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Background The pathways by which air pollution affects cognition remain to be explored. This study aimed to explore how single air pollutants [including nitrogen oxide (NO X ), nitrogen dioxide (NO2), particulate matter with a diameter of 2.5 micrometers (PM2.5), PM10, and PM2.5–10], and air pollution mixture could affect cognitive function and the incidence of dementia, and determine whether pulmonary function (PF) could play a mediating role in the relationship. Methods Multiple statistical methods were employed to evaluate association of 5 air pollutants (NO X , NO2, PM2.5, PM10, and PM2.5–10) with cognitive function. Bootstrap method was used to estimate mediating role of PF in the association of air pollutants with cognition or the incidence of dementia. Results A mixture of air pollutants was associated with performance on 5 cognitive tests, and global cognition (p  < .05). Significantly negative association was also identified between mixture of air pollutants and PF (β= −0.020, 95% confidence interval (CI) = −0.029 to −0.011). In addition, as PF scores increase, performance on all cognitive tests significantly improve, although the risk of dementia correspondingly decreases. It was noted that PF was shown to mediate the effects of air pollution mixtures on all cognitive tests as well as global cognition. For global cognition, PF mediated 6.08% of the association. PF was also found to have a mediating role in the association between NO X , NO2, PM2.5, and the risk of dementia. Conclusions Mixed air pollution may impact cognitive function, with PF potentially mediating this relationship. [ABSTRACT FROM AUTHOR]

OBJECTIVES: Early studies of venovenous extracorporeal membrane oxygenation (ECMO) in COVID-19 have revealed similar outcomes to historical cohorts. Changes in the disease and treatments have led to differences in the patients supported on venovenous ECMO in the first and second waves. We aimed to compare these two groups in both the acute and follow-up phase. DESIGN: Retrospective single-center cohort study comparing mortality at censoring date (November 30, 2021) and decannulation, patient characteristics, complications and lung function and quality of life (QOL—by European Quality of Life 5 Dimensions 3 Level Version) at first follow-up in patients supported on venovenous ECMO between wave 1 and wave 2 of the COVID-19 pandemic. SETTING: Critical care department of a severe acute respiratory failure service. PATIENTS: Patients supported on ECMO for COVID-19 between wave 1 (March 17, 2020, to August 31, 2020) and wave 2 (January 9, 2020, to May 25, 2021). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: One hundred twenty-three patients were included in our analysis. Survival at censoring date (χ2, 6.35; p = 0.012) and decannulation (90.4% vs 70.0%; p < 0.001) was significantly lower in the second wave, while duration of ECMO run was longer (12.0 d [18.0–30.0 d] vs 29.5 d [15.5–58.3 d]; p = 0.005). Wave 2 patients had longer application of noninvasive ventilation (NIV) prior to ECMO and a higher frequency of barotrauma. Patient age and NIV use were independently associated with increased mortality (odds ratio 1.07 [1.01–1.14]; p = 0.025 and 3.37 [1.12–12.60]; p = 0.043, respectively). QOL and lung function apart from transfer coefficient of carbon monoxide corrected for hemoglobin was similar at follow-up across the waves. CONCLUSIONS: Most patients with COVID-19 supported on ECMO in both waves survived in the short and longer term. At follow-up patients had similar lung function and QOL across the two waves. This suggests that ECMO has an ongoing role in the management of a carefully selected group of patients with COVID-19. [ABSTRACT FROM AUTHOR]

Lung function decline varies significantly in patients with lymphangioleiomyomatosis (LAM), impeding individualized clinical decision-making. Can we aid individualized decision-making in LAM by developing a dynamic prediction model that can estimate the probability of clinically relevant FEV 1 decline in patients with LAM before treatment initiation? Patients observed in the US National Heart, Lung, and Blood Institute (NHLBI) Lymphangioleiomyomatosis Registry were included. Using routinely available variables such as age at diagnosis, menopausal status, and baseline lung function (FEV 1 and diffusing capacity of the lungs for carbon monoxide [D lco ]), we used novel stochastic modeling and evaluated predictive probabilities for clinically relevant drops in FEV 1. We formed predictive probabilities of transplant-free survival by jointly modeling longitudinal FEV 1 and lung transplantation or death events. External validation used the UK Lymphangioleiomyomatosis Natural History cohort. Analysis of the NHLBI Lymphangioleiomyomatosis Registry and UK Lymphangioleiomyomatosis Natural History cohorts consisted of 216 and 185 individuals, respectively. We derived a joint model that accurately estimated the risk of future lung function decline and 5-year probabilities of transplant-free survival in patients with LAM not taking sirolimus (area under the receiver operating characteristic curve [AUC], approximately 0.80). The prediction model provided estimates of forecasted FEV 1 , rate of FEV 1 decline, and probabilities for risk of prolonged drops in FEV 1 for untreated patients with LAM with a high degree of accuracy (AUC > 0.80) for the derivation cohort as well as the validation cohort. Our tool is freely accessible at: https://anushkapalipana.shinyapps.io/testapp%5fv2/. Longitudinal modeling of routine clinical data can allow individualized LAM prognostication and assist in decision-making regarding the timing of treatment initiation. [ABSTRACT FROM AUTHOR]

Background: Although pulmonary function has been studied in relationship to individual cardiometabolic diseases, uncertainty persists about the difference in risk magnitudes of pulmonary function for these diseases and its association with cardiometabolic multimorbidity (CM).Research Question: Does pulmonary function have different risk magnitudes for cardiometabolic diseases and CM?Study Design and Methods: This study used data from the UK Biobank, including 357,433 individuals with no cardiometabolic diseases at baseline (stage I) and 35,034 individuals with one cardiometabolic disease at baseline (stage II). Pulmonary function was measured by FVC or FEV1. We defined CM as the coexistence of at least two cardiometabolic diseases: type 2 diabetes (T2D), coronary heart disease (CHD), and stroke. Multinomial logistic regression models and Cox proportional hazards models were performed to estimate ORs or hazard ratios (HRs) and their 95% CIs for the longitudinal relationship between baseline pulmonary function and incident cardiometabolic outcomes.Results: In stage I, FVC showed the most pronounced associations with new-onset CM and T2D among the four mutually exclusive end points. Compared with the lowest quartile (quartile 1), the adjusted ORs of quartile 4 of FVC were 0.525 (95% CI, 0.468-0.589) for CM, 0.534 (95% CI, 0.498-0.572) for T2D alone, 0.817 (95% CI, 0.751-0.888) for stroke alone, and 0.800 (95% CI, 0.764-0.837) for CHD alone. In stage II, FVC also was associated with the risk of CM in patients with T2D (HR of quartile 4, 0.727; 95% CI, 0.649-0.814), patients with CHD (HR, 0.635; 95% CI, 0.555-0.727), and patients who experienced stroke (HR, 0.783, 95% CI, 0.642-0.955). Similar results were observed for FEV1 in both stages.Interpretation: This study revealed the different risk associations of pulmonary function with individual cardiometabolic diseases and CM. Tailor-made screening and monitoring through pulmonary function may be applicable for the precise prevention and control of these conditions. [ABSTRACT FROM AUTHOR]

Pulmonary function is associated with the development of chronic liver disease. However, evidence of the association between pulmonary function and cirrhosis risk is still lacking. This study aimed to investigate the longitudinal associations of pulmonary function with the development of cirrhosis, and to explore whether genetic predisposition to cirrhosis could modify these associations. Of 294,835 participants free of cirrhosis and had undergone spirometry at baseline from the UK Biobank were included. Cirrhosis diagnoses were ascertained through linked hospital records and death registries. Cox proportional hazard models were employed to investigate the longitudinal associations between pulmonary function, genetic predisposition, and cirrhosis risk. During a median follow-up of 12.0 years, 2598 incident cirrhosis cases were documented. Compared to individuals with normal spirometry findings, those with preserved ratio impaired spirometry (PRISm) findings (hazard ratio [HR] and 95% confidence interval [CI]: 1.32 [1.18, 1.48]) and airflow obstruction (HR [95%CI]: 1.19 [1.07, 1.31]) had a higher risk of developing cirrhosis after adjustments. These associations were consistent across all categories of genetic predisposition, with no observed modifying effect of genetic predisposition. In joint exposure analyses, the highest risk was observed in individuals with both a high genetic predisposition for cirrhosis and PRISm findings (HR [95% CI]: 1.74 [1.45, 2.08]). Our findings indicate that worse pulmonary function is a significant risk factor of cirrhosis, irrespective of genetic predisposition. Early identification and appropriate intervention for pulmonary function may lead to more effective healthcare resource utilization and reduce the burden associated with cirrhosis. • PRISm and genetic risk were associated with development of cirrhosis, respectively. • No significant interaction found between genetic risk and lung function. • In joint, highest risk was observed in those with high genetic risk and PRISm. • PRISm is associated with cirrhosis onset, aiding early detection. [ABSTRACT FROM AUTHOR]

Telomere length (TL) shortens over time in most human cell types and is a potential biomarker of aging. However, the causal association of TL on physical and cognitive traits that decline with age has not been extensively examined in middle-aged adults. Using a Mendelian randomization (MR) approach, we utilized genetically increased TL (GI-TL) to estimate the impact of TL on aging-related traits among U.K. Biobank (UKB) participants (age 40-69 years). We manually curated 53 aging-related traits from the UKB and restricted to unrelated participants of British ancestry (n = 337,522). We estimated GI-TL as a linear combination of nine TL-associated single nucleotide polymorphisms (SNPs), each weighted by its previously-reported association with leukocyte TL. Regression models were used to assess the associations between GI-TL and each trait. We obtained MR estimates using the two-sample inverse variance weighted (IVW) approach. We identified six age-related traits associated with GI-TL (Bonferroni-corrected threshold p < .001): pulse pressure (PP) (p = 5.2 × 10-14), systolic blood pressure (SBP) (p = 2.9 × 10-15), diastolic blood pressure (DBP) (p = 5.5 × 10-6), hypertension (p = 5.5 × 10-11), forced expiratory volume (FEV1) (p = .0001), and forced vital capacity (FVC) (p = 3.8 × 10-6). Under MR assumptions, one standard deviation increase in TL (~1,200 base pairs) increased PP, SBP, and DBP by 1.5, 2.3, and 0.8 mmHg, respectively, while FEV1 and FVC increased by 34.7 and 52.2 mL, respectively. The observed associations appear unlikely to be due to selection bias based on analyses including inverse probability weights and analyses of simulated data. These findings suggest that longer TL increases pulmonary function and blood pressure traits among middle-aged UKB participants. [ABSTRACT FROM AUTHOR]

Summary: Pneumonia is a common and severe infectious lung disease. Host genetics, together with underlying medical and lifestyle conditions, determine pneumonia susceptibility. We performed a secondary analysis of the results of two genome‐wide studies for pneumonia in 23andMe participants (40 600 cases/90 039 controls) (Tian et al., 2017) and UK Biobank (BB) participants (12 614 cases/324 585 controls) (via the Global Biobank Engine) and used the GTEx database to correlate the results with expression quantitative trait loci (eQTLs) data in lung and whole blood. In the 23andMe pneumonia single nucleotide polymorphism (SNP) set, 177 genotyped SNPs in the human leukocyte antigen (HLA) region satisfied the genome‐wide significance level, P ≤ 5·0E‐08. Several target genes (e.g. C4A, VARS2, SFTA2, HLA‐C, HLA‐DQA2) were unidirectionally regulated by many HLA eSNPs associated with a higher risk of pneumonia. In lung, C4A transcript was up‐regulated by 291 pneumonia risk alleles spanning the half the HLA region. Among SNPs correlated with the expression levels of SFTA2 and VARS2, approximately 75% overlapped: all risk alleles were associated with VARS2 up‐regulation and SFTA2 down‐regulation. To find shared gene loci between pneumonia and pulmonary function (PF), we used data from the Global Biobank Engine and literature on genome‐wide association studies (GWAS) of PF in general populations. Numerous gene loci overlapped between pneumonia and PF: 28·8% in the BB data set and 49·2% in the 23andMe data set. Enrichment analysis within the database of Genotypes and Phenotypes (dbGaP) and National Human Genome Research Institute‐European Bioinformatics Institute (NHGRI‐EBI) Catalog of pneumonia and pneumonia/PF gene sets identified significant overlap between these gene sets and genes related to inflammatory, developmental, neuropsychiatric and cardiovascular and obesity‐related traits. [ABSTRACT FROM AUTHOR]

Background: Reduced lung function is common and associated with increased cardiovascular morbidity and mortality, even in asymptomatic individuals without diagnosed respiratory disease. Previous studies have identified relationships between lung function and cardiovascular structure in individuals with pulmonary disease, but the relationships in those free from diagnosed cardiorespiratory disease have not been fully explored. Methods: UK Biobank is a prospective cohort study of community participants in the United Kingdom. Individuals self-reported demographics and co-morbidities, and a subset underwent cardiovascular magnetic resonance (CMR) imaging and spirometry. CMR images were analysed to derive ventricular volumes and mass. The relationships between CMR-derived measures and spirometry and age were modelled with multivariable linear regression, taking account of the effects of possible confounders. Results: Data were available for 4,975 individuals, and after exclusion of those with pre-existing cardiorespiratory disease and unacceptable spirometry, 1,406 were included in the analyses. In fully-adjusted multivariable linear models lower FEV1 and FVC were associated with smaller left ventricular end-diastolic (−5.21ml per standard deviation (SD) change in FEV1, −5.69ml per SD change in FVC), end-systolic (−2.34ml, −2.56ml) and stroke volumes (−2.85ml, −3.11ml); right ventricular end-diastolic (−5.62ml, −5.84ml), end-systolic (−2.47ml, −2.46ml) and stroke volumes (−3.13ml, −3.36ml); and with lower left ventricular mass (−2.29g, −2.46g). Changes of comparable magnitude and direction were observed per decade increase in age. Conclusions: This study shows that reduced FEV1 and FVC are associated with smaller ventricular volumes and reduced ventricular mass. The changes seen per standard deviation change in FEV1 and FVC are comparable to one decade of ageing. [ABSTRACT FROM AUTHOR]

Introduction: Ventolin Nebules® (reference product; GlaxoSmithKline) was the first licensed nebulizer solution containing the rapid-onset, short-acting β2-agonist salbutamol. Salbutamol Steri-Neb™ (comparator; Teva Pharmaceuticals, Inc.) has the same chemical composition as the reference product. This study evaluated whether the effectiveness of the comparator is non-inferior to the reference product alongside concomitant medications during real-life clinical management of COPD exacerbations. Safety in terms of adverse events (AEs) was also examined. Methods: This matched (1:1) historical cohort study evaluated data from 2 UK primary care databases on patients prescribed the salbutamol comparator or reference. The study included a 1-year baseline period, starting 1 year before the index prescription date, and 1-year outcome period. Cohorts were matched for baseline COPD respiratory medications. The primary outcome was analysis of non-inferiority for the comparator versus reference product for the rate of moderate and severe COPD exacerbations. Non-inferiority was satisfied if the 95% confidence interval (CI) upper limit for mean differences in proportions between treatments was <15%. Secondary outcomes were examined through rate ratios (RR) of severe exacerbations and AEs. Results: After matching, 1191 patients were included in each cohort. Adjusted upper 95% CI for the difference in proportion of patients experiencing moderate or severe exacerbations between comparator and reference groups was 0.032 (3.2%), demonstrating non-inferiority. No significant differences were observed in rates of moderate and severe exacerbations (RR: 1.00; 95% CI: 0.91, 1.10), severe exacerbations (RR: 0.76; 95% CI: 0.49, 1.17), or AEs (RR: 0.98; 95% CI: 0.78, 1.22) after adjusting for baseline confounders. No significant differences across cohorts were observed for rates of any AE or death. Conclusion: This matched cohort study of real-life management of COPD patients supports the salbutamol comparator as non-inferior to the reference product, providing an effective treatment alternative for COPD exacerbations. Comparator and reference safety profiles were similar. [ABSTRACT FROM AUTHOR]

Abstract: Introduction and Objectives: To investigate the clinical value of fractional exhaled nitric oxide (FeNO) in lung cancer patients. Methods: A total of 172 healthy control subjects and 164 patients with histopathologically confirmed lung cancer were enrolled in this study. The FeNO measurements and pulmonary function tests were conducted in the Chinese PLA General Hospital. The recorded data included FeNO, the forced expiratory volume in one second (FEV1), the forced vital capacity (FVC), FEV1/FVC, the FEV1 (% predicted), the demographic characteristics, the presence of complications and the smoking status. Results: The patients with lung cancer had a significantly higher level of eNO than the healthy control subjects (33.85 ± 15.63 ppb, n = 163; 16.83 ± 4.17 ppb, n = 172; P < 0.01). The areas under receiver operating characteristic curves for eNO predicting airway inflammation in lung cancer subjects and healthy control subjects was 0.932 (95% confidence interval: 0.904–0.961). In the lung cancer group, the eNO levels in the squamous cell carcinoma, adenocarcinoma, small‐cell lung cancer and lung carcinoid tumor groups were significantly different (P < 0.01). Lung cancer patients with a predicted FEV1% value <80% had a higher level of eNO than the patients with a predicted FEV1% value ≥80%. Conclusions: The eNO levels in patients with lung cancer were higher than the normal level, especially in the patients with squamous cell carcinoma and small‐cell lung cancer. The differences in eNO among the lung cancer subtypes were statistically significant. Measuring eNO will be helpful in diagnosing airway inflammation in lung cancer and in the classification of lung cancer. [ABSTRACT FROM AUTHOR]

Objectives. The prevalence of interstitial lung disease (ILD) in RA is ∼5%. Previous work identified increasing age, active articular disease and articular damage as risk factors for RA-associated ILD (RA-ILD). The roles of high-resolution CT (HRCT) and lung function testing in defining the nature and extent of pulmonary involvement have recently been explored. This study is the first to examine predictive and prognostic factors for the development of RA-ILD and to report on the physiological and radiological characteristics of the condition from a large multicentre UK network.Methods. We collected data from centres across the UK on patients with both RA and ILD (proved on HRCT) diagnosed over a 25-year period from 1987 to 2012 using a standard pro forma. Potential predictors of RA-ILD were analysed. Baseline lung function data were recorded and related to HRCT findings. We analysed HRCT for subtype and extent of lung involved and examined the relationship between these and both all-cause and pulmonary mortality. We compared our results with case controls matched for age and gender using computer-generated selection from the RA population from one contributing centre.Results. A total of 230 patients were identified from across the UK with proven RA-ILD diagnosed over 25 years. Median age at diagnosis was 64 years and the male:female ratio was 1:1.09. Univariate analysis showed anti-CCP antibody titres to be the single most strongly associated predictor of RA-ILD. Male gender, age at onset, smoking and RF were all independently associated with RA-ILD on multivariate analysis. Vital capacity (VC) was preserved in limited disease but reduced in extensive disease, while gas transfer was reduced in both. Usual interstitial pneumonia (UIP) was the most common subtype on HRCT and both this and extensive disease were associated with increased all-cause mortality.Conclusion. This is the largest study of RA-ILD in the UK. Anti-CCP antibodies were strongly associated with RA-ILD in both sexes. Smoking was strongly associated with ILD in males, which may explain the higher frequency of RA-ILD in men. The predominant HRCT pattern was UIP and most patients had limited disease at presentation. The presence of UIP and extensive disease are associated with increased mortality. Baseline gas transfer is a useful screening tool for ILD, while the preservation of VC at baseline might predict limited disease on HRCT. [ABSTRACT FROM AUTHOR]