Observational human studies in allergic diseases: design concepts and highlights of recent National Institute of Allergy and Infectious Diseases-funded research

PURPOSE OF REVIEW To present and discuss key design concepts for optimizing the impact of observational studies in the field of allergy and to highlight recent findings from NIAID-funded research networks. RECENT FINDINGS We discuss three concepts. First, the benefit of prospective, longitudinal observational studies exemplified by recent findings on the seasonal nature of all rhinitis phenotypes in children with asthma and the protective effects of high house dust allergen content during the first year of life on the development of asthma at age 7 years. Second, the benefit of detailed (deep) phenotyping exemplified by the identification of a MALT1 gene variant as a strong genetic link to peanut allergy and the determination that atopic dermatitis with food allergy constitutes a distinct cutaneous endotype, compared with atopic dermatitis alone. Third, the benefit of hypothesis-generating research combined with prospective design and deep phenotyping as exemplified by the unveiling of potential pathophysiologic pathways leading to asthma exacerbations in children, after a 'cold'. SUMMARY Observational studies can be highly impactful if designed well. Longitudinal study design, deep phenotyping, and hypothesis-generating research are three major design concepts that should be considered in the development of these studies.