Weekly monitoring of children with asthma for infections and illness during common cold seasons

Olenec, Jaime; Kim, Woo Kyung; Lee, Wai Ming; Vang, Fue; Pappas, T.E.; Salazar, L.E.P.; Evans, Michael D.; Bork, Jack A.; Roberg, K.A.; Lemanske, Robert F.; Gern, James E.

doi:10.1016/j.jaci.2010.01.059

Cited by 167 publications

(155 citation statements)

References 18 publications

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“…(6) These findings strongly suggest that there are cofactors which affect the relationship between RV infection and illness, and suggest that airway bacteria might contribute in this regard. Furthermore, a recent study found an increase in invasive pneumococcal disease during peak RV activity.…”

Section: Introductionmentioning

confidence: 82%

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Detection of pathogenic bacteria during rhinovirus infection is associated with increased respiratory symptoms and asthma exacerbations

Kloepfer

Lee

Pappas

et al. 2014

Journal of Allergy and Clinical Immunology

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243

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Background Detection of either viral or bacterial pathogens is associated with wheezing in children, however the influence of both bacteria and virus on illness symptoms has not been described. Objective We evaluated bacterial detection during peak RV season in children with and without asthma to determine if an association exists between bacterial infection and the severity of RV illnesses. Methods 308 children (166 with asthma, 142 without asthma) ages 4–12 years provided five consecutive weekly nasal samples during September, and scored cold and asthma symptoms daily. Viral diagnostics and quantitative PCR for Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis were performed on all nasal samples. Results Detection rates were 53%, 17% and 11% for H. influenzae, S. pneumoniae and M. catarrhalis, respectively, with detection of RV increasing the risk of detecting bacteria within the same sample (OR 2.0, 95% CI 1.4–2.7, p<0.0001) or the following week (OR 1.6 (1.1–2.4), p=0.02). In the absence of RV, S. pneumoniae was associated with increased cold symptoms (mean 2.7 (95% CI 2.0–3.5) vs. 1.8 (1.5–2.2), p=0.006) and moderate asthma exacerbations (18% (12%–27%) vs. 9.2% (6.7%–12%), p=0.006). In the presence of RV, S. pneumoniae was associated with increased moderate asthma exacerbations (22% (16%–29%) vs. 15% (11%–20%), p=0.01). Furthermore, M. catarrhalis detected alongside RV increased the likelihood of experiencing cold and/or asthma symptoms compared to isolated detection of RV (OR 2.0 (1.0–4.1), p=0.04). Regardless of RV status, H. influenzae was not associated with respiratory symptoms. Conclusion RV infection enhances detection of specific bacterial pathogens in children with and without asthma. Furthermore, these findings suggest that M. catarrhalis and S. pneumoniae contribute to the severity of respiratory illnesses, including exacerbations of asthma.

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Section: Introductionmentioning

confidence: 82%

“…(6, 8) These samples were analyzed for common respiratory viruses by Respiratory Multicode Assay, EraGen Biosciences, Madison, Wisconsin. (9)…”

Section: Methodsmentioning

confidence: 99%

Detection of pathogenic bacteria during rhinovirus infection is associated with increased respiratory symptoms and asthma exacerbations

Kloepfer

Lee

Pappas

et al. 2014

Journal of Allergy and Clinical Immunology

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243

206

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“…This issue is pertinent, especially in the context of evidence that asthmatics are more susceptible to develop lower respiratory viral infections [4] and that their infections are of greater severity [49]. Infections in asthmatics have also been reported to persist for longer, although this is controversial and the increase in RV-related illness may instead be a result of re-infection [4,50-53].…”

Section: Discussionmentioning

confidence: 99%

Response of airway epithelial cells to double-stranded RNA in an allergic environment

et al. 2014

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BackgroundRespiratory viral infections are the most common trigger of acute exacerbations in patients with allergic asthma. The anti-viral response of airway epithelial cells (AEC) may be impaired in asthmatics, while cytokines produced by AEC may drive the inflammatory response. We investigated whether AEC cultured in the presence of Th2 cytokines associated with an allergic environment exhibited altered responses to double-stranded RNA, a virus-like stimulus.MethodsWe undertook preliminary studies using the MLE-12 cell line derived from mouse distal respiratory epithelial cells, then confirmed and extended our findings using low-passage human AEC. Cells were cultured in the absence or presence of the Th2 cytokines IL-4 and IL-13 for 48 hours, then stimulated with poly I:C for 4 hours. Expression of relevant anti-viral response and cytokine genes was assessed by quantitative real-time PCR. Secretion of cytokine proteins was assessed by immunoassay.ResultsFollowing stimulation with poly I:C, MLE-12 cells pre-treated with Th2 cytokines exhibited significantly higher levels of expression of mRNA for the cytokine genes Cxcl10 and Cxcl11, as well as a trend towards increased expression of Cxcl9 and Il6. Expression of anti-viral response genes was mostly unchanged, although Stat1, Ifit1 and Ifitm3 were significantly increased in Th2 cytokine pre-treated cells. Human AEC pre-treated with IL-4 and IL-13, then stimulated with poly I:C, similarly exhibited significantly higher expression of IL8, CXCL9, CXCL10, CXCL11 and CCL5 genes. In parallel, there was significantly increased secretion of CXCL8 and CCL5, as well as a trend towards increased secretion of CXCL10 and IL-6. Again, expression of anti-viral response genes was not decreased. Rather, there was significantly enhanced expression of mRNA for type III interferons, RNA helicases and other interferon-stimulated genes.ConclusionThe Th2 cytokine environment appears to promote increased production of pro-inflammatory chemokines by AEC in response to double-stranded RNA, which could help explain the exaggerated inflammatory response to respiratory viral infection in allergic asthmatics. However, any impairment of anti-viral host defences in asthmatics appears unlikely to be a consequence of Th2 cytokine-induced downregulation of the expression of viral response genes by AEC.

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“…Cold and asthma symptom severity was scored based on a four-point scoring system (Table E2), as described previously [17]. Subjects were also trained to collect nasal mucus using a nose-blowing technique as previously described [18, 19].…”

Section: Methodsmentioning

confidence: 99%

Genetic associations with viral respiratory illnesses and asthma control in children

Loisel

Ahluwalia

et al. 2015

Clin Experimental Allergy

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Background Viral respiratory infections can cause acute wheezing illnesses in children and exacerbations of asthma. Objective We sought to identify variation in genes with known antiviral and pro-inflammatory functions to identify specific associations with more severe viral respiratory illnesses and the risk of virus-induced exacerbations during the peak fall season. Methods The associations between genetic variation at 326 SNPs in 63 candidate genes and 10 phenotypes related to viral respiratory infection and asthma control were examined in 226 children enrolled in the RhinoGen study. Replication of asthma control phenotypes was performed in 2,128 children in the Copenhagen Prospective Study on Asthma in Childhood (COPSAC). Significant associations in RhinoGen were further validated using virus-induced wheezing illness and asthma phenotypes in an independent sample of 122 children enrolled in the Childhood Origins of Asthma birth cohort study (COAST). Results A significant excess of P values smaller than 0.05 was observed in the analysis of the 10 RhinoGen phenotypes. Polymorphisms in 12 genes were significantly associated with variation in the four phenotypes showing a significant enrichment of small P values. Six of those genes (STAT4, JAK2, MX1, VDR, DDX58, and EIF2AK2) also showed significant associations with asthma exacerbations in the COPSAC study or with asthma or virus-induced wheezing phenotypes in the COAST study. Conclusions We identified genetic factors contributing to individual differences in childhood viral respiratory illnesses and virus-induced exacerbations of asthma. Defining mechanisms of these associations may provide insight into the pathogenesis of viral respiratory infections and virus-induced exacerbations of asthma.

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Weekly monitoring of children with asthma for infections and illness during common cold seasons

Abstract: Background-Exacerbations of childhood asthma and rhinovirus infections both peak during the spring and fall, suggesting that viral infections are major contributors to seasonal asthma morbidity.

Cited by 167 publications

References 18 publications

Detection of pathogenic bacteria during rhinovirus infection is associated with increased respiratory symptoms and asthma exacerbations

Detection of pathogenic bacteria during rhinovirus infection is associated with increased respiratory symptoms and asthma exacerbations

Response of airway epithelial cells to double-stranded RNA in an allergic environment

Genetic associations with viral respiratory illnesses and asthma control in children

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