Green spaces and respiratory, cardiometabolic, and neurodevelopmental outcomes: An individual-participant data meta-analysis of >35.000 European children.

Studies evaluating the benefits and risks of green spaces on children's health are scarce. The present study aimed to examine the associations between exposure to green spaces during pregnancy and early childhood with respiratory, cardiometabolic, and neurodevelopmental outcomes in school-age children. We performed an Individual-Participant Data (IPD) meta-analysis involving 35,000 children from ten European birth cohorts across eight countries. For each participant, we calculated residential Normalized Difference Vegetation Index (NDVI) within a 300 m buffer and the linear distance to green spaces (meters) during prenatal life and childhood. Multiple harmonized health outcomes were selected: asthma and wheezing, lung function, body mass index, diastolic and systolic blood pressure, non-verbal intelligence, internalizing and externalizing problems, and ADHD symptoms. We conducted a two-stage IPD meta-analysis and evaluated effect modification by socioeconomic status (SES) and sex. Between-study heterogeneity was assessed via random-effects meta-regression. Residential surrounding green spaces in childhood, not pregnancy, was associated with improved lung function, particularly higher FEV1 (ß = 0.06; 95 %CI: 0.03, 0.09 I2 = 4.03 %, p < 0.001) and FVC (ß = 0.07; 95 %CI: 0.04, 0.09 I2 = 0 %, p < 0.001) with a stronger association observed in females (p < 0.001). This association remained robust after multiple testing correction and did not change notably after adjusting for ambient air pollution. Increased distance to green spaces showed an association with lower FVC (ß = -0.04; 95 %CI: -0.07, -0.02, I2 = 4.8, p = 0.001), with a stronger effect in children from higher SES backgrounds (p < 0.001). No consistent associations were found between green spaces and asthma, wheezing, cardiometabolic, or neurodevelopmental outcomes, with direction of effect varying across cohorts. Wheezing and neurodevelopmental outcomes showed high between-study heterogeneity, and the age at outcome assessment was only associated with heterogeneity in internalizing problems.. This large European meta-analysis suggests that childhood exposure to green spaces may lead to better lung function. Associations with other respiratory outcomes and selected cardiometabolic and neurodevelopmental outcomes remain inconclusive.

Demographic factors associated with within-individual variability of lung function for adults with cystic fibrosis: A UK registry study.

BACKGROUND: Lung function is a key outcome used in the evaluation of disease progression in cystic fibrosis. The variability of individual lung function measurements over time (within-individual variability) has been shown to predict subsequent lung function changes. Nevertheless, the association between within-individual lung function variability and demographic and genetic covariates has not been quantified. METHODS: We performed a longitudinal analysis of data from a cohort of 7099 adults with cystic fibrosis (between 18 and 49 years old) from the UK cystic fibrosis registry, containing annual review data between 1996 and 2020. A mixed-effects location-scale model is used to quantify mean FEV1 (forced expiratory volume in 1 s) trajectories and FEV1 within-individual variability as a function of sex, age at annual review, diagnosis after first year of life, homozygous F508 genotype and birth cohort. RESULTS: Mean FEV1 decreased with age and lung function variability showed a near-quadratic trend by age. Males showed higher FEV1 mean and variability than females across the whole age range. Earlier diagnosis and homozygous F508 genotype were also associated with higher FEV1 mean and variability. Individuals who died during follow-up showed on average higher lung function variability than those who survived. CONCLUSIONS: Key variables known to be linked with mean lung function in cystic fibrosis are also associated with an individual's lung function variability. This work opens new avenues to understand the role played by lung function variability in disease progression and its utility in predicting key outcomes such as mortality.

Assessment of bronchodilator response in preschoolers: A systematic review.

BACKGROUND: Several techniques can be used to assess bronchodilator response (BDR) in preschool-aged children, including spirometry, respiratory oscillometry, the interrupter technique, and specific airway resistance. However, there has not been a systematic comparison of BDR thresholds across studies yet. METHODS: A systematic review was performed on all studies up to May 2023 measuring a bronchodilator effect in children 2-6 years old using one of these techniques (PROSPERO CRD42021264659). Studies were identified using MEDLINE, Cochrane, EMBASE, CINAHL via EBSCO, Web of Science databases, and reference lists of relevant manuscripts. RESULTS: Of 1224 screened studies, 43 were included. Over 85% were from predominantly European ancestry populations, and only 22 studies (51.2%) calculated a BDR cutoff based on a healthy control group. Five studies included triplicate testing with a placebo to account for the within-subject intrasession repeatability. A relative BDR was most consistently reported by the included studies (95%) but varied widely across all techniques. Various statistical methods were used to define a BDR, with six studies using receiver operating characteristic analyses to measure the discriminative power to distinguish healthy from wheezy and asthmatic children. CONCLUSION: A BDR in 2- to 6-year-olds cannot be universally defined based on the reviewed literature due to inconsistent methodology and cutoff calculations. Further studies incorporating robust methods using either distribution-based or clinical anchor-based approaches to define BDR are required.

Bioelectrical impedance and lung function-associations with gender and central obesity: results of the EpiHealth study.

BACKGROUND: Obesity is a major public health concern associated with various health problems, including respiratory impairment. Bioelectrical impedance (BIA) is used in health screening to assess body fat. However, there is no consensus in healthcare on how body fat should be assessed in relation to lung function. In this study, we aimed to investigate how BIA in relation to waist circumference contribute, using data from a large Swedish population study. METHODS: A total of 17,097 participants (aged 45-75 years) were included in the study. The relationships between fat mass, waist circumference, and lung function were analysed using weighted quantile sum regression. RESULTS: Increased fat mass was significantly associated with decreased lung function (FEV1, FVC) in both sexes. Also, the influence of trunk fat and waist circumference on FVC and FEV1 differed by sex: in males, waist circumference and trunk fat had nearly equal importance for FVC (variable weights of 0.42 and 0.41), whereas in females, trunk fat was significantly more important (variable weights 0.84 and 0.14). For FEV1, waist circumference was more important in males, while trunk fat was more significant in females (variable weights male 0.68 and 0.28 and 0.23 and 0.77 in female). CONCLUSIONS: Our results suggest that trunk fat should be considered when assessing the impact of adipose tissue on lung function and should potentially be included in the health controls.

Home and School Pollutant Exposure, Respiratory Outcomes, and Influence of Historical Redlining.

BACKGROUND: The discriminatory and racist policy of historical redlining in the United States (U.S.) during the 1930s played a role in perpetuating contemporary environmental health disparities. OBJECTIVE: Our objectives were to determine associations between home and school pollutant exposure (fine particulate matter (PM2.5), nitrogen dioxide (NO2)) and respiratory outcomes (Composite Asthma Severity Index (CASI), lung function) among school-aged children with asthma and examine whether associations differed between children who resided and/or attended school in historically redlined compared to non-redlined neighborhoods. METHODS: Children ages 6 to 17 with moderate-to-severe asthma (N=240) from 9 U.S. cities were included. Combined home and school exposure to PM2.5 and NO2 was calculated based on geospatially assessed monthly averaged outdoor pollutant concentrations. Repeated measures of CASI and lung function were collected. RESULTS: Overall, 37.5% of children resided and/or attended schools in historically redlined neighborhoods. Children in historically redlined neighborhoods had greater exposure to NO2 (median: 15.4 vs 12.1 ppb) and closer distance to a highway (median: 0.86 vs 1.23 km), compared to those in non-redlined neighborhoods (p<0.01). Overall, PM2.5 was not associated with asthma severity or lung function. However, among children in redlined neighborhoods, higher PM2.5 was associated with worse asthma severity (p<0.005). No association was observed between pollutants and lung function or asthma severity among children in non-redlined neighborhoods (p>0.005). CONCLUSIONS: Our findings highlight the significance of historical redlining and current environmental health disparities among school-aged children with asthma, specifically, the environmental injustice of PM2.5 exposure and its associations with respiratory health.

Is there a correlation between the changes in airway inflammation and the changes in respiratory mechanics after vaping in patients with asthma?

BACKGROUND: Electronic cigarettes (ECs) have been promoted as alternatives to traditional cigarettes. AIM: To investigate ECs' effects on respiratory system, especially in patients with respiratory diseases. METHODS: We randomly selected 25 smokers with stable moderate asthma and matched them with 25 healthy smokers. All were subjucted to pulmonary function tests (PFTs), impulse oscillometry (IOS), fraction exhaled Nitric Oxide (FeNO), exhaled breathe condensate (EBC) and biomarker measurements before and after vaping one nicotine-containing EC. RESULTS: The increase in FeNO 30 minutes after EC, reflecting airway inflammation, significantly correlated with increase of residual volume (RV), total lung capacity, respiratory impedance at 5 Hz (Z5Hz) and respiratory resistance at 5 and 20 Hz (R5Hz and R20Hz). No significant correlations were found between EBC biomarkers' changes and respiratory mechanics. CONCLUSION: This is the first study demonstrating that the changes in airway inflammation caused by EC have direct effects in respiratory mechanics of asthmatic patients.

Efficacy and safety of LAU-7b in a Phase 2 trial in adults with cystic fibrosis.

BACKGROUND: Lung inflammation is associated with tissue damage in cystic fibrosis (CF). LAU-7b, a novel oral drug candidate, was shown to control inflammation and stabilize CFTR protein in the epithelial membrane during inflammatory stress in preclinical models of CF. METHODS: A double-blind, randomized, placebo-controlled Phase 2 study was conducted to evaluate efficacy and safety of LAU-7b in adults with CF. LAU-7b or placebo was administered over 24 weeks as six 21-day treatment cycles each separated by 7 days. The primary efficacy endpoint was the absolute change from baseline in percent predicted forced expiratory volume in 1 second (ppFEV1) at 24 weeks. RESULTS: A total of 166 subjects received at least one dose of study drug (Intent-To-Treat population, ITT), of which 122 received ≥5 treatment cycles (Per-Protocol population, PP). Both treatment arms showed a mean lung function loss at 24 weeks of 1.18 ppFEV1 points with LAU-7b and 1.95 ppFEV1 with placebo, a 0.77 ppFEV1 (40 s) difference, p=0.345, and a 0.95 ppFEV1 (49 %) difference in the same direction in PP population, p=0.263. Primary analysis of mean ppFEV1 through 24 weeks showed differences of 1.01 and 1.23 ppFEV1, in the ITT (65 % less loss, p=0.067) and PP populations (78 % less loss, reaching statistical significance p=0.049), respectively. LAU-7b had an acceptable safety profile. CONCLUSION: Although the study did not meet its primary efficacy endpoint in the ITT population, LAU-7b was generally well tolerated and showed evidence of preservation of lung function to support further development.

The mediating role of air pollutants in the association between education and lung function among the elderly, the HAPIEE study.

BACKGROUND: Chronic exposure to air pollutants harms human health, and at a geographical level, concentrations of air pollutants are often associated with socioeconomic disadvantage. OBJECTIVES: The aim of this study was to investigate the effects of educational attainment and air pollution on lung function in older adults, and whether air pollution may mediate the effect of education. METHODS: The study included 6381 individuals (mean age 58.24 ± 7.14 years) who participated in the Czech HAPPIE (Health, Alcohol, and Psychosocial Factors in Eastern Europe) study. Participants' residential addresses were linked to air pollution data, including mean exposures to PM10 (particulate matter of aerodynamic diameter below 10 µm) and NO2 (nitrogen dioxide). We used path analysis to link educational attainment and air pollutants to a standardized measure of the Forced Expiratory Volume in the first second (FEV1). RESULTS: Higher levels of participants' education were associated with lower exposures to PM10 and NO2. Individuals with tertiary education had higher standardized FEV1 than individuals with primary education (88 % vs 95 %). Path analysis revealed a direct positive effect of education on FEV1, while about 12 % of the relationship between education and lung function was mediated by PM10 and NO2. CONCLUSIONS: Education (typically completed at young ages) appeared to have a protective effect on lung function later in life, and a small part of this effect was mediated by air pollution.

Socioeconomic differences in limited lung function: a cross-sectional study of middle-aged and older adults in Germany.

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.

Association Between Urinary Phthalate Metabolites and Chronic Obstructive Pulmonary Disease: A Cross-Sectional Study.

Objective: To determine the association of urinary phthalate metabolites with chronic obstructive pulmonary disease (COPD), airflow obstruction, lung function and respiratory symptoms. Methods: Our study included a total of 2023 individuals aged ≥ 40 years old in the National Health and Nutrition Examination Survey (NHANES). Multivariate logistic regression was conducted to explore the correlation of eleven urinary phthalate metabolites (MCNP, MCOP, MECPP, MnBP, MCPP, MEP, MEHHP, MEHP, MiBP, MEOHP, and MBzP) with COPD, airflow obstruction and respiratory symptoms. Linear regression analyses were used to evaluate the relationship between urinary phthalate metabolites and lung function. Results: When compared to the first tertile, the third tertile of MEHHP was associated with the risk of COPD [OR: 2.779; 95% confidence interval (CI): 1.129-6.840; P = 0.026]. Stratified analysis showed that MEHHP increased the risk of COPD by 7.080 times in male participants. Both MCPP and MBzP were positively correlated with the risk of airflow obstruction. The third tertile of MBzP increased the risk of cough by 1.545 (95% CI: 1.030-2.317; P = 0.035) times. Both FEV1 and FVC were negatively associated with MEHHP, MECPP, MnBP, MEP, MiBP and MEOHP. Conclusion: Higher levels of MEHHP are associated with increased risk of COPD, and lower measures of FEV1 and FVC. MBzP is positively related to airflow obstruction and cough.

Expiratory Venous Volume and Arterial Tortuosity are Associated with Disease Severity and Mortality Risk in Patients with COPD: Results from COSYCONET.

Purpose: The aim of this study was to evaluate the association between computed tomography (CT) quantitative pulmonary vessel morphology and lung function, disease severity, and mortality risk in patients with chronic obstructive pulmonary disease (COPD). Patients and Methods: Participants of the prospective nationwide COSYCONET cohort study with paired inspiratory-expiratory CT were included. Fully automatic software, developed in-house, segmented arterial and venous pulmonary vessels and quantified volume and tortuosity on inspiratory and expiratory scans. The association between vessel volume normalised to lung volume and tortuosity versus lung function (forced expiratory volume in 1 sec [FEV1]), air trapping (residual volume to total lung capacity ratio [RV/TLC]), transfer factor for carbon monoxide (TLCO), disease severity in terms of Global Initiative for Chronic Obstructive Lung Disease (GOLD) group D, and mortality were analysed by linear, logistic or Cox proportional hazard regression. Results: Complete data were available from 138 patients (39% female, mean age 65 years). FEV1, RV/TLC and TLCO, all as % predicted, were significantly (p < 0.05 each) associated with expiratory vessel characteristics, predominantly venous volume and arterial tortuosity. Associations with inspiratory vessel characteristics were absent or negligible. The patterns were similar for relationships between GOLD D and mortality with vessel characteristics. Expiratory venous volume was an independent predictor of mortality, in addition to FEV1. Conclusion: By using automated software in patients with COPD, clinically relevant information on pulmonary vasculature can be extracted from expiratory CT scans (although not inspiratory scans); in particular, expiratory pulmonary venous volume predicted mortality. Trial Registration: NCT01245933.

Association of preserved ratio impaired spirometry with mortality and cardiovascular diseases: a systematic review and meta-analysis.

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.

[Pulmonary function test: The testing of children]. / Exploration fonctionnelle respiratoire : explorer l'enfant.

In paediatrics, the pulmonary function test (PFT) is most often performed to support the diagnosis or in follow-up of asthma patients. Whatever the pathology responsible for respiratory symptoms and/or functional impairment, repeated PFTs make it possible to establish a prognosis (pulmonary function trajectories…) and to orient preventive interventions. PFT can be performed routinely from the age of three years, provided that the following requirements are met: suitable techniques and equipment, staff trained to apply the techniques and to receive young children, reference values for each technique indicating the limits of normal values and of between-test significant variation. From the age of three, children can be subjected to tidal breathing measurement of: resistance of the respiratory system (oscillometry, Rrs; airflow interruption, Rint) or of airways specific resistance (sRaw) and functional residual capacity (by applying a dilution technique). With maturity, the child will become capable of mobilizing his or her slow vital capacity to measure total lung capacity (TLC), once again by applying a dilution technique, then later by breathing against a closed shutter (plethysmography TLC and Raw). Finally, the child will be able to carry out forced expiration (forced spirometry) along with all of the other PFTs. It is important to take into account the paediatric adaptations specified in the international recommendations regarding the performance, reproducibility and quality of PFTs targeting this population.

Treatment of small as well as large declines in lung function enhances recovery to baseline in people with CF.

BACKGROUND: The benefit of antibiotic treatment of acute drops in FEV1 percent predicted (FEV1pp) has been clearly established, but data from the early 2000s showed inconsistent treatment. Further, there is no empirical evidence for what magnitude of drop is clinically significant. METHODS: We used data from the CF Foundation Patient Registry (CFFPR) from 2016 to 2019 to determine the association between treatment (any IV antibiotics, only oral or newly prescribed inhaled antibiotics, or no antibiotic therapy) following a decline of ≥5% from baseline FEV1pp and return to 100% baseline FEV1pp days using multivariable logistic regression including an interaction between the magnitude of decline and treatment category. RESULTS: Overall, 16,495 PWCF had a decline: 16.5% were treated with IV antibiotics, 25.0% non-IV antibiotics, and 58.5% received no antibiotics. Antibiotic treatment was more likely for those with lower lung function, history of a positive PA culture, older age and larger FEV1 decline (p < 0.001). Treatment with IV antibiotics or oral/inhaled antibiotics was associated with a higher odds of recovery to baseline compared to no treatment across all levels of decline, including declines of 5%-10%. CONCLUSIONS: A large proportion of acute drops in FEV1pp continue to be untreated, especially in younger patients and those with higher baseline lung function. Acute drops as small as 5% predicted are less likely to be recovered if antibiotic treatment is not prescribed. These findings suggest the need for more aggressive antimicrobial treatment of acute drops in FEV1, including those of a magnitude previously believed to be associated with self-recovery.

Dupilumab 200 mg was efficacious in children (6-11 years) with moderate-to-severe asthma for up to 2 years: EXCURSION open-label extension study.

BACKGROUND: The phase 3 VOYAGE (NCT02948959) and open-label extension EXCURSION (NCT03560466) studies evaluated dupilumab in children (6-11 years) with uncontrolled moderate-to-severe asthma. This post hoc analysis assessed the efficacy and safety of add-on dupilumab 200 mg every 2 weeks (q2w), the largest dose cohort in both studies, in children from VOYAGE who participated in EXCURSION. METHODS: Annualized rate of severe asthma exacerbations (AERs), change in prebronchodilator percent predicted forced expiratory volume in 1 s (ppFEV1), and treatment-emergent adverse events were assessed in children with moderate-to-severe asthma who received dupilumab 200 mg q2w in VOYAGE and EXCURSION (dupilumab/dupilumab arm) and those who received placebo in VOYAGE and dupilumab 200 mg q2w in EXCURSION (placebo/dupilumab arm). These endpoints were also assessed in children with moderate-to-severe type 2 asthma (defined as blood eosinophil count ≥150 cells/µL or FeNO ≥20 ppb at the parent study baseline [PSBL]). RESULTS: In the overall population, dupilumab reduced AER and improved prebronchodilator ppFEV1 in the dupilumab/dupilumab arm (n = 158) for up to 2 years. Children receiving placebo/dupilumab (n = 85) showed similar reductions after initiation of dupilumab 200 mg q2w in EXCURSION. Similar results were observed for children with type 2 asthma at PSBL. The safety profile was consistent with the known safety profile of dupilumab. CONCLUSION: In children (6-11 years) with uncontrolled moderate-to-severe type 2 asthma, dupilumab 200 mg reduced exacerbation rates and improved lung function for up to 2 years and showed safety consistent with the known dupilumab safety profile.

Associations of Cardiorespiratory Fitness and Muscular Endurance Fitness With Pulmonary Function in Physically Active Young Adults.

RATIONALE: While the beneficial effects of physical fitness on general health are well-documented, the specific relationship between different types of physical fitness, particularly cardiorespiratory fitness (CRF) and muscular endurance fitness (MEF), and lung function in physically active young adults remains less explored. OBJECTIVE: This study investigated the relationship between CRF and MEF, and their correlation with lung function in physically active young adults. METHODS: This cross-sectional study involved a cohort of 1227 physically active young adults without lung diseases. Lung function was assessed using FEV1, FVC, and FEV1/FVC measurements. The 3000-m run was used to assess CRF, and the 2-min push-up and sit-up tests were used to assess MEF. Multivariable linear regression analysis was used to evaluate the relationships between these fitness measures and lung function, adjusting for potential covariates. RESULTS: Enhanced CRF was associated with superior FEV1 and FVC after adjusting for covariates (ß=-.078, p=.015 for FEV1; ß=-.086, p=.009 for FVC). Push-ups were positively associated with FEV1 (ß=.102, p=.014), but not with FVC. In contrast, sit-ups showed no significant correlation with lung function in the fully adjusted model. CONCLUSION: The study demonstrated a clear association between improved physical fitness and better lung function in physically active young adults, with various exercises showing distinct associations with lung metrics. Notably, push-ups were particularly associated with higher FEV1. A future prospective study is necessary to determine whether routine exercises, such as push-ups, might lead to greater lung function.

Hypercapnia and lung function parameters in chronic obstructive pulmonary disease.

BACKGROUND: In advanced chronic obstructive pulmonary disease (COPD), hypercapnia may occur due to severe bronchial obstruction with lung hyperinflation. Non-invasive ventilation (NIV) provides the standard of care intended to achieve physiological PCO2 levels, thereby reducing overall mortality. The present study aimed to evaluate pulmonary function parameters derived from spirometry (forced vital capacity [FVC], forced expiratory volume in 1 s [FEV1]), body plethysmography (residual volume [RV], total lung capacity [TLC]), and lung diffusion capacity for carbon monoxide (single-breath method [DCO-SB], alveolar-volume corrected values [DCO-VA]) as predictors of chronic hypercapnia in patients with advanced COPD. METHODS: This monocentric, retrospective observational study included 423 COPD patients. Receiver operating characteristic (ROC) curve analysis and cross-validation were used to assess lung function parameters' diagnostic accuracy for predicting chronic hypercapnia, with the resulting performance expressed as area under the ROC curve (AUROC). We performed univariable and multivariable binary logistic regression analysis to determine if these parameters were independently associated with chronic hypercapnia, with probabilities reported as odds ratios [OR] with 95% confidence intervals [95%CI]. RESULTS: FVC% (AUROC 0.77 [95%CI 0.72-0.81], P < 0.01) and FEV1% (AURIC 0.75 [95%CI 0.70-0.79], P < 0.01) exhibited reasonable accuracy in the prediction of chronic hypercapnia, whereas lung diffusion capacity performed poorly (AUROC 0.64 [95%CI 0.58-0.71] for DCO-SB%, P < 0.01). FVC% (OR 0.95 [95%CI 0.93-0.97], P < 0.01) and FEV1% (OR 0.97 [95%CI 0.94-0.99], P = 0.029) were the only parameters associated independently with chronic hypercapnia in logistic regression analysis. FVC and FEV1 thresholds that best separated hypercapnic from normocapnic subjects reached 56% and 33% of predicted values. CONCLUSIONS: Routinely collected pulmonary function parameters, particularly FVC% and FEV1%, may predict chronic hypercapnia during COPD progression.

COPD, PRISm and lung function reduction affect the brain cortical structure: a Mendelian randomization study.

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.