cystic fibrosis ( cf ) is the most common autosomal recessive disorder among caucasians with an incidence rate of 1 in 2,500 individuals . the epithelial cells of several organs , including respiratory tract , exocrine pancreas , intestine , vas deferens , hepatobiliary system and also exocrine sweat glands are involved in cf .
therefore several clinical features , including suppurative lung disease , pancreatic insufficiency , neonatal bowel obstruction ( meconium ileus ) , multifocal biliary cirrhosis , absent vas deferens to malabsorbtive condition and growth retardation could be seen in affected patients [ 2 , 3 ] .
high sweat electrolytes ( chloride and sodium ) concentration , which is seen in cf patients became basis for sweat chloride test since 1949 .
the measurement of sweat electrolyte concentrations was established as a standard procedure for diagnosis of cf and remained the gold standard test for the diagnosis of cf .
the diagnosis of cf could easily be made in the majority of cases based on typical clinical features and abnormal sweat chloride values . in such situations ,
genetic analysis of cystic fibrosis transmembrane conductance regulator ( cftr ) gene is not necessary .
however , it may be useful in confirming the diagnosis , which also enables carrier testing and prenatal diagnosis [ 6 , 7 ] .
the universally accepted reference intervals for sweat chloride concentrations regardless of age or sex are > 60 mmol / l , which is considered diagnostic of cf ; 4060 mmol / l is considered borderline , whilst < 40
in addition to sweat chloride concentrations , sweat sodium is also usually measured , as there is little difference between sweat sodium and chloride concentrations [ 810 ] in order to ensure accurate results from a quantitative sweat test using filter paper , a minimum sweat rate of 1g / m / min corresponding to 75 mg collected in 30 minutes is required ( for a 22 inch filter paper ) .
conventionally , it takes around 45 minutes to collect proper volume ( 50400 mg ) sweat for accurate test , which makes the classic sweat test as a time consuming procedure .
indeed many local laboratories in developing countries have not been approved to do the test for both techniques of sweat gathering and also electrolytes measuring . forming of salt crystallization of perspiration described by ferre calvete
et al   could be considered as a useful and alternative test for easy detecting cf patients in these regions .
therefore , we designed this study to compare the results obtained by these two methods . in this study , 60 children with clinical signs suggestive of cf , who were referred to the children 's medical center , pediatrics center of excellence in iran , were investigated .
the study protocol was approved by the research ethics board of the childrens medical center , tehran university of medical sciences .
classic sweat tests ( gibson and cooke sweat test ) and crystallization test were performed for each subject for at least two times in the referral laboratory of the hospital .
localized sweating was produced by iontophoresis of pilocarpine nitrate ( gibson and cook method ) using wescor gel discs [ 5 , 12 ] a copper electrode was then attached and a weak electrical current of about 3 milli - amperes ( ma ) was generated using a 9-volt battery for 5 minutes to stimulate sweating . immediately following stimulation ,
a preweighed filter paper was placed directly over the site of the positive electrode . at the end of the collection
about one hour later , the filter paper was removed and the weight was determined .
the test was repeated for two or three times in all subjects to confirm the results .
meanwhile one drop of each sample was put on lamella and heated by the light of microscope for 5 minutes .
sixty children ( 29 females and 31 males ) with age range of 9 months to 2 years had taken part in this study .
meq / l , while it was 49.81meq / l in the male group without any significant difference between genders ( p>0.05 ) .
cf was diagnosed for the remaining 29 patients who showed positive values of sweat classic test .
1 ) , which provided the test with 100% sensitivity ( ci : 93.1100 ) . only one of 31 subjects without cf ( 17 males and 14 females ; aged 9 months to 2 years ) had positive crystallization test , which provided the test with 96.7% specificity ( 95%ci : 92.9100 ) .
crystal formation in sweat sample of cystic fibrosis patients cystic fibrosis ( cf ) is one of the most frequent ( 1 in 2500 ) autosomal recessive diseases characterized by substantial clinical heterogeneity recent studies have begun to identify chromosomal locations that identify specific genes contributing to this variation . over the past several decades , there has been substantial progress toward diagnostic tools of cf .
determination of chloride concentration in sweat is the current diagnostic gold standard for cf . 
 
the conventional sweat test with elevated sweat sodium and chloride concentration after iontophoresis of pilocarpine is the standard laboratory test for cf .
an accurate sweat test relies on coordination of several factors . technical error of instrument calibration and result reporting
the tests should be performed by expert personnel to ensure sufficient sweat volumes and proper use of equipment .
the centers doing such tests should follow standard guidelines to reduce complexity in interpreting a variety of result ranges [ 14 , 15 ] advanced equipments and experienced personnel which are necessary for accurate classic sweat test made this test unavailable for many centers , especially in developing countries .
although sweat studies became standard diagnostic strategy for diagnosis of cf , it has some limitations whilst it may be unreliable due to not enough collected sweat or borderline values .
indeed genetic studies to detect cftr mutation(s ) take time and may even find no useful information . therefore selecting the best cost - benefit method with high sensitivity and specificity
is needed for diagnosis of cf . for this reasons nanoduct as a new analyzing system measuring conductivity which requires only 3 microliters of sweat and gives results within 30 minutes is also introduced as a reliable diagnostic tool .
nanoduct has a failure rate comparable to other sweat tests and can be used as a simple bedside test for fast and reliable exclusion , diagnosis or suspicion of cf .
sands and his colleagues indicated that simultaneous bilateral sweat testing with two different methods ( concentration and conductivity or nonoduct ) provides an extra quality control system , allowing more time efficient organization of the diagnostic and training procedures . 
 
forming of salt crystallization of perspiration seems as an attractive and alternative test for easy detecting cf patients . in this study , we have shown that looking for salt crystals in just one drop of sweat could diagnose cf , since crystal formation of sweat under light microscope was detected in a significant number of cf patients .
comparing these two methods of sweat test showed good positive predictive value of 96.7% and the negative predictive value of 100% with specificity and sensitivity of 96.7% and 100% , respectively .
therefore , the test could be a very useful alternative test , whenever the classic test is not accessible .
since the classic sweat test measuring chloride levels with the use of acceptable methods ( gibson - cooke or wescor macroduct ) should be performed in centers that conduct sweat tests frequently with properly documented controls , we recommend sweat crystallization test as an alternative test for cf diagnosis at least in areas where neither classic sweat test nor genotyping are accessible .
limitations : there were some limiting factors to consider in interpreting the study 's result .
first , this study was conducted on a relatively small sample size . ideally , a larger and more popular sample size would perhaps delineate more suitable differences between the two methods of cf diagnosis in children with cystic fibrosis .
second , this study compared two kinds of test in children whose first presentation was compatible with cystic fibrosis , although this would not be statistically a problem .
as further study , comparing two methods of the mentioned tests between cf patients and normal children could be more helpful .
this study demonstrates the validity of sweat crystal formation test to support a diagnosis of cf in children whenever conventional sweat test is unavailable .
in this study , 60 children with clinical signs suggestive of cf , who were referred to the children 's medical center , pediatrics center of excellence in iran , were investigated .
the study protocol was approved by the research ethics board of the childrens medical center , tehran university of medical sciences .
classic sweat tests ( gibson and cooke sweat test ) and crystallization test were performed for each subject for at least two times in the referral laboratory of the hospital .
localized sweating was produced by iontophoresis of pilocarpine nitrate ( gibson and cook method ) using wescor gel discs [ 5 , 12 ] a copper electrode was then attached and a weak electrical current of about 3 milli - amperes ( ma ) was generated using a 9-volt battery for 5 minutes to stimulate sweating . immediately following stimulation ,
a preweighed filter paper was placed directly over the site of the positive electrode . at the end of the collection about one hour later , the filter paper was removed and the weight was determined .
the test was repeated for two or three times in all subjects to confirm the results .
meanwhile one drop of each sample was put on lamella and heated by the light of microscope for 5 minutes .
sixty children ( 29 females and 31 males ) with age range of 9 months to 2 years had taken part in this study .
meq / l , while it was 49.81meq / l in the male group without any significant difference between genders ( p>0.05 ) .
cf was diagnosed for the remaining 29 patients who showed positive values of sweat classic test .
1 ) , which provided the test with 100% sensitivity ( ci : 93.1100 ) . only one of 31 subjects without cf ( 17 males and 14 females ; aged 9 months to 2 years ) had positive crystallization test , which provided the test with 96.7% specificity ( 95%ci : 92.9100 ) .
cystic fibrosis ( cf ) is one of the most frequent ( 1 in 2500 ) autosomal recessive diseases characterized by substantial clinical heterogeneity recent studies have begun to identify chromosomal locations that identify specific genes contributing to this variation . over the past several decades , there has been substantial progress toward diagnostic tools of cf .
determination of chloride concentration in sweat is the current diagnostic gold standard for cf . 
 
the conventional sweat test with elevated sweat sodium and chloride concentration after iontophoresis of pilocarpine is the standard laboratory test for cf .
technical error of instrument calibration and result reporting are major factors that affect the results .
the tests should be performed by expert personnel to ensure sufficient sweat volumes and proper use of equipment .
the centers doing such tests should follow standard guidelines to reduce complexity in interpreting a variety of result ranges [ 14 , 15 ] advanced equipments and experienced personnel which are necessary for accurate classic sweat test made this test unavailable for many centers , especially in developing countries .
although sweat studies became standard diagnostic strategy for diagnosis of cf , it has some limitations whilst it may be unreliable due to not enough collected sweat or borderline values .
indeed genetic studies to detect cftr mutation(s ) take time and may even find no useful information . therefore selecting the best cost - benefit method with high sensitivity and specificity
is needed for diagnosis of cf . for this reasons nanoduct as a new analyzing system measuring conductivity which requires only 3 microliters of sweat and gives results within 30 minutes is also introduced as a reliable diagnostic tool .
nanoduct has a failure rate comparable to other sweat tests and can be used as a simple bedside test for fast and reliable exclusion , diagnosis or suspicion of cf .
sands and his colleagues indicated that simultaneous bilateral sweat testing with two different methods ( concentration and conductivity or nonoduct ) provides an extra quality control system , allowing more time efficient organization of the diagnostic and training procedures . 
 
forming of salt crystallization of perspiration seems as an attractive and alternative test for easy detecting cf patients . in this study , we have shown that looking for salt crystals in just one drop of sweat could diagnose cf , since crystal formation of sweat under light microscope was detected in a significant number of cf patients .
comparing these two methods of sweat test showed good positive predictive value of 96.7% and the negative predictive value of 100% with specificity and sensitivity of 96.7% and 100% , respectively .
therefore , the test could be a very useful alternative test , whenever the classic test is not accessible .
since the classic sweat test measuring chloride levels with the use of acceptable methods ( gibson - cooke or wescor macroduct ) should be performed in centers that conduct sweat tests frequently with properly documented controls , we recommend sweat crystallization test as an alternative test for cf diagnosis at least in areas where neither classic sweat test nor genotyping are accessible .
limitations : there were some limiting factors to consider in interpreting the study 's result .
ideally , a larger and more popular sample size would perhaps delineate more suitable differences between the two methods of cf diagnosis in children with cystic fibrosis .
second , this study compared two kinds of test in children whose first presentation was compatible with cystic fibrosis , although this would not be statistically a problem .
as further study , comparing two methods of the mentioned tests between cf patients and normal children could be more helpful .
this study demonstrates the validity of sweat crystal formation test to support a diagnosis of cf in children whenever conventional sweat test is unavailable .
 objectivesweat chloride measurement is considered a standard diagnostic tool for cystic fibrosis ( cf ) . 
 this study was performed to compare sweat chloride values obtained by quantitative pilocarpine iontophoresis ( classic test ) with sweat crystallization detected by direct observation of a drop of perspiration under light microscopy in patients with and without cf.methodsthe tests using both techniques were performed simultaneously in patients with and without cf . 
 cutoff values of 60 mmol / l of chloride concentration for the classic sweat test was considered for diagnosis of cf . in crystallization method , 
 observation of typical dendritic forms of salt crystals under light microscopy was interpreted positive.findingssixty patients suspected to cf ( 31 males and 29 females ) with age range of 9 months to 2 years underwent the sweat test using both techniques . 
 median sweat chloride values was 26.13 + 10.85 in group with negative and 72.76 + 12.78 
 mmol / l in group with positive sweat test , respectively . 
 all the patients who had positive sweat test in classic method showed typical dendritic forms of salt crystal in sweat crystallization test , which provided the test with 100% sensitivity ( 95%ci : 93.1100 ) . 
 only one of the 31 subjects with negative results for classic sweat test had positive result for crystallization sweat test , which provided the test with 96.7% specificity ( 95%ci : 92.9100 ) . 
 time spent to perform the crystallization test was significantly shorter than the classic method whereas its cost was also lower than the second method.conclusionthere was a good correspondence between two studied methods of sweat test . 
 these results suggested the sweat crystallization test as an alternative test for detecting cf disease with high sensitivity and specificity . 