Dear editor,

I read with curiosity the remarkable article of Mallol et al.¹ aiming at determining the performance of commonly used tests for asthma diagnosis – that is, spirometry, bronchodilator responsiveness (BDR) to salbutamol, methacholine challenge test, and fractional exhaled nitric oxide (F_eNO) to validate the diagnosis of asthma in children. I acknowledge the authors for their captivating idea, and I agree with their conclusion that “spirometry, BDR, and F_eNO have a poor performance to corroborate asthma diagnosis in children.” However, in the methodology section of the aforementioned article,¹ three points related to the bronchodilator test caught my intention.

1. Mallol et al.¹ have defined the positive BDR as ≥12% increase from baseline in forced expiratory volume in 1 s (ΔFEV_1%B), and they have argued their choice by citing as a reference the 2005 task force published by the American thoracic and the European respiratory societies (ATS/ERS).² The approach of Mallol et al.¹ is practical but “debatable.” In fact, according to the ATS/ERS,² a positive BDR (regardless of the age) is a ΔFEV_1%B ≥ 12% and a ΔFEV_1AC (absolute change) ≥200 mL and/or an increase from baseline in forced vital capacity (ΔFVC_%B) ≥12%, and a ΔFVC_AC ≥200 mL. Consequently, Mallol et al.¹ “omitted” to express the FEV₁ BDR as an increase in Δ_AC, and to evaluate an important spirometric datum (i.e., FVC). Notwithstanding its huge use in real-life clinical situation, Δ_%B presents two key limitations.³ On one hand, Δ_%B reveals sex- bias and size-bias in evaluating BDR.³ On the other hand, patients with the highest basal FEV₁ displayed the smallest ΔFEV_1%B.³ The approach of Mallol et al.¹ to “omit” ΔFEV_1AC is realistic, since ΔFEV_1AC exhibits some correlations to age and height, and its changes are greater in tall children than in short ones.³ In children, some scholarly societies^2,4 still indorse one spirometric standardized and reproducible datum (i.e., FVC) for at least two reasons. First, FVC provides useful information about peripheral airways function and lung hyperinflation/air trapping.^5,6 Secondly, a decrease in FVC is linked to an increase in air trapping.⁵ Again, the choice of Mallol et al.¹ to “omit” changes in FVC is reasonable since the discrepancy between the flow and the volume impacts on BDR is partially comprehended.⁷

2. The global initiative for asthma (GINA)⁸ recommends to report FEV₁ change to the predicted value derived from spirometric norms (Δ_%PV). Contrary to the two previous BDR expressions (i.e., Δ_%B, Δ_%AC), Δ_%PV presents one main merit. It permits the comparison of children irrespective of their height [in the Chilean study,¹ the 95% confidence interval of height was huge, equal to 102–120 cm]. Once more, the approach of Mallol et al.¹ to “omit” Δ_%PV is convincing since its use is a bit difficult in daily practice (e.g., it cannot be applied in some countries where spirometric norms are missing).

3. The definition adopted by Mallol et al.¹ (i.e., ΔFEV_1%B ≥ 12%) is the one advanced by the British thoracic society (BTS).⁹ This choice is understandable. In fact, several scholarly societies^2,4,8–11 failed to standardize the expression of BDR in children. Table 1 exposes certain definitions of a “clinically significant” BDR adopted by some scholarly societies. In future studies, the following three questions related to the BDR in children should be treated: (i) which datum/data should be analyzed (FEV₁, FVC, peak expiratory flow)? (ii) which BDR expression mode should be used (Δ_AC, Δ_%B, Δ_%PV)? and (iii) which thresholds should be applied (12%, 20%, and 200 mL)? In adults, the issue related to which BDR definition should be applied was largely addressed.^12–15 In children with asthma, the question related to which BDR definition should be applied is still under debate.¹⁶

To conclude, the lack of a clear consensus about the BDR in children is a source of confusion for pediatricians, and can hinder asthma diagnosis. Therefore, it is high time for the scholarly societies to standardize the BDR in pediatric populations.