Cell-Free Methylated PTGER4 and SHOX2 Plasma DNA as a Biomarker for Therapy Monitoring and Prognosis in Advanced Stage NSCLC Patients.

Notwithstanding some improvement in the earlier detection of patients with lung cancer, most of them still present with a late-stage disease at the time of diagnosis. Next to the most frequently utilized factors affecting the prognosis of lung cancer patients (stage, performance, and age), the recent application of biomarkers obtained by liquid profiling has gained more acceptance. In our study, we aimed to answer these questions: (i) Is the quantification of free-circulating methylated PTGER4 and SHOX2 plasma DNA a useful method for therapy monitoring, and is this also possible for patients treated with different therapy regimens? (ii) Is this approach possible when blood-drawing tubes, which allow for a delayed processing of blood samples, are utilized? Baseline values for mPTGER4 and mSHOX2 do not allow for clear discrimination between different response groups. In contrast, the combination of the methylation values for both genes shows a clear difference between responders vs. non-responders at the time of re-staging. Furthermore, blood drawing into tubes stabilizing the sample allows researchers more flexibility.

The Correlation of Lung Function Parameters, Blood Pressure and Beta-Blocker Medication in a General Population.

OBJECTIVES: Prior studies have investigated possible links between blood pressure, antihypertensive medication, especially beta-blockers and impairment of lung function. The aim of our study was to investigate an association between blood pressure, antihypertensive medication, focusing on beta-blockers, and its influence on lung function parameters in our adult population. METHODS: From the two analysed cohorts of the population-based Study of Health in Pomerania (SHIP-1 and SHIP-TREND), pooled data for interview-based information, lung function variables including bodyplethysmography and blood pressure variables were used to perform adjusted linear regression analyses. Association analyses were conducted for the pooled population. RESULTS: Within the whole pooled population we found some minor statistically significant interrelations in the multivariate analyses for blood pressure and lung function parameters. Statistical correlation between lung function and blood pressure were significant but too weak to be deemed clinically relevant.We also found interrelations between lung function and use of beta-blocker medication. Within the subgroup of individuals with antihypertensive medication containing beta-blockers compared to the reference group we found lower dynamic and static volumes e. g. for FEV1 (-70 ml), FVC (-90 ml), a reduction of TLC (-130 ml) and ITGV (-100 ml), however we did not find an increase in airway resistance (Rtot). CONCLUSION: Based on the data of SHIP-1 and SHIP TREND our results confirm a minor association between blood pressure and lung function. More importantly, we have seen a significant decrease of lung volumes for hypertensive patients with beta- blocker medication as described in literature before. To the best of our knowledge, we are the first to examine the interrelation between blood pressure, medication and lung function in an epidemiological study using data of spirometry, body plethysmography and CO transfer.

The Influence of Type 1 Diabetes Mellitus on Pulmonary Function and Exercise Capacity - Results from the Study of Health in Pomerania (SHIP).

Background: Diabetes mellitus Type 1 (T1DM) is associated with metabolic and microvascular diseases as part of a multi-organ and multi-systemic disorder. The dense network of capillary vessels in the lungs may change during the course of the development of microangiopathy. The connective tissue as well as alveoli may be subjected to non-enzymatic glycosylation of proteins which may in turn affect pulmonary function. Previous studies investigating lung function in patients with type 1 diabetes have only been performed on small numbers of patients. Our study is based on population data of the Study of Health in Pomerania (SHIP). Objective: To investigate the influence of metabolic control on pulmonary system function and to establish a decreased pulmonary system function as a late complication of T1DM in a population based setting. Methods: The study is a case matched study with multiple controls based on participants with T1DM (SHIP-DM-1, n=73) and non-diabetics (SHIP-1, n=292) from the population based study of Pomerania. Data on lung function and exercise performance stratified by age, sex, body mass index and smoking habits in participants with T1DM and without diabetes were matched. Results: Participants with T1DM showed a significantly lower total lung capacity, residual volume and forced vital capacity. The transfer factor for carbon monoxide, the maximum power output and oxygen uptake during exercise were significantly decreased in comparison to the general population without diabetes. Conclusion: The pattern of abnormal pulmonary function as observed in the present study with a reduction in lung volume parameters and reduced oxygen uptake in participants with T1DM suggests a restrictive type of lung disease caused by an intrinsic lung tissue derangement as well as pulmonary microangiopathy.

Pulmonary hypertension in patients with idiopathic pulmonary fibrosis - the predictive value of exercise capacity and gas exchange efficiency.

Exercise capacity and survival of patients with IPF is potentially impaired by pulmonary hypertension. This study aims to investigate diagnostic and prognostic properties of gas exchange during exercise and lung function in IPF patients with or without pulmonary hypertension. In a multicentre setting, patients with IPF underwent right heart catheterization, cardiopulmonary exercise and lung function testing during their initial evaluation. Mortality follow up was evaluated. Seventy-three of 135 patients [82 males; median age of 64 (56; 72 years)] with IPF had pulmonary hypertension as assessed by right heart catheterization [median mean pulmonary arterial pressure 34 (27; 43) mmHg]. The presence of pulmonary hypertension was best predicted by gas exchange efficiency for carbon dioxide (cut off ≥152% predicted; area under the curve 0.94) and peak oxygen uptake (≤56% predicted; 0.83), followed by diffusing capacity. Resting lung volumes did not predict pulmonary hypertension. Survival was best predicted by the presence of pulmonary hypertension, followed by peak oxygen uptake [HR 0.96 (0.93; 0.98)]. Pulmonary hypertension in IPF patients is best predicted by gas exchange efficiency during exercise and peak oxygen uptake. In addition to invasively measured pulmonary arterial pressure, oxygen uptake at peak exercise predicts survival in this patient population.

Exercise blood pressure and heart rate reference values.

BACKGROUND: Besides their prognostic impact blood pressure and peak heart rate are widely used endpoint parameters for incremental exercise tests. Reference equations and ranges on both are sparse. OBJECTIVE: This study aims to describe prediction equations and reference ranges for systolic and diastolic blood pressure as well as for peak heart rate assessed during a symptom limited incremental exercise test based on a population based study--the Study of Health in Pomerania. DESIGN: For this purpose, 1708 individuals aged 25-85 years underwent cardiopulmonary exercise testing. RESULTS: After exclusion of subjects with cardiopulmonary diseases and antihypertensive medications regression analyses revealed age, sex and body mass index as statistically significant interfering factors. In accordance, prediction equations and reference ranges for blood pressure and peak heart rate with respect to sex, age and BMI have been established. CONCLUSION: This study provides a reliable set of prediction equations for blood pressure and heart rate values at peak exercise, assessed in a general population over a wide age range.

Influence of smoking and obesity on alveolar-arterial gas pressure differences and dead space ventilation at rest and peak exercise in healthy men and women.

BACKGROUND AND AIMS: Besides exercise intolerance, the assessment of ventilatory and perfusion adequacy allows additional insights in the disease pathophysiology in many cardiovascular or pulmonary diseases. Valid measurements of dead space/tidal volume ratios (VD/VT), arterial (a') - end-tidal (et) carbon dioxide (CO2) and oxygen (O2) pressure differences (p(a'-et)CO2) and (p(et-a')O2), and alveolar (A)-a' O2 pressure differences (p(A-a')O2) require using blood samples in addition to gas exchange analyses on a breath-by-breath-basis. Smoking and nutritional status are also important factors in defining disorders. Using a large healthy population we considered the impact of these factors to develop useful prediction equations. METHODS AND RESULTS: Incremental cycle exercise protocols were applied to apparently healthy volunteer adults who did not have structural heart disease or echocardiographic or lung function pathologies. Age, height, weight, and smoking were analysed for their influence on the target parameters in each gender. Reference values were determined by regression analyses. The final study sample consisted of 476 volunteers (190 female), aged 25-85 years. Smoking significantly influences p(A-a')O2 and p(a'-et)CO2 at rest and peak exercise, and VD/VT during exercise. Obesity influences upper limits of VD/VT, p(a'-et)CO2 and p(et-a')O2 at rest as well as p(A-a')O2 and p(et-a')O2 at exercise. Reference equations for never-smokers as well as for apparently healthy smokers considering influencing factors are given. CONCLUSION: Gender, age, height, weight, and smoking significantly influence gas exchange. Considering all of these factors this study provides a comprehensive set of reference equations derived from a large number of participants of a population-based study.

Static lung volumes and airway resistance reference values in healthy adults.

BACKGROUND AND OBJECTIVE: The assessment of static lung volumes and airway resistance is a frequently performed diagnostic procedure and considered as an important tool in medical surveillance to detect pulmonary diseases. The objectives of the study are to establish reference equations for body plethysmographic parameters in a representative adult population across a wide age range and to compare the normative values from this sample with previous ones. METHODS: Body plethysmography was applied in 1809 participants (885 males) of a cross-sectional, population-based survey (Study of Health in Pomerania). Individuals with cardiopulmonary disorders and/or a pack-year smoking history >10 years and participants with a body mass index >30 kg/m(2) were excluded. In total, 686 healthy individuals (275 males) aged 25-85 years were assessed. RESULTS: Prediction equations for both genders were established by quantile regression analysis taking into account the influence of age, height and weight. CONCLUSIONS: The study provides a novel set of prediction equations for static lung volumes and airway resistance obtained using body plethysmography. Compared with our findings, existing equations underestimated some normal values. The results emphasize the need for up-to-date reference equations.

Periodontitis is related to lung volumes and airflow limitation: a cross-sectional study.

This study aimed to assess the potential association of periodontal diseases with lung volumes and airflow limitation in a general adult population. Based on a representative population sample of the Study of Health in Pomerania (SHIP), 1463 subjects aged 25-86 years were included. Periodontal status was assessed by clinical attachment loss (CAL), probing depth and number of missing teeth. Lung function was measured using spirometry, body plethysmography and diffusing capacity of the lung for carbon monoxide. Linear regression models using fractional polynomials were used to assess associations between periodontal disease and lung function. Fibrinogen and high-sensitivity C-reactive protein (hs-CRP) were evaluated as potential intermediate factors. After full adjustment for potential confounders mean CAL was significantly associated with variables of mobile dynamic and static lung volumes, airflow limitation and hyperinflation (p<0.05). Including fibrinogen and hs-CRP did not change coefficients of mean CAL; associations remained statistically significant. Mean CAL was not associated with total lung capacity and diffusing capacity of the lung for carbon monoxide. Associations were confirmed for mean probing depth, extent measures of CAL/probing depth and number of missing teeth. Periodontal disease was significantly associated with reduced lung volumes and airflow limitation in this general adult population sample. Systemic inflammation did not provide a mechanism linking both diseases.

Mental health problems, obstructive lung disease and lung function: findings from the general population.

OBJECTIVE: There is cumulative evidence for a strong association of obstructive lung disease, i.e. asthma and COPD, with poor mental health, particularly with anxiety disorders and major depression. However, studies relating mental health problems to objective measures of lung function as assessed by spirometry are lacking. METHODS: The 12-month prevalence of specific psychopathological syndromes among 1772 adults from the general population was estimated by a structured interview. Additionally, participants underwent spirometry and were asked about obstructive lung disease in the year prior to the study. Logistic and linear regression models were used to relate obstructive lung disease and spirometrically defined airway obstruction to mental health problems. RESULTS: Mental health problems were found in 35.7% of the participants. After adjusted for sociodemographic, clinical and life-style factors, asthma and chronic bronchitis were associated with almost all domains of mental health problems. In contrast, independent of its definition, spirometric airflow limitation was only related to generalized anxiety (odds ratios ranging from 2.3 to 2.7). A reduced ratio of forced expiratory volume in one second to forced vital capacity was associated with mental health problems in general and panic and general anxiety in particular. CONCLUSION: Our findings suggest an association of objective measure of airflow limitation to generalized anxiety and panic. While the causal relationship between obstructive lung disease, airflow limitation and anxiety remains to be determined, clinicians should pay diagnostic attention to the significant overlap of these conditions.

Inhaled iloprost for therapy in pulmonary arterial hypertension.

Iloprost (Ventavis, Bayer Schering Pharma, Germany) is a synthetic prostacyclin that is used in its inhalative form for the therapy of pulmonary arterial hypertension. Long-term therapy can increase exercise capacity and quality of life. The use of modern nebulizers especially designed for the administration of iloprost guarantees the pulmonary deposition of the required doses and systematically minimizes side effects. Regarding existing data, inhalative iloprost acts in effective and safe combination with other classes of medication; indeed, such combination therapy is frequently necessary in pulmonary arterial hypertension.

Peripheral endothelial dysfunction is associated with gas exchange inefficiency in smokers.

AIMS: To assess the cross-sectional association between exercise capacity, gas exchange efficiency and endothelial function, as measured by flow-mediated dilation (FMD) and nitroglycerin-mediated dilation (NMD) of the brachial artery, in a large-scale population-based survey. METHODS: The study population was comprised of 1416 volunteers 25 to 85 years old. Oxygen uptake at anaerobic threshold (VO2@AT), peak exercise (peakVO2) and ventilatory efficiency (VE vs. VCO2 slope and VE/VCO2@AT) were assessed on a breath-by-breath basis during incremental symptom-limited cardiopulmonary exercise. FMD and NMD measurements at rest were performed using standardised ultrasound techniques. RESULTS: Multivariable logistic regression analyses revealed a significant association between FMD and ventilatory efficiency in current smokers but not in ex-smokers or non-smokers. There was no association between FMD and VO2@AT or peak VO2. In current smokers, for each one millimetre decrement in FMD, VE/VCO2@AT improved by -3.6 (95% CI -6.8, -0.4) in the overall population [VE vs. VCO2 slope -3.9 (-7.1, -0.6)]. These results remained robust after adjusting for all major influencing factors. Neither exercise capacity nor ventilatory efficiency was significantly associated with NMD. CONCLUSION: In current smokers, FMD is significantly associated with ventilatory efficiency. This result may be interpreted as a potential clinical link between smoking and early pulmonary vasculopathy due to smoking.

Association between serum testosterone and sex hormone-binding globulin and exercise capacity in men: results of the Study of Health in Pomerania (SHIP).

Testosterone exerts a widespread pattern of effects on metabolism and body composition, and interest is gaining in its correlation with physical fitness. The main focus of our study was to investigate the association of total serum testosterone and sex hormone-binding globulin (SHBG) levels on exercise capacity and maximal power output in men using a cross-sectional, population-based adult cohort. From the Study of Health in Pomerania (SHIP), 624 men age 25 to 85 years who underwent a standardized progressive incremental exercise protocol on a cycle ergometer were included in the analyses. Exercise capacity was characterized by oxygen uptake at anaerobic threshold (V'O(2) at L) and peak exercise (V'O(2 peak)) as well as maximal power output at peak exertion. Multivariable linear regression analyses adjusted for age, sex, body mass index, physical activity, and smoking were performed. Further, linear regression analyses with cubic splines and sensitivity analyses were undertaken. At peak exercise performance, testosterone and SHBG levels showed no associations with V'O(2 peak), V'O(2) at L as well as maximal power output, even after controlling for confounding factors including age, body mass index, physical activity, and smoking. An adverse association between the free testosterone index and V'O(2) at L was found. Linear regression analyses with cubic splines did not change the main results. In conclusion, this is the first study focusing on the association of total serum testosterone and SHBG on exercise capacity and physical performance in healthy volunteers based on a large-scale population-based study. After adjustment for relevant influencing factors, neither total serum testosterone nor SHBG levels had any interference with peak exercise capacity, aerobic exercise capacity, or maximal power output in men.

Omalizumab treatment and exercise capacity in severe asthmatics - results from a pilot study.

BACKGROUND: In patients with moderate to severe allergic asthma, clinical effectiveness of omalizumab, an approved anti-IgE-reacting substance, is usually assessed by pulmonary function testing (PFT), symptom scores and physicians judgement. AIMS: We postulate that cardiopulmonary exercise testing (CPET) may provide an additional option to verify symptomatic changes in patients with allergic asthma. METHODS: Ten consecutive patients with allergic asthma were treated with omalizumab. Prior to and after 16 weeks of treatment all patients underwent PFT and symptom-limited CPET. Results were compared to 10 asthmatic controls without omalizumab medication. Symptoms were assessed according to investigators judgement (IGETE). RESULTS: All 20 patients showed a significantly impaired exercise capacity at baseline [peak oxygen uptake (VO(2)) 71 ± 16% predicted]. In patients with omalizumab, peakVO(2) increased from 13.8 (8.4-21.4) to 16.8 (11.2-23.9) ml/kg/min (p < 0.05), VO(2) at anaerobic threshold increased by 22% [9.8 (3.3-15.2) to 12.3 (6.7-14.4) ml/kg/min (p < 0.05)]. There was no improvement in the controls. The increase in VO(2) was significantly correlated to the improvement in symptoms. All patients revealed dynamic hyperinflation under exercise with a decreasing extent with omalizumab treatment. CONCLUSION: This study suggests that CPET may provide additional and useful tools to assess and verify the individual clinical response to omalizumab treatment. An improvement in exercise capacity can reliably mirror changes in quality of life and IGETE. Patients with omalizumab experience significant improvements in their initially impaired exercise capacity. CPET can be safely accomplished in patients with severe asthma.

Lung function reference values in different German populations.

BACKGROUND: Spirometry is a frequently performed lung function test and an important tool in medical surveillance examinations of pulmonary diseases. The interpretation of lung function relies on the comparison to reference values derived from a healthy population. The study aim was to compare the lung function data of three representative population-based German studies (Study of Health in Pomerania [SHIP-1], Cooperative Health Research in the Region of Augsburg [KORA-S3] and European Community Respiratory Health Survey Erfurt [ECRHS-I Erfurt]) with existing European spirometry reference values and to establish a new set of comprehensive German prediction equations. METHODS: Spirometry was performed in 4133 participants of three population-based surveys using almost identical standardised methods. Current and former smokers, subjects with cardiopulmonary disorders or on medication with potential influence on lung function were excluded. Sex specific prediction equations were established by quantile regression analyses. Comparison was performed to existing European reference values. RESULTS: The healthy reference sample consisted of 1302 (516 male) individuals, aged 20-80 years. Sex specific comprehensive prediction equations adjusted for age and height are provided. Significant differences were found in comparison to previous studies with pronounced lower values of the current population if applying historic prediction equations. CONCLUSION: The results contribute to the interpretation of lung function examination in providing a comprehensive set of spirometry reference values obtained in a large number of healthy volunteers. Whereas the differences in between the investigated studies are negligible, striking divergence was detected in comparison to historic and recent European spirometry prediction values.

Association of circulating IGF-I and IGFBP-3 concentrations and exercise capacity in healthy volunteers: results of the Study of Health in Pomerania.

BACKGROUND: Insulin-like growth factor I (IGF-I) and its binding protein 3 (IGFBP-3) are central mediators of endocrine effects of growth hormone and there is increasing evidence for an association with muscle strength and exercise capacity. The aim of the present study was to clarify the possible association of circulating IGF-I and IGFBP-3 concentrations and exercise capacity in a general adult population. MATERIALS AND METHODS: From the Study of Health in Pomerania (SHIP) 1332 subjects aged 25 to 85 years participated in a standardised symptom limited cardiopulmonary exercise test on a bicycle. Exercise capacity was characterized by oxygen uptake at anaerobic threshold (VO2@AT), peak exercise (peakVO2), oxygen pulse and maximum power output at peak exertion. Multivariable linear regression analyses adjusted for age, sex, body mass index, physical activity and smoking were performed. RESULTS: At peak exercise performance, in women IGF-I showed significant associations to peakVO2 and maximum power output, IGF-I/IGFBP-3 ratio was associated with maximum power output. In men, this association was not consistently reproducible. Neither IGF-I nor IGFBP-3 did reveal any association to VO2@AT in both genders. CONCLUSION: Serum IGF-I concentrations are associated with peak exercise capacity in healthy women, but not in men over a wide range in ages, body sizes and activity scores.

Symptoms and diagnosis of asthma in a general population – longitudinal results from the SHIP database.

BACKGROUND: Against the background of an increasing prevalence of allergies, the epidemiology of asthma in relation to age is still a matter of debate. To further clarify the prevalence of asthma, asthmatic symptoms, and their change over time within a population sample, we analyzed longitudinal data from the Study of Health in Pomerania (SHIP). METHODS: Standardized questionnaires for asthma and asthmatic symptoms were available in 4310 individuals aged 20­79 years [corrected]. The population sample underwent a 5-year follow-up with 3300 subjects reexamined. The questionnaire evaluated estimates to describe the prevalence in wheeze, chest tightness, shortness of breath, coughing, nocturnal symptoms, and asthma attacks in the past 12 months, current medications, current asthma, and nasal allergies at baseline and its longitudinal net change. RESULTS: The prevalence of current asthma at the baseline study was 1.8% [95% confidence interval (CI 1.4­2.2)], those of nasal allergies 16.7% (95% CI 15.6­17.9). Sixteen percent of asthmatic individuals were not medically treated. The net changes in asthmatic symptoms per 60 months of follow-up ranged between a decrease by 2.0% (chest tightness at night) and an increase by 1.2% (nocturnal attack of coughing). The proportions of subjects with current asthma remained unchanged. The prevalence of current asthma and symptoms was higher in young individuals, whereas the net change over time was slightly increasing at the age of 36 and above. CONCLUSION: Despite the fact of a high prevalence of subjects complaining of nasal allergies, the overall prevalence of current asthma remained low over time. The prevalence in asthma and asthmatic symptoms as well as its net changes over 5 years were age dependent.

Reference values for respiratory pressures in a general adult population--results of the Study of Health in Pomerania (SHIP).

BACKGROUND AND OBJECTIVE: Respiratory muscle pressures have been gaining increasing interest because of prognostic value. The study aim was to acquire reference values for respiratory pressures in a large-scale population-based survey--the Study of Health in Pomerania (SHIP). METHODS: One thousand eight hundred and nine participants (885 men) of a cross-sectional epidemiologic survey, called 'Study of Health in Pomerania--SHIP', underwent lung function and respiratory muscle pressure measurements. After excluding individuals with cardiopulmonary disorders, prediction equations for men and women were established by quantile regression analysis. RESULTS: The final study population comprised 912 individuals (432 men), aged 25-80 years. The study provides a representative set of sex-specific prediction equations of respiratory muscle strength. Respiratory pressures are decreasing with age and are lower in women when compared to men. CONCLUSIONS: Prediction equations for relevant respiratory pressures are given. Based on this well-described population-based survey with extensive cardiopulmonary investigations to exclude relevant interfering disorders a sufficient comprehensive set of reference values was obtained.

Regional differences in prediction models of lung function in Germany.

BACKGROUND: Little is known about the influencing potential of specific characteristics on lung function in different populations. The aim of this analysis was to determine whether lung function determinants differ between subpopulations within Germany and whether prediction equations developed for one subpopulation are also adequate for another subpopulation. METHODS: Within three studies (KORA C, SHIP-I, ECRHS-I) in different areas of Germany 4059 adults performed lung function tests. The available data consisted of forced expiratory volume in one second, forced vital capacity and peak expiratory flow rate. For each study multivariate regression models were developed to predict lung function and Bland-Altman plots were established to evaluate the agreement between predicted and measured values. RESULTS: The final regression equations for FEV1 and FVC showed adjusted r-square values between 0.65 and 0.75, and for PEF they were between 0.46 and 0.61. In all studies gender, age, height and pack-years were significant determinants, each with a similar effect size. Regarding other predictors there were some, although not statistically significant, differences between the studies. Bland-Altman plots indicated that the regression models for each individual study adequately predict medium (i.e. normal) but not extremely high or low lung function values in the whole study population. CONCLUSIONS: Simple models with gender, age and height explain a substantial part of lung function variance whereas further determinants add less than 5% to the total explained r-squared, at least for FEV1 and FVC. Thus, for different adult subpopulations of Germany one simple model for each lung function measures is still sufficient.

Influence of age, sex, body size, smoking, and beta blockade on key gas exchange exercise parameters in an adult population.

AIMS: Cardiopulmonary exercise testing (CPET) is a widely applied clinical procedure. There is uncertainty to what extent nutritional status, beta blockers and smoking should be taken into account in the interpretation of exercise parameters to describe abnormality. This study planned to consider the impact of these factors on CPET values and develop reference equations on the basis of a large-scale population-based survey. METHODS AND RESULTS: An incremental cycle exercise protocol was applied to 1708 volunteers. Individuals with structural heart disease, echocardiographic or lung function pathologies were excluded. Age, height, weight, smoking, and beta blockers were analysed for their influencing power in each sex. Reference values of CPET parameters were determined by regression analyses. The final study sample consisted of 1203 volunteers (626 female), aged 25-85 years. Exercise capacity, gas exchange, and ventilatory efficiency for carbon dioxide removal were significantly dependent on sex, age, height, weight, and cigarette smoking. In the dosages used, beta blockers did not significantly interfere with gas exchange. CONCLUSION: Sex, height, weight, and age significantly influence gas exchange. This study provides a comprehensive set of reference values in a large number of volunteers within a population-based survey, with reference values corrected for influencing factors.