Comment on: Rectifying COPD management: a critical analysis of the global initiative for chronic obstructive lung disease strategy

Extract

We read with great interest the review by Park [1], which provides a thought-provoking reappraisal of several assumptions underlying the current conceptual framework of COPD. By discussing the limitations of spirometric thresholds and highlighting the persistent diagnostic uncertainty in distinguishing asthma and COPD, the author invites the respiratory community to reconsider how chronic airway diseases are defined and studied.

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COPD diagnosis should move beyond spirometry toward a multidimensional framework integrating symptoms, imaging and biology, enabling better recognition of disease overlap and more precise, treatable trait-based management https://bit.ly/4sKXmyv

To the Editor:

We read with great interest the review by Park [1], which provides a thought-provoking reappraisal of several assumptions underlying the current conceptual framework of COPD. By discussing the limitations of spirometric thresholds and highlighting the persistent diagnostic uncertainty in distinguishing asthma and COPD, the author invites the respiratory community to reconsider how chronic airway diseases are defined and studied.

This perspective is timely. Despite decades of research, the distinction between asthma and COPD remains imperfect in both clinical practice and clinical trials. Diagnostic labels frequently rely on combinations of clinical history, spirometry and physician judgement rather than biological criteria. Consequently, the possibility that patients with asthma may be inadvertently included in COPD cohorts is plausible and deserves attention, particularly when interpreting treatment responses in clinical trials.

One of the key arguments raised in the review is that eosinophilia and corticosteroid responsiveness observed in some COPD populations might partly reflect the inclusion of patients with undiagnosed asthma [1]. While this hypothesis is provocative, it also highlights a broader issue: the biological heterogeneity of chronic airway diseases. Blood eosinophilia has been associated with exacerbation risk and response to inhaled corticosteroids in several COPD studies, leading to its adoption as a biomarker guiding therapeutic decisions [2]. However, the biological interpretation of eosinophilia remains debated.

Peripheral blood eosinophil counts represent only an indirect surrogate of airway biology. Evidence indicates that circulating eosinophilia does not necessarily reflect eosinophilic inflammation within lung tissue nor consistently correlate with disease severity or outcomes in COPD [3]. This discrepancy highlights the limitations of relying exclusively on peripheral biomarkers to infer airway inflammatory mechanisms.

Pathological studies comparing asthma and COPD provide additional insights. Bronchial eosinophilia may occur in both conditions during exacerbations, yet only asthma shows increased expression of interleukin-5 in bronchial tissue, suggesting distinct immunological mechanisms despite partially overlapping inflammatory patterns [4]. Structural alterations, such as thickening of the reticular basement membrane, can also be observed in both diseases but differ in organisation and composition, reflecting distinct airway remodelling processes [5].

These observations emphasise that similar inflammatory profiles do not necessarily imply identical disease mechanisms. Consequently, the presence of eosinophils alone cannot reliably distinguish asthma from COPD or fully explain treatment responsiveness. Rather than viewing eosinophilic COPD solely as misclassified asthma, it may be more appropriate to recognise that chronic airway diseases encompass multiple inflammatory and structural endotypes that only partially overlap with traditional diagnostic categories.

The discussion raised by Park [1] also underscores an important limitation of the current diagnostic framework for COPD, namely the strong reliance on spirometric thresholds. We agree with the author that spirometry alone cannot fully capture the complexity of chronic airway diseases. In this context, multidimensional diagnostic approaches represent a promising step forward. Bhatt and colleagues proposed a framework integrating spirometry with respiratory symptoms, quality-of-life impairment and structural abnormalities detected on computed tomography [6]. This approach identified individuals with clinically significant disease who would not have been classified as having COPD using spirometry alone, yet who exhibited increased risks of exacerbations, lung function decline and mortality. Such strategies do not negate the value of spirometry but instead place it within a broader multidimensional assessment of airway disease (figure 1).

FIGURE 1.

From spirometry-based diagnosis to multidimensional characterisation of chronic airway diseases. Schematic representation of the transition from a traditional spirometry-based definition of COPD to a multidimensional airway disease framework. The conventional approach relies mainly on airflow limitation (forced expiratory volume in 1s (FEV₁)/forced vital capacity (FVC) <0.7) and blood eosinophils (Eos), with limited characterisation of underlying mechanisms and frequent under-recognition of disease overlap. In contrast, the multidimensional framework integrates lung function, respiratory symptoms, quality of life, imaging and a broader range of biomarkers, including airway tissue in selected contexts, allowing improved recognition of overlapping conditions and supporting individualised treatment based on treatable traits. PFT: pulmonary function test; QoL: quality of life; Bx: bronchiectasis; TT: treatable trait.

More precise characterisation of airway diseases may also have implications beyond COPD itself. Bronchiectasis frequently coexists with asthma or COPD, and studies combining clinical features, lung function and imaging have highlighted the importance of recognising these overlap phenotypes, which are often associated with worse clinical outcomes [7]. As new treatments for bronchiectasis are emerging, including the dipeptidyl peptidase-1 inhibitor brensocatib, accurate identification of the dominant airway disease may become increasingly relevant in clinical practice [8, 9].

Finally, we share the view of Park [1] that our understanding of airway disease biology remains incomplete. While bronchial biopsies are unlikely to become routine diagnostic tools in everyday practice, their use in mechanistic studies could improve characterisation of airway diseases. In other fields, such as gastroenterology, tissue-based phenotyping has long been central in distinguishing inflammatory disorders and guiding therapeutic development. A similar translational approach –combining imaging, molecular biomarkers and, in selected contexts, airway tissue analysis – may help bridge the gap between clinical phenotypes and underlying airway biology [10].

Viewed in this light, the review by Park [1] reminds us that disease classification must evolve alongside advances in pathobiology and imaging. Rather than assuming eosinophilic COPD simply reflects misclassified asthma, it may be more appropriate to recognise that current diagnostic categories remain too coarse to capture the complexity of chronic airway diseases.

Ultimately, the challenge ahead is not merely to separate asthma from COPD more rigorously, but to characterise airway disease phenotypes with sufficient precision to enable personalised therapeutic strategies. Constructive debate on diagnostic uncertainty, such as that stimulated by the review by Park [1], represents an important step toward a more precise and biologically grounded understanding of chronic airway disease.