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.

Right Heart Catheterization During Exercise in Patients with COPD-An Overview of Clinical Results and Methodological Aspects.

While right heart catheterization (RHC) at rest is the gold standard to assess pulmonary hemodynamics in patients with chronic obstructive pulmonary disease (COPD) and pulmonary hypertension (PH), the invasive measurement of exercise hemodynamics is less well established in this group. Since exercise hemodynamics are increasingly recognized as important clinical information in patients with PH, our goal was to review the literature in this field to provide a basis for clinical use, further studies, and future recommendations. We identified 69 studies (published since 1968) reporting RHC data in 2819 patients with COPD, of whom 2561 underwent exercise testing. Few studies simultaneously measured gas exchange during exercise. Overall, these studies showed large variations in the patient populations and research questions studied and the methods and definitions employed. Despite these limitations, the data consistently demonstrated the presence of precapillary PH at rest in up to 38% of patients with COPD. With exercise, a relevant proportion of patients developed an abnormal hemodynamic response, depending on the definition used. Furthermore, some studies assessed right ventricular function during exercise and showed a blunted increase in right ventricular ejection fraction. Drug effects and the impact of interventional procedures were also studied. Again, due to large variations in the patients studied and the methods used, firm conclusions are difficult to derive. Despite the limitations of this dataset, several recommendations with respect to technical aspects (body position, exercise protocol, and data acquisition) can be inferred for this challenging patient population and may be helpful for further studies or recommendations.

MR-proADM Predicts Exercise Capacity and Survival Superior to Other Biomarkers in PH.

PURPOSE: Besides the established biomarker NT-proBNP, the new cardiovascular biomarkers MR-proANP, MR-proADM, Copeptin, and CT-proET-1 are promising to evaluate hemodynamics, exercise parameters, and prognosis in patients with pulmonary hypertension (PH). METHODS: 125 consecutive patients with pulmonary arterial hypertension (PAH) or chronic thromboembolic pulmonary hypertension (CTEPH) were prospectively enrolled at five German PH centers. Blood samples were taken during right heart catheterization. The primary study endpoint was the correlation between biomarkers and hemodynamic and exercise parameters. As secondary endpoint, prediction of 1-year mortality was evaluated. RESULTS: MR-proADM showed the strongest correlations with 6MWD and VO2peak, whereas NT-proBNP showed the strongest correlations with PVR, PAPm, and CI. In multivariate analysis, only MR-proADM was independently associated with exercise variables, whereas only NT-proBNP independently predicted hemodynamic parameters. All biomarkers were associated with 1-year survival, with MR-proADM showing the highest C index of 0.78. In multivariate analysis, MR-proADM predicted survival independent of age, 6-MWD, CI, RAP, and NT-proBNP. The cut-off of 1.08 nmol/l provided a sensitivity of 83 % and specificity of 66 %. CONCLUSIONS: Different biomarkers reflect distinctive disease aspects in PH. NT-proBNP best predicts hemodynamic impairment while MR-proADM strongly correlates with exercise capacity. Additionally, MR-proADM represents a promising new marker to evaluate prognosis in patients with PAH and CTEPH. Multi-marker strategies should further be evaluated.

Association of circulating irisin and cardiopulmonary exercise capacity in healthy volunteers: results of the Study of Health in Pomerania.

BACKGROUND: Irisin, a recently discovered myokine, is assumed to be secreted by muscle cells in response to exercise and is involved in the regulation of energy metabolism by browning white adipose tissue cells. However, due to the fact that previous studies revealed conflicting results concerning the association between irisin and exercise, the aim of the present study was to investigate the potential relationship between irisin and exercise capacity in a population-based setting. METHODS: From the population-based Study of Health in Pomerania (SHIP-TREND) 334 men and 406 women with irisin measurements were selected and a standardised symptom limited cardiopulmonary exercise test was used. Exercise capacity was quantified by oxygen uptake at anaerobic threshold (VO2@AT), peak exercise (peakVO2) and maximum power output at peak exertion. In addition, the oxygen pulse was assessed. ANOVA and multivariable linear regression analyses were performed stratified by sex and adjusted for age, weight, height and smoking. RESULTS: In men, we observed inverse associations between irisin serum concentration and exercise capacity assessed by peakVO2 and maximum power output. In contrast, in women a trend towards a positive relationship between irisin and peakVO2 was detected, whereas none of the other parameters showed significant associations with irisin. CONCLUSION: Based on a large population sample, our results did not confirm the previous reported positive linkage between exercise and irisin. Thus the relationship needs further investigation in particular with respect to sex differences.

Tobacco smoke exposure in pulmonary arterial and thromboembolic pulmonary hypertension.

BACKGROUND: Animal studies and data from a single-center study suggest that tobacco smoke exposure may be a risk factor for precapillary pulmonary hypertension (PH). OBJECTIVE: We aimed to survey tobacco smoke exposure in a large PH collective and to compare it with epidemiological data from healthy subjects. METHODS: This is an international, multicenter, case-control study including patients with pulmonary arterial and chronic thromboembolic PH. All patients were asked specific questions about tobacco smoke exposure. Healthy controls were retrieved from the Swiss Health Survey (n = 18,747). RESULTS: Overall (n = 472), 49% of PH patients were smokers and there was a clear sex difference (women 37%, men 71%). Significantly more PH men were smokers compared with healthy controls, whereas less PH women were ever active smokers. However, 50% of the non-smoking PH women were exposed to secondhand smoke, leading to a significantly higher number of tobacco smoke-exposed individuals compared to healthy controls. PH smokers were significantly younger compared to those not exposed. CONCLUSION: Active and environmental tobacco smoke exposure is common in PH. The higher prevalence of male PH smokers, the higher exposure to environmental tobacco smoke in PH women compared to healthy controls and the lower age at PH diagnosis in smokers may indicate a pathogenic role of tobacco smoke exposure in PH.

Spontaneous haemoptysis as a late complication of plombage in a tuberculosis patient.

The endemic spread of tuberculosis after World War II and the deficiency of appropriate antituberculous drugs had led to a renaissance of the surgical tuberculosis therapy until the early 1950s. Late complications of plombage performed decades before are rare and are mainly related to infection and/or migration of the inserted foreign material and are scarcely recognized today. We report on a 73-year-old male patient, who was admitted to the emergency room of our hospital with acute massive haemoptysis for four days. On physical examination the patient presented with decreased breath sounds over the left lung and an old left-sided thoracotomy scar. Radiological findings and bronchoscopy revealed an empyema and a fistula as late complications 53 years after collapse therapy with insertion of a plombage for the treatment of pulmonary tuberculosis. The endobronchial nylon threads in the left bronchial tree and the fistula ending in the left lower bronchus confirmed our diagnosis. The patient was successfully treated by resection of the affected lower lobe. The present casuistic demonstrates a rare cause of spontaneous haemoptysis: late complications after extrapleural pneumolysis and plombage for cavitary tuberculosis over 50 years after the initial operation.

A 10-year follow-up of key gas exchange exercise parameters in a general population: results of the Study of Health in Pomerania.

BACKGROUND: Cardiopulmonary exercise testing (CPET) is a frequently used method for the evaluation of the cardiorespiratory system. The prognostic relevance of the measured parameters is commonly known. Longitudinal data on cardiorespiratory fitness in a large sample of well-characterised healthy volunteers are rare in the literature. METHODS: CPET data of 615 healthy individuals who voluntarily took part in the Study of Health in Pomerania (SHIP) at three different measurement times were analysed. The median observation time was 10.5 years. The age range was 25-85 years. RESULTS: Over the observed timeframe and with increasing age, a decline in maximum power, peak oxygen uptake (V'O2peak) and oxygen uptake at anaerobic threshold (V'O2 @AT) was detectable. This decline was aggravated with increasing age. For the minute ventilation (V'E)/carbon dioxide production (V'CO2 ) slope, an increase was measured in individuals aged ≥50 years only. CONCLUSION: The present study affirms the decrease in aerobic capacity with increasing age in a selected, well-characterised, healthy study sample, which seems to be less pronounced in females.

Predictors of survival after prolonged weaning from mechanical ventilation.

PURPOSE: Weaning from mechanical ventilation is a key component of intensive care treatment; however, this process may be prolonged as some patients require care at specialised centres. Current data indicate that weaning from invasive mechanical ventilation is successful in approximately 65% of patients; however, data on long-term survival after discharge from a weaning centre are limited. MATERIALS AND METHODS: We analysed predictors of survival among 597 patients (392 men, mean age 68 ± 11) post-discharge from a specialised German weaning centre. RESULTS: Complete weaning from mechanical ventilation was achieved in 407 (57.8%) patients, and 106 patients (15.1%) were discharged with non-invasive ventilation; thus, prolonged weaning was successful in 72.9% of the patients. The one-year and five-year survival rates post-discharge were 66.5% and 37.1%, respectively. Age, duration of mechanical ventilation, certain clusters of comorbidities, and discharged with mechanical ventilation significantly influenced survival (p < .001). Completely weaned patients who were discharged with a tracheostomy had a significantly reduced survival rate than did those who were completely weaned and discharged with a closed tracheostomy (p = .004). CONCLUSIONS: The identified predictors of survival after prolonged weaning could support therapeutic strategies during patients' intensive care unit stay. Patients should be closely monitored after discharge from a weaning centre.

Exercise and fluid challenge during right heart catheterisation for evaluation of dyspnoea.

This prospective study compared exercise test and intravenous fluid challenge in a single right heart catheter procedure to detect latent diastolic heart failure in patients with echocardiographic heart failure with preserved ejection function. We included 49 patients (73% female) with heart failure with preserved ejection function and pulmonary artery wedge pressure ≤15 mmHg. A subgroup of 26 patients had precapillary pulmonary hypertension. Invasive haemodynamic and gas exchange parameters were measured at rest, 45° upright position, during exercise, after complete haemodynamic and respiratory recovery in lying position, and after rapid infusion of 500 mL isotonic solution. Most haemodynamic parameters increased at both exercise and intravenous fluid challenge, with the higher increase at exercise. Pulmonary vascular resistance decreased by -0.21 wood units at exercise and -0.56 wood units at intravenous fluid challenge (p = 0.3); 20% (10 of 49) of patients had an increase in pulmonary artery wedge pressure above the upper limit of 20 mmHg at exercise, and 20% above the respective limit of 18 mmHg after intravenous fluid challenge. However, only three patients exceeded the upper limit of pulmonary artery wedge pressure in both tests, i.e. seven patients only at exercise and seven other patients only after intravenous fluid challenge. In the subgroup of pulmonary hypertension patients, only two patients exceeded pulmonary artery wedge pressure limits in both tests, further five patients at exercise and four patients after intravenous fluid challenge. A sequential protocol in the same patient showed a significantly higher increase in haemodynamic parameters at exercise compared to intravenous fluid challenge. Both methods can unmask diastolic dysfunction at right heart catheter procedure, but in different patient groups.

Flow rate variance of a fully implantable pump for the delivery of intravenous treprostinil in pulmonary arterial hypertension.

Implantable infusion pumps might improve the convenience and safety of intravenous treprostinil for pulmonary arterial hypertension. The LENUS Pro® pump (approved in Europe) has a fixed flow rate. Based on 126 pumps and 2853 refills, we retrospectively analyzed the actual flow rate from 09/2010 to 09/2018. A relevant flow rate variance is evident after three years; therefore, flow rate monitoring and dose adjustment are mandatory.

Voriconazole as mono-therapy in orbitofrontal erosive aspergillosis without gross total resection: A case report and review of literature.

In this case report we present an immunocompetent 64-year-old patient presenting with an orbitofrontal invasive aspergillosis treated successfully with voriconazole monotherapy following biopsy and orbital decompression.

Long-term safety and outcome of intravenous treprostinil via an implanted pump in pulmonary hypertension.

BACKGROUND: We examined safety and long-term outcomes of intravenous treprostinil administered via the implantable LENUS Pro pump in patients with severe pulmonary hypertension (PH). METHODS: Patients with PH undergoing pump implantation between December 2009 and October 2016 in German referral centers were retrospectively analyzed (end of follow-up: May 2017). The primary objective was to determine long-term safety of the implantable pump. Secondary end points were 3-year survival and prognostic relevance of pre-implantation hemodynamics. RESULTS: We monitored 129 patients (120 with pulmonary arterial hypertension, 1 with PH due to lung diseases, and 8 with inoperable chronic thromboembolic PH) for 260 patient-years (median follow-up, 19 months; interquartile range, 11-34 months). There were 82 complications/peri-procedural events in 60 patients; of these, 57 were serious adverse events (0.60 per 1,000 treatment-days), including 2 periprocedural deaths due to right heart failure. The incidence of complications related to the pump, catheter, infection, and pump pocket per 1,000 treatment-days was 0.074, 0.264, 0.032 (3 local infections; no bloodstream infections), and 0.380, respectively. Three-year overall and transplant-free survival were 66.5% and 55.7%, respectively (39 patients died; 16 underwent lung transplantation). Baseline cardiac index independently predicted transplant-free survival (multivariate hazard ratio, 1.90; 95% confidence interval, 1.11-3.28; p = 0.019; n = 95). CONCLUSIONS: Our data suggest that intravenous treprostinil via the LENUS Pro pump in advanced PH is associated with a very low risk of bloodstream infections, but other serious adverse events may occur. Therefore, this therapy needs standardization and should be offered in specialized PH centers only. Further technical advances of the pump system and prospective studies are needed.

Impaired peripheral endothelial function in severe idiopathic pulmonary hypertension correlates with the pulmonary vascular response to inhaled iloprost.

BACKGROUND: Pulmonary endothelial function is known to be impaired in subjects with idiopathic pulmonary arterial hypertension (IPAH), but peripheral endothelial dysfunction and its predictive value for pulmonary vasoreactivity have not been previously investigated. METHODS: Measurements of peripheral endothelium-dependent and endothelium-independent vasoreactivity using flow-mediated dilation (FMD) and nitroglycerin-mediated dilation of the brachial artery were performed in 18 patients with severe IPAH (15 women; mean age 50 years [95% confidence interval 46-55 years], mean pulmonary artery pressure [PAP] 51 mm Hg [43-59 mm Hg], pulmonary vascular resistance [PVR] 1239 dyn s cm(-5) [861-1618 dyn s cm(-5)] at baseline) and in 36 age- and sex-matched controls. In patients with IPAH, acute pulmonary vasoreactivity was measured as pulmonary vascular response to inhaled iloprost (PVRII) during pulmonary catheterization. RESULTS: Compared to controls, patients with IPAH demonstrated impaired peripheral endothelial function (FMD, 0.19 [0.07-0.31] vs 0.38 [0.30-0.44] mm among controls; P =.002). No such impairment was observed for nitroglycerin-mediated dilation (0.34 [0.23-0.46] vs 0.36 [0.20-0.51] mm among controls; P = .679). Among patients with IPAH, iloprost lowered mean PAP by 8.2 mm Hg (2.0-14.5 mm Hg) (P = .001) and PVR by 395 dyn s cm(-5) (109-680 dyn s cm(-5)) (P < .001). Subsequent analysis of the association between peripheral endothelial function and PVRII disclosed a correlation of FMD with the percent decrease in mean PAP (r = .65, P = .003) and PVR (r = 0.67, P = .002), in which patients with IPAH with the greatest PVRII also exhibited the highest FMD values. CONCLUSIONS: Idiopathic pulmonary arterial hypertension is associated with peripheral endothelial dysfunction. Peripheral endothelium-dependent vasoreactivity correlates with the PVRII. It remains to be established if FMD has the potential as a clinical tool for noninvasive estimation of pulmonary vasoreactivity in IPAH.

Cardiopulmonary exercise testing for detecting pulmonary arterial hypertension in systemic sclerosis.

OBJECTIVES: Pulmonary arterial hypertension (PAH) is a devastating disease with limited survival and occurs as a frequent complication in patients with systemic sclerosis (SSc). A definite diagnosis of PAH is obtained by right heart catheterisation (RHC); however, the initial suspicion is raised by non-invasive methods. We assessed the diagnostic accuracy of key parameters derived from cardiopulmonary exercise testing (CPET) for detecting and ruling out SSc-associated PAH. METHODS: In a multicentre setting, we prospectively evaluated 173 consecutive patients with SSc without known PAH, but with clinical suspicion of PAH. Each patient underwent CPET and RHC. RESULTS: RHC identified PAH in 48 patients (27.8%), postcapillary pulmonary hypertension (PH) in 10 patients (5.8%) and ruled out PH in 115 patients (66.5%). CPET parameters correlated significantly with pulmonary haemodynamics. PeakVO2 and VE/VCO2 showed highest correlations with pulmonary arterial pressure, transpulmonary pressure gradient and pulmonary vascular resistance. Several parameters showed high sensitivity and specificity for PAH detection by receiver operating characteristic analysis. However, peakVO2 showed highest diagnostic accuracy (sensitivity 87.5%, specificity 74.8% at a threshold level of 13.8 mL/min/kg). A peakVO2 of >18.7 mL/kg/min was reached by 38/173 patients (22%) and excluded PAH in our cohort (negative predictive value 1.0). A nadir VE/VCO2 ratio of >45.5 showed a positive predictive value of 1.0. Diagnostic accuracy was highest in patients with low pulmonary arterial wedge pressure (<12 mm Hg). There were no study-related serious adverse events. CONCLUSIONS: CPET is a safe and valuable method in the non-invasive detection of SSc-associated PAH. It may be particularly beneficial for reducing unnecessary RHC procedures.

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.

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.

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.