Cohort Profile: Burden of Obstructive Lung Disease (BOLD) study

The Burden of Obstructive Lung Disease (BOLD) study was established to assess the prevalence of chronic airflow obstruction, a key characteristic of chronic obstructive pulmonary disease, and its risk factors in adults (≥40 years) from general populations across the world. The baseline study was conducted between 2003 and 2016, in 41 sites across Africa, Asia, Europe, North America, the Caribbean and Oceania, and collected high-quality pre- and post-bronchodilator spirometry from 28 828 participants. The follow-up study was conducted between 2019 and 2021, in 18 sites across Africa, Asia, Europe and the Caribbean. At baseline, there were in these sites 12 502 participants with high-quality spirometry. A total of 6452 were followed up, with 5936 completing the study core questionnaire. Of these, 4044 also provided high-quality pre- and post-bronchodilator spirometry. On both occasions, the core questionnaire covered information on respiratory symptoms, doctor diagnoses, health care use, medication use and ealth status, as well as potential risk factors. Information on occupation, environmental exposures and diet was also collected

Spirometry in Central Asian lowlanders and highlanders, a population based study

Introduction: The purpose of the study was to establish spirometric reference values for a Central Asian population of highlanders and lowlanders. Methods: Spirometries from a population-based cross-sectional study performed in 2013 in rural areas of Kyrgyzstan were analyzed. Using multivariable linear regression, Global Lung Function Initiative (GLI) equations were fitted separately for men and women, and altitude of residence (700-800 m, 1,900-2,800 m) to data from healthy, never-smoking Kyrgyz adults. The general GLI equation was applied: Predicted value = e a 0 + a 1 × ln ( Height ) + a 2 × ln ( Age ) + b 1 × ln ( Age 100 ) + b 2 × ln ( Age 100 ) 2 + b 3 × ln ( Age 100 ) 3 + b 4 × ln ( Age 100 ) 4 + b 5 × ln ( Age 100 ) 5 Results: Of 2,784 screened Kyrgyz, 448 healthy, non-smoking highlanders (379 females) and 505 lowlanders (368 females), aged 18-91 years, were included. Predicted FVC in Kyrgyz fit best with GLI "North-East Asians," predicted FEV1 fit best with GLI "Other/Mixed." Predicted FEV1/FVC was lower than that of all GLI categories. Age- and sex-adjusted mean FVC and FEV1 were higher in highlanders (+0.138l, +0.132l) than in lowlanders (P < 0.001, all comparisons), but FEV1/FVC was similar. Conclusion: We established prediction equations for an adult Central Asian population indicating that FVC is similar to GLI "North-East Asian" and FEV1/FVC is lower than in all other GLI population categories, consistent with a relatively smaller airway caliber. Central Asian highlanders have significantly greater dynamic lung volumes compared to lowlanders, which may be due to environmental and various other effects

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

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

Clinical Characteristics, Treatment Patterns and Economic Burden of COPD in Kyrgyzstan:A FRESH AIR Study

Background: COPD prevalence and mortality in Kyrgyzstan are high. Data on clinical and economic impact of COPD in Kyrgyzstan are scarce. This study was part of the FRESH AIR research project that focused on prevention, diagnosis and treatment of chronic lung diseases in low-resource settings.Aim: We aimed to evaluate the clinical characteristics, treatment patterns and economic burden of COPD in Kyrgyzstan.Methods: A representative sample of patients with a spirometry-confirmed diagnosis of COPD was included. All patients were registered in one of the five major hospitals in Kyrgyzstan. Patients were surveyed on COPD risk factors, health-care utilization and patient reported outcomes (CCQ, MRC). Associations with high symptom burden (MRC score >= 4) and cost were assessed using logistic regression analyses.Results: A total of 306 patients were included with mean age 62.1 (SD: 11.2), 61.4% being male, mean BMI 26.9 (SD: 5.2) and mean monthly income $85.1 (SD: 75.4). Biomass was used for heating and cooking by 71.2$107) and co-payments ($224, ie, 22$331. We found that only GOLD IV and hypertension were significantly associated with high symptom burden. Exacerbations and hypertension were significantly associated with high cost.Conclusion: The clinical and economic burden of COPD on patients and the government in Kyrgyzstan is considerable. Notably, almost half of interviewed patients were current or exsmokers and biomass exposure was high.Public Health and primary carePrevention, Population and Disease management (PrePoD

Dexamethasone improves pulmonary hemodynamics in COPD-patients going to altitude: A randomized trial

Background Chronic obstructive pulmonary disease (COPD) may predispose to symptomatic pulmonary hypertension at high altitude. We investigated hemodynamic changes in lowlanders with COPD ascending rapidly to 3100 m and evaluated whether preventive dexamethasone treatment would mitigate the altitude-induced increase in pulmonary artery pressure. Methods In this placebo-controlled, double-blind trial, non-hypercapnic COPD patients living <800 m, were randomized to receive either dexamethasone (8 mg/day) or placebo tablets one day before ascent from 760 m and during a 3-day-stay at 3100 m. Echocardiography was performed at 760 m and after the first night at 3100 m. The trans-tricuspid pressure gradient (RV/RA, main outcome), cardiac output (Q) by velocity-time integral of left ventricular outflow, indices of right and left heart function, blood gases and pulse-oximetry (SpO2) were compared between groups. Results 95 patients, 79 men, mean ± SD age 57 ± 8y FEV1 89 ± 21% pred, SpO2 95 ± 2% were included in the analysis. In 52 patients receiving dexamethasone, RV/RA, Q and SpO2 at 760 and 3100 m were 19 ± 5 mm Hg and 26 ± 7 mm Hg, 4.9 ± 0.7 and 5.7 ± 1.1 l/min, SpO2 95 ± 2% and 90 ± 3% (P < 0.05 all changes). In 43 patients receiving placebo the corresponding values were 20 ± 4 mm Hg and 31 ± 9 mm Hg, 4.7 ± 0.9 l/min and 95 ± 3% and 89 ± 3% (P < 0.05 all changes) between group differences of altitude-induced changes were (mean, 95% CI): RV/RA −4.8 (−7.7 to −1.8) mm Hg, Q 0.13 (−0.3 to 0.6) l/min and SpO2 1 (−1 to 2) %. Conclusions In lowlanders with COPD travelling to 3100 m preventive dexamethasone treatment mitigates the altitude-induced rise in RV/RA potentially along with a reduced pulmonary vascular resistance and improved oxygenation. Abbreviation 6MWD six-minute-walking distance BMI body mass index CI confidence interval COPD chronic obstructive pulmonary disease eNOS endothelial NO synthase FAC fractional area change FEV1 forced expiratory volume in 1 s FVC forced vital capacity GOLD global Initiative for Chronic Obstructive Lung Disease HAPE high altitude pulmonary edema HPV hypoxic pulmonary vasoconstriction mPAP mean pulmonary arterial pressure NO nitric oxide PaO2 partial pressure of oxygen in arterial blood PAP pulmonary artery pressure PAWP pulmonary artery wedge pressure PH pulmonary hypertension Q cardiac output RAP right atrial pressure RV right ventricle RV-ESPAR right ventricular end-systolic pressure-area relation sPAP systolic pulmonary artery pressure SpO2 oxygen saturation SV stroke volume TAPSE tricuspid annular plane systolic excursion RV/RA trans-tricuspid or right ventricular to right atrial pressure gradient Keywords COPD Dexamethasone Hypobaric hypoxia Altitude Pulmonary artery pressure Hemodynamic

Postural Control in Lowlanders With COPD Traveling 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 y, living near Bishkek (760 m), were randomized to receive either dexamethasone (2x4 mg/d 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 one 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 -4.0 to 3.6, P=0.925), even when controlled for several potential confounders. PL changes were related more to antero-posterior than lateral sway. 22 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. Conclusions: 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