Defining Airflow Obstruction: More Data, Further Clarity.
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ABSTRACT:
SUBMITTER: Calverley PMA
PROVIDER: S-EPMC7462413 | biostudies-literature | 2020 Sep
REPOSITORIES: biostudies-literature
Publications
Defining Airflow Obstruction: More Data, Further Clarity.
American journal of respiratory and critical care medicine 20200901 5
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Project description:Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality within the Veterans Healthcare Administration (VHA) and is frequently under-diagnosed. We developed the Veterans Airflow Screening Questionnaire (VAFOSQ) to improve the identification of Veterans with airflow obstruction (AFO), the most commonly used criterion for the diagnosis of COPD.We created an initial survey with 78 variables that have been associated with AFO. A total of 825 patients in 3 primary care clinics performed spirometry after bronchodilator administration and completed the initial survey. Best sets regression was used to build a model that predicted AFO optimally. A total of 195 of 825 (23.3%) patients had AFO and 7 items positively predicted AFO. When the questionnaire score was greater than 25, the VAFOSQ accurately identified AFO with an area under the receiver operating curve of 0.72. In a prospective validation cohort of 376 participants, the positive predictive value was 32% and negative predictive value 81%. The VAFOSQ is a reliable and valid instrument for the identification of veterans at risk for AFO who would benefit from further evaluation with spirometry and assessment for COPD. The VAFOSQ is straightforward to use and can be easily self-administered and self-scored enabling widespread application within the VHA.
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Project description:The diagnosis of chronic obstructive pulmonary disease (COPD) relies on demonstration of airflow obstruction. Traditional spirometric indices miss a number of subjects with respiratory symptoms or structural lung disease on imaging. We hypothesized that utilizing all data points on the expiratory spirometry curves to assess their shape will improve detection of mild airflow obstruction and structural lung disease. We analyzed spirometry data of 8307 participants enrolled in the COPDGene study, and derived metrics of airflow obstruction based on the shape on the volume-time (Parameter D), and flow-volume curves (Transition Point and Transition Distance). We tested associations of these parameters with CT measures of lung disease, respiratory morbidity, and mortality using regression analyses. There were significant correlations between FEV1/FVC with Parameter D (r = -0.83; p < 0.001), Transition Point (r = 0.69; p < 0.001), and Transition Distance (r = 0.50; p < 0.001). All metrics had significant associations with emphysema, small airway disease, dyspnea, and respiratory-quality of life (p < 0.001). The highest quartile for Parameter D was independently associated with all-cause mortality (adjusted HR 3.22,95% CI 2.42-4.27; p < 0.001) but a substantial number of participants in the highest quartile were categorized as GOLD 0 and 1 by traditional criteria (1.8% and 33.7%). Parameter D identified an additional 9.5% of participants with mild or non-recognized disease as abnormal with greater burden of structural lung disease compared with controls. The data points on the flow-volume and volume-time curves can be used to derive indices of airflow obstruction that identify additional subjects with disease who are deemed to be normal by traditional criteria.
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Project description:Chronic respiratory disorders are important contributors to the global burden of disease. Genome-wide association studies (GWASs) of lung function measures have identified several trait-associated loci, but explain only a modest portion of the phenotypic variability. We postulated that integrating pathway-based methods with GWASs of pulmonary function and airflow obstruction would identify a broader repertoire of genes and processes influencing these traits. We performed two independent GWASs of lung function and applied gene set enrichment analysis to one of the studies and validated the results using the second GWAS. We identified 131 significantly enriched gene sets associated with lung function and clustered them into larger biological modules involved in diverse processes including development, immunity, cell signaling, proliferation and arachidonic acid. We found that enrichment of gene sets was not driven by GWAS-significant variants or loci, but instead by those with less stringent association P-values. Next, we applied pathway enrichment analysis to a meta-analyzed GWAS of airflow obstruction. We identified several biologic modules that functionally overlapped with those associated with pulmonary function. However, differences were also noted, including enrichment of extracellular matrix (ECM) processes specifically in the airflow obstruction study. Network analysis of the ECM module implicated a candidate gene, matrix metalloproteinase 10 (MMP10), as a putative disease target. We used a knockout mouse model to functionally validate MMP10's role in influencing lung's susceptibility to cigarette smoke-induced emphysema. By integrating pathway analysis with population-based genomics, we unraveled biologic processes underlying pulmonary function traits and identified a candidate gene for obstructive lung disease.
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Project description:Chronic obstructive pulmonary disease (COPD) is a disease with marked metabolic disturbance. Previous studies have shown the association between single metabolites and lung function for COPD, but whether a combination of metabolites could predict phenotype is unknown. We developed metabolomic severity scores using plasma metabolomics from the Metabolon platform from two US cohorts of ever-smokers: the Subpopulations and Intermediate Outcome Measures in COPD Study (SPIROMICS) (n = 648; training/testing cohort; 72% non-Hispanic, white; average age 63 years) and the COPDGene Study (n = 1120; validation cohort; 92% non-Hispanic, white; average age 67 years). Separate adaptive LASSO (adaLASSO) models were used to model forced expiratory volume at one second (FEV1) and MESA-adjusted lung density using 762 metabolites common between studies. Metabolite coefficients selected by the adaLASSO procedure were used to create a metabolomic severity score (metSS) for each outcome. A total of 132 metabolites were selected to create a metSS for FEV1. The metSS-only models explained 64.8% and 31.7% of the variability in FEV1 in the training and validation cohorts, respectively. For MESA-adjusted lung density, 129 metabolites were selected, and metSS-only models explained 59.0% of the variability in the training cohort and 17.4% in the validation cohort. Regression models including both clinical covariates and the metSS explained more variability than either the clinical covariate or metSS-only models (53.4% vs. 46.4% and 31.6%) in the validation dataset. The metabolomic pathways for arginine biosynthesis; aminoacyl-tRNA biosynthesis; and glycine, serine, and threonine pathway were enriched by adaLASSO metabolites for FEV1. This is the first demonstration of a respiratory metabolomic severity score, which shows how a metSS can add explanation of variance to clinical predictors of FEV1 and MESA-adjusted lung density. The advantage of a comprehensive metSS is that it explains more disease than individual metabolites and can account for substantial collinearity among classes of metabolites. Future studies should be performed to determine whether metSSs are similar in younger, and more racially and ethnically diverse populations as well as whether a metabolomic severity score can predict disease development in individuals who do not yet have COPD.
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Project description:Few studies have examined the contribution of life-course factors in explaining familial aggregation of chronic lung conditions. Using data from the 1958 British Birth Cohort, a life-course approach was used to examine whether, and how, exposure to risk factors through one's life explained the association between parental respiratory disease history and symptomatic airflow obstruction (AO). Cohort participants (n=6212) were characterised in terms of parental respiratory disease history and symptomatic AO at 45?years. Life-course factors (e.g. smoking, asthma and early-life factors) were operationalised as life period-specific and cumulative measures. Logistic regression and path analytic models predicting symptomatic AO adjusted for parental respiratory disease history were used to test different life-course models (critical period, accumulation- and chain-of-risks models). While some life-course factors (e.g. childhood passive smoking and occupational exposure) were individually associated with parental respiratory disease history and symptomatic AO, asthma (OR 6.44, 95% CI 5.01-8.27) and persistent smoking in adulthood (OR 5.42, 95% CI 4.19-7.01) had greater impact on the association between parental respiratory disease history and symptomatic AO. A critical period model provided a better model fit compared with an accumulation-of-risk model and explained 57% of the effect of parental respiratory disease history on symptomatic AO. Adulthood asthma and smoking status explained around half of the effect of parental respiratory disease history on chronic obstructive pulmonary disease. Beyond smoking history, the combination of parental respiratory disease history and adulthood asthma may provide an opportunity for early diagnosis and intervention.
| S-EPMC7049733 | biostudies-literature
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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Project description:BACKGROUND:Low muscle mass is associated with increased mortality in the general population but its prognostic value in at-risk smokers, those without expiratory airflow obstruction, is unknown. We aimed to test the hypothesis that reduced muscle mass is associated with increased mortality in at-risk smokers. METHODS:Measures of both pectoralis and paravertebral erector spinae muscle cross-sectional area (PMA and PVMA, respectively) as well as emphysema on chest computed tomography (CT) scans were performed in 3705 current and former at-risk smokers (≥10 pack-years) aged 45-80 years enrolled into the COPDGene Study between 2008 and 2013. Vital status was ascertained through death certificate. The association between low muscle mass and mortality was assessed using Cox regression analysis. RESULTS:During a median of 6.5 years of follow-up, 212 (5.7%) at-risk smokers died. At-risk smokers in the lowest (vs. highest) sex-specific quartile of PMA but not PVMA had 84% higher risk of death in adjusted models for demographics, smoking, dyspnea, comorbidities, exercise capacity, lung function, emphysema on CT, and coronary artery calcium content (hazard ratio [HR] 1.85 95% Confidence interval [1.14-3.00] P = 0.01). Results were consistent when the PMA index (PMA/height2) was used instead of quartiles. The association between PMA and death was modified by smoking status (P = 0.04). Current smokers had a significantly increased risk of death (lowest vs. highest PMA quartile, HR 2.25 [1.25-4.03] P = 0.007) while former smokers did not. CONCLUSIONS:Low muscle mass as measured on chest CT scans is associated with increased mortality in current smokers without airflow obstruction. TRIAL REGISTRATION:NCT00608764.
| S-EPMC5894181 | biostudies-literature
Project description:BackgroundDiagnosis 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.MethodsData 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.Results7743 subjects were included. There was very good agreement between the two spirometric cutoffs (κ=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.ConclusionsCompared with the fixed ratio, the use of LLN fails to identify a number of patients with significant pulmonary pathology and respiratory morbidity.
| S-EPMC4146523 | biostudies-literature
Project description:Airflow obstruction is an independent risk factor for cardiovascular events in the general population. The affected vascular bed and contribution of emphysema to cardiovascular risk are unclear. We examined whether an obstructive pattern of spirometry and quantitatively defined emphysema were associated with subclinical atherosclerosis in the carotid, peripheral and coronary circulations. The Multi-Ethnic Study of Atherosclerosis recruited participants aged 45-84 yrs without clinical cardiovascular disease. Spirometry, carotid intima-media thickness (IMT), ankle-brachial index (ABI) and coronary artery calcium (CAC) were measured using standard protocols. Percentage of emphysema-like lung was measured in the lung windows of cardiac computed tomography scans among 3,642 participants. Multiple linear regression was used to adjust for cardiac risk factors, including C-reactive protein. Decrements in forced expiratory volume in 1 s (FEV(1)) and FEV(1)/forced vital capacity ratio were associated with greater internal carotid IMT, particularly among smokers (p=0.03 and p<0.001, respectively) whereas percentage emphysema was associated with reduced ABI regardless of smoking history (p=0.004). CAC was associated with neither lung function (prevalence ratio for the presence of CAC in severe airflow obstruction 0.99, 95% CI 0.91-1.07) nor percentage emphysema. An obstructive pattern of spirometry and emphysema were associated distinctly and independently with subclinical atherosclerosis in the carotid arteries and peripheral circulation, respectively, and were not independently related to CAC.
| S-EPMC3616898 | biostudies-literature
Project description:RationaleTo study the relationship between emphysema and/or airflow obstruction and lung cancer in a high-risk population.ObjectiveWe studied lung cancer related to radiographic emphysema and spirometric airflow obstruction in tobacco-exposed persons who were screened for lung cancer using chest computed tomography (CT).MethodsSubjects completed questionnaires, spirometry, and low-dose helical chest CT. CT scans were scored for emphysema based on National Emphysema Treatment Trial criteria. Multiple logistic regressions estimated the independent associations between various factors, including radiographic emphysema and airflow obstruction, and subsequent lung cancer diagnosis.Measurements and main resultsAmong 3,638 subjects, 57.5, 18.8, 14.6, and 9.1% had no, trace, mild, and moderate-severe emphysema, and 57.3, 13.6, 22.8, and 6.4% had no, mild (Global Initiative for Chronic Obstructive Lung Disease [GOLD] I), moderate (GOLD II), and severe (GOLD III-IV) airflow obstruction. Of 3,638 subjects, 99 (2.7%) received a lung cancer diagnosis. Adjusting for sex, age, years of cigarette smoking, and number of cigarettes smoked daily, logistic regression showed the expected lung cancer association with the presence of airflow obstruction (GOLD I-IV, odds ratio [OR], 2.09; 95% confidence interval [CI], 1.33-3.27). A second logistic regression showed lung cancer related to emphysema (OR, 3.56; 95% CI, 2.21-5.73). After additional adjustments for GOLD class, emphysema remained a strong and statistically significant factor related to lung cancer (OR, 3.14; 95% CI, 1.91-5.15).ConclusionsEmphysema on CT scan and airflow obstruction on spirometry are related to lung cancer in a high-risk population. Emphysema is independently related to lung cancer. Both radiographic emphysema and airflow obstruction should be considered when assessing lung cancer risk.
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