Erratum to: Quality of sweat test (ST) based on the proportion of sweat sodium (Na) and sweat chloride (Cl) as diagnostic parameter of cystic fibrosis: are we on the right way?

Patients attending cystic fibrosis clinics had sweat sodium and chloride concentrations measured, were reassessed clinically and had DNA studies performed. Sweat test results were compared with a matched control population. In both populations sweat sodium increased with age up to 12 years, and did not change significantly thereafter. The age-related increase was significantly less in the cystic fibrosis group. Sweat chloride increased with age in normal, but not in cystic fibrosis children. After age 12 years there was no age-related change in the normal group, and a fall with age in the cystic fibrosis group. Sweat chloride provided the best discrimination between normal and cystic fibrosis populations and this was particularly important in older subjects. Combining sweat sodium and chloride results did not improve discrimination. Nine patients were identified with equivocal sweat chloride results. DNA studies showed six of these subjects were heterozygous for the ΔF508 mutation in the cystic fibrosis gene. Clinical assessment did not always resolve cases with borderline sweat chloride results.

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Elexacaftor-Tezacaftor-Ivacaftor: The First Triple-Combination Cystic Fibrosis Transmembrane Conductance Regulator Modulating Therapy

The Journal of Pediatric Pharmacology and Therapeutics ◽

10.5863/1551-6776-25.3.192 ◽

2020 ◽

Vol 25 (3) ◽

pp. 192-197 ◽

Cited By ~ 4

Author(s):

Kaden Ridley ◽

Michelle Condren

Keyword(s):

Cystic Fibrosis ◽

Clinical Trials ◽

Genetic Mutations ◽

Transmembrane Conductance Regulator ◽

Triple Combination ◽

Transmembrane Conductance ◽

Sweat Chloride ◽

Cystic Fibrosis Transmembrane

Elexacaftor-tezacaftor-ivacaftor is a newly approved triple-combination cystic fibrosis transmembrane conductance regulator (CFTR) modulating therapy that contains 2 correctors and a potentiator of the CFTR channel. Its labeled indication for use is for persons 12 years of age and older with at least 1 F508del mutation for the CFTR gene. This drug combination provides potential therapy to many patients who had previously been excluded from CFTR modulation therapy due to the nature of their genetic mutations. The efficacy demonstrated in clinical trials surpasses the currently available therapies related to lung function, quality of life, sweat chloride reduction, and reducing exacerbations. The most common adverse events seen in clinical trials included rash and headache, and laboratory monitoring is recommended to evaluate liver function. Continued evaluation of patient data is needed to confirm its long-term safety and efficacy. Elexacaftor-tezacaftor-ivacaftor is a monumental and encouraging therapy for cystic fibrosis; however, approximately 10% of the CF population are not candidates for this or any other CFTR modulation therapy.

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Cystic Fibrosis and Non-Cystic Fibrosis Bronchiectasis

10.2310/fm.1327 ◽

2014 ◽

Author(s):

Michael J Stephen

Keyword(s):

Cystic Fibrosis ◽

Differential Diagnosis ◽

Forced Expiratory Volume ◽

Sweat Test ◽

Inherited Disease ◽

Injury Rates ◽

Computed Tomographic ◽

Sweat Chloride ◽

Average Survival ◽

Pancreatic Exocrine Deficiency

Cystic fibrosis (CF) is an autosomal recessive disease characterized by an elevated sweat chloride level, diffuse bronchiectasis, and pancreatic exocrine deficiency. It is the most common lethal inherited disease in whites. Most patients present at birth or early childhood, although later diagnoses are not infrequent. Once CF was uniformly fatal at an early age, but advances in nutrition, airway clearance, and infection management have led to an average survival of 37 years. The newest aspect of care is the advent of protein modulators, which may increase life expectancy even further. This chapter discusses the epidemiology, genetics, pathophysiology and pathogenesis, diagnosis, differential diagnosis, and treatment of CF. The definition, epidemiology, etiology, pathogenesis, diagnosis, management, and prognosis of non-CF bronchiectasis are also covered. Figures illustrate normal and abnormal CF transmembrane conductance regulators, the vicious cycle hypothesis of lung injury, rates of respiratory germs by age, the diagnosis of CF, the therapeutics pipeline for CF, forced expiratory volume in 1 second lung function percent predicted versus body mass index, and the median predicted survival age of patients with CF. A chest x-ray and chest computed tomographic scan of CF are also provided. Tables outline the most common CF mutations in 2011, class mutations of CF, a mnemonic for acute exacerbations of CF, the diagnosis of CF-related diabetes in a stable patient, sweat test values, and the differential diagnosis of bronchiectasis.This chapter contains 9 highly rendered figures, 6 tables, 143 references, 1 teaching slide set, and 5 MCQs.

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Test for the Concentration of Electrolytes in Cystic Fibrosis of the Pancreas Utilizing Pilocarpine by Iontophoresis, by Lewis E. Gibson and Robert E. Cooke,Pediatrics; 1959;24:545–549

PEDIATRICS ◽

10.1542/peds.102.s1.230 ◽

1998 ◽

Vol 102 (Supplement_1) ◽

pp. 230-231

Author(s):

Victor Chernick

Keyword(s):

Cystic Fibrosis ◽

Filter Paper ◽

Direct Injection ◽

Heat Stroke ◽

Chloride Concentration ◽

Hot Water ◽

Sweat Test ◽

High Concentration ◽

Sweat Chloride ◽

Plastic Bag

Aim. To develop a method for stimulating sweating that is rapid, painless, and avoids the risk of heat stress. Background. Since the discovery that there is a high concentration of sodium and chloride in the sweat of patients with cystic fibrosis of the pancreas in 1953, the sweat test has been performed by placing the patient's body in a plastic bag with or without hot water bottles to stimulate sweating. This method is unsatisfactory because of complications such as hyperpyrexia and heat stroke. Direct injection of a cholinergic agent intradermally is painful and therefore not practical. Methods. A rheostat with a milliampere meter was constructed at a cost of ∼$7 that allowed the iontophoresis of pilocarpine into the skin using negative and positive (2-cm diameter) electrocardiography electrodes. The positive electrode was placed on the flexor surface of the arm over a filter paper soaked in 0.2 mL of 0.2% pilocarpine nitrate. Current (0.2 mA) was applied for 5 minutes and then sweat was collected onto a preweighed filter paper for 30 minutes. Sweat chloride was determined by a polarographic method. Sweat tests were performed on 25 patients with cystic fibrosis (CF), 17 asymptomatic relatives and 27 control patients. Patients with CF had sweat chloride concentration >80 mEq/L; relatives, 32.5 mEq/L (highest 57 mEq/L); and control subjects, 21.1 mEq/L (highest 60 mEq/L). Conclusions. The iontophoresis of pilocarpine into the skin is a rapid, painless, safe, and reliable method for stimulating sweating and facilitating the determination of sweat chloride concentration.

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Cystic Fibrosis and Non-Cystic Fibrosis Bronchiectasis

10.2310/im.1327 ◽

2014 ◽

Author(s):

Michael J Stephen

Keyword(s):

Cystic Fibrosis ◽

Differential Diagnosis ◽

Forced Expiratory Volume ◽

Sweat Test ◽

Inherited Disease ◽

Injury Rates ◽

Computed Tomographic ◽

Sweat Chloride ◽

Average Survival ◽

Pancreatic Exocrine Deficiency

Cystic fibrosis (CF) is an autosomal recessive disease characterized by an elevated sweat chloride level, diffuse bronchiectasis, and pancreatic exocrine deficiency. It is the most common lethal inherited disease in whites. Most patients present at birth or early childhood, although later diagnoses are not infrequent. Once CF was uniformly fatal at an early age, but advances in nutrition, airway clearance, and infection management have led to an average survival of 37 years. The newest aspect of care is the advent of protein modulators, which may increase life expectancy even further. This chapter discusses the epidemiology, genetics, pathophysiology and pathogenesis, diagnosis, differential diagnosis, and treatment of CF. The definition, epidemiology, etiology, pathogenesis, diagnosis, management, and prognosis of non-CF bronchiectasis are also covered. Figures illustrate normal and abnormal CF transmembrane conductance regulators, the vicious cycle hypothesis of lung injury, rates of respiratory germs by age, the diagnosis of CF, the therapeutics pipeline for CF, forced expiratory volume in 1 second lung function percent predicted versus body mass index, and the median predicted survival age of patients with CF. A chest x-ray and chest computed tomographic scan of CF are also provided. Tables outline the most common CF mutations in 2011, class mutations of CF, a mnemonic for acute exacerbations of CF, the diagnosis of CF-related diabetes in a stable patient, sweat test values, and the differential diagnosis of bronchiectasis.This chapter contains 9 highly rendered figures, 6 tables, 143 references, 1 teaching slide set, and 5 MCQs.

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Cystic fibrosis newborn screening: outcome of infants with normal sweat tests

Archives of Disease in Childhood ◽

10.1136/archdischild-2017-313290 ◽

2017 ◽

Vol 103 (8) ◽

pp. 753-756 ◽

Cited By ~ 6

Author(s):

Claire Edmondson ◽

Christopher Grime ◽

Ammani Prasad ◽

Jacqui Cowlard ◽

Chinedu E C Nwokoro ◽

...

Keyword(s):

Cystic Fibrosis ◽

Newborn Screening ◽

Genome Sequencing ◽

Dna Analysis ◽

Gene Mutations ◽

High Serum ◽

Sweat Test ◽

Sweat Chloride ◽

South East England

Newborn babies positively screened for cystic fibrosis (CF) (high serum immunoreactive trypsin (IRT) with DNA analysis) are referred for a diagnostic sweat test, which may be normal (sweat chloride <30 mmol/L). Unless two gene mutations are identified during Newborn screening (NBS), the babies are discharged from follow-up. We wished to check that none had subsequently developed symptoms suggestive of CF. We retrospectively reviewed patient notes and contacted general practitioners of all babies with a negative sweat test, conducted in one of the four paediatric specialist CF centres in London, over the first 6 years of screening in South East England.Of 511 babies referred, 95 (19%) had a normal sweat test. Five (5%) had CF diagnosed genetically, two of them on extended genome sequencing after clinical suspicion. Eleven (12%) were designated as CF screen positive inconclusive diagnosis (CFSPID); one of the five CF children was originally designated as CFSPID. Seventy-nine (83%) were assumed to be false-positive cases and discharged; follow-up data were available for 51/79 (65%); 32/51 (63%) had no health issues, 19/51 (37%) had other significant non-CF pathology.These results are reassuring in that within the limitations of those lost to follow-up, CF symptoms have not emerged in the discharged children. The high non-CF morbidity in these children may relate to known causes of high IRT at birth. Clinicians need to be aware that a child can have CF despite a normal sweat test following NBS, and if symptoms suggest the diagnosis, further testing, including extended genome sequencing, is required.

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Quality of sweat test performance in the diagnosis of cystic fibrosis.

Clinical Chemistry ◽

10.1093/clinchem/25.1.158 ◽

1979 ◽

Vol 25 (1) ◽

pp. 158-161 ◽

Cited By ~ 15

Author(s):

H Shwachman ◽

A Mohmoodian

Keyword(s):

Cystic Fibrosis ◽

Test Performance ◽

Clinical Laboratory ◽

Current Situation ◽

Sweat Test ◽

Small Community ◽

Community Hospitals ◽

Cystic Fibrosis Foundation

Abstract The sweat test, correctly performed, appears to be reliable, but results were found to be unreliable about half the time in 84 small community hospitals assessed. The reasons are inexperienced and untrained technicians, the infrequency of test performance, the use of unstandardized equipment, and the lack of appropriate standards. It behooves all clinical laboratory directors to re-examine and standardize their procedures and use the recommendations of the Cystic Fibrosis Foundation. Physicians should be made aware of the current situation and send their patients only to laboratories that perform the test reliably.

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Cystic Fibrosis Diagnosed Using Indigenously Wrapped Sweating Technique: First Large-Scale Study Reporting Socio-Demographic, Clinical, and Laboratory Features among the Children in Bangladesh A Lower Middle Income Country

Global Pediatric Health ◽

10.1177/2333794x20967585 ◽

2020 ◽

Vol 7 ◽

pp. 2333794X2096758

Author(s):

ARM Luthful Kabir ◽

Sudipta Roy ◽

Rahat Bin Habib ◽

Kazi Selim Anwar ◽

Md. Abid Hossain Mollah ◽

...

Keyword(s):

Cystic Fibrosis ◽

Large Scale ◽

Tertiary Care ◽

Disease Onset ◽

Severe Malnutrition ◽

Sweat Test ◽

Cross Sectional ◽

Middle Income ◽

Sweat Chloride ◽

Radio Imaging

Due to lack of robust data on childhood cystic fibrosis (CF) in Bangladesh we sought to evaluate their clinico-epidemiology. A cross-sectional observation was conducted adopting CF-foundation consensus-panel-diagnostic criteria in 3 tertiary-care-hospitals in Bangladesh from 2000 to 2017. Clinically suspected 95 CF-cases were subjected to sweat-chloride testing using locally-developed a fast, cheap and effective indigenously body-wrapped sweating technique measured by US-Easy Lyte-automated microprocessor-controlled analyzer marking ≥60 mmol/L as positive. Mean-age of CF-cases at disease-onset was 16.9 ± 26.6 months that significantly differed with age-at-diagnosis ( P < .02). Pulmonary syndromes included chronic wet cough in 100%, respiratory distress in 90.5%, digital-clubbing in 78%, mucopurulent-sputum in 74%-cases, and crepitation in 82%. Radio-imaging revealed bronchiectasis in 60%, hyperinflation/peribronchial-thickening in 22% and, pan-sinusitis in 89%-cases. While 37% had history-of malabsorption, high-fecal-fat revealed in 53%-cases. Malnutrition prevailed as severe-underweight in 87%-cases and all CF-cases (100%) had high sweat-chloride (mean = 118 ± 53.34 mmol/L). Thus, children with pulmonary features coupled with severe malnutrition and associated radio-imaging bronchiectasis should be screened for CF with a fast, cheap and effective sweat test in resource poor settings.

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Chronic Sinusitis and a Negative Sweat Test in a Patient with Cystic Fibrosis

American Journal of Rhinology ◽

10.2500/105065895781873773 ◽

1995 ◽

Vol 9 (4) ◽

pp. 225-228 ◽

Cited By ~ 4

Author(s):

Todd T Kingdom ◽

Kelvin C. Lee ◽

Gerd J. Cropp

Keyword(s):

Cystic Fibrosis ◽

Unusual Case ◽

Dna Analysis ◽

Chronic Sinusitis ◽

Carrier State ◽

Sweat Test ◽

Genetic Mutations ◽

Dna Mutation ◽

Sweat Chloride ◽

Sweat Testing

The diagnosis of cystic fibrosis (CF) is based on sweat chloride and DNA mutation testing. A subset of CF patients may have normal sweat chloride levels, thus requiring DNA analysis for confirmation of the diagnosis. These patients may escape diagnosis if sweat testing is the only modality used for screening. Recently, the putative structural gene for CF was localized to chromosome 7. The delta-F508 mutation accounts for approximately 70% of the CF chromosomes identified in North American Caucasians. Over 400 identified mutations constitute the remainder. It is now possible to screen patients for the presence of many of these genetic mutations, thus establishing the diagnosis of CF or defining a carrier state. We report an unusual case of a 17-year-old male with chronic sinusitis, mild pulmonary disease, and pancreatic sufficiency with nondiagnostic sweat chloride levels diagnosed to have CF after DNA analysis. This technique may thus serve as an important tool that pediatricians and otolaryngologists can use to diagnose children suspected of having CF.

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