Rhinovirus-induced Interferon-γ and Airway Responsiveness in Asthma

Brooks, G. Daniel; Buchta, Kim A.; Swenson, Cheri A.; Gern, James E.; Busse, William W.

doi:10.1164/rccm.200306-737oc

Cited by 99 publications

(69 citation statements)

References 28 publications

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“…Perhaps individuals with asthma have increased protease activation leading to increased susceptibility to infection. Alternatively, several studies have provided evidence that asthma is associated with impaired innate antiviral responses (20,21). In our study, peripheral blood mononuclear cell innate responses to HRV or RSV between children with and without asthma were similar, suggesting that increased H1N1 infectivity in individuals with asthma is not the result of a defect in innate immunity.…”

Section: Discussionsupporting

confidence: 61%

Increased H1N1 Infection Rate in Children with Asthma

Kloepfer¹,

Olenec²,

Lee³

et al. 2012

Am J Respir Crit Care Med

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Rationale: The 2009 H1N1 flu appeared to cause more severe cold symptoms during the 2009-2010 flu season. Objectives: We evaluated H1N1 infections during peak viral season in children with and without asthma to determine whether the H1N1 infectivity rate and illness severity were greater in subjects with asthma. Methods: One hundred and eighty children, 4-12 years of age, provided eight consecutive weekly nasal mucus samples from September 5 through October 24, 2009, and scored cold and asthma symptoms daily. Viral diagnostics were performed for all nasal samples. Measurements and Main Results: One hundred and sixty-one children (95 with asthma, 66 without asthma) completed at least 6 of the 8 nasal samples. The incidence of H1N1 infection was significantly higher in children with asthma (41%) than in children without asthma (24%; odds ratio, 4; 95% confidence interval, 1.8-9; P , 0.001), but rates of human rhinovirus infection (90% each) and other viral infections (47 vs. 41%) were similar. In children with asthma, there was a nonsignificant trend for increased loss of asthma control during H1N1 infections compared with human rhinovirus infections (38 vs. 21%; odds ratio, 2.6; 95% confidence interval, 0.9-7.2; P ¼ 0.07). Conclusions: During peak 2009 H1N1 flu season, children with asthma were infected almost twice as often with H1N1 compared with other respiratory viruses. H1N1 infection also caused increased severity of cold symptoms compared with other viral infections. Given the increased susceptibility of children with asthma to infection, these findings reinforce the need for yearly influenza vaccination to prevent infection, and raise new questions about the mechanism for enhanced susceptibility to influenza infection in asthma.Keywords: asthma; viral infection; influenza 2009 H1N1 Flu was first reported in the United States in the spring of 2009, and eventually affected 61 million people (1), one-third of them children. Morbidity was high, with 87,000 children requiring hospitalization. The most common comorbidity for patients hospitalized as a result of H1N1 infection was asthma (2), and the percentage of children with asthma hospitalized because of the 2009 H1N1 virus was two-to fivefold higher than previous reports of hospitalization due to seasonal influenza (3, 4). Despite the observation that subjects with asthma suffer H1N1 illness with increased severity, it remains unclear at what rate they are infected and whether their symptom severity is greater than those of their nonasthmatic counterparts. Previous studies of H1N1 infectivity reflect symptomatic infections with limited reporting of mild or asymptomatic infection (5-7).A study by our group demonstrated that 90% of children with asthma are infected with human rhinoviruses (HRVs) during the month of September, and that the severity of clinical illness varies from no symptoms to severe wheezing illnesses (8). This study provided the foundation on which we designed a larger cohort to prospectively examine the relationship between illness symptom...

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Section: Discussionsupporting

confidence: 61%

Increased H1N1 Infection Rate in Children with Asthma

Kloepfer¹,

Olenec²,

Lee³

et al. 2012

Am J Respir Crit Care Med

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“…In our studies, neither atopy nor asthma were associated with impaired virus‐induced interferon responses (IFN‐γ or IFN‐α responses to RSV, RV, or TLR3), which differs from results of several previously published studies 7, 8, 28. The reason for the lack of association could be related to either age or cell source.…”

Section: Discussioncontrasting

confidence: 99%

“…Similarly, studies of mononuclear cells and cloned T cells from peripheral blood of atopic asthmatic adults and children have described a Th2 bias to antigen 7, 10. In addition, there is evidence that deficient interferon responses in asthma may promote virus‐induced wheezing illnesses, and in children, the development of asthma 8, 13, 14, 15, 16, 17. Further investigation of the immune response to microbial and antigenic stimuli in allergic and asthmatic adults are needed, particularly in the urban population, where asthma prevalence and morbidity is especially high.…”

Section: Introductionmentioning

confidence: 99%

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The influence of atopy and asthma on immune responses in inner‐city adults

Kakumanu

Jaffee

Visness

et al. 2016

Immunity, Inflammation and Disease

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Asthma in the inner‐city population is usually atopic in nature, and is associated with significant morbidity and mortality. However, the underlying immune abnormalities that underlie asthma in urban adults have not been well defined. We investigated the influence of atopy and asthma on cytokine responses of inner‐city adult women to define immune abnormalities associated with asthma and atopy. Blood samples were collected from 509 of 606 inner‐city women enrolled in the Urban Environment and Childhood Asthma (URECA) study. We tested for associations between atopy and asthma status and cytokine responses in peripheral blood mononuclear cells incubated ex vivo with a panel of innate and adaptive immune stimulants. Atopic subjects had heightened Th2 cytokine responses (IL‐4, IL‐5, IL‐13) to cockroach and dust mite antigens, tetanus toxoid, and phytohemagglutinin (P < 0.05 for all). Differences in cytokine responses were greatest in response to stimulation with cockroach and dust mite. In a multivariate analysis, atopy was broadly related to increased Th2‐like responses to all antigens and PHA, while asthma was only weakly related to mitogen‐induced IL‐4 and IL‐5 responses. There were few asthma or allergy‐related differences in responses to innate stimuli, including IFN‐α and IFN‐γ responses. In this inner‐city adult female population, atopy is associated with enhanced Th2 responses to allergens and other stimuli, and there was little or no additional signal attributable to asthma. In particular, these data indicate that altered systemic interferon and innate immune responses are not associated with allergies and/or asthma in inner‐city women.

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“…In addition, the skewing of the cytokine phenotype away from an IFN-g-induced intracellular pathogen-clearing response toward a cytokine-directing ''reparative response'' may leave the host at risk for an exacerbated viral infection. Previous reports have demonstrated that decreased IFN-g production is associated with more severe rhinovirus infection and a delay in the elimination of the virus (23). This reduced type 1 response to rhinovirus has been reported to increase both asthma severity and viral shedding during rhinovirus infection.…”

Section: Cytokine Polarization and The Exacerbation Of Pulmonary Viramentioning

confidence: 95%