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Comparison of spirometric thresholds in diagnosing smoking-related airflow obstruction.

ABSTRACT: Diagnosis of chronic obstructive pulmonary disease is based on detection of airflow obstruction on spirometry. There is no consensus regarding using a fixed threshold to define airflow obstruction versus using the lower limit of normal (LLN) adjusted for age. We compared the accuracy and discrimination of the Global Initiative for Chronic Obstructive Lung Disease (GOLD) recommended fixed ratio of forced expiratory volume in the first second/forced vital capacity<0.70 with LLN in diagnosing smoking-related airflow obstruction using CT-defined emphysema and gas trapping as the disease gold standard.Data from a large multicentre study (COPDGene), which included current and former smokers (age range 45-80 years) with and without airflow obstruction, were analysed. Concordance between spirometric thresholds was measured. The accuracy of the thresholds in diagnosing emphysema and gas trapping was assessed using quantitative CT as gold standard.7743 subjects were included. There was very good agreement between the two spirometric cutoffs (?=0.85; 95% CI 0.83 to 0.86, p<0.001). 7.3% were discordant. Subjects with airflow obstruction by fixed ratio only had a greater degree of emphysema (4.1% versus 1.2%, p<0.001) and gas trapping (19.8% vs 7.5%, p<0.001) than those positive by LLN only, and also smoking controls without airflow obstruction (4.1% vs 1.9% and 19.8% vs 10.9%, respectively, p<0.001). On follow-up, the fixed ratio only group had more exacerbations than smoking controls.Compared with the fixed ratio, the use of LLN fails to identify a number of patients with significant pulmonary pathology and respiratory morbidity.

SUBMITTER: Bhatt SP

PROVIDER: S-EPMC4146523 | biostudies-literature | 2014 May

REPOSITORIES: biostudies-literature

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Comparison of spirometric thresholds in diagnosing smoking-related airflow obstruction.

Bhatt Surya P SP Sieren Jessica C JC Dransfield Mark T MT Washko George R GR Newell John D JD Stinson Douglas S DS Zamba Gideon K D GK Hoffman Eric A EA

Thorax 20130323 5

<h4>Background</h4>Diagnosis of chronic obstructive pulmonary disease is based on detection of airflow obstruction on spirometry. There is no consensus regarding using a fixed threshold to define airflow obstruction versus using the lower limit of normal (LLN) adjusted for age. We compared the accuracy and discrimination of the Global Initiative for Chronic Obstructive Lung Disease (GOLD) recommended fixed ratio of forced expiratory volume in the first second/forced vital capacity<0.70 with LLN ...[more]

PMID: 23525095

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Project description:Chronic obstructive pulmonary disease (COPD) is a leading cause of global morbidity and mortality and, whilst smoking remains the single most important risk factor, COPD risk is heritable. Of 26 independent genomic regions showing association with lung function in genome-wide association studies, eleven have been reported to show association with airflow obstruction. Although the main risk factor for COPD is smoking, some individuals are observed to have a high forced expired volume in 1 second (FEV1) despite many years of heavy smoking. We hypothesised that these "resistant smokers" may harbour variants which protect against lung function decline caused by smoking and provide insight into the genetic determinants of lung health. We undertook whole exome re-sequencing of 100 heavy smokers who had healthy lung function given their age, sex, height and smoking history and applied three complementary approaches to explore the genetic architecture of smoking resistance. Firstly, we identified novel functional variants in the "resistant smokers" and looked for enrichment of these novel variants within biological pathways. Secondly, we undertook association testing of all exonic variants individually with two independent control sets. Thirdly, we undertook gene-based association testing of all exonic variants. Our strongest signal of association with smoking resistance for a non-synonymous SNP was for rs10859974 (P = 2.34 × 10(-4)) in CCDC38, a gene which has previously been reported to show association with FEV1/FVC, and we demonstrate moderate expression of CCDC38 in bronchial epithelial cells. We identified an enrichment of novel putatively functional variants in genes related to cilia structure and function in resistant smokers. Ciliary function abnormalities are known to be associated with both smoking and reduced mucociliary clearance in patients with COPD. We suggest that genetic influences on the development or function of cilia in the bronchial epithelium may affect growth of cilia or the extent of damage caused by tobacco smoke.

Project description:BackgroundExercise capacity is an important feature in patients with COPD. Its impairment drives disability and dependency for daily activities performance. This study evaluated the six years change in exercise capacity in subjects with airflow obstruction and compared this to subjects without airflow obstruction, with and without a smoking history.MethodsCardiopulmonary exercise tests (CPET) were repeatedly performed during a six years follow up period. Peak oxygen uptake (VO2peak), work rate (WRpeak), heart rate (HRpeak), minute ventilation (VEpeak), respiratory exchange ratio (RERpeak) and ventilatory reserve (VE/MVV) were collected as effort dependent outcomes. The slopes of oxygen uptake, ventilatory and mechanical efficiency (OUES, ΔVE/ΔVCO2 and ΔVO2/ΔWR) were collected as effort independent outcomes.ResultsOne hundred and thirty-eight subjects were included. Thirty-eight presented airflow obstruction (63±6 years, 74% men, FEV1 90±15%pred), 44 had a smoking history but no airflow obstruction (61±5 years, 61% men, FEV1 105±15%pred) and 56 had never smoked (61±7 years, 57% men, FEV1 117±18%pred). At baseline, the airflow obstruction group had slightly worse exercise capacity in comparison to the never smoking control group, in absolute terms and expressed as percentage of the predicted value (VO2peak = 27±5 versus 32±8 ml/min/kg, p<0.01; 112±29 versus 130±33%pred, p = 0.04). Most exercise variables showed a statistically significant yearly deterioration, with exception of VE/MVV, ΔVE/ΔVCO2 and ΔVO2/ΔWR. The yearly decline in VO2peak and OUES was not faster in subjects with airflow obstruction than in smoking and never smoking controls (VO2peak -67 (9) versus -76 (9) ml/min, p = 0.44 and versus -58 (9), p = 0.47; OUES -32 (11) versus -68 (10), p = 0.03 and versus -68 (13), p = 0.03).ConclusionsWith exception of VO2peak, effort dependent variables deteriorated faster in subjects with airflow obstruction compared to never smoking controls. The deterioration of effort independent variables, however, was not accelerated in the airflow obstruction group compared to controls.

Project description:Consistent estimation of the burden of chronic obstructive pulmonary disease (COPD) has been hindered by differences in methods, including different spirometric cut-offs for impaired lung function. The impact of different definitions on the prevalence of potential airflow obstruction, and its associations with key risk factors, is evaluated using cross-sectional data from two nationally representative population surveys.Pooled cross-sectional analysis of Wave 2 of the UK Household Longitudinal Survey and the Health Survey for England 2010, including 7879 participants, aged 40-95?years, who lived in England and Wales, without diagnosed asthma and with good-quality spirometry data. Potential airflow obstruction was defined using self-reported physician-diagnosed COPD; a fixed threshold (FT) forced expiratory volume in 1?s/forced vital capacity (FEV1/FVC) ratio <0.7 and an age-specific, sex-specific, height-specific and ethnic-specific lower limit of normal (LLN). Standardised questions elicited self-reported information on demography, smoking history, ethnicity, occupation, respiratory symptoms and cardiovascular disease.Consistent across definitions, participants classed with obstructed airflow were more likely to be older, currently smoke, have higher pack-years of smoking and be engaged in routine occupations. The prevalence of airflow obstruction was 2.8% (95% CI 2.3% to 3.2%), 22.2% (21.2% to 23.2%) and 13.1% (12.2% to 13.9%) according to diagnosed COPD, FT and LLN, respectively. The gap in prevalence between FT and LLN increased in older age groups. Sex differences in the risk of obstruction, after adjustment for key risk factors, was sensitive to the choice of spirometric cut-off, being significantly higher in men when using FT, compared with no significant difference using LLN.Applying FT or LLN spirometric cut-offs gives a different picture of the size and distribution of the disease burden. Longitudinal studies examining differences in unscheduled hospital admissions and risk of death between FT and LLN may inform the choice as to the best way to include spirometry in assessments of airflow obstruction.

Project description:BackgroundVery severe chronic obstructive pulmonary disease causes cor pulmonale with elevated pulmonary vascular resistance and secondary reductions in left ventricular filling, stroke volume, and cardiac output. We hypothesized that emphysema, as detected on computed tomography (CT), and airflow obstruction are inversely related to left ventricular end-diastolic volume, stroke volume, and cardiac output among persons without very severe lung disease.MethodsWe measured left ventricular structure and function with the use of magnetic resonance imaging in 2816 persons who were 45 to 84 years of age. The extent of emphysema (expressed as percent emphysema) was defined as the percentage of voxels below -910 Hounsfield units in the lung windows on cardiac computed tomographic scans. Spirometry was performed according to American Thoracic Society guidelines. Generalized additive models were used to test for threshold effects.ResultsOf the study participants, 13% were current smokers, 38% were former smokers, and 49% had never smoked. A 10-point increase in percent emphysema was linearly related to reductions in left ventricular end-diastolic volume (-4.1 ml; 95% confidence interval [CI], -3.3 to -4.9; P<0.001), stroke volume (-2.7 ml; 95% CI, -2.2 to -3.3; P<0.001), and cardiac output (-0.19 liters per minute; 95% CI, -0.14 to -0.23; P<0.001). These associations were of greater magnitude among current smokers than among former smokers and those who had never smoked. The extent of airflow obstruction was similarly associated with left ventricular structure and function, and smoking status had similar modifying effects on these associations. Percent emphysema and airflow obstruction were not associated with the left ventricular ejection fraction.ConclusionsIn a population-based study, a greater extent of emphysema on CT scanning and more severe airflow obstruction were linearly related to impaired left ventricular filling, reduced stroke volume, and lower cardiac output without changes in the ejection fraction.

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Comparison of spirometric thresholds in diagnosing smoking-related airflow obstruction.

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Comparison of spirometric thresholds in diagnosing smoking-related airflow obstruction.

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