The Linkage Between Low Pulmonary Function and Subclinical Cerebrovascular Lesion in Never-Smokers

ABSTRACTImpaired lung function is often caused by cigarette smoking, making it challenging to disentangle its role in lung cancer susceptibility. Investigation of the shared genetic basis of these phenotypes in the UK Biobank and International Lung Cancer Consortium (29,266 cases, 56,450 controls) shows that lung cancer is genetically correlated with reduced forced expiratory volume in one second (FEV1: rg=0.098, p=2.3×10−8) and the ratio of FEV1 to forced vital capacity (FEV1/FVC: rg=0.137, p=2.0×10−12). Mendelian randomization analyses demonstrate that reduced FEV1 increases squamous cell carcinoma risk (odds ratio (OR)=1.51, 95% confidence intervals: 1.21-1.88), while reduced FEV1/FVC increases the risk of adenocarcinoma (OR=1.17, 1.01-1.35) and lung cancer in never smokers (OR=1.56, 1.05-2.30). These findings support a causal role of pulmonary impairment in lung cancer etiology. Integrative analyses reveal that pulmonary function instruments, including 73 novel variants, influence lung tissue gene expression and implicate immune-related pathways in mediating the observed effects on lung carcinogenesis.

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Pulmonary ventilation defects in older never-smokers

Journal of Applied Physiology ◽

10.1152/japplphysiol.00046.2014 ◽

2014 ◽

Vol 117 (3) ◽

pp. 297-306 ◽

Cited By ~ 13

Author(s):

Khadija Sheikh ◽

Gregory A. Paulin ◽

Sarah Svenningsen ◽

Miranda Kirby ◽

Nigel A. M. Paterson ◽

...

Keyword(s):

Pulmonary Function ◽

Lung Disease ◽

Obstructive Lung Disease ◽

Pulmonary Function Tests ◽

Pulmonary Ventilation ◽

Forced Expiratory Volume ◽

Airflow Limitation ◽

Second Hand Smoke ◽

Chronic Obstructive ◽

Never Smokers

Hyperpolarized 3He MRI previously revealed spatially persistent ventilation defects in healthy, older compared with healthy, younger never-smokers. To understand better the physiological consequences and potential relevance of 3He MRI ventilation defects, we evaluated 3He-MRI ventilation-defect percent (VDP) and the effect of deep inspiration (DI) and salbutamol on VDP in older never-smokers. To identify the potential determinants of ventilation defects in these subjects, we evaluated dyspnea, pulmonary function, and cardiopulmonary exercise test (CPET) measurements, as well as occupational and second-hand smoke exposure. Fifty-two never-smokers (71 ± 6 yr) with no history of chronic respiratory disease were evaluated. During a single visit, pulmonary function tests, CPET, and 3He MRI were performed and the Burden of Obstructive Lung Disease questionnaire administered. For eight of 52 subjects, there was spirometry evidence of airflow limitation (Global Initiative for Chronic Obstructive Lung Disease-Unclassified, I, and II), and occupational exposure was reported in 13 of 52 subjects. In 13 of 52 (25%) subjects, there were no ventilation defects and in 39 of 52 (75%) subjects, ventilation defects were observed. For those subjects with ventilation defects, six of 39 showed a VDP response to DI/salbutamol. Ventilation heterogeneity and VDP were significantly greater, and forced expiratory volume in 1 s (FEV1)/forced vital capacity was significantly lower ( P < 0.05) for subjects with ventilation defects with a response to DI/salbutamol than subjects with ventilation defects without a response to DI/salbutamol and subjects without ventilation defects. In a step-wise, forward multivariate model, FEV1, inspiratory capacity, and airway resistance significantly predicted VDP ( R2 = 0.45, P < 0.001). In conclusion, most never-smokers had normal spirometry and peripheral ventilation defects not reversed by DI/salbutamol; such ventilation defects were likely related to irreversible airway narrowing/collapse but not to dyspnea and decreased exercise capacity.

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Immune-mediated genetic pathways resulting in pulmonary function impairment increase lung cancer susceptibility

Nature Communications ◽

10.1038/s41467-019-13855-2 ◽

2020 ◽

Vol 11 (1) ◽

Cited By ~ 2

Author(s):

Linda Kachuri ◽

Mattias Johansson ◽

Sara R. Rashkin ◽

Rebecca E. Graff ◽

Yohan Bossé ◽

...

Keyword(s):

Lung Cancer ◽

Pulmonary Function ◽

Cancer Susceptibility ◽

Forced Expiratory Volume ◽

Lung Carcinogenesis ◽

Cancer Etiology ◽

Impaired Lung Function ◽

Never Smokers ◽

The Uk ◽

Lung Cancer Susceptibility

AbstractImpaired lung function is often caused by cigarette smoking, making it challenging to disentangle its role in lung cancer susceptibility. Investigation of the shared genetic basis of these phenotypes in the UK Biobank and International Lung Cancer Consortium (29,266 cases, 56,450 controls) shows that lung cancer is genetically correlated with reduced forced expiratory volume in one second (FEV1: rg = 0.098, p = 2.3 × 10−8) and the ratio of FEV1 to forced vital capacity (FEV1/FVC: rg = 0.137, p = 2.0 × 10−12). Mendelian randomization analyses demonstrate that reduced FEV1 increases squamous cell carcinoma risk (odds ratio (OR) = 1.51, 95% confidence intervals: 1.21–1.88), while reduced FEV1/FVC increases the risk of adenocarcinoma (OR = 1.17, 1.01–1.35) and lung cancer in never smokers (OR = 1.56, 1.05–2.30). These findings support a causal role of pulmonary impairment in lung cancer etiology. Integrative analyses reveal that pulmonary function instruments, including 73 novel variants, influence lung tissue gene expression and implicate immune-related pathways in mediating the observed effects on lung carcinogenesis.

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Periodical Multiphasic Screening and Lung Cancer Prevention

Methods of Information in Medicine ◽

10.1055/s-0038-1634518 ◽

1998 ◽

Vol 37 (02) ◽

pp. 182-187

Author(s):

R. S. Carel

Keyword(s):

Lung Cancer ◽

Smoking Cessation ◽

Pulmonary Function ◽

High Risk Group ◽

Smoking Prevention ◽

Factors Affecting ◽

Cancer Occurrence ◽

Never Smokers ◽

Heavy Smokers

AbstractThe purpose of this work is to evaluate the utilization of information gathered by multiphasic screening with respect to lung cancer detection and smoking cessation techniques. A cohort (follow-up) study is reported in which cancer incidence and factors affecting its occurrence are evaluated in a group of about 20,000 presumably healthy adults along a period of approximately 10 years following comprehensive multiphasic health examinations. Lung cancer occurrence is primarily related to smoking. The risk is higher in smokers and is dose-dependent; OR = 0.21, (CI = 0.08,.53) in never smokers, OR = 1.53 (CI = 0.8,3.2) in past and current moderate smokers, OR = 4.92 (CI = 2.18,11.11) in current heavy smokers. Moreover, smokers with compromised pulmonary function (FEVI/FVC < 75%) are at an even higher risk of developing lung cancer OR = 4.22 (CI = 2.2, 8.2) for past and current moderate smokers; and OR = 10.7 (CI-2.5, 38.6) in current heavy smokers. Information gathered in periodical multiphasic health examinations could be utilized by health professionals to encourage smoking cessation and smoking prevention in the appropriate screenees. Various elements of the multiphasic test results could contribute to such prevention efforts. While every smoker should receive appropriate evaluation and consultation regarding nicotine dependence, smokers with reduced pulmonary function represent an extra high risk group to which special attention should be given.

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Association of pulmonary function with cognitive decline in older adults: a nationwide longitudinal study in China

The Journals of Gerontology Series A ◽

10.1093/gerona/glab096 ◽

2021 ◽

Author(s):

Xianwen Shang ◽

David Scott ◽

Roseanne Kimberley Chan ◽

Lei Zhang ◽

Mingguang He

Keyword(s):

Older Adults ◽

Longitudinal Study ◽

Cognitive Function ◽

Pulmonary Function ◽

Cognitive Decline ◽

Multiple Time ◽

Inverse Association ◽

Immediate Memory ◽

Never Smokers

Abstract This study aimed to examine whether pulmonary function and cognition are independently associated at multiple time points. We included 8264 participants (49.9% women) aged 50-94 years at baseline from the China Health and Retirement Longitudinal Study in our analysis. Participants were enrolled in 2011 and followed up in 2013 and 2015. Cognitive function was assessed through a face-to-face interview in each survey. Pulmonary function was assessed via peak expiratory flow. Pulmonary function and cognitive function decreased significantly with age in both genders. Individuals in quintile 5 of pulmonary function had a relative increase in immediate memory (β (95% CI): 0.19 (0.09, 0.30)) and delayed memory (0.16 (0.04, 0.28)) during follow-up compared with those in quintile 1. In the repeated-measures analysis, each standard deviation increment of pulmonary function was associated with a 0.44 (95% CI: 0.34, 0.53), 0.12 (0.09, 0.15), 0.12 (0.08, 0.16), 0.08 (0.06, 0.11), and 0.10 (0.07, 0.14) higher increase in global cognitive score, immediate memory, delayed memory, orientation and subtraction calculation, respectively. The inverse association between pulmonary function and cognitive decline during follow-up was more evident in women (P for interaction=0.0333), low educated individuals (P for interaction=0.0002), or never smokers (P for interaction=0.0412). In conclusion, higher baseline pulmonary function was independently associated with a lower rate of cognitive decline in older adults. The positive association between pulmonary function and cognition was stronger in women, lower educated individuals, or never smokers.

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Meta-analysis across Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium provides evidence for an association of serum vitamin D with pulmonary function

British Journal Of Nutrition ◽

10.1017/s0007114518002180 ◽

2018 ◽

Vol 120 (10) ◽

pp. 1159-1170 ◽

Cited By ~ 2

Author(s):

Jiayi Xu ◽

Traci M. Bartz ◽

Geetha Chittoor ◽

Gudny Eiriksdottir ◽

Ani W. Manichaikul ◽

...

Keyword(s):

Vitamin D ◽

Pulmonary Function ◽

Fixed Effects ◽

Meta Analysis ◽

Serum Vitamin ◽

European Ancestry ◽

Race Difference ◽

Aging Research ◽

Genomic Epidemiology ◽

Never Smokers

AbstractThe role that vitamin D plays in pulmonary function remains uncertain. Epidemiological studies reported mixed findings for serum 25-hydroxyvitamin D (25(OH)D)–pulmonary function association. We conducted the largest cross-sectional meta-analysis of the 25(OH)D–pulmonary function association to date, based on nine European ancestry (EA) cohorts (n 22 838) and five African ancestry (AA) cohorts (n 4290) in the Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium. Data were analysed using linear models by cohort and ancestry. Effect modification by smoking status (current/former/never) was tested. Results were combined using fixed-effects meta-analysis. Mean serum 25(OH)D was 68 (sd 29) nmol/l for EA and 49 (sd 21) nmol/l for AA. For each 1 nmol/l higher 25(OH)D, forced expiratory volume in the 1st second (FEV1) was higher by 1·1 ml in EA (95 % CI 0·9, 1·3; P<0·0001) and 1·8 ml (95 % CI 1·1, 2·5; P<0·0001) in AA (Prace difference=0·06), and forced vital capacity (FVC) was higher by 1·3 ml in EA (95 % CI 1·0, 1·6; P<0·0001) and 1·5 ml (95 % CI 0·8, 2·3; P=0·0001) in AA (Prace difference=0·56). Among EA, the 25(OH)D–FVC association was stronger in smokers: per 1 nmol/l higher 25(OH)D, FVC was higher by 1·7 ml (95 % CI 1·1, 2·3) for current smokers and 1·7 ml (95 % CI 1·2, 2·1) for former smokers, compared with 0·8 ml (95 % CI 0·4, 1·2) for never smokers. In summary, the 25(OH)D associations with FEV1 and FVC were positive in both ancestries. In EA, a stronger association was observed for smokers compared with never smokers, which supports the importance of vitamin D in vulnerable populations.

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Smoking cessation, decline in pulmonary function and total mortality: a 30 year follow up study among the Finnish cohorts of the Seven Countries Study

Thorax ◽

10.1136/thx.56.9.703 ◽

2001 ◽

Vol 56 (9) ◽

pp. 703-707

Author(s):

M Pelkonen ◽

I-L Notkola ◽

H Tukiainen ◽

M Tervahauta ◽

J Tuomilehto ◽

...

Keyword(s):

Smoking Cessation ◽

Pulmonary Function ◽

Total Mortality ◽

Forced Expiratory Volume ◽

Rapid Decline ◽

Seven Countries Study ◽

Never Smokers ◽

The Relationship

BACKGROUNDPermanent smoking cessation reduces loss of pulmonary function. Less is known in the long term about individuals who give up smoking temporarily or quitters with lower initial pulmonary function. Little is known also about the relationship between decline in pulmonary function and mortality. We examined these aspects and the association between smoking, decline in pulmonary function, and mortality.METHODSTwo middle aged male Finnish cohorts of the Seven Countries Study and their re-examinations on five occasions during a 30 year period of follow up were analysed.RESULTSDuring the first 15 years (n=1007) adjusted decline in forced expiratory volume in 0.75 seconds (FEV0.75) was 46.4 ml/year in never smokers, 49.3 ml/year in past smokers, 55.5 ml/year in permanent quitters, 55.5 ml/year in intermittent quitters, and 66.0 ml/year in continuous smokers (p<0.001 for trend). Quitters across the entire range of baseline FEV0.75 had a slower decline in FEV0.75 than continuous smokers. Among both continuing smokers and never smokers, non-survivors had a significantly (p<0.001) more rapid decline in FEV0.75 than survivors. The adjusted relative hazard for total mortality was 1.73 (95% confidence interval (CI) 1.41 to 2.11) and 1.24 (95% CI 1.02 to 1.52) in the lowest and middle tertiles of decline in FEV0.75. Never smokers, past smokers, and quitters had significantly lower total mortality than continuous smokers, partly because of their slower decline in FEV0.75.CONCLUSIONThese results highlight the positive effect of smoking cessation, even intermittent cessation, on decline in pulmonary function. Accelerated decline in pulmonary function was found to be a risk factor for total mortality. The beneficial effect of smoking cessation on mortality may partly be mediated through a reduced decline in pulmonary function.

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