Dataset Information

The clinical impact of non-obstructive chronic bronchitis in current and former smokers.

ABSTRACT: As the clinical significance of chronic bronchitis among smokers without airflow obstruction is unclear, we sought to determine morbidity associated with this disorder.We examined subjects from the COPDGene study and compared those with FEV1/FVC ? 0.70, no diagnosis of asthma and chronic bronchitis as defined as a history of cough and phlegm production for ? 3 months/year for ? 2 years (NCB) to non-obstructed subjects without chronic bronchitis (CB-). Multivariate analysis was used to determine factors associated with and impact of NCB.We identified 597 NCB and 4283 CB- subjects. NCB participants were younger (55.4 vs. 57.2 years, p < 0.001) with greater tobacco exposure (42.9 vs. 37.8 pack-years, p < 0.001) and more often current smokers; more frequently reported occupational exposure to fumes (52.8% vs. 42.2%, p < 0.001), dust for ? 1 year (55.3% vs. 42.0%, p < 0.001) and were less likely to be currently working. NCB subjects demonstrated worse quality-of-life (SGRQ 35.6 vs. 15.1, p < 0.001) and exercise capacity (walk distance 415 vs. 449 m, p < 0.001) and more frequently reported respiratory "flare-ups" requiring treatment with antibiotics or steroids (0.30 vs. 0.10 annual events/subject, p < 0.001) prior to enrollment and during follow-up (0.34 vs. 0.16 annual events/subject, p < 0.001). In multivariate analysis, current smoking, GERD, sleep apnea and occupational exposures were significantly associated with NCB.While longitudinal data will be needed to determine whether NCB progresses to COPD, NCB patients have poorer quality-of-life, exercise capacity and frequent respiratory events. Beyond smoking cessation interventions, further research is warranted to determine the benefit of other therapeutics in this population. Clinical Trials Registration # NCT00608764 (http://clinicaltrials.gov/show/NCT00608764). Link to study protocol: http://www.copdgene.org/sites/default/files/COPDGeneProtocol-5-0_06-19-2009.pdf.

SUBMITTER: Martinez CH

PROVIDER: S-EPMC3943716 | biostudies-literature | 2014 Mar

REPOSITORIES: biostudies-literature

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The clinical impact of non-obstructive chronic bronchitis in current and former smokers.

Martinez Carlos H CH Kim Victor V Chen Yahong Y Kazerooni Ella A EA Murray Susan S Criner Gerard J GJ Curtis Jeffrey L JL Regan Elizabeth A EA Wan Emily E Hersh Craig P CP Silverman Edwin K EK Crapo James D JD Martinez Fernando J FJ Han Meilan K MK

Respiratory medicine 20131115 3

<h4>Background</h4>As the clinical significance of chronic bronchitis among smokers without airflow obstruction is unclear, we sought to determine morbidity associated with this disorder.<h4>Methods</h4>We examined subjects from the COPDGene study and compared those with FEV1/FVC ≥ 0.70, no diagnosis of asthma and chronic bronchitis as defined as a history of cough and phlegm production for ≥ 3 months/year for ≥ 2 years (NCB) to non-obstructed subjects without chronic bronchitis (CB-). Multivari ...[more]

PMID: 24280543

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Project description:Background DNA methylation (DNAm) performs excellently in the discrimination of current and former smokers from never smokers, where AUCs > 0.9 are regularly reported using a single CpG site (cg05575921; AHRR). However, there is a paucity of DNAm models which attempt to distinguish current, former and never smokers as individual classes. Derivation of a robust DNAm model that accurately distinguishes between current, former and never smokers would be particularly valuable to epidemiological research (as a more accurate smoking definition vs. self-report) and could potentially translate to clinical settings. Therefore, we appraise 4 DNAm models of ternary smoking status (that is, current, former and never smokers): methylation at cg05575921 (AHRR model), weighted scores from 13 CpGs created by Maas et al. (Maas model), weighted scores from a LASSO model of candidate smoking CpGs from the literature (candidate CpG LASSO model), and weighted scores from a LASSO model supplied with genome-wide 450K data (agnostic LASSO model). Discrimination is assessed by AUC, whilst classification accuracy is assessed by accuracy and kappa, derived from confusion matrices. Results We find that DNAm can classify ternary smoking status with reasonable accuracy, including when applied to external data. Ternary classification using only DNAm far exceeds the classification accuracy of simply assigning all classes as the most prevalent class (63.7% vs. 36.4%). Further, we develop a DNAm classifier which performs well in discriminating current from former smokers (agnostic LASSO model AUC in external validation data: 0.744). Finally, across our DNAm models, we show evidence of enrichment for biological pathways and human phenotype ontologies relevant to smoking, such as haemostasis, molybdenum cofactor synthesis, body fatness and social behaviours, providing evidence of the generalisability of our classifiers. Conclusions Our findings suggest that DNAm can classify ternary smoking status with close to 65% accuracy. Both the ternary smoking status classifiers and current versus former smoking status classifiers address the present lack of former smoker classification in epigenetic literature; essential if DNAm classifiers are to adequately relate to real-world populations. To improve performance further, additional focus on improving discrimination of current from former smokers is necessary. Supplementary Information The online version contains supplementary material available at 10.1186/s13148-021-01191-6.

Project description:The human microbiome has a role in the development of multiple diseases. Individual microbiome profiles are highly personalized, though many species are shared. Understanding the relationship between the human microbiome and disease may inform future individualized treatments. We hypothesize the blood microbiome signature may be a surrogate for some lung microbial characteristics. We sought associations between the blood microbiome signature and lung-relevant host factors. Based on reads not mapped to the human genome, we detected microbial nucleic acids through secondary use of peripheral blood RNA-sequencing from 2,590 current and former smokers with and without chronic obstructive pulmonary disease (COPD) from the COPDGene study. We used the Genome Analysis Toolkit (GATK) microbial pipeline PathSeq to infer microbial profiles. We tested associations between the inferred profiles and lung disease relevant phenotypes and examined links to host gene expression pathways. We replicated our analyses using a second independent set of blood RNA-seq data from 1,065 COPDGene study subjects and performed a meta-analysis across the two studies. The four phyla with highest abundance across all subjects were Proteobacteria, Actinobacteria, Firmicutes and Bacteroidetes. In our meta-analysis, we observed associations (q-value < 0.05) between Acinetobacter, Serratia, Streptococcus and Bacillus inferred abundances and Modified Medical Research Council (mMRC) dyspnea score. Current smoking status was associated (q < 0.05) with Acinetobacter, Serratia and Cutibacterium abundance. All 12 taxa investigated were associated with at least one white blood cell distribution variable. Abundance for nine of the 12 taxa was associated with sex, and seven of the 12 taxa were associated with race. Host-microbiome interaction analysis revealed clustering of genera associated with mMRC dyspnea score and smoking status, through shared links to several host pathways. This study is the first to identify a bacterial microbiome signature in the peripheral blood of current and former smokers. Understanding the relationships between systemic microbial signatures and lung-related phenotypes may inform novel interventions and aid understanding of the systemic effects of smoking.

Project description:Background Heavy smokers perform worse on neuropsychological assessment than age-matched peers. However, traditional pulmonary measures of airflow limitation and hypoxemia explain only a modest amount of variance in cognition. The current objective was to determine whether carotid artery stiffness is associated with cognition in former smokers beyond the effects of amount of smoking and pulmonary function. Methods and Results Eighty-four former smokers including individuals across a spectrum of airflow limitation severity were included: 30 without chronic obstructive pulmonary disease (Global Initiative for Chronic Obstructive Lung Disease [GOLD] 0 with normal spirometry and lung computed tomography), 31 with mild-moderate chronic obstructive pulmonary disease (GOLD 1-2), and 23 with severe-very severe chronic obstructive pulmonary disease (GOLD 3-4). Participants completed questionnaires, spirometry, carotid ultrasonography, and neuropsychological testing. Multiple linear regression was used to determine whether carotid artery stiffness is associated with neuropsychological performance in 4 cognitive domains after adjusting for age, sex, pack-years of smoking, estimated premorbid intellectual functioning, and airflow limitation. Higher carotid artery β-stiffness index was associated with reduced executive functioning-processing speed in the fully adjusted model (β=-0.49, SE=0.14; P=0.001). Lower premorbid intellectual function, male sex, and presence of airflow limitation (GOLD 1 or 2 and GOLD 3 or 4) were also associated with worse executive functioning-processing speed. β-Stiffness index was not significantly associated with performance in other cognitive domains. Conclusions Carotid artery stiffness is associated with worse performance on executive functioning-processing speed in former smokers beyond the effects of aging, amount of past smoking, severity of airflow limitation, and hypoxemia. Future research should examine whether carotid stiffness can be used to identify former smokers at risk for subsequent cognitive impairment.

Dataset Information

The clinical impact of non-obstructive chronic bronchitis in current and former smokers.

Publications

The clinical impact of non-obstructive chronic bronchitis in current and former smokers.

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