Childhood Wheezing

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• Asthma is defined (1) according to the United States National Heart, Lung and Blood Institute as a chronic inflammatory disorder of the airways in which many cells play a role, in particular mast cells and eosinophils. In susceptible individuals, this inflammation causes symptoms that are usually associated with widespread but variable airflow obstruction that is often reversible, either spontaneously or with treatment, and that causes an associated increase in airway responsiveness to a variety of stimuli.
   
• Up to 30% of all 3 year old children and 50% of children up to 6 years have had wheezing (2).
   
• 60% of early wheezers became wheeze-free ("transient wheezers") after the age of three years and did not develop asthma, but had lower levels of lung function prior to the start of wheezing illness (2).
   
• Most episodes of wheezing occurring in early life are due to viral infections and are predominantly associated with respiratory syncytial virus (RSV) (3).
   
• Lung function in early childhood appears to deteriorate from previously normal levels but does not deteriorate further from the age of 6 years (2) up to the age of 35 years, except in those with moderately severe asthma (4).
   
• With increasing age, particularly beyond 3 years, the diagnosis of asthma becomes progressively more definitive, and beyond 6 years of age, the NHLBI (1) definition can be accepted (5).
   
• Childhood asthma begins in early childhood, with 80% of children experiencing their first episode of wheezing before the age of 3 years (6).
   
• Studies in twins have suggested that in more than half of the cases, susceptibility to childhood asthma is genetic (7).
   
• There is now overwhelming evidence that allergy is a very important prerequisite for the development of asthma, and at least 75-90% of childhood asthmatics beyond 4-5 years of age have evidence of allergy (5).
   
• Early-onset atopy is a risk factor for the persistence of bronchial hyperresponsiveness and symptoms of asthma (8).
   
• High serum IgE level at birth appears to be associated with an increased risk of developing allergic conditions such as atopic dermatitis in early life (9), but it does not appear to be a risk factor for developing persistent wheezing (2, 9).
   
• Serum IgE level at 9 months of age is a significant predictor of persistent wheezing (2) beyond early life.
   
• Specific IgE levels in infancy, particularly to house dust mite (10, 11) and cat dander (11), predict persistent wheezing in childhood.
   
• 80.8% of children below 5 years of age with three or more episodes of wheezing had raised levels of total IgE, and in children up to 3 years of age and allergen specific, IgE was positive in 83.9% of the cases (12).
   
• Sensitization to both indoor and outdoor aeroallergens occurring early in life is strongly associated with the risk of developing asthma-like symptoms (8,10,13), whereas sensitization to similar allergens later in life has less bearing on asthma (8).
   
• There is a relationship between allergen exposure and sensitization (10) and increase in asthma symptoms in children (10).
   
• Children with early onset of atopic dermatitis (< 2 years of age) had a greater probability of developing respiratory symptoms compared with children with later onset (14, 15).
   
• Infants who subsequently develop asthma symptoms are more likely than other children to be sensitized to foods and to have had RSV-infection (16).
   
• About 50% of preschool children with eczema also had asthma, with the highest prevalence of asthma in children with onset of eczema before 3 months of age (17).

References:

1. Global Strategy for Asthma Management and Prevention. NHLBI/WHO workshop report. Publication no. 95-3659. National Institutes of Health, Bethesda, MD, 1995.
2. Martinez FD, Wright AL, Taussig LM, Holberg CJ, Halonen M, Morgan WJ et al. Asthma and wheezing in the first years of life. The Group Health Medical Associates. N Engl J Med 1995;332:133-8.
3. Wright AL, Taussig LM, Ray CG, Harrison HR, Holberg CJ. The Tucson Children´s Respiratory Study. II. Lower respiratory tract illnesses in the first year of life. Am J Epidemiol 1989;129:1232-46.
4. Oswal H, Phelan P, Lanigan A, Hibbert M, Carlin JB, Bowes G et al. Childhood asthma and lung function in mid-adult life. Pediatr Pulmonol 1997;23:14-20.
5. Warner JO, Naspitz CK, Cropp GJA. Third international pediatric consensus statement on the management of childhood asthma. Pediatr Pulmonol 1998;25:1-17.
6. Wright AL, Taussig LM. Lessons from long-term cohort studies. Childhood asthma. Eur Respir J Suppl 1998;27:17s-22s.
7. Duffy DL, Martin NG, Battistutta D, Hopper JL, Mathews JD. Genetics of asthma and hay fever in Australian twins. Am Rev Respir Dis 1990;142:1351-8.
8. Peat JK, Salome CM, Woolcock AJ. Longitudinal changes in atopy during a 4-year period: relation to bronchial hyperresponsiveness and respiratory symptoms in a population sample of Australian schoolchildren. J Allergy Clin Immunol 1990;85:65-74.
9. Halonen M, Stern D, Taussig LM, Wright A, Ray CG, Martinez FD. The predictive relationship between serum IgE levels at birth and subsequent incidences of lower respiratory illnesses and eczema in infants. Am Rev Respir Dis 1992;146:866-70.
10. Sporik R, Holgate ST, Platts-Mills TA, Cogswell JJ. Exposure to house-dust mite allergen (Der p 1) and the development of asthma in childhood. A prospective study. N Engl J Med 1990;323:502-7.
11. Delacourt C, Labbe D, Vassault A, Brunet-Langot D, de Blic J, Scheinmann P. Sensitization to inhalant allergens in wheezing infants is predictive of the development of infantile asthma. Allergy 1994;49:843-7.
12. Trindade JC. The importance of diagnosis of allergy in early wheezing. Pediatr Allergy Immunol 1998;9:23-9.
13. Henderson FW, Stewart PW, Burchinal MR, Voter KZ, Strope GL, Ivins SS et al. Respiratory allergy and the relationship between early childhood lower respiratory illness and subsequent lung function. Am Rev Respir Dis 1992;145:283-90.
14. Kjellman B, Hattevig G. Allergy in early and late onset of atopic dermatitis. Acta Paediatr 1994;83:229-31.
15. Åberg N, Engström I. Natural history of allergic diseases in children. Acta Paediatr Scand 1990;79:206-11.
16. Sigurs N, Bjarnason R, Sigurbergsson F, Kjellman B, Björksten B. Asthma and immunoglobulin E antibodies after respiratory syncytial virus bronchiolitis: a prospective study with matched controls. Pediatrics 1995;95:500-5.
17. Pasternack D. The prediction of asthma in infantile eczema: a statistical approach. J Paediatr 1965;66:164-5.

• References