Effect of acetazolamide on visuomotor performance at high altitude in healthy people 40 years of age or older-RCT.

OBJECTIVE: Altitude travel is increasingly popular also for middle-aged and older tourists and professionals. Due to the sensitivity of the central nervous system to hypoxia, altitude exposure may impair visuomotor performance although this has not been extensively studied. Therefore, we investigated whether a sojourn at moderately high altitude is associated with visuomotor performance impairments in healthy adults, 40y of age or older, and whether this adverse altitude-effect can be prevented by acetazolamide, a drug used to prevent acute mountain sickness. METHODS: In this randomized placebo-controlled parallel-design trial, 59 healthy lowlanders, aged 40-75y, were assigned to acetazolamide (375 mg/day, n = 34) or placebo (n = 25), administered one day before ascent and while staying at high altitude (3100m). Visuomotor performance was assessed at 760m and 3100m after arrival and in the next morning (post-sleep) by a computer-assisted test (Motor-Task-Manager). It quantified deviation of a participant-controlled cursor affected by rotation during target tracking. Primary outcome was the directional error during post-sleep recall of adaptation to rotation estimated by multilevel linear regression modeling. Additionally, adaptation, immediate recall, and correct test execution were evaluated. RESULTS: Compared to 760m, assessments at 3100m with placebo revealed a mean (95%CI) increase in directional error during adaptation and immediate recall by 1.9° (0.2 to 3.5, p = 0.024) and 1.1° (0.4 to 1.8, p = 0.002), respectively. Post-sleep recall remained unchanged (p = NS), however post-sleep correct test execution was 14% less likely (9 to 19, p<0.001). Acetazolamide improved directional error during post-sleep recall by 5.6° (2.6 to 8.6, p<0.001) and post-sleep probability of correct test execution by 36% (30 to 42, p<0.001) compared to placebo. CONCLUSION: In healthy individuals, 40y of age or older, altitude exposure impaired adaptation to and immediate recall and correct execution of a visuomotor task. Preventive acetazolamide treatment improved visuomotor performance after one night at altitude and increased the probability of correct test execution compared to placebo. CLINICALTRIALS.GOV IDENTIFIER: ClinicalTrials.gov NCT03536520.

Effect of altitude and acetazolamide on postural control in healthy lowlanders 40 years of age or older. Randomized, placebo-controlled trial.

Background: Hypoxia and old age impair postural control and may therefore enhance the risk of accidents. We investigated whether acetazolamide, the recommended drug for prevention of acute mountain sickness, may prevent altitude-induced deterioration of postural control in older persons. Methods: In this parallel-design trial, 95 healthy volunteers, 40 years of age or older, living <1,000 m, were randomized to preventive therapy with acetazolamide (375 mg/d) or placebo starting 24 h before and during a 2-day sojourn at 3,100 m. Instability of postural control was quantified by a balance platform with the center of pressure path length (COPL) as primary outcome while pulse oximetry (SpO2) was monitored. Effects of altitude and treatment on COPL were evaluated by ordered logistic regression. www.ClinicalTrials.gov NCT03536429. Results: In participants taking placebo, ascent from 760 m to 3,100 m increased median COPL from 25.8 cm to 27.6 cm (odds ratio 3.80, 95%CI 2.53-5.70) and decreased SpO2 from 96% to 91% (odds ratio 0.0003, 95%CI 0.0002-0.0007); in participants taking acetazolamide, altitude ascent increased COPL from 24.6 cm to 27.3 cm (odds ratio 2.22, 95%CI 1.57-3.13), while SpO2 decreased from 96% to 93% (odds ratio 0.007, 95%CI 0.004-0.012). Altitude-induced increases in COPL were smaller with acetazolamide vs. placebo (odds ratio 0.58, 95%CI 0.34-0.99) while drops in SpO2 were mitigated (odds ratio 19.2, 95%CI 9.9-37.6). Conclusion: In healthy individuals, 40 years of age or older, postural control was impaired after spending a night at 3,100 m. The altitude-induced deterioration of postural control was mitigated by acetazolamide, most likely due to the associated improvement in oxygenation.

Culturally adapted pulmonary rehabilitation for adults living with post-tuberculosis lung disease in Kyrgyzstan: protocol for a randomised controlled trial with blinded outcome measures.

INTRODUCTION: Pulmonary rehabilitation (PR) is a programme of individually prescribed physical exercise, education and self-management activities. PR is recommended in international guidelines for managing chronic obstructive pulmonary disease (COPD) and other chronic respiratory diseases. PR is still under-recognised in tuberculosis (TB) guidelines and PR is not available in many low and middle-income countries and for people with post-TB lung disease (PTBLD). The main aims of the study are to adapt and define a culturally appropriate PR programme in Kyrgyzstan for people living with PTBLD and to test, in a fully powered randomised controlled trial (RCT), the effectiveness of PR in improving exercise capacity for people living with PTBLD. METHODS AND ANALYSIS: The study will be divided into three stages: stage 1: focus group discussions with patients living with PTBLD and interviews with PR referrers will be conducted to explore initial perceptions and inform the cultural adaptation, structure and content of PR. Stage 2a: a single-blind RCT evaluating the effectiveness of a culturally adapted 6-week PR programme on maximal exercise capacity, assessed by the incremental shuttle walking test, before and after PR. Participants will be additionally followed-up 12 weeks postbaseline. Additional outcomes will include health-related quality of life, respiratory symptoms, psychological well-being and physical function. Stage 2b: participants' experience of PR will be collected through interviews and using a log book and a patient evaluation form. Staff delivering PR will be interviewed to explore their experience of delivering the intervention and refining the delivery for future implementation. ETHICS AND DISSEMINATION: The study was approved 22/07/2019 by Ethics Committee National Center for Cardiology and Internal Medicine (reference number 17) and by University of Leicester ethics committee (reference number 22293). Study results will be disseminated through appropriate peer-reviewed journals, national and international respiratory/physiotherapy conferences, social media, and through patient and public involvement events in Kyrgyzstan and in the UK. TRIAL REGISTRATION NUMBER: ISRCTN11122503.

Effect of High-Flow Oxygen on Exercise Performance in COPD Patients. Randomized Trial.

Background: High-flow oxygen therapy (HFOT) provides oxygen-enriched, humidified, and heated air at high flow rates via nasal cannula. It could be an alternative to low-flow oxygen therapy (LFOT) which is commonly used by patients with chronic obstructive pulmonary disease (COPD) during exercise training. Research Question: We evaluated the hypothesis that HFOT improves exercise endurance in COPD patients compared to LFOT. Methods: Patients with stable COPD, FEV1 40-80% predicted, resting pulse oximetry (SpO2) ≥92%, performed two constant-load cycling exercise tests to exhaustion at 75% of maximal work rate on two different days, using LFOT (3 L/min) and HFOT (60 L/min, FiO2 0.45) in randomized order according to a crossover design. Primary outcome was exercise endurance time, further outcomes were SpO2, breath rate and dyspnea. Results: In 79 randomized patients, mean ± SD age 58 ± 9 y, FEV1 63 ± 9% predicted, GOLD grades 2-3, resting PaO2 9.4 ± 1.0 kPa, intention-to-treat analysis revealed an endurance time of 688 ± 463 s with LFOT and 773 ± 471 s with HFOT, mean difference 85 s (95% CI: 7 to 164, P = 0.034), relative increase of 13% (95% CI: 1 to 28). At isotime, patients had lower respiratory rate and higher SpO2 with HFOT. At end-exercise, SpO2 was higher by 2% (95% CI: 2 to 2), and Borg CR10 dyspnea scores were lower by 0.8 points (95% CI: 0.3 to 1.2) compared to LFOT. Interpretation: In mildly hypoxemic patients with COPD, HFOT improved endurance time in association with higher arterial oxygen saturation, reduced respiratory rate and less dyspnea compared to LFOT. Therefore, HFOT is promising for enhancing exercise performance in COPD. Clinical Trial Registration: www.ClinicalTrials.gov, identifier: NCT03955770.