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      A novel group of rhinoviruses is associated with asthma hospitalizations

      research-article
      , MD, MPH a , , , MD a , , MD b , , PhD, MPH c , , MD, MPH d , , MD b , , MD, MS e , , MD, MPH b , , BS a , a , , MS c , , MD a , f , New Vaccine Surveillance Network
      The Journal of Allergy and Clinical Immunology
      American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc.
      Human rhinoviruses, asthma, children, wheezing, hospitalized, genetic diversity, ARI, Acute respiratory tract infection, hMPV, Human metapneumovirus, HRV, Human rhinovirus, HRVA, Group A human rhinovirus, HRVB, Group B human rhinovirus, HRVC, Group C human rhinovirus, NCR, Noncoding region, PIV, Parainfluenza virus, RSV, Respiratory syncytial virus

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          Abstract

          Background

          Although recent studies have identified new group C human rhinoviruses (HRVCs), their spectrum of pediatric disease is unknown.

          Objective

          We sought to determine the presentation and burden of disease caused by HRVCs among young hospitalized children.

          Methods

          We conducted prospective population-based surveillance in 2 US counties among children less than 5 years of age hospitalized with acute respiratory illness or fever from October 2001 through September 2003. Nasal/throat swabs were obtained and tested for HRVs, as determined by means of RT-PCR and then characterized by means of partial sequencing.

          Results

          Of 1052 children enrolled and tested during the 2-year period, 167 (16%) had HRVs detected. Of 147 samples successfully sequenced, 64 were group A HRVs, 6 were group B HRVs, and 77 were HRVCs. Children with HRVCs were significantly more likely than those with group A HRVs to have underlying high-risk conditions, such as asthma (42% vs 23%, P = .023) and to have had a discharge diagnosis of asthma (55% vs 36%, P = .022).

          Conclusions

          Overall, HRVCs were detected in 7% of children hospitalized for fever or respiratory conditions and constituted almost half of all rhinovirus-associated hospitalizations, suggesting that this novel group causes a substantial burden of pediatric disease.

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          Most cited references46

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          The economic burden of non-influenza-related viral respiratory tract infection in the United States.

          Viral respiratory tract infection (VRTI) is the most common illness in humans. Despite the high incidence, the economic impact of non-influenza-related VRTI has not been rigorously explored. Our objectives were to obtain an updated incidence of non-influenza-related VRTI in the United States and to quantify the health care resource use (direct costs) and productivity losses (indirect costs) associated with these infections. A nationwide telephone survey of US households (N = 4051) was conducted between November 3, 2000, and February 12, 2001 to obtain a representative estimate of the self-reported incidence of non-influenza-related VRTI and related treatment patterns. Direct treatment costs measured included outpatient clinician encounters, use of over-the-counter and prescription drugs, and associated infectious complications of non-influenza-related VRTI. Absenteeism estimates for infected individuals and parents of infected children were extrapolated from National Health Interview Survey data. Of survey respondents, 72% reported a non-influenza-related VRTI within the past year. Respondents who experienced a self-reported non-influenza-related VRTI averaged 2.5 episodes annually. When these rates are extrapolated to the entire US population, approximately 500 million non-influenza-related VRTI episodes occur per year. Similarly, if the treatment patterns reported by the respondents are extended to the population, the total economic impact of non-influenza-related VRTI approaches $40 billion annually (direct costs, $17 billion per year; and indirect costs, $22.5 billion per year). Largely because of the high attack rate, non-influenza-related VRTI imposes a greater economic burden than many other clinical conditions. The pending availability of effective antiviral therapies warrants increased attention be paid to this common and expensive illness.
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            Rhinovirus illnesses during infancy predict subsequent childhood wheezing.

            The contribution of viral respiratory infections during infancy to the development of subsequent wheezing and/or allergic diseases in early childhood is not established. To evaluate these relationships prospectively from birth to 3 years of age in 285 children genetically at high risk for developing allergic respiratory diseases. By using nasal lavage, the relationship of timing, severity, and etiology of viral respiratory infections during infancy to wheezing in the 3rd year of life was evaluated. In addition, genetic and environmental factors that could modify risk of infections and wheezing prevalence were analyzed. Risk factors for 3rd year wheezing were passive smoke exposure (odds ratio [OR]=2.1), older siblings (OR=2.5), allergic sensitization to foods at age 1 year (OR=2.0), any moderate to severe respiratory illness without wheezing during infancy (OR=3.6), and at least 1 wheezing illness with respiratory syncytial virus (RSV; OR=3.0), rhinovirus (OR=10) and/or non-rhinovirus/RSV pathogens (OR=3.9) during infancy. When viral etiology was considered, 1st-year wheezing illnesses caused by rhinovirus infection were the strongest predictor of subsequent 3rd year wheezing (OR=6.6; P < .0001). Moreover, 63% of infants who wheezed during rhinovirus seasons continued to wheeze in the 3rd year of life, compared with only 20% of all other infants (OR=6.6; P < .0001). In this population of children at increased risk of developing allergies and asthma, the most significant risk factor for the development of preschool childhood wheezing is the occurrence of symptomatic rhinovirus illnesses during infancy that are clinically and prognostically informative based on their seasonal nature.
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              Role of respiratory viruses in acute upper and lower respiratory tract illness in the first year of life: a birth cohort study.

              Although acute respiratory illnesses (ARI) are major causes of morbidity and mortality in early childhood worldwide, little progress has been made in their control and prophylaxis. Most studies have focused on hospitalized children or children from closed populations. It is essential that the viral etiology of these clinical diseases be accurately defined in the development of antiviral drugs. To investigate the role of all common respiratory viruses as upper and lower respiratory tract pathogens in the first year of life. This community-based birth cohort study prospectively collected detailed information on all ARI contracted by 263 infants from birth until 1 year of age. Nasopharyngeal aspirates were collected for each ARI episode, and all common respiratory viruses were detected by polymerase chain reaction. Episodes were classified as upper respiratory illnesses or lower respiratory illnesses (LRI), with or without wheeze. The majority reported 2-5 episodes of ARI in the first year (range, 0-11 episodes; mean, 4.1). One-third were LRI, and 29% of these were associated with wheeze. Viruses were detected in 69% of ARI; most common were rhinoviruses (48.5%) and respiratory syncytial virus (RSV) (10.9%). Compared with RSV, >10 times the number of upper respiratory illnesses and >3 times the number of both LRI and wheezing LRI were attributed to rhinoviruses. Rhinoviruses are the major upper and lower respiratory pathogens in the first year of life. Although RSV is strongly associated with severe LRI requiring hospitalization, the role of rhinoviruses as the major lower respiratory pathogens in infants has not previously been recognized.
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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
                22 November 2008
                January 2009
                22 November 2008
                : 123
                : 1
                : 98-104.e1
                Affiliations
                [a ]Department of Pediatrics, Vanderbilt University Medical Center, Nashville, Tenn
                [d ]Department of Preventative Medicine, Vanderbilt University Medical Center, Nashville, Tenn
                [e ]Department of Biostatistics, Vanderbilt University Medical Center, Nashville, Tenn
                [f ]Department of Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, Tenn
                [b ]Department of Pediatrics, University of Rochester School of Medicine and Dentistry, Rochester, NY
                [c ]National Immunization Program, Respiratory and Enteric Viruses Branch, Centers for Disease Control and Prevention, Atlanta, Ga
                Author notes
                []Reprint requests: E. Kathryn Miller, MD, MPH, Pediatric Allergy and Immunology, Vanderbilt Children's Hospital, 2200 Children's Way, 11215 Doctors' Office Tower, Nashville, TN 37232-9500. eva.k.miller@ 123456vanderbilt.edu
                Article
                S0091-6749(08)01847-2
                10.1016/j.jaci.2008.10.007
                7112283
                19027147
                0e4d73e0-b438-4a2c-ad86-586d383fd5c5
                Copyright © 2009 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
                : 14 February 2008
                : 30 September 2008
                : 1 October 2008
                Categories
                Article

                Immunology
                human rhinoviruses,asthma,children,wheezing,hospitalized,genetic diversity,ari, acute respiratory tract infection,hmpv, human metapneumovirus,hrv, human rhinovirus,hrva, group a human rhinovirus,hrvb, group b human rhinovirus,hrvc, group c human rhinovirus,ncr, noncoding region,piv, parainfluenza virus,rsv, respiratory syncytial virus

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