Asthma and lower airway diseaseInterferon regulatory factor 7 is a major hub connecting interferon-mediated responses in virus-induced asthma exacerbations in vivo
Section snippets
Study population
The study population consisted of 16 children from a larger prospective study of 218 children with mild-to-moderate asthma who were followed for 18 months or until they had an exacerbation. The protocol design and follow-up have been described previously.9 Briefly, at enrollment, subjects were assessed by a study physician, and if necessary, adjustments were made to achieve national guideline recommendations for asthma control. When a child experienced symptoms of an exacerbation (cough,
Gene expression profiling of virus-induced asthma exacerbations in nasal lavage cells
To investigate the mechanisms underlying asthma exacerbations, children with mild-to-moderate asthma (n = 16) were followed prospectively, and nasal lavage samples were obtained during an acute, picornavirus-induced exacerbation and 7 to 14 days later. The characteristics of the study population are presented in Table I, and it is noteworthy that these were moderate exacerbations defined with criteria equivalent to the American Thoracic Society/European Respiratory Society consensus.15 The
Discussion
Acute exacerbations have a substantial effect on health care use and treatment costs for children with asthma. Although inhaled corticosteroids can reduce the frequency of exacerbations, they cannot entirely prevent them, and they are not effective at controlling neutrophilic inflammation, which is increasingly recognized as playing a major role in pathogenesis.33 New drugs are urgently needed. However, selection of drug targets based on oversimplified, gene/factor-centric paradigms of
References (46)
- et al.
Gene expression signatures diagnose influenza and other symptomatic respiratory viral infections in humans
Cell Host Microbe
(2009) - et al.
Altered gene expression profiles in nasal respiratory epithelium reflect stable versus acute childhood asthma
J Allergy Clin Immunol
(2005) - et al.
Rhinovirus-induced modulation of gene expression in bronchial epithelial cells from subjects with asthma
Mucosal Immunol
(2010) - et al.
Decreased activation of inflammatory networks during acute asthma exacerbations is associated with chronic airflow obstruction
Mucosal Immunol
(2010) Convergence of the NF-kappaB and IRF pathways in the regulation of the innate antiviral response
Cytokine Growth Factor Rev
(2007)- et al.
Interleukin-27 inhibition of HIV-1 involves an intermediate induction of type I interferon
Blood
(2009) - et al.
A modular analysis framework for blood genomics studies: application to systemic lupus erythematosus
Immunity
(2008) - et al.
Boosting signal-to-noise in complex biology: prior knowledge is power
Cell
(2011) - et al.
Type I interferon [corrected] gene induction by the interferon regulatory factor family of transcription factors
Immunity
(2006) - et al.
Acute exacerbations of asthma: epidemiology, biology and the exacerbation-prone phenotype
Clin Exp Allergy
(2009)
Respiratory viruses and exacerbations of asthma in adults
BMJ
Community study of role of viral infections in exacerbations of asthma in 9-11 year old children
BMJ
Gene expression profiles during in vivo human rhinovirus infection: insights into the host response
Am J Respir Crit Care Med
Interactions between innate antiviral and atopic immunoinflammatory pathways precipitate and sustain asthma exacerbations in children
J Immunol
Network biology: understanding the cell’s functional organization
Nat Rev Genet
From molecular to modular cell biology
Nature
Hierarchical organization of modularity in metabolic networks
Science
Molecular networks as sensors and drivers of common human diseases
Nature
WGCNA: an R package for weighted correlation network analysis
BMC Bioinformatics
An official American Thoracic Society/European Respiratory Society statement: asthma control and exacerbations: standardizing endpoints for clinical asthma trials and clinical practice
Am J Respir Crit Care Med
A network modeling approach to analysis of the Th2 memory responses underlying human atopic disease
J Immunol
Linear models and empirical Bayes methods for assessing differential expression in microarray experiments
Stat Appl Genet Mol Biol
Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources
Nat Protocol
Cited by (0)
Supported by National Institutes of Health grant HL080083. A.B. is the recipient of a Medical Research Fellowship from the Faculty of Medicine, Dentistry and Health Sciences, University of Western Australia.
Disclosure of potential conflict of interest: F. D. Martinez has consultant arrangements with MedImmune and Bayer. The rest of the authors declare that they have no relevant conflicts of interest.