Long-term follow-up of distal intestinal obstruction syndrome in cystic fibrosis

AIM: To investigate the long-term follow-up of distal intestinal obstruction syndrome(DIOS) in Israeli cystic fibrosis(CF) patients.METHODS: This is a multi-center,comparative,retrospective study in which we reviewed the medical records of all CF patients from three major CF centers in Israel who were treated in the period from 1980 to 2012.Patients diagnosed with DIOS were defined as the study group.The patients were diagnosed with DIOS based on their clinical presentation and typical findings on either abdominal X-ray or computerized tomography scan.For the control group,CF patients with no DIOS were matched to the patients in the study group for age,sex,and cystic fibrosis transmembrane conductance regulator(CFTR) mutations.For both groups,the collected data included age,sex,CFTR genotype,weight,height,and body mass index.Clinical data included respiratory function tests in the last five years prior to the study,respiratory function test immediately before and after the DIOS event,number of hospitalizations,sputum culture results,and CFrelated conditions diagnosed according to the CF clinical practice guidelines.In the study group,data on the DIOS treatment and tendency for DIOS recurrence were also analyzed.RESULTS: The medical charts for a total of 350 CF patients were reviewed.Of the 350 CF patients,26(7.4%) were diagnosed with DIOS.The control group included 31 CF patients with no DIOS diagnosis.The mean follow-up period was 21.6 ± 8.2 years.The total of DIOS episodes in the follow-up period was 60.The distribution of DIOS episodes was as follows: 6/26(23.1%) study patients had one episode of DIOS intheir lifetime,7/26(26.9%) had two episodes,7/26(26.9%) had three episodes,and 6/26(23.1%) had four or more episodes.Compared to the control group,DIOS patients had a significantly higher incidence of meconium ileus in the past(65.4% vs 0%,respectively,P < 0.02),more Aspergillus spp.colonization(34.6% vs 3.2%,respectively,P < 0.02),and a higher number of hospitalizations due to respiratory exacerbations(8.6 vs 6.2 mean total hospitalizations per follow-up period,respectively,P < 0.02).No other significant differences were found between the control and study groups.The conservative treatment of DIOS,which mainly includes hydration and stool softeners,was successful in 82% of the episodes.The survival rate was similar for both groups.CONCLUSION: CF patients with DIOS suffer from recurrent hospitalizations and airway pathogen acquisition.Although recurrence of DIOS is common,conservative treatment is successful in most patients.

Cystic fibrosis transmembrane conductance regulator functional evaluations in a G542X+/-IVS8Tn:T7/9 patient with acute recurrent pancreatitis

BACKGROUND Acute recurrent pancreatitis(ARP)is characterized by episodes of acute pancreatitis in an otherwise normal gland.When no cause of ARP is identifiable,the diagnosis of"idiopathic"ARP is given.Mutations in the cystic fibrosis transmembrane conductance regulator(CFTR)gene increase the risk of ARP by 3-to 4-times compared to the general population,while cystic fibrosis(CF)patients present with a 40-to 80-times higher risk of developing pancreatitis.CASE SUMMARY In non-classical CF or CFTR-related disorders,CFTR functional tests can help to ensure a proper diagnosis.We applied an individualized combination of standardized and new CFTR functional bioassays for a patient referred to the Verona CF Center for evaluation after several episodes of acute pancreatitis.The CFTR genotype was G542X+/-with IVS8Tn:T7/9 polymorphism.The sweat(Cl-)values were borderline.Intestinal current measurements were performed according to the European Cystic Fibrosis Society Standardized Operating Procedure.Recent nasal surgery for deviated septum did not allow for nasal potential difference measurements.Lung function and sputum cultures were normal;azoospermia was excluded.Pancreas divisum was excluded by imaging but hypoplasia of the left hepatic lobe was detected.Innovative tests applied in this case include sweat rate measurement by image analysis,CFTR function in monocytes evaluated using a membrane potential-sensitive fluorescent probe,and the intestinal organoids forskolin-induced swelling assay.CONCLUSION Combination of innovative CFTR functional assays might support a controversial diagnosis when CFTR-related disorders and/or non-classical CF are suspected.

Risk factors for hepatic steatosis in adults with cystic fibrosis: Similarities to non-alcoholic fatty liver disease

AIM To investigate the clinical, biochemical and imaging characteristics of adult cystic fibrosis(CF) patients with hepatic steatosis as compared to normal CF controls.METHODS We performed a retrospective review of adult CF patients in an academic outpatient setting during 2016. Baseline characteristics, genetic mutation analysis as well as laboratory values were collected. Abdominal imaging(ultrasound, computed tomography, magnetic resonance) was used to determine presence of hepatic steatosis. We compare patients with hepatic steatosis to normal controls.RESULTS Data was collected on 114 patients meeting inclusion criteria. Seventeen patients(14.9%) were found to have hepatic steatosis on imaging. Being overweight(BMI > 25)(P = 0.019) and having a higher pp FEV1(75 vs 53, P = 0.037) were significantly associated with hepatic steatosis. Patients with hepatic steatosis had a significantly higher median alanine aminotransferase level(27 vs 19, P = 0.048). None of the hepatic steatosis patients had frank CF liver disease, cirrhosis or portal hypertension. We found no significant association with pancreatic insufficiency or CF related diabetes.CONCLUSION Hepatic steatosis appears to be a clinically and phenotypically distinct entity from CF liver disease. The lack of association with malnourishment and the significant association with higher BMI and higher pp FEV1 demonstrate similarities with non-alcoholic fatty liver disease. Long term prospective studies are needed to ascertain whether CF hepatic steatosis progresses to fibrosis and cirrhosis.

Acquired cystic fibrosis transmembrane conductance regulator dysfunction

Sinonasal respiratory epithelium is a highly regulated barrier that employs mucociliary clearance(MCC)as the airways first line of defense.The biological properties of the airway surface liquid(ASL),combined with coordinated ciliary beating,are critical components of the mucociliary apparatus.The ASL volume and viscosity is modulated,in part,by the cystic fibrosis transmembrane conductance regulator(CFTR).The CFTR is an anion transporter of chloride(Cl-)and bicarbonate(HCO 3-)that is located on the apical surface of respiratory epithelium and exocrine glandular epithelium.Improved understanding of how dysfunction or deficiency of CFTR influences the disease process in both genetically defined cystic fibrosis(CF)and acquired conditions has provided further insight into potential avenues of treatment.This review discusses the latest data regarding acquired CFTR deficiency and use of CFTR specific treatment strategies for CRS and other chronic airway diseases.