Tobacco smoking is the greatest preventable cause of death and illness in the world that attributed to more than 7 million deaths in 2015 ¹ . Smoking is associated with elevated risk of mortality from lung and other cancers, heart disease, stroke, chronic obstructive pulmonary disease (COPD) and other respiratory diseases, and other conditions ² . The Global Adult Tobacco Survey (GATS) conducted in Kazakhstan in 2014 found that 19.1% of the study population were daily smokers (36.9% of males and 3.2% of females) ( http://apps.who.int/tobacco/surveillance/survey/gats/kaz_countryreport_en.pdf?ua=1). COPD accounted for 3.2 million deaths worldwide in 2015 ³ and is the fourth leading cause of death globally ⁴ . In Kazakhstan, an expected 1.4 million people might have COPD based on estimations from neighboring countries ⁵ .

Metabolic syndrome (MetS), or the set of specific cardiovascular risk factors, is also identified as a significant public health challenge that increases risk of developing type 2 diabetes, cardiovascular disease and several cancers ^{6, 7} . MetS is prevalent among patients with COPD ⁸ . It was shown that cardiovascular disease, hypertension and diabetes in patients with COPD are associated with higher hospitalization and mortality rates ⁹ .

The presence of respiratory symptoms prompts to recognize and diagnose respiratory disease including COPD ¹⁰ and is often used to evaluate a severity of disease ¹¹ .

Smoking cessation has proven to have significant health benefits, including reduction in cardiovascular and COPD morbidity and mortality ^{12– 15} , and decrease in outset of respiratory symptoms ¹⁴ . Some studies demonstrated that smoking is associated with metabolic syndrome and quitting smoking is recommended for the prevention and management of metabolic syndrome ^{16, 17} .

Assessment of the associations between several health outcomes, including COPD, respiratory symptoms, MetS and functional incapacity, and cigarette smoking status has not been done in Kazakhstan.

This study investigated these associations by comparing prevalence of these outcomes in smokers, ex-smokers, and never-smokers aged 40–59 in Almaty City, Kazakhstan.

Basic characteristics and smoking patterns of study participants by study group are summarized in Table 1. The study participants were approximately equally distributed as those who were younger than 50 years and older than 50 years of age. There were about twice as many participants of Kazakh ethnicity (Asian origin) compared to Russians (European origin). Most of the participants had higher education. Majority of those who were smoking had more than 20 pack-years of smoking (61%).

Data on COPD prevalence, CAT-test, functional capacity based on 6MWT and prevalence of MetS are shown in Table 2. The prevalence of COPD among smokers, ex-smokers and never-smokers were 5.5%, 3.0% and 3.0%, respectively. Respiratory symptoms based on CAT were more prevalent among smokers (42.8%) as compared to ex-smokers (17.0%) and never-smokers (12.5%). Proportion of participants with MetS varied across the study groups from 28.6% among never-smokers to 37.5% among currents smokers. Current smokers were more likely (16.7%) to walk less than 450 meters during the 6MWT as compared to never-smokers (5.0%).

Mean scores of CAT components are show in Figure 1. Smokers had significantly worse mean scores in all CAT components than ex-smokers and never-smokers except in the sleeping category. There were statistically significant (p<0.017) differences between mean scores of ex-smokers and never-smokers for cough, phlegm, and chest tightness.

The relationship between the smoking status and the prevalence of metabolic syndrome components is presented in Table 3. The prevalence of reduced levels of high-density lipoproteins was significantly higher for the group of current smokers than for ex-smokers and never smokers. No significant relationship was found between the prevalence of other components and the smoking status (P>0.017).

Crude and adjusted odds ratios (aOR) between COPD, respiratory symptoms, MetS, functional incapacity and the smoking status are presented in Table 4. Current smokers were significantly associated with increased prevalence of functional incapacity (6MWT<450 meters) while comparing with never-smokers (aOR 3.72, 95% CI 1.86–7.44). Current smokers had more prevalent respiratory symptoms than ex-smokers (aOR 3.43, 95% CI 2.25–5.23) and never-smokers (aOR 5.44, 95% CI 3.42–8.65). No significant association was found between the smoking status and prevalence of COPD and MetS in all three pairwise comparisons.

This study was the first in Kazakhstan to assess prevalence of COPD, respiratory symptoms, MetS, functional exercise incapacity in adults aged 40–59, those who smoked cigarettes, quit smoking and never smoked. The study demonstrated that at least 3% of the study population were affected by COPD. This value is much higher than the rate of previously reported COPD cases of 340.5 per 100,000 population ( http://www.mz.gov.kz/en/pages/statistical-symposium-health-republic-kazakhstans-population-and-activity-health-service).

Two of four health outcomes assessed in the study, respiratory symptoms and functional exercise incapacity, were significantly worse among current smokers than among those participants who never smoked cigarettes. Two other study outcomes, COPD and MetS, were more prevalent in current smokers, but the study couldn’t demonstrate statistically significant association with the smoking status.

The presence of all symptoms and signs of respiratory disease that are used as CAT components were significantly lower among ex-smokers compared to those who continued smoking. This study is in line with other studies, suggesting that respiratory symptoms improve after smoking cessation, however remain worse or at least similar to those found in never-smokers ¹⁹ . One may assume that respiratory symptoms may be a significant reason for smoking cessation in a number of cases.

It is important to notice that a substantial proportion of the current smokers or 42.8% had respiratory symptoms, even if most of them had preserved pulmonary function defined by spirometry. It was shown that high CAT scores in current or ex-smokers are associated with exacerbation-like events, i.e. that symptomatic smokers with preserved pulmonary function have evidence of airway disease even when they do not meet the current definition for COPD ²⁴ . Exacerbation-like events in individuals without COPD raise the burden of respiratory disease and are associated with considerable health outcomes ²⁵ . Thus, even proper diagnosis of COPD based on the spirometric criterion substantially underestimates the effect of smoking on the individual with smoking history.

The study has several limitations. This was cross-sectional study that was not designed to determine causal relationship. Second, although we adjusted for the known potential confounders, residual bias attributable to uncontrolled confounding variables may exist and cannot be estimated. Third, we used a quota sample which may have affected the generalizability of the study results to the study population. Fourth, our study participants were adults aged 40–59 from Almaty city, and further assessment is needed to determine whether the results are applicable to the other population groups.

The data referenced by this article are under copyright with the following copyright statement: Copyright: � 2018 Zhussupov B et al.

Data associated with the article are available under the terms of the Creative Commons Zero "No rights reserved" data waiver (CC0 1.0 Public domain dedication).

Dataset 1. Raw data behind the results of this study.

The main data are provided for 900 subjects who completed the study (500 smokers, 200 ex-smokers, and 200 never-smokers). Missing data were not replaced.

Subject ID (ID), study group, gender, age, ethnicity, education, cigarette consumption (expressed as a number of pack-year), regular secondary smoking in past 12 months (for ex- and never-smokers), airflow obstruction by spirometry (FEV1/FVC < 70%), Six minute walk test, CAT total score, CAT components: - cough; - phlegm; - tightness of chest; - shortness of breath (SOB); - limited doing activities at home; - not confident leaving home; - not sleeping soundly; - no energy, metabolic syndrome (1 – yes, 0 – no), central obesity (1 – yes, 0 – no), raised triglyceride (≥ 150 mg/dL: 1 – yes, 0 – no), reduced high-density lipoprotein (< 40 mg/dL for males and < 50 mg/dL for females: 1 – yes, 0 – no), raised blood pressure (≥130/85 mm Hg: 1 – yes, 0 – no), raised fasting plasma glucose (≥ 100 mg/dL: 1 – yes, 0 – no). F1000Research: Dataset 1. Raw data behind the results of this study, 10.5256/f1000research.14614.d203456 ²⁶

The National Central Ethic Committee under Ministry of Health and Social Development of the Republic of Kazakhstan approved this study on August 19, 2016. Written informed consent was obtained from all participants. The study has been registered in ClinicalTrial.gov (the release date: October 3, 2016; Identification No. NCT02926534) ²⁷ .