Long-term use of tube feeding in children with cystic fibrosis: results from two Belgian CF centers.

BACKGROUND: Enteral tube feeding (ETF) is often used in an attempt to optimize the nutritional status. The aim of this study was to observe the long term effect of ETF and to compare the start of ETF with the current European guidelines on nutrition care in CF. METHOD: From all patients who received ETF (ETFp) between February 2000 and September 2016 in the Ghent University Hospital (GUH) or Brussels University Hospital (BUH), z-scores for body weight (W), height (H), growth velocity (GV) and BMI, FEV1%, and FVC% were retrospectively collected from the patients' medical record, 3 years before and 5 years after the year of ETF initiation. Gender, age, and pancreatic status matched controls were selected from the GUH database. RESULTS: All baseline (T0) measurements in ETFp were worse compared to controls. Only 11% of the controls had a Hz < -1.6 compared 58% of the ETFp. After the initiation of ETF a rapid weight gain was noted until the second year (T + 2:-1.9 (-2.8; -1.0) vs. T0:-2.7 (-3.2; -2.1) (p = 0.01) with a stabilization afterwards. A rapid GVz increase was noted at T + 1:1.0 (-0.8; 1.9) vs. T0:-1.5 (-2.0;-0.3). After the start of ETF until T + 3, a stabilization of FEV1% was noted. However, compared to controls, it remained significantly lower (p < 0.05). CONCLUSION: ETF as a nutritional intervention has its effect on weight, height, GV, and BMI. To our knowledge this is the first study that describes the evolution of growth in ETFp. The effect on GV argues for a faster introduction of ETF in malnourished children with CF.

Gastro-intestinal manifestations in cystic fibrosis patients.

Cystic fibrosis (CF) is a life-limiting disorder caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR). This defective chloride channel, present in different organ systems such as respiratory system, gastrointestinal tract, reproductive system and sweat glands, disturbs the ion and water transport over the membranes leading to the well known CF symptoms. CF has outgrown paediatric care, as half of CF patients are currently adults. The CF gastrointestinal tract has its own particularities. Some gastrointestinal manifestations are the direct consequence of the CFTR defect whilst others are secondary to treatment. The gastrointestinal diseases are classified according to the way they usually present in symptoms at diagnosis, acute and chronic abdominal pain and silently evolving conditions. (Acta gastroenterol. belg., 2016, 79, 481-486).

Tuberculin skin test versus interferon-gamma release assays for the diagnosis of tuberculosis infection.

OBJECTIVE: Accurate detection of latent tuberculosis infection (LTBI) is becoming increasingly important due to the increasing use of immunosuppressive medications and the human immunodeficiency epidemic, which have increased the risk for reactivation to active tuberculosis (TB) infection. LTBI is detected by tuberculin skin test (TST) and interferon-gamma release assays (IGRAs). The latter include T-SPOT(®).TB (Oxford Immunotec) and QuantiFERON(®)-TB Gold In-Tube (QFT-GIT; Cellestis). We examined the value of TST versus IGRAs in the diagnosis of TB infection by meta-analysis based on data derived from a systematic literature review. METHODS: PubMed was searched for articles in English published between January 2010 and July 2012 in which TST and IGRA were performed simultaneously in individuals with and without active TB infection. A random effect model meta-analysis was performed to determine pooled sensitivity and specificity values for TST, T-SPOT.TB, and QFT-GIT. Owing to the absence of a gold standard for the diagnosis of LTBI, active TB infection was used as a surrogate for LTBI. RESULTS: Nineteen studies were included. T-SPOT.TB was significantly more sensitive [90% (95% confidence interval: 85-95) versus 64% (46-81)] than TST. The specificity of T-SPOT.TB was higher than the specificity of TST, but there was overlap between confidence intervals [77% (68-85) versus 57% (41-72)]. QFT-GIT seemed to be more sensitive than TST [75% (61-86) versus 64% (48-78)] but similarly specific [71% (62-86) versus 70% (57-81)]. CONCLUSIONS: IGRAs, especially T-SPOT.TB, are more effective at detecting TB infection than TST. Despite their higher cost, they have added value and can be requested in addition to TST.

Achromobacter xylosoxidans induced bronchiolitis obliterans in cystic fibrosis.

We report a 12-year-old boy with progressive bronchiolitis obliterans caused by Achromobacter xylosoxidans (Ax) colonization after liver transplantation, resulting in a steep decline in lung function.

Genetic variations in toll-like receptor pathway and lung function decline in Cystic fibrosis patients.

The toll-like receptor (TLR) family maintains pulmonary homeostasis by pathogen recognition, clearance and regulation of inflammation. Genes affecting inflammation response play a key role in modifying Cystic fibrosis (CF) lung disease severity. We assessed the impact of single nucleotide polymorphisms (SNPs) of TLR genes (TLR1 to TLR10, CD14, lipopolyssacharide-binding protein (LBP)) on lung function in CF patients. Each SNP was tested for time-dependent effect on FEV1, using six genetic models. In addition, we investigated associations between SNP genotypes and extreme subject specific slopes of FEV1 decline. Variant alleles of polymorphisms of TLR2 rs1898830, rs5743708, and rs3804100 demonstrated a consistent association with lung disease severity (p = 0.008, p = 0.006 and p = 0.029 respectively). Patients homozygous for variant C allele of TLR5 polymorphism rs5744174 are more frequently associated with extreme fast FEV1 decline (OR: 20 (95% Confidence Interval:1.85-216.18)). Patients homozygous AA for TLR1 polymorphism rs5743551 are more frequently associated with faster decline of FEV1 compared to heterozygous genotype (OR:7.33 (95% CI:1.63-33.11). Our findings indicate that variations in TLR1, TLR2 and TLR5 genes may influence CF lung function decline. Further functional analysis is required to provide new insights into the pathogenesis of TLRs in CF lung disease severity.

Polymorphisms in the lectin pathway genes as a possible cause of early chronic Pseudomonas aeruginosa colonization in cystic fibrosis patients.

Genes of innate immunity may be involved in early onset of chronic Pa (Pseudomonas aeruginosa) colonization (cPaC) in cystic fibrosis (CF) patients. We studied 19 single nucleotide polymorphisms (SNPs) in 5 genes coding for proteins of the lectin complement pathway: MBL2 (Mannose binding lectin 2), MASP 1, 2, 3 (MBL-associated serine Protease) and FCN 1, 2 (Ficolin) gene in 96 CF patients. Association survival analysis using different genetic models was performed looking for an association between SNPs and age at onset of cPaC. CF patients who are MBL deficient are earlier chronic Pa colonized compared to MBL sufficient patients. Also patients with MBL2 genotype YO/YO, YO/XA, XA/XA, YA/YO and YA/XA are earlier chronic Pa colonized. CF patients heterozygous or homozygous for mutant alleles of two linked SNPs in the FCN1 gene (rs2989727 and rs1071583) are earlier colonized with Pa. Similarly, earlier onset of Pa colonization is seen in CF patients heterozygous for linked SNPs of FCN2 gene (rs7865453 and rs7851696) and MASP3 gene (rs7851696). Variants in MBL2, FCN1, FCN2 and MASP3 genes are significantly associated with earlier onset of chronic P. aeruginosa colonization.

Malacia, inflammation and bronchoalveolar lavage culture in children with persistent respiratory symptoms.

In children with persistent respiratory symptoms despite regular anti-asthma inhalation treatment, diagnostic investigations to exclude underlying disease are warranted. 124 children were prospectively enrolled, and 24-h oesophageal pH measurement and fibreoptic bronchoscopy with bronchoalveolar lavage (BAL) were performed. BAL fluid (BALF) was processed for neutrophil counting and bacterial culture. Inflammation of the respiratory mucosa was assessed. A structural abnormality of the central airways was found in 47% of subjects (40% females). In 19% of subjects, neither anatomical anomalies nor inflamed respiratory mucosa were observed, whereas in 64%, definite macroscopic mucosal inflammation was observed. Inflammation of the respiratory mucosa was associated with a significantly higher percentage of neutrophils in the BALF: median (interquartile range) 48 (14-82)% compared with 7 (0-16)% (p<0.025). A positive BALF culture was found in 62% of the infants with mucosal inflammation compared with 25% in the group without inflammation (p<0.016). 56% of the BALF samples were positive for bacterial culture. In children with persistent respiratory symptoms, nearly half have anatomical anomalies of the central airways. In 62% of the children with mucosal inflammation, a positive BAL culture and a significantly higher percentage of BALF neutrophils were detected.

Exposure to pets and the association with sensitization and allergic disease in Belgian schoolchildren.

Prolonged domestic exposure, from birth on, to dog allergen may protect against sensitization.

Body mass index in Belgian schoolchildren and its relationship with sensitization and allergic symptoms.

Results of studies of the influence of body mass index (BMI) on the allergic status are controversial. As a part of the Aalst Allergy Study, we assessed the prevalence of the different BMI categories (underweight, normal weight, overweight, and obesity) and a possible association between BMI and atopy in 1576 unselected Belgian schoolchildren, aged from 3.4 to 14.8 yr. BMI was used to determine weight status. Skin prick testing with the most common aeroallergens was performed. A parental questionnaire documented data on respiratory and allergic disorders, demographic characteristics and other potential risk factors for sensitization. Among the total children, 4.1% of the children were underweight, 14.5% were overweight, and 7.4% were obese. More girls than boys were overweight (p = 0.015). In the group of children older than 12 yr, we found more overweight (p = 0.03) and obese (p = 0.004) girls, and more obese boys (p = 0.004) than in the younger age groups. In contrast with reports in the literature, an increased prevalence of allergic sensitization in underweight girls only [adjusted odd ratio (OR(adj)) = 2.9, 95% confidence interval (CI): 1.3-6.4] was documented. A strong association between obesity and exercise-induced respiratory symptoms was found in both boys (OR(adj) = 14.5, 95% CI: 2.9-73.3) and girls (OR(adj) = 4.9, 95% CI: 1.3-17.4). No correlations with allergic respiratory symptoms, eczema, or rhinoconjunctivitis could be documented.

Early referral to cystic fibrosis specialist centre impacts on respiratory outcome.

BACKGROUND: Published studies concerning the impact of specialist care on lung disease in cystic fibrosis remain limited and most are either biased due to comparison with historical controls and/or underpowered. METHODS: In this retrospective multicentric study, data from all CF children fulfilling the following criteria were collected: 1) Age 6-<18 at the end of 2003; 2) diagnosis before 8 y; 3) follow-up in an accredited CF Belgian centre; 4) at least 1 spirometry and respiratory culture available for 2003. Group A included children referred > or =2 years after the diagnosis. Patients from Group A were then matched with a single early referred patient on the basis of 2 criteria: same centre, as closest age as possible (Group B). RESULTS: Data from 217 children were collected (Group A: 67/217). Late referred patients had a lower FEV(1) (77.2%+/-22.4 vs 86.7% pred.+/-19.4, p=0.01) and a higher prevalence of Pseudomonas aeruginosa (38.6 vs 17.5%, p<0.05). CONCLUSION: In this population of CF children, a delay of 6.1 y (vs 0.1 y) between diagnosis and referral to a specialist clinic resulted in poorer respiratory outcome at age 13.

Pseudomonas aeruginosa in the home environment of newly infected cystic fibrosis patients.

The source of acquisition of Pseudomonas aeruginosa in cystic fibrosis (CF) patients remains unknown. Patient-to-patient transmission has been well documented but the role of the environment as a source of initial infection is as yet unclear. In the present study, the origin of the first P. aeruginosa isolate in CF patients was investigated by comparing the P. aeruginosa genotype(s) from newly infected patients with genotypes of P. aeruginosa isolates from the home environment and from other patients from the same CF centre. A total of 50 newly infected patients were studied. P. aeruginosa could be cultured from 5.9% of the environmental samples, corresponding to 18 patients. For nine of these, the genotype of the environmental P. aeruginosa isolate was identical to the patient's isolate. In total, 72% of the environmental P. aeruginosa isolates were encountered in the bathroom. Patient-to-patient transmission within the CF centre could not be ruled out for three patients. In summary, a low prevalence of Pseudomonas aeruginosa was found in the home environment of the newly infected cystic fibrosis patients. The bathroom should be targeted in any preventive cleaning procedures. An environmental source of the new infection could not be ruled out in nine patients.

The influence of bedroom environment on sensitization and allergic symptoms in schoolchildren.

BACKGROUND: Bedroom conditions have been associated with an increased risk of allergy. OBJECTIVE: The aim of this study was to evaluate the relationship between sleeping environment and sensitization and allergic symptoms in schoolchildren. METHODS: A cross-sectional study, the Aalst Allergy Study, was performed in an unbiased community population of 2021 Belgian schoolchildren, aged 3.4 to 14.8 years. Skin prick testing was performed with the most common aeroallergens and bedroom conditions (presence of stuffed toys, type of flooring, and bedding material) were documented through a parental questionnaire. RESULTS: The presence of stuffed toys in the bedroom was associated with a lower prevalence of overall sensitization and a lower prevalence of conjunctivitis and allergic respiratory symptoms. That effect was almost exclusively present in children with a positive family history of atopy and was more pronounced as the number of stuffed toys increased. A significantly lower prevalence of overall sensitization, sensitization to house dust mite, and wheezing was documented in children with nonsynthetic bedding materials. That effect was exclusive to children with a positive family history of atopy. Type of flooring was not associated with sensitization or allergic symptoms. CONCLUSION: Our data suggest that bedroom exposure to stuffed toys and nonsynthetic bedding materials may have a protective effect against sensitization and allergic symptoms in genetically predisposed children. Confirmation of these findings will require further prospective studies that include measurement of levels of mite allergens and endotoxins and assessment of the time, degree, and duration of the exposure.

Smoking in young people with asthma.

BACKGROUND: Modern guidelines for the management of asthma state that asthmatic patients should be strongly advised not to smoke. However, it remains unclear to what extend young people with asthma actually behave like this. This study compares the prevalence of daily smoking between 15-year adolescents with diagnosed asthma and without asthma, and evaluates to what extent risk factors for smoking play a comparable role in the smoking behaviour of these two groups. METHODS: The study is part of the 2001-2002 international HBSC study. Besides questions about health behaviour, individual and social resources, a set of asthma questions were included in six countries. RESULTS: Adolescents with diagnosed asthma are more likely to be daily smokers than non-asthmatic adolescents. In asthmatic and non-asthmatic adolescents, similar associations with risk factors are found for daily smoking (drunkenness, cannabis use, low life satisfaction, spending evenings with friends, having smoking parents and peers). Diagnosed asthmatics are more prone to score high on these factors than non-asthmatics. CONCLUSIONS: Smoking in adolescents with asthma is a public health problem. Smoking prevention efforts directed towards young people should pay attention to young people with asthma and the curative sector should increase their efforts to motivate asthmatic adolescents not to smoke.

Beclometasone dipropionate extrafine aerosol versus fluticasone propionate in children with asthma.

Beclometasone dipropionate (BDP) extrafine is a hydrofluoroalkane-based, chlorofluorocarbon (CFC)-free inhalation aerosol. This study was conducted to determine whether BDP extrafine and CFC-fluticasone proprionate (FP) aerosols were equivalent in terms of efficacy and tolerability in children with symptomatic mild-to-moderate asthma. Male and female patients (aged 5-12 yr) with an asthma diagnosis for > or =3 months, peak expiratory flow (PEF) > or =60% of predicted normal and suboptimal asthma control were randomised to double-blind treatment with BDP extrafine 200 microg day(-1) (n=139) or CFC-FP 200 microg day(-1) (n=141) for up to 18 weeks. After 6 and 12 weeks, study medication was 'stepped down' to 100 and 50 microg day(-1), respectively, if patients had achieved good asthma control. Patients with poor asthma control discontinued from the study and those with intermediate control continued in the study but did not undergo a dose reduction. The estimated treatment difference in morning PEF% predicted at 6 weeks was -1.9% (90% CI -4.9, 1.0). There was a trend towards a greater increase in forced vital capacity (% predicted) in the BDP extrafine group (5.3 versus 0.4%; p=0.084). A 'step-down' in therapy to 100 microg day(-1) was possible in 36% and 42% of patients in the BDP extrafine and CFC-FP groups, respectively, at 6 weeks. Both drugs were well tolerated. BDP extrafine and CFC-FP aerosols were equally effective at improving asthma control in children with mild-to-moderate asthma at the same daily dose.

Survey of Pseudomonas aeruginosa genotypes in colonised cystic fibrosis patients.

The current authors aimed to examine whether cystic fibrosis (CF) patients in Belgium shared Pseudomonas aeruginosa genotypes and to compare the genotypes of isolates from the same patients during two consecutive years. A Belgian databank of the P. aeruginosa genotypes of all colonised CF patients was created. Sputum samples from a total of 276 P. aeruginosa colonised patients during 2003, and from a subgroup of 95 patients in 2004, were analysed. Patients were asked about any social contact between each other by questionnaire. All P. aeruginosa isolates exhibiting different colonial morphology on McConkey agar were first genotyped using arbitrarily primed PCR, whereafter single representatives of each randomly amplified polymorphic DNA-type were further genotyped by fluorescent amplified fragment length polymorphism analysis. In the 213 patients from whom P. aeruginosa could be cultured (resulting in 910 isolates), a total of 163 genotypes were found. The majority (75%) of patients harboured only one genotype. In most of the limited number of clusters, previous contacts between patients could be suspected. In 80% of the patients studied during both years, P. aeruginosa genotype remained unchanged. In conclusion, most colonised cystic fibrosis patients harbour only one Pseudomonas aeruginosa genotype, despite showing different colonial morphotypes. The number of clusters is limited, and most patients seem to retain the same genotypic strain during both years.

Epidemiology of Pseudomonas aeruginosa in a cystic fibrosis rehabilitation centre.

Pseudomonas aeruginosa is the leading pathogen in cystic fibrosis (CF) lungs. Since there is great concern about clonal spread in CF centres, this study examined the P. aeruginosa genotypes of colonised residents of a CF rehabilitation centre. The isolates from the sputum of 76 P. aeruginosa-colonised patients were genotyped by fluorescent amplified fragment length polymorphism on arrival and departure. A total of 71 different P. aeruginosa genotypes were identified from 749 isolates. Forty-nine patients had one genotype, 20 had two genotypes and seven had three. Forty-four patients had one or more genotypes in common with other patients (i.e. cluster types). Thirty-two patients were colonised by a single genotype not shared by any other patient. Thirty-eight of the 44 patients with a cluster type already carried their cluster type strain(s) on arrival. Patient-to-patient transmission could not be excluded for eight patients. For five of these, this infection was transient. None of the environmental P. aeruginosa isolates had a genotype similar to the patients' genotypes. In summary, most patients were colonised by only one or two P. aeruginosa genotypes and the risk of persistent patient-to-patient transmission was low during the study period (4%). Most patients with a cluster-type strain carried this strain on arrival, indicating that transmission could have happened in the past. No environmental contamination could be established.

Oral health and habits in children with asthma related to severity and duration of condition.

AIM: This study was designed to examine the oral health status of asthmatic children and to compare the oral health condition and habits of different groups of asthmatic children. METHODS: 140 asthmatic children were involved in the present study. Of those, 30 were younger than 7 years of age, 73 were between 7 and 12, 37 were older than 12. Dental caries was scored according to the guidelines of the BASCD. No radiographs were taken. The gingival health and the amount of plaque were assessed using the bleeding index described by Mühleman and Son [1971] and the plaque index of Silness and Löe [1964] respectively. To differentiate between the asthmatic children three explanatory variables were used: the time the asthmatic symptoms had lasted, the exposure time to the medication and the severity of the asthmatic condition. Finally the parents and children were asked to fill in a questionnaire referring to oral health habits. RESULTS: The mean dmft was 1.99 (SD+/-2.74) and the mean DMFT was 1.10 (SD+/-1.98). Non-parametric correlation and multiple logistic regression analyses showed no significant difference between the caries (dmft/s, DMFT/S), the gingival health (bleeding index) and plaque indices and the three explanatory variables. The impact of possible compensatory factors as oral hygiene and dietary habits was of no significant importance. CONCLUSION: This analysis revealed that neither the period (of the disease and the medication) nor the severity of the asthma had a significant influence on the risk of caries and gingivitis in asthmatic children. No reported oral health and dietary habits could explain this lack of correlation.

Asphyxiating tracheal bronchogenic cyst.

We report on a 7-month old infant with severe respiratory distress secondary to a paratracheal bronchogenic cyst. Respiratory relief was achieved by transtracheal puncture of the cyst. Surgical removal of the cyst was performed 1 week later because of radiological evidence of reaccumulation of fluid.

[Immune deficiencies: diagnosis, management, some perspectives]. / Déficits immunitaires primaires: diagnostic, prise en charge, quelques perspectives.

Severe primary immunodeficiencies (PID) are rare; their global incidence is comparable to that of childhood leukemia; they include more than 100 different entities. Clinical manifestations are: unusually severe or frequent infections or infections that do not respond to adequate treatment; an increased risk of certain malignancies; sometimes auto-immune manifestations. Delayed diagnosis and management of PID can lead to severe and irreversible complications or to death. PID can become manifest only in the adult; in common variable immune deficiency, the median age at diagnosis is between the 2nd and the 3rd decade of life. PID are often transmitted genetically; recent progresses in molecular biology have allowed more precise and earlier, including antenatal, diagnosis. Molecular treatment of 3 infants with a severe immunodeficiency has recently been achieved in April 2000. Those progresses were mostly based on the study of immunodeficiency databases. We present here the work of a Belgian group specialized in PID; meetings have started in June 1997. This group establishes guidelines for the diagnosis and treatment of PID, adapted to the local situation. The elaboration of a national register of PID is also underway; this has to provide all guaranties of anonymity to patients and families. Such a register already exists at the European level; it has provided the basis for new diagnostic and therapeutic possibilities. The inclusion of Belgian data in this register should allow essential progresses essential for our patients.