Summary

Wheezing in infants and young children is a common problem that pediatricians face, and it presents specific diagnostic difficulties. The prevalence may be as high as 34%,[1] which is likely due to the pathophysiologic properties that predispose infantile lungs to wheeze. Infants’ bronchioles (compared to older children and adults) have decreased smooth muscle content, hyperplasia of mucus glands, and a smaller radius, which in turn increases resistance considerably.[2] These factors increase risk of obstruction and may manifest as cough, wheeze, chest tightness, shortness of breath, or tachypnea. Wheezing specific to this age group is most commonly due to respiratory viruses and early asthma, which may be difficult to distinguish initially, complicating management. The following discussion will focus on the epidemiology of wheezing in this age group, the distinction between typical and atypical wheezing, and review of the diagnosis and management of asthma in the preschool-aged child.

Educational objectives

At the conclusion of this activity, participants will be able to:

• List the criteria of the Asthma Predictive Index
• Identify the clinical features of typical versus atypical wheezing in this age group
• Determine the most appropriate treatment for the atopic wheezing infant

CME credit

This is an article from The Child's Doctor, Spring 2005 issue. You may take the quiz for learning purposes, but credits are no longer valid.

Author disclosures

Dr. Kim has no industry relationships to disclose and does not refer to products that are still investigational or not labeled for the use in discussion.

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Epidemiology

Wheezing is very uncommon during the first 2 months of life. After 2 months of age, the incidence of first-time wheezing increases markedly, peaking between 2 and 5 months of age. Most wheezing, primary or recurrent, during the first 3 years of life is associated with viral respiratory infections, such as respiratory syncytial virus (RSV). Typically, the infant will have the first wheezing attack during a winter epidemic within the first 6 months of life. Infants with an atopic background may wheeze or cough at any age although not necessarily related to RSV season. Recurrent viral-induced wheezers will be otherwise well between illnesses. Physical examination is also generally normal in these children between attacks.

Recurrent wheezing in infants and preschool children may also be the harbinger of asthma. Initially, however, it may be difficult to distinguish which children will develop a chronic disease such as asthma. A landmark birth cohort study called the Tuscon Children's Respiratory Study (TCRS) [3] set out to determine the causes of recurrent wheezing. Early wheezing, it turns out, is not a single entity, but rather embodies at least 3 different phenotypes: transient wheezers, non-atopic persistent wheezers, and atopic wheezers.

Transient early wheezing

Infants and young children with transient early wheezing, who make up 60% of all wheezers under 3 years of age, present with recurrent wheezing during the first year of life, but the wheezing goes into remission by 3 to 6 years of age. These children are not more likely to be atopic or have an atopic background when compared to children who do not wheeze during the first 6 years of life.[1] Children in this group tend to have symptoms only during viral infections although the episodes may be quite severe. Therefore, the severity of wheezing episodes in the first years of life does not necessarily portend asthma. Children in this group are more likely to have diminished lung function at birth and have mothers who smoke. Other associations with transient early wheezing include day care attendance or living with older siblings at home, male sex, and bottle-feeding. The protective effect of breast-feeding, however, disappears with age and is not observed with persistent wheezing.

Non-atopic persistent wheezing

About 40% of all children who wheeze during the first 3 years of life continue to wheeze by 6 years of age. About half of these persistent wheezers are sensitized to environmental aeroallergens at 6 years of age. The other half (20%) are not atopic. Although having a lower respiratory tract infection with RSV increases a child's propensity to wheeze by 3 to 5 times at 6 years of age, RSV does not increase the likelihood of atopy. These children are probably more likely to wheeze with viral insults. This increased susceptibility may be attributable to an intrinsic abnormality in airway tone.

Atopic wheezing

Atopic asthma can start at any age, but most children develop their first symptoms before 6 years of age. If symptoms of asthma start before 3 years of age or allergic sensitization develops in early childhood, there is an increased risk for severe disease and decreased lung function. Wheezing usually starts later in this group than in other young wheezers, more often beyond the first year of life. Atopic wheezers are more likely to have a family history of asthma or a personal history of atopic dermatitis. This group also has a higher prevalence of peripheral eosinophilia ( >/= 4% of white blood cells). Skin testing and serologic specific-IgE testing to local environmental aeroallergens, however, are not predictive of future sensitization in this age group, although most of these children will eventually be sensitized later in life. [4] Nevertheless, the few infants in whom specific-IgE against aeroallergens is detectable (either by skin testing or in serum) are expected to wheeze past early childhood.

Asthma Predictive Index

Currently, there are no genetic markers to distinguish the atopic wheezers from other phenotypes. The TCRS, however, developed the Asthma Predictive Index (API). [5]To be positive for this index, children need to have reports of recurrent episodes of wheezing during the previous year and either 1 major criterion or 2 minor criteria. The major criteria are (1) physician-diagnosed atopic dermatitis and (2) physician-diagnosed parental asthma. The minor criteria are defined as (1) peripheral blood eosinophilia >/= 4%, (2) wheezing apart from colds, and (3) physician-diagnosed allergic rhinitis. More than 75% of children with a positive index had active asthma at least once between 6 and 13 years of age, whereas 68% of those with a negative index never had symptoms within the same age range. Notably, this index had an extremely high specificity (97%), but a low sensitivity (15%). Of note, "recurrent episodes of wheezing" has been defined by the National Asthma Education and Prevention Program Expert Panel as more than 3 episodes of wheezing in the past year that lasted more than 1 day and affected sleep. [6]

Clinical features of typical wheezing

Typical wheezing infants usually have their first episodes within the first 2 years of life. Some of these infants will have an atopic background, while others will only manifest wheezing during respiratory viral infections. None will have an underlying disease. Wheezing indicative of asthma may be triggered by "exercise" (ie, running, climbing stairs, jumping for the preschool child) as well as vigorous crying or laughing. Nocturnal symptoms may be prominent. An important feature of the typical wheezing infants is that they are symptom-free for long intervals. If the wheeze is continuous, this would indicate a potentially serious diagnosis such as cystic fibrosis (CF), a congenital anomaly, or inhaled foreign body.

Plain chest radiography (postero-anterior and lateral) is indicated in any infant or preschool child with recurrent wheezing and should be inspected by a pediatric radiologist. Generally, findings are normal or consist of symmetrical bilateral hyperinflation. In some cases, if wheezing recurs often and is relatively difficult to control, a sweat test is indicated given the variability in the CF phenotype.

Clinical features of atypical wheezing

Atypical wheezers' initial symptoms may present at any time, but cannot be attributed to atopy or a virus. Gastroesophageal reflux (GER) and aspiration, in particular, are not uncommon causes of wheezing, especially during the first year of life, in otherwise healthy infants. These children may present with excessive vomiting or "spitting up," coughing, or choking during feeds. On the other hand, they may present only with wheezing without any other clues to the underlying diagnosis. Therefore, "silent" aspiration must be considered in a child with troublesome wheezing. Of note, wheezing due to milk allergy is very uncommon in this age group.

The following historical features should alert pediatricians to the possibility of an atypical problem: (1) initial symptoms at birth or shortly thereafter, (2) continuous wheezing without symptom-free intervals (weeks to months), (3) failure to thrive, (4) failure to respond to anti-asthmatic medications.[7] The differential diagnosis includes aspiration either after reflux or due to an abnormal swallow mechanism, CF, foreign body aspiration, primary ciliary dyskinesia, or congenital abnormalities of the heart or airway.[8] Evaluation of these infants may include chest radiography, sweat chloride testing, videofluoroscopic swallow study, barium swallow, and an upper gastrointestinal radiographic examination with barium.

Management of wheezing

Due to the difficulty in distinguishing early asthmatics from the recurrent viral wheezers in this age group, the approach to treatment is similar initially. Primary wheezing episodes are most often treated with an inhaled bronchodilator, such as albuterol. Proper administration is vitally important. Mask delivery with jet nebulizer or metered dose inhaler (MDI)/spacer is crucial in this age group for maximal lung deposition. "Blow by" or use of mouthpieces are ineffective and wasteful of prescription medications. The second episode may require administration of a short burst of oral corticosteroids, such as prednisolone 1-2 mg/kg/day for 5 days. Response to these medications should be documented.

A third attack would warrant a trial of controller medication. For the infant who is atopic or has a positive API, however, physicians may consider initiating therapy with the second occurrence.[7] Inhaled corticosteroids (ICS) are first-line therapy.[9-11] Appropriate starting dose would be fluticasone propionate (Flovent) 176-220 mcg daily or budesonide (Pulmicort respules) 250-500 mcg daily. If wheezing recurs or if daily symptoms are difficult to control, ICS treatment can be doubled or another agent, such as a leukotriene-receptor antagonist (montelukast [Singulair]), can be added.

Patients who are recalcitrant to medical therapy must be assessed further by a physician to consider ineffective delivery of inhaled medication, alternative diagnoses, or failed response to medical therapy. Poor inhalation technique can also result in unnecessary systemic absorption of the drug (via oral deposition). Side effects are uncommon and final adult height has shown to be normal in children treated with ICS.[12] Note that poorly controlled asthma has an adverse effect on growth.[13]

Conclusion

Wheezing in infants and preschoolers is a common problem most often attributable to viral respiratory infections and early asthma. The difficulty lies in distinguishing the 2 groups at this early age. There are historical and serologic markers, however imprecise, that can assist the clinician in assessing these patients. Identifying the atypical wheezer is also crucial so that proper management of CF or GER, for example, can be initiated promptly with minimal pulmonary consequence. This is an exciting area of research where much attention is being focused. Results from studies in progress will hopefully fine-tune current management practices for wheezing in infants and preschool children.

References

1. Martinez FD, et al. Asthma and wheezing in the first six years of life. NEJM 1995;332(3):133-138.
2. Krawiec M, Lemanske RF Jr. Wheezing in infants. In: Behrman RE, Kliegman RM, Jenson HB, eds. Nelson Textbook of Pediatrics. 17 th ed. Philadelphia : Saunders; 2004:1417-1419.
3. Taussig LM, et al. Tuscon Children's Respiratory Study: 1980 to present. JACI 2003;111:661-675.
4. Staat MA. Respiratory syncytial virus infections in children. Semin Resp Inf 2002;17:15-20.
5. Castro-Rodriguez JA, et al. A clinical index to define risk of asthma in young children with recurrent wheezing. Am J Respir Crit Care Med 2000;162:1403-1406.
6. NAEPP Expert Panel Report. Guidelines for the diagnosis and management of asthma – Update on selected topics. June 2002. NIH Publication No. 02-5075.
7. Martinez FD, Godfrey S. Wheezing Disorders in the Preschool Child. 1 st ed. London : Martin Dunitz; 2003.
8. Strunk RC. Defining asthma in the preschool-aged child. Pediatrics 2002;109:357-361.
9. de Blic J, Delacourt C, Le Bourgeois M, et al. Efficacy of nebulized budesonide in treatment of severe infantile asthma: A double-blind study. J Allergy Clin Immunol 1996;98:14-20.
10. Nielsen KG, Bisgaard H. The effect of inhaled budesonide on symptoms, lung function, and cold air and methacholine responsiveness in 2- to 5-year-old asthmatic children. Am J Resp Crit Care Med 2000;162:1500-1506.
11. Bisgaard H, Gillies J, Groenewald M, Maden C. The effect of inhaled fluticasone propionate in the treatment of young asthmatic children: A dose comparison study. Am J Resp Crit Care Med 1999;160:126-131.
12. Agertoft L, Pedersen S. Effect of long-term treatment of inhaled budesonide on adult height in children with asthma. N Engl J Med 2000;343:1064-1069.
13. Ninan TK, Russell G. Asthma, inhaled corticosteroid treatment and growth. Arch Dis Child 1992;67:703-705.