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      The Burden and Long-term Respiratory Morbidity Associated with Respiratory Syncytial Virus Infection in Early Childhood

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          Abstract

          Introduction

          The REGAL (RSV Evidence—a Geographical Archive of the Literature) series provide a comprehensive review of the published evidence in the field of respiratory syncytial virus (RSV) in Western countries over the last 20 years. The objective of this fifth publication was to determine the long-term respiratory morbidity associated with RSV lower respiratory tract infection (RSV LRTI) in early life.

          Methods

          A systematic review was undertaken for articles published between January 1, 1995 and December 31, 2015. This was supplemented by inclusion of papers published whilst drafting the manuscript. Studies reporting data on the incidence and long-term wheezing and asthma following RSV LRTI in early life were included. Study quality and strength of evidence (SOE) were graded using recognized criteria.

          Results

          A total of 2337 studies were identified of which 74 were included. Prospective, epidemiologic studies consistently demonstrated that RSV LRTI is a significant risk factor for on-going respiratory morbidity characterized by transient early wheezing and recurrent wheezing and asthma within the first decade of life and possibly into adolescence and adulthood (high SOE). RSV LRTI was also associated with impaired lung function in these children (high SOE). Respiratory morbidity has been shown to result in reduced quality of life and increased healthcare resource use (moderate SOE). The mechanisms through which RSV contributes to wheezing/asthma development are not fully understood, but appear to relate to the viral injury, preexisting abnormal lung function and/or other factors that predispose to wheezing/asthma, including genetic susceptibility, altered immunology, eosinophilia, and associated risk factors such as exposure to environmental tobacco smoke (high SOE).

          Conclusion

          There is growing evidence that RSV LRTI in early childhood is associated with long-term wheezing and asthma and impaired lung function. Future research should aim to fully elucidate the pathophysiological mechanisms through which RSV causes recurrent wheezing/asthma.

          Electronic supplementary material

          The online version of this article (doi:10.1007/s40121-017-0151-4) contains supplementary material, which is available to authorized users.

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          Most cited references79

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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

                Contributors
                carbonell@comb.cat
                Journal
                Infect Dis Ther
                Infect Dis Ther
                Infectious Diseases and Therapy
                Springer Healthcare (Cheshire )
                2193-8229
                2193-6382
                29 March 2017
                29 March 2017
                June 2017
                : 6
                : 2
                : 173-197
                Affiliations
                [1 ]ISNI 0000 0004 0593 9113, GRID grid.412134.1, , Necker University Hospital and Paris 5 University, ; Paris, France
                [2 ]ISNI 0000 0001 0703 675X, GRID grid.430503.1, , University of Colorado School of Medicine, and Center for Global Health, Colorado School of Public Health, ; Aurora, CO USA
                [3 ]ISNI 0000 0001 2200 2638, GRID grid.416975.8, Baylor College of Medicine, , Texas Children’s Hospital Houston, ; Houston, TX USA
                [4 ]ISNI 0000 0004 1936 8227, GRID grid.25073.33, Department of Paediatrics (Neonatal Division), , McMaster University, ; Hamilton, Canada
                [5 ]ISNI 0000 0004 1937 0247, GRID grid.5841.8, Hospital Clínic, Catedràtic de Pediatria, , Universitat de Barcelona, ; Barcelona, Spain
                [6 ]ISNI 0000 0004 1789 4557, GRID grid.415236.7, , Sant’Anna Hospital, ; Turin, Italy
                [7 ]ISNI 0000000090126352, GRID grid.7692.a, , University Medical Center Utrecht, ; Utrecht, The Netherlands
                [8 ]ISNI 0000 0000 9635 9413, GRID grid.410458.c, , Hospital Clinic, Institut d’Investigacions Biomediques August Pi Suñer (IDIBAPS), ; Barcelona, Spain
                Article
                151
                10.1007/s40121-017-0151-4
                5446364
                28357706
                bc20d526-4787-4cb1-aac6-292ffd683959
                © The Author(s) 2017
                History
                : 1 February 2017
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/100006483, AbbVie;
                Categories
                Review
                Custom metadata
                © Springer Healthcare 2017

                asthma,bronchial hyperreactivity,bronchiolitis,lower respiratory tract infection,lung function,recurrent wheezing,respiratory morbidity,sensitization,wheezing

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