Proton transfer mediated recognition of amines by ionizable macrocyclic receptors.

Ammonium ion/carboxylate ion pairing is a key interaction ubiquitous in biological systems, but amine recognition by ionizable molecular receptors, mediated by host-to-guest proton transfer, has too often been overlooked as a design element for molecular recognition. This survey will show that proton transfer mediated recognition is a powerful and versatile tool that can be made to work with different amines and diverse macrocyclic scaffolds, such as crown ethers, calixarenes or pillararenes. We will trace the history of this recognition motif since Cram's first report half a century ago down to the latest applications in supramolecular sensing, drug-delivery and materials science, highlighting along the way the impact of host-to-guest proton transfer on self-assembly and molecular recognition.

Allergen-specific IL-5 responses in early childhood predict asthma at age eight.

BACKGROUND: The pattern of development of allergen-specific T cell cytokine responses in early childhood and their relation to later disease is poorly understood. Here we describe longitudinal changes in allergen-stimulated T cell cytokine responses and their relation to asthma and allergic disease during the first 8 years of life. METHODS: Subjects with a family history of asthma, who were enrolled antenatally in the Childhood Asthma Prevention Study (public trials registration number ACTRN12605000042640), had skin prick tests, clinical evaluation for asthma and eczema, and in vitro assessment of T cell cytokine responses to HDM extract performed at ages 18 months (n = 281), 3 years (n = 349), 5 years (n = 370) and 8 years (n = 275). We measured interleukin (IL-) 13 at 3, 5 and 8 years, and IL-5, IL-10, and interferon-γ (IFN-γ), at 18 months, 3, 5 and 8 years by ELISA. A cohort analysis was undertaken. Independent effects of cytokine responses at each age on the risk of asthma and allergic outcomes at age 8 years were estimated by multivariable logistic regression. RESULTS: HDM-specific IL-5 responses increased with age. HDM-specific IL-13 and IL-10 responses peaked at age 5 years. HDM-specific IL-5 responses at 3 years, 5 years and 8 years were significantly associated with the presence of asthma and atopy at 8 years. IL-13 responses at 3 years, 5 years and 8 years were significantly associated with atopy at 8 years, but this association was not independent of the effect of IL-5. Other HDM-specific cytokine responses were not independently related to asthma or eczema at 8 years. CONCLUSION: HDM-specific IL-5 responses at age 3 years or later are the best measure of T cell function for predicting asthma at age 8 years.

Most personal exposure to house dust mite aeroallergen occurs during the day.

BACKGROUND: The bed is commonly regarded as the main site of house dust mite exposure; however this has not been directly established by continuous measurements. The objective of this study was to determine the pattern of personal exposure to mite aeroallergen over 24 hours. METHODS: 12 adults each collected 9 sequential samples (8 during the day, mean 115 mins, and one overnight, mean 514 mins) over 24 hours using a portable air-pump (2L/min) connected to an IOM filter located on the shoulder during the day and on the bed head overnight. Samples were analysed for mite allergen Der p 1 by ELISA. Location and activity were recorded. A mixed model analysis was performed to determine exposure as a function of 14 categories of activity. RESULTS: Personal aeroallergen exposure differed widely over time, both within and between subjects. The highest average exposure (1117 pg/m(3), 95% CI: 289-4314) occurred on public transport and the lowest overnight in bed (45 pg/m(3), 95% CI: 17-17), which contributed only 9.8% (95% CI: 4.4%-15.1%) of total daily exposure. Aeroallergens were not related to bed reservoirs. CONCLUSION: The study challenges the current paradigm that the bed is the main site of HDM exposure and instead suggests most exposure occurs in association with domestic activity and proximity to other people. Effective mite interventions, designed to improve asthma outcomes, need to first identify and then address the multiple sources of aeroallergen exposure.

Nonlinear relationship of mite allergen exposure to mite sensitization and asthma in a birth cohort.

BACKGROUND: There is uncertainty about the nature of the relationship between mite allergen exposure during infancy and the expression of allergic diseases in childhood. OBJECTIVE: We sought to explore the relationships between repeated measurements of mite allergen exposure during the first 5 years of life and clinical allergic disease outcomes at age 5 years. METHODS: In a birth cohort of 516 at-risk children, 13 bed dust samples were collected between birth and 5 years of age and analyzed for mite allergen. At age 5 years, the presence of mite atopy was assessed based on skin prick test results, and clinical assessments for asthma, eczema, and wheeze were conducted. The association of allergen exposure with each clinical outcome was examined by means of logistic regression, with adjustments for potential confounders. RESULTS: The lowest and highest mite exposure quintiles, expressed as mean allergen concentration averaged over 0 to 5 years, were associated with a lower prevalence of mite atopy and of asthma compared with intermediate levels of exposure. These relationships, when determined by using average allergen concentration over 0 to 18 months, were weaker. CONCLUSIONS: This study demonstrates a nonlinear relationship between mite allergen exposure and clinical outcomes in this generally high mite allergen environment.