Increased Prevalence of Asthma Symptoms in Nigerian Children with Sickle Cell Disease Compared to Children without Sickle Cell Disease
Authors: Galadanci Najibah Aliyu , Liang Wayne , Aliyu Muktar , Jibir Binta Wudil , Karaye Ibraheem , Inusa Baba PD , Vermund Sten , DeBaun Michael R. 
Published: October 2019

Abstract
Abstract 4760

Background:
Nigeria has the largest population of children and adults with sickle cell disease (SCD) in the world. Approximately 150,000 children are born with SCD each year (incident cases) in Nigeria, compared to a total of approximately 100,000 children and adults living with SCD in the United States (prevalent cases). Pulmonary complications, including asthma and asthma-like symptoms are leading causes of morbidity and mortality in SCD. However, the natural history, risk factors and biological basis of asthma and SCD-associated asthma-like symptoms in SCD are poorly defined. The primary aim of this study is to determine the prevalence of asthma and asthma-like symptoms among children with and without SCD in Nigeria. In a 1:1 case-control study design, we tested the hypothesis that children with SCD would have a higher rate of asthma-like symptoms when compared to children without SCD.

Methods:
We enrolled 250 cases with SCD and controls, children without SCD, from patients presenting for routine medical care at the Murtala Mohammed Specialist Hospital (MMSH) in Kano, Nigeria over a 4-month period (12/2011 to 04/2012). A structured questionnaire was employed to capture participants' demographic information, medical history (including history of asthma symptoms and allergies), environmental factors (e.g., cooking, presence of animals in the home) and parental behavior (e.g., smoking). Asthma symptoms were identified based on responses to questions adapted from the American Thoracic Society Division of Lung Disease (ATS-DLD-78) questionnaire. Chi-square test of association was used for categorical variables; Wilcoxon rank-sum tests and Kruskal-Wallis U test were used for continuous and ordinal variables.

Results:
No differences in sex, ethnicity, or place of residence were noted between cases and controls. The average age for the cases was 5.7 years and for controls was 2.8 years (P<0.01). In both cases and controls, affirmative responses to ATS-DLD questions were unrelated to age. Cases were more likely than controls to report a history of cough that worsens with a cold (28.0% vs. 16.8%, P<0.01), cough without a cold (16.0% vs. 9.6%, P=0.03), chest congestion that worsens with a cold (8.0% vs. 1.2%, P<0.01), wheezing that worsens with a cold (19.6% vs. 6.4%, P<0.01), and wheezing without a cold (5.6% vs. 1.6%, P=0.02). Participants with SCD were more likely to have eczema (4.4% vs. 0.4%, P<0.01). Surprisingly, despite the high prevalence of asthma-like symptoms in cases when compared to controls, the prevalence of physician diagnosis of asthma was low in both groups. Only two children were reported as having asthma among cases, compared to none in the control group. No participant reported a history of wheezing attacks with shortness of breath. No difference between cases and controls existed in the distribution of risk factors for asthma, namely: mode of delivery, gestational age at delivery, parental history of asthma, maternal smoking during pregnancy, and exposure to smoking as a child. No association was observed between respiratory symptoms in either group and age, household income, household size, mode of delivery, gestational age, parental history of asthma, or use of firewood/charcoal. Subgroup analysis was performed on participants 4 years of age and older (163 cases and 96 controls). No substantial differences in the results were noted when compared to the entire cohort of 250 cases and controls (results not shown).

Conclusions/Recommendation:
Nigerian children with SCD have a much higher prevalence of asthma-like symptoms when compared to controls. Despite asthma symptoms being common, a diagnosis of asthma is rare in both cases and controls, suggesting under-ascertainment of an asthma diagnosis. Future work in low income countries directed towards improving co-morbid respiratory disease in children with SCD should focus on the presence of asthma-like symptoms and not a physician diagnosis of asthma. Better understanding of the biological basis for why children with SCD have a higher rate of asthma-like symptoms and atopy may lead to targeted therapy.

Disclosures:
No relevant conflicts of interest to declare.