Gastrointestinal Manifestations Of Cystic Fibrosis Research Articles

Presentation, characteristics and management of obstructive intestinal conditions in cystic fibrosis

ObjectiveConstipation and distal intestinal obstruction syndrome (DIOS) are common gastrointestinal manifestations of cystic fibrosis (CF). The primary aim was to describe the characteristics of constipation and DIOS hospitalisations in a...

316: Assessment of course on gastrointestinal manifestations of cystic fibrosis in addressing knowledge and practice gaps

316: Assessment of course on gastrointestinal manifestations of cystic fibrosis in addressing knowledge and practice gaps

The Intestinal Microbiome and Cystic Fibrosis Transmembrane Conductance Regulator Modulators: Emerging Themes in the Management of Gastrointestinal Manifestations of Cystic Fibrosis.

While commonly associated with pulmonary manifestations, cystic fibrosis (CF) is a systemic disease with wide-ranging effects on the gastrointestinal (GI) tract. This article reviews major recent updates in gastroenterological CF care and research. The high burden of GI symptoms in CF has led to recent studies assessing GI-specific symptom questionnaires and scoring systems. Intestinal dysbiosis potentially contributes to gastrointestinal symptoms in patients with CF and an increased risk of gastrointestinal cancers in CF. An increased incidence of colorectal cancer (CRC) has led to CF-specific CRC screening and surveillance recommendations. Pharmacologic therapies targeting specific cystic fibrosis transmembrane conductance regulator (CFTR) mutations have shown promise in treating GI manifestations of CF. New research has highlighted the importance of intestinal dysbiosis in CF. Future studies should assess whether CFTR modulators affect the gut microbiome and whether altering the gut microbiome will impact GI symptoms and GI cancer risk.

Gastrointestinal manifestations of cystic fibrosis in children

Cystic fibrosis (CF) is a multisystemic disease, with high morbidity and mortality, and its early diag nosis improves results. Lung conditions are the main cause of morbidity and mortality and are clo sely related to nutritional status and survival. There is little national information about the liver and gastrointestinal characteristics in pediatric patients with CF. to describe at a gastrointes tinal level, the general, nutritional, and genetic characteristics and the evolution of CF carriers with/ without neonatal screening. Retrospective study carried out in 4 public referral hospitals in the Metropolitan Region. The diagnosis of CF confirmed with two positive sweat tests (Gibson and Cooke method) was considered as an inclusion criterion. Those patients with unconfir med neonatal screening tests through Immunoreactive Trypsinogen (IRT) or with only one positive sweat test were excluded. Sex, age, nutritional status, date of diagnosis, clinical presentation at the onset, evolution, and therapies received were recorded as clinical variables, and as laboratory ones, genetic study by means of a diagnostic panel with 36 mutations. The STATA 12 software was used for statistical analysis. 127 patients were included. Respiratory manifestations (recurrent obstructive bronchial syndrome and pneumonia) were present in >60% and gastrointestinal ones (mainly malabsorption and malnutrition syndrome) in >80% of patients. On average, diagnostic confirmation took 4 months. The diagnosis guided by IRT was associated with better nutritional outcomes in the evolution of the patient. In 81.1% of the patients, the genetic study was performed. The most frequent mutations were those associated with DF508 (deletion of phenylalanine 508). 5.8% of the patients presented mutations not included in the gene panel used. Gas trointestinal CF appears with pancreatic, intestinal, and hepatic pathology throughout life. Malnutri tion is a frequently present factor, which worsens the prognosis. The management of gastrointestinal manifestations and malnutrition are relevant to improve the morbidity and mortality of CF patients.

Practical approach to the gastrointestinal manifestations of cystic fibrosis.

Cystic fibrosis (CF) is the most common, life-shortening, genetic illness affecting children in Australia and New Zealand. The genetic abnormality results in abnormal anion transport across the apical membrane of epithelial cells in a number of organs, including the lungs, gastrointestinal tract, liver and genito-urinary tract. Thus, CF is a multi-system disorder that requires a multi-disciplinary approach. Respiratory disease is the predominant cause of both morbidity and mortality in patients with CF. However, there are significant and clinically relevant gastrointestinal, liver, pancreatic and nutritional manifestations that must be detected and managed in a timely and structured manner. The aim of this review is to provide evidence-based information and clinical algorithms to guide the nutritional and gastrointestinal management of patients with CF.

Cystic Fibrosis & disorders of the large intestine: DIOS, constipation, and colorectal cancer

Since 1966 when the Cystic Fibrosis Foundation Patient Registry (CFFPR) was founded, clinicians have witnessed significant advances in both the quality and quantity of life for patients living with Cystic Fibrosis (CF). As patients with CF live longer and fuller lives, increasing encumbrances from gastrointestinal manifestations of CF will be observed. This article serves to discuss “below the diaphragm” concerns involving the large intestine (Distal Intestinal Obstruction Syndrome, Constipation, and Colorectal Cancer). Avenues for development and implementation of clinical care protocols, particularly regarding proactive management of known associated conditions and cancer screening, will continue to be refined in the coming years. It falls to the multidisciplinary CF care team to be actively engaged in addressing these concerns effectively as priority shifts from relative acuity (typically related to early nutrition and lung function) to the travails of longevity as the CF population continues to age.

Longitudinal Cystic Fibrosis Care

Cystic fibrosis is a complex disease entity that presents considerable lifelong challenges. Implementation of medical and surgical treatment options involves multisystem interventions to prevent and treat lung and gastrointestinal manifestations of cystic fibrosis and associated comorbidities. From birth through adulthood, cystic fibrosis care entails a longitudinal regimen aimed at achieving relief of disease symptoms and enhanced life expectancy. With increased knowledge of the molecular behavior of the cystic fibrosis transmembrane conductance regulator (CFTR) in health and disease, clinical practice has been enriched by the prospect of novel strategies, including mutation-specific drug and gene therapy targeting restoration of corrupted transepithelial ion transport. Emerging paradigms of comprehensive care increasingly enable personalized solutions to address the root cause of disease-transforming management options for individuals with cystic fibrosis.

The ESPGHAN Cystic Fibrosis Working Group: Defining DIOS and Constipation in Cystic Fibrosis With a Multicenter Study on the Incidence, Characteristics, and Treatment of DIOS

In 2005 a group of pediatric gastroenterologists convened at the annual meeting of the European Society for Pediatric Gastroenterology and Nutrition (ESPGHAN) to reevaluate some important gastrointestinal manifestations of cystic fibrosis (CF). It had become evident that the key gastrointestinal symptoms of the disease, such as distal intestinal obstruction syndrome (DIOS), meconium ileus equivalent (MIE), and constipation, were ill-defined. Such a limitation could not only represent a bias for clinical studies evaluating the incidence and prevalence of these gastrointestinal manifestations in CF but also negatively influence the diagnosis and treatment of these manifestations of CF. The results of the activity of the ESPGHAN CF Working Group appear in this issue of JPGN, specifically in the article by Houwen et al (1). Cystic fibrosis is the most common fatal autosomal recessive disease among white populations, with a frequency of 1 in 2000 to 3000 live births. It is generally thought of as a lung disease because much of the associated morbidity rate and mortality rate is related to pulmonary complications (2). However, gastrointestinal complications also have become an increasingly important cause of the morbidity rate in part because of the improved life expectancy of patients with CF. The underlying pathophysiology of CF is related to abnormal chloride transport caused by mutations in the CF transmembrane conductance regulator gene (CFTR) located on chromosome 7. The mutations cause the production of abnormally tenacious mucus and secretions in the lungs, gut, pancreas, and hepatobiliary system. The gastrointestinal manifestations of CF can be broken down into 3 categories: intestinal, pancreatic, and hepatobiliary. One of the most common intestinal abnormalities is the DIOS, formerly known as “meconium ileus equivalent,” which is characterized by complete or partial obstruction of the bowel lumen by intestinal contents. Distal intestinal obstruction syndrome is caused by inspissated intestinal contents that completely or partially block the intestinal lumen, although a detailed understanding of this process remains unclear. In the last few years, different definitions of DIOS, MIE, and constipation in patients with CF have been used, but better definitions for the 3 conditions would now seem to be necessary for an improved assessment and management of these patients (3,4). The new definition proposed by the ESPGHAN CF Working Group for incomplete or impending DIOS is “a short history (days) of abdominal pain and/or distension and a faecal mass in ileo-caecum, but without signs of complete obstruction.” Constipation was defined as “abdominal pain and/or distension or a decline in the frequency of bowel movements in the last few weeks to months and/or increased consistency of stools in the last few weeks or months, while the symptoms are relieved by the use of laxatives.” Meconium ileus equivalent was identified with DIOS. The most important outcome of the consensus is that these specific definitions could avoid misdiagnosis between DIOS and constipation in patients with CF, as sometimes occurred in the past. The practical result of this update was immediately seen in the study because the impact of this review was evaluated in a questionnaire-based multicenter survey in which the new definitions were applied to a large number of patients younger than 18 years with CF, enrolled between 2001 and 2005 in 8 medical centers. Using the new criteria, the incidence of both DIOS and meconium ileus at birth resulted to be far higher than that reported in previous studies. It seems clear that the higher incidence of DIOS is mainly due to the newly established definitions, although new therapeutic approaches could have partly influenced the results of other recent studies. The authors have also reevaluated the correlation between DIOS and CFTR mutations, as organized into 5 classes (I–III severe mutations, IV–V mild mutations), comparing the CFTR genotype with the DIOS-positive or DIOS-negative phenotype. The great majority of the subjects with CF had a severe genotype, being homozygous for the most common mutation, ΔF508. The results of the present study seem to confirm the association between major CFTR dysfunction and DIOS, whereas the possible role of other genetic factors such as dysmotility and inflammatory status could be evaluated in the next clinical trials. In conclusion, the new definitions established by the consensus conference of the ESPGHAN CF Working Group are important for 2 main reasons: the epidemiology of the gastrointestinal complications of CF could be profoundly modified, and the new definitions will help the clinician perform a more specific diagnosis of MIE, DIOS, and constipation, thus improving not only the diagnostic accuracy but also the effectiveness of treatment.

Cystic Fibrosis in Children and Young Adults: Findings on Routine Abdominal Sonography

The gastrointestinal manifestations of cystic fibrosis predispose patients to morbid conditions involving the pancreas, liver, biliary tract, spleen, and intestine. This article reviews the sonographic appearance of these abdominal manifestations. Numerous gastrointestinal complications have sonographic manifestations that must be interpreted correctly to ensure appropriate therapy.

Meconium Ileus–Is a Single Surgical Procedure Adequate?

Meconium ileus is one of the gastrointestinal manifestations of cystic fibrosis (CF), and affects 15% of neonates. The condition results from the accumulation of sticky inspissated meconium. Both nonoperative and operative therapies may be effective in relieving obstruction. The treatment of choice for uncomplicated meconium ileus is the use of enteral N-acetylcysteine or Gastrografin enemata. Once such therapy fails, surgery is indicated. A number of operative procedures are in use, including Bishop-Koop enterostomy, T-tube irrigation, resection and primary anastomosis, and enterotomy with irrigation and primary closure. During the period 1991-2003, five newborns required surgical intervention for uncomplicated meconium ileus. None responded to conservative management. All were males, including one set of twins. All underwent laparotomy, enterotomy, appendectomy, irrigation and closure of enterotomy. None required a second surgical procedure. CF was confirmed in all, and in each case, both parents were found to be genetic carriers of a mutational form of CF. A single surgical intervention is preferable in these patients, in view of the high rate of pulmonary involvement in CF patients. Enterotomy, irrigation and primary closure are the treatment of choice for uncomplicated meconium ileus.

Modifier genes in cystic fibrosis

Although over 1,000 disease-causing mutations in the CFTR gene have been described, the highly variable disease phenotype in cystic fibrosis (CF) cannot be explained on the basis of this gene alone. Both the environment and other non-CFTR genes are likely to be important. The increased understanding of pathophysiological processes in the CF lung has led to several studies on genes in these pathways, including those involved in host defense, mucin production, and airway responsiveness. Additionally, candidate modifiers of the gastrointestinal manifestations of CF have been explored. One of the major aims of such studies is to produce targets for novel drug developments. This review will summarize the field to date and discuss some of the methodological issues important in the design and interpretation of such studies.

Abdominal manifestations of cystic fibrosis in adults: A review

Gastrointestinal manifestations of disease are present in most adults with cystic fibrosis. Radiologists are familiar with the classical imaging characteristics of end-stage pulmonary disease and the radiological findings of meconium ileus in neonates. As most patients now live into adulthood, recognition of the imaging appearances of abdominal disease is important to enable prompt diagnosis and treatment. Accordingly, this article presents typical imaging appearances of the adult gastrointestinal manifestations of cystic fibrosis.

Sublingual Tacrolimus for Immunosuppression in Lung Transplantation

Lung transplantation has emerged as an option to prolong and increase the quality of life in patients with end-stage pulmonary lung disease. In lung transplant recipients, because of the high potential for acute and chronic allograft rejection, optimal selection, dosage and delivery of immunosuppressive medications is critical. Cystic fibrosis (CF), a multi-organ system disease that often includes pulmonary and gastrointestinal manifestations, represents the leading indication for bilateral lung transplantation. The gastrointestinal manifestations of CF, however, confound post-transplant management by causing significant variation in the rate and extent of absorption of orally administered immunosuppressive medications. Tacrolimus, a new calcineurin inhibitor, is increasingly employed as the primary immunosuppressive agent in lung transplant recipients. Unfortunately, tacrolimus itself exhibits variable bioavailability, particularly in CF transplant recipients. A novel approach to the absorption dilemma is administration of tacrolimus via the sublingual (SL) route. Little published information exists concerning the use of SL immunosuppression in transplant recipients. However, emerging evidence suggests that SL tacrolimus provides is an effective means of drug delivery particularly for CF lung transplant recipients. Preliminary results from a pilot study, demonstrate that SL delivery of tacrolimus achieves therapeutic serum levels, in lung transplant recipients with CF, over the first few postoperative months. In addition, the early postoperative use of SL tacrolimus has been associated with acceptable rates of transplant rejection and normal renal function in a cohort of 22 lung transplant recipients that included CF and non-CF transplant recipients. Potential pharmacokinetic advantages of the SL route of delivery include good permeability, rapid absorption, acceptable bioavailability and easy accessibility. From an economic standpoint, considerable cost savings could be achieved by using the SL rather than the intravenous route of drug delivery for tacrolimus. Comparative, prospective randomized trials are necessary to evaluate the long-term safety and efficacy of SL tacrolimus in lung transplant patients. Until such data are available, the use of SL tacrolimus should be considered in situations where alternative routes of delivery are unavailable or as part of ongoing research studies. Ultimately, SL tacrolimus may prove efficacious for short-term use in the early postoperative lung transplant recipients, particularly in patients with malabsorption problems such as CF transplant recipients.

Imaging appearance of the gastrointestinal manifestations of cystic fibrosis

Imaging appearance of the gastrointestinal manifestations of cystic fibrosis

Gastrointestinal manifestations of cystic fibrosis.

Cystic fibrosis is clearly a multisystem disease, which the potential for prominent gastrointestinal and hepatobiliary involvement. While the routine patient with pancreatic insufficiency may be easily managed with pancreatic enzyme and nutritional therapy, a large number of individuals with cystic fibrosis will present the clinician with gastrointestinal problems requiring additional thoughtful evaluation and treatment. Familiarity with the common gastrointestinal manifestations of cystic fibrosis and emerging therapies is necessary to provide the comprehensive care these patients deserve.

Diseases of the pancreas, including cystic fibrosis

The identification and cloning of the cystic fibrosis gene has broadened the scientific research base, with particular opportunities for biochemical and physiologic investigation of the basic defect. Gene therapy is an exciting prospect, and clinical research of the gastrointestinal manifestations of cystic fibrosis provide further understanding. Imaging, surgical, and therapeutic advances continue to benefit the child with pancreatic disease.

Gastrointestinal manifestations of cystic fibrosis

Gastrointestinal manifestations of cystic fibrosis

Gastrointestinal manifestations of cystic fibrosis: A review: Roger W. Park and Richard J. Grand. Gastroenterol 81:1143–1161, (December), 1981

Gastrointestinal manifestations of cystic fibrosis: A review: Roger W. Park and Richard J. Grand. Gastroenterol 81:1143–1161, (December), 1981

Gastrointestinal manifestations of cystic fibrosis: Harry Shwachman. Pediatr clin north am 22:787–805 (November), 1975

Gastrointestinal manifestations of cystic fibrosis: Harry Shwachman. Pediatr clin north am 22:787–805 (November), 1975

The late gastrointestinal manifestations of cystic fibrosis of the pancreas.

The gastrointestinal manifestations of cystic fibrosis which occur in older children and young adults are numerous. When recognized radiographically, they allow the radiologist to make the diagnosis of the disease in the absence of the typical pulmonary changes. The findings of meconium ileus equivalent, an adherent fecalith, splenomegaly, esophageal varices, unusual gallbladder abnormalities, and pneumatosis coli are suggestive of cystic fibrosis and its complications. The hyperplastic-looking cobblestone appearance of the colonic mucosa observed in many older patients is distinctive. Nodular mucosal changes in the small intestine may also be present.