Christoph Schäper

Reference values for cardiopulmonary exercise testing in healthy volunteers: the SHIP study

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 β-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.

Impact of pulmonary hypertension on gas exchange and exercise capacity in patients with pulmonary fibrosis

Pulmonary hypertension is a relevant interceding morbidity in patients with pulmonary fibrosis that has significant impact on exercise tolerance and outcome. The aim of this study was to further characterize the exercise intolerance, dyspnoea and ventilatory inefficiency of patients with pulmonary fibrosis in the presence or absence of pulmonary hypertension via cardiopulmonary exercise testing. Thirty-four patients underwent pulmonary function testing, symptom-limited exercise testing on a bicycle and dyspnoea evaluation according to the BORG scale. Pulmonary hypertension was assessed by echocardiography and in a subset of patients right heart catheterization. Sixteen of 34 patients with pulmonary fibrosis revealed pulmonary hypertension. While all study patients did not differ in lung functions and demographic characteristics, patients suffering from pulmonary hypertension showed a significantly impaired exercise tolerance and worsened ventilatory inefficiency. The extent of pulmonary artery pressure elevation impacted significantly on ventilatory inefficiency. In addition, the increased ventilatory requirements significantly influenced the extent of dyspnoea in patients with pulmonary hypertension. We conclude that pulmonary hypertension has a significant impact on exercise capacity and dyspnoea in patients with interstitial lung disease (ILD). The further impairment of exercise capacity as well as the extent of dyspnoea in patients with interceding PHT is attributable to a significantly impaired ventilatory inefficiency.

Association of airflow limitation with trauma exposure and post-traumatic stress disorder

Trauma exposure and post-traumatic stress disorder (PTSD) are associated with self-reported asthma and chronic obstructive pulmonary disease. However, these conditions have not yet been related to objective measures of lung function. 1,772 adults from the general population were assessed regarding their medical histories and spirometric lung function. Additionally, they were administered a PTSD interview, and assigned to three groups: no trauma; trauma, but no PTSD; and trauma with PTSD. Adjusting for sociodemographic, clinical and lifestyle factors, subjects with PTSD had significantly higher odds ratios for most asthma-related symptoms than PTSD-negative participants (OR 3.2–8.8). The mean ratio of forced expiratory volume in 1 s (FEV1) to forced vital capacity (FVC) was lowest in the PTSD group and highest in those without trauma exposure. Traumatic stress was independently associated with FEV1 and FEV1/FVC. Participants with PTSD, compared with those without, had a significantly increased risk for airflow limitation independent of its definition (OR 4.2–7.8). This is the first study relating traumatic stress and PTSD, respectively, to objective parameters of lung function. Our findings suggest an association of trauma exposure and PTSD with airflow limitation, which may be mediated by inflammatory processes.

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.

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.

Impact of Different Definitions of Airflow Limitation on the Prevalence of Chronic Obstructive Pulmonary Disease in the General Population

Background: Recent surveys report a surprisingly high prevalence of chronic obstructive pulmonary disease (COPD) worldwide. However, there is evidence that the application of a fixed ratio of forced expiratory volume in 1 s (FEV1) to forced vital capacity (FVC) may result in a relevant misclassification of airflow limitation. Objectives: The definition of airflow limitation does have a significant impact on its prevalence. Methods: Individual values of lung volumes were assessed in comparison to a reference population by applying either a fixed ratio below 0.7 or the fifth percentile of FEV1 in relation to FVC. Based on a large-scale population-based survey, reference equations for lung volumes were derived by quantile regression analysis based on 1,809 subjects aged 25–85 years. Both functional definitions were applied to calculate the prevalence of airflow limitation. Results: The prevalence of airflow limitation was significantly higher when applying the fifth percentile compared to the fixed ratio of 0.7 for all age groups and both sexes (all 6.7 vs. 1.9%; women 6.7 vs. 1.3%; men 6.6 vs. 2.6%). Almost 26% of the subjects with airflow limitation complained of dyspnea, whereas COPD had not been previously diagnosed by a physician in 87%. Conclusion: The definition of airflow limitation has a major impact on the observed prevalence rates.

Association between Serum Insulin-Like Growth Factor (IGF) I and IGF Binding Protein-3 and Lung Function

BACKGROUND There is strong evidence that IGF-I and IGF binding protein 3 (IGFBP-3), as central mediators of endocrine and finally metabolic or anabolic effects of GH, were associated with increased lung size in acromegaly or a decrease of respiratory muscle pressures in patients with GH deficiency. The aim of the present study was to further clarify the impact of IGF-I and IGFBP-3 levels on lung volumes and respiratory pressures in a general adult population. MATERIAL AND METHODS From the Study of Health in Pomerania, 1326 subjects aged 25 to 85 yr participated in standardized pulmonary function testing. IGF-I and IGFBP-3 levels were measured with the Immulite 2500 system. Multivariable linear regression analyses adjusted for age, sex, body mass index, physical activity, and smoking were performed. RESULTS In men, positive linear associations between IGF-I and IGF-I/IGFBP-3 ratio with forced expiratory volume in 1 sec (FEV1) as well as with forced vital capacity (FVC) were detected across all ages, whereas in women this positive association was only detectable above 50 yr. Furthermore, the analyses indicated positive linear relations of IGF-I/IGFBP-3 ratio with FEV1 and FVC, respectively. No significant relations between IGF-I or IGFBP-3 and maximal inspiratory pressure was detectable in both sexes. CONCLUSION In conclusion, higher IGF-I levels were associated with higher lung volumes in men, whereas in women this association was only detectable in subjects older than 50 yr. Higher IGF-I values were not associated with increased respiratory muscle strength measured as maximal inspiratory pressure.

Airflow limitation, lung volumes and systemic inflammation in a general population

Although several levels of evidence have suggested an association between systemic inflammation and spirometric lung volumes, data addressing the potential interrelationship between airflow limitation and inflammatory markers are sparse and remain controversial. Potential associations between high-sensitivity C-reactive protein (hsCRP), fibrinogen and lung function were investigated in 1,466 individuals aged 25–85 yrs, representing a general population. Within this cross-sectional population, data on body plethysmography, spirometry, helium dilution and diffusing capacity of the lung for carbon monoxide (DL,CO) were analysed. After adjustment for potential confounding factors, such as smoking, obesity and cardiorespiratory fitness, there was an inverse association of hsCRP with forced expiratory and static lung volumes. In neither apparently healthy nor the entire population was inflammation associated with airflow limitation in central airways. In smokers only, higher hsCRP and fibrinogen were associated with an impaired DL,CO. This study shows that higher levels of hsCRP are associated with decreased lung volumes in a general population over a wide age range. A consistent interrelationship of central airflow limitation and inflammation was not verifiable. Smoking is related to an impaired DL,CO in association with an increase in systemic inflammation.

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.

Inhalative iloprost - pharmacology and clinical application.

Iloprost, as a stable analog of endogenous prostacyclin, has far-reaching pharmacological effects. For several years already it has been used successfully in its intravenous and inhalative forms for treating patients with pulmonary hypertension (PH). Since the development of efficient nebulizers that guarantee a constant output of the effective agent, inhalative iloprost has become an important alternative in the drug treatment of PH. Inhalative iloprost is an effective and safe partner for other classes of substances in combination therapy, which is becoming ever more frequently necessary. In addition, it is also used in the acute testing of pulmonary vasoreactivity and in intensive care therapy of manifest right heart failure.