Recurrent lower respiratory illnesses among young children in rural Kyrgyzstan:overuse of antibiotics and possible under-diagnosis of asthma. A qualitative FRESH AIR study

Abstract Lower respiratory tract illnesses (LRT-illnesses) in children under 5 years (U5s) are a leading cause of morbidity, hospitalisations and mortality worldwide, particularly in low-income countries. It is pertinent to understand possible inconsistent management. This study explored perceptions and practices among caregivers and health professionals on recurrent LRT-illnesses in U5s. Semi-structured interviews with 13 caregivers to U5s with recurrent LRT-illnesses and with 22 primary care health professional interviews in two rural provinces in Kyrgyzstan were triangulated. Data were thematically analysed. The majority (8/13) of caregivers described their young children as having recurrent coughing, noisy breathing and respiratory distress of whom several had responded positively to acute salbutamol and/or had been repeatedly hospitalised for LRT-illness. Family stress and financial burdens were significant. The health professionals classified young children with recurrent LRT-illnesses primarily with pneumonia and/or a multitude of bronchitis diagnoses. Broad-spectrum antibiotics and supportive medicine were used repeatedly, prescribed by health professionals or purchased un-prescribed by the caregivers at the pharmacy. The health professionals had never applied the asthma diagnosis to U5s nor had they prescribed inhaled steroids, and none of the interviewed caregivers’ U5s were diagnosed with asthma. Health professionals and caregivers shared a common concern for the children’s recurrent respiratory illnesses developing into a severe chronic pulmonary condition, including asthma. In conclusion, the study identified an inconsistent management of LRT-illnesses in U5s, with exorbitant use of antibiotics and an apparently systemic under-diagnosis of asthma/wheeze. When the diagnosis asthma is not used, the illness is not considered as a long-term condition, requiring preventer/controller medication

Prevalence and Economic Burden of Respiratory Diseases in Central Asia and Russia:A Systematic Review

Prevalence data of respiratory diseases (RDs) in Central Asia (CA) and Russia are contrasting. To inform future research needs and assist government and clinical policy on RDs, an up-to-date overview is required. We aimed to review the prevalence and economic burden of RDs in CA and Russia. PubMed and EMBASE databases were searched for studies that reported prevalence and/or economic burden of RDs (asthma, chronic obstructive pulmonary disease (COPD), cystic fibrosis, interstitial lung diseases (ILD), lung cancer, pulmonary hypertension, and tuberculosis (TB)) in CA (Kyrgyzstan, Uzbekistan, Tajikistan, Kazakhstan, and Turkmenistan) and Russia. A total of 25 articles (RD prevalence: 18; economics: 7) were included. The majority (n = 12), mostly from Russia, reported on TB. TB prevalence declined over the last 20 years, to less than 100 per 100,000 across Russia and CA, yet in those, multidrug-resistant tuberculosis (MDR-TB) was alarming high (newly treated: 19-26%, previously treated: 60-70%). COPD, asthma (2-15%) and ILD (0.006%) prevalence was only reported for Russia and Kazakhstan. No studies on cystic fibrosis, lung cancer and pulmonary hypertension were found. TB costs varied between US$400 (Tajikistan) and US$900 (Russia) for drug-susceptible TB to >= US$10,000 for MDR-TB (Russia). Non-TB data were scarce and inconsistent. Especially in CA, more research into the prevalence and burden of RDs is needed.Public Health and primary carePrevention, Population and Disease management (PrePoD

Echocardiography and extravascular lung water during 3 weeks of exposure to high altitude in otherwise healthy asthmatics

Background: Asthma rehabilitation at high altitude is common. Little is known about the acute and subacute cardiopulmonary acclimatization to high altitude in middle-aged asthmatics without other comorbidities.Methods: In this prospective study in lowlander subjects with mostly mild asthma who revealed an asthma control questionnaire score >0.75 and participated in a three-week rehabilitation program, we assessed systolic pulmonary artery pressure (sPAP), cardiac function, and extravascular lung water (EVLW) at 760 m (baseline) by Doppler-echocardiography and on the second (acute) and last day (subacute) at a high altitude clinic in Kyrgyzstan (3100 m).Results: The study included 22 patients (eight male) with a mean age of 44.3 ± 12.4 years, body mass index of 25.8 ± 4.7 kg/m$^{2}$, a forced expiratory volume in 1 s of 92% ± 19% predicted (post-bronchodilator), and partially uncontrolled asthma. sPAP increased from 21.8 mmHg by mean difference by 7.5 [95% confidence interval 3.9 to 10.5] mmHg (p < 0.001) during acute exposure and by 4.8 [1.0 to 8.6] mmHg (p = 0.014) during subacute exposure. The right-ventricular-to-pulmonary-artery coupling expressed by TAPSE/sPAP decreased from 1.1 by −0.2 [−0.3 to −0.1] mm/mmHg (p < 0.001) during acute exposure and by −0.2 [−0.3 to −0.1] mm/mmHg (p = 0.002) during subacute exposure, accordingly. EVLW significantly increased from baseline (1.3 ± 1.8) to acute hypoxia (5.5 ± 3.5, p < 0.001) but showed no difference after 3 weeks (2.0 ± 1.8).Conclusion: In otherwise healthy asthmatics, acute exposure to hypoxia at high altitude increases pulmonary artery pressure (PAP) and EVLW. During subacute exposure, PAP remains increased, but EVLW returns to baseline values, suggesting compensatory mechanisms that contribute to EVLW homeostasis during acclimatization

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

Effect of acetazolamide on pulmonary vascular haemodynamics in patients with COPD going to altitude: a randomised, placebo-controlled, double-blind trial

Background: COPD may predispose to symptomatic pulmonary hypertension at high altitude. We investigated haemodynamic changes in lowlanders with COPD ascending to 3100 m and evaluated whether preventive acetazolamide treatment would attenuate the altitude-induced increase in pulmonary artery pressure (PAP). Methods: In this randomised, placebo-controlled, double-blind, parallel-group trial, patients with COPD Global Initiative for Chronic Obstructive Lung Disease grades 2–3 who were living 92% and arterial carbon dioxide tension <6 kPa were randomised to receive either acetazolamide (125–250 mg·day$^{−1}$) or placebo capsules, starting 24 h before ascent from 760 m and during a 2-day stay at 3100 m. Echocardiography, pulse oximetry and clinical assessments were performed at 760 m and after the first night at 3100 m. Primary outcome was PAP assessed by tricuspid regurgitation pressure gradient (TRPG). Results: 112 patients (68% men, mean±sdage 59±8 years, forced expiratory volume in 1 s (FEV$_{1}$) 61±12% pred,S$_{pO_{2}}$95±2%) were included. Mean±sdTRPG increased from 22±7 to 30±10 mmHg in 54 patients allocated to placebo and from 20±5 to 24±7 mmHg in 58 patients allocated to acetazolamide (both p<0.05) resulting in a mean (95% CI) treatment effect of −5 (−9 to −1) mmHg (p=0.015). In patients assigned to placebo at 760/3100 m, mean±sdS$_{pO_{2}}$was 95±2%/88±3%; in the acetazolamide group, the respective values were 94±2%/90±3% (both p<0.05), resulting in a treatment effect of +2 (1 to 3)% (p=0.001). Conclusions: In lowlanders with COPD travelling to 3100 m, preventive acetazolamide treatment attenuated the altitude-induced rise in PAP and improved oxygenation

Time course of cerebral oxygenation and cerebrovascular reactivity in Kyrgyz highlanders. A five-year prospective cohort study

Introduction: This prospective cohort study assessed the effects of chronic hypoxaemia due to high-altitude residency on the cerebral tissue oxygenation (CTO) and cerebrovascular reactivity.Methods: Highlanders, born, raised, and currently living above 2,500 m, without cardiopulmonary disease, participated in a prospective cohort study from 2012 until 2017. The measurements were performed at 3,250 m. After 20 min of rest in supine position while breathing ambient air (FiO$_{2}$ 0.21) or oxygen (FiO$_{2}$ 1.0) in random order, guided hyperventilation followed under the corresponding gas mixture. Finger pulse oximetry (SpO$_{2}$) and cerebral near-infrared spectroscopy assessing CTO and change in cerebral haemoglobin concentration (cHb), a surrogate of cerebral blood volume changes and cerebrovascular reactivity, were applied. Arterial blood gases were obtained during ambient air breathing.Results: Fifty three highlanders, aged 50 ± 2 years, participated in 2017 and 2012. While breathing air in 2017 vs. 2012, PaO$_{2}$ was reduced, mean ± SE, 7.40 ± 0.13 vs. 7.84 ± 0.13 kPa; heart rate was increased 77 ± 1 vs. 70 ± 1 bpm (p &lt; 0.05) but CTO remained unchanged, 67.2% ± 0.7% vs. 67.4% ± 0.7%. With oxygen, SpO$_{2}$ and CTO increased similarly in 2017 and 2012, by a mean (95% CI) of 8.3% (7.5–9.1) vs. 8.5% (7.7–9.3) in SpO$_{2}$, and 5.5% (4.1–7.0) vs. 4.5% (3.0–6.0) in CTO, respectively. Hyperventilation resulted in less reduction of cHb in 2017 vs. 2012, mean difference (95% CI) in change with air 2.0 U/L (0.3–3.6); with oxygen, 2.1 U/L (0.5–3.7).Conclusion: Within 5 years, CTO in highlanders was preserved despite a decreased PaO$_{2}$. As this was associated with a reduced response of cerebral blood volume to hypocapnia, adaptation of cerebrovascular reactivity might have occurred

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 &lt;800 m, FEV1 ≥40 to &lt;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 &lt; 0.001), during immediate recall by 5.3°, 4.6° to 6.1° (p &lt; 0.001), and post-sleep recall by 5.8°, 5.0 to 6.7° (p &lt; 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 &lt; 0.001) and −3.1° (−4.3° to −2.0°, p &lt; 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

Hypoxia-altitude simulation test to predict altitude-related adverse health effects in COPD patients

Background/aims: Amongst numerous travellers to high altitude (HA) are many with the highly prevalent COPD, who are at particular risk for altitude-related adverse health effects (ARAHE). We then investigated the hypoxia-altitude simulation test (HAST) to predict ARAHE in COPD patients travelling to altitude. Methods: This prospective diagnostic accuracy study included 75 COPD patients: 40 women, age 58±9 years, forced expiratory volume in 1 s (FEV$_{1}$) 40–80% pred, oxygen saturation measured by pulse oximetry (S$_{pO_{2}}$) ≥92% and arterial carbon dioxide tension (P$_{aCO_{2}}$) 30 min or 75% for >15 min) or intercurrent illness was observed. Results: ARAHE occurred in 50 (66%) patients and 23 out of 75 (31%) were positive on HAST according toS$_{pO_{2}}$, and 11 out of 64 (17%) according toP$_{aO_{2}}$. ForS$_{pO_{2}}$/P$_{aO_{2}}$we report a sensitivity of 46/25%, specificity of 84/95%, positive predictive value of 85/92% and negative predictive value of 44/37%. Conclusion: In COPD patients ascending to HA, ARAHE are common. Despite an acceptable positive predictive value of the HAST to predict ARAHE, its clinical use is limited by its insufficient sensitivity and overall accuracy. Counselling COPD patients before altitude travel remains challenging and best focuses on early recognition and treatment of ARAHE with oxygen and descent