Spirometric Measures Of Lung Function Research Articles

Dupilumab sustains lung function improvements in patients with moderate-to-severe asthma

BackgroundTRAVERSE (NCT02134028), a phase 3 open-label extension study, assessed dupilumab safety and efficacy in patients with asthma aged ≥12 years who completed a previous dupilumab asthma study. This analysis evaluated changes in multiple lung function parameters in patients with moderate-to-severe asthma with elevated type 2 biomarkers (baseline eosinophils ≥150 cells·μL−1 or fractional exhaled nitric oxide ≥25 ppb) who completed QUEST (parent study) and 2 years of dupilumab treatment in TRAVERSE. MethodsEndpoints analyzed included: pre-bronchodilator forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), forced expiratory flow (FEF25-75 %), and pre- and post-bronchodilator FEV1/FVC at parent study baseline (PSBL) at Weeks 0, 2, 48, and 96 in TRAVERSE, as well as pre- and post-bronchodilator FEV1 slopes in QUEST and TRAVERSE. Statistical analyses were descriptive. ResultsDupilumab improved pre-bronchodilator FEV1, FVC, and FEF25–75 % in QUEST; these improvements were sustained in TRAVERSE. In QUEST patients who received placebo, dupilumab initiation in TRAVERSE resulted in rapid lung function improvements. Mean (standard deviation) changes from PSBL at TRAVERSE Weeks 48 and 96 in pre-bronchodilator FEV1 were 0.52 (0.59) and 0.45 (0.49) L in the dupilumab/dupilumab group and 0.47 (0.42) and 0.44 L (0.45) in the placebo/dupilumab group, respectively. Similar trends were observed for FVC and FEF25–75 %. Dupilumab also improved FEV1 slopes in QUEST and TRAVERSE. ConclusionDupilumab demonstrated sustained improvements across multiple spirometric lung function measurements for up to 3 years; patients who received placebo in QUEST experienced rapid lung function improvement upon initiation of dupilumab in TRAVERSE.

The Effect of Deployment on Pulmonary Function in Military Personnel With Asthma.

Military personnel with a diagnosis of asthma report increased respiratory symptoms in the deployment and post-deployment periods. The long-term effect of deployment on pulmonary function in this population is unknown. This study sought to determine the effect of deployment on post-deployment pulmonary function in active duty military personnel with asthma. A retrospective chart review of active duty military personnel with deployment to southwest Asia and an ICD-9 diagnosis of asthma with documented pre- and post-deployment spirometry was performed. A total of 642 active duty individuals with a diagnosis of asthma and documented spirometry with deployment to southwest Asia between 2006 and 2015 were identified. Of these, 76 individuals were identified with pre- and post-deployment spirometry. There was no significant change in the post-deployment forced expiratory volume at 1 second (% predicted), from 86.0 ± 14.8 to 87.6 ± 14.4 (P = .30). There was no significant change in post-deployment forced vital capacity (% predicted), from 93.8 ± 12.4 to 94.9 ± 12.1 (P = .42). The absolute change in forced expiratory volume at 1 second (L) after bronchodilator administration was decreased from pre-deployment to post-deployment (+0.31 ± 0.26 to +0.16 ± 0.23; P = .02). There was no significant post-deployment change in spirometry in this military population with asthma deployed to southwest Asia. These findings suggest that deployment itself is not associated with any short-term deleterious effect on post-deployment spirometric measures of lung function in many military personnel with asthma.

57-Year-Old Man With Hip Pain and Lytic Bone Lesions

57-year-old man presented to his primary care physician with a 2-year history of progressive right hip pain. His medical history was notable for hyperlipidemia. He was up-to-date on sex- and agespecific cancer screening. The patient had no history of chest pain, palpitations, shortness of breath, cough, or other cardiac, respiratory, neurologic, or visual symptoms. He had no recent travel history or occupational or social contact with persons who were ill. Physical examination revealed an obese man (body mass index [calculated as weight in kilograms divided by height in meters squared], 40.34 kg/m 2 ) with normal vital signs and unremarkable findings on cardiac, respiratory, abdominal, neurologic, and lymphatic examination. No pain or tenderness was elicited on examination. He was treated initially with nonopioid pain medications. Sacroiliac corticosteroid injections were minimally beneficial. Results of a complete blood cell count (CBC) and electrolyte panel were normal with the exception of an elevated serum calcium level of 11.7 mg/dL (reference range, 8.9-10.1 mg/dL). Ultimately, magnetic resonance imaging (MRI) of his lumbar spine revealed numerous punched-out lytic lesions in the lumbar vertebra and pelvis. He underwent computed tomography (CT) of his chest, abdomen, and pelvis that identified further lytic lesions as well as multiple splenic lesions concerning for metastases. Two separate CT-guided bone biopsy samples of the lytic lesions in the lumbar vertebra did not elicit an etiology of the lesions.

Healthy Eating Index 2005 and selected macronutrients are correlated with improved lung function in humans

A number of dietary components have been associated with lung function. However, a comprehensive measure of a healthy diet has not been compared with lung function. Herein, we test the hypothesis that a healthy overall diet, as assessed by the Healthy Eating Index 2005 (HEI-2005), will be associated with increased lung function. This is an investigation using the Atherosclerosis Risk in Communities Research Materials obtained from the National Heart Lung Blood Institute. The study surveyed dietary habits of 15 567 American subjects from 4 communities in 1987 to 1990. Spirometric measures of lung function were also taken at entry to the study and a second time 3 years later. Based on food and nutritional data collected by food frequency questionnaire, an HEI-2005 score was calculated for each subject. This total score, together with its 12 components scores and associated macronutrient, was compared with lung function results by linear regression. Models were controlled for smoking behavior, demographics, and other important covariates. The HEI-2005 total scores were positively associated with forced expiratory volume in 1 second per forced vital capacity (FEV(1)/FVC) at visit 1 (β = .101 per increase in 1 quintile of HEI-2005) and visit 2 (β = .140), and FEV(1) as percentage of the predicted FEV(1) at visit 2 (β = .215) (P < .05). In addition, HEI-2005 component scores that represented high intakes of whole grains (β = .127 and .096); saturated fats (β = −.091); and solid fats, alcohol, and added sugar (β = −.109 and −.131) were significantly associated with FEV(1)/FVC at either visit 1 or visit 2. Intakes of total calories (β =−.082 at visit 1) and saturated fatty acids (β = −.085 at visit 2) were negatively associated with FEV(1)/FVC. Dietary polyunsaturated fatty acids (β = .085 and .116) and long-chain omega-3 fatty acids (β = .109 and .103), animal protein (β = .132 and .093), and dietary fiber (β = .129) were positively associated with lung health. An overall healthy diet is associated with higher lung function.

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To evaluate pulmonary function tests and blood parameters and their relationship with sociodemographic data for radiology staff continuously exposed to ionizing radiation. Thirty-eight personnel from Suleyman Demirel University Training and Research Hospital, Radiology Unit, were included in this study. Sociodemographic data were evaluated by a questionnare that was developed by the researchers. Height and weight measurements were performed with a standard scale and meter. Routine blood parameters and spirometric lung function measurements of the cases were recorded. Statistical significances were determined by independent t-test, analysis of variance (ANOVA), bivariate correlation and Kruskal-Wallis tests using SPSS 18.0. The mean age was 32.42 ± 5.5 years; 19 patients (50%) were male and 19 patients (50%) were female. Body mass index (BMI) was calculated as 25.68 ± 0.47 for men and 24.58 ± 1.13 for women. Forced vital capacity (FVC), forced expiratory volume in the 1st second (FEV1), peak expiratory flow (PEF) and maximum mid-expiratory flow (FEF25-75) showed negatively statistically significant differences between gender (p < 0.01). In addition, FEV1 and FEF25-75 also demonstrated statistically negatively significant difference with the type of task (p < 0.05). A statistically significant negative difference was found between FEF25-75 value and time to start smoking (p < 0.05). Among FVC, FEV1, PEF and FEF25-75 values and alcohol usage, statistically significant positive difference was detected (p < 0.05). Statistically significant positive difference was found among FVC, PEF and FEF25-75 values and sports activity (p < 0.05). According to BMI groups, statistically significant positive difference with FVC, FEV1 and PEF values were found (p < 0.05). Statistically significant correlations were found among FVC value and haemoglobin level (Hgb), haematocrit level (Hct) and mean corpuscular volume (MCV), among FEV1 value and Hgb, MCV, among PEF value and red blood cell count (RBC), Hgb, Hct, MCV, red cell distribution width (RDW), and between FEF25-75 value and MCV. Although respiratory functions of radiology staff are affected by many factors, continuous exposure to ionizing radiation is one of the important parameters. Radiology staff should be informed about factors that negatively affect the respiratory functions.

The impact of switching to the new global lung function initiative equations on spirometry results in the UK CF Registry

The Quanjer et al. Global Lung Function Initiative (GLI)-2012 multi-ethnic all-age reference equations for spirometry are endorsed by all major respiratory societies and are the new gold standard. Before the GLI equations are implemented for use in CF patients, the impact of changing equations from those currently used needs to be better understood. Annual review data submitted to the UK CF Trust Registry between 2007 and 2011 were used to calculate %predicted FEV1, FVC and FEV1/FVC using three widely used reference equations (Wang-Hankinson and Knudson) and the new GLI-2012 equations. Overall, Knudson and Wang equations overestimated %predicted values in paediatric patients, such that a greater proportion of patients had lung function values in the normal range. Within individual patients, the impact of switching equations varied greatly depending on the patients' age, and which equations were used. A unified approach to interpreting spirometric lung function measurements would help facilitate more appropriate comparison both within and between centres and countries. Interpretation of longitudinal measurements using a continuous reference equation across all-ages, like the GLI, may further improve our understanding of CF lung disease.

Serum Methylarginines and Spirometry-Measured Lung Function in Older Adults

RationaleMethylarginines are endogenous nitric oxide synthase inhibitors that have been implicated in animal models of lung disease but have not previously been examined for their association with spirometric measures of lung function in humans.ObjectivesThis study measured serum concentrations of asymmetric and symmetric dimethylarginine in a representative sample of older community-dwelling adults and determined their association with spirometric lung function measures.MethodsData on clinical, lifestyle, and demographic characteristics, methylated arginines, and L-arginine (measured using LC-MS/MS) were collected from a population-based sample of older Australian adults from the Hunter Community Study. The five key lung function measures included as outcomes were Forced Expiratory Volume in 1 second, Forced Vital Capacity, Forced Expiratory Volume in 1 second to Forced Vital Capacity ratio, Percent Predicted Forced Expiratory Volume in 1 second, and Percent Predicted Forced Vital Capacity.Measurements and Main ResultsIn adjusted analyses there were statistically significant independent associations between a) higher asymmetric dimethylarginine, lower Forced Expiratory Volume in 1 second and lower Forced Vital Capacity; and b) lower L-arginine/asymmetric dimethylarginine ratio, lower Forced Expiratory Volume in 1 second, lower Percent Predicted Forced Expiratory Volume in 1 second and lower Percent Predicted Forced Vital Capacity. By contrast, no significant associations were observed between symmetric dimethylarginine and lung function.ConclusionsAfter adjusting for clinical, demographic, biochemical, and pharmacological confounders, higher serum asymmetric dimethylarginine was independently associated with a reduction in key measures of lung function. Further research is needed to determine if methylarginines predict the decline in lung function.

Predictors for Asthma at Age 7 Years for Low-Income Children Enrolled in the Childhood Asthma Prevention Study

To identify the predictive factors of early childhood wheezing in children of low socioeconomic status. The Childhood Asthma Prevention Study enrolled 177 low-income children (9-24 months old) with frequent wheezing. At age 7 years, presence of asthma was assessed through caregiver reports of physician diagnosis of asthma (CRPDA) and corroborated by assessment of bronchial hyperresponsiveness (BHR). Lung function, inflammatory markers, and asthma symptom severity were compared for children with ±CRPDA, ±BHR, and asthma. Baseline predictors for CRPDA, BHR, and asthma at 7 years of age were examined. Maternal symptom report strongly differentiated children with +CRPDA (49%) despite comparable airflow measurements (P<.0001), and spirometric lung function measurements were different for +BHR (65%) versus -BHR (P<.005). Univariate analyses revealed different baseline predictors of +CRPDA and +BHR for children at age 7 years. Higher levels of maternal psychological resources were associated with +CRPDA, but not +BHR. Only 39% of children with a history of frequent wheezing met the conservative definition of asthma at age 7 years, with the following significant predictors found: low birth weight, baseline symptom severity, and maternal psychological resources. This low-income, multi-ethnic group of wheezing infants represents a unique population of children with distinct characteristics and risks for persistent asthma. Determination of asthma status at 7 years of age required objective measurement of BHR in addition to CRPDA. The association of maternal psychological resources with +CRPDA may represent a previously unrecognized factor in the determination of asthma status among low-income groups.

Association Between Childhood Asthma and Chronic Obstructive Pulmonary Disease in Later Life

Persistent chronic inflammation and impaired lung growth due to asthma in childhood may have long-term impact on pulmonary function and increase susceptibility to chronic obstructive pulmonary disease (COPD) in later life. To investigate whether childhood asthma is associated with adult lung function and the risk of developing COPD among Japanese older adults, a case-control study was conducted in central Japan. A total of 300 patients with COPD aged 50 to 75 years were referred by respiratory physicians, while 400 controls were recruited from the community. All participants underwent spirometric measurements of lung function. Information on childhood asthma, demographic characteristics, and lifestyle characteristics was obtained by face-to-face interview using a structured questionnaire. The prevalence of childhood asthma was higher (P = .015) among the cases (6.3%) than among the control group (2.4%). Childhood asthma was significantly associated with the risk of COPD (adjusted odds ratio 3.32, 95% confidence interval 1.05-10.45). Participants with childhood asthma had lower (P = .010) forced expiratory volume in 1 second (mean 1.63 L, standard deviation [SD] 0.64 L) than those without (mean 2.04 L, SD 0.75 L). However, the adjusted lung function difference did not attain statistical significance after controlling for confounding variables such as age and cumulative smoking exposure. The epidemiological evidence suggested a positive association between childhood asthma and COPD in later life. Further study of the effect of adequate childhood asthma treatment on future risk of COPD should be undertaken.

Image analysis for cystic fibrosis: computer-assisted airway wall and vessel measurements from low-dose, limited scan lung CT images.

Cystic fibrosis (CF) is a life-limiting genetic disease that affects approximately 30,000 Americans. When compared to those of normal children, airways of infants and young children with CF have thicker walls and are more dilated in high-resolution computed tomographic (CT) imaging. In this study, we develop computer-assisted methods for assessment of airway and vessel dimensions from axial, limited scan CT lung images acquired at low pediatric radiation doses. Two methods (threshold- and model-based) were developed to automatically measure airway and vessel sizes for pairs identified by a user. These methods were evaluated on chest CT images from 16 pediatric patients (eight infants and eight children) with different stages of mild CF related lung disease. Results of threshold-based, corrected with regression analysis, and model-based approaches correlated well with both electronic caliper measurements made by experienced observers and spirometric measurements of lung function. While the model-based approach results correlated slightly better with the human measurements than those of the threshold method, a hybrid method, combining these two methods, resulted in the best results.

Roflumilast in Asian patients with COPD: A randomized placebo‐controlled trial

Roflumilast, an oral, selective phosphodiesterase 4 inhibitor, has been shown to reduce exacerbations and improve pulmonary function in patients with COPD. This study examined the efficacy, safety and tolerability of roflumilast in Asian patients with COPD. Patients with COPD were randomized 1:1 to enter a 12-week treatment period and receive either oral roflumilast, 500 µg once daily, or placebo, following a single-blind, 4-week baseline period in which all patients received placebo. The primary end point was mean change in FEV₁ from baseline to each postrandomization visit during the treatment period. Other spirometric lung function measurements were evaluated as secondary end points. COPD exacerbations were monitored. Safety was assessed from clinical laboratory tests, vital signs, physical examination (including electrocardiogram) and monitoring of adverse events (AEs). Of 551 patients recruited, 410 were randomized and received at least one dose of study medication (roflumilast, n = 203; placebo, n = 207). Superiority of roflumilast over placebo was demonstrated by a statistically significant difference in postbronchodilator FEV₁ (79 mL, P < 0.0001). Other spirometry end points, including prebronchodilator FEV₁, pre-and postbronchodilator FEV₆, forced vital capacity and peak expiratory flow significantly favoured roflumilast over placebo. AEs were more common with roflumilast than with placebo, but were comparable with those reported in previous studies. Roflumilast, 500 µg once daily, improves pulmonary function in Asian patients with COPD. The safety and tolerability of roflumilast in this population was similar to that in a Caucasian population.

Fibroblast growth factor 10 haploinsufficiency causes chronic obstructive pulmonary disease

BackgroundGenetic factors influencing lung function may predispose to chronic obstructive pulmonary disease (COPD). The fibroblast growth factor 10 (FGF10) signalling pathway is critical for lung development and lung epithelial renewal....

Determinants of Lung Function, COPD, and Asthma

To the Editor: In a genomewide association study from the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium, we identified several loci as genetic determinants of spirometric measures of lung function in more than 20,000 adults from population-based cohorts.1 Moffatt et al. (Sept. 23 issue)2 attributed to us the statement that “genetic determinants of lung function influence susceptibility to asthma” and indicated that their own data “do not support this hypothesis.” Because chronic obstructive pulmonary disease (COPD) is defined on the basis of the same spirometric measures of lung function, it is not surprising that some loci . . .

Dietary intake of six minerals in relation to the risk of chronic obstructive pulmonary disease

To investigate the relationship between dietary intake of minerals and the risk of chronic obstructive pulmonary disease (COPD), a case-control study was conducted in central Japan. A total of 278 referred patients (244 men and 34 women) aged 50-75 years with COPD diagnosed within the past four years and 340 community-based controls undertook spirometric measurements of lung function. A structured questionnaire was administered face-to-face to obtain information on demographics and habitual food consumption. Dietary intakes of six major minerals were derived from the Japanese food composition tables. The COPD patients had lower habitual energy-adjusted intakes of calcium, phosphorus and iron than controls, but not sodium. A significant reduction in prevalence of COPD was observed for calcium, with adjusted odds ratio 0.65 (95% confidence interval: 0.37- 0.98) for the highest level versus lowest level of intake. A high iron intake was also inversely associated with the COPD risk. In conclusion, an inverse association was evident between dietary calcium intake and the risk of COPD for Japanese adults.

Life-Long Physical Activity Involvement Reduces the Risk of Chronic Obstructive Pulmonary Disease: A Case-Control Study in Japan

Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality worldwide. Because only 20% of cigarette smokers develop COPD, certain environmental and lifestyle factors may protect against the disease development. To investigate the relationship between life-long physical activity involvement and the COPD risk, a case-control study was conducted in central Japan. A total of 278 eligible patients (244 men and 34 women) age 50 to 75 years were referred by respiratory physicians, while 335 controls (267 men and 68 women) were recruited from the community. All participants underwent spirometric measurements of lung function. Information on demographic and lifestyle characteristics was obtained by face-to-face interview using a structured questionnaire. Older adults who remained physically active had better lung function than others inactive over the life course. The COPD patients were found to be less active than their healthy counterparts. Significant reductions in risk of COPD and breathlessness were evident by being active life-long, with adjusted odds ratio 0.59 (95% CI 0.36-0.97) and 0.56 (95% CI 0.36-0.88), respectively. The study suggested an inverse association between life-long physical activity and the risk of COPD and breathlessness. Promotion of physical activity to prevent this major disease should be encouraged.

060 An analysis of the effect of intrauterine growth retardation on spirometric lung function measures of 8-year-old children

ObjectiveIncreasing evidence suggests that intrauterine growth retardation (IUGR) is associated with long-term morbidities, including respiratory outcomes. The relationship between IUGR and lung function has been studied in adults, but few...

1H Nuclear Magnetic Resonance Metabolomics Analysis Identifies Novel Urinary Biomarkers for Lung Function

Chronic obstructive pulmonary disease (COPD), characterized by chronic airflow limitation, is a serious public health concern. In this study, we used proton nuclear magnetic resonance ((1)H NMR) spectroscopy to identify and quantify metabolites associated with lung function in COPD. Plasma and urine were collected from 197 adults with COPD and from 195 without COPD. Samples were assayed using a 600 MHz NMR spectrometer, and the resulting spectra were analyzed against quantitative spirometric measures of lung function. After correcting for false discoveries and adjusting for covariates (sex, age, smoking) several spectral regions in urine were found to be significantly associated with baseline lung function. These regions correspond to the metabolites trigonelline, hippurate and formate. Concentrations of each metabolite, standardized to urinary creatinine, were associated with baseline lung function (minimum p-value = 0.0002 for trigonelline). No significant associations were found with plasma metabolites. Urinary hippurate and formate are often related to gut microflora. This could suggest that the microbiome varies between individuals with different lung function. Alternatively, the associated metabolites may reflect lifestyle differences affecting overall health. Our results will require replication and validation, but demonstrate the utility of NMR metabolomics as a screening tool for identifying novel biomarkers of pulmonary outcomes.

Folate intake associated with lung function, breathlessness and the prevalence of chronic obstructive pulmonary disease.

A case-control study was conducted in central Japan to investigate the relationship between dietary intake of folate and lung function, breathlessness and chronic obstructive pulmonary disease (COPD). A total of 278 referred patients (244 men and 34 women) aged 50-75 years with COPD diagnosed within the past four years and 340 community-based controls (272 men and 68 women) were assessed for dyspnoea and undertook spirometric measurements of lung function. A structured questionnaire was administered face-to-face to obtain information on demographics, lifestyle and habitual food consumption. Folate intake was derived from the Japanese food composition tables. The COPD patients had significantly lower habitual intake of folate (mean 231, SD 90 microg/day) than control subjects (mean 261, SD 110 microg/day), p<0.001. Lung function measures were found to be positively associated with dietary folate level. Reductions in prevalence of COPD and especially breathlessness were observed, the respective adjusted odds ratio (OR) being 0.74 (95% confidence interval (CI) 0.35 to 1.58) and 0.43 (95% CI 0.21 to 0.91) for the highest versus lowest quartile of folate intake. The corresponding tests for linear trend were also significant (p<0.05). In conclusion, an inverse association was evident between dietary folate intake and the prevalence of breathlessness for Japanese adults, together with a significant dose-response relationship for the COPD risk. Moreover, increased folate intake might be beneficial to lung function.

Dietary intake of isoflavones and polyunsaturated fatty acids associated with lung function, breathlessness and the prevalence of chronic obstructive pulmonary disease: Possible protective effect of traditional Japanese diet

The Japanese diet is high in soy products and fish. A case-control study was conducted in Japan to investigate the relationship between dietary intake of isoflavones and fatty acids and lung function, breathlessness and chronic obstructive pulmonary disease (COPD). A total of 278 referred patients aged 50-75 years with COPD diagnosed within the past 4 years, and 340 community-based controls were assessed for respiratory symptoms and undertook spirometric measurements of lung function. A validated food frequency questionnaire was administered face-to-face to obtain information on habitual food consumption. Dietary intakes of isoflavones and fatty acids were derived from the Japanese food composition tables. The COPD patients had significantly lower habitual intakes of isoflavones (genistein and daidzein) and polyunsaturated fatty acids (PUFA; both omega-3 and omega-6) than control subjects. Lung function measures were found to be positively associated with isoflavones and PUFA intake. Substantial reductions in prevalence of COPD and breathlessness were observed for isoflavones, the respective adjusted odds ratio being 0.36 (95% confidence interval 0.19-0.68) and 0.60 (95% confidence interval 0.33-1.10) for the highest versus lowest levels of total isoflavone intake. The corresponding tests for linear trend were significant. High intakes of PUFA and omega-6 fatty acids (derived from foods excluding oils and fats as seasonings) also appeared to reduce the risks of COPD and breathlessness symptom, but no evidence of association was found for other types of fatty acids. The study provided evidence of possible protective effect of traditional Japanese diet against tobacco carcinogens.

Meta-analyses of genome-wide association studies identify multiple loci associated with pulmonary function

Spirometric measures of lung function are heritable traits that reflect respiratory health and predict morbidity and mortality. We meta-analyzed genome-wide association studies for two clinically important lung-function measures: forced expiratory volume in the first second (FEV(1)) and its ratio to forced vital capacity (FEV(1)/FVC), an indicator of airflow obstruction. This meta-analysis included 20,890 participants of European ancestry from four CHARGE Consortium studies: Atherosclerosis Risk in Communities, Cardiovascular Health Study, Framingham Heart Study and Rotterdam Study. We identified eight loci associated with FEV(1)/FVC (HHIP, GPR126, ADAM19, AGER-PPT2, FAM13A, PTCH1, PID1 and HTR4) and one locus associated with FEV(1) (INTS12-GSTCD-NPNT) at or near genome-wide significance (P < 5 x 10(-8)) in the CHARGE Consortium dataset. Our findings may offer insights into pulmonary function and pathogenesis of chronic lung disease.