Abstract
Spirometry forced expiratory time is weakly correlated to age and lung volume, but strongly correlated to airflow limitation that increases it. Consequently, it should significantly decrease in case of significant bronchial reversibility. https://bit.ly/3uG77nd
To the Editor:
Recent international recommendations on spirometry have removed the minimal expiratory time of 6 s as a criterion for full expiration (achievement of the true forced vital capacity (FVC) expiration) and replaced it by one of three other criteria [1]. The achievement of a 15 s duration expiration can be used, but in a paediatric setting it is the achievement of a 1 s plateau, or more frequently the third criterion, i.e. FVC within the repeatability tolerance of the maximum FVC of the set of blows, that are the most useful.
Because chest wall compliance is high in young children and the peak of airway growth precedes that of alveoli in adolescents, it was found that children often fail to expire for a period of 6 s [2, 3]. However, a short expiration manoeuvre always raises suspicion of a possible incomplete expiration, especially since the performance of an inspiratory capacity right after the forced expiration, in order to confirm the pre-forced-expiration inspiration up to total lung capacity (TLC), is also a difficult manoeuvre to achieve in children [1].
We hypothesised that in case of: 1) poor cooperation, forced expiratory time (FET) would have a tendency to be low at baseline and increase after bronchodilation (learning effect); and 2) good spirometry technique, FET would not depend on the expired volume but on the children's central airway patency and consequently, would increase with airflow limitation and decrease after significant bronchodilation.
To evaluate the relationships between FET in asthmatic children and age, expired volume and bronchodilation, we retrieved retrospectively all files of our lung function test department that encompassed spirometry performed in asthmatic patients with FET recorded at baseline and after bronchodilator (BD) between June 2018 and January 2021. In patients with plethysmography static volume measurements we distinguished and compared different baseline abnormal lung function patterns (low forced expiratory volume in 1 s (FEV1) to FVC ratio with normal TLC, i.e. airflow limitation (AFL); low FVC with normal FEV1/FVC ratio and normal TLC, i.e. peripheral airway obstruction (PAO); low TLC, i.e. restrictive defect; and low FEV1/FVC ratio and TLC, i.e. mixed defect) [4, 5]. Patients over 8 years of age and all legal guardians gave oral consent for a possible retrospective use of the lung function results.
Baseline and post-BD (salbutamol 400 µg) spirometry (BodyBox; Medisoft, Sorinnes, Belgium) were performed according to international guidelines [1, 6]. Anthropometric and clinical data were recorded to compute z-scores and percentages [7, 8]. The lower limit of normal (LLN) was set at −1.645 z-score for spirometry indices, and 80% and 70% for TLC in Caucasian and non-Caucasian patients, respectively [7, 9]. Significant FEV1 reversibility was an at least 12% baseline increase [4]. Post-BD changes in FET were the difference between pre- and post-BD FET expressed as raw value or as percentage baseline. Statistical analyses used paired and unpaired t-tests, Wilcoxon–Mann–Whitney test, Kruskal–Wallis test, Sidak test and Chi-squared test, as appropriate, and Spearman correlation. The p-value was significant when <0.05 (two-sided). All statistical analysis was performed with Graph Pad Prism (v 6.07, San Diego, CA, USA).
We included 3992 files of asthmatic patients (median (interquartile range) age 11.6 (9.0–14.3) years, males 62.9%, Caucasian 66.7%). At baseline, median (interquartile range) FET was 3.0 (2.4–3.9) s and only 143 (3.6%, 95% CI 3.0–4.2%) patients had a FET ≥6 s. Correlations between FET and age or FVC z-score were significant but weak (r=0.21 and 0.11, respectively, both p<0.0001) while there was a strong and negative correlation between FET and FEV1/FVC (r=−0.74, 95% CI −0.75 to −0.73, p<0.0001).
The distribution of spirometry results across 3121 (78.2%, 95% CI 76.9–79.4%) files with baseline plethysmography measurements are given in table 1. The FET was significantly different across patients with normal lung function, AFL or PAO pattern (p<0.001), with higher FET in AFL group (p<0.05). Conversely, FET did not differ between normal group and groups with low TLC (restrictive and mixed patterns) (p=0.39).
After BD inhalation, FVC slightly but significantly increased (p=0.02), while FET significantly decreased from baseline (p<0.0001) (table 1). The correlation between changes in FET and FEV1 reversibility was weak (r=−0.20 and r=−0.12 for FET changes in s or in % baseline, respectively, both p<0.0001). However, there was a significant difference in FET changes between patients with or without significant FEV1 reversibility (median (interquartile range) −0.8 (−1.4 to −0.2) and −0.2 (−0.6 to 0.2) s, respectively, p<0.0001).
In this study, we confirmed that children could rarely expire for the 6-s period, which has led to the recent deletion of this unmet criterion as the end of expiration definition [1]. Arets et al. [2] published that 15.3% of children could expire 6 s or more, compared to 3.6% in our study, and that the oldest patients were markedly more able to achieve a 6 s expiration than the youngest (8.6% of those aged <8 years, and 36% in those >15 years). However, very similarly to our results, they found a weak significant correlation between FET and age (r=0.30), and a stronger correlation between FET and AFL (assessed by FEV1/FVC; r=0.72) [2].
Neither our study nor that of Arets et al. [2] included preschool children, in whom FET can never reach 6 s (mean±sd FET 1.7±0.1 s) [3]. In healthy anaesthetised children (1 month to 6.3 years of age) respiratory system compliance decreased with age, while in awake healthy children (6 month to 18 years of age) static recoil increased during childhood [10–12]. The high thoraco-pulmonary compliance associated with a low elastic recoil in the youngest is a suitable mechanism to explain the inability of these children to maintain a prolonged lung compression once the FVC has been expired. To explain the lack of longer FET in the oldest study patients, we can invoke the dysanaptic lung growth in adolescence which results in a quicker total expiration (higher FEV1/FVC ratio) [7].
Lastly, we confirmed our hypothesis that AFL was the main determinant of FET by demonstrating higher FET at baseline in the AFL group compared to the normal and PAO groups (in the latter early airway closure (air trapping) prevents any increase of FET). The larger post-BD decrease in FET in the group with significant FEV1 reversibility is in agreement with this mechanism. Consequently, children with significant FEV1 reversibility and increased post-BD FET could be suspected of poor baseline cooperation.
In practice, recent recommendations advocate for reporting FET since no minimal time is now required. Development of portable devices for primary settings or home-based use should include this new recommendation in their algorithm in order to avoid unjustified deletions of less than 6 s duration expirations, and to allow the use of FEV1 from expirations at least 1 s which show a correct start. They could also include a warning message in case of simultaneous post-BD increase in FET and FEV1.
In conclusion, we confirmed that asthmatic children with good spirometry technique are rarely able to perform a 6 s duration forced expiration and that the main mechanism driving the increase in FET is an airflow limitation sensitive to bronchodilation. This should be taken into account by clinicians and device manufacturers.
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Acknowledgements
We are grateful to Jessica Assouline, Michèle Boulé, Houda Guillo, Marie-Claude La Rocca, Fatama Lacin, Lucia Maingot, and Noria Medjahdi for their help in supervising the children's lung function tests, and to Claire Goaguen, Pascale Jacquemart, Fanny Koëth, Valérie Le Bail, Isabelle Schmitt, and Françoise Vallée for their technical assistance, all working in Unité d'Exploration Fonctionnelle Respiratoire, Hôpital Armand Trousseau, Paris, France.
Footnotes
Conflict of interest: All authors have nothing to disclose.
- Received October 3, 2021.
- Accepted January 27, 2022.
- Copyright ©The authors 2022. For reproduction rights and permissions contact permissions{at}ersnet.org