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International audience; Rationale: Elexacaftor-tezacaftor-ivacaftor is a CFTR (cystic fibrosis [CF] transmembrane conductance regulator) modulator combination, developed for patients with CF with at least one Phe508del mutation. Objectives: To evaluate the effects of elexacaftor-tezacaftor- ivacaftor in patients with CF and advanced respiratory disease. Methods: A prospective observational study, including all patients aged ⩾12 years and with a percent-predicted FEV1 (ppFEV1)

Lung damage in cystic fibrosis (CF) is strongly associated with lower airway infections. Early treatment of Pseudomonas aeruginosa is recommended. Pathogen detection requires sampling of lower airway secretions, which remains a challenge in nonexpectorating patients. Our hypothesis was that chest physiotherapy would improve the quality of airway secretion samples and increase the rates of pathogens detected in nonexpectorating patients.This prospective multicentre study compared three successive methods for sampling airway secretions applied through the same session: 1) an oropharyngeal swab (OP), 2) a chest physiotherapy session followed by a provoked cough to obtain sputum (CP-SP) and 3) a second oropharyngeal swab collected after chest physiotherapy (CP-OP). Haemophilus influenzae, Staphylococcus aureus and P. aeruginosa growth cultures were assessed. Accuracy tests and an equivalence test were performed to compare the three successive methods of collection.300 nonexpectorating children with CF were included. P. aeruginosa was detected cumulatively in 56 (18.9%) children, and according to the different collection methods in 28 (9.8%), 37 (12.4%) and 44 (14.7%) children by using OP, CP-OP and CP-SP, respectively. Compared with OP, the increased detection rate was +22% for CP-OP (p=0.029) and +57% for CP-SP (p=0.003). CP-SP had the best positive predictive value (86.3%) and negative predictive value (96.0%) for P. aeruginosa compared with the overall detection.The results of this adequately powered study show differences in the rates of pathogens detected according to the sampling method used. Chest physiotherapy enhanced detection of P. aeruginosa in nonexpectorating children with CF.

Lung damage in cystic fibrosis (CF) is strongly associated with lower airway infections. Early treatment of Pseudomonas aeruginosa is recommended. Pathogen detection requires sampling of lower airway secretions, which remains a challenge in nonexpectorating patients. Our hypothesis was that chest physiotherapy would improve the quality of airway secretion samples and increase the rates of pathogens detected in nonexpectorating patients. This prospective multicentre study compared three successive methods for sampling airway secretions applied through the same session: 1) an oropharyngeal swab (OP), 2) a chest physiotherapy session followed by a provoked cough to obtain sputum (CP-SP) and 3) a second oropharyngeal swab collected after chest physiotherapy (CP-OP). Haemophilus influenzae, Staphylococcus aureus and P. aeruginosa growth cultures were assessed. Accuracy tests and an equivalence test were performed to compare the three successive methods of collection. 300 nonexpectorating children with CF were included. P. aeruginosa was detected cumulatively in 56 (18.9%) children, and according to the different collection methods in 28 (9.8%), 37 (12.4%) and 44 (14.7%) children by using OP, CP-OP and CP-SP, respectively. Compared with OP, the increased detection rate was +22% for CP-OP (p=0.029) and +57% for CP-SP (p=0.003). CP-SP had the best positive predictive value (86.3%) and negative predictive value (96.0%) for P. aeruginosa compared with the overall detection. The results of this adequately powered study show differences in the rates of pathogens detected according to the sampling method used. Chest physiotherapy enhanced detection of P. aeruginosa in nonexpectorating children with CF., Sputum collection after a chest physiotherapy session strongly enhances the detection of P. aeruginosa in nonexpectorating CF children compared with the commonly used oropharyngeal swab method. Oropharyngeal swab after physiotherapy may be an acceptable alternative. https://bit.ly/3757ewq

Summary Background As survival among patients with cystic fibrosis has improved in recent decades, complications have become increasingly relevant. The most frequent complication is cystic-fibrosis-related diabetes. The recommended treatment is injected insulin, but some patients are treated with oral antidiabetic drugs to ease the treatment burden. We assessed the efficacy and safety of oral antidiabetic drugs. Methods We did a multicentre, open-label, comparative, randomised trial in 49 centres in Austria, France, Germany, and Italy. Eligible patients had cystic fibrosis, were older than 10 years, and had newly diagnosed diabetes. We used a central randomisation schedule derived from a Geigy random number table to assign patients 1:1 to receive insulin or repaglinide, stratified by sex and age (10–15 years or >15 years). The primary outcome was glycaemic control assessed by mean change in HbA 1c concentration from baseline after 24 months of treatment. Differences between groups were assessed by linear models. The primary and safety analyses were done in the modified intention-to-treat population (including patients who stopped treatment early because of lack of efficacy). This trial is registered with ClinicalTrials.gov, number NCT00662714. Findings We enrolled 34 patients in the repaglinide group and 41 in the insulin group, of whom 30 and 37, respectively, were included in the analyses. At 24 months, glycaemic control was similar in the repaglinide and insulin groups (mean change in HbA 1c concentration from baseline 0·2% [SD 0·7%], 1·7 mmol/mol [8·1 mmol/mol] with repaglinide vs −0·2% [1·3%], −2·7 mmol/mol, [14·5 mmol/mol] with insulin; mean difference between groups −0·4%, (95% CI −1·1 to 0·2 [−4·4 mmol/mol, −11·5 to 2·7], p=0·15). The most frequent adverse events were pulmonary events (43 [40%] of 107 in the repaglinide group and 60 [45%] of 133 in the insulin group), and the most frequent serious adverse events were pulmonary events leading to hospital admission (five [50%] of ten and seven [54%] of 13, respectively). Interpretation Repaglinide for glycaemic control in patients with cystic-fibrosis-related diabetes is as efficacious and safe as insulin. Funding Mukoviszidose eV, Vaincre la Mucoviscidose, ABCF Association, and Novo Nordisk.

International audience; Rationale: Lumacaftor-ivacaftor is a CFTR (cystic fibrosis transmembrane conductance regulator) modulator combination recently approved for patients with cystic fibrosis (CF) homozygous for the Phe508del mutation.Objectives: To evaluate the safety and effectiveness of lumacaftor-ivacaftor in adolescents (≥12 yr) and adults (≥18 yr) in a real-life postapproval setting.Methods: The study was conducted in the 47 CF reference centers in France. All patients who initiated lumacaftor-ivacaftor from January 1 to December 31, 2016, were eligible. Patients were evaluated for lumacaftor-ivacaftor safety and effectiveness over the first year of treatment following the French CF Learning Society's recommendations.Measurements and Main Results: Among the 845 patients (292 adolescents and 553 adults) who initiated lumacaftor-ivacaftor, 18.2% (154 patients) discontinued treatment, often owing to respiratory (48.1%, 74 patients) or nonrespiratory (27.9%, 43 patients) adverse events. In multivariable logistic regression, factors associated with increased rates of discontinuation included adult age group, percent predicted FEV1 (ppFEV1) less than 40%, and numbers of intravenous antibiotic courses during the year before lumacaftor-ivacaftor initiation. Patients with continuous exposure to lumacaftor-ivacaftor showed an absolute increase in ppFEV1 (+3.67%), an increase in body mass index (+0.73 kg/m2), and a decrease in intravenous antibiotic courses by 35%. Patients who discontinued treatment had significant decrease in ppFEV1, without improvement in body mass index or decrease in intravenous antibiotic courses.Conclusions: Lumacaftor-ivacaftor was associated with improvement in lung disease and nutritional status in patients who tolerated treatment. Adults who discontinued lumacaftor-ivacaftor, often owing to adverse events, were found at high risk of clinical deterioration.

To evaluate nutritional status and associated factors in a cystic fibrosis (CF) cohort diagnosed by newborn screening and followed up to month 24.A prospective longitudinal multicenter study assessing nutritional status according to pancreatic status, feeding modalities, prescriptions, pulmonary outcome, and biological nutritional parameters.One hundred and five infants were recruited and 99 completed the study. Nutritional care management prevented undernutrition and stunting in those with exocrine pancreatic sufficiency (EPS), but affected (13/87) 15% and (21/86) 24%, respectively, of infants with exocrine pancreatic insufficiency (EPI). The logistic regression model found a positive association between both weight and length z scores "at risk" at month 24, and initial pulmonary symptoms (odds ratio [OR] 0.06, P 0.01 and OR 0.08, P 0.01, respectively); these symptoms were less frequent when age at first visit was earlier than 1.2 months (33% vs 67%, P = 0.02); stunting was also associated with high-calorie density intake and Staphylococcus aureus (OR 0.05, P = 0.01 and OR 0.17, P 0.01). Pulmonary outcome did not differ according to pancreatic status; breast-feeding for at least 3 months delayed first acquisition of Pseudomonas aeruginosa. Despite sodium and fat-soluble vitamin supplementation, half of both cohorts had low urinary sodium output and half of the EPI cohort had low vitamin D levels.Our data shed light on the fact that stunting was more frequent than undernutrition, while both parameters involved only patients with pancreatic insufficiency. Modalities of feeding were not associated with nutritional status; breast-feeding may provide some protection against acquisition of P aeruginosa.

Resting energy expenditure (REE) increases during pulmonary exacerbation by Pseudomonas aeruginosa in cystic fibrosis (CF) patients, and decreases after i.v. anti-Pseudomonas aeruginosa antibiotic therapy (IVAT). However, the impact of IVAT on total energy expenditure (TEE) is unknown. The aim of this study was to assess the changes in TEE and its main components after IVAT administered at home. Body composition measured by skinfold thickness and bio-impedance analysis, energy intake (EI) assessed by a weekly diary, REE measured by indirect calorimetry (IC), TEE assessed by a technique using 24-h heart-rate monitoring method and physical activity (PA) monitored using an activity diary (AD) were assessed in 16 patients (9 boys and 7 girls) aged 12.1 +/- 2.3 y (range, 7.1-14.6 y), before and after 28 +/- 4 d including a 14-d IVAT course. After IVAT, weight increased significantly by 1.9% (32.1 +/- 7.5 versus 32.7 +/- 7.6 kg; p < 0.05), while fat mass and fat free mass increased non significantly. EI increased by 4.6% (10,797 +/- 3039 versus 11320 +/- 3074 kJ/d; p < 0.05). TEE was not affected by IVAT (7014 +/- 1929 versus 7081 +/- 1478 kJ/d) whereas REE decreased by 4.1% (5295 +/- 909 versus 5093 +/- 837 kJ/d; p < 0.05), resulting in 9.3% increase in PA assessed by AD converted to metabolic equivalent tasks (MET) (37.0 +/- 3.1 versus 40.7 +/- 4.5 MET; p < 0.05). The improvement in nutritional status after IVAT is not related to a decrease in TEE, but probably to an increase in EI and a decrease of REE after IVAT. After IVAT, the reduction in REE is probably compensated by an increase in PA in CF patients.

The aim of the study was to identify familial and community environmental risk factors associated with Helicobacter pylori infection in a pediatric population.Children requiring diagnostic upper endoscopy were included in the study during a 2-year period. During endoscopy, five gastric biopsies were performed for the histologic or bacteriologic diagnosis, or both, of H. pylori infection. Epidemiologic data collected by a questionnaire were analyzed using the chi-square test or Fisher test and stepwise logistic regression.The authors included 436 patients (242 boys), aged 2 days to 17.9 years (median, 2.7 years). H. pylori prevalence was 7.3%. Univariate analysis found H. pylori was more common in older patients (P0.00001), in children who had at least one parent born in a developing country (P0.02) or with a low socioeconomic status (P0.02), and in those living in crowded conditions (P0.02). Children whose mother worked at home were more frequently infected than children whose mother worked outside the home (P0.02). Attendance at nursery or school before the age of 6 years was not associated with infection. Logistic regression showed a strong association with H. pylori only for age and number of persons at home.The source of H. pylori is intrafamilial rather than from a community, such as nursery and school attended at a young age. The number of persons in the home influences the infection status of children but not by the presence of the mother in home. These data suggest that H. pylori infection transmission occurs from siblings or the father rather than from mother.

Resume Des 1994, nous avons debute la rhDNase chez tous les patients atteints de mucoviscidose âges de plus de 5 ans et ayant une CVF ≥ 40 % de la valeur theorique. Population et methodes Nous avons analyse retrospectivement les effets de la rhDNase au cours de 2 ans de traitement chez 69 enfants et adolescents. Les patients ( 35 garcons, 34 filles) ont recu une dose unique journaliere de 2,5 mg de rhDNase. Ils etaient âges initialement de 8,5 ans (5 a 16,4 ans). Les valeurs spirometriques (pourcentage de la valeur theorique) et le statut nutritionnel de base etaient les suivants: CVF = 84,8 ± 21,7, VEMS = 80,8 ± 22,2, DEP = 89,7 ± 34,2, DEM 25-75 = 71, 8 ± 32,8, Z score poids/taille = -0,41 ± 1,14, Z-score poids/âge = −0,48 ± 1,25, index de Quetelet = 15,4 ± 1,8, ration calorique = 107 ± 25 % des apports journaliers recommandes. Les donnees spirometriques et nutritionnelles ont ete analysees apres 1, 3, 6, 12, 18 et 24 mois de traitement et comparees aux valeurs de base (resultats spirometriques exprimes en pourcentage des valeurs de base moyennes). Le score de Shwachman-Kulczycki etait de 87 ± 9 avant le traitement et a ete releve 24 mois plus tard. Resultats Une amelioration de la CVF (+ 10,7 %, p p p ≤ 0,01 ). Ceci a ete note en particulier chez les enfants âges de 5 a 10 ans, chez les garcons et chez les patients dont la CVF de base etait e ( p e mois ( p ≤ 0,02), essentiellement chez les filles. Les Z scores poids/âge et poids/taille se sont ameliores respectivement pendant les 3 premiers mois et apres 2 ans de traitement. Le score de Shwachman-Kulczycki est reste stable. Conclusion La rhDNase ameliore donc la fonction respiratoire et le statut nutritionnel des jeunes patients atteints de mucoviscidose et la reponse au traitement peut etre evaluee des les 3 premiers mois.

Resume Le microbiote pulmonaire est aujourd’hui considere comme une communaute poly-microbienne composee de bacteries (bacteriote), de virus et phages, mais aussi de micromycetes (mycobiote) [1] , [2] , [3] , [4] . Dans le cas de la mucoviscidose–qui nous interesse dans ce travail–la composition de ce microbiote est correlee a l’evolution clinique des patients [1] , [2] , [3] , [4] . Nous rapportons ici la caracterisation par sequencage haut-debit, des microbiotes bacteriens et fongiques respiratoire et de l’environnement interieur immediat d’une patiente mucoviscidosique. Cette patiente etait porteuse d’une atteinte pulmonaire assez severe avec aspergillose bronchopulmonaire allergique (ABPA), compliquee au moment de l’analyse NGS d’une exacerbation pulmonaire aigue. Le recueil de la contamination environnementale interieure a ete realise grâce au depot d’un piege a poussiere durant 10 semaines dans la chambre de la patiente, selon le protocole etabli en etroite collaboration avec l’equipe du CHU de Besancon [5] . Les resultats et l’interet clinique d’une telle approche sont discutes, en tenant compte des etudes recentes [5] , [6] montrant l’importance de l’exposition fongique comme facteur favorisant la survenue d’une ABPA dans la mucoviscidose.

Early detection of Pseudomonas aeruginosa and early aggressive treatment are recommended to delay chronic infection in cystic fibrosis (CF) patients. The aim of this study was to assess a quantitative PCR (q-PCR) assay for the diagnosis of early P. aeruginosa colonization in 23 young CF patients (group A, age range 7–18 years) and to survey the eradication of P. aeruginosa in 10 young CF patients (group B, age range 5–18 years) after an initial antibiotic treatment. q-PCR results for consecutive sputum samples from each patient during a period of 18 months were compared with bacterial cultures during the same period plus an additional period of 12 months, and with concomitant clinical signs of pulmonary exacerbation. The q-PCR and bacterial cultures were negative for 17 of the 23 patients in group A and six of the 10 patients in group B during the study period. However, consecutive positive q-PCR results were observed for one patient in group A and three patients in group B, while the bacterial cultures for the same sputum sample remained negative. They preceded positive P. aeruginosa bacterial cultures at 7 and 8 months for two patients in group B. These positive results were associated with a worsening of the clinical status of patients, but pulmonary exacerbation appeared non-specific for the diagnosis of early P. aeruginosa colonization since pulmonary exacerbations were observed in patients in whom q-PCR or bacterial culture remained negative. In conclusion, q-PCR may be a useful additional tool to provide information on the P. aeruginosa status of CF patients.

These guidelines aim to standardize the standard operating procedures for the sweat test in newborn cystic fibrosis (CF) screening. They have been implemented by the national Neonatal Screening working group of the French Federation for Cystic Fibrosis. It is recommended that the sweat test be performed when the infant weighs more than 3 kg and is at least 3 weeks of age. Sweat gland secretion is stimulated by transdermal administration of pilocarpine by iontophoresis. Sweat is preferentially collected in a Macroduct coil. Diagnosis of CF is based on the sweat chloride level. A sweat chloride level below 30 mmol/l very probably rules out CF; 60 mmol/l or higher supports the diagnosis of CF. Values between 30 and 60 mmol/l are considered abnormal.

The present multicenter, randomized crossover study compared the safety and efficacy of continuous infusion with those of short infusions of ceftazidime in patients with cystic fibrosis. Patients with chronic Pseudomonas aeruginosa colonization received two successive courses of intravenous tobramycin and ceftazidime (200 mg/kg of body weight/day) for pulmonary exacerbation administered as thrice-daily short infusions or as a continuous infusion. The primary endpoint was the variation in the forced expiratory volume in 1 s (FEV 1 ) during the course of antibiotic treatment. Sixty-nine of the 70 patients enrolled in the study received at least one course of antibiotic treatment. The improvement in FEV 1 at the end of therapy was not statistically different between the two treatment procedures (+7.6% after continuous infusion and +5.5% after short infusions) but was better after continuous ceftazidime treatment in patients harboring resistant isolates ( P < 0.05). The interval between the course of antibiotic treatments was longer after the continuous infusion than after the short infusion of ceftazidime ( P = 0.04). The mean serum ceftazidime concentration during the continuous infusion was 56.2 ± 23.2 μg/ml; the mean peak and trough concentrations during the short infusions were 216.3 ± 71.5 and 12.1 ± 8.7 μg/ml, respectively. The susceptibility profiles of the P. aeruginosa isolates remained unchanged and were similar for both regimens. Quality-of-life scores were similar whatever the treatment procedure, but 82% of the patients preferred the continuous-infusion regimen. Adverse events were not significantly different between the two regimens. In conclusion, the continuous infusion of ceftazidime did not increase its toxicity and appeared to be as efficient as short infusions in patients with cystic fibrosis as a whole, but it gave better results in patients harboring resistant isolates of P. aeruginosa .

Repeated intravenous antibiotic therapy (IVAT) against chronic pulmonary infection with Pseudomonas aeruginosa is often necessary in cystic fibrosis patients (CF). The aim of this study was to monitor kinetics of degradation of pulmonary and nutritional status after IVAT in CF patients.Lung function, nutritional status and physical activity (PA) were measured for 21 CF patients (mean +/- SD age, 16 +/- 1.9 years; 9 boys) who were chronically colonized by P. aeruginosa. Each parameter was measured every 15 days during 3-6 months.Nutritional status as well as PA did not change in the interval of 2 IVAT. In contrary, lung function worsened with a decrease of -14.6% of the FEV(1) (P0.05).In CF, there is a progressive decrease in lung function without any evident deterioration of nutritional status and PA between two IVAT.

175 Evaluation and management of fungal risk in Cystic Fibrosis: first results of a national French study S. Leroy1, V. Conseil1, B. Coltey2, Y. Lemeille2, S. Dominique3, G. Gargala3, P. Domblides4, I. Accoceberry4, G. Loeuille5, I. Durand-Joly5, A. Fanton6, O. Vagnier6, F. Dalle6, A. Boldron5, C. Llerena2, C. Pinel2, J.L. Ginies7, M. Pihet7, C. Person7, J. Bouchara7, N. Wizla1, C. Marguet3, L. Favenne3, S. Bui4, L. Delhaes1. 1CHRU, Lille, France; 2CHU, Grenoble, France; 3CHU, Rouen, France; 4CHU, Bordeaux, France; 5CHG, Dunkerque, France; 6CHU, Dijon, France; 7CHU, Angers, France

Chronic pulmonary infection by Pseudomonas aeruginosa is observed in 50% of patients with cystic fibrosis and requires the use of recurrent intravenous therapy. A decrease of resting energy expenditure (REE) and an increase of physical activity (PA) after intravenous anti-P. aeruginosa therapy (IVAT) is observed while total energy expenditure (TEE) does not change. A decrease in the energetic cost of physical activity (ECPA) could be hypothesized but has never been studied. Our aim was to assess the evolution of ECPA after home IVAT in both standardized condition at hospital and in free-living condition twice before and after IVAT. Sixteen CF patients (nine boys, seven girls) chronically colonized by P. aeruginosa with a mean age of 12.1+/-2.3 years (range 7.1-14.6) were studied before and after IVAT. Each patient passed throughout a visit in hospital: weight, height and fat-free mass were measured. Then, energy expenditure (EE) measured by indirect calorimetry and heart rate (HR) were simultaneously recorded at different levels of PA: REE, and at different intensity of physical activities on a cycloergometer using an incremental increase of the power brake force. Physical activity energy expenditure (PAEE) was computed in laboratory condition using PAEE=EE-BEE (basal energy expenditure). Linear regression between PAEE and power brake force was fitted for each patient before and after IVAT. ECPA in standardized conditions was compared at different range of power brake force using area under the curve (AUC). After coming back at home, 24 h TEE using the heart rate monitoring technique and PA by triaxial accelerometry were simultaneously measured in free-living condition for 24 h during a school day. ECPA in free-living conditions was compared by the ratio PAEE:PA where PAEE=DEE-REE (DEE=daily energy expenditure). After IVAT, median AUC between 60 and 90 W in standardized condition decreased significantly by -15.4% (median 14.9, range 8.8-30.3 vs. median 12.6, range 8.5-17.6; P0.05, Wilcoxon rank test) while the decrease for lower range of power work load did not reach significance. Spearman correlation was significant between variations of forced expiratory volume in 1 s and variation of AUC at 30-60 W before and after IVAT in standardized condition. In free-living conditions, ratio PAEE/PA did not vary significantly (median 3.4, range 1.6-6.4 vs. median 2.8, range 1.4-4.8; NS). Our data demonstrate a decrease of ECPA after IVAT in standardized conditions for moderate level of PA (60-90 W), but not in free-living conditions. The decrease of ECPA was probably due to a decrease in the energetic cost of breathing after IVAT, that is particularly relevant to promote PA in CF patients.

Present in 85-90% of patients, pancreatic exocrine insufficiency contributes to growth retardation and delayed puberty in the child, and low weight in the adult. The incidence of hepatic disease varies according to whether one considers the discovery of histological abnormalities at autopsy of patients who have died from other complications (20-70%) or the presence of a focal or multilobular biliary cirrhosis complicated or not by portal hypertension (2-10%). Gastro-oesophageal reflux can contribute to the degradation of the nutritional state and exacerbate the respiratory symptomatology. All deviations of anthropometric parameters (weight/height ratio, body mass index) from standard references are a warning sign and justify nutritional assistance, of which one distinguishes 3 successive stages by chronological order: fractionated oral supplementation, nasogastric enteral nutrition and parenteral nutrition.

Background and Objectives. It is known that Helicobacter pylori can be acquired in early childhood. There is not enough data to know whether or not infected children should be treated. A better knowledge of the natural outcome and implications of H pylori infection may provide evidence that eradication therapy is beneficial in childhood. This prospective study looks at clinical symptoms, endoscopic, microbial, and histologic changes during a 2-year period in infected asymptomatic children. It is hoped that some prognostic indicators will be found that select out the children that later need therapy. Patients and Methods. During epidemiologic study of the prevalence of H pylori infection, 18 children aged 7 ± 4 years (mean ± 1 SD) were discovered to have H pylori infection and enrolled in the 2-year follow-up study. These patients had received no eradication therapy because they were asymptomatic. The follow-up for each patient consisted of an initial assessment, a clinical examination every 6 months, and an endoscopic reevaluation at the end of the first and second years. Gastric mucosal samples were analyzed for bacteriologic and histologic changes. Various factors were initially recorded: individual factors included sex, age, and housing conditions; microbial factors included bacterial load and the presence of the CagA gene. Inflammatory changes were also noted, such as the presence of active gastritis and nodular formation, and these were correlated with the histology which was described using the Sydney classification. Typing polymerase chain reaction-restriction fragment length polymorphism was performed to check the persistence of the same strain of H pyloriin each patient. Results. All of the children were still infected after 2 years with the same strain as in the initial assessment with the exception of 1 child whose infection cleared spontaneously. The density of antral and fundal mucosal colonization with H pylorialso remained stable. There were progressive inflammatory changes in this cohort, particularly between the first and second year (histologic score, 3.5 ± 1.3 vs 5 ± 1). Active antral gastritis occurred in 3 out of 14 and 1 out of 8 children during the first and second year, respectively. Gastritis became active in the fundus in 2 out of 14 and 2 out of 8 children during the same period. Increases in the histologic score were found particularly in male children, and children colonized by cagA− strains of H pylori during the follow-up. The frequency of nodular gastritis significantly rose from 11% (2 out of 18 children) to 64% (9 out of 14 children) after 1 year, and to 80% (8 out of 10 children) after 2 years. Conclusion. These findings demonstrate a deterioration in the histologic features of the gastric mucosa of infected children despite stable H pylori colonization and the absence of symptoms.

Editor,—We read with interest the paper by Dominguez-Munos et al ( Gut 1997; 40 :459–62) describing an optimal test drink in the13C-urea breath test (13C UBT) for the diagnosis of Helicobacter pylori infection. In this study all H pylori negative subjects (adults with dyspeptic symptoms) had a negative result with the 13C UBT (specificity 100%) after different meals. In other studies, using13C UBT to document H pylori infection both in adults and children, the sensitivity of the test ranged from 92 to 100% whereas specificity was usually above 92%.1 2However, no explanation has been given for the occurrence of false positive tests. Methodological bias and problems in defining the cut off value are possible reasons. However, there are …