Letter to the Editor

The patient reported in the foregoing letter is of particular interest in view of the recent observations on patients with tnisomy 21 and cystic fibrosis. The multiple possibilities that could explain the clinical presentation have no doubt been considered by the authors. However, the description of "hypoplastic thrombocytopenia" and later pancytopenia in this patient, associated with pancreatic insufficiency, leads to the serious consideration of Shwachman's syndrome (pancreatic insufficiency and bone marrow dysfunction). The wide discrepancy between the sodium and chloride concentrations in the sweat reported in their letter indicates that evaporation of water may have occurred from the sweat sample, leading to an apparently higher sodium and chloride concentration.

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Detection of Anomalous Sodium Chloride Concentrations in Perspiration Using Microsensors

Volume 10: Micro- and Nano-Systems Engineering and Packaging ◽

10.1115/imece2014-39526 ◽

2014 ◽

Author(s):

David Gaibor ◽

Mehdi Goulamaly ◽

Nilu Jariwala ◽

Mark Piontkowski ◽

Mansour Zenouzi ◽

...

Keyword(s):

Cystic Fibrosis ◽

Sodium Chloride ◽

Bacterial Infections ◽

Low Cost ◽

Common Knowledge ◽

Chloride Concentration ◽

Electrical Signal ◽

Electrical Signals ◽

Early Disease Detection ◽

Sweat Sample

It is common knowledge that an early diagnosis of a disease improves the treatment provided to a patient. With the advent of nanotechnology, engineers and scientists are beginning to utilize these nanoscale capabilities in the hope of - early disease detection. Viral, bacterial infections and other chronic diseases seem to alter the concentrations of some compounds present in sweat [1,2]. This project attempts to detect some of these diseases by measuring the variation in salinity of sweat that differs from the commonly accepted level [2]. By creating a low-cost, reusable and portable microsensor, it can then apply the same principles to construct a nanosensor to yield even more accurate results. The electrical signals obtained by the sensor produce data that translates into diagnostic medical results for sweat-related illnesses such as cystic fibrosis [3]. For a deeper and thorough understanding of all aspects of the sensor, multiple concepts for measuring sweat using electrical signals were considered. Ultimately, the concept chosen to measure varying sweat concentrations was through a capacitor. Multiple capacitor designs were simulated to determine the best way of maximizing performance. After the sensors were constructed, they were tested using various concentrations of sodium chloride (NaCl), from 0.1 grams per liter to 5 grams per liter, dissolved in distilled water to mimic the effect of authentic human sweat [4]. The designed sensor is successfully able to determine the likelihood of a person having cystic fibrosis using a sweat sample as their sweat sodium chloride concentration will correspond to an electrical signal obtained throughout the testing process.

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The 3849+10 kB C—>T Mutation in a 21-Year-Old Patient with Cystic Fibrosis

Ear Nose & Throat Journal ◽

10.1177/014556139607501212 ◽

1996 ◽

Vol 75 (12) ◽

pp. 793-795 ◽

Cited By ~ 2

Author(s):

D.M. Kaplan ◽

A. Niv ◽

M. Aviram ◽

R. Parvari ◽

A. Leiberman ◽

...

Keyword(s):

Cystic Fibrosis ◽

Dna Analysis ◽

Pancreatic Insufficiency ◽

Clinical Status ◽

Chloride Concentration ◽

Inherited Disease ◽

Normal Limits ◽

The Relationship ◽

Sinonasal Symptoms ◽

Sweat Tests

Cystic fibrosis (CF) is the most common lethal inherited disease in the white population. It is characterized by exocrine gland epithelia dysfunction, which leads to pulmonary and pancreatic insufficiency. Since the cloning of the CF gene in 1989 and the identification of the most common CF mutation (ΔF508), more than 400 different mutations have been described. These mutations appear to contribute to the heterogeneity of the CF phenotype and several reports have speculated on the relationship between the most common CF mutations and the patient's clinical status. We report the case of a 21-year-old woman with longstanding chronic pansinusitis, nasal polyposis, chronic cough and severe nasal crusting. During a period of five years she had been followed by her otolaryngologist and pediatric pulmonologist. Sweat tests performed at the age of 17 and 18 were within normal limits and she underwent repeated conventional sinonasal procedures, with no improvement in her clinical status. On her present admission, sweat tests showed a 70 meq/l chloride concentration. The diagnosis of CF was then confirmed by DNA analysis and the patient was found to carry the 3849+10 kB C—>T mutation. The early detection of this newly recognized form of CF in adults as well as in children presenting with sinonasal symptoms is critical for life expectancy and quality.

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Stratifying infants with cystic fibrosis for disease severity using intestinal organoid swelling as a biomarker of CFTR function

European Respiratory Journal ◽

10.1183/13993003.02529-2017 ◽

2018 ◽

Vol 52 (3) ◽

pp. 1702529 ◽

Cited By ~ 18

Author(s):

Karin M. de Winter-de Groot ◽

Hettie M. Janssens ◽

Rick T. van Uum ◽

Johanna F. Dekkers ◽

Gitte Berkers ◽

...

Keyword(s):

Cystic Fibrosis ◽

Disease Severity ◽

Gastrointestinal Disease ◽

Pancreatic Insufficiency ◽

Chloride Concentration ◽

Individual Level ◽

Outcome Parameters ◽

Sweat Chloride ◽

Intestinal Organoids ◽

Residual Capacity

Forskolin-induced swelling (FIS) of intestinal organoids from individuals with cystic fibrosis (CF) measures function of the cystic fibrosis transmembrane conductance regulator (CFTR), the protein mutated in CF.We investigated whether FIS corresponds with clinical outcome parameters and biomarkers of CFTR function in 34 infants diagnosed with CF. Relationships with FIS were studied for indicators of pulmonary and gastrointestinal disease.Children with low FIS had higher levels of immunoreactive trypsinogen (p=0.030) and pancreatitis-associated protein (p=0.039), more often had pancreatic insufficiency (p<0.001), had more abnormalities on chest computed tomography (p=0.049), and had lower z-scores for maximal expiratory flow at functional residual capacity (p=0.033) when compared to children with high FIS values. FIS significantly correlated with sweat chloride concentration (SCC) and intestinal current measurement (ICM) (r= −0.82 and r=0.70, respectively; both p<0.001). Individual assessment of SCC, ICM and FIS suggested that FIS can help to classify individual disease severity.Thus, stratification by FIS identified subgroups that differed in pulmonary and gastrointestinal outcome parameters. FIS of intestinal organoids correlated well with established CFTR-dependent biomarkers such as SCC and ICM, and performed adequately at group and individual level in this proof-of-concept study.

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Increased Sweat Chloride Concentrations in Adult Patients with Pancreatic Insufficiency: Cystic Fibrosis Phenotype or Lack of Specificity of Sweat Test?

Scandinavian Journal of Gastroenterology ◽

10.1080/003655299750024814 ◽

1999 ◽

Vol 34 (12) ◽

pp. 1260-1260

Author(s):

Isabelle Durieu, S. Durupt, R. Nove

Keyword(s):

Cystic Fibrosis ◽

Pancreatic Insufficiency ◽

Adult Patients ◽

Sweat Test ◽

Sweat Chloride ◽

Chloride Concentrations

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Evaluation of a cystic fibrosis screening system incorporating a miniature sweat stimulator and disposable chloride sensor.

Clinical Chemistry ◽

10.1093/clinchem/32.5.850 ◽

1986 ◽

Vol 32 (5) ◽

pp. 850-853 ◽

Cited By ~ 26

Author(s):

W J Warwick ◽

N N Huang ◽

W W Waring ◽

A G Cherian ◽

I Brown ◽

...

Keyword(s):

Cystic Fibrosis ◽

Chloride Concentration ◽

Test System ◽

Sweat Test ◽

Sweat Chloride ◽

The Subject ◽

New System ◽

Chloride Concentrations ◽

Cystic Fibrosis Screening ◽

Center Study

Abstract A new sweat test (CF Indicator; Medtronic, Inc.) for cystic fibrosis (CF) features a compact, portable configuration of electrodes that dispense pilocarpine for iontophoresis. A disposable chloride sensor patch absorbs a specified volume of sweat, in which the chloride concentration is immediately determined as less than 40, 40-60, or greater than 60 mmol/L. We assessed the performance of the system in a five-center study, in relation to the clinical diagnosis and to the Gibson-Cooke sweat test (GCST) as a control test. With sweat chloride concentrations of less than or equal to 40 mmol/L defined as normal and greater than 40 mmol/L as indicating persons at risk for CF, the new system showed 91% specificity and 100% sensitivity for CF, as compared with 92.8% and 100%, respectively, for the GCST. When we used sweat chloride concentrations of less than or equal to 60 mmol/L as probably normal and greater than 60 mmol/L as probably indicative of CF, the new system showed a 99.1% specificity and 98.6% sensitivity, vs 97.8% specificity and 97.9% sensitivity for the GCST test. In both procedures, occasionally insufficient sweat was collected, and this appeared related to the age of the subject. We conclude that the new sweat test system is potentially useful in physicians' offices, in clinics, and similar settings.

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Cystic fibrosis with normal sweat chloride concentration: case report

Revista do Hospital das Clínicas ◽

10.1590/s0041-87812003000500005 ◽

2003 ◽

Vol 58 (5) ◽

pp. 260-262 ◽

Cited By ~ 1

Author(s):

Luiz Vicente Ferreira da Silva Filho ◽

Maria Helena de Carvalho Ferreira Bussamra ◽

Cleyde Miriam Aversa Nakaie ◽

Fabíola Villac Adde ◽

Joaquim Carlos Rodrigues ◽

...

Keyword(s):

Cystic Fibrosis ◽

Genetic Disease ◽

Gold Standard ◽

Diagnostic Tests ◽

Chloride Concentration ◽

Rapid Decrease ◽

Compound Heterozygous ◽

Sweat Chloride ◽

Sweat Testing ◽

Chloride Concentrations

Cystic fibrosis is a genetic disease usually diagnosed by abnormal sweat testing. We report a case of an 18-year-old female with bronchiectasis, chronic P. aeruginosa infection, and normal sweat chloride concentrations who experienced rapid decrease of lung function and clinical deterioration despite treatment. Given the high suspicion ofcystic fibrosis, broad genotyping testing was performed, showing a compound heterozygous with deltaF508 and 3849+10kb C->T mutations, therefore confirming cystic fibrosis diagnosis. Although the sweat chloride test remains the gold standard for the diagnosis of cystic fibrosis, alternative diagnostic tests such as genotyping and electrophysiologic measurements must be performed if there is suspicion of cystic fibrosis, despite normal or borderline sweat chloride levels.

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Forskolin-induced swelling of intestinal organoids predicts long-term cystic fibrosis disease progression

10.1101/2021.02.01.21250609 ◽

2021 ◽

Author(s):

D. Muilwijk ◽

E. de Poel ◽

P. van Mourik ◽

S.W.F. Suen ◽

A.M. Vonk ◽

...

Keyword(s):

Cystic Fibrosis ◽

Disease Progression ◽

Pancreatic Insufficiency ◽

Chloride Concentration ◽

Predictive Biomarker ◽

Sweat Chloride ◽

Intestinal Organoids ◽

Clinical Consequences ◽

Related Liver Disease

ABSTRACTPatient-derived organoids hold great potential as predictive biomarker for disease expression or therapeutic response. Here, we used intestinal organoids to estimate individual cystic fibrosis transmembrane conductance regulator (CFTR) function of people with cystic fibrosis, a monogenic life-shortening disease associated with more than 2000 CFTR mutations and highly variable disease progression. In vitro CFTR function in CF intestinal organoids of 176 individuals with diverse CFTR mutations was quantified by forskolin induced swelling and was strongly associated with longitudinal changes of lung function and development of pancreatic insufficiency, CF-related liver disease and diabetes. This association was not observed when the commonly used biomarker of CFTR function sweat chloride concentration was used. The data strongly exemplifies the value of an organoid-based biomarker in a clinical disease setting and supports the prognostic value of forskolin induced swelling of intestinal organoids, especially for people with CF who have rare CFTR genotypes with unclear clinical consequences.

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