Medication availability and economic barriers to adherence in asthma and COPD patients in low-resource settings

Inhaled medication is essential to control asthma and COPD, but availability and proper adherence are challenges in low-middle income countries (LMIC). Data on medication availability and adherence in Central Asia are lacking. We aimed to investigate the availability of respiratory medication and the extent of financially driven non-adherence in patients with COPD and asthma in Kyrgyzstan. A cross-sectional study was conducted in two regions of Kyrgyzstan. Patients with a physician- and spirometry confirmed diagnosis of asthma and/or COPD were included. The main outcomes were (1) availability of respiratory medication in hospitals and pharmacies, assessed by a survey, and (2) medication adherence, assessed by the Test of Adherence to Inhalers (TAI). Logistic regression analyses were used to identify predictors for adherence. Of the 300 participants (COPD: 264; asthma: 36), 68.9% were buying respiratory medication out-of-pocket. Of all patients visiting the hospital, almost half reported medication not being available. In pharmacies, this was 8%. Poor adherence prevailed over intermediate and good adherence (80.7% vs. 12.0% and 7.3%, respectively). Deliberate and erratic non-adherence behavior patterns were the most frequent (89.7% and 88.0%), followed by an unconscious non-adherent behavioral pattern (31.3%). In total, 68.3% reported a financial reason as a barrier to proper adherence. Low BMI was the only factor significantly associated with good adherence. In this LMIC population, poor medication availability was common and 80% were poorly adherent. Erratic and deliberate non-adherent behaviors were the most common pattern and financial barriers play a role in over two-thirds of the population.Public Health and primary carePrevention, Population and Disease management (PrePoD

Visuomotor performance at high altitude in COPD patients. Randomized placebo-controlled trial of acetazolamide

Introduction: We evaluated whether exposure to high altitude impairs visuomotor learning in lowlanders with chronic obstructive pulmonary disease (COPD) and whether this can be prevented by acetazolamide treatment.Methods: 45 patients with COPD, living <800 m, FEV1 ≥40 to <80%predicted, were randomized to acetazolamide (375 mg/d) or placebo, administered 24h before and during a 2-day stay in a clinic at 3100 m. Visuomotor performance was evaluated with a validated, computer-assisted test (Motor-Task-Manager) at 760 m above sea level (baseline, before starting the study drug), within 4h after arrival at 3100 m and in the morning after one night at 3100 m. Main outcome was the directional error (DE) of cursor movements controlled by the participant via mouse on a computer screen during a target tracking task. Effects of high altitude and acetazolamide on DE during an adaptation phase, immediate recall and post-sleep recall were evaluated by regression analyses. www.ClinicalTrials.gov NCT03165890.Results: In 22 patients receiving placebo, DE at 3100 m increased during adaptation by mean 2.5°, 95%CI 2.2° to 2.7° (p < 0.001), during immediate recall by 5.3°, 4.6° to 6.1° (p < 0.001), and post-sleep recall by 5.8°, 5.0 to 6.7° (p < 0.001), vs. corresponding values at 760 m. In 23 participants receiving acetazolamide, corresponding DE were reduced by −0.3° (−0.6° to 0.1°, p = 0.120), −2.7° (−3.7° to −1.6°, p < 0.001) and −3.1° (−4.3° to −2.0°, p < 0.001), compared to placebo at 3100 m.Conclusion: Lowlanders with COPD travelling to 3100 m experienced altitude-induced impairments in immediate and post-sleep recall of a visuomotor task. Preventive acetazolamide treatment mitigated these undesirable effects

Acetazolamide to Prevent Adverse Altitude Effects in COPD and Healthy Adults

Background We evaluated the efficacy of acetazolamide in preventing adverse altitude effects in patients with moderate to severe chronic obstructive pulmonary disease (COPD) and in healthy lowlanders 40 years of age or older. Methods Trial 1 was a randomized, double-blind, parallel-design trial in which 176 patients with COPD were treated with acetazolamide capsules (375 mg/day) or placebo, starting 24 hours before staying for 2 days at 3100 m. The mean (±SD) age of participants was 57±9 years, and 34% were women. At 760 m, COPD patients had oxygen saturation measured by pulse oximetry of 92% or greater, arterial partial pressure of carbon dioxide less than 45 mm Hg, and mean forced expiratory volume in 1 second of 63±11% of predicted. The primary outcome in trial 1 was the incidence of the composite end point of altitude-related adverse health effects (ARAHE) at 3100 m. Criteria for ARAHE included acute mountain sickness (AMS) and symptoms or findings relevant to well-being and safety, such as severe hypoxemia, requiring intervention. Trial 2 comprised 345 healthy lowlanders. Their mean age was 53±7 years, and 69% were women. The participants in trial 2 underwent the same protocol as did the patients with COPD in trial 1. The primary outcome in trial 2 was the incidence of AMS assessed at 3100 m by the Lake Louise questionnaire score (the scale of self-assessed symptoms ranges from 0 to 15 points, indicating absent to severe, with 3 or more points including headache, indicating AMS). Results In trial 1 of patients with COPD, 68 of 90 (76%) receiving placebo and 42 of 86 (49%) receiving acetazolamide experienced ARAHE (hazard ratio, 0.54; 95% confidence interval [CI], 0.37 to 0.79; P<0.001). The number needed to treat (NNT) to prevent one case of ARAHE was 4 (95% CI, 3 to 8). In trial 2 of healthy individuals, 54 of 170 (32%) receiving placebo and 38 of 175 (22%) receiving acetazolamide experienced AMS (hazard ratio, 0.48; 95% CI, 0.29 to 0.80; chi-square statistic P=0.035). The NNT to prevent one case of AMS was 10 (95% CI, 5 to 141). No serious adverse events occurred in these trials. Conclusions Preventive treatment with acetazolamide reduced the incidence of adverse altitude effects requiring an intervention in patients with COPD and the incidence of AMS in healthy lowlanders 40 years of age or older during a high-altitude sojourn. (Funded by the Swiss National Science Foundation [Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung], Lunge Zürich, and the Swiss Lung Foundation; ClinicalTrials.gov numbers, NCT03156231 and NCT03561675.

‘Frisse’ berglucht toch niet altijd gezond?

Eerdere onderzoeken naar de relatie tussen hoogte en COPD trokken tegenstrijdige conclusies. Een van de belangrijkste risicofactoren voor COPD wereldwijd namen ze daarbij echter vrijwel niet mee: fijnstof binnenshuis. Daarom vergeleken wij fijnstofconcentraties en COPD-prevalentie binnenshuis tussen hooglanden en laaglanden in Kirgistan. Zowel fijnstof als COPD kwam alarmerend veel voor in de hooglanden. Maar ook in onze lage landen kunnen de fijnstofconcentraties binnenshuis oplopen tot ver boven de aanbevolen waarden, bijvoorbeeld tijdens het koken en openhaardgebruik

Effects and acceptability of implementing improved cookstoves and heaters to reduce household air pollution: a FRESH AIR study

The objective was to evaluate the effectiveness and acceptability of locally tailored implementation of improved cookstoves/heaters in low- and middle-income countries. This interventional implementation study among 649 adults and children living in rural communities in Uganda, Vietnam and Kyrgyzstan, was performed after situational analyses and awareness programmes. Outcomes included household air pollution (PM2.5 and CO), self-reported respiratory symptoms (with CCQ and MRC-breathlessness scale), chest infections, school absence and intervention acceptability. Measurements were conducted at baseline, 2 and 6-12 months after implementing improved cookstoves/heaters. Mean PM2.5 values decrease by 31% (to 95.1 µg/m3) in Uganda (95%CI 71.5-126.6), by 32% (to 31.1 µg/m3) in Vietnam (95%CI 24.5-39.5) and by 65% (to 32.4 µg/m3) in Kyrgyzstan (95%CI 25.7-40.8), but all remain above the WHO guidelines. CO-levels remain below the WHO guidelines. After intervention, symptoms and infections diminish significantly in Uganda and Kyrgyzstan, and to a smaller extent in Vietnam. Quantitative assessment indicates high acceptance of the new cookstoves/heaters. In conclusion, locally tailored implementation of improved cookstoves/heaters is acceptable and has considerable effects on respiratory symptoms and indoor pollution, yet mean PM2.5 levels remain above WHO recommendations.European Union’s Horizon 2020 programme under grant agreement no. 680997, TRIAL ID NTR5759, http://www.trialregister.nl/trialreg/admin/rctsearch.asp?Term=23332. The devices, measuring the personal HAP, were funded by Netherlands Enterprise Agency (RVO

COPD’s early origins in low-and-middle income countries: what are the implications of a false start?

[Excerpt] The Global Initiative for chronic Obstructive Lung disease (GOLD)guideline of 2018 describes COPD as‘the result of a complexinterplay of long-term cumulative exposure to noxious gases andparticles, combined with a variety of host factors includinggenetics, airway hyper-responsiveness and poor lung growthduring childhood’.1Tobacco smoking is traditionally viewed as themain contributing factor to the development of COPD. However,COPD also occurs among non-smokers, especially in low-incomeand middle-income countries (LMICs).2,3Notably, more than 90%of COPD-related deaths occur in LMICs.4For these countries, otherrisk factors, such as ambient, occupational and household airpollution play a significant role in the development of COPD.1,2,5–7Does COPD in these settings have a different pathophysiologicaltrajectory compared to COPD in high-income countries, and if so:what does this imply?In normal lung development, airway branching is completed bythe 17th week of gestation, after which airways increase in volumeuntil young adulthood. Alveoli are present at birth and developfurther during childhood. Lung volume and airflow continue toincrease as the thorax grows, influenced by age, sex, and ethnicity,reaching a peak at young adulthood. Lung function then remainsconstant for about 10 years (the plateau phase), after which itgradually declines.8In the‘classic’COPD patient, the decline inlung function is more rapid than in healthy individuals. However,in a considerable proportion of COPD patients, lung function doesnot decline rapidly, but reaches a lower plateau phase in earlyadulthood instead. For these patients, a completely differentpathophysiological trajectory seems to lead to the diagnosis ofCOPD: the decline in lung function follows a normal pattern, yetthey seem to have a‘false start’by attaining a lower maximumlung function. [...

Indoor pollutions and the prevalence of respiratory symptoms among highlanders in Kyrgyzstan

Public Health and primary carePrevention, Population and Disease management (PrePoD

Pulmonary haemodynamic response to exercise in highlanders versus lowlanders

The aim of the study was to investigate the pulmonary haemodynamic response to exercise in Central Asian high- and lowlanders. This was a cross-sectional study in Central Asian highlanders (living >2500 m) compared with lowlanders (living <800 m), assessing cardiac function, including tricuspid regurgitation pressure gradient (TRPG), cardiac index and tricuspid annular plane systolic excursion (TAPSE) by echocardiography combined with heart rate and oxygen saturation measured by pulse oximetry (SpO2) during submaximal stepwise cycle exercise (10 W increase per 3 min) at their altitude of residence (at 760 m or 3250 m, respectively). 52 highlanders (26 females; aged 47.9±10.7 years; body mass index (BMI) 26.7±4.6 kg·m−2; heart rate 75±11 beats·min−1; SpO2 91±5%;) and 22 lowlanders (eight females; age 42.3±8.0 years; BMI 26.9±4.1 kg·m−2; heart rate 68±7 beats·min−1; SpO2 96±1%) were studied. Highlanders had a lower resting SpO2 compared to lowlanders but change during exercise was similar between groups (highlanders versus lowlanders −1.4±2.9% versus −0.4±1.1%, respectively, p=0.133). Highlanders had a significantly elevated TRPG and exercise-induced increase was significantly higher (13.6±10.5 mmHg versus 6.1±4.8 mmHg, difference 7.5 (2.8 to 12.2) mmHg; p=0.002), whereas cardiac index increase was slightly lower in highlanders (2.02±0.89 L·min−1 versus 1.78±0.61 L·min−1, difference 0.24 (−0.13 to 0.61) L·min−1; p=0.206) resulting in a significantly steeper pressure–flow ratio (ΔTRPG/Δcardiac index) in highlanders 9.4±11.4 WU and lowlanders 3.0±2.4 WU (difference 6.4 (1.4 to 11.3) WU; p=0.012). Right ventricular-arterial coupling (TAPSE/TRPG) was significantly lower in highlanders but no significant difference in change with exercise in between groups was detected (−0.01 (−0.20 to 0.18); p=0.901). In highlanders, chronic exposure to hypoxia leads to higher pulmonary artery pressure and a steeper pressure–flow relation during exercise

Medication availability and economic barriers to adherence in asthma and COPD patients in low-resource settings

Inhaled medication is essential to control asthma and COPD, but availability and proper adherence are challenges in low-middle income countries (LMIC). Data on medication availability and adherence in Central Asia are lacking. We aimed to investigate the availability of respiratory medication and the extent of financially driven non-adherence in patients with COPD and asthma in Kyrgyzstan. A cross-sectional study was conducted in two regions of Kyrgyzstan. Patients with a physician- and spirometry confirmed diagnosis of asthma and/or COPD were included. The main outcomes were (1) availability of respiratory medication in hospitals and pharmacies, assessed by a survey, and (2) medication adherence, assessed by the Test of Adherence to Inhalers (TAI). Logistic regression analyses were used to identify predictors for adherence. Of the 300 participants (COPD: 264; asthma: 36), 68.9% were buying respiratory medication out-of-pocket. Of all patients visiting the hospital, almost half reported medication not being available. In pharmacies, this was 8%. Poor adherence prevailed over intermediate and good adherence (80.7% vs. 12.0% and 7.3%, respectively). Deliberate and erratic non-adherence behavior patterns were the most frequent (89.7% and 88.0%), followed by an unconscious non-adherent behavioral pattern (31.3%). In total, 68.3% reported a financial reason as a barrier to proper adherence. Low BMI was the only factor significantly associated with good adherence. In this LMIC population, poor medication availability was common and 80% were poorly adherent. Erratic and deliberate non-adherent behaviors were the most common pattern and financial barriers play a role in over two-thirds of the population

Effect of Dexamethasone on Nocturnal Oxygenation in Lowlanders With Chronic Obstructive Pulmonary Disease Traveling to 3100 Meters

Importance: During mountain travel, patients with chronic obstructive pulmonary disease (COPD) are at risk of experiencing severe hypoxemia, in particular, during sleep. Objective: To evaluate whether preventive dexamethasone treatment improves nocturnal oxygenation in lowlanders with COPD at 3100 m. Design, Setting, and Participants: A randomized, placebo-controlled, double-blind, parallel trial was performed from May 1 to August 31, 2015, in 118 patients with COPD (forced expiratory volume in the first second of expiration [FEV1] >50% predicted, pulse oximetry at 760 m ≥92%) who were living at altitudes below 800 m. The study was conducted at a university hospital (760 m) and high-altitude clinic (3100 m) in Tuja-Ashu, Kyrgyz Republic. Patients underwent baseline evaluation at 760 m, were taken by bus to the clinic at 3100 m, and remained at the clinic for 2 days and nights. Participants were randomized 1:1 to receive either dexamethasone, 4 mg, orally twice daily or placebo starting 24 hours before ascent and while staying at 3100 m. Data analysis was performed from September 1, 2015, to December 31, 2016. Interventions: Dexamethasone, 4 mg, orally twice daily (dexamethasone total daily dose, 8 mg) or placebo starting 24 hours before ascent and while staying at 3100 m. Main Outcomes and Measures: Difference in altitude-induced change in nocturnal mean oxygen saturation measured by pulse oximetry (Spo2) during night 1 at 3100 m between patients receiving dexamethasone and those receiving placebo was the primary outcome and was analyzed according to the intention-to-treat principle. Other outcomes were apnea/hypopnea index (AHI) (mean number of apneas/hypopneas per hour of time in bed), subjective sleep quality measured by a visual analog scale (range, 0 [extremely bad] to 100 [excellent]), and clinical evaluations. Results: Among the 118 patients included, 18 (15.3%) were women; the median (interquartile range [IQR]) age was 58 (52-63) years; and FEV1 was 91% predicted (IQR, 73%-103%). In 58 patients receiving placebo, median nocturnal Spo2 at 760 m was 92% (IQR, 91%-93%) and AHI was 20.5 events/h (IQR, 12.3-48.1); during night 1 at 3100 m, Spo2 was 84% (IQR, 83%-85%) and AHI was 39.4 events/h (IQR, 19.3-66.2) (P < .001 both comparisons vs 760 m). In 60 patients receiving dexamethasone, Spo2 at 760 m was 92% (IQR, 91%-93%) and AHI was 25.9 events/h (IQR, 16.3-37.1); during night 1 at 3100 m, Spo2 was 86% (IQR, 84%-88%) (P < .001 vs 760 m) and AHI was 24.7 events/h (IQR, 13.2-33.7) (P = .99 vs 760 m). Altitude-induced decreases in Spo2 during night 1 were mitigated by dexamethasone vs placebo by a mean of 3% (95% CI, 2%-3%), and increases in AHI were reduced by 18.7 events/h (95% CI, 12.0-25.3). Similar effects were observed during night 2. Subjective sleep quality was improved with dexamethasone during night 2 by 12% (95% CI, 0%-23%). Sixteen (27.6%) patients using dexamethasone had asymptomatic hyperglycemia. Conclusions and Relevance: In lowlanders in Central Asia with COPD traveling to a high altitude, preventive dexamethasone treatment improved nocturnal oxygen saturation, sleep apnea, and subjective sleep quality