Asthma and allergy patterns over 18 years after severe RSV bronchiolitis in the first year of life

Department of Paediatrics, Borås Central Hospital, Borås S-50182, Sweden.
Thorax (Impact Factor: 8.29). 12/2010; 65(12):1045-52. DOI: 10.1136/thx.2009.121582
Source: PubMed


An increased prevalence of asthma/recurrent wheeze (RW), clinical allergy and allergic sensitisation up to age 13 years has previously been reported in subjects hospitalised with respiratory syncytial virus (RSV) bronchiolitis in their first year of life compared with matched controls. A study was undertaken to examine whether these features persist into early adulthood, to report longitudinal wheeze and allergy patterns, and to see how large and small airway function relates to RSV infection and asthma.
Follow-up at age 18 years was performed in 46 of 47 subjects with RSV and 92 of 93 controls. Assessments included questionnaire, clinical examination, skin prick tests, serum IgE antibodies to inhaled allergens, blood eosinophils, fraction of exhaled nitric oxide (FeNO), spirometry, multiple breath washout (lung clearance index, LCI) and dry air hyperventilation challenge.
Increased prevalence of asthma/RW (39% vs 9%), clinical allergy (43% vs 17%) and sensitisation to perennial allergens (41% vs 14%) were present at age 18 in the RSV cohort compared with controls. Persistent/relapsing wheeze associated with early allergic sensitisation predominated in the RSV cohort compared with controls (30% vs 1%). Spirometric function was reduced in subjects with RSV with or without current asthma, but not in asthmatic controls. LCI was linked only to current asthma, airway hyperresponsiveness and FeNO.
Severe early RSV bronchiolitis is associated with an increased prevalence of allergic asthma persisting into early adulthood. Small airway dysfunction (LCI) is related to current asthma and airway inflammation but not to RSV bronchiolitis. Reduced spirometry after RSV may reflect airway remodelling.

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    • "Zomer-Kooijker et al. demonstrated increased risk of wheeze and decreased lung function after RSV infection [12]. Similarly, studies of Sigurs et al. also reported that severe early RSV bronchiolitis is associated with an increased prevalence of allergic asthma persisting into early adulthood [13]. Although the literature has reported viruses as precipitants of asthma symptoms [10], there have been few clinical studies that assess trends of RSV-infection on diseases associated with 0198-8859/Ó 2015 Published by Elsevier Inc. on behalf of American Society for Histocompatibility and Immunogenetics. "
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    ABSTRACT: Respiratory syncytial virus (RSV) causes lower respiratory tract disease in infants and young children, and is a public health concern, as is the increase in pediatric asthma. Respiratory viral infections may trigger asthma exacerbations. However, it remains unknown whether RSV infection may have a specific association with asthma. Total serum IgE, and IgE- and IgG- anti-RSV Ab responses were studied in older asthmatic compared with non-asthmatic children (M/F, mean age: 14) (N= 30, N=43, respectively) We found: (1) total serum IgE was higher in asthmatic compared with non-asthmatics (P< 0.001); (2) total serum IgE did correlate with IgE anti-RSV Abs (P<0.001), and with IgG anti-RSV Abs (P=0.008) in all subjects; (3) total serum IgE levels did correlate with IgE anti-RSV in asthmatics (P=0.047), but not in non-asthmatics (P=0.13); (4) IgE anti-RSV Abs did correlate with IgG anti-RSV Abs in all subjects (P=0.001); (5) IgE- and IgG- anti RSV Abs were higher in asthma compared with no asthma (, P=0.003; <0.001, respectively); (6) there was a significant association between age and IgE anti-RSV in non-asthma (P=0.008), but not in asthma (P= 0.64). Our findings indicate that IgE- anti-RSV Ab responses may play important roles in RSV infection and asthma. Copyright © 2015. Published by Elsevier Inc.
    Human immunology 06/2015; 76(7). DOI:10.1016/j.humimm.2015.06.002 · 2.14 Impact Factor
    • "The symptoms of RSV infection include labored breathing, coughing, and wheezing that resemble a " violent attack of asthma " . Although exposure to RSV early in life was initially associated with increased susceptibility to suffer recurrent allergic wheezing and asthma later in life [4] [5], recent studies have proposed that asthma-related genetic traits themselves could predispose to severe disease after RSV infection [6] [7]. "
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    ABSTRACT: Subunit vaccines comprised of glycoprotein D (gD-2) failed to prevent HSV-2 highlighting need for novel strategies. To test the hypothesis that deletion of gD-2 unmasks protective antigens, we evaluated the efficacy and safety of an HSV-2 virus deleted in gD-2 and complemented allowing a single round of replication on cells expressing HSV-1 gD (Delta gD(-/+gD-1)). Subcutaneous immunization of C57BL/6 or BALB/c mice with Delta gD(-/+gD1) provided 100% protection against lethal intravaginal or skin challenges and prevented latency. Delta gD(-/+gD1) elicited no disease in SCID mice, whereas 1000-fold lower doses of wild-type virus were lethal. HSV-specific antibodies were detected in serum (titer 1:800,000) following immunization and in vaginal washes after intravaginal challenge. The antibodies elicited cell-mediated cytotoxicity, but little neutralizing activity. Passive transfer of immune serum completely protected wild-type, but not Fc gamma-receptor or neonatal Fc-receptor knock-out mice. These studies demonstrate that non-neutralizing Fc-mediated humoral responses confer protection and support advancement of this attenuated vaccine.
    eLife Sciences 03/2015; 4. DOI:10.7554/eLife.06054 · 9.32 Impact Factor
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    • "Infections with RSV and hMPV are clinically indistinguishable with overlapping spectra of disease symptoms. Moreover, both RSV and hMPV can cause wheezing and exacerbations of asthma in children and adults [1]–[3] and severe disease has been linked to the development of asthma and atopy [4]–[9]. RSV and hMPV are single-stranded RNA viruses belonging to the Paramyxoviridae family, and despite similarities in their genomic organization, two major differences do exist: hMPV lacks the nonstructural proteins NS1 and NS2 and the gene order is different [10]. "
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    ABSTRACT: Respiratory syncytial virus (RSV) and human Metapneumovirus (hMPV), viruses belonging to the family Paramyxoviridae, are the most important causes of lower respiratory tract infection in young children. Infections with RSV and hMPV are clinically indistinguishable, and both RSV and hMPV infection have been associated with aberrant adaptive immune responses. Myeloid Dendritic cells (mDCs) play a pivotal role in shaping adaptive immune responses during infection; however, few studies have examined how interactions of RSV and hMPV with individual mDC subsets (BDCA-1+ and BDCA-3+ mDCs) affect the outcome of anti-viral responses. To determine whether RSV and hMPV induce virus-specific responses from each subset, we examined co-stimulatory molecules and cytokines expressed by BDCA-1+ and BDCA-3+ mDCs isolated from peripheral blood after infection with hMPV and RSV, and examined their ability to stimulate T cell proliferation and differentiation. Our data show that RSV and hMPV induce virus-specific and subset-specific patterns of co-stimulatory molecule and cytokine expression. RSV, but not hMPV, impaired the capacity of infected mDCs to stimulate T cell proliferation. Whereas hMPV-infected BDCA-1+ and BDCA-3+ mDCs induced expansion of Th17 cells, in response to RSV, BDCA-1+ mDCs induced expansion of Th1 cells and BDCA-3+ mDCs induced expansion of Th2 cells and Tregs. These results demonstrate a virus-specific and subset-specific effect of RSV and hMPV infection on mDC function, suggesting that these viruses may induce different adaptive immune responses.
    PLoS ONE 06/2014; 9(6):e99227. DOI:10.1371/journal.pone.0099227 · 3.23 Impact Factor
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