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Background: In asthma, sex-steroids signaling is recognized as a critical regulator of disease pathophysiology. However, the paradoxical role of sex-steroids, especially estrogen, suggests that an upstream mechanism or even independent of estrogen plays an important role in regulating asthma pathophysiology. In this context, in our previous studies, we explored kisspeptin (Kp) and its receptor Kiss1R's signaling in regulating human airway smooth muscle cell remodeling in vitro and airway hyperresponsiveness (AHR) in vivo in a mouse (wild-type, WT) model of asthma. In this study, we evaluated the effect of endogenous Kp in regulating AHR and remodeling using Kiss1R knockout (Kiss1R−/−) mice. Methods: C57BL/6J WT (Kiss1R+/+) and Kiss1R−/− mice, both male and female, were intranasally challenged with mixed-allergen (MA) and/or phosphate-buffered saline (PBS). We used flexiVent analysis to assess airway resistance (Rrs), elastance (Ers), and compliance (Crs). Following this, broncho-alveolar lavage (BAL) was performed for differential leukocyte count (DLC) and cytokine analysis. Histology staining was performed using hematoxylin and eosin (H&E) for morphological analysis and Masson's Trichrome (MT) for collagen deposition. Additionally, lung sections were processed for immunofluorescence (IF) of Ki-67, α-smooth muscle actin (α-SMA), and tenascin-c. Results: Interestingly, the loss of Kiss1R exacerbated lung function and airway contractility in mice challenged with MA, with more profound effects in Kiss1R−/− female mice. MA-challenged Kiss1R−/− mice showed a significant increase in immune cell infiltration and proinflammatory cytokine levels. Importantly, the loss of Kiss1R aggravated Th2/Th17 biased cytokines in MA-challenged mice. Furthermore, histology of lung sections from Kiss1R−/− mice showed increased collagen deposition on airway walls and mucin production in airway cells compared to Kiss1R+/+ mice. In addition, immunofluorescence analysis showed loss of Kiss1R significantly aggravated airway remodeling and subsequently AHR. Conclusions: These findings demonstrate the importance of inherent Kiss1R signaling in regulating airway inflammation, AHR, and remodeling in the pathophysiology of asthma. [ABSTRACT FROM AUTHOR]

Background: Foundry workers are occupationally exposed to a variety of inhalable chemical substances. Occupational exposure to vapors, gases, dusts, and fumes can lead to adverse health effects on the respiratory system and cause chronic respiratory diseases, such as interstitial lung diseases (ILDs), chronic obstructive lung disease (COPD), chronic bronchitis, and emphysema. Research on respiratory symptoms, diseases, and lung function in foundry workers over the past few decades has been limited. The aim of this cross-sectional study was to assess the prevalence of respiratory symptoms and diseases and declined lung function of current foundry workers, ex-foundry workers, and unexposed controls. Methods: We assessed respiratory symptoms, diseases, and lung function among 335 current foundry workers, 64 ex-foundry workers, and 161 unexposed controls. The cumulative dust exposure (mg-y) of each participant was calculated, and the median cumulative dust exposure according to the main places of exposure was determined. Results: A higher prevalence of chronic bronchitis, as reported in a questionnaire, was found among current and ex-foundry workers compared to unexposed controls, even after adjusting for pack-years of smoking (p = 0.009). Additionally, cough and wheezing in adulthood without respiratory infection, and chronic rhinitis symptoms were more common among current and ex-foundry workers compared to unexposed controls. These differences remained significant even after adjusting for pack-years of smoking and body mass index (BMI) (p = 0.007 and p < 0.001, respectively). Impaired lung function was more prevalent among both ex-foundry workers (29.7%) and current foundry workers (15.5%) compared to the unexposed controls (8.7%), with the difference remaining significant even after adjusting for the pack-years of smoking and BMI (p = 0.009). According to the questionnaire, the number of physician-diagnosed cases of chronic obstructive pulmonary disease (COPD) or chronic bronchitis was unexpectedly low compared to the indications from the symptom questionnaire and lung function test results, suggesting a potential underdiagnosis. The prevalence of silicosis was low (0.8%) among current and ex-foundry workers. Conclusions: Respiratory symptoms are common among foundry workers. Current and ex-foundry workers exhibited lower lung function in spirometry compared to unexposed controls. There is a potential underdiagnosis of COPD and chronic bronchitis among foundry workers. [ABSTRACT FROM AUTHOR]

Background: The impact of polycyclic aromatic hydrocarbons (PAHs) on lung function has garnered attention, but studies mostly focus on individual effect. This study investigates urinary PAH metabolites as biomarkers of exposure and assesses the relationships between single and combined exposures to nine urinary PAH metabolites and lung function in adults. Methods: Data from 4040 adults in the 2007–2012 National Health and Nutrition Examination Survey (NHANES) were analyzed. Weighted generalized linear models estimated the effects of individual PAH metabolites on lung function. Additionally, weighted quantile sum (WQS) regression, quantile g-computation (qgcomp), and Bayesian kernel machine regression (BKMR) were employed to evaluate the combined impacts of multiple PAH metabolites. Results: Analyses of individual PAH metabolites revealed negative associations with lung function, excluding forced vital capacity (FVC). The WQS, qgcomp, and BKMR models consistently showed that exposure to multiple PAH metabolites was associated with lung function decrease. WQS indicated that 2-hydroxynaphthalene (2-NAP) was the largest contributor to the reductions in forced expiratory volume in 1 s (FEV1), FVC, peak expiratory flow (PEF), and forced expiratory flow from 25 to 75% of FVC (PEF25-75%). Additionally, 1-hydroxypyrene (1-PYR) was the primary PAH metabolite contributing to the decreases in FEV1/FVC and fractional exhaled nitric oxide (FeNO). The combined effect of urinary PAH metabolites did not affect FVC in the current smokers or FeNO in nonsmokers, but decreased FEV1/FVC in current smokers. Conclusion: This study strengthens the negative relationships between multiple PAH metabolites exposure and lung function in adults. Given the limitations of this study, including the lack of knowledge of other exposure pathways and the uncertainty of urinary metabolites, further research is necessary to explore the mechanisms underlying these associations and to address the limitations in exposure assessment. [ABSTRACT FROM AUTHOR]

We evaluated the utility of transmission electron microscopy (TEM) in transbronchial lung cryobiopsy (TBLC) samples from 16 consecutive patients undergoing routine evaluation of fibrotic interstitial lung disease (ILD). Next to routine pathology examination, 1 to 2 TBLC samples were prepared for TEM analysis and evaluated using a Zeiss LEO EM 910. Subpleural cryobiopsies and unfrozen excision biopsies from fresh lobectomy tissue of non-ILD lung cancer patients served as controls. TEM provided high-quality images with only minor cryoartifacts as compared to controls. Furthermore, in several ILD patients we found marked microvascular endothelial abnormalities like luminal pseudopodia-like protrusions and inner surface defects. These were extensively present in four (25%), moderately present in seven (43.8%), and largely absent in five (31.3%) patients. A higher degree of TEM endothelial abnormalities was associated with younger age, non-specific interstitial pneumonia pattern, higher broncho-alveolar lavage lymphocyte count, positive autoantibodies, and lower spirometry, diffusion capacity and oxygenation biomarkers. We conclude that TEM evaluation of TBLC samples from ILD patients is feasible, while the observed microvascular alterations warrant further evaluation. [ABSTRACT FROM AUTHOR]

Background: Extracorporeal membrane oxygenation (ECMO) is increasingly employed to support lung function in patients with acute respiratory failure (ARF). However, the long-term outcomes of the approach have not been encouraging when compared to those of conventional mechanical ventilation. Further, the long-term effects of ECMO on lung function and recovery are unclear. For this review, we examined the long-term lung function outcomes of patients with ARF treated with and without ECMO. Methods: We searched the Embase, CENTRAL, Web of Science, and PubMed sites for studies comparing long-term (≥ 6 months) pulmonary function test results in patients with ARF treated with and without ECMO published until January 2024. We conducted a meta-analysis for percentage predicted values. Results: We included five studies. Our meta-analysis showed similar values of forced vital capacity (FVC%) (MD, 0.47; 95% CI, -3.56–4.50) and forced expiratory flow in the first second % (MD, 1.79; 95% CI, -2.17–5.75) in patients with ARF treated with or without ECMO. The FEV1/FVC % values were slightly higher in patients treated with ECMO than in those without ECMO (MD, 2.03; 95% CI, 0.01–4.04; p-value = 0.05). According to the meta-analysis, the values for total lung capacity % (MD, -3.20; 95% CI, -8.83–2.44) and carbon monoxide diffusion capacity % (MD, -0.72; 95% CI, -3.83–2.39) were also similar between patients undergoing ECMO and those without it. Conclusion: The meta-analysis of a small number of studies with significant selection bias indicates that patients with ARF treated with ECMO may have comparable long-term pulmonary function recovery to those treated with conventional strategies. Further investigations including a larger number of patients and focusing on the long-term impact of ECMO are needed to supplement the current evidence. [ABSTRACT FROM AUTHOR]

Objective: To investigate the correlation between serum Rac1 enzyme (Rac1) level with asthma control, airway inflammatory response and lung function in asthmatic children. Methods: A retrospective analysis was performed on 79 children with asthma who were diagnosed and treated in our hospital from June 2020 to January 2023. According to the severity of the disease, the children were divided into mild group (25 cases), moderate group (30 cases) and severe group (24 cases). 36 healthy children who underwent physical examination at the same period in our hospital were selected as the control group. The state of an illness, control level, serum mRNA Rac1, inflammatory factors, and lung function of the children in two groups were compared between the control group and the observation group. Results: The Rac1 mRNA levels, forced vital capacity (FVC), forced expiratory volume in one second/FVC (FEV1/FVC), peak expiratory flow (PEF), and maximum mid-expiratory flow (MMEF) in the observation group were significantly lower than these in the control group (P < 0.05). The tumor necrosis factor-alpha (TNF-α), interleukin-5 (IL-5), IL-6, and IL-33 in the observation group were markedly higher than these in the control group (P < 0.05). As the state of an illness worsened, the Rac1 mRNA levels, FVC, FEV1/FVC, PEF, and MMEF gradually reduced (P < 0.05), while the levels of TNF-α, IL-5, IL-6, and IL-33 increased (P < 0.05). As the degree of disease control improved, the Rac1 mRNA levels, FVC, FEV1/FVC, PEF, and MMEF gradually elevated (P < 0.05), and the levels of TNF- α, IL-5, IL-6, and IL-33 showed the opposite trend (P < 0.05). Rac1 was negatively related to the levels of TNF-α, IL-5, IL-6 and IL-33 (P < 0.05), and positively to the levels of FVC, FEV1/FVC, PEF and MMEF (P < 0.001). Rac1 mRNA levels, FVC, FEV1/FVC, PEF and MMEF were protective factors, while TNF-α, IL-5, IL-6 and IL-33 were risk factors for the prognosis of children with asthma (P < 0.05). Conclusion: Children with asthma have obviously lower serum Rac1 mRNA levels, higher inflammatory factor levels and lower lung function. Serum Rac1 mRNA level may be associated with better asthma control, lower airway inflammatory response, better lung function and lower disease severity. It has important reference value for the evaluation of the state of an illness, efficacy and prognosis of children with bronchial asthma. [ABSTRACT FROM AUTHOR]

Background: Pulmonary complications are common among children with sickle cell disease (SCD). However, there is little literature on associated lung function abnormalities in Uganda. We aimed to determine the prevalence, patterns, and factors associated with abnormal lung function among children with SCD in a tertiary care hospital in Uganda. Method: A cross-sectional study was conducted among children aged 6 to 18 years at the SCD clinic (SCC) of Mulago National Super-Specialized Hospital between January 2020 and April 2021. Data on sociodemographic and clinical characteristics was collected using a standardized questionnaire. Laboratory investigations, including a complete blood count and serum lactate dehydrogenase (LDH), were done. Spirometry was performed following the ATS/ERS standards. Multivariable modified Poisson regression analysis was performed to determine factors associated with abnormal lung function. Results: A total of 332 participants were enrolled. The mean age was 11.7 ± 3.4 years, and 184 (55.4%) were female. Overall, 126 (37.9%) participants had abnormal lung function: 67/126 (53.2%) restrictive, 57/126 (45.2%) obstructive, and 2/126 (1.6%) mixed-ventilatory patterns. Factors associated with abnormal lung function were; serum LDH level > 600UL (aIRR: 1.89 95% CI: 1.2 — 7.4, p = 0.049), a history of acute chest syndrome (aIRR: 1.55, 95% CI: 1.06–2.25, p = 0.024), wasting (aIRR: 1.33, 95%CI: 1.02 — 1.72, p = 0.032), and use of charcoal for household cooking (aIRR: 1.49, 95% CI: 1.03–2.15, p = 0.035). Conclusion: More than one-third of children with SCD in Uganda have lung function abnormalities. Strategies to improve nutrition, reduce exposure to charcoal smoke, and monitoring serum LDH levels may be important in preventing or managing abnormal lung function in this population. The identification of reversible and irreversible airway obstruction in children with sickle cell disease also highlights the need for targeted interventions to address these specific patterns of abnormal lung function. [ABSTRACT FROM AUTHOR]

Background: Polycyclic aromatic hydrocarbons (PAHs) and metals were associated with decreased lung function, but co-exposure effects and underlying mechanism remained unknown. Methods: Among 1,123 adults from National Health and Nutrition Examination Survey 2011–2012, 10 urinary PAHs, 11 urinary metals, and peripheral white blood cell (WBC) count were determined, and 5 lung function indices were measured. Least absolute shrinkage and selection operator, Bayesian kernel machine regression, and quantile-based g-computation were used to estimate co-exposure effects on lung function. Mediation analysis was used to explore mediating role of WBC. Results: These models demonstrated that PAHs and metals were significantly associated with lung function impairment. Bayesian kernel machine regression models showed that comparing to all chemicals fixed at median level, forced expiratory volume in 1 s (FEV1)/forced vital capacity, peak expiratory flow, and forced expiratory flow between 25 and 75% decreased by 1.31% (95% CI: 0.72%, 1.91%), 231.62 (43.45, 419.78) mL/s, and 131.64 (37.54, 225.74) mL/s respectively, when all chemicals were at 75th percentile. In the quantile-based g-computation, each quartile increase in mixture was associated with 104.35 (95% CI: 40.67, 168.02) mL, 1.16% (2.11%, 22.40%), 294.90 (78.37, 511.43) mL/s, 168.44 (41.66, 295.22) mL/s decrease in the FEV1, FEV1/forced vital capacity, peak expiratory flow, and forced expiratory flow between 25% and 75%, respectively. 2-Hydroxyphenanthrene, 3-Hydroxyfluorene, and cadmium were leading contributors to the above associations. WBC mediated 8.22%-23.90% of association between PAHs and lung function. Conclusions: Co-exposure of PAHs and metals impairs lung function, and WBC could partially mediate this relationship. Our findings elucidate co-exposure effects of environmental mixtures on respiratory health and underlying mechanisms, suggesting that focusing on highly prioritized toxicants would effectively attenuate adverse effects. [ABSTRACT FROM AUTHOR]

Background: Japanese guidelines recommend triple inhaled corticosteroid (ICS)/long-acting muscarinic antagonist (LAMA)/long-acting β2-agonist (LABA) therapy in patients with chronic obstructive pulmonary disease (COPD) and no concurrent asthma diagnosis who experience frequent exacerbations and have blood eosinophil (EOS) count ≥ 300 cells/mm3, and in patients with COPD and asthma with continuing/worsening symptoms despite receiving dual ICS/LABA therapy. These post-hoc analyses of the KRONOS study in patients with COPD and without an asthma diagnosis, examine the effects of fixed-dose triple therapy with budesonide/glycopyrronium/formoterol fumarate dihydrate (BGF) versus dual therapies on lung function and exacerbations based on blood EOS count – focusing on blood EOS count 100 to < 300 cells/mm3 – as a function of exacerbation history and COPD severity. Methods: In KRONOS, patients were randomized to receive treatments that included BGF 320/14.4/10 µg, glycopyrronium/formoterol fumarate dihydrate (GFF) 14.4/10 µg, or budesonide/formoterol fumarate dihydrate (BFF) 320/10 µg via metered dose inhaler (two inhalations twice-daily for 24 weeks). These post-hoc analyses assessed changes from baseline in morning pre-dose trough forced expiratory volume in 1 s (FEV1) over 12–24 weeks and moderate or severe COPD exacerbations rates over 24 weeks. The KRONOS study was not prospectively powered for these subgroup analyses. Results: Among patients with blood EOS count 100 to < 300 cells/mm3, least squares mean treatment differences for lung function improvement favored BGF over BFF in patients without an exacerbation history in the past year and in patients with moderate and severe COPD, with observed differences ranging from 62 ml to 73 ml across populations. In this same blood EOS population, moderate or severe exacerbation rates were reduced for BGF relative to GFF by 56% in patients without an exacerbation history in the past year, by 47% in patients with moderate COPD, and by 50% in patients with severe COPD. Conclusions: These post-hoc analyses of patients with moderate-to-very severe COPD from the KRONOS study seem to indicate clinicians may want to consider a step-up to triple therapy in patients with persistent/worsening symptoms with blood EOS count > 100 cells/mm3, even if disease severity is moderate and there is no recent history of exacerbations. Trial registration: ClinicalTrials.gov registry number NCT02497001 (registration date, 13 July 2015). [ABSTRACT FROM AUTHOR]

Purpose: Studies have recently shown a correlation between the elemental components of coal dusts, including potassium aluminosilicates, and the lung response as a potential driver for lung diseases associated with inhalation of coal dust. Here we aimed to systematically review the evidence for the association between exposure to potassium bearing dusts and lung outcomes in human studies as well as adverse cellular response in animal/cell culture studies. Methods: A systematic search of the National Library of Medicine (PubMed), Embase and Web of Science was conducted in May 2024. Studies regarding exposure to potassium bearing dusts and aluminosilicates and respiratory consequence were included in the search. Articles were screened, with a secondary assessment for relevance and extraction of key information using a systematic review process. Results: We identified 64 studies, of which 35 were human studies, 22 involved animal experiments and 12 were in vitro studies with 5 papers having both in vivo and in vitro studies. Our review found some evidence that a range of potassium rich dusts increased incidence of respiratory symptoms and lung diseases, although the effect on radiological changes in the lung and pulmonary function loss was not consistent. The in vivo animal and in vitro studies consistently demonstrated an inflammatory response and cytotoxic effect after exposure to these dusts. Conclusion: Given complexity in the dust compositions and lack of direct evidence attributing these specific responses to potassium, we are not able to conclude the effect of potassium minerals in coal on development of respiratory diseases, warranting further research. [ABSTRACT FROM AUTHOR]

Purpose: The present study aimed to investigate the clinical characteristics and lung function impairment in young people diagnosed with chronic obstructive pulmonary disease (COPD). Patients and methods: We retrospectively enrolled patients with COPD who underwent symptom assessment and comprehensive pulmonary function tests at the First Affiliated Hospital of Guangzhou Medical University between August 2017 and March 2022. The patients were categorized into two groups based on age: a young COPD group (aged 20–50 years) and an old COPD group (aged > 50 years). Results: A total of 1282 patients with COPD were included in the study, with 76 young COPD patients and 1206 old COPD patients. Young COPD patients exhibited a higher likelihood of being asymptomatic, lower rates of smoking, and a lower smoking index compared to old COPD patients. Although young COPD patients had higher median post-bronchodilator forced expiratory volume in 1 s (post-BD FEV1) (1.4 vs.1.2 L, P = 0.019), diffusing capacity of the lung for carbon monoxide (DLCO) (7.2 vs. 4.6, P<0.001), and a lower median residual volume to total lung capacity ratio (RV/TLC) compared to their older counterparts, there were no differences observed in severity distribution by GOLD categories or the proportion of lung hyperinflation (RV/TLC%pred > 120%) between two groups. Surprisingly, the prevalence of reduced DLCO was found to be 71.1% in young COPD, although lower than in old COPD (85.2%). Conclusion: Young COPD showed fewer respiratory symptoms, yet displayed a similar severity distribution by GOLD categories. Furthermore, a majority of them demonstrated lung hyperinflation and reduced DLCO. These results underscore the importance of a comprehensive assessment of lung function in young COPD patients. [ABSTRACT FROM AUTHOR]

Chronic obstructive pulmonary disease (COPD) has been associated with alterations in the brain cortical structure. Nonetheless, the causality between COPD and brain cortical structure has not been determined. In the present study, we used Mendelian randomization (MR) analysis to explore the causal effects of genetic predicated COPD on brain cortical structure, namely cortical surface area (SA) and cortical thickness (TH). Genetic association summary data for COPD were obtained from the FinnGen consortium (N = 358,369; Ncase = 20,066). PRISm summary genetic data were retrieved from a case–control GWAS conducted in the UK Biobank (N = 296,282). Lung function indices, including forced expiratory volume in one second (FEV1), forced vital capacity (FVC), and FEV1/FVC, were extracted from a meta-analysis of the UK Biobank and SpiroMeta consortium (N = 400,102). Brain cortical structure data were obtained from the ENIGMA consortium (N = 51,665). Inverse-variance weighted (IVW) method was used as the primary analysis, and a series of sensitivity tests were exploited to evaluate the heterogeneity and pleiotropy of our results. The results identified potential causal effects of COPD on several brain cortical specifications, including pars orbitalis, cuneus and inferior parietal gyrus. Furthermore, genetic predicated lung function index (FEV1, FVC and FEV1/FVC), as well as PRISm, also has causal effects on brain cortical structure. According to our results, a total of 15 functional specifications were influenced by lung function index and PRISm. These findings contribute to understanding the causal effects of COPD and lung function to brain cortical structure. [ABSTRACT FROM AUTHOR]

Background: Limited lung function represents a serious health impairment. However, studies investigating social inequalities in limited lung function are rare. Thus, the current study investigates which socioeconomic groups are the most affected by overall limited lung function and severely limited lung function. Methods: Data from the population-based German Aging Survey were used (N = 4472), with participants being 40 + years old. Lung function was assessed by the peak flow test. Education, income, and occupational prestige were used as socioeconomic indicators. Results: We found that overall limited lung function was highly prevalent across the whole sample, with about 33% (Women: 35%; Men: 30%) having overall limited lung function and 8% (Women: 7%; Men: 8%) having severely limited lung function. Socioeconomic differences in limited lung function emerged for all three indicators, education, income, and occupational prestige, in both men and women in single effect analyses. These differences persisted for occupational prestige and income when controlling for all indicators simultaneously. Conclusions: Thus, overall and severely limited lung function are highly prevalent health conditions. Men and women with a low occupational position and those with low income are the most affected. Socioeconomic indicators cannot be used interchangeably when studying health inequalities in lung functioning. Occupational hazards and physical working conditions are likely to constitute major risks of health inequalities in limited lung functioning and should be investigated as such by future studies. [ABSTRACT FROM AUTHOR]

Background: Preserved ratio impaired spirometry (PRISm) is a type of abnormal lung function. PRISm and mortality have been explored in several studies, but a comprehensive evaluation of the associations is limited. The current study aims to conduct a systematic review and meta-analysis in order to investigate the mortality and cardiovascular diseases in patients with PRISm. Methods: PubMed, Embase, and Web of Science databases, as well as gray literature sources, were searched for relevant studies published up to 7 September 2023 without language restrictions. This review included all published observational cohort studies that investigated the association of PRISm with mortality in the general population, as well as subgroup analyses in smokers and pre-bronchodilation spirometry studies. The outcomes of interest were all-cause mortality, cardiovascular mortality, and respiratory-related mortality. The Newcastle–Ottawa scale assessed study quality. Sensitivity and subgroup analyses explored heterogeneity and robustness. Publication bias was assessed with Egger's and Begg's tests. Results: Overall, eight studies were included in this meta-analysis. The pooled HR was 1.60 (95% CI, 1.48–1.74) for all-cause mortality, 1.68 (95% CI, 1.46–1.94) for CVD mortality, and 3.09 (95% CI, 1.42–6.71) for respiratory-related mortality in PRISm group compared to normal group. In the subgroup analysis, participants with PRISm had a higher effect (HR, 2.11; 95% CI, 1.74–2.54) on all-cause mortality among smokers relative to participants with normal spirometry. Furthermore, the association between PRISm and mortality risk was consistent across several sensitivity analyses. Conclusions: People with PRISm were associated with an increased risk of all-cause mortality, CVD mortality, and respiratory-related mortality as compared to those with normal lung function in the general population. Systematic review registration: PROSPERO CRD42023426872. [ABSTRACT FROM AUTHOR]

Purpose: There is a major epidemic of obesity, and many obese patients suffer from respiratory symptoms and disease. However, limited research explores the associations between abdominal obesity and lung function indices, yielding mixed results. This study aims to analyze the association between waist circumference (WC), an easily measurable marker of abdominal obesity, and lung function parameters in middle-aged and older adults using the National Health and Nutrition Examination Survey (NHANES). Methods: This study utilized data obtained from the National Health and Nutrition Examination Survey (NHANES) spanning 2007 to 2012, with a total sample size of 6089 individuals. A weighted multiple regression analysis was conducted to assess the relationship between WC and three pulmonary function parameters. Additionally, a weighted generalized additive model and smooth curve fitting were applied to capture any potential nonlinear relationship within this association. Results: After considering all confounding variables, it was observed that for each unit increase in WC, in males, Forced Vital Capacity (FVC) increased by 23.687 ml, Forced Expiratory Volume in one second (FEV1) increased by 12.029 ml, and the FEV1/FVC ratio decreased by 0.140%. In females, an increase in waist circumference by one unit resulted in an FVC increase of 6.583 ml and an FEV1 increase of 4.453 ml. In the overall population, each unit increase in waist circumference led to a FVC increase of 12.014 ml, an FEV1 increase of 6.557 ml, and a decrease in the FEV1/FVC ratio by 0.076%. By constructing a smooth curve, we identified a positive correlation between waist circumference and FVC and FEV1. Conversely, there was a negative correlation between waist circumference and the FEV1/FVC ratio. Conclusions: Our findings indicate that in the fully adjusted model, waist circumference, independent of BMI, positively correlates with FVC and FEV1 while exhibiting a negative correlation with FEV1/FVC among middle-aged and older adults in the United States. These results underscore the importance of considering abdominal obesity as a potential factor influencing lung function in American middle-aged and older adults. [ABSTRACT FROM AUTHOR]

Background: There is no known effective pharmacological therapy for long COVID, which is characterized by wide-ranging, multisystemic, fluctuating, or relapsing symptoms in a large proportion of survivors of acute COVID. This randomized controlled trial aims to assess the safety and efficacy of an anti-inflammatory agent colchicine, to reduce symptoms among those at high risk of developing long COVID. Methods: This multi-centre, parallel arm, 1:1 individual randomized, placebo-controlled, double-blind superiority trial will enrol 350 individuals with persistent post-COVID symptoms. Participants will be randomized to either colchicine 0.5 mg once daily (< 70 kg) or twice daily (≥ 70 kg) or matched placebo for 26 weeks and will be followed up until 52 weeks after randomization. The primary trial objective is to demonstrate the superiority of colchicine over a placebo in improving distance walked in 6 min at 52 weeks from baseline. The secondary objectives are to assess the efficacy of colchicine compared to placebo with respect to lung function, inflammatory markers, constitutional symptoms, and mental health state. In a sub-sample of 100 participants, cardiac biomarkers of myocardial injury and myocardial oedema using MRI will be compared. Discussion: Persistent inflammatory response following SARS-CoV-19 is one of the postulated pathophysiological mechanisms of long COVID. Colchicine, a low-cost anti-inflammatory agent, acts via multiple inflammatory pathways and has an established safety profile. This trial will generate evidence for an important health priority that can rapidly translate into practice. Trial registration: This clinical trial has been registered prospectively on www.clinicaltrials.gov with registration CTRI/2021/11/038234 dated November 24, 2021. [ABSTRACT FROM AUTHOR]

Background: The relationship between lung function and sarcopenia remains ambiguous. The primary aim of this study was to investigate the potential association between lung function and sarcopenia in the older adults, as well as to examine the mediating role of cognitive function in this relationship. Methods: The participants were selected from a nationally representative population-based cohort in China. The peak expiratory flow (PEF) measurement was used to evaluate the lung function in older persons. The sarcopenia was diagnosed using the guidelines of the Asian Working Group for Sarcopenia (AWGS) in 2019. The Cox proportional hazard model was utilized to perform primary analyses of the relationship between PEF and sarcopenia. The mediating effect of cognitive function was evaluated using the counterfactual mediation method. Results: This cohort study included 4,011 older adults (average age, 66.6 years; 53.3% males). During a follow-up period of 3.86 years, 349 individuals were diagnosed with sarcopenia. After adjusting for potential confounders, each one-standard-deviation increase in PEF was associated with a 28% reduction in the risk of sarcopenia (hazard ratio [HR]: 0.72; 95% confidence interval [CI]: 0.63, 0.80). There was a significant mediation of cognition for the association between PEF and incident sarcopenia, and the proportion mediated was 12.2% (95% CI: 4.5%, 23.1%). Conclusions: Older adults with impaired lung function are more likely to develop sarcopenia. Nevertheless, cognition can explain only a small portion of this association. Thus, other potential pathways between lung function and sarcopenia must be elucidated. [ABSTRACT FROM AUTHOR]

Background: Previous research has emphasized the potential benefits of anti-diabetic medications in inhibiting the exacerbation of Chronic Obstructive Pulmonary Disease (COPD), yet the role of anti-diabetic drugs on COPD risk remains uncertain. Methods: This study employed a Mendelian randomization (MR) approach to evaluate the causal association of genetic variations related to six classes of anti-diabetic drug targets with COPD. The primary outcome for COPD was obtained from the Global Biobank Meta-analysis Initiative (GBMI) consortium, encompassing a meta-analysis of 12 cohorts with 81,568 cases and 1,310,798 controls. Summary-level data for HbA1c was derived from the UK Biobank, involving 344,182 individuals. Positive control analysis was conducted for Type 2 Diabetes Mellitus (T2DM) to validate the choice of instrumental variables. The study applied Summary-data-based MR (SMR) and two-sample MR for effect estimation and further adopted colocalization analysis to verify evidence of genetic variations. Results: SMR analysis revealed that elevated KCNJ11 gene expression levels in blood correlated with reduced COPD risk (OR = 0.87, 95% CI = 0.79–0.95; p = 0.002), whereas an increase in DPP4 expression corresponded with an increased COPD incidence (OR = 1.18, 95% CI = 1.03–1.35; p = 0.022). Additionally, the primary method within MR analysis demonstrated a positive correlation between PPARG-mediated HbA1c and both FEV1 (OR = 1.07, 95% CI = 1.02–1.13; P = 0.013) and FEV1/FVC (OR = 1.08, 95% CI = 1.01–1.14; P = 0.007), and a negative association between SLC5A2-mediated HbA1c and FEV1/FVC (OR = 0.86, 95% CI = 0.74–1.00; P = 0.045). No colocalization evidence with outcome phenotypes was detected (all PP.H4 < 0.7). Conclusion: This study provides suggestive evidence for anti-diabetic medications' role in improving COPD and lung function. Further updated MR analyses are warranted in the future, following the acquisition of more extensive and comprehensive data, to validate our results. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study is to investigate the clinical value and potential prognostic significance of lung function assessment and Testin expression in non-small cell lung cancer (NSCLC) patients. Methods: The NSCLC patients were classified into three groups according to lung function: group of normal lung function, group of PRISm (preserved ratio impaired spirometry) (FEV1, forced expiratory volume during the first second < 80% predicted and FEV1/FVC (forced vital capacity) ≥ 70%) and group of COPD (chronic obstructive pulmonary disease) (FEV1/FVC < 70%). The pre-operational clinicopathological characteristics of these patients were recorded and the markers of systemic inflammatory response, including neutrophil to lymphocyte ratio (NLR), lymphocyte to monocyte ratio (LMR), platelet to lymphocyte ratio (PLR) and eosinophils (EOS), were compared between three groups. The expression of Testin in NSCLC samples was detected by IHC and we further explored the correlation between Testin expression and clinicopathological characteristics and prognosis of NSCLC patients. Finally, Cox regression analysis was conducted to study the prognostic factors of NSCLC patients. Results: Of the 158 NSCLC patients, percentages of normal lung function, PRISm and COPD were 41.4%, 22.8% and 36.1%, respectively. Patients with tumor in the left lung were more likely to have pulmonary dysfunction (PRISm and COPD) than the right lung. The markers of systemic inflammatory response showed differences to various degree in the three groups and NSCLC patients with PRISm or COPD presented more unfavorable prognosis than patients with normal function. The expression of Testin correlated with lymph node metastasis, TNM stage and tumor invasion of NSCLC patients. Moreover, patients with low Testin expression exhibited poorer disease-free survival and overall survival than those with high Testin expression. In Cox regression analysis, we found that PRISm, COPD and Testin expression served as prognostic factors in NSCLC patients. Conclusions: The presence of COPD or PRISm influenced systemic inflammatory response and prognosis of NSCLC patients. Testin expression correlated with clinicopathological features and could be potentially used as a prognostic marker in NSCLC. [ABSTRACT FROM AUTHOR]

Background: Reference values for lung volumes are necessary to identify and diagnose restrictive lung diseases and hyperinflation, but the values have to be validated in the relevant population. Our aim was to investigate the Global Lung Function Initiative (GLI) reference equations in a representative healthy Austrian population and create population-derived reference equations if poor fit was observed. Methods: We analysed spirometry and body plethysmography data from 5371 respiratory healthy subjects (6–80 years) from the Austrian LEAD Study. Fit with the GLI equations was examined using z-scores and distributions within the limits of normality. LEAD reference equations were then created using the LMS method and the generalized additive model of location shape and scale package according to GLI models. Results: Good fit, defined as mean z-scores between + 0.5 and -0.5,was not observed for the GLI static lung volume equations, with mean z-scores > 0.5 for residual volume (RV), RV/TLC (total lung capacity) and TLC in both sexes, and for expiratory reserve volume (ERV) and inspiratory capacity in females. Distribution within the limits of normality were shifted to the upper limit except for ERV. Population-derived reference equations from the LEAD cohort showed superior fit for lung volumes and provided reproducible results. Conclusion: GLI lung volume reference equations demonstrated a poor fit for our cohort, especially in females. Therefore a new set of Austrian reference equations for static lung volumes was developed, that can be applied to both children and adults (6–80 years of age). [ABSTRACT FROM AUTHOR]

Background: Lung function throughout adulthood predicts morbidity and mortality even among adults without chronic respiratory disease. Diet quality may represent a modifiable risk factor for lung function impairment later in life. We investigated associations between nutritionally-rich plant-centered diet and lung function across early and middle adulthood from the Coronary Artery Risk Development in Young Adults (CARDIA) Study. Methods: Diet was assessed at baseline and years 7 and 20 of follow-up using the validated CARDIA diet history questionnaire. Plant-centered diet quality was scored using the validated A Priori Diet Quality Score (APDQS), which weights food groups to measure adherence to a nutritionally-rich plant-centered diet for 20 beneficially rated foods and 13 adversely rated foods. Scores were cumulatively averaged over follow-up and categorized into quintiles. The primary outcome was lung function decline, including forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC), measured at years 0, 2, 5, 10, 20, and 30. We estimated the association of APDQS with annual pulmonary function changes and cross-sectional differences in a repeated measures regression model, adjusting for clinically relevant covariates. Results: The study included 3,787 Black and White men and women aged 18–30 in 1985–86 and followed for 30 years. In multivariable repeated measures regression models, individuals in the lowest APDQS quintile (poorest diet) had declines in FEV1 that were 1.6 ml/year greater than individuals in the highest quintile (35.0 vs. 33.4 ml/year, ß ± SE per 1 SD change APDQS 0.94 ± 0.36, p = 0.009). Additionally, declines in FVC were 2.4 ml/year greater in the lowest APDQS quintile than those in the highest quintile (37.0 vs 34.6 ml/year, ß ± SE per 1 SD change APDQS 1.71 ± 0.46, p < 0.001). The association was not different between never and ever smokers (pint = 0.07 for FVC and 0.32 for FEV1). In sensitivity analyses where current asthma diagnosis and cardiorespiratory fitness were further adjusted, results remained similar. Cross-sectional analysis at each exam year also showed significant differences in lung function according to diet after covariate adjustment. Conclusions: In this 30-year longitudinal cohort study, long-term adherence to a nutritionally-rich plant-centered diet was associated with cross-sectional differences in lung function as well as slower decline in lung function, highlighting diet quality as a potential treatable trait supporting long-term lung health. [ABSTRACT FROM AUTHOR]

Background: Respiratory diseases are a major health burden, and educational inequalities may influence disease prevalence. We aim to evaluate the causal link between educational attainment and respiratory disease, and to determine the mediating influence of several known modifiable risk factors. Methods: We conducted a two-step, two-sample Mendelian randomization (MR) analysis using summary statistics from genome-wide association studies (GWAS) and single nucleotide polymorphisms (SNPs) as instrumental variables for educational attainment and respiratory diseases. Additionally, we performed a multivariable MR analysis to estimate the direct causal effect of each exposure variable included in the analysis on the outcome, conditional on the other exposure variables included in the model. The mediating roles of body mass index (BMI), physical activity, and smoking were also assessed. Findings: MR analyses provide evidence of genetically predicted educational attainment on the risk of FEV1 (β = 0.10, 95% CI 0.06, 0.14), FVC (β = 0.12, 95% CI 0.07, 0.16), FEV1/FVC (β = - 0.005, 95% CI - 0.05, 0.04), lung cancer (OR = 0.54, 95% CI 0.45, 0.65) and asthma (OR = 0.86, 95% CI 0.78, 0.94). Multivariable MR dicated the effect of educational attainment on FEV1 (β = 0.10, 95% CI 0.04, 0.16), FVC (β = 0.07, 95% CI 0.01, 0.12), FEV1/FVC (β = 0.07, 95% CI 0.01, 0.01), lung cancer (OR = 0.55, 95% CI 0.42, 0.71) and asthma (OR = 0.88, 95% CI 0.78, 0.99) persisted after adjusting BMI and cigarettes per day. Of the 23 potential risk factors, BMI, smoking may partially mediate the relationship between education and lung disease. Conclusion: High levels of educational attainment have a potential causal protective effect on respiratory diseases. Reducing smoking and adiposity may be a target for the prevention of respiratory diseases attributable to low educational attainment. [ABSTRACT FROM AUTHOR]

Background: Occupational exposure to artificial stone, a popular material used for countertops, can cause accelerated silicosis, but the precise relationship between silica dose and disease development is unclear. Objectives: This study evaluated the impact of silica exposure on lung function and chest imaging in artificial stone manufacturing workers. Methods: Questionnaire and spirometry assessments were administered to workers in two plants. A high-exposure subset underwent further evaluation, including chest CT and DLco. Weighting factors, assigned as proxies for silica exposure, were based on work tasks. Individual cumulative exposures were estimated using area concentration measurements and time spent in specific areas. Exposure-response associations were analyzed using linear and logistic regression models. Results: Among 65 participants, the mean cumulative silica exposure was 3.61 mg/m3-year (range 0.0001 to 44.4). Each 1 mg/m3-year increase was associated with a 0.46% reduction in FVC, a 0.45% reduction in FEV1, and increased lung function abnormality risk (aOR = 1.27, 95% CI = 1.03–1.56). Weighting factors correlated with cumulative exposures (Spearman correlation = 0.59, p < 0.0001), and weighted tenure was associated with lung function abnormalities (aOR = 1.04, 95% CI = 1.01–1.09). Of 37 high-exposure workers, 19 underwent chest CT, with 12 (63%) showing abnormal opacities. Combining respiratory symptoms, lung function, and chest X-ray achieved 91.7% sensitivity and 75% specificity for predicting chest CT abnormalities. Conclusion: Lung function and chest CT abnormalities occur commonly in artificial stone workers. For high-exposure individuals, abnormalities on health screening could prompt further chest CT examination to facilitate early silicosis detection. [ABSTRACT FROM AUTHOR]

Background: Randomized controlled trials described beneficial effects of inhaled triple therapy (LABA/LAMA/ICS) in patients with chronic obstructive pulmonary disease (COPD) and high risk of exacerbations. We studied whether such effects were also detectable under continuous treatment in a retrospective observational setting. Methods: Data from baseline and 18-month follow-up of the COPD cohort COSYCONET were used, including patients categorized as GOLD groups C/D at both visits (n = 258). Therapy groups were defined as triple therapy at both visits (triple always, TA) versus its complement (triple not always, TNA). Comparisons were performed via multiple regression analysis, propensity score matching and inverse probability weighting to adjust for differences between groups. For this purpose, variables were divided into predictors of therapy and outcomes. Results: In total, 258 patients were eligible (TA: n = 162, TNA: n = 96). Without adjustments, TA patients showed significant (p < 0.05) impairments regarding lung function, quality of life and symptom burden. After adjustments, most differences in outcomes were no more significant. Total direct health care costs were reduced but still elevated, with inpatient costs much reduced, while costs of total and respiratory medication only slightly changed. Conclusion: Without statistical adjustment, patients with triple therapy showed multiple impairments as well as elevated treatment costs. After adjusting for differences between treatment groups, differences were reduced. These findings are compatible with beneficial effects of triple therapy under continuous, long-term treatment, but also demonstrate the limitations encountered in the comparison of controlled intervention studies with observational studies in patients with severe COPD using different types of devices and compounds. [ABSTRACT FROM AUTHOR]

Background: Increasing evidence is appearing that ozone has adverse effects on health. However, the association between long-term ozone exposure and lung function is still inconclusive. Objectives: To investigate the associations between long-term exposure to ozone and lung function in Chinese young adults. Methods: We conducted a prospective cohort study among 1594 college students with a mean age of 19.2 years at baseline in Shandong, China from September 2020 to September 2021. Lung function indicators were measured in September 2020 and September 2021, including forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), forced expiratory flow at the 25th, 50th, and 75th percentile of the FVC (FEF25, FEF50, and FEF75) and mean flow rate between 25% and 75% of the FVC (FEF25-75) were measured. Daily 10 km×10 km ozone concentrations come from a well-validated data-fusion approach. The time-weighted average concentrations in 12 months before the lung function test were defined as the long-term ozone exposure. The associations between long-term ozone exposure and lung function indicators in Chinese young adults were investigated using a linear mixed effects model, followed by stratified analyses regarding sex, BMI and history of respiratory diseases. Results: Each interquartile range (IQR) (8.9 µg/m3) increase in long-term ozone exposure were associated with a -204.3 (95% confidence interval (CI): -361.6, -47.0) ml/s, -146.3 (95% CI: -264.1, -28.4) ml/s, and − 132.8 (95% CI: -239.2, -26.4) ml/s change in FEF25, FEF50, and FEF25-75, respectively. Stronger adverse associations were found in female participants or those with BMI ≥ 24 kg/m2 and history of respiratory diseases. Conclusion: Long-term exposure to ambient ozone is associated with impaired small airway indicators in Chinese young adults. Females, participants with BMI ≥ 24 kg/m2 and a history of respiratory disease have stronger associations. [ABSTRACT FROM AUTHOR]

Background: We previously reported in the "Vitamin C to Decrease the Effects of Smoking in Pregnancy on Infant Lung Function" randomized clinical trial (RCT) that vitamin C (500 mg/day) supplementation to pregnant smokers is associated with improved respiratory outcomes that persist through 5 years of age. The objective of this study was to assess whether buccal cell DNA methylation (DNAm), as a surrogate for airway epithelium, is associated with vitamin C supplementation, improved lung function, and decreased occurrence of wheeze. Methods: We conducted epigenome-wide association studies (EWAS) using Infinium MethylationEPIC arrays and buccal DNAm from 158 subjects (80 placebo; 78 vitamin C) with pulmonary function testing (PFT) performed at the 5-year visit. EWAS were performed on (1) vitamin C treatment, (2) forced expiratory flow between 25 and 75% of expired volume (FEF25–75), and (3) offspring wheeze. Models were adjusted for sex, race, study site, gestational age at randomization (≤ OR > 18 weeks), proportion of epithelial cells, and latent covariates in addition to child length at PFT in EWAS for FEF25–75. We considered FDR p < 0.05 as genome-wide significant and nominal p < 0.001 as candidates for downstream analyses. Buccal DNAm measured in a subset of subjects at birth and near 1 year of age was used to determine whether DNAm signatures originated in utero, or emerged with age. Results: Vitamin C treatment was associated with 457 FDR significant (q < 0.05) differentially methylated CpGs (DMCs; 236 hypermethylated; 221 hypomethylated) and 53 differentially methylated regions (DMRs; 26 hyper; 27 hypo) at 5 years of age. FEF25–75 was associated with one FDR significant DMC (cg05814800), 1,468 candidate DMCs (p < 0.001), and 44 DMRs. Current wheeze was associated with 0 FDR-DMCs, 782 candidate DMCs, and 19 DMRs (p < 0.001). In 365/457 vitamin C FDR significant DMCs at 5 years of age, there was no significant interaction between time and treatment. Conclusions: Vitamin C supplementation to pregnant smokers is associated with buccal DNA methylation in offspring at 5 years of age, and most methylation signatures appear to be persistent from the prenatal period. Buccal methylation at 5 years was also associated with current lung function and occurrence of wheeze, and these functionally associated loci are enriched for vitamin C associated loci. Clinical trial registration ClinicalTrials.gov, NCT01723696 and NCT03203603. [ABSTRACT FROM AUTHOR]

Background: Chronic obstructive pulmonary disease (COPD) and asthma associate with high morbidity and mortality. High levels of advanced glycation end products (AGEs) were found in tissue and plasma of COPD patients but their role in COPD and asthma is unclear. Methods: In the Rotterdam Study (n = 2577), AGEs (by skin autofluorescence (SAF)), FEV1 and lung diffusing capacity (DLCOc and DLCOc /alveolar volume [VA]) were measured. Associations of SAF with asthma, COPD, GOLD stage, and lung function were analyzed using logistic and linear regression adjusted for covariates, followed by interaction and stratification analyses. sRAGE and EN-RAGE associations with COPD prevalence were analyzed by logistic regression. Results: SAF associated with COPD prevalence (OR = 1.299 [1.060, 1.591]) but not when adjusted for smoking (OR = 1.106 [0.89, 1.363]). SAF associated with FEV1% predicted (β=-3.384 [-4.877, -1.892]), DLCOc (β=-0.212 [-0.327, -0.097]) and GOLD stage (OR = 4.073, p = 0.001, stage 3&4 versus 1). Stratified, the association between SAF and FEV1%predicted was stronger in COPD (β=-6.362 [-9.055, -3.670]) than non-COPD (β=-1.712 [-3.306, -0.118]). Association of SAF with DLCOc and DLCOc/VA were confined to COPD (β=-0.550 [-0.909, -0.191]; β=-0.065 [-0.117, -0.014] respectively). SAF interacted with former smoking and COPD prevalence for associations with lung function. Lower sRAGE and higher EN-RAGE associated with COPD prevalence (OR = 0.575[0.354, 0.931]; OR = 1.778[1.142, 2.768], respectively). Conclusions: Associations between SAF, lung function and COPD prevalence were strongly influenced by smoking. SAF associated with COPD severity and its association with lung function was more prominent within COPD. These results fuel further research into interrelations and causality between SAF, smoking and COPD. Take-home message: Skin AGEs associated with prevalence and severity of COPD and lung function in the general population with a stronger effect in COPD, calling for further research into interrelations and causality between SAF, smoking and COPD. [ABSTRACT FROM AUTHOR]

Background: Epidemiological evidence has suggested a relationship between lung function and frailty, but the precise nature of the causality remains unclear. In this study, we applied a two-sample Mendelian randomization (MR) analysis to determine the causal effects of lung function on frailty. Methods: Single nucleotide polymorphisms (SNPs) independently related (P ≤ 5E−08) to lung function, as identified by genome-wide association study (GWAS), were applied as instrumental variables (IV). The association with frailty index (FI) was investigated using summary-level data from the latest GWAS on FI (n = 175,226). Different statistical methods were employed to evaluate the causal estimates between lung function and FI. The pleiotropy, heterogeneity, and leave-one-out analysis were applied to confirm the stability of the MR estimates. Results: Using the random-effect inverse-variance weighted approach, genetically proxied forced expiratory volume in the first second (FEV1), ratio of FEV1 on forced vital capacity (FVC) [FEV1/FVC], and peak expiratory flow (PEF) were significantly and inversely associated with FI (FEV1, β = −0.08, P = 2.03E−05; FEV1/FVC, β = −0.06, P = 9.51E−06; PEF, β = −0.07, P = 4.09E−04) with good statistical power (99.7–100%). However, no significant association was observed between FVC and FI (β = −0.01, P = 0.681). Leave-one-out analysis showed that there was no single SNP driving the bias of the estimates. There was potential heterogeneity, but no obvious pleiotropy was founded in this MR study. Conclusions: Our findings indicate that impaired pulmonary function is closely related to the risk of frailty. Enhancing lung function in the elderly population may contribute to the prevention of frailty to a certain extent. [ABSTRACT FROM AUTHOR]

Background: Fighter aircraft pilots are regularly exposed to physiological challenges from high acceleration (Gz) forces, as well as increased breathing pressure and oxygen supply in the support systems. We studied whether effects on the lung and systemic oxidative stress were detectable after real training flights comprising of a wide variety of exposure conditions, and their combinations. Methods: Thirty-five pilots of the German Air Force performed 145 flights with the Eurofighter Typhoon. Prior to and after flight lung diffusing capacity for carbon monoxide (DLCO) and nitric oxide (DLNO), alveolar volume (VA), and diffusing capacities per volume (KCO, KNO) were assessed. In addition, the fractional concentration of exhaled nitric oxide (FeNO) was determined, and urine samples for the analysis of molecular species related to 8-hydroxy-2'-deoxyguanosine (8-OHdG) were taken. For statistical analysis, mixed ANOVA models were used. Results: DLNO, DLCO, KNO, KCO and VA were reduced (p < 0.001) after flights, mean ± SD changes being 2.9 ± 5.0, 3.2 ± 5.2, 1.5 ± 3.7, 1.9 ± 3.7 and 1.4 ± 3.1%, respectively, while FeNO decreased by 11.1% and the ratio of 8-OHdG to creatinine increased by 15.7 ± 37.8%. The reductions of DLNO (DLCO) were smaller (p < 0.001) than those of KNO (KCO). In repeated flights on different days, baseline values were restored. Amongst various flight parameters comprising Gz-forces and/or being indicative of positive pressure breathing and oxygenation support, the combination of long flight duration and high altitude appeared to be linked to greater changes in DLNO and DLCO. Conclusions: The pattern of reductions in diffusing capacities suggests effects arising from atelectasis and increased diffusion barrier, without changes in capillary blood volume. The decrease in exhaled endogenous NO suggests bronchial mucosal irritation and/or local oxidative stress, and the increase in urinary oxidized guanosine species suggests systemic oxidative stress. Although changes were small and not clinically relevant, their presence demonstrated physiological effects of real training flights in a modern 4th generation fighter jet. [ABSTRACT FROM AUTHOR]

DNA methylation (DNAm) changes play a key role in regulating gene expression in asthma. To investigate the role of epigenetics and transcriptomics change in asthma, we used publicly available DNAm (asthmatics, n = 96 and controls, n = 46) and gene expression (asthmatics, n = 79 and controls, n = 39) data derived from bronchial epithelial cells (BECs). We performed differential methylation/expression and weighted co-methylation/co-expression network analyses to identify co-methylated and co-expressed modules associated with asthma severity and lung function. For subjects with both DNAm and gene expression data (asthmatics, n = 79 and controls, n = 39), machine-learning technique was used to prioritize CpGs and differentially expressed genes (DEGs) for asthma risk prediction, and mediation analysis was used to uncover DEGs that mediate the effect of DNAm on asthma severity and lung function in BECs. Finally, we validated CpGs and their associated DEGs and the asthma risk prediction model in airway epithelial cells (AECs) dataset. The asthma risk prediction model based on 18 CpGs and 28 DEGs showed high accuracy in both the discovery BEC dataset with area under the receiver operating characteristic curve (AUC) = 0.99 and the validation AEC dataset (AUC = 0.82). Genes in the three co-methylated and six co-expressed modules were enriched in multiple pathways including WNT/beta-catenin signaling and notch signaling. Moreover, we identified 35 CpGs correlated with DEGs in BECs, of which 17 CpGs including cg01975495 (SERPINE1), cg10528482 (SLC9A3), cg25477769 (HNF1A) and cg26639146 (CD9), cg17945560 (TINAGL1) and cg10290200 (FLNC) were replicated in AECs. These DEGs mediate the association between DNAm and asthma severity and lung function. Overall, our study investigated the role of DNAm and gene expression change in asthma and provided an insight into the mechanisms underlying the effects of DNA methylation on asthma, asthma severity and lung function. [ABSTRACT FROM AUTHOR]

Background: Peak expiratory flow rate (PEFR) is an important tool for assessing lung function, which can be affected by environmental and physical factors such as altitude, nutrition, genetics, age, height, and weight. Conducting a study to assess the correlation between peak expiratory flow rate and anthropometric measurements in Tanzanian schoolchildren is crucial to derive a population-specific prediction formula and further simplify respiratory health assessment. Methods: This cross-sectional study was conducted in a single center private primary and secondary school in Dar es Salaam, Tanzania using data from an asthma screening camp. Variables of interest were height, weight, Body Mass Index (BMI) and PEFR. Independent t-test was performed to identify any differences in mean flow rate values between different ethnicities and genders. Correlation coefficients (r) were used to observe the relationship between PEFR and anthropometric measurements. A prediction equation by gender was generated using linear regression analysis. Statistical significance was set at the 5% level. All statistical data was analyzed using SPSS version 25.0. Results: The study involved 260 participants with a mean age of 9.5 years. Males were 51.2% and 65% of participants were of Asian ethnicity. PEFR was not observed to differ across the different ethnic groups and genders. Height was found to have the strongest correlation coefficient of 0.745, while BMI had the weakest correlation coefficient of 0.366. The strongest correlation was found with height for females (r = 0.787), while the weakest was with body mass index for boys (r = 0.203). The derived prediction equation for males was PEFR = 279.169 (Height of Student in meters) —134.12, while the predictive equation for females was PEFR = 318.32 (Height of Student in meters) —195.69. Conclusion: This study found a strong correlation between PEFR and anthropometric characteristics in school children from Dar es Salaam, Tanzania. A prediction equation by gender for PEFR was developed based on anthropometric characteristics. This equation may be applied in population-based studies or situations where peak flow meters are not readily available. Further research is needed to explore how well this prediction formula performs in other Tanzanian settings and to determine other factors that may affect lung function in this population. [ABSTRACT FROM AUTHOR]

Background: The two-way communications along the gut-lung axis influence the immune function in both gut and lung. However, the shared genetic characteristics of lung function with gastrointestinal tract (GIT) diseases remain to be investigated. Methods: We first investigated the genetic correlations between three lung function traits and four GIT diseases. Second, we illustrated the genetic overlap by genome-wide pleiotropic analysis (PLACO) and further pinpointed the relevant tissue and cell types by partitioning heritability. Furthermore, we proposed pleiotropic genes as potential drug targets by drug database mining. Finally, we evaluated the causal relationships by epidemiologic observational study and Mendelian randomization (MR) analysis. Results: We found lung function and GIT diseases were genetically correlated. We identified 258 pleiotropic loci, which were enriched in gut- and lung-specific regions marked by H3K4me1. Among these, 16 pleiotropic genes were targets of drugs, such as tofacitinib and baricitinib targeting TYK2 for the treatment of ulcer colitis and COVID-19, respectively. We identified a missense variant in TYK2, exhibiting a shared causal effect on FEV1/FVC and inflammatory bowel disease (rs12720356, PPLACO=1.38 × 10− 8). These findings suggested TYK2 as a promising drug target. Although the epidemiologic observational study suggested the protective role of lung function in the development of GIT diseases, no causalities were found by MR analysis. Conclusions: Our study suggested the shared genetic characteristics between lung function and GIT diseases. The pleiotropic variants could exert their effects by modulating gene expression marked by histone modifications. Finally, we highlighted the potential of pleiotropic analyses in drug repurposing. [ABSTRACT FROM AUTHOR]

Background: Little is known about the differences in medium to long-term recovery on spirometry, 6-minute walking distance (6MWD) and health-related quality of life (HRQoL) between COVID-19 and SARS. Methods: We performed a 12-month prospective study on COVID-19 survivors. The changes in dynamic lung volumes at spirometry (%predicted FEV1, %predicted FVC), 6MWD and HRQoL at 1–3, 6 to 12 months were compared against a historical cohort of SARS survivors using the same study protocol. The residual radiological changes in HRCT in COVID-19 survivors were correlated with their functional capacity. Results: 108 COVID-19 survivors of various disease severity (asymptomatic 2.9%, mild 33.3%, moderate 47.2%, severe 8.3%, critical 8.3%) were recruited. When compared with 97 SARS survivors, 108 COVID-19 survivors were older (48.1 ± 16.4 vs. 36.1 ± 9.5 years, p < 0.001) and required less additional support during hospitalization; with lower dynamic lung volumes, shorter 6MWD and better physical component score. Both groups of survivors had comparable changes in these parameters at subsequent follow-ups. Both COVID-19 and SARS survivors had similar mental component score (MCS) at 6 and 12 months. COVID-19 survivors initially experienced less (between-group difference, -3.1, 95% confidence interval [CI] -5.5 to -0.7, p = 0.012) and then more improvement (between-group difference 2.9, 95%, CI 0.8 to 5.1, p = 0.007) than SARS survivors in the MCS at 1–3 to 6 months and 6 to 12 months respectively. Forty (44.0%) out of 91 COVID-19 survivors had residual abnormalities on HRCT at 12 months, with a negative correlation between the severity scores of parenchymal changes and 6MWD (r=-0.239, p < 0.05). Conclusions: COVID-19 survivors demonstrated a similar recovery speed in dynamic lung volumes and exercise capacity, but different paces of psychological recovery as SARS survivors in the convalescent phase. The severity of parenchymal changes in HRCT is negatively correlated with the 6MWD of COVID-19 survivors. Trial registration: This prospective study was registered at ClinicalTrials.gov on 2 November 2020 (Identifier: NCT04611243). [ABSTRACT FROM AUTHOR]

Background: Idiopathic pulmonary fibrosis (IPF) is the most common idiopathic interstitial lung disease. Clinical models to accurately evaluate the prognosis of IPF are currently lacking. This study aimed to construct an easy-to-use and robust prediction model for transplant-free survival (TFS) of IPF based on clinical and radiological information. Methods: A multicenter prognostic study was conducted involving 166 IPF patients who were followed up for 3 years. The end point of follow-up was death or lung transplantation. Clinical information, lung function tests, and chest computed tomography (CT) scans were collected. Body composition quantification on CT was performed using 3D Slicer software. Risk factors in blood routine examination-radiology-pulmonary function (BRP) were identified by Cox regression and utilized to construct the "BRP Prognosis Model". The performance of the BRP model and the gender-age-physiology variables (GAP) model was compared using time-ROC curves, calibration curves, and decision curve analysis (DCA). Furthermore, histopathology fibrosis scores in clinical specimens were compared between the different risk stratifications identified by the BRP model. The correlations among body composition, lung function, serum inflammatory factors, and profibrotic factors were analyzed. Results: Neutrophil percentage > 68.3%, pericardial adipose tissue (PAT) > 94.91 cm3, pectoralis muscle radiodensity (PMD) ≤ 36.24 HU, diffusing capacity of the lung for carbon monoxide/alveolar ventilation (DLCO/VA) ≤ 56.03%, and maximum vital capacity (VCmax) < 90.5% were identified as independent risk factors for poor TFS among patients with IPF. We constructed a BRP model, which showed superior accuracy, discrimination, and clinical practicability to the GAP model. Median TFS differed significantly among patients at different risk levels identified by the BRP model (low risk: TFS > 3 years; intermediate risk: TFS = 2–3 years; high risk: TFS ≈ 1 year). Patients with a high-risk stratification according to the BRP model had a higher fibrosis score on histopathology. Additionally, serum proinflammatory markers were positively correlated with visceral fat volume and infiltration. Conclusions: In this study, the BRP prognostic model of IPF was successfully constructed and validated. Compared with the commonly used GAP model, the BRP model had better performance and generalization with easily obtainable indicators. The BRP model is suitable for clinical promotion. [ABSTRACT FROM AUTHOR]

Background: Air pollution harms health across the life course. Children are at particular risk of adverse effects during development, which may impact on health in later life. Interventions that improve air quality are urgently needed both to improve public health now, and prevent longer-term increased vulnerability to chronic disease. Low Emission Zones are a public health policy intervention aimed at reducing traffic-derived contributions to urban air pollution, but evidence that they deliver health benefits is lacking. We describe a natural experiment study (CHILL: Children's Health in London and Luton) to evaluate the impacts of the introduction of London's Ultra Low Emission Zone (ULEZ) on children's health. Methods: CHILL is a prospective two-arm parallel longitudinal cohort study recruiting children at age 6–9 years from primary schools in Central London (the focus of the first phase of the ULEZ) and Luton (a comparator site), with the primary outcome being the impact of changes in annual air pollutant exposures (nitrogen oxides [NOx], nitrogen dioxide [NO2], particulate matter with a diameter of less than 2.5micrograms [PM2.5], and less than 10 micrograms [PM10]) across the two sites on lung function growth, measured as post-bronchodilator forced expiratory volume in one second (FEV1) over five years. Secondary outcomes include physical activity, cognitive development, mental health, quality of life, health inequalities, and a range of respiratory and health economic data. Discussion: CHILL's prospective parallel cohort design will enable robust conclusions to be drawn on the effectiveness of the ULEZ at improving air quality and delivering improvements in children's respiratory health. With increasing proportions of the world's population now living in large urban areas exceeding World Health Organisation air pollution limit guidelines, our study findings will have important implications for the design and implementation of Low Emission and Clean Air Zones in the UK, and worldwide. ClinicalTrials.gov: NCT04695093 (05/01/2021). [ABSTRACT FROM AUTHOR]

Background: E-cigarettes (electronic nicotine delivery system, ENDS) have been presented as a harm reduction strategy for people who smoke tobacco cigarettes but who cannot achieve abstinence, or for those who wish to continue to enjoy nicotine and the habit of smoking. What are the health effects of the substitution of ENDS for tobacco cigarettes? This systematic review evaluates the evidence of human clinical tests on the respiratory effects of ENDS use in participants who smoke tobacco cigarettes. Methods: A registered and published protocol was developed conforming to PRISMA 2020 and AMSTAR2 standards. The literature search was conducted in PubMed, Scopus, and the CENTRAL Cochrane Library and updated to May 2022. Three supplementary searches and a grey literature search were performed. Studies were evaluated with the JBI quality tools and the Oxford Catalogue of Bias. Due to the heterogeneity (diversity) of the studies, a narrative data synthesis was performed on the test findings plus three sub-group analyses. Results: The review consists of sixteen studies and twenty publications. Spirometry tests comprised the majority of the data. In total, 66 respiratory test measurements were reported, out of which 43 (65%) were not significant. Statistically significant findings were mixed, with 9 tests showing improvements and 14 measuring declines, none of which was clinically relevant. Ten studies were rated at a high risk of bias, and six had some concerns primarily due to inadequate research designs and the conduct of the studies. Reporting bias was documented in thirteen studies. Conclusions: Most of the studies showed no difference in respiratory parameters. This indicates that ENDS substitution for smoking likely does not result in additional harm to respiratory health. Due to the low quality of the studies, confidence in the conclusions is rated as low. Robust studies with a longer duration and sufficient power are required to validate any potential benefits or possible harms of ENDS substitution. Registration PROSPERO #CRD42021239094, International Registered Report Identifier (IRRID): DERR1-10.2196/29084. [ABSTRACT FROM AUTHOR]

Background: Many types of interstitial lung diseases (ILDs) may transition to progressive chronic-fibrosing ILDs with rapid lung function decline and a negative survival prognosis. In real-world clinical settings, forced vital capacity (FVC) measures demonstrating progressive decline may be linked to negative outcomes, including increased risks of costly healthcare resource utilization (HRU). Thus, we assessed the relationship between rate of decline in lung function and an increase in HRU, specifically inpatient hospitalization, among patients with chronic fibrosing ILD. Methods: This study utilized electronic health records from 01-Oct-2015 to 31-Oct-2019. Eligible patients (≥ 18 years old) had ≥ 2 fibrosing ILD diagnosis codes, clinical activity for ≥ 15 months, and ≥ 2 FVC tests occurring 6 months apart. Patients with missing demographic data, IPF, or use of nintedanib or pirfenidone were excluded. Two groups were defined by relative change in percent of predicted FVC (FVC% pred) from baseline to 6 months: significant decline (≥ 10%) vs. marginal decline/stable FVC (decrease < 10% or increase). The primary outcome was defined as the occurrence of an inpatient hospitalization 6 months after the first FVC value. Descriptive and multivariable analysis was conducted to examine the impact of FVC decline on occurrence of inpatient hospitalization. Results: The sample included 566 patients: 13% (n = 75) with significant decline and 87% (n = 491) with marginal decline/stable FVC; their mean age (SD) was 65 (13.7) years and 56% were female. Autoimmune diagnoses were observed among 40% of patients with significant decline, and 27% with marginal decline/stable FVC. The significant decline group had better lung function at baseline than the marginal/stable group. For patients with FVC% <80% at baseline, reduction of FVC% ≥10% was associated with significantly increased odds of an inpatient hospitalization (odds ratio [OR] 2.85; confidence interval [CI] 1.17, 6.94 [p = 0.021]). Conclusion: Decline in FVC% ≥10% was associated with increased odds of inpatient hospitalization among patients with reduced lung function at baseline. These findings support the importance of preserving lung function among patients with fibrosing ILD. [ABSTRACT FROM AUTHOR]

Background: Restrictive spirometry pattern (RSP), defined as reduced forced vital capacity (FVC) in absence of airflow obstruction (AFO), is associated with increased risk of mortality in general population. However, evidence in the patients with silicosis is limited. This study was aimed to investigate the relationship between RSP and the risk of death in a silicotic cohort. Method: This retrospective cohort study used data from the Pneumoconiosis Clinic, Hong Kong Department of Health that containing 4315 patients aged 18–80 years and diagnosed with silicosis during 1981–2019, with a follow-up till 31 December 2019. Spirometry was carried out at the diagnostic examination of silicosis. Lung function categories were classified as normal spirometry (FEV1/FVC ≥ 0.7, FVC ≥ 80% predicted), RSP only (FEV1/FVC ≥ 0.7, FVC < 80% predicted), AFO only (FEV1/FVC < 0.7, FVC ≥ 80% predicted), and RSP&AFO mixed (FEV1/FVC < 0.7, FVC < 80% predicted). The hazard ratio (HR) and 95% confidence intervals (95% CI) were computed using a Cox proportional hazards model adjusting for age, body mass index, history of tuberculosis, smoking status, pack-years, and radiographic characteristics of silicotic nodules. Results: Among the 4315 patients enrolled in the study, the prevalence of RSP was 24.1% (n = 1038), including 11.0% (n = 473) with RSP only and 13.1% (n = 565) with mixed RSP and AFO. During the follow-up period, a total of 2399 (55.6%) deaths were observed. Compared with the silicotics with normal spirometry, those with RSP only had significantly increased risk of all-cause mortality (HR = 1.63, 95% CI 1.44–1.85) and respiratory-related mortality (HR = 1.56, 95% CI 1.31–1.85). Notably, a higher risk of mortality was observed in silicotics with mixed ventilatory defects of both RSP and AFO (all-cause mortality: HR = 2.22, 95% CI 1.95–2.52; respiratory-related mortality: HR = 2.59, 95% CI 2.18–3.07) than in those with RSP only. Conclusion: RSP is significantly associated with increased risk of all-cause and respiratory-related mortality in the silicotics, and patients with mixed restrictive and obstructive ventilatory defect have higher risk of mortality than those with single RSP or AFO. These findings emphasize the importance of recognizing RSP in the occupational settings, especially for the silicotic patients with mixed ventilatory defect. [ABSTRACT FROM AUTHOR]

Background: The main aim of this systematic review was to determine the effectiveness of postoperative rehabilitation interventions that include breathing exercises as a component to prevent atelectasis in lung cancer resection patients. Methods: In this review, we systematically and comprehensively searched the Cochrane Library, PubMed, EMBASE, and Web of Science in English and CNKI and Wanfang in Chinese from 2012 to 2022. The review included any randomized controlled trials focusing on the effectiveness of postoperative rehabilitation interventions that include breathing exercises to prevent pulmonary atelectasis in lung cancer patients. Participants who underwent anatomic pulmonary resection and received postoperative rehabilitation interventions that included breathing exercises as a component were included in this review. The study quality and risks of bias were measured with the GRADE and Cochrane Collaboration tools, and statistical analysis was performed utilizing RevMan 5.3 software. Results: The incidence of atelectasis was significantly lower in the postoperative rehabilitation intervention group (OR = 0.35; 95% CI, 0.18 to 0.67; I2 = 0%; P = 0.67) than in the control group. The patients who underwent the postoperative rehabilitation program that included breathing exercises (intervention group) had higher forced vital capacity (FVC) scores (MD = 0.24; 95% CI, 0.07 to 0.41; I2 = 73%; P = 0.02), forced expiratory volume in one second (FEV1) scores (MD = 0.31; 95% CI, 0.03 to 0.60; I2 = 98%; P < 0.01) and FEV1/FVC ratios (MD = 9.09; 95% CI, 1.50 to 16.67; I2 = 94%; P < 0.01). Conclusion: Postoperative rehabilitation interventions that included breathing exercises decreased the incidence rate of atelectasis and improved lung function by increasing the FVC, FEV1, and FEV1/FVC ratio. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to evaluate the associations between particulate matter (PM), lung function and Impulse Oscillometry System (IOS) parameters in chronic obstructive pulmonary disease (COPD) patients and identity effects between different regions in Beijing, China. Methods: In this retrospective study, we recruited 1348 outpatients who visited hospitals between January 2016 and December 2019. Ambient air pollutant data were obtained from the central monitoring stations nearest the participants' residential addresses. We analyzed the effect of particulate matter with aerodynamic diameter ≤ 2.5 μm (PM2.5) exposure on lung function and IOS parameters using a multiple linear regression model, adjusting for sex, smoking history, education level, age, body mass index (BMI), mean temperature, and relative humidity. Results: The results showed a relationship between PM2.5, lung function and IOS parameters. An increase of 10 µg/m3 in PM2.5 was associated with a decline of 2.083% (95% CI: −3.047 to − 1.103) in forced expiratory volume in one second /predict (FEV1%pred), a decline of 193 ml/s (95% CI: −258 to − 43) in peak expiratory flow (PEF), a decline of 0.932% (95% CI: −1.518 to − 0.342) in maximal mid-expiratory flow (MMEF); an increase of 0.732 Hz (95% CI: 0.313 to 1.148) in resonant frequency (Fres), an increase of 36 kpa/(ml/s) (95% CI: 14 to 57) in impedance at 5 Hz (Z5) and an increase of 31 kpa/(ml/s) (95% CI: 2 to 54) in respiratory impedance at 5 Hz (R5). Compared to patients in the central district, those in the southern district had lower FEV1/FVC, FEV1%pred, PEF, FEF75%, MMEF, X5, and higher Fres, Z5 and R5 (p < 0.05). Conclusion: Short-term exposure to PM2.5 was associated with reductions in lung function indices and an increase in IOS results in patients with COPD. The heavier the PM2.5, the more severe of COPD. [ABSTRACT FROM AUTHOR]

Background: The oral cavity is the gateway to the bacteria community in the lung. Disruption of the symbiotic balance of the oral microbiota has been associated with respiratory diseases. However, little is known about the relationship between oral bacteria and respiratory outcomes in the general population. We aimed to describe the associations between oral bacteria, lung function, and lung inflammation in a community-based population. Methods: Oral (gingival) samples were collected concurrently with spirometry tests in 477 adults (47% males, median age 28 years) from the RHINESSA study in Bergen, Norway. Bacterial DNA from the 16S rRNA gene from gingival fluid were sequenced by Illumina®MiSeq. Lung function was measured using spirometry and measurement of fractional exhaled nitric oxide (FeNO) were performed to examine airway inflammation. Differential abundance analysis was performed using ANCOM-BC, adjusting for weight, education, and smoking. Results: The abundance of the genera Clostridiales, Achromobacter, Moraxella, Flavitalea and Helicobacter were significantly different among those with low FEV1 (< lower limit of normal (LLN)) as compared to normal FEV1 i.e. ≥ LLN. Twenty-three genera differed in abundance between among those with low FVC < LLN as compared to normal FEV1 ≥ LLN. The abundance of 27 genera from phyla Actinobacteria, Bacteroidetes, Firmicutes, Proteobacteria and Sacchribacteria differed significantly between elevated FeNO levels (≥ 50 ppb) compared to FeNO ≤ 25 ppb. Conclusion: Oral bacterial composition was significantly different for those with low FEV or FVC as compared to those with normal lung function equal to or higher than LLN. Differential bacterial composition was also observed for elevated FeNO levels. [ABSTRACT FROM AUTHOR]

Background: To compare the severity of radiation-induced lung injury (RILI) after the right lung of SD rats received interstitial brachytherapy and stereotactic radiotherapy (SBRT). Methods: RILI rat model was established using interstitial brachytherapy and SBRT methods, respectively. CT scan was performed to analyze the lung volume and the CT value difference between the left and right lungs in rats. Then the lung tissues were analyzed through H&E staining, peripheral blood was extracted to detect the expression levels of serum inflammatory cytokines, pro-fibrotic cytokines, and fibrotic-inhibiting cytokines by ELISA. Results: The difference between right and left lung CT values was significantly elevated in the SBRT group when compared with the control group and the interstitial brachytherapy group (P < 0.05). The IFN-γ expression in the interstitial brachytherapy group was significantly different from that in the SBRT group at week 1, 4, 8 and 16. Besides, the expressions of IL-2, IL-6 and IL-10 in SBRT group were significantly higher than that of interstitial brachytherapy group (P < 0.05). The TGF-β expression in interstitial brachytherapy group reached its peak with the increase of time from week 1 to week 16, and it was significantly lower than SBRT group (P < 0.05). The mortality rate in the SBRT group was 16.7%, which was significantly higher than that in the interstitial brachytherapy group. Conclusion: The treatment method of interstitial brachytherapy is considered as an effective and safe tool by reducing the side effects of radiotherapy and increasing the radiation dose of radiotherapy. [ABSTRACT FROM AUTHOR]

Background: The association between periodontitis and post-bronchodilator lung function is unclear. We aimed to determine the associations between symptoms of severe periodontitis (SSP) and post-bronchodilator lung function in the Chinese population. Methods: A cross-sectional study (China Pulmonary Health study) was conducted from 2012 to 2015 in a large Chinese nationally representative sample of 49,202 participants aged 20–89 years. Data on demographic characteristics and periodontal symptoms of participants were collected by questionnaire. Participants who had at least one of the two severe symptoms (tooth mobility and natural tooth loss) in the past year were defined to have SSP, which was set as one variable for analyses. Post-bronchodilator lung function data including forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) were collected by spirometry. Results: The values of post-FEV1, post-FVC and post-FEV1/FVC of the participants with SSP were all significantly lower than the participants without SSP (all p < 0.001). SSP were significantly associated with post-FEV1/FVC < 0.7 (p < 0.001). In the multiple regression analyses, SSP were still negatively associated with post-FEV1(b = -0.04, 95%CI (-0.05 -0.03), p < 0.001), post-FEV1/FVC (b = -0.45, 95%CI (-0.63, -0.28), p < 0.001) and significantly associated with post-FEV1/FVC < 0.7 (OR = 1.08, 95%CI 1.01—1.16, p = 0.03) after full adjustment for potential confounders. Conclusions: Our data suggest that SSP were negatively associated with post-bronchodilator lung function in the Chinese population. Longitudinal cohort studies are needed to confirm these associations in the future. [ABSTRACT FROM AUTHOR]

Introduction: In this study, we will combine the traditional Baduanjin with Yijin Jing and Wuqinxi to create an optimized Baduanjin exercise program with three different forms (vertical, sitting, and horizontal) to adapt to idiopathic pulmonary fibrosis (IPF) patients in vairous stages of the disease. The purpose of this study is to explore and compare the therapeutic effects of this multi-form Baduanjin, traditional Baduanjin, and resistance training on lung function and limb motor function in IPF patients. The goal of this study is to prove a novel optimal exercise prescription strategy of Baduanjin exercise for improving and protecting lung function in IPF patients. Methods/design: A single-blind and randomized controlled trial is used to conduct this study, while the randomization list will be generated using a computerized random number generator and opaque sealed envelopes with group allocation will be prepared. It will be strictly followed to blind the outcome assessors. and until the experiment's conclusion, participants won't know which group they are enrolled in. Patients between the ages of 35 and 80 who have stable diseases and have not regularly practiced Baduanjin exercise in the past will be included. They are divvied up into the following five groups at random: (1) The conventional care group (control group, CG), (2) The traditional Baduanjin exercise group (TG), (3) The modified Baduanjin exercise group (IG), (4) The resistance exercise group (RG) (5) The modified Baduanjin exercise combined with resistance exercise group (IRG). Those CG participants only received the usual treatment, while TC, IG, and RG participants exercised 1 h twice a day for 3 months. MRG participants will have a 3-month intervention with 1 h of Modified Baduanjin Exercise and 1 H of Resistance Training for each day. Every week, all groups underwent will supervis one-day training, with the exception of the control group. The Pulmonary Function Testing (PFT), HRCT, and 6MWT are the main outcome variables. The St. George Respiratory Questionnaire and mMRC are used as secondary outcome measures. Discussion: This study may produce a new Baduanjin exercise prescription that is user-friendly, simple to execute, more targeted, and adaptable. Because it consists of three forms, including vertical, sitting, and horizontal, it is more adaptable to the various disease stages and actual situations of IPF patients and may compensate for the shortcomings of conventional pulmonary rehabilitation and traditional Baduanjin. Trial registration: Chinese Clinical Trial Registry, ChiCTR2200055559. Registered on 12 January 2022. [ABSTRACT FROM AUTHOR]

Flavored electronic cigarettes (ECs) present a serious health challenge globally. Currently, it is unknown whether the addition of highly popular menthol flavoring to e-liquid is associated with changes in the number of aerosolized particles generated or altered lung function. Here, we first performed preclinical studies using our novel robotic platform Human Vaping Mimetic Real-Time Particle Analyzer (HUMITIPAA). HUMITIPAA generates fresh aerosols for any desired EC in a very controlled and user-definable manner and utilizes an optical sensing system to quantitate and analyze sub-micron and microparticles from every puff over the course of vaping session in real-time while emulating clinically relevant breathing mechanics and vaping topography. We discovered that addition of menthol flavoring to freshly prepared e-liquid base propylene glycol–vegetable glycerin leads to enhanced particle counts in all tested size fractions, similar to the effect of adding vitamin E acetate to e-liquid we previously reported. Similarly, we found that menthol vs. non-menthol (tobacco) flavored pods from commercially available ECs leads to generation of significantly higher quantities of 1–10 µm particles upon inhalation. We then retrospectively analyzed data from the COPDGene study and identified an association between the use of menthol flavored ECs and reduced FEV1% predicted and FEV1/FVC independent of age, gender, race, pack-years of smoking, and use of nicotine or cannabis-containing vaping products. Our results reveal an association between enhanced inhaled particle due to menthol addition to ECs and worse lung function indices. Detailed causal relation remains to be demonstrated in future large-scale prospective clinical studies. Importantly, here we demonstrate utility of the HUMITIPAA as a predictive enabling technology to identify inhalation toxicological potential of emerging ECs as the chemical formulation of e-liquid gets modified. [ABSTRACT FROM AUTHOR]

Background: Dynamic spirometry is an important investigation to differentiate between impaired and normal lung function. This study aimed to evaluate the results of lung function testing in a cohort of subjects from Northern Sweden without any known heart or pulmonary disease. Our focus was to compare with two reference materials that have showed differences in the age-dependency of lung function in Swedish subjects. Methods: The study population consisted of 285 healthy adults (148 males, 52%) between 20–90 years of age. The subjects had been randomly selected from the population register for inclusion in a study investigating cardiac function in heart-healthy subjects, but were also assessed with dynamic spirometry. At least seven percent reported smoking. Sixteen subjects presented with pulmonary functional impairments and were excluded from the current study. The sex-specific age-dependency in lung volumes was estimated using the LMS model, where non-linear equations were derived for the mean value (M), the location (L) or skewness, and the scatter (S) or coefficient of variation. This model of the observed lung function data was compared with reference values given by the original LMS model published by the Global Lung Initiative (GLI), and with the model from the recent Obstructive Lung Disease In Norrbotten (OLIN) study, where higher reference values were presented for Swedish subjects than those given by the GLI model. Results: No differences were found in the age-dependency of pulmonary function between the LMS model developed in the study and the OLIN model. Although the study group included smokers, the original GLI reference values suggested significantly lower normal values of FEV1 (forced expiratory volume) and FVC (forced vital capacity), and consequently fewer subjects below the lower limit of normality, than both the rederived LMS and OLIN models. Conclusions: Our results are in line with previous reports and support that the original GLI reference values underestimate pulmonary function in the adult Swedish population. This underestimation could be reduced by updating the coefficients in the underlying LMS model based on a larger cohort of Swedish citizens than was available in this study. [ABSTRACT FROM AUTHOR]

Background: While benefits of greenness exposure to health have been reported, findings specific to lung function are inconsistent. The purpose of this study is to assess the correlations of greenness exposure with multiple lung function indicators based on chronic obstructive pulmonary disease (COPD) monitoring database from multiple cities of Anhui province in China. Methods: We assessed the greenness using the annual average of normalized difference vegetation index (NDVI) with a distance of 1000-meter buffer around each local community or village. Three types of lung function indicators were considered, namely indicators of obstructive ventilatory dysfunction (FVC, FEV1, FEV1/FVC, and FEV1/FEV3); an indicator of large-airway dysfunction (PEF); indicators of small-airway dysfunction (FEF25%, FEF50%, FEF75%, MMEF, FEV3, FEV6, and FEV3/FVC). Linear mixed effects model was used to analyze associations of greenness exposure with lung function through adjusting age, sex, educational level, occupation, residence, smoking status, history of tuberculosis, family history of lung disease, indoor air pollution, occupational exposure, PM2.5, and body mass index. Results: A total of 2768 participants were recruited for the investigations. An interquartile range (IQR) increase in NDVI was associated with better FVC (153.33mL, 95%CI: 44.07mL, 262.59mL), FEV1 (109.09mL, 95%CI: 30.31mL, 187.88mL), FEV3 (138.04mL, 95%CI: 39.43mL, 236.65mL), FEV6 (145.42mL, 95%CI: 42.36mL, 248.47mL). However, there were no significant associations with PEF, FEF25%, FEF50%, FEF75%, MMEF, FEV1/FVC, FEV1/FEV6, FEV3/FVC. The stratified analysis displayed that an IQR increase in NDVI was related with improved lung function in less than 60 years, females, urban populations, nonsmokers, areas with medium concentrations of PM2.5 and individuals with BMI of less than 28 kg/m2. Sensitivity analyses based on another greenness indice (enhanced vegetation index, EVI) and annual maximum of NDVI remained consistent with the main analysis. Conclusions: Our findings supported that exposure to greenness was strongly related with improved lung function. [ABSTRACT FROM AUTHOR]

Background/Objective: Metabolic syndrome (MS) is related to lung dysfunction. However, its impact according to insulin resistance (IR) remains unknown. Therefore, we evaluated whether the relation of MS with lung dysfunction differs by IR. Subject/Methods: This cross-sectional study included 114,143 Korean adults (mean age, 39.6 years) with health examinations who were divided into three groups: metabolically healthy (MH), MS without IR, and MS with IR. MS was defined as presence of any MS component, including IR estimated by HOMA-IR ≥ 2.5. Adjusted odds ratios (aORs) and 95% confidence intervals (CIs) for lung dysfunction were obtained in MS, MS without IR, and MS with IR groups compared with the MH (reference) group. Results: The prevalence of MS was 50.7%. The percent predicted forced expiratory volume in 1 s (FEV1%) and forced vital capacity (FVC%) showed statistically significant differences between MS with IR and MH and between MS with IR and MS without IR (all P < 0.001). However, those measures did not vary between MH and MS without IR (P = 1.000 and P = 0.711, respectively). Compared to MH, MS was not at risk for FEV1% < 80% (1.103 (0.993–1.224), P = 0.067) or FVC% < 80% (1.011 (0.901–1.136), P = 0.849). However, MS with IR was clearly associated with FEV1% < 80% (1.374 (1.205–1.566) and FVC% < 80% (1.428 (1.237–1.647) (all p < 0.001), though there was no evident association for MS without IR (FEV1%: 1.078 (0.975–1.192, P = 0.142) and FVC%: 1.000 (0.896–1.116, p = 0.998)). Conclusion: The association of MS with lung function can be affected by IR. However, longitudinal follow-up studies are required to validate our findings. [ABSTRACT FROM AUTHOR]