Prevalence and determinants of chronic respiratory diseases in adults in rural Sudan

BACKGROUND: Chronic respiratory diseases (CRDs) greatly contribute to worldwide mortality. Despite new data emerging from Africa, prevalence estimates and determinants of CRDs in rural settings are limited. This study sought to extend the existing research conducted in urban Sudan by conducting a rural comparison. METHODS: Participants aged ≥18 years (n = 1,850), living in rural Gezira State completed pre-and post-bronchodilator spirometry and a questionnaire. Prevalence of respiratory symptoms and spirometric abnormalities were reported. Regression analyses were used to identify risk factors for CRDs. RESULTS: Prevalence of chronic airflow obstruction (CAO) was 4.1% overall and 5.5% in those aged ≥40 years. Reversibility was seen in 6.4%. Low forced vital capacity (FVC) was seen in 58.5%, and at least one respiratory symptom was present in 40.7% of the participants. CAO was more common among people aged 60–69 years (OR 2.07, 95% CI 1.13–3.82) and less common among highly educated participants (OR 0.50, 95% CI 0.27–0.93). Being underweight was associated with lower FVC (OR 3.07, 95% CI 2.24–4.20). CONCLUSIONS: A substantial burden of CRD exists among adults in rural Sudan. Investment in CRD prevention and management strategies is needed.

Although the global burden of chronic respiratory diseases (CRDs) such as chronic obstructive pulmonary disease (COPD) and asthma is high and expected to increase, 1,2 they receive limited attention. 2The Global Burden of Disease study estimated that COPD affected almost 212 million adults in 2019 and resulted in 3 million deaths, with 62.6% of the burden of COPD and lung cancer occurring in low-and middle-income countries (LMICs). 2,3COPD is poorly recognised and undertreated in most populations. 4sthma affected 262 million people and resulted in almost half a million deaths in 2019. 1 Asthma-related deaths in LMICs account for 96% of global asthmarelated deaths and 84% of global disability-adjusted life-years (DALYs).1,3 Data about CRDs in sub-Saharan Africa (SSA) and the Middle East and North Africa (MENA) regions are scarce, but suggest the burden is high.4 High prevalence of chronic airflow obstruction (CAO) has been documented across the region, 5 with spirometric obstruction seen in 10% of urban Sudanese adults in a recent study.6 The prevalence and underlying causes of low forced vital capacity (FVC) in SSA remain poorly understood; 7 nonetheless, its association with mortality is well-documented.8 TB, early childhood infection, low body mass index, biomass fuel use, smoking and poverty are believed to be associated with CRDs in LMICs. Moreover, a high burden of uncontrolled asthma exists even in tertiary level hospitals in Khartoum, Sudan.13 The Burden of Obstructive Lung Disease (BOLD) Initiative developed standardised methods for estimating the burden and determinants of CAO in populations aged 40 years.14,15 Following an urban study in Khartoum State, 6 we conducted a population-based cross-sectional (BOLD) study in rural Gezira State, Sudan, to explore the prevalence and determinants of CRD symptoms and spirometric abnormalities among adults in rural Sudan.

Setting
Gezira State is situated in central Sudan, and has an estimated population of 3,780,915, most of which (80.4%) live in rural areas. 16This population is distributed across seven localities, 40 administrative units and 689 villages.

Sampling
Three localities were randomly selected for inclusion in this study.Thirty-five villages were randomly selected and 30 households per village were included.Households included nomadic and Cambo (rural, mixedcomposition, displaced community) families present at the time of mapping and sampling. 17rticipants Using the BOLD protocol, 15 participants aged 18 years living in rural Gezira State were included.We excluded institutionalised people, the medically unfit and pregnant women in their last trimester.

Data collection and management
All participants completed a structured interview in the local Arabic language administered by trained interviewers.Anthropometric measurements, pre-bronchodilator (pre-BD) and post-BD spirometry data were collected following American Thoracic Society (ATS) guidelines using the Easy One system (ndd Medizintechnik, Zurich, Switzerland) by three trained certified technicians. 15A basic information or refusal questionnaire was filled out for those not willing to participate in the full study.The clinical data obtained included height, weight, pulse rate, and waist and hip circumference.Quality control was done at the BOLD coordinating centre.Usable spirometry was defined as two or more acceptable blows, with forced expiratory volume in 1 sec (FEV 1 ) and FVC repeatability within 200 mL.Acceptable manoeuvres were defined as those with a rapid start (back-extrapolated volume, 150 mL or 5% of the FVC), lack of cough during the first second and a small end-of-test volume (<40 mL during the final second).Calibration of all spirometers was verified to be accurate within 3.0% using a 3.00 L syringe at the beginning of each day of testing.Spirometry traces were then classified according to FEV 1 /FVC < lower limit of normality (LLN).

Statistical analysis
Prevalence estimates of spirometric abnormalities stratified by age and sex were reported using the US National Health and Nutrition Examination Study III (NHANES III) reference equations for White Americans (Caucasians). 15CAO Stage 1 or higher was defined by the LLN for post-BD FEV 1 /FVC, based on the NHANES III Caucasian reference equations for age and sex. 18Reversibility was defined using ATS and European Respiratory Society guidelines; difference in FEV 1 (post BD minus pre-BD) 200 mL and percentage change in FEV 1 12%.Prevalence estimates using locally derived spirometry values were also reported.These were derived from non-smoking Sudanese adults with no respiratory symptoms or diagnoses in the previous urban study. 6nivariable and multivariable logistic regression analyses were used to test associations between spirometry abnormalities and exposure variables, including age, sex, body mass index, education level, smoking status, smoking pack-years, exposure to indoor smoke from biomass fuel, occupation, and self-reported history of TB, hypertension, diabetes, and heart disease.A wealth score based on household asset ownership was used as a proxy for socio-economic status. 9,19ultivariable logistic regression models including sex, age and all variables from the univariable analysis with a P < 0.2 were developed.Prevalence of respiratory symptoms was reported and associations with study variables were tested using regression analysis.Associations between abnormal spirometry and respiratory symptoms were reported.Data were analysed using Stata IC v15 (StataCorp, College Station, TX, USA).Prevalence estimates and regression models were developed using survey weighting with the Svy package in Stata v15.To allow comparisons with the previous urban study, age groups were stratified to below and above 40 years.

Ethical considerations
Written informed consent was obtained from study participants before data collection.Ethical approval was obtained from the Imperial College London, London, UK; the Ethics Committee at Gezira State Ministry of Health, Wad Medani, Sudan; and Liverpool School of Tropical Medicine, Liverpool, UK (11.03RS).

RESULTS
Between August 2015 and December 2016, 3,281 participants from 35 villages in Gezira were approached and invited to participate in the study.Of these, 2,395 were eligible for inclusion and 1,850 (response rate 56.3%) consented to take part.Questionnaires and spirometry were completed to the required standard by 1,308 participants (Figure 1).

Participant characteristics
The mean age was 39.3 years, and 50% were women.Participants aged 40 years represented 45% of all participants.Almost 11% were current smokers.About 44% had high school or above education, with younger participants (<40 years) being more educated than older groups (66% vs. 36% higher education attainment, respectively).Overall, 17.3% of participants owned 6 of the 10 considered assets used in the construction of the wealth score, and 92% owned their own home.The average number of members in a household was 7. Farming was the most common occupation (39%), with 15% of farmers reporting more than 5 years of activity; 48% of participants had exposure to biomass fuels for more than 6 months in their lives.Moreover, 47% of participants had a normal body mass index (BMI).Hypertension was self-reported by 6.4% of participants (70% were women), followed by diabetes (3.3%, of whom 57% were women).Both heart disease and TB were reported by 0.3% (Table 1).

Respiratory symptoms
At least one respiratory symptom was reported by 40.7% of participants, with those over 70 years old showing the highest prevalence of symptoms (60.6%).Usual cough was the most frequently reported symptom (19.5%), with the highest prevalence recorded in participants aged 18-29 years (22.5%).Chronic cough (lasting for more than 3 months per year) was reported by 2.4% (standard error [SE] 0.02).Production of phlegm was reported by 14% (SE 1.9) and chronic production of phlegm was reported by 2.7% (SE 0.001).Shortness of breath was reported by 18.7%.Wheeze was the least commonly reported symptom (4.9%).Overall, females and participants over 70 were more symptomatic than other groups.Among participants with respiratory symptoms, 48.3% were ever smokers and 45.5% used biomass for 6 months.Participants aged 40 years showed higher prevalence of respiratory symptoms 42.2%.Medically diagnosed respiratory disease was reported by 7.4% of the participants.Asthma and COPD, whether or not diagnosed by a physician, were reported by respectively 6.4% and 7.4% of participants.Chronic bronchitis or emphysema was reported by 1.7%.

Spirometry
The prevalence of CAO using NHANES III criteria was 4.1% (3.1% in men and 4.8% in women).The prevalence was about the same when using local reference equations (3.4% in men and 3.1% in women).Participants aged 60-69 years and participants who smoked over 20 years had the highest prevalence of Stage 1 and Stage 2 CAO (8.2%, SE 2.3 vs. 7.1%, SE 4.2; and 7.6%, SE 2.7 vs. 4.1%, SE 2.5, respectively) (Figure 2).
Participants aged 40 years had higher estimates of Stage 1 CAO (5.5%, SE 0.8; and 4.1%, SE 0.8) and CAO Stage 2 (5%, SE 0.6; and 2.7%, SE 0.5) using local reference range and NHANES III reference range, respectively.No association was identified between CAO and age using LLN.
Using the NHANES III reference equations, the prevalence of low FVC (FVC < LLN), was 58.5% in both men and women.Using local reference equations, the prevalence was 5.3% in men and 9.1% in women.Participants in the younger group (18-39 years) had a higher prevalence of low FVC than those aged 40 years (61.5% vs. 52.6%).
Airway reversibility was present in 6.4%, and was more common in men (7.2%) than in women (5.7%).Airway reversibility scores were higher in those aged Participants aged 40 years had higher estimates of Stage 1 CAO (5.5%, SE 0.8; and 4.1%, SE 0.8) and Stage 2 (5%, SE 0.6; and 2.7%, SE 0.5) using local and NHANES III reference ranges, respectively.No association was identified between CAO and age using LLN.

Factors associated with low FVC (FVC < LLN)
Being underweight had the highest odds of having low FVC using NHANES III reference ranges in both univariable and multivariable analysis (OR 2.25, 95% CI 1.13-5.64).Moreover, participants who had smoked for more than 20 pack-years were less likely to have low FVC in both univariable and multivariable analyses (OR 0.36, 95% CI 0.25-0.50).Participants aged 70 years were less likely to have low FVC in both univariable and multivariable analyses (OR 0.19, 95% CI 0.09-0.40;and OR 0.19, 95% CI 0.09-0.40)(Table 3).Using the local reference range, no association was identified between low FVC and any of the potential risk factors.

DISCUSSION
Building on an earlier BOLD study conducted in urban Sudan, 6 we conducted this population-based The prevalence of CAO as indicated by persistent post-BD obstruction was 4.1%.Based on the LLN, in participants aged 40 years, the CAO prevalence was 5.5% and 3% using NHANES and local reference equations, respectively.These are lower than 10% and 5.7% from recent findings of an urban study in Sudan using NHANES and local reference equations, respectively. 6sing NHANES III reference equations shows a higher prevalence of obstruction compared to local reference equations, according to prior research. 8ocal values may be more ethnically suitable than NHANES III despite being the only data available.However, as varying exposures in this environment might limit its application, 8,20 using a standard reference when comparing prevalence across populations may be preferable.
The prevalence of CAO was higher than in other rural SSA settings, including Rwanda. 21These rates were however, far lower than those found in Uganda and rural Malawi. 22,23BOLD studies from countries in SSA such as South Africa 24 and Nigeria, 25 reported higher prevalence estimates compared to this study.However, similar studies from MENA countries, including Tunisia 26 and Morocco, 27 reported lower prevalence estimates, with the exception of Algeria. 28ge was the main risk factor for CAO in this study.This is consistent with the previous urban Sudan study and literature demonstrating that population ageing is one of the primary COPD risk factors, especially in developing countries with lower levels of smoking. 14,29The finding of those with high education level were less likely to have CAO is compatible with studies reporting an association of lower education with COPD. 30n line with the findings from the urban Sudan study, we did not observe any association between exposure to biomass fuel and obstruction.This is consistent with the 25 BOLD sites study which found no association between airflow obstruction and the use of solid fuels for cooking or heating. 31A recent review of studies on COPD and household air pollution concluded that it was not possible to define clear causal links between the two. 32n contrast to previous studies that have indicated a link between crowded housing and low socioeconomic status with the progression of airflow limitation, our research reveals no such association between CAO and increased numbers of household inhabitants or low socio-economic status. 29,33These findings are consistent with the previous study in urban Sudan. 6A possible explanation for this discrepancy could be attributed to the unique nature of Sudanese housing, characterised by spacious living environments that may reduce the impact of exposure to household air pollution in these settings.
In this study, a high prevalence of respiratory symptoms was reported by 40% of the participants, with cough and shortness of breath being the most common symptoms.As expected, Stage 1 CAO was Table 2 Multivariable associations of risk factors with Stage 1 CAO defined using the NHANES III reference range (post-BD FEV 1 /FVC < LLN; n ¼ 61/1320) and with Stage 2 CAO defined using NHANES III reference range (post-BD FEV 1 /FVC < LLN and post-BD FEV 1 < 80% predicted; n ¼ 55/1320) associated with breathing difficulties that interfered with daily activities.Moreover, respiratory symptoms were higher in those with Stage 1 CAO and breathing difficulty was the most common symptom among this group.
It is surprising to note that we found no association between respiratory symptoms and exposure to biomass fuel, even though 48% of the total participants were exposed to biomass fuels for 6 months, and females had the highest odds of having shortness of breath.This may be attributed to the higher prevalence of cough, shortness of breath and functional limitation due to breathing problems in the younger age group (18-39 years), 67% of which had no exposure to any biomass fuel.It is likely that the younger generation use gas and other cooking methods in these settings.
The absence of the association between respiratory symptoms and smoking might be explained by having 69% of those who ever smoked had less than 10 years of exposure.In addition, childhood respiratory infections may have contributed to this high prevalence, as pneumonia is the second highest cause of hospitalisation in Sudan. 12 high prevalence of low FVC (58.5%), which is indicative of reduced lung volumes, was found in the overall population, and women tended to have a higher prevalence of low FVC than men.This finding is lower than the finding from the BOLD study in Ile-Ife, Nigeria (70.4%). 7In contrast, this is higher than the findings from a recent study from Tunisia that reported a prevalence of 26%. 34The reasons behind this high prevalence are not known but studies suggested that unknown environmental factors, genetics, early exposure to biomass fuels, preterm delivery, malnutrition, childhood respiratory infections, TB and persistent HIV infection may influence lung development and result in lung damage or abnormal lung functioning in such settings. 2,7,8,34These factors may have contributed to the high estimates of low FVC in this study.
Exposure to other environmental factors such as living in poor communities may also have been a factor, as 9 of 35 villages were 'Cambo'.Mostly displaced from underdeveloped and conflicts areas, these populations are among the poorest in Sudan.The association between poverty and lung abnormality has previously been reported in several studies. 9,24he association between low FVC and being underweight in this study is consistent with previous studies suggesting that being underweight or obese is a risk factor associated with 'restricted' lung function. 7,34,35o note, higher estimates of low FVC were identified in those younger than 40 years, whereas participants aged >70 and those who smoked >20 years were less likely to have low FVC.This is in contrast to studies reporting that ageing and smoking were associated with low FVC. 7,34,35It is difficult to explain this finding, but the small number of participants who were >70 years and smoked for more than 20 years could be considered a survivor effect.
Comparisons with the Urban Khartoum study Overall, CAO, a key characteristic of COPD was more prevalent in the urban (Khartoum) vs. rural (Gezira) study for participants aged 40 years.A higher educational level reported in Gezira State compared to Khartoum State may have contributed to the lower levels of post-BD obstruction observed. 30Furthermore, although Gezira State is officially classified as a rural state, it is relatively wealthy as it used to have the largest agriculture project in the country. 17oreover, the high prevalence of CAO in Khartoum might be due to exposure to air pollutants as a result of the large number of factories and cars in the State.Despite a relatively high smoking prevalence, cigarette smoking was not associated with CAO in either study.This might be because respectively 50% and 94% of the smokers reported a smoking history of fewer than 10 pack-years in urban and rural studies.
Rural participants had a lower FVC prevalence estimate and higher respiratory symptoms in the overall population compared to urban ones.We did not explore the reasons for low FVC in this study.Our findings suggest the need for more research in this area.However, early life exposures as a consequence of living in a poor environment, malnutrition and respiratory infections during childhood may have contributed to the high levels of low FVC in this study. 8In addition, the higher estimates of low FVC using NHANES III compared to local values suggest that the Sudanese have smaller lungs than Europeans, which is consistent with other studies in Africa. 8,25indings from both studies suggest that the burden of low FVC requires more attention and investigation.Airway reversibility in both rural and urban studies highlights the need for further investigation of asthma in the region.
This study is the first of its kind in rural Sudan; the inclusion of a younger age group of 18 years allowed us to explore different conditions and lung abnormalities.Spirometry was conducted according to ATS standards with careful quality control.The use of the BOLD standardised method allowed comparability with other findings from the continent and worldwide.This study acknowledges certain limitations, notably a response rate of 56%, with 22% of the initial sample having relocated from the area.
In conclusion, the prevalence of CAO in participants aged 40 years, airway reversibility and high prevalence of respiratory symptoms across age groups, especially in younger ones, suggest that CRDs are a serious public health problem in rural Sudanese adults, and highlights the need for more investment in prevention and management of CRDs.The high prevalence of low FVC is one of the key findings in both urban and studies.There is a need for further investigation of the reasons behind the reduced lung volumes in Sudanese adults given its association with increased mortality in other settings.

R É S U M É
C O N T E X T E : Les maladies respiratoires chroniques (CRD) contribuent grandement a la mortalit e mondiale.Malgr e l'apparition de nouvelles donn ees en Afrique, les estimations de la pr evalence et les d eterminants des maladies respiratoires chroniques en milieu rural sont limit es.Cette etude visait a etendre les recherches existantes men ees dans les zones urbaines du Soudan en effectuant une comparaison avec les zones rurales.M É T H O D E S : Les participants âg es de ‡18 ans (n 5 1 850), vivant dans l' Etat rural de Gezira, ont effectu e une spirom etrie pr e et post-bronchodilatateur et r epondu a un questionnaire.La pr evalence des symptômes respiratoires et des anomalies spirom etriques a et e rapport ee.Des analyses de r egression ont et e utilis ees pour identifier les facteurs de risque des maladies respiratoires chroniques.
The International Journal of Tuberculosis and Lung Disease i

Figure 2
Figure 2 Estimated population prevalence of airway obstruction by age and sex using National Health and Nutrition Examination Survey reference ranges for the Sudanese population in participants completing standard American Thoracic Society spirometry (n ¼ 1,308).A) Prevalence of Stage 1 CAO (post-BD FEV 1 /FVC < LLN); B) prevalence of Stage 2 CAO (post-BD FEV 1 /FVC < LLN and post-BD FEV 1 <80% predicted).LLN ¼ lower limit of normal; CAO ¼ chronic airflow obstruction; BD ¼ bronchodilator; FEV 1 ¼ forced expiratory volume in 1 sec; FVC ¼ forced vital capacity.

Table 1
Characteristics of all participants who completed a full BOLD core questionnaire, including those with and without spirometry results by age groups* Stage 2 CAO using the local reference range (OR 2.07, 95% CI 1.13-3.82).In univariable analysis, participants with higher educational levels were less likely to have Stage 1 CAO (OR 0.50, 95% CI 0.27-0.93),as were those who used firewood for water heating (OR 0.32, 95% CI 0.13-0.77).