The all age asthma cohort (ALLIANCE) - from early beginnings to chronic disease: a longitudinal cohort study

Abstract

BackgroundAsthma and wheezing disorders in childhood and adulthood are clinically heterogeneous regarding disease presentation, natural course, and response to treatment. Deciphering common disease mechanisms in distinct subgroups requires harmonized molecular (endo-) phenotyping of both children and adult patients with asthma in a prospective, longitudinal setting.MethodsThe ALL Age Asthma Cohort (ALLIANCE) of the German Center for Lung Research (DZL) is a prospective, multi-center, observational cohort study with seven recruiting sites across Germany. Data are derived from four sources: (a) patient history from medical records, (b) standardized questionnaires and structured interviews, (c) telephone interviews, and (d) objective measurements. Objective measurements include amongst others lung function and quantitative assessment of airway inflammation and exhaled breath, peripheral blood, skin, nasal, pharyngeal, and nasopharyngeal swabs, nasal secretions, primary nasal epithelial cells, and induced sputum. In cases, objective measurements and biomaterial collection are performed regularly, while control subjects are only examined once at baseline.DiscussionThe standardized and detailed collection of epidemiological and physiological data, and the molecular deep phenotyping of a comprehensive range of biomaterials in a considerable number of study participants across all ages are the outstanding characteristics of this multi-center cohort. Despite extensive biomaterial sampling, and a recruitment strategy that also includes pre-school children as young as 6 months, attrition is low. In children 83.9%, and in adults 90.5% attended the 12-month follow-up. The earliest time-point to include cases, however, is disease manifestation. Therefore, unraveling mechanisms that drive disease onset is limited, as this question can only be answered in a population-based birth cohort. Nonetheless, ALLIANCE offers a unique, integrative and inter-disciplinary framework with a comprehensive molecular approach in a prospective and identical fashion across ages in order to identify biomarkers and predictors for distinct childhood wheeze and asthma trajectories as well as their further course during adulthood. Ultimately, this approach aims to translate its most significant findings into clinical practice, and to improve asthma transition from adolescence to adulthood.Trial registrationNCT02496468 for pediatric arm, NCT02419274 for adult arm.

Precision medicine and phenotypes, endotypes, genotypes, regiotypes, and theratypes of allergic diseases

“…The "lung-and small airway-on-a-chip" technologies will rapidly contribute to filling the current translational gap in lung research and advance drug development, biomarker identifica- between age groups is also interesting. The ALL Age Asthma Cohort (ALLIANCE) offers a unique, integrative, and interdisciplinary framework with a comprehensive molecular approach in a prospective and identical fashion across ages in order to identify biomarkers and predictors for distinct childhood wheeze and asthma trajectories as well as their further course during adulthood (125). Taken together, the implementation of precision medicine in clinical practice should consider insight into high-risk groups indicated by public health studies, including those linked to age, sex, and ethnicity.…”

Breath volatile organic compounds and inflammatory markers in adult asthma patients: negative results from the ALLIANCE cohort

“…In the adult arm of the ALLIANCE asthma cohort we prospectively recruited patients with an established diagnosis of asthma [7] across different severity grades and inflammatory phenotypes as identified by FeNO, blood and sputum differential cell counts [8]. As recently recommended [5], the patients were clinically well characterized, the asthma diagnosis was thoroughly established, and breath VOCs were compared between different asthma phenotypes.…”

Leonurus sibiricus root extracts decrease airway remodeling markers expression in fibroblasts

“…At present, no effective treatments are known that can halt or reverse the changes of airway remodeling and influence lung function [11]. Longitudinal research has indicated that current therapeutic interventions are relatively ineffective in reversing or inhibiting the development of airway changes [8,[12][13][14]. However, an alternative form of treatment may lie in the use of natural products as complementary therapy.…”