People with Cystic Fibrosis (CF), especially solid organ transplant recipients, have been prioritized in the SARS-CoV-2 vaccination program. This study assesses antibody response of patients with CF who have undergone liver (CF-LI) or lung (CF-LU) transplantation, and compares results to published data of patients with solid organ transplantation without CF as underlying disease. Antibodies against the spike receptor-binding domain were measured within the routine visits at the CF Centre in Innsbruck, Austria, after the second and third doses of SARS-CoV-2 mRNA vaccines. We report on 13 adult CF patients who are recipients of solid organ transplant, including five CF-LI and eight CF-LU. Overall, 69% had measurable antibody response after two, and 83% after three doses of SARS-CoV-2 vaccines. In CF-LI, positive serological response amounted to 100% after two and three doses, while CF-LU showed only a 50% and a 71% response rate, respectively. Clear differences are seen between the CF-LI and CF-LU groups in our cohort, with worse response rate for lung transplant recipients. Immune response between CF-LI and CF-LU, therefore, must be considered in a differentiated manner, and the importance of booster vaccination is once more emphasized with these data.

Background Previous reports have shown an increased number of colorectal cancers in patients with cystic fibrosis. We assessed the database of our cystic fibrosis center to identify patients with all kinds of cancer retrospectively. All patients visiting the Cystic Fibrosis Centre Innsbruck between 1995 and 2019 were included. Case presentation Among 229 patients with cystic fibrosis treated at the Cystic Fibrosis Centre in Innsbruck between 1995 and 2019, 11 subjects were diagnosed with a malignant disease. The median age at diagnosis was 25.2 years (mean 24.3 years). There were four gynecological malignancies (cervical intraepithelial neoplasia and cervical cancer), two hematological malignancies (acute lymphocytic leukemia), one gastrointestinal malignancy (peritoneal mesothelioma), and four malignancies from other origins (malignant melanoma, neuroblastoma, adrenocortical carcinoma, and thyroid cancer). One malignancy occurred after lung transplantation. There was a strong preponderance of females, with 10 of the 11 cases occurring in women. Six deaths were attributed to cancer. Conclusions Most diagnoses were made below 30 years of age, and half of the subjects died from the malignant disease. Awareness of a possible malignancy is needed in patients with atypical symptoms. Regular screenings for cancer should also be considered, not only for gastrointestinal tumors.

Cystic fibrosis (CF) is caused by two mutations in the Cystic Fibrosis Transmembrane Conductance Regulator ( CFTR) gene. In the last years, drugs targeting the underlying protein defect like lumacaftor/ivacaftor (LUM/IVA) or tezacaftor/ivacaftor (TEZ/IVA) and more recently elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) were admitted. Outcome parameters evaluating therapy response like forced expiratory pressure in 1 s (FEV1), body mass index (BMI) or the efficacy of CFTR function in sweat glands showed improvement in several cases. Other, CFTR biomarkers were analysed rarely. This prospective observational study was aimed at evaluating CFTR function in patients treated with different CFTR modulators together with common valid clinical outcome parameters at standardized appointments (day 0, week 2, 4, 16). We followed four patients with the same mutation ( F508del-CFTR), sex, age and disease severity. Monitoring focused on lung function, gastrointestinal aspects and CFTR function of sweat glands, nasal and intestinal epithelium. Sweat tests were performed by pilocarpine iontophoresis. Nasal potential difference (NPD) measured transepithelial voltage in vivo and potential increased when CFTR function improved. Rectal biopsies were obtained for intestinal current measurements (ICM) ex vivo. Intestinal CFTR function was assessed by stimulating chloride secretion with different reagents. Response to CFTR modulators regarding clinical outcome parameters was rather variable. A sweat chloride reduction of 35.3 mmol/L, nasal CFTR rescue of 4.4% and fivefold higher CFTR function in the intestine was seen at week 16 post-LUM/IVA. Due to our monitoring, we identified a non-responder to LUM/IVA and TEZ/IVA. In case of ELX/TEZ/IVA, clinical parameters and CFTR bioassays improved and were concordant. Although our cohort is small, results emphasize that non-responders exist and conclusions could not be drawn if patients were not monitored. Data on CFTR function can confirm or disprove ongoing CFTR dysfunction and might be helpful selectively. Non-responders need other alternative therapy options as demonstrated with ELX/TEZ/IVA.