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HIGH ALTITUDE MEDICINE & BIOLOGYVolume 12, Number 1, 2011ª Mary Ann Liebert, Inc.
DOI: 10.1089/ham 2010.1033 Four-Year Prospective Study of Lung Function in Workers in a High Altitude (4000 m) Mine Denis Vinnikov,1 Nurlan Brimkulov,2 and Rupert Redding-Jones1 Vinnikov, Denis, Nurlan Brimkulov, and Rupert Redding-Jones. Four-year prospective study of lung function inworkers in a high altitude (4000 m) mine. High Alt. Med. Biol. 12:XXX–XXX, 2011.—The aim of this study was todetermine if work at high altitude is associated with accelerated lung function decline and if smoking couldfurther accelerate this decline. Subjects working at high altitude (3800 to 4500 m) in a gold mine on shift-rotationbasis 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 Æ 8.6 yr we analyzedannual decline in vital capacity (VC), forced vital capacity (FVC), and forced expiratory volume during the firstsecond (FEV1). VC was reduced by 46.5 mL, FVC by 67.8 mL, and FEV1 by 74.5 mL a year, greater than in AU5 c historical controls. In those having initial FEV1/FVC below 70%, yearly VC decline was 59.4 mL, FEV1 À58.6 mL.
In long-term workers with no initial obstruction, FEV1 declined slower (67.2 vs. 101.3 mL/yr ( p < 0.001); but VCand FVC decline did not differ. Work at high altitude for years may be a factor that accelerates lung functiondecline, and the rate of decline along with confounding factors should be the subject of future studies.
Key Words: spirometry; lung function; intermittent hypoxia; high altitude; mining pressure, low ambient temperature, and low air humidity(Hultgren, 1997; Luks and Swenson, 2007). People working at Kyrgyzstan is a mountainous country with a great altitude are subjected to intermittent hypoxia, but studies of number of constant residents at an altitude exceeding the latter have mainly been made in mountaineers (Powel and 2500 m above sea level. It has one of the greatest burdens of respiratory disease, including chronic respiratory disease The effect of hypoxia on CRD and COPD patients has been (CRD); mortality from CRD is 4 times greater compared with studied widely (Moore et al., 1982; Bedu et al., 1996; Cogo average European deaths (European Respiratory Society, et al., 2004). In Kyrgyzstan there are a few open-pit mines at 2003). It has been demonstrated that, besides other reasons, high altitude, and delivering medical service to people living at high altitude plays a role in higher respiratory working in one of them, we found some accelerated lung morbidity and mortality, and strategies have been proposed aging; however, not many of these people had contact with to fight CRD, as in other high altitude countries (Bousquet et the mine itself. We hypothesized that working at a high alti- al., 2007). Further, residence at high altitude results in higher tude mine could lead to accelerated annual lung function mortality in chronic obstructive pulmonary disease (COPD) decline, and thus aging of lungs. The aim of this study was to patients (Cote et al., 1993); this is meaningful for Kyrgyzstan, detect if work at high altitude is associated with accelerated which has a very high smoking rate for males; standardized lung function decline and if smoking could further accelerate age male prevalence rate is 46.9% (Cote et al., 1993; Tobacco Atlas, 2010). Given the remarkable number of local peopleworking in the mining industry (including gold mining) at high altitude, for these subjects smoking may have a greater potential negative effect, and this becomes a relevant localpublic health issue.
The study was conducted at a high altitude gold mine It has been shown that high altitude has a diverse effect on a operating at 3800 to 4500 m above sea level in the Issykul area subject’s health owing to hypoxia, decrease in barometric of Kyrgyzstan. Mining is performed in an open-pit mine.
1Kumtor Operating Company, Bishkek, Kyrgyzstan.
2Kyrgyz State Medical Academy, Bishkek, Kyrgyzstan.
Except for some occupations, local employees living in the mL increase in FEV1 after bronchodilation, as advised by the Issykul area work 2- or 3-week shifts at altitude and then national guidelines, were classified as asthma and thus unfit descend to their homes for 2 or 3 weeks in either Bishkek to work at high altitude. They are not present in the datasheet.
(780 m) or Issykul (1600 m). Following local legislation, all Quality control was performed by the technician: maximum high altitude workers must undergo annual screening in a visible muscle effort, flow–volume curve shape subsequent specially designated clinic in Bishkek. Apart from clinical analysis, and attainment of maximal PEF. Best curves were examination and specialist counseling, as required by the identified as those having maximal FEV1 þ FVC.
health-care regulations, clinical lab (blood cell count, urine The spirometry datasheet included only prebronchodilator analysis, and biochemistry) and instrument (electrocardiog- raphy, cardiac ultrasonography upon indications, chest X-ray,and office spirometry) investigations were carried out. An- nual screening normally took 2 days.
Initially, 7320 spirometries were analyzed, and only those Smoking status and working history were recorded and patients who had had four complete annual spirometry ses- analyzed afterward. Smoking status was analyzed to distin- sions were included. Patients having three or less spirometries guish between current smokers (smoking daily), former during the observation period were excluded. Reasons for the smokers, and never-smokers. The number of cigarettes missed sessions were vacations, sick leaves, work discontin- smoked and smoking duration are expressed as pack-years.
uation, and the like. Also, all subjects working in other de- Screening is done for both permanent and new employees.
partments of the company, such as the middle-altitude Data for this prospective observational study were collected Balychky and Bishkek offices, were excluded from analyses.
during 4 yr of screening, from August 2005 to August 2009.
Not all variables included had normal distribution; hence, Hence, all permanent employees were ideally screened 4 nonparametric tests were used: a 2 by 2 test for differences times at yearly intervals. During the observation period, 7320 between categorical data when w2 and p were calculated; office spirometries were performed. The overall numbers of otherwise, a Mann–Whitney test. Data are shown as employees varied between 2000 and 2500. In general, people mean Æ SD or as a percent for all the observations in a group.
working at the mine are healthy and fit, with no serious All datasheets were analyzed using NCSS 2001 (PASS 2002) chronic diseases, which would be contraindications to work at and Statistica 7.0 (StatSoft, Tulsa, OK, USA).
high altitude. These contraindications are listed in Order 70 ofthe Ministry of Health of the Kyrgyz Republic dated 2000.
Only local subjects were included. These are either Kyrgyz or Russian ethnic workers in all the different occupations of When patients with irrelevant spirometry reports along open-blast mining: drillers, mine truck drivers, engineers, with those not working at altitude and those having three or mine surveyors, foremen, metalworkers, gold factory opera- less reports were excluded, a group of 842 patients was ob- tors, kitchen workers, cleaners, security staff, and others. Only tained with a total of 3368 spirometry reports. Demographic a very few employees have direct contact with the mine.
characteristics and the smoking status of these subjects are Many others work as engineers in separate and remote buildings, cleaners in a living camp, kitchen staff, and other The group in general had good lung function indexes.
occupations with no physical contact with the mine.
(103.8 Æ 13.5%); FVC: 4.78 Æ 0.84 L (103.8 Æ 13.5%); FEV1:3.81 Æ 0.73 (104.6 Æ 13.2%); PEF: 563 Æ 113 L/min (107.7 Æ 17.6%); FEV1/FVC: 79.9 Æ 7.0% (99.3 Æ 8.2% to predicted Office spirometry was performed with MicroMedical Mi- value), and MEF50: 4.31 Æ 1.41 (88.8 Æ 26.7%). We found no croLab (United Kingdom) at fasting in the morning after at differences in lung function indexes (percent of predicted least 3 h since the last cigarette smoked, with the patient values) in daily smokers compared to never-smokers. When standing, as recommended by the national guidelines on compared to a group of recently employed people entering spirometry (Brimkulov et al., 2005). Because suspected or di- the company and having their first spirometry, those working agnosed bronchial asthma is a contraindication to work at for years had poorer FEV1 (103.9 Æ 13.2% vs. 107.7 Æ 13.0%).
high altitude, there were no subjects with this disease in the Over the 4 yr of the observation period, we observed a company except for one man and one woman, and they were reduction of all lung function indexes in the entire group, except for PEF (which is a marker of good muscle effort In accordance with national guidelines (Brimkulov et al., during forced expiration). VC was reduced from 4.692 to 2005), at least one tidal volume maneuver followed by twovital capacity (VC) maneuvers with reproducibility less than Table 1. Demographic Data and Smoking Status 4% and three forced vital capacity (FVC) maneuvers with reproducibility less than 4% were accomplished. VC, FVC,(FEV1), Tiffeneau index (FEV1 to VC or FVC ratio, whichever is larger), peak expiratory flow (PEF), and maximal instan- taneous forced expiratory flow at 50% FVC (MEF50) were measured. The European Community for Steel and Coal (ECSC) II reference set for all indexes was used, and the actual index ratio to reference reading was calculated. To exclude reversible obstruction, all patients having FEV tion to 70% were subjected to a bronchodilation test with two doses of salbutamol with spacer. Patients having a 15% or 200- LUNG FUNCTION IN WORKERS IN A HIGH ALTITUDE MINE Annual FEV1 and VC decline in the whole group. Data shown as means with 95% confidence intervals.
4.506 L (46.5 mL/yr), FVC from 4.779 to 4.508 L (67.8 mL/yr), from 4.650 to 4.472 L (44.5 mL/yr), FVC from 4.717 to 4.481 L FEV1 from 3.815 to 3.517 L (74.5 mL/yr), and MEF50 from 4.314 (58.9 mL/yr), FEV1 from 3.798 to 3.529 L (67.2 mL/yr), PEF to 3.860 L (113.5 mL/yr). FEV1 declined gradually, but not from 568 to 554 L/min (3 L/yr), and MEF50, 102 mL/yr.
F1 c equally, throughout the observation period (Fig. 1), as did VC.
The opposite group of subjects entering the company at the At baseline, 66 (7.83%) patients in this group had FEV1/ beginning of the current study and not having bronchial ob- FVC below 70% (with all other indicators of good-quality struction had an almost similar lung function decline: VC was maneuver attained, such as high PEF, maximum muscle ef- reduced by 41.5 mL/yr and FVC by 67.3 mL/yr; but FEV1 was fort, and others), 90.9% (n ¼ 60) of which were males. At the reduced much greater in this group (101.3 mL/yr, p < 0.001).
end of the observation, there were 81 (9.6%) patients withsuch a reduction. In those having initial FEV1/FVC below 70% (COPD or other obstructive syndrome), yearly decline in The purpose of our study was to determine if work on a VC was 59.4 mL, and in FEV1 it was 58.6 mL. PEF did not shift-rotation basis at an altitude of 4000 m could lead to sig- change; its decline was 3.2 L. In this group there were 36 nificant changes in lung function, first of all to an accelerated (54.5%) daily smokers in the beginning; however, this number was reduced insignificantly to 27 (40.9%) by the end of ob- prevalence of bronchial obstruction as measured by FEV servation. Number of smoked cigarettes did not change ei- FVC reduction to less than 70%. Bronchial obstruction in our ther. This group of obstructive patients had a longer work subjects was likely to have the same prevalence as in the duration (8.4 Æ 6.0 yr vs. 6.5 Æ 5.1, p < 0.001) compared with general population in other studies (Halbert et al., 2006).
the entire group in the beginning of the study and was older When measured with the use of spirometry, but not based on (45.0 Æ 7.6 vs. 38.9 Æ 8.6 yr, p < 0.001).
subjects’ complaint questionnaires, meta-analysis showed We found no correlation of age, work duration, or body mass index with annual decline in any of the indexes: VC, prevalent in 9.2% (patients’ reported prevalence was 4.9%).
Our subjects were also likely to have the same prevalence of The entire group on study commencement also included obstructive ventilation defect (OVD). When subjects over 39 people who had had their first screening and were entering yr old were screened for OVD in a large study in Poland the company at that moment. We hypothesized that their (11,027 subjects), bronchial obstruction was found in 24.3% decline during the following 4 yr would be different from that (Zielinski and Bednarek, 2001). In that study, 9.6% was the of those already working in intermittent hypoxia for years.
prevalence of only moderate OVD and, in general, obstruction Thus we separated a group of 616 subjects who met both was found to be more prevalent than we had believed.
criteria: (1) at inclusion had already been working at high The obvious limitation of the present study was the use of altitude for a certain number of years, and (2) had FEV1/FVC prebronchodilator spirometry for the analysis. The screening above 70%. In this group we found overall declines for VC procedures and time allowed hampered us from performingbronchodilation in all subjects, and we could perform it onlywith those patients having OVD.
Table 2. FEV1 Decline in Different Categories In population studies of healthy adult never-smokers, FEV1 declined slowly over time (20 to 30 mL/yr), with some ac-celeration with age (Fletcher et al., 1976; Kerstjens et al., 1996; James et al., 2004). In smokers developing chronic obstructive pulmonary disease (COPD), the rate of decline in FEV1 was larger; but after smoking cessation, the decline slowed to the normal rate (Tashkin et al., 1984). A recent TORCH study in which postbronchodilator FEV1 readings were used revealed slower lung function decline (55 mL in a placebo group), and smokers had accelerated decline; but the COPD treatment had Controls are subjects from Busselton Health Surveys from 1966 to 1981 up to 1994 ( James et al., 2005).
an opposite effect (Celli et al., 2008). Different data were obtained in an UPLIFT study with COPD patients: pre- bronchodilator annual FEV1 decline was 37 mL/yr (Decramer Workers at a high altitude gold mine in Kyrgyzstan have et al., 2009), but was also slower than in our patients.
accelerated age-related lung function decline. The greatest In this prospective 4-yr study, we found annual FEV1 de- rate of decline is in new workers just starting their work at the cline was around 70 mL/yr in both smoking and nonsmok- ing patients. To draw scientific conclusions about therelevance of this annual decline, there should be a historical control group in the Kyrgyzstan population, but no studies ofthis kind have ever been conducted. Although not ultimately Authors express their gratitude to the former medical ad- relevant, we have attempted to compare our data on lung visor of Kumtor Operating Company, Dr. Hans LeRoux, for function decline with historical controls; these are the sub- aid in conducting this study. This study would not have been jects of the Busselton Health study ( James et al., 2005). This possible without the help of all the other staff of the medical comparison clearly shows that our subjects have an almost clinic of the company in Bishkek, including doctors and nurses.
double annual lung function decline. We believed that highaltitude itself could be a factor accelerating lung function decline; however, it cannot explain the full range of possible This study was conducted as part of a planned medical mechanisms, among which could be some kind of chronic screening procedure for company employees and was funded inflammation, some cellular mechanisms, and others. It is by the company. The authors have no conflicts of interest or well documented that other exposures at the workplace can lead to an accelerated decline, such as coal mining (Beeckmanet al., 2001) and farming (Dalphin et al., 1996; Iversenand Dahl, 2000), as can hereditary conditions such as a1- antitrypsin deficiency (Seersholm et al., 1995). In manyrelated studies, accelerated decline was associated with self- American Thoracic Society, Standardization of Spirometry, 1994 Update (1995). Am. J. Respir. Crit. Care Med. 152:1107–1136.
Subjects in the current study were not subjected to a pure Bedu M., Giraldo H., Janicot H., Fellmann N., and Coudert J.
intermittent hypoxia, but instead worked in a gold mine, (1996). Interaction between cold and hypoxia on pulmonary where dust could be a contributing factor to their accelerated circulation in COPD. Am. J. Respir. Crit. Care. Med. 153:1242– lung function decline. This is certainly one limitation of the Beeckman L.F., Wang M.L., Petsonk E., and Wagner G. (2001).
study; however, only a very few people working there had Rapid declines in FEV1 and subsequent respiratory symp- contact with the mine itself (mine truck drivers and drillers).
toms, illnesses, and mortality in coal miners in the United Many employees work in service departments and never have States. Am. J. Respir. Crit. Care Med. 163:633–639.
contact with the mine itself, but they have the same lung Bousquet J., Dahl R., and Khaltaev N. (2007). Global alliance function decline indexes as those working in this open-pit against chronic respiratory diseases. Eur. Respir. J. 29:233–239.
mine. Probably, it may be long-term work in conditions of Brimkulov N., Vinnikov D.V., Davletalieva N.E., Nyholm J., intermittent hypoxia that leads to accelerated lung aging.
Uchkempirova B., and Erhola M. (2005). Guidelines on Besides, all employees at the mine strictly follow safety reg- Spirometry for Medicals of Kyrgyzstan. Bishkek, Kyrgyzstan ulations and wear personal protective equipment to minimize Celli B.R., Thomas N.E., Anderson J.A., Ferguson G.T., Jenkins As reported by internal agencies, silicon content in this C.R., Jones P.W., Vestbo J., Knobil K., Yates J.C., and Calverley mine’s dust is very low, and throughout this 4-yr observation P. (2008). Effect of pharmacotherapy on rate of decline of lung we did not have a case of respiratory occupational disease; all function in chronic obstructive pulmonary disease: results this together probably minimizes the role of the mine in lung from the TORCH study. Am. J. Respir. Crit. Care Med.
Data obtained in the current study demonstrate that people Cogo A., Fischer R., and Schoene R. (2004). Respiratory diseases working shifts at high altitude have accelerated lung function and high altitude. High Alt. Med. Biol. 5:435–444.
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compared with new people in the company working for the Decramer M., Celli B., Kesten S., Lystig T., Mehra S., Tashkin first 4 yr. We hypothesize that this accelerated decline of FEV1 D.P., for the UPLIFT investigators. (2009). Effect of tiotropium in new healthy employees is a result of acute stress reaction on outcomes in patients with moderate chronic obstructive and that gradually, with time, annual FEV1 decline will not be pulmonary disease (UPLIFT): a prespecified subgroup analy- so fast. Working at high altitude must be also considered an sis of a randomised controlled trial. Lancet. 9696:1171–1178.
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this exposure on respiratory function, first with respect to age- (2003). European Lung White Book. The First Comprehensive related decline in FEV1. Very few studies have reported an- Survey on Respiratory Health in Europe. European Re- nual ventilation indexes for a decline in people constantly spiratory Journal Ltd., Sheffield, UK.
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Natural History of Chronic Bronchitis and Emphysema: An LUNG FUNCTION IN WORKERS IN A HIGH ALTITUDE MINE Eight Year Study of Early Chronic Obstructive Lung Disease in tization near home? Early respiratory changes after short-term Working Men in London. Oxford University Press, Oxford, UK.
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Ricart A., Casas H., Casas M., Pages T., Palacios L., Rama R., Rodriguez F.A., Viscor G., and Ventura J.L. (2000). Acclima- accepted in final form October 4, 2010.
AUTHOR QUERY FOR HAM-2010-1033-VINNIKOV_1P AU1: Pls.give city name.
AU2: Punctuation thruout this listing OK?AU3: Pls. clarify. 1966 to 1994?AU4: Update, if necessary.
AU5: OK?AU6: How many cigarettes in a pack?AU7: Pls. cite Table 2 in text.
AU8: Pls. cite this ref in text or delete here.

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