Indirect measurements of sweat electrolyte concentration in the laboratory diagnosis of cystic fibrosis

Mary E Heeley; David A Woolf; Anthony F Heeley

doi:10.1136/adc.82.5.420

Responses

Methodology

Indirect measurements of sweat electrolyte concentration in the laboratory diagnosis of cystic fibrosis

Compose a Response to This Article

Compose Response

Title *

Author Information

Contributors
First Name and Middle Initial * First or given name, e.g. 'Peter'. Last Name * Your last, or family, name, e.g. 'MacMoody'. Email Address * Your email address, e.g. higgs-boson@gmail.com Occupation * Your role and/or occupation, e.g. 'Orthopedic Surgeon'. Affiliation * Your organization or institution (if applicable), e.g. 'Royal Free Hospital'.

Statement of Competing Interests

Competing interests? *

Yes

Please describe the competing interests

PLEASE NOTE:

A rapid response is a moderated but not peer reviewed online response to a published article in a BMJ journal; it will not receive a DOI and will not be indexed unless it is also republished as a Letter, Correspondence or as other content. Find out more about rapid responses.
We intend to post all responses which are approved by the Editor, within 14 days (BMJ Journals) or 24 hours (The BMJ), however timeframes cannot be guaranteed. Responses must comply with our requirements and should contribute substantially to the topic, but it is at our absolute discretion whether we publish a response, and we reserve the right to edit or remove responses before and after publication and also republish some or all in other BMJ publications, including third party local editions in other countries and languages
Our requirements are stated in our rapid response terms and conditions and must be read. These include ensuring that: i) you do not include any illustrative content including tables and graphs, ii) you do not include any information that includes specifics about any patients,iii) you do not include any original data, unless it has already been published in a peer reviewed journal and you have included a reference, iv) your response is lawful, not defamatory, original and accurate, v) you declare any competing interests, vi) you understand that your name and other personal details set out in our rapid response terms and conditions will be published with any responses we publish and vii) you understand that once a response is published, we may continue to publish your response and/or edit or remove it in the future.
By submitting this rapid response you are agreeing to our terms and conditions for rapid responses and understand that your personal data will be processed in accordance with those terms and our privacy notice.

I agree to and have read the terms and conditions for rapid responses and BMJ Privacy Notice *

CAPTCHA

This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.

Vertical Tabs

Other responses

Jump to comment:

Sweat chloride and conductivity
H Lewis Webster
Published on: 22 March 2016
Re: Sweat chloride and conductivity
Mary Heeley
Published on: 22 March 2016
Sweat chloride and conductivity
Vicky A LeGrys
Published on: 22 March 2016

Published on: 22 March 2016
Sweat chloride and conductivity
- H Lewis Webster, Senior Research Scientist
Dear Editor
As I understand the Scientific Method, a statement purporting to be factual, either in a scientific article or in a discussion with peers, must be supported by cited evidence that may be publicly examined for its scientific veracity.
The paper by Heeley et al provides data to illustrate the equivalence of conductivity and chloride in cystic fibrosis (CF) diagnosis,[1] and therefore corrob...
Show More

Dear Editor
As I understand the Scientific Method, a statement purporting to be factual, either in a scientific article or in a discussion with peers, must be supported by cited evidence that may be publicly examined for its scientific veracity.
The paper by Heeley et al provides data to illustrate the equivalence of conductivity and chloride in cystic fibrosis (CF) diagnosis,[1] and therefore corroborates the findings of an earlier clinical trial by Hammond et al.[2] Further, a statistical comparison of the extensive published sweat chloride data of Shwachman et al[3] with the conductivity data of Hammond et al shows that the two are of equal discriminatory power in CF diagnosis.
Despite this evidence, LeGrys has written a document[4] that contains a number of assertions on this subject and on other aspects of sweat testing, that are not supported by any published results of original work of which I am aware. No clinical trial data exist which show that conductivity should only be used as a screen, that it is in any way inferior to chloride as a reliable diagnostic discriminator, or that conductivity readings of 50 mmol/L are positive for CF. LeGrys's call for more studies on this matter may be seen as an evasion of the true issue.[5] I suggest that the time has come, albeit belatedly, for her to substantiate her case, not with opinions, but by providing proper citations for relevant experimentally-obtained data to support her contentions in the said document.
In a separate article[6] LeGrys refers to conductivity as a "qualitative" assay, appearing to infer that it is less reliable than chloride analysis. The term "quantitative", used in the pad-absorption method merely indicates that gravimetric means are used to measure the obtained sweat. It is obvious that this must be done to allow measurement of chloride concentration since elution of collecting pads is involved. The conductivity method is unequivocally quantitative because it measures a solution property in a micro-cell of defined geometry. The inference is therfore absurd and irrelevant.
LeGrys, in her eLetter,[5] makes the incredible statement that since sodium is not as reliable as chloride as a discriminator it would seem "logical" (sic) that because conductivity measures both, the discriminatory advantage of chloride would be cancelled out. The logic of this is difficult to comprehend. Increase in sweat chloride due to functional aberration of the chloride channel must be compensated by increase of one or another of the available cation species eg, potassium, sodium or ammonium in order to satisfy the Law of Electrical Equivalence. Such an increase in chloride will therefore be reflected by a proportionate increase in the total electrolyte concentration, which is the basis of analysis by electrical conductivity.
It is regrettable that lack of proper attention to basic scientific principles has persisted in the NCCLS Guidelines for sweat testing for a considerable time without correction and has produced increasing confusion among medical technologists, particularly in the United States. It is sincerely hoped that the author of this document will see fit to amend it appropriately by substituting scientific accuracy for prejudice.
References
(1) Heeley ME, Woolf DA, Heeley AF. Indirect measurements of sweat electrolyte concentration in the laboratory diagnosis of cystic fibrosis. Arch Dis Child 2000;82:420-4.
(2) Hammond KB, Turcios NL, Gibson LE. Clinical evaluation of the macroduct sweat collection system and conductivity analyser in the diagnosis of cystic fibrosis. J Pediatr 1994;124:255-60.
(3) Webster HL. Sweat conductivity is a valid analysis for cystic fibrosis diagnosis. Proceedings of the International Conference; Neonatal Screening for Cystic Fibrosis. Caen, Sept. 10-11, 1998:101-5
(4) Sweat Testing: Sample collection and Quantitative Analysis: Approved Guideline. National Committee for Clinical Laboratory Standards (NCCLS) Document C34-A, 1994.
(5) LeGrys VA. Sweat chloride and conductivity. Arch Dis Child [Rapid Response] 17 July 2000.
(6) LeGrys VA. Sweat Testing for the Diagnosis of Cystic Fibrosis; Practical Considerations. J Pediatr 1996;129:892-7.
Show Less

Conflict of Interest:
None declared.
- Back to top
Published on: 22 March 2016
Re: Sweat chloride and conductivity
- Mary Heeley, Medical Scientist
Dear Editor
As the principal author of the NCCLS guideline on sweat testing methodology, Dr Le Grys should be better informed of its content. It includes the clear statement that when sweat test results are obtained by conductivity measurement "the patient should be referred for quantitative sweat electrolyte testing". In our paper we refer to this statement as implying that sweat conductivity measurement should be re...
Show More

Dear Editor
As the principal author of the NCCLS guideline on sweat testing methodology, Dr Le Grys should be better informed of its content. It includes the clear statement that when sweat test results are obtained by conductivity measurement "the patient should be referred for quantitative sweat electrolyte testing". In our paper we refer to this statement as implying that sweat conductivity measurement should be regarded as "unreliable for diagnostic purposes". This surely cannot be conceived as misrepresenting the NCCLS position, as claimed by Dr Le Grys. Although the NCCLS does, by reference, attribute this advice to Cystic Fibrosis Foundation (CFF)(USA) policy, by including it in their guideline without comment or qualification, the NCCLS authors are actively promoting it.
The medical politics of the USA do not concern us, but rather the question as to whether there is any scientific evidence underpinning this advice which the NCCLS upholds. The result of our study suggests there is none.
Dr Le Grys quotes research findings (reference 4) which supports the conclusion that sweat conductivity measurement is appropriate only for initial screening purposes. We contend that there is no data presented in this otherwise excellent paper which provides scientific justification for that conclusion.
Dr Le Grys is of the opinion that the conclusion we draw from our own study should have been supported by appropriate linear regression and bias plots of the data. The ADC's professional statistical adviser reviewing our manuscript, which included such data analysis, thought otherwise and requested us to remove it.
It is rather ironic that Dr Le Grys should now be pleading for more studies to be carried out to resolve the issue of the diagnostic equivalence of indirect and direct sweat electrolyte measurement, focusing on patients who produce results which are equivocal. Considering the relative rarity of such patients in general paediatric practice, if the problem revolves around these cases why did the NCCLS guideline not clearly state this in the first place? In reality, the final diagnosis of CF in these cases is likely to be resolved by the results of investigations other than the sweat test.
Mary Heeley
David Woolf
Anthony Heeley
Show Less

Conflict of Interest:
None declared.
- Back to top
Published on: 22 March 2016
Sweat chloride and conductivity
- Vicky A LeGrys, Professor
Dear Editor
As a principal author of the sweat testing document published by National Committee for Clinical Laboratory Standards (NCCLS) and consultant to the Cystic Fibrosis Foundation (CFF)(US), I write to address an inaccuracy in the article by Heeley et al (Indirect measurement of sweat electrolyte concentration in the laboratory diagnosis of cystic fibrosis. Arch Dis Child 2000;82:420-4). The authors misrepresent...
Show More

Dear Editor
As a principal author of the sweat testing document published by National Committee for Clinical Laboratory Standards (NCCLS) and consultant to the Cystic Fibrosis Foundation (CFF)(US), I write to address an inaccuracy in the article by Heeley et al (Indirect measurement of sweat electrolyte concentration in the laboratory diagnosis of cystic fibrosis. Arch Dis Child 2000;82:420-4). The authors misrepresent the NCCLS document on the role of conductivity analysis. Nowhere does the NCCLS document refer to the current conductivity methods described in the paper as unreliable; it does restate the widely accepted fact that some older conductivity methods are subject to evaporation error. The NCCLS document goes on to state that the CFF has approved the use of newer conductivity analyzers for the screening of CF at community hospitals, using a decision level of 50 mmol/L.[1] This decision level is supported by the data presented in the Heeley article. The data presented in the article concerning equivocal patients also supports the US reference interval for sweat chloride as normal below 40 mmol/L.[2, 3] Patients with chloride values greater than 40 mmol/L should be further evaluated.
The reluctance of many to accept the use of sweat conductivity in place of sweat chloride for confirming a diagnosis of CF is based on the fact that chloride determinations directly reflect the genetic mutation of the disease. Conductivity is a property of all the charged species in a sample (i.e. sodium, potassium, chloride, lactate, bicarbonate, etc). As the authors' point out, chloride provides greater discrimination than sweat sodium i.e. less overlap between diagnostic categories. It would seem logical then, that combining sodium with chloride in a conductivity measurement would effectively cancel out the discrimination advantage of chloride alone. Referring to the data presented in Table 2, there were twice as many patients with equivocal conductivity concentrations as with chloride (albeit a very limited sample size). Additionally, there exists a paucity of data in the scientific literature comparing conductivity and chloride values in CF and non-CF individuals. Even the scientists publishing such research support the conclusion that conductivity is appropriate for initial screening and chloride for confirmatory diagnosis.[4]
Heeley et al's article attempts to provide relevant data, however it is most unfortunate that the authors failed to include in their analysis, a linear regression plot of chloride versus conductivity along with a bias plot of the data so that the reader could assess the correlation. More studies need to be published comparing conductivity with chloride, particularly in patients with results in the equivocal range, before the conclusion can be made that sweat conductivity is as effective as chloride measurement for the diagnosis of CF.
Sincerely
Vicky A. LeGrys, Dr.A.
Professor, Division of Clinical Laboratory Science
School of Medicine, University of North Carolina at Chapel Hill
References
(1) Sweat Testing: Sample Collection and Quantitative Analysis; Approved Guideline. National Committee for Clinical Laboratory Standards (NCCLS) Document C34-A, 1994.
(2) Rosenstein BJ, Cutting GR: The diagnosis of cystic fibrosis: A consensus statement. J Pediatr 1998;132:589-95.
(3) Farrell PM, Koscik RE: Sweat chloride concentrations in infants homozygous or heterozygous for delta 508 cystic fibrosis. Pediatrics 1996;97:524-8.
(4) Hammond KB, Turcios NL, Gibson LE: Clinical evaluation of the macroduct sweat collection system and conductivity analyzer in the diagnosis of cystic fibrosis. J Pediatr 1994;124:255-60.
Show Less

Conflict of Interest:
None declared.
- Back to top

Main menu

Plain text

PLEASE NOTE:

Vertical Tabs

Other responses

Jump to comment:

Log in using your username and password

Main menu

Log in using your username and password

You are here

Plain text

PLEASE NOTE:

Vertical Tabs

Other responses

Jump to comment:

Read the full text or download the PDF:

Log in using your username and password