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

Oliver Fuchs, Thomas Bahmer, Markus Weckmann, Anna-Maria Dittrich, Bianca Schaub, Barbara Rösler, Christine Happle, Folke Brinkmann, Isabell Ricklefs, Inke R König, Henrik Watz, Klaus F Rabe, Matthias V Kopp, Gesine Hansen, Erika von Mutius, ALLIANCE Study Group as part of the German Centre for Lung Research (DZL), Oliver Fuchs, Thomas Bahmer, Markus Weckmann, Anna-Maria Dittrich, Bianca Schaub, Barbara Rösler, Christine Happle, Folke Brinkmann, Isabell Ricklefs, Inke R König, Henrik Watz, Klaus F Rabe, Matthias V Kopp, Gesine Hansen, Erika von Mutius, ALLIANCE Study Group as part of the German Centre for Lung Research (DZL)

Abstract

Background: Asthma 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.

Methods: The 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.

Discussion: The 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 registration: NCT02496468 for pediatric arm, NCT02419274 for adult arm.

Keywords: Asthma; Biomarker; Endotype; Pediatric pulmonology; Phenotype; Wheeze.

Conflict of interest statement

Ethics approval and consent to participate

All studies were approved by the local ethics committees (leading ethics committee: University Luebeck, Ethics Committee, Ratzeburger Allee 160, 23,538-Luebeck, Germany; reference number: Az 12–215) and are registered at Consent for publication

Not applicable.

Competing interests

The author’s declare that they have no competing interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
Wheeze and asthma phenotypes during childhood and adulthood. About 25–30% of children have at least one episode of wheeze before their 3rd birthday, but considerable clinical heterogeneity exists (broken line box I). Children with transient wheeze become symptom-free before school-age, those with non-atopic asthma after about 8 years of age. However, some, especially those with persistent atopic wheeze and seasonal triggers of wheeze go on to persistent asthma in later childhood and adulthood. Interestingly, girls present with new-onset asthma in significant numbers during adolescence, thereby adding to turning the sex-based bias from male towards female sex. While there is also new-onset-asthma during adulthood, it is unclear whether differences between persistent childhood asthma phenotypes continue throughout transition (broken line box II) into adulthood
Fig. 2
Fig. 2
Consolidated Standards of Reporting Trials (Consort) Diagram displaying details for recruitment of participants of the DZL All Age Asthma Cohort (ALLIANCE). See text for details.
Fig. 3
Fig. 3
a,b: The DZL All Age Asthma Cohort (ALLIANCE): time-flow of recorded data (a), as well as of tests and procedures (b). See text for details.

References

    1. Matricardi PM, Illi S, Gruber C, et al. Wheezing in childhood: incidence, longitudinal patterns and factors predicting persistence. Eur Respir J. 2008;32:585–592. doi: 10.1183/09031936.00066307.
    1. Martinez FD, Vercelli D. Asthma. Lancet. 2013;382:1360–1372. doi: 10.1016/S0140-6736(13)61536-6.
    1. Fuchs O, Bahmer T, Rabe KF, von Mutius E. Asthma transition from childhood into adulthood. Lancet Respir Med. 2017;5(3):224–34. 10.1016/S2213-2600(16)30187-4
    1. Bush A, Menzies-Gow A. Phenotypic differences between pediatric and adult asthma. Proc Am Thorac Soc. 2009;6:712–719. doi: 10.1513/pats.200906-046DP.
    1. Wenzel SE. Asthma phenotypes: the evolution from clinical to molecular approaches. Nat Med. 2012;18:716–725. doi: 10.1038/nm.2678.
    1. Raedler D, Ballenberger N, Klucker E, et al. Identification of novel immune phenotypes for allergic and nonallergic childhood asthma. J Allergy Clin Immunol. 2015;135:81–91. doi: 10.1016/j.jaci.2014.07.046.
    1. Anderson GP. Endotyping asthma: new insights into key pathogenic mechanisms in a complex, heterogeneous disease. Lancet. 2008;372:1107–1119. doi: 10.1016/S0140-6736(08)61452-X.
    1. Levy BD, Noel PJ, Freemer MM, et al. Future research directions in asthma. An NHLBI working group report. Am J Respir Crit Care Med. 2015;192:1366–1372. doi: 10.1164/rccm.201505-0963WS.
    1. Pavord ID, Beasley R, Agusti A, et al. After asthma: redefining airways diseases. Lancet. 2018;391(10118):350–400.
    1. GINA Report . Global strategy for asthma management and prevention. 2017.
    1. Nationale Versorgungsleitlinie Asthma Langfassung, 2 . Auflage Version 1.3, Juli. 2009.
    1. Postma DS, Rabe KF. The asthma-COPD overlap syndrome. N Engl J Med. 2015;373:1241–1249. doi: 10.1056/NEJMra1411863.
    1. Fabbri LM, Romagnoli M, Corbetta L, et al. Differences in airway inflammation in patients with fixed airflow obstruction due to asthma or chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2003;167:418–424. doi: 10.1164/rccm.200203-183OC.
    1. Asher MI, Keil U, Anderson HR, et al. International study of asthma and allergies in childhood (ISAAC): rationale and methods. Eur Respir J. 1995;8:483–491. doi: 10.1183/09031936.95.08030483.
    1. Nathan RA, Sorkness CA, Kosinski M, et al. Development of the asthma control test: a survey for assessing asthma control. J Allergy Clin Immunol. 2004;113:59–65. doi: 10.1016/j.jaci.2003.09.008.
    1. Juniper EF, O'Byrne PM, Guyatt GH, Ferrie PJ, King DR. Development and validation of a questionnaire to measure asthma control. Eur Respir J. 1999;14:902–907. doi: 10.1034/j.1399-3003.1999.14d29.x.
    1. Juniper EF, Guyatt GH, Epstein RS, Ferrie PJ, Jaeschke R, Hiller TK. Evaluation of impairment of health related quality of life in asthma: development of a questionnaire for use in clinical trials. Thorax. 1992;47:76–83. doi: 10.1136/thx.47.2.76.
    1. Smets EM, Garssen B, Bonke B, De Haes JC. The multidimensional fatigue inventory (MFI) psychometric qualities of an instrument to assess fatigue. J Psychosom Res. 1995;39:315–325. doi: 10.1016/0022-3999(94)00125-O.
    1. Robinson PD, Latzin P, Verbanck S, et al. Consensus statement for inert gas washout measurement using multiple- and single- breath tests. Eur Respir J. 2013;41:507–522. doi: 10.1183/09031936.00069712.
    1. American Thoracic S, European Respiratory S ATS/ERS recommendations for standardized procedures for the online and offline measurement of exhaled lower respiratory nitric oxide and nasal nitric oxide, 2005. Am J Respir Crit Care Med. 2005;171:912–930. doi: 10.1164/rccm.200406-710ST.
    1. van der Schee MP, Hashimoto S, Schuurman AC, et al. Altered exhaled biomarker profiles in children during and after rhinovirus-induced wheeze. Eur Respir J. 2015;45:440–448. doi: 10.1183/09031936.00044414.
    1. Meyer N, Dallinga JW, Nuss SJ, et al. Defining adult asthma endotypes by clinical features and patterns of volatile organic compounds in exhaled air. Respir Res. 2014;15:136. doi: 10.1186/s12931-014-0136-8.
    1. Bickel S, Popler J, Lesnick B, Eid N. Impulse oscillometry: interpretation and practical applications. Chest. 2014;146:841–847. doi: 10.1378/chest.13-1875.
    1. Steiss JO, Rudloff S, Landmann E, Zimmer KP, Lindemann H. Capnovolumetry: a new tool for lung function testing in children with asthma. Clin Physiol Funct Imaging. 2008;28:332–336. doi: 10.1111/j.1475-097X.2008.00815.x.
    1. Watz H, Pitta F, Rochester CL, et al. An official European Respiratory Society statement on physical activity in COPD. Eur Respir J. 2014;44:1521–1537. doi: 10.1183/09031936.00046814.
    1. Waschki B, Kirsten AM, Holz O, et al. Disease progression and changes in physical activity in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2015;192:295–306. doi: 10.1164/rccm.201501-0081OC.
    1. van’t Hul AJ, Frouws S, van den Akker E, et al. Decreased physical activity in adults with bronchial asthma. Respir Med. 2016;114:72–77. doi: 10.1016/j.rmed.2016.03.016.
    1. Beydon N, Davis SD, Lombardi E, et al. An official American Thoracic Society/European Respiratory Society statement: pulmonary function testing in preschool children. Am J Respir Crit Care Med. 2007;175:1304–1345. doi: 10.1164/rccm.200605-642ST.
    1. Miller MR, Hankinson J, Brusasco V, et al. Standardisation of spirometry. Eur Respir J. 2005;26:319–338. doi: 10.1183/09031936.05.00034805.
    1. Robinson PD, Goldman MD, Gustafsson PM. Inert gas washout: theoretical background and clinical utility in respiratory disease. Respiration. 2009;78:339–355. doi: 10.1159/000225373.
    1. Macintyre N, Crapo RO, Viegi G, et al. Standardisation of the single-breath determination of carbon monoxide uptake in the lung. Eur Respir J. 2005;26:720–735. doi: 10.1183/09031936.05.00034905.
    1. Oostveen E, MacLeod D, Lorino H, et al. The forced oscillation technique in clinical practice: methodology, recommendations and future developments. Eur Respir J. 2003;22:1026–1041. doi: 10.1183/09031936.03.00089403.
    1. Wanger J, Clausen JL, Coates A, et al. Standardisation of the measurement of lung volumes. Eur Respir J. 2005;26:511–522. doi: 10.1183/09031936.05.00035005.
    1. Narayanan M, Owers-Bradley J, Beardsmore CS, et al. Alveolarization continues during childhood and adolescence: new evidence from helium-3 magnetic resonance. Am J Respir Crit Care Med. 2012;185:186–191. doi: 10.1164/rccm.201107-1348OC.
    1. Douglas RM, Woodward A, Miles H, Buetow S, Morris D. A prospective study of proneness to acute respiratory illness in the first two years of life. Int J Epidemiol. 1994;23:818–826. doi: 10.1093/ije/23.4.818.
    1. Fuchs O, Latzin P, Kuehni CE, Frey U. Cohort profile: the Bern infant lung development cohort. Int J Epidemiol. 2012;41:366–376. doi: 10.1093/ije/dyq239.
    1. Liu AH, Zeiger R, Sorkness C, et al. Development and cross-sectional validation of the childhood asthma control test. J Allergy Clin Immunol. 2007;119:817–825. doi: 10.1016/j.jaci.2006.12.662.
    1. Crapo RO, Casaburi R, Coates AL, et al. Guidelines for methacholine and exercise challenge testing-1999. This official statement of the American Thoracic Society was adopted by the ATS Board of directors, July 1999. Am J Respir Crit Care Med. 2000;161:309–329. doi: 10.1164/ajrccm.161.1.ats11-99.
    1. Scala E, Alessandri C, Palazzo P, et al. IgE recognition patterns of profilin, PR-10, and tropomyosin panallergens tested in 3,113 allergic patients by allergen microarray-based technology. PLoS One. 2011;6:e24912. doi: 10.1371/journal.pone.0024912.
    1. Leimgruber A, Mosimann B, Claeys M, et al. Clinical evaluation of a new in-vitro assay for specific IgE, the immuno CAP system. Clin Exp Allergy. 1991;21:127–131. doi: 10.1111/j.1365-2222.1991.tb00814.x.
    1. Hennig C, Adams N, Hansen G. A versatile platform for comprehensive chip-based explorative cytometry. Cytometry Part A. 2009;75:362–370. doi: 10.1002/cyto.a.20668.

Source: PubMed

Sponsor e collaboratori

Condizioni mediche

Interventi farmacologici

3
Sottoscrivi