<?xml version="1.0" encoding="utf-8"?>
<!DOCTYPE article PUBLIC "-//NLM//DTD Journal Publishing DTD v2.0 20040830//EN" "http://dtd.nlm.nih.gov/publishing/2.0/journalpublishing.dtd">
<article xmlns:xlink="http://www.w3.org/1999/xlink" article-type="research-article" dtd-version="2.0">
  <front>
    <journal-meta>
      <journal-id journal-id-type="publisher-id">ResProt</journal-id>
      <journal-id journal-id-type="nlm-ta">JMIR Res Protoc</journal-id>
      <journal-title>JMIR Research Protocols</journal-title>
      <issn pub-type="epub">1929-0748</issn>
      <publisher>
        <publisher-name>JMIR Publications</publisher-name>
        <publisher-loc>Toronto, Canada</publisher-loc>
      </publisher>
    </journal-meta>
    <article-meta>
    <article-id pub-id-type="publisher-id">v6i7e143</article-id>
    <article-id pub-id-type="pmid">28743683</article-id>
    <article-id pub-id-type="doi">10.2196/resprot.7422</article-id>
    <article-categories>
      <subj-group subj-group-type="heading">
        <subject>Protocol</subject>
      </subj-group>
      <subj-group subj-group-type="article-type">
        <subject>Protocol</subject>
      </subj-group>
    </article-categories>
    <title-group>
      <article-title>Cross-Sectional Study of Chronic Obstructive Pulmonary Disease Prevalence Among Smokers, Ex-Smokers, and Never-Smokers in Almaty, Kazakhstan: Study Protocol</article-title>
    </title-group>
    <contrib-group>
      <contrib contrib-type="editor">
        <name>
          <surname>Eysenbach</surname>
          <given-names>Gunther</given-names>
        </name>
      </contrib>
    </contrib-group>
    <contrib-group>
      <contrib contrib-type="reviewer">
        <name>
          <surname>Pourmalek</surname>
          <given-names>Farshad</given-names>
        </name>
      </contrib>
    </contrib-group>
    <contrib-group>
      <contrib contrib-type="author" id="contrib1">
        <name name-style="western">
          <surname>Sharman</surname>
          <given-names>Almaz</given-names>
        </name>
        <degrees>MD, PhD</degrees>
        <xref rid="aff1" ref-type="aff">1</xref>
        <ext-link ext-link-type="orcid">http://orcid.org/0000-0003-3977-3636</ext-link>
      </contrib>
      <contrib contrib-type="author" id="contrib2" corresp="yes">
      <name name-style="western">
        <surname>Zhussupov</surname>
        <given-names>Baurzhan</given-names>
      </name>
      <degrees>MSc Epi</degrees>
      <xref rid="aff1" ref-type="aff">1</xref>
      <address>
        <institution>Kazakhstan Academy оf Preventive Medicine</institution>
        <addr-line>66 Klochkov St.</addr-line>
        <addr-line>Almaty,</addr-line>
        <country>Kazakhstan</country>
        <phone>7 727 317 88 55</phone>
        <email>baurzhan.zhussupov@gmail.com</email>
      </address>  
      <ext-link ext-link-type="orcid">http://orcid.org/0000-0002-8240-2753</ext-link></contrib>
      <contrib contrib-type="author" id="contrib3">
        <name name-style="western">
          <surname>Sharman</surname>
          <given-names>Dana</given-names>
        </name>
        <degrees>MPH, MD</degrees>
        <xref rid="aff1" ref-type="aff">1</xref>
        <ext-link ext-link-type="orcid">http://orcid.org/0000-0002-6845-4602</ext-link>
      </contrib>
      <contrib contrib-type="author" id="contrib4">
        <name name-style="western">
          <surname>Stambekova</surname>
          <given-names>Assel</given-names>
        </name>
        <degrees>MD</degrees>
        <xref rid="aff1" ref-type="aff">1</xref>
        <ext-link ext-link-type="orcid">http://orcid.org/0000-0003-4014-7368</ext-link>
      </contrib>
      <contrib contrib-type="author" id="contrib5">
        <name name-style="western">
          <surname>Yeraliyev</surname>
          <given-names>Sattar</given-names>
        </name>
        <degrees>MD</degrees>
        <xref rid="aff1" ref-type="aff">1</xref>
        <ext-link ext-link-type="orcid">http://orcid.org/0000-0001-6744-2282</ext-link>
      </contrib>
    </contrib-group>
    <aff id="aff1">
      <sup>1</sup>
      <institution>Kazakhstan Academy оf Preventive Medicine</institution>
      <addr-line>Almaty</addr-line>
      <country>Kazakhstan</country>
    </aff>
    <author-notes>
      <corresp>Corresponding Author: Baurzhan Zhussupov 
      <email>baurzhan.zhussupov@gmail.com</email></corresp>
    </author-notes>
    <pub-date pub-type="collection"><month>07</month><year>2017</year></pub-date>
    <pub-date pub-type="epub">
      <day>25</day>
      <month>07</month>
      <year>2017</year>
    </pub-date>
    <volume>6</volume>
    <issue>7</issue>
    <elocation-id>e143</elocation-id>
    <!--history from ojs - api-xml-->
    <history>
      <date date-type="received">
        <day>27</day>
        <month>1</month>
        <year>2017</year>
      </date>
      <date date-type="rev-request">
        <day>20</day>
        <month>3</month>
        <year>2017</year>
      </date>
      <date date-type="rev-recd">
        <day>16</day>
        <month>5</month>
        <year>2017</year>
      </date>
      <date date-type="accepted">
        <day>23</day>
        <month>5</month>
        <year>2017</year>
      </date>
    </history>
    <!--(c) the authors - correct author names and publication date here if necessary. Date in form ', dd.mm.yyyy' after jmir.org-->
    <copyright-statement>©Almaz Sharman, Baurzhan Zhussupov, Dana Sharman, Assel Stambekova, Sattar Yeraliyev. Originally published in JMIR Research Protocols (http://www.researchprotocols.org), 25.07.2017.</copyright-statement>
    <copyright-year>2017</copyright-year>
    <license license-type="open-access" xlink:href="https://creativecommons.org/licenses/by/4.0/">
      <p>This is an open-access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work, first published in JMIR Research Protocols, is properly cited. The complete bibliographic information, a link to the original publication on http://www.researchprotocols.org, as well as this copyright and license information must be included.</p>
    </license>  
    <self-uri xlink:href="http://www.researchprotocols.org/2017/7/e143/" xlink:type="simple"/>
    <abstract>
      <sec sec-type="background">
        <title>Background</title>
        <p>Chronic obstructive pulmonary disease (COPD) is significantly underdiagnosed in Kazakhstan, and there is no previously conducted study on COPD prevalence in the country.</p>
      </sec>
      <sec sec-type="objective">
        <title>Objective</title>
        <p>The purpose of this study is to assess the prevalence of COPD among individuals aged 40 to 59 years based on results of spirometry before and after bronchodilator, presence of structural changes in the lungs (emphysema, inflammatory changes, and thickening of the walls of the large and small airways) detected by computer tomography, and the symptoms of COPD. The study has 3 study groups: smokers of conventional cigarettes, those who had quit smoking 1 to 5 years ago, and those who haven’t smoked cigarettes.</p>
      </sec>
      <sec sec-type="methods">
        <title>Methods</title>
        <p>This is an observational study with a cross-sectional design among individuals aged 40 to 59 years in Almaty, Kazakhstan. The sample of 900 individuals of both sexes contains 500 smokers, 200 ex-smokers, and 200 never-smokers. Study measures include spirometry, chest computed tomography, electrocardiography, physical exams, laboratory testing of serum, anthropometry, and 6-minute walk test. Data are collected by computer-assisted personal interviewing with tablets. The questionnaire was designed to explore possible COPD risk factors including history of smoking, current smoking, level of smoking exposure (in pack-years), passive smoking, occupational and environmental hazards, and covariates: age, gender, ethnicity, education, occupation, and self-reported morbidity. COPD Assessment Test (CAT) is used to collect information about COPD symptoms.</p>
      </sec>
      <sec sec-type="results">
        <title>Results</title>
        <p>We have completed the participant recruitment and study procedures. Currently, we are working on data processing and data analysis. The authors anticipate the preliminary results should be available by September 2017. Study results will be published in peer-reviewed scientific journals.</p>
      </sec>
      <sec sec-type="conclusions">
        <title>Conclusions</title>
        <p>This is the first study in Kazakhstan that assesses prevalence of COPD and its comorbidities in the adult population aged 40 to 59 years. The results of the study will be useful for improving COPD preventive measures, better COPD screening, identification, and registration. Findings of the study will also contribute to global knowledge on the epidemiology of COPD.</p>
      </sec>
      <sec sec-type="Trial Registration">
        <title>Trial Registration</title>
        <p>ClinicalTrials.gov NCT02926534; https://clinicaltrials.gov/ct2/show/NCT02926534 (Archived by WebCite at http://www.webcitation.org/6rjwGsPOZ)</p>
      </sec>
    </abstract>
    <kwd-group>
      <kwd>COPD</kwd>
      <kwd>Kazakhstan</kwd>
      <kwd>cross-sectional</kwd>
      <kwd>study protocol</kwd>
      <kwd>tobacco smoking, risk factors</kwd>
    </kwd-group></article-meta>
  </front>
  <body>
    <sec sec-type="introduction">
      <title>Introduction</title>
      <p>Chronic obstructive pulmonary disease (COPD) is the fourth leading cause of death worldwide [<xref ref-type="bibr" rid="ref1">1</xref>]. The number of affected individuals and deaths from COPD are expected to increase as the population ages [<xref ref-type="bibr" rid="ref2">2</xref>]. In Russia, the largest neighboring country of Kazakhstan, the prevalence of symptomatic COPD in the adult population was estimated to be 15.3% [<xref ref-type="bibr" rid="ref3">3</xref>]. An estimated 1.4 million individuals in Kazakhstan may be affected by COPD. This estimate is based on studies that have been conducted in other countries in the World Health Organization European Region [<xref ref-type="bibr" rid="ref4">4</xref>] but not in Kazakhstan, because a study on the prevalence of COPD has not been conducted in the country yet. COPD is significantly underdiagnosed in Kazakhstan. In 2013, the rate of reported COPD cases was 315.9 per 100,000 or around 53,000 registered cases of COPD [<xref ref-type="bibr" rid="ref5">5</xref>]. A better understanding of the epidemiology and social and other determinants of the disease is needed in order to recognize the true magnitude of the problem and develop effective treatments and prevention strategies.</p>
      <p>Various criteria for COPD have been used in population-based studies. The most common criterion is airflow obstruction detected by spirometry testing, defined as a postbronchodilator ratio of forced expiratory volume in 1 second (FEV<sub>1</sub>) to forced vital capacity (FVC) less than 0.7 or 70% [<xref ref-type="bibr" rid="ref6">6</xref>]. This criterion is simple to implement and widely used in epidemiological surveys. However, COPD prevalence based on this could be slightly biased—overestimated in old subjects and underestimated in younger ones [<xref ref-type="bibr" rid="ref7">7</xref>]. For this reason, the fifth percentile of the FEV<sub>1</sub>/FVC ratio or the lower limit of normal distribution of the FEV<sub>1</sub>/FVC ratio defined for specific age-gender group is also recommended for use in epidemiological studies [<xref ref-type="bibr" rid="ref8">8</xref>].</p>
      <p>Respiratory symptoms [<xref ref-type="bibr" rid="ref9">9</xref>] and physical examination [<xref ref-type="bibr" rid="ref10">10</xref>] were frequently used to evaluate COPD prevalence. However, collecting such data is more important for establishing the clinical diagnosis of COPD [<xref ref-type="bibr" rid="ref6">6</xref>]. The specific symptoms of COPD include progressive dyspnea, cough, and sputum production [<xref ref-type="bibr" rid="ref6">6</xref>]. The COPD Assessment Test (CAT) was specially designed to measure how COPD symptoms lead to health status impairment. The test is derived from 8 items, and the score varies from 0 to 40. The cut-off point for the CAT is 10, after which regular treatment for symptoms is recommended [<xref ref-type="bibr" rid="ref6">6</xref>]. Although a physical examination is rarely used in COPD diagnosis, particularly in detecting mild to moderate COPD, thoracic examination of patients with severe disease can usually reveal the following signs: hyperinflation, wheezing, diffusely decreased breath sounds, hyperresonance on percussion, and prolonged expiration [<xref ref-type="bibr" rid="ref11">11</xref>].</p>
      <p>Chest computed tomography (CT) scan is recommended for subjects with airflow limitation and signs and symptoms suggestive of COPD for making an accurate diagnosis of COPD to exclude other conditions [<xref ref-type="bibr" rid="ref12">12</xref>]. CT scan also helps to separate COPD patients into 2 main phenotypes, emphysema and small airway disease [<xref ref-type="bibr" rid="ref13">13</xref>]. CT images can be visually assessed by qualified observers to describe patterns of altered lung structure or quantified for assessment of the extent of emphysema, gas trapping, and airway abnormality [<xref ref-type="bibr" rid="ref14">14</xref>]. Some studies suggested that severity of emphysema detected by CT scan is associated with greater lung function decline even if airway obstruction is not currently presented [<xref ref-type="bibr" rid="ref15">15</xref>,<xref ref-type="bibr" rid="ref16">16</xref>]. As a result, CT-detected emphysema may predict future development of airflow obstruction [<xref ref-type="bibr" rid="ref16">16</xref>,<xref ref-type="bibr" rid="ref17">17</xref>].</p>
      <p>Tobacco smoking, occupational and environmental exposures including workplace dusts and chemicals, and smoke from home cooking and heating fuels are the main risk factors for COPD [<xref ref-type="bibr" rid="ref8">8</xref>]. In addition, advanced age, chronic respiratory infections such as tuberculosis, low socioeconomic status, and being underweight may influence COPD development [<xref ref-type="bibr" rid="ref18">18</xref>,<xref ref-type="bibr" rid="ref19">19</xref>]. Genetic predisposition also plays an important role in COPD development. Originally described more than 50 years ago, α<sub>1</sub>-antitrypsin deficiency may cause COPD and accounts for 1% to 2% of all COPD cases. There are other genome variants currently being investigated as candidates for COPD genes, but only the Z variant of α<sub>1</sub>-antitrypsin is accepted as a COPD gene at the present time [<xref ref-type="bibr" rid="ref20">20</xref>].</p>
      <p>Comorbidities are frequently found in persons with COPD. Some of them have risk factors, which are the same as for COPD, particularly tobacco smoking and aging. Moreover, systemic inflammation and chronic hypoxia present in COPD patients may cause other health-related conditions. Common comorbidities include heart disease, lung cancer, osteoporosis, metabolic syndrome and diabetes, anemia, anxiety, cognitive decline, and sleep disorders [<xref ref-type="bibr" rid="ref21">21</xref>,<xref ref-type="bibr" rid="ref22">22</xref>]. Specific comorbidities increase mortality and poor outcome in COPD, so management of main comorbidities has been included to COPD guidelines [<xref ref-type="bibr" rid="ref6">6</xref>].</p>
      <p>The aim of the study is to assess the prevalence of COPD among smokers, ex-smokers, and never-smokers aged 40 to 59 years based on pulmonary function assessment (spirometry), structural changes (emphysema and large and small airway inflammation with thickening) identified by high-resolution CT, COPD symptoms, and exercise limitations. In addition, the study objectives include comparing the prevalence of health conditions considered as COPD comorbidities (heart disease, hypertension, metabolic syndrome, diabetes mellitus) in 3 study groups and their interaction with COPD.</p>
    </sec>
    <sec sec-type="methods">
      <title>Methods</title>
      <sec>
        <title>Study Design</title>
        <p>This is an observational study with a cross-sectional design to assess the prevalence of COPD in Almaty, Kazakhstan, among individuals aged 40 to 59 years based on results of spirometry, the presence of structural changes in the lungs, and symptoms of COPD.</p>
        <p>The study population is 3 groups of male and female residents of Almaty, the largest city in Kazakhstan, with a population of 1.7 million people, 9% of whom are aged 40 to 59 years. Members of the first group include current smokers with more than a 10 pack-year history of smoking (smokers). The second group comprises individuals who quit smoking from 1 to 5 years ago and have more than a 10 pack-year history of smoking (ex-smokers). The third group comprises persons who have never smoked regularly (ie, smoked less than 100 cigarettes in their lifetime) (never-smokers).</p>
        <p>We recruited individuals who are 40 years of age or older because most people are at least 40 years old when the symptoms of COPD first appear [<xref ref-type="bibr" rid="ref23">23</xref>]. The same age limit is selected for many COPD prevalence studies [<xref ref-type="bibr" rid="ref24">24</xref>-<xref ref-type="bibr" rid="ref26">26</xref>]. The upper age was set at 59 years to avoid survival bias [<xref ref-type="bibr" rid="ref27">27</xref>] possibly leading to underestimating the effects of risk factors on COPD. We have taken into account that the life expectancy at birth among males was only 66 years in Kazakhstan in 2015 [<xref ref-type="bibr" rid="ref28">28</xref>].</p>
      </sec>
      <sec>
        <title>Inclusion and Exclusion Criteria</title>
        <p>Male and female participants aged 40 to 59 years who have a 10 pack-year and more of smoking history (for smokers and ex-smokers) or fewer than 100 cigarettes in their lifetime (for never-smokers) and are able to provide informed consent can be included in this study.</p>
        <p>Exclusion criteria:</p>
        <list list-type="bullet">
          <list-item>
            <p>Pregnancy</p>
          </list-item>
          <list-item>
            <p>Fever (37°C or higher) at the time of the visit or during the 2 weeks preceding the visit</p>
          </list-item>
          <list-item>
            <p>Legally incapable</p>
          </list-item>
          <list-item>
            <p>Chronic infectious and noninfectious lung disease except asthma (eg, pulmonary fibrosis, bronchiectasis, cystic fibrosis, tuberculosis)</p>
          </list-item>
          <list-item>
            <p>Resection of at least one lobe (or performing procedures to reduce lung volume)</p>
          </list-item>
          <list-item>
            <p>Any cancer; receiving a course of radiation or chemotherapy at the time of the visit</p>
          </list-item>
          <list-item>
            <p>Suspected lung cancer (presence of significant lung neoplasm)</p>
          </list-item>
          <list-item>
            <p>Presence of metal in the chest</p>
          </list-item>
          <list-item>
            <p>Ophthalmic surgery within the last 12 months prior to the visit</p>
          </list-item>
          <list-item>
            <p>Myocardial infarction or other form of acute or chronic coronary insufficiency or cardiac arrhythmia diagnosed at least 6 months prior to the visit</p>
          </list-item>
          <list-item>
            <p>Myocardial infarction or other form of acute or chronic coronary insufficiency or cardiac arrhythmia for which an individual regularly receives medication</p>
          </list-item>
          <list-item>
            <p>Severely elevated blood pressure (equal to or greater than a systolic 180 or diastolic of 100)</p>
          </list-item>
          <list-item>
            <p>History of cerebrovascular accident</p>
          </list-item>
          <list-item>
            <p>Thoracic or abdominal surgery within the last 6 months</p>
          </list-item>
          <list-item>
            <p>Contraindications to use salbutamol or its analogs</p>
          </list-item>
          <list-item>
            <p>CT scan or other research using ionizing radiation within the last 6 months</p>
          </list-item>
        </list>
      </sec>
      <sec>
        <title>Sampling</title>
        <p>According to the Burden of Obstructive Lung Disease (BOLD) protocol, a minimal sample size of 600 is recommended to achieve an acceptable level of precision for estimating COPD prevalence [<xref ref-type="bibr" rid="ref29">29</xref>]. Our goal is for a sample size of 900 including 500 smokers, 200 ex-smokers, and 200 never-smokers. We have used the National Health and Nutrition Examination Surveys data to assume COPD prevalence in these 3 groups [<xref ref-type="bibr" rid="ref30">30</xref>]. The sample size of 500 allows for achieving the precision of 3.5% with the expected prevalence of obstructive impairment of 20%. The sample size of 200 and the expected prevalence of pulmonary obstruction of 10% and 2% among ex-smokers and never-smokers, respectively, provides sample estimates with 4.2% and 1.9% precision, respectively [<xref ref-type="bibr" rid="ref31">31</xref>].</p>
        <p>The 3 study groups are planned to have the same gender and age distribution by implementing age-gender quota to eliminate age and gender potential confounding effect to the associations between smoking status and outcomes.</p>
        <p>It was shown that the sample characteristics depend on recruitment method used [<xref ref-type="bibr" rid="ref32">32</xref>]. To recruit study participants, active and passive approaches are used. Participants are recruited by using personal networks of investigators and persons who are already participating in the study (snowball), placing an advertisement of the study in social media (Facebook) targeting those individuals who are potentially eligible to participate (live in Almaty, specific age group), and meeting with the owners and managerial staff of several large companies located in Almaty to explain the benefits of participation in the study. Employees of these companies who are potentially eligible to participate in the study are contacted by phone calls.</p>
      </sec>
      <sec>
        <title>Study Procedures</title>
        <p>The study flow is shown in  <xref ref-type="fig" rid="figure1">Figure 1</xref>. Participants are expected to attend 2 to 3 visits for the study, for a total of about 3 hours. Completing study procedures for each participant, including sharing the study results with the participant, is expected to take up to 2 weeks.</p>
        <fig id="figure1" position="float">
          <label>Figure 1</label>
          <caption>
            <p>Patient recruitment, enrollment, and data collection and sharing.</p>
          </caption>
          <graphic xlink:href="resprot_v6i7e143_fig1.jpg" alt-version="no" mimetype="image" position="float" xlink:type="simple"/>
        </fig>
        <sec>
          <title>Spirometry</title>
          <p>Spirometry is performed by trained investigators, with 3 technically satisfactory maneuvers performed by each study participant. The largest value of FEV<sub>1</sub> and the respective value FVC are selected to calculate ratio of FEV<sub>1</sub> to FVC. The CardioTouch 3000-S (BiTech Medical Corp), a 12-lead resting electrocardiogram (ECG) machine with a spirometer with a measuring accuracy that complies with American Thoracic Society requirements [<xref ref-type="bibr" rid="ref33">33</xref>], is used to perform lung function tests. Calibration of the spirometer was performed every day before using it. A 3-L syringe was pumped through to check that accuracy did not exceed a tolerance of 3% [<xref ref-type="bibr" rid="ref33">33</xref>].</p>
        </sec>
        <sec>
          <title>Computed Tomography</title>
          <p>Study subjects undergo 64-channel CT scans of the chest (Philips Brilliance CT 64). Subjects with restrictive (FEV<sub>1</sub>/FVC from 70% to 80%) and obstructive (FEV<sub>1</sub>/FVC less than 70%) lung diseases or signs and symptoms of COPD found during the physical examination and survey undergo inspiratory-expiratory CT scans obtained at the following settings: detector collimation 0.6-0.75 mm, 0.625-0.9 mm reconstructed slice thickness, 0.45-0.625 mm slice interval, 120 kV, 200 (inspiratory) and 50 (expiratory) mAs. Other subjects have only inspiratory CT scans: 0.8 mm reconstructed slice thickness, 0.4 mm slice interval, smooth reconstruction algorithm iDose 7, matrix size 512×512, range = –500 to 1500, 120 kV, 40 mAs [<xref ref-type="bibr" rid="ref34">34</xref>].</p>
          <p>CT scans are evaluated by 3 independent qualified observers to produce semiquantified measures that characterize the extent of emphysema, severity of bronchial dilatation, traction bronchiectasis, bronchial wall thickening, and small airway disease. We use the Bhala scoring system [<xref ref-type="bibr" rid="ref35">35</xref>] modified by Tulek at al [<xref ref-type="bibr" rid="ref36">36</xref>]. The kappa test will be used to evaluate interrater reliability of visual CT scan analysis. The median score by 3 observers will be recorded for each participant.</p>
        </sec>
        <sec>
          <title>Electrocardiography</title>
          <p>A standard 12-lead ECG is performed with the CardioTouch 3000-S for each study subject by employing strictly standardized procedures. Research staff members were trained to properly place electrodes. At least 4 cardiac cycles are taken from each of 12 leads. The machine runs at 50 mm/sec. The following ECG parameters are evaluated by a trained clinical researcher: waves and complexes, presence and description of ECG abnormalities including pathologic q-waves, ST elevation, ST depression, T-wave inversion, hypertrophy, QRS axis deviation, block, and arrhythmia. ECGs were visually inspected for technical errors and were interpreted by a qualified cardiologist. The prevalence of specific ECG abnormalities as well as grouped abnormalities will be reported for each study group. Associations between COPD and ECG abnormalities, crude and adjusted by sex, age, and smoking status, will be measured and presented.</p>
        </sec>
        <sec>
          <title>Physical Exam</title>
          <p>Clinical investigators were trained to conduct the pulmonary (percussion and inspection) exam and technique for listening to second heart sounds. Two Stanford Medicine 25 modules were used as study materials in hands-on sessions [<xref ref-type="bibr" rid="ref37">37</xref>,<xref ref-type="bibr" rid="ref38">38</xref>]. The prevalence of individual pathological findings will be presented for each study group. Associations between pathological findings from 2 exams and COPD will be evaluated.</p>
        </sec>
        <sec>
          <title>Anthropometry</title>
          <p>Anthropometry measures include height, weight, waist circumference, heart rate, blood pressure, and pulse oximetry.</p>
        </sec>
        <sec>
          <title>Six-Minute Walk Test</title>
          <p>All study subjects will take a 6-minute walk test to evaluate functional exercise capacity. Investigators assess whether contraindication exists or not. Absolute contraindications are unstable angina and myocardial infarction during the previous month. Relative contraindications are blood pressure more than 180/100 mm Hg and a resting heart rate of more than 120 beats per minute [<xref ref-type="bibr" rid="ref39">39</xref>]. Subjects with any of the contraindications are referred to the clinical coordinator for a decision about the conduct of the test. Posttest dyspnea is measured using the Borg scale [<xref ref-type="bibr" rid="ref40">40</xref>].</p>
        </sec>
        <sec>
          <title>Laboratory Data</title>
          <p>Serum from each participant is tested for blood cholesterol level, high-density lipoprotein (HDL), low-density lipoprotein (LDL)), triglycerides, C-reactive protein, fibrinogen, glucose, hepatitis B and C IgM and IgG antigens and antibodies, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) liver enzymes, and α<sub>1</sub>-antitrypsin.</p>
        </sec>
        <sec>
          <title>Questionnaire</title>
          <p>The questionnaire was designed to collect data on possible COPD risk factors including history of smoking; current smoking; level of smoking exposure (in pack-year); passive smoking; and occupational and environmental hazards including dusts, chemicals, and indoor fuel pollution. The questionnaire contains the following covariates: age, gender, ethnicity, education, occupation, and self-reported morbidity. CAT is used to collect Information about COPD symptoms. The test was designed and validated for use in routine clinical practice to evaluate the health status of patients with COPD [<xref ref-type="bibr" rid="ref41">41</xref>]. Computer-assisted personal interviewing (CAPI) with tablets has been implemented to collect, store, and transmit data related to a personal survey interview.</p>
          <p>The questionnaire was piloted by interviewing 7 testers—3 smokers, 2 ex-smokers, and 2 never-smokers. After completing pilot interviews, the testers were asked to answer specific questions and then provide comments and suggestions on the whole questionnaire. The questions that were not clear enough were identified and have been improved.</p>
        </sec>
      </sec>
      <sec>
        <title>Statistical Analysis</title>
        <p>Data from all CAPI devices will be exported to one database, and R version 3.3.1 (The R Foundation) will be used for data analysis. Descriptive analyses will be performed using mean, median, interquartile interval, and standard deviation for quantitative variables and frequency tables for categorical variables. Depending on the nature of outcome and exposure variables, type of data distribution, and the sample size, bivariate comparisons will be made by the following tests: chi-square test, Fisher’s exact test, analysis of variance, <italic>t</italic> test, and the Mann-Whitney test.</p>
        <p>A multivariable analysis (generalized linear models) will be conducted to control for confounding. Presence of effect modification/interaction terms will be explored. An alpha &#60;.05 will be considered significant. To construct the optimal model, backward elimination will be used. The full models will contain all independent effects and some important interactions. Mediators (variables that lie on the causal pathway between exposure and outcome) will not be included in the model. To avoid multicollinearity, we will examine the tolerance for each independent variable. If the tolerance value is less than 0.1, we will omit a variable from the analysis. The optimal model will be defined based on the Akaike Information Criterion. Model diagnostic plots will be generated to test model assumptions (eg, normality of deviance residuals).</p>
      </sec>
      <sec>
        <title>Ethics Approval</title>
        <p>The National Central Ethics Committee under the Ministry of Health and Social Development in the Republic of Kazakhstan approved this study on August 19, 2016. The study has been registered at ClinicalTrials.gov [NCT02926534].</p>
      </sec>
    </sec>
    <sec sec-type="results">
      <title>Results</title>
      <p>We have completed the participant recruitment and study procedures. Currently, we are working on data processing and data analysis. The authors anticipate the preliminary results should be available by September 2017. Study results will be published in peer-reviewed scientific journals.</p>
    </sec>
    <sec sec-type="discussion">
      <title>Discussion</title>
      <p>To the best of our knowledge, this is the first study in Kazakhstan that assesses COPD prevalence in the general population aged 40 to 59 years, specifically smokers, ex-smokers, and never-smokers. The study also aims to investigate COPD comorbidities and their interaction with COPD. Improving COPD preventive measures, COPD screening, identification, and registration requires obtaining this epidemiological information. Study strengths include its relatively large sample size and collection of comprehensive medical, behavioral, and other health-related data from each study participant.</p>
      <p>However, there remain some limitations. First, the study is observational. Thus, the possibility of unidentified or unmeasured confounders exists. We are going to conduct the sensitivity analysis to assess a covariate that could eliminate the effect of smoking on COPD. Second, the study is cross-sectional, and the time when COPD occurred cannot be identified. The values of potential confounders measured in the study could differ from ones when symptoms of COPD first appeared and could be diagnosed. As a result, causal inferences cannot be made. Third, the study includes many components to be measured, which makes it impossible to employ probability sampling to select participants. The main risk of nonprobability sampling is that the distribution of important covariates in the sample will differ significantly from their distribution in the study population. We employ quota sampling to set quotas for gender and age, 2 important covariates for COPD, to balance them in the sample. In addition, we measure all known important covariates or confounders to make the desired adjustments in our data analysis. Fourth, the study is conducted in one city, Almaty, which reduces the generalizability of the study results to the country population. Finally, we expect some measurement bias that arises from errors in the data collection. For example, participants could avoid socially undesirable answers. To reduce the latter bias, all data collection procedures were tested and the research staff members were trained.</p>
    </sec>
  </body>
  <back>
    <glossary>
      <title>Abbreviations</title>
      <def-list>
        <def-item>
          <term id="abb1">BOLD</term>
          <def>
            <p>Burden of Obstructive Lung Disease</p>
          </def>
        </def-item>
        <def-item>
          <term id="abb2">CAT</term>
          <def>
            <p>COPD Assessment Test</p>
          </def>
        </def-item>
        <def-item>
          <term id="abb3">CAPI</term>
          <def>
            <p>computer-assisted personal interviewing</p>
          </def>
        </def-item>
        <def-item>
          <term id="abb4">COPD</term>
          <def>
            <p>chronic obstructive pulmonary disease</p>
          </def>
        </def-item>
        <def-item>
          <term id="abb5">CT</term>
          <def>
            <p>computed tomography</p>
          </def>
        </def-item>
        <def-item>
          <term id="abb6">ECG</term>
          <def>
            <p>electrocardiogram</p>
          </def>
        </def-item>
        <def-item>
          <term id="abb7">FEV1</term>
          <def>
            <p>forced expiratory volume in 1 second</p>
          </def>
        </def-item>
        <def-item>
          <term id="abb8">FVC</term>
          <def>
            <p>forced vital capacity</p>
          </def>
        </def-item>
      </def-list>
    </glossary>
    <ack>
      <p>This study is supported with resources and the use of facilities at Kazakhstan Academy оf Preventive Medicine, the HealthCity Clinic, and Synergy Group Kazakhstan. The project is partially funded by a grant from Philip Morris International (IIS.PMI.2016.001). This funder had no role in collection, analysis, or interpretation of data or in writing the manuscript.</p>
    </ack>
    <fn-group>
      <fn fn-type="con">
        <p>The study was designed by AS, DS, and BZ. AS and BZ drafted the manuscript. All authors critically revised the manuscript. All authors read and approved the final manuscript.</p>
      </fn>
      <fn fn-type="conflict">
        <p>None declared.</p>
      </fn>
    </fn-group>
    <ref-list>
      <ref id="ref1">
        <label>1</label>
        <nlm-citation citation-type="journal">
        <person-group person-group-type="author">
          <name name-style="western">
            <surname>Lozano</surname>
            <given-names>R</given-names>
          </name>
          <name name-style="western">
            <surname>Naghavi</surname>
            <given-names>M</given-names>
          </name>
          <name name-style="western">
            <surname>Foreman</surname>
            <given-names>K</given-names>
          </name>
          <name name-style="western">
            <surname>Lim</surname>
            <given-names>S</given-names>
          </name>
          <name name-style="western">
            <surname>Shibuya</surname>
            <given-names>K</given-names>
          </name>
          <name name-style="western">
            <surname>Aboyans</surname>
            <given-names>V</given-names>
          </name>
          <name name-style="western">
            <surname>Abraham</surname>
            <given-names>J</given-names>
          </name>
          <name name-style="western">
            <surname>Adair</surname>
            <given-names>T</given-names>
          </name>
          <name name-style="western">
            <surname>Aggarwal</surname>
            <given-names>R</given-names>
          </name>
          <name name-style="western">
            <surname>Ahn</surname>
            <given-names>SY</given-names>
          </name>
          <name name-style="western">
            <surname>Alvarado</surname>
            <given-names>M</given-names>
          </name>
          <name name-style="western">
            <surname>Anderson</surname>
            <given-names>HR</given-names>
          </name>
          <name name-style="western">
            <surname>Anderson</surname>
            <given-names>LM</given-names>
          </name>
          <name name-style="western">
            <surname>Andrews</surname>
            <given-names>KG</given-names>
          </name>
          <name name-style="western">
            <surname>Atkinson</surname>
            <given-names>C</given-names>
          </name>
          <name name-style="western">
            <surname>Baddour</surname>
            <given-names>LM</given-names>
          </name>
          <name name-style="western">
            <surname>Barker-Collo</surname>
            <given-names>S</given-names>
          </name>
          <name name-style="western">
            <surname>Bartels</surname>
            <given-names>DH</given-names>
          </name>
          <name name-style="western">
            <surname>Bell</surname>
            <given-names>ML</given-names>
          </name>
          <name name-style="western">
            <surname>Benjamin</surname>
            <given-names>EJ</given-names>
          </name>
          <name name-style="western">
            <surname>Bennett</surname>
            <given-names>D</given-names>
          </name>
          <name name-style="western">
            <surname>Bhalla</surname>
            <given-names>K</given-names>
          </name>
          <name name-style="western">
            <surname>Bikbov</surname>
            <given-names>B</given-names>
          </name>
          <name name-style="western">
            <surname>Bin</surname>
            <given-names>AA</given-names>
          </name>
          <name name-style="western">
            <surname>Birbeck</surname>
            <given-names>G</given-names>
          </name>
          <name name-style="western">
            <surname>Blyth</surname>
            <given-names>F</given-names>
          </name>
          <name name-style="western">
            <surname>Bolliger</surname>
            <given-names>I</given-names>
          </name>
          <name name-style="western">
            <surname>Boufous</surname>
            <given-names>S</given-names>
          </name>
          <name name-style="western">
            <surname>Bucello</surname>
            <given-names>C</given-names>
          </name>
          <name name-style="western">
            <surname>Burch</surname>
            <given-names>M</given-names>
          </name>
          <name name-style="western">
            <surname>Burney</surname>
            <given-names>P</given-names>
          </name>
          <name name-style="western">
            <surname>Carapetis</surname>
            <given-names>J</given-names>
          </name>
          <name name-style="western">
            <surname>Chen</surname>
            <given-names>H</given-names>
          </name>
          <name name-style="western">
            <surname>Chou</surname>
            <given-names>D</given-names>
          </name>
          <name name-style="western">
            <surname>Chugh</surname>
            <given-names>SS</given-names>
          </name>
          <name name-style="western">
            <surname>Coffeng</surname>
            <given-names>LE</given-names>
          </name>
          <name name-style="western">
            <surname>Colan</surname>
            <given-names>SD</given-names>
          </name>
          <name name-style="western">
            <surname>Colquhoun</surname>
            <given-names>S</given-names>
          </name>
          <name name-style="western">
            <surname>Colson</surname>
            <given-names>KE</given-names>
          </name>
          <name name-style="western">
            <surname>Condon</surname>
            <given-names>J</given-names>
          </name>
          <name name-style="western">
            <surname>Connor</surname>
            <given-names>MD</given-names>
          </name>
          <name name-style="western">
            <surname>Cooper</surname>
            <given-names>LT</given-names>
          </name>
          <name name-style="western">
            <surname>Corriere</surname>
            <given-names>M</given-names>
          </name>
          <name name-style="western">
            <surname>Cortinovis</surname>
            <given-names>M</given-names>
          </name>
          <name name-style="western">
            <surname>Couser</surname>
            <given-names>W</given-names>
          </name>
          <name name-style="western">
            <surname>Cowie</surname>
            <given-names>BC</given-names>
          </name>
          <name name-style="western">
            <surname>Criqui</surname>
            <given-names>MH</given-names>
          </name>
          <name name-style="western">
            <surname>Cross</surname>
            <given-names>M</given-names>
          </name>
          <name name-style="western">
            <surname>Dabhadkar</surname>
            <given-names>KC</given-names>
          </name>
          <name name-style="western">
            <surname>Dahodwala</surname>
            <given-names>N</given-names>
          </name>
          <name name-style="western">
            <surname>Degenhardt</surname>
            <given-names>L</given-names>
          </name>
          <name name-style="western">
            <surname>Delossantos</surname>
            <given-names>A</given-names>
          </name>
          <name name-style="western">
            <surname>Denenberg</surname>
            <given-names>J</given-names>
          </name>
          <name name-style="western">
            <surname>Dharmaratne</surname>
            <given-names>SD</given-names>
          </name>
          <name name-style="western">
            <surname>Dorsey</surname>
            <given-names>ER</given-names>
          </name>
          <name name-style="western">
            <surname>Driscoll</surname>
            <given-names>T</given-names>
          </name>
          <name name-style="western">
            <surname>Duber</surname>
            <given-names>H</given-names>
          </name>
          <name name-style="western">
            <surname>Ebel</surname>
            <given-names>B</given-names>
          </name>
          <name name-style="western">
            <surname>Erwin</surname>
            <given-names>PJ</given-names>
          </name>
          <name name-style="western">
            <surname>Espindola</surname>
            <given-names>P</given-names>
          </name>
          <name name-style="western">
            <surname>Ezzati</surname>
            <given-names>M</given-names>
          </name>
          <name name-style="western">
            <surname>Feigin</surname>
            <given-names>V</given-names>
          </name>
          <name name-style="western">
            <surname>Flaxman</surname>
            <given-names>AD</given-names>
          </name>
          <name name-style="western">
            <surname>Forouzanfar</surname>
            <given-names>MH</given-names>
          </name>
          <name name-style="western">
            <surname>Fowkes</surname>
            <given-names>FGR</given-names>
          </name>
          <name name-style="western">
            <surname>Franklin</surname>
            <given-names>R</given-names>
          </name>
          <name name-style="western">
            <surname>Fransen</surname>
            <given-names>M</given-names>
          </name>
          <name name-style="western">
            <surname>Freeman</surname>
            <given-names>MK</given-names>
          </name>
          <name name-style="western">
            <surname>Gabriel</surname>
            <given-names>SE</given-names>
          </name>
          <name name-style="western">
            <surname>Gakidou</surname>
            <given-names>E</given-names>
          </name>
          <name name-style="western">
            <surname>Gaspari</surname>
            <given-names>F</given-names>
          </name>
          <name name-style="western">
            <surname>Gillum</surname>
            <given-names>RF</given-names>
          </name>
          <name name-style="western">
            <surname>Gonzalez-Medina</surname>
            <given-names>D</given-names>
          </name>
          <name name-style="western">
            <surname>Halasa</surname>
            <given-names>YA</given-names>
          </name>
          <name name-style="western">
            <surname>Haring</surname>
            <given-names>D</given-names>
          </name>
          <name name-style="western">
            <surname>Harrison</surname>
            <given-names>JE</given-names>
          </name>
          <name name-style="western">
            <surname>Havmoeller</surname>
            <given-names>R</given-names>
          </name>
          <name name-style="western">
            <surname>Hay</surname>
            <given-names>RJ</given-names>
          </name>
          <name name-style="western">
            <surname>Hoen</surname>
            <given-names>B</given-names>
          </name>
          <name name-style="western">
            <surname>Hotez</surname>
            <given-names>PJ</given-names>
          </name>
          <name name-style="western">
            <surname>Hoy</surname>
            <given-names>D</given-names>
          </name>
          <name name-style="western">
            <surname>Jacobsen</surname>
            <given-names>KH</given-names>
          </name>
          <name name-style="western">
            <surname>James</surname>
            <given-names>SL</given-names>
          </name>
          <name name-style="western">
            <surname>Jasrasaria</surname>
            <given-names>R</given-names>
          </name>
          <name name-style="western">
            <surname>Jayaraman</surname>
            <given-names>S</given-names>
          </name>
          <name name-style="western">
            <surname>Johns</surname>
            <given-names>N</given-names>
          </name>
          <name name-style="western">
            <surname>Karthikeyan</surname>
            <given-names>G</given-names>
          </name>
          <name name-style="western">
            <surname>Kassebaum</surname>
            <given-names>N</given-names>
          </name>
          <name name-style="western">
            <surname>Keren</surname>
            <given-names>A</given-names>
          </name>
          <name name-style="western">
            <surname>Khoo</surname>
            <given-names>J</given-names>
          </name>
          <name name-style="western">
            <surname>Knowlton</surname>
            <given-names>LM</given-names>
          </name>
          <name name-style="western">
            <surname>Kobusingye</surname>
            <given-names>O</given-names>
          </name>
          <name name-style="western">
            <surname>Koranteng</surname>
            <given-names>A</given-names>
          </name>
          <name name-style="western">
            <surname>Krishnamurthi</surname>
            <given-names>R</given-names>
          </name>
          <name name-style="western">
            <surname>Lipnick</surname>
            <given-names>M</given-names>
          </name>
          <name name-style="western">
            <surname>Lipshultz</surname>
            <given-names>SE</given-names>
          </name>
          <name name-style="western">
            <surname>Ohno</surname>
            <given-names>SL</given-names>
          </name>
          <name name-style="western">
            <surname>Mabweijano</surname>
            <given-names>J</given-names>
          </name>
          <name name-style="western">
            <surname>MacIntyre</surname>
            <given-names>MF</given-names>
          </name>
          <name name-style="western">
            <surname>Mallinger</surname>
            <given-names>L</given-names>
          </name>
          <name name-style="western">
            <surname>March</surname>
            <given-names>L</given-names>
          </name>
          <name name-style="western">
            <surname>Marks</surname>
            <given-names>GB</given-names>
          </name>
          <name name-style="western">
            <surname>Marks</surname>
            <given-names>R</given-names>
          </name>
          <name name-style="western">
            <surname>Matsumori</surname>
            <given-names>A</given-names>
          </name>
          <name name-style="western">
            <surname>Matzopoulos</surname>
            <given-names>R</given-names>
          </name>
          <name name-style="western">
            <surname>Mayosi</surname>
            <given-names>BM</given-names>
          </name>
          <name name-style="western">
            <surname>McAnulty</surname>
            <given-names>JH</given-names>
          </name>
          <name name-style="western">
            <surname>McDermott</surname>
            <given-names>MM</given-names>
          </name>
          <name name-style="western">
            <surname>McGrath</surname>
            <given-names>J</given-names>
          </name>
          <name name-style="western">
            <surname>Mensah</surname>
            <given-names>GA</given-names>
          </name>
          <name name-style="western">
            <surname>Merriman</surname>
            <given-names>TR</given-names>
          </name>
          <name name-style="western">
            <surname>Michaud</surname>
            <given-names>C</given-names>
          </name>
          <name name-style="western">
            <surname>Miller</surname>
            <given-names>M</given-names>
          </name>
          <name name-style="western">
            <surname>Miller</surname>
            <given-names>TR</given-names>
          </name>
          <name name-style="western">
            <surname>Mock</surname>
            <given-names>C</given-names>
          </name>
          <name name-style="western">
            <surname>Mocumbi</surname>
            <given-names>AO</given-names>
          </name>
          <name name-style="western">
            <surname>Mokdad</surname>
            <given-names>AA</given-names>
          </name>
          <name name-style="western">
            <surname>Moran</surname>
            <given-names>A</given-names>
          </name>
          <name name-style="western">
            <surname>Mulholland</surname>
            <given-names>K</given-names>
          </name>
          <name name-style="western">
            <surname>Nair</surname>
            <given-names>MN</given-names>
          </name>
          <name name-style="western">
            <surname>Naldi</surname>
            <given-names>L</given-names>
          </name>
          <name name-style="western">
            <surname>Narayan</surname>
            <given-names>KMV</given-names>
          </name>
          <name name-style="western">
            <surname>Nasseri</surname>
            <given-names>K</given-names>
          </name>
          <name name-style="western">
            <surname>Norman</surname>
            <given-names>P</given-names>
          </name>
          <name name-style="western">
            <surname>O'Donnell</surname>
            <given-names>M</given-names>
          </name>
          <name name-style="western">
            <surname>Omer</surname>
            <given-names>SB</given-names>
          </name>
          <name name-style="western">
            <surname>Ortblad</surname>
            <given-names>K</given-names>
          </name>
          <name name-style="western">
            <surname>Osborne</surname>
            <given-names>R</given-names>
          </name>
          <name name-style="western">
            <surname>Ozgediz</surname>
            <given-names>D</given-names>
          </name>
          <name name-style="western">
            <surname>Pahari</surname>
            <given-names>B</given-names>
          </name>
          <name name-style="western">
            <surname>Pandian</surname>
            <given-names>JD</given-names>
          </name>
          <name name-style="western">
            <surname>Rivero</surname>
            <given-names>AP</given-names>
          </name>
          <name name-style="western">
            <surname>Padilla</surname>
            <given-names>RP</given-names>
          </name>
          <name name-style="western">
            <surname>Perez-Ruiz</surname>
            <given-names>F</given-names>
          </name>
          <name name-style="western">
            <surname>Perico</surname>
            <given-names>N</given-names>
          </name>
          <name name-style="western">
            <surname>Phillips</surname>
            <given-names>D</given-names>
          </name>
          <name name-style="western">
            <surname>Pierce</surname>
            <given-names>K</given-names>
          </name>
          <name name-style="western">
            <surname>Pope</surname>
            <given-names>CA</given-names>
          </name>
          <name name-style="western">
            <surname>Porrini</surname>
            <given-names>E</given-names>
          </name>
          <name name-style="western">
            <surname>Pourmalek</surname>
            <given-names>F</given-names>
          </name>
          <name name-style="western">
            <surname>Raju</surname>
            <given-names>M</given-names>
          </name>
          <name name-style="western">
            <surname>Ranganathan</surname>
            <given-names>D</given-names>
          </name>
          <name name-style="western">
            <surname>Rehm</surname>
            <given-names>JT</given-names>
          </name>
          <name name-style="western">
            <surname>Rein</surname>
            <given-names>DB</given-names>
          </name>
          <name name-style="western">
            <surname>Remuzzi</surname>
            <given-names>G</given-names>
          </name>
          <name name-style="western">
            <surname>Rivara</surname>
            <given-names>FP</given-names>
          </name>
          <name name-style="western">
            <surname>Roberts</surname>
            <given-names>T</given-names>
          </name>
          <name name-style="western">
            <surname>Rosenfeld</surname>
            <given-names>LC</given-names>
          </name>
          <name name-style="western">
            <surname>Rushton</surname>
            <given-names>L</given-names>
          </name>
          <name name-style="western">
            <surname>Sacco</surname>
            <given-names>RL</given-names>
          </name>
          <name name-style="western">
            <surname>Salomon</surname>
            <given-names>JA</given-names>
          </name>
          <name name-style="western">
            <surname>Sampson</surname>
            <given-names>U</given-names>
          </name>
          <name name-style="western">
            <surname>Sanman</surname>
            <given-names>E</given-names>
          </name>
          <name name-style="western">
            <surname>Schwebel</surname>
            <given-names>DC</given-names>
          </name>
          <name name-style="western">
            <surname>Segui-Gomez</surname>
            <given-names>M</given-names>
          </name>
          <name name-style="western">
            <surname>Shepard</surname>
            <given-names>DS</given-names>
          </name>
          <name name-style="western">
            <surname>Singh</surname>
            <given-names>D</given-names>
          </name>
          <name name-style="western">
            <surname>Singleton</surname>
            <given-names>J</given-names>
          </name>
          <name name-style="western">
            <surname>Sliwa</surname>
            <given-names>K</given-names>
          </name>
          <name name-style="western">
            <surname>Smith</surname>
            <given-names>E</given-names>
          </name>
          <name name-style="western">
            <surname>Steer</surname>
            <given-names>A</given-names>
          </name>
          <name name-style="western">
            <surname>Taylor</surname>
            <given-names>JA</given-names>
          </name>
          <name name-style="western">
            <surname>Thomas</surname>
            <given-names>B</given-names>
          </name>
          <name name-style="western">
            <surname>Tleyjeh</surname>
            <given-names>IM</given-names>
          </name>
          <name name-style="western">
            <surname>Towbin</surname>
            <given-names>JA</given-names>
          </name>
          <name name-style="western">
            <surname>Truelsen</surname>
            <given-names>T</given-names>
          </name>
          <name name-style="western">
            <surname>Undurraga</surname>
            <given-names>EA</given-names>
          </name>
          <name name-style="western">
            <surname>Venketasubramanian</surname>
            <given-names>N</given-names>
          </name>
          <name name-style="western">
            <surname>Vijayakumar</surname>
            <given-names>L</given-names>
          </name>
          <name name-style="western">
            <surname>Vos</surname>
            <given-names>T</given-names>
          </name>
          <name name-style="western">
            <surname>Wagner</surname>
            <given-names>GR</given-names>
          </name>
          <name name-style="western">
            <surname>Wang</surname>
            <given-names>M</given-names>
          </name>
          <name name-style="western">
            <surname>Wang</surname>
            <given-names>W</given-names>
          </name>
          <name name-style="western">
            <surname>Watt</surname>
            <given-names>K</given-names>
          </name>
          <name name-style="western">
            <surname>Weinstock</surname>
            <given-names>MA</given-names>
          </name>
          <name name-style="western">
            <surname>Weintraub</surname>
            <given-names>R</given-names>
          </name>
          <name name-style="western">
            <surname>Wilkinson</surname>
            <given-names>JD</given-names>
          </name>
          <name name-style="western">
            <surname>Woolf</surname>
            <given-names>AD</given-names>
          </name>
          <name name-style="western">
            <surname>Wulf</surname>
            <given-names>S</given-names>
          </name>
          <name name-style="western">
            <surname>Yeh</surname>
            <given-names>P</given-names>
          </name>
          <name name-style="western">
            <surname>Yip</surname>
            <given-names>P</given-names>
          </name>
          <name name-style="western">
            <surname>Zabetian</surname>
            <given-names>A</given-names>
          </name>
          <name name-style="western">
            <surname>Zheng</surname>
            <given-names>Z</given-names>
          </name>
          <name name-style="western">
            <surname>Lopez</surname>
            <given-names>AD</given-names>
          </name>
          <name name-style="western">
            <surname>Murray</surname>
            <given-names>CJL</given-names>
          </name>
          <name name-style="western">
            <surname>AlMazroa</surname>
            <given-names>MA</given-names>
          </name>
          <name name-style="western">
            <surname>Memish</surname>
            <given-names>ZA</given-names>
          </name>
        </person-group>
        <article-title>Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: a systematic analysis for the Global Burden of Disease Study 2010</article-title>
        <source>Lancet</source>  
        <year>2012</year>  
        <month>12</month>  
        <day>15</day>  
        <volume>380</volume>  
        <issue>9859</issue>  
        <fpage>2095</fpage>  
        <lpage>2128</lpage>  
        <pub-id pub-id-type="doi">10.1016/S0140-6736(12)61728-0</pub-id>
        <pub-id pub-id-type="medline">23245604</pub-id>
        <pub-id pub-id-type="pii">S0140-6736(12)61728-0</pub-id></nlm-citation>
      </ref>
      <ref id="ref2">
        <label>2</label>
        <nlm-citation citation-type="journal">
        <person-group person-group-type="author">
          <name name-style="western">
            <surname>Murray</surname>
            <given-names>CJ</given-names>
          </name>
          <name name-style="western">
            <surname>Lopez</surname>
            <given-names>AD</given-names>
          </name>
        </person-group>
        <article-title>Alternative projections of mortality and disability by cause 1990-2020: Global Burden of Disease Study</article-title>
        <source>Lancet</source>  
        <year>1997</year>  
        <month>05</month>  
        <day>24</day>  
        <volume>349</volume>  
        <issue>9064</issue>  
        <fpage>1498</fpage>  
        <lpage>1504</lpage>  
        <pub-id pub-id-type="doi">10.1016/S0140-6736(96)07492-2</pub-id>
        <pub-id pub-id-type="medline">9167458</pub-id>
        <pub-id pub-id-type="pii">S0140-6736(96)07492-2</pub-id></nlm-citation>
      </ref>
      <ref id="ref3">
        <label>3</label>
        <nlm-citation citation-type="journal">
        <person-group person-group-type="author">
          <name name-style="western">
            <surname>Chuchalin</surname>
            <given-names>AG</given-names>
          </name>
          <name name-style="western">
            <surname>Khaltaev</surname>
            <given-names>N</given-names>
          </name>
          <name name-style="western">
            <surname>Antonov</surname>
            <given-names>NS</given-names>
          </name>
          <name name-style="western">
            <surname>Galkin</surname>
            <given-names>DV</given-names>
          </name>
          <name name-style="western">
            <surname>Manakov</surname>
            <given-names>LG</given-names>
          </name>
          <name name-style="western">
            <surname>Antonini</surname>
            <given-names>P</given-names>
          </name>
          <name name-style="western">
            <surname>Murphy</surname>
            <given-names>M</given-names>
          </name>
          <name name-style="western">
            <surname>Solodovnikov</surname>
            <given-names>AG</given-names>
          </name>
          <name name-style="western">
            <surname>Bousquet</surname>
            <given-names>J</given-names>
          </name>
          <name name-style="western">
            <surname>Pereira</surname>
            <given-names>MHS</given-names>
          </name>
          <name name-style="western">
            <surname>Demko</surname>
            <given-names>IV</given-names>
          </name>
        </person-group>
        <article-title>Chronic respiratory diseases and risk factors in 12 regions of the Russian Federation</article-title>
        <source>Int J Chron Obstruct Pulmon Dis</source>  
        <year>2014</year>  
        <volume>9</volume>  
        <fpage>963</fpage>  
        <lpage>974</lpage>  
        <comment>
          <ext-link xmlns:xlink="http://www.w3.org/1999/xlink" xlink:type="simple" xlink:href="https://dx.doi.org/10.2147/COPD.S67283"/>
        </comment>  
        <pub-id pub-id-type="doi">10.2147/COPD.S67283</pub-id>
        <pub-id pub-id-type="medline">25246783</pub-id>
        <pub-id pub-id-type="pii">copd-9-963</pub-id>
        <pub-id pub-id-type="pmcid">PMC4166963</pub-id></nlm-citation>
      </ref>
      <ref id="ref4">
        <label>4</label>
        <nlm-citation citation-type="journal">
        <person-group person-group-type="author">
          <name name-style="western">
            <surname>Adeloye</surname>
            <given-names>D</given-names>
          </name>
          <name name-style="western">
            <surname>Chua</surname>
            <given-names>S</given-names>
          </name>
          <name name-style="western">
            <surname>Lee</surname>
            <given-names>C</given-names>
          </name>
          <name name-style="western">
            <surname>Basquill</surname>
            <given-names>C</given-names>
          </name>
          <name name-style="western">
            <surname>Papana</surname>
            <given-names>A</given-names>
          </name>
          <name name-style="western">
            <surname>Theodoratou</surname>
            <given-names>E</given-names>
          </name>
          <name name-style="western">
            <surname>Nair</surname>
            <given-names>H</given-names>
          </name>
          <name name-style="western">
            <surname>Gasevic</surname>
            <given-names>D</given-names>
          </name>
          <name name-style="western">
            <surname>Sridhar</surname>
            <given-names>D</given-names>
          </name>
          <name name-style="western">
            <surname>Campbell</surname>
            <given-names>H</given-names>
          </name>
          <name name-style="western">
            <surname>Chan</surname>
            <given-names>KY</given-names>
          </name>
          <name name-style="western">
            <surname>Sheikh</surname>
            <given-names>A</given-names>
          </name>
          <name name-style="western">
            <surname>Rudan</surname>
            <given-names>I</given-names>
          </name>
        </person-group>
        <article-title>Global and regional estimates of COPD prevalence: systematic review and meta-analysis</article-title>
        <source>J Glob Health</source>  
        <year>2015</year>  
        <month>12</month>  
        <volume>5</volume>  
        <issue>2</issue>  
        <fpage>020415</fpage>  
        <comment>
          <ext-link xmlns:xlink="http://www.w3.org/1999/xlink" xlink:type="simple" xlink:href="http://europepmc.org/abstract/MED/26755942"/>
        </comment>  
        <pub-id pub-id-type="doi">10.7189/jogh.05-020415</pub-id>
        <pub-id pub-id-type="medline">26755942</pub-id>
        <pub-id pub-id-type="pii">jogh-05-020415</pub-id>
        <pub-id pub-id-type="pmcid">PMC4693508</pub-id></nlm-citation>
      </ref>
      <ref id="ref5">
        <label>5</label>
        <nlm-citation citation-type="web">
        <source>National Center for the Problems of Forming the Healthy Lifestyle: press release</source>  
        <access-date>2017-07-06</access-date>
        <comment>
          <ext-link xmlns:xlink="http://www.w3.org/1999/xlink" xlink:type="simple" xlink:href="http://www.hls.kz/rus/press-releases_1_61">http://www.hls.kz/rus/press-releases_1_61</ext-link>
          <ext-link ext-link-type="webcite" xlink:href="6qQFCdjB"/>
        </comment> </nlm-citation>
      </ref>
      <ref id="ref6">
        <label>6</label>
        <nlm-citation citation-type="web">
        <person-group person-group-type="author">
          <collab>Global Initiative for Chronic Obstructive Lung Disease</collab>
        </person-group>
        <source>Global strategy for the diagnosis, management, and prevention of COPD</source>  
        <access-date>2017-01-25</access-date>
        <comment>
          <ext-link xmlns:xlink="http://www.w3.org/1999/xlink" xlink:type="simple" xlink:href="http://goldcopd.org/global-strategy-diagnosis-management-prevention-copd-2016/">http://goldcopd.org/global-strategy-diagnosis-management-prevention-copd-2016/</ext-link>
          <ext-link ext-link-type="webcite" xlink:href="6nmH3nBW5"/>
        </comment> </nlm-citation>
      </ref>
      <ref id="ref7">
        <label>7</label>
        <nlm-citation citation-type="journal">
        <person-group person-group-type="author">
          <name name-style="western">
            <surname>Swanney</surname>
            <given-names>MP</given-names>
          </name>
          <name name-style="western">
            <surname>Ruppel</surname>
            <given-names>G</given-names>
          </name>
          <name name-style="western">
            <surname>Enright</surname>
            <given-names>PL</given-names>
          </name>
          <name name-style="western">
            <surname>Pedersen</surname>
            <given-names>OF</given-names>
          </name>
          <name name-style="western">
            <surname>Crapo</surname>
            <given-names>RO</given-names>
          </name>
          <name name-style="western">
            <surname>Miller</surname>
            <given-names>MR</given-names>
          </name>
          <name name-style="western">
            <surname>Jensen</surname>
            <given-names>RL</given-names>
          </name>
          <name name-style="western">
            <surname>Falaschetti</surname>
            <given-names>E</given-names>
          </name>
          <name name-style="western">
            <surname>Schouten</surname>
            <given-names>JP</given-names>
          </name>
          <name name-style="western">
            <surname>Hankinson</surname>
            <given-names>JL</given-names>
          </name>
          <name name-style="western">
            <surname>Stocks</surname>
            <given-names>J</given-names>
          </name>
          <name name-style="western">
            <surname>Quanjer</surname>
            <given-names>PH</given-names>
          </name>
        </person-group>
        <article-title>Using the lower limit of normal for the FEV1/FVC ratio reduces the misclassification of airway obstruction</article-title>
        <source>Thorax</source>  
        <year>2008</year>  
        <month>12</month>  
        <volume>63</volume>  
        <issue>12</issue>  
        <fpage>1046</fpage>  
        <lpage>1051</lpage>  
        <pub-id pub-id-type="doi">10.1136/thx.2008.098483</pub-id>
        <pub-id pub-id-type="medline">18786983</pub-id>
        <pub-id pub-id-type="pii">thx.2008.098483</pub-id></nlm-citation>
      </ref>
      <ref id="ref8">
        <label>8</label>
        <nlm-citation citation-type="journal">
        <person-group person-group-type="author">
          <name name-style="western">
            <surname>Bakke</surname>
            <given-names>PS</given-names>
          </name>
          <name name-style="western">
            <surname>Rönmark</surname>
            <given-names>E</given-names>
          </name>
          <name name-style="western">
            <surname>Eagan</surname>
            <given-names>T</given-names>
          </name>
          <name name-style="western">
            <surname>Pistelli</surname>
            <given-names>F</given-names>
          </name>
          <name name-style="western">
            <surname>Annesi-Maesano</surname>
            <given-names>I</given-names>
          </name>
          <name name-style="western">
            <surname>Maly</surname>
            <given-names>M</given-names>
          </name>
          <name name-style="western">
            <surname>Meren</surname>
            <given-names>M</given-names>
          </name>
          <name name-style="western">
            <surname>Vermeire</surname>
            <given-names>DP</given-names>
          </name>
          <name name-style="western">
            <surname>Vestbo</surname>
            <given-names>J</given-names>
          </name>
          <name name-style="western">
            <surname>Viegi</surname>
            <given-names>G</given-names>
          </name>
          <name name-style="western">
            <surname>Zielinski</surname>
            <given-names>J</given-names>
          </name>
          <name name-style="western">
            <surname>Lundbäck</surname>
            <given-names>B</given-names>
          </name>
        </person-group>
        <article-title>Recommendations for epidemiological studies on COPD</article-title>
        <source>Eur Respir J</source>  
        <year>2011</year>  
        <month>12</month>  
        <volume>38</volume>  
        <issue>6</issue>  
        <fpage>1261</fpage>  
        <lpage>1277</lpage>  
        <comment>
          <ext-link xmlns:xlink="http://www.w3.org/1999/xlink" xlink:type="simple" xlink:href="http://erj.ersjournals.com/cgi/pmidlookup?view=long&#38;pmid=22130763"/>
        </comment>  
        <pub-id pub-id-type="doi">10.1183/09031936.00193809</pub-id>
        <pub-id pub-id-type="medline">22130763</pub-id>
        <pub-id pub-id-type="pii">09031936.00193809</pub-id></nlm-citation>
      </ref>
      <ref id="ref9">
        <label>9</label>
        <nlm-citation citation-type="journal">
        <person-group person-group-type="author">
          <name name-style="western">
            <surname>Lundbäck</surname>
            <given-names>B</given-names>
          </name>
          <name name-style="western">
            <surname>Stjernberg</surname>
            <given-names>N</given-names>
          </name>
          <name name-style="western">
            <surname>Nyström</surname>
            <given-names>L</given-names>
          </name>
          <name name-style="western">
            <surname>Forsberg</surname>
            <given-names>B</given-names>
          </name>
          <name name-style="western">
            <surname>Lindström</surname>
            <given-names>M</given-names>
          </name>
          <name name-style="western">
            <surname>Lundbäck</surname>
            <given-names>K</given-names>
          </name>
          <name name-style="western">
            <surname>Jönsson</surname>
            <given-names>E</given-names>
          </name>
          <name name-style="western">
            <surname>Rosenhall</surname>
            <given-names>L</given-names>
          </name>
        </person-group>
        <article-title>Epidemiology of respiratory symptoms, lung function and important determinants. Report from the Obstructive Lung Disease in Northern Sweden Project</article-title>
        <source>Tuber Lung Dis</source>  
        <year>1994</year>  
        <month>04</month>  
        <volume>75</volume>  
        <issue>2</issue>  
        <fpage>116</fpage>  
        <lpage>126</lpage>  
        <pub-id pub-id-type="doi">10.1016/0962-8479(94)90040-X</pub-id>
        <pub-id pub-id-type="medline">8032044</pub-id>
        <pub-id pub-id-type="pii">0962-8479(94)90040-X</pub-id></nlm-citation>
      </ref>
      <ref id="ref10">
        <label>10</label>
        <nlm-citation citation-type="journal">
        <person-group person-group-type="author">
          <name name-style="western">
            <surname>Bakke</surname>
            <given-names>P</given-names>
          </name>
          <name name-style="western">
            <surname>Eide</surname>
            <given-names>GE</given-names>
          </name>
          <name name-style="western">
            <surname>Hanoa</surname>
            <given-names>R</given-names>
          </name>
          <name name-style="western">
            <surname>Gulsvik</surname>
            <given-names>A</given-names>
          </name>
        </person-group>
        <article-title>Occupational dust or gas exposure and prevalences of respiratory symptoms and asthma in a general population</article-title>
        <source>Eur Respir J</source>  
        <year>1991</year>  
        <month>03</month>  
        <volume>4</volume>  
        <issue>3</issue>  
        <fpage>273</fpage>  
        <lpage>278</lpage>  
        <pub-id pub-id-type="medline">1864342</pub-id></nlm-citation>
      </ref>
      <ref id="ref11">
        <label>11</label>
        <nlm-citation citation-type="journal">
        <person-group person-group-type="author">
          <name name-style="western">
            <surname>Koff</surname>
            <given-names>RS</given-names>
          </name>
        </person-group>
        <article-title>Fundamentals of lung auscultation</article-title>
        <source>N Engl J Med</source>  
        <year>2014</year>  
        <month>05</month>  
        <day>22</day>  
        <volume>370</volume>  
        <issue>21</issue>  
        <fpage>2053</fpage>  
        <pub-id pub-id-type="doi">10.1056/NEJMc1403766#SA3</pub-id>
        <pub-id pub-id-type="medline">24849098</pub-id></nlm-citation>
      </ref>
      <ref id="ref12">
        <label>12</label>
        <nlm-citation citation-type="journal">
        <person-group person-group-type="author">
          <name name-style="western">
            <surname>Make</surname>
            <given-names>BJ</given-names>
          </name>
          <name name-style="western">
            <surname>Martinez</surname>
            <given-names>FJ</given-names>
          </name>
        </person-group>
        <article-title>Assessment of patients with chronic obstructive pulmonary disease</article-title>
        <source>Proc Am Thorac Soc</source>  
        <year>2008</year>  
        <month>12</month>  
        <day>15</day>  
        <volume>5</volume>  
        <issue>9</issue>  
        <fpage>884</fpage>  
        <lpage>890</lpage>  
        <comment>
          <ext-link xmlns:xlink="http://www.w3.org/1999/xlink" xlink:type="simple" xlink:href="http://europepmc.org/abstract/MED/19056711"/>
        </comment>  
        <pub-id pub-id-type="doi">10.1513/pats.200808-093QC</pub-id>
        <pub-id pub-id-type="medline">19056711</pub-id>
        <pub-id pub-id-type="pii">5/9/884</pub-id>
        <pub-id pub-id-type="pmcid">PMC2720107</pub-id></nlm-citation>
      </ref>
      <ref id="ref13">
        <label>13</label>
        <nlm-citation citation-type="journal">
        <person-group person-group-type="author">
          <name name-style="western">
            <surname>Pistolesi</surname>
            <given-names>M</given-names>
          </name>
          <name name-style="western">
            <surname>Camiciottoli</surname>
            <given-names>G</given-names>
          </name>
          <name name-style="western">
            <surname>Paoletti</surname>
            <given-names>M</given-names>
          </name>
          <name name-style="western">
            <surname>Marmai</surname>
            <given-names>C</given-names>
          </name>
          <name name-style="western">
            <surname>Lavorini</surname>
            <given-names>F</given-names>
          </name>
          <name name-style="western">
            <surname>Meoni</surname>
            <given-names>E</given-names>
          </name>
          <name name-style="western">
            <surname>Marchesi</surname>
            <given-names>C</given-names>
          </name>
          <name name-style="western">
            <surname>Giuntini</surname>
            <given-names>C</given-names>
          </name>
        </person-group>
        <article-title>Identification of a predominant COPD phenotype in clinical practice</article-title>
        <source>Respir Med</source>  
        <year>2008</year>  
        <month>03</month>  
        <volume>102</volume>  
        <issue>3</issue>  
        <fpage>367</fpage>  
        <lpage>376</lpage>  
        <comment>
          <ext-link xmlns:xlink="http://www.w3.org/1999/xlink" xlink:type="simple" xlink:href="https://linkinghub.elsevier.com/retrieve/pii/S0954-6111(07)00442-8"/>
        </comment>  
        <pub-id pub-id-type="doi">10.1016/j.rmed.2007.10.019</pub-id>
        <pub-id pub-id-type="medline">18248806</pub-id>
        <pub-id pub-id-type="pii">S0954-6111(07)00442-8</pub-id></nlm-citation>
      </ref>
      <ref id="ref14">
        <label>14</label>
        <nlm-citation citation-type="journal">
        <person-group person-group-type="author">
          <name name-style="western">
            <surname>Lynch</surname>
            <given-names>DA</given-names>
          </name>
          <name name-style="western">
            <surname>Austin</surname>
            <given-names>JHM</given-names>
          </name>
          <name name-style="western">
            <surname>Hogg</surname>
            <given-names>JC</given-names>
          </name>
          <name name-style="western">
            <surname>Grenier</surname>
            <given-names>PA</given-names>
          </name>
          <name name-style="western">
            <surname>Kauczor</surname>
            <given-names>H</given-names>
          </name>
          <name name-style="western">
            <surname>Bankier</surname>
            <given-names>AA</given-names>
          </name>
          <name name-style="western">
            <surname>Barr</surname>
            <given-names>RG</given-names>
          </name>
          <name name-style="western">
            <surname>Colby</surname>
            <given-names>TV</given-names>
          </name>
          <name name-style="western">
            <surname>Galvin</surname>
            <given-names>JR</given-names>
          </name>
          <name name-style="western">
            <surname>Gevenois</surname>
            <given-names>PA</given-names>
          </name>
          <name name-style="western">
            <surname>Coxson</surname>
            <given-names>HO</given-names>
          </name>
          <name name-style="western">
            <surname>Hoffman</surname>
            <given-names>EA</given-names>
          </name>
          <name name-style="western">
            <surname>Newell</surname>
            <given-names>JD</given-names>
          </name>
          <name name-style="western">
            <surname>Pistolesi</surname>
            <given-names>M</given-names>
          </name>
          <name name-style="western">
            <surname>Silverman</surname>
            <given-names>EK</given-names>
          </name>
          <name name-style="western">
            <surname>Crapo</surname>
            <given-names>JD</given-names>
          </name>
        </person-group>
        <article-title>CT-definable subtypes of chronic obstructive pulmonary disease: a statement of the Fleischner Society</article-title>
        <source>Radiology</source>  
        <year>2015</year>  
        <month>10</month>  
        <volume>277</volume>  
        <issue>1</issue>  
        <fpage>192</fpage>  
        <lpage>205</lpage>  
        <comment>
          <ext-link xmlns:xlink="http://www.w3.org/1999/xlink" xlink:type="simple" xlink:href="http://europepmc.org/abstract/MED/25961632"/>
        </comment>  
        <pub-id pub-id-type="doi">10.1148/radiol.2015141579</pub-id>
        <pub-id pub-id-type="medline">25961632</pub-id>
        <pub-id pub-id-type="pmcid">PMC4613878</pub-id></nlm-citation>
      </ref>
      <ref id="ref15">
        <label>15</label>
        <nlm-citation citation-type="journal">
        <person-group person-group-type="author">
          <name name-style="western">
            <surname>Mohamed</surname>
            <given-names>HFAA</given-names>
          </name>
          <name name-style="western">
            <surname>Zanen</surname>
            <given-names>P</given-names>
          </name>
          <name name-style="western">
            <surname>Gietema</surname>
            <given-names>H</given-names>
          </name>
          <name name-style="western">
            <surname>Kruitwagen</surname>
            <given-names>CLJJ</given-names>
          </name>
          <name name-style="western">
            <surname>Isgum</surname>
            <given-names>I</given-names>
          </name>
          <name name-style="western">
            <surname>Mol</surname>
            <given-names>C</given-names>
          </name>
          <name name-style="western">
            <surname>Dijkstra</surname>
            <given-names>AE</given-names>
          </name>
          <name name-style="western">
            <surname>Groen</surname>
            <given-names>HJM</given-names>
          </name>
          <name name-style="western">
            <surname>Boezen</surname>
            <given-names>HM</given-names>
          </name>
          <name name-style="western">
            <surname>Postma</surname>
            <given-names>DS</given-names>
          </name>
          <name name-style="western">
            <surname>Prokop</surname>
            <given-names>M</given-names>
          </name>
          <name name-style="western">
            <surname>Lammers</surname>
            <given-names>JJ</given-names>
          </name>
        </person-group>
        <article-title>CT-quantified emphysema in male heavy smokers: association with lung function decline</article-title>
        <source>Thorax</source>  
        <year>2011</year>  
        <month>09</month>  
        <volume>66</volume>  
        <issue>9</issue>  
        <fpage>782</fpage>  
        <lpage>787</lpage>  
        <pub-id pub-id-type="doi">10.1136/thx.2010.145995</pub-id>
        <pub-id pub-id-type="medline">21474499</pub-id>
        <pub-id pub-id-type="pii">thx.2010.145995</pub-id></nlm-citation>
      </ref>
      <ref id="ref16">
        <label>16</label>
        <nlm-citation citation-type="journal">
        <person-group person-group-type="author">
          <name name-style="western">
            <surname>Koo</surname>
            <given-names>H</given-names>
          </name>
          <name name-style="western">
            <surname>Jin</surname>
            <given-names>KN</given-names>
          </name>
          <name name-style="western">
            <surname>Kim</surname>
            <given-names>DK</given-names>
          </name>
          <name name-style="western">
            <surname>Chung</surname>
            <given-names>HS</given-names>
          </name>
          <name name-style="western">
            <surname>Lee</surname>
            <given-names>C</given-names>
          </name>
        </person-group>
        <article-title>Association of incidental emphysema with annual lung function decline and future development of airflow limitation</article-title>
        <source>Int J Chron Obstruct Pulmon Dis</source>  
        <year>2016</year>  
        <volume>11</volume>  
        <fpage>161</fpage>  
        <lpage>166</lpage>  
        <comment>
          <ext-link xmlns:xlink="http://www.w3.org/1999/xlink" xlink:type="simple" xlink:href="https://dx.doi.org/10.2147/COPD.S96809"/>
        </comment>  
        <pub-id pub-id-type="doi">10.2147/COPD.S96809</pub-id>
        <pub-id pub-id-type="medline">26893550</pub-id>
        <pub-id pub-id-type="pii">copd-11-161</pub-id>
        <pub-id pub-id-type="pmcid">PMC4745855</pub-id></nlm-citation>
      </ref>
      <ref id="ref17">
        <label>17</label>
        <nlm-citation citation-type="journal">
        <person-group person-group-type="author">
          <name name-style="western">
            <surname>Sin</surname>
            <given-names>DD</given-names>
          </name>
          <name name-style="western">
            <surname>Leipsic</surname>
            <given-names>J</given-names>
          </name>
          <name name-style="western">
            <surname>Man</surname>
            <given-names>SFP</given-names>
          </name>
        </person-group>
        <article-title>CT in COPD: just a pretty picture or really worth a thousand words (or dollars)?</article-title>
        <source>Thorax</source>  
        <year>2011</year>  
        <month>09</month>  
        <volume>66</volume>  
        <issue>9</issue>  
        <fpage>741</fpage>  
        <lpage>742</lpage>  
        <pub-id pub-id-type="doi">10.1136/thx.2011.161430</pub-id>
        <pub-id pub-id-type="medline">21572118</pub-id>
        <pub-id pub-id-type="pii">thx.2011.161430</pub-id></nlm-citation>
      </ref>
      <ref id="ref18">
        <label>18</label>
        <nlm-citation citation-type="journal">
        <person-group person-group-type="author">
          <name name-style="western">
            <surname>Rosenberg</surname>
            <given-names>SR</given-names>
          </name>
          <name name-style="western">
            <surname>Kalhan</surname>
            <given-names>R</given-names>
          </name>
          <name name-style="western">
            <surname>Mannino</surname>
            <given-names>DM</given-names>
          </name>
        </person-group>
        <article-title>Epidemiology of chronic obstructive pulmonary disease: prevalence, morbidity, mortality, and risk factors</article-title>
        <source>Semin Respir Crit Care Med</source>  
        <year>2015</year>  
        <month>08</month>  
        <volume>36</volume>  
        <issue>4</issue>  
        <fpage>457</fpage>  
        <lpage>469</lpage>  
        <pub-id pub-id-type="doi">10.1055/s-0035-1555607</pub-id>
        <pub-id pub-id-type="medline">26238634</pub-id></nlm-citation>
      </ref>
      <ref id="ref19">
        <label>19</label>
        <nlm-citation citation-type="journal">
        <person-group person-group-type="author">
          <name name-style="western">
            <surname>Lee</surname>
            <given-names>SJ</given-names>
          </name>
          <name name-style="western">
            <surname>Kim</surname>
            <given-names>SW</given-names>
          </name>
          <name name-style="western">
            <surname>Kong</surname>
            <given-names>KA</given-names>
          </name>
          <name name-style="western">
            <surname>Ryu</surname>
            <given-names>YJ</given-names>
          </name>
          <name name-style="western">
            <surname>Lee</surname>
            <given-names>JH</given-names>
          </name>
          <name name-style="western">
            <surname>Chang</surname>
            <given-names>JH</given-names>
          </name>
        </person-group>
        <article-title>Risk factors for chronic obstructive pulmonary disease among never-smokers in Korea</article-title>
        <source>Int J Chron Obstruct Pulmon Dis</source>  
        <year>2015</year>  
        <volume>10</volume>  
        <fpage>497</fpage>  
        <lpage>506</lpage>  
        <comment>
          <ext-link xmlns:xlink="http://www.w3.org/1999/xlink" xlink:type="simple" xlink:href="https://dx.doi.org/10.2147/COPD.S77662"/>
        </comment>  
        <pub-id pub-id-type="doi">10.2147/COPD.S77662</pub-id>
        <pub-id pub-id-type="medline">25784796</pub-id>
        <pub-id pub-id-type="pii">copd-10-497</pub-id>
        <pub-id pub-id-type="pmcid">PMC4356706</pub-id></nlm-citation>
      </ref>
      <ref id="ref20">
        <label>20</label>
        <nlm-citation citation-type="journal">
        <person-group person-group-type="author">
          <name name-style="western">
            <surname>Berndt</surname>
            <given-names>A</given-names>
          </name>
          <name name-style="western">
            <surname>Leme</surname>
            <given-names>AS</given-names>
          </name>
          <name name-style="western">
            <surname>Shapiro</surname>
            <given-names>SD</given-names>
          </name>
        </person-group>
        <article-title>Emerging genetics of COPD</article-title>
        <source>EMBO Mol Med</source>  
        <year>2012</year>  
        <month>11</month>  
        <volume>4</volume>  
        <issue>11</issue>  
        <fpage>1144</fpage>  
        <lpage>1155</lpage>  
        <comment>
          <ext-link xmlns:xlink="http://www.w3.org/1999/xlink" xlink:type="simple" xlink:href="http://EMBOMolMed.embopress.org/cgi/pmidlookup?view=long&#38;pmid=23090857"/>
        </comment>  
        <pub-id pub-id-type="doi">10.1002/emmm.201100627</pub-id>
        <pub-id pub-id-type="medline">23090857</pub-id>
        <pub-id pub-id-type="pmcid">PMC3494872</pub-id></nlm-citation>
      </ref>
      <ref id="ref21">
        <label>21</label>
        <nlm-citation citation-type="journal">
        <person-group person-group-type="author">
          <name name-style="western">
            <surname>Cavaillès</surname>
            <given-names>A</given-names>
          </name>
          <name name-style="western">
            <surname>Brinchault-Rabin</surname>
            <given-names>G</given-names>
          </name>
          <name name-style="western">
            <surname>Dixmier</surname>
            <given-names>A</given-names>
          </name>
          <name name-style="western">
            <surname>Goupil</surname>
            <given-names>F</given-names>
          </name>
          <name name-style="western">
            <surname>Gut-Gobert</surname>
            <given-names>C</given-names>
          </name>
          <name name-style="western">
            <surname>Marchand-Adam</surname>
            <given-names>S</given-names>
          </name>
          <name name-style="western">
            <surname>Meurice</surname>
            <given-names>J</given-names>
          </name>
          <name name-style="western">
            <surname>Morel</surname>
            <given-names>H</given-names>
          </name>
          <name name-style="western">
            <surname>Person-Tacnet</surname>
            <given-names>C</given-names>
          </name>
          <name name-style="western">
            <surname>Leroyer</surname>
            <given-names>C</given-names>
          </name>
          <name name-style="western">
            <surname>Diot</surname>
            <given-names>P</given-names>
          </name>
        </person-group>
        <article-title>Comorbidities of COPD</article-title>
        <source>Eur Respir Rev</source>  
        <year>2013</year>  
        <month>12</month>  
        <volume>22</volume>  
        <issue>130</issue>  
        <fpage>454</fpage>  
        <lpage>475</lpage>  
        <comment>
          <ext-link xmlns:xlink="http://www.w3.org/1999/xlink" xlink:type="simple" xlink:href="http://err.ersjournals.com/cgi/pmidlookup?view=long&#38;pmid=24293462"/>
        </comment>  
        <pub-id pub-id-type="doi">10.1183/09059180.00008612</pub-id>
        <pub-id pub-id-type="medline">24293462</pub-id>
        <pub-id pub-id-type="pii">22/130/454</pub-id></nlm-citation>
      </ref>
      <ref id="ref22">
        <label>22</label>
        <nlm-citation citation-type="journal">
        <person-group person-group-type="author">
          <name name-style="western">
            <surname>Chatila</surname>
            <given-names>WM</given-names>
          </name>
          <name name-style="western">
            <surname>Thomashow</surname>
            <given-names>BM</given-names>
          </name>
          <name name-style="western">
            <surname>Minai</surname>
            <given-names>OA</given-names>
          </name>
          <name name-style="western">
            <surname>Criner</surname>
            <given-names>GJ</given-names>
          </name>
          <name name-style="western">
            <surname>Make</surname>
            <given-names>BJ</given-names>
          </name>
        </person-group>
        <article-title>Comorbidities in chronic obstructive pulmonary disease</article-title>
        <source>Proc Am Thorac Soc</source>  
        <year>2008</year>  
        <month>05</month>  
        <day>01</day>  
        <volume>5</volume>  
        <issue>4</issue>  
        <fpage>549</fpage>  
        <lpage>555</lpage>  
        <comment>
          <ext-link xmlns:xlink="http://www.w3.org/1999/xlink" xlink:type="simple" xlink:href="http://europepmc.org/abstract/MED/18453370"/>
        </comment>  
        <pub-id pub-id-type="doi">10.1513/pats.200709-148ET</pub-id>
        <pub-id pub-id-type="medline">18453370</pub-id>
        <pub-id pub-id-type="pii">5/4/549</pub-id>
        <pub-id pub-id-type="pmcid">PMC2645334</pub-id></nlm-citation>
      </ref>
      <ref id="ref23">
        <label>23</label>
        <nlm-citation citation-type="journal">
        <person-group person-group-type="author">
          <name name-style="western">
            <surname>Shavelle</surname>
            <given-names>RM</given-names>
          </name>
          <name name-style="western">
            <surname>Paculdo</surname>
            <given-names>DR</given-names>
          </name>
          <name name-style="western">
            <surname>Kush</surname>
            <given-names>SJ</given-names>
          </name>
          <name name-style="western">
            <surname>Mannino</surname>
            <given-names>DM</given-names>
          </name>
          <name name-style="western">
            <surname>Strauss</surname>
            <given-names>DJ</given-names>
          </name>
        </person-group>
        <article-title>Life expectancy and years of life lost in chronic obstructive pulmonary disease: findings from the NHANES III Follow-up Study</article-title>
        <source>Int J Chron Obstruct Pulmon Dis</source>  
        <year>2009</year>  
        <volume>4</volume>  
        <fpage>137</fpage>  
        <lpage>148</lpage>  
        <comment>
          <ext-link xmlns:xlink="http://www.w3.org/1999/xlink" xlink:type="simple" xlink:href="https://www.dovepress.com/articles.php?article_id=2967"/>
        </comment>  
        <pub-id pub-id-type="medline">19436692</pub-id>
        <pub-id pub-id-type="pmcid">PMC2672796</pub-id></nlm-citation>
      </ref>
      <ref id="ref24">
        <label>24</label>
        <nlm-citation citation-type="journal">
        <person-group person-group-type="author">
          <name name-style="western">
            <surname>Daldoul</surname>
            <given-names>H</given-names>
          </name>
          <name name-style="western">
            <surname>Denguezli</surname>
            <given-names>M</given-names>
          </name>
          <name name-style="western">
            <surname>Jithoo</surname>
            <given-names>A</given-names>
          </name>
          <name name-style="western">
            <surname>Gnatiuc</surname>
            <given-names>L</given-names>
          </name>
          <name name-style="western">
            <surname>Buist</surname>
            <given-names>S</given-names>
          </name>
          <name name-style="western">
            <surname>Burney</surname>
            <given-names>P</given-names>
          </name>
          <name name-style="western">
            <surname>Tabka</surname>
            <given-names>Z</given-names>
          </name>
          <name name-style="western">
            <surname>Harrabi</surname>
            <given-names>I</given-names>
          </name>
        </person-group>
        <article-title>Prevalence of COPD and tobacco smoking in Tunisia—results from the BOLD study</article-title>
        <source>Int J Environ Res Public Health</source>  
        <year>2013</year>  
        <month>12</month>  
        <day>17</day>  
        <volume>10</volume>  
        <issue>12</issue>  
        <fpage>7257</fpage>  
        <lpage>7271</lpage>  
        <comment>
          <ext-link xmlns:xlink="http://www.w3.org/1999/xlink" xlink:type="simple" xlink:href="http://www.mdpi.com/resolver?pii=ijerph10127257"/>
        </comment>  
        <pub-id pub-id-type="doi">10.3390/ijerph10127257</pub-id>
        <pub-id pub-id-type="medline">24351745</pub-id>
        <pub-id pub-id-type="pii">ijerph10127257</pub-id>
        <pub-id pub-id-type="pmcid">PMC3881165</pub-id></nlm-citation>
      </ref>
      <ref id="ref25">
        <label>25</label>
        <nlm-citation citation-type="journal">
        <person-group person-group-type="author">
          <name name-style="western">
            <surname>Alhamad</surname>
            <given-names>EH</given-names>
          </name>
          <name name-style="western">
            <surname>Alorainy</surname>
            <given-names>HS</given-names>
          </name>
          <name name-style="western">
            <surname>Lababidi</surname>
            <given-names>H</given-names>
          </name>
          <name name-style="western">
            <surname>Al-Hajjaj</surname>
            <given-names>MS</given-names>
          </name>
        </person-group>
        <article-title>The prevalence of chronic obstructive pulmonary disease in Riyadh, Saudi Arabia: a BOLD study</article-title>
        <source>Int J Tuberc Lung Dis</source>  
        <year>2015</year>  
        <month>10</month>  
        <volume>19</volume>  
        <issue>10</issue>  
        <fpage>1252</fpage>  
        <lpage>1257</lpage>  
        <pub-id pub-id-type="doi">10.5588/ijtld.14.0939</pub-id>
        <pub-id pub-id-type="medline">26459542</pub-id></nlm-citation>
      </ref>
      <ref id="ref26">
        <label>26</label>
        <nlm-citation citation-type="journal">
        <person-group person-group-type="author">
          <name name-style="western">
            <surname>Danielsson</surname>
            <given-names>P</given-names>
          </name>
          <name name-style="western">
            <surname>Ólafsdóttir</surname>
            <given-names>IS</given-names>
          </name>
          <name name-style="western">
            <surname>Benediktsdóttir</surname>
            <given-names>B</given-names>
          </name>
          <name name-style="western">
            <surname>Gíslason</surname>
            <given-names>T</given-names>
          </name>
          <name name-style="western">
            <surname>Janson</surname>
            <given-names>C</given-names>
          </name>
        </person-group>
        <article-title>The prevalence of chronic obstructive pulmonary disease in Uppsala, Sweden—the Burden of Obstructive Lung Disease (BOLD) study: cross-sectional population-based study</article-title>
        <source>Clin Respir J</source>  
        <year>2012</year>  
        <month>04</month>  
        <volume>6</volume>  
        <issue>2</issue>  
        <fpage>120</fpage>  
        <lpage>127</lpage>  
        <pub-id pub-id-type="doi">10.1111/j.1752-699X.2011.00257.x</pub-id>
        <pub-id pub-id-type="medline">21651748</pub-id></nlm-citation>
      </ref>
      <ref id="ref27">
        <label>27</label>
        <nlm-citation citation-type="book">
        <person-group person-group-type="author">
          <name name-style="western">
            <surname>Rothman</surname>
            <given-names>RJ</given-names>
          </name>
          <name name-style="western">
            <surname>Greenland</surname>
            <given-names>S</given-names>
          </name>
          <name name-style="western">
            <surname>Lash</surname>
            <given-names>TL</given-names>
          </name>
        </person-group>
        <source>Modern Epidemiology. Third Edition</source>  
        <year>2008</year>  
        <publisher-loc>Philadelphia</publisher-loc>
        <publisher-name>Lippincott-Williams &#38; Wilkins Publishers</publisher-name></nlm-citation>
      </ref>
      <ref id="ref28">
        <label>28</label>
        <nlm-citation citation-type="web">
        <person-group person-group-type="author">
          <collab>World Health Organization</collab>
        </person-group>
        <source>The WHO country health profile of Kazakhstan</source>  
        <access-date>2017-05-14</access-date>
        <comment>
          <ext-link xmlns:xlink="http://www.w3.org/1999/xlink" xlink:type="simple" xlink:href="http://www.who.int/countries/kaz/en/">http://www.who.int/countries/kaz/en/</ext-link>
          <ext-link ext-link-type="webcite" xlink:href="6qS2v7MOo"/>
        </comment> </nlm-citation>
      </ref>
      <ref id="ref29">
        <label>29</label>
        <nlm-citation citation-type="journal">
        <person-group person-group-type="author">
          <name name-style="western">
            <surname>Buist</surname>
            <given-names>AS</given-names>
          </name>
          <name name-style="western">
            <surname>Vollmer</surname>
            <given-names>WM</given-names>
          </name>
          <name name-style="western">
            <surname>Sullivan</surname>
            <given-names>SD</given-names>
          </name>
          <name name-style="western">
            <surname>Weiss</surname>
            <given-names>KB</given-names>
          </name>
          <name name-style="western">
            <surname>Lee</surname>
            <given-names>TA</given-names>
          </name>
          <name name-style="western">
            <surname>Menezes</surname>
            <given-names>AMB</given-names>
          </name>
          <name name-style="western">
            <surname>Crapo</surname>
            <given-names>RO</given-names>
          </name>
          <name name-style="western">
            <surname>Jensen</surname>
            <given-names>RL</given-names>
          </name>
          <name name-style="western">
            <surname>Burney</surname>
            <given-names>PGJ</given-names>
          </name>
        </person-group>
        <article-title>The Burden of Obstructive Lung Disease Initiative (BOLD): rationale and design</article-title>
        <source>COPD</source>  
        <year>2005</year>  
        <month>06</month>  
        <volume>2</volume>  
        <issue>2</issue>  
        <fpage>277</fpage>  
        <lpage>283</lpage>  
        <pub-id pub-id-type="medline">17136954</pub-id></nlm-citation>
      </ref>
      <ref id="ref30">
        <label>30</label>
        <nlm-citation citation-type="journal">
        <person-group person-group-type="author">
          <name name-style="western">
            <surname>Ford</surname>
            <given-names>ES</given-names>
          </name>
          <name name-style="western">
            <surname>Mannino</surname>
            <given-names>DM</given-names>
          </name>
          <name name-style="western">
            <surname>Wheaton</surname>
            <given-names>AG</given-names>
          </name>
          <name name-style="western">
            <surname>Giles</surname>
            <given-names>WH</given-names>
          </name>
          <name name-style="western">
            <surname>Presley-Cantrell</surname>
            <given-names>L</given-names>
          </name>
          <name name-style="western">
            <surname>Croft</surname>
            <given-names>JB</given-names>
          </name>
        </person-group>
        <article-title>Trends in the prevalence of obstructive and restrictive lung function among adults in the United States: findings from the National Health and Nutrition Examination surveys from 1988-1994 to 2007-2010</article-title>
        <source>Chest</source>  
        <year>2013</year>  
        <month>05</month>  
        <volume>143</volume>  
        <issue>5</issue>  
        <fpage>1395</fpage>  
        <lpage>1406</lpage>  
        <comment>
          <ext-link xmlns:xlink="http://www.w3.org/1999/xlink" xlink:type="simple" xlink:href="http://europepmc.org/abstract/MED/23715520"/>
        </comment>  
        <pub-id pub-id-type="doi">10.1378/chest.12-1135</pub-id>
        <pub-id pub-id-type="medline">23715520</pub-id>
        <pub-id pub-id-type="pii">S0012-3692(13)60339-6</pub-id>
        <pub-id pub-id-type="pmcid">PMC4563801</pub-id></nlm-citation>
      </ref>
      <ref id="ref31">
        <label>31</label>
        <nlm-citation citation-type="book">
        <person-group person-group-type="author">
          <name name-style="western">
            <surname>Lohr</surname>
            <given-names>SL</given-names>
          </name>
        </person-group>
        <source>Sampling: Design and Analysis. 2nd Edition</source>  
        <year>2010</year>  
        <publisher-loc>Boston</publisher-loc>
        <publisher-name>Cengage Learning</publisher-name></nlm-citation>
      </ref>
      <ref id="ref32">
        <label>32</label>
        <nlm-citation citation-type="journal">
        <person-group person-group-type="author">
          <name name-style="western">
            <surname>Hoving</surname>
            <given-names>C</given-names>
          </name>
          <name name-style="western">
            <surname>Mudde</surname>
            <given-names>AN</given-names>
          </name>
        </person-group>
        <article-title>Effect of recruitment method and setting on the composition of samples consisting of adult smokers</article-title>
        <source>Patient Educ Couns</source>  
        <year>2007</year>  
        <month>01</month>  
        <volume>65</volume>  
        <issue>1</issue>  
        <fpage>79</fpage>  
        <lpage>86</lpage>  
        <pub-id pub-id-type="doi">10.1016/j.pec.2006.05.008</pub-id>
        <pub-id pub-id-type="medline">16872796</pub-id>
        <pub-id pub-id-type="pii">S0738-3991(06)00179-0</pub-id></nlm-citation>
      </ref>
      <ref id="ref33">
        <label>33</label>
        <nlm-citation citation-type="journal">
        <person-group person-group-type="author">
          <name name-style="western">
            <surname>Miller</surname>
            <given-names>MR</given-names>
          </name>
          <name name-style="western">
            <surname>Hankinson</surname>
            <given-names>J</given-names>
          </name>
          <name name-style="western">
            <surname>Brusasco</surname>
            <given-names>V</given-names>
          </name>
          <name name-style="western">
            <surname>Burgos</surname>
            <given-names>F</given-names>
          </name>
          <name name-style="western">
            <surname>Casaburi</surname>
            <given-names>R</given-names>
          </name>
          <name name-style="western">
            <surname>Coates</surname>
            <given-names>A</given-names>
          </name>
          <name name-style="western">
            <surname>Crapo</surname>
            <given-names>R</given-names>
          </name>
          <name name-style="western">
            <surname>Enright</surname>
            <given-names>P</given-names>
          </name>
          <name name-style="western">
            <surname>Gustafsson</surname>
            <given-names>P</given-names>
          </name>
          <name name-style="western">
            <surname>Jensen</surname>
            <given-names>R</given-names>
          </name>
          <name name-style="western">
            <surname>Johnson</surname>
            <given-names>DC</given-names>
          </name>
          <name name-style="western">
            <surname>MacIntyre</surname>
            <given-names>N</given-names>
          </name>
          <name name-style="western">
            <surname>McKay</surname>
            <given-names>R</given-names>
          </name>
          <name name-style="western">
            <surname>Navajas</surname>
            <given-names>D</given-names>
          </name>
          <name name-style="western">
            <surname>Pedersen</surname>
            <given-names>OF</given-names>
          </name>
          <name name-style="western">
            <surname>Pellegrino</surname>
            <given-names>R</given-names>
          </name>
          <name name-style="western">
            <surname>Viegi</surname>
            <given-names>G</given-names>
          </name>
          <name name-style="western">
            <surname>Wanger</surname>
            <given-names>J</given-names>
          </name>
        </person-group>
        <article-title>Standardisation of spirometry</article-title>
        <source>Eur Respir J</source>  
        <year>2005</year>  
        <month>08</month>  
        <volume>26</volume>  
        <issue>2</issue>  
        <fpage>319</fpage>  
        <lpage>338</lpage>  
        <comment>
          <ext-link xmlns:xlink="http://www.w3.org/1999/xlink" xlink:type="simple" xlink:href="http://erj.ersjournals.com/cgi/pmidlookup?view=long&#38;pmid=16055882"/>
        </comment>  
        <pub-id pub-id-type="doi">10.1183/09031936.05.00034805</pub-id>
        <pub-id pub-id-type="medline">16055882</pub-id>
        <pub-id pub-id-type="pii">26/2/319</pub-id></nlm-citation>
      </ref>
      <ref id="ref34">
        <label>34</label>
        <nlm-citation citation-type="web">
        <person-group person-group-type="author">
          <name name-style="western">
            <surname>Beigelman-Aubry</surname>
            <given-names>C</given-names>
          </name>
        </person-group>
        <source>Advanced chest imaging</source>  
        <access-date>2017-07-06</access-date>
        <comment>
          <ext-link xmlns:xlink="http://www.w3.org/1999/xlink" xlink:type="simple" xlink:href="http://clinical.netforum.healthcare.philips.com/us_en/Explore/Abstracts/CT/Advanced-chest-imaging">http://clinical.netforum.healthcare.philips.com/us_en/Explore/Abstracts/CT/Advanced-chest-imaging</ext-link>
          <ext-link ext-link-type="webcite" xlink:href="6qSQyIBzY"/>
        </comment> </nlm-citation>
      </ref>
      <ref id="ref35">
        <label>35</label>
        <nlm-citation citation-type="journal">
        <person-group person-group-type="author">
          <name name-style="western">
            <surname>Bhalla</surname>
            <given-names>M</given-names>
          </name>
          <name name-style="western">
            <surname>Turcios</surname>
            <given-names>N</given-names>
          </name>
          <name name-style="western">
            <surname>Aponte</surname>
            <given-names>V</given-names>
          </name>
          <name name-style="western">
            <surname>Jenkins</surname>
            <given-names>M</given-names>
          </name>
          <name name-style="western">
            <surname>Leitman</surname>
            <given-names>BS</given-names>
          </name>
          <name name-style="western">
            <surname>McCauley</surname>
            <given-names>DI</given-names>
          </name>
          <name name-style="western">
            <surname>Naidich</surname>
            <given-names>DP</given-names>
          </name>
        </person-group>
        <article-title>Cystic fibrosis: scoring system with thin-section CT</article-title>
        <source>Radiology</source>  
        <year>1991</year>  
        <month>06</month>  
        <volume>179</volume>  
        <issue>3</issue>  
        <fpage>783</fpage>  
        <lpage>788</lpage>  
        <pub-id pub-id-type="doi">10.1148/radiology.179.3.2027992</pub-id>
        <pub-id pub-id-type="medline">2027992</pub-id></nlm-citation>
      </ref>
      <ref id="ref36">
        <label>36</label>
        <nlm-citation citation-type="journal">
        <person-group person-group-type="author">
          <name name-style="western">
            <surname>Tulek</surname>
            <given-names>B</given-names>
          </name>
          <name name-style="western">
            <surname>Kivrak</surname>
            <given-names>AS</given-names>
          </name>
          <name name-style="western">
            <surname>Ozbek</surname>
            <given-names>S</given-names>
          </name>
          <name name-style="western">
            <surname>Kanat</surname>
            <given-names>F</given-names>
          </name>
          <name name-style="western">
            <surname>Suerdem</surname>
            <given-names>M</given-names>
          </name>
        </person-group>
        <article-title>Phenotyping of chronic obstructive pulmonary disease using the modified Bhalla scoring system for high-resolution computed tomography</article-title>
        <source>Can Respir J</source>  
        <year>2013</year>  
        <volume>20</volume>  
        <issue>2</issue>  
        <fpage>91</fpage>  
        <lpage>96</lpage>  
        <comment>
          <ext-link xmlns:xlink="http://www.w3.org/1999/xlink" xlink:type="simple" xlink:href="http://europepmc.org/abstract/MED/23616965"/>
        </comment>  
        <pub-id pub-id-type="medline">23616965</pub-id>
        <pub-id pub-id-type="pmcid">PMC3630042</pub-id></nlm-citation>
      </ref>
      <ref id="ref37">
        <label>37</label>
        <nlm-citation citation-type="web">
        <source>Stanford Medicine 25</source>  
        <access-date>2017-07-06</access-date>
        <comment>Pulmonary exam: percussion and inspection 
        <ext-link xmlns:xlink="http://www.w3.org/1999/xlink" xlink:type="simple" xlink:href="http://stanfordmedicine25.stanford.edu/the25/pulmonary.html">http://stanfordmedicine25.stanford.edu/the25/pulmonary.html</ext-link>
        <ext-link ext-link-type="webcite" xlink:href="6nmHVisJP"/></comment> </nlm-citation>
      </ref>
      <ref id="ref38">
        <label>38</label>
        <nlm-citation citation-type="web">
        <source>Stanford Medicine 25</source>  
        <access-date>2017-01-25</access-date>
        <comment>Cardiac second sounds 
        <ext-link xmlns:xlink="http://www.w3.org/1999/xlink" xlink:type="simple" xlink:href="http://stanfordmedicine25.stanford.edu/the25/cardiac.html">http://stanfordmedicine25.stanford.edu/the25/cardiac.html</ext-link>
        <ext-link ext-link-type="webcite" xlink:href="6nmHu2tbb"/></comment> </nlm-citation>
      </ref>
      <ref id="ref39">
        <label>39</label>
        <nlm-citation citation-type="journal">
        <person-group person-group-type="author">
          <collab>American Thoracic Society</collab>
        </person-group>
        <article-title>ATS statement: guidelines for the six-minute walk test</article-title>
        <source>Am J Respir Crit Care Med</source>  
        <year>2002</year>  
        <month>07</month>  
        <day>1</day>  
        <volume>166</volume>  
        <issue>1</issue>  
        <fpage>111</fpage>  
        <lpage>117</lpage>  
        <pub-id pub-id-type="doi">10.1164/ajrccm.166.1.at1102</pub-id>
        <pub-id pub-id-type="medline">12091180</pub-id></nlm-citation>
      </ref>
      <ref id="ref40">
        <label>40</label>
        <nlm-citation citation-type="journal">
        <person-group person-group-type="author">
          <name name-style="western">
            <surname>Mahler</surname>
            <given-names>DA</given-names>
          </name>
          <name name-style="western">
            <surname>Horowitz</surname>
            <given-names>MB</given-names>
          </name>
        </person-group>
        <article-title>Perception of breathlessness during exercise in patients with respiratory disease</article-title>
        <source>Med Sci Sports Exerc</source>  
        <year>1994</year>  
        <month>09</month>  
        <volume>26</volume>  
        <issue>9</issue>  
        <fpage>1078</fpage>  
        <lpage>1081</lpage>  
        <pub-id pub-id-type="medline">7808239</pub-id></nlm-citation>
      </ref>
      <ref id="ref41">
        <label>41</label>
        <nlm-citation citation-type="journal">
        <person-group person-group-type="author">
          <name name-style="western">
            <surname>Jones</surname>
            <given-names>PW</given-names>
          </name>
          <name name-style="western">
            <surname>Harding</surname>
            <given-names>G</given-names>
          </name>
          <name name-style="western">
            <surname>Berry</surname>
            <given-names>P</given-names>
          </name>
          <name name-style="western">
            <surname>Wiklund</surname>
            <given-names>I</given-names>
          </name>
          <name name-style="western">
            <surname>Chen</surname>
            <given-names>W</given-names>
          </name>
          <name name-style="western">
            <surname>Kline</surname>
            <given-names>LN</given-names>
          </name>
        </person-group>
        <article-title>Development and first validation of the COPD Assessment Test</article-title>
        <source>Eur Respir J</source>  
        <year>2009</year>  
        <month>09</month>  
        <volume>34</volume>  
        <issue>3</issue>  
        <fpage>648</fpage>  
        <lpage>654</lpage>  
        <comment>
          <ext-link xmlns:xlink="http://www.w3.org/1999/xlink" xlink:type="simple" xlink:href="http://erj.ersjournals.com/cgi/pmidlookup?view=long&#38;pmid=19720809"/>
        </comment>  
        <pub-id pub-id-type="doi">10.1183/09031936.00102509</pub-id>
        <pub-id pub-id-type="medline">19720809</pub-id>
        <pub-id pub-id-type="pii">34/3/648</pub-id></nlm-citation>
      </ref>
    </ref-list>
  </back>
</article>
