VCD/ILO phenotypes
Clinical expression of ILO/VCD is heterogeneous, an observation supported by a myriad of names describing the condition. Currently, ILO/VCD is comparable to the historical situation in asthma where the ‘homogenous’ nature of asthma was eventually disproved and asthma phenotypes became established. Targeted treatments were then devised. Similarly, phenotyping in ILO/VCD could identify patient clusters, fast-track diagnoses and support more effectual randomised trials of treatment.
The characteristics and variable nature of ILO/VCD are well recognised and the notion of ILO/VCD phenotypes is highly plausible. At a clinical level it is possible to identify phenotypes by a combination of symptoms, comorbidities, and diagnostic findings (Leong et al., 2022) These phenotypes are: classic ILO/VCD, lung disease-associated ILO/VCD, exercise-associated ILO/VCD (EILO), and (iv) incident-associated ILO/VCD. Cough associated ILO/VCD may be another readily identifiable type.
Classic VCD/ILO
Classic ILO/VCD is the leading phenotype first described by Christopher and co-workers (1983) and characterised by intermittent breathlessness often with complaints of a ‘tight throat’ and dysphonia. The initial diagnosis is often asthma and there can be characteristic comorbidities such as anxiety and reflux. Spirometry is often normal.
Lung disease-associated VCD/ILO phenotype
Lung disease-associated ILO/VCD phenotype is characterised by coexistent lung disease, chiefly asthma and Chronic Obstructive Pulmonary Disease. Symptoms are concordant with the underlying lung disease but with additional ILO/VCD like symptoms. Spirometry and other lung function measures are often abnormal. Laryngoscopy may show inspiratory closure and often also expiratory narrowing (‘braking’).
Exercise-associated VCD/ILO phenotype
Exercise-associated ILO/VCD phenotype has been expertly described by Roksund, Halvorsen and others (Røksund et al., 2017). Typical people are young, and/or competitive athletes who have exertional dyspnoea that is sudden in onset. Lung function is normal and exercise-induced asthma is often the initial diagnosis. Continuous Laryngoscopy during Exercise (CLE) during exercise reveals laryngeal closure, with supraglottal movement abnormalities being characteristic.
Incident-associated VCD/ILO phenotype
Incident-associated ILO/VCD phenotype is associated with stressful events that are often medically-associated such as vaccination. Onset is rapid with breathlessness, throat tightness and voice changes. The provisional diagnosis is frequently anaphylaxis or an allergic reaction, but typical inspiratory closure can be visualised, usually without oedema or allergic features (Leong et al., 2022). Importantly, anaphylaxis and incident-associated ILO/VCD can co-occur.
Additional phenotypes
Additional phenotypes, such as cough-associated ILO/VCD, irritant-associated ILO/VCD or obesity-associated ILO/VCD, may be important and there may be overlap between phenotypes.
ILO/VCD phenotyping is an important concept. Firstly, phenotypes can be used to design personalised diagnostic pathways. For example, the diagnostic pathway for suspected exercise-associated ILO/VCD will be different to the pathway for lung-disease associated ILO/VCD. Secondly, phenotypes can enable focused patient recruitment and optimised research design of randomised controlled trials to provide evidence-based treatments for ILO/VCD. It is likely that treatment responses will vary according to patient phenotype but to date treatment studies have not employed a phenotyping strategy to target particular treatments to specific patient phenotypes.
The phenotyping approach now needs to be validated. There is a developing consensus that a framework that uses this strategy may be an optimal way to improve diagnosis, clinical management and future research.