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Fecal Elastase-1 Is Superior to Fecal Chymotrypsin in the Assessment of Pancreatic Involvement in Cystic Fibrosis

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Fecal Elastase-1 Is Superior to Fecal Chymotrypsin in the Assessment of Pancreatic Involvement in Cystic Fibrosis Fecal Elastase-1 Is Superior to Fecal Chymotrypsin in the Assessment of Pancreatic Involvement in Cystic Fibrosis Jaroslaw Walkowiak, MD, PhD*; Karl-Heinz Herzig, MD, PhD§; Krystyna Strzykala, M ChemA, Dr Nat Sci*; Juliusz Przyslawski, M Phar, Dr Phar‡; and Marian Krawczynski, MD, PhD* ABSTRACT. Objective. Exocrine pancreatic function ystic fibrosis (CF) is the most common cause in patients with cystic fibrosis (CF) can be evaluated by of exocrine pancreatic insufficiency in child- direct and indirect tests. In pediatric patients, indirect hood. Approximately 85% of CF patients are tests are preferred because of their less invasive charac- C 1,2 pancreatic insufficient (PI). Thus, the assessment of ter, especially in CF patients with respiratory disease. exocrine pancreatic function in CF patients is of great Fecal tests are noninvasive and have been shown to have clinical importance. For the evaluation, both direct a high sensitivity and specificity. However, there is no 3,4 comparative study in CF patients. Therefore, the aim of and indirect tests are used. The gold standard is the present study was to compare the sensitivity and the the secretin-pancreozymin test (SPT) or one of its specificity of the fecal elastase-1 (E1) test with the fecal modifications. However, this test is invasive, time chymotrypsin (ChT) test in a large cohort of CF patients consuming, expensive, and not well standardized in and healthy subjects (HS). children. Therefore, its use is limited to qualified Design. One hundred twenty-three CF patients and gastroenterologic centers. 105 HS were evaluated. In all subjects, E1 concentration Several indirect tests, such as serum tests—amy- and ChT activity were measured. In the CF group, fecal lase, lipase, trypsin, and the pancreolauryl or benti- fat excretion was also determined. The sensitivity and romide test, 72-hour fecal fat analysis, fecal elastase-1 specificity of the fecal E1 test and ChT test were com- (E1) and chymotrypsin (ChT) analysis, and breath pared. tests—have been developed. The sensitivity of these Results. With a cutoff level of 3 U/g, ChT specificity in HS was similar to that of E1, but E1 sensitivity in CF tests is limited in pancreatic-sufficient (PS) CF pa- 3,4 patients was significantly higher (90.2% vs 81.3%). With tients. The use of the SPT in children, on the other a cutoff level of 6 U/g, ChT and E1 sensitivity in CF hand, is controversial because of its invasive charac- patients was identical, but E1 specificity in HS was again ter, especially in CF patients with pulmonary dis- significantly higher (98.1% vs 90.5%). In all CF patients ease. Thus, in pediatric CF patients, indirect tests are with severe steatorrhea (>15 g/d), E1 concentrations were commonly used. Among the indirect tests, because of abnormal and ChT activity was lower than 3 U/g. In their low invasiveness and high sensitivity and spec- contrast, in pancreatic-sufficient patients and patients ificity, the measurement of pancreatic enzymes in < with mild steatorrhea ( 15 g/d), the E1 sensitivity was feces seems to be the most appropriate one. significantly higher compared with ChT (69.2% vs Determination of fecal ChT has been an accepted 41.0%). indirect test in the pediatric routine for several Conclusions. The fecal E1 test is superior to fecal ChT 5–8 determination in the assessment of CF pancreatic in- years. However, because of the colorimetric volvement in pancreatic-sufficient patients and those pa- method, there is an interference with the enzyme tients with mild steatorrhea. Pediatrics 2002;110(1). URL: substitution therapy.9 Thus, pancreatic enzyme sup- http://www.pediatrics.org/cgi/content/full/110/1/e7; fecal plementation should be stopped for at least 3 days. elastase-1, fecal chymotrypsin, exocrine pancreatic func- On the contrary, fecal E1 test (enzyme-linked immu- tion, cystic fibrosis. nosorbent assay [ELISA]) is specific for the human enzyme and not influenced by exogenous enzyme 9–11 ABBREVIATIONS. CF, cystic fibrosis; PI, pancreatic insufficient; supplementation. In adult chronic pancreatitis SPT, secretin-pancreozymin test; E1, elastase-1; ChT, chymotryp- patients, the determination of E1 and ChT were usu- sin; PS, pancreatic sufficient; ELISA, enzyme-linked immunosor- ally performed in small groups of patients and bent assay; HS, healthy subjects. healthy subjects (HS).9,12–15 Moreover, the statistical analysis was conducted only in 1 of them.15 There- fore, the aim of the study was to compare the sensi- From the *Institute of Pediatrics and ‡Department of Bromatology and tivity and the specificity of the fecal E1 test with the Human Nutrition, Karol Marcinkowski University of Medical Sciences, fecal ChT test in a large cohort of CF patients and HS. Poznan, Poland; and §A.I. Virtanen-Institute for Molecular Sciences, De- partment of Medicine, University of Kuopio, Kupio, Finland. Received for publication Aug 14, 2001; accepted Mar 14, 2002. MATERIALS AND METHODS Reprint requests to (J.W.) Institute of Pediatrics, Karol Marcinkowski Uni- One hundred twenty-three patients with CF (60 females and 63 versity of Medical Sciences, Szpitalna 27/33, 60–572 Poznan, Poland. E- males), aged from 7 months to 25 years (meanϩSEM: 8.8ϩ0.4 mail: [email protected] years), were evaluated during 1997–2000. The diagnosis of the PEDIATRICS (ISSN 0031 4005). Copyright © 2002 by the American Acad- disease was based on clinical manifestation, chloride sweat con- emy of Pediatrics. centration, and confirmed by CFTR gene analysis (29 most com- http://www.pediatrics.org/cgi/content/full/110/1/Downloaded from www.aappublications.org/newse7 by guestPEDIATRICS on September Vol.29, 2021 110 No. 1 July 2002 1of4 mon mutations). In all patients, fecal E1 concentration, ChT activ- cretion lower than 15 g/d, fecal E1 and fecal ChT ity, and fecal fat excretion were measured. During the study, no tests were compared in a similar manner. In 27 patient suffered an acute episode of diarrhea. The control group (69.2%) of 39 selected patients, fecal E1 concentration (HS) consisted of 105 children and adolescents (55 females and 50 ␮ males) aged from 7 months to 40 years (meanϩSEM: 13.3ϩ0.5 was lower than 200 g/g and ChT activity was lower years) without any gastrointestinal diseases. In all HS, E1 concen- than 6 U/g. With a cutoff level of 3 U/g, ChT was trations were determined. The protocol of the investigation was abnormal in 16 (41.0%) patients. The E1 sensitivity in approved by the Ethical Committee of the Medical Faculty, Karol PS patients and patients with mild steatorrhea (Յ15 Marcinkowski University of Medical Sciences in Poznan, Poland. Fecal E1 was measured by an ELISA (ScheBo⅐Tech, Giessen, g/d) was significantly higher than that of ChT with Germany).16 Fecal ChT was measured by colorimetric method a cutoff level of 3 U/g (P Ͻ .006). In all patients with (Roche Diagnostics GmbH, Mannheim, Germany).17 For addi- severe steatorrhea (Ͼ15 g/d), fecal E1 concentration tional analysis, the mean value from 3 nonrelated measurements was abnormal, and ChT activity was lower than 3 was taken. Fecal fat was analyzed according to van de Kamer et al.18 The U/g. diet regimens were standardized for age, weight, and sex before and during the 3-day collection of stool.19 Daily fecal fat excretion was defined as a mean of a 72-hour collection period. According to DISCUSSION fecal fat excretion, CF patients were defined as PI (7 month-10 Fecal ChT activity in randomly collected stool years: Ն5 g/d; above 10 years Ն7 g/d) or PS (7 month-10 years: specimen of CF patients poorly correlates to pancre- Ͻ Ͻ 20–22 5 g/d; above 10 years 7 g/d). In addition, steatorrhea was 7 defined as a mild (Ͻ15 g/d) and severe (Ն15 g/d). Fecal E1 atic output measured by direct stimulation by SPT. concentrations below 200 ␮g/g of feces and ChT activities lower In contrast, the correlation between fecal E1 concen- than 3 U/g were considered to be abnormal. Because fecal ChT tration and single parameters of secretin-cholecysto- activity between 3 U/g and 6 U/g of feces is indicative of exocrine kinin has been shown to be highly significant, both in pancreatic insufficiency, the analysis for cutoff level of 6 U/g was CF patients24 and HS.9 The day-to-day variation in also performed. The sensitivity and specificity of the fecal E1 test and ChT test were compared. For the statistical evaluation of the fecal ChT activity is a disadvantage of this meth- results of fecal tests, the McNemar test was used.23 od,7,14 while fecal E1 concentrations seem to be more stable.14 Moreover, with the use of the fecal E1 test RESULTS (ELISA) exclusively endogenous enzyme release is Fecal E1 concentrations were abnormal in 2 (1.9%) measured. In the ChT test (colorimetric method), out of 105 HS and in 111 (90.2%) of 123 CF patients both endogenous and exogenous enzymes are eval- (Table 1). Fecal ChT activity was abnormal in 3 uated.9,11 The sensitivity of ChT test in CF patients (2.9%) HS and 100 (81.3%) CF patients with 3 U/g as has been shown to be high in PI patients and poor in a lower limit of normal, and in 10 (9.5%) HS and 111 those who are PS.6–8 More recently, fecal E1 test has (90.2%) CF patients with 6 U/g as a lower limit of been demonstrated to have very good sensitivity in normal. With a cutoff level of 3 U/g, ChT specificity PI CF patients.11,25–27 Yet, in milder forms of CF in HS was similar to that of E1, but E1 sensitivity in pancreatic insufficiency, the sensitivity of the test CF patients was significantly higher compared with was reduced.24,27 Therefore, one could expect a ChT (90.2% vs 81.3%; P Ͻ .006).
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