Marieke M. van der Zalm

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.

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.

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.

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.

Tobacco smoke exposure of pregnant mothers and blood pressure in their newborns: results from the wheezing illnesses study Leidsche Rijn birth cohort.

There is evidence to suggest that exposure of pregnant women to tobacco smoke is related to higher childhood blood pressure in their offspring. It is not well known whether this association is set in utero or by shared postnatal environments. The objective of this study was to assess the association between tobacco smoke exposure of pregnant mothers and blood pressure and heart rate of their newborns. In an unselected birth cohort, blood pressure and heart rate were measured in 456 infants at ≈2 months of age. Smoking exposure of mothers in pregnancy was obtained by questionnaire. Of 456 mothers whose infants had blood pressure measured, 363 (79.6%) were not exposed to tobacco smoke in pregnancy, 63 (13.8%) did not smoke in pregnancy but were exposed by others, and 30 (6.6%) smoked. Infant offspring of mothers who had smoked during pregnancy had 5.4 mm Hg (95% CI: 1.2 to 9.7; P=0.01) higher systolic blood pressure levels than offspring of mothers who were not exposed to tobacco smoke in pregnancy, taking account of birth weight, infant age, gender, nutrition, and age of mother. No associations were found between maternal exposure to tobacco smoke in pregnancy and diastolic blood pressure. A positive association between maternal exposure to tobacco smoke and heart rate was largely explained by confounding. It can be concluded that maternal exposure to tobacco smoke in pregnancy has a substantial increasing effect on systolic blood pressure in early infancy.

The Influence of Neonatal Lung Function on Rhinovirus-associated Wheeze

RATIONALE Several studies have shown that the occurrence of wheezing illnesses during the first year of life is associated with lower levels of lung function shortly after birth and before any respiratory illness. It has been suggested that reduced lung function early in life predisposes infants to wheezing during viral respiratory infections, but the association between neonatal lung function and subsequent confirmed viral infections has never been investigated. OBJECTIVES To study the influence between neonatal lung function and the occurrence of human rhinovirus (HRV)-associated wheeze. METHODS In a prospective birth cohort study, infants were followed from birth through the first year of life with daily questionnaires about respiratory symptoms. Neonatal lung function was performed within the first 2 months of life. Nose and throat swabs were collected during episodes with respiratory symptoms. Polymerase chain reaction was used to detect single HRV infections. MEASUREMENTS AND MAIN RESULTS In 176 of the 202 infants (87%) with a single HRV infection, valid lung function measurements were obtained. The risk of wheeze was 1.49 times higher for each SD increase of airway resistance. The adjusted risk (corrected for possible important confounders) for wheeze was 1.77 (95% confidence interval, 1.16-2.69; P = 0.01) times higher for each SD increase of airway resistance. Maternal smoking during pregnancy was independently associated with wheeze (odds ratio 4.42; 95% confidence interval, 1.27-15.5; P = 0.02). CONCLUSIONS This study showed that total lung resistance is clearly associated with HRV-associated wheeze. Moreover, HRV-associated wheeze might be the first sign to recognize infants with reduced neonatal lung function.

Human Rhinovirus and Wheezing: Short and Long-term Associations in Children

Objectives: Human rhinoviruses (HRVs) have been suggested to play a role in the development of childhood wheezing. However, whether HRV is causally related to the development of wheezing or HRV-associated wheeze is merely an indicator of disease susceptibility is unclear. Our aim was to study the role of HRV during infancy in the development of lower respiratory disease during infancy and childhood. Methods: In a population-based birth cohort, during the 1st year of life, nose and throat swabs were collected on a monthly basis, regardless of any symptoms. Polymerase chain reaction was used to detect an extensive panel of respiratory pathogens. Lung function was measured before 2 months of age. Information on respiratory symptoms was collected by daily questionnaires and electronic patient files. Results: 1425 samples were collected in 140 infants. Both the presence of (single or multiple) pathogens (HRV equal to other pathogens) and increased respiratory system resistance were significantly associated with lower respiratory symptoms during infancy. HRV presence during infancy was not associated with the risk of wheezing at age 4, but every HRV episode with wheezing increased the risk of wheezing at age 4 (odds ratio 1.9, 1.1–3.5). This association weakened after adjustment for lung function (odds ratio 1.4, 0.7–2.9). Conclusions: HRV and other viruses are associated with lower respiratory symptoms during infancy, as well as a high presymptomatic respiratory system resistance. HRV presence during infancy is not associated with childhood wheezing, but wheeze during a HRV episode is an indicator of children at high risk for childhood wheeze, partly because of a reduced neonatal lung function.

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.

Determinants of health care utilization for respiratory symptoms in the first year of life.

Objective:Health care utilization for respiratory symptoms is very common in infancy. Little is known about the determinants of visiting a physician for such complaints in infants. We investigated which factors determine the likelihood of visiting a physician for respiratory symptoms in the first year of life of their offspring. Patients and Methods:Infants were participants of the ongoing Wheezing Illnesses Study Leidsche Rijn (WHISTLER), a prospective birth cohort study on respiratory illnesses. Parental reports on respiratory symptoms and possible risk factors were assessed by daily questionnaires. Physician diagnosed respiratory symptoms were classified in medical records using the International Classification of Primary Care. Outcome was defined as a having a child visit a general practitioner for respiratory symptoms in the first year of life. Logistic regression was used to study the likelihood of outcome (yes/no) as a function of putative predictors. Results:Forty-seven percent of the infants visited a physician for respiratory symptoms in the first year of life. Every extra week of respiratory symptoms was associated with a 4.3% higher chance (odds ratio [OR], 1.043; 95% confidence interval [CI], 1.022–1.065) of visiting a physician. Furthermore, the chance was higher in boys (OR, 1.5; 95% CI, 1.1–2.1), children attending day care (OR, 1.9; 95% CI, 1.2–3.0), children with nonwhite mothers (OR, 1.9; 95% CI, 1.1–3.2), and children whose mother had supplementary health care insurance (OR, 1.7; 95% CI, 1.1–2.7). Findings were similar within the subgroup of children with serious respiratory symptoms (>median: 46 d/yr), but in that group parental age over 30 also determined physician visits (OR, 3.8; 95% CI, 1.6–8.9). Conclusions:Child and parent characteristics, besides complaints per se, play an important role in health care utilization for respiratory illnesses in infancy.

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

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.