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      Impact of Prematurity and Severe Viral Bronchiolitis on Asthma Development at 6–9 Years

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          Abstract

          Background

          Premature birth is associated with increased susceptibility for viral infections and chronic airway morbidity. Preterm children, even moderate and late, may be at risk for short- and long-term respiratory morbidities.

          Objective

          Our main goal was to compare the burden of two conditions, severe bronchiolitis and prematurity (early and moderate-late), on asthma development at 6–9 years.

          Patients and Methods

          A retrospective cohort of all preterm (<37weeks gestational age) and full-term children hospitalized for bronchiolitis, with current age between 6 and 9 years, was created. A second cohort was made up of preterm children, without admission for bronchiolitis, randomly chosen from the hospital premature births database. Prevalence and risk factors for asthma were analysed. Parents completed the International Study of Asthma and Allergies in Childhood (ISAAC) Questionnaire for asthma symptoms for children 6–7 years. Lung function and aeroallergen sensitization were evaluated.

          Results

          Of the 480 selected children, 399 could be contacted and agreed to participate: 133 preterm and 114 full-term cases with admission for bronchiolitis and 146 preterm control children without admission for bronchiolitis. The frequency of current asthma at 6–9 years was higher in preterm cases (27%) compared with full-term-cases (15%) and preterm controls (14%) (p=0.04). Among hospitalized-bronchiolitis children, prematurity (p=0.04), rhinovirus infection (p=0.03), viral coinfection (p=0.04) and paternal asthma (p=0.003) were risk factors for asthma at 6–9 years. Among premature children, with and without bronchiolitis admission, the risk factors for asthma at 6–9 years were admission for bronchiolitis (p=0.03) and aeroallergen sensitisation (p=0.01). Moderate and late preterm children without admission for bronchiolitis showed similar prevalence of current asthma than full-term ones, previously admitted for bronchiolitis.

          Conclusion

          Preterm birth is an important early life risk factor for asthma in childhood. The addition of other risk factors, such as severe bronchiolitis, especially by rhinovirus or viral coinfections, are associated with even higher risk for subsequent asthma.

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          Most cited references34

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          Wheezing rhinovirus illnesses in early life predict asthma development in high-risk children.

          Virus-induced wheezing episodes in infancy often precede the development of asthma. Whether infections with specific viral pathogens confer differential future asthma risk is incompletely understood. To define the relationship between specific viral illnesses and early childhood asthma development. A total of 259 children were followed prospectively from birth to 6 years of age. The etiology and timing of specific viral wheezing respiratory illnesses during early childhood were assessed using nasal lavage, culture, and multiplex reverse transcriptase-polymerase chain reaction. The relationships of these virus-specific wheezing illnesses and other risk factors to the development of asthma were analyzed. Viral etiologies were identified in 90% of wheezing illnesses. From birth to age 3 years, wheezing with respiratory syncytial virus (RSV) (odds ratio [OR], 2.6), rhinovirus (RV) (OR, 9.8), or both RV and RSV (OR , 10) was associated with increased asthma risk at age 6 years. In Year 1, both RV wheezing (OR, 2.8) and aeroallergen sensitization (OR, 3.6) independently increased asthma risk at age 6 years. By age 3 years, wheezing with RV (OR, 25.6) was more strongly associated with asthma at age 6 years than aeroallergen sensitization (OR, 3.4). Nearly 90% (26 of 30) of children who wheezed with RV in Year 3 had asthma at 6 years of age. Among outpatient viral wheezing illnesses in infancy and early childhood, those caused by RV infections are the most significant predictors of the subsequent development of asthma at age 6 years in a high-risk birth cohort.
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            Respiratory syncytial virus in early life and risk of wheeze and allergy by age 13 years.

            The relation between lower respiratory tract illnesses in early life caused by the respiratory syncytial virus (RSV) and the subsequent development of wheezing and atopy in childhood is not well understood. We studied this relation in children who had lower respiratory tract illnesses that occurred before 3 years of age. Children were enrolled at birth and cases of lower respiratory tract illness were ascertained by a physician. Viral tests were done for specimens collected at the time of the illness. Children were classified into five groups according to type and cause of lower respiratory tract illness. Children were then followed prospectively up to age 13, and we measured frequency of wheezing, pulmonary function, and atopic status (allergy skin-prick tests, serum IgE concentrations). RSV lower respiratory tract illnesses were associated with an increased risk of infrequent wheeze (odds ratio 3.2 [95% CI 2.0-5.0], p < 0.001), and an increased risk of frequent wheeze (4.3 [2.2-8.7], p < or = 0.001) by age 6. Risk decreased markedly with age and was not significant by age 13. There was no association between RSV lower respiratory tract illnesses and subsequent atopic status. RSV lower respiratory tract illnesses were associated with significantly lower measurements of forced expiratory volume (2.11 [2.05-2.15], p < or = 0.001) when compared with those of children with no lower respiratory tract illnesses, but there was no difference in forced expiratory volume after inhalation of salbutamol. RSV lower respiratory tract illnesses in early childhood are an independent risk factor for the subsequent development of wheezing up to age 11 years but not at age 13. This association is not caused by an increased risk of allergic sensitisation.
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              Asthma and allergy patterns over 18 years after severe RSV bronchiolitis in the first year of life.

              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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                Author and article information

                Journal
                J Asthma Allergy
                J Asthma Allergy
                jaa
                jaa
                Journal of Asthma and Allergy
                Dove
                1178-6965
                18 September 2020
                2020
                : 13
                : 343-353
                Affiliations
                [1 ]Pediatrics Department, Severo Ochoa University Hospital, Fundación IDIPHISA, Alfonso X El Sabio University Madrid, Spain. Translational Research Network in Pediatric Infectious Diseases (RITIP) , Madrid, Spain
                [2 ]Department, Severo Ochoa University Hospital, Fundación IDIPHISA. Alfonso X El Sabio University , Madrid, Spain
                [3 ]Respiratory Virus and Influenza Unit, National Microbiology Center (ISCIII) , Madrid, Spain
                [4 ]Pediatric Infectious Diseases Department, Fundación IdiPaz, Translational Research Network in Pediatric Infectious Diseases (RITIP), Madrid, Spain. TEDDY Network (European Network of Excellence for Pediatric Clinical Research), Italy. La Paz University Hospital , Madrid, Spain
                Author notes
                Correspondence: Maria Luz Garcia-Garcia Email marialuz.hso@gmail.com
                Author information
                http://orcid.org/0000-0003-4906-4227
                http://orcid.org/0000-0003-3661-973X
                http://orcid.org/0000-0003-1828-733X
                http://orcid.org/0000-0003-1840-1198
                http://orcid.org/0000-0002-6503-3423
                Article
                258447
                10.2147/JAA.S258447
                7509474
                32982322
                a42dec48-7491-4fc5-8432-d4b5ebef59e2
                © 2020 Garcia-Garcia et al.

                This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms ( https://www.dovepress.com/terms.php).

                History
                : 24 April 2020
                : 10 August 2020
                Page count
                Figures: 1, Tables: 10, References: 39, Pages: 11
                Funding
                Funded by: FIS (Fondo de Investigaciones Sanitarias – Spanish Health Research Fund);
                This study has been supported by FIS (Fondo de Investigaciones Sanitarias – Spanish Health Research Fund) Grants Nº:, PI15CIII/00028,  PI18CIII/00009.
                Categories
                Original Research

                Immunology
                asthma,wheezing,prematurity,bronchiolitis,rhinovirus,respiratory syncytial virus
                Immunology
                asthma, wheezing, prematurity, bronchiolitis, rhinovirus, respiratory syncytial virus

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