed group 35.5%. In adjusted models, exposed to incense smoke remained positively associated with respiratory symptoms: wheezing or whistling; breathlessness; chest tightness shortness of breath; woken up by an attack of coughing. Our study suggests that inhaled incense smoke in occupation or at home is a risk factor of lung function impairments among adult population in Saudi Arabia.

Lung function impairment and cardiometabolic risks among rural adults: implication for an aging society.

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.

Influence of Lung Function and Sleep-disordered Breathing on All-Cause Mortality. A Community-based Study.

RATIONALE: 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. OBJECTIVES: 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. METHODS: 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 FEV1 and apnea-hypopnea index (AHI) as the primary exposure indicators along with several potential confounders. MEASUREMENTS AND MAIN RESULTS: 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 FEV1, 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 FEV1, 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 FEV1, 0.004). CONCLUSIONS: Lung function was associated with risk for all-cause mortality. The incremental contribution of lung function to mortality diminishes with increasing severity of SDB.

Gender Difference in the Relationship between Extrapulmonary Factors and Reduced Lung Function in Early Adulthood.

(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.

Successful pregnancy in a cystic fibrosis patient with a severe impairment of lung function receiving Elexacaftor-Tezacaftor-Ivacaftor.

Before the arrival of Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) modulators women with CF and impaired lung function were experiencing a high risk of complications and mortality during and the years after pregnancy. The arrival of the highly efficient CFTR modulator, Elexacaftor-Tezacaftor-Ivacaftor (ETI) resulted in an improvement of lung function, quality of life and fertility. Here we report a case of successful pregnancy and uncomplicated delivery for a CF patient with severely impaired lung function receiving ETI prior to conception.

Focusing on the long-term recovery of severe acute respiratory syndrome coronavirus 2 infection: Clinically relevant observations.

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.

Thoracoscopic lobectomy for non-small-cell lung cancer in patients with impaired pulmonary function: analysis from a national database.

OBJECTIVES: The objective of this retrospective multi-institutional study was to evaluate the postoperative outcomes of video-assisted thoracoscopic surgery (VATS)-lobectomy (VATS-L) for non-small-cell lung cancer (NSCLC) in patients with impaired lung function. The second end point was to illustrate the effective role of forced expiratory volume in 1 s (FEV1%) and the diffusing capacity of the lung for carbon monoxide (DLCO%) in predicting complications in this population. METHODS: Data from patients who underwent VATS-L at participating centres were analysed and divided into 2 groups: group A comprised patients with FEV1% and/or DLCO% >60% and group B included patients with impaired lung function defined as FEV1% and/or DLCO% ≤60%. To define clinical predictors of death and complications, we performed univariate and multivariable regression analyses. RESULTS: A total of 5562 patients underwent VATS-L, 809 (14.5%) of whom had impaired lung function. The postoperative mortality rate did not differ between the 2 groups (2.3% vs 3.2%; P = 0.77). The percentage of patients who had any complication (21.4% vs 34.2%; P ≤ 0.001), the complication rate (28% vs 49.8%; P ≤ 0.001) and the length of hospital stay (P ≤ 0.001) were higher for patients with limited pulmonary function. Impaired lung function was a strong predictor of overall and pulmonary complications at multivariable analysis. CONCLUSIONS: VATS-L for NSCLC can be performed in patients with impaired lung function without increased risk of postoperative death and with an acceptable incidence of overall and respiratory complications. Our analysis suggested that FEV1% and DLCO% play a substantial role in estimating the risk of complications after VATS-L, but their role was less reliable for estimating the mortality.

Non-intubated anaesthetic technique in open bilobectomy in a patient with severely impaired lung function.

General anaesthesia has been the most commonly used method for almost all types of thoracic surgery. Recently, there has been a growing interest in non-intubated anaesthetic techniques. The rationale being, to prevent complications related to general anaesthesia and positive pressure ventilation such as barotrauma or ventilation-perfusion mismatch. We present a case with severely impaired forced expiration volume (26%), carbon monoxide diffusing capacity (26%) and VO2max (13.9 mL/kg/min). According to current guidelines, this patient was suitable to undergo one-lung ventilation only with high risk of morbidity and mortality. Therefore, we chose the non-intubated technique for thoracotomy. Oxygenation was satisfactory throughout, the patient remained hemodynamically stable and the operation was uneventful. Oxygen supplementation was stopped from day 2 and he was discharged on day 7. To our knowledge, this is the first case report where a planned non-intubated method was applied for thoracotomy, and our results suggest that it might be a feasible and safe approach for open thoracotomy in difficult cases where severely impaired lung function indicates that one lung ventilation may carry significant risks.

Altered lung function test in asymptomatic women using biomass fuel for cooking.

BACKGROUND: One third of the world's population use biomass fuel like wood, dung or charcoal for cooking. The smoke from these organic materials increases the incidence of respiratory illness including chronic obstructive pulmonary disease and lung cancer. AIM: To evaluate forced expiratory lung volumes in asymptomatic women previously exposed to biomass fuel smoke. MATERIALS AND METHODS: The study was done in 74 healthy asymptomatic women divided into two age matched groups of 37 each. Pulmonary function tests (PFT) were assessed by computerised spirometry and statistical comparisons done on women using biomass fuel (study group) and women using other sources of fuel (LPG/ electric stove) for cooking (control group). RESULTS: The PFT results showed significant reduction in forced expiratory lung volumes like Forced Vital Capacity (FVC), Forced Expiratory Volume in 1(st) sec (FEV1), Forced Expiratory Flow between 25-75% (FEF 25-75%) and Forced Expiratory Volume percentage (FEV1%) in biomass fuel users as compared to those not exposed to biomass fuel smoke. CONCLUSION: The results of this study suggest that biomass fuel smoke may produce definite impairment in lung function, especially with regard to the smaller airways.