Letter to the Editor

It is high time for the scholarly societies to standardize the bronchodilator responsiveness in children

Helmi Ben Saad*

Heart Failure (LR12SP09) Research Laboratory, Farhat HACHED Hospital of Sousse, University of Sousse, Sousse, Tunisia

Key words: ATS/ERS, bronchodilator reversibility, FEV1, FVC, GINA, spirometry

*Corresponding author: Helmi Ben Saad (M.D., Ph.D.). Laboratory of Physiology, Faculty of Medicine of Sousse, Street Mohamed KAROUI, Sousse 4000, Tunisia. E-mail address: [email protected]

DOI: 10.15586/aei.v49i2.98

Received 3 January 2021; Accepted 4 January 2021; Available online 1 March 2021

Copyright: Saad HB
License: This open access article is licensed under Creative Commons Attribution 4.0 International (CC BY 4.0).

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 (FeNO) 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 FeNO 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 (ΔFEV1%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 ΔFEV1%B ≥ 12% and a ΔFEV1AC (absolute change) ≥200 mL and/or an increase from baseline in forced vital capacity (ΔFVC%B) ≥12%, and a ΔFVCAC ≥200 mL. Consequently, Mallol et al.1 “omitted” to express the FEV1 BDR as an increase in ΔAC, 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 ΔFEV1%B.3 The approach of Mallol et al.1 to “omit” ΔFEV1AC is realistic, since ΔFEV1AC exhibits some correlations to age and height, and its changes are greater in tall children than in short ones.3 In children, some scholarly societies2,4 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., ΔFEV1%B ≥ 12%) is the one advanced by the British thoracic society (BTS).9 This choice is understandable. In fact, several scholarly societies2,4,811 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 (ΔAC, 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.1215 In children with asthma, the question related to which BDR definition should be applied is still under debate.16

Table 1 Definitions of a “clinically significant” bronchodilator responsiveness adopted by some scholarly societies.

Scholarly society Reference Definition
GINA 10 ΔFEV1%PV > 12%
BTS 9 ΔFEV1%B ≥ 12%
GRAPP 8 ΔFEV1%B ≥ 12% or ΔPEF%B ≥ 20%
NAEPP 11 ΔFEV1%B ≥ 12% and ΔFEV1 > 200 mL
ATS–ERS 2 (ΔFEV1%B ≥ 12% and ΔFEV1 ≥ 200 mL) and/or (ΔFVC%B ≥ 12% and ΔFVC ≥ 200 mL)
SATS 4 (ΔFEV1%B ≥ 12% or ΔFEV1 > 200 mL) and/or (ΔFVC%B ≥ 12% or ΔFVC > 200 mL)

ATS: American thoracic society. B: basal value. BTS: British thoracic society. ERS: European respiratory society. FEV1: forced expiratory volume in 1 s. FVC: forced vital capacity. GINA: global initiative for asthma. GRAPP: research group on advances in pediatric pneumology. NAEPP: national asthma education and prevention program. PEF: peak expiratory flow. PV: predicted value. SATS: South African thoracic society.

Δ: after bronchodilator value – basal value. Δ%PV: 100 × Δ/Predicted value. Δ%IB: 100 × Δ/basal value.

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.

Competing interest

I report personal fees from Opalia Recordati and Chiesi.


This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.


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