Bart E. van Ewijk

Respiratory Pathogens in Children with and without Respiratory Symptoms

Objectives To investigate the occurrence of respiratory pathogens in samples from children with and without respiratory symptoms and to identify whether age and/ or coinfections modify the impact of respiratory pathogens on symptoms. Study design In a prospective longitudinal study, 18 children were sampled biweekly for respiratory pathogens, irrespective of respiratory symptoms. Polymerase chain reaction was performed for 13 respiratory pathogens. Episodes were defined “asymptomatic” if no symptoms of any respiratory tract illness were present between 1 week before and 1 week after sampling. Results A total of 230 samples were collected. In 56% of the symptomatic episodes, a pathogen was detected, compared with 40% of the asymptomatic episodes (P = .03). Rhinovirus and coronaviruses were most prevalent in both symptomatic and asymptomatic episodes. In the youngest children, 9% of the pathogen-positive episodes were asymptomatic, compared with 36% in the oldest children (P = .01). Multiple pathogens were found in 17% of the symptomatic episodes and in 3% of the asymptomatic episodes (P = .02). Conclusions Respiratory pathogens are frequently detected in samples from children with no respiratory symptoms. Symptomatic cases occurred more often in younger children and with detections of more than 1 respiratory pathogen.

RSV Mediates Pseudomonas aeruginosa Binding to Cystic Fibrosis and Normal Epithelial Cells

Cystic fibrosis lung disease typically has a course of exacerbations and remissions, suggesting that external factors like viral infections can influence this course. Clinical data suggest synergism between respiratory syncytial virus (RSV) infections and Pseudomonas aeruginosa in cystic fibrosis (CF) lung disease. We studied the influence of RSV infection on adherence of P. aeruginosa to IB3-1, HEp-2, and A549 epithelial cell monolayers in vitro. RSV infection of epithelial cells as well as simultaneous addition of RSV and P. aeruginosa to noninfected cells both strongly enhanced the pseudomonal adherence to epithelial cells. The increased adherence varied from 1.2- to 8.2-fold in case of previous RSV infection, and from 1.7- to 16.1-fold in case of simultaneous addition. We observed direct binding of RSV to P. aeruginosa, and blocking of RSV with heparin eliminated the effect on increased adherence. This suggests that RSV possibly acts as a coupling agent between P. aeruginosa and epithelial cells. In conclusion, RSV enhances P. aeruginosa infection of respiratory epithelial cells. It suggests a role of specific viral–bacterial interactions in exacerbations of CF lung disease, which could have important implications on prevention and treatment.

Prevalence and impact of respiratory viral infections in young children with cystic fibrosis: prospective cohort study.

OBJECTIVE. We aimed to investigate differences in upper and lower respiratory tract symptoms in relation to respiratory viral infections detected with polymerase chain reaction assays in young children with cystic fibrosis and healthy control subjects. METHODS. In a 6-month winter period, 20 young children with cystic fibrosis and 18 age-matched, healthy, control subjects were contacted twice per week for detection of symptoms of an acute respiratory illness. If any symptom was present, then a home visit was made for physical examination and collection of nasopharyngeal swabs for viral analysis. In addition, parents were instructed to collect nasopharyngeal swabs every 2 weeks. RESULTS. Children with cystic fibrosis and healthy control subjects had similar frequencies of acute respiratory illnesses (3.8 ± 1.0 and 4.2 ± 1.7 episodes, respectively). Although there were no significant differences in upper respiratory tract symptoms, the children with cystic fibrosis had longer periods of lower respiratory tract symptoms (22.4 ± 22.2 vs 12.8 ± 13.8 days) and a higher mean severity score per episode (2.35 ± 0.64 vs 1.92 ± 0.46). In addition, similar increases in upper respiratory tract symptom scores were associated with significantly greater increases in lower respiratory tract symptom scores in children with cystic fibrosis. No differences in the seasonal occurrences and distributions of respiratory viruses were observed, with picornaviruses and coronaviruses being the most prevalent. CONCLUSIONS. Although there were no differences in the seasonal occurrences and distributions of polymerase chain reaction-detected respiratory viruses, acute respiratory illnesses were frequently associated with increased lower respiratory tract morbidity in young children with cystic fibrosis.

Strong association between respiratory viral infection early after hematopoietic stem cell transplantation and the development of life-threatening acute and chronic alloimmune lung syndromes

Alloimmune lung syndromes (allo-LS), including idiopathic pneumonia syndrome, bronchiolitis obliterans syndrome, and bronchiolitis obliterans organizing pneumonia, are severe complications after hematopoietic stem cell transplantation (HSCT). In our cohort of 110 pediatric patients, 30 had allo-LS (27.3%), 18 with ideopathic pneumonia syndrome and 12 with bronchiolitis obliterans syndrome. Multivariate analysis showed that respiratory viral infection early after HSCT is an important predictor for the development of allo-LS (P <.0001). This was true for all viruses tested. In multivariate analysis, allo-LS was the only predictor for higher mortality (P = .04). Paradoxically, prolonged administration of immunosuppressive agents because of acute graft-versus-host disease had a protective effect on the development of allo-LS (P = .004). We hypothesize that early infection of the respiratory tract with a common cold virus makes the lungs a target for alloimmunity.

Highly frequent infections with human rhinovirus in healthy young children: A longitudinal cohort study

BACKGROUND Human rhinoviruses (HRVs) are an important cause of respiratory tract infections. OBJECTIVES We questioned whether the high prevalence rates of HRVs found in epidemiological studies is due to long-term individual continuity or a result of frequent infections with different HRV subtypes. STUDY DESIGN In a 6-month winter period 18 healthy controls, aged 0-7 years, were at least sampled every two weeks for HRV-PCR, irrespective of respiratory symptoms. All HRV positive samples were genotyped to determine HRV diversity. RESULTS In total 272 samples were collected. HRV was found in 101/272 (37%) samples. Genotyping revealed 27 different HRV subtypes. A median of 3.0 different HRV subtypes was found per child. Re-infections and continuity with identical HRV sequences were observed. The number of HRVs were higher in the youngest age group (p=0.01) and they had more different HRV subtypes (p=0.05) compared to oldest age group. CONCLUSIONS We found a high HRV exposition with a considerable diverse population of HRV subtypes in young children. These results have major implications for future research into the pathogenic role of HRV in respiratory diseases. Characterisation of subtypes will be necessary to discriminate between prolonged continuity and re-infections in patients with respiratory diseases.

Prevalence and pathogenicity of WU and KI polyomaviruses in children, the Netherlands

A longitudinal study in 2004 and 2005 detected polyomaviruses WU and KI in 44% and 17% of children with and without respiratory symptoms, respectively, in the Netherlands. In some children both viruses were detected for long periods. In several symptomatic children no other respiratory pathogen was detected.

Frequency and Duration of Rhinovirus Infections in Children with Cystic Fibrosis and Healthy Controls : A Longitudinal Cohort Study

Background: Respiratory viral infections are an important cause of morbidity in patients with chronic respiratory diseases, such as cystic fibrosis (CF). We hypothesized that patients with CF are more susceptible to human rhinovirus (HRV) infections than healthy controls. Methods: In a 6-month winter period, 20 young children with CF (0–7 years) and 18 age-matched healthy controls were sampled biweekly for HRV-polymerase chain reaction using nasopharyngeal swabs, irrespective of respiratory symptoms. Respiratory symptoms were scored twice a week. If any symptom was present, an additional sample was obtained. All HRV-positive samples were genotyped to distinguish HRV subtypes. Results: We analyzed 645 samples, with comparable total numbers of samples in both groups. HRV was detected in 40.8% of all analyzed samples. Children with CF had significantly more HRV-positive samples compared with healthy controls, with a mean number (± standard deviation) of 8.1 ± 2.3 versus 5.7 ± 2.9 positive samples per individual (P < 0.01). Prolonged detection (>2 weeks) with the same HRV subtype occurred more frequently in the CF patients (P < 0.01). The genetic distribution and pattern of phylogenetic diversity of the different HRV subtypes were similar in both groups. Conclusions: This is the first in vivo longitudinal study showing that HRV is detected more frequently and persists for longer periods in CF patients compared with healthy controls. This might indicate increased viral replication and/or decreased antiviral defense in patients with CF.

Respiratory tract infections and asthma control in children

INTRODUCTION Asthma control is considered the major goal of asthma management, while many determinants of control are difficult to modify. We studied the association between respiratory infection episodes (RTIs) of various types and asthma control. METHODS Cross-sectional data were used from children aged 4-18 years with physician-diagnosed asthma who participated in a web-based electronic portal for children with asthma, allergies or infections. Asthma control was measured using the Childhood Asthma Control Test (C-ACT) or the Asthma Control Test (ACT). Linear regression was used to analyse the association between categories of numbers of various types of RTIs sustained in the preceding 12 months (categorized) and asthma control, adjusted for potential confounders. RESULTS Asthma control was assessed in 654 children, and 68.5% were clinically well controlled (ACT ≥ 20). Higher total numbers of RTIs in the last 12 months were strongly associated with a lower level of asthma control (p(trend) < 0.001). Similarly strong statistically significant associations were found for subtypes of RTI: ≥4 vs. 0 otitis episodes: coefficient -1.7 (95% CI -3.3 to -0.2); ≥5 vs.0 colds: coefficient -2.3 (95% CI -3.0 to -1.6); ≥3 vs. 0 bronchitis episodes: coefficient -3.1 (95% CI -4.0 to -2.3), each with p(trend) < 0.05. CONCLUSION Higher numbers of reported respiratory tract infections are associated with lower level of asthma control. The different type of respiratory tract infections contribute equally to less controlled asthma.