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Objectives: Initial studies suggest HIV-positive persons may be at increased risk for chronic lung diseases such as chronic obstructive pulmonary disease, but have commonly relied on single-center designs, lacked HIV-negative controls, or assessed lung function with only spirometry. We tested differences in spirometry and single-breath diffusing capacity for carbon monoxide (DLCO) in persons with and without HIV., Design: Cross-sectional, observational study., Methods: Participants were enrolled from the Multicenter AIDS Cohort Study, a longitudinal cohort study of men who have sex with men (both HIV-positive and HIV-negative) at four sites in the United States. Standardized spirometry and DLCO testing were performed in all eligible, consenting participants at routine study visits. We tested associations between HIV status and spirometry and DLCO results, using linear and logistic regression., Results: Among 1067 men, median age was 57 years, prevalence of current marijuana (30%), and cigarette (24%) use was high, and another 45% were former cigarette smokers. Median forced expiratory volume in 1 s was 97% of predicted normal and DLCO was 85% of predicted normal. HIV-positive persons demonstrated no statistical difference in forced expiratory volume in 1 s compared with HIV-negative persons, but had worse DLCO (adjusted difference -2.6% of predicted; 95% confidence interval: -4.7 to -0.6%) and a higher risk of DLCO impairment (odds ratio for DLCO < 60% of predicted 2.97; 95% confidence interval: 1.36-6.47). Lower DLCO was associated with lower nadir CD4 cell counts., Conclusion: HIV-positive men are at increased risk of abnormal gas exchange, indicated by low DLCO, compared with men without HIV.

Rationale: Current guidelines recommend using forced expiratory volume in 1 second (FEV 1 ) % predicted to categorize the severity of airflow obstruction. There are limitations to using FEV 1 % predicted for this purpose, including bias associated with demographic factors and the inability to correct for "lung size." Other methods for grading the severity of airflow obstruction have been proposed to address these limitations., Objectives: Our objectives were to categorize airflow obstruction severity using these methods and then determine which method results in a categorization most closely associated with mortality., Methods: Study subjects were patients aged 40-80 years tested in our pulmonary function test laboratories in the period 2002 to 2013 with airflow obstruction based on an FEV 1 /forced vital capacity (FVC) less than the lower limit of normal. Categorization of airflow obstruction severity was determined using four methods: FEV 1 % predicted; FEV 1 % predicted adjusted by FVC % predicted; FEV 1 /FVC confidence interval approach; and FEV 1 z-scores. Receiver operating characteristic curve analysis was used to determine which categorization method best predicts 5-year survival., Results: We identified 2,000 patients with airflow obstruction. Important differences in the categorization of airflow obstruction severity were observed using the different methods. More patients were categorized as having severe obstruction using FEV 1 % predicted and FEV 1 z-scores compared with FEV 1 % predicted adjusted by FVC % predicted and FEV 1 /FVC confidence interval approach. FEV 1 % predicted was the best predictor of 5-year survival among the four methods studied., Conclusions: In our study, categorizing airflow obstruction severity using FEV 1 % predicted best predicted 5-year survival. This validates the current guideline recommendation that FEV 1 % predicted be used to categorize the severity of airflow obstruction.

The American Thoracic Society (ATS) and European Respiratory Society (ERS) recommend that spirometry prediction equations be derived from samples of similar race/ethnicity. Malagasy prediction equations do not exist. The objectives of this study were to establish prediction equations for healthy Malagasy adults, and then compare Malagasy measurements with published prediction equations. We enrolled 2491 healthy Malagasy subjects aged 18-73 years (1428 males) from June 2006 to April 2008. The subjects attempted to meet the ATS/ERS 2005 guidelines when performing forced expiratory spirograms. We compared Malagasy measurements of forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC) and FEV1/FVC with predictions from the European Community for Steel and Coal (ECSC), the third National Health and Nutrition Examination Survey (NHANES III) and the ERS Global Lung Function Initiative (GLI) 2012 study. A linear model for the entire population, using age and height as independent variables, best predicted all spirometry parameters for sea level and highland subjects. FEV1, FVC and FEV1/FVC were most accurately predicted by NHANES III African-American male and female, and by GLI 2012 black male and black and South East Asian female equations. ECSC-predicted FEV1, FVC and FEV1/FVC were poorly matched to Malagasy measurements. We provide the first spirometry reference equations for a healthy adult Malagasy population, and the first comparison of Malagasy population measurements with ECSC, NHANES III and GLI 2012 prediction equations., (Copyright ©ERS 2015.)

Background: The objective of the study was to characterize the biological and technical components of variability associated with longitudinal measurements of FEV(1) and carbon monoxide diffusing capacity (Dlco). Variability was apportioned to subject and instrument for five commercially available pulmonary function testing (PFT) systems: Collins CPL (Ferraris Respiratory; Louisville, CO); Morgan Transflow Test PFT System (Morgan Scientific; Haverhill, MA); SensorMedics Vmax 22D (VIASYS Healthcare; Yorba Linda, CA); Jaeger USA Masterscreen Diffusion TP (VIASYS Healthcare; Yorba Linda, CA); and Medical Graphics Profiler DX System (Medical Graphics Corporation; St. Paul, MN)., Methods: This was a randomized, replicated cross-over, single-center methodology study in 11 healthy subjects aged 20 to 65 years. Spirometry and Dlco measurements were performed at baseline, 3 months, and 6 months. Repetitive simulations of FEV(1) and Dlco were performed on the same instruments on four occasions over a 90-day period using a spirometry waveform generator and a Dlco simulator., Results: The coefficient of variation associated with repetitive measurements of FEV(1) or Dlco in subjects was consistently larger than that associated with repetitive simulated waveforms across the five instruments. Instrumentation accounted for 13 to 58% of the total FEV(1) and 36 to 70% of the total Dlco variability observed in subjects. Sample size estimates of hypothetical studies designed to detect treatment group differences of 0.050 L in FEV(1) and 0.5 mL/min/mm Hg in Dlco varied as much as four times depending on the instrument utilized., Conclusions: These results provide a semiquantitative assessment of the biological and technical components of PFT variability in a highly standardized setting. They illustrate how instrument choice and test variability can impact sample size determinations in clinical studies that use FEV(1) and Dlco as end points.

The purpose of the study was to determine the best surrogate for FVC when performing spirometry to detect obstruction or restriction. Volume-time curves from 3,539 participants in the Family Heart Study with acceptable quality test sessions were analyzed. An index of the variability of each timed volume (FEVx) from 1 to 12 s was determined for each subject. The least within-test session variability was seen for forced expired volume in 6 s (FEV(6)) and forced expired volume in 7 s (for both, mean range was 95 mL). The sensitivity and specificity for detecting obstruction and restriction when substituting the FEV(6) for the FVC were then determined before and after allowing for measurement errors of 50 mL (approximately the lower limit of spirometers ability to detect volume). Sensitivity was 76% before the 50-mL error analysis and 95% after. Specificity was 98% before the 50-mL error analysis and 99.5% after. We conclude that use of FEV(6) to replace the FVC for spirometry testing will result in improved reproducibility, with no significant loss of sensitivity or specificity, after allowing a 50-mL measurement error, for detecting obstruction or restriction.

Objectives: (1) To compare the performance of three spirometric algorithms developed to predict whether the total lung capacity (TLC) is reduced vs normal or increased, (2) to determine if forced expiratory volume at 6 s (FEV(6)) can be substituted for FVC in these algorithms, and (3) to determine if ascertainment bias was present in patients referred for the measurement of spirometry and TLC compared to patients referred for spirometry only., Methods: We analyzed the results of 219 consenting consecutive patients referred to a New Zealand tertiary hospital respiratory laboratory for spirometry and TLC measurements. Spirometry results from 370 patients referred for spirometry but not lung volumes were used to test for potential ascertainment bias. Spirometry results were analyzed using the lower limit of normal (LLN) values from the third National Health and Nutrition Examination Study reference equations. The equations of Goldman and Becklake, and Crapo were used to classify TLC as normal or abnormal. Receiver operator characteristic curves were used to produce an algorithm using the LLN for FVC and FEV(6). The performances of previous algorithms and our own algorithms were analyzed for predicting a reduced lung volume against the "gold standard," plethysmographic TLC., Results: All three algorithms predicted a reduced TLC with an accuracy of approximately 50%. In contrast, all algorithms predicted TLC was either normal or increased with an accuracy of > or = 99% regardless of the reference set used. The algorithms based on FEV(6) performed equally as well as the FVC algorithms. No ascertainment bias was found., Conclusions: This study provides evidence that spirometry-based algorithms can accurately predict when TLC is either normal or increased, and can also increase the a priori probability that TLC is reduced to approximately 50%. FEV(6) is equivalent to FVC in these predictions.

BackgroundDiffusing capacity of the lung for carbon monoxide (Dlco) is inconsistently obtained in patients with COPD, and the added benefit of Dlco testing beyond that of more common tools is unknown.ObjectiveThe goal of this study was to determine whether lower Dlco is associated with increased COPD morbidity independent of emphysema assessed via spirometry and CT imaging.MethodsData for 1,806 participants with COPD from the Genetic Epidemiology of COPD (COPDGene) study 5-year visit were analyzed, including pulmonary function testing, quality of life, symptoms, exercise performance, and exacerbation rates. Dlco percent predicted was primarily analyzed as a continuous variable and additionally categorized into four groups: (1) Dlco and FEV1 > 50% (reference); (2) only Dlco ≤ 50%; (3) only FEV1 ≤ 50%; and (4) both ≤ 50% predicted. Outcomes were modeled by using multivariable linear and negative binomial regression, including emphysema and FEV1 percent predicted among other confounders.ResultsIn multivariable analyses, every 10% predicted decrease in Dlco was associated with symptoms and quality of life (COPD Assessment Test, 0.53 [P < .001]; St. George's Respiratory Questionnaire, 1.67 [P < .001]; Medical Outcomes Study Short Form 36 Physical Function, -0.89 [P < .001]), exercise performance (6-min walk distance, -45.35 feet; P < .001), and severe exacerbation rate (rate ratio, 1.14; P < .001). When categorized, severe impairment in Dlco alone, FEV1 alone, or both Dlco and FEV1 were associated with significantly worse morbidity compared with the reference group (P < .05 for all outcomes).ConclusionsImpairment in Dlco was associated with increased COPD symptoms, reduced exercise performance, and severe exacerbation risk even after accounting for spirometry and CT evidence of emphysema. These findings suggest that Dlco should be considered for inclusion in future multidimensional tools assessing COPD.

RationaleThe Global Lung Initiative (GLI) provides age-appropriate criteria for establishing spirometric impairment, including mild, moderate, and severe chronic obstructive pulmonary disease (COPD) and restrictive pattern, but its association with respiratory-related phenotypes has not been evaluated.ObjectivesTo evaluate respiratory-related phenotypes in GLI-defined spirometric impairment.MethodsIn COPDGene (N = 10,131 patients; age range, 45-81 yr; average smoking history, 44.3 pack-years), we evaluated spirometry, dyspnea (modified Medical Research Council grade, ≥2), poor respiratory health-related quality of life (St. George's Respiratory Questionnaire total score, ≥25), poor exercise performance (6-minute-walk distance, 12% and ≥200 ml), and computed tomography-diagnosed emphysema and gas trapping (>5% and >15% of lung, respectively).Measurements and main resultsGLI established normal spirometry in 5,100 patients (50.3%), mild COPD in 669 (6.6%), moderate COPD in 865 (8.5%), severe COPD in 2,522 (24.9%), and restrictive pattern in 975 (9.6%). Relative to normal spirometry, graded associations with respiratory-related phenotypes were found for mild, moderate, and severe COPD, with respective adjusted odds ratios (95% confidence intervals) as follows: dyspnea-1.31 (1.10-1.56), 2.20 (1.81-2.68), and 10.73 (8.04-14.33); poor respiratory health-related quality of life-1.49 (1.28-1.75), 2.69 (2.08-3.47), and 14.61 (10.09-21.17); poor exercise performance-1.11 (0.94-1.31), 1.58 (1.33-1.88), and 4.58 (3.42-6.12); bronchodilator reversibility-2.76 (2.24-3.40), 5.18 (4.29-6.27), and 6.21 (5.06-7.62); emphysema-4.86 (3.16-7.47), 6.41 (4.09-10.05), and 17.79 (10.79-29.32); and gas trapping-3.92 (3.12-4.93), 5.20 (3.82-7.07), and 16.28 (9.71-27.30). Restrictive pattern was also associated with multiple respiratory-related phenotypes at a level similar to moderate COPD, but it was otherwise not associated with emphysema (0.89 [0.60-1.32]) or gas trapping (1.15 [0.92-1.42]).ConclusionsGLI-defined spirometric impairment establishes clinically meaningful respiratory disease, as validated by graded associations with respiratory-related phenotypes.

BackgroundPulmonary function decline is a major contributor to morbidity and mortality among smokers. Post bronchodilator FEV1 and FEV1/FVC ratio are considered the standard assessment of airflow obstruction. We performed a genome-wide association study (GWAS) in 9919 current and former smokers in the COPDGene study (6659 non-Hispanic Whites [NHW] and 3260 African Americans [AA]) to identify associations with spirometric measures (post-bronchodilator FEV1 and FEV1/FVC). We also conducted meta-analysis of FEV1 and FEV1/FVC GWAS in the COPDGene, ECLIPSE, and GenKOLS cohorts (total n = 13,532).ResultsAmong NHW in the COPDGene cohort, both measures of pulmonary function were significantly associated with SNPs at the 15q25 locus [containing CHRNA3/5, AGPHD1, IREB2, CHRNB4] (lowest p-value = 2.17 × 10(-11)), and FEV1/FVC was associated with a genomic region on chromosome 4 [upstream of HHIP] (lowest p-value = 5.94 × 10(-10)); both regions have been previously associated with COPD. For the meta-analysis, in addition to confirming associations to the regions near CHRNA3/5 and HHIP, genome-wide significant associations were identified for FEV1 on chromosome 1 [TGFB2] (p-value = 8.99 × 10(-9)), 9 [DBH] (p-value = 9.69 × 10(-9)) and 19 [CYP2A6/7] (p-value = 3.49 × 10(-8)) and for FEV1/FVC on chromosome 1 [TGFB2] (p-value = 8.99 × 10(-9)), 4 [FAM13A] (p-value = 3.88 × 10(-12)), 11 [MMP3/12] (p-value = 3.29 × 10(-10)) and 14 [RIN3] (p-value = 5.64 × 10(-9)).ConclusionsIn a large genome-wide association study of lung function in smokers, we found genome-wide significant associations at several previously described loci with lung function or COPD. We additionally identified a novel genome-wide significant locus with FEV1 on chromosome 9 [DBH] in a meta-analysis of three study populations.

The article examines the correlation between the peak forced expiratory flow (PEF) and the forced expiratory volume (FEV) during a single spirometry test session. A total of 2,464 healthy adults from the Health, Aging, and Body Composition Study whose spirometry results met American Thoracic Society acceptability criteria were screened and analyzed. It was found that PEF and FEV contained independent information within a single spirometry test session.

A letter to the editor is presented in response to the article on the significance of under diagnosis of chronic obstructive pulmonary disease (COPED).

Abstract: Using data from NHANES III, we evaluated the effect of diabetes on the age-related decline in lung function. The Diabetes group (n =471) had significantly lower mean FEV1 and FVC values than the No Diabetes group (n =4317), but pulmonary function declined with increasing age at a similar rate for both groups. [Copyright &y& Elsevier]