To the Editors:
I read with interest the study by van den Nieuwenhof et al. 1, which appeared in a recent issue of the European Respiratory Journal. The study’s conclusion is certainly of interest: screening for asymptomatic airway hyperresponsiveness (AHR) in adolescents does not identify subjects at risk of developing asthma, whilst the presence of allergy is a risk factor for asthma. However, the observations leading to this statement should be interpreted with caution.
I agree with the authors that AHR may be variable. It can improve significantly at adolescence, the period associated with the highest incidence of asthma remission. The situation seems different in adults, however.
In some subjects, AHR may reflect a previous “insult” to the airways, either of infectious, toxic or allergic origin, or it could be the consequence of past airway inflammatory responses and associated structural changes, with persistence of the latter. In other subjects, however, AHR could reflect an ongoing inflammatory/remodelling process either from current environmental exposure or from a persistent activation of the immune system of undetermined origin.
In a previous study, my colleagues and I reported that atopic subjects with asymptomatic AHR and a family history of asthma, who were chronically exposed to indoor allergens to which they were sensitised (particularly domestic animals), were at higher risk of developing asthma in the near future 2. Our study documented the changes occurring in the airways when subjects with asymptomatic AHR developed symptomatic asthma. These changes consisted mostly of an increase in airway remodelling and reversal of the CD4+/CD8+ lymphocyte ratio. Although the study included a limited number of subjects, these features were quite striking.
I had a chance to review this topic in recent years and my conclusions were that in some specific subgroups of patients, asymptomatic AHR is associated with an increased risk for the development of asthma 3. More studies should be performed to define the population in which screening could be beneficial. Unfortunately, when symptomatic asthma develops, airway structural changes, which perhaps explain a large part of the physiological features observed, are largely irreversible and symptoms are persistent. The ideal would be to prevent this condition instead of simply trying to achieve optimal control once developed. In a recent editorial, P.J. Sterk and I suggested that we should try to prevent potentially detrimental airway structural changes, perhaps by controlling triggering mechanisms of the disease at an early stage or by adequately treating conditions associated with an increased risk of developing lower airways diseases (e.g. rhinitis) 4.
The risk of developing asthma is thought to be related to a combination of genetic and environmental factors. AHR per se may not be a predicting factor of asthma but when associated with atopy or a strong family history of asthma, it may indicate that a given subject is closer to the “asthmatic range” of airway responsiveness, and, as suggested in previous studies 2, 3, if exposed to a pro-inflammatory trigger, the subject may develop full-blown asthma in the coming months/years.
A study such as the one by van den Nieuwenhof et al. 1 is welcome in terms of improving knowledge about the significance of airway hyperresponsiveness, but much remains to be determined if we are to more accurately identify those at risk of developing asthma in the near future and those who would benefit from early intervention for the prevention of asthma. The suggestion that screening for asymptomatic airway hyperresponsiveness cannot be generally recommended seems appropriate in the population studied but even then, it should not prevent investigation of the possibility that specific high-risk groups could be identified early and become candidates for preventative measures in order to try to avoid the development of symptomatic asthma. With regard to atopy as a risk factor of asthma, only a minority will develop asthma in the future and more emphasis should be placed upon finding ways to identify allergic subjects at high risk to develop asthma.
Statement of interest
A statement of interest for L-P. Boulet can be found at www.erj.ersjournals.com/misc/statements.shtml
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