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Clinical and Radiologic Disease in Smokers With Normal Spirometry.

ABSTRACT: Airflow obstruction on spirometry is universally used to define chronic obstructive pulmonary disease (COPD), and current or former smokers without airflow obstruction may assume that they are disease free.To identify clinical and radiologic evidence of smoking-related disease in a cohort of current and former smokers who did not meet spirometric criteria for COPD, for whom we adopted the discarded label of Global Initiative for Obstructive Lung Disease (GOLD) 0.Individuals from the Genetic Epidemiology of COPD (COPDGene) cross-sectional observational study completed spirometry, chest computed tomography (CT) scans, a 6-minute walk, and questionnaires. Participants were recruited from local communities at 21 sites across the United States. The GOLD 0 group (n?=?4388) (ratio of forced expiratory volume in the first second of expiration [FEV1] to forced vital capacity >0.7 and FEV1 ?80% predicted) from the COPDGene study was compared with a GOLD 1 group (n?=?794), COPD groups (n?=?3690), and a group of never smokers (n?=?108). Recruitment began in January 2008 and ended in July 2011.Physical function impairments, respiratory symptoms, CT abnormalities, use of respiratory medications, and reduced respiratory-specific quality of life.One or more respiratory-related impairments were found in 54.1% (2375 of 4388) of the GOLD 0 group. The GOLD 0 group had worse quality of life (mean [SD] St George's Respiratory Questionnaire total score, 17.0 [18.0] vs 3.8 [6.8] for the never smokers; P?

SUBMITTER: Regan EA

PROVIDER: S-EPMC4564354 | biostudies-literature | 2015 Sep

REPOSITORIES: biostudies-literature

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Clinical and Radiologic Disease in Smokers With Normal Spirometry.

Regan Elizabeth A EA Lynch David A DA Curran-Everett Douglas D Curtis Jeffrey L JL Austin John H M JH Grenier Philippe A PA Kauczor Hans-Ulrich HU Bailey William C WC DeMeo Dawn L DL Casaburi Richard H RH Friedman Paul P Van Beek Edwin J R EJ Hokanson John E JE Bowler Russell P RP Beaty Terri H TH Washko George R GR Han MeiLan K MK Kim Victor V Kim Song Soo SS Yagihashi Kunihiro K Washington Lacey L McEvoy Charlene E CE Tanner Clint C Mannino David M DM Make Barry J BJ Silverman Edwin K EK Crapo James D JD

JAMA internal medicine 20150901 9

<h4>Importance</h4>Airflow obstruction on spirometry is universally used to define chronic obstructive pulmonary disease (COPD), and current or former smokers without airflow obstruction may assume that they are disease free.<h4>Objective</h4>To identify clinical and radiologic evidence of smoking-related disease in a cohort of current and former smokers who did not meet spirometric criteria for COPD, for whom we adopted the discarded label of Global Initiative for Obstructive Lung Disease (GOLD ...[more]

PMID: 26098755

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Project description:BackgroundThe burden of frequent respiratory exacerbations in COPD patients with mild-to-moderate spirometric impairment and smokers with preserved lung function is unknown.MethodsWe categorized COPD participants in COPDGene with post-bronchodilator FEV1%predicted≥50% by the annual exacerbation frequency into three groups: i)frequent exacerbators (top 5%; n = 109), ii)exacerbators (>0 but less than frequent exacerbators; n = 1,009), and iii)No exacerbation (n = 981). Exacerbations were defined as respiratory episodes requiring antibiotics and/or systemic steroids. We performed a Cox proportional hazards regression analysis to examine the association with mortality. We repeated the same process in current/former smokers with preserved spirometry (FEV1≥80%predicted and FEV1/FVC≥0.7).ResultsAmong 2,099 COPD participants, frequent exacerbators had ≥1.8 exacerbations/year and were responsible for 34.3% of the total exacerbations. There were 102 (10.4%) deaths in the group with no exacerbations, 119 (11.8%) in the exacerbator group, and 24 (22%) in the frequent exacerbators. Adjusted mortality in frequent exacerbators was higher relative to individuals with no exacerbations (hazard ratio (HR) = 1.98; 95%CI = 1.25-3.13). An increase in frequency of exacerbations by one exacerbation/year was associated with increased mortality (HR = 1.40,95%CI = 1.21-1.62). Among 3,143 participants with preserved spirometry, frequent exacerbators had ≥0.8 exacerbations/year and were responsible for more than half of the exacerbations. There were 93 (4.2%) deaths in the group with no exacerbations, 28 (3.8%) in the exacerbator group, and 14 (7.6%) in the frequent exacerbators. The adjusted mortality was increased in frequent exacerbators with preserved spirometry relative to those with no exacerbations (HR = 2.25; 95%CI = 1.26-4.01).ConclusionsIn COPD participants with mild-to-moderate spirometric impairment and smokers with preserved spirometry, the frequent exacerbator phenotype is responsible for a large proportion of total exacerbations and associated with high mortality.

Project description:Upregulation of Expression of the Ubiquitin Carboxyl Terminal Hydrolase L1 Gene in Human Airway Epithelium of Cigarette Smokers The microarray data deposited here is from 39 HG-U133 Plus 2.0 GeneChips, from 12 normal non-smokers, 12 phenotypic normal smokers, 9 Early COPD and 6 COPD individuals, all small airways, all small airway. A subset of these samples have been already submitted under GEO Accession Number GSE 4498. These are: 12 non-smokers samples (GSM101095-GSM101106) and 10 smoker samples (GSM101107-GSM101116). These 22 samples that are also in GSE4498 were described in Harvey, B-G; Heguy, A.; Leopold, P.L.; Carolan, B.; Ferris, B. and Crystal R.G. Modification of Gene Expression of the Small Airway Epithelium in Response to Cigarette Smoking. J. Mol. Med (in press). These data are part of a study aimed at understanding how cigarette smoking modifies neuroendocrine cells, in which microarray analysis with TaqMan confirmation was used to assess airway epithelial samples obtained by fiberoptic bronchoscopy from 81 individuals (normal nonsmokers, normal smokers, smokers with early COPD and smokers with established COPD). Of 11 genes considered to be neuroendocrine cell-specific, only ubiquitin C-terminal hydrolase L1(UCHL1), a member of the ubiquitin proteasome pathway, was consistently upregulated in smokers compared to nonsmokers. Up-regulation of UCHL1 at the protein level was observed with immunohistochemistry of bronchial biopsies of smokers compared to nonsmokers. Interestingly, however, while UCHL1 expression was present only in neuroendocrine cells of the airway epithelium in nonsmokers, UCHL1 expression was also expressed in ciliated epithelial cells in smokers, an intriguing observation in light of recent observations that ciliated cells can are capable of transdifferentiating to other airway epithelium. In the context that UCHL1 is involved in the degradation of unwanted, misfolded or damaged proteins within the cell and is overexpressed in >50% of lung cancers, its overexpression in chronic smokers may represent an early event in the complex transformation from normal epithelium to overt malignancy. Keywords: non-smokers vs phenotypic normal smokers, smokers with early COPD, and smokers with COPD

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Clinical and Radiologic Disease in Smokers With Normal Spirometry.

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Clinical and Radiologic Disease in Smokers With Normal Spirometry.

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