Defining asthma in children: how well do parents, doctors and spirometry agree?

Background: Because diagnosing asthma in school-aged children is challenging, a variety of proxies for asthma are used in clinical practice and research settings as indicators of this disease. We aimed to provide insight into the agreement between various asthma indicators based on parental report, medical diagnosis and spirometry. Methods: Children from the WHISTLER birth cohort performed spirometry and were followed up with parental ISAAC (International Study of Asthma and Allergies in Childhood) questionnaires about asthma at 5 and 8 years of age. Medical data were extracted from primary care records. We compared 15 asthma indicators based on parental report, medical diagnosis and spirometry using positive agreement, κ statistics and latent class cluster analysis. Results: At 5 years of age, 1007 children completed a study visit, while 803 children visited at 8 years of age. Depending on the indicator, the responder and child's age, the asthma prevalence ranged from 0.2% to 26.6%. Cluster analysis revealed classes related to the presence of recent symptoms and a decreased lung function. Agreement between parents and doctors was generally low with κ coefficients ranging from 0.07 (recent wheeze) to 0.52 (recent asthma medication). Additionally, parental report showed to be sensitive to recall bias over time. Conclusions: Dependent on the asthma indicator, the responder and the age of the child, substantial differences in agreement were observed between commonly used indicators associated with asthmatic disease in school-aged children. Most agreement between parents and doctors was seen for objective and recent indicators such as the recent use of asthma medication. We advocate caution when literature with different asthma indicators is compared

Economic burden and health-related quality-of-life among infants with respiratory syncytial virus infection: a multi-country prospective cohort study in Europe

Background: Respiratory syncytial virus (RSV) causes a considerable disease burden in young children globally, but reliable estimates of RSV-related costs and health-related quality-of-life (HRQoL) are scarce. This study aimed to evaluate the RSV-associated costs and HRQoL effects in infants and their caregivers in four European countries. Methods: Healthy term-born infants were recruited at birth and actively followed up in four European countries. Symptomatic infants were systematically tested for RSV. Caregivers recorded the daily HRQoL of their child and themselves, measured by a modified EQ-5D with Visual Analogue Scale, for 14 consecutive days or until symptoms resolved. At the end of each RSV episode, caregivers reported healthcare resource use and work absenteeism. Direct medical costs per RSV episode were estimated from a healthcare payer's perspective and indirect costs were estimated from a societal perspective. Means and 95% confidence intervals (CI) of direct medical costs, total costs (direct costs + productivity loss) and quality-adjusted life-day (QALD) loss per RSV episode were estimated per RSV episode, as well as per subgroup (medical attendance, country). Results: Our cohort of 1041 infants experienced 265 RSV episodes with a mean symptom duration of 12.5 days. The mean (95% CI) cost per RSV episode was €399.5 (242.3, 584.2) and €494.3 (317.7, 696.1) from the healthcare payer's and societal perspective, respectively. The mean QALD loss per RSV episode of 1.9 (1.7, 2.1) was independent of medical attendance (in contrast to costs, which also differed by country). Caregiver and infant HRQoL evolved similarly. Conclusion: This study fills essential gaps for future economic evaluations by prospectively estimating direct and indirect costs and HRQoL effects on healthy term infants and caregivers separately, for both medically attended (MA) and non-MA laboratory-confirmed RSV episodes. We generally observed greater HRQoL losses than in previous studies which used non-community and/or non-prospective designs

Respiratory syncytial virus infections on both ends of the age spectrum

During my PhD I have looked at disease caused by the respiratory syncytial virus (RSV) in both children and older adults. In children we updated a prediction tool which can identify children at higher risk of severe infection in the first year of life. Next I have looked at the development of asthmatic symptoms such as wheeze in childhood following severe RSV infection in early life. We found that RSV is an independent risk factor for wheezing illness in those without atopic disease but not in those with an atopic constitution. Furthermore, I investigated the agreement between the many surrogates of asthmatic disease that are used interchangeably to define asthma in children. We observed that there is major disagreement between definitions and advise caution in head-to-head comparison. In the second part of my thesis described the incidence and disease burden of RSV in community-dwelling older adults (adults ≥60 years living independently at home). In a large European prospective cohort we observed that RSV is prevalent in community-dwelling older adults but rarely causes severe disease. This suggests that watchful waiting, using a continuity of care approach to identify those who do need more intensive care is often justified when RSV is suspected in family practice. We also observed that exposure to young children may play an important role in the occurrence of respiratory infection in older adults. Last, we observed that worldwide surveillance programs may not detect RSV infection if they use the influenza-like-illness (ILI) case definition because it does not match the clinical symptoms often seen in RSV

Respiratory syncytial virus infections on both ends of the age spectrum

During my PhD I have looked at disease caused by the respiratory syncytial virus (RSV) in both children and older adults. In children we updated a prediction tool which can identify children at higher risk of severe infection in the first year of life. Next I have looked at the development of asthmatic symptoms such as wheeze in childhood following severe RSV infection in early life. We found that RSV is an independent risk factor for wheezing illness in those without atopic disease but not in those with an atopic constitution. Furthermore, I investigated the agreement between the many surrogates of asthmatic disease that are used interchangeably to define asthma in children. We observed that there is major disagreement between definitions and advise caution in head-to-head comparison. In the second part of my thesis described the incidence and disease burden of RSV in community-dwelling older adults (adults ≥60 years living independently at home). In a large European prospective cohort we observed that RSV is prevalent in community-dwelling older adults but rarely causes severe disease. This suggests that watchful waiting, using a continuity of care approach to identify those who do need more intensive care is often justified when RSV is suspected in family practice. We also observed that exposure to young children may play an important role in the occurrence of respiratory infection in older adults. Last, we observed that worldwide surveillance programs may not detect RSV infection if they use the influenza-like-illness (ILI) case definition because it does not match the clinical symptoms often seen in RSV

Prediction model of RSV-hospitalization in late preterm infants : An update and validation study

BACKGROUND: New vaccines and RSV therapeutics have been developed in the past decade. With approval of these new pharmaceuticals on the horizon, new challenges lie ahead in selecting the appropriate target population. We aimed to improve a previously published prediction model for prediction of RSV-hospitalization within the first year of life. METHODS: Two consecutive prospective multicenter birth cohort studies were performed from June 2008 until February 2015. The first cohort (RISK-I, n=2524, 2008-2011) was used to update the existing model. The updated model was subsequently validated in the RISK-II cohort (n=1564, 2011-2015). We used the TRIPOD criteria for transparent reporting. RESULTS: 181 infants (n=127 in RISK-I, n=54 in RISK-II) were hospitalized for RSV within their first year of life. The updated model included the following predictors; day care attendance and/or siblings (OR: 5.3; 95% CI 2.8-10.1), birth between Aug. 14th and Dec. 1st (OR: 2.4; 1.8-3.2), neonatal respiratory support (OR 2.2; 1.6-3.0), breastfeeding ≤4months (OR 1.6; 1.2-2.2) and maternal atopic constitution (OR 1.5; 1.1-2.1). The updated models' discrimination was superior to the original model in the RISK-II cohort (AUROC 0.72 95% CI 0.65-0.78 versus AUROC 0.66, 95% CI 0.60-0.73, respectively). The updated model was translated into a simple nomogram to be able to distinguish infants with high versus low risk of RSV-hospitalization. CONCLUSION: We developed and validated a clinical prediction model to be able to predict RSV-hospitalization in preterm infants born within 32-35weeks gestational age. A simple nomogram was developed to target RSV therapeutics to those children who will benefit the most