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. 2023 Jan 6:9:1034290.
doi: 10.3389/fmed.2022.1034290. eCollection 2022.

TRACK-CF prospective cohort study: Understanding early cystic fibrosis lung disease

Eva Steinke  1   2   3 , Olaf Sommerburg  4   5 , Simon Y Graeber  1   2   3 , Cornelia Joachim  4   5 , Christiane Labitzke  1 , Gyde Nissen  6   7 , Isabell Ricklefs  6   7 , Isa Rudolf  8   9 , Matthias V Kopp  6   7   10 , Anna-Maria Dittrich  8   9 , Marcus A Mall  1   2   3 , Mirjam Stahl  1   2   3
Affiliations

TRACK-CF prospective cohort study: Understanding early cystic fibrosis lung disease

Eva Steinke et al. Front Med (Lausanne). .

Abstract

Background: Lung disease as major cause for morbidity in patients with cystic fibrosis (CF) starts early in life. Its large phenotypic heterogeneity is partially explained by the genotype but other contributing factors are not well delineated. The close relationship between mucus, inflammation and infection, drives morpho-functional alterations already early in pediatric CF disease, The TRACK-CF cohort has been established to gain insight to disease onset and progression, assessed by lung function testing and imaging to capture morpho-functional changes and to associate these with risk and protective factors, which contribute to the variation of the CF lung disease progression.

Methods and design: TRACK-CF is a prospective, longitudinal, observational cohort study following patients with CF from newborn screening or clinical diagnosis throughout childhood. The study protocol includes monthly telephone interviews, quarterly visits with microbiological sampling and multiple-breath washout and as well as a yearly chest magnetic resonance imaging. A parallel biobank has been set up to enable the translation from the deeply phenotyped cohort to the validation of relevant biomarkers. The main goal is to determine influencing factors by the combined analysis of clinical information and biomaterials. Primary endpoints are the lung clearance index by multiple breath washout and semi-quantitative magnetic resonance imaging scores. The frequency of pulmonary exacerbations, infection with pro-inflammatory pathogens and anthropometric data are defined as secondary endpoints.

Discussion: This extensive cohort includes children after diagnosis with comprehensive monitoring throughout childhood. The unique composition and the use of validated, sensitive methods with the attached biobank bears the potential to decisively advance the understanding of early CF lung disease.

Ethics and trial registration: The study protocol was approved by the Ethics Committees of the University of Heidelberg (approval S-211/2011) and each participating site and is registered at clinicaltrials.gov (NCT02270476).

Keywords: biomarkers in cystic fibrosis; cystic fibrosis; early lung disease; magnetic resonance imaging (MRI); multiple-breath washout (MBW); non-invasive monitoring; risk factors in cystic fibrosis.

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Conflict of interest statement

OS reports grants by the German Center for Lung Research (DZL) and Vertex Pharmaceuticals with payments to the institution. SG reports grants by the Mukoviszidose e.V., Vertex Pharmaceuticals and the German Research Foundation (DFG) with payments to the institution and received personal fees from Chiesi GmbH and Vertex Pharmaceuticals. MK reports grants by the German Center for Lung Research (DZL) and received personal fees from Sanofi Aventis GmbH, Chiesi GmbH, Allergopharma GmbH, Infectopharm GmbH, Vertex Pharma GmbH, Leti GmbH and Nutricia GmbH. A-MD reports grants by the German Center for Lung Research (DZL) and Vertex Pharmaceuticals with payments to the institution and received personal fees from Vertex Pharmaceuticals. MS reports grants by the Mukoviszidose e.V., the German Center for Lung Research (DZL), the Christiane Herzog Foundation and Vertex Pharmaceuticals. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
TRACK-CF summary. The strategy to examine the different stages of CF lung disease development (“Background”) is presented on top. The study endpoints and regularly performed examinations from birth to adulthood are displayed in the center and the endpoints and covered aspects of early CF lung disease are shown at the bottom of the figure. The overall aims are to improve the quality of life and the survival through the identification of risk factors, biomarkers and novel therapeutic targets (right). This figure was created with BioRender.com.
Figure 2
Figure 2
TRACK-CF study design. Exemplary scheme for the first year following diagnosis. Black arrows indicate quarterly routine visits at the CF center; gray arrows indicate study visits performed as telephone interviews in months without a visit to the CF center. This assessment routine is repeated each year. CF, cystic fibrosis; QoL, quality of life questionnaire; MBW, multiple-breath washout; MRI, magnetic resonance imaging.
See this image and copyright information in PMC

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