Intestinal current measurement versus nasal potential difference measurements for diagnosis of cystic fibrosis: a case–control study

Bagheri-Hanson, Azadeh; Nedwed, Sebastian; Rueckes-Nilges, Claudia; Naehrlich, Lutz

doi:10.1186/1471-2466-14-156

Cited by 19 publications

(12 citation statements)

References 40 publications

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“…Our preliminary data also support this notion since cigarette smoke extract dose-dependently inhibited pancreatic ductal CFTR activity and HCO 3 − secretion in guinea pigs. In fact, the latter results are in accord with those found in other organs such as the airway [64] or intestinal epithelial cells [65]. It seems that CFTR dysfunction due to smoking is primarily an acquired phenomenon and is not affected by the presence of heterozygous CFTR mutations [66].…”

supporting

confidence: 79%

CFTR: A new horizon in the pathomechanism and treatment of pancreatitis

Hegyi

2016

Pancreatology

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Cystic fibrosis transmembrane conductance regulator (CFTR) is an ion channel that conducts chloride and bicarbonate ions across epithelial cell membranes. Mutations in the CFTR gene diminish the ion channel function and lead to impaired epithelial fluid transport in multiple organs such as the lung and the pancreas resulting in cystic fibrosis. Heterozygous carriers of CFTR mutations do not develop cystic fibrosis but exhibit increased risk for pancreatitis and associated pancreatic damage characterized by elevated mucus levels, fibrosis and cyst formation. Importantly, recent studies demonstrated that pancreatitis causing insults, such as alcohol, smoking or bile acids strongly inhibit CFTR function. Furthermore, human studies showed reduced levels of CFTR expression and function in all forms of pancreatitis. These findings indicate that impairment of CFTR is critical in the development of pancreatitis; therefore, correcting CFTR function could be the first specific therapy in pancreatitis. In this review, we summarize recent advances in the field and discuss new possibilities for the treatment of pancreatitis.Corresponding author: Prof. Dr. Peter Hegyi, Doctor of the Hungarian Academy of Sciences, First Department of Medicine, University of Szeged, Koranyi fsr. 8-10, SZEGED, H6720, Hungary, TEL: +3662545200, FAX: +3662545185, MOBILE: +36703751031, hegyi.peter@med.u-szeged.hu. Conflict of interest statement: the authors have no conflict of interest to declare HHS Public Access I. Basics of CFTR a. Biosynthesis and degradationThe cystic fibrosis transmembrane conductance regulator (CFTR) protein is a cyclic AMP (cAMP)-regulated chloride (Cl − )/bicarbonate (HCO 3 − ) channel, expressed in the apical plasma membrane (PM) of secretory epithelia in the airways, pancreas, intestine, reproductive organs and exocrine glands [1]. CFTR consists of two homologous halves, each containing a hexa-helical membrane spanning domain (MSD1 and MSD2) and a nucleotide binding domain (NBD1 and NBD2) (Figure 1). The two halves are connected by the R domain [2]. The NBDs contain conserved ATP-binding sequences: Walker A and B motifs, classifying CFTR as a member of the ATP-binding cassette (ABC) transporter family. Structural, biochemical and functional evidence suggest that the two NBD domains interact and the ATP-binding site of one NBD is complemented by the ABC signature motif of the other [2].While NBD1 folds largely co-translationally, the native fold of NBD2 as well as CFTR are attained post-translationally [3]. Assembly of MSD1, NBD1, R domain and MSD2 is necessary and sufficient to form the minimal folding unit of CFTR [4]. These and other observations support the cooperative domain folding model and ensure the dynamic conformational coupling between the cytosolic NBDs and the pore-forming MSDs in the native molecule and provide a structural explanation for the cooperative domain unfolding, caused by cystic fibrosis (CF) mutations [4].Despite interactions with several cytosolic and endoplasmic reticulum (ER) chapero...

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confidence: 79%

CFTR: A new horizon in the pathomechanism and treatment of pancreatitis

Hegyi

2016

Pancreatology

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“…Written informed consent was obtained from participant’s parents or legal guardian. Requirements for a CF diagnosis included either positive genetic testing or positive sweat chloride test findings and at least one clinical manifestation including typical chronic obstructive pulmonary disease (COPD), documented exocrine pancreatic insufficiency, and positive family history (usually an affected sibling) ( 14 ).…”

Section: Methodsmentioning

confidence: 99%

Evaluation of Serum Adenosine Deaminase in Cystic Fibrosis Patients in an Iranian Referral Hospital

et al. 2016

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Background:Adenosine, a signaling nucleoside, is controlled in part by the enzyme adenosine deaminase (ADA). There are rare reports on the role of adenosine levels and ADA in cystic fibrosis (CF) patients.Objectives:The aim of this study was to assess serum ADA in CF patients in order to find whether the severity of lung disease in CF is related to significant changes of ADA or not.Patients and Methods:Venous blood serum ADA was measured in CF patients (3-15 years) and 49 healthy children (3-15 years) referred to Children’s Medical Center. Classification of respiratory and gastrointestinal disease severity in CF patients as well as Body Mass Index (BMI) was performed. The results were compared with values obtained from healthy children matched for age and gender.Results:This study included 49 children of both genders (20 females and 29 males) with CF (mean age: 6.36 ± 2.22 years). Mean serum ADA in CF patients group and control group was 9.38 ± 2.72 and 16.04 ± 1.27, respectively (P value = 0.001). Mean serum ADA in CF patients with normal BMI was higher than in patients with low BMI (P value = 0.002).Conclusions:In this study the lower serum level of ADA was seen in CF patients compared to control group. The clinical symptoms, especially respiratory symptoms, in CF patients might be associated with reduction of serum ADA and rising serum adenosine; therefore, further studies on the use of ADA enzyme therapy in CF patients are highly recommended.

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“…Clear-cut reference/threshold values between CF-PS and control subjects have been identified, supporting the role of ICM in the diagnosis of CF. [159][160][161][162] Future efforts should be put into the description of ICM values in larger groups of obligate heterozygotes and patients with CFTR-related disorders.…”

Section: Intestinal Current Measurementmentioning

confidence: 99%

Cystic Fibrosis Diagnosis in Newborns, Children, and Adults

Castellani

Linnane

Pranke

et al. 2019

Semin Respir Crit Care Med

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The diagnosis of cystic fibrosis (CF) has traditionally relied on the presence of clinical features of the disease. Today, diagnosis through newborn screening (NBS) is becoming the standard of modern CF care. CF NBS programs can identify CF prior to clinical presentation, but for the advantages of an early diagnosis to accrue a scrupulous system must be in place to ensure all steps in the program are performing. As we move rapidly into the era of CF transmembrane conductance regulator (CFTR) protein modulators, the opportunity to start a presymptomatic infant, identified through CF NBS, on these agents offers the prospect of true disease-modifying interventions which could result in a paradigm shift in CF care.Conversely, the introduction of NBS has resulted in many children being asymptomatic at the time of diagnosis. Some screened newborns are classified as “CF Screening Positive, Inconclusive Diagnosis”, or “CFTR-related metabolic syndrome” when the diagnosis can neither be confirmed nor excluded. Appropriate assessment and follow-up should be arranged at specialist centers as a proportion of these infants and adults will eventually be diagnosed with CF.Symptoms and signs are particularly pertinent when considering a diagnosis of CF outside the context of NBS. In older patients with a late diagnosis, the spectrum of clinical presentation can be very variable with vigilant clinicians from multiple specialties suspecting the diagnosis in conditions such as recurrent pulmonary infections, male infertility, pancreatitis, nasal polyposis, and malabsorption.In addition to clinical symptoms or positive NBS results, sweat test and genetic analysis are cornerstones in the diagnosis of CF, but in some cases the diagnosis cannot be confirmed on genetic or sweat testing. Difficult diagnosis may be supported by in vivo or ex vivo electrophysiology measurements on respiratory or intestinal epithelia. This can be done by either measuring transepithelial nasal potential difference or intestinal current measurements.

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Intestinal current measurement versus nasal potential difference measurements for diagnosis of cystic fibrosis: a case–control study

Cited by 19 publications

References 40 publications

CFTR: A new horizon in the pathomechanism and treatment of pancreatitis

CFTR: A new horizon in the pathomechanism and treatment of pancreatitis

Evaluation of Serum Adenosine Deaminase in Cystic Fibrosis Patients in an Iranian Referral Hospital

Cystic Fibrosis Diagnosis in Newborns, Children, and Adults

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