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Risk factors of chronic obstructive pulmonary disease among adults in Chinese mainland: A systematic review and meta-analysis
Accepted Manuscript Risk factors of chronic obstructive pulmonary disease among adults in Chinese mainland: A systematic review and meta-analysis Ying Yang, Jing Mao, Zhiying Ye, Jie Li, Huimin Zhao, Yueting Liu PII:
S0954-6111(17)30288-3
DOI:
10.1016/j.rmed.2017.08.018
Reference:
YRMED 5239
To appear in:
Respiratory Medicine
Received Date: 5 June 2017 Revised Date:
16 August 2017
Accepted Date: 17 August 2017
Please cite this article as: Yang Y, Mao J, Ye Z, Li J, Zhao H, Liu Y, Risk factors of chronic obstructive pulmonary disease among adults in Chinese mainland: A systematic review and meta-analysis, Respiratory Medicine (2017), doi: 10.1016/j.rmed.2017.08.018. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT Risk factors of chronic obstructive pulmonary disease among adults in Chinese mainland: A systematic review and meta-analysis Authors： ：
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Ying Yang a, Jing Mao a, Zhiying Ye b, Jie Li a, *, Huimin Zhao a, Yueting Liu a Authors Affiliations: a
School of Nursing, Tongji Medical College, Huazhong University of Science and Technology, Hangkong Road 13,
Wuhan 430030, China.
Huazhong University of Science and Technology Hospital, Luoyu Road 1037, Wuhan 430074, China
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b
Corresponding Author:
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Jie Li, PhD, RN, School of Nursing, Tongji Medical College, Huazhong University of Science and Technology, Hangkong Road 13, Qiaokou District, Wuhan 430030, China. Tel: +86 18971097091 E-mail: [email protected] E-mail address:
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[email protected] (Ying Yang), [email protected] (Jing Mao), [email protected] (Zhiying Ye),
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[email protected] (Jie Li), [email protected] (Huimin Zhao), [email protected] (Yueting Liu).
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ACCEPTED MANUSCRIPT ABSTRACT Background: Identifying risk factors is a key point for preventive strategies to reduce the incidence of COPD. The aim of this systematic review and meta-analysis was to determine the most important risk factors for COPD among adults in Chinese Mainland, so as to provide some precautions and interventions on this disease and preventing further
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recurrences.
Methods: A comprehensive literature review relating to risk factors for COPD through PubMed, EMBASE, Cochrane Library, China National Knowledge Infrastructure (CNKI), Wanfang database and VIP database was conducted before
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March 31, 2017. Odds ratio (OR) with 95% confidence interval (CI) was calculated after data combination to assess the associations between risk factors and COPD. Heterogeneity between the studies was assessed by I² and Cochran’s Q
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test. Egger’s test was used to assess publication bias.
Results: A total of 13893 participants (6383 cases and 7510 controls) from 19 case-controls studies were included. 12 risk factors with significant differences found between COPD and control groups were listed as follows: male sex (OR=1.467; 95%CI: 1.097-1.962), smoking (OR=2.092; 95%CI: 1.707-2.565), low educational level (OR=1.609; 95%CI: 1.206-2.147), low BMI (OR=3.831; 95%CI: 2.223-6.603), family history of respiratory disease (OR=2.068;
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95%CI: 1.466-2.918), allergy history (OR=2.381; 95%CI: 1.385-4.093), respiratory infection during childhood (OR=2.695; 95%CI: 1.504-4.828), recurrent respiratory infection (OR=15.015; 95%CI: 4.538-49.684), occupational dust exposure (OR=1.791; 95%CI: 1.151-2.788), biomass burning (OR=2.218; 95%CI: 1.308-3.762), poor housing ventilation (OR=3.993; 95%CI: 1.244-12.820), and living around polluted area (OR=1.631; 95%CI: 1.202-2.214).
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Conclusion: Twelve risk factors are associated with the occurrence of COPD in Chinese Mainland, which can be used to distinguish high-risk population. Health education and promotion campaigns should be designed in order to
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minimize or prevent the occurrence of COPD in Chinese Mainland. Keywords: Pulmonary disease, chronic obstructive; Risk factors; Meta-analysis; Systematic review; China
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ACCEPTED MANUSCRIPT 1. Introduction Chronic obstructive pulmonary disease (COPD) is one of the common respiratory diseases, characterized by airflow limitation, which can be prevented and treated. The airflow limitation develops not fully reversibly and progressively [1]. According to the estimate of World Health Organization (WHO), about 3 million people died of
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COPD in 2005, which count for 5% of the total mortality worldwide. It is expected that by 2030, COPD will become the world’s third largest lethal disease [2]. In a time of aging populations, COPD is becoming more and more serious, with high and increasing morbidity and mortality [1], especially in developing countries. In China, the overall
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prevalence of COPD in people older than 40 was 8.2% according to a large, population-based survey [3]. Because of the great impact on patients' health and quality of life, and high cost for the patients, their relatives, governments, and
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society, COPD has become an important public health problem in China [4].
Many human activities and environmental factors are associated with the incidence of COPD. A previous meta-analysis done by Zhang et al. [5] points out that seven factors may increase the risk of developing COPD, including smoking, occupational exposure and educational level, etc. Data from Chinese population are more convincing in health promotions and policy advocacies in China. In recent years, numerous epidemiological surveys
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have been conducted to identify the risk factors of COPD in various regions of China, but inconsistency has been presented among various study populations. On account of the demand for early detection of high-risk population, we
2. Methods
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operated this meta-analysis to investigate the overall risk factors of COPD in Chinese Mainland.
2.1. Search strategy and study selection
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Two reviewers independently identified relevant studies published in English and Chinese before March 31, 2017 by searching the following electronic databases: PubMed, EMBASE, the Cochrane Library, China National Knowledge Infrastructure (CNKI), Wanfang database and VIP database. Following search terms were used: “Chronic Obstructive Pulmonary Disease” or “COPD” in combination with “risk factors”. References cited in published original and review articles were searched to find out additional studies. We identified studies in accordance with the following inclusion criteria: (1) the participants came from Chinese Mainland; (2) concerning risk factors related to COPD; (3) odds ratio (OR) of each risk factors were reported with 95% confidence interval (CI) or raw data were given for calculating; and (4) the study followed a case-control or cohort 3
ACCEPTED MANUSCRIPT design. We excluded studies if they were reviews, letters, case reports, case series, cross sectionals and the studies that did not report obviously the population sources or the available data to calculate the OR. The discrepancies were resolved through discussion.
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2.2. Data extraction
Data were screened closely and extracted independently by two investigators (J. M. and Z. Y.). A third reviewer (J. L.) made the final decision when inconsistency occurred between the above two reviewers. Data were collected from
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the included studies as follows: first author’s name, year of publication, study design, study region, sample size, number of cases and controls, potential risk factors for COPD, and OR with 95% CIs.
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2.3. Quality assessment
The Newcastle-Ottawa Scale (NOS) [6], which is one of the most useful for assessing methodological quality of non-randomized studies, was used to assess the risk of bias in the included studies. The criteria included three categories: (1) selection (4 items); (2) comparability (1 item); and (3) exposure for case-control study (3 items). A study can be awarded a maximum of one star for each numbered item within the selection and exposure categories. A
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maximum of two stars can be given for comparability [7]. Articles with more than seven stars were considered to be of
fewer than four stars.
2.4. Statistical analysis
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a high quality; those with four to six stars were considered as moderate quality studies; and of a poor quality if they had
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The statistical analysis was conducted using Comprehensive Meta-Analysis (CMA) version 2.0 software [8]. The results were reported as pooled odds ratios (ORs) and corresponding 95% confidence intervals (CI). A two-sided P<0.05 was considered statistically significant. The heterogeneity of the included studies was evaluated using the Cochran’s Q test and the I2 test [9]. I2 is the proportion of total variation attributable to between-study heterogeneity as opposed to random error or chance, and I2 values of 25%, 50% and 75% are considered to indicate low, moderate, and high heterogeneity, respectively [10]. Commonly, we selected a random-effects model to calculate corresponding parameters when the I2 value was more than 50%. Otherwise, a fixed-effects model was used. Egger’s test [11] was used to assess publication bias, the statistical publication bias was set at P<0.10. 4
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3. Results 3.1. Identification of selected studies From the 654 studies identified using our search strategy, 42 potentially relevant articles were retrieved and
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assessed for eligibility. In total, 19 papers were included in this meta-analysis [12-30]. The flow diagram summarizing the study identification and selection is shown in Figure 1. There was good agreement between the reviewers in regards to the validity assessments, the quality assessment of all the published studies were shown in Table 1. Of these, 8
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articles earned seven stars, were considered as high quality. The remaining 11 papers were moderate quality. Hence, the
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included studies were of a relatively high quality.
3.2. Study characteristics
A total of 13893 participants (6383 cases and 7510 controls) from 19 case-controls studies were enrolled. The basic characteristics of these studies are summarized in Table 1.
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3.3. Assessment of heterogeneity
The results of heterogeneity test are listed in Table 2. Heterogeneities were discovered in 15 potential risk factors associated with COPD (I2>50%). Therefore, we calculated the pooled OR values of these factors using a
3.4. Risk factors
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random-effects model.
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This review identified 20 potential risk factors associated with COPD. Of these, four factors (hyperglycemia, history of asthma, history of depression, and drinking) were considered not possible to estimate the pooled ORs, since they were examined in only one or two studies. We then estimated the remaining 16 factors, which were included in three or more studies. The results of the pooled analysis are displayed in Table 3. The forest plots for the risk factors are shown in supplementary materials. The pooled OR suggests that, male sex (OR=1.467; 95% CI: 1.097-1.962; P=0.010), smoking (OR=2.092; 95% CI: 1.707-2.565; P <0.0001), low educational level (OR=1.609; 95% CI: 1.206-2.147; P=0.001), low BMI (OR=3.831; 95% CI: 2.223-6.603; P<0.0001), family history of respiratory disease (OR=2.068; 95% CI: 1.466-2.918; P<0.0001), allergy 5
ACCEPTED MANUSCRIPT history (OR=2.381; 95% CI: 1.385-4.093; P=0.002), respiratory infection during childhood (OR=2.695; 95% CI: 1.504-4.828; P=0.001), recurrent respiratory infection (OR=15.015; 95% CI: 4.538-49.684; P<0.0001), occupational dust exposure (OR=1.791; 95% CI: 1.151-2.788; P=0.010), biomass burning (OR=2.218; 95% CI: 1.308-3.762; P=0.003), poor housing ventilation (OR=3.993; 95% CI: 1.244-12.820; P=0.020), and living around polluted area
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(OR=1.631; 95% CI: 1.202-2.214; P=0.002) are risk factors of COPD in Chinese Mainland. Passive smoking (OR=0.982; 95%CI: 0.716-1.346; P=0.908), cooking frequently (OR=1.525; 95% CI: 0.793-2.933; P=0.206), living in city or town vs living in countryside (OR=1.123; 95% CI: 0.671-1.881; P=0.659), and doing physical labor work
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(OR=1.290; 95% CI: 0.806-2.066; P=0.288) are not associated with COPD in Chinese Mainland.
3.5. Publication bias
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We conducted the Egger’s test to evaluate potential publication bias. The results of the Egger’s test (shown in Table 4) suggested that the publication biases among all of the risk factors were not statistically significant (P>0.10). Hence, our investigation indicated no severe publication biases.
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4. Discussion
This review makes an attempt to sum up the findings concerning the risk factors of COPD in Chinese Mainland during the past decade. Our findings revealed that male sex, smoking, low educational level (≤ 9 years), low BMI (< 18.5 kg/m2), family history of respiratory disease, allergy history, respiratory infection during childhood, recurrent
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respiratory infection, occupational dust exposure, biomass burning, poor housing ventilation, and living around polluted area are significant risk factors relating to the occurrence of COPD in Chinese Mainland. When compared with the
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previous report in China [5], this meta-analysis included more newly published articles and determined more number of risk factors. The new findings and differences indicate that identifying risk factors of COPD among Chinese population is still at an exploration stage, and there is still need for close attention. COPD is one of the leading cause of mobility and mortality worldwide and results in an economic and social burden that is both substantial and increasing[1]. COPD ranks fourth as a leading cause of death in urban areas and third in rural areas [32]. Therefore, future study is needed in order to explore on how the risk factors interact with each other.
4.1. Male sex 6
ACCEPTED MANUSCRIPT The pooled analysis of eight studies suggested that males were more likely to have COPD than females, which was in agreement with the findings of the half of the included papers [15-17, 29]. The result was supported by prior study, showing that all cause and respiratory mortality are significantly lower in females than in males with similar COPD severity [33]. Nevertheless, recent data from developed countries has reported that the prevalence of COPD is
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now almost equal in men and women, probably reflecting the changing patterns of tobacco smoking [1, 34]. Although controversial, some studies have even suggested that women are more susceptible to the effects of tobacco smoke than men [35-37], leading to more severe disease for the equivalent quantity of cigarettes, which have demonstrated a
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greater burden of small airway disease in females compared with males with COPD despite a similar history of tobacco smoke exposure [38, 39]. These discoveries implied that gender-related differences regarding to COPD may be affected by national situation and cultural discrepancies. Thus, as a typical developing country, future researches are needed in
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China to reveal this controversy.
4.2. Smoking
Across the world, cigarette smoking is the most commonly encountered risk factor for COPD [1]. Cigarette smokers have a higher prevalence of respiratory symptoms and lung function abnormalities, a greater annual rate of
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decline in FEV1, and a greater COPD mortality rate than non-smokers [40]. Ministry of Health of the People’s Republic of China released China Report on the Health Hazards of Smoking on May 31, 2012 [41], which sufficiently inferred a causal relationship between smoking and COPD. Similarly, the risk of COPD is higher for smokers and ever smokers
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than never smokers (OR=2.092; 95% CI: 1.707-2.565) according to our review. The result is consistent with former meta-analysis done by Wang et al. (OR=2.90, 95% CI: 2.22-3.80) [42] and Forey et al. (OR=2.89, 95% CI: 2.63-3.17)
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[43]. In view of this, smoking cessation should be advocated as a key measure and important intervention to prevent the occurrence of COPD in China.
4.3. Low educational level (≤ 9 years) Lower socioeconomic status is associated with an increased risk for developing COPD [44], but the components of educational level that contribute are unclear. Nevertheless, our findings indicate that educational level below senior high school degree is a risk factor against the occurrence of COPD. There is strong evidence that risk of developing COPD is inversely related to socioeconomic status. Low educational level is often a reflection of poor socioeconomic 7
ACCEPTED MANUSCRIPT status, individuals with low educational level may live and work in worse environment and lack health care protection information, thus suffering greater risk [44, 45]. On the contrary, the higher one’s educational level, the more attention he/she trends to personal health status. However, we did not analyze income level as a risk factor because there were
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differences in the income level segmentations between the studies.
4.4. Low BMI (<18.5kg/m2)
Body mass index (BMI) was recommended by WHO as an important marker to reflect total body nutrition. Our
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meta-analysis showed that low BMI (<18.5kg/m2) is a risk factor for COPD (OR=3.831; 95% CI: 2.223-6.603) in Chinese Mainland. The incidence of COPD in underweight group was significantly higher compared with normal group probably due to malnutrition and poor immune response to infections [46]. Being underweight might be related to
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malnutrition and/or low socioeconomic status, which is regarded as environmental risk factors for COPD. On the other hand, being underweight might be one of the symptoms in patients with advanced COPD since these patients often experience weight loss, loss of appetite, as well as depression and anxiety [47].
4.5. Family history of respiratory disease
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Results from this review indicate that individuals exposure to a family history of respiratory disease are more likely to develop COPD, with a 2.1-fold greater OR of COPD. A significant familial risk of airflow limitation has been observed in people who smoke and are siblings of patients with severe COPD [48], suggesting that genetics together
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with environmental factors could influence this susceptibility. Association of family history and COPD shown in
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current study has also supported by the Global Initiative for Chronic Obstructive Lung Disease (GOLD) [1].
4.6. Allergy history
A variety of studies suggested the significant relationship between and COPD [16, 29], our meta-analysis further confirmed this result and declared allergy history to be a risk factor of COPD in Chinese Mainland. To the best of our knowledge, airway hyper- reactivity and asthma are independent predictors of COPD and respiratory mortality in population studies [49], as well as an indicator of risk of excess decline in lung function in patients with mild COPD [50]. However, more evidences are required to reveal the correlation among allergy history, airway hyper- reactivity and asthma. 8
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4.7. Respiratory infection during childhood Respiratory infection during childhood is a risk factor for COPD according to this meta-analysis. A history of severe childhood respiratory infection has been associated with reduced lung function and increased respiratory
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symptoms in adulthood [51]. Therefore, continuously attention should be paid to the lung health of children, so as to decrease the risk of COPD in adulthood.
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4.8. Recurrent respiratory infection
Previous studies have consistently documented that infection, especially respiratory infection, is one of the environmental risk factors for COPD and plays an important role in the pathogenesis and progression of COPD [1]. In
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addition, it was suggested that the infection of Mycoplasma pneumoniae and Chlamydia pneumoniae might be crucial for the occurrence and development of COPD [52]. Evidence from this review mentioned that recurrent respiratory infection is a risk factor, which can enhance the danger of developing COPD. It is noteworthy that, postinfectious obstructive pattern changes in the lung, such as Postinfectious Bronchiolitis Obliterans (PIBO), may also trigger airway obstruction and pulmonary function impairment [53], and then lead to an overestimation of COPD. Thus, it’s of great
infection.
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4.9. Occupational dust exposure
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importance to distinguish COPD caused by recurrent respiratory infection from PIBO when regarding to the effect of
This review demonstrates that occupational dust exposure increases the risk of COPD, consistent with current
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literature [54]. Occupational dust was confirmed to be an important cause of COPD by Andrew et al. [55] twenty years ago. As an under-appreciated risk factor for COPD, it is not only associated with increased airflow limitation and respiratory symptoms, but also with more emphysema and gas trapping, assessed by computed tomography scan, in both men and women [56]. There is good evidence that exposure to occupational dust can cause chronic bronchitis and clinically important losses of lung function in both smokers and nonsmokers, and that it can be a cause of marked COPD in smokers [55]. American Thoracic Society stated that occupational exposures account for 10-20% of either symptoms or functional impairment of COPD, and the risk from occupational exposures in less regulated areas of the world is likely to be much higher than other region [57]. However, the relative effects of short-term, high-peak 9
ACCEPTED MANUSCRIPT exposures and long-term, low-level exposures are yet to be resolved, which may be a potential valuable research orientation.
4.10. Biomass burning
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Biomass fuels (e.g., wood, animal dung, crop residues, and coal) typically burned in open fires or poorly functioning stoves, may lead to very high levels of indoor air pollution [58]. Prior studies conducted in China pointed out that indoor pollution from biomass cooking and heating was associated with an increased risk of COPD, respiratory
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symptoms, and impaired lung function [59, 60], especially in low and middle-income countries [61]. What’s more, almost three billion people worldwide use biomass as their main source of energy for cooking, heating, and other household needs [62]. Similar finding was detected in this review, indicating that biomass burning at home is a risk
COPD among Chinese mainland population.
4.11. Poor housing ventilation
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factor for COPD in China. Thus, reducing the burning of biomass fuels in might be an effective prevention measure for
Based on our pooled analysis, exposure to poor housing ventilation is associated with 2.2-fold increase in OR of
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COPD, which indicated that poor housing ventilation is a risk factor for COPD among Chinese Mainland population. A 9-year Chinese prospective study confirmed that long-term interventions to improve kitchen ventilation was associated with improved indoor air quality, a reduced decline of lung function and reduced spirometry-measured COPD
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incidence [60]. Living in poorly ventilated dwellings may possibly lead to a reduction in inhaling fresh air. Hence, implementing community health guidance to change individuals’ living habit might be a low-cost intervention
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regarding to the prevention of COPD.
4.12. Living around polluted area
Evidence to date has confirmed that ambient air pollution is associated with an increased risk of COPD [63, 64]. Due to it has a significant impact on lung maturation and development [1]. Individuals exposed to higher levels of air pollution had nearly 3-fold greater odds of developing COPD [65]. However, the role of outdoor air pollution as a risk factor for COPD remains unclear. Living around Polluted Area, as the indication of outdoor air pollution, was detected to be a risk factor of COPD in Chinese mainland population according to our meta-analysis. It’s generally known that 10
ACCEPTED MANUSCRIPT China is the largest developing country, along with rapid industry growth. While enhanced industrial activity has contributed to massive air and water pollution. Consequently, pollution factors should not be ignored when it comes to the prediction and prevention of COPD in China.
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Limitations
This systematic review has several limitations. Firstly, the most noteworthy limitation was that there was substantial heterogeneity. The important factor that contributed to between-study heterogeneity was source of control,
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while almost half of included studies were hospital-based in this review. What’s more, this point could limit the generalizability of the findings to all Chinese Mainland population. Secondly, all the articles included in our review are retrospective observational studies. A long-term prospective study to specifically define risk factors of COPD in
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Chinese Mainland would be instructive. Thirdly, as a known risk factor for COPD, history of asthma did not been analyzed in this review. Because only one study clearly reported history of asthma among all the nineteen articles, thus it was not possible to estimate the pooled OR. Fourthly, we did not analyze age as a risk factor because the age division of included studies were wildly inconsistent in this review. In consequence, future researches are needed to further
5. Conclusions
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investigate the effect of asthma and age changes upon the occurrence of COPD among Chinese population.
Our systematic review and meta-analysis concluded that male sex, smoking, low educational level (≤ 9 years), low
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BMI (< 18.5 kg/m2), family history of respiratory disease, allergy history, respiratory infection during childhood, recurrent respiratory infection, occupational dust exposure, biomass burning, poor housing ventilation, and living
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around polluted area might be significant risk factors relating to the occurrence of COPD in Chinese Mainland. The 12 risk factors declared in this study can be used to identify high-risk population, but also should be considered in the risk prediction model of COPD among Chinese Mainland population to improve predictive and discriminative abilities. Undoubtedly, further prospective studies with larger samples and precise controls are demanded for more accurate and reliable conclusions.
Conflict of interest The authors of this study are responsible for its content. All authors declare that they have no competing interests. 11
ACCEPTED MANUSCRIPT This systematic review involved only the extraction of data from other published studies, thus, there is no need of patients’ consent and ethics committee approval was not necessary.
Author contribution
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YY, JM, and JL worked on the conception and design of this study. JM, ZY, JL and YY performed the literature search, data extraction and analysis. YY and JL drafted the manuscript. HZ and YL helped with the collection, analysis and interpretation of data, as well as writing of the report. All authors read and approved the final version of the
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manuscript.
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Funding
This work was supported by the National Natural Science Foundation of China (NNSFC) [grant number 71503088].
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Table 1. Characteristics and methodological quality assessments
First Author
Year of
Study
Study
Sample
Cases
Controls
Source of
Publication
Region
Design
Size
(n)
(n)
Control
Ling Liu [12]
2016
Beijing
case-control
770
480
2
Zheng Tan [13]
2015
Nantong
case-control
124
64
3
Pei Sun [14]
2015
Hainan
case-control
584
277
4
Yuanrong Zhang [15]
2015
Taian
case-control
818
5
Junping Qi [16]
2015
Lanzhou
case-control
367
6
Duosheng Wu [17]
2015
Hainan
case-control
7
Caihong Chang [18]
2015
Gansu
case-control
8
Xingbang Qian [19]
2014
Zhaoqing
case-control
9
Shanfang Qin [20]
2013
Guangxi
case-control
10
Wenfeng Chen [21]
2013
Xinjiang
case-control
11
Cuijuan Wu [22]
2013
Guangdong
case-control
12
Qing Su [23]
2011
Zhumadian
13
Yuan Guo [24]
2011
Guangzhou
14
Yi Jiang [25]
2011
Yantai
15
Wenfeng Li [26]
2010
16
Ling Yun [27]
2009
17
Weiguo Chen [28]
2008
18
Xin Xu [29]
2008
19
Fei Xu [30]
2008
HB: hospital-based; PB: population-based
Newcastle-Ottawa Scale Selection
Comparability
Exposure
290
HB
★★☆★
☆☆
☆★☆
60
HB
★★☆★
☆☆
☆★☆
307
PB
★★★★
☆☆
☆★☆
409
409
HB
★★☆★
☆★
☆★☆
164
203
HB
★★☆★
☆★
☆★☆
291
301
PB
★★★★
☆☆
☆★☆
600
300
300
PB
★★★★
★★
☆★☆
864
115
749
HB
★★☆★
★★
★★☆
240
120
120
PB
★★★★
★★
☆★☆
256
128
128
HB
★★☆★
★★
☆★☆
168
56
112
HB
★★☆★
★★
☆★☆
case-control
762
254
508
HB
★★☆★
★★
☆★☆
case-control
914
403
511
PB
★★☆★
★★
☆★☆
case-control
818
409
409
PB
★★★★
★★
☆★☆
Guangdong
case-control
672
336
336
PB
★★★★
★★
☆★☆
Tangshan
case-control
570
190
380
PB
★★★★
★★
☆★☆
Jinhua
case-control
418
209
209
PB
★★★★
★★
☆★☆
Liaoning
case-control
870
435
435
HB
★★☆★
☆★
☆★☆
Nanjing
case-control
3486
1743
1743
PB
★★★★
★★
☆★☆
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592
EP
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SC
1
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NO.
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Table 2. Results of heterogeneity test
Risk Factors
Number of Studies
Q-Value
P
I2 (%)
Meta Analytical Model
8 [12-17, 20, 29]
35.102
Smoking
18 [13-30]
93.095
<0.0001
81.739
Random
Passive smoking
7 [14, 19, 24, 25, 27, 28, 30]
35.647
<0.0001
83.168
Random
Low educational level (≤ 9 years)
9 [14, 15, 17, 18, 21-24, 30]
49.100
<0.0001
83.707
Random
Low BMI (<18.5kg/m2)
7 [14, 15, 18, 21, 24, 26, 27]
30.109
<0.0001
80.072
Random
Family history of respiratory disease
14 [14-18, 20-28]
Allergy history
7 [14-17, 20, 27, 29] infection
during
80.058
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Random
78.441
<0.0001
83.427
Random
41.565
<0.0001
85.565
Random
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Respiratory
<0.0001
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Male sex
8 [12, 15, 18, 22, 23, 26-28]
66.743
<0.0001
89.512
Random
Recurrent respiratory infection
3 [12, 14, 17]
23.356
<0.0001
91.437
Random
Occupational dust exposure
11 [15, 18-20, 22-28]
96.358
<0.0001
89.622
Random
Biomass burning
8 [14, 17, 19, 20, 22, 23, 27, 30]
100.521
<0.0001
93.036
Random
5 [19, 20, 22, 23, 27]
69.168
<0.0001
94.217
Random
4 [12, 20, 24, 27]
38.357
<0.0001
92.179
Random
3 [14, 17, 27]
3.780
0.151
47.088
Fixed
4 [17, 21-23]
18.324
<0.0001
83.628
Random
3 [14, 17, 30]
10.516
0.005
80.981
Random
Poor housing ventilation Cooking frequently Living around polluted area
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childhood
countryside
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Living in city or town vs living in
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Doing physical labor work
ACCEPTED MANUSCRIPT
Table 3. Meta-analysis of the risk factors for COPD in Chinese Mainland 95% CI
Z
P
1.467
1.097-1.962
2.587
0.010
7220
2.092
1.707-2.565
7.102
<0.0001
4308
0.982
0.716-1.346
-0.116
0.908
4319
1.609
1.206-2.147
3.236
0.001
2371
3.831
2.223-6.603
4.836
<0.0001
4233
2.068
1.466-2.918
4.138
<0.0001
1886
2155
2.381
1.385-4.093
3.139
0.002
8
2234
2544
2.695
1.504-4.828
3.331
0.001
Recurrent respiratory infection
3
1048
898
15.015
4.538-49.684
4.437
<0.0001
Occupational dust exposure
11
2801
4043
1.791
1.151-2.788
2.583
0.010
Biomass burning
8
3046
4220
2.218
1.308-3.762
2.957
0.003
Poor housing ventilation
5
735
1869
3.993
1.244-12.820
2.327
0.020
Cooking frequently
4
1193
1301
1.525
0.793-2.933
1.266
0.206
3
758
988
1.631
1.202-2.214
3.139
0.002
4
729
1049
1.123
0.671-1.881
0.442
0.659
3
2311
2351
1.290
0.806-2.066
1.062
0.288
Total Cases (n)
Total Controls (n)
Male sex
8
2240
2125
Smoking
18
5903
Passive smoking
7
3346
Low educational level (≤ 9 years)
9
3861
Low BMI (<18.5kg/m2)
7
2043
Family history of respiratory disease
14
3546
Allergy history
7
Respiratory infection during childhood
Living around polluted area Living in city or town vs living in countryside Doing physical labor work
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Pooled OR
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Number of Studies
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Risk Factors
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Table 4. Publication bias of the risk factors for COPD in Chinese Mainland Egger's Test (P-Value)
Male sex
8
0.642
Smoking
18
0.041
Low educational level (≤ 9 years)
9
Low BMI (< 18.5kg/m2)
7
Family history of respiratory disease
14
Allergy history
7
Respiratory infection during childhood
8
Recurrent respiratory infection
3
RI PT
Number of Studies
0.297
0.193
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0.777
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Risk Factors
Occupational dust exposure Biomass burning Poor housing ventilation
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EP
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Living around polluted area
0.420 0.117
0.531
11
0.648
8
0.066
5
0.424
3
0.359
Additional records identified through other sources (n=7)
Records after duplicates removed (n=305)
Records excluded (n=201)
Eligibility
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Records screened (n=243)
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Full-text articles assessed for eligibility (n=42)
Studies included in quantitative synthesis (meta-analysis) (n=19)
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Included
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Records identified through database searching (n=647)
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Screening
Identification
ACCEPTED MANUSCRIPT
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Fig 1. PRISMA flowchart of study selection. Adapted from Moher et al. [31]
Full-text articles excluded, with reasons (n=23)
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Highlights
Identifying risk factors is a key point for preventive strategies to reduce the incidence of COPD
•
Twelve risk factors are considered to be associated with the occurrence of COPD in Chinese Mainland.
•
Risk factors of COPD can be used to distinguish high-risk population.
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•
S0954-6111(17)30288-3
DOI:
10.1016/j.rmed.2017.08.018
Reference:
YRMED 5239
To appear in:
Respiratory Medicine
Received Date: 5 June 2017 Revised Date:
16 August 2017
Accepted Date: 17 August 2017
Please cite this article as: Yang Y, Mao J, Ye Z, Li J, Zhao H, Liu Y, Risk factors of chronic obstructive pulmonary disease among adults in Chinese mainland: A systematic review and meta-analysis, Respiratory Medicine (2017), doi: 10.1016/j.rmed.2017.08.018. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT Risk factors of chronic obstructive pulmonary disease among adults in Chinese mainland: A systematic review and meta-analysis Authors： ：
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Ying Yang a, Jing Mao a, Zhiying Ye b, Jie Li a, *, Huimin Zhao a, Yueting Liu a Authors Affiliations: a
School of Nursing, Tongji Medical College, Huazhong University of Science and Technology, Hangkong Road 13,
Wuhan 430030, China.
Huazhong University of Science and Technology Hospital, Luoyu Road 1037, Wuhan 430074, China
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b
Corresponding Author:
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Jie Li, PhD, RN, School of Nursing, Tongji Medical College, Huazhong University of Science and Technology, Hangkong Road 13, Qiaokou District, Wuhan 430030, China. Tel: +86 18971097091 E-mail: [email protected] E-mail address:
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[email protected] (Ying Yang), [email protected] (Jing Mao), [email protected] (Zhiying Ye),
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[email protected] (Jie Li), [email protected] (Huimin Zhao), [email protected] (Yueting Liu).
1
ACCEPTED MANUSCRIPT ABSTRACT Background: Identifying risk factors is a key point for preventive strategies to reduce the incidence of COPD. The aim of this systematic review and meta-analysis was to determine the most important risk factors for COPD among adults in Chinese Mainland, so as to provide some precautions and interventions on this disease and preventing further
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recurrences.
Methods: A comprehensive literature review relating to risk factors for COPD through PubMed, EMBASE, Cochrane Library, China National Knowledge Infrastructure (CNKI), Wanfang database and VIP database was conducted before
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March 31, 2017. Odds ratio (OR) with 95% confidence interval (CI) was calculated after data combination to assess the associations between risk factors and COPD. Heterogeneity between the studies was assessed by I² and Cochran’s Q
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test. Egger’s test was used to assess publication bias.
Results: A total of 13893 participants (6383 cases and 7510 controls) from 19 case-controls studies were included. 12 risk factors with significant differences found between COPD and control groups were listed as follows: male sex (OR=1.467; 95%CI: 1.097-1.962), smoking (OR=2.092; 95%CI: 1.707-2.565), low educational level (OR=1.609; 95%CI: 1.206-2.147), low BMI (OR=3.831; 95%CI: 2.223-6.603), family history of respiratory disease (OR=2.068;
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95%CI: 1.466-2.918), allergy history (OR=2.381; 95%CI: 1.385-4.093), respiratory infection during childhood (OR=2.695; 95%CI: 1.504-4.828), recurrent respiratory infection (OR=15.015; 95%CI: 4.538-49.684), occupational dust exposure (OR=1.791; 95%CI: 1.151-2.788), biomass burning (OR=2.218; 95%CI: 1.308-3.762), poor housing ventilation (OR=3.993; 95%CI: 1.244-12.820), and living around polluted area (OR=1.631; 95%CI: 1.202-2.214).
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Conclusion: Twelve risk factors are associated with the occurrence of COPD in Chinese Mainland, which can be used to distinguish high-risk population. Health education and promotion campaigns should be designed in order to
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minimize or prevent the occurrence of COPD in Chinese Mainland. Keywords: Pulmonary disease, chronic obstructive; Risk factors; Meta-analysis; Systematic review; China
2
ACCEPTED MANUSCRIPT 1. Introduction Chronic obstructive pulmonary disease (COPD) is one of the common respiratory diseases, characterized by airflow limitation, which can be prevented and treated. The airflow limitation develops not fully reversibly and progressively [1]. According to the estimate of World Health Organization (WHO), about 3 million people died of
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COPD in 2005, which count for 5% of the total mortality worldwide. It is expected that by 2030, COPD will become the world’s third largest lethal disease [2]. In a time of aging populations, COPD is becoming more and more serious, with high and increasing morbidity and mortality [1], especially in developing countries. In China, the overall
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prevalence of COPD in people older than 40 was 8.2% according to a large, population-based survey [3]. Because of the great impact on patients' health and quality of life, and high cost for the patients, their relatives, governments, and
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society, COPD has become an important public health problem in China [4].
Many human activities and environmental factors are associated with the incidence of COPD. A previous meta-analysis done by Zhang et al. [5] points out that seven factors may increase the risk of developing COPD, including smoking, occupational exposure and educational level, etc. Data from Chinese population are more convincing in health promotions and policy advocacies in China. In recent years, numerous epidemiological surveys
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have been conducted to identify the risk factors of COPD in various regions of China, but inconsistency has been presented among various study populations. On account of the demand for early detection of high-risk population, we
2. Methods
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operated this meta-analysis to investigate the overall risk factors of COPD in Chinese Mainland.
2.1. Search strategy and study selection
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Two reviewers independently identified relevant studies published in English and Chinese before March 31, 2017 by searching the following electronic databases: PubMed, EMBASE, the Cochrane Library, China National Knowledge Infrastructure (CNKI), Wanfang database and VIP database. Following search terms were used: “Chronic Obstructive Pulmonary Disease” or “COPD” in combination with “risk factors”. References cited in published original and review articles were searched to find out additional studies. We identified studies in accordance with the following inclusion criteria: (1) the participants came from Chinese Mainland; (2) concerning risk factors related to COPD; (3) odds ratio (OR) of each risk factors were reported with 95% confidence interval (CI) or raw data were given for calculating; and (4) the study followed a case-control or cohort 3
ACCEPTED MANUSCRIPT design. We excluded studies if they were reviews, letters, case reports, case series, cross sectionals and the studies that did not report obviously the population sources or the available data to calculate the OR. The discrepancies were resolved through discussion.
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2.2. Data extraction
Data were screened closely and extracted independently by two investigators (J. M. and Z. Y.). A third reviewer (J. L.) made the final decision when inconsistency occurred between the above two reviewers. Data were collected from
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the included studies as follows: first author’s name, year of publication, study design, study region, sample size, number of cases and controls, potential risk factors for COPD, and OR with 95% CIs.
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2.3. Quality assessment
The Newcastle-Ottawa Scale (NOS) [6], which is one of the most useful for assessing methodological quality of non-randomized studies, was used to assess the risk of bias in the included studies. The criteria included three categories: (1) selection (4 items); (2) comparability (1 item); and (3) exposure for case-control study (3 items). A study can be awarded a maximum of one star for each numbered item within the selection and exposure categories. A
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maximum of two stars can be given for comparability [7]. Articles with more than seven stars were considered to be of
fewer than four stars.
2.4. Statistical analysis
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a high quality; those with four to six stars were considered as moderate quality studies; and of a poor quality if they had
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The statistical analysis was conducted using Comprehensive Meta-Analysis (CMA) version 2.0 software [8]. The results were reported as pooled odds ratios (ORs) and corresponding 95% confidence intervals (CI). A two-sided P<0.05 was considered statistically significant. The heterogeneity of the included studies was evaluated using the Cochran’s Q test and the I2 test [9]. I2 is the proportion of total variation attributable to between-study heterogeneity as opposed to random error or chance, and I2 values of 25%, 50% and 75% are considered to indicate low, moderate, and high heterogeneity, respectively [10]. Commonly, we selected a random-effects model to calculate corresponding parameters when the I2 value was more than 50%. Otherwise, a fixed-effects model was used. Egger’s test [11] was used to assess publication bias, the statistical publication bias was set at P<0.10. 4
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3. Results 3.1. Identification of selected studies From the 654 studies identified using our search strategy, 42 potentially relevant articles were retrieved and
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assessed for eligibility. In total, 19 papers were included in this meta-analysis [12-30]. The flow diagram summarizing the study identification and selection is shown in Figure 1. There was good agreement between the reviewers in regards to the validity assessments, the quality assessment of all the published studies were shown in Table 1. Of these, 8
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articles earned seven stars, were considered as high quality. The remaining 11 papers were moderate quality. Hence, the
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included studies were of a relatively high quality.
3.2. Study characteristics
A total of 13893 participants (6383 cases and 7510 controls) from 19 case-controls studies were enrolled. The basic characteristics of these studies are summarized in Table 1.
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3.3. Assessment of heterogeneity
The results of heterogeneity test are listed in Table 2. Heterogeneities were discovered in 15 potential risk factors associated with COPD (I2>50%). Therefore, we calculated the pooled OR values of these factors using a
3.4. Risk factors
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random-effects model.
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This review identified 20 potential risk factors associated with COPD. Of these, four factors (hyperglycemia, history of asthma, history of depression, and drinking) were considered not possible to estimate the pooled ORs, since they were examined in only one or two studies. We then estimated the remaining 16 factors, which were included in three or more studies. The results of the pooled analysis are displayed in Table 3. The forest plots for the risk factors are shown in supplementary materials. The pooled OR suggests that, male sex (OR=1.467; 95% CI: 1.097-1.962; P=0.010), smoking (OR=2.092; 95% CI: 1.707-2.565; P <0.0001), low educational level (OR=1.609; 95% CI: 1.206-2.147; P=0.001), low BMI (OR=3.831; 95% CI: 2.223-6.603; P<0.0001), family history of respiratory disease (OR=2.068; 95% CI: 1.466-2.918; P<0.0001), allergy 5
ACCEPTED MANUSCRIPT history (OR=2.381; 95% CI: 1.385-4.093; P=0.002), respiratory infection during childhood (OR=2.695; 95% CI: 1.504-4.828; P=0.001), recurrent respiratory infection (OR=15.015; 95% CI: 4.538-49.684; P<0.0001), occupational dust exposure (OR=1.791; 95% CI: 1.151-2.788; P=0.010), biomass burning (OR=2.218; 95% CI: 1.308-3.762; P=0.003), poor housing ventilation (OR=3.993; 95% CI: 1.244-12.820; P=0.020), and living around polluted area
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(OR=1.631; 95% CI: 1.202-2.214; P=0.002) are risk factors of COPD in Chinese Mainland. Passive smoking (OR=0.982; 95%CI: 0.716-1.346; P=0.908), cooking frequently (OR=1.525; 95% CI: 0.793-2.933; P=0.206), living in city or town vs living in countryside (OR=1.123; 95% CI: 0.671-1.881; P=0.659), and doing physical labor work
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(OR=1.290; 95% CI: 0.806-2.066; P=0.288) are not associated with COPD in Chinese Mainland.
3.5. Publication bias
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We conducted the Egger’s test to evaluate potential publication bias. The results of the Egger’s test (shown in Table 4) suggested that the publication biases among all of the risk factors were not statistically significant (P>0.10). Hence, our investigation indicated no severe publication biases.
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4. Discussion
This review makes an attempt to sum up the findings concerning the risk factors of COPD in Chinese Mainland during the past decade. Our findings revealed that male sex, smoking, low educational level (≤ 9 years), low BMI (< 18.5 kg/m2), family history of respiratory disease, allergy history, respiratory infection during childhood, recurrent
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respiratory infection, occupational dust exposure, biomass burning, poor housing ventilation, and living around polluted area are significant risk factors relating to the occurrence of COPD in Chinese Mainland. When compared with the
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previous report in China [5], this meta-analysis included more newly published articles and determined more number of risk factors. The new findings and differences indicate that identifying risk factors of COPD among Chinese population is still at an exploration stage, and there is still need for close attention. COPD is one of the leading cause of mobility and mortality worldwide and results in an economic and social burden that is both substantial and increasing[1]. COPD ranks fourth as a leading cause of death in urban areas and third in rural areas [32]. Therefore, future study is needed in order to explore on how the risk factors interact with each other.
4.1. Male sex 6
ACCEPTED MANUSCRIPT The pooled analysis of eight studies suggested that males were more likely to have COPD than females, which was in agreement with the findings of the half of the included papers [15-17, 29]. The result was supported by prior study, showing that all cause and respiratory mortality are significantly lower in females than in males with similar COPD severity [33]. Nevertheless, recent data from developed countries has reported that the prevalence of COPD is
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now almost equal in men and women, probably reflecting the changing patterns of tobacco smoking [1, 34]. Although controversial, some studies have even suggested that women are more susceptible to the effects of tobacco smoke than men [35-37], leading to more severe disease for the equivalent quantity of cigarettes, which have demonstrated a
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greater burden of small airway disease in females compared with males with COPD despite a similar history of tobacco smoke exposure [38, 39]. These discoveries implied that gender-related differences regarding to COPD may be affected by national situation and cultural discrepancies. Thus, as a typical developing country, future researches are needed in
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China to reveal this controversy.
4.2. Smoking
Across the world, cigarette smoking is the most commonly encountered risk factor for COPD [1]. Cigarette smokers have a higher prevalence of respiratory symptoms and lung function abnormalities, a greater annual rate of
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decline in FEV1, and a greater COPD mortality rate than non-smokers [40]. Ministry of Health of the People’s Republic of China released China Report on the Health Hazards of Smoking on May 31, 2012 [41], which sufficiently inferred a causal relationship between smoking and COPD. Similarly, the risk of COPD is higher for smokers and ever smokers
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than never smokers (OR=2.092; 95% CI: 1.707-2.565) according to our review. The result is consistent with former meta-analysis done by Wang et al. (OR=2.90, 95% CI: 2.22-3.80) [42] and Forey et al. (OR=2.89, 95% CI: 2.63-3.17)
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[43]. In view of this, smoking cessation should be advocated as a key measure and important intervention to prevent the occurrence of COPD in China.
4.3. Low educational level (≤ 9 years) Lower socioeconomic status is associated with an increased risk for developing COPD [44], but the components of educational level that contribute are unclear. Nevertheless, our findings indicate that educational level below senior high school degree is a risk factor against the occurrence of COPD. There is strong evidence that risk of developing COPD is inversely related to socioeconomic status. Low educational level is often a reflection of poor socioeconomic 7
ACCEPTED MANUSCRIPT status, individuals with low educational level may live and work in worse environment and lack health care protection information, thus suffering greater risk [44, 45]. On the contrary, the higher one’s educational level, the more attention he/she trends to personal health status. However, we did not analyze income level as a risk factor because there were
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differences in the income level segmentations between the studies.
4.4. Low BMI (<18.5kg/m2)
Body mass index (BMI) was recommended by WHO as an important marker to reflect total body nutrition. Our
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meta-analysis showed that low BMI (<18.5kg/m2) is a risk factor for COPD (OR=3.831; 95% CI: 2.223-6.603) in Chinese Mainland. The incidence of COPD in underweight group was significantly higher compared with normal group probably due to malnutrition and poor immune response to infections [46]. Being underweight might be related to
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malnutrition and/or low socioeconomic status, which is regarded as environmental risk factors for COPD. On the other hand, being underweight might be one of the symptoms in patients with advanced COPD since these patients often experience weight loss, loss of appetite, as well as depression and anxiety [47].
4.5. Family history of respiratory disease
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Results from this review indicate that individuals exposure to a family history of respiratory disease are more likely to develop COPD, with a 2.1-fold greater OR of COPD. A significant familial risk of airflow limitation has been observed in people who smoke and are siblings of patients with severe COPD [48], suggesting that genetics together
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with environmental factors could influence this susceptibility. Association of family history and COPD shown in
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current study has also supported by the Global Initiative for Chronic Obstructive Lung Disease (GOLD) [1].
4.6. Allergy history
A variety of studies suggested the significant relationship between and COPD [16, 29], our meta-analysis further confirmed this result and declared allergy history to be a risk factor of COPD in Chinese Mainland. To the best of our knowledge, airway hyper- reactivity and asthma are independent predictors of COPD and respiratory mortality in population studies [49], as well as an indicator of risk of excess decline in lung function in patients with mild COPD [50]. However, more evidences are required to reveal the correlation among allergy history, airway hyper- reactivity and asthma. 8
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4.7. Respiratory infection during childhood Respiratory infection during childhood is a risk factor for COPD according to this meta-analysis. A history of severe childhood respiratory infection has been associated with reduced lung function and increased respiratory
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symptoms in adulthood [51]. Therefore, continuously attention should be paid to the lung health of children, so as to decrease the risk of COPD in adulthood.
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4.8. Recurrent respiratory infection
Previous studies have consistently documented that infection, especially respiratory infection, is one of the environmental risk factors for COPD and plays an important role in the pathogenesis and progression of COPD [1]. In
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addition, it was suggested that the infection of Mycoplasma pneumoniae and Chlamydia pneumoniae might be crucial for the occurrence and development of COPD [52]. Evidence from this review mentioned that recurrent respiratory infection is a risk factor, which can enhance the danger of developing COPD. It is noteworthy that, postinfectious obstructive pattern changes in the lung, such as Postinfectious Bronchiolitis Obliterans (PIBO), may also trigger airway obstruction and pulmonary function impairment [53], and then lead to an overestimation of COPD. Thus, it’s of great
infection.
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4.9. Occupational dust exposure
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importance to distinguish COPD caused by recurrent respiratory infection from PIBO when regarding to the effect of
This review demonstrates that occupational dust exposure increases the risk of COPD, consistent with current
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literature [54]. Occupational dust was confirmed to be an important cause of COPD by Andrew et al. [55] twenty years ago. As an under-appreciated risk factor for COPD, it is not only associated with increased airflow limitation and respiratory symptoms, but also with more emphysema and gas trapping, assessed by computed tomography scan, in both men and women [56]. There is good evidence that exposure to occupational dust can cause chronic bronchitis and clinically important losses of lung function in both smokers and nonsmokers, and that it can be a cause of marked COPD in smokers [55]. American Thoracic Society stated that occupational exposures account for 10-20% of either symptoms or functional impairment of COPD, and the risk from occupational exposures in less regulated areas of the world is likely to be much higher than other region [57]. However, the relative effects of short-term, high-peak 9
ACCEPTED MANUSCRIPT exposures and long-term, low-level exposures are yet to be resolved, which may be a potential valuable research orientation.
4.10. Biomass burning
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Biomass fuels (e.g., wood, animal dung, crop residues, and coal) typically burned in open fires or poorly functioning stoves, may lead to very high levels of indoor air pollution [58]. Prior studies conducted in China pointed out that indoor pollution from biomass cooking and heating was associated with an increased risk of COPD, respiratory
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symptoms, and impaired lung function [59, 60], especially in low and middle-income countries [61]. What’s more, almost three billion people worldwide use biomass as their main source of energy for cooking, heating, and other household needs [62]. Similar finding was detected in this review, indicating that biomass burning at home is a risk
COPD among Chinese mainland population.
4.11. Poor housing ventilation
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factor for COPD in China. Thus, reducing the burning of biomass fuels in might be an effective prevention measure for
Based on our pooled analysis, exposure to poor housing ventilation is associated with 2.2-fold increase in OR of
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COPD, which indicated that poor housing ventilation is a risk factor for COPD among Chinese Mainland population. A 9-year Chinese prospective study confirmed that long-term interventions to improve kitchen ventilation was associated with improved indoor air quality, a reduced decline of lung function and reduced spirometry-measured COPD
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incidence [60]. Living in poorly ventilated dwellings may possibly lead to a reduction in inhaling fresh air. Hence, implementing community health guidance to change individuals’ living habit might be a low-cost intervention
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regarding to the prevention of COPD.
4.12. Living around polluted area
Evidence to date has confirmed that ambient air pollution is associated with an increased risk of COPD [63, 64]. Due to it has a significant impact on lung maturation and development [1]. Individuals exposed to higher levels of air pollution had nearly 3-fold greater odds of developing COPD [65]. However, the role of outdoor air pollution as a risk factor for COPD remains unclear. Living around Polluted Area, as the indication of outdoor air pollution, was detected to be a risk factor of COPD in Chinese mainland population according to our meta-analysis. It’s generally known that 10
ACCEPTED MANUSCRIPT China is the largest developing country, along with rapid industry growth. While enhanced industrial activity has contributed to massive air and water pollution. Consequently, pollution factors should not be ignored when it comes to the prediction and prevention of COPD in China.
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Limitations
This systematic review has several limitations. Firstly, the most noteworthy limitation was that there was substantial heterogeneity. The important factor that contributed to between-study heterogeneity was source of control,
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while almost half of included studies were hospital-based in this review. What’s more, this point could limit the generalizability of the findings to all Chinese Mainland population. Secondly, all the articles included in our review are retrospective observational studies. A long-term prospective study to specifically define risk factors of COPD in
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Chinese Mainland would be instructive. Thirdly, as a known risk factor for COPD, history of asthma did not been analyzed in this review. Because only one study clearly reported history of asthma among all the nineteen articles, thus it was not possible to estimate the pooled OR. Fourthly, we did not analyze age as a risk factor because the age division of included studies were wildly inconsistent in this review. In consequence, future researches are needed to further
5. Conclusions
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investigate the effect of asthma and age changes upon the occurrence of COPD among Chinese population.
Our systematic review and meta-analysis concluded that male sex, smoking, low educational level (≤ 9 years), low
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BMI (< 18.5 kg/m2), family history of respiratory disease, allergy history, respiratory infection during childhood, recurrent respiratory infection, occupational dust exposure, biomass burning, poor housing ventilation, and living
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around polluted area might be significant risk factors relating to the occurrence of COPD in Chinese Mainland. The 12 risk factors declared in this study can be used to identify high-risk population, but also should be considered in the risk prediction model of COPD among Chinese Mainland population to improve predictive and discriminative abilities. Undoubtedly, further prospective studies with larger samples and precise controls are demanded for more accurate and reliable conclusions.
Conflict of interest The authors of this study are responsible for its content. All authors declare that they have no competing interests. 11
ACCEPTED MANUSCRIPT This systematic review involved only the extraction of data from other published studies, thus, there is no need of patients’ consent and ethics committee approval was not necessary.
Author contribution
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YY, JM, and JL worked on the conception and design of this study. JM, ZY, JL and YY performed the literature search, data extraction and analysis. YY and JL drafted the manuscript. HZ and YL helped with the collection, analysis and interpretation of data, as well as writing of the report. All authors read and approved the final version of the
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manuscript.
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Funding
This work was supported by the National Natural Science Foundation of China (NNSFC) [grant number 71503088].
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Table 1. Characteristics and methodological quality assessments
First Author
Year of
Study
Study
Sample
Cases
Controls
Source of
Publication
Region
Design
Size
(n)
(n)
Control
Ling Liu [12]
2016
Beijing
case-control
770
480
2
Zheng Tan [13]
2015
Nantong
case-control
124
64
3
Pei Sun [14]
2015
Hainan
case-control
584
277
4
Yuanrong Zhang [15]
2015
Taian
case-control
818
5
Junping Qi [16]
2015
Lanzhou
case-control
367
6
Duosheng Wu [17]
2015
Hainan
case-control
7
Caihong Chang [18]
2015
Gansu
case-control
8
Xingbang Qian [19]
2014
Zhaoqing
case-control
9
Shanfang Qin [20]
2013
Guangxi
case-control
10
Wenfeng Chen [21]
2013
Xinjiang
case-control
11
Cuijuan Wu [22]
2013
Guangdong
case-control
12
Qing Su [23]
2011
Zhumadian
13
Yuan Guo [24]
2011
Guangzhou
14
Yi Jiang [25]
2011
Yantai
15
Wenfeng Li [26]
2010
16
Ling Yun [27]
2009
17
Weiguo Chen [28]
2008
18
Xin Xu [29]
2008
19
Fei Xu [30]
2008
HB: hospital-based; PB: population-based
Newcastle-Ottawa Scale Selection
Comparability
Exposure
290
HB
★★☆★
☆☆
☆★☆
60
HB
★★☆★
☆☆
☆★☆
307
PB
★★★★
☆☆
☆★☆
409
409
HB
★★☆★
☆★
☆★☆
164
203
HB
★★☆★
☆★
☆★☆
291
301
PB
★★★★
☆☆
☆★☆
600
300
300
PB
★★★★
★★
☆★☆
864
115
749
HB
★★☆★
★★
★★☆
240
120
120
PB
★★★★
★★
☆★☆
256
128
128
HB
★★☆★
★★
☆★☆
168
56
112
HB
★★☆★
★★
☆★☆
case-control
762
254
508
HB
★★☆★
★★
☆★☆
case-control
914
403
511
PB
★★☆★
★★
☆★☆
case-control
818
409
409
PB
★★★★
★★
☆★☆
Guangdong
case-control
672
336
336
PB
★★★★
★★
☆★☆
Tangshan
case-control
570
190
380
PB
★★★★
★★
☆★☆
Jinhua
case-control
418
209
209
PB
★★★★
★★
☆★☆
Liaoning
case-control
870
435
435
HB
★★☆★
☆★
☆★☆
Nanjing
case-control
3486
1743
1743
PB
★★★★
★★
☆★☆
AC C
TE D
592
EP
M AN U
SC
1
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NO.
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Table 2. Results of heterogeneity test
Risk Factors
Number of Studies
Q-Value
P
I2 (%)
Meta Analytical Model
8 [12-17, 20, 29]
35.102
Smoking
18 [13-30]
93.095
<0.0001
81.739
Random
Passive smoking
7 [14, 19, 24, 25, 27, 28, 30]
35.647
<0.0001
83.168
Random
Low educational level (≤ 9 years)
9 [14, 15, 17, 18, 21-24, 30]
49.100
<0.0001
83.707
Random
Low BMI (<18.5kg/m2)
7 [14, 15, 18, 21, 24, 26, 27]
30.109
<0.0001
80.072
Random
Family history of respiratory disease
14 [14-18, 20-28]
Allergy history
7 [14-17, 20, 27, 29] infection
during
80.058
SC
Random
78.441
<0.0001
83.427
Random
41.565
<0.0001
85.565
Random
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Respiratory
<0.0001
RI PT
Male sex
8 [12, 15, 18, 22, 23, 26-28]
66.743
<0.0001
89.512
Random
Recurrent respiratory infection
3 [12, 14, 17]
23.356
<0.0001
91.437
Random
Occupational dust exposure
11 [15, 18-20, 22-28]
96.358
<0.0001
89.622
Random
Biomass burning
8 [14, 17, 19, 20, 22, 23, 27, 30]
100.521
<0.0001
93.036
Random
5 [19, 20, 22, 23, 27]
69.168
<0.0001
94.217
Random
4 [12, 20, 24, 27]
38.357
<0.0001
92.179
Random
3 [14, 17, 27]
3.780
0.151
47.088
Fixed
4 [17, 21-23]
18.324
<0.0001
83.628
Random
3 [14, 17, 30]
10.516
0.005
80.981
Random
Poor housing ventilation Cooking frequently Living around polluted area
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childhood
countryside
EP
Living in city or town vs living in
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Doing physical labor work
ACCEPTED MANUSCRIPT
Table 3. Meta-analysis of the risk factors for COPD in Chinese Mainland 95% CI
Z
P
1.467
1.097-1.962
2.587
0.010
7220
2.092
1.707-2.565
7.102
<0.0001
4308
0.982
0.716-1.346
-0.116
0.908
4319
1.609
1.206-2.147
3.236
0.001
2371
3.831
2.223-6.603
4.836
<0.0001
4233
2.068
1.466-2.918
4.138
<0.0001
1886
2155
2.381
1.385-4.093
3.139
0.002
8
2234
2544
2.695
1.504-4.828
3.331
0.001
Recurrent respiratory infection
3
1048
898
15.015
4.538-49.684
4.437
<0.0001
Occupational dust exposure
11
2801
4043
1.791
1.151-2.788
2.583
0.010
Biomass burning
8
3046
4220
2.218
1.308-3.762
2.957
0.003
Poor housing ventilation
5
735
1869
3.993
1.244-12.820
2.327
0.020
Cooking frequently
4
1193
1301
1.525
0.793-2.933
1.266
0.206
3
758
988
1.631
1.202-2.214
3.139
0.002
4
729
1049
1.123
0.671-1.881
0.442
0.659
3
2311
2351
1.290
0.806-2.066
1.062
0.288
Total Cases (n)
Total Controls (n)
Male sex
8
2240
2125
Smoking
18
5903
Passive smoking
7
3346
Low educational level (≤ 9 years)
9
3861
Low BMI (<18.5kg/m2)
7
2043
Family history of respiratory disease
14
3546
Allergy history
7
Respiratory infection during childhood
Living around polluted area Living in city or town vs living in countryside Doing physical labor work
SC
M AN U
TE D EP
Pooled OR
RI PT
Number of Studies
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Risk Factors
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Table 4. Publication bias of the risk factors for COPD in Chinese Mainland Egger's Test (P-Value)
Male sex
8
0.642
Smoking
18
0.041
Low educational level (≤ 9 years)
9
Low BMI (< 18.5kg/m2)
7
Family history of respiratory disease
14
Allergy history
7
Respiratory infection during childhood
8
Recurrent respiratory infection
3
RI PT
Number of Studies
0.297
0.193
SC
0.777
M AN U
Risk Factors
Occupational dust exposure Biomass burning Poor housing ventilation
AC C
EP
TE D
Living around polluted area
0.420 0.117
0.531
11
0.648
8
0.066
5
0.424
3
0.359
Additional records identified through other sources (n=7)
Records after duplicates removed (n=305)
Records excluded (n=201)
Eligibility
M AN U
Records screened (n=243)
TE D
Full-text articles assessed for eligibility (n=42)
Studies included in quantitative synthesis (meta-analysis) (n=19)
EP
Included
RI PT
Records identified through database searching (n=647)
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Screening
Identification
ACCEPTED MANUSCRIPT
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Fig 1. PRISMA flowchart of study selection. Adapted from Moher et al. [31]
Full-text articles excluded, with reasons (n=23)
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Highlights
Identifying risk factors is a key point for preventive strategies to reduce the incidence of COPD
•
Twelve risk factors are considered to be associated with the occurrence of COPD in Chinese Mainland.
•
Risk factors of COPD can be used to distinguish high-risk population.
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•