0031-3955/92 $0.00
ASTHMA
+ .20
RISK FACTORS FOR DEVELOPING WHEEZING AND ASTHMA IN CHILDHOOD Wayne
J.
Morgan, MO, and Fernando O. Martinez, MO
Wheezing respiratory illness and asthma are responsible for a significant proportion of both acute and chronic illness in childhood. 7 Affecting approximately 5% to 10% of children/ asthma is of growing concern because of an apparent increase in mortality and morbidity.13 The risk factors associated with the development of wheezing illness and asthma have therefore been the focus of much investigation in the last two decades. The study of asthma risk factors is complicated by their multiplicity and by the difficulty of defining the outcome variables. Asthma is a heterogeneous condition that varies substantially in presentation, severity, and clinical course among individuals. The pattern and severity of an individual's asthma also may wax and wane over his or her life span. To further cloud the picture, infants and toddlers develop a high rate of wheezing lower respiratory tract illness93 triggered by viral infection. The investigation of risk factors for asthma is necessarily confused by these early wheezing illnesses, which resemble clinical asthma, but may not bear any direct relationship to its ultimate development. Most investigators would agree that asthma is a condition characterized by acute attacks of shortness of breath and wheezing associated with at least partially reversible airway obstruction. 7 This airway obstruction is believed to be caused by allergic inflammation leading to mucosal infiltration and edema with mucus hypersecretion combined From the University of Arizona; Department of Pediatrics, Arizona Respiratory Sciences Center; Steele Memorial Children's Research Center; and Arizona Health Sciences Center, Tucson, Arizona
PEDIATRIC CLINICS OF NORTH AMERICA VOLUME 39 • NUMBER 6 • DECEMBER 1992
1185
1186
MORGAN & MARTINEZ
with either primary or secondary smooth muscle hypertrophy and bronchial hyperreactivity. Although cellular inflammation, edema, and mucus production are present in infantile wheezing lower respiratory tract illness,31 the role of smooth muscle response remains unclear. Recent evidence l5, 51, 85 suggests that it may be most rewarding to view infantile wheezing lower respiratory tract illness and asthma as related but separate conditions. Although immune response, viral infection, passive smoking, and lung function are risk factors for both of these conditions, their relative importance differs between each condition. The risk for wheezing lower respiratory tract illness in infancy and the toddler years appears to be closely related to initial lung function 51 and chance of exposure to viral infection. 40, 91 In contrast, asthma in older children is closely associated with the development of allergy. Further, although many infants and toddlers wheeze,93 most do not go on to develop asthma. 81 This article first reviews risk factors for wheezing in infancy and the toddler years. The possibility that early viral-related wheezing illness predisposes to later asthma and chronic lung dysfunction is then discussed. With this background, risk factors for the development of persistent asthma in later childhood are explored, with particular attention to the role of allergy in the pathogenesis of chronic airway inflammation and asthma. WHEEZING IN INFANCY
Wheeze-associated lower respiratory tract illness occurs in 20% of all children and accounts for more than 60% of all lower respiratory tract illness. 93 Wheezing lower respiratory tract illness is of concern not only because of its acute morbidity but also because it has been suggested that children and adults with respiratory problems in early childhood may have suffered irreversible airway damage leading to long-term lung dysfunction and a higher risk for clinical respiratory disease, including asthma. 70 Risk Factors for Wheezing in Infancy and the Toddler Years
Both exogenous factors deriving from the child's life experience . and endogenous (congenital) factors may increase the risk of wheezing in infancy (Table 1). Exogenous Risk Factors
Because most wheezing lower respiratory tract illnesses in infancy are viral associated, social factors playa leading role in their development, and risk of exposure to viral contagion is a major determinant of
RISK FACTORS FOR DEVELOPING WHEEZING AND ASTHMA IN CHILDHOOD
1187
Table 1. EXOGENOUS AND ENDOGENOUS RISK FACTORS FOR WHEEZING
ASTHMA
+ .20
RISK FACTORS FOR DEVELOPING WHEEZING AND ASTHMA IN CHILDHOOD Wayne
J.
Morgan, MO, and Fernando O. Martinez, MO
Wheezing respiratory illness and asthma are responsible for a significant proportion of both acute and chronic illness in childhood. 7 Affecting approximately 5% to 10% of children/ asthma is of growing concern because of an apparent increase in mortality and morbidity.13 The risk factors associated with the development of wheezing illness and asthma have therefore been the focus of much investigation in the last two decades. The study of asthma risk factors is complicated by their multiplicity and by the difficulty of defining the outcome variables. Asthma is a heterogeneous condition that varies substantially in presentation, severity, and clinical course among individuals. The pattern and severity of an individual's asthma also may wax and wane over his or her life span. To further cloud the picture, infants and toddlers develop a high rate of wheezing lower respiratory tract illness93 triggered by viral infection. The investigation of risk factors for asthma is necessarily confused by these early wheezing illnesses, which resemble clinical asthma, but may not bear any direct relationship to its ultimate development. Most investigators would agree that asthma is a condition characterized by acute attacks of shortness of breath and wheezing associated with at least partially reversible airway obstruction. 7 This airway obstruction is believed to be caused by allergic inflammation leading to mucosal infiltration and edema with mucus hypersecretion combined From the University of Arizona; Department of Pediatrics, Arizona Respiratory Sciences Center; Steele Memorial Children's Research Center; and Arizona Health Sciences Center, Tucson, Arizona
PEDIATRIC CLINICS OF NORTH AMERICA VOLUME 39 • NUMBER 6 • DECEMBER 1992
1185
1186
MORGAN & MARTINEZ
with either primary or secondary smooth muscle hypertrophy and bronchial hyperreactivity. Although cellular inflammation, edema, and mucus production are present in infantile wheezing lower respiratory tract illness,31 the role of smooth muscle response remains unclear. Recent evidence l5, 51, 85 suggests that it may be most rewarding to view infantile wheezing lower respiratory tract illness and asthma as related but separate conditions. Although immune response, viral infection, passive smoking, and lung function are risk factors for both of these conditions, their relative importance differs between each condition. The risk for wheezing lower respiratory tract illness in infancy and the toddler years appears to be closely related to initial lung function 51 and chance of exposure to viral infection. 40, 91 In contrast, asthma in older children is closely associated with the development of allergy. Further, although many infants and toddlers wheeze,93 most do not go on to develop asthma. 81 This article first reviews risk factors for wheezing in infancy and the toddler years. The possibility that early viral-related wheezing illness predisposes to later asthma and chronic lung dysfunction is then discussed. With this background, risk factors for the development of persistent asthma in later childhood are explored, with particular attention to the role of allergy in the pathogenesis of chronic airway inflammation and asthma. WHEEZING IN INFANCY
Wheeze-associated lower respiratory tract illness occurs in 20% of all children and accounts for more than 60% of all lower respiratory tract illness. 93 Wheezing lower respiratory tract illness is of concern not only because of its acute morbidity but also because it has been suggested that children and adults with respiratory problems in early childhood may have suffered irreversible airway damage leading to long-term lung dysfunction and a higher risk for clinical respiratory disease, including asthma. 70 Risk Factors for Wheezing in Infancy and the Toddler Years
Both exogenous factors deriving from the child's life experience . and endogenous (congenital) factors may increase the risk of wheezing in infancy (Table 1). Exogenous Risk Factors
Because most wheezing lower respiratory tract illnesses in infancy are viral associated, social factors playa leading role in their development, and risk of exposure to viral contagion is a major determinant of
RISK FACTORS FOR DEVELOPING WHEEZING AND ASTHMA IN CHILDHOOD
1187
Table 1. EXOGENOUS AND ENDOGENOUS RISK FACTORS FOR WHEEZING
