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Background: Eczema in early childhood is associated with developing subsequent allergic diseases, including food allergy, asthma and hay fever. However, eczema has a heterogenous presentation regarding age of onset and persistence, which may lead to different allergic outcomes during childhood/adolescence. Recently, sub-phenotypes of eczema have been suggested as predictor for allergic multimorbidity. Objective: To identify associations of eczema phenotypes with food allergy, asthma and hay fever during childhood/adolescence. Additionally, we aimed to describe the trajectories of eczema, asthma and hay fever, stratifying by food allergy presence. Methods: TRACKER (Trajectories of Allergy in Children in Real Life Databases) is a prospective cross-sectional population-based cohort study of 6,852 children/adolescents from the Lifelines cohort. We investigated associations of seven eczema phenotypes, based on age of onset and persistence, with food allergy, asthma and hay fever using logistic regression, adjusted for appropriate covariates. Disease trajectories were determined by calculating prevalence at different ages. Results: Participants who suffered from eczema throughout childhood showed higher risks of developing food allergy, hay fever and asthma. “Very early onset – persistent” eczema showed the strongest associations with food allergy, asthma and hay fever. The prevalence of eczema, asthma and hay fever at all ages were significantly higher in participants with food allergy, compared to those without. Conclusion: The largest cohort study on this topic to date shows that (very) early onset and persistent eczema increases the risk for allergic multimorbidity. Identification of infants at risk for developing (very) early onset eczema is of utmost importance to prevent allergic multimorbidity.

Background Respiratory syncytial virus (RSV), parainfluenza virus (PIV), and human metapneumovirus (hMPV) are increasingly associated with chronic lung allograft dysfunction (CLAD) in lung transplant recipients (LTR). This systematic review primarily aimed to assess outcomes of RSV/PIV/hMPV infections in LTR and secondarily to assess evidence regarding the efficacy of ribavirin. Methods Relevant databases were queried and study outcomes extracted using a standardized method and summarized. Results Nineteen retrospective and 12 prospective studies were included (total 1060 cases). Pooled 30-day mortality was low (0–3%), but CLAD progression 180–360 days postinfection was substantial (pooled incidences 19–24%) and probably associated with severe infection. Ribavirin trended toward effectiveness for CLAD prevention in exploratory meta-analysis (odds ratio [OR] 0.61, [0.27–1.18]), although results were highly variable between studies. Conclusions RSV/PIV/hMPV infection was followed by a high CLAD incidence. Treatment options, including ribavirin, are limited. There is an urgent need for high-quality studies to provide better treatment options for these infections.

BackgroundSmall airways dysfunction (SAD) in asthma is difficult to measure and a gold standard is lacking. The aim of this study was to develop a simple tool including items of the Small Airways Dysfunction Tool (SADT) questionnaire, basic patient characteristics and respiratory tests available depending on the clinical setting to predict SAD in asthma.MethodsThis study was based on the data of the multinational ATLANTIS (Assessment of Small Airways Involvement in Asthma) study including the earlier developed SADT questionnaire. Key SADT items together with clinical information were now used to build logistic regression models to predict SAD group (less likely or more likely to have SAD). Diagnostic ability of the models was expressed as area under the receiver operating characteristic curve (AUC) and positive likelihood ratio (LR+).ResultsSADT item 8, “I sometimes wheeze when I am sitting or lying quietly”, and the patient characteristics age, age at asthma diagnosis and body mass index could reasonably well detect SAD (AUC 0.74, LR+ 2.3). The diagnostic ability increased by adding spirometry (percentage predicted forced expiratory volume in 1 s: AUC 0.87, LR+ 5.0) and oscillometry (resistance difference between 5 and 20 Hz and reactance area: AUC 0.96, LR+ 12.8).ConclusionsIf access to respiratory tests is limited (e.g.primary care in many countries), patients with SAD could reasonably well be identified by asking about wheezing at rest and a few patient characteristics. In (advanced) hospital settings patients with SAD could be identified with considerably higher accuracy using spirometry and oscillometry.

Chronic obstructive pulmonary disease (COPD) is a complex genetic disorder, strongly associated with smoking. However, 25-45% of the individuals who develop COPD have never been exposed to (environmental) smoking. We hypothesize that these individuals have a strong genetic susceptibility for COPD with rare, pathogenic genetic variants underlying its development. We studied 36 individuals from the prospective Dutch Lifelines cohort with COPD (LLN of FEV1/FVC In total, we found 7,638 unique predicted pathogenic genetic variants in the 36 selected individuals. All 36 individuals carry at least 1 variant (range 1-7) in the top-100 prioritized genes in the COPD network. GeneNetwork pathway analysis revealed that 56 of the prioritized genes were significantly enriched for biological processes involved in cilium functioning. Our results suggest that rare pathogenic variants in ciliary genes underlie non-smoking related COPD and their role in a mono- or oligogenic form of COPD should be further investigated.