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      Rhinovirus and asthma: Challenges and opportunities

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          Summary

          Human rhinoviruses (RVs) are the primary aetiological agent of the common cold. Generally, the associated infection is mild and self‐limiting, but may also be associated with bronchiolitis in infants, pneumonia in the immunocompromised and exacerbation in patients with pulmonary conditions such as asthma or chronic obstructive pulmonary disease. Viral infection accounts for as many as two thirds of asthma exacerbations in children and more than half in adults. Allergy and asthma are major risk factors for more frequent and severe RV‐related illnesses. The prevalence of RV‐induced wheezing will likely continue to increase given that asthma affects a significant proportion of the population, with allergic asthma accounting for the majority. Several new respiratory viruses and their subgroups have been discovered, with various degrees of relevance. This review will focus on RV infection in the context of the epidemiologic evidence, genetic variability, pathobiology, clinical studies in the context of asthma, differences with other viruses including COVID‐19 and current treatment interventions.

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          Most cited references72

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          Clinical Characteristics of Covid-19 in New York City

          To the Editor: The world is in the midst of the coronavirus disease 2019 (Covid-19) pandemic, 1,2 and New York City has emerged as an epicenter. Here, we characterize the first 393 consecutive patients with Covid-19 who were admitted to two hospitals in New York City. This retrospective case series includes adults 18 years of age or older with confirmed Covid-19 who were consecutively admitted between March 3 (date of the first positive case) and March 27, 2020, at an 862-bed quaternary referral center and an affiliated 180-bed nonteaching community hospital in Manhattan. Both hospitals adopted an early-intubation strategy with limited use of high-flow nasal cannulae during this period. Cases were confirmed through reverse-transcriptase–polymerase-chain-reaction assays performed on nasopharyngeal swab specimens. Data were manually abstracted from electronic health records with the use of a quality-controlled protocol and structured abstraction tool (details are provided in the Methods section in the Supplementary Appendix, available with the full text of this letter at NEJM.org). Among the 393 patients, the median age was 62.2 years, 60.6% were male, and 35.8% had obesity (Table 1). The most common presenting symptoms were cough (79.4%), fever (77.1%), dyspnea (56.5%), myalgias (23.8%), diarrhea (23.7%), and nausea and vomiting (19.1%) (Table S1 in the Supplementary Appendix). Most of the patients (90.0%) had lymphopenia, 27% had thrombocytopenia, and many had elevated liver-function values and inflammatory markers. Between March 3 and April 10, respiratory failure leading to invasive mechanical ventilation developed in 130 patients (33.1%); to date, only 43 of these patients (33.1%) have been extubated. In total, 40 of the patients (10.2%) have died, and 260 (66.2%) have been discharged from the hospital; outcome data are incomplete for the remaining 93 patients (23.7%). Patients who received invasive mechanical ventilation were more likely to be male, to have obesity, and to have elevated liver-function values and inflammatory markers (ferritin, d-dimer, C-reactive protein, and procalcitonin) than were patients who did not receive invasive mechanical ventilation. Of the patients who received invasive mechanical ventilation, 40 (30.8%) did not need supplemental oxygen during the first 3 hours after presenting to the emergency department. Patients who received invasive mechanical ventilation were more likely to need vasopressor support (95.4% vs. 1.5%) and to have other complications, including atrial arrhythmias (17.7% vs. 1.9%) and new renal replacement therapy (13.3% vs. 0.4%). Among these 393 patients with Covid-19 who were hospitalized in two New York City hospitals, the manifestations of the disease at presentation were generally similar to those in a large case series from China 1 ; however, gastrointestinal symptoms appeared to be more common than in China (where these symptoms occurred in 4 to 5% of patients). This difference could reflect geographic variation or differential reporting. Obesity was common and may be a risk factor for respiratory failure leading to invasive mechanical ventilation. 3 The percentage of patients in our case series who received invasive mechanical ventilation was more than 10 times as high as that in China; potential contributors include the more severe disease in our cohort (since testing and hospitalization in the United States is largely limited to patients with more severe disease) and the early-intubation strategy used in our hospitals. Regardless, the high demand for invasive mechanical ventilation has the potential to overwhelm hospital resources. Deterioration occurred in many patients whose condition had previously been stable; almost a third of patients who received invasive mechanical ventilation did not need supplemental oxygen at presentation. The observations that the patients who received invasive mechanical ventilation almost universally received vasopressor support and that many also received new renal replacement therapy suggest that there is also a need to strengthen stockpiles and supply chains for these resources.
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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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              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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                Author and article information

                Contributors
                hortega@gossamerbio.com
                Journal
                Rev Med Virol
                Rev Med Virol
                10.1002/(ISSN)1099-1654
                RMV
                Reviews in Medical Virology
                John Wiley and Sons Inc. (Hoboken )
                1052-9276
                1099-1654
                20 November 2020
                July 2021
                : 31
                : 4 ( doiID: 10.1002/rmv.v31.4 )
                : e2193
                Affiliations
                [ 1 ] Gossamer Bio Inc. San Diego California USA
                Author notes
                [*] [* ] Correspondence

                Hector Ortega, Gossamer Bio Inc., 3013 Science Park Rd, San Diego, CA 92121, USA.

                Email: hortega@ 123456gossamerbio.com

                Author information
                https://orcid.org/0000-0002-2632-6370
                Article
                RMV2193
                10.1002/rmv.2193
                8365703
                33217098
                c8325d46-cf23-4672-8c12-a79dc743001f
                © 2020 The Authors. Reviews in Medical Virology published by John Wiley & Sons Ltd.

                This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.

                History
                : 29 October 2020
                : 20 August 2020
                : 30 October 2020
                Page count
                Figures: 4, Tables: 2, Pages: 10, Words: 0
                Categories
                Review
                Reviews
                Custom metadata
                2.0
                July 2021
                Converter:WILEY_ML3GV2_TO_JATSPMC version:6.0.5 mode:remove_FC converted:16.08.2021

                Microbiology & Virology
                asthma exacerbations,influenza,rhinovirus,sars‐cov‐2
                Microbiology & Virology
                asthma exacerbations, influenza, rhinovirus, sars‐cov‐2

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