Recurrent wheezing 36 months after bronchiolitis is associated with rhinovirus infections and blood eosinophilia

Midulla, Fabio; Nicolai, Ambra; Ferrara, Marianna; Gentile, Federico; Pierangeli, Alessandra; Bonci, Enea; Scagnolari, Carolina; Moretti, Corrado; Antonelli, Guido; Papoff, Paola

doi:10.1111/apa.12720

Cited by 57 publications

(61 citation statements)

References 30 publications

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“…Interestingly, our results add to previous findings that RV-A and RV-C wheezing illnesses contribute to the risk for recurrent wheezing (3, 5, 41, 42). In addition, Linsuwanon et al have earlier shown that RV-A and RV-C detected together with RSV were associated with recurrent wheezing (41, 43).…”

Section: Discussionsupporting

confidence: 86%

Clinical and Virus Surveillance After the First Wheezing Episode

Turunen

Vuorinen

Bochkov

et al. 2017

Pediatric Infectious Disease Journal

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Background Susceptibility to rhinovirus (RV) induced early wheezing episode has been recognized as an important risk factor for asthma but the data on different RV species is limited. Our aim was to investigate the risk for recurrences in first-time wheezing children with special focus on RV species. Methods First-time wheezing children (88/23 in-/outpatients) were prospectively followed at 2-week, 2-month and 12-month time-points, and at first recurrence within 12 months. The respiratory virus etiology was analyzed using PCR. RV positive samples were sequenced. The primary outcomes were time to a new physician-confirmed wheezing episode and time to the initiation of regular controller medication for asthma symptoms. Results The median age of the children was 12 months (SD 6.0), 67% were males and 23% were sensitized. RV dominated in symptomatic and asymptomatic infections. Different virus strains caused 97 % of the consecutive RV infections. First-time wheezing children with RV-C (respectively 3.6; p < 0.001) and RV-A (hazard ratio 3.6, p = 0.002) had an increased risk for a new wheezing episode than non-RV group. Also, the risk for the initiation of regular controller medication was increased in RV-A and RV-C groups (both p < 0.05), respectively. There was no difference in response on oral prednisolone between RV-A and RV-C. Conclusions RV causes reinfections with different strains in small children after the first wheezing episode. Both RV-A and RV-C affected children have an increased risk for recurrence and initiation of regular controller medication than those with other viruses.

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Section: Discussionsupporting

confidence: 86%

Clinical and Virus Surveillance After the First Wheezing Episode

Turunen

Vuorinen

Bochkov

et al. 2017

Pediatric Infectious Disease Journal

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“…This previously unreported finding suggests that recurrent wheezing after bronchiolitis depends on the type of virus the infants were found positive to, regardless of whether it was detected as a single or as a multiple virus. We previously reported a positive association between recurrent wheezing after bronchiolitis and hRV detection and in a later study a higher RSV‐RNA load . This issue merits clarification in a study with a larger number of cases and a longer follow‐up.…”

Section: Discussionmentioning

confidence: 86%

“…Around 40‐50% of infants hospitalized for bronchiolitis will have wheezing episodes in the first year of life. Although ample literature describes RSV, hRV, and the presence of higher blood eosinophil counts as factors predisposing to recurrent wheezing after bronchiolitis, the role of co‐infection is poorly understood. Enlarging current knowledge on the role of multiple viral detection in the clinical manifestation of bronchiolitis as well as in recurrent wheezing episodes would probably change the way we manage and follow‐up infants with acute bronchiolitis.…”

Section: Introductionmentioning

confidence: 99%

Acute bronchiolitis: Influence of viral co‐infection in infants hospitalized over 12 consecutive epidemic seasons

Petrarca

Nenna

Frassanito

et al. 2017

Journal of Medical Virology

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Bronchiolitis is the first lower respiratory tract viral infection manifesting in infants younger than 12 months of age. Our aim was to evaluate clinical and serological differences in infants with bronchiolitis from a single or from multiple viruses. Our secondary aim was to investigate differences in recurrent wheezing episodes after 12-24-36 months of follow-up. We reviewed the clinical records for 486 full-term infants hospitalized for bronchiolitis with at least one virus detected in the nasopharyngeal aspirate. In 431 (88.7%) patients one virus was detected and in 55 (11.3%) infants more than one virus was found. No differences were observed in the length of hospitalization, clinical severity score, O supplementation or admission to the intensive care unit. Single virus was associated with higher serum C-reactive protein (C-RP) than infants with multiple viruses and higher blood neutrophil counts. Respiratory syncytial virus (RSV) was the most frequently detected virus. RSV alone was associated with higher C-RP (P = 0.007), compared to RSV coinfection. Infants with human rhinovirus (hRV) alone had higher white blood cell counts, higher blood neutrophils, and higher serum C-RP levels than hRV co-infection (P = 0.029, P = 0.008, P = 0.008). RSV + hRV, the most frequent co-infection, was associated with lower neutrophil count and lower C-RP levels (P = 0.008, P = 0.016) and less fever (P = 0.012), when comparing RSV versus hRV versus RSV + hRV. No differences were found in the frequency of recurrent wheezing between single versus multiple viruses after bronchiolitis. Our findings suggest that in infants with bronchiolitis multiple viral co-infections can occur, without influence in the clinical severity of the disease. Infants with co-infection seems to mount a lower inflammatory response.

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“…RV-induced severe bronchiolitis/early wheezing is a more robust marker of asthma risk than wheezing episodes caused by RSV or other viruses (Table I). 6,8,13,14,38,39 High-risk birth cohorts, which have included wheezing children with at least 1 atopic parent, have shown a close association between early-life RV-induced wheezing and school-age asthma. 6,9 The Childhood Origins of Asthma (COAST) study demonstrated that the risk for asthma by age 6 years was increased if the children had wheezing with RV (odds ratio [OR], 9.8) versus RSV (OR, 2.6) during the first 3 years, and furthermore, 90% of the children with RV-induced wheezing in the third year of life had asthma by age 6 years (OR, 26).…”

Section: Virus Characteristics Rvsmentioning

confidence: 99%

“…Acute wheezing illnesses with RV and respiratory syncytial virus (RSV) are early markers for recurrent wheezing. 6,[8][9][10][11][12][13][14] In addition, RV-induced wheezing episodes in infancy are a major risk factor for later asthma, especially in children with atopic features. Once asthma is established, exposure to allergens and RV infections are important triggers of asthma exacerbations in children.…”

mentioning

confidence: 99%

Role of viral infections in the development and exacerbation of asthma in children

Jartti

Gern

2017

Journal of Allergy and Clinical Immunology

359

372

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Viral infections are closely linked to wheezing illnesses in children of all ages. Respiratory syncytial virus (RSV) is the main causative agent of bronchiolitis, whereas rhinovirus (RV) is most commonly detected in wheezing children thereafter. Severe respiratory illness induced by either of these viruses is associated with subsequent development of asthma, and the risk is greatest for young children who wheeze with RV infections. Whether viral illnesses actually cause asthma is the subject of intense debate. RSV-induced wheezing illnesses during infancy influence respiratory health for years. There is definitive evidence that RSV-induced bronchiolitis can damage the airways to promote airway obstruction and recurrent wheezing. RV likely causes less structural damage and yet is a significant contributor to wheezing illnesses in young children and in the context of asthma. For both viruses, interactions between viral virulence factors, personal risk factors (eg, genetics), and environmental exposures (eg, airway microbiome) promote more severe wheezing illnesses and the risk for progression to asthma. In addition, allergy and asthma are major risk factors for more frequent and severe RV-related illnesses. Treatments that inhibit inflammation have efficacy for RV-induced wheezing, whereas the anti-RSV mAb palivizumab decreases the risk of severe RSV-induced illness and subsequent recurrent wheeze. Developing a greater understanding of personal and environmental factors that promote more severe viral illnesses might lead to new strategies for the prevention of viral wheezing illnesses and perhaps reduce the subsequent risk for asthma.

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Recurrent wheezing 36 months after bronchiolitis is associated with rhinovirus infections and blood eosinophilia

Abstract: Recurrent wheezing 36 months after infant bronchiolitis was associated with rhinoviruses and blood eosinophilia.

Cited by 57 publications

References 30 publications

Clinical and Virus Surveillance After the First Wheezing Episode

Clinical and Virus Surveillance After the First Wheezing Episode

Acute bronchiolitis: Influence of viral co‐infection in infants hospitalized over 12 consecutive epidemic seasons

Role of viral infections in the development and exacerbation of asthma in children

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