Mini organs could solve cystic fibrosis diagnosis puzzle

Copied word for word from the study's registry entry, so the wording is the study team's rather than ours.

Inclusion Criteria: Group A: Difficult Cystic Fibrosis Diagnosis Cohort Inclusion criteria: 1. Patients with difficult-to-diagnose CF\* 2. Adults (≥16y) 3. Willing to undergo rectal biopsy 4. Able to comply with the study * Definition: Non-diagnostic first line CFTR testing (individuals who do not fulfil CF diagnostic criteria \[2 CF-causing CFTR variants and/or sweat chloride concentration ≥60 mmol/L\]). Of note, there are some individuals with \<2 CF-causing CFTR variants after extended CFTR genetic analysis but with a SCC \>60mmol/L. Expansion of the patient pool to include these is permissible. Group B: Cystic Fibrosis Patient Cohort Inclusion criteria: 1. Patients with confirmed Cystic Fibrosis 2. Adults (≥16y) 3. Willing to undergo rectal biopsy for this study 4. Able to comply with the study Group C: Non-Cystic Fibrosis Patient Cohort Inclusion criteria: 1. Patients without Cystic Fibrosis or CFTR-related disorder 2. Adults (≥16y) 3. Willing to undergo rectal biopsy for this study (if undergoing a lower GI endoscopy for other purposes) 4. Able to comply with the study Exclusion Criteria: Group A: Difficult Cystic Fibrosis Diagnosis Cohort Exclusion criteria: 1. Contra-indication to rectal biopsy (e.g. significant bleeding diathesis) 2. History of lung transplantation 3. Receiving CFTR modulator treatment 4. Current participation (or participation within one month of enrolment) in a clinical trial of an investigational medicinal product which affects CFTR function (e.g. CFTR modulators, genetic therapies) 5. Female who is pregnant or breastfeeding 6. Unable to provide informed consent Group B: Cystic Fibrosis Patient Cohort Exclusion criteria: 1. Contra-indication to rectal biopsy (e.g. significant bleeding diathesis) 2. Current participation (or participation within one month of enrolment) in a clinical trial of an investigational medicinal product which affects CFTR function (e.g. CFTR modulators, genetic therapies) 3. Female who is pregnant or breastfeeding 4. Unable to provide informed consent 5. Exclude all subjects where diagnosis of CF is in doubt Group C: Non-Cystic Fibrosis Patient Cohort Exclusion criteria: 1. Contra-indication to rectal biopsy (e.g. significant bleeding diathesis) 2. Female who is pregnant or breastfeeding 3. Unable to provide informed consent