Sayaka S. Aeschbacher

Association between sleep apnoea and pulmonary hypertension in Kyrgyz highlanders

This case–control study evaluates a possible association between high altitude pulmonary hypertension (HAPH) and sleep apnoea in people living at high altitude. Ninety highlanders living at altitudes >2500 m without excessive erythrocytosis and with normal spirometry were studied at 3250 m (Aksay, Kyrgyzstan); 34 healthy lowlanders living below 800 m were studied at 760 m (Bishkek, Kyrgyzstan). Echocardiography, polysomnography and other outcomes were assessed. Thirty-six highlanders with elevated mean pulmonary artery pressure (mPAP) >30 mmHg (31–42 mmHg by echocardiography) were designated as HAPH+. Their data were compared to that of 54 healthy highlanders (HH, mPAP 13–28 mmHg) and 34 healthy lowlanders (LL, mPAP 8–24 mmHg). The HAPH+ group (median age 52 years (interquartile range 47–59) had a higher apnoea–hypopnoea index (AHI) of 33.8 events·h−1 (26.9–54.6) and spent a greater percentage of the night-time with an oxygen saturation <90% (T<90; 78% (61–89)) than the HH group (median age 39 years (32–48), AHI 9.0 events·h−1 (3.6–16), T<90 33% (10–69)) and the LL group (median age 40 years (30–47), AHI 4.3 events·h−1 (1.4–12.6), T<90 0% (0–0)); p<0.007 for AHI and T<90, respectively, in HAPH+ versus others. In highlanders, multivariable regression analysis confirmed an independent association between mPAP and both AHI and T<90, when controlled for age, gender and body mass index. Pulmonary hypertension in highlanders is associated with sleep apnoea and hypoxaemia even when adjusted for age, gender and body mass index, suggesting pathophysiologic interactions between pulmonary haemodynamics and sleep apnoea. PH in highland residents is associated with sleep apnoea, suggesting a pathophysiologic interaction http://ow.ly/CQ1k305CQeq

Postural control in lowlanders with COPD travelling to 3100 m; data from a randomized trial evaluating the effect of preventive dexamethasone treatment

Objective: To evaluate the effects of acute exposure to high altitude and preventive dexamethasone treatment on postural control in patients with chronic obstructive pulmonary disease (COPD). Methods: In this randomized, double-blind parallel-group trial, 104 lowlanders with COPD GOLD 1-2 age 20–75 years, living near Bishkek (760 m), were randomized to receive either dexamethasone (2 × 4 mg/day p.o.) or placebo on the day before ascent and during a 2-day sojourn at Tuja-Ashu high altitude clinic (3100 m), Kyrgyzstan. Postural control was assessed with a Wii Balance BoardTM at 760 m and 1 day after arrival at 3100 m. Patients were instructed to stand immobile on both legs with eyes open during five tests of 30 s each, while the center of pressure path length (PL) was measured. Results: With ascent from 760 to 3100 m the PL increased in the placebo group from median (quartiles) 29.2 (25.8; 38.2) to 31.5 (27.3; 39.3) cm (P < 0.05); in the dexamethasone group the corresponding increase from 28.8 (22.8; 34.5) to 29.9 (25.2; 37.0) cm was not significant (P = 0.10). The mean difference (95% CI) between dexamethasone and placebo groups in altitude-induced changes (treatment effect) was -0.3 (-3.2 to 2.5) cm, (P = 0.41). Multivariable regression analysis confirmed a significant increase in PL with higher altitude (coefficient 1.6, 95% CI 0.2 to 3.1, P = 0.031) but no effect of dexamethasone was shown (coefficient -0.2, 95% CI -0.4 to 3.6, P = 0.925), even when controlled for several potential confounders. PL changes were related more to antero-posterior than lateral sway. Twenty-two of 104 patients had an altitude-related increase in the antero-posterior sway velocity of >25%, what has been associated with an increased risk of falls in previous studies. Conclusion: Lowlanders with COPD travelling from 760 to 3100 m revealed postural instability 24 h after arriving at high altitude, and this was not prevented by dexamethasone. Trial Registration: clinicaltrials.gov Identifier: NCT02450968.

Efficacy of Dexamethasone in Preventing Acute Mountain Sickness in COPD Patients: Randomized Trial

Background Patients with COPD may experience acute mountain sickness (AMS) and other altitude‐related adverse health effects (ARAHE) when traveling to high altitudes. This study evaluated whether dexamethasone, a drug used for the prevention of AMS in healthy individuals, would prevent AMS/ARAHE in patients with COPD. Methods This placebo‐controlled, double‐blind, parallel‐design trial included patients with COPD and Global Initiative for Obstructive Lung Disease grade 1 to 2 who were living below 800 m. Patients were randomized to receive dexamethasone (8 mg/d) or placebo starting on the day before ascent and while staying in a high‐altitude clinic at 3,100 m for 2 days. The primary outcome assessed during the altitude sojourn was the combined incidence of AMS/ARAHE, defined as an Environmental Symptoms Questionnaire cerebral score evaluating AMS ≥ 0.7 or ARAHE requiring descent or an intervention. Results In 60 patients randomized to receive dexamethasone (median [quartiles] age: 57 years [50; 60], FEV1 86% predicted [70; 104]; PaO2 at 760 m: 9.6 kPa [9.2; 10.0]), the incidence of AMS/ARAHE was 22% (13 of 60). In 58 patients randomized to receive placebo (age: 60 y [53; 64]; FEV1 94% predicted [76; 103]; PaO2: 10.0 kPa [9.1; 10.5]), the incidence of AMS/ARAHE was 24% (14 of 58) (χ2 statistic vs dexamethasone, P = .749). Dexamethasone mitigated the altitude‐induced PaO2 reduction compared with placebo (mean between‐group difference [95% CI], 0.4 kPa [0.0‐0.8]; P = .028). Conclusions In lowlanders with mild to moderate COPD, the incidence of AMS/ARAHE at 3,100 m was moderate and not reduced by dexamethasone treatment. Based on these findings, dexamethasone cannot be recommended for the prevention of AMS/ARAHE in patients with COPD undertaking high‐altitude travel, although the drug mitigated the altitude‐induced hypoxemia. Trial Registry ClinicalTrials.gov; No.: NCT02450968; URL: www.clinicaltrials.gov.

Right-to-left shunt in COPD at high altitude - randomized, controlled trail with dexamethasone

Objective: To study the prevalence of right-to-left shunts (RLS) in COPD patients traveling to altitude with and without dexamethasone prophylaxis. Methods: Lowlanders with COPD, GOLD 1-2, SpO2 >93%, were randomized to Dexamethasone (4mg, bid) or placebo, starting one day before ascent from 760m and during a 3-day-stay at 3200m. RLS was assessed by saline contrast echocardiography at 760m and after the first night at 3200m by visible bubbles in the left atrium and classified as intracardiac (within 3 cardiac cycles) or intrapulmonary. Results: Of 87 patients (84% male, mean±SD age 57.0±8.8, BMI 25±4 kg/m2, FEV1 89±22%pred, SpO2 95±2%) 39 were assigned to placebo, 48 to dexamethasone. With placebo, 19/39 (49%) had RLS (11 intracardiac); with dexamethasone 23/48 (48%) had RLS (13 intracardiac), p=NS. With altitude, 12 resp. 17 patients with placebo resp. dexamethasone developed new or changed from intrapulmonary to intracardiac RLS, p = 0.018 resp. 0.011, p=NS between groups). The prevalence of RLS at 3200m was 30/39(77%) with placebo and 36/48(75%) with dexamethasone (p= NS). A higher increase in systolic pulmonary artery pressure (SPAP) but not treatment allocation was an independent predictor of new RLS development at 3200m. Independent predictors of SPAP were altitude, dexamethasone, FEV1, age and new/changed RLS. Conclusion: In lowlanders with mild COPD, travelling to 3200m increases the prevalence of RLS and Dexamethasone is not preventive. An increase in SPAP may be a cause or a consequence of RLS at altitude.