To the Editors:
In a recent issue of the journal, Ricart et al1 published their interesting observations on apnea associated with bronchiolitis in infants <12 months of age based on prospectively collected data. The 51 infants with apnea represented 5.2% (95% confidence interval: 3.94–6.72%) of the 989 <12-month-old infants hospitalized for bronchiolitis during the 34-month-study period. The gestational age was <37 weeks in 54.9% of patients, the chronologic age was in mean 41.7 weeks, and 78.4% needed intensive care (47.1% needed mechanical ventilation).
Viruses were studied with polymerase chain reaction for 15 respiratory viruses or viral subgroups in respiratory samples, and at least 1 virus was detected in 39 (76.5%) cases. Respiratory syncytial virus (RSV) was identified in 24 (47.1%) cases (as a single infection in 17 cases) and rhinovirus in 14 (27.5%) cases (as a single infection in 7 cases). Thus, 50% of rhinovirus findings were multiple findings with some other virus, compared only with 22.7% of RSV findings.
Young age and prematurity were the only statistically significant risk factors for apnea independently of the RSV status.1 However, this conclusion may not be valid, because it was based on subgroup analyses. Multivariable analyses with the potential risk factors included as covariates in the same model would have been a more reliable approach.
The results highlight—once again—the importance of age in the definition of bronchiolitis. The mean age of the infants with bronchiolitis and apnea was less than 2 months. The frequency of wheezing was not reported, but a third of the patients presented with apnea before any respiratory symptoms.1 Is virus-induced wheezing in 12- to 24-month-old infants the same disease as bronchiolitis in less than 6-month-old infants, and can they be treated according to the same principles? Maybe, the best treatment for young infants with bronchiolitis would be “not to do anything” except than to give oxygen and fluids when needed. Wheezing older infants may benefit from inhaled sympathomimetics on-demand—at least in selected cases.2
Ricart et al1 highlight that in the non-RSV group, prematurity and recurrent apneas were more common than in the RSV group. However, the non-RSV group was rather heterogeneous including metapneumovirus, adenovirus, parainfluenza virus type 1 and type 2, and coronavirus V229E infections. In the subgroup analysis, comparing RSV-positive and rhinovirus-positive cases, the only significant difference was a higher proportion of premature infants in the rhinovirus group. Rhinovirus is no doubt an important agent in wheezing children at >12 months of age,3 but it is still unresolved what is the role of rhinoviruses in bronchiolitis in 0- to 12-month-old infants, and especially in 0- to 6-month-old infants.4 Rhinovirus studies are challenging, because antibody assays are not available, culture of rhinoviruses is slow and insensitive, and polymerase chain reaction may give positive findings in nonsymptomatic children and for long times after the symptoms of acute infection have improved.5
In conclusion, the definition of infant bronchiolitis should be re-visited. One possibility is to classify cases based on the etiology, and for example, speak about RSV or rhinovirus infections of lower airways without any age limits or demands of certain clinical criteria, such as wheezing, crackles, retractions or tachypnea. However, we cannot find causative agents in all cases when large test panels are used, as was seen in the study of Ricart et al.1 Their panel included nearly all respiratory viruses except bocavirus, but 23.5% of the cases remained virus-negative. In addition, multiple viral agents are common, especially in rhinovirus-positive infections in infants.6 Therefore, age limits are needed, and for bronchiolitis, the upper age limit should be 12 months or even 6 months, but not 24 months.
Matti Korppi, MD, PhD
Tampere Center for Child Health Research
Tampere University and University Hospital
1. Ricart S, Rovira N, Garcia-Garcia JJ, et al. Frequency of apnea and respiratory viruses in infants with bronchiolitis. Pediatr Infect Dis J. 2014;33:988–990
2. Jartti T, Korppi M.. Rhinovirus-induced bronchiolitis and asthma development. Pediatr Allergy Immunol. 2011;22:350–355
3. American Academy of Pediatrics Subcommittee on Diagnosis and Management of Bronchiolitis. . Diagnosis and management of bronchiolitis. Pediatrics. 2006;118:1774–1793
4. Korppi M.. Rhinovirus bronchiolitis: to be or not to be? Acta Paediatr. 2014;103:997–999
5. Jartti T, Lehtinen P, Vuorinen T, et al. Persistence of rhinovirus and enterovirus RNA after acute respiratory illness in children. J Med Virol. 2004;72:695–699
6. Jartti T, Aakula M, Mansbach JM, et al. Hospital length-of-stay is associated with rhinovirus etiology of bronchiolitis. Pediatr Infect Dis J. 2014;33:829–834