No abstract

Pulmonary function measures are heritable traits that predict morbidity and mortality and define chronic obstructive pulmonary disease (COPD). We tested genome-wide association with forced expiratory volume in 1 s (FEV1) and the ratio of FEV1 to forced vital capacity (FVC) in the SpiroMeta consortium (n = 20,288 individuals of European ancestry). We conducted a meta-analysis of top signals with data from direct genotyping (n ≤ 32,184 additional individuals) and in silico summary association data from the CHARGE Consortium (n = 21,209) and the Health 2000 survey (n ≤ 883). We confirmed the reported locus at 4q31 and identified associations with FEV1 or FEV1/FVC and common variants at five additional loci: 2q35 in TNS1 (P = 1.11 × 10−12), 4q24 in GSTCD (2.18 × 10−23), 5q33 in HTR4 (P = 4.29 × 10−9), 6p21 in AGER (P = 3.07 × 10−15) and 15q23 in THSD4 (P = 7.24 × 10−15). mRNA analyses showed expression of TNS1, GSTCD, AGER, HTR4 and THSD4 in human lung tissue. These associations offer mechanistic insight into pulmonary function regulation and indicate potential targets for interventions to alleviate respiratory disease.

Pulmonary function measures reflect respiratory health and predict mortality, and are used in the diagnosis of chronic obstructive pulmonary disease (COPD). We tested genome-wide association with the forced expiratory volume in 1 second (FEV1) and the ratio of FEV1 to forced vital capacity (FVC) in 48,201 individuals of European ancestry, with follow-up of top associations in up to an additional 46,411 individuals. We identified new regions showing association (combined P<5×10−8) with pulmonary function, in or near MFAP2, TGFB2, HDAC4, RARB, MECOM (EVI1), SPATA9, ARMC2, NCR3, ZKSCAN3, CDC123, C10orf11, LRP1, CCDC38, MMP15, CFDP1, and KCNE2. Identification of these 16 new loci may provide insight into the molecular mechanisms regulating pulmonary function and into molecular targets for future therapy to alleviate reduced lung function.

Cardiopulmonary exercise testing (CPET) is a widely applied clinical procedure. The aim of the present study was to acquire a comprehensive set of reference values for cardiopulmonary responses to exercise and to evaluate possible associations with sex, age and body mass index (BMI).A standardised progressive incremental exercise protocol on a cycle ergometer was applied to 1,708 volunteers of a cross-sectional epidemiologic survey, called ''Study of Health in Pomerania''. Individuals with cardiopulmonary disorders, or echocardiographic or lung function pathologies, were excluded. The influence of potential confounding factors, such as smoking, taking b-blockers, hypertension, diastolic dysfunction, BMI and physical activity, were analysed for their influencing power. Reference values of CPET parameters were determined by regression analyses.Of the volunteers, 542 current smokers and obese individuals were excluded for not being representative of a healthy population. The final sample size was 534 (253 males), with age 25-80 yrs. The current study provides a representative set of reference values for CPET parameters based on age and weight.Sex and age have a significant influence on exercise parameters. While addressing the problem of a selection bias, the current study provides the first comprehensive set of reference values obtained in a large number of healthy volunteers within a population-based survey.KEYWORDS: Cardiopulmonary exercise testing, oxygen uptake, reference values, Study of Health in Pomerania, ventilatory efficiency C ardiopulmonary exercise testing (CPET) is a widely applied routine procedure in daily clinical work, used for the investigation of cardiac and pulmonary disorders. Due to their prognostic and therapeutic implications [1,2], the normalcy of response to incremental exercise is usually considered with respect to particular functional indices, such as the peak oxygen uptake (V9O 2 ,peak), the estimated lactate threshold (hL) and the characterisation of ventilatory efficiency expressed by the minute ventilation (V9E) changes as a function of the pulmonary carbon dioxide output (V9E-V9CO 2 slope). Reference values for these indices have been established, usually with respect to sex, age, body features and physical activity, by several investigators [3][4][5]. The interpretation of the results of exercise tests requires knowledge of the normal response [6], but a consensus has not been reached on the definition of normalcy. The commonly used reference values are based on exercise capacities of shipyard workers [3] or university members [4]. ''Healthy volunteers'' were usually defined as subjects without self-reported evidence or clinical symptoms and signs of heart and lung disease, a normal resting electrocardiogram (ECG), a normal 12-lead ECG response to an exercise stress test and the absence of any medication, especially any with cardiorespiratory effects. However, obtainable reference data sets show relevant limitations, considering their sample recruitment, age distributi...