BackgroundThe six-minute walk test (6MWT) is a simple, low tech, safe and well established, self-paced assessment tool to quantify functional exercise capacity in adults. The definition of normal 6MWT in children is especially demanding since not only parameters like height, weight and ethnical background influence the measurement, but may be as crucial as age and the developmental stage. The aim of this study is establishing reference values for the 6MWT in healthy children and adolescents in Switzerland and to investigate the influence of age, anthropometrics, heart rate, blood pressure and physical activity on the distance walked.MethodsChildren and adolescents between 5–17 years performed a 6MWT. Short questionnaire assessments about their health state and physical activities. anthropometrics and vitals were measured before and after a 6-minute walk test and were previously defined as secondary outcomes.ResultsAge, height, weight and the heart rate after the 6MWT all predicted the distance walked according to different regression models: age was the best single predictor and mostly influenced walk distance in younger age, anthropometrics were more important in adolescents and females. Heart rate after the 6MWT was an important distance predictor in addition to age and outreached anthropometrics in the majority of subgroups assessed.ConclusionsThe 6MWT in children and adolescents is feasible and practical. The 6MWT distance depends mainly on age; however, heart rate after the 6MWT, height and weight significantly add information and should be taken into account mainly in adolescents. Reference equations allow predicting 6-minute walk test distance and may help to better assess and compare outcomes in young patients with cardiovascular and respiratory diseases and are highly warranted for different populations.

BackgroundIndividuals with precapillary pulmonary hypertension (PH) experience severely impaired quality of life. A disease-specific outcome measure for PH, the Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR) was developed and validated in the UK and subsequently adapted for use in additional countries. The aim of this study was to translate and assess the reliability and validity of the CAMPHOR for German-speaking populations.MethodsThree main adaptation stages involved; translation (employing bilingual and lay panels), cognitive debriefing interviews with patients and validation (assessment of the adaptation’s psychometric properties). The psychometric evaluation included 107 patients with precapillary PH (60 females; age mean (standard deviation) 60 (15) years) from 3 centres in Austria, Germany and Switzerland.ResultsNo major problems were found with the translation process with most items easily rendered into acceptable German. Participants in the cognitive debriefing interviews found the questionnaires relevant, comprehensive and easy to complete. Psychometric analyses showed that the adaptation was successful. The three CAMPHOR scales (symptoms, activity limitations and quality of life) had excellent test-retest reliability correlations (Symptoms = 0.91; Activity limitations = 0.91; QoL = 0.90) and internal consistency (Symptoms = 0.94; Activity limitations = 0.93; QoL = 0.94). Predicted correlations with the Nottingham Health Profile provided evidence of the construct validity of the CAMPHOR scales. The CAMPHOR adaptation also showed known group validity in its ability to distinguish between participants based on perceived general health, perceived disease severity, oxygen use and NYHA classification.ConclusionsThe CAMPHOR has been shown to be valid and reliable in the German population and is recommend for use in clinical practice.

Background: Pulmonary hypertension (PH) is prognosti- cally important in chronic obstructive pulmonary disease (COPD). Since PH only weakly correlates with hypoxemia, other factors must play a role. Objective: To investigate whether polymorphisms of the serotonin transporter (5HTT), serotonin-2a receptor (5HTR2a) and endothelial nitric oxide synthetase (eNOS) are related to PH in COPD. Methods: In 59 COPD patients who underwent right heart catheterization, 6-min walking distance, NYHA functional class, pulmonary function tests, blood gases and 5HTT, 5HTR2a and eNOS (4ab and T298C) polymorphisms were determined. Results: Forty-nine COPD patients in NYHA functional class III–IV were included. Ten were excluded due to comorbid causes of PH (mainly chronic thromboembolic). PH (mPAP ≧25 mm Hg) was present in 55% and usually mild, but out of proportion (mPAP ≧40 mm Hg) in 12%. Patients with PH had significantly higher frequencies of the 5HTT-L-allele (52%) compared to individuals without PH (36%), and LL homozygote patients had more severe PH. In patients with out-of-proportion PH, the L-allelic frequency was even 75%. We found no association of 5HTR2a and eNOS polymorphism with PH in COPD. Conclusions: In this COPD cohort we confirm that PH is frequent and usually mild, but out of proportion in a subgroup. We found a significant association of the L-allelic variant of 5HTT with PH overall and especially in out-of-proportion PH. These findings may point towards a role of the serotonin system in COPD-PH and warrant further studies.

Background: Antiproliferative strategies have emerged as a potential therapeutic option for pulmonary arterial hypertension (PAH). Objective: To evaluate the long-term efficacy and safety of imatinib. Methods: This is an observational study of 15 patients with idiopathic PAH (n = 13) or PAH associated with connective tissue disease (n = 2) treated off-label with imatinib 400 mg daily. Pulmonary hypertension-specific therapy was established in all patients (triple therapy in 10, dual therapy in 3, and monotherapy in 2 patients). Results: After 6 months, improvement in hemodynamics (p < 0.01), functional class (p = 0.035), and quality of life (p = 0.005) was observed. After a median follow-up of 37 months, there was a sustained improvement in functional class (p = 0.032), quality of life (p = 0.019), and echocardiographic parameters of right ventricular function (p < 0.05). Three patients (20%) presented with completely normal echocardiography, absent tricuspid regurgitation, and normal pro-brain natriuretic peptide levels, indicative of ‘hemodynamic remission'. Of note, however, only 1 case was assessed by invasive hemodynamics. The overall 1- and 3-year survival was 100 and 90%, respectively. Two patients experienced a subdural hematoma (SDH), which in both cases resolved without sequelae. After careful consultation of the potential risks and benefits, all patients as well as a safety cohort of 9 subsequent cases decided to continue the imatinib therapy. After adjusting the target international normalized ratio (INR) to around 2.0, no further cases of SDH occurred during 50 patient-years. Conclusions: Long-term treatment with imatinib may improve the functional class and quality of life. Single cases might even attain hemodynamic remission. The occurrence of 5% SDH per patient-years is concerning. However, adjusting the INR to around 2.0 might obviate this complication.

Abstract:Background: Low bone mineral density (BMD) is common in chronic lung diseases and associated with reduced quality of life. Little is known about BMD in pulmonary hypertension (PH).Methods: Steroid-naïve patients with PH (n=34; 19 idiopathic, 15 chronic thromboembolic) had BMD measured by DXA at the time of diagnostic right heart catheterization. Exercise capacity, quality of life and various parameters related to PH severity and bone metabolism were also assessed. 24 patients with left heart failure (LHF) were similarly assessed as controls.Results: The prevalence of osteopenia was high both in PH (80%) and in controls with LHF (75%). Low BMD was associated with lean body mass, age, lower BMI, impaired exercise capacity and in PH with higher pulmonary vascular resistance. Serum parathyroid hormone (PTH) was elevated and considerably higher in PH than in LHF (above normal, in 55 vs 29%). Secondary hyperparathyroidism was not related to impaired renal function but possibly to low vitamin D status. Conclusions:Osteopenia is common in PH and in chronically ill patients with LHF. Osteopenia is associated with known risk factors but in PH also with disease severity. Preventive measures in an increasingly chronic ill PH population should be considered. Secondary hyperparathyroidism is highly prevalent in PH and might contribute to bone and possibly pulmonary vascular disease. Whether adequate vitamin D substitution could prevent low BMD in PH remains to be determined.