Evaluation of airway reactivity and immune characteristics as risk factors for wheezing early in life

Yao, Weiguo; Barbé-Tuana, Florencia Marı́a; Llapur, Conrado J.; Jones, Marcus Herbert; Tiller, Christina; Kimmel, Risa; Kisling, Jeffrey; Nguyen, Evelyn T.; Nguyen, James; Yu, Zhangsheng; Kaplan, Mark H.; Tepper, Robert S.

doi:10.1016/j.jaci.2010.06.028

Cited by 30 publications

(53 citation statements)

References 20 publications

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“…The function of type I IFNs, particularly from pDCs, is thought to be anti-viral, and increases might be expected to aid in clearance of viral infections, which might decrease virus-induced wheezing. Indeed, we, and others have observed that increasing percentages of pDC and cDC in infants are negatively correlated with the development of subsequent wheezy illness or asthma [11; 16]. However, IL-10, produced in the highest amounts by cDC, can inhibit Th1 cytokine production, and IL-6 can promote Th2 and Th17 development.…”

Section: Discussionmentioning

confidence: 77%

“…The patient population in this study has been described in detail elsewhere [16; 17]. Briefly, infants were enrolled in the study between the ages of 2 and 19 months when they presented in the clinic with dermatitis.…”

Section: Methodsmentioning

confidence: 99%

“…This may be important since there are age-related changes in DC numbers and function [8]. In a population of infants with atopic or non-atopic dermatitis, we have shown that increasing percentages of cDC are associated with a protective effect from the development of wheezing episodes in subsequent years [16]. In this report we have examined DC function in infants upon entry into the study and one year later.…”

Section: Introductionmentioning

confidence: 99%

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Altered cytokine production by dendritic cells from infants with atopic dermatitis

Yao

Chang

Sehra

et al. 2010

Clinical Immunology

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Dendritic cells (DC) are potent initiators of immune responses, compared to other professional antigen-presenting cells, based on their ability to capture antigen, express high amounts of MHC and co-stimulatory molecules, and to secrete immunostimulatory cytokines. Altered functions of DC in atopic individuals have been observed, though it is not clear if this is a cause or a result of the development of allergic disease. In this report we demonstrate altered cytokine production by DC isolated from infants with atopic dermatitis but without a diagnosis of asthma, compared to infants with non-atopic dermatitis. Increased production of IL-6, IL-10 and IFNα from DC isolated from atopic infants is less apparent when DC from infants were examined one year later. An increase in the same cytokines was observed in neonatal mice that are genetically predisposed towards allergic inflammation. These results suggest that an atopic environment promotes altered cytokine production by DC from infants.

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Section: Discussionmentioning

confidence: 77%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Altered cytokine production by dendritic cells from infants with atopic dermatitis

Yao

Chang

Sehra

et al. 2010

Clinical Immunology

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“…Further, while asthma, which is difficult to diagnose in young children, was based on doctor diagnosis as reported in the age 4 years interview, asthma in this study may have been better classified with latent class analyses if we had additional information on lung function, cytokines, and eosinophils to combine with sIgE results in order to examine potential risk factors(19, 23, 25, 27). We also acknowledge that the outcome of parental report of wheeze can be non-specific; however, it is only one outcome we examined and parental report of wheeze has been used in numerous important allergic disease studies (22, 28, 29). …”

Section: Discussionmentioning

confidence: 99%

Atopic phenotypes identified with latent class analyses at age 2 years

Havstad

Johnson

Kim

et al. 2014

Journal of Allergy and Clinical Immunology

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Background Atopic sensitization or atopy is the most commonly reported risk factor for asthma. Recent studies have begun to suggest that atopy, as conventionally defined, may be an umbrella term that obfuscates more specific allergic disease types. Objective To determine if distinct and meaningful atopic phenotypes exist within a racially diverse birth cohort using ten allergen-specific IgE (sIgE) measurements from children of age 2 years. Methods Using the WHEALS birth cohort (62% Black), we analyzed sIgE data from ten allergens (Der f, dog, cat, Timothy grass, ragweed, Alternaria alternata, egg, peanut, milk, and German cockroach) among 594 children measured at age 2 years. Conventional atopy was defined as at least one sIgE ≥ 0.35 IU/ml. Results A four-class solution (latent class model) was the best fit. Class types were labeled “Low to no sensitization (76.9% of sample)”, “Highly sensitized (2.7%)”, “Milk and egg dominated (15.3%)” and “Peanut and inhalant(s) (5.1%)”. Almost one-third (32.2%) of the “low to no sensitization” group met the criteria for conventional atopy. The “Highly sensitized” group was significantly associated with doctor diagnosis of asthma after age 4 years, odds ratio [OR]=5.3, 95% Cl, 1.6–17.4) while the “Milk and egg dominated” and “Peanut and inhalant(s)” groups were not, OR=1.6 (0.8–3.0) and OR=1.8 (0.6–4.9), respectively. Children of Black race were more likely to be in the three multi-sensitized groups, p=0.04. Conclusion Classification by sIgE patterns defined groups whose membership is more strongly associated, as compared to conventional atopy, with atopic dermatitis, wheeze, and asthma.

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“…Peripheral blood mononuclear cells (PBMC) were isolated from the venous blood, cultured and stimulated with PMA (12-O-Tetradecanoylphorbol 13-acetate)/ionomycin to assess cytokine production (interleukin (IL)-4, IL-5, IL-13, IL-17, IL-9, IL-10 and interferon (IFN)γ) [21]. The ratios of individual cytokines to IFNγ were employed to assess the balance between the T-helper cell (Th)2 and Th1 responses [21, 22].…”

Section: Methodsmentioning

confidence: 99%

Exhaled nitric oxide during infancy as a risk factor for asthma and airway hyperreactivity

et al. 2014

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Childhood asthma is often characterised by elevated exhaled nitric oxide (eNO), decreased lung function, increased airway reactivity and atopy; however, our understanding of when these phenotypic airway characteristics develop remains unclear. This study evaluated whether eNO, lung function, airway reactivity and immune characteristics during infancy are risk factors of asthma at age 5 years. Infants with eczema, enrolled prior to wheezy illness (n=116), had eNO, spirometry, airway reactivity and allergen sensitisation assessed at entry to the study and repeated at age 5 years (n=90). Increasing eNO at entry was associated with an increased risk of asthma (p=0.037) and increasing airway reactivity (p=0.015) at age 5 years. Children with asthma at 5 years of age had a greater increase in eNO between infancy and age 5 years compared with those without asthma (p=0.002). Egg sensitisation at entry was also associated with an increased risk of asthma (p=0.020), increasing eNO (p=0.002) and lower forced expiratory flows (p=0.029) as a 5 year-old. Our findings suggest that, among infants at high risk for developing asthma, eNO early in life may provide important insights into the subsequent risk of asthma and its airway characteristics.

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Evaluation of airway reactivity and immune characteristics as risk factors for wheezing early in life

Cited by 30 publications

References 20 publications

Altered cytokine production by dendritic cells from infants with atopic dermatitis

Altered cytokine production by dendritic cells from infants with atopic dermatitis

Atopic phenotypes identified with latent class analyses at age 2 years

Exhaled nitric oxide during infancy as a risk factor for asthma and airway hyperreactivity

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