Search

BACKGROUND Diagnostic sweat testing is required for infants with positive newborn-screening (NBS) tests for cystic fibrosis (CF). Infants have "quantity not sufficient" (QNS) sweat volumes more often than older children. A comprehensive study of QNS sweat volumes in infants has not previously been reported. METHODS We surveyed US CF Centers to obtain QNS rates in all infants who had sweat testing at under 14 days and under 3 months of age. We then calculated QNS rates reported to the Cystic Fibrosis Foundation Patient Registry (CFFPR) 2010-2018 in 10-day increments from 1 to 60 days of life. We compared QNS sweat test rates in preterm (

Objective We evaluated the prevalence, Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene profile, clinical data, management and outcome for infants with a CFTR-related metabolic syndrome/CF Screen Positive, Inconclusive Diagnosis (CRMS/CFSPID) designation from six Italian centres. Methods All newborn bloodspot screening (NBS) positive infants born from January 2011 to August 2018 with a CF diagnosis or a CRMS/CFSPID designation were enrolled. Data on sweat testing, genetics, clinical course and management were collected. Results We enrolled 257 CF patientsand 336 infants with a CRMS/CFSPID designation (CF: CRMS/CFSPID ratio of 1:1.30).Blood immuno-reactive trypsinogen (IRT) was significantly lower in CRMS/CFSPID infants and the F508del variant accounted for only 20% of alleles. Children with CRMS/CFSPID showed a milder clinical course, pancreatic sufficiency compared to CF infants. Varied practice across centres was identified regarding sweat testing, chest radiograph (8-100%) and salt supplementation (11-90%). Eighteen (5.3%) CRMS/CFSPID infants converted or were reclassified to diagnosis of CF. Four infants (1.3%) developed a clinical feature consistent with a CFTR-related disorder (1.2%). Twenty-seven were re-classified as healthy carriers (8.0%) and 16 as healthy infants (4.8%). Conclusions We have identified considerable variability in the evaluation and management of infants with an inconclusive diagnosis following NBS across six Italian centres. CRMS/CFSPID is more regularly seen in this population compared to countries with higher prevalence of F508del.Conversion to a CF diagnosis was recorded in 18 (5.3%) of CRMS/CFSPID infants and in 16 was as a result of increasing sweat chloride concentration.

Cystic fibrosis (CF) is the most common fatal genetic disease of the Caucasian population. Sweat testing is the principal diagnostic test for CF, and it is used for the evaluation of infants with positive CF newborn screening (NBS) and in patients with clinical findings suggesting CF. This article describes the classical sweat test method in detail and also provides an overwiew of recent advances.

The sweat test is the gold standard for the diagnosis of cystic fibrosis (CF). The test utilizes iontophoresis to administer pilocarpine to the skin to induce sweating for measurement of chloride concentration in sweat. However, the sweat test procedure needs to be conducted in an accredited lab with dedicated instrumentation, and it can lead to inadequate sweat samples being collected in newborn babies and young children due to variable sweat production with pilocarpine iontophoresis. We tested the feasibility of using microneedle (MN) patches as an alternative to iontophoresis to administer pilocarpine to induce sweating. Pilocarpine‐loaded MN patches were developed. Both MN patches and iontophoresis were applied on horses to induce sweating. The sweat was collected to compare the sweat volume and chloride concentration. The patches contained an array of 100 MNs measuring 600 μm long that were made of water‐soluble materials encapsulating pilocarpine nitrate. When manually pressed to the skin, the MN patches delivered >0.5 mg/cm2 pilocarpine, which was double that administered by iontophoresis. When administered to horses, MN patches generated the same volume of sweat when normalized to drug dose and more sweat when normalized to skin area compared to iontophoresis using a commercial device. Moreover, both MN patches and iontophoresis generated sweat with comparable chloride concentration. These results suggest that administration of pilocarpine by MN patches may provide a simpler and more‐accessible alternative to iontophoresis for performing a sweat test for the diagnosis of CF.

Background The sweat test has been the "gold standard" diagnostic test for cystic fibrosis for more than 40 years. We hypothesized that there would be a change in the pattern of sweat testing in Ireland since the introduction of cystic fibrosis newborn screening in 2011, when practices were last reviewed. This is a follow up survey looking at sweat testing numbers and practices. Methods A national survey compiled data on sweat collection, conductivity and sweat chloride testing in all hospitals previously identified as performing sweat tests. Results All 13 centres in Ireland performing sweat testing in 2018 responded to the survey (100% return rate). Our results indicate that 1007 sweat tests were performed in 2018 compared to 2555 in 2011, equating to a 61% reduction. Seven out of 13 centres are performing less than 50 sweat tests per year. Nine out of 13 centres (69%) had a sweat test failure rate greater than the recommended allowable rate of ≤ 10%. We detected a trend of sweat testing in patients with an existing diagnosis of CF who had commenced cystic fibrosis transmembrane conductance regulator (CFTR) modulators. Conclusions There has been a significant reduction in the number of sweat tests performed in Ireland since the introduction of newborn screening for CF. There remains a lack of standardisation in many aspects of the service ranging from sample collection to reporting of results. We have identified a new trend of sweat testing in the cystic fibrosis transmembrane conductance regulator modulator era.

To the Editor, Sweat conductivity (SC) is a well-established screening test for Cystic Fibrosis (CF).1,2 It is semi-automated, fast, doesn’t require skilled technicians or specialized personnel, and needs a small amount of sweat. Moreover, one response to the demanding and labour-intensive requirement for robust quality sweat testing has been the testing of sweat samples by electrical conductivity.3As every laboratory method, SC is subject to error. Then, it should be assessed and tested to ensure that it produces results which make it reliable and suitable for the intended purpose, i.e., its role as screening method. Repeatability is one of these vital requirements.The International Organization for Standardization defines repeatability as the nearest agreement between independent test results performed in identical conditions in a short period of time, i.e., same test items and steps, same equipment, same technician, same laboratory.4Although SC is adopted worldwide there is no study evaluating specifically that requirement in any age group, including newborns and young infants. Therefore, the present study aimed to assess the correlation between two concomitant SC assays.We prospectively and consecutively recruited clinically stable infants younger than 3 months. They had two previous positive immunoreactive trypsin results (IRT), and then, two concomitant SC assays, performed by the same technician in the same facility. IRT and SC were carried out in the single accredited Reference Center for Newborn Screening and Genetic Diagnosis, located in the city of Belo Horizonte, State of Minas Gerais, Brazil.Sweat samples were obtaining from each forearm through the Wescor Macroduct system and then analyzed through a SC analyzer (Sweat-Chek analyzer, model 3120, Wescor Inc., USA). All steps were performed according to the manufacturer’s recommendations, and described elsewhere.1,2Apart from descriptive statistics, to assess the relationship between the two SC assays we used Spearman’s rank correlation coefficient. SPSS software, version 18.0 (SPSS Inc., Chicago, Illinois) was used for statistical analyses. The research protocol was approved by the Research Ethics Committee of Federal University of Minas Gerais, under number CAAE 21958014.1.0000.5149.A total of 322 young infants were recruited. Most of them (89%) were from smaller towns within the same State, and 11% lived in Belo Horizonte, the State capital. There was a slightly predominance of males (54%), and the majority (59%) were younger than 60 days, being 15.2% of them aged up to 30 days of life. Mean and median age was 52 and 46 days (range, 19-89 days), respectively.A sufficient amount of sweat was obtained from all participants. Means and medians for the first and second SC values were 37.0 mmol/L, and 34.3 mmol/L (range, 29.0-39.6 mmol/L), and 38.0 mmol/L and 35.3 mmol/L (range 30.0-40.7), respectively.Figure 1 displays the Spearman’s correlation scatter plot for the two SC results.

Background: Benefits of early Cystic Fibrosis (CF) detection using newborn screening (NBS) lead to widespread use in NBS programs. Since 2002, a two-stage immunoreactive trypsinogen (IRT/IRT) screening strategy has been used as CFNBS method in all public maternities in the City of Buenos Aires, Argentina. However, novel screening strategies may be more efficient. The aim of the study is to prospectively compare two CFNBS strategies, IRT/IRT and IRT/PAP (pancreatitis-associated protein). Methods: A two-year prospective study was performed. IRT was measured in dried blood samples collected 48–72 hours after birth. When IRT value was abnormal, PAP was determined, and a second visit was scheduled to obtain another sample for IRT before 25 days of life. Newborns with a positive CFNBS were referred for confirmatory sweat test. Results: There were 69,827 births in the City of Buenos Aires during the period studied; 918 (1.31%) had an abnormal IRT. A total of 207 children (22.5%) failed to return for the second IRT, but only two PAP (0.2%) were not performed. IRT/IRT was more likely to lead to a referral for sweat testing than IRT/PAP (OR 2.3 [95% CI 1.8;2.9], p

Sweat is used to examine fluid and electrolyte loss, ion correlations, and glucose dynamics in healthy and diabetic cohorts., Recent technological advancements in wearable sensors have made it easier to detect sweat components, but our limited understanding of sweat restricts its application. A critical bottleneck for temporal and regional sweat analysis is achieving uniform, high-throughput fabrication of sweat sensor components, including microfluidic chip and sensing electrodes. To overcome this challenge, we introduce microfluidic sensing patches mass fabricated via roll-to-roll (R2R) processes. The patch allows sweat capture within a spiral microfluidic for real-time measurement of sweat parameters including [Na+], [K+], [glucose], and sweat rate in exercise and chemically induced sweat. The patch is demonstrated for investigating regional sweat composition, predicting whole-body fluid/electrolyte loss during exercise, uncovering relationships between sweat metrics, and tracking glucose dynamics to explore sweat-to-blood correlations in healthy and diabetic individuals. By enabling a comprehensive sweat analysis, the presented device is a crucial tool for advancing sweat testing beyond the research stage for point-of-care medical and athletic applications.

OBJECTIVES In the national newborn screening programme for CF in Switzerland, we compared the performance of two sweat test methods, by investigating the feasibility and diagnostic performance of the Macroduct collection method (with chloride mesurement) and Nanoduct test (measuring conductivity) for diagnosing CF. STUDY-DESIGN We included all newborns with a positive screening result between 2011 and 2015 who were referred to a CF-centre for sweat testing. In the CF-centre, a Macroduct and Nanoduct sweat test were performed simultaneously. If sweat test results were positive or borderline, a DNA analysis was performed. Final diagnosis was based on genetic mutations. RESULTS Over 5 years, 445 children were screened positive and in 413 (114 with CF) at least one sweat test was performed (median age at first test, 22 days); both tests were performed in 371 children. A sweat test result was more often available with the Nanoduct compared to the Macroduct (79 vs 60%, P

Cystic fibrosis (CF) is a genetic disease caused by a bi-allelic mutation of the cystic fibrosis transmembrane conductance regulator (CFTR) gene. When the diagnosis cannot be confirmed by a positive sweat test or/and the identification of two CF-causing variants, international guidelines recommend the use of CFTR functional assays. These tests assess whether CFTR activity is normal or diminished/absent through measurement of CFTR-mediated chloride secretion/absorption., CFTR functional assays are not only useful for diagnostic purposes but can also serve as a surrogate outcome for clinical trials of CFTR modulators, which are emerging therapeutic agents designed to correct the malfunctioning protein. In the near future they could also be used as precision-medicine techniques, to help guidance and optimisation of treatment., Until now, sweat testing has been the only CFTR functional assay available in Switzerland. Since 2020, the Centre Hospitalier Universitaire Vaudois (CHUV) at Lausanne and the Lucerne Children's Hospital perform nasal potential difference measurement. Moreover, The Ecole Poly-technique Federale de Lausanne (EPFL) established a reliable procedure to generate adult intestinal organoids, i.e., stem cell-derived in-vitro grown mini tissues, extracted from rectal biopsies, which can be used to assess CFTR function in vitro., This narrative review describes the most popular CFTR functional assays, as well as their indications, limitations and availability in Switzerland.

Background: The objective of the study was to assess the diagnostic efficacy of the coulometric endpoint method and compare it with classic Gibson&Cooke and chloridometer methods. Methods: This study is a prospective clinical study comparing two conventional sweat testing methods with the coulometric endpoint method in previously diagnosed cystic fibrosis (CF) patients and a non-CF control group. All individuals underwent two simultaneous sweat collections. One sample of sweat, collected by the CF Delta collector coil system, was analyzed by two methods: the titrimetric Cl- measurement (Sherwood (R) Chloridometer 926S, Sherwood Scientific Ltd., Cambridge, UK) and the coulometric endpoint method (CF Delta Collection System (R), UTSAT/Turkey); the second sample was collected from the other forearm by the Gibson&Cooke method and the collected sweat was analyzed by manual titration in accordance with the Schales&Schales method. Within-run and between-run imprecisions were evaluated via Cl- concentrations of 40, 70, and 130 mmol/L samples. Results: One hundred and seventy (60 CF and 110 controls) subjects were included in the study. All three sweat test methods discriminated CF subjects from the healthy individuals. The mean difference between the coulometric endpoint and titrimetric Cl - measurement methods was -1.5 mmol/L, (95% confidence limits of agreement, ranging from -8.9 to 15.9 mmol/L); the mean difference between manual titration vs. coulometric endpoint methods was 12.8 mmol/L, (95% confidence limits of agreement ranging from -9.7 to 45.3 mmol/L) and the mean difference between the manual titration and titrimetric Cl - measurement methods was 11.3 mmol/L, (95% confidence limits of agreement ranging from -7.8 to 40.5 mmol/L) based on a Bland-Altman analysis. In the Receiver operating characteristic (ROC) analysis, made on the basis that Cl- concentration values

Evidence based guidelines exist for sweat testing, which remains a key component of a diagnosis of cystic fibrosis (CF), especially following newborn bloodspot screening (NBS). There are emerging challenges with respect to maintaining a valid sweat test service, notably a smaller number of sweat tests ordered in regions with established NBS programmes where Pediatricians refer less children for sweat testing, younger patients and equipment becoming obsolete. The ECFS Diagnostic Network Working Group has undertaken a comprehensive survey to better define sweat test practice across Europe. The survey was completed by 136 European respondents representing a CF center or laboratory providing a sweat test service (65% from regions with NBS for CF). There was considerable variance in practice, often not consistent with guidelines. In particular collection of sweat from two sites was rarely reported in European centres in contrast to US guidelines. There was a range of different references quoted for cut-off for both a positive and intermediate test. Most responses suggest cost is becoming an increasing issue and is not sufficiently reimbursed. This work will inform best practice guidelines and resources to sustain and improve sweat testing in Europe.

To assess whether reporting "possible cystic fibrosis (CF)" newborn screening (NBS) results via fax plus simultaneous telephone contact with primary care providers (PCPs) versus fax alone influenced 3 outcomes: undergoing a sweat chloride test, age at sweat chloride testing, and undergoing sweat testing before age 8 weeks.This was a retrospective cohort comparison of infants born in Wisconsin whose PCP received a telephone intervention (n = 301) versus recent historical controls whose PCP did not (n = 355). Intervention data were collected during a longitudinal research and quality improvement effort; deidentified comparison data were constructed from auxiliary NBS tracking information. Parametric and nonparametric statistical analyses were performed for group differences.Most infants (92%) with "possible CF" NBS results whose PCP lacked telephone intervention ultimately underwent sweat testing, underlining efficacy for fax-only reporting. Telephone intervention was significantly associated with improvements in the infants undergoing sweat testing at age ≤6 weeks and8 weeks and a slight, statistically nonsignificant 3.5-day reduction in the infants' age at sweat testing. The effect of telephone intervention was greater for PCPs whose patients underwent sweat testing at community-affiliated medical centers versus those whose patients did so at academic medical centers (P = .008).Reporting "possible CF" NBS results via fax plus simultaneous telephone follow-up with PCPs increases the rate of sweat chloride testing before 8 weeks of age, when affected infants are more likely to receive full benefits of early diagnosis and treatment.

Introduction: Sweat test has a diagnostic role in evaluation of cystic fibrosis. Its performance includes sweat stimulation, collection and analysis. All listed may be sources of inconsistencies in everyday practice. The aim of this study was an evaluation of external quality assessment (EQA) of sweat chloride measurement including sweat test performance in medical biochemistry laboratories in Croatia. Materials and methods: EQA for sweat chloride measurement was provided by Croatian Centre for Quality Assessment in Laboratory Medicine (CROQALM) in five consecutive exercises to medical biochemistry laboratories (MBL) that offered sweat testing. A questionnaire regarding all phases of testing was mailed to involved MBL (N = 10). Survey results were compared to current guidelines for sweat test performance. Results: Reported results of EQA in 2015 exercises showed coefficients of variation (CV) from 28.9%, 29.0% to 35.3%, respectively. An introduction of uniform sweat chloride measurement protocol resulted in CV of 15.5% and 14.7% reported in following two exercises in 2016. All MBL included in this study replied to the questionnaire. Results reported by MBL indicated: lack of patient information policy (7/10), use of unacceptable electrodes (6/9), misuse of minimum of acceptable sweat weight (6/9), lack of internal quality assessment (5/9) and recommended reference ranges (5/9 and 4/9). Agreements to guidelines were found in approach to unsuitable patients (9/10) and sweat collection (8/9). Conclusion: Presented results indicate major weak points of current practice in sweat test performance in Croatian MBL and stress the need for its standardization on a national level.

Objectives Rapid and reliable confirmatory sweat testing following a positive newborn screen (NBS) for cystic fibrosis (CF) is preferred to allow for early diagnosis and to decrease parental anxiety. The Cystic Fibrosis Foundation (CFF) recently recommended a quantity not sufficient (QNS) rate of ≤ 10% in infants < 3 months of age referred for quantitative sweat chloride analysis. Two CFF-approved methods are available by which to quantitatively measure chloride concentration in sweat. Our objective was to compare the performance of the Macroduct® sweat collection system (MSCS) with the Gibson and Cooke technique (GCT) in the acquisition of samples for the determination of sweat chloride concentration in infants with a positive Minnesota State NBS for cystic fibrosis.

Newborn screening is a public health policy program involving the centralized testing laboratory, infant and their family, primary care provider, and subspecialist for confirmatory testing and follow-up of abnormal results. Cystic fibrosis (CF) newborn screening has now been enacted in all 50 states and the District of Columbia and throughout many countries in the world. Although CF neonatal screening will identify the vast majority of infants with CF, there are many factors in the newborn screening system that can lead to a missed diagnosis of CF. To inform clinicians, this article summarizes the CF newborn screening system and highlights 14 factors that can account for a missed diagnosis of CF. Care providers should maintain a high suspicion for CF if there are compatible symptoms, regardless of the results of the newborn screening test. These factors in newborn screening programs leading to a missed diagnosis of CF present opportunities for quality improvement in specimen collection, laboratory analysis of immunoreactive tryspinogen (IRT) and CF mutation testing, communication, and sweat testing.

Screening newborns for cystic fibrosis (CF) is considered to be an ethical undertaking in regions with a significant incidence of the condition. Current screening protocols result in recognition of infants with an equivocal diagnosis. A survey of European practice suggested inconsistencies in the evaluation and management of these infants.We have undertaken a consensus process using a modified Delphi method. This has enabled input of CF specialists from a wide geographical area to a rigorous process that has provided a clear pathway to a consensus statement. A core group produced 21 statements, which were modified over a series of three rounds (including a meeting arranged at the European CF Conference). A final document of 19 statements was produced, all of which achieved a satisfactory level of consensus. The statements cover four themes; sweat testing, further assessments and investigations, review arrangements and database.This consensus document will provide guidance to CF specialists with established screening programmes and those who are in the process of implementing newborn screening in their region.

Sudomotor dysfunction is common in many subtypes of neuropathy but is one of the earliest detectable neurophysiologic abnormalities in distal small fiber neuropathy. Clinical assessments of sudomotor function include thermoregulatory sweat testing (TST), quantitative sudomotor axon reflex testing (QSART), silicone impressions, the sympathetic skin response (SSR), the acetylcholine sweat-spot test and quantitative direct and indirect axon reflex testing (QDIRT). These testing techniques, when used in combination, can detect and localize pre- and postganglionic lesions, can provide early diagnosis of sudomotor dysfunction and can monitor disease progression or disease recovery. In this article, we describe many of the common clinical tests available for evaluation of sudomotor function with focus on the testing methodology and limitations while providing concrete examples of test results.

Background: Obtaining an adequate volume of sweat to measure chloride is a challenge for many cystic fibrosis centers. The standard for patients older than 3 months is a less than 5% quantity not sufficient (QNS) rate; the suggested goal for patients aged 3 months or younger is a less than 10% QNS rate. St. Alexius Medical Center (SAMC) began performing sweat chloride testing in 2008. After an initial period of testing, a quality improvement (QI) program for sweat testing was instituted to improve QNS rates. Methods: Quantity not sufficient rates were evaluated before and after implementation for patients aged 3 months or younger and those older than 3 months. The QNS rates for each technician performing the tests were also evaluated. Results: Improvement was observed in QNS rates after implementation of the QI initiative regardless of patient age. After QI was implemented, QNS rates improved for most technicians. Conclusion: This study demonstrates how a QI improvement initiative can significantly improve QNS rates in sweat testing of infants, especially under 3 months of age. * CF : cystic fibrosis QNS : quantity not sufficient CFCC : Cystic Fibrosis Center of Chicago SAMC : St. Alexius Medical Center QI : quality improvement CAP : College of American Pathologists CLSI : Clinical and Laboratory Standards Institute

Background According to consensus documents, sweat testing remains the standard for diagnosing cystic fibrosis. We studied a novel method of sweat analysis on two chemistry platforms: Dimension Vista (Siemens Healthcare Diagnostics) and Aeroset (Abbott). Methods Sweat collected from healthy individuals and aqueous samples in the critical range for sweat analysis were measured using the Orion 290 plus (Thermo Electron Corporation), Chiron 925 chloride analyser (Sherwood Scientific Ltd), flame photometry, sweat-chek analyser and indirect ion-selective electrodes (ISE) of Vista and Aeroset. For measurement on ISE, an addition protocol was designed. Results Within-run and between-run variation coefficients of Aeroset and Vista remained 2 0.990) and y = 0.97x + 1.10 ( r2 0.930) and between sweat-chek (conductivity) and sodium concentrations analysed on Vista or Aeroset was, respectively, y = 1.08x - 4.0 ( r2 0.967) and y = 1.13x - 1.00 ( r2 0.939). When classified according to medical decision rules (30 mmol/L and 60 mmol/L chloride, combined with sodium concentration), the same classification was found with the ISE-module and conventional methods for all samples. Conclusion We describe a simple procedure for sweat analysis using the ISE-module of two different chemistry platforms. This procedure meets the requirements as described in UK guidelines.

Objective.—To describe the results of the College of American Pathologists survey questions assessing the current practice of sweat testing in North America and to identify areas in which improvement is needed. Data Source.—Results of the supplemental questions to the SW-B 2000 survey. Study Selection.—Supplemental questions were designed to assess variation in sweat collection, analysis, and interpretation. Data Extraction.—Extractions of the data were made based on the relevance of the data to the objectives of the review. Data Synthesis.—The majority of laboratories surveyed performed sweat testing according to the procedures described in the National Committee for Clinical Laboratory Standards' document. The study revealed that a number of laboratories have adopted poor practice standards and are potentially compromising patient care. Areas of concern include the number of laboratories performing few sweat tests per year, the persistence of unreliable methodology, misunderstanding of collection parameters, lack of patient education, and erroneous result reporting. Conclusions.—The study identified areas of concern toward which educational efforts can be directed. Such efforts include the development of a College of American Pathologists accreditation checklist for sweat testing and targeted responses in the sweat analysis participant summary report.

The proportion of insufficient sweat tests after positive newborn screening for cystic fibrosis was determined. Infants ≤ 3 months old had a mean (± standard deviation) rate of 7.2% (± 7.6) (range, 0% to 40%). Collection methods did not affect the rates. The high and variable rates indicate a need for quality improvement.

Purpose: In children there is frequently a reason to exclude cystic fibrosis. Sweat testing is used for this. Because sweat testing has some disadvantages we investigated whether analyzing DNA for the local most common CFTR mutations, harvested from buccal cells, is reliable as a method to exclude cystic fibrosis. Methods: In patients in whom a sweat test had been ordered during the period January 1, 2002 to December 31, 2004, we harvested buccal cell DNA for analysis. When blood was available, DNA from leukocytes was also analyzed. Results: A total of 73 sweat tests were ordered during the two-year study period, mostly because of recurrent pulmonary infections (36; 49%), failure to thrive (20; 27%) and chronic diarrhea (10, 14%). In 70, children the results of the sweat test were normal, in three patients the results were borderline. Sixty buccal smears were analyzed and no patient was homozygous for cystic fibrosis, two were heterozygous for cystic fibrosis. In none of the children the diagnosis of cystic fibrosis was established. Conclusion: Analyzing DNA in cells, harvested from the buccal cells, is a reliable alternative to exclude cystic fibrosis. It is safe, simple, and child-friendly.

BackgroundConventional methods of sweat testing are time consuming and have many steps that can and do lead to errors. This study compares conventional sweat testing to a new quantitative method, the CF Quantum® (CFQT) sweat test. This study tests the diagnostic accuracy and analytic validity of the CFQT.MethodsPreviously diagnosed CF patients and patients who required a sweat test for clinical indications were invited to have the CFQT test performed. Both conventional sweat testing and the CFQT were performed bilaterally on the same day. Pairs of data from each test are plotted as a correlation graph and Bland–Altman plot. Sensitivity and specificity were calculated as well as the means and coefficient of variation by test and by extremity. After completing the study, subjects or their parents were asked for their preference of the CFQT and conventional sweat testing.ResultsThe correlation coefficient between the CFQT and conventional sweat testing was 0.98 (95% confidence interval: 0.97–0.99). The sensitivity and specificity of the CFQT in diagnosing CF was 100% (95% confidence interval: 94–100%) and 96% (95% confidence interval: 89–99%), respectively. In one center in this three center multicenter study, there were higher sweat chloride values in patients with CF and also more tests that were invalid due to discrepant values between the two extremities. The percentage of invalid tests was higher in the CFQT method (16.5%) compared to conventional sweat testing (3.8%) (p

Recent advances in sensitive analytical techniques have enabled the analysis of drugs in unconventional biological materials such as sweat. In a study conducted during a heroin maintenance program, 14 subjects had sweat patches applied, then received intravenously two or three doses of heroin hydrochloride ranging from 80 to 1000 mg/day. The sweat patch was applied 10 min before the first dosage and removed ∼24 h later, minutes before the next dosage. Absorbent pads were stored at −20 °C in plastic tubes until analysis. The target drugs were extracted in 5 mL of acetonitrile in the presence of 100 ng each of heroin-d9, 6-acetylmorphine-d3, and morphine-d3. After agitation for 30 min, the acetonitrile solution was divided into two portions: 2 mL for heroin testing and the remainder for testing for the other compounds. After evaporation, the residue of the first portion was reconstituted in 35 μL of acetonitrile; the second was derivatized by silylation with 40 μL of N,O-bis(trimethylsilyl)trifluoroacetamide containing 10 mL/L trimethylchlorosilane. Drugs were analyzed by GC-MS in electron impact mode. Concentrations (nanograms per patch) ranged from 2.1 to 96.3 for heroin, 0 to 24.6 for 6-acetylmorphine, and 0 to 11.2 morphine. Except in one case, heroin was the major drug present in sweat, followed by 6-acetylmorphine and morphine. We observed no correlation between the doses of heroin administered and the concentrations of heroin measured in sweat.

The ability to detect cocaine use/exposure by either hair or sweat analysis was compared in a random population of adults at a major US university. Sweat was obtained by wiping the forehead with a cosmetic puff containing isopropanol. Using cut-off levels for sweat of 2.2 ng cocaine/wipe and of hair of 0.05 ng cocaine/mg hair, sweat detected two times more cocaine use/exposure than did hair. Sweat analysis detected a use rate of 12% compared to a 6% rate by hair analysis, both greater than the 2% that would be expected in this population. The high rate of detection was surprising and suggests that use of, if not exposure to, cocaine is underreported. Controlled experiments showed that cocaine could remain on the skin for about 3 days after external exposure. At the current state of knowledge, sweat appears to measure both use and exposure. Nevertheless, sweat testing could be used in several scenarios (such as roadside driving while intoxicated) where the case of collection and testing of sweat could outweigh the passive exposure considerations. Cocaine concentrations in skin swabs > 15 ng/swab would appear to indicate recent use/exposure.

Objectives: Sweat testing following pilocarpin iontophoresis is the preferred method to check for cystic fibrosis. Correct measurement and interpretation of results are essential components of cystic fibrosis testing. Methods: All sweat tests performed in the years 2005 to 2010 in our cystic fibrosis centre were analyzed retrospectively. Pilocarpin iontophoresis was in accordance to established international guidelines. All samples were analyzed using chloridometry (Chloridmeter, Kreienbaum, Germany) and conductivity measurement (SweatCheck, WesCor Inc., USA). Results were interpreted as negative, indeterminate or positive according to international guidelines (chloridometry) or manufacturer’s recommendation (conductivity measurement). Results: 1246 sweat tests were performed on 1077 patients. 68 patients were 18 years or older. Median age at testing was 1.58 years (min. 14 days, max. 77 years). Comparison of conductivity measurement and chloridometry reveals a constantly higher NaCl equivalent in conductivity measurement (mean value of difference 24.1±10.7mmol/l). In 91.4% the assessment of test results reveals consistent diagnoses. 0.9% of patients would not have received a second test if only conductivity measurement had been used although chloridometry revealed positive or indeterminate results. Discussion: Sweat testing remains a particularly paediatric topic. The gold standard is chloridometry. This study underlines the inappropriate comparability of conductivity measurement and chloridometry with consequently higher values in conductivity measurement. Special reference values allow a consistent interpretation in many cases but not in all.

International audience; Several diseases have been clinically or genetically related to cystic fibrosis (CF), but a consensus definition is lacking. Here, we present a proposal for consensus guidelines on cystic fibrosis transmembrane conductance regulator (CFTR)-related disorders (CFTR-RDs), reached after expert discussion and two dedicated workshops. A CFTR-RD may be defined as "a clinical entity associated with CFTR dysfunction that does not fulfil diagnostic criteria for CF". The utility of sweat testing, mutation analysis, nasal potential difference, and/or intestinal current measurement for the differential diagnosis of CF and CFTR-RD is discussed. Algorithms which use genetic and functional diagnostic tests to distinguish CF and CFTR-RDs are presented. According to present knowledge, congenital bilateral absence of vas deferens (CBAVD), acute recurrent or chronic pancreatitis and disseminated bronchiectasis, all with CFTR dysfunction, are CFTR-RDs.