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Rationale: Chronic obstructive pulmonary disease (COPD) mortality risk is often estimated using the BODE (body mass index, obstruction, dyspnea, exercise capacity) index, including body mass index, forced expiratory volume in 1 second, dyspnea score, and 6-minute walk distance. Diffusing capacity of the lung for carbon monoxide (DLCO) is a potential predictor of mortality that reflects physiology distinct from that in the BODE index. Objectives: This study evaluated DLCO as a predictor of mortality using participants from the COPDGene study. Methods: We performed time-to-event analyses of individuals with COPD (former or current smokers with forced expiratory volume in 1 second/forced vital capacity,0.7) and DLCO measurements from the COPDGene phase 2 visit. Cox proportional hazard methods were used to model survival, adjusting for age, sex, pack-years, smoking status, BODE index, computed tomography (CT) percent emphysema (low attenuation areas below 2950 Hounsfield units), CT airway wall thickness, and history of cardiovascular or kidney diseases. C statistics for models with DLCO and BODE scores were used to compare discriminative accuracy. Results: Of 2,329 participants, 393 (16.8%) died during the follow-up period (median = 4.9 yr). In adjusted analyses, for every 10% decrease in DLCO percent predicted, mortality increased by 28% (hazard ratio = 1.28; 95% confidence interval, 1.17-1.41, P,0.001). When compared with other clinical predictors, DLCO percent predicted performed similarly to BODE (C statistic DLCO = 0.68; BODE = 0.70), and the addition of DLCO to BODE improved its discriminative accuracy (C statistic = 0.71). Conclusions: Diffusing capacity, a measure of gas transfer, strongly predicted all-cause mortality in individuals with COPD, independent of BODE index and CT evidence of emphysema and airway wall thickness. These findings support inclusion of DLCO in prognostic models for COPD. [ABSTRACT FROM AUTHOR]

Abstract Background Lung function at the end of life depends on its peak and subsequent decline. Because obesity is epidemic in young adulthood, we quantified age-related changes in lung function relative to body mass index (BMI). Methods The Coronary Artery Risk Development in Young Adults (CARDIA) study in 1985–86 (year 0) recruited 5,115 black and white men and women, aged 18–30. Spirometry testing was conducted at years 0, 2, 5 and 10. We estimated 10 year change in FVC, FEV1 and FEV1/FVC according to baseline BMI and change in BMI within birth cohorts with initial average ages 20, 24, and 28 years, controlling for race, sex, smoking, asthma, physical activity, and alcohol consumption. Measurements and Main Results Participants with baseline BMI < 21.3 kg/m2 experienced 10 year increases of 71 ml in FVC and 60 ml in FEV1 and neither measure declined through age 38. In contrast, participants with baseline BMI ≥ 26.4 kg/m2 experienced 10 year decreases of 185 ml in FVC and 64 ml in FEV1. FEV1/FVC increased with increasing BMI. Weight gain was also associated with lung function. Those who gained the most weight over 10 years had the largest decrease in FVC, but FVC increased with weight gain in those initially thinnest. In contrast, FEV1 decreased with increasing weight gain in all participants, with maximum decline in obese individuals who gained the most weight during the study. Conclusion Among healthy young adults, increasing BMI in the initially thin participants was associated with increasing then stable lung function through age 38, but there were substantial lung function losses with higher and increasing fatness. These results suggest that the obesity epidemic threatens the lung health of the general population.

Rationale: Current guidelines recommend using forced expiratory volume in 1 second (FEV1) % predicted to categorize the severity of airflow obstruction. There are limitations to using FEV1 % 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 FEV1/forced vital capacity (FVC) less than the lower limit of normal. Categorization of airflow obstruction severity was determined using four methods: FEV1 % predicted; FEV1 % predicted adjusted by FVC % predicted; FEV1/FVC confidence interval approach; and FEV1 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 FEV1 % predicted and FEV1 z-scores compared with FEV1 % predicted adjusted by FVC % predicted and FEV1/FVC confidence interval approach. FEV1 % predicted was the best predictor of 5-year survival among the four methods studied.Conclusions: In our study, categorizing airflow obstruction severity using FEV1 % predicted best predicted 5-year survival. This validates the current guideline recommendation that FEV1 % predicted be used to categorize the severity of airflow obstruction. [ABSTRACT FROM AUTHOR]

Background: Pulmonary 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). Results: Among 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). Conclusions: In 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. [ABSTRACT FROM AUTHOR]

Rationale: In aging populations, the commonly used Global Initiative for Chronic Obstructive Lung Disease (GOLD) may misclassify normal spirometry as respiratory impairment (airflow obstruction and restrictive pattern), including the presumption of respiratory disease (chronic obstructive pulmonary disease [COPD]).Objectives: To evaluate the phenotype of normal spirometry as defined by a new approach from the Global Lung Initiative (GLI), overall and across GOLD spirometric categories.Methods: Using data from COPDGene (n = 10,131; ages 45-81; smoking history, ≥10 pack-years), we evaluated spirometry and multiple phenotypes, including dyspnea severity (Modified Medical Research Council grade 0-4), health-related quality of life (St. George's Respiratory Questionnaire total score), 6-minute-walk distance, bronchodilator reversibility (FEV1 % change), computed tomography-measured percentage of lung with emphysema (% emphysema) and gas trapping (% gas trapping), and small airway dimensions (square root of the wall area for a standardized airway with an internal perimeter of 10 mm).Measurements and Main Results: Among 5,100 participants with GLI-defined normal spirometry, GOLD identified respiratory impairment in 1,146 (22.5%), including a restrictive pattern in 464 (9.1%), mild COPD in 380 (7.5%), moderate COPD in 302 (5.9%), and severe COPD in none. Overall, the phenotype of GLI-defined normal spirometry included normal adjusted mean values for dyspnea grade (0.8), St. George's Respiratory Questionnaire (15.9), 6-minute-walk distance (1,424 ft [434 m]), bronchodilator reversibility (2.7%), % emphysema (0.9%), % gas trapping (10.7%), and square root of the wall area for a standardized airway with an internal perimeter of 10 mm (3.65 mm); corresponding 95% confidence intervals were similarly normal. These phenotypes remained normal for GLI-defined normal spirometry across GOLD spirometric categories.Conclusions: GLI-defined normal spirometry, even when classified as respiratory impairment by GOLD, included adjusted mean values in the normal range for multiple phenotypes. These results suggest that among adults with GLI-defined normal spirometry, GOLD may misclassify normal phenotypes as having respiratory impairment. [ABSTRACT FROM AUTHOR]

BACKGROUND: Measuring diffusing capacity of the lung for carbon monoxide (DLCO) is complex and associated with wide intra- and inter-laboratory variability. Increased DLCO variability may have important clinical consequences. The objective of the study was to assess instrument performance across hospital pulmonary function testing laboratories using a DLCO simulator that produces precise and repeatable DLCO values. METHODS: DLCO instruments were tested with CO gas concentrations representing medium and high range DLCO values. The absolute difference between observed and target DLCO value was used to determine measurement accuracy; accuracy was defined as an average deviation from the target value of < 2.0 mL/min/mm Hg. Accuracy of inspired volume measurement and gas sensors were also determined. RESULTS: Twenty-three instruments were tested across 3 healthcare systems. The mean absolute deviation from the target value was 1.80 mL/min/mm Hg (range 0.24 – 4.23) with 10 of 23 instruments (43%) being inaccurate. High volume laboratories performed better than low volume laboratories, although the difference was not significant. There was no significant difference among the instruments by manufacturers. Inspired volume was not accurate in 48% of devices; mean absolute deviation from target value was 3.7%. Instrument gas analyzers performed adequately in all instruments. CONCLUSIONS: DLCO instrument accuracy was unacceptable in 43% of devices. Instrument inaccuracy can be primarily attributed to errors in inspired volume measurement and not gas analyzer performance. DLCO instrument performance may be improved by regular testing with a simulator. Caution should be used when comparing DLCO results reported from different laboratories. [ABSTRACT FROM AUTHOR]

Background: Lung function at the end of life depends on its peak and subsequent decline. Because obesity is epidemic in young adulthood, we quantified age-related changes in lung function relative to body mass index (BMI). Methods: The Coronary Artery Risk Development in Young Adults (CARDIA) study in 1985-86 (year 0) recruited 5,115 black and white men and women, aged 18-30. Spirometry testing was conducted at years 0, 2, 5 and 10. We estimated 10 year change in FVC, FEV1 and FEV1/FVC according to baseline BMI and change in BMI within birth cohorts with initial average ages 20, 24, and 28 years, controlling for race, sex, smoking, asthma, physical activity, and alcohol consumption. Measurements and Main Results: Participants with baseline BMI < 21.3 kg/m² experienced 10 year increases of 71 ml in FVC and 60 ml in FEV1 and neither measure declined through age 38. In contrast, participants with baseline BMI ≥ 26.4 kg/m² experienced 10 year decreases of 185 ml in FVC and 64 ml in FEV1. FEV1/FVC increased with increasing BMI. Weight gain was also associated with lung function. Those who gained the most weight over 10 years had the largest decrease in FVC, but FVC increased with weight gain in those initially thinnest. In contrast, FEV1 decreased with increasing weight gain in all participants, with maximum decline in obese individuals who gained the most weight during the study. Conclusion: Among healthy young adults, increasing BMI in the initially thin participants was associated with increasing then stable lung function through age 38, but there were substantial lung function losses with higher and increasing fatness. These results suggest that the obesity epidemic threatens the lung health of the general population. [ABSTRACT FROM AUTHOR]

Quantifying COPD prevalence worldwide is needed to document COPD's effect on disability, health care costs, and impaired quality of life and to inform governments and health planners. As an adjunct to data obtained from population-based studies, and for countries where a fully powered prevalence survey cannot be done, modeling of COPD prevalence and its economic burdens can help estimate potential health care needs and costs. For comparability, standardized methods for prevalence surveys are needed that can be used in countries at all levels of economic development. The Burden of Obstructive Lung Disease (BOLD) Initiative has developed a set of methods for estimating COPD prevalence and a model for assessing its economic impact, and piloted these methods in China and Turkey. The methods were revised to reflect the findings in the pilot studies, and BOLD is now making the standardized methods available worldwide. The BOLD Operations Center provides training, materials, quality control, and data analysis. BOLD emphasizes data quality control at every stage of the process. Data from paper forms completed in the field are entered electronically to a specially designed secure Web platform. Pre- and post-bronchodilator spirometry testing is done on all participants, and all spirometry data are reviewed for quality. Questionnaires are used to obtain information about respiratory symptoms, health status, exposure to risk factors, and economic data about the burden of COPD. BOLD's standardized methods will provide a uniform way to compare COPD burden within and between countries, and where differences are found, to explore explanations for these differences. [ABSTRACT FROM AUTHOR]

Study objectives: Nasal continuous positive airway pressure (CPAP) is standard therapy for obstructive sleep apnea syndrome. The effective nasal mask pressure may be adversely affected by factors that increase system resistance (eg, long tubing and/or water condensation) and by dynamic variables (breathing frequency [f] and tidal volume [VT]). The present study was conducted in order to assess the performance of CPAP machines throughout a range of simulated clinical conditions. Design: Four currently used CPAP machines were tested at settings of 5, 10, 15, and 20 cm H[sub 2]O using a pulmonary waveform generator to produce VTS of 0.4, 0.8, and 1.2 L at frequencies of 10, 20, and 30 breaths/min. Machines were tested under five conditions: 6-foot and 12-foot tubing, with and without an in-line humidifier, and 12-foot tubing with humidifier and water condensation. Measurements: Maximum and minimum mask pressure measurements were obtained during five respiratory cycles for each dynamic variable under each of the five conditions and CPAP settings (180 experiments on each of four CPAP models). Results: Using typical clinical parameters (VT, 0.4 L and 0.8 L; f, 10 breaths/min and 20 breaths/min; and CPAP, 5 to 15 cm H[sub 2]O), mask pressure consistently varied above and below the set point when additional tubing and/or a humidifier were added to the system (0.7 to 2.9 cm H[sub 2]O below and 0.5 to 1.0 cm H[sub 2]O above the set pressure). Water condensation caused large pressure deviations (inspiratory pressure ranged from 3.5 to 5.6 cm H[sub 2]O below set pressure, and expiratory pressure ranged from 0.7 to 3.5 cm H[sub 2]O above set pressure). Conclusions: Therapy and compliance could be adversely affected because some CPAP machines in current use do not maintain constant continuous mask pressure when tested using simulated conditions, especially when water condenses in the tubing. [ABSTRACT FROM AUTHOR]