The prevalence and the diagnosis of Chronic Obstructive Pulmonary Disease (COPD) and its tobacco related etiology in North-Western Russia
(2018)
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- Chronic obstructive pulmonary disease (COPD) remains a major public health problem in the 21st century. COPD is one of the leading causes of morbidity and mortality worldwide and results in an economic and social burden that is both substantial and increasing. The development of COPD is multifactorial, and the risk factors include both genetic and environmental ones, of which tobacco remains worldwide the dominant one. It remains however unclear why some smokers develop COPD whereas others do not. In spite of the huge smoking behavior in Russia (a total of 37.3 % of all Russians are current smokers), the burden and prevalence of COPD in Russia have been underestimated, in particular, because of the high cardiovascular mortality rate. A gap between the “epidemiological” and the “clinical” definitions, uncertainty in the diagnosis over time and the potential role of different biomarkers remain key issues regarding the diagnosis of COPD. The aim of this thesis was to gain a better understanding of the prevalence, pathogenesis and symptoms of early COPD. The data for my PhD project were obtained from a population-based epidemiological study (RESPECT) that was set up as collaborative research project of three universities. The design of the study was created by the research team among whom I was one of the principal investigators and pulmonologists. The preparatory phase of the project included a pilot study, the development of the distance-learning course on spirometry (SpiroCourse), and the development of a quality control system for all spirometry data. 3133 individuals aged 35-70 years from 15 participating centers in St. Petersburg and Arkhangelsk were screened. Symptoms and risk factors were collected and pre- and post-BD spirometry was performed. The final diagnosis of COPD was based on a comprehensive assessment including a repeated spirometry with BD test and a rigorous clinical examination performed by a pulmonologist. The entire study includes three parts: a cross-sectional study (prevalence), a cohort study (a diagnostic follow-up) and a comparative (case-control) study. First of all, a cross-sectional study was conducted to estimate the prevalence of AO based on sex, age, smoking status, environmental and socioeconomic conditions using both cut-off values. A relatively low prevalence of AO in the RESPECT population (6.8% and 4.8% according to the fixed and GLI-LLN cut-offs, respectively) was observed. But in man the overall and age-specific AO prevalence was relatively higher compared with some European countries, in spite of low life expectancy at birth and a huge cardio-vascular mortality rate in the Russian male population. From all the environmental factors studied, only smoking was independently associated with AO (OR 2.47, 95% CI 1.60–3.82). Further research was performed in order to assess the diagnostic value of respiratory symptoms and to identify risk factors for AO. We found that chronic respiratory symptoms had a low PPV but a high NPV for the diagnosis of chronic AO as defined by any of both cut-off values. A clinical definition of COPD was used in the second part of the study, which aimed to differentiate the disease from spirometrically defined AO. During the follow-up examination of obstructed participants we encountered diagnostic shifts of the initial diagnosis at baseline. As a result, from all 167 invited participants who were pre- and post-BD obstructive at the first spirometry examination 46.1% remained obstructive at the second spirometry measurement. The participants with an initial label of AO were diagnosed later as having COPD (68.8%), ACO (19.5%) and asthma with fixed obstruction (7.8%). The PPVs of a chronic respiratory symptoms was low for the diagnosis of COPD, asthma, ACO and chronic bronchitis. Further, we conducted a third study aimed to compare serum proinflammatory profiles and biomarkers in heavy smokers (smoking history ≥ 10 pack-years) with and without COPD. We found that 44.9% of the smokers with normal spirometry and 28.3% of the smokers with COPD did not have any abnormal biomarker levels, while 56.5% of the patients with COPD and 17.4% without AO demonstrated two+ elevated biomarker levels (we labeled them as “inflamed smokers”). They were older and had a more cumulative smoking history compared to non-inflamed ones. Among all the risk factors, only COPD was associated with systemic inflammation (OR 4.38, 95% CI 1.57 – 12.24). In conclusion, this work allowed to estimate the prevalence of COPD in a cohort of adults aged 35-70 years in North-Western Russia using both cutoff values, to identify the diagnostic value of symptoms and background characteristics for the diagnosis of COPD as well as to demonstrate uncertainty in the diagnosis of COPD over time and the way it relates to ACO. We were able to demonstrate that one spirometric assessment is not enough to make a final diagnosis of CODP and that serial longitudinal spirometric assessments are needed and have to be complemented by a comprehensive clinical assessment when diagnosing COPD. Finally, the third part of the RESPECT study allowed us to explore differences in background characteristics, inflammatory biomarkers, and pneumoproteins in smokers with and without COPD. We hope our work will inspire further research, particularly toward determining various aspects of the complex relationship between tobacco exposure and development of COPD.
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Andreeva, E. (2018). The prevalence and the diagnosis of Chronic Obstructive Pulmonary Disease (COPD) and its tobacco related etiology in North-Western Russia. https://hdl.handle.net/2078.5/53299