A Pediatric Allergist's Approach to Asthma

Educational Objectives

The goal of this program is to improve management of asthma. After hearing and assimilating this program, the clinician will be better able to:

1. Identify risk factors associated with development of asthma in children.
2. Perform a differential diagnosis for asthma.
3. Develop management strategies for asthma in children based on recommended guidelines.

Summary

Introduction: endotypes reveal underlying immunologic pathways and inflammation types, while phenotypes represent observable clinical characteristics; they can affect the response to therapy and prognosis, as well as aid in establishing the correct diagnosis; chronic conditions in children include asthma, allergic rhinitis, atopic dermatitis, and food allergies

Risk factors: growing up in a home with cats or dogs can protect against allergic sensitization and the development of atopic diseases; a family history of allergies is also a significant risk factor; children of individuals with allergies are predisposed to the allergic march, which often begins with early-onset infantile eczema at ≤6 mo of age; it is important to diagnose allergies and identify children with persistent symptoms; the absence of risk factors does not prevent the development of allergic conditions

Allergic march: does not always follow a consistent order; atopic dermatitis usually improves in the first few years; food allergies may present and either become persistent or resolve later; environmental allergies typically appear in children ≥1 yr of age; persistent moderate to severe eczema in infants <6 mo of age should be monitored for changes over time

Inflammation: T helper type 1 (Th1) vs T helper type 2 (Th2) — affects response to therapy; Th1-mediated inflammation follows a distinct inflammatory pathway in autoimmune conditions; Th2-mediated inflammation involves interleukins (IL)-4, -5, -10, and -13, and eosinophils (the hallmark of allergic disease); Th1-mediated inflammation is primarily characterized by neutrophils, interferon-γ, and IL-2; allergic inflammation can affect the skin, upper respiratory tract, and lungs; IL-4 and IL-13 are important for immunoglobulin E (IgE) production; IL-5 level is a key indicator of eosinophils

Asthma: a chronic condition characterized by varying degrees of inflammation and hyper-responsive airways; reversible airflow obstruction can lead to bronchoconstriction, resulting in recurrent symptoms; airflow limitation — bronchoconstriction can be reversed with bronchodilators; swelling in the airways, often exacerbated with mucus and goblet cells, can further restrict airflow; multiple medications are needed to manage exacerbation in asthma; asthma is frequently underdiagnosed and can change over time, necessitating individualized care; intermittent symptoms during upper respiratory infections are the most common presentation in toddlers (cough is often the main manifestation); types — include intermittent asthma with infrequent symptoms or chronic asthma with more frequent symptoms, and it may be categorized as mild, moderate, or severe

Diagnosis: obtaining a clinical history of recurrent respiratory symptoms, comorbid conditions, and risk factors is essential; consider improvement with bronchodilators or corticosteroids; spirometry — recommended for children ≥5 yr of age with suspected asthma; does not diagnose asthma but demonstrates lung function at that point in time; spirometry can be normal in children with asthma; asthma is a clinical diagnosis in children; exhaled nitric oxide (FeNO) test — often used with spirometry; measures eosinophilia in the lower airways; elevated eosinophil levels can help diagnose asthma

Asthma predictive index: is used for children ≤3 yr of age to predict the likelihood of developing asthma, particularly more persistent asthma; 4 separate wheezing episodes in the past year (can use cough episodes also) is a key factor; major criteria — family history of asthma, history of atopic dermatitis, sensitization to allergens; minor criteria — comorbid food allergies, wheezing or coughing, and elevated eosinophil levels; serves as both a prognostic and diagnostic tool; the presence of one major or 2 minor criteria indicates a high likelihood of having persistent symptoms at 7 yr of age; zero criteria indicate a very low likelihood of developing asthma; children (≤4 yr of age) coughing for 1 or 2 wk every time they get sick is considered asthma until proven otherwise; consider albuterol as the first-line diagnostic and therapeutic trial

Management: Th1-mediated inflammation typically presents with adult onset or a history of smoking and is characterized by neutrophil dominance; steroids may not be effective in cases of persistent bronchospasm; Th2-mediated inflammation responds well to inhaled corticosteroids (ICS); type 2 asthma — biologics targeting IL-4, IL-13, or IL-5, and ICS can be used; steroids may not be beneficial in Th2-low asthma (use other types of bronchodilators); intermittent asthma — reevaluate every few months, provide on-demand therapy, and counsel families; persistent asthma — consider daily anti-inflammatory medication, address comorbid conditions, and conduct environmental assessment

Tips: asthma requires education for families, self-management skills, recognition of asthma symptoms, follow-up plans, written treatment plans, and support

Goals of therapy: are to reduce chronic burden, prevent exacerbations, keep patients active, prevent hospitalizations, and monitor and minimize adverse effects (AEs) of treatment; relievers are used on demand, work quickly, and treat symptoms; the controllers work long term; different types of inhalers are available, eg, metered-dose inhalers and dry powder inhalers

Acute asthma treatment: dilate the airways using β-adrenergic agonists, long-acting bronchodilators (eg, formoterol), anticholinergic drugs, and antimuscarinic drugs; albuterol — a reliever, not an emergency inhaler (use when symptoms occur); the National Heart, Lung, and Blood Institute (NHLBI) guidelines (2007) recommend administering 2 to 6 puffs of albuterol every 3 to 4 hr for the first 1 to 2 days; the Global Initiative for Asthma guidelines (2018) recommend 4 to 10 puffs every 20 min for the first hour; if >2 puffs are needed every 4 hr, the patient should visit the emergency department; inhalers vs nebulizers — Raissy et al (2004) found that metered-dose inhalers with spacers and nebulizers have equivalent efficacy; nebulizers were associated with more AEs; spacers are important for metered-dose inhalers; albuterol may cause jitteriness and tachycardia but is generally well tolerated in children

SMART therapy: most people with asthma experience intermittent symptoms (3-4 times/yr) and can use inhalers at the onset of symptoms for 3 to 4 days; inhalers can be used daily and increase ≤4 times a day when acutely ill or start on demand; formoterol is the key component and works ≤15 min and lasts for ≈12 hr; NHLBI guidelines — for individuals ≥4 yr of age with moderate to severe persistent asthma, ICS-formoterol can be used in a single inhaler for both daily controller and reliever therapy; for individuals ≥12 yr of age with moderate to severe asthma, the ICS-formoterol can be used as daily controller and reliever therapy; check adherence before increasing therapy; high-dose ICS monotherapy is not indicated; consider adding a long-acting β-agonist if the patient is not responding to low- or medium-dose ICS; reassess before increasing the dose of steroids; montelukast is not a primary treatment for asthma or allergic rhinitis and carries a black box warning for potential behavioral AEs (counsel parents)

Biologics: are for patients who do not benefit from medical therapy; different age indications and biomarkers may be necessary for prescription; omalizumab is used for patients with elevated IgE levels to any perennial aeroallergen and poorly controlled asthma; 3 agents that target IL-5 are available; dupilumab targets IL-4 and IL-13 receptors; tezepelumab targets the TSLP pathway (biomarkers are not needed)

Additional options: epinephrine inhalation aerosol (Primatene MIST) is approved for ≥12 yr of age and is available over the counter; the albuterol-budesonide fixed-dose combination rescue inhaler is approved for ≥18 yr of age

Differential diagnosis: rhinitis is a common symptom in children, typically characterized by recurrent rhinorrhea, nasal congestion, and sneezing; allergic rhinitis can be classified as seasonal, perennial, or mixed; many children experience seasonal pollen allergies and severe nonallergic rhinitis during winter, which require different therapies; the symptoms that occur from allergic rhinitis can also occur from nonallergic rhinitis; check for other causes if oral antihistamines do not cause improvement; oral antihistamines do not treat nasal congestion or postnasal drip (consider ICS); IgE testing identifies sensitization (a negative test suggests no antihistamine treatment); second-generation antihistamines offer a faster onset of action and fewer AEs compared with first-generation antihistamines

Mitigation strategies: use multifactorial approaches based on specific allergens; for dust mite allergies, use impermeable dust mite covers for pillows and mattresses, wash linens in hot water weekly, and avoid using humidifiers; for pollen allergies, keep windows closed, change clothing, and bathe before bed; for pet allergies, keep pets out of the room and use a HEPA filters on vacuums

Inhaled corticosteroids: daily ICS are the first-line treatment for symptoms associated with allergic rhinitis, including itching, sneezing, runny nose, congestion, and postnasal drip; different formulations are available; for pollen allergies, start using ICS 2 wk before the onset of symptoms; can add on oral antihistamine; second-generation nonsedating antihistamines are particularly effective for itching or sneezing; eye or nose drops can also be effective, but avoid vasoconstrictors because they may cause rebound effects if used long term

Long-term therapy: immunotherapy is recommended for patients with severe symptoms and comorbid asthma, even after trying multiple medications; subcutaneous immunotherapy allergy injections do not provide immediate benefits (may see effects after ≈6 mo); asthma must be well controlled in order to receive the treatment; 3 sublingual immunotherapy options approved by the US Food and Drug Administration are available for ragweed, grass pollen, and dust mites

Readings

Castro-Rodriguez JA, Forno E, Padilla O, et al. The asthma predictive index as a surrogate diagnostic tool in preschoolers: analysis of a longitudinal birth cohort. Pediatr Pulmonol. 2021;56(10):3183-3188. doi:10.1002/ppul.25592; Incorvaia C, Mauro M, Riario-Sforza GG, et al. Current and future applications of the anti-IgE antibody omalizumab. Biologics. 2008;2(1):67–73. doi:10.2147/btt.s1800; Jat KR. Spirometry in children. Prim Care Respir J. 2013;22(2):221–229. doi:10.4104/pcrj.2013.00042; Mullol J, Cuvillo AD, Lockey RF. Rhinitis phenotypes. J Allergy Clin Immunol Pract. 2020;8(5):1492-1503. doi:10.1016/j.jaip.2020.02.004; Paller AS, Spergel JM, Mina-Osorio P, et al. The atopic march and atopic multimorbidity: many trajectories, many pathways. J Allergy Clin Immunol. 2019;143(1):46-55. doi:10.1016/j.jaci.2018.11.006; Raissy HH, Kelly HW. MDI versus nebulizers for acute asthma. J Pediatr Pharmacol Ther. 2004;9(4):226-34. doi:10.5863/1551-6776-9.4.226; Reddel HK, Bacharier LB, Bateman ED, et al. Global initiative for asthma strategy 2021: executive summary and rationale for key changes. Am J Respir Crit Care Med. 2021;205(1):17–35. doi:10.1164/rccm.202109-2205PP; Varricchi G, Bagnasco D, Borriello F, et al. Interleukin-5 pathway inhibition in the treatment of eosinophilic respiratory disorders: evidence and unmet needs. Curr Opin Allergy Clin Immunol. 2016;16(2):186–200. doi:10.1097/ACI.0000000000000251.

Disclosures

For this program, the following relevant financial relationships were disclosed and mitigated to ensure that no commercial bias has been inserted into this content: Dr. Stukus has been a consultant for ARS Pharmaceuticals and Genentech and received research support from DBV Technologies. Members of the planning committee reported nothing relevant to disclose.

Acknowledgements

Dr. Stukus was recorded at the 48th Annual Melvin L. Cohen, MD, Pediatric Update Conference 2025, held March 3-6, 2025, in Scottsdale, AZ, and presented by Phoenix Children’s Hospital, Phoenix, AZ. For information on upcoming CME activities from this presenter, please visit https://phoenixchildrens.org/healthcare-professionals/continuing-medical-education. Audio Digest thanks Dr. Stukus and Phoenix Children’s Hospital for their cooperation in the production of this program.

CME/CE INFO

Accreditation:

Lecture ID:

PD712801

Qualifies for:

ABP MOC, Clinical Pharmacology

Expiration:

This CME course qualifies for AMA PRA Category 1 Credits™ for 3 years from the date of publication.

Instructions:

To earn CME/CE credit for this course, you must complete all the following components in the order recommended: (1) Review introductory course content, including Educational Objectives and Faculty/Planner Disclosures; (2) Listen to the audio program and review accompanying learning materials; (3) Complete posttest (only after completing Step 2) and earn a passing score of at least 80%. Taking the course Pretest and completing the Evaluation Survey are strongly recommended (but not mandatory) components of completing this CME/CE course.

Estimated time to complete this CME/CE course:

Approximately 2x the length of the recorded lecture to account for time spent studying accompanying learning materials and completing tests.