Causal Relationship Between Lung Function and Atrial Fibrillation: A Two Sample Univariable and Multivariable, Bidirectional Mendelian Randomization Study

Background: Observational studies have identified impaired lung function accessed by forced expiratory volume in one second (FEV1), forced vital capacity (FVC) or the ratio of FEV1 over FVC (FEV1/FVC) as an independent risk factor for atrial fibrillation (AF). However, the result may be affected by confounders or reverse causality.Methods: We performed univariable MR (uvMR), multivariable MR (mvMR) and bidirectional two-sample MR to jointly estimate the causality of lung function with AF. Apart from the inverse variance weighted (IVW) approach as the main MR analysis, three complementary sensitive analyses approaches including MR-Egger regression, weighted median (WM) MR and Pleiotropy Residual Sum and Outlier (MR-PRESSO) in uvMR as well as mvMR-Egger and mvMR-PRESSO in mvMR were applied to control for pleiotropy. Linkage disequilibrium score (LDSC) regression was applied to estimate genetic correlation between lung function and AF.Results: All forward and reverse uvMR analyses consistently suggested absent causal relations between lung function and AF risk [forward IVW: odds ratio (OR)FEV1 = 1.031, 95% CI = 0.909–1.169, P = 0.630; ORFVC = 1.002, 95% CI = 0.834–1.204, P = 0.982; ORFEV1/FVC = 1.076, 95% CI = 0.966–1.199, P = 0.182; reverse IVW: ORFEV1 = 0.986, 95% CI = 0.966–1.007, P = 0.187; ORFVC = 0.985, 95% CI = 0.965–1.006, P = 0.158; ORFEV1/FVC = 0.994, 95% CI = 0.973–1.015, P = 0.545]. The forward MR-Egger showed that each standard deviation (SD) increase in FEV1/FVC was related to a higher AF risk (OR = 1.502, 95% CI = 1.178–1.915, P = 0.006) without heterogeneity (Q_pval = 0.064), but pleiotropy effect exist (intercept = −0.017, P = 0.012). However, this significant effect disappeared after adjustment of FEV1 and FVC (OR = 1.523, 95% CI = 0.445–5.217, P = 0.503) in mvMR. No evidence was found for independent causal effects of FEV1 and FVC on AF in mvMR analysis by using mvIVW method (ORFEV1 = 0.501, 95% CI = 0.056–4.457, P = 0.496; ORFVC = 1.969, 95% CI = 0.288–13.474, P = 0.490). Notably, the association between lung function and AF were replicated using the FinnGen cohort data.Conclusions: Our findings reported no coheritability between lung function and AF, and failed to find substantial causal relation between decreased lung function and risk of AF. However, lung function and AF were both associated with inflammation, which may be potential pathway, warranting further study.

Download Full-text

The CRP genotype, serum levels and lung function in men: the Caerphilly Prospective Study

Clinical Science ◽

10.1042/cs20100504 ◽

2010 ◽

Vol 120 (8) ◽

pp. 347-355 ◽

Cited By ~ 23

Author(s):

Charlotte E. Bolton ◽

Wiebke Schumacher ◽

John R. Cockcroft ◽

Nicholas J. Timpson ◽

George Davey Smith ◽

...

Keyword(s):

Lung Function ◽

Prospective Study ◽

Causal Effect ◽

Serum Levels ◽

Forced Expiratory Volume ◽

Reverse Causality ◽

Lung Function Decline ◽

Impaired Lung Function ◽

Serum Crp

Systemic CRP (C-reactive protein) has been associated with impaired lung function. A causal relationship would increase the value of CRP as both a diagnostic and therapeutic tool. We assessed the association between lung function parameters, circulating CRP and CRP polymorphisms using Mendelian randomization in efforts to attribute causality to known associations. Spirometric parameters of FEV1 (forced expiratory volume in 1 s) and FVC (forced vital capacity) were determined in 2173 men participating in the Caerphilly Prospective Study. Lung function measures on 1021 participants were available at follow-up (mean, 16.8 years later). Serum CRP levels were measured at baseline, and three CRP polymorphisms were analysed. Haplotype analysis was performed. Serum CRP levels at baseline were inversely associated with contemporaneous FEV1 and FVC as well as at follow-up (P<0.001) even after adjustment for conventional confounders. Serum CRP was associated with FEV1 decline (P=0.04). All three CRP polymorphisms (rs1800947, rs1130864 and rs1205) predicted serum CRP; however, there were no clear associations of the polymorphisms or haplotypes with lung function or with lung function decline. In conclusion, serum CRP was associated with lung function cross-sectionally; however, CRP polymorphisms were not associated with lung function or decline, suggesting that the CRP–lung function relationship is due to reverse causality, an unmeasured confounding factor or only has a modest causal effect.

Download Full-text

No effect of artificial gravity on lung function with exercise training during head-down bed rest

International Journal of Astrobiology ◽

10.1017/s1473550415000294 ◽

2015 ◽

pp. 1-7

Author(s):

Longxiang Su ◽

Yinghua Guo ◽

Yajuan Wang ◽

Delong Wang ◽

Changting Liu

Keyword(s):

Lung Function ◽

Pulse Rate ◽

Vital Capacity ◽

Pulmonary Ventilation ◽

Bed Rest ◽

Forced Expiratory Volume ◽

Observation Time ◽

Artificial Gravity ◽

Postural Changes ◽

Expiratory Flow

AbstractTo explore the effectiveness of microgravity simulated by head-down bed rest (HDBR) and artificial gravity (AG) with exercise on lung function. Twenty-four volunteers were randomly divided into control and exercise countermeasure (CM) groups for 96 h of 6° HDBR. Comparisons of pulse rate, pulse oxygen saturation (SpO2) and lung function were made between these two groups at 0, 24, 48, 72, 96 h. Compared with the sitting position, inspiratory capacity and respiratory reserve volume were significantly higher than before HDBR (0° position) (P< 0.05). Vital capacity, expiratory reserve volume, forced vital capacity, forced expiratory volume in 1 s, forced inspiratory vital capacity, forced inspiratory volume in 1 s, forced expiratory flow at 25, 50 and 75%, maximal mid-expiratory flow and peak expiratory flow were all significantly lower than those before HDBR (P< 0.05). Neither control nor CM groups showed significant differences in the pulse rate, SpO2, pulmonary volume and pulmonary ventilation function over the HDBR observation time. Postural changes can lead to variation in lung volume and ventilation function, but a HDBR model induced no changes in pulmonary function and therefore should not be used to study AG CMs.

Download Full-text

Nociceptive mechanisms modulate ozone-induced human lung function decrements

Journal of Applied Physiology ◽

10.1152/jappl.1998.85.5.1863 ◽

1998 ◽

Vol 85 (5) ◽

pp. 1863-1870 ◽

Cited By ~ 38

Author(s):

Anthony N. Passannante ◽

Milan J. Hazucha ◽

Philip A. Bromberg ◽

Elston Seal ◽

Larry Folinsbee ◽

...

Keyword(s):

Lung Function ◽

Intermittent Exercise ◽

Forced Expiratory Volume ◽

Endogenous Opioids ◽

Functional Responses ◽

Double Blind ◽

C Fibers ◽

Impaired Lung Function ◽

Opioid Receptor Agonists ◽

Double Blind Crossover Study

We have previously suggested that ozone (O3)-induced pain-related symptoms and inhibition of maximal inspiration are due to stimulation of airway C fibers (M. J. Hazucha, D. V. Bates, and P. A. Bromberg. J. Appl. Physiol. 67: 1535–1541, 1989). If this were so, pain suppression or inhibition by opioid-receptor agonists should partially or fully reverse O3-induced symptomatic and lung functional responses. The objectives of this study were to determine whether O3-induced pain limits maximal inspiration and whether endogenous opioids contribute to modulation of the effects of inhaled O3 on lung function. The participants in this double-blind crossover study were healthy volunteers (18–59 yr) known to be “weak” (WR; n = 20) and “strong” O3 responders (SR; n = 42). They underwent either two 2-h exposures to air or two 2-h exposures to 0.42 parts/million O3 with moderate intermittent exercise. Immediately after post-O3 spirometry, the WR were randomly given either naloxone (0.15 mg/kg iv) or saline, whereas SR randomly received either sufentanil (0.2 μg/kg iv) or saline. O3 exposure significantly ( P < 0.001) impaired lung function. In SR, sufentanil rapidly, although not completely, reversed both the chest pain and spirometric effects (forced expiratory volume in 1 s; P < 0.0001) compared with saline. Immediate postexposure administration of saline or naloxone had no significant effect on WR. Plasma β-endorphin levels were not related to an individual’s O3responsiveness. Cutaneous pain variables showed a nonsignificant weak association with O3responsiveness. These observations demonstrate that nociceptive mechanisms play a key role in modulating O3-induced inhibition of inspiration but not in causing lack of spirometric response to O3 exposure in WR.

Download Full-text

Impact of Lung Biopsy on Lung Function in Idiopathic Pulmonary Fibrosis

Respiration ◽

10.1159/000509557 ◽

2020 ◽

pp. 1-8

Author(s):

Pierre-Henri Aussedat ◽

Nader Chebib ◽

Kais Ahmad ◽

Jean-Charles Glerant ◽

Gabrielle Drevet ◽

...

Keyword(s):

Lung Function ◽

Idiopathic Pulmonary Fibrosis ◽

Pulmonary Fibrosis ◽

Forced Vital Capacity ◽

Lung Biopsy ◽

Vital Capacity ◽

Forced Expiratory Volume ◽

Surgical Lung Biopsy ◽

Before And After ◽

The Impact

Background: Video-assisted surgical lung biopsy (SLB) is performed in 10–30% of cases to establish the diagnosis of idiopathic pulmonary fibrosis (IPF). Objectives: The aim of the study was to analyze the impact of SLB on lung function in patients eventually diagnosed with IPF. Methods: This is an observational, retrospective, monocentric study of all consecutive patients eventually diagnosed with IPF in multidisciplinary discussion who underwent SLB over 10 years in a specialized center. The primary end point was the variation in forced vital capacity (FVC) before and after the SLB. The secondary end points were the variations in forced expiratory volume in one second (FEV1), total lung capacity (TLC), carbon monoxide diffusion capacity (DLCO), and morbidity and mortality associated with the SLB. Results: In 118 patients who underwent SLB and were diagnosed with IPF, a relative decrease in FVC of 4.8% (p < 0.001) was found between measurements performed before and after the procedure. The mean FVC decrease was 156 ± 386 mL in an average period of 185 days, representing an annualized decline of 363 ± 764 mL/year. A significant decrease was also observed after SLB in FEV1, TLC, and DLCO. Complications within 30 days of SLB occurred in 14.4% of patients. Two patients (1.7%) died within 30 days, where one of them had poor lung function. Survival at 1 year was significantly poorer in patients with FVC <50% at baseline. Conclusion: In this uncontrolled study in patients ultimately diagnosed with IPF, SLB was followed by a significant decline in FVC, which appears to be numerically greater than the average decline in the absence of treatment in the literature. Summary at a Glance: This study evaluated the change in lung function in 118 consecutive patients diagnosed with idiopathic pulmonary fibrosis by surgical lung biopsy. Forced vital capacity decreased by 156 ± 386 mL in a mean of 185 days between the last measurement before and first measurement after biopsy, representing an annualized decline of 363 ± 764 mL/year.

Download Full-text

Global Lung Function Initiative 2012 reference equations for spirometry in the Norwegian population

European Respiratory Journal ◽

10.1183/13993003.00443-2016 ◽

2016 ◽

Vol 48 (6) ◽

pp. 1602-1611 ◽

Cited By ~ 33

Author(s):

Arnulf Langhammer ◽

Ane Johannessen ◽

Turid L. Holmen ◽

Hasse Melbye ◽

Sanja Stanojevic ◽

...

Keyword(s):

Lung Function ◽

Reference Values ◽

Vital Capacity ◽

Population Based ◽

Forced Expiratory Volume ◽

Female Adolescents ◽

Norwegian Population ◽

Reference Equations ◽

Z Scores ◽

Lower Limit Of Normal

We studied the fit of the Global Lung Function Initiative (GLI) all-age reference values to Norwegians, compared them with currently used references (European Community for Steel and Coal (ECSC) and Zapletal) and estimated the prevalence of obstructive lung disease.Spirometry data collected in 30 239 subjects (51.7% females) aged 12–90 years in three population-based studies were converted to z-scores.We studied healthy non-smokers comprising 2438 adults (57.4% females) aged 20–90 years and 8725 (47.7% female) adolescents aged 12–19 years. The GLI-2012 prediction equations fitted the Norwegian data satisfactorily. Median±sd z-scores were respectively 0.02±1.03, 0.01±1.04 and −0.04±0.91 for forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC) and FEV1/FVC in males, and −0.01±1.02, 0.07±0.97 and −0.21±0.82 in females. The ECSC and Zapletal references significantly underestimated FEV1 and FVC. Stricter criteria of obstruction (FEV1/FVC <GLI-2012 lower limit of normal (LLN)) carried a substantially higher risk of obstructive characteristics than FEV1/FVC <0.7 and >GLI-2012 LLN. Corresponding comparison regarding myocardial infarction showed a four-fold higher risk for women.The GLI-2012 reference values fit the Norwegian data satisfactorily and are recommended for use in Norway. Correspondingly, the FEV1/FVC GLI-2012 LLN identifies higher risk of obstructive characteristics than FEV1/FVC <0.7.

Download Full-text

Associations between blood eosinophils and decline in lung function among adults with and without asthma

European Respiratory Journal ◽

10.1183/13993003.02536-2017 ◽

2018 ◽

Vol 51 (4) ◽

pp. 1702536 ◽

Cited By ~ 29

Author(s):

Robert J. Hancox ◽

Ian D. Pavord ◽

Malcolm R. Sears

Keyword(s):

Lung Function ◽

Vital Capacity ◽

Airflow Obstruction ◽

Population Based ◽

Forced Expiratory Volume ◽

Lung Function Decline ◽

Characteristic Features ◽

Predicted Values ◽

Blood Eosinophils ◽

Eosinophil Counts

Eosinophilic inflammation and airway remodelling are characteristic features of asthma, but the association between them is unclear. We assessed associations between blood eosinophils and lung function decline in a population-based cohort of young adults.We used linear mixed models to analyse associations between blood eosinophils and spirometry at 21, 26, 32 and 38 years adjusting for sex, smoking, asthma and spirometry at age 18 years. We further analysed associations between mean eosinophil counts and changes in spirometry from ages 21 to 38 years.Higher eosinophils were associated with lower forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) ratios and lower FEV1 % predicted values for both pre- and post-bronchodilator spirometry (all p-values ≤0.048). Although eosinophil counts were higher in participants with asthma, the associations between eosinophils and spirometry were similar among participants without asthma or wheeze. Participants with mean eosinophil counts >0.4×109 cells·L−1 between 21 and 38 years had greater declines in FEV1/FVC ratios (difference 1.8%, 95% CI 0.7–2.9%; p=0.001) and FEV1 values (difference 3.4% pred, 95% CI 1.5–5.4% pred); p=0.001) than those with lower counts.Blood eosinophils are associated with airflow obstruction and enhanced decline in lung function, independently of asthma and smoking. Eosinophilia is a risk factor for airflow obstruction even in those without symptoms.

Download Full-text

Impact of chronic khat (Catha edulis Forsk) chewing on pulmonary function test and oxygen saturation in humans: A comparative study

SAGE Open Medicine ◽

10.1177/2050312118824616 ◽

2019 ◽

Vol 7 ◽

pp. 205031211882461 ◽

Cited By ~ 1

Author(s):

Gashaw Garedew Woldeamanuel ◽

Teshome Gensa Geta

Keyword(s):

Lung Function ◽

Pulmonary Function ◽

Oxygen Saturation ◽

Vital Capacity ◽

Forced Expiratory Volume ◽

Mean Values ◽

Khat Chewing ◽

Significant Difference ◽

The Mean

Background: Chronic consumption of khat affects many organ systems and leads to various health disturbances in the chewers. Few studies examined the acute effects of khat ingestion on lung function parameters. However, studies which assessed the long-term effects of khat chewing on pulmonary function parameters and oxygen saturation are lacking. Objective: The aim of this study was to assess the impact of chronic Khat chewing on pulmonary function parameters and oxygen saturation among chronic Khat chewers in Wolkite, Ethiopia. Methods: A community-based comparative cross-sectional study was conducted in Wolkite, Ethiopia from 1 June 2018 to 15 August 2018. A total of 324 participants, 162 khat chewers and 162 non-chewers were included in the study. The data were collected through face-to-face interview by trained data collectors. British Medical Research Council respiratory questionnaire was used to assess respiratory symptoms. A spirometer was used to assess various lung function parameters. Moreover, oxygen saturation of hemoglobin was measured using pulse oximeter. Data were entered into CSPro version 6.2 and analyzed using SPSS version 23. Results: This study showed statistically significant (p < 0.05) reduction in the mean values of forced vital capacity, forced expiratory volume in first second and maximum ventilation volume among khat chewers as compared to non-chewers. There was no significant difference in the mean values of other lung function parameters between the two groups. Similarly, there was no significant difference (p = 0.642) in mean oxygen saturation of hemoglobin (SaO2) across the two groups. Conclusion: It is evident from this study that long-term khat consumption is associated with decreased mean forced vital capacity, forced expiratory volume in first second and maximum ventilation volume. Hence, there is a need for further study to strengthen the current findings and to explore the mechanisms of khat chewing effect on lung function parameters.

Download Full-text

Serum 25-hydroxyvitamin D levels and lung function in adults with asthma: the HUNT Study

European Respiratory Journal ◽

10.1183/09031936.00069714 ◽

2014 ◽

Vol 45 (4) ◽

pp. 1019-1026 ◽

Cited By ~ 15

Author(s):

Tricia L. Larose ◽

Arnulf Langhammer ◽

Yue Chen ◽

Carlos A. Camargo ◽

Pål Romundstad ◽

...

Keyword(s):

Allergic Rhinitis ◽

Lung Function ◽

Vital Capacity ◽

Forced Expiratory Volume ◽

Health Study ◽

Linear Regression Models ◽

Cross Sectional ◽

Hydroxyvitamin D ◽

25 Hydroxyvitamin D ◽

Hunt Study

The association between vitamin D status and lung function in adults with asthma remains unclear.We studied this cross-sectional association and possible modification by sex and allergic rhinitis in 760 adults (aged 19–55 years) with self-reported asthma in the Nord-Trøndelag Health Study. Serum 25-hydroxyvitamin D (25(OH)D) level <50 nmol·L−1was considered deficient. Lung function measurements included forced expiratory volume in 1 s (FEV1) % predicted, forced vital capacity (FVC) % predicted and FEV1/FVC ratio. Multiple linear regression models were used to estimate adjusted regression coefficients (β) and 95% confidence intervals.44% of asthma adults had serum 25(OH)D levels <50 nmol·L−1. Its associations with lung function measures seemed to be modified by sex and allergic rhinitis (p<0.03 for three-way interaction term). Overall, a serum 25(OH)D level <50 nmol·L−1was not associated with lung function measurements in subjects with allergic rhinitis in this asthma cohort. In men with asthma but without allergic rhinitis, however, a serum 25(OH)D level <50 nmol·L−1was significantly associated with lower FEV1/FVC ratio (β=−8.60%; 95% CI: −16.95%– −0.25%).Low serum 25(OH)D level was not associated with airway obstruction in most asthma adults with the exception of men with asthma but without allergic rhinitis.

Download Full-text

Longitudinal analysis of lung function growth in healthy children and adolescents

Journal of Applied Physiology ◽

10.1152/jappl.1991.70.2.770 ◽

1991 ◽

Vol 70 (2) ◽

pp. 770-777 ◽

Cited By ~ 30

Author(s):

J. L. Hopper ◽

M. E. Hibbert ◽

G. T. Macaskill ◽

P. D. Phelan ◽

L. I. Landau

Keyword(s):

Lung Function ◽

Early Detection ◽

Vital Capacity ◽

Forced Expiratory Volume ◽

Healthy Children ◽

Normal Model ◽

Multivariate Normal ◽

Pronounced Increase ◽

Multivariate Normal Model ◽

Healthy Lung

Lung function and height in 242 8-yr-old and 299 12-yr-old children without known or suspected predisposition to lung disease were measured annually over 6 and 8 yr, respectively. Growth of forced expiratory volume in 1 s (FEV1), vital capacity, and expiratory flow after expiring 50% of vital capacity were statistically modeled by age and height by use of a multivariate normal model for longitudinal data. This method has the flexibility to fit an appropriate (not necessarily linear) mathematical description of average lung function while concurrently modeling the covariance between measures on the same individual. Differences in lung function growth between girls and boys, pre- and post-puberty, showed that girls had a steadier though less pronounced increase in lung function with height. In boys, before puberty there was deficit in lung volume relative to height (not evident in girls), which was compensated for by rapid growth after puberty. The standard error of FEV1 predictions based on current height and age were more than halved when measurements of FEV1, age, and height taken 1 yr before were incorporated. We found evidence for dysanaptic growth in childhood. Fitted models have application to early detection of departures from healthy lung function.

Download Full-text

The Global Lung Function Initiative 2012 Equations Are as Well-Suited as Local Population Derived Equations to a Sample of Healthy Professional Firefighters

Canadian Respiratory Journal ◽

10.1155/2017/6327180 ◽

2017 ◽

Vol 2017 ◽

pp. 1-6 ◽

Cited By ~ 1

Author(s):

Flynn Slattery ◽

Tjard Schermer ◽

Adrian Esterman ◽

Kylie Johnston ◽

Alan Crockett

Keyword(s):

Lung Function ◽

Vital Capacity ◽

Normal Values ◽

Local Population ◽

Fire Service ◽

Forced Expiratory Volume ◽

Prediction Methods ◽

Lower Limits ◽

Good Agreement

Background and Objective. We aimed to assess the validity of using the Global Lung Function Initiative’s (GLI) 2012 equations to interpret lung function data in a healthy workforce of South Australian Metropolitan Fire Service (SAMFS) personnel.Methods. Spirometry data from 212 healthy, nonsmoking SAMFS firefighters were collected and predicted normal values were calculated using both the GLI and local population derived (Gore) equations for forced expiratory volume in one second (FEV1), forced vital capacity (FVC), and FEV1/FVC. Two-tailed paired sample Student’st-tests, Bland-Altman assessments of agreement, andz-scores were used to compare the two prediction methods.Results. The equations showed good agreement for mean predicted FEV1, FVC, and FEV1/FVC. Meanz-scores were similar for FEV1and FVC, although not FEV1/FVC, but greater than 0.5. Differences between the calculated lower limits of normal (LLN) were significant (p<0.01), clinically meaningful, and resulted in an 8% difference in classification of abnormality using the FEV1/FVC ratio.Conclusions. The GLI equations predicted similar lung function as population-specific equations and resulted in a lower incidence of obstruction in this sample of healthy SAMFS firefighters. Further, interpretation of spirometry data as abnormal should be based on both an FEV1and FEV1/FVC ratio < LLN.

Download Full-text