Nurlan Brimkulov

Exhaled nitric oxide is reduced upon chronic intermittent hypoxia exposure in well-acclimatized mine workers

The aim of this study was to assess how exhaled nitric oxide (NO) levels in healthy subjects changed upon exposure to intermittent hypoxia at high altitude. Eighty-one healthy subjects with a mean age of 31.8±6.7 years, well acclimatized at altitudes of 3800-4000m above sea level, and employed by a gold-mining company were recruited for the study. Baseline, altitude-corrected partial exhaled NO levels (PE(NO)) were measured in Bishkek, Kyrgyzstan (780m). Measurements were then taken on day 1 of the ascent to the mine, which is located at an altitude of 4000m, on day 3 and finally at the end of the 2- or 3-week shifts. The mean PE(NO) level was 9.49±3.66nmHg in Bishkek and was lower in females than in males (9.76±3.58nmHg vs. 7.03±3.71nmHg). When compared to the first day at altitude, exhaled NO was reduced by 17.2% on day 3 (p=0.001) and 29.6% by the end of the shift (p<0.001). In summary, this study of well-acclimatized high-altitude miners demonstrates that despite the absence of clinical signs of desadaptation, there is an apparent reduction in exhaled NO.

Five-year lung function observations and associations with a smoking ban among healthy miners at high altitude (4000 m).

Objective: To assess the annual lung function decline associated with the reduction of secondhand smoke exposure in a high-altitude industrial workforce. Methods: We performed pulmonary function tests annually among 109 high-altitude gold-mine workers over 5 years of follow-up. The first 3 years included greater likelihood of exposure to secondhand smoke exposure before the initiation of extensive smoking restrictions that came into force in the last 2 years of observation. Results: In repeated measures modeling, taking into account the time elapsed in relation to the smoking ban, there was a 115 ± 9 (standard error) mL per annum decline in lung function before the ban, but a 178 ± 20 (standard error) mL per annum increase afterward (P < 0.001, both slopes). Conclusion: Institution of a workplace smoking ban at high altitude may be beneficial in terms of lung function decline.

High-altitude alpine therapy and lung function in asthma: systematic review and meta-analysis

We used meta-analysis to measure the effect of high-altitude climate therapy (HACT) on lung function outcomes in asthma, and systematically searched PubMed, Embase and www.elibrary.ru for publications appearing from 1970 to mid-2015. We included studies carried out with children or adults with an exposure of up to 12 weeks at an altitude of ≥1500 m above sea level. Changes in forced expiratory volume in 1 s (FEV1), FEV1/vital capacity ratio or peak expiratory flow rate as the HACT intervention outcomes were analysed. We included data for 907 participants (age range 4–58 years) from 21 studies, altogether including 28 substrata based on asthma type or severity. Only three of 21 included studies had high quality, whereas 93% of substudies reported lung function improvement with an overall pooled standardised mean difference (SMD) of 0.53 (95% CI 0.43–0.62). The measured effect of HACT was greater in adults (SMD 0.75, 95% CI 0.63–0.88, n=14) than in children (SMD 0.24, 95% CI 0.09–0.38, n=14). Studies at altitude >2000 m above sea level yielded the same effect as those at lower altitude. Based on a cut-point of a 0.50 change in SMD to define a meaningful clinical difference, HACT appears to have efficacy as an intervention. This extent of benefit appears to be limited to adults with asthma. High-altitude alpine therapy may be an effective intervention to improve lung function in patients with asthma http://ow.ly/u3i23008vU5

Smoking Increases the Risk of Acute Mountain Sickness

OBJECTIVE We aimed to ascertain risk factors for acute mountain sickness (AMS) in miners exposed to chronic intermittent high altitude conditions. METHODS All new hires (2009-2012) for mine employment (4000 m above sea level) were followed up for 12 months after first ascent. Demographics, physiologic data, and cigarette smoking were assessed at preemployment screening. Mine site clinic care for AMS defined incident events. Cox regression analysis estimated risk of AMS associated with smoking and selected covariates. RESULTS There were 46 AMS cases among 569 individuals during the first 12 months of employment. Adjusted for age, sex, and altitude of permanent residence, cigarettes smoked per day before hiring were prospectively associated with AMS (hazard ratio [HR], 1.9; 95% CI, 1.1 to 3.2 per 10 cigarettes smoked). This risk was higher in the subset of workers with less demanding physical work (n=336; HR, 3.3; 95% CI, 1.7 to 6.3), whereas among those with more physically demanding jobs (n=233), smoking was not associated with increased risk (HR, 0.6; 95% CI, 0.1 to 2.3). CONCLUSIONS In workers newly hired to work at high altitude, smoking increases the likelihood of AMS, but this effect appears to be operative only among those with less physically demanding work duties.

Four-Year Prospective Study of Lung Function in Workers in a High Altitude (4000 m) Mine

The aim of this study was to determine if work at high altitude is associated with accelerated lung function decline and if smoking could further accelerate this decline. Subjects working at high altitude (3800 to 4500 m) in a gold mine on shift-rotation basis were included, and 7320 spirometry reports were obtained throughout a 4-yr observation period (2005-2009). Out of 3368 selected reports with acceptable quality, for 842 patients aged 38.9 ± 8.6 yr we analyzed annual decline in vital capacity (VC), forced vital capacity (FVC), and forced expiratory volume during the first second (FEV(1)). VC was reduced by 46.5 mL, FVC by 67.8 mL, and FEV(1) by 74.5 mL a year, greater than in historical controls. In those having initial FEV(1)/FVC below 70%, yearly VC decline was 59.4 mL, FEV(1) -58.6 mL. In long-term workers with no initial obstruction, FEV(1) declined slower (67.2 vs. 101.3 mL/yr (p < 0.001); but VC and FVC decline did not differ. Work at high altitude for years may be a factor that accelerates lung function decline, and the rate of decline along with confounding factors should be the subject of future studies.

Risk factors for occupational acute mountain sickness

BACKGROUND Studies of occupational acute mountain sickness (AMS) have not focused on the more severe end of the spectrum to date. AIMS To examine risk factors associated with the development of occupational AMS severe enough to receive treatment in a compression chamber. METHODS A nested case referent study in a cohort of high-altitude (4000 m) mine workers, comparing cases of severe, chamber-treated AMS to matched referents. Using logistic regression, we tested potential risk factors based on premorbid surveillance examinations, including cigarette smoking (current smoking, smoking intensity and exhaled carbon monoxide [CO]). RESULTS There were 15 cases and 30 controls. In multivariate analysis including age, sex and place of residence, current smoking was associated with increased risk of severe AMS (odds ratio [OR] 10.0; 95% confidence interval [CI] 1.5-67.4), taking into account any prior, less severe AMS event, which was also a potent risk factor (OR 33.3; 95% CI 2.8-390). Smoking intensity (cigarettes per day) and exhaled CO were also statistically significantly associated with severe AMS. CONCLUSIONS Cigarette smoking is a strong, previously under-appreciated risk factor for severe AMS. Because this is a modifiable factor, these findings suggest that workplace-based smoking cessation should be tested as an intervention to prevent such morbidity.

Spirometry reference values for a Kyrgyz population.

Normative data derived from local populations are critical in lung function testing (LFT). The population of Central Asia reflects a heterogeneous mix of races and ethnicities, suggesting that neither standard Caucasian or East Asian reference values may be appropriate to PFT interpretation for this region. To address this question, we assessed the performance of estimating equations for PFT values for a Kyrgyz population. We extracted surveillance lung function data from an occupational screening clinic serving a mining population among whom annual spirometry is required. Lung function testing using standardized procedures and appropriate quality control was carried out in Bishkek, Kyrgyzstan (altitude 700–800 m above sea level [MASL]). Most of those tested traveled to Bishkek from residences in the Lake Issykul valley (altitude 1600 MASL). The workplace site is at 3800 MASL. Spirometric testing (MicroMedical MicroLab device; UK) conformed to Kyrgyz guidelines consistent with international standards for reproducibility. We limited analysis to PFTs of Kyrgyz ethnic employees. We excluded 45 non-Kyrgyz. Potential employees with serious chronic conditions would not be active in workforce: nonetheless, certain conditions may not have precluded employment. We, therefore, excluded otherwise eligible Kyrgyz with confirmed bronchial asthma or COPD (n=58). Both smoking and non-smoking subjects of both sexes were included in the analysis, but only data from never-smokers was used in the derivation of normal predictive equations. The observed forced expiratory value in one second (FEV1), forced vital capacity (FVC), and FEV1/ FVC ratio values for the never smokers were tested in multiple regression models (sex stratified; age and height as independent variables; analyses using NCSS 10 software), to yield predictive equations. Using the examples of a 40year-old 175 cm male and a 40-year old and 160 cm female, we compared our Kyrgyz predicted values and the lower limit of normal (LLN) cut-points to values based on published Global Lung Function Initiative (GLI) European, GLI Northeast Asian (NEA), GLI Southeast Asian (SEA) and Mongolian reference equations. We applied the predicted LLN cut-points for the FEV1/FVC ratio from each predictive formula to categorize the members of our surveillance cohort as meeting or not meeting criteria for an obstructive ventilatory deficit. We included 2076 individuals in the analysis (mean age 38.8± 9.4 years; range 18-64 years; 88% male). Ever smokers were 55% and 11% among men and women, respectively. Among men, the mean observed FEV1/FVC was 76.9% ±6.2%; among women, 78.7%±6.9%. We derived six equations (Table 1) for nonsmoking men (N=821) and women (N=223). Compared to other reference values, the Kyrgyz specific equations yielded substantially higher predicted values for FVC. In contradistinction, the predicted FEV1 values were quite close for the Kyrgyz compared to the other predictive formulae. The LLN of the FEV1/FVC ratio derived for the Kyrgyz formula was closest to the GLI European estimates and differed to the greatest degree from the Mongolian-based cutoffs. Applying the FEV1/FVC ratio LLN values from these four formulae to the actual observations in our complete data set including smokers defined 86 (4%) as having an obstructed ventilatory deficit based on the Kyrgyz predictive value, compared to 285 (14%) for the GLI European; 559 (27%) for the GLI NEA; 660 (32%) for the GLI SEA formulae, and 772 (37%) based on Mongolian data. Ours is first analysis to estimate spirometric reference equations for a Kyrgyz ethnic population. The FVC, in particular, was under-estimated by other formulae, with a net effect that more normal persons would be defined as having airflow obstruction based on a higher predicted LLN for the FEV1/FVC ratio being applied to the Kyrgyz population. This phenomenon was manifest to the greatest degree applying a Mongolian-specific equation to the Kyrgyz population. Mongolian equations have been applied in at least one study to serve as the reference for Kyrgyz and Kazakh data with adequate performance in a small study group. We did not limit the study population on the basis of job duties entailing potential inhalational exposures that might affect lung function. In general, this potential confounding would have led to a decrease in observed lung volumes, which would not explain the larger than predicted FVC that we observed. Ethnicity interacting with altitude may explain our findings. Genetic data indicate that Kyrgyz ethnicity subsumes a mix of Yenisei (South-Siberian) and Turkic tribes. Residence at

Excessive Exposure to Secondhand Tobacco Smoke among Hospitality Workers in Kyrgyzstan

The aim of this study was to assess the levels of secondhand smoke (SHS) exposure of men and women in public places in Kyrgyzstan. This cross-sectional study involved 10 bars and restaurants in Bishkek the capital city of Kyrgyzstan. Smoking was allowed in all establishments. Median (interquartile range) air nicotine concentrations were 6.82 (2.89, 8.86) μg/m3. Employees were asked about their smoking history and exposure to SHS at work. Employees were exposed to SHS for mean (SD) 13.5 (3.6) hours a day and 5.8 (1.4) days a week. Women were exposed to more hours of SHS at work compared to men. Hospitality workers are exposed to excessive amounts of SHS from customers. Legislation to ban smoking in public places including bars and restaurants is urgently needed to protect workers and patrons from the harmful effects of SHS.