Asthma exacerbations account for approximately 5% of visits to Pediatric Emergency Departments (PED), a figure that rises to 15% during the autumn season⁽¹⁾. However, on­going controversy exists regarding the optimal treatment for moderate asthma exacerbations in the emergency setting^(2,3).

According to the most recent Spanish asthma guide­lines (GEMA 5.5, 2025), the recommended treatment for moderate asthma exacerbations in children consists of short-acting beta-2 agonists (SABA), such as salbutamol, combined with systemic corticosteroids. Ipratropium bro­mide (IB) is not included as part of the standard treatment protocol⁽²⁾. Furthermore, the Global Initiative for Asthma (GINA 2025) classifies IB as an optional adjunct thera­py (level B recommendation) for patients with moderate exacerbations, but its use is not mandatory⁽³⁾.

In this context, standardized treatment for moder­ate asthma exacerbations in our PED changed in 2021. Before 2021, moderate exacerbations were treated with oral glucocorticoids and inhaled bronchodilators (SABA and IB). After 2021, IB was no longer used as standardized treatment⁽⁸⁾.

The primary objective of this study was to analyze the impact of removing IB from the standardized management of moderate asthma exacerbations in our PED, with regard to hospitalization rates. Secondary objectives included comparing pulmonary scores (PS) at discharge, length of stay in the PED, and revisit rates.

A retrospective, single-center cohort study was con­ducted in the PED of a tertiary hospital with 60,000 an­nual visits.

Two cohorts were analyzed. Cohort 1 (September/2018– September/2019): patients received oral corticosteroids, salbutamol, and IB. Cohort 2 (September/2021–September/2022): patients received oral corticosteroids and salbu­tamol. Updated treatment guidelines were distributed among clinical staff. Data were obtained from electronic medical records. The study was approved by the institu­tional ethics committee.

All patients aged 6 to 16 years who visited the PED with moderate asthma exacerbation during the predefined study periods were included. Asthma exacerbation was defined as an episode characterized by dyspnea, respira­tory difficulty, chest tightness, cough, and wheezing. The pulmonary score (PS) was used to grade the severity of the exacerbation. A moderate asthma exacerbation was defined as a PS between 4 and 6 points and a peripheral oxygen saturation above 90%⁽²⁾.

Patients who did not receive treatment according to the protocol in place during each study period were excluded. Those who did not receive oral glucocorticoids or who had received nebulized bronchodilators were also excluded.

Statistical analysis was performed using IBM SPSS Sta­tistics version 25.0 (IBM Corp., Chicago, Illinois, USA). Quan­titative variables were expressed as median and interquartile range. Qualitative variables were expressed as percentages. The chi-square test was used for comparative analysis of qualitative variables, and the Mann-Whitney U test was used for quantitative variables. A multivariate logistic regres­sion model was performed to assess possible associations between variables and predictors of hospitalization. Results with p < 0.05 were considered statistically significant.

A total of 424 patients were initially selected, of whom 73 were excluded. The final sample included 351 patients: 174 (49.6%) in Cohort 1 and 177 (50.4%) in Cohort 2 (Figure 1). Baseline characteristics of both cohorts are shown in Table 1.

No significant differences were observed in hospitaliza­tion rates between Cohort 1 (15 patients, 8.6%) and Cohort 2 (7 patients, 4%) (p = 0.07). There were also no significant differences in PS at discharge (0.78 points [SD 0.85] in Cohort 1 vs. 0.92 points [SD 0.79] in Cohort 2; p = 0.137), length of stay in the PED (2.33 h [SD 0.66] vs. 2.33 h [SD 0.85]; p = 0.207), or revisit rates (14.5% vs. 7.9%; p = 0.052).

In the multivariable analysis, not using IB was not associated with an increased risk of hospitalization (Table 2). However, an altered PAT score during the first evaluation, previous hospital admissions, and a family his­tory of asthma were associated with a higher hospitaliza­tion risk (Table 2).

Our study analyzes the impact of excluding IB from the standardized treatment of moderate asthma exacer­bations. The findings indicate that the use of IB did not influence hospitalization rates, PS at discharge, length of stay, nor revisit rates.

Evidence regarding the use of IB in moderate asthma exacerbations has evolved. Some studies⁽⁴⁾ reported reduced hospitalization rates when IB was added to short-acting beta agonists in moderate or severe exac­erbations, whereas others^(5,6,7) found no benefit of IB use in moderate cases. These findings are consistent with our results and support the most recent national and interna­tional recommendations^(2,3).

In our research, we did not observe differences in PS scores at discharge. Previous studies^(8,9) reported non-significant clinical improvements with the addition of IB in moderate asthma exacerbations. Iramain et al.⁽⁵⁾ suggest­ed benefits in respiratory parameters (oxygen saturation, pulmonary score, %FEV1, and %PEF), mainly in severe exacerbations.

Other studies ^(10–12) have focused on the impact of add­ing IB on hospital length of stay, showing that IB does not reduce admission duration. However, no prior liter­ature exists regarding its impact on PED length of stay. In our study, we did not observe differences between cohorts for this outcome. Additionally, unlike previous literature, our study evaluated revisit rates and found no significant differences. Only Cooper et al.⁽⁴⁾ reported that IB does not appear to reduce the risk of recurrent asthma exacerbations.

Multiple factors increase the risk of hospitalization among children presenting to the PED with moderate asth­ma exacerbation, such as exposure to environmental pol­lutants, previous hospitalizations for asthma exacerbations, or greater severity of symptoms on arrival⁽¹⁴⁾. In our study, Cohort 1 showed a proportionally higher, although non-significant, number of hospitalizations. In multivari­able analysis, this increase was not associated with IB use, but rather with the presence of respiratory distress on initial PAT assessment. It was also associated with prior hospitalization episodes, consistent with the literature⁽¹⁵⁾.

This study has several limitations. Its retrospective and single-center design may introduce selection and infor­mation bias, limiting the generalizability of findings. The study was conducted two years after the change in treat­ment protocol; therefore, other uncontrolled factors (e.g., environmental exposures) may have influenced results. Additionally, the impact of the COVID-19 pandemic during the second study period cannot be fully excluded. Finally, the analysis was limited to short-term outcomes, with no long-term follow-up.

Despite its limitations, the clearly defined inclusion criteria and relatively large sample size support its inter­nal validity. The results reinforce current recommendations and clarify the limited role of IB in moderate asthma ex­acerbations. Avoiding routine IB use may reduce adverse effects⁽¹³⁾ and simplify treatment. Although the findings provide useful clinical information, they may not be gen­eralizable to all settings and should be interpreted with caution. Prospective, randomized, multicenter studies are needed to confirm these results.

In conclusion, ipratropium bromide does not appear to provide additional benefit in moderate asthma exacerba­tions. Treatment with salbutamol and corticosteroids alone is effective and aligned with current guidelines.

Ethical statement

This study was approved by the hospital’s Ethics and Clinical Research Committee in September 2022.

Conflicts of interest and funding sources

All authors declare no conflicts of interest related to the manuscript, including financial, consulting, institutional, or other relationships that could create bias or conflict of interest.

Meetings where the work was presented

The study was presented as an oral communication at the XXVII Meeting of the Spanish Society of Pediatric Emergency Care in May 2023.

The investigation was conducted in accordance with the ethical standards outlined in the 1964 Declaration of Helsinki and its subsequent amendments, or comparable ethical guidelines.

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