Should asthma evaluation include assessment of small airway function?

Abstract

Scioscia et al1Scioscia S Lacedonia D Quarato CMI Tondo P Del Colle A Sperandeo M et al.Could transthoracic ultrasound be useful to suggest a small airways disease in severe uncontrolled asthma.Ann Allergy Asthma Immunol. 2022; 129: 461-466Abstract Full Text Full Text PDF PubMed Scopus (1) Google Scholar describes in this issue a novel method to identify small airway disease in severe uncontrolled asthma. Current common practice does not include any routine assessment of small airway function. Does examination of small airway function have the potential to improve care of asthma? What do we know and what should we know about small airway function in asthma? What are the “small” airways? The airways of the lungs include conducting airways that consist of the trachea, bronchi, and their multiple branches that result in as many as 60,000 terminal bronchioles that are less than 0.5 cm in diameter. These serve to deliver respiratory gas to and from the respiratory bronchioles. The respiratory bronchioles, each at approximately 0.05 cm in diameter, connect to approximately 8 million alveolar sacs. These respiratory bronchioles and alveolar sacs constitute the small airways. Although the individual respiratory bronchioles and their connected alveolar sacs are small, the cross-sectional area of the respiratory portion of the lung is approximately 10,000 cm2, 1 m2, compared with 180 cm2 for the total cross-sectional area of the conducting airways. The small airways are the part of the lung which provide gas exchange. What are the physiological implications of the small airways? Because resistance to flow relates to the fourth power of the radius, the resistance in individual small airways will be high. However, the extensive downstream branching of the airways means that there are many small airways in parallel. The total cross-section of the small airways reduces the total resistance to air flow in that portion of the lung. Owing to the vast number of bronchioles running in parallel, the large bronchi and trachea with their smaller total cross-sectional area have the highest resistance. Traditional spirometric assessment of lung function primarily measures the rate of flow from the high-resistance proximal conducting airways, that is, forced expiratory volume in 1 second, and clinical judgments tend to be highly influenced by the value of that measurement. Attempts to use spirometry to assess function of the peripheral small airways have used midflow measurements, forced expiratory flow (FEF)25-75, FEF50, and FEF75. Because those spirometric values are influenced by the magnitude of the inconstant vital capacity, assessment of small airway function is limited, resulting in that portion of the lung being called the “quiet zone.”2Mead J. The lung’s “quiet zone”.N Engl J Med. 1970; 282: 1318-1319Crossref PubMed Google Scholar This quiet zone of the lung has been investigated for its potential role in asthma. Asthma had previously been considered a large airway disease where smooth muscle can readily narrow the diameter and thereby markedly increase resistance to air flow. In a systemic review, van der Wiel et al3van der Wiel E ten Hacken NHT 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: 646-657Abstract Full Text Full Text PDF PubMed Scopus (122) Google Scholar concluded that small-airway dysfunction is associated with worse asthma control and increased frequency of exacerbations. In another review, Bjermer4Bjermer L. The role of small airway disease in asthma.Curr Opin Pulm Med. 2014; 20: 23-30Crossref PubMed Scopus (31) Google Scholar further concluded “it is of utmost importance to treat and control small airway inflammation to achieve optimal disease control.” The use of smaller-particle inhaled corticosteroids has been proposed as a means for improving asthma control by potentially reaching the small airway region.5Usmani OS. Small-airway disease in asthma: pharmacological considerations.Curr Opin Pulm Med. 2015; 21: 55-67Crossref PubMed Scopus (43) Google Scholar A large multinational prospective study reported on the relevance and extent of small airway dysfunction in asthma (ATLANTIS). That study revealed small airway dysfunction across all stages and severities of asthma with greater small airway dysfunction relating to increased asthma severity. Small airway dysfunction has also been evaluated in pediatric asthma.6Cottini M Lombardi C Berti A Comberiati P. Small-airway dysfunction in paediatric asthma.Curr Opin Allergy Clin Immunol. 2021; 21: 128-134Crossref PubMed Scopus (4) Google Scholar Spirometry provides little recognition of small airway dysfunction. Impulse oscillometry and multiple breath washout have enabled demonstration of small airway dysfunction that influences asthma control. Thus, evidence has accumulated suggesting small airway disease is present in asthma and relates to the severity of asthma. The potential clinical importance then warrants consideration of how to identify the presence of small airway disease. Scioscia et al, in the current issue of the Annals of Allergy, Asthma & Immunology, evaluates the use of transthoracic ultrasound as a means to assess the presence of hyperinflation, a consequence of small airway obstruction. Of the various ways of assessing the small airways, which is most applicable in the clinical setting? Transthoracic ultrasound is noninvasive, subjects the patient to no radiation, and compares reasonably well with high-resolution computed tomography.1Scioscia S Lacedonia D Quarato CMI Tondo P Del Colle A Sperandeo M et al.Could transthoracic ultrasound be useful to suggest a small airways disease in severe uncontrolled asthma.Ann Allergy Asthma Immunol. 2022; 129: 461-466Abstract Full Text Full Text PDF PubMed Scopus (1) Google Scholar However, Scioscia et al acknowledge the highly operator dependence of the method which would limit routine use in the clinical setting. In contrast, impulse oscillometry is a clinically applicable means of identifying airway resistance for both upper and lower airways.7Shirai T Kurosawa H. Clinical application of the forced oscillation technique.Intern Med. 2016; 55: 559-566Crossref PubMed Scopus (65) Google Scholar Noninvasive and easy to perform, only passive patient cooperation with tidal volume breathing is needed. Impulse oscillometry can therefore be used in children or adults incapable of performing satisfactory spirometric testing.8Bickel S Popler J Lesnick B Eid N. Impulse oscillometry - interpretation and practical applications.Chest. 2014; 146: 841-847Abstract Full Text Full Text PDF PubMed Scopus (186) Google Scholar When spirometry can be performed, spirometry and impulse oscillometry provide complementary clinically relevant measurements of lung function. Ultrasound provides an interesting method to assess the small airways, but the combination of spirometry and impulse oscillometry currently provides the standard for clinical practice. Could transthoracic ultrasound be useful to suggest a small airways disease in severe uncontrolled asthma?Annals of Allergy, Asthma & ImmunologyVol. 129Issue 4PreviewTransthoracic ultrasound (TUS) is an accepted complementary tool in the diagnostic process of several pleuro-pulmonary diseases. However, to the best of our knowledge, TUS findings in patients with severe asthma have never been systematically described. Full-Text PDF