BACKGROUND



Small airways are defined as those with a diameter ≤ 2 mm.(1) There is a current focus on small airway dysfunction (SAD) in asthma and the techniques used in order to measure this.(1-3) Postma et al. reported that SAD is present across all severities of asthma and can be measured using different techniques, including lung volumes and oscillometry.(1,3) The case histories described here illustrate how these methods can be applied in a clinical setting to identify SAD in asthma.



CASE HISTORIES



Table 1 shows data from two patients with moderate to severe asthma (Global Initiative for Asthma classification system = 4) who attended our research centre for lung function assessment. Both were non-smoking females of a similar age with uncontrolled asthma; both had Asthma Control Questionnaire scores = 2.3. There were similar levels of fractional exhaled nitric oxide (21 and 12 ppb), FEV1 (68% and 72% of the predicted value), and FEV1/FVC ratio (0.61 and 0.70). Patient 1 demonstrated greater reversibility than patient 2 (420 mL and 22% and 240 mL and 12%, respectively).

 






Body plethysmography was used to assess lung volumes (Autobox 6200 DL; Sensormedics Corporation, CA, USA). Residual volume (RV) was increased (153% of predicted) in patient 1, indicating gas trapping due to SAD. There was no evidence of gas trapping in patient 2. Impulse oscillometry was used in order to measure airway resistance (Masterscreen IOS; Erich Jaeger, Hoechenberg, Germany), with peripheral airway resistance measured by resistance at 5 Hz minus resistance at 20 Hz (R5 − R20).(3) Patient 1 demonstrated a value of 0.23 kPa/L/s, whereas patient 2 had a much lower value of 0.01 kPa/L/s, indicating minimal peripheral airway resistance. These differences in R5 − R20 can be due to small airway inflammation, remodelling or bronchoconstriction.



CLINICAL MESSAGE



The evidence that SAD is present from mild to severe asthma(3) raises the practical issue of how to diagnose and monitor SAD in clinical practice. SAD was previously thought to be difficult to measure due to the inaccessible nature of the lung periphery.(1) However, these case studies show the potential value of RV and oscillometry measurements in clinical practice; the two cases presented here had very similar clinical characteristics based on spirometry and asthma control, but only one had evidence of significant SAD.



Although normal ranges for oscillometry measurements have yet to be firmly established,(4) the R5 − R20 value for patient 1 is beyond the threshold for SAD used in previous publications.(4,5) Establishing normal ranges for oscillometry is an important future consideration for this technique in clinical practice.



The clinical management of SAD can include the use of inhaled treatments with smaller particle sizes that target the small airways. The diagnosis of SAD may therefore lead to different clinical management. The cases presented here show that the use of RV and R5 − R20 measurements can facilitate the diagnosis of SAD. We believe that diagnosing SAD in asthma should not be overlooked as the opportunity for targeted treatment may be missed.



AUTHOR CONTRIBUTIONS



DS and JR designed the research. JR and NJ organised data collection. DS and NJ wrote the manuscript. JR reviewed and approved the manuscript.



ACKNOWLEDGMENTS



Dave Singh is supported by the National Institute for Health Research (NIHR) Manchester Biomedical Research Centre (BRC).



REFERENCES



1. van der Wiel E, ten Hacken NH, Postma DS, van den Berge M. Small-airways dysfunction associates with respiratory symptoms and clinical features of asthma: a systematic review. J Allergy Clin Immunol. 2013;131(3):646-657. https://doi.org/10.1016/j.jaci.2012.12.1567

2. Postma DS, Brighling C, Fabbri L, van der Molen T, Nicolini G, Papi A, et al. Unmet needs for the assessment of small airways dysfunction in asthma: introduction to the ATLANTIS study. Eur Respir J. 2015;45(6):1534-1538. https://doi.org/10.1183/09031936.00214314

3. Postma DS, Brighling C, Baldi S, Van den Berge M, Fabbri LM, Gagnatelli A, et al. Exploring the relevance and extent of small airways dysfunction in asthma (ATLANTIS): baseline data from a prospective cohort study [published correction appears in Lancet Respir Med. 2019 Sep;7(9):e28]. Lancet Respir Med. 2019;7(5):402-416. https://doi.org/10.1016/S2213-2600(19)30049-9

4. Galant SP, Komarow HD, Shin HW, Siddiqui S, Lipworth BJ. The case for impulse oscillometry in the management of asthma in children and adults. Ann Allergy Asthma Immunol. 2017;118(6):664-671. https://doi.org/10.1016/j.anai.2017.04.009

5. Usmani OS, Singh D, Spinola M, Bizzi A, Barnes PJ. The prevalence of small airways disease in adult asthma: A systematic literature review. Respir Med. 2016;116:19-27. https://doi.org/10.1016/j.rmed.2016.05.006