A Comprehensive Evaluation of Nasal and Bronchial Cytokines and Chemokines Following Experimental Rhinovirus Infection in Allergic Asthma: Increased Interferons (IFN-γ and IFN-λ) and Type 2 Inflammation (IL-5 and IL-13).

BACKGROUND: Rhinovirus infection is a major cause of asthma exacerbations. OBJECTIVES: We studied nasal and bronchial mucosal inflammatory responses during experimental rhinovirus-induced asthma exacerbations. METHODS: We used nasosorption on days 0, 2-5 and 7 and bronchosorption at baseline and day 4 to sample mucosal lining fluid to investigate airway mucosal responses to rhinovirus infection in patients with allergic asthma (n=28) and healthy non-atopic controls (n=11), by using a synthetic absorptive matrix and measuring levels of 34 cytokines and chemokines using a sensitive multiplex assay. RESULTS: Following rhinovirus infection asthmatics developed more upper and lower respiratory symptoms and lower peak expiratory flows compared to controls (all P<0.05). Asthmatics also developed higher nasal lining fluid levels of an anti-viral pathway (including IFN-γ, IFN-λ/IL-29, CXCL11/ITAC, CXCL10/IP10 and IL-15) and a type 2 inflammatory pathway (IL-4, IL-5, IL-13, CCL17/TARC, CCL11/eotaxin, CCL26/eotaxin-3) (area under curve day 0-7, all P<0.05). Nasal IL-5 and IL-13 were higher in asthmatics at day 0 (P<0.01) and levels increased by days 3 and 4 (P<0.01). A hierarchical correlation matrix of 24 nasal lining fluid cytokine and chemokine levels over 7days demonstrated expression of distinct interferon-related and type 2 pathways in asthmatics. In asthmatics IFN-γ, CXCL10/IP10, CXCL11/ITAC, IL-15 and IL-5 increased in bronchial lining fluid following viral infection (all P<0.05). CONCLUSIONS: Precision sampling of mucosal lining fluid identifies robust interferon and type 2 responses in the upper and lower airways of asthmatics during an asthma exacerbation. Nasosorption and bronchosorption have potential to define asthma endotypes in stable disease and at exacerbation.

Body composition in childhood inflammatory bowel disease.

BACKGROUND & AIMS: Little is known about the impact of disease and treatment on the pattern of growth in children with Inflammatory Bowel Disease (IBD). Significant deficits in height and weight in children with Crohn's disease have been reported but changes in fat and fat free mass are less well defined. This study aims to describe the height, weight and body composition of a cohort of children with IBD. METHODS: Height, weight, skinfold thicknesses and bioelectrical impedance analysis was performed. Disease activity was assessed with clinical scoring systems. RESULTS: 55 children, median age 13.7 years (range 6.5-17.7) were studied. Median (25th, 75th percentile) Standard Deviation Score for BMI, Height and Weight were - 0.3 (- 0.97, 0.65), - 0.56 (- 1.42, 0.06), - 0.62 (- 1.43, 0.19). In Crohn's disease, using multiple regression analysis disease activity measured by PCDAI was significantly inversely related to fat free mass (ß - 0.2, 95% CI -0.17, -0.03, p 0.005). CONCLUSIONS: Children with IBD were both under and overweight. Nutritional deficits were more common in Crohn's disease. Fat free mass was related to disease activity in children with Crohn's disease regardless of changes in weight. Weight or BMI may mask deficits in lean tissue in the presence of normal or increased proportions of body fat.