DETERMINING THE RELATIONSHIP BETWEEN EARLY LIFE EXPOSURES AND THE DEVELOPMENT OF ASTHMA AND ALLERGIC DISEASES

UNIVERSITY OF GHANA
SCHOOL OF PUBLIC HEALTH

DETERMINING THE RELATIONSHIP BETWEEN EARLY LIFE EXPOSURES AND THE DEVELOPMENT OF ASTHMA AND ALLERGIC DISEASES AMONG CHILDREN VISITING SELECTED PAEDIATRIC CLINICS IN ACCRA.

BY

BETHEL AMEI DZOBO

FEBRUARY, 2014

A RESEARCH PROPOSAL PRESENTED TO THE SCHOOL OF PUBLIC HEALTH

1.0 INTRODUCTION
In the proposed study we seek to examine the relationship between early life exposures and the development of asthma and allergic diseases in children. In addition this study will determine the prevalence of asthma and allergic diseases in childhood in the city of Accra-Ghana. Although there is insufficient data on the prevalence of asthma in Ghana, a few studies conducted in this country have shed light on the disease aetiology and associated risk factors. Different markers for the disease have been used such as clinician- diagnosed asthma, exercise-induced bronchospasm (EIB) as well as questionnaire-derived symptoms of asthma. Factors found to be associated with asthma in Ghana include atopic sensitisation to environmental allergens, inner-city residence and socioeconomic differences. Other implicated factors are family history of asthma, sib-ship position, breast-feeding duration and helminth infections. There has been no research showing the relationship between early life exposures and the development of asthma and allergic diseases in Ghana. There has been no asthma research conducted among the age group 0-7. Therefore this study will focus on this age group and examine the influence that earl life exposures have on the development of asthma and allergic diseases.
According to the series of ISAAC written questionnaires, it has been reported that there has been an increase in the prevalence of asthma and other atopic disorders in the world. As developing countries adopt an industrialized style of living, an increase in asthma prevalence is likely to increase. The development of asthma is determined by complex interactions between genetic and environmental factors.
Despite modern treatment approaches recommending usage of potent anti-inflammatory (corticosteroid) drugs, asthma prevalence, morbidity and mortality in childhood are all increasing worldwide (Von, 2000; Kalyoncu et al., 1994; Aligne et al., 2000 and Gibson et al., 1998). Several studies from different parts of the world that used serial questionnaires surveys are reporting an increased prevalence of asthma, and also that there is wide variability in prevalence between populations (Ones et al., 1997 and Mallol et al., 2000). It appears that differences in asthma prevalence between population groups are due to differential exposure to environmental factors; genetic variation alone could not account for the rise in the prevalence of the disease over a few decades (Aligne et al., 2000). Allergen exposure in early life appears to correlate with sensitization and expression of asthma and atopy. Lifestyle factors, including diet and ambient air quality may be disease modifiers (Shapiro and Stout, 2002).
The aetiology of these conditions remains poorly understood, despite a large volume of clinical and epidemiological research within populations that has been directed at explaining why some individuals and not others develop asthma and allergies (ISAAC, 1998). Numerous surveys have been conducted in various countries, and there is a large body of literature on the subject (Ones et al., 1997). At the moment, there is considerable interest in the international comparison of asthma prevalence, stimulated by the growing evidence of an increment in the frequency (Miralles Lopez et., 1999). The International Study of Asthma and Allergies in Childhood (ISAAC) was the first study carried out worldwide using standardized questionnaires in order to create a reliable global map of childhood allergy. Phase one of the ISAAC developed simple methods for measuring the prevalence of childhood asthma, allergic rhinitis and atopic eczema for international comparisons, suitable for different geographical locations and languages (El-Sharif et al., 2002).
2.0 LITERATURE REVIEW
Asthma is a major chronic disease, and several studies indicate that it is on the rise worldwide (Woolcock and Peat, 1997). A recent report from the Centers for Disease Control and Prevention estimated that the prevalence of self-reported asthma in the United States rose 75 percent from 1980 to 1994, with 17.3 million asthmatics in 1998 (Rappaport and Boodram, 1998). In 2000, asthma accounted for more than 11.2 million medical visits, including 1.8 million to emergency rooms (Cherry and woodwell, 2000). Asthma is characterized by lung inflammation, reversible airflow obstruction, and enhanced airway responsiveness to a variety of environmental stimuli and is a phenotypically heterogeneous disorder with variable disease expression.
Pediatric asthma is a major health problem worldwide and represents a huge burden on families and society. It accounts for a large number of lost school days and may deprive the child of both academic achievement and social interaction (Mutis, 2000). Serial studies suggest that the prevalence of asthma and allergic diseases in children are increasing in industrialized regions, and also there is wide variability in the prevalence between populations (Mallol et al., 2000).
This study will consider perinatal risk factors, including intrauterine exposure and influence of the fetal environment and also lactation and diet, early neonatal exposure, and environmental risk factors in the development of asthma.
2.1 Genetic factors
Although environmental factors are clearly important determinants of asthma, numerous studies have revealed that asthma has a strong genetic component but does not follow monogenic patterns of inheritance (Bleeker et al., 1997). For a long time, asthma has been known to cluster in families, and family studies were the first to suggest that the disease was genetically inherited. More recent family studies found, for example, a 60 percent increased risk of atopy when both parents were affected (Aberg, 1993), and the odds of asthma in a child increased from 3 when one parent was affected to 6 when both were (Litonjua et al., 1998). Maternal asthma appears to be more influential than paternal asthma, particularly in children less than age 5 years (Litonjua et al., 1998). Twin studies were among the earliest to demonstrate the importance of genetic factors in the aetiology of asthma. One of these, conducted in Sweden (Edfors-Lubs, 1971), reported concordance rates for self-reported asthma of 19.0 percent in monozygotic and 4.8 percent in dizygotic twins.
2.2 Perinatal Risk Factors
The greater influence of maternal compared with paternal asthma and atopy on the development of asthma in offspring suggests a role of the perinatal environment. Environmental risk factors occurring during the intrauterine period are often neglected even in studies that follow up children from birth. Factors that influence asthma development through allergic sensitization of the fetus or through alteration of the fetal environment will be considered. In addition, factors occurring in the neonatal period, including diet and lactation, the nursery environment cum environmental risk factors in early childhood will be examined.
2.2.1 Intrauterine risk factors for atopy and asthma development
Despite a large literature on risk factors for the development of asthma in children, almost nothing is known about the role of intrauterine factors (Bjorksten and Kjellman, 1998). Aspects of the fetal environment that have been implicated in asthma development in the offspring include in utero immune responses and inadequate oxygenation and lung maturation.
Atopy is one of the most important risk factors for developing asthma, and nearly all asthmatics have altered immune responses.
2.2.2 Influences of the fetal neonatal environment
An adequate fetal environment is critical to the growth and development of the fetus. Inadequate oxygenation and/or nutrition can lead to disruption of lung maturation. If early or severe enough, irreversible pulmonary abnormalities may persist (Horowitz and Davis, 1997). Maternal smoking during pregnancy is indisputably linked to fetal growth retardation, and passive smoke exposure may have similar effects (Martin and Bracken 1986). Maternal smoking also appears to increase the risk of asthma in the infant (138–144), although it has been difficult to disentangle the intra-uterine risk from the effects of passive neonatal exposure (Lux et al., 2000). Recent work suggests that in utero exposure to maternal smoking without postpartum exposure to environmental tobacco smoke increases the risk of a child having physician-diagnosed asthma, although exposure to environmental tobacco smoke during childhood was related to wheeze but not asthma (Gilliland et al., 2000).
A particularly important indoor air contaminant in the exacerbation of asthma, environmental tobacco smoke, is associated with a wide range of acute and chronic effects. A recent California study reported that maternal smoking primarily increased the risk of early-onset persistent asthma, particularly in children with a history of parental asthma, suggesting the importance of further defining the genotype of at-risk children (London et al., 2001).
According to Melia et al., 1985, use of gas stoves and nitrogen dioxide exposure have been related to increased infant respiratory symptoms.

2.3 Microbial exposure and antibiotic use
Exposure to antibiotics early in life increases the risk of developing allergic disease (Wickens et al., 1999; Alm et al., 1999). Because the immune system develops in utero, factors that modify microbial exposure at this time may have a long-term impact on the risk of developing allergic disease, but research in this area has been limited. Antibiotics can cross the placenta and enter the fetal circulation (Joint Formulary Committee, 2001), and there are data that suggests that exposure to antibiotics early in life may increase the child 's risk of developing allergic disease (Droste et al., 2000).
3.0 JUSTIFICATION There has been no research in Ghana examining the relationship between early life exposures and the development of asthma allergic diseases. Due to the difficulty in diagnosing asthma in children, the knowledge of perinatal exposures and neonatal exposures which exacerbate asthma and its related conditions will help curb the development these conditions. The outcome of this study may be the beginning of the awareness of the needed education on asthma and allergic diseases prevention in Ghana.
4.0 STATEMENT OF THE PROBLEM Most studies have focused on asthma among individuals 5 to 16 years and therefore there is the need to conduct research into asthma and allergic diseases among individuals between the ages of 0 and 7. Paediatric asthma is a major health problem worldwide and represents a huge burden on families and society. It accounts for a large number of lost school days and may deprive the child of both academic achievement and social interaction (Mutis, 2000).
As developing countries adopt an industrialized style of living, an increase in asthma prevalence is likely to increase. Asthma has a considerably greater impact on Hispanics and African Americans than on Whites in the United States (Mannino et al., 1998). Compared with Whites, African-American children have higher (1.1–1.7 times) asthma prevalence rates (Mannino et al., 1998), 2–3.5 times the hospital admission rate for asthma, and approximately 2–5 times the asthma mortality rate. There is insufficient information on Asthma in Ghana and with the global rise in the prevalence of the disease, research into this area is very necessary.
5.0 OBJECTIVES OF THE STUDY The principal objective of this study is to determine the relationship between early life exposures and the development of asthma and allergic diseases in Ghanaian children in the city of Accra.
This study in detail seeks to:
1- Determine the relationship between early life exposures and the development of asthma and allergic conditions
2- Find out the prevalence of asthma among children who visit selected paediatric clinics in Accra. 5.1 Limitations of the study This study will use the quantitative self-report which will involve the use of written questionnaires. There are potential validity problems associated with the use of written questionnaires in that some reports may contain errors due to deception, inaccurate recall or the unavailability of the information to conscious processing.
6.0 HYPOTHESIS Early life exposures increase the risk of developing asthma and allergic diseases.
7.0 METHOD
7.1 STUDY SITE
Accra is the capital city and largest city of Ghana, with an estimated urban population of 2.269 million as of 2012. It is also the capital of the Greater Accra Region. Accra is furthermore the anchor of a larger metropolitan area, the Greater Accra Metropolitan Area (GAMA), which is inhabited by about 4 million people, making it the second largest metropolitan conglomeration in Ghana by population, and the eleventh-largest metropolitan area in Africa. The city of Accra has a total area of 200 square kilometres (77 sq mi), and is the anchor city of the Greater Accra Metropolitan Area (GAMA). The intersection of the Lafa stream and Mallam junction serves as the western border of the city, the Great Hall of the University of Ghana forms Accra 's northern border, while the Nautical College forms the eastern border and The Gulf of Guinea forms the southern border.
The gross density of population for the Accra Metropolitan Area in 2000 was 10.03 persons per hectare, compared to 6.23 per hectare in 1970. The highest densities were recorded in the Accra Metropolitan Assembly, with an overall average of 69.3 persons per hectare.
Accra is located in the Dahomey Gap, where the coast runs parallel to the prevailing moist monsoonal winds, Accra features a tropical savanna climate that borders on a semi-arid climate. The average annual rainfall is about 730 mm, which falls primarily during Ghana 's two rainy seasons. There is very little variation in temperature throughout the year. The mean monthly temperature ranges from 24.7 °C (76.5 °F) in August (the coolest) to 28 °C (82.4 °F) in March (the hottest), with an annual average of 26.8 °C (80.2 °F).
7.2 SOURCE OF DATA This study will be conducted using the parent respondent questionnaire that is the standard written questionnaire designed for the ISAAC (Asher et al., 1995). The environmental questionnaire will also be administered. In addition some factors that influence the asthma and atopic status in childhood will be assessed.
This study will determine the relationship between early life exposures and the development of asthma and allergic diseases in 0-7 year old children. A total of 500 mothers will be interviewed. The prevalence of asthma and allergic diseases in this age group will also be assessed. The ISAAC questionnaires will be completed by the principal investigator with the help of doctors interviewing random selected parents who visit paediatric clinics in Accra.
7.3 ANALYSES
Statistical analyses will be performed with the SPSS for Windows statistic program and Epi Info 6.0 program. Statistical significance of differences will be assessed by the chi-square test, and odds ratios (ORs) will be calculated to evaluate the various independent variables. The frequencies procedure will be used for cross tabulation and odds ratios.
7.4 ETHICAL CONSIDERATION
This project topic will seek approval from the University of Ghana Institutional Review Board. Consent will be sought from the parents who will be interviewed be the questionnaires will be administered.
8.0 IMPORTANCE AND CONTRIBUTION OF THE STUDY There is insufficient information on Asthma in Ghana, this study will add to the pool of knowledge on asthma in Ghana. The outcome of this policy will enable the Ministry of Health and the Ghana Health Service to include education on the impact of early life exposures on the development of asthma and allergic diseases at Antenatal Clinics and Child Welfare Clinics around the country.
The awareness of the relationship between early life exposures and the development of asthma can help reduce the precedented increase in the burden of asthma both on the individual and the Ghanaian economy. Understanding the genetic and environmental factors that regulate the maturation of the immune response during early life will greatly enhance the development of strategies for the primary and secondary prevention of asthma (Martinez, 1999). In line with Ghana’s current goal to achieve universal health coverage under the National Health insurance Scheme, this will help prevent future asthmatic and allergy cases hence reducing the pressure on hospital facilities.

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