Respiratory syncytial virus and recurrent wheeze in healthy preterm infants.

BACKGROUND: Respiratory syncytial virus (RSV) infection is associated with subsequent recurrent wheeze. Observational studies cannot determine whether RSV infection is the cause of recurrent wheeze or the first indication of preexistent pulmonary vulnerability in preterm infants. The monoclonal antibody palivizumab has shown efficacy in preventing severe RSV infection in high-risk infants. METHODS: In the double-blind, placebo-controlled MAKI trial, we randomly assigned 429 otherwise healthy preterm infants born at a gestational age of 33 to 35 weeks to receive either monthly palivizumab injections (214 infants) or placebo (215 infants) during the RSV season. The prespecified primary outcome was the total number of parent-reported wheezing days in the first year of life. Nasopharyngeal swabs were taken during respiratory episodes for viral analysis. RESULTS: Palivizumab treatment resulted in a relative reduction of 61% (95% confidence interval, 56 to 65) in the total number of wheezing days during the first year of life (930 of 53,075 days in the RSV-prevention group [1.8%] vs. 2309 of 51,726 days [4.5%] in the placebo group). During this time, the proportion of infants with recurrent wheeze was 10 percentage points lower in patients treated with palivizumab (11% vs. 21%, P=0.01). CONCLUSIONS: In otherwise healthy preterm infants, palivizumab treatment resulted in a significant reduction in wheezing days during the first year of life, even after the end of treatment. These findings implicate RSV infection as an important mechanism of recurrent wheeze during the first year of life in such infants. (Funded by Abbott Laboratories and by the Netherlands Organization for Health Research and Development; MAKI Controlled Clinical Trials number, ISRCTN73641710.).

The impact of chronic fatigue syndrome on cognitive functioning in adolescents.

Chronic fatigue syndrome (CFS) is characterized by persistent fatigue and severe disability. Most adolescent patients report attention and concentration problems, with subsequent poor performance at school. This study investigated the impact of CFS on intellectual capacity by (1) assessing discrepancies between current intelligence quotient (IQ) and school level and (2) exploring differences in current IQ and pre-CFS school performance, compared with healthy individuals. Current data was cross-sectionally gathered and compared with retrospective pre-CFS school performance data. Fifty-nine CFS adolescents and 40 controls were evaluated on performance on age-appropriate intelligence tests and school level. Current IQ scores of CFS adolescents were lower than expected on the basis of their school level. Furthermore, there was a difference in intelligence performance across time when current IQ scores were compared with pre-CFS cognitive achievement. Healthy controls did not show any discrepancies. CONCLUSION: According to their pre-CFS intelligence assessments, CFS patients started with appropriate secondary school levels at the age of 12. Our data suggest that CFS may be accompanied by a decline in general cognitive functioning. Given the critical age for intellectual development, we recommend a timely diagnosis followed by appropriate treatment of CFS in adolescents. WHAT IS KNOWN: Adolescent chronic fatigue syndrome (CFS) is a debilitating condition with major impact on social and intellectual development. Most patients report concentration problems, with subsequent poor performance at school. Little is known about the influence of CFS on intellectual performances. WHAT IS NEW: IQ scores of CFS adolescents are lower than the IQ scores of healthy peers with an equivalent school level. There is a decrease in intelligence performance across time when current IQ scores are compared with pre-CFS cognitive achievement. Healthy controls do not show any discrepancies between their current IQ, school level and previous cognitive functioning. This suggest that adolescent CFS may be accompanied by a decline in general cognitive functioning.

Effectiveness of internet-based cognitive behavioural treatment for adolescents with chronic fatigue syndrome (FITNET): a randomised controlled trial.

BACKGROUND: Chronic fatigue syndrome is characterised by persistent fatigue and severe disability. Cognitive behavioural therapy seems to be a promising treatment, but its availability is restricted. We developed Fatigue In Teenagers on the interNET (FITNET), the first dedicated internet-based therapeutic program for adolescents with this disorder, and compared its effectiveness with that of usual care. METHODS: Adolescents aged 12-18 years with chronic fatigue syndrome were assigned to FITNET or usual care in a 1:1 ratio at one tertiary treatment centre in the Netherlands by use of a computer-generated blocked randomisation allocation schedule. The study was open label. Primary outcomes were school attendance, fatigue severity, and physical functioning, and were assessed at 6 months with computerised questionnaires. Analysis was by intention to treat. Thereafter, all patients were offered FITNET if needed. This trial is registered, number ISRCTN59878666. FINDINGS: 68 of 135 adolescents were assigned to FITNET and 67 to usual care, and 67 and 64, respectively, were analysed. FITNET was significantly more effective than was usual care for all dichotomised primary outcomes at 6 months-full school attendance (50 [75%] vs 10 [16%], relative risk 4·8, 95% CI 2·7-8·9; p<0·0001), absence of severe fatigue (57 [85%] vs 17 [27%], 3·2, 2·1-4·9; p<0·0001), and normal physical functioning (52 [78%] vs 13 [20%], 3·8, 2·3-6·3; p<0·0001). No serious adverse events were reported. INTERPRETATION: FITNET offers a readily accessible and highly effective treatment for adolescents with chronic fatigue syndrome. The results of this study justify implementation on a broader scale. FUNDING: Netherlands Organisation for Health Research and Development.

Proteins involved in extracellular matrix dynamics are associated with respiratory syncytial virus disease severity.

Severity of respiratory syncytial virus (RSV) infection ranges widely. To what extent the local immune response is involved in RSV disease pathogenesis and which markers of this response are critical in determining disease severity is still a matter of debate. The local immune response was studied in nasopharyngeal aspirates (NPAs) during RSV infection. 47 potential markers of disease severity were analysed in a screening cohort of RSV-infected infants with mild disease at home (n = 8), hospitalised infants (n = 10) and infants requiring mechanical ventilation (n = 7). Results were confirmed in a cohort of infants hospitalised for RSV infection (n = 200). Finally, genetic validation was studied in a cohort of infants hospitalised for RSV infection (n = 465) and healthy controls (n = 930). The concentration of TIMP-1 (tissue inhibitor of metalloproteinase) was higher in the NPAs of hospitalised infants compared with the NPAs of infants at home (1,199 versus 568 ng · mL(-1); p<0.0001). Similar results were found for matrix metalloproteinase (MMP)-3 (765 versus 370 pg · mL(-1); p = 0.004). MMP-3 was confirmed as a marker of disease severity in a larger cohort and MMP3 gene polymorphism rs522616 was associated with severe RSV infection (OR 0.82, p<0.05). In conclusion, extracellular matrix proteinases play an important role in the pathogenesis of RSV bronchiolitis.

Early life lung function and respiratory outcome in the first year of life.

Abnormal early life lung function is related to wheezing in childhood; however, data on the association with cough are not available. We determined the relationship between early life lung function and wheeze and cough during the first year of life, adjusted for other possible risk factors. Infants were participants of the Wheezing Illnesses Study Leidsche Rijn (WHISTLER). Lung function measurements were performed before the age of 2 months. Information on pre- and perinatal factors, general characteristics and anthropometrics were assessed by questionnaires. Follow-up data on respiratory symptoms were assessed by daily questionnaires. 836 infants had valid lung function measurements and complete follow-up data for respiratory symptoms at 1 yr of age. Multivariable Poisson analysis showed that higher values of respiratory resistance (R(rs)) and time constant (τ(rs)) were associated with an increased risk for wheeze and cough during the first year of life. Higher values of respiratory compliance (C(rs)) were associated with a decreased risk for wheeze and cough. R(rs), C(rs) and τ(rs) measured shortly after birth were independently associated with wheeze and cough during the first year of life. As the strength of the relationships were different for wheeze and cough, they should be used as two separate entities.

Gene expression differences in lungs of mice during secondary immune responses to respiratory syncytial virus infection.

Vaccine-induced immunity has been shown to alter the course of a respiratory syncytial virus (RSV) infection both in murine models and in humans. To elucidate which mechanisms underlie the effect of vaccine-induced immunity on the course of RSV infection, transcription profiles in the lungs of RSV-infected mice were examined by microarray analysis. Three models were used: RSV reinfection as a model for natural immunity, RSV challenge after formalin-inactivated RSV vaccination as a model for vaccine-enhanced disease, and RSV challenge following vaccination with recombinant RSV virus lacking the G gene (DeltaG-RSV) as a model for vaccine-induced immunity. Gene transcription profiles, histopathology, and viral loads were analyzed at 1, 2, and 5 days after RSV challenge. On the first 2 days after challenge, all mice displayed an expression pattern in the lung similar of that found in primary infection, showing a strong innate immune response. On day 5 after RSV reinfection or after challenge following DeltaG-RSV vaccination, the innate immune response was waning. In contrast, in mice with vaccine-enhanced disease, the innate immune response 5 days after RSV challenge was still present even though viral replication was diminished. In addition, only in this group was Th2 gene expression induced. These findings support a hypothesis that vaccine-enhanced disease is mediated by prolonged innate immune responses and Th2 polarization in the absence of viral replication.

A systemic neutrophil response precedes robust CD8(+) T-cell activation during natural respiratory syncytial virus infection in infants.

Severe primary respiratory syncytial virus (RSV) infections are characterized by bronchiolitis accompanied by wheezing. Controversy exists as to whether infants suffer from virus-induced lung pathology or from excessive immune responses. Furthermore, detailed knowledge about the development of primary T-cell responses to viral infections in infants is lacking. We studied the dynamics of innate neutrophil and adaptive T-cell responses in peripheral blood in relation to the viral load and parameters of disease in infants admitted to the intensive care unit with severe RSV infection. Analysis of primary T-cell responses showed substantial CD8(+) T-cell activation, which peaked during convalescence. A strong neutrophil response, characterized by mobilization of bone marrow-derived neutrophil precursors, preceded the peak in T-cell activation. The kinetics of this neutrophil response followed the peak of clinical symptoms and the viral load with a 2- to 3-day delay. From the sequence of events, we conclude that CD8(+) T-cell responses, initiated during primary RSV infections, are unlikely to contribute to disease when it is most severe. The mobilization of precursor neutrophils might reflect the strong neutrophil influx into the airways, which is a characteristic feature during RSV infections and might be an integral pathogenic process in the disease.

IL10 family member genes IL19 and IL20 are associated with recurrent wheeze after respiratory syncytial virus bronchiolitis.

Mechanisms underlying the increased risk of recurrent wheeze after respiratory syncytial virus lower respiratory tract infection (RSV LRTI) are unclear. Specifically, information about genetic determinants of recurrent wheeze after RSV LRTI is limited. We performed a candidate gene association study to identify genetic determinants of recurrent wheeze after RSV LRTI. We investigated 346 single nucleotide polymorphisms (SNPs) in 220 candidate genes in 166 Dutch infants hospitalized for RSV LRTI. Logistic regression analysis was used to study associations between genotypes and haplotypes and recurrent wheeze after RSV LRTI. We found associations with recurrent wheeze for SNPs in IL19, IL20, MUC5AC, TNFRSF1B, C3, CTLA4, CXCL9, IL4R, and IL7 genes. Haplotype analysis of the combined IL19/IL20 genotyped polymorphisms demonstrated an inverse association between the TGG haplotype and recurrent wheeze after RSV LRTI. IL19 and IL20 genes were notably associated with recurrent wheeze in infants without asthmatic parents. The association of IL20 SNP rs2981573 with recurrent wheeze was confirmed in a healthy birth cohort. We concluded that genetic variation in adaptive immunity genes and particularly in IL19/IL20 genes associates with the development of recurrent wheeze after RSV LRTI, suggesting a role for these IL10 family members in the etiology of airway disease during infancy.

Fatigue In Teenagers on the interNET--the FITNET Trial. A randomized clinical trial of web-based cognitive behavioural therapy for adolescents with chronic fatigue syndrome: study protocol. [ISRCTN59878666].

BACKGROUND: Chronic Fatigue Syndrome (CFS) is increasingly recognized as a cause of disability and inactivity in adolescents in the Netherlands. CFS is characterized by unexplained fatigue lasting more than 6 months. Cognitive Behavioural Therapy (CBT) has proven to be effective. However, CBT availability for adolescents with CFS is limited and requires special therapeutic skills not always readily available. An alternative to the face-to-face CBT is FITNET, a web-based therapeutic program designed specifically for adolescents diagnosed with CFS, and their parents. This new CBT approach appeals to the modern youth, who grow up with internet as their main source of information. A web-based program offers the opportunity to lower thresholds for the acceptance and realization of healthcare. This treatment can be activated at any chosen time. The communication between patient and therapist can elapse asynchronously. If effective, this web-based program would greatly increase the therapeutic accessibility. METHODS/DESIGN: A randomized clinical trial is currently conducted. One-hundred-forty adolescents aged 12-18 years diagnosed with CFS will be recruited and randomized to one of two groups: FITNET or usual care. After 6 months, the usual care group will have access to the FITNET program. Outcomes will be assessed at baseline, post intervention, and at 6 months follow-up. Primary outcome measures are school presence, fatigue severity, and physical functioning. DISCUSSION: The FITNET study is the first randomized clinical trial which evaluates the effect of web-based CBT versus usual care in adolescents with CFS. The intervention is based on a theoretical existing model of CBT for patients with CFS. The results of this study will provide information about the possibility and efficacy of web-based CBT for adolescents with CFS and will reveal predictors of efficacy. TRIAL REGISTRATION: ISRCTN: ISRCTN59878666 and ClinicalTrials.gov: NCT00893438.

Psychiatric disorders in children and adolescents presenting with unexplained chronic pain: what is the prevalence and clinical relevancy?

The prevalence of psychiatric disorders among children with unexplained chronic pain (UCP) is high in unselected populations and pain clinics, yet the clinical relevance of these disorders in children referred for unexplained pain is not known. This study assessed the prevalence of clinically relevant psychiatric disorders and their predictors in children referred to a children's hospital for UCP. Psychiatry morbidity was assessed in 134 children, aged 8-17 years, using the Diagnostic Interview Schedule for Children-parent version (DISC-P) and the Semi-structured Clinical Interview for Children and Adolescents (SCICA). Clinical relevance was determined using a maladjustment criterion of 61 or lower on the Children's Global Assessment Scale (CGAS). Pain parameters were measured with standardized questionnaires. Results were analysed by logistic regression. According to the DISC-P, 21% of the children had clinically relevant psychiatric disorders, predominantly anxiety disorders (18%). According to the SCICA, 28% of the children had clinically relevant psychiatric disorders, consisting of anxiety, affective, and disruptive disorders (12, 19, and 9%, respectively). Headache (compared to musculoskeletal pain) was an independent clinical predictor of psychiatric morbidity (OR = 3.10; 95% CI 1.07-8.92, p = 0.04/adjusted OR 2.99; 95% CI 1.02-8.74, p = 0.04). In conclusion, clinically relevant psychiatric disorders are common among children and adolescents referred for UCP. Adding a child psychiatrist assessment, treatable affective and disruptive disorders become identifiable. Children with an additional risk are those presenting with headache.

Controlled trial of cycled antibiotic prophylaxis to prevent initial Pseudomonas aeruginosa infection in children with cystic fibrosis.

BACKGROUND: Initial pulmonary Pseudomonas aeruginosa infection in patients with cystic fibrosis (CF) is currently treated with intensive antibiotic therapy. At this stage, inflammation and tissue injury might have already occurred. Moreover, bacterial eradication is not always achieved. Prophylactic treatment against P aeruginosa seemed to have a preventive effect in retrospective studies. A study was undertaken to establish prospectively the effect of cycled prophylactic treatment on prevention of initial P aeruginosa infection in children with CF. METHODS: This 3-year triple-blind randomised controlled trial included 65 children with CF without P aeruginosa infection. Intervention existed of 3-monthly 3-week treatments with oral ciprofloxacin and inhaled colistin or both placebo controls. The primary outcome was P aeruginosa infection. Secondary outcomes were serum anti-Pseudomonas antibodies, pulmonary function, exacerbations, chest x-ray scores, inflammation parameters, respiratory pathogens and antimicrobial resistance. RESULTS: There was no difference in acquisition of P aeruginosa infection between the control and treatment groups (annual incidence 14% vs 11%; HR 0.738, 95% CI 0.299 to 1.822). Anti-Pseudomonas antibodies emerged earlier in the control group, but this difference had disappeared after 3 years. Chronic infection was observed in 19% of controls and 12% of treated patients. Decline in pulmonary function and other clinical outcomes did not differ between the two groups. In the treatment group, significantly fewer Gram-positive bacteria and Enterobacteriaceae were observed but there were more non-P aeruginosa non-fermentative Gram-negative bacteria. Conclusions Three-monthly cycled anti-P aeruginosa prophylaxis does not reduce the risk of initial and chronic infection in P aeruginosa-negative children with CF of all ages. Shifts in bacterial colonisation demand caution. Trial Registration Number ISRCTN 11604593.

Molecular quantification of respiratory syncytial virus in respiratory samples: reliable detection during the initial phase of infection.

Quantitative real-time PCR for the detection of respiratory syncytial virus (RSV) RNA is increasingly used to study the causal role of RSV in lower airway disease. The objective of our study was to evaluate variations in RSV RNA loads at different steps in the RNA quantification process: (i) variation in RSV RNA load within one sample (step 1), (ii) variation in the load in samples from patients who were sampled twice on the same day (step 2), and (iii) variation in the load between simultaneously taken nasopharyngeal aspirate (NPA) samples and tracheal aspirate (TA) samples (step 3). Thirty-two infants with RSV infection at the pediatric intensive care unit (PICU) were included. NPA and TA samples were taken three times a week during ventilation and were not diluted. Intrasample variation (step 1) was shown to be minimal (<0.5 log(10) particles/ml). Intraday variation (step 2) was the lowest for samples with high viral loads (95% limits of agreement, -1.3 to +0.9 log(10)), whereas it increased for samples with relatively lower viral loads (viral load, <6.0 log(10) particles/ml; n = 138 sample pairs from 20 patients). RSV loads in NPA and TA samples (step 3) were found to be the most comparable during the early phase of infection (95% limits of agreement, -1.5 to +1.4 log(10)). The variation increased during the late phase of infection (i.e., in follow-up samples), with the loads in NPA samples remaining significantly higher than the loads in TA samples (n = 138 sample pairs from 31 patients). In conclusion, quantitative detection of RSV RNA in undiluted mucus is a reliable method to quantify viral loads. Nasopharyngeal aspirate samples collected in the initial phase of infection can be used to predict RSV RNA loads in the lower airways.

Respiratory syncytial virus-induced activation and migration of respiratory dendritic cells and subsequent antigen presentation in the lung-draining lymph node.

In the respiratory tract, different dendritic cell (DC) populations guard a tight balance between tolerance and immunity to infectious or harmless materials to which the airways are continuously exposed. For infectious and noninfectious antigens administered via different routes, different subsets of DC might contribute during the induction of T-cell tolerance and immunity. We studied the impact of primary respiratory syncytial virus (RSV) infection on respiratory DC composition in C57BL/6 mice. We also tracked the migration of respiratory DC to the lymph nodes and studied antigen presentation by lung-derived and lymph node-resident DC to CD4(+) and CD8(+) T cells. We observed a massive influx of mainly CD103(-) CD11b(high) CD11c(+) conventional DC (cDC) and plasmacytoid DC during the first 7 days of RSV infection, while CD103(+) CD11b(low) CD11c(+) cDC disappeared from the lung. The two major subsets of lung tissue DC, CD103(+) CD11b(low) CD11c(+) and CD103(-) CD11b(high) CD11c(+) cDC, both transported RSV RNA to the lung-draining lymph node. Furthermore, these lung-derived cDC subsets as well as resident LN DC, which did not contain viral RNA, displayed viral antigen by major histocompatibility complex class I and class II to CD8(+) and CD4(+) T cells. Taken together, our data indicate that during RSV infections, at least three DC subsets might be involved during the activation of lymph node-homing naïve and memory CD4(+) and CD8(+) T cells.

Distinct abnormalities in the innate immune system of children with Down syndrome.

OBJECTIVE: To analyze the frequency and phenotype of cells of the innate immune system in the peripheral blood of children with Down syndrome (DS). STUDY DESIGN: Flow cytometric analysis of expression of cell surface markers was performed in children with DS (n = 41) and healthy age-matched controls (n = 41). RESULTS: Compared with controls, children with DS had significantly lower absolute total leukocyte counts, lymphocytes, monocytes, and granulocytes, but 1.5-times higher absolute numbers of CD14(dim)CD16(+) monocytes (147 x 10(6)/L vs 93 x 10(6)/L; P = .02). This difference is fully explained by a higher percentage of CD14(dim)CD16(+) monocytes within the monocyte compartment (28.7% vs 13.4%; P <.001). The absolute numbers of myeloid dendritic cells were lower in DS (13.8 x 10(6)/L vs 22.7 x 10(6)/L; P <.001). The numbers of plasmacytoid dendritic cells and natural killer cells were normal. Absolute numbers of invariant natural killer T cells were very low overall, but significantly lower in children with DS than in controls (1.2 x 10(6)/L vs 3.7 x 10(6)/L; P = .01). CONCLUSIONS: Children with DS exhibited distinct abnormalities in cells of the innate immune system. Most strikingly, they had a high number of proinflammatory CD14(dim)CD16(+) monocytes. This elevated level of CD14(dim)CD16(+) monocytes may play an important role in the onset and maintenance of chronic inflammatory disease in DS.

Dynamics of human respiratory virus-specific CD8+ T cell responses in blood and airways during episodes of common cold.

We determined the dynamics of CD8(+) T cells specific for influenza virus and respiratory syncytial virus in blood and tracheostoma aspirates of children during the course of respiratory infections. We showed that during localized respiratory infections the ratio of activated effector CD8(+) T cells to resting memory/naive CD8(+) T cells in peripheral blood increased significantly. Furthermore, the number of effector/memory T cells specific for respiratory viruses declined in blood and increased in the airways, suggesting that these T cells redistributed from blood to airways. T cells specific for the infecting virus were present in the airways for longer periods at increased levels than nonspecifically recruited bystander T cells. After clearance of the infection, the ratio of resting memory and naive CD8(+) T cells normalized in peripheral blood and also memory T cell numbers specific for unrelated viruses that declined during the infection due to bystander recruitment were restored. Taken together, these results showed a significant systemic T cell response during relatively mild secondary infections and extensive dynamics of virus-specific and nonspecific Ag-experienced T cells.

Human bocavirus and KI/WU polyomaviruses in pediatric intensive care patients.

We evaluated the prevalence of human bocavirus and KI and WU polyomaviruses in pediatric intensive care patients with and without lower respiratory tract infection (LRTI). The prevalence of these viruses was 5.1%, 0%, and 2.6%, respectively, in children with LRTI and 4.8%, 4.8%, and 2.4%, respectively, in those without LRTI.

Respiratory pathogens in respiratory tract illnesses during the first year of life: a birth cohort study.

BACKGROUND: Respiratory virus infections are the most important trigger of respiratory illnesses in childhood. Data on the occurrence and the clinical impact of respiratory pathogens in the general population of infants are scarce. Therefore, we described the occurrence and clinical impact of respiratory pathogens in infants with respiratory tract infections during the first year of life. METHODS: In a prospective birth cohort study, infants were followed from birth through the first year of life with daily questionnaires about respiratory symptoms. Nose and throat swabs were collected during episodes with respiratory symptoms. Polymerase chain reaction was used to detect an extensive panel of respiratory pathogens. RESULTS: The parents reported a median of 5 respiratory episodes per infant per year. A total of 668 respiratory samples were collected in 305 infants. One or more respiratory pathogens were detected in 85% of the samples. The most common respiratory pathogens were human rhinovirus (HRV) (73% of the samples), respiratory syncytial virus (RSV) (11%), and coronavirus (8%). HRV infections were associated with a prolonged period of symptoms compared with RSV (P = 0.03). Infections with RSV were associated with more physician visits than HRV infections (P = 0.06). CONCLUSION: We found a high prevalence of respiratory pathogens among infants with parent-reported respiratory illnesses in the first year of life, with HRV being the most prevalent. Although RSV infections seemed to be responsible for the most severe symptoms compared with HRV, the overall burden of disease was highest for HRV infections.

Genetic susceptibility to respiratory syncytial virus bronchiolitis in preterm children is associated with airway remodeling genes and innate immune genes.

Prematurity is a risk factor for severe respiratory syncytial virus bronchiolitis. We show that genetic factors in innate immune genes (IFNA13, IFNAR2, STAT2, IL27, NFKBIA, C3, IL1RN, TLR5), in innate and adaptive immunity (IFNG), and in airway remodeling genes (ADAM33 and TGFBR1), affect disease susceptibility to a different extent in preterm children, born with underdeveloped lungs, than in term children.

Respiratory symptoms in young infancy: child, parent and physician related determinants of drug prescription in primary care.

PURPOSE: Respiratory symptoms account for the majority of drug prescriptions in the first year of life. We investigated the influence of child, parent and physician factors on drug prescriptions for respiratory symptoms in primary care in infancy. METHODS: Infants participated in the WHeezing Illnesses STudy LEidsche Rijn (WHISTLER), a prospective birth cohort on respiratory illnesses. Outcome was defined as having received a prescription of antibiotics or of anti-asthma medication for respiratory symptoms by a physician. RESULTS: Nearly 60% of all children ever visited a physician for respiratory symptoms during the first year of life, of which 40% received a prescription. Every extra day with symptoms during the month before consultation and each extra visit to a physician were associated with a higher chance for prescription (respectively odds ratios (OR) 1.07/2.63, 95% confidence intervals (CI) 1.02-1.12/1.83-3.76). Further, we found a higher chance for drug prescribing for boys (2.7, 2.0-3.7), children attending day care (1.17, 1.09-1.25), mothers with higher education (2.3, 1.2-4.6), working mothers (4.5, 0.9-22.0) and older mothers (years) (1.09, 1.02-1.16). Furthermore, physicians' years of experience was a determinant for receiving a prescription (2.5, 1.1-6.0). Accounting for symptoms and visits as strong predictors of prescribing, infant gender and day care attendance were still predictors. Furthermore, infant gender, day care attendance, family history of asthma and physicians' years of experience were independent determinants of the number of prescriptions besides symptoms and visits. CONCLUSION: In young infancy, besides the severity of symptoms there are child, physician and particularly maternal characteristics that influence the decision of general practitioners to prescribe drugs for respiratory symptoms.

A dietary fiber mixture versus lactulose in the treatment of childhood constipation: a double-blind randomized controlled trial.

BACKGROUND: Constipation is a common problem in children. As first-line treatment, increased dietary fiber is often advocated. To our knowledge, however, no large studies evaluating the effect of dietary fibers in childhood constipation have been published. PATIENTS AND METHODS: A randomized, double-blind, prospective controlled study was performed. Patients received either a fiber mixture or lactulose in a yogurt drink. After a baseline period of 1 week, patients were treated for 8 weeks followed by 4 weeks of weaning. Polyethylene glycol 3350 was added if no clinical improvement was observed after 3 weeks. Using a standardized bowel diary, parents recorded defecation frequency during the treatment period. In addition, incontinence frequency, stool consistency, presence of abdominal pain and flatulence, necessity for step-up medication, and dry weight of feces were recorded, as were adverse effects. RESULTS: A total of 147 children were eligible; 12 children wished not to participate. Of the remaining children, 65 were randomized to treatment with fiber mixture and 70 to treatment with lactulose. In all, 97 children completed the study. No difference was found between the groups after the treatment period concerning defecation frequency (P = 0.481) and fecal incontinence frequency (P = 0.084). However, consistency of stools was softer in the lactulose group (P = 0.01). Abdominal pain and flatulence scores were comparable (P = 0.395 and P = 0.739, respectively). The necessity of step-up medication during the treatment period was comparable (P = 0.996), as were taste scores (P = 0.657). No serious adverse effects were registered. CONCLUSIONS: A fluid fiber mixture and lactulose give comparable results in the treatment of childhood constipation.