Longitudinal Observational Study on the Course of Cystic Fibrosis Lung Disease in Patients Following Newborn Screening

Conditions

Cystic Fibrosis Lung Disease

Keywords

Cystic Fibrosis, Infant, Toddler, Children, Newborn screening

Brief summary

The purpose of this study is to further characterize early CF lung disease in newborns, infants and toddlers with cystic fibrosis (CF).

Detailed description

Cystic fibrosis (CF) is the most common lethal genetic multisystem disease in Germany. Although life expectancy increased over the last decades, most of the CF patients die in young adulthood due to chronic CF lung disease with respiratory failure. CF lung disease is caused by a disturbed transport of salt and water by airway epithelia and dehydration of airway surfaces as a result of the underlying genetic defect in the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gen. Up to now, no causal therapies for the majority of patients with CF are available. Little is known about onset and natural course as well as influencing factors of CF lung disease. Therefore, the first aim of this prospective, multicenter, uncontrolled, non-randomized, explorative longitudinal study is characterization of the onset and early course of CF lung disease. For this reason we will primarily include patients diagnosed by CF newborn screening (CF-NBS) or for any other reason in the first four months of life (early diagnosed, ED). In a second step we will compare data from these patients to those diagnosed clinically later in life (late diagnosed, LD). This will allow us to investigate the effect of early diagnosis and start of therapy. Starting at diagnosis, we will use data from annual routine check-ups (imaging like chest MRI, pulmonary function tests, microbiology from swabs and sputum, laboratory values, anthropometry) as well as data from a facultative, study-related bronchoscopy with lavage (microbiology, inflammation and immunology) for correlation with the course of CF lung disease (generation of hypotheses). Further study-related investigations are monthly telephone interviews on bronchopulmonary symptoms by a study nurse on the basis of a questionnaire and quarterly assessment of health-related quality of life on the basis of a validated questionnaire. We expect to gain a deeper insight into onset and early course of CF lung disease from the results of this study. So far, there is no trial that investigated the different aspects of CF lung disease (function, morphology, infectiology, inflammation) complementary in a longitudinal setting. We assume that knowledge on the natural history of CF lung disease in the vulnerable phase of early childhood has a great impact on the future development of new therapies (from symptomatic to causal). This shall lead to a further improvement in life expectancy and quality of life of patients with CF.

Mark O. Wielpütz, Mirjam Stahl, Simon M. F. Triphan, Lena Wucherpfennig, Patricia Leutz-Schmidt et al. (15 authors)

Annals of the American Thoracic Society2024-09-106 citations

10.1513/annalsats.202404-396oc

Longitudinal Magnetic Resonance Imaging Detects Onset and Progression of Chronic Rhinosinusitis from Infancy to School Age in Cystic Fibrosis.

Wucherpfennig L, Wuennemann F, Eichinger M, Schmitt N, Seitz A, Baumann I, Stahl M, Graeber SY, Chung J, Schenk JP, Alrajab A, Kauczor HU, Mall MA, Sommerburg O, Wielpütz MO.

2023-05-0113 citations

10.1513/annalsats.202209-763oc

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

Eva Steinke, Olaf Sommerburg, Simon Y. Graeber, Cornelia Joachim, Christiane Labitzke et al. (12 authors)

Frontiers in Medicine2023-01-064 citations

10.3389/fmed.2022.1034290

Magnetic Resonance Imaging Detects Progression of Lung Disease and Impact of Newborn Screening in Preschool Children with Cystic Fibrosis

Mirjam Stahl, Eva Steinke, Simon Y. Graeber, Cornelia Joachim, Christoph Seitz et al. (11 authors)

American Journal of Respiratory and Critical Care Medicine2021-07-2068 citations

10.1164/rccm.202102-0278oc

Interventions

None listed

Study design

Observational model

COHORT

Time perspective

PROSPECTIVE

Eligibility

Sex/Gender

ALL

Healthy volunteers

No

Inclusion criteria

1. Newly diagnosed patients with Cystic Fibrosis (CF). Diagnosis of CF: at least one of the following three international accepted criteria is fulfilled: i) sweat chloride ≥ 60mEq/L and/or ii) 2 CF-causing mutations in the CFTR gene and/or iii) changes typical for CF in the transepithelial potential difference in nasal or rectal epithelium. 2. Age and mode of diagnosis: * Early diagnosed (ED): Initial diagnosis following CF-NBS or for other reasons in the first 4 months of life (in preterms corrected age of 4 months) after January 1st, 2006. Other reasons could be prenatal diagnostics, meconium ileus or positive family history. * Late diagnosed (LD): Diagnosed after the fourth month of life due to clinical symptoms; initial diagnosis after January 1st, 2006.

Exclusion criteria

All patients are excluded who themselves or whose parents do not want to participate or that withdraw from the study; or those in whom the diagnosis of CF is unsure. Further

Design outcomes

Primary

Measure	Time frame
Proportion with morphological and/or perfusion changes due to CF lung disease after chest MRI score in both groups	At age of 1, 2, 3, ...., 10 years of age
Proportion of patients with impairments in pulmonary function tests (e.g. multiple breath washout (MBW)) in both groups	At age of 1, 2, 3, ...., 10 years of age

Secondary

Measure	Time frame
Rate of protocol-defined pulmonary exacerbations in both groups (ED vs. LD) that are necessitating an antibiotic therapy orally, intravenously or per inhalation	At age of 1, 2, 3, ...., 10 years of age
Spontaneous development of infection or spectrum of pathogens, respectively, in throat and nose swabs as well as other airway secretions from routine diagnostics and if applicable bronchoalveolar lavage fluid (BALF)	At age of 1, 2, 3, ...., 10 years of age
From the patients in whom PsA or other CF pathogens could not be isolated at the beginning of their participation, comparison of the portion of patients with a positive culture during participation in both groups (ED and LD)	At age of 1, 2, 3, ...., 10 years of age
Time to first detection of a CF pathogen in both groups	At age of 1, 2, 3, ...., 10 years of age
Time to first pulmonary exacerbation in both groups	At age of 1, 2, 3, ...., 10 years of age
Frequency of symptoms from monthly telephone interviews in both groups	At age of 1, 2, 3, ...., 10 years of age
Development of body weight, body height, ideal weight-for-height (IWFH), Body-Mass-Index (BMI), respiratory rate and oxygen saturation at room air in both groups	At age of 1, 2, 3, ...., 10 years of age
Proportion with morphological changes due to CF lung disease after modified Chrispin-Norman Score for assessment of chest X-ray in both groups	At age of 1, 2, 3, ...., 10 years of age
Magnitude and severity of alterations typical for CF by assessment with chest MRI and X-ray score in both groups	At age of 1, 2, 3, ...., 10 years of age
Magnitude of impairment of pulmonary function test in both groups	At age of 1, 2, 3, ...., 10 years of age
Portion of patients with increased biochemical inflammatory markers in both groups and magnitude of elevation	At age of 1, 2, 3, ...., 10 years of age
Health-related quality of life in both groups quarterly via Cystic Fibrosis Questionnaire (CFQ)	At age of 1, 2, 3, ...., 10 years of age

Countries

Germany

Contacts

Primary ContactMarcus A Mall, MD

Marcus.Mall@med.uni-heidelberg.de+49 6221 56 4502

Backup ContactMirjam Stahl, MD

Mirjam.Stahl@med.uni-heidelberg.de+49 6221 56 37049

Outcome results