Asthma: onset at young, persist when grow up

Introduction

Asthma is one of the common diseases worldwide that affects patients of all age groups. The estimated global prevalence was 260 million (1). The distinctive feature of asthma, as a chronic medical disease, is that it can have an onset from childhood to adulthood (2), while childhood onset asthma can persist when the patients grow up (3). There are also differences in terms of pathophysiology and clinical features of childhood-onset and adult-onset asthma (4,5). Diversity and heterogeneity are the key features of asthma. In this review article, we shall review on childhood-onset asthma, a distinctive phenotype within the multiple asthma phenotypes. The pathophysiology, phenotypes, clinical features and diagnosis shall be covered in this article. Published peer-reviewed article on PubMed and Global Initiative for Asthma (GINA) recommendations were extracted and summarized to present the key findings in each sub-section.

Pathophysiology and phenotype of childhood-onset asthma

Asthma pathogenesis involves interactions between genetic susceptibility, immune dysregulation, environmental exposures, and microbial factors, often starting in early life (6). Airway inflammation in asthma involves complex interactions among inflammatory and resident airway cells, particularly involving the activation of mast cells by cytokines and other mediators (7).

Asthma comprises multiple phenotypes and underlying endotypes. Phenotypes represent clinically defined subtypes characterized by shared features such as symptom triggers, atopic predisposition, disease severity, and treatment response. In contrast, endotypes are subtypes defined by distinct underlying biological mechanisms (8). Identification of specific asthma phenotypes and endotypes enables a more individualized, pathophysiology-driven approach to treatment (9).

Key endotypes include ‘type 2 (T2)-high’ and ‘type 2-low’ asthma (10).

T2-high asthma

This represents the most prevalent phenotype and typically has its onset in childhood (11). It is closely linked to allergic sensitization and is frequently associated with a personal or family history of atopic conditions, including eczema, allergic rhinitis, and food or drug allergies (12). Patients have airway and systemic eosinophilia, and they may have raised IgE and fractional exhaled nitric oxide (FeNO) levels (11). Biomarkers of type 2 inflammation in blood and exhaled air can identify individuals with asthma. This typically responds well to inhaled corticosteroids (ICS) treatment, and are showing promise as predictors of responsiveness to a growing list of type 2 cytokine inhibitors that are in late-phase clinical trials for asthma (10).

T2-low asthma

This phenotype is comparatively less prevalent (Table 1) (13). Sputum cellular profiles in affected individuals may demonstrate neutrophilic or paucigranulocytic patterns, and in some cases, a mixed inflammatory pattern involving type 2, type 1, and T-helper 17 pathways (6). Neutrophilic disease may be more common in preschool asthma (6). This phenotype may show a lesser short-term response to ICS, and in severe cases, innate mediators like interleukin (IL)-33 may dominate the immune response, contributing to the activation of type 2 innate lymphoid cells (ILC2s), which can be relatively steroid-resistant (6). Some children born preterm, with or without bronchopulmonary dysplasia (BPD), may exhibit a distinct “asthma-like” phenotype characterized by neutrophilic inflammation, which may demonstrate a limited response to inhaled ICS (6).

Clinical features and trajectory

Childhood-onset asthma

Children with asthma commonly present with a triad of wheeze, dyspnea, and cough. These symptoms are typically intermittent and tend to worsen at night or in the early morning hours (7). They are frequently precipitated by viral respiratory infections, physical exertion, allergen exposure, weather changes, laughter, or environmental irritants such as passive tobacco smoke, incense, vehicle exhaust, or strong odors (6,12). Wheeze is a key symptom of asthma, described as an expiratory high-pitched whistle from inflamed narrowed airways (11). However, parents’ understanding of wheeze can vary, necessitating clarification (12). Cough is also often reported, sometimes as the sole symptom. Asthma should be considered when evaluating a child with a cough, especially if it is primarily nocturnal or triggered by cold air or exercise. Asthma-related cough is generally recurrent, and/or persistent, often accompanied with wheezing and breathlessness (12). Depending on age, older children may be able to describe as chest tightness. All these symptoms should be considered when making the diagnosis.

Transition of childhood-onset asthma in adulthood

When patients with childhood-onset asthma grow up, asthma can persist or worsen or remit.

It is not uncommon to see patients with childhood-onset asthma remit when they reach adolescence. According to a Canada national cohort, nearly half of the patients with childhood-onset asthma go into remission by the age of 12 years (14). But being free of symptoms does not mean complete remission (14). In a Dutch cohort, among the patients without symptoms at adulthood, less than half of them had complete remission as defined by lack of symptoms, free from steroid use, normal lung function and no airway hyper-responsiveness (15). Having lung function impairment or airway hyper-responsiveness in symptom-free patients are not uncommon which reflect that underlying airway changes persisted in these patients though they did not report any symptoms. Airway inflammation or remodelling could be present to explain these changes (16). As such, when encountering adult patients with childhood asthma, apart from symptom assessment, it is also important to assess for any lung function impairment and airway hyper-responsiveness and determine on follow-up and management strategies.

At the same time, patients with childhood-onset asthma who remit during adolescence can also have disease relapses when they become adults. The reported risk factors for relapsing adulthood include active smoking, especially for those without atopy (17), sensitisation at age 13 years and asymptomatic airway hyper-responsiveness during adolescence (3).

Persistent symptoms and diseases when the patients grow up are also well reported. The risk factors include cigarette smoking, a positive history of asthma or atopy in the family (18-20) as well as personal history of atopy or allergic comorbidities (21,22). Certain genetic loci or epigenetic changes were also reported to be potentially linked to symptom or disease persistence in adulthood, such as gasdermin B/orosomucoid like 3 (GSDMB-ORMDL3) loci on chromosome 17q21 (20) and differentially methylated position near the HLX1 gene (23). Apart from persistent symptoms, these patients also had lung function impairment (24) and airway hyper-responsiveness (20).

Clinical features, comorbidities, and disease burden in adults with childhood-onset asthma

In adults with childhood-onset asthma, common symptoms include cough, wheeze, dyspnea, and chest tightness. These manifestations are typically episodic and exhibit diurnal variation. Symptoms are often exacerbated by exposure to triggers such as allergens, physical exertion, or viral infections, and generally improve with trigger avoidance or appropriate asthma therapy (25-27).

Regarding asthma control, differences among patients with different ages of onset were reported. Patients with adult-onset asthma had significantly more uncontrolled asthma than subjects with childhood-onset asthma (28).

In patients with childhood-onset asthma, apart from respiratory symptoms, the presence of co-morbidities is also common. Regarding atopic comorbidities, the prevalence was reported to be higher among childhood-onset asthma (45%) and was lower among adult-onset (35%) and in late-onset asthma (25%) (28). For nasal polyposis, it was more common among late-onset asthma than childhood-onset asthma. Compared with patients without asthma, patients with childhood-onset asthma were reported to have increased risks of obesity, diabetes mellitus, hypertension, cardiovascular diseases, rheumatoid arthritis, osteoarthritis and cancer (5). Alternatively, when patients with childhood-onset and adult-onset asthma were compared, patients with childhood-onset asthma were associated with lower risks of obesity, hyperlipidemia and osteoarthritis (5). Regarding lung function parameters and airway inflammatory parameters by FeNO, there were no significant difference in childhood-onset and adult-onset asthma (5). The study also suggested that adult-onset asthma is associated with slightly greater severity of major depressive disorder (29).

Beyond its clinical consequences, the socio-economic burden of childhood-onset asthma should also be recognized. A prospective cohort study indicated that childhood-onset asthma may adversely affect long-term educational attainment in early adulthood (30). This Swedish study found that individuals with childhood-onset asthma were more likely to have only completed compulsory education as their highest level of education by 28 years of age (30).

Diagnosis, including newer diagnostic tools

Standard methods for diagnosing asthma

The diagnosis of asthma should be established based on characteristic symptom patterns, objective evidence of variable airflow limitation and airway inflammation, careful exclusion of alternative diagnoses, and a documented response to appropriate therapy (11,12). Clinical history is the foundation of diagnosis of asthma, focusing on the pattern of respiratory symptoms like wheeze, cough and shortness of breath, precipitating factors and known risk factors (7).

Apart from clinical history, the GINA recommends the use of lung function tests, either peak expiratory flow (PEF) or spirometry, in the diagnosis of asthma in patients over 5 years (12). It is recommended that this be undertaken if the diagnosis of asthma has not been previously confirmed. PEF can be used to detect diurnal variation, which is a typical feature of asthma. Spirometry aims to assess airflow obstruction and reversibility (6). Asthma typically presents as an obstructive pattern with a significant bronchodilator reversibility. Objective testing should be repeated if there is poor response to treatment or diagnostic uncertainty (11).

Diagnosing preschool wheeze and asthma: evidence and challenges

Diagnosing asthma in children aged 5 years and younger is particularly challenging because objective measures like spirometry cannot be reliably performed. Historically, classifications like “episodic wheeze” (viral-induced) and “multiple-trigger wheeze” (persistent) were used, but their clinical utility is limited, and they can only be reliably assigned retrospectively (6).

The GINA 2025 guidelines have undergone extensive review for this age group, confirming that a diagnosis can be made. It recommends moving away from rigid wheeze phenotypes (e.g., “episodic viral” vs. “multiple-trigger”) and instead uses a probability-based clinical assessment for preschool children with recurrent wheeze. This approach integrates the pattern of symptoms, response to therapy, and exclusion of alternative diagnoses (12).

Key diagnostic criteria: the diagnosis should be considered when all of the following are present—

• Recurrent acute wheezing episodes: defined as at least two documented acute wheezing episodes within the preceding 12 months, or one acute wheezing episode accompanied by interval asthma-like symptoms (e.g., dry cough, paroxysmal coughing, nocturnal symptoms, or symptoms triggered by laughing, crying, or physical activity). At least one episode should be confirmed by a healthcare professional or reliably described by a caregiver.
• Exclusive of other likely alternative diagnosis except for a concurrent viral respiratory infection.
• Timely clinical response to asthma therapy: demonstrated improvement in respiratory symptoms and/or clinical signs within 20–60 minutes following administration of a short-acting β₂-agonist (SABA) during an acute episode, or improvement observed during a 2–3 month diagnostic trial of daily inhaled ICS with as-needed SABA.

The GINA 2025 update provides a structured, evidence-based framework for diagnosing asthma in preschool children, focusing on clinical patterns, exclusion of other causes, and response to therapy, while discouraging reliance on retrospective phenotypes and emphasizing ongoing assessment and safety.

Newer diagnostic tools for preschool and school-age children

FeNO measurement is used to detect and quantify eosinophilic airway inflammation, with elevated levels suggesting a T2-high asthma phenotype (11). The European Respiratory Society (ERS) task force strongly recommends incorporating FeNO testing into the diagnostic evaluation of children aged 5–16 years with suspected asthma (strong recommendation, moderate quality evidence) (31). In symptomatic children, a FeNO level ≥25 ppb should be regarded as supportive of an asthma diagnosis. Among patients with characteristic asthma symptoms, higher FeNO values (children: >35 ppb) are associated with an increased risk of exacerbations and a favorable response to ICS (13). However, FeNO may also be elevated in conditions other than asthma, and low values do not exclude the diagnosis (12,32).

Forced oscillation technique (FOT)/impulse oscillometry (IOS) is an effort-independent method for preschool children who cannot perform spirometry (12). It measures airway resistance via sound waves during tidal breathing (33). Additionally, intrabreath variations in oscillometric indices may offer further insights beyond conventional parameters; in preschoolers, these measures have been shown to enhance the detection of acute airway obstruction and to differentiate recurrent wheezers from healthy controls (34).

The latest ERS technical standards propose cut-off values for a significant bronchodilator response (BDR) based on oscillometric indices derived from studies in healthy adults and children, including a 40% reduction in resistance at 5 Hz (Rrs5), a 50% increase in reactance at 5 Hz (Xrs5), and an 80% decrease in area under the reactance curve (AX) relative to baseline (35). Several studies have demonstrated that BDR assessed using oscillometric parameters more effectively distinguishes children with asthma from healthy controls compared with BDR defined by forced expiratory volume in 1 second (FEV₁) (36,37). Emerging evidence further suggests that oscillometry-based BDR measurements are reproducible across different devices and populations (38). Despite this robustness, systematic reviews reveal considerable heterogeneity among oscillometric reference equations, especially between populations of different ethnic backgrounds and age groups (39-41). Device-specific and population-specific reference values are often necessary, as equations developed in one group (e.g., Caucasians) may not be directly applicable to others, such as Asian populations. Current evidence supports the use of oscillometry as a complementary tool, but further large-scale, multi-ethnic studies are needed to refine BDR thresholds and develop reference formulas tailored to local populations (42).

Diagnosis of childhood-onset asthma in adults

Similarly in adults, the most frequently used diagnostic tool is spirometry that assesses FEV₁, forced vital capacity (FVC) and bronchodilator reversibility (43). Bronchoprovocation testing can also be considered in diagnosing asthma in patients with normal baseline spirometry (44).

FeNO can also be used in detecting eosinophilic airway inflammation associated with asthma which also demonstrated a negative correlation with the FEV₁, FEV₁/FVC ratio, and a positive correlation with bronchodilator reversibility, as well as with blood eosinophil levels (45). According to the American Thoracic Society Clinical Practice Guideline for interpretation of FeNO, a value below 25 ppb in adults implies the absence of eosinophilic airway inflammation. A FeNO greater than 50 ppb in adults suggests eosinophilic airway inflammation (32,46). But it is important to note the factors that could affect FeNO results, such as age, sex, height, atopy, and cigarette smoking (47-49). FeNO values have been shown to be able to predict which patients will respond to ICS treatment (50). FeNO values can also be used to dictate biologics treatment, especially dupilumab (51).

Blood test including blood eosinophil count and serum IgE levels are also important in asthma diagnosis and management. They can also determine if certain biologics are suitable for severe asthma (52,53). Other blood tests to consider include allergen-specific IgE by enzyme-linked immunosorbent assays (ELISA). Alternative way to test for allergens is allergy skin test, which can be done by prick and intradermal techniques. Allergy testing can assist in confirming sensitization to suspected allergic triggers of respiratory symptoms, guiding ongoing asthma management, and evaluating eligibility for biologic therapies such as omalizumab.

Treatment updates

Effective management includes pharmacological interventions, non-pharmacological strategies, and self-management practises.

Pharmacological management of childhood asthma

The pharmacological treatment of childhood asthma is structured around two key components: maintenance therapy for long-term control and reliever therapy for acute symptom management. Maintenance therapy, primarily consisting of ICS or ICS and long-acting bronchodilators (LABAs), forms the foundation of asthma management, with the ultimate goal of minimising reliance on reliever medications. The reliever therapy is typically SABA.

The management of chronic asthma has undergone significant refinement in the GINA guideline since 2019 and the British Thoracic Society (BTS), Scottish Intercollegiate Guidelines Network (SIGN), and National Institute for Health and Care Excellence (NICE) 2024. Notably, SABA monotherapy is no longer advised for those over five years of age due to its association with increased asthma-related mortality. Instead, combination therapy with ICS and SABA is now the preferred initial approach. For children aged six and above, symptom-driven SABA couples with ICS use has been shown to be as effective as daily ICS administration in preventing exacerbations while reducing cumulative corticosteroid exposure. An emerging development in asthma pharmacotherapy is the use of Single Maintenance and Reliever Therapy (SMART) inhalers, which combine ICS and fast-acting LABAs (e.g., formoterol) in a single device. These inhalers have demonstrated efficacy in reducing exacerbation rates, improving lung function, and decreasing reliance on additional reliever medication. SMART inhalers can be considered for adolescents (12 years and older), especially for adolescent who have compliance issues with regular maintenance therapy. For children with severe asthma unresponsive to conventional therapies, biologic agents targeting specific inflammatory pathways (e.g., anti-IgE, anti-IL-5) offer a promising treatment option. However, their use is restricted to specialist care due to cost implications and the need for precise patient selection (12).

Chronic asthma management in adolescents and adults (12+ years)

For patients aged 12 years and above, both guidelines strongly advocate for ICS-formoterol-based strategies, but with key differences in implementation. BTS introduces a flexible stepwise approach, starting with as-needed ICS-formoterol [anti-inflammatory reliever (AIR) therapy] for mild asthma, escalating to maintenance and reliever therapy (MART) if symptoms persist, and then to higher-dose MART or add-on therapies [leukotriene receptor antagonists (LTRA)/long-acting muscarinic antagonists (LAMA)] if needed. A major divergence occurs in moderate asthma (Step 3), where BTS prioritizes MART escalation, while GINA offers three equally valid options: low-dose ICS-LABA or MART with low-dose ICS-formoterol. According to GINA recommendations, for all patients, low-dose ICS combined with formoterol as both MART was proposed, which is also called the Track 1 in GINA recommendations (54). Track 2 was also proposed which include ICS and SABA to be taken together as needed as the step 1 of the treatment ladder. In track 2, step 2 involves maintenance low-dose ICS. When the asthma remains uncontrolled with escalating dose of LABA/ICS, LAMA can also be added, which was shown to reduce exacerbations, increase asthma control, and improve quality of life (QoL) in patients who were already treated with LABA/ICS. LAMA also has a good safety profile (55). This reflects GINA’s recognition of varying patient phenotypes and preferences, whereas BTS follows a more linear escalation (Table 2) (12,56).

Key clinical implications and practical considerations

The BTS guidelines provide a pragmatic approach, particularly in primary care, where transitioning patients from SABA-based regimens may be challenging. By allowing SABA + ICS in children and retaining flexibility in adults, BTS acknowledges real-world constraints, such as drug availability, cost, and patient adherence. GINA’s stance on SABA elimination may be more suitable for settings with robust ICS-formoterol access but could pose implementation challenges in resource-limited environments.

Both guidelines indicate a paradigm shift towards an anti-inflammatory-focused approach to asthma management. Clinicians must consider patient-specific factors—particularly for paediatric patients—such as inhaler education and regular re-assessment to ensure competence in using the ICS-formoterol inhaler, as well as local drug availability and healthcare system constraints when applying these guidelines. Future research should concentrate on real-world outcomes, such as exacerbation rates, adherence patterns, growth impacts, and carers’ and patients’ QoL—ensuring benefits translate beyond clinical trials into daily life.

In recent years, the development of biologics also revolutionizes the asthma management paradigm. In general, severe asthma patients who experience frequent exacerbations, have poor symptom control or are oral corticosteroids (OCS)-dependent should be considered for further biologic therapy (Table 3) (53). Currently approved biologic therapies for asthma target immunoglobulin E, IL-5/IL-5Rα, IL-4Rα and thymic stromal lymphopoietin. These agents have demonstrated efficacy in reducing exacerbation rates, decreasing healthcare resource utilization (HCRU), lowering maintenance oral corticosteroid (mOCS) requirements, and improving QoL (52). Biologic agents are now approved for use in children as young as 6 years, with tezepelumab available for those aged 12 and above. The choices of biologics rely on the phenotype as determined by biomarkers such as blood eosinophil count, FeNO, IgE level; co-morbidities such as atopic dermatitis, eosinophilic esophagitis, chronic rhinosinusitis with nasal polyposis and the need for mOCS (57). Currently, omalizumab (anti-IgE), mepolizumab (anti-IL5), and dupilumab (anti-IL4 and anti-IL13) are approved for use in children from age 6 to 12 years (6). Tezepelumab (anti-TSLP) is approved for severe asthma in patients aged ≥12 years (12). These illustrated the importance of phenotyping and co-morbidities assessment in asthma as it would impact the most appropriate treatment options for these patients.

Non-pharmacological management

Non-pharmacological management is important in asthma care, to complement pharmacological interventions to optimize control. Recent international and national guidelines—including those from the GINA, the National Asthma Education and Prevention Program (NAEPP)—emphasize a multifaceted approach. Key strategies include identification and mitigation of environmental triggers (such as allergens, air pollutants, and tobacco smoke), patient and caregiver education, and regular assessment and review of asthma control. Allergen avoidance is recommended for patients with known sensitivities, with interventions tailored to individual exposures and needs (58). Multicomponent, home-based interventions targeting multiple triggers (such as dust mites, pests, and mold) are effective in reducing asthma exacerbations, improving QoL, and decreasing healthcare utilization (59). Education on asthma pathophysiology, inhaler technique, and adherence is fundamental, as poor technique and non-adherence are common barriers to effective management (12). Self-management education—including the development and use of written personalized asthma action plan (PAAPs)—is strongly advocated. Studies consistently show that a significant proportion of children with asthma do not receive or consistently use written action plans. In a large US national survey, only about half of children with asthma had ever received a PAAP by 2013, with disparities by race, insurance status, and preventive medication use (60). The National Review of Asthma Deaths (NRAD) in the UK identified the lack of PAAPs as a key factor in preventable childhood asthma deaths, highlighting the need for their routine implementation (61). However, real-world data show that only a minority of UK children consistently receive all recommended non-pharmacological interventions, including PAAPs, asthma reviews, and inhaler technique checks, despite evidence that these activities—especially when combined—significantly reduce asthma exacerbations (62). Recent research also explores digital formats for action plans to improve accessibility and adherence (63). Overall, non-pharmacological management—including environmental control, education, and especially the consistent use of asthma action plans—remains integral to effective asthma care and should be individualized, evidence-based, and regularly updated in line with evolving guidelines and patient needs, to ensure universal and coordinated implementation (64).

Long-term outcomes of childhood-onset asthma in adults

In a recently published 60-year follow-up study of adults with a history of severe childhood asthma, 89.7% of the patients still have a current diagnosis of asthma when they become adults, with 9.6% of all the participants having a Medical Research Council dyspnoea scale of ≥3 and 15.7% being treated in secondary care. The findings in this study suggest that patients with severe childhood asthma could have high chance of having asthma when they become adult (65). The lung function among those who have early-onset wheeze were also lower than those do not when they grow into adulthood. There were also subgroups of patients with persistent asthma, who had progressive declines in lung function and enter adulthood with even lower lung function.

In addition to persisting into adulthood, childhood-onset asthma may predispose individuals to the development of chronic obstructive pulmonary disease (COPD), specifically the COPD-A subtype. A Danish study reported that 13% of adults with a history of severe childhood asthma developed COPD-A. Compared with individuals without airflow limitation, those with COPD-A experienced worse clinical outcomes over the preceding 12 months. When compared with patients with smoking-related COPD-C subtype, the COPD-A group demonstrated higher FeNO levels. Furthermore, individuals with COPD-A had an increased risk of comorbidities, including osteoporosis and depression. Among patients with COPD-A, those with a smoking history of fewer than 10 pack-years exhibited better pulmonary function, higher body mass index (BMI), lower erythrocyte sedimentation rate (ESR), and a lower prevalence of osteoporosis. Notably, inhaled ICS use did not reduce exacerbation rates in this population.

Other than COPD, other co-morbid conditions can also be present in childhood-onset asthma, including allergic rhinitis, eczema, hypertension and cataracts. Childhood-onset asthma should not be considered as a sole disease but a condition that will have dynamic evolution over time and associated with other medical conditions.

Conclusions

Childhood-onset asthma represents a distinctive asthma phenotype which has different clinical features as adult-onset asthma. The evolution of childhood-onset asthma upon growing up differs in different patients and various clinical markers and genetic changes have been proposed which can mediate these differences. With the advances in diagnostics and therapeutics for asthma, further stratification of childhood-onset asthma into distinctive subgroups may be warranted which can help to determine the most suitable treatment option for the patients.

Acknowledgments

None.

Footnote

Peer Review File: Available at https://tp.amegroups.com/article/view/10.21037/tp-2025-aw-823/prf

Funding: None.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tp.amegroups.com/article/view/10.21037/tp-2025-aw-823/coif). W.C.K. serves as an unpaid editorial board member of Translational Pediatrics from August 2025 to July 2027. The other authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

References

1. Global, regional, and national burden of asthma and atopic dermatitis, 1990-2021, and projections to 2050: a systematic analysis of the Global Burden of Disease Study 2021. Lancet Respir Med 2025;13:425-46.
2. Pividori M, Schoettler N, Nicolae DL, et al. Shared and distinct genetic risk factors for childhood-onset and adult-onset asthma: genome-wide and transcriptome-wide studies. Lancet Respir Med 2019;7:509-22. [Crossref] [PubMed]
3. Fuchs O, Bahmer T, Rabe KF, et al. Asthma transition from childhood into adulthood. Lancet Respir Med 2017;5:224-34. [Crossref] [PubMed]
4. Zaied RE, Gokuladhas S, Walker C, et al. Unspecified asthma, childhood-onset, and adult-onset asthma have different causal genes: a Mendelian randomization analysis. Front Immunol 2024;15:1412032. [Crossref] [PubMed]
5. Mendy A, Mersha TB. Comorbidities in childhood-onset and adult-onset asthma. Ann Allergy Asthma Immunol 2022;129:327-34. [Crossref] [PubMed]
6. Pijnenburg MW, Frey U, De Jongste JC, et al. Childhood asthma: pathogenesis and phenotypes. Eur Respir J 2022;59:2100731. [Crossref] [PubMed]
7. Lizzo JM, Goldin J, Cortes S, et al. Pediatric Asthma (Nursing) [Updated 2024 May 4]. In: StatPearls. Treasure Island (FL): StatPearls Publishing; 2026.
8. Licari A, Castagnoli R, Brambilla I, et al. Asthma Endotyping and Biomarkers in Childhood Asthma. Pediatr Allergy Immunol Pulmonol 2018;31:44-55. [Crossref] [PubMed]
9. Brusselle GG, Koppelman GH. Biologic Therapies for Severe Asthma. N Engl J Med 2022;386:157-71. [Crossref] [PubMed]
10. Fahy JV. Type 2 inflammation in asthma--present in most, absent in many. Nat Rev Immunol 2015;15:57-65. [Crossref] [PubMed]
11. Martin J, Townshend J, Brodlie M. Diagnosis and management of asthma in children. BMJ Paediatr Open 2022;6:e001277. [Crossref] [PubMed]
12. Global Strategy for Asthma Management and Prevention. 2025 GINA Strategy Report, 2025. Available online: https://ginasthma.org/2025-gina-strategy-report/
13. Conrad LA, Cabana MD, Rastogi D. Defining pediatric asthma: phenotypes to endotypes and beyond. Pediatr Res 2021;90:45-51. [Crossref] [PubMed]
14. To T, Gershon A, Wang C, et al. Persistence and remission in childhood asthma: a population-based asthma birth cohort study. Arch Pediatr Adolesc Med 2007;161:1197-204. [Crossref] [PubMed]
15. Vonk JM, Postma DS, Boezen HM, et al. Childhood factors associated with asthma remission after 30 year follow up. Thorax 2004;59:925-9. [Crossref] [PubMed]
16. Bergeron C, Tulic MK, Hamid Q. Airway remodelling in asthma: from benchside to clinical practice. Can Respir J 2010;17:e85-93. [Crossref] [PubMed]
17. Tsukioka K, Toyabe S, Akazawa K. Risk factors for persistent and relapsed childhood-onset asthma. Arerugi 2010;59:699-705.
18. Henderson J, Granell R, Heron J, et al. Associations of wheezing phenotypes in the first 6 years of life with atopy, lung function and airway responsiveness in mid-childhood. Thorax 2008;63:974-80. [Crossref] [PubMed]
19. Depner M, Fuchs O, Genuneit J, et al. Clinical and epidemiologic phenotypes of childhood asthma. Am J Respir Crit Care Med 2014;189:129-38. [Crossref] [PubMed]
20. Stern DA, Morgan WJ, Halonen M, et al. Wheezing and bronchial hyper-responsiveness in early childhood as predictors of newly diagnosed asthma in early adulthood: a longitudinal birth-cohort study. Lancet 2008;372:1058-64. [Crossref] [PubMed]
21. Tai A, Tran H, Roberts M, et al. Outcomes of childhood asthma to the age of 50 years. J Allergy Clin Immunol 2014;133:1572-8.e3. [Crossref] [PubMed]
22. Andersson M, Hedman L, Bjerg A, et al. Remission and persistence of asthma followed from 7 to 19 years of age. Pediatrics 2013;132:e435-42. [Crossref] [PubMed]
23. Murphy TM, Wong CC, Arseneault L, et al. Methylomic markers of persistent childhood asthma: a longitudinal study of asthma-discordant monozygotic twins. Clin Epigenetics 2015;7:130. [Crossref] [PubMed]
24. Izadi N, Baraghoshi D, Curran-Everett D, et al. Factors Associated with Persistence of Severe Asthma from Late Adolescence to Early Adulthood. Am J Respir Crit Care Med 2021;204:776-87. [Crossref] [PubMed]
25. El-Saify MY, Shaheen MA, Sabbour SM, et al. Nocturnal attacks, emergency room visits and ICU admission of pediatric asthma: frequency and associated factors. J Egypt Public Health Assoc 2008;83:353-67.
26. Fagnano M, Bayer AL, Isensee CA, et al. Nocturnal asthma symptoms and poor sleep quality among urban school children with asthma. Acad Pediatr 2011;11:493-9. [Crossref] [PubMed]
27. Aaron SD, Vandemheen KL, FitzGerald JM, et al. Reevaluation of Diagnosis in Adults With Physician-Diagnosed Asthma. JAMA 2017;317:269-79. [Crossref] [PubMed]
28. Baan EJ, de Roos EW, Engelkes M, et al. Characterization of Asthma by Age of Onset: A Multi-Database Cohort Study. J Allergy Clin Immunol Pract 2022;10:1825-1834.e8. [Crossref] [PubMed]
29. Faruqui Z, Thakker Z, Parveen D, et al. Depression in Childhood Asthma vs. Adult-Onset Asthma: A Cross-Sectional Study from the National Health and Nutrition Examination Survey (NHANES). Children (Basel) 2022;9:1797.
30. Schyllert C, Andersson M, Backman H, et al. Childhood onset asthma is associated with lower educational level in young adults - A prospective cohort study. Respir Med 2021;186:106514. [Crossref] [PubMed]
31. Gaillard EA, Kuehni CE, Turner S, et al. European Respiratory Society clinical practice guidelines for the diagnosis of asthma in children aged 5-16 years. Eur Respir J 2021;58:2004173. [Crossref] [PubMed]
32. Khatri SB, Iaccarino JM, Barochia A, et al. Use of Fractional Exhaled Nitric Oxide to Guide the Treatment of Asthma: An Official American Thoracic Society Clinical Practice Guideline. Am J Respir Crit Care Med 2021;204:e97-e109. [Crossref] [PubMed]
33. Mochizuki H, Hirai K, Tabata H. Forced oscillation technique and childhood asthma. Allergol Int 2012;61:373-83. [Crossref] [PubMed]
34. Czövek D, Shackleton C, Hantos Z, et al. Tidal changes in respiratory resistance are sensitive indicators of airway obstruction in children. Thorax 2016;71:907-15. [Crossref] [PubMed]
35. King GG, Bates J, Berger KI, et al. Technical standards for respiratory oscillometry. Eur Respir J 2020;55:1900753. [Crossref] [PubMed]
36. Song TW, Kim KW, Kim ES, et al. Utility of impulse oscillometry in young children with asthma. Pediatr Allergy Immunol 2008;19:763-8. [Crossref] [PubMed]
37. Marotta A, Klinnert MD, Price MR, et al. Impulse oscillometry provides an effective measure of lung dysfunction in 4-year-old children at risk for persistent asthma. J Allergy Clin Immunol 2003;112:317-22. [Crossref] [PubMed]
38. Oostveen E, Boda K, van der Grinten CP, et al. Respiratory impedance in healthy subjects: baseline values and bronchodilator response. Eur Respir J 2013;42:1513-23. [Crossref] [PubMed]
39. Valach C, Wouters EFM, Ofenheimer A, et al. Oscillometry reference values for children and adolescents. ERJ Open Res 2024;10:00278-2024. [Crossref] [PubMed]
40. Deprato A, Ferrara G, Bhutani M, et al. Reference equations for oscillometry and their differences among populations: a systematic scoping review. Eur Respir Rev 2022;31:220021. [Crossref] [PubMed]
41. Gochicoa-Rangel L, Martínez-Briseño D, Guerrero-Zúñiga S, et al. Reference equations using segmented regressions for impulse oscillometry in healthy subjects aged 2.7-90 years. ERJ Open Res 2023;9:00503-2023. [Crossref] [PubMed]
42. Kaminsky DA, Simpson SJ, Berger KI, et al. Clinical significance and applications of oscillometry. Eur Respir Rev 2022;31:210208. [Crossref] [PubMed]
43. Graham BL, Steenbruggen I, Miller MR, et al. Standardization of Spirometry 2019 Update. An Official American Thoracic Society and European Respiratory Society Technical Statement. Am J Respir Crit Care Med 2019;200:e70-88.
44. Park HW, Song WJ, Chang YS, et al. Bronchodilator response following methacholine-induced bronchoconstriction predicts acute asthma exacerbations. Eur Respir J 2016;48:104-14. [Crossref] [PubMed]
45. Kwok WC, Ip MSM, Tam TCC, et al. Correlation of FE(NO) With Spirometric Measurements and Blood Eosinophil Level in Patients With Severe Asthma. Clin Respir J 2025;19:e70094. [Crossref] [PubMed]
46. Dweik RA, Boggs PB, Erzurum SC, et al. An official ATS clinical practice guideline: interpretation of exhaled nitric oxide levels (FENO) for clinical applications. Am J Respir Crit Care Med 2011;184:602-15. [Crossref] [PubMed]
47. Collaro AJ, Chang AB, Marchant JM, et al. Developing Fractional Exhaled Nitric Oxide Predicted and Upper Limit of Normal Values for a Disadvantaged Population. Chest 2023;163:624-33. [Crossref] [PubMed]
48. Olin AC, Rosengren A, Thelle DS, et al. Height, age, and atopy are associated with fraction of exhaled nitric oxide in a large adult general population sample. Chest 2006;130:1319-25. [Crossref] [PubMed]
49. Travers J, Marsh S, Aldington S, et al. Reference ranges for exhaled nitric oxide derived from a random community survey of adults. Am J Respir Crit Care Med 2007;176:238-42. [Crossref] [PubMed]
50. Donohue JF, Jain N. Exhaled nitric oxide to predict corticosteroid responsiveness and reduce asthma exacerbation rates. Respir Med 2013;107:943-52. [Crossref] [PubMed]
51. Castro M, Corren J, Pavord ID, et al. Dupilumab Efficacy and Safety in Moderate-to-Severe Uncontrolled Asthma. N Engl J Med 2018;378:2486-96. [Crossref] [PubMed]
52. Gyawali B, Georas SN, Khurana S. Biologics in severe asthma: a state-of-the-art review. Eur Respir Rev 2025;34:240088. [Crossref] [PubMed]
53. Shah PA, Brightling C. Biologics for severe asthma-Which, when and why? Respirology 2023;28:709-21. [Crossref] [PubMed]
54. Aziz DA, Viquar W. Comparing Global Initiative for Asthma guideline approaches to asthma control in adolescents aged 12 and above. Monaldi Arch Chest Dis 2025; Epub ahead of print. [Crossref]
55. Mahay G, Zysman M, Guibert N, et al. Long-acting muscarinic antagonists (LAMA) in asthma: What is the best strategy? Respir Med Res 2025;87:101157. [Crossref] [PubMed]
56. British Thoracic Society (BTS). Scottish Intercollegiate Guidelines Network (SIGN). BTS/NICE/SIGN joint guideline on asthma: diagnosis, monitoring and chronic asthma management (November 2024) - summary of recommendations. Thorax 2025;80:416-24.
57. Israel E, Wechsler ME, Jackson DJ, et al. Anti-cytokine biologics for asthma in adults. Lancet 2025;406:2282-94. [Crossref] [PubMed]
58. Arshad SH, Bateman B, Sadeghnejad A, et al. Prevention of allergic disease during childhood by allergen avoidance: the Isle of Wight prevention study. J Allergy Clin Immunol 2007;119:307-13. [Crossref] [PubMed]
59. Cox NS, Dal Corso S, Hansen H, et al. Telerehabilitation for chronic respiratory disease. Cochrane Database Syst Rev 2021;1:CD013040. [Crossref] [PubMed]
60. Simon AE, Akinbami LJ. Asthma Action Plan Receipt among Children with Asthma 2-17 Years of Age, United States, 2002-2013. J Pediatr 2016;171:283-9.e1. [Crossref] [PubMed]
61. Levy ML, Fleming L, Warner JO, et al. Paediatric asthma care in the UK: fragmented and fatally fallible. Br J Gen Pract 2019;69:405-6. [Crossref] [PubMed]
62. Daines L, Morrow S, Wiener-Ogilvie S, et al. Understanding how patients establish strategies for living with asthma: a qualitative study in UK primary care as part of IMP(2)ART. Br J Gen Pract 2020;70:e303-11. [Crossref] [PubMed]
63. Beydon N, Taillé C, Corvol H, et al. Digital Action Plan (Web App) for Managing Asthma Exacerbations: Randomized Controlled Trial. J Med Internet Res 2023;25:e41490. [Crossref] [PubMed]
64. Khalaf Z, Saglani S, Bloom CI. Implementation and Effectiveness of Guideline-Recommended Clinical Activities for Children With Asthma: Population-Based Cohort. Chest 2025;167:665-74. [Crossref] [PubMed]
65. Savran O, Bønnelykke K, Ulrik CS. Characteristics of Adults With Severe Asthma in Childhood: A 60-Year Follow-Up Study. Chest 2024;166:676-84. [Crossref] [PubMed]