Elke De Wachter

Microbiology of Bronchoalveolar Lavage Fluid in Children With Acute Nonresponding or Recurrent Community-Acquired Pneumonia: Identification of Nontypeable Haemophilus influenzae as a Major Pathogen

Childhood community-acquired pneumonia (CAP) is a heterogeneous and polymicrobial entity. Using flexible fiberoptic bronchoscopy with bronchoalveolar lavage, we identified nontypeable Haemophilus influenzae as one of the major pathogens involved in recurrent or non-responsive CAP in children.

Inhaled budesonide induced Cushing's syndrome in cystic fibrosis patients, due to drug inhibition of cytochrome P450

Two CF patients developed Cushings syndrome during administration of inhaled budesonide (400 microg/d) with oral itraconazole in one and with clarithromycin in the other patient. Clinical features appeared respectively after 2 and 6 weeks of drug co-administration, with prolonged adrenal suppression, and a slow recovery after ceasing the drugs. Inhibitors of the cytochrome P450 interfere with the metabolism of corticosteroids. Combination of these drugs even with moderate doses of budesonide should be closely monitored.

Rapidly developing Cushing syndrome in a 4-year-old patient during combined treatment with itraconazole and inhaled budesonide.

A 4-year-old boy with cystic fibrosis developed hypertension, rapid weight gain and a moon face 2 weeks after starting a combined treatment of oral itraconazole and inhaled budesonide for a suspected allergic bronchopulmonary aspergillosis. Adrenal suppression was documented and found to persist 3 months after stopping this combined treatment. Conclusion:to the best of our knowledge, this is the first time that an iatrogenic Cushing syndrome in a young child with cystic fibrosis after such combined treatment is reported. The inhibition of cytochrome P4503A by intraconazole and a higher glucocorticoid tissue sensitivity is suggested as the underlying mechanism.

Eradication of chronic methicillin-resistant Staphylococcus aureus infection in cystic fibrosis patients. An observational prospective cohort study of 11 patients

BACKGROUND Chronic airway infection with methicillin-resistant Staphylococcus aureus (MRSA) in patients with cystic fibrosis (CF) is an increasing clinical problem, and therapeutic options are limited. Because chronic infection with MRSA can be associated with accelerated decline in lung function, eradication of MRSA is attempted in most CF centres today. The aim of this observational prospective cohort study was to determine whether it is possible to eradicate MRSA from airways of CF patients using prolonged oral antibiotic combination therapy together with topical decolonization measures. RESULTS Eleven CF patients, (median age: 9 years (range 1-43); median FEV1: 91%pred (95%CI 74%-100%pred)) who were chronically infected with MRSA, were treated daily for six months with rifampicin and fusidic acid orally. This study did not include a patient control group. Two patients had to switch to an alternative schedule, using rifampicin and clindamycin, due to the resistance pattern of MRSA. Topical decolonization measures were applied to all patients and included mupirocin-containing nasal ointment in both nostrils three times daily for five days and chlorhexidine hair and body wash once daily for five days. Microbiological eradication was achieved in all patients at the end of the six-month eradication protocol, even when significant time (range 18 months to 9 years) had elapsed since initial isolation. In only one patient MRSA reappeared in the six-month follow-up period after the initial study period. Side-effects, like nausea, vomiting and diarrhoea were seen in five out of eleven patients, but did not lead to therapy cessation. CONCLUSION Chronic MRSA infection can be eradicated from respiratory tract samples using a six month dual antibiotic regimen and topical MRSA decolonization measures.

Comparative bone status assessment by dual energy X-ray absorptiometry, peripheral quantitative computed tomography and quantitative ultrasound in adolescents and young adults with cystic fibrosis

PURPOSE Quantitative ultrasound bone sonometry (QUS) might be a promising screening method for cystic fibrosis (CF)-related bone disease, given its absence of radiation exposure, portability of the equipment and low cost.The value of axial transmission forearm QUS in detecting osteopenia in CF was therefore studied. METHODS We investigated the application of QUS in the evaluation of bone status in a group of 64 adolescents (>12 years) and young adults (<40 years) with CF in a comparison with a dual X-ray absorptiometry (DXA) of the whole body and peripheral quantitative computed tomography (pQCT) of the radius at 4% and 66% sites. RESULTS Mean (SD) Z-scores of speed of sound (SOS), whole body bone mineral content (BMC), radial trabecular bone mineral density (BMD), and radial cortical BMD were respectively -0.31 (0.78), -0.09 (1.28), 0.10 (1.16) and -0.62 (2.88). The pQCT determined bone geometry values (cortical bone area and cortical thickness) were more depressed than the BMD data. QUS had a sensitivity and specificity of respectively 0% and 96% for diagnosing osteopenia (based on a whole body BMC Z-score<-2). CONCLUSIONS QUS cannot replace DXA, but can screen out patients with normal bone mass. Further and larger studies are needed to examine if QUS may reflect other aspects than bone mass, or if it is possible to improve its sensitivity by supplementing the SOS results with clinical risk factors.

Comparison of culture and qPCR for the detection of Pseudomonas aeruginosa in not chronically infected cystic fibrosis patients

BackgroundPseudomonas aeruginosa is the major respiratory pathogen causing severe lung infections among CF patients, leading to high morbidity and mortality. Once infection is established, early antibiotic treatment is able to postpone the transition to chronic lung infection. In order to optimize the early detection, we compared the sensitivity of microbiological culture and quantitative PCR (qPCR) for the detection of P. aeruginosa in respiratory samples of not chronically infected CF patients.ResultsIn this national study, we followed CF patients during periods between 1 to 15 months. For a total of 852 samples, 729 (86%) remained P. aeruginosa negative by both culture and qPCR, whereas 89 samples (10%) were positive by both culture and qPCR.Twenty-six samples were negative by culture but positive by qPCR, and 10 samples were positive by culture but remained negative by qPCR. Five of the 26 patients with a culture negative, qPCR positive sample became later P. aeruginosa positive both by culture and qPCR.ConclusionBased on the results of this study, it can be concluded that qPCR may have a predictive value for impending P. aeruginosa infection for only a limited number of patients.

Pulmonary Disease in Cystic Fibrosis: Assessment with Chest CT at Chest Radiography Dose Levels

PURPOSE To investigate a computed tomographic (CT) protocol with iterative reconstruction at conventional radiography dose levels for the assessment of structural lung abnormalities in patients with cystic fibrosis ( CF cystic fibrosis ). MATERIALS AND METHODS In this institutional review board-approved study, 38 patients with CF cystic fibrosis (age range, 6-58 years; 21 patients <18 years and 17 patients >18 years) underwent investigative CT (at minimal exposure settings combined with iterative reconstruction) as a replacement of yearly follow-up posteroanterior chest radiography. Verbal informed consent was obtained from all patients or their parents. CT images were randomized and rated independently by two radiologists with use of the Bhalla scoring system. In addition, mosaic perfusion was evaluated. As reference, the previous available conventional chest CT scan was used. Differences in Bhalla scores were assessed with the χ(2) test and intraclass correlation coefficients ( ICC intraclass correlation coefficient s). Radiation doses for CT and radiography were assessed for adults (>18 years) and children (<18 years) separately by using technical dose descriptors and estimated effective dose. Differences in dose were assessed with the Mann-Whitney U test. RESULTS The median effective dose for the investigative protocol was 0.04 mSv (95% confidence interval [ CI confidence interval ]: 0.034 mSv, 0.10 mSv) for children and 0.05 mSv (95% CI confidence interval : 0.04 mSv, 0.08 mSv) for adults. These doses were much lower than those with conventional CT (median: 0.52 mSv [95% CI confidence interval : 0.31 mSv, 3.90 mSv] for children and 1.12 mSv [95% CI confidence interval : 0.57 mSv, 3.15 mSv] for adults) and of the same order of magnitude as those for conventional radiography (median: 0.012 mSv [95% CI confidence interval : 0.006 mSv, 0.022 mSv] for children and 0.012 mSv [95% CI confidence interval : 0.005 mSv, 0.031 mSv] for adults). All images were rated at least as diagnostically acceptable. Very good agreement was found in overall Bhalla score ( ICC intraclass correlation coefficient , 0.96) with regard to the severity of bronchiectasis ( ICC intraclass correlation coefficient , 0.87) and sacculations and abscesses ( ICC intraclass correlation coefficient , 0.84). Interobserver agreement was excellent ( ICC intraclass correlation coefficient , 0.86-1). CONCLUSION For patients with CF cystic fibrosis , a dedicated chest CT protocol can replace the two yearly follow-up chest radiographic examinations without major dose penalty and with similar diagnostic quality compared with conventional CT.

Gastric emptying and gastro-oesophageal reflux in children with cystic fibrosis☆

BACKGROUND Gastro-oesophageal reflux (GOR) is common in patients with cystic fibrosis (CF). The aim of this study was to investigate the relationship between gastric emptying (GE) and GOR in children with CF. METHODS Multichannel intraluminal impedance-pH monitoring (MII-pH) to measure GOR and GE breath test (GEBT) to measure GE were performed in 28 children with symptoms suggestive for GOR disease (GORD) (group 1). GEBT was performed in another 28 children with/without GOR symptoms who agreed to undergo GEBT but not MII-pH (group 2). RESULTS In group 1, we found increased acid GOR (AGOR) in 46.4% and delayed GE (DGE) in 21.4% but no relationship between increased AGOR and DGE. There was no DGE in group 2. We found DGE in 10.7% and rapid GE in 12.5% of the whole group. CONCLUSIONS Almost half of the children with CF and symptoms suggestive for GORD have increased AGOR and almost a quarter has DGE. However, there was no relation between GOR and GE.

Milk protein and Oil-Red-O staining of alveolar macrophages in chronic respiratory disease of infancy.

Aspiration is a suspected cause of chronic respiratory disease in infants. We assessed the probability of aspiration by immunocytochemical staining of alveolar macrophages for milk proteins (α‐lactalbumin and β‐lactoglobulin) and compared these findings with the Oil‐Red‐O staining score. Broncho‐alveolar lavage (BAL), 24‐hr esophageal pH‐measurement and/or gastro‐esophageal scintigraphy were performed in 111 children. Seventy‐nine patients were enrolled. Ten exclusively soya milk formula fed children served as a control group. Individual scores, expressed as the mean percentage of positive staining macrophages counted by three blinded authors were made. Relying on the control group, a positive score was defined as a value higher than 1%. A positive score was found in 26% (18/69). Forty‐four percent (8/18) of them had positive gastro‐esophageal reflux (GER) tests. In 61% (11/18) a concomitant diagnosis of laryngo‐/tracheomalacia was made. A positive score was found in 48% (11/23) of patients with laryngo‐/tracheomalacia, compared to 15% (7/46) in infants with normal laryngeal and tracheal anatomy. No correlation was found between the immunocytochemical staining score for milk proteins and the Oil‐Red‐O staining score. We conclude that assuming the 1% criterion, persistent respiratory symptoms were associated with a positive immunostaining score, suggestive for aspiration, in 26% of infants, in 48% in case of concomitant laryngo‐ and/or tracheomalacia and in 15% of infants with normal laryngeal and tracheal anatomy. No correlation was found between the immunocytochemical staining score for cow milk proteins and the Oil‐Red‐O staining score. Pediatr Pulmonol. 2010;45:1213–1219.

Isolated tracheoesophageal fistula in a 10-year-old girl.

Isolated tracheoesophageal fistula (H-TOF) is a rare type of tracheoesophageal anomaly and is in most cases diagnosed in the neonatal period because of choking and cyanosis during feeding. Diagnosis may be delayed even until adulthood because of nonspecific and sometimes intermittent symptoms, and because false-negative results of all diagnostic tools are not uncommon. We report a 10-year-old child with H-TOF, whose symptoms had nearly disappeared completely between the ages of 4 and 10 years. Diagnosis was only possible after the recurrence of the symptoms at the time of an episode of bronchitis, profound interrogation of the child’s medical history, and questioning of the results of a former diagnostic work-up. In this article, we discuss the potential pitfalls in both clinical diagnosis and diagnostic work-up.