Longitudinal decline in lung function: a community-based cohort study in Korea

Abstract Progressive decline in lung function is the hallmark of chronic obstructive pulmonary disease (COPD). We aimed to assess the rate of decline in forced expiratory volume in 1 second (FEV1) in patients from a community cohort database in Korea. 5,865 subjects aged 40–69 years from the Ansung-Ansan cohort database I–III (2001–2006) were included in this study. We assessed the annual rate of decline in FEV1 over time in relation to smoking status, patient sex, and presence or absence of pre-bronchodilator airflow limitation using a generalized additive mixed model. The mean follow-up duration was 3.8 years. The annual mean decline in FEV1 in the entire cohort was significantly more rapid for men than women (31.3 mL vs 27.0 mL, P = 0.003). Among men without pre-bronchodilator airflow limitation, annual mean declines in FEV1 were 31.5, 35.5, and 40.1 mL for never smokers, former smokers (P = 0.09 vs. never smokers), and current smokers (P < 0.001 vs. never smokers), respectively; and 23.4, 19.7, and 33.9 mL, respectively, for men with pre-bronchodilator airflow limitation. Thus, among Korean males, smoking accelerates lung function decline over time whereas smoking cessation slows the rate of FEV1 decline regardless of pre-bronchodilator airflow limitation. This underscores the importance of smoking cessation in Koreans.

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Improved outcomes in ex-smokers with COPD: a UK primary care observational cohort study

European Respiratory Journal ◽

10.1183/13993003.02114-2016 ◽

2017 ◽

Vol 49 (5) ◽

pp. 1602114 ◽

Cited By ~ 12

Author(s):

Lynn Josephs ◽

David Culliford ◽

Matthew Johnson ◽

Mike Thomas

Keyword(s):

Primary Care ◽

Emergency Department ◽

Smoking Cessation ◽

Lung Function ◽

Cox Regression ◽

Smoking Status ◽

Chronic Obstructive ◽

Emergency Department Attendance ◽

Risk Of Death ◽

Never Smokers

Smoking cessation in chronic obstructive pulmonary disease (COPD) reduces accelerated forced expiratory volume in 1 s decline, but impact on key health outcomes is less clear. We studied the relationship of smoking status to mortality and hospitalisation in a UK primary care COPD population.Using patient-anonymised routine data in the Hampshire Health Record Analytical Database, we identified a prevalent COPD cohort, categorising patients by smoking status (current, ex- or never-smokers). Three outcomes were measured over 3 years (2011–2013): all-cause mortality, respiratory-cause unplanned hospital admission and respiratory-cause emergency department attendance. Survival analysis using multivariable Cox regression after multiple imputation was used to estimate hazard ratios for each outcome by smoking status, adjusting for measured confounders (including age, lung function, socioeconomic deprivation, inhaled medication and comorbidities).We identified 16 479 patients with COPD, mean±sd age 70.1±11.1 years. Smoking status was known in 91.3%: 35.1% active smokers, 54.3% ex-smokers, 1.9% never-smokers. Active smokers predominated among younger patients. Compared with active smokers (n=5787), ex-smokers (n=8941) had significantly reduced risk of death, hazard ratio (95% confidence interval) 0.78 (0.70–0.87), hospitalisation, 0.82 (0.74–0.89) and emergency department attendance, 0.78 (0.70–0.88).After adjusting for confounders, ex-smokers had significantly better outcomes, emphasising the importance of effective smoking cessation support, regardless of age or lung function.

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Radiographic lung volumes predict progression to COPD in smokers with preserved spirometry in SPIROMICS

European Respiratory Journal ◽

10.1183/13993003.02214-2018 ◽

2019 ◽

Vol 54 (4) ◽

pp. 1802214 ◽

Cited By ~ 7

Author(s):

Mehrdad Arjomandi ◽

Siyang Zeng ◽

Igor Barjaktarevic ◽

R. Graham Barr ◽

Eugene R. Bleecker ◽

...

Keyword(s):

Smoking Status ◽

Airflow Obstruction ◽

Rapid Decline ◽

Chronic Obstructive ◽

Differential Rate ◽

Lung Function Decline ◽

Air Trapping ◽

Mixed Effect ◽

Lung Volumes ◽

Rate Of Decline

The characteristics that predict progression to overt chronic obstructive pulmonary disease (COPD) in smokers without spirometric airflow obstruction are not clearly defined.We conducted a post hoc analysis of 849 current and former smokers (≥20 pack–years) with preserved spirometry from the Subpopulations and Intermediate Outcome Measures in COPD Study (SPIROMICS) cohort who had baseline computed tomography (CT) scans of lungs and serial spirometry. We examined whether CT-derived lung volumes representing air trapping could predict adverse respiratory outcomes and more rapid decline in spirometry to overt COPD using mixed-effect linear modelling.Among these subjects with normal forced expiratory volume in 1 s (FEV1) to forced vital capacity (FVC) ratio, CT-measured residual volume (RVCT) to total lung capacity (TLCCT) ratio varied widely, from 21% to 59%. Over 2.5±0.7 years of follow-up, subjects with higher RVCT/TLCCT had a greater differential rate of decline in FEV1/FVC; those in the upper RVCT/TLCCT tertile had a 0.66% (95% CI 0.06%–1.27%) faster rate of decline per year compared with those in the lower tertile (p=0.015) regardless of demographics, baseline spirometry, respiratory symptoms score, smoking status (former versus current) or smoking burden (pack–years). Accordingly, subjects with higher RVCT/TLCCT were more likely to develop spirometric COPD (OR 5.7 (95% CI 2.4–13.2) in upper versus lower RVCT/TLCCT tertile; p<0.001). Other CT indices of air trapping showed similar patterns of association with lung function decline; however, when all CT indices of air trapping, emphysema, and airway disease were included in the same model, only RVCT/TLCCT retained its significance.Increased air trapping based on radiographic lung volumes predicts accelerated spirometry decline and progression to COPD in smokers without obstruction.

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Interaction between asthma and smoking increases the risk of adult airway obstruction

European Respiratory Journal ◽

10.1183/09031936.00055514 ◽

2014 ◽

Vol 45 (3) ◽

pp. 635-643 ◽

Cited By ~ 44

Author(s):

Marianne Aanerud ◽

Anne-Elie Carsin ◽

Jordi Sunyer ◽

Julia Dratva ◽

Thorarinn Gislason ◽

...

Keyword(s):

Airway Obstruction ◽

Early Onset ◽

Linear Models ◽

Late Onset ◽

Smoking Status ◽

Random Effect ◽

Chronic Obstructive ◽

Lung Function Decline ◽

Increased Risk ◽

Never Smokers

The aim of the present study was to analyse the interaction between asthma and smoking in the risk of adult airway obstruction, accounting for atopy.In the European Community Respiratory Health Survey, 15 668 persons aged 20–56 years underwent spirometry in 1991–1993 and 9 years later (n=8916). Risk of airway obstruction and lung function decline associated with smoking and early-onset (<10 years of age) and late-onset (>10 years of age) asthma were analysed with generalised estimating equation models and random-effect linear models, adjusting for covariates. Interaction of asthma with smoking was expressed as relative excess risk due to interaction (RERI).A 20-fold increase in adult airway obstruction was found among those with early-onset asthma independently of smoking status (never-smokers: OR 21.0, 95% CI 12.7–35; current smokers: OR 23.7, 95% CI 13.9–40.6). Late-onset asthma was associated with airway obstruction, with a stronger association among current smokers (OR 25.6, 95% CI 15.6–41.9) than among never-smokers (OR 11.2, 95% CI 6.8–18.6) (RERI 12.02, 95% CI 1.96–22.07). Stratifying by atopy, the association between smoking and asthma was most pronounced among nonatopics.Early- and late-onset asthma were associated with 10–20-fold increased risk of adult airway obstruction. Smoking increased the risk of adult airway obstruction in subjects with asthma onset after age 10 years. Investigation of measures potentially preventive of chronic obstructive pulmonary disease development following asthma is urgently needed.

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Fibrocyte accumulation in bronchi: a cellular hallmark of COPD

10.1101/449843 ◽

2018 ◽

Author(s):

Isabelle Dupin ◽

Matthieu Thumerel ◽

Elise Maurat ◽

Florence Coste ◽

Hugues Begueret ◽

...

Keyword(s):

Lung Function ◽

Ct Scan ◽

Wall Thickness ◽

High Density ◽

Airflow Limitation ◽

Normal Lung ◽

Chronic Obstructive ◽

Lung Function Decline ◽

Control Subjects ◽

Copd Patients

AbstractBackgroundThe remodeling mechanism and cellular players causing persistent airflow limitation in chronic obstructive pulmonary disease (COPD) remain largely elusive. We have recently demonstrated that circulating fibrocytes, a rare population of fibroblast-like cells produced by the bone marrow stroma, are increased in COPD patients during an exacerbation. It remains, however, unclear, whether fibrocytes are present in bronchial tissue of COPD patients.ObjectiveWe aimed to quantify fibrocytes density in bronchial specimens from both control subjects and COPD patients, and to define associations with clinical, functional and computed tomography relevant parameters.Methods17 COPD patients and 25 control subjects with normal lung function testing and no chronic symptoms, all of them requiring thoracic surgery, were recruited. LFT and CT-scan were performed before surgery. Using co-immunostaining and image analysis, we identify CD45+ FSP1+ cells as tissue fibrocytes and quantify their density in distal and proximal bronchial specimens from the whole series.ResultsHere, we demonstrate that fibrocytes are increased in both distal and proximal tissue specimens of COPD patients, compared to those of controls. The density of fibrocytes is negatively correlated with lung function parameters, such as FEV1 and FEV1/FVC, and positively with bronchial wall thickness assessed by CT scan. High density of distal bronchial fibrocytes predicts presence of COPD with a sensitivity of 83% and a specificity of 70%.ConclusionsOur results thus suggest that recruitment of fibrocytes in the bronchi may participate to lung function decline during COPD progression.Clinical ImplicationsHigh density of tissue fibrocytes is associated with a deteriorated lung function and an increase in airway wall thickness. A low density tissue fibrocytes virtually eliminates the presence of COPD.Capsule summaryBlood fibrocytes assessed during exacerbation is a predictor of mortality in COPD. This study shows an increase of bronchial fibrocytes, that is associated with lower lung function, increased bronchial thickness and air trapping in COPD.

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The effects of marijuana smoking on lung function in older people

European Respiratory Journal ◽

10.1183/13993003.00826-2019 ◽

2019 ◽

Vol 54 (6) ◽

pp. 1900826 ◽

Cited By ~ 7

Author(s):

Wan C. Tan ◽

Jean Bourbeau ◽

Shawn D. Aaron ◽

James C. Hogg ◽

François Maltais ◽

...

Keyword(s):

Lung Function ◽

Population Based ◽

Forced Expiratory Volume ◽

Chronic Obstructive ◽

Long Term Effects ◽

Obstructive Pulmonary Disease ◽

Before And After ◽

Rate Of Decline ◽

Never Smokers

BackgroundPrevious studies have associated marijuana exposure with increased respiratory symptoms and chronic bronchitis among long-term cannabis smokers. The long-term effects of smoked marijuana on lung function remain unclear.MethodsWe determined the association of marijuana smoking with the risk of spirometrically defined chronic obstructive pulmonary disease (COPD) (post-bronchodilator forced expiratory volume in 1 s (FEV1)/forced vital capacity ratio <0.7) in 5291 population-based individuals and the rate of decline in FEV1 in a subset of 1285 males and females, aged ≥40 years, who self-reported use (or non-use) of marijuana and tobacco cigarettes and performed spirometry before and after inhaled bronchodilator on multiple occasions. Analysis for the decline in FEV1 was performed using random mixed effects regression models adjusted for age, sex and body mass index. Heavy tobacco smoking and marijunana smoking was defined as >20 pack-years and >20 joint-years, respectively.Results∼20% of participants had been or were current marijuana smokers with most having smoked tobacco cigarettes in addition (83%). Among heavy marijuana users, the risk of COPD was significantly increased (adjusted OR 2.45, 95% CI 1.55–3.88). Compared to never-smokers of marijuana and tobacco, heavy marijuana smokers and heavy tobacco smokers experienced a faster decline in FEV1 by 29.5 mL·year−1 (p=0.0007) and 21.1 mL·year−1 (p<0.0001), respectively. Those who smoked both substances experienced a decline of 32.31 mL·year−1 (p<0.0001).InterpretationHeavy marijuana smoking increases the risk of COPD and accelerates FEV1 decline in concomitant tobacco smokers beyond that observed with tobacco alone.

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Identifying miRNA-mRNA Networks Associated With COPD Phenotypes

Frontiers in Genetics ◽

10.3389/fgene.2021.748356 ◽

2021 ◽

Vol 12 ◽

Author(s):

Yonghua Zhuang ◽

Brian D Hobbs ◽

Craig P Hersh ◽

Katerina Kechris

Keyword(s):

Lung Function ◽

Mrna Expression ◽

Statistical Power ◽

Biomarker Discovery ◽

Smoking Status ◽

Airflow Limitation ◽

Covariate Adjustment ◽

Chronic Obstructive ◽

Sequencing Data ◽

Network Identification

Chronic obstructive pulmonary disease (COPD) is characterized by expiratory airflow limitation and symptoms such as shortness of breath. Although many studies have demonstrated dysregulated microRNA (miRNA) and gene (mRNA) expression in the pathogenesis of COPD, how miRNAs and mRNAs systematically interact and contribute to COPD development is still not clear. To gain a deeper understanding of the gene regulatory network underlying COPD pathogenesis, we used Sparse Multiple Canonical Correlation Network (SmCCNet) to integrate whole blood miRNA and RNA-sequencing data from 404 participants in the COPDGene study to identify novel miRNA–mRNA networks associated with COPD-related phenotypes including lung function and emphysema. We hypothesized that phenotype-directed interpretable miRNA–mRNA networks from SmCCNet would assist in the discovery of novel biomarkers that traditional single biomarker discovery methods (such as differential expression) might fail to discover. Additionally, we investigated whether adjusting -omics and clinical phenotypes data for covariates prior to integration would increase the statistical power for network identification. Our study demonstrated that partial covariate adjustment for age, sex, race, and CT scanner model (in the quantitative emphysema networks) improved network identification when compared with no covariate adjustment. However, further adjustment for current smoking status and relative white blood cell (WBC) proportions sometimes weakened the power for identifying lung function and emphysema networks, a phenomenon which may be due to the correlation of smoking status and WBC counts with the COPD-related phenotypes. With partial covariate adjustment, we found six miRNA–mRNA networks associated with COPD-related phenotypes. One network consists of 2 miRNAs and 28 mRNAs which had a 0.33 correlation (p = 5.40E-12) to forced expiratory volume in 1 s (FEV1) percent predicted. We also found a network of 5 miRNAs and 81 mRNAs that had a 0.45 correlation (p = 8.80E-22) to percent emphysema. The miRNA–mRNA networks associated with COPD traits provide a systems view of COPD pathogenesis and complements biomarker identification with individual miRNA or mRNA expression data.

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NFE2L2 pathway polymorphisms and lung function decline in chronic obstructive pulmonary disease

Physiological Genomics ◽

10.1152/physiolgenomics.00027.2012 ◽

2012 ◽

Vol 44 (15) ◽

pp. 754-763 ◽

Cited By ~ 16

Author(s):

Andrew J. Sandford ◽

Deepti Malhotra ◽

H. Marike Boezen ◽

Mateusz Siedlinski ◽

Dirkje S. Postma ◽

...

Keyword(s):

Chronic Obstructive Pulmonary Disease ◽

Lung Function ◽

Pulmonary Disease ◽

Defense Mechanism ◽

Health Study ◽

Chronic Obstructive ◽

Related Factor ◽

Lung Function Decline ◽

Obstructive Pulmonary Disease ◽

Rate Of Decline

An oxidant-antioxidant imbalance in the lung contributes to the development of chronic obstructive pulmonary disease (COPD) that is caused by a complex interaction of genetic and environmental risk factors. Nuclear erythroid 2-related factor 2 (NFE2L2 or NRF2) is a critical molecule in the lung's defense mechanism against oxidants. We investigated whether polymorphisms in the NFE2L2 pathway affected the rate of decline of lung function in smokers from the Lung Health Study (LHS)( n = 547) and in a replication set, the Vlagtwedde-Vlaardingen cohort ( n = 533). We selected polymorphisms in NFE2L2 in genes that positively or negatively regulate NFE2L2 transcriptional activity and in genes that are regulated by NFE2L2. Polymorphisms in 11 genes were significantly associated with rate of lung function decline in the LHS. One of these polymorphisms, rs11085735 in the KEAP1 gene, was previously shown to be associated with the level of lung function in the Vlagtwedde-Vlaardingen cohort but not with decline of lung function. Of the 23 associated polymorphisms in the LHS, only rs634534 in the FOSL1 gene showed a significant association in the Vlagtwedde-Vlaardingen cohort with rate of lung function decline, but the direction of the association was not consistent with that in the LHS. In summary, despite finding several nominally significant polymorphisms in the LHS, none of these associations were replicated in the Vlagtwedde-Vlaardingen cohort, indicating lack of effect of polymorphisms in the NFE2L2 pathway on the rate of decline of lung function.

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Epigenome-wide association study on asthma and chronic obstructive pulmonary disease overlap reveals aberrant DNA methylations related to clinical phenotypes

Scientific Reports ◽

10.1038/s41598-021-83185-1 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Yung-Che Chen ◽

◽

Ying-Huang Tsai ◽

Chin-Chou Wang ◽

Shih-Feng Liu ◽

...

Keyword(s):

Chronic Obstructive Pulmonary Disease ◽

Lung Function ◽

Pulmonary Disease ◽

Airflow Limitation ◽

Chronic Obstructive ◽

Lung Function Decline ◽

Obstructive Pulmonary Disease ◽

Copd Patients ◽

Dna Methylations

AbstractWe hypothesized that epigenetics is a link between smoking/allergen exposures and the development of Asthma and chronic obstructive pulmonary disease (ACO). A total of 75 of 228 COPD patients were identified as ACO, which was independently associated with increased exacerbations. Microarray analysis identified 404 differentially methylated loci (DML) in ACO patients, and 6575 DML in those with rapid lung function decline in a discovery cohort. In the validation cohort, ACO patients had hypermethylated PDE9A (+ 30,088)/ZNF323 (− 296), and hypomethylated SEPT8 (− 47) genes as compared with either pure COPD patients or healthy non-smokers. Hypermethylated TIGIT (− 173) gene and hypomethylated CYSLTR1 (+ 348)/CCDC88C (+ 125,722)/ADORA2B (+ 1339) were associated with severe airflow limitation, while hypomethylated IFRD1 (− 515) gene with frequent exacerbation in all the COPD patients. Hypermethylated ZNF323 (− 296) / MPV17L (+ 194) and hypomethylated PTPRN2 (+ 10,000) genes were associated with rapid lung function decline. In vitro cigarette smoke extract and ovalbumin concurrent exposure resulted in specific DNA methylation changes of the MPV17L / ZNF323 genes, while 5-aza-2′-deoxycytidine treatment reversed promoter hypermethylation-mediated MPV17L under-expression accompanied with reduced apoptosis and decreased generation of reactive oxygen species. Aberrant DNA methylations may constitute a determinant for ACO, and provide a biomarker of airflow limitation, exacerbation, and lung function decline.

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Smoking Interaction with a Polygenic Risk Score for Reduced Lung Function

10.1101/2021.03.26.21254415 ◽

2021 ◽

Author(s):

Woori Kim ◽

Matthew Moll ◽

Dandi Qiao ◽

Brian D. Hobbs ◽

Nick Shrine ◽

...

Keyword(s):

Lung Function ◽

Genetic Risk ◽

Smoking Status ◽

Airflow Limitation ◽

European Ancestry ◽

Chronic Obstructive ◽

Polygenic Risk Score ◽

Polygenic Risk ◽

Product Term ◽

Smoking Exposure

Importance: Risk to airflow limitation and Chronic Obstructive Pulmonary Disease (COPD) is influenced by combinations of cigarette smoking and genetic susceptibility, yet it remains unclear whether gene-by-smoking interactions contribute to quantitative measures of lung function. Objective: Determine whether smoking modifies the effect of a polygenic risk score's (PRS's) association with reduced lung function. Design: United Kingdom (UK) Biobank prospective cohort study. Setting: Population cohort. Participants: UK citizens of European ancestry aged 40-69 years, with genetic and spirometry data passing quality control metrics. Exposures: PRS, self-reported pack-years of smoking, ever- versus never-smoking status, and current- versus former-/never-smoking status. Main Outcomes and Measures: Forced expiratory volume in 1 second (FEV1)/forced vital capacity (FVC). We tested for interactions with models including the main effects of PRS, different smoking variables, and their cross-product term(s). We also compared the effects of pack-years of smoking on FEV1/FVC for those in the highest versus lowest decile of predicted genetic risk for low lung function. Results: We included 319,730 individuals (24,915 with moderate-to-severe COPD). The PRS and pack-years were significantly associated with lower FEV1/FVC, as was the interaction term (β [interaction] = -0.0028 [95% CI: -0.0029, -0.0026]; all p < 0.0001). A stepwise increment in estimated effect sizes for these interaction terms was observed per 10 pack-years of smoking exposure (all p < 0.0001). There was evidence of significant interaction between PRS with ever/never smoking status (β [interaction] = -0.0064 [95% CI: -0.0068, -0.0060]) and current/not-current smoking (β [interaction] = -0.0091 [95% CI: -0.0097, -0.0084]). For any given level of pack-years of smoking exposure, FEV1/FVC was significantly lower for individuals in the tenth compared to the first decile of genetic risk (p < 0.0001). For every 20 pack-years of smoking, those in the top compared to the bottom decile of genetic risk showed nearly a twofold reduction in FEV1/FVC. Conclusions and Relevance: COPD is characterized by diminished lung function, and our analyses suggest there is substantial interaction between genome-wide PRS and smoking exposures. While smoking has negative effects on lung function across all genetic risk categories, effects of smoking are highest in those with higher predicted genetic risk.

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Plasma pro-surfactant protein B and lung function decline in smokers

European Respiratory Journal ◽

10.1183/09031936.00184214 ◽

2015 ◽

Vol 45 (4) ◽

pp. 1037-1045 ◽

Cited By ~ 8

Author(s):

Janice M. Leung ◽

John Mayo ◽

Wan Tan ◽

C. Martin Tammemagi ◽

Geoffrey Liu ◽

...

Keyword(s):

Lung Cancer ◽

Lung Function ◽

Surfactant Protein ◽

Airflow Limitation ◽

Ct Scans ◽

Rapid Decline ◽

Chronic Obstructive ◽

Lung Function Decline ◽

Surfactant Protein B ◽

Protein B

Plasma pro-surfactant protein B (pro-SFTPB) levels have recently been shown to predict the development of lung cancer in current and ex-smokers, but the ability of pro-SFTPB to predict measures of chronic obstructive pulmonary disease (COPD) severity is unknown. We evaluated the performance characteristics of pro-SFTPB as a biomarker of lung function decline in a population of current and ex-smokers.Plasma pro-SFTPB levels were measured in 2503 current and ex-smokers enrolled in the Pan-Canadian Early Detection of Lung Cancer Study. Linear regression was performed to determine the relationship of pro-SFTPB levels to changes in forced expiratory volume in 1 s (FEV1) over a 2-year period as well as to baseline FEV1 and the burden of emphysema observed in computed tomography (CT) scans.Plasma pro-SFTPB levels were inversely related to both FEV1 % predicted (p=0.024) and FEV1/forced vital capacity (FVC) (p<0.001), and were positively related to the burden of emphysema on CT scans (p<0.001). Higher plasma pro-SFTPB levels were also associated with a more rapid decline in FEV1 at 1 year (p=0.024) and over 2 years of follow-up (p=0.004).Higher plasma pro-SFTPB levels are associated with increased severity of airflow limitation and accelerated decline in lung function. Pro-SFTPB is a promising biomarker for COPD severity and progression.

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