Asthma rehabilitation at high vs. low altitude and its impact on exhaled nitric oxide and sensitization patterns: Randomized parallel-group trial.

BACKGROUND: Allergens and pollution are reduced at high altitude. We investigated the effect of asthma rehabilitation at high altitude (HA, 3100 m) compared to low altitude (LA, 760 m) on exhaled nitric oxide (FeNO) and on specific IgE levels for house dust mites (HDM,d1) and common pollen (sx1). METHODS: For this randomized controlled trial adult asthmatics living <1000 m were randomly assigned to a 3-week in-hospital-rehabilitation (education, physical- and breathing-exercises) at either LA or HA. Changes in FeNO, d1 and sx1 from baseline to end-rehabilitation were measured. RESULTS: 50 asthmatics (34 females) were randomized [mean ± standard deviation LA: n = 25, 44 ± 11 years, total IgE 267 ± 365kU/l; HA: n = 25, 43 ± 13 years, total IgE 350 ± 445kU/l]. FeNO significantly improved at HA from 69 ± 56 ppb at baseline to the first day at altitude 23 ± 19 ppb and remained decreased until end-rehabilitation with 37 ± 23 ppb, mean difference 95%CI -31(-50 to -13, p = 0.001) whereas at LA FeNO did not change. A significant decrease in d1 and sx1 at end-rehabilitation was observed in the LA-group [mean difference 95%CI -10.2 kUA/l (-18.9 to -1.4) for d1 and -4.95 kUA/l(-9.69 to -0.21) for sx1] but not in the HA-group. No significant difference between groups [d1 5.9 kUA/l(-4.2 to 16.2) and sx1 4.4 kUA/l(-3.5 to 12.4)] was found. CONCLUSION: Rehabilitation at HA led to significant FeNO reduction starting from the first day until end-rehabilitation despite unchanged levels of specific IgE. The significant decrease in d1 and sx1 at end-rehabilitation in the LA group might be explained by less HDM in the hospital and/or reduced seasonal pollen, as this decrease was not observed at HA.

Asthma rehabilitation at high vs. low altitude: randomized parallel-group trial.

BACKGROUND: To investigate the effect of asthma rehabilitation at high altitude (3100 m, HA) compared to low altitude (760 m, LA). METHODS: For this randomized parallel-group trial insufficiently controlled asthmatics (Asthma Control Questionnaire (ACQ) > 0.75) were randomly assigned to 3-week in-hospital rehabilitation comprising education, physical-&breathing-exercises at LA or HA. Co-primary outcomes assessed at 760 m were between group changes in peak expiratory flow (PEF)-variability, and ACQ) from baseline to end-rehabilitation and 3 months thereafter. RESULTS: 50 asthmatics were randomized [median (quartiles) LA: ACQ 2.7(1.7;3.2), PEF-variability 19%(14;33); HA: ACQ 2.0(1.6;3.0), PEF-variability 17%(12;32)]. The LA-group improved PEF-variability by median(95%CI) -7%(- 14 to 0, p = 0.033), ACQ - 1.4(- 2.2 to - 0.9, p < 0.001), and after 3 months by - 3%(- 18 to 2, p = 0.103) and - 0.9(- 1.3 to - 0.3, p = 0.002). The HA-group improved PEF-variability by - 10%(- 21 to - 3, p = 0.004), ACQ - 1.1(- 1.3 to - 0.7, p < 0.001), and after 3 months by - 9%(- 10 to - 3, p = 0.003) and - 0.2(- 0.9 to 0.4, p = 0.177). The additive effect of HA vs. LA directly after the rehabilitation on PEF-variability was - 6%(- 14 to 2), on ACQ 0.3(- 0.4 to 1.1) and after 3 months - 5%(- 14 to 5) respectively 0.4(- 0.4 to 1.1), all p = NS. CONCLUSION: Asthma rehabilitation is highly effective in improving asthma control in terms of PEF-variability and symptoms, both at LA and HA similarly. TRIAL REGISTRATION: Clinicaltrials.gov: NCT02741583, Registered April 18, 2016.

Acute hemodynamic changes by breathing hypoxic and hyperoxic gas mixtures in pulmonary arterial and chronic thromboembolic pulmonary hypertension.

BACKGROUND: There is insufficient evidence to counsel patients with pulmonary hypertension undergoing altitude or air travel. We thus aimed to study hemodynamic response of patients with pulmonary arterial or chronic thromboembolic pulmonary hypertension (PAH/CTEPH) during changes in inspiratory oxygen partial pressure. METHODS AND RESULTS: Consecutive patients undergoing right heart catheterization had hemodynamic assessments whilst breathing ambient air (normoxia, FiO2 0.21, at altitude 490 m), nitrogen-enriched air (hypoxia, FiO2 0.16, simulated altitude 2600 m) and oxygen (hyperoxia, FiO2 1.0), each for 10 min. Data from patients with PAH/CTEPH with mean pulmonary artery pressure (mPAP) ≥25 mmHg, pulmonary artery wedge pressure ≤15 mmHg, were compared to data from controls, mPAP <20 mmHg. 28 PAH/CTEPH-patients, 15 women, median age (quartiles) 62y (49;73), mPAP 35 mmHg (31;44), PaO2 7.1 kPa (6.8;9.3) and 16 controls, 12 women, 60y (52;69), mPAP 18 mmHg (16;18), PaO2 9.5 kPa (8.5;10.6) were included. Hypoxia reduced the PaO2 in PAH/CTEPH-patients by median of 2.3 kPa, in controls by 3.3 kPa, difference (95%CI) in change 1.0 (0.02 to 1.9), p < 0.05. Corresponding changes in pulmonary vascular resistance, mPAP and cardiac output were nonsignificant in both groups. Hyperoxia decreased mPAP in PAH/CTEPH-patients by 4 mmHg (2 to 6), in controls by 2 mmHg (0 to 3), difference in change 3 mmHg (0 to 5), p < 0.05. CONCLUSIONS: In patients with PAH/CTEPH, very short-term exposure to moderate hypoxia similar to 2600 m altitude or during commercial air travel did not deteriorate hemodynamics. These results encourage studying the response of PAH/CTEPH during daytrips to the mountain or air travel.