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      Early-life respiratory viral infections, atopic sensitization, and risk of subsequent development of persistent asthma

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          Abstract

          Background

          Severe lower respiratory infections (LRIs) and atopic sensitization have been identified as independent risk factors for asthma.

          Objective

          The nature of potential interactions between these risk factors was the subject of this study.

          Methods

          A community-based cohort of 198 children at high atopic risk was followed from birth to 5 years. All episodes of acute respiratory illness in the first year were recorded and postnasal aspirates were collected for viral identification. History of wheeze and asthma was collected annually, and atopy was assessed at 6 months, 2 years, and 5 years.

          Results

          A total of 815 episodes of acute respiratory illness were reported, and 33% were LRIs. Viruses were detected in 69% of aspirates, most commonly rhinoviruses (48.3%) and respiratory syncytial virus (10.9%). At 5 years, 28.3%(n = 56) had current wheeze, and this was associated with wheezy [odds ratio (OR), 3.4 (1.2-9.7); P = .02] and/or febrile LRI [OR, 3.9 (1.4-10.5); P = .007], in particular those caused by respiratory syncytial virus or rhinoviruses [OR, 4.1 (1.3-12.6); P = .02]. Comparable findings were made for current asthma. Strikingly these associations were restricted to children who displayed early sensitization (≤2 years old) and not observed in nonatopic patients or those sensitized later.

          Conclusion

          These data suggest viral infections interact with atopy in infancy to promote later asthma. Notably the occurrence of both of these events during this narrow developmental window is associated with maximal risk for subsequent asthma, which suggests a contribution from both classes of inflammatory insults to disease pathogenesis.

          Clinical implications

          Protection of “high-risk” children against the effects of severe respiratory infections during infancy may represent an effective strategy for primary asthma prevention. The potential benefits of these strategies merit more careful evaluation in this age group.

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          Most cited references26

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          Community study of role of viral infections in exacerbations of asthma in 9-11 year old children.

          To study the association between upper and lower respiratory viral infections and acute exacerbations of asthma in schoolchildren in the community. Community based 13 month longitudinal study using diary card respiratory symptom and peak expiratory flow monitoring to allow early sampling for viruses. 108 Children aged 9-11 years who had reported wheeze or cough, or both, in a questionnaire. Southampton and surrounding community. Upper and lower respiratory viral infections detected by polymerase chain reaction or conventional methods, reported exacerbations of asthma, computer identified episodes of respiratory tract symptoms or peak flow reductions. Viruses were detected in 80% of reported episodes of reduced peak expiratory flow, 80% of reported episodes of wheeze, and in 85% of reported episodes of upper respiratory symptoms, cough, wheeze, and a fall in peak expiratory flow. The median duration of reported falls in peak expiratory flow was 14 days, and the median maximum fall in peak expiratory flow was 81 l/min. The most commonly identified virus type was rhinovirus. This study supports the hypothesis that upper respiratory viral infections are associated with 80-85% of asthma exacerbations in school age children.
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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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              Respiratory viruses and exacerbations of asthma in adults.

              To study the role of respiratory viruses in exacerbations of asthma in adults. Longitudinal study of 138 adults with asthma. Leicestershire Health Authority. 48 men and 90 women 19-46 years of age with a mean duration of wheeze of 19.6 years. 75% received regular treatment with bronchodilators; 89% gave a history of eczema, hay fever, allergic rhinitis, nasal polyps, or allergies; 38% had been admitted to hospital with asthma. Symptomatic colds and asthma exacerbations; objective exacerbations of asthma with > or = 50 l/min reduction in mean peak expiratory flow rate when morning and night time readings on days 1-7 after onset of symptoms were compared with rates during an asymptomatic control period; laboratory confirmed respiratory tract infections. Colds were reported in 80% (223/280) of episodes with symptoms of wheeze, chest tightness, or breathlessness, and 89% (223/250) of colds were associated with asthma symptoms. 24% of 115 laboratory confirmed non-bacterial infections were associated with reductions in mean peak expiratory flow rate > or = 50 l/min through days 1-7 and 48% had mean decreases > or = 25 l/min. 44% of episodes with mean decreases in flow rate > or = 50 l/min were associated with laboratory confirmed infections. Infections with rhinoviruses, coronaviruses OC43 and 229E, influenza B, respiratory syncytial virus, parainfluenza virus, and chlamydia were all associated with objective evidence of an exacerbation of asthma. These findings show that asthma symptoms and reductions in peak flow are often associated with colds and respiratory viruses; respiratory virus infections commonly cause or are associated with exacerbations of asthma in adults.
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                Author and article information

                Contributors
                Journal
                J Allergy Clin Immunol
                J. Allergy Clin. Immunol
                The Journal of Allergy and Clinical Immunology
                American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc.
                0091-6749
                1097-6825
                13 March 2007
                May 2007
                13 March 2007
                : 119
                : 5
                : 1105-1110
                Affiliations
                [a ]From the Telethon Institute for Child Health Research, Centre for Child Health Research, University of Western Australia
                [b ]National Heart and Lung Institute, Imperial College, London
                Author notes
                []Reprint requests: Merci M. H. Kusel, MBBS, PhD, Senior Research Officer, Division of Clinical Sciences, Telethon Institute for Child Health Research, P.O. Box 855, West Perth 6872, Australia. mercik@ 123456ichr.uwa.edu.au
                Article
                S0091-6749(07)00238-2
                10.1016/j.jaci.2006.12.669
                7125611
                17353039
                afdf64bc-f95a-4489-8be8-5c38bb7f881a
                Copyright © 2007 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

                Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.

                History
                : 6 September 2006
                : 5 December 2006
                : 11 December 2006
                Categories
                Article

                Immunology
                acute respiratory infections,childhood asthma,persistent wheeze,rhinovirus,rsv,ari, acute respiratory illness,lri, lower respiratory illness,npa, nasopharyngeal aspirate,or, odds ratio,rsv, respiratory syncytial virus,spt, skin prick test,wlri, wheezy lower respiratory tract illness

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