Association between chronic airflow obstruction and socio- economic position in Morocco: BOLD results

B A C K G R O U N D : Chronic obstructive lung disease (COPD) is the third most common cause of death in the world. Factors other than smoking, such as socioeconomic status, could be involved in the development of COPD. O B J E C T I V E : To investigate the association between chronic airflow obstruction and socio-economic status in Morocco. D E S I G N : Questionnaires were administered and spirometry tests performed as part of the BOLD (Burden of Obstructive Lung Disease) Study carried out in Fez, Morocco. Socio-economic status was evaluated using a wealth score (0–10) based on household assets. The ratio of forced expiratory volume in 1 s (FEV1) to forced vital capacity (FVC) was used to measure airflow obstruction. R E S U LT S : A total of 760 subjects were included in the analysis. The mean age was 55.3 years (standard deviation [SD] 10.2); the average wealth score was 7.54 (SD 1.63). After controlling for other factors and potential confounders, FEV1/FVC increased by 0.4% (95%CI 0.01–0.78; P , 0.04) per unit increase in wealth score. Ageing, tobacco smoking, underweight, history of tuberculosis and asthma were also independently associated with a higher risk of airflow obstruction. C O N C L U S I O N : Our findings suggest that airflow obstruction is associated with poverty in Morocco. Further investigations are needed to better understand the mechanisms of this association. K E Y W O R D S : chronic obstructive lung disease; BOLD study; poverty; Morocco

B A C K G R O U N D : Chronic obstructive lung disease (COPD) is the third most common cause of death in the world. Factors other than smoking, such as socioeconomic status, could be involved in the development of COPD. O B J E C T I V E : To investigate the association between chronic airflow obstruction and socio-economic status in Morocco. D E S I G N : Questionnaires were administered and spirometry tests performed as part of the BOLD (Burden of Obstructive Lung Disease) Study carried out in Fez, Morocco. Socio-economic status was evaluated using a wealth score (0-10) based on household assets. The ratio of forced expiratory volume in 1 s (FEV 1 ) to forced vital capacity (FVC) was used to measure airflow obstruction.
R E S U LT S : A total of 760 subjects were included in the analysis. The mean age was 55.3 years (standard deviation [SD] 10.2); the average wealth score was 7.54 (SD 1.63). After controlling for other factors and potential confounders, FEV 1 /FVC increased by 0.4% (95%CI 0.01-0.78; P , 0.04) per unit increase in wealth score. Ageing, tobacco smoking, underweight, history of tuberculosis and asthma were also independently associated with a higher risk of airflow obstruction. C O N C L U S I O N : Our findings suggest that airflow obstruction is associated with poverty in Morocco. Further investigations are needed to better understand the mechanisms of this association. K E Y W O R D S : chronic obstructive lung disease; BOLD study; poverty; Morocco CHRONIC OBSTRUCTIVE PULMONARY disease (COPD) is a lung disease characterised by chronic airflow obstruction that interferes with normal breathing and is not fully reversible; 1 COPD is the third most common cause of death in the world. 2 According to the World Health Organization (WHO) estimates, almost 90% of COPD deaths occur in lowand middle-income countries (LMICs). 3 The main risk factor for COPD is tobacco smoking, 4-6 but emerging evidence suggests that other risk factors are important, especially in LMICs. According to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2017, in addition to tobacco smoking, COPD is related to the following factors: age and sex, indoor and outdoor air pollution, occupational exposures, lung growth and development, and chronic respiratory infections such as tuberculosis (TB) and socio-economic status. 5 There is less information on the association of airflow obstruction with these factors in LMICs.
The relationship between socio-economic position and the presence of airflow obstruction has not been sufficiently investigated at an individual level. An ecological analysis, conducted as part of the Burden of Obstructive Lung Disease (BOLD) study, showed little association between air obstruction and per capita Gross National Income (GNI). 7 Although information about the link between obstruction and poverty is available at individual level from previous studies, most of these have been conducted in high-income countries and do not measure obstruction for the majority or provided controversial results. 8 An analysis carried out recently by Townend et al., 9 combining results from 12 sites participating in the BOLD study, showed that airflow obstruction is consistently associated with poverty at both individual and community levels.
According to previous results from the BOLD study conducted in Morocco in 2010, 10 the prevalence of COPD was 12.6% for GOLD stage 1 and 7.9% for GOLD stage 2. The authors showed that prevalence increased with age and the number of pack years smoked. However, the link between airflow obstruction and socio-economic position has not been studied yet. The present study is the first in Morocco to answer the question whether or not socioeconomic level could have an impact on airflow obstruction; we also hypothesised that the risk of airflow obstruction is higher among people with low socio-economic level in Morocco.

The BOLD study
The BOLD study is a multisite, international study carried out in many regions in the world to estimate the prevalence and the determinants of obstructive lung disease. The details of the study design and methodology have been described elsewhere. 11 At each site, a questionnaire was administered and spirometry tests performed in a representative sample of adults aged 40 years.
Spirometry tests were conducted using a standardised BOLD protocol; each spirogram was read and qualitychecked by the BOLD Pulmonary Function Reading Centre at the Imperial College London, London, UK.
The study protocol was approved by the ethics committee of the University Hospital Center Hassan II, Fez, Morocco; all participants provided written informed consent.
Wealth score calculation method The socio-economic position was assessed using a wealth score, which is an international scale based on household assets. 12 The score met the requirements of a Mokken scale; 13,14 for example, all of the items were related to wealth and the ownership of one was independent of the others. The 10 items selected were electricity, television, cell phone, refrigerator, indoor bath, indoor tap, flush toilet, washing machine, car and landline telephone. The score was calculated by adding up the total number of these assets owned by the respondents or their household. The total score ranged from 0 (no assets) to 10 (all assets). 9,12 As the score is approximately suggestive of an individual's wealth, we will use the term 'wealth score' to refer to the score calculated by this method.

Statistical analyses
Means and standard deviations (SDs) were provided for quantitative variables and frequencies for categorical ones. The association between the wealth score and the airflow obstruction was estimated using linear regression of the post-bronchodilator forced expiratory volume in 1 s (FEV 1 )/forced vital capacity (FVC) ratio expressed in percentage (%). Low scores indicate increased airflow obstruction. The analysis was firstly adjusted for age and sex and secondarily adjusted to potential confounding factors in order to investigate the effect of these latter on the association between the wealth score and airflow obstruction. Factors included in the multivariate analysis were body mass index (BMI), education, smoking status, whether or not dusty job, TB and familial history of COPD; these factors have been previously identified as having both an effect on airflow obstruction and poverty. 9,15 Educational level was defined as six levels of completed education (none, primary school, middle school, secondary school, technical college and university), and also by the number of completed education years. The BMI was included in the models as a categorical variable (underweight, ,18.5 kg/m 2 ; normal, 18.5-25 kg/m 2 ; overweight, 25-30 kg/m 2 ; or obesity, .30 kg/m 2 ). Tobacco smoking was defined as the respondents' total consumption of cigarettes in their lifetimes. Exposure to a dusty job was defined by an exposure for over 1 year. Except for education and BMI, all other potential confounders were included as binary variables. Age was included as continuous variable assuming a linear relation to obstruction with increasing age.
All statistical analyses were conducted using R software v3.5.1 (R Core Team, R Foundation for Statistical Computing, Vienna, Austria).

Characteristics of the study population
A total of 760 participants provided adequate spirometry and questionnaire information and were included in the analysis. Among these, 350 (46%) were male and the mean age was 55.3 years 6 10.2. The majority were illiterate or had a primary educational level; only 6.5% had university level education. More than half were overweight or obese (respectively 38.1% and 31%). Smoking was moderate, 27.2% had smoked cigarettes in their lives and 13.9% were exposed to cigarette smoke in their familial environment. The exposure to dusty job for over a year was mentioned for 325 subjects (42.7%).
The mean FEV 1 /FVC ratio was 78.0 6 8.3; family history of COPD was noted in 10% of the sample. Other conditions reported included 13 (1.7%) with TB, 58 (9.2%) with asthma or respiratory allergy and 5 (0.6%) who were hospitalised for breathing problems before the age of 10 years (Table 1).

Assets ownership items and wealth score
The current wealth score was calculated using 10 items, more than 90% owned electricity, television, cell phone, refrigerator and indoor tap. Only 26.7% had a car, and almost half had flush toilet. An indoor bathroom and a washing machine were owned by 82% and 72% of the sample. Finally, as fixed phones are less often used now, only 41.4% declared that they possessed a landline. The mean wealth score calculated based on these items was 7.54 (SD 1.63) ( Table 2).
Association between FEV 1 /FVC ratio and the wealth score Linear regression analysis adjusted for age and sex showed that FEV 1 /FVC (%) was significantly associated with the wealth score, and increased on average by 0.50% for each increased point in the wealth score (95% confidence interval [CI] 0.16-0.84; P , 0.003); it also increased by 2.28% in women compared to men, and decreased by 0.23% for each increasing year of age. After adjusting for tobacco smoking, the association between airway obstruction and sex disappeared but the association between FEV 1 /FVC (%) and wealth remained significant following adjustment for other risk factors. An increase on average of 0.4% per one increased point in the wealth score was noted (95%CI 0.01-0.78; P , 0.04). Age, tobacco smoking, low BMI and a history of TB or asthma were all associated with lower FEV 1 /FVC values (Table 3).

DISCUSSION
The objective of our study was to assess the association between airflow obstruction assessed using the FEV 1 /FVC ratio and socio-economic status in Morocco. Our results showed a significant inverse association between airflow obstruction and wealth: the FEV 1 /FVC ratio increased significantly with increasing wealth score. We also demonstrated significant associations with age, tobacco smoking, BMI, TB and asthma.
These findings are consistent with those reported by Townend et al. 9 In an analysis conducted at 12 BOLD sites located in 11 countries, they reported a strong inverse association between airflow obstruction and wealth, both within and across the 12 sites. Similar associations have also been reported by previous studies which have examined the link between poverty and poor lung function, 8 although  in an earlier ecological analysis from the BOLD study, 7 Burney et al. showed little relationship between the prevalence of chronic airflow limitation at the 22 BOLD sites where this ecological study was conducted and the gross national income (GNI) of the country and a much stronger association with the mean pack years of cigarettes smoked. In this study, wealth was assessed based on the ownership of household assets, which is an easy way to assess one component of socio-economic status. Townend et al. showed that the mean scores for the centres correlated well with the GNI of the country. 12 Although an inverse association between wealth and airflow obstruction has been reported, the mechanisms that could explain this association are unknown. In our study and a previous analysis from the BOLD study, 9 age and tobacco smoking were strong confounders; however, adjustment for these and other potential confounders did not explain the majority of the association with the wealth score. Although some of the residual association could be explained by these and other risk factors where they have not been precisely measured, this seems an unlikely explanation by itself.
Our findings indicate significant associations between airflow obstruction and other factors such as age, tobacco smoking, BMI and a history of TB or asthma. The impact of age and tobacco smoking has been widely described in previous studies. 7,9,15 In our study, we showed that lifetime consumption of cigarettes is a strong risk factor for airflow obstruction. In a secondary analysis, we tested the dose-effect relationship between smoking and airflow obstruction, we found that the risk of COPD was only significant among subjects who had smoked more than 20 pack years. A dose-effect relationship between cigarette smoking and COPD has been previously reported. 4 The association between sex and airflow obstruction disappeared after adjusting for smoking. Smoking could be a potential confounder in this association. In fact, the majority of participants who smoked in our study were male (98%). However, in secondary analyses, sex was associated with airflow obstruction in non-smokers after stratification on smoking status. This suggests that smoking modifies the effect of sex on airflow. In previous studies, it has been suggested that women may be at different risk from men because of factors such as airway geometry, how particles are deposited in the airway and hormonal factors. 16 These findings are consistent with previous studies, although COPD prevalence in the PLATINO study was similar in males and females. 17 Nevertheless, in other BOLD analyses, Hooper et al. showed that the ratio of FEV 1 / FVC was higher for women than for men; 15 the same finding was reported by Townend et al. 9 These differences with our study could be explained by the large number of participants, as these studies included 14 and 12 BOLD sites respectively in the analyses. As in this study, Townend et al. also noted the decline in the association between sex and FEV 1 /FVC ratio; however, as in our study, this was not statistically significant.
The antecedent of TB has been shown to be associated with a higher risk of airflow obstruction. 15,18,19 Similarly, our results showed that after controlling for sex, age, smoking and the other factors, TB remained independently associated with an increased risk of airflow obstruction. Furthermore, poverty is widely recognised as an important risk factor for TB. 20 Poverty and TB could act jointly to increase the risk of airflow obstruction. The present study was conducted following the BOLD protocol, a representative sample of participants was included and data were collected using standardised methods and by well trained staff. Collected data and spirometry tests results were sent to London, UK, for quality control, and data that did not meet the quality criteria were removed from the analysis. Nevertheless, the study could have some biases, as exposures were evaluated using a questionnaire, exposures were self-reported, which could lead to bias, particularly in case of exposures or events that may have occurred early in life. Recall bias should thus be considered before interpreting results from such studies. Another possible limitation is the location of the survey, which may have impacted the socio-economic level of the participants and the association with airflow obstruction. Findings might have been different if the study had been conducted at other lower or higher income level sites.
In conclusion, in a low-middle income country such as Morocco, factors other than smoking, such as socio-economic position, should be considered in the management of COPD. Our study revealed that a higher FEV 1 /FVC ratio is associated with increased wealth. These findings implied that the measure of socio-economic position may be useful to describe the social distribution of chronic airflow obstruction, and underline the importance of considering the socioeconomic position by health decision makers when implementing health strategies. Further studies are needed to investigate the mechanisms by which socioeconomic position generates health differences. R É S U LTAT S : Au total, 760 sujets ontété inclus dans l'analyse. L'âge moyen aété de 55,3 ans (déviation standard [DS] 10,2) ; le score de ressources aété en moyenne de 7,54 (DS 1,63). Après contrôle des autres facteurs et des facteurs de confusion potentiels, le rapport FEV 1 /FVC a augmenté de 0,4% (IC95% 0,01-0,78 ; P , 0,04) par augmentation d'une unité du score de ressources. L'âge, le tabagisme, la maigreur, des antécédents de tuberculose et d'asthme ont egalementété indépendamment associésà un risque plusélevé d'obstruction.
C O N C L U S I O N : Nos résultats suggèrent que l'obstruction des voies aériennes est associéeà la pauvreté au Maroc. Davantage de recherche est requise pour mieux comprendre les mécanismes de cette association.

R E S U M E N M A R C O D E R E F E R E N C I A:
La enfermedad pulmonar obstructiva crónica (EPOC) es la tercera causa más frecuente de defunción en el mundo. Otros factores diferentes del tabaquismo, como la situación socioeconómica, podrían participar en la aparición de la EPOC. O B J E T I V O: Investigar la asociación entre la obstrucción crónica del flujo aéreo y la situación socioeconómica en Marruecos. M É T O D O: El estudio BOLD (Burden of Obstructive Lung Disease) realizado en Fez, en Marruecos, comportó cuestionarios y pruebas espirométricas. La situación socioeconómica se evaluó mediante una escala de la riqueza (0-10) basada en los bienes familiares. Se utilizó el cociente del volumen espiratorio forzado en el primer segundo (FEV 1 ) y la capacidad vital forzada (FVC) a fin de medir la obstrucción del flujo aéreo.