当前位置： SCI文献检索 > AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE期刊下所有文献 > Cytokine Responses to Rhinovirus and Development of Asthma, Allergic Sensitization, and Respiratory Infections during Childhood.

Cytokine Responses to Rhinovirus and Development of Asthma, Allergic Sensitization, and Respiratory Infections during Childhood.

Abstract：

RATIONALE:Immunophenotypes of antiviral responses, and their relationship with asthma, allergy, and lower respiratory tract infections, are poorly understood. OBJECTIVES:We characterized multiple cytokine responses of peripheral blood mononuclear cells to rhinovirus stimulation, and their relationship with clinical outcomes. METHODS:In a population-based birth cohort, we measured 28 cytokines after stimulation with rhinovirus-16 in 307 children aged 11 years. We used machine learning to identify patterns of cytokine responses, and related these patterns to clinical outcomes, using longitudinal models. We also ascertained phytohemagglutinin-induced T-helper cell type 2 (Th2)-cytokine responses (PHA-Th2). MEASUREMENTS AND MAIN RESULTS:We identified six clusters of children based on their rhinovirus-16 responses, which were differentiated by the expression of four cytokine/chemokine groups: interferon-related (IFN), proinflammatory (Inflam), Th2-chemokine (Th2-chem), and regulatory (Reg). Clusters differed in their clinical characteristics. Children with an IFNmodInflamhighestTh2-chemhighestReghighest rhinovirus-16-induced pattern had a PHA-Th2low response, and a very low asthma risk (odds ratio [OR], 0.08; 95% confidence interval [CI], 0.01-0.81; P = 0.03). Two clusters had a high risk of asthma and allergic sensitization, but with different trajectories from infancy to adolescence. The IFNlowestInflamhighTh2-chemlowRegmod cluster exhibited a PHA-Th2lowest response and was associated with early-onset asthma and sensitization, and the highest risk of asthma exacerbations (OR, 1.37; 95% CI, 1.07-1.76; P = 0.014) and lower respiratory tract infection hospitalizations (OR, 2.40; 95% CI, 1.26-4.58; P = 0.008) throughout childhood. In contrast, the IFNhighestInflammodTh2-chemmodReghigh cluster with a rhinovirus-16-cytokine pattern was characterized by a PHA-Th2highest response, and a low prevalence of asthma/sensitization in infancy that increased sharply to become the highest among all clusters by adolescence (but with a low risk of asthma exacerbations). CONCLUSIONS:Early-onset troublesome asthma with early-life sensitization, later-onset milder allergic asthma, and disease protection are each associated with different patterns of rhinovirus-induced immune responses.

journal_name

Am J Respir Crit Care Med

journal_title

American journal of respiratory and critical care medicine

authors

Custovic A,Belgrave D,Lin L,Bakhsoliani E,Telcian AG,Solari R,Murray CS,Walton RP,Curtin J,Edwards MR,Simpson A,Rattray M,Johnston SL

doi

10.1164/rccm.201708-1762OC

subject

Has Abstract

pub_date

2018-05-15 00:00:00

pages

1265-1274

issue

eissn

1073-449X

issn

1535-4970

journal_volume

197

pub_type

杂志文章

在线工具

Cytokine Responses to Rhinovirus and Development of Asthma, Allergic Sensitization, and Respiratory Infections during Childhood.