Radiographic lung volumes predict progression to COPD in smokers with preserved spirometry in SPIROMICS.
ABSTRACT: 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.
Project description:BACKGROUND:Abnormal lung volumes that reflect air trapping are common in COPD. However, their significance in smokers with preserved spirometry (normal FEV1 to FVC ratio) is unclear. METHODS:Using the Veterans Administration Informatics and Computing Infrastructure database, we identified 7479 patients at risk for COPD (ever smokers >40 years of age without restrictive lung disease) who had preserved spirometry and concomitant lung volume measurements, and examined their subsequent health records for clinical diagnoses of COPD, healthcare utilisation, follow-up spirometry and mortality. RESULTS:Air trapping was prevalent, with 31% of patients having residual volume to total lung capacity ratio (RV:TLC) greater than the upper limit of normal (ULN). RV:TLC varied widely from 14% to 77% (51% to 204% of predicted) across the normal ranges of FEV1:FVC and FEV1. Patients with RV:TLC greater than the ULN were more likely to receive subsequent clinical diagnoses of COPD (HR (95%?CI)=1.55 (1.42 to 1.70), p<0.001) and had higher all-cause mortality (HR (95%?CI)=1.41 (1.29 to 1.54), p<0.001). They had higher rates of respiratory medication prescriptions and hospital and intensive care unit admissions. Other air trapping and static hyperinflation indices showed similar associations with health outcomes. Additionally, high-normal RV:TLC was associated with intermediate adverse health outcomes compared with low-normal and abnormal RV:TLC. Abnormal RV:TLC predicted higher likelihood of progression to spirometric COPD (OR (95%?CI)=1.30 (1.03 to 1.65), p=0.027). CONCLUSION:In this study of the Veterans Affairs electronic health records, air trapping was common in smokers with preserved spirometry and predicted adverse respiratory outcomes and progression to overt COPD.
Project description:RATIONALE:Given that the diagnosis of chronic obstructive pulmonary disease (COPD) relies on demonstrating airflow limitation by spirometry, which is known to be poorly sensitive to early disease, and to regional differences in emphysema, we sought to evaluate individual lobar contributions to global spirometric measures. METHODS:Subjects with COPD were compared with smokers without airflow obstruction, and non-smokers. Emphysema (% low attenuation area, LAAinsp<-950 HU, at end-inspiration) and gas trapping (%LAAexp<-856 HU at end-expiration) on CT were quantified using density mask analyses for the whole lung and for individual lobes, and distribution across lobes and strength of correlation with spirometry were compared. RESULTS:The right middle lobe had the highest %LAAinsp<-950 HU in smokers and controls, and the highest %LAAexp<-856 HU in all three groups. While RML contributed to emphysema and gas trapping disproportionately to its relatively small size, it also showed the least correlation with spirometry. There was no change in correlation of whole lung CT metrics with spirometry when the middle lobe was excluded from analyses. Similarly, RML had the highest %LAAexp<-856 HU while having the least correlation with spirometry. CONCLUSIONS:Because of the right middle lobe's disproportionate contribution to CT-based emphysema measurements, and low contribution to spirometry, longitudinal studies of emphysema progression may benefit from independent analysis of the middle lobe in whole lung quantitative CT assessments. Our findings may also have implications for heterogeneity assessments and target lobe selection for lung volume reduction. CLINICAL TRIAL REGISTRATION:ClinicalTrials.gov NCT00608764.
Project description:Background:Chronic obstructive pulmonary disease (COPD) remains a major cause of morbidity and mortality. Present-day diagnostic criteria are largely based solely on spirometric criteria. Accumulating evidence has identified a substantial number of individuals without spirometric evidence of COPD who suffer from respiratory symptoms and/or increased morbidity and mortality. There is a clear need for an expanded definition of COPD that is linked to physiologic, structural (computed tomography [CT]) and clinical evidence of disease. Using data from the COPD Genetic Epidemiology study (COPDGene®), we hypothesized that an integrated approach that includes environmental exposure, clinical symptoms, chest CT imaging and spirometry better defines disease and captures the likelihood of progression of respiratory obstruction and mortality. Methods:Four key disease characteristics - environmental exposure (cigarette smoking), clinical symptoms (dyspnea and/or chronic bronchitis), chest CT imaging abnormalities (emphysema, gas trapping and/or airway wall thickening), and abnormal spirometry - were evaluated in a group of 8784 current and former smokers who were participants in COPDGene® Phase 1. Using these 4 disease characteristics, 8 categories of participants were identified and evaluated for odds of spirometric disease progression (FEV1 > 350 ml loss over 5 years), and the hazard ratio for all-cause mortality was examined. Results:Using smokers without symptoms, CT imaging abnormalities or airflow obstruction as the reference population, individuals were classified as Possible COPD, Probable COPD and Definite COPD. Current Global initiative for obstructive Lung Disease (GOLD) criteria would diagnose 4062 (46%) of the 8784 study participants with COPD. The proposed COPDGene® 2019 diagnostic criteria would add an additional 3144 participants. Under the new criteria, 82% of the 8784 study participants would be diagnosed with Possible, Probable or Definite COPD. These COPD groups showed increased risk of disease progression and mortality. Mortality increased in patients as the number of their COPD characteristics increased, with a maximum hazard ratio for all cause-mortality of 5.18 (95% confidence interval [CI]: 4.15-6.48) in those with all 4 disease characteristics. Conclusions:A substantial portion of smokers with respiratory symptoms and imaging abnormalities do not manifest spirometric obstruction as defined by population normals. These individuals are at significant risk of death and spirometric disease progression. We propose to redefine the diagnosis of COPD through an integrated approach using environmental exposure, clinical symptoms, CT imaging and spirometric criteria. These expanded criteria offer the potential to stimulate both current and future interventions that could slow or halt disease progression in patients before disability or irreversible lung structural changes develop.
Project description:BACKGROUND:The identification of smoking-related lung disease in current and former smokers with normal FEV1 is complex, leading to debate regarding using a ratio of forced expiratory volume in 1 s to forced vital capacity (FEV1/FVC) of less than 0.70 versus the predicted lower limit of normal (LLN) for diagnosis of airflow obstruction. We hypothesized that the discordant group of ever-smokers with FEV1/FVC between the LLN and 0.70 is heterogeneous, and aimed to characterize the burden of smoking-related lung disease in this group. METHODS:We compared spirometry, chest CT characteristics, and symptoms between 161 ever-smokers in the discordant group and 940 ever-smokers and 190 never-smokers with normal FEV1 and FEV1/FVC?>?0.70 in the SPIROMICS cohort. We also estimated sensitivity and specificity for diagnosing objective radiographic evidence of chronic obstructive pulmonary disease (COPD) using different FEV1/FVC criteria thresholds. RESULTS:The discordant group had more CT defined emphysema and non-emphysematous gas trapping, lower post-bronchodilator FEV1 and FEF25-75, and higher respiratory medication use compared with the other two groups. Within the discordant group, 44% had radiographic CT evidence of either emphysema or non-emphysematous gas trapping; an FEV1/FVC threshold of 0.70 has greater sensitivity but lower specificity compared with LLN for identifying individuals with CT abnormality. CONCLUSIONS:Ever-smokers with normal FEV1 and FEV1/FVC?<? 0.70 but > LLN are a heterogeneous group that includes significant numbers of individuals with and without radiographic evidence of smoking-related lung disease. These findings emphasize the limitations of diagnosing COPD based on spirometric criteria alone.
Project description:BACKGROUND:Although COPD among non-smokers (NS-COPD) is common, little is known about this phenotype. We compared NS-COPD subjects with smoking COPD (S-COPD) patients in a rural Indian population using a variety of clinical, physiological, radiological, sputum cellular and blood biomarkers. METHODS:Two hundred ninety subjects (118 healthy, 79?S-COPD, 93 NS-COPD) performed pre- and post-bronchodilator spirometry and were followed for 2?years to study the annual rate of decline in lung function. Body plethysmography, impulse oscillometry, inspiratory-expiratory HRCT, induced sputum cellular profile and blood biomarkers were compared between 49 healthy, 45?S-COPD and 55 NS-COPD subjects using standardized methods. Spirometric response to oral corticosteroids was measured in 30 female NS-COPD patients. RESULTS:Compared to all male S-COPD subjects, 47% of NS-COPD subjects were female, were younger by 3.2?years, had greater body mass index, a slower rate of decline in lung function (80 vs 130?mL/year), more small airways obstruction measured by impulse oscillometry (p <?0.001), significantly less emphysema (29% vs 11%) on CT scans, lower values in lung diffusion parameters, significantly less neutrophils in induced sputum (p <?0.05) and tended to have more sputum eosinophils. Hemoglobin and red cell volume were higher and serum insulin lower in S-COPD compared to NS-COPD. Spirometric indices, symptoms and quality of life were similar between S-COPD and NS-COPD. There was no improvement in spirometry in NS-COPD patients after 2?weeks of an oral corticosteroid. CONCLUSIONS:Compared to S-COPD, NS-COPD is seen in younger subjects with equal male-female predominance, is predominantly a small-airway disease phenotype with less emphysema, preserved lung diffusion and a slower rate of decline in lung function.
Project description: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?<?.001) and a lower 6-minute walk distance, and 42.3% (127 of 300) of the GOLD 0 group had CT evidence of emphysema or airway thickening. The FEV1 percent predicted distribution and mean for the GOLD 0 group were lower but still within the normal range for the population. Current smoking was associated with more respiratory symptoms, but former smokers had greater emphysema and gas trapping. Advancing age was associated with smoking cessation and with more CT findings of disease. Individuals with respiratory impairments were more likely to use respiratory medications, and the use of these medications was associated with worse disease.Lung disease and impairments were common in smokers without spirometric COPD. Based on these results, we project that there are 35 million current and former smokers older than 55 years in the United States who may have unrecognized disease or impairment. The effect of chronic smoking on the lungs and the individual is substantially underestimated when using spirometry alone.
Project description:Performing lung function test in geriatric patients has never been an easy task. With well-established evidence indicating impaired small airway function and air trapping in patients with geriatric COPD, utilizing forced oscillation technique (FOT) as a supplementary tool may aid in the assessment of lung function in this population.To study the use of FOT in the assessment of airflow limitation and air trapping in geriatric COPD patients.A cross-sectional study in a public hospital in Hong Kong. ClinicalTrials.gov ID: NCT01553812.Geriatric patients who had spirometry-diagnosed COPD were recruited, with both FOT and plethysmography performed. "Resistance" and "reactance" FOT parameters were compared to plethysmography for the assessment of air trapping and airflow limitation.In total, 158 COPD subjects with a mean age of 71.9±0.7 years and percentage of forced expiratory volume in 1 second of 53.4±1.7 L were recruited. FOT values had a good correlation (r=0.4-0.7) to spirometric data. In general, X values (reactance) were better than R values (resistance), showing a higher correlation with spirometric data in airflow limitation (r=0.07-0.49 vs 0.61-0.67), small airway (r=0.05-0.48 vs 0.56-0.65), and lung volume (r=0.12-0.29 vs 0.43-0.49). In addition, resonance frequency (Fres) and frequency dependence (FDep) could well identify the severe type (percentage of forced expiratory volume in 1 second <50%) of COPD with high sensitivity (0.76, 0.71) and specificity (0.72, 0.64) (area under the curve: 0.8 and 0.77, respectively). Moreover, X values could stratify different severities of air trapping, while R values could not.FOT may act as a simple and accurate tool in the assessment of severity of airflow limitation, small and central airway function, and air trapping in patients with geriatric COPD who have difficulties performing conventional lung function test. Moreover, reactance parameters were better than resistance parameters in correlation with air trapping.
Project description:Exercise tolerance in COPD is only moderately well predicted by airflow obstruction assessed by FEV(1). We determined whether other phenotypic characteristics, including CT scan measures, are independent predictors of 6-min walk distance (6MWD) in the COPDGene cohort.COPDGene recruits non-Hispanic Caucasian and African American current and ex-smokers. Phenotyping measures include postbronchodilator FEV(1) % predicted and inspiratory and expiratory CT lung scans. We defined % emphysema as the percentage of lung voxels < -950 Hounsfield units on the inspiratory scan and % gas trapping as the percentage of lung voxels < -856 Hounsfield units on the expiratory scan.Data of the first 2,500 participants of the COPDGene cohort were analyzed. Participant age was 61 ± 9 years; 51% were men; 76% were non-Hispanic Caucasians, and 24% were African Americans. Fifty-six percent had spirometrically defined COPD, with 9.3%, 23.4%, 15.0%, and 8.3% in GOLD (Global Initiative for Chronic Obstructive Lung Disease) stages I to IV, respectively. Higher % emphysema and % gas trapping predicted lower 6MWD (P < .001). However, in a given spirometric group, after adjustment for age, sex, race, and BMI, neither % emphysema nor % gas trapping, or their interactions with FEV(1) % predicted, remained a significant 6MWD predictor. In a given spirometric group, only 16% to 27% of the variance in 6MWD could be explained by age, male sex, Caucasian race, and lower BMI as significant predictors of higher 6MWD.In this large cohort of smokers in a given spirometric stage, phenotypic characteristics were only modestly predictive of 6MWD. CT scan measures of emphysema and gas trapping were not predictive of 6MWD after adjustment for other phenotypic characteristics.
Project description:BACKGROUND:Chronic obstructive pulmonary disease (COPD) is a heterogeneous condition with respect to onset, progression, and response to therapy. Incorporating clinical- and imaging-based features to refine COPD phenotypes provides valuable information beyond that obtained from traditional clinical evaluations. We characterized the spectrum of COPD-related phenotypes in a sample of former and current smokers and evaluated how these subgroups differ with respect to sociodemographic characteristics, COPD-related comorbidities, and subsequent risk of lung cancer. METHODS:White (N = 659) and African American (N = 520) male and female participants without lung cancer (controls) in the INHALE study who completed a chest CT scan, interview, and spirometry test were used to define distinct COPD-related subgroups based on hierarchical clustering. Seven variables were used to define clusters: pack years, quit years, FEV1/FVC, % predicted FEV1, and from quantitative CT (qCT) imaging, % emphysema, % air trapping, and mean lung density ratio. Cluster definitions were then applied to INHALE lung cancer cases (N = 576) to evaluate lung cancer risk. RESULTS:Five clusters were identified that differed significantly with respect to sociodemographic (e.g., race, age) and clinical (e.g., BMI, limitations due to breathing difficulties) characteristics. Increased risk of lung cancer was associated with increasingly detrimental lung function clusters (when ordered from most detrimental to least detrimental). CONCLUSIONS:Measures of lung function vary considerably among smokers and are not fully explained by smoking intensity. IMPACT:Combining clinical (spirometry) and radiologic (qCT) measures of COPD defines a spectrum of lung disease that predicts lung cancer risk differentially among patient clusters.
Project description:<h4>Background</h4>Thoracic computed tomography (CT) scans are widely performed in clinical practice, often leading to detection of airway or parenchymal abnormalities in asymptomatic or minimally symptomatic individuals. However, clinical relevance of CT abnormalities is uncertain in the general population.<h4>Methods</h4>We evaluated data from 1361 participants aged ?40 years from a Canadian prospective cohort comprising 408 healthy never-smokers, 502 healthy ever-smokers, and 451 individuals with spirometric evidence of chronic obstructive pulmonary disease (COPD) who had thoracic CT scans. CT images of subjects were visually scored for respiratory bronchiolitis(RB), emphysema(E), bronchial-wall thickening(BWT), expiratory air-trapping(AT), and bronchiectasis(B). Multivariable logistic regression models were used to assess associations of CT features with respiratory symptoms, dyspnea, health status as determined by COPD assessment test, and risk of clinically significant exacerbations during 12 months follow-up.<h4>Results</h4>About 11% of life-time never-smokers demonstrated emphysema on CT scans. Prevalence increased to 30% among smokers with normal lung function and 36%, 50%, and 57% among individuals with mild, moderate or severe/very severe COPD, respectively. Presence of emphysema on CT was associated with chronic cough (OR,2.11; 95%CI,1.4-3.18); chronic phlegm production (OR,1.87; 95% CI,1.27-2.76); wheeze (OR,1.61; 95% CI,1.05-2.48); dyspnoea (OR,2.90; 95% CI,1.41-5.98); CAT score?10(OR,2.17; 95%CI,1.42-3.30) and risk of ?2 exacerbations over 12 months (OR,2.17; 95% CI, 1.42-3.0).<h4>Conclusions</h4>Burden of thoracic CT abnormalities is high among Canadians ?40 years of age, including never-smokers and smokers with normal lung function. Detection of emphysema on CT scans is associated with pulmonary symptoms and increased risk of exacerbations, independent of smoking or lung function.