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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. [ABSTRACT FROM AUTHOR]

Summary: 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. [ABSTRACT FROM AUTHOR]

Summary: 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 (VO2) 71 ± 16% predicted]. In patients with omalizumab, peakVO2 increased from 13.8 (8.4–21.4) to 16.8 (11.2–23.9) ml/kg/min (p < 0.05), VO2 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 VO2 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. [ABSTRACT FROM AUTHOR]

Abstract: 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 85years 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. [ABSTRACT FROM AUTHOR]

Abstract: Background: Neurotrophins are involved in inflammatory pathways influencing several cells in healthy states and in diseases such as bronchial asthma. Recent studies have shown that nerve growth factor (NGF) is expressed in various non-neuronal cells. Furthermore, little is known about the different origins and regulation of NGF. In the present study, the expression of NGF and its regulation by dexamethasone was investigated in cultured human smooth muscle cells derived from umbilical veins (HSMC) and human iliacal arteries (HISMC). Methods: Vascular smooth muscle cells were prepared. The presence of NGF was demonstrated by APAAP staining, western blotting, ELISA, and reverse transcription polymerase chain reaction. Vascular smooth muscle cells were incubated with dexamethasone, and cells and supernatants were collected for the measurement of NGF. Results: Vascular smooth muscle cells demonstrate mRNA for NGF. Proteins were detectable by western blot, ELISA, and APAAP staining. NGF Protein and mRNA were suppressed after incubation with dexamethasone (0.1 µM) for 48 h in the vascular smooth muscle cells. NGF protein was also detected in cell supernatant and was suppressed by dexamethasone as well. Conclusion: These data indicate that vascular smooth muscle cells are a source of circulating NGF and thus may be involved in inflammatory responses mediated by neurotrophins. The suppression of NGF synthesis by dexamethasone might be a hint of further anti-inflammatory mechanisms of glucocorticoids. [Copyright &y& Elsevier]

Summary: 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 patient''s 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. [Copyright &y& Elsevier]

Abstract: 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. [Copyright &y& Elsevier]