Evidence‑based clinical practice guideline (2025): Diagnosis, treatment, management and prevention of recurrent wheezing in infants and toddlers

Full‑text published in Pediatric Investigation, March‑June 2026, Volume 10, Issue 3, pages 199‑218, DOI: 10.1002/ped4.70046PubMed. Chinese original: Chinese Journal of Applied Clinical Pediatrics, Oct 2025, DOI: 10.3760/cma.j.cn101070‑20250811‑00604. ⚠️This summary is a structured English abstract‑level overview; not a substitute for the original guideline. For clinical practice, please refer to the full‑text original article.

Abstract

Recurrent wheezing is very common among infants and toddlers aged 0‑3 years, with heterogeneous aetiologies including viral‑triggered wheeze, atopic‑associated airway inflammation, airway malformation, gastro‑oesophageal reflux, and aspiration‑related disorders. It imposes heavy disease burden and may impair long‑term lung function. This Chinese national evidence‑based guideline was developed by a multi‑disciplinary paediatric respiratory working group using GRADE methodology, integrating domestic real‑world data and international evidence, to standardise diagnostic workflow, stratified therapy, long‑term follow‑up and preventive strategies for Chinese children.

1. Definition & clinical phenotypes

Recurrent wheezing: ≥2 episodes of documented wheezing before 3 years of age. Three major clinical phenotypes are recognised:

1. Virus‑induced transient wheeze: wheeze mainly triggered by respiratory viral infections; few/no symptoms between episodes; low atopic risk.
2. Atopic‑persistent wheeze: atopy‑positive (eczema, food allergy, elevated eosinophil / FeNO); frequent wheeze even outside infection periods; high risk of progression to childhood asthma.
3. Secondary wheeze: wheeze secondary to gastro‑oesophageal reflux, tracheobronchial mal‑development, aspiration, cardiac or immunological disease.

2. Diagnostic work‑flow

2.1 Clinical history & physical examination (core)

• History: timing, triggers (virus‑cold, exercise, night‑time), family atopy / asthma history, eczema, feeding‑related symptoms, choking‑aspiration events, growth and development.
• Physical exam: general growth status, skin atopic manifestations, auscultation of lung, signs suggesting cardiac or upper‑airway disease.
• Red‑flag features requiring further work‑up: persistent‑focal‑unilateral wheeze, stridor, choking‑aspiration‑history, failure‑to‑thrive, cyanosis, recurrent‑pneumonia, clubbing, cardiac murmurs.

2.2 Laboratory & auxiliary tests (conditional indications only)

1. Peripheral blood eosinophil count, total‑IgE, specific‑IgE: evaluate type‑2 inflammatory / atopic risk (strong‑recommendation for high‑risk subjects).
2. Fractional exhaled nitric oxide (FeNO): help evaluate eosinophilic airway‑inflammation; not for standalone diagnosis.
3. Radiology:
   • Chest‑X‑ray: mandatory when red‑flags present; not for routine‑screening of simple‑recurrent‑wheeze.
   • Chest‑CT‑+‑air‑trapping‑evaluation: suspected airway‑anomaly, foreign‑body, structural‑lung‑disease.
4. Flexible bronchoscopy: indicated for suspected foreign‑body‑aspiration, fixed‑focal‑wheeze, suspected airway‑malformation.
5. Gastro‑intestinal work‑up: only for patients with prominent reflux‑/‑feeding‑related‑symptoms; do‑not‑test‑all‑wheezers for GERD.

Spirometry / lung‑function testing is difficult to‑perform‑reliably in most children < 3 years‑old.

2.3 Diagnostic‑approach principle

• No single‑biomarker can confirm‑or‑exclude‑the‑diagnosis.
• Classify‑patients‑into‑phenotypes‑based‑on‑history‑atopy‑risk‑and‑investigations; rule‑out‑secondary‑causes‑first.

3. Acute‑exacerbation‑management

1. Bronchodilator: short‑acting‑β₂‑agonist (SABA, e.g. salbutamol) via‑inhalation‑with‑spacer‑/‑nebuliser‑for‑relief‑of‑bronchospasm.
2. Inhaled‑corticosteroids‑(ICS)‑nebulised‑budesonide: for‑moderate‑to‑severe‑acute‑wheeze‑episodes.
3. Systemic‑corticosteroids: reserved‑for‑moderate‑severe‑exacerbations‑with‑significant‑respiratory‑distress‑(conditional‑recommendation).
4. Antibiotics: not‑routinely‑prescribed. Only‑administer‑when‑bacterial‑co‑infection‑is‑confirmed‑or‑highly‑suspected.
5. Oxygen‑supplementation:‑maintain‑SpO₂ ≥ 94 %‑during‑acute‑phase.

4. Long‑term‑controller‑therapy (remission‑phase‑stratified‑recommendations)

All‑therapy‑decisions‑balance‑frequency‑of‑exacerbations,‑atopic‑risk‑and‑safety‑profile.

1. Low‑dose‑inhaled‑corticosteroids‑(ICS):
   • Recommended‑for‑children‑with‑frequent‑recurrent‑wheeze,‑atopic‑features‑or‑high‑asthma‑risk‑(weak‑recommendation).‑Initial‑duration‑2‑to‑3‑months;‑re‑evaluate‑clinical‑response‑after‑treatment‑course.‑Optimal‑delivery‑via‑nebuliser‑or‑pressurised‑MDI‑with‑valved‑holding‑chamber‑spacer.
2. Leukotriene‑receptor‑antagonists‑(LTRA,‑montelukast):
   • Alternative‑controller‑option‑for‑patients‑who‑cannot‑tolerate‑/‑refuse‑ICS‑(weak‑recommendation).‑Monitor‑neuro‑psychiatric‑adverse‑events‑during‑montelukast‑therapy.
3. Intermittent‑pre‑emptive‑high‑dose‑ICS‑strategy:‑May‑be‑considered‑for‑selected‑virus‑triggered‑frequent‑wheeze‑patients‑(conditional‑recommendation).
4. Antihistamines‑/‑anti‑IgE‑biologics:‑only‑used‑when‑concomitant‑allergic‑comorbidities‑are‑present.

After‑controller‑treatment‑course‑complete,‑systematically‑reassess‑whether‑therapy‑can‑be‑stepped‑down‑or‑discontinued.‑Do‑not‑indefinitely‑maintain‑controller‑treatment‑without‑periodic‑re‑evaluation.

5. Comprehensive‑long‑term‑management

1. Comorbidity‑evaluation:‑Assess‑and‑manage‑comorbid‑atopic‑diseases‑(atopic‑dermatitis,‑food‑allergy,‑allergic‑rhinitis)‑strong‑recommendation.
2. Exposure‑modification:‑Avoid‑tobacco‑smoke‑(prenatal‑and‑post‑natal),‑indoor‑mould‑and‑major‑aero‑allergen‑exposures‑where‑causally‑linked‑to‑symptoms.
3. Education‑of‑caregivers:‑Correct‑inhalation‑technique‑training,‑recognition‑of‑warning‑signs‑of‑severe‑exacerbation,‑written‑action‑plan‑for‑wheeze‑attacks.
4. Follow‑up‑schedule:‑Re‑assess‑every‑1‑to‑3‑months‑during‑active‑treatment‑phase;‑after‑stabilisation‑follow‑up‑every‑6‑months‑until‑pre‑school‑age.‑Monitor‑growth‑parameters‑when‑using‑ICS.

6. Prevention‑strategies

1.‑Avoid‑tobacco‑smoke‑exposure‑through‑pregnancy‑and‑infancy. 2.‑Viral‑respiratory‑infection‑prevention:‑hand‑hygiene,‑mask‑protection‑during‑epidemic‑seasons;‑RSV‑prophylaxis‑for‑high‑risk‑infants‑per‑local‑recommendations. 3.‑Early‑recognition‑and‑control‑of‑atopic‑diseases‑(eczema‑management). 4.‑No‑universal‑prophylactic‑anti‑asthma‑medication‑for‑asymptomatic‑wheeze‑prone‑infants.

7. Core‑summary‑statements

✅Recommendations 1.‑Classify‑recurrent‑wheeze‑into‑clinical‑phenotypes‑based‑on‑history,‑atopy‑risk‑and‑investigations;‑exclude‑secondary‑causes‑first. 2.‑Blood‑eosinophil‑count‑and‑atopy‑evaluation‑are‑strongly‑recommended‑for‑risk‑stratification. 3.‑Acute‑exacerbations‑treat‑with‑SABA‑relief‑plus‑optional‑nebulised‑ICS;‑systemic‑steroids‑only‑for‑severe‑distress. 4.‑Low‑dose‑ICS‑is‑preferred‑controller‑therapy‑for‑high‑risk‑frequent‑wheeze‑infants‑(2‑3‑months‑initial‑course,‑then‑re‑assessment).‑Montelukast‑is‑an‑alternative‑option. 5.‑Antibiotics‑are‑not‑routinely‑indicated‑for‑wheezing‑episodes‑of‑presumed‑viral‑aetiology. 6.‑Long‑term‑care‑includes‑comorbidity‑management,‑trigger‑avoidance,‑caregiver‑education‑and‑scheduled‑re‑evaluation‑to‑step‑therapy‑up‑or‑down.

⚠️Caveats 1.‑No‑single‑diagnostic‑test‑can‑confirm‑recurrent‑wheeze‑aetiology‑in‑infants‑and‑toddlers. 2.‑Do‑not‑prescribe‑long‑term‑controller‑medication‑without‑periodic‑re‑assessment‑of‑treatment‑response‑and‑treatment‑need. 3.‑Monitor‑for‑montelukast‑associated‑neuro‑psychiatric‑adverse‑reactions.

❌Not‑recommended 1.‑Routine‑broad‑spectrum‑antibiotic‑prescription‑for‑uncomplicated‑viral‑wheezing‑episodes. 2.‑Universal‑screening‑of‑all‑wheezing‑infants‑for‑gastro‑oesophageal‑reflux‑disease‑without‑relevant‑clinical‑symptoms. 3.‑Indefinite‑continuous‑controller‑anti‑inflammatory‑therapy‑without‑regular‑clinical‑re‑evaluation.

8. Evidence‑gaps

1.‑Optimal‑duration‑and‑timing‑of‑controller‑therapy‑for‑different‑wheeze‑phenotypes‑in‑Chinese‑infants. 2.‑Biomarker‑cut‑off‑values‑predicting‑progression‑from‑infant‑recurrent‑wheeze‑to‑childhood‑asthma‑in‑Chinese‑populations. 3.‑Real‑world‑comparative‑effectiveness‑between‑intermittent‑versus‑continuous‑ICS‑strategies‑in‑mainland‑Chinese‑infant‑co‑horts.