Asthma is the most common chronic disease of childhood, affecting an estimated 16% of African American children and 7% of white children in the United States.1 Asthma exacerbations are the number one reason for admission to children's hospitals outside the neonatal period (aside from acute bronchiolitis), although the hospitalization rate for asthma has been decreasing in recent years.2 Asthma care costs an estimated $81.9 billion per year in the US alone.3 Although decreasing in recent years, mortality from asthma, which should be preventable, still occurs.4 To improve morbidity and mortality in children with asthma, several organizations have published guidelines to aid in identifying and managing childhood asthma.5–7
Making the Diagnosis
The diagnosis of asthma can be made on clinical grounds based on a history of recurrent cough, wheezing, and shortness of breath that is triggered by a variety of stimuli that usually do not irritate people without asthma. Triggers can be categorized as viral infections, exercise, allergens, irritants, and emotions (Table 1). A positive response to a short-acting bronchodilator such as albuterol or a short course of oral steroids is also suggestive of asthma. Other supporting evidence is a positive atopic family history, particularly with parental asthma, or a personal history of eczema, seasonal rhinitis, or food allergen sensitivity. Many attempts have been made to find which characteristics of wheezing in young children predict the presence of asthma later in childhood. The asthma predictive index and its various versions8–10 are strong predictors of asthma in younger children with recurrent wheezing, although its greatest strength may be the negative predictive value (Table 2). These predictive indices are commonly used in research studies involving young children with recurrent wheeze and are most likely applicable in clinical practice as well.11 For infants and toddlers with multiple episodes of wheezing (eg, three or more per year) who have a positive predictive index, therapy with inhaled corticosteroids may help reduce their symptoms, exacerbations, rescue medication use, and improve their quality of life.12
Common Triggers for Symptoms of Asthma in Children
Predictors of Subsequent Asthma in Young Children with Recurrent Wheezing
Examination of the child with asthma in the absence of an active exacerbation is usually normal. Chest auscultation during an exacerbation may reveal diminished intensity breath sounds, a prolonged expiratory phase, and polyphonic high-pitched wheezing heard diffusely throughout the chest. If the exacerbation is severe, the chest may be silent with poor intensity breath sounds due to low flow rates; this is an ominous sign. If the wheezing is isolated to a single lobe, an alternative diagnosis such as foreign body aspiration should be considered. Other findings on examination supportive of atopy might include nasal congestion with edematous turbinates and pale dusky mucosa, clear rhinorrhea, bluish discoloration under the eyes (“allergic shiners”), and eczema. If digital clubbing is present, a diagnosis other than asthma should be pursued such as suppurative lung disease, bronchiectasis, or cystic fibrosis.
The pathophysiologic hallmarks of asthma include airway inflammation, hyper-reactive airways, and airway remodeling. The airway's hyper-reactivity or reversible airflow obstruction can be documented in a variety of ways. Pulmonary function testing prior to and after bronchodilator use is commonly done in children age 4 years and older (Figure 1). In children younger than age 4 years, auscultation documenting improvement or resolution of wheezing after inhalation of a bronchodilator is also supportive evidence. For children with complaints of cough or wheeze who are not wheezing at the time of the clinic visit, a trial of short-acting bronchodilators at home may document the improvement to support an asthma diagnosis. Challenge testing may be used to document reversible airflow obstruction and can be achieved by methacholine, exercise, or cold air challenges; these are usually only done in sophisticated pulmonary function-testing laboratories.
(A) Time-volume curve. The blue line is prior to taking albuterol and the red line is after 4 puffs of albuterol. (B) Flow-volume curve. Expiration is the top loop and inspiration is the bottom loop. The blue expiratory loop appears concave with regard to the volume axis, suggesting airway obstruction. (C) Pre- and post-bronchodilator spirometry numerical values demonstrating reversible airflow obstruction. The pre-bronchodilator FEV1/FVC and FEF25-75% are reduced (below the Z-score −1.64), consistent with obstruction. There is an 18% increase in the FEV1 and a 55% increase in the FEF25-75% after bronchodilator use and all values normalize post-bronchodilator. The eNO #1 is the fractional excretion of exhaled nitric oxide and is elevated (normal is <25 parts per billion for a child older than age 12 years), suggesting allergic airway inflammation. % Chg, the percent change in the value after bronchodilator; %Ref Pre, percent of predicted prior to albuterol; % Ref Post, percent predicted after bronchodilator; FEF25-75%, forced expiratory flow between 25% and 75% of the vital capacity; FEV1, forced expiratory volume in the first second; FVC, forced vital capacity; PEF, peak expiratory flow rate; Post, value measured after bronchodilator; Pre, value measured before bronchodilator; Ref, predicted value; VBe%FV, percent back extrapolation; Z-score, number of standard deviations from the mean.
Children may present with symptoms that are not obvious manifestations of asthma. The classic triad of cough, wheeze, and dyspnea may not always be present, and some children may only have a dry cough. Children with cough-variant asthma have similar triggers (viral infection, exercise, allergen, irritants) and also respond well to asthma medications but typically do not respond to antibiotics or antihistamines. Exercise or methacholine challenge testing demonstrates bronchial reactivity identical to classical asthma.
Another less obvious presentation of childhood asthma is recurrent pneumonia. The usual history of this presentation is that of a viral upper respiratory tract infection associated with fever, cough, perhaps wheezing, and an opacity on the chest radiograph. The examination may demonstrate both wheezing and crackles. The constellation of respiratory symptoms, abnormal auscultation, fever, and radiographic abnormality is often labelled pneumonia and treated as though it is a bacterial pneumonia. The viral infection, however, causes both the fever and the asthma exacerbation, which then causes mucus plugging and atelectasis, which account for the radiographic abnormality. These children may have cough with other triggers besides viral infection, including excessive nocturnal coughing and exercise intolerance, which is a clue that asthma is the underlying issue. A chest radiograph with diffuse increased peri-bronchial markings and over-inflation may also support a diagnosis of asthma (Figure 2). To help identify asthma as the reason for the recurrent pneumonia, one should seek a history with typical asthma presentations including a high asthma predictive index, positive family history, personal history of atopic diseases, and other nonviral triggers. A comprehensive evaluation for other causes of recurrent pneumonia that fails to identify an alternative explanation is also supportive of asthma. Treating these children for persistent asthma often ameliorates the episodes of recurrent pneumonia.
Frontal (A) and lateral (B) chest radiographs of a 2-year-old child with an acute asthma exacerbation due to rhinovirus and coronavirus showing diffuse bilateral increases in peri-bronchial markings and overinflation. These are the most common radiographic findings in children with an acute asthma exacerbation. There are no segmental opacities, pleural effusions, or cardiomegaly. There is a left-sided aortic arch (normal).
Chest pain is an often-overlooked manifestation of asthma. Chest pain or dyspnea with exertion, even without accompanying cough or wheeze, may be caused by exercise-induced bronchospasm. This can be documented by an exercise challenge study. Managing the asthma usually helps resolve the symptoms. Children with chest pain from heart disease usually have a history that suggests a cardiac problem or an examination that raises appropriate concern. An exercise challenge test is usually diagnostic, and treatment with a short acting bronchodilator often improves the symptoms.
Recurrent cough and wheeze are frequently encountered in small children, so it can be challenging to determine if there is an underlying predisposition for asthma. Many physicians are still taught that the diagnosis of asthma cannot be made until the child is age 3 or 4, or even 5 years, which is clearly an outdated concept. Viral illnesses commonly make children without asthma wheeze, with bronchiolitis being the classic example. The diagnosis of acute bronchiolitis and asthma may not be mutually exclusive, and a single episode of bronchiolitis increases the child's risk of subsequent wheezing with viral infections.13,14 Although the response to inhaled short-acting bronchodilators is absent or minimal with acute bronchiolitis, there may be a good response with subsequent viral-triggered wheezing, which supports a diagnosis of viral-triggered asthma. Recurrent viral-triggered asthma in young children is controversial and challenging to manage. Despite many attempts to identify the best approach to these children, one has not been found.15,16–18 The number of exacerbations, oral steroid bursts, emergency department visits, and hospitalizations seems to be the same whether the children are treated with daily inhaled corticosteroids, intermittent inhaled steroids, or have their dose of inhaled steroids increased during illnesses. These children may benefit from an asthma specialist consultation to help confirm the diagnosis, exclude alternative diagnoses, and individualize a treatment plan.
Ancillary testing may be useful to exclude other disease processes and help direct management. The two-view chest radiograph in children not acutely ill with suspected asthma has little to offer but is commonly ordered during acute illness. The most common findings include increased peribronchial markings and hyperinflation, but these are not specific to asthma and may be seen with viral pneumonitis (Figure 2). Allergy testing is recommended for children with moderate persistent and more severe asthma to identify allergens that may be promoting allergic inflammation in the airways. This can be achieved by either skin-prick testing or immunologic assay on serum. Knowing specific allergens to avoid may help with asthma control. Immunotherapy has had minimal success for controlling asthma as compared to improving allergic rhinitis. The fractional exhaled nitric oxide (FeNO) test can be useful to help identify allergic airway inflammation, establish the specific asthma phenotype, and help verify the asthma diagnosis. A persistently elevated FeNO while taking inhaled steroids and/or leukotriene-modifying medications may be an indicator of nonadherence. However, managing asthma with the addition of FeNO to other markers of asthma control does not appear to improve asthma control.19
Other testing should be considered if diagnoses other than asthma are likely, especially in younger children, for whom the diagnosis of asthma can be more challenging.16,17,20
The first cornerstone of asthma management is to avoid triggers once they are known or suspected to contribute to acute symptoms and exacerbations. This may be challenging given that viral infections are the most common trigger for childhood exacerbations. Tobacco poisoning as a result of cigarette and other products with nicotine smoked in the home is another difficult challenge to overcome, as ending nicotine addiction is difficult, even for those who are motivated. Similarly, avoiding airborne allergens might mean being restricted to the indoors for the duration of the allergy season, which may not be either desirable or feasible. Limiting contact with the family pets and keeping the pets out of the child's bedroom might be more acceptable to the family than giving away the pets. Outdoor activities can be curtailed on “bad air” days, when ozone or other pollutants are at moderate or higher levels. During the colder months of the year, asthma triggered by playing outdoors in cold air can be ameliorated with a scarf partially covering the child's nose and mouth.5
Once the diagnosis of asthma is established, an attempt should be made to estimate the severity for the purpose of matching the appropriate intensity of therapy with the severity of asthma (ie, a step-wise approach).5 Asthma is considered intermittent if symptoms occur twice a week or less, if night cough is twice a month or less, and if rescue albuterol is used twice a week or less. A short-acting bronchodilator such as albuterol may be all that is required for children with intermittent asthma. Asthma is considered persistent if the symptoms are more frequent than intermittent, and daily controller therapy should be offered for children with persistent asthma. The preferred initial controller therapy for mild persistent asthma is low-dose inhaled corticosteroids (ICS), although leukotriene modifiers may be an acceptable alternative for daily controller therapy. The intensity of therapy is increased if asthma control is not achieved within a few months. Guidelines recommend consultation with an asthma specialist for children younger than age 3 years who have persistent asthma and all children with persistent asthma who require at least two controller medications or medium- to high-dose ICS.5 Initially, children should be seen routinely for follow-up about every 3 months to reassess asthma control; this interval can be extended once control is assured. Step-down therapy should only be considered after full asthma control is established for 3 or more months.5 The obvious goal is to keep the child's asthma controlled with the least amount of medication needed.
Other key elements for good asthma control include education for the patient and family about asthma and its management, including a written asthma action plan, purpose of controller and reliever medications, appropriate use of their inhaler devices with spacers, and recognition and management of exacerbations. Asthma education, including inhaler technique, should be reinforced with each visit.5
The goals of successful asthma control include full, unlimited exercise tolerance (as appropriate for age), no school or day care absences due to asthma exacerbations, and sleeping through the night without coughing. The chest auscultation should be normal and the pulmonary function testing should be normal for those old enough to perform the test. Asthma self-assessment scorecards (such as the Asthma Control Test) are recommended to allow the patient and/or family to actively participate in the assessment of the child's control.21 In addition to control of symptoms, the risks of poor asthma control and the side effects of asthma therapy should be regularly assessed in an effort to minimize urgent care or emergency department visits, hospitalizations, steroid bursts (ideally less than 2 to 3 times per year), and potential side effects of treatments, both short-term and long-term.5
Despite the advances in our understanding of asthma pathobiology and the increased numbers of medications available to improve asthma control,22 acute asthma exacerbations continue to occur frequently.2 More than one-half of children with self-reported asthma in 2016 had an asthma attack in the prior year, 16.7% had an urgent care or emergency department visit, and 4.7% were hospitalized.2 The most common etiology of these asthma exacerbations is acute viral infections. As our understanding of the risks for exacerbation improves, it may be possible to intervene sooner to reduce this burden on the children, their families, and the health care system.23 Currently, the most successful options to treat acute exacerbations are oral or systemic steroids,24 short-acting bronchodilators, and supportive care such as supplemental oxygen.
Severe or Difficult to Manage Asthma
A small percentage of children with asthma (2%–5%) have asthma that is difficult to control, and this is an area in which consultation with an asthma specialist may be helpful.25,26 Some children with asthma that is difficult to control have social determinants contributing to poor control, including nonadherence, lack of available medications, improper delivery techniques, inability to understand the asthma plan, and unresolved environmental exposures such as tobacco poisoning,27 mold, dust mites, pests, or pets.28 Other causes of poorly controlled asthma might include having the incorrect diagnosis or confounding diagnoses26 that make asthma harder to control. Vocal cord dysfunction (VCD), or paradoxical vocal cord adduction, is commonly confused with asthma, which is further complicated by the fact that about 50% of children with VCD also have asthma. Potentially confounding conditions might include uncontrolled nasal and sinus inflammation, atopic dermatitis, gastroesophageal reflux, aspiration, and obesity. Obesity makes asthma harder to control and may cause incident asthma.29 Technology now offers the opportunity to accurately measure medication use, and some advocate that monitoring should be a part of all treatment plans for severe asthma.30,31
The prognosis for most children with asthma is favorable over time with age and growth and many become symptom free; however, these children remain at risk for relapse in adulthood.32 Most young children who have transient wheeze associated with viral infections will no longer have wheezing episodes by school age.33 Children with associated atopic diseases may continue to have asthma through adolescence into adulthood.32 A small percentage are at risk for persistent low lung function and early progressive loss of lung function with possible development of chronic obstructive pulmonary disease in adulthood. It may be important to identify this at-risk group early in life prior to the development of fixed airflow obstruction.34
Childhood asthma remains a common problem despite much improved understanding in the disease pathobiology and advances in treatment options. Although traditional asthma is often easy to recognize in school-age and older children, more obscure presentations can make it challenging to identify asthma as the cause of the child's symptoms. The diagnosis of asthma in preschool children with wheezing is both challenging and controversial. The intensity of recommended therapy should match the severity of the asthma and be escalated until satisfactory control is achieved. After control has been achieved, step-down therapy can be considered. The prognosis for childhood asthma is generally good, but children with asthma that is difficult to control might benefit from specialty consultation.
- Centers for Disease Control and Prevention. Most recent asthma data. https://www.cdc.gov/asthma/most_recent_data.htm. Accessed February 16, 2019.
- Zahran HS, Bailey CM, Damon SA, Garbe P, Breysse PN. Vital signs: asthma in children — United States, 2001–2016. MMWR Morb Mortal Wkly Rep. 2018;67:149–155. doi:. doi:10.15585/mmwr.mm6705e1 [CrossRef]
- Nurmagambetov T, Kuwahara R, Garbe P. The economic burden of asthma in the United States, 2008–2013. Ann Am Thorac Soc. 2018;15(3):348–356. doi:. doi:10.1513/AnnalsATS.201703-259OC [CrossRef]
- Bush A, Griffiths C. Improving treatment of asthma attacks in children. BMJ. 2017;359:j5763. doi:. doi:10.1136/bmj.j5763 [CrossRef]
- National Heart, Lung, and Blood Institute. Guidelines for the diagnosis and management of asthma. (EPR 3). https://www.nhlbi.nih.gov/health-topics/guidelines-for-diagnosis-management-of-asthma. Accessed February 16, 2019.
- Global Strategy for Asthma Management and Prevention--Updated 2018. https://ginasthma.org/gina-reports/. Accessed February 27, 2019.
- Reddel HK, Taylor DR, Bateman ED, et al. An official American Thoracic Society/European Respiratory Society statement: asthma control and exacerbations: standardizing endpoints for clinical asthma trials and clinical practice. Am J Respir Crit Care Med. 2009;180(1):59–99. doi:. doi:10.1164/rccm.200801-060ST [CrossRef]
- Bacharier LB, Guilbert TW. Diagnosis and management of early asthma in preschool-aged children. J Allergy Clin Immunol.2012;130(2):287–296. doi:. doi:10.1016/j.jaci.2012.04.025 [CrossRef]
- Castro-Rodriguez JA, Holberg CJ, Wright AL, Martinez FD. A clinical index to define risk of asthma in young children with recurrent wheezing. Am J Respir Crit Care Med. 2000;162(4 Pt 1):1403–1406. doi:. doi:10.1164/ajrccm.162.4.9912111 [CrossRef]
- Guilbert TW, Morgan WJ, Zeiger RS, et al. Atopic characteristics of children with recurrent wheezing at high risk for the development of childhood asthma. J Allergy Clin Immunol. 2004;114(6):1282–1287. doi:. doi:10.1016/j.jaci.2004.09.020 [CrossRef]
- Castro-Rodriguez JA. The Asthma Predictive Index: a very useful tool for predicting asthma in young children. J Allergy Clin Immunol. 2010;126(2):212–216. doi:. doi:10.1016/j.jaci.2010.06.032 [CrossRef]
- Guilbert TW, Morgan WJ, Zeiger RS, et al. Long-term inhaled corticosteroids in preschool children at high risk for asthma. N Engl J Med. 2006;354(19):1985–1997. doi:. doi:10.1056/NEJMoa051378 [CrossRef]
- Kim CK, Callaway Z, Gern JE. Viral infections and associated factors that promote acute exacerbations of asthma. Allergy Asthma Immunol Res. 2018;10(1):12–17. doi:. doi:10.4168/aair.2018.10.1.12 [CrossRef]
- Feldman AS, He Y, Moore ML, Hershenson MB, Hartert TV. Toward primary prevention of asthma. Reviewing the evidence for early-life respiratory viral infections as modifiable risk factors to prevent childhood asthma. Am J Respir Crit Care Med. 2015;191(1):34–44. doi:. doi:10.1164/rccm.201405-0901PP [CrossRef]
- Ducharme FM, Tse SM, Chauhan B. Diagnosis, management, and prognosis of preschool wheeze. Lancet. 2014;383(9928):1593–1604. doi:. doi:10.1016/S0140-6736(14)60615-2 [CrossRef]
- Bush A, Grigg J, Saglani S. Managing wheeze in preschool children. BMJ. 2014;348:g15. doi:. doi:10.1136/bmj.g15 [CrossRef]
- Gergen PJ. The challenge of treating preschool wheezing. J Allergy Clin Immunol. 2013;131(6):1526–1527. doi:. doi:10.1016/j.jaci.2013.03.011 [CrossRef]
- Beigelman A, King TS, Mauger D, et al. Do oral corticosteroids reduce the severity of acute lower respiratory tract illnesses in preschool children with recurrent wheezing?J Allergy Clin Immunol. 2013;131(6):1518–1525. doi:. doi:10.1016/j.jaci.2013.01.034 [CrossRef]
- Rao DR, Phipatanakul W. An overview of fractional exhaled nitric oxide and children with asthma. Expert Rev Clin Immunol.2016;12(5):521–530. doi:. doi:10.1586/1744666X.2016.1141049 [CrossRef]
- Ren CL, Esther CR Jr, Debley JS, et al. ATS Ad Hoc Committee on Infants with Recurrent or Persistent Wheezing. Official American Thoracic Society Clinical Practice Guidelines: diagnostic evaluation of infants with recurrent or persistent wheezing. Am J Respir Crit Care Med. 2016;194(3):356–373. doi:. doi:10.1164/rccm.201604-0694ST [CrossRef]
- Dinakar C, Chipps BE. Clinical tools to assess asthma control in children. Pediatrics. 2017;139(1):e20163438. doi:. doi:10.1542/peds.2016-3438 [CrossRef]
- Anderson WC 3rd, Gleason MC, Miyazawa N, Szefler SJ. Approaching current and new drug therapies for pediatric asthma. Pediatr Clin North Am. 2017;64(6):1197–1207. doi:. doi:10.1016/j.pcl.2017.08.001 [CrossRef]
- Hoch HE, Calatroni A, West JB, et al. Can we predict fall asthma exacerbations? Validation of the seasonal asthma exacerbation index. J Allergy Clin Immunol. 2017;140(4):1130–1137.e5. doi:. doi:10.1016/j.jaci.2017.01.026 [CrossRef]
- Foster SJ, Cooper MN, Oosterhof S, Borland ML. Oral prednisolone in preschool children with virus-associated wheeze: a prospective, randomised, double-blind, placebo-controlled trial. Lancet Respir Med. 2018;6(2):97–106. doi:. doi:10.1016/S2213-2600(18)30008-0 [CrossRef]
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Common Triggers for Symptoms of Asthma in Children
||All common upper respiratory tract infections
||Human rhinovirus and respiratory syncytial virus are common triggers
||Running, laughing, singing
||Worse with cold air; better with humid air
||Smoke, strong smells, weather changes, strong winds, cleaning fluids, perfumes, ozone, particulates
||May occur in the school environment
||Animal danders, pollens, molds, dust mites, pests, foods
||Can be indoor and/or outdoor allergens
||Anger, fear, stress, anxiety
||Often more common in adolescents; may be associated with unsafe living situations
Predictors of Subsequent Asthma in Young Children with Recurrent Wheezing
|Original Asthma Predictive Indexa9
||Modified Asthma Predictive Indexa10
||Other Related Risks11
Parental history of asthma
Physician-diagnosed atopic dermatitis
Parental history of asthma
Physician-diagnosed atopic dermatitis
Allergic sensitization to one or more aeroallergens
||Family history of atopy
African American ethnicity
Puerto Rican ancestry
Prenatal tobacco exposure
Early in life moderate to severe bronchiolitis
Physician-diagnosed allergic rhinitis
Wheezing unrelated to colds
Blood eosinophils ≥4%
Allergic sensitization to milk, egg, or peanut
Wheezing unrelated to colds
Blood eosinophils ≥4%