Why do we still cling to spirometry for assessing small airway function?

To the Editor:

With great interest we read the article by Arshad et al. [1] and the accompanying editorial [2] in the March 2020 issue of the European Respiratory Journal. We fully agree that early detection and small airway function are both of utmost importance for the management of obstructive lung disease. However, we have some methodological concerns in this context. These should be discussed as certain imitations of the important work at hand.

Since James Hogg's ground-breaking publication in the New England Journal of Medicine, more than 50 years have now passed [3]. Ever since, it has been discussed that considerable destruction must be present in the small airways before it can be detected clinically or with commonly used diagnostic tests [4, 5]. The latter has not much changed, neither in clinical routine nor research until today. Therefore, the small airways still remain what was previously described as “the lung's quiet zone” [6]. This is important, as the small airways are increasingly recognised to be involved early in the pathogenesis of both bronchial asthma and COPD. Hence, the work by Arshad et al. [1] tackles an important topic and potentially provides a link between both entities. We agree that forced expiratory flow at 25–75% of forced vital capacity (FEF_25–75) intuitively is more sensitive than parameters of central obstruction, such as forced expiratory volume in 1 s alone [1, 2]. However, we want to emphasise that small airway function should not be simply reduced to airway obstruction. In contrast, small airway function comprises heterogenous interactions between ventilation, diffusion, perfusion and inflammation.

Publication of the cross-sectional results from ATLANTIS revealed that small airway function is impaired in over 90% of asthmatic patients [7]. These changes cannot be addressed by spirometric parameters alone, which must be considered as rather insensitive in general. Recent studies further underline these findings. More advanced techniques, such as multiple breath washout (MBW) testing and oscillometry were demonstrated to be feasible in asthmatic patients. Both add considerable information for the differentiation of asthmatic patients with normal spirometry from non-asthmatic controls, respectively [8]. Likewise, parameters of oscillometry outperformed spirometric parameters for differentiating patients at risk for the development of COPD from healthy controls, as well as from diagnosed COPD patients [9]. Most notably, diagnostic performance of FEF_25–75 was just above chance when being used as a single parameter. This also has clinical implications. Lately, oscillometry was shown to be more sensitive than spirometry in identifying bronchodilator response as well as patients with poor asthma control [10].

Oscillometry is recognised as one of the most promising techniques for assessing small airway function in research and clinical practice. This is not only because of the recently demonstrated direct relationship to peripheral obstruction [11]. In contrast to spirometry, oscillometry uses tidal breathing not requiring forced and artificial manoeuvres. This makes it easily applicable, even in early childhood. However, we also see other additional techniques to be valuable in the assessment of small airway function. These include, but are not limited to, well-known conventional tests such as body plethysmography and transfer factor for carbon monoxide (formerly “diffusing capacity”). In addition, more advanced functional techniques such as MBW, capnovolumetry or fractional exhaled nitric oxide are now clinically available. Capnovolumetry seems to be especially interesting for detection of peripheral obstruction in outpatient settings [12], being both inexpensive and easy to perform. Imaging techniques comprise quantitative computed tomography or magnetic resonance imaging. Available data strongly supports the idea of combined approaches. Neither a single test nor even a distinct parameter will ever be sufficient for future assessment of small airway function. The aforementioned techniques provide information about the small airways while addressing different aspects (figure 1).

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FIGURE 1

Diagnostic tools. Schematic overview of conventional, advanced and imaging techniques for assessment of small airway function with the respective aspects addressed.

We believe that it is important to longitudinally assess lung function changes together with risk factors, as proposed in the Isle of Wight Birth Cohort Study. We are aware that today's technology was not readily available at the time of planning the cohort. However, when started today, research should also include more sensitive measures of early changes. There are currently several ongoing multicentre studies investigating both childhood and adult asthma. For example, both the ATLANTIS [7] and ALLIANCE [13] cohorts include measurements of small airway function over time. They will provide additional mechanistic insights into the development and course of disease.

Taken together, those days for spirometry as sole assessment of airway function should be long gone. It is often argued that world-wide availability of other methods is not given, and we want to emphasise that spirometry is not worthless for managing airway disease in general. However, its use for early detection of airway disease is limited. Spirometry should be reasonably extended by techniques aiming, in particular, at small airway function, as they provide additional information. Their final value remains to be determined in future research. However, the availability of such methods must not hinder scientific progress.

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