Chronic Obstructive Pulmonary Disease (COPD) is the most common chronic lung disease. Characterized by partially irreversible airflow limitation, it mainly ...
Chronic Obstructive Pulmonary Disease & Risk Factors In Middle Eastern Countries: Facts from Lebanon SALAMEH Pascale1 & WAKED Mirna2 1 Clinical and Epidemiological Research Laboratory, Faculty of Pharmacy, Lebanese University, Beirut, Lebanon 2 Pulmonology Department, Saint George Hospital & Faculty of Medicine, Balamand University, Beirut, Lebanon
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Contents SECTION 0 ................................................................................................................................................ 4 INTRODUCTION AND OBJECTIVES OF THE PROJECT ................................................................ 4 References .................................................................................................................................................................5
SECTION I ................................................................................................................................................. 6 STUDY 1 - CHRONIC OBSTRUCTIVE PULMONARY DISEASE PREVALENCE IN LEBANON: A CROSS-SECTIONAL STUDY .............................................................................................................. 6 1-Rationale ............................................................................................................................................................ 6 2-Methods ............................................................................................................................................................. 6 2.1-Study design and population ..............................................................................................................................6 2.2-Procedure ............................................................................................................................................................7 2.3-Definitions ...........................................................................................................................................................8 2.4-Sample size calculation .......................................................................................................................................9 2.5-Statistical analysis ...............................................................................................................................................9 2.6-Clinical COPD Questionnaire (CCQ) analysis specific methods .........................................................................10 2.7-Gender and smoking specific methods .............................................................................................................11 3 - Results & Discussion ....................................................................................................................................... 11 3.1 - Description of the population .........................................................................................................................11 3.2 - COPD prevalence according to definitions ......................................................................................................12 3.3 - Smoking prevalence and smokers’ characteristics ..........................................................................................16 3.4 - Respiratory related Quality of Life (QOL) ........................................................................................................19 3.5 - Smoking and Gender .......................................................................................................................................26 3.6 - Waterpipe dependence predictors .................................................................................................................31 3.7 - COPD in Non-smokers .....................................................................................................................................35 4 – References ..................................................................................................................................................... 39 5- Related publications ....................................................................................................................................... 45
SECTION II .............................................................................................................................................. 47 STUDY 2 - CHRONIC OBSTRUCTIVE PULMONARY DISEASE AND SELECTED RISK FACTORS: A CASE-CONTROL STUDY ............................................................................................. 47 1 - Rationale ........................................................................................................................................................ 47 Waterpipe (WP) smoking and dependence in Lebanon ..........................................................................................47
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Pollution in Lebanon ...............................................................................................................................................47 2 - Methods ......................................................................................................................................................... 48 2.1-Study design ......................................................................................................................................................48 2.2-Study population ...............................................................................................................................................48 2.3-Data collection ..................................................................................................................................................49 2.4-Sample calculation ............................................................................................................................................50 2.5-Statistical analysis .............................................................................................................................................51 3 - Results & Discussion ....................................................................................................................................... 53 3.1 - Waterpipe and COPD ......................................................................................................................................53 3. 2 - Waterpipe and chronic bronchitis ..................................................................................................................62 3.3 - Pollution and COPD/chronic bronchitis...........................................................................................................69 4 – References ..................................................................................................................................................... 75 5 - Related publications ....................................................................................................................................... 77
SECTION III ............................................................................................................................................ 79 SCALES DEVELOPMENT, VALIDATION AND USE IN THE LEBANESE POPULATION ...... 79 0 - Rationale for developing Lebanese adapted scores ........................................................................................ 79 References ...............................................................................................................................................................79 Related publications ................................................................................................................................................79 1 - Diagnosis Score – Chronic Obstructive Pulmonary Disease (DS-COPD) development ...................................... 81 Rationale for scale development ............................................................................................................................81 Methods ..................................................................................................................................................................81 Results & Discussion ................................................................................................................................................82 References ...............................................................................................................................................................87 2 - DS-COPD validation in the clinical setting ....................................................................................................... 88 Rationale .................................................................................................................................................................88 Methods ..................................................................................................................................................................89 Results & Discussion ................................................................................................................................................90 References ...............................................................................................................................................................95 3 - Respiratory Toxic Exposure Score (RTES) development and validation ........................................................... 97 Rationale .................................................................................................................................................................97 Methods ..................................................................................................................................................................99 Results & Discussion ..............................................................................................................................................100 References .............................................................................................................................................................105 4 - Lebanese Cigarette Dependence Scale (LCD) development ........................................................................... 107 Rationale ...............................................................................................................................................................107
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Methods ................................................................................................................................................................108 Results & Discussion ..............................................................................................................................................109 References .............................................................................................................................................................117 5 - Cigarette smoking, dependence and COPD ................................................................................................... 119 Rationale ...............................................................................................................................................................119 Methods ................................................................................................................................................................120 Results & Discussion ..............................................................................................................................................121 References .............................................................................................................................................................126
CONCLUSION ...................................................................................................................................... 128
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Section 0 Introduction and objectives of the project Chronic Obstructive Pulmonary Disease (COPD) is the most common chronic lung disease. Characterized by partially irreversible airflow limitation, it mainly presents as chronic bronchitis phenotype [Rabe et al, 2007]. In 2002, it was the fifth leading cause of death worldwide, while by 2020, it is estimated to climb to third place [Murray, 1997]. It is mainly linked to tobacco smoking - considered one of the leading causes of deadly diseases in the world – with total tobacco-attributable deaths projected to rise to 8.3 million in 2020; almost 10% of all deaths globally, mainly in developing countries [World Health Organization, 2008]. Although it is a preventable disease - 80% of cases are thought to be due to smoking - its treatment is not curative [Rabe et al, 2007]. Furthermore, it goes largely undiagnosed and is largely unrecognized by governments’ officials and the general population, particularly in developing countries [Soriano et al, 2010; Bridevaux et al, 2010; Idrees et al, 2012]. In the Middle East and North Africa (MENA) region, it is also inadequately evaluated and treated. Furthermore, its risk factors - in particular smoking and pollution - are inadequately addressed [Idrees et al, 2012]. Objectives of the project In this project, our aim was to evaluate COPD prevalence in the Lebanese adult population, to evaluate tobacco smoking prevalence and characteristics and to evaluate the respiratory Quality of Life (QOL) of the Lebanese population.
We also aimed to assess the association between: waterpipe (WP) smoking, waterpipe dependence, chronic bronchitis and COPD. The second association we wanted to evaluate was that of exposure to passive smoking and air pollution with chronic bronchitis and COPD. Furthermore, we intended to develop and validate useful adapted scales in the domain, such as: the Respiratory Toxic Exposure Scale (RTES) to screen for COPD, the Lebanese Cigarette Dependence (LCD) scale to evaluate cigarette dependence and the COPD Diagnosis Scale (DSCOPD) to diagnose COPD without spirometry.
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Conducted studies To reach these objectives, two studies were conducted. Study 1: was a cross-sectional study on a nationally representative sample of 2201 Lebanese adults (presented in Section 1). Study 2: was a case-control study, including 211 COPD cases and 527 controls, taken from two tertiary care hospitals in Beirut (presented in Section 2). Furthermore, we presented the scales that we derived from both studies in Section 3. References
Bridevaux PO, Probst-Hensch NM, Schindler C, et al. Prevalence of airflow obstruction in smokers and never-smokers in Switzerland. Eur Respir J. 2010; 36:1259–1269. Idrees M, Koniski ML, Taright S, Shahrour N, Polatli M, Ben Kheder A, Alzaabi A, Iraqi G, Khattab A, Javed A, Rashid N, El Hasnaoui A, BREATHE Study Group. Management of chronic obstructive pulmonary disease in the Middle East and North Africa: Results of the BREATHE study. Respir Med. 2012; 106 Suppl 2:S33-44. DOI: 10.1016/S09546111(12)70013-6. Murray CJ, Lopez AD. Alternative projections of mortality and disability by cause 1990– 2020: Global Burden of Disease Study. Lancet 1997; 349: 1498–1504. DOI:10.1016/S01406736(96)07492-2 Rabe KF, Hurd S, Anzueto A et al. Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: GOLD executive summary. Am J Respir Crit Care Med. 2007; 176:532-555. Soriano JB, Ancochea J, Miravitlles M, et al. Recent trends in COPD prevalence in Spain: a repeated cross-sectional survey 1997–2007. Eur Respir J. 2010; 36:758–765. World Health Organization. The global Burden of disease, 2004 update. World Health Organization. 2008, Geneva. Retrieved from: www.who.int. No DOI available.
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Section I Study 1 - Chronic obstructive pulmonary disease prevalence in Lebanon: a cross-sectional study 1-Rationale As stated previously, Chronic Obstructive Pulmonary Disease (COPD) is projected to rank third as a cause of mortality by 2020 [Rabe et al, 2007] and its burden is increasing worldwide. Risk factors and clinical context are important for a positive diagnosis but pulmonary function tests are needed for confirmation [Rabe et al, 2007; Celli et al, 2004]. However, defining COPD on the flow volume curve is restricted to one criterion: the post-bronchodilator forced expiratory volume at 1 second (FEV1)/forced vital capacity (FVC) ratio being less than 70% [Rabe; 2007; Celli et al, 2004; Vollmer et al, 2009]. This is why new insights have arisen with regard to the limitations of such a diagnostic criterion [Vollmer et al, 2009; Vas Fragoso et al, 2010], with some having argued that the value of the 5% Lower Limit of Normal (LLN) is a more accurate COPD diagnosis [Vollmer et al, 2009; Swanney et al, 2008]. Data was lacking in Lebanon when the ban on smoking in public places was finally enacted in August 2012. This was the first national cross-sectional study carried out with the objective of determining the prevalence of COPD in the Lebanese adult population. Our hope is that it will become the starting point for building health policies for smoking-related diseases in the country.
2-Methods 2.1-Study design and population
A cross-sectional study was carried out between October 2009 and September 2010, using a multistage cluster sample all over Lebanon. Lebanese residents aged 40 years plus were enrolled in the study, with no exclusion criteria. The total number of males in this population is 614564, while the total number of females is 653751 [MOSA, 2008]. The Institutional review Board approval was unnecessary as the study was an observational one, not experimental nor clinical nor interventional.
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2.2-Procedure
From the list of circumscriptions in Lebanon, villages, towns and cities [CAS, 2005], we randomly selected one hundred; this randomization was achieved via computerized software. We then chose at random individuals to be interviewed from a list provided to us via a representative of local authorities of occupied households, with inhabitants aged 40 years and above. After obtaining an oral informed consent, each subject underwent a baseline spirometry (Micro Lab, Micro Medical Limited, England) by a trained technician and answered a questionnaire. Thirty minutes after the inhalation of 2 puffs of ipratropium bromide (18 µg/actuation) and albuterol sulfate (103 µg/actuation) (Combivent®) in a pressurized metereddose aerosol unit, a post bronchodilator spirometry was performed. The best result out of three trials was taken into account. Moreover, carbon monoxide (CO) levels were measured in exhaled air using a CO– Tester apparatus (NG, F.I.M).
We used the questionnaire of the American Thoracic Society (ATS) for our evaluation of chronic pulmonary disease [Ferris, 1978] and the Medical Research Council (MRC) score to evaluate dyspnea [Mahler, 1988]. Questionnaires were translated into Arabic by an independent translator and cross checked by investigators. A reverse translation was undertaken by another translator to ensure lack of discrepancy between the English and Arabic versions and was pretested in a pilot sample of 20 individuals before finalizing the details. Moreover, questions about weight, height and a diagnosed cardiac problem were also asked. In addition to health questions, data was collected concerning socio-demographic characteristics - age, sex, education, marital status, area of residence - and cigarette and waterpipe smoking history current, previous or non-smokers. Moreover, respiratory related quality of life (QOL) was measured by the Clinical COPD Questionnaire (CCQ) [Van der Molen, 2003]. The questionnaires were administered in the local Arabic dialect with a translation process as follows: first, two of the researchers, both bilingual, translated the questions into Arabic. Instructions were given to them with regard to the translation with emphasize on conceptual rather than literal translations, as well as the need to use natural and acceptable language for the broadest audience. Second, discrepancies were resolved by consensus between them and two other researchers; this panel included the original translators, experts in health, as well as experts with experience in instrument development and translation. Third, an independent translator with no knowledge of the questionnaire reverse translated the questions into English. Translation discrepancies were resolved by consensus between the researchers and the translator. Fourth, the questionnaire was pilot tested on twenty individuals; all questions were deemed clear by these individuals, and no further changes were made to the initial questions. 7
2.3-Definitions
COPD was defined and classified according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines [Rabe, 2007] and according to the Lower Limit of Normal (FEV1/FVC post-bronchodilator < 5th percentile of the healthy population having the same age and gender of the individual) [Swanney, 2008]. The latter equations were calculated according to the method described by Cole and collaborators, separately for males and females [Cole, 1992], used to predict the expected 5th percentile for every individual’s healthy population according to age and gender. An individual was considered “healthy” from the respiratory point of view if he/she had no respiratory symptoms and no respiratory disease. Moreover, patients with reversible obstruction but still post bronchodilator FEV1/FVC less than 70%, with clinical features of asthma, were considered mixed Asthma and COPD; they are termed “reversible COPD”. Chronic bronchitis was defined as the declaration of a morning cough and expectorations for more than three months a year over more than two years, in individuals with no COPD [Gold, 2009]. Moreover, individuals showing a reversible obstruction on spirometry such as an increase in FEV1 of 12% or more and 200mL or more after a bronchodilator administration were considered as having “airway hyperreactivity” and those with “physician diagnosed asthma” with or without reversibility on spirometry as confirmed “asthma” [Pellegrino, 2005; GINA guidelines, 2011]. Cigarette smoking was defined as smoking more than one pack in a lifetime, while current waterpipe smoking was defined as a positive answer to the question “do you regularly smoke waterpipe” and previous waterpipe smoking as a positive answer to the question “were you a regular smoker of waterpipes”. Individuals were considered light smokers if they consumed equal to or less than five cigarettes/day for more than two years, in comparison with heavy smokers; if they smoked more than five cigarettes/day for more than two years during their lifetime [Shiffman, 2006, Kirchner, 2007]. Moreover, cigarette dependence was defined using the Fagerström Test for Nicotine Dependence (FTND) [Fagerström, 1989, Heatherton, 1991]. Cumulative dosing of cigarettes was calculated as the mean number of daily packs multiplied by the duration of smoking (pack*years), while that of waterpipe was calculated as the mean number of weekly waterpipes, multiplied by the duration of smoking (waterpipe*years). Waterpipe dependence was defined according to the Lebanese Waterpipe Dependence Scale (LWDS-11) [Salameh, 2008].
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Level of education was divided into: “Never been to school”, “Primary school or less”, “Complementary school or less”, “Secondary school or less” and “University degree”, while age categories were bracketed as: 40–44 years, 45–49 years, 50–54 years, 55–59 years, 60–64 years and 65 years plus. 2.4-Sample size calculation
A minimal simple random sample size of n= 1015 was required to measure the prevalence of COPD in the Lebanese adult population, aged 40 years plus. In accordance with other studies in the world that showed a variation of COPD prevalence between 9-12 % [Soriano, 2010; Caballero, 2008] a worst acceptable result of +/- 2% difference with the above mentioned prevalence and a 95% confidence interval were added to the multistage sampling design, through which a minimal sample size of 2030 individuals was calculated. Finally, we decided to target 3000 individuals requiring a response rate of at least 67%.
2.5-Statistical analysis
The Statistical Package for Social Sciences [SPSS; version 17.0; IBM, Armonk, NY] was used to enter and analyze data. Weighting was performed according to the numbers published by the Lebanese Ministry of Social Affairs and the Central Administration of Statistics in 2007, taking into account gender, age and area of residence [MOSA, 2008]. Cluster effect was taken into account according to Rumeau-Rouquette and collaborators [Rumeau-Rouquette, 1985]. A pvalue of less than 0.05 was considered significant; however, a Bonferroni adjustment was applied in case of multiple comparisons. The Chi Square test was used for cross tabulation of qualitative variables in bivariate analysis, and prevalence ratios (PR) or odds ratios (OR) was calculated. Somers’d test was used to evaluate trends between ordinal variables. Student’s test was used to compare quantitative variable means between two groups, after checking distribution normality and homoscedasticity. ANOVA (Analysis of Variance between groups) and Kruskal-Wallis tests were used to compare between three groups or more, and a Pearson correlation coefficient was used to correlate between quantitative variables. Bonferroni adjustment was used for ANOVA post hoc tests of between group comparisons. Chi Square trend tests were used to evaluate dose-effect relationships [Epi Info 6 trend test, version 6.04d, Center for Disease Control & World Health Organization].
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Backward or forward stepwise likelihood ratio logistic regressions were performed for multivariate analysis, when dependent variables were dichotomous. After ensuring model adequacy by utilizing the Hosmer-Lemeshow test of adequacy to data, adjusted odds ratios (ORa) were calculated. Moreover, stepwise descendent multiple linear regression analyses were performed to evaluate predictors of quantitative dependent variables. Potential confounding variables were used as independent variables. Linearity of the relationship, normality of residuals and non-co-linearity of retained variables were ensured before the models were accepted. 2.6-Clinical COPD Questionnaire (CCQ) analysis specific methods
To confirm the CCQ construct validity in the Lebanese population a factorial analysis was launched for CCQ items, using the principal component analysis technique, with a promax rotation since the extracted factors were found to be significantly correlated. The KaiserMeyer-Olkin (KMO) measure of sampling adequacy and Bartlett’s test of sphericity were ensured to be adequate. The retained number of factors corresponded to Eigenvalues higher than one. Factors loading of items were recorded. Moreover, Cronbach’s alphas were recorded for reliability analysis for the total score and for subscale factors. The total CCQ score represents the sum of the 10 CCQ items divided by 10 (as recommended in the CCQ manual) [Van der Molen, 2003] while the factors one and two are the sums of their respective items. Factors and items correlation with postbronchodilator spirometric FEV1/FVC were reported, in addition to factors and scale association with COPD and its severity. Afterwards, backward linear multiple regression was performed for multivariate analyses, with CCQ score as the dependent variable and socio-demographic characteristics and other potentially harmful exposures as the independent variables; after ensuring model adequacy to data, relationship linearity, dependent variable normality and lack of colinearity between covariates. We utilized this method to find significant predictors of respiratory QOL in all individuals; in patients with COPD and in nonsmokers. Moreover, partial correlation with CCQ score was presented, taking other covariates into account.
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2.7-Gender and smoking specific methods
An automated backward stepwise likelihood ratio multiple logistic regression was performed for multivariable analyses. One model was generated, with waterpipe dependence as the dependent variable, sex as the independent variable and socio-demographic characteristics (including age group, marital status, working status and education level) as covariates. These covariates were selected to be included in the multivariable regression because they showed significant differences (p
