Cytokine Responses to Rhinovirus and Development of Asthma, Allergic Sensitization, and Respiratory Infections during Childhood.
Am J Respir Crit Care Med
; 197(10): 1265-1274, 2018 05 15.
Article
em En
| MEDLINE
| ID: mdl-29466680
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 MAINRESULTS:
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.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Antivirais
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Infecções Respiratórias
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Asma
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Rhinovirus
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Citocinas
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Infecções por Picornaviridae
Tipo de estudo:
Observational_studies
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Prognostic_studies
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Risk_factors_studies
Limite:
Adolescent
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Child
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Child, preschool
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Female
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Humans
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Infant
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Male
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article