Introduction: 

Acute asthma exacerbation is one of the most common causes of pediatric emergency department presentation which can lead to hospital admission, intensive care unit admission and ventilatory support if not treated in timely manner. In effective hospital systems, the timely administration of bronchodilators and systemic corticosteroids is a core indicator of high-quality emergency care.

Objectives: 

The goal of this review was to determine whether time-to-treatment is related to clinical outcomes in children presenting to an emergency department with acute asthma exacerbation (AAE). The review summarized the literature related to pre-hospital delay, emergency department (ED) workflow, guideline-concordant care and other system-wide interventions.

Methods:

A narrative review approach was utilized to synthesize evidence in pediatric acute asthma exacerbation from the literature describing pathophysiology, definitions of time-to-treatment, determinants of treatment delay and outcomes with early therapeutic intervention.

Results: 

Time-to-treatment, also termed as onset-to-treatment time, door-to-treatment time, and triage-to-drug time. The first group of delays may occur before arrival at the hospital, due to either recognition by caregivers, transport barriers, lack of access to care, or delays in the emergency department, due to either lack of bed space, triage delays, or physician-dependent ordering systems. Early administration of bronchodilators and corticosteroids, leads to improved clinical outcomes. For instance, it reduces the chance that the patient will need to be admitted to hospital. The use of nurse-initiated protocols, triage pathways, electronic alerts, and standardized emergency workflows may improve timely treatment delivery.

Conclusion:

Time-to-treatment is meaningful in the conclusion of the pediatric asthma emergency. The early identification, rapid triage, and speedier delivery of medicine may improve outcomes and lessen the strain on the health facility.

Asthma is the most common chronic pediatric disease treated in the emergency department (ED) (Martin et al., 2022). Rapid corticosteroid administration is associated with improved outcomes, but achieving this in a busy ED is challenging (Shipp et al., 2023). The primary aim was to decrease the time to corticosteroid administration in a pediatric ED (Reyes-Angel et al., 2022). An intervention was designed where bedside nurses initiated oral dexamethasone, replacing the previous system of physician-initiated orders for oral prednisone (Pijnenburg and Frey, 2022). The intervention showed improvement within two months and was sustained, with no unforeseen harm to patients. Children presenting with acute asthma exacerbations are treated with beta agonists and systemic corticosteroids, with doses varying based on weight and age (Brown et al., 2016). Severe asthma exacerbations requiring emergency visits and hospitalization are common in children aged 1-5 years (Donath et al., 2020).

Acute asthma exacerbations persist as a significant cause of pediatric morbidity despite advances in managing chronic asthma (Fainardi. et al., 2021). In young children, treatment delays compound the risk of adverse sequelae, including hospitalization, intensive care unit transfer, or mechanical ventilation (Øymar and Halvorsen, 2009). Exacerbations stem from a relatively consistent pathophysiological process, underscoring the urgency of early intervention (Robinson et al., 2022). Prompt treatment has been shown to improve important short-term clinical outcomes such as hospital admission and the need for intensive care (Kapri et al., 2023; Zhang et al., 2024). Dissecting the concept of time-to-treatment, its multiple definitions, determinants, and consequences, therefore constitutes a critical prerequisite for developing primary and secondary prevention strategies (Jones et al., 2022; Merhej and Zein, 2023).  Acute exacerbations of asthma involve a consistent pathophysiological sequence of events in children, sharing features with adults yet exhibiting distinctive characteristics that influence the time-to-treatment framework (Diaconu et al., 2024). The initiating mechanism for acute asthma is airway inflammation elicited by exposure to allergens or irritants (Plaza-González et al., 2022). A plethora of inflammatory cells, principally eosinophils, mast cells, and T-lymphocytes, are recruited to the airway epithelium, releasing numerous mediators that augment vascular permeability, stimulate mucus production, and provoke bronchospasm (Listyoko et al., 2024). Sustained bronchospasm and acute mucous plugging further exacerbate airflow limitation, facilitating the onset of respiratory distress (Andrenacci et al., 2022). If the episode is not resolved, hyperinflation and impaired gas exchange ensue due to a combination of secretions, bronchoconstriction, and wall edema (Jones et al., 2022; Zhang et al., 2024).

Acute asthma remains a leading cause of respiratory emergency visits and hospitalizations in children (Pijnenburg and Frey, 2022). Significant morbidity and mortality can result from untreated exacerbations as gas exchange becomes compromised, airway obstruction leads to ventilatory fatigue, and increased work of breathing escalates oxygen demand (Diaconu et al., 2024). Controlled studies indicate that early initiation of effective treatment, typically a fast-acting beta-agonist, but also systemic corticosteroids in moderate-to-severe cases, greatly improves the clinical trajectory and reduces the burden of acute exacerbations (Kapri et al., 2023). Although timely care is a pivotal element of guideline-concordant therapy, treatment delays for children presenting with acute asthma exacerbations are common. (Robinson et al., 2022; Zhang et al., 2024) In the literature, a variety of terms such as timeliness, time-to-treatment, or time-to-medication have been used to express the concept of treatment delay (McLoone et al., 2022). Specifically, the elapsed time between the onset of the acute exacerbation and the initiation of the first dose of rescue therapeutic medication is termed the onset-to-treatment interval (Nyenhuis et al., 2022). Within the emergency department setting, door in to treatment time refers to the period from arrival in the emergency department to the first dose of a rescue therapeutic medication (Zhang et al., 2024). Door-to-treatment time combines the pre-ambulance or pre-door intervals with the door in to treatment interval (Andrenacci et al., 2022; Jones et al., 2022). While all measures of time-to-treatment are meaningful, the methods used to estimate these intervals in individual studies show marked heterogeneity (Table 1. Operational definitions and measurement points for time-to-treatment metrics Gray et al., 2023) (table 1, figure 1).

Table 1: Operational definitions and measurement points for time-to-treatment metrics

Figure 1: Time-to-treatment framework from symptom onset to clinical outcome.

Before arriving at the ED, delays may accrue due to patient or caregiver recognition of a problem, patient transport to the facility, and either ED triage or subsequent waits due to crowding (Kramer et al., 2024). These pre-hospital and ED delays can potentially influence a patient’s clinical trajectory, prolong the overall ED visit, and increase health care resource utilization (Kramer et al., 2024). Pre-hospital and emergency department delays are also commonly cited contributory factors to poorer clinical outcomes following an acute exacerbation (Johnson et al., 2016). Recognizing that a breathing problem has arisen may take time (Homaira et al., 2020). The patient may have mild symptoms initially and possibly require several minutes to hours to recognize that symptoms have worsened sufficiently to warrant a visit to the ED (Braithwaite et al., 2025). This patient, subsequently transported to a facility within their local area, is then triaged on arrival (Braithwaite et al., 2025). Nevertheless, despite the relatively short distance from home to the ED, there remains the potential for greater than one hour of pre-hospital delay (Brown et al., 2016) (table 2).

Table 2: Determinants of treatment delay in children presenting with acute asthma exacerbation.

Pediatric asthma guidelines frequently emphasize the need for timely delivery of medication when patients experience acute symptoms (Brown et al., 2016). Prior work in adult emergency patients found a nonlinear association between time-to-treatment and clinical outcomes, suggesting that delayed therapy has increasingly detrimental effects when the time to treatment exceeds a critical threshold (Chaib et al., 2022; Lustberg et al., 2023). The consequences of therapeutic delays in children with asthma, particularly those influenced by age, severity, and comorbidity, remain largely unexplored (Boere et al., 2022; Janjigian et al., 2025).  Timeliness of medication delivery in children with acute asthma encompasses four distinct time-to-treatment metrics: onset-to-treatment, door-in to treatment intervals (Guo et al., 2023; Xia et al., 2026). Time-to-treatment factors influence disease trajectory, clinical status, and resource utilization during asthma exacerbations in both adult and pediatric populations (Mudzingwa et al., 2025; Kapatais et al., 2026). The location (home, emergency department) where medication is administered influences the urgency with which patients seek therapy (pre-hospital) and the elapsed time to receipt of the first therapeutic dose (emergency department delay) (Michalsen et al., 2024; Soni and Agrawal, 2025).

A reduced time-to-treatment for hospitalized children presenting with acute asthma exacerbations is associated with improved clinical outcomes, including lower likelihood of hospital admission, intensive care unit transfer, prolonged symptomatic periods, the need for invasive ventilatory support, and recurrent episodes within 30 days (Gray et al., 2023). Empirical investigations spanning various contexts, including the administration of bronchodilators for asthma, have described a dose–response relationship: shorter delays correlated with greater therapeutic benefits and diminished risk of adverse events (Tordoff et al., 2022; Liu et al., 2024). Analogous associations are evident even when the assessment framework is limited to drugs with clear physiological activity in the acute phase of the disorder (Kirolos et al., 2022). However, moving beyond such constraints is desirable, and explicit longitudinal modeling of different time-to-treatment dimensions is warranted (Jakimovski et al., 2022; Daníelsdóttir et al., 2024).  A consistent and urgent pharmacological intervention can radically alter the clinical trajectory in the first minutes that a child presents with an exacerbation of asthma (Ezeamii et al., 2024). Options include the administration of a rapid-acting β2 adrenergic agonist (Williams et al. 2022). Guidelines emphasize that bronchodilator therapy should be initiated as soon as the diagnosis of asthma is suspected (Gorgojo-Martínez, 2025). Prompt treatment is pivotal far beyond the immediate phase of the acute exacerbation (Mehta et al., 2023). For controlled asthmatic children, the indication for bronchodilator therapy is clear, even when pulmonary function testing is not available (Liu et al., 2024). Systemic corticosteroids are frequently recommended in combination with inhaled β2-adrenergic agonists. Additional investigations, including blood sampling, may be performed when clinically indicated to evaluate potential comorbidities or complications, without delaying asthma treatment (Kirolos et al., 2022; Daníelsdóttir et al., 2024) (table 3).

Table 3: Treatment timeliness and expected clinical impact in pediatric acute asthma care.

Every health-care system employs a variety of strategies dedicated to improving the quality of care for asthma exacerbations in children, which is crucial for limiting the impact of the disease on both individuals and society (Ezeamii et al., 2024). Such strategies can address the associations between pediatric acute asthma exacerbations and time-to-treatment (Williams et al., 2022). Improving treatment safety is already a key objective for numerous hospitals (Mehta et al., 2023). Four complementary strategies have been developed and can be relatively easily implemented across centers (Liu et al., 2024). The first three aim to enhance the timeliness of acute care for children at risk of serious or very serious asthma exacerbations (Brown et al., 2016). The final one targets the organizational workflow within the emergency department (Gorgojo-Martínez, 2025). Evaluating these strategies can allow administrators to establish suitable selection criteria based on urgency (Kirolos et al., 2022). The first strategy involves the introduction of a simple triage algorithm designed for children (Ezeamii et al., 2024). Its implementation has been associated with a significant decrease in time from arrival to first β-agonist administration (Gorgojo-Martínez, 2025). The second strategy consists of a protocol that allows standby bronchodilator therapy to be initiated by emergency personnel before the child enters the emergency department (Mehta et al., 2023). In a cohort of children experiencing acute asthma symptoms, the median time taken from the call for emergency help to the first bronchodilator treatment was 82 minutes for the patients subjected to a standby protocol, compared with 103 minutes for those without (Gorgojo-Martínez, 2025). The third strategy consists of an alert mechanism aimed at identifying children at high risk of serious or very serious exacerbations, so that they are attended to more rapidly (Gorgojo-Martínez, 2025). When the acute symptom score was employed to flag the most severely affected children at the first point of contact, a substantial reduction in the door-to-first treatment delay was achieved (Gorgojo-Martínez, 2025). Finally, the fourth strategy targets overall workflow organization within the emergency department, streamlining patient tracking and recording through dedicated administrative personnel and electronic systems (Liu et al., 2024).

The time-to-treatment interval for children with acute asthma exacerbations is influenced by patient-, family-, and socioeconomic-related determinants (Ezeamii et al.2024). These risk factors directly affect treatment delays and subsequently impact patient outcomes (Williams et al., 2022). Age, gender, prior asthma attacks, duration of asthma symptoms prior to an exacerbation, and other patient-level factors have been shown to affect pre-hospital time-to-treatment intervals (Green, 2015; Kirolos et al., 2022). Family-related socioeconomic status such as maternal education, caregiver perceived stress, lack of access to care, and insurance coverage can strongly influence time to treatment (Mehta et al., 2023; Liu et al., 2024). Child-specific characteristics such as young age, black race, severity of asthma, parental stress, and neighborhood-level factors have been shown to influence the time between exacerbation onset and systemic corticosteroid initiation (Williams et al., 2022; Daníelsdóttir et al., 2024).  Further complicating matters is the lack of standardization in how time-to-treatment metrics are defined and the methods used to obtain measurements (Ezeamii et al., 2024). Studies have ranged from including only pre-hospital time to more complex multi-scale attempts that fail to improve diagnostics or prove generalizable across institution types (Williams et al., 2022). These factors collectively serve to confound causal inference in the existing literature when modeling how delays impact time-to-treatment (Gorgojo-Martínez, 2025). Correctly identifying the dependencies present and when measurement occurs offers an opportunity to mitigate this issue by delineating exogenous specification from time-to-treatment and patient outcomes (Mehta et al., 2023) (table 4).

Table 4: Suggested variables for a future audit or observational study.

Research on time-to-treatment spans prospective and retrospective designs. Prospective investigations yield precise event timings, theoretically eliminating bias, yet may not enable sufficiently large sample sizes (Ezeamii et al., 2024). Retrospective assessments often rely on administrative or clinical data (Williams et al., 2022). These timelines  reflect clinically relevant intervals but are subject to confounding (Gorgojo-Martínez, 2025). Data clustering by hospital center can further obscure collective estimates (Mehta et al., 2023). Timing-misclassification risk is pronounced when analytic windows exceed a few hours (Gorgojo-Martínez, 2025). Although such temporal uncertainty routinely negotiates social and physical science, longitudinal time-to-treatment studies demanding interval measurement warrant methodical scrutiny (Gorgojo-Martínez, 2025). Timelines spanning six after-service hours may yield clinically indistinct mortality associations (Mehta et al., 2023). Uninvited attempts to quantify broad periods provoke skepticism (Gray et al., 2023). Event-time gap analyses abstractly signal timeliness, availability, or deviance without explicit remapping onto screening, intervention, or population intervals (Gray et al., 2023).

Children aged 0 to 5 years’ old who experience asthma exacerbations often find themselves in situations where they must rely on emergency care services (Gray et al., 2023). Prioritizing the duration of time that elapses between the onset of symptoms and the initiation of treatment could potentially enhance the delivery of evidence-based therapies (Ezeamii et al., 2024). This aspect deserves further detailed investigation and exploration within this particular population to ensure better health outcomes (Williams et al., 2022).  Two critical knowledge gaps regarding time-to-treatment in pediatric asthma that warrant further investigation are the efficacy of shorter intervals before and after care, specifically, during the prehospital phase as well as within the emergency department periods (Williams et al., 2022). Additionally, there exists an important question concerning the applicability of physiopathological insights that have already been identified in the broader literature surrounding asthma care and treatment (Mehta et al., 2023). Understanding the impact of timely interventions in these crucial timeframes remains essential for improving outcomes in pediatric patients suffering from asthma (Liu et al., 2024). 

In considering pediatric patients presenting with acute asthma, time-to-treatment is defined as the elapsed time from the onset of an exacerbation until the first dose of therapy is administered. During a child’s first acute asthma exacerbation, typically before the disease has been diagnosed and a treatment plan established, even the residual time following triage to initial drug delivery is considered time-to-treatment. For subsequent exacerbations, treatment guidelines specify maximum tolerable delays for various therapeutic interventions relative to symptom onset that reflect the increasing urgency of treatment as control of the condition declines and that are designed to optimize time-to-treatment. Features of the time-to-treatment interval such as the delay from entry to drug delivery or the onset to treatment time prior to arrival at the healthcare facility, expressed as minutes, are straightforward to capture. Out-of-hospital delay is usually estimated from caregiver-reported time of symptom onset to the first administration of rescue medication, along with a parental or outpatient provider report on precise onset, although inaccuracies may arise if the patient did not remain continuously symptomatic.The underlying pathophysiology of a pediatric acute asthma exacerbation in a child who has a pre-existing diagnosis consists of airway inflammation leading to bronchospasm, mucus plugging, and gas exchange impairment. The pathophysiologic events that accompany a pediatric acute asthma exacerbation, therefore, correspond with the urgency of delivering medical care, and the time-to-treatment interval should improve as timeliness of intervention increases.