The clinical importance of rhinovirus-associated early wheezing
To the Editors:
In a recent report by a European Respiratory Society Task Force 1, human rhinovirus (HRV)-associated bronchiolitis and wheezing illness were not sufficiently discussed. Several recent observations highlight the importance of HRV infections in young wheezing children.
First, HRV is commonly associated with bronchiolitis and early-life wheezing, second only to respiratory syncytial virus (RSV). Detection rates have reached 40% in hospitalised wheezing infants 2, 3. Moreover, HRV infection has been associated with the severity of illness 4.
Secondly, HRV infection among early wheezers is an important independent risk factor for recurrent wheezing 2, 5–8. In population-based studies on young hospitalised children with acute wheezing, HRV infection has been associated with recurrent wheezing (≥3 physician-confirmed episodes) during a 12-month follow-up period after the first episode (hazard ratio 5.1, 95% confidence interval (CI) 1.0–25, versus RSV-positive cases) and with the development of asthma at school-age (odds ratio 4.1, 95% CI 1.0–17, versus HRV-negative cases) 2, 6.
In outpatient populations with increased risk for atopic illnesses, ≥1 wheezing illness during infancy with HRV markedly increased the risk for third-year wheezing (odds ratio 10, 95% CI 4.1–26, versus HRV-positive cases with no moderate-to-severe respiratory infections) and modestly increased the risk for asthma at age 6 yrs (odds ratio 2.8, 95% CI 1.1–7.5, versus HRV-positive cases with no wheezing) 5, 8. Interestingly at the third year of life, wheezing with HRV was markedly associated with asthma at age 6 yrs (odds ratio 26, 95% CI 8.2–80, versus those with no third-year wheezing and with no aeroallergen sensitisation) 8. Nearly 90% of children who wheezed with HRV in year 3 had asthma at age 6 yrs. In the same study, aeroallergen sensitisation during infancy and at age 3 yrs only modestly increased the risk for asthma at age 6 yrs (odds ratio 3.6, 95% CI 1.7–7.7, and odds ratio 3.4, 95% CI 1.7–6.9, versus those with no wheezing and those with no aeroallergen sensitisation, respectively) 8. In another study on a high-risk cohort, wheezing with HRV during the first year of life was associated with wheezing at age 5 yrs (odds ratio 3.2, 95% CI 1.1–9.5) 7. Comparable findings were made for current asthma. Strikingly, these associations were restricted to children who displayed early sensitisation (age ≤2 yrs). Two other studies have also reported an association between HRV-induced early wheezing and atopy/atopic characteristic 9, 10.
Thirdly, systemic corticosteroids as short 1–5-day courses are one of the cornerstones of the management of acute asthma in children, but their efficacy among young wheezing children has thus far remained obscure. RSV bronchiolitis does not respond to systemic corticosteroids, but most of the previous studies have not tried to identify other potential responders. Only one study has studied the efficacy of systemic corticosteroids in relation to HRV aetiology among young first-time wheezers 6, 10. A 3-day course of oral prednisolone decreased the probability of recurrent wheezing (≥3 physician-confirmed episodes) in children with eczema (hazard ratio 0.2, 95% CI 0.0–0.6) and HRV (hazard ratio 0.2, 95% CI 0.1–0.7). Prednisolone decreased recurrent wheezing by 48% over a 12-month study period in these first-time wheezers affected by HRV.
Taken together, many studies have consistently shown that HRV infections are common among early wheezers and they are markedly associated with recurrent wheezing and the development of asthma up to school-age. In addition, there are preliminary data that first-time wheezers affected by human rhinovirus are likely respond to prednisolone in terms of less recurrent wheezing at least for the subsequent 12 months. Clinically, a rapid respiratory syncytial virus detection test is useful in placing patients at ward, but for the assessment of long-term prognosis human rhinovirus PCR is needed. Considering that aeroallergen sensitisation develops usually after 2–3 yrs of life, human rhinovirus detection seems already to give clinically highly relevant information during infancy.
Support statement
Supported by the Academy of Finland (Helsinki, Finland).
Statement of interest
None declared.
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