Table I.

Summary of studies showing impaired or defective expression of interferon mRNA or protein in cells from asthmatic patients

Reference	Cell type	Phenotype of asthma and age	Interferons studied	Evidence	Main findings
Bufe et al4	PBMCs	Atopic asthmatic children	IFN-α	∗, †	First report of impaired interferon using NDV
Wark et al5	HBECs	Mild atopic asthmatic adults	IFN-β	∗, ‡, §, ‖	Associated with apoptosis and not steroid dependent
Contoli et al6	HBECs/BAL cells	Mild atopic asthmatic adults	IFN-λs	∗, †	Associated with clinical end points after experimental rhinovirus challenge
Gehlhar et al32	PBMCs	Atopic asthmatic adults	IFN-α	∗	RSV and NDV
Sykes et al30	BAL cells	Mild-to-moderate atopic asthmatic patients	IFN-α, IFN-β	∗, †	No impairment of critical signaling molecules, related to atopy
Edwards et al36	HBECs	STRA atopic asthmatic children	IFN-β, IFN-λs	∗, ‡, ‖	Interferon mRNA impaired to rhinovirus and poly I:C
Uller et al35	HBECs	Mostly atopic, mixed asthma severity, adults	IFN-β	∗, ‖	TSLP levels greater in asthmatic group
Wark et al44	HBECs	Mild persistent atopic asthmatic patients	IFN-β	∗	IFN-β protein studied only
Gill et al28	Blood pDCs	Atopic asthmatic adults and children	IFN-α	∗, ‖	Influenza virus, related to IgE
Iikura et al47	PBMCs	Atopic mild-to-moderate asthmatic adults and children	IFN-α	∗	Impaired IFN-α in children only also impaired proinflammatory cytokine
Durrani et al29	Blood pDCs	Atopic asthmatic children	IFN-α, IFN-λs	∗	Rhinovirus, related to asthma not atopy
Baraldo et al34	HBECs	Atopic and nonatopic asthmatic children	IFN-β, IFN-λs	∗, †, ‡	Associated with increased IL-4 staining, eosinophilia, and IgE in atopic subjects
Wagener et al46	NECs/HBECs	Atopic asthmatic patients	IFN-β, IFN-λs	∗	Poly I:C IFN-β and IL-28 mRNA expression in asthmatic patients by microarray
Collison et al50	HBECs	Persistent asthmatic adults	IFN-λs	∗	No difference in intracellular viral RNA
Spann et al45	NECs/TECs	Atopic children with wheeze	IFN-β, IFN-λs	∗	Impaired IFN-β only in NECs with RSV
Hatchwell et al49	Bronchial biopsy specimens	Patients with moderate-to-severe eosinophilic asthma	IFN-α/β, IFN-λs	∗	Impaired IL-28 related to impaired TLR7
Rupani et al31	AMs	Severe nonatopic asthma	IFN-α, IFN-β	∗	Identification of mir-150, 152, and 375 as associated with impaired interferons
Kicic et al33	HBECs	Atopic asthmatic children	IFN-β	∗, ‡, §, ‖	Related to defective wound repair
Teach et al51	PBMCs	Atopic asthmatic children	IFN-α	∗, †	Restored by anti-IgE therapy
Lin et al48	PBMCs	Atopic asthmatic children	IFN-α, IFN-β	∗, ‖	Impaired interferon group identified by using cluster analysis had higher rates of asthma.

BAL, Bronchoalveolar lavage; NDV, Newcastle disease virus; NECs, nasal epithelial cells; pDCs, plasmacytoid dendritic cells; STRA, severe therapy-resistant asthma; TEC, tracheal epithelial cell; TSLP, thymic stromal lymphopoietin.

Level of evidence:

^∗Interferon levels in asthmatic donors were significantly lower than those of control subjects.

^†Deficient interferon levels were related to clinical disease, such as number of AEs, eosinophilia, lung function, IgE levels, atopy, and T_H2 markers.

^‡Significantly higher viral loads in asthmatic patients or significantly lower interferon levels that were negatively correlated with higher viral loads in asthmatic patients.

^§Exogenous IFN-β restored the antiviral response.

^‖Other noninterferon cytokines were not significantly different between asthmatic donors and control subjects.