Understanding the asthmatic response to an experimental rhinovirus infection: Exploring the effects of blocking IgE

Abstract

Background: Rhinovirus frequently causes asthma exacerbations among children and young adults who are allergic. The interaction between allergen and rhinovirusinduced symptoms and inflammation over time is unclear. Objective: Our aim was to compare the response to an experimental inoculation with rhinovirus-16 in allergic asthmatics with the response in healthy controls and to evaluate the effects of administrating omalizumab before and during the infection. Methods: Two clinical trials were run in parallel. In one of these trials, the response to an experimental inoculation with rhinovirus-16 among asthmatics with high levels of total IgE was compared to the response in healthy controls. The other trial compared the effects of administering omalizumab versus placebo to asthmatics in a randomized, double-blind placebocontrolled investigation. The primary outcome for both trials compared lower respiratory tract symptoms (LRTSs) between study groups over the first 4 days of infection. Results: Frequent comparisons of symptoms, lung function, and blood eosinophil counts revealed differences that were more pronounced among allergic asthmatics than among controls by days 2 and 3 after virus inoculation. Additionally, an From a the Asthma and Allergic Diseases Center,

Human TH1 and TH2 cells targeting rhinovirus and allergen coordinately promote allergic asthma

“…Our multifaceted approach enabled comprehensive longitudinal sampling of the blood and airways in allergic asthmatic subjects across a broad range of serum IgE levels, and comparisons with healthy nonallergic controls. 35 Our findings support the coordinated actions of T H 1 and T H 2 cells in driving asthma in response to RV.…”

“…Asthmatic subjects with suitable IgE levels (133-493 IU/mL) participated in a double-blind placebocontrolled trial of omalizumab starting 8 weeks before RV-A16 challenge (n 5 10 per group) ( Fig 6, A and B). 35 At study entry, subjects receiving anti-IgE had lung function similar to asthmatic subjects outside the trial (FEV 1 /FVC 5 0.77 vs 0.80), whereas the placebo group had normal lung function (FEV 1 /FVC 5 0.87) (Fig 6, B). This difference was reflected in the higher numbers of RV-specific T cells (P 5 .01) and their activated signature ([PD-1 and YIL-7Ra) in the anti-IgE versus placebo group at the same time point (see Fig E11, A, in this article's Online Repository at www.jacionline.org).…”

“…Subjects were adults with mild allergic asthma (n 5 31, total IgE > 125 IU/mL) and healthy nonallergic controls (n 5 13, total IgE < 50 IU/mL) who tested seronegative for RV-A16. 35 All asthmatic subjects had airway hyperreactivity based on positive methacholine challenge, were allergic by positive skin prick test, and had specific IgE (>0.70 kU A /L, CAP class 2) to 1 or more common aeroallergen (see Fig E1 and Additional asthmatic subjects who had total IgE levels within the dosing range for anti-IgE received omalizumab (Genentech, USA, Inc, San Francisco, Calif) beginning 8 weeks before RV challenge in a double-blind placebocontrolled trial (treatment group, n 5 10; placebo group, n 5 10) ( Fig E2). Studies were approved by the Food and Drug Administration, the National Institute of Allergy and Infectious Diseases Safety Committee, and the University of Virginia Human Investigations Committee (Clinical Trials.gov ID: NCT02111772 and NCT02388997).…”

“…Subjects were challenged with live RV-A16 by intranasal administration of 1 mL inoculum containing 300 TCID 50 of virus (0.5 mL per nostril) 7,35,36 ( Fig E2, A). Subjects were considered infected on the basis of following criteria: (1) greater than or equal to 4-fold increase in RV-A16 serum-neutralizing antibody titer at day 21 postinoculation, (2) 1 or more positive RV-A16 cultures from nasal washes on days 1 to 4, and (3) 1 or more positive RV quantitative PCR test results from nasal washes on days 1 to 4.…”

“…with a return to baseline levels by day 14 (see Fig E6 in this article's Online Repository at www.jacionline.org). 35 Circulating antigen-specific T cells were monitored during acute infection (day 4), at the T-cell effector phase (day 7), and at convalescence (day 21). Results showed that asthmatic subjects mounted a more rapid and robust T-cell response to RV compared with controls, based on higher numbers of virus-specific T cells during acute infection (day 4: GM 5 13/10 6 vs 4/10 6 , P < _ .001) and in the effector phase (day 7: 45/10 6 vs 19/10 6 , P 5 .003) (Fig 3, C-F).…”