ORIGINAL PAPERS
Almagate interference in breath test results for the diagnosis of Helicobacter pylori infection
Interferencia del almagato con el resultado del test del aliento para el diagnóstico de la infección por Helicobacter pylori
Carles Pons1,2, Sandra Maisterra1,2, Sílvia Salord1,2, Àngels Pla2, David Asensio3, Francisco Javier Fernández3, Gerard Traveria4 and Guillem Roura4
1Hospital de Bellvitge. Hospitalet de Llobregat, Barcelona. Spain.
2CAP Just Oliveres. Hospitalet de Llobregat, Barcelona. Spain. ]]>
3Almirall, S.A. Barcelona, Spain.
4Adknoma Health Research, S.L. Barcelona, Spain
The present study was made possible thanks to the support of Almirall, S.A. Barcelona, Spain.
ABSTRACT
Background: Infection by Helicobacter pylori is common and affects both genders at any age. The 13C-urea breath test is a widely used test for the diagnosis of this infection. However, multiple drugs used for the treatment of Helicobacter pylori infection symptoms have interactions with this breath test that generate false negative results. This observational study was to assess the potential interaction between almagate and the breath test.
Methods: Thirty subjects on almagate therapy who underwent a breath test were included. If the result was negative, almagate was withdrawn for a month and the breath test was then repeated.
Results: In general, 51.9 % of assessed subjects had a negative result after the first test, and 100 % of these also had a negative result after the second test. ]]>
Conclusions: It was concluded that the use of almagate does not interfere in breath test results. These results provide a drug therapy option for the treatment of symptoms associated with Helicobacter pylori infection during the diagnostic process.
Key words: Breath test. Omeprazole. Almagate. Helicobacter pylori.
RESUMEN
Introducción: la infección por Helicobacter pylori es muy frecuente y afecta a cualquier edad y sexo. El test del aliento con urea 13C es una prueba ampliamente utilizada para el diagnóstico de esta infección. Sin embargo, múltiples fármacos utilizados para tratar los síntomas de la infección por Helicobacter pylori presentan interacciones con la realización del test del aliento dando como resultado falsos negativos. Este estudio observacional tiene como objetivo evaluar la posible interacción entre el uso de almagato y el test del aliento.
Métodos: se incluyeron 30 participantes en tratamiento con almagato y se les realizó el test del aliento. En caso de resultado negativo, se les retiró la administración de almagato durante un mes y se les repitió el test del aliento.
Resultados: el 51,9 % de los participantes analizados presentaron un resultado negativo en el primer test y el 100 % de estos se les confirmó el resultado negativo en el segundo test.
Conclusiones: se concluyó que el uso de almagato no interfiere con el resultado del test del aliento. Estos resultados aportan una alternativa farmacológica para tratar la sintomatología de la infección por Helicobacter pylori durante el periodo de su diagnóstico.
Palabras clave: Test del aliento. Omeprazol. Almagato. Helicobacter pylori.
Introduction
]]> Helicobacter pylori infection is one of the commonest chronic infectious diseases worldwide (1), and is directly related to chronic gastritis, adenocarcinoma, and predisposition to gastroduodenal ulcer disease (2). Prevalence may vary from 20 % to 60 % according to geographic region (3). In a healthy population from Madrid, the prevalence of Helicobacter pylori infection was found to be 60.3 % (4), a higher percentage as compared to figures detected in Germany (5) or the United States (6).The 13C-urea breath test (UBT) is a common non-invasive test that provides an accurate diagnosis of Helicobacter pylori infection. However, previous studies showed that the use of proton pump inhibitors, a class of drugs widely used to relieve symptoms from this infection, may change UBT results (7-9). Graham et al. observed that the use of omeprazole is associated with a decrease in urease activity for patients infected with Helicobacter pylori (p = 0.031). Thirty-three percent of infected patients obtained a false negative UBT result. After 14 days following omeprazole therapy withdrawal all these patients had a positive result and baseline urease activity was back in place (9). The use of omeprazole has also been shown to interfere in Helicobacter pyloriserology test results. In a study performed in Italy, omeprazole administration for two weeks in patients defined as positive reduced the sensitivity of antigen serology tests by 22 %. After drug discontinuation for two weeks, all patients obtained a positive result with this same test (7).
An alternative to proton pump inhibitors is almagate, but whether this drug interferes in UBT sensitivity had not been analyzed to this day. The goal of our study was to assess the potential interference of almagate in UBT results for the diagnosis of Helicobacter pylori infection, and to describe patient profiles according to UBT results.
Methods
This was an observational, single-center, pilot study carried out following the standard clinical practice of Primary Care Center Just Oliveres (Hospitalet de Llobregat, Barcelona. Spain). Participants included subjects ≥ 18 years of age scheduled to undergo UBT while on almagate, who had received no proton pump inhibitors or antibiotics in the last 30 days. Doses administered were 1.5 grams every 12 hours for 30 days until the day before the breath test, which was performed after fasting for 8 to 10 hours. Recruitment took place from November 2011 to May 2012. All participants underwent UBT for the diagnosis of Helicobacter pylori infection. Only subjects with a negative result had a repeat test after one month off almagate. UBT was performed using the TAUKIT kit with 100 mg of 13C-urea (Isomed Pharma).
All participants gave their written informed consent. The study was conducted according to Declaration of Helsinki principles and good clinical practice tenets (ICH guideline for Good Clinical Practice, 1996). The study was submitted for consideration to the Ethics Committee/Review Board of IDIAP Jordi Gol i Gurina.
Given the absence of medical literature on the interference of almagate in UBT results, sample size could not be established with statistical accuracy. A pilot study was decided upon, which would include 30 participants. Qualitative variables were described using absolute and relative frequencies. Mean and standard deviation (SD) were chosen to describe quantitative variables. The chi-squared test and Fisher's test were used to compare qualitative variables, according to variable type. For comparison of quantitative variables the Mann-Whitney nonparametric U-test was used. Statistical analyses were performed with the SAS 9.3 software package.
Results
]]> Of all subjects recruited by the study, three were excluded because of unavailable UBT results, hence the analysis was carried out in 27 participants (90 % of the eligible population). In all, 70.4 % (n = 19) were females, mean age was 56.9 years (SD = 17.4), mean BMI was 26.2 kg/m2 (SD = 4.9), and 96.2 % were Hispanics. Mean time from treatment onset to first test was 30.2 days (SD = 1.4). Table I includes all histories of gastric disease and gastric symptoms. Among participants, 74.1 % reported a history of gastric or duodenal ulcer, and 92.6 % suffered from dyspepsia; 44.4 % had been previously diagnosed with Helicobacter pylori infection.
As regards the first UBT performed, 51.9 % of participants had a negative result. Mean time between the first and second tests was 153.4 days (SD = 76.3). A first negative test followed by a second positive one was considered a false negative result. No false negative results were obtained.
Table II lists subject characteristics according to UBT result -38.5 % of participants with a positive result and 21.4 % of those with a negative result were males. Differences were not statistically significant (Fisher's test, p > 0.05). The history of gastric disease was similar for both UBT result groups. Symptoms according to the presence or absence of infection by Helicobacter pylori are also listed in table II. The percentage of participants with abdominal pain and heartburn was higher among individuals with Helicobacter pylori infection as compared with non-infected subjects. Of all participants with a positive result, 69.2 % had abdominal pain and 61.5 % had heartburn, as compared with 14.3 % and 14.3 % of those with a negative result, respectively. These were the only statistically significant differences observed according to UBT results. All subjects had dyspepsia, and anthropometric measurements were similar in both groups.
Discussion
]]> Proton pump inhibitors such as omeprazole are among the most widely used drugs against infection with Helicobacter pylori. However, this drug has often been seen to interfere with UBT providing false negative results (7). Omeprazole may reduce Helicobacter pylori bacteria load and inhibit gastric urease activity. It is not until two weeks after omeprazole therapy discontinuation that UBT results become really reliable (9). This is why, in clinical practice, health care providers must forbid patients from using this drug before a diagnosis of infection with Helicobacter pylori is reached. Our results open up a new alternative to omeprazole in order to alleviate infection manifestations without interfering with its diagnosis.The present pilot study is the first one to show that almagate therapy does not interfere in UBT results for the diagnosis of infection with Helicobacter pylori. Of all subjects evaluated, 51.9 % had a negative result in the first test. When the same test was repeated to all these participants following almagate discontinuation 100 % of cases were still negative, and no false negatives were observed. It was concluded that almagate use does not interfere in UBT results for the diagnosis of infection with Helicobacter pylori.
The fact that this was a pilot study with a limited sample size should be highlighted. However, these results show that there is a need for a multicenter study allowing greater statistical power.
References
1. Cave DR. Transmission and epidemiology of Helicobacter pylori. Am J Med 1996;100:12-8. [ Links ]
2. Brown LM. Helicobacter pylori: Epidemiology and routes of transmission. Epidemiol Rev 2000;22:283-97. [ Links ]
3. Calvet X, Ramírez Lázaro MJ, Lehours P, Mégraud F. Diagnosis and epidemiology of Helicobacter pylori infection. Helicobacter 2013;18:5-11. [ Links ]
4. Sánchez Ceballos F, Taxonera Samsó C, García Alonso C, Alba López C, Sainz de los Terreros Soler L, Díaz-Rubio M. Prevalence of Helicobacter pylori infection in the healthy population of Madrid (Spain). Rev Esp Enferm Dig 2007;99:497-501. [ Links ]
5. Breuer T, Sudhop T, Hoch J, Sauerbruch T, Malfertheiner P. Prevalence of and risk factors for Helicobacter pylori infection in the western part of Germany. Eur J Gastroenterol Hepatol 1996;8:47-52. [ Links ]
6. Everhart JE, Kruszon-Moran D; Perez-Perez GI, Sue Tralka T, McQuillan G. Seroprevalence and Ethnic Differences in Helicobacter pylori Infection among Adults in the United States. J Infec Dis 2000;181:1359-63. [ Links ]
7. Manes G, Balzano A, Iaquinto G, Ricci C, Piccirillo MM, Giardullo N, et al. Accuracy of the stool antigen test in the diagnosis of Helicobacter pylori infection before treatment and in patients on omeprazole therapy. Aliment Pharmacol Ther 2001;15:73-9. [ Links ]
8. Parente F, Sainaghi M, Sangaletti O, Imbesi V, Maconi G, Anderloni A, et al. Different effects of short-term omeprazole, lansoprazole or pantoprazole on the accuracy of the (13)C-urea breath test. Aliment Pharmacol Ther 2002;16:553-7. [ Links ]
9. Graham DY, Opekun AR, Hammoud F, Yamaoka Y, Reddy R, Osato MS, et al. Studies regarding the mechanism of false negative urea breath tests with proton pump inhibitors. Am J Gastroenterol 2003;98:1005-9. [ Links ]
Correspondence:
Carles Pons Vilardell.
Hospital de Bellvitge.
Feixa Llarga, s/n.
08907 Hospitalet de Llobregat, Barcelona. Spain ]]>
e-mail: cpons@bellvitgehospital.cat
Received: 31-03-2014
Accepted: 27-08-2014