Arjen Pelgröm

Background: Although rare, COVID‐19 in children may lead to hospitalization due to severe respiratory symptoms, or a hyperinflammatory state called Multisystem Inflammatory Syndrome in Children (MIS‐C). This study examined respiratory morbidity in children 5 to 12 months after hospitalization for MIS‐C or COVID‐19. Methods: In this multi‐center, prospective cohort study, children (0–17 years) with a history of hospitalization for MIS‐C or COVID‐19 in Dutch hospitals were invited for follow‐up. Visits were scheduled in one of three academic hospitals, to evaluate current clinical status and health‐related quality of life (HRQoL), and perform lung function tests and cardiopulmonary exercise testing (CPET). Results: 72 children were included (43 MIS‐C, 29 COVID‐19), of whom 19% (5% and 41%, respectively) reported long‐term respiratory symptoms including dyspnea and cough, a median of 8 months after hospitalization. Fatigue was the most common non‐respiratory symptom. HRQoL was more frequently (60%) impaired in the COVID‐19 group than the MIS‐C group (14%). Spirometry ( n = 48) and CPET ( n = 40) were conducted in children aged > 4 and > 6 years, respectively. Spirometry was abnormal in 15% of the MIS‐C group and 44% of COVID‐19 group, CPET in 41% and 75%, respectively. Deconditioning patterns were the most common reason (30%) for abnormal CPET results. Conclusion: Long‐term respiratory sequelae and fatigue occurred after both MIS‐C and severe COVID‐19, but respiratory symptoms and impaired HRQoL were more frequent after COVID‐19. Lung function and CPET abnormalities in children with COVID‐19 often corresponded with symptoms. Children with MIS‐C often showed CPET abnormalities without respiratory complaints or lung function changes.

Background: Small airway dysfunction (SAD) is associated with impaired asthma control, but small airway physiology is not routinely assessed in clinical practice. Previously, we demonstrated impulse oscillometry (IOS)-defined small airway dysfunction (SAD) in dual responders (DRs) upon bronchoprovocation with various allergens. Aim: To compare lung physiology using spirometry and IOS following bronchoprovocation with methacholine (M) and inhaled house dust mite (HDM) extract in corticosteroid-naïve asthmatic subjects. Methods: Non-smoking, clinically stable HDM-allergic asthmatic subjects (18–55 years, FEV₁ > 70% of pred.) underwent an M and inhaled HDM challenge on two separate days. Airway response was measured by IOS and spirometry, until a drop in FEV₁ ≥ 20% (PC₂₀) from post-diluent baseline (M), and up to 8 h post-allergen (HDM). Early (EAR) and late asthmatic response (LAR) to HDM were defined as ≥20% and ≥15% fall in FEV₁ from post-diluent baseline during 0–3 h and 3–8 h post-challenge, respectively. IOS parameters (Rrs5, Rrs20, Rrs5-20, Xrs5, AX, Fres) were compared between mono-responders (MRs: EAR only) and dual responders (EAR + LAR). Correlations between maximal % change from baseline after the two airway challenges were calculated for both FEV₁ and IOS parameters. Results: A total of 47 subjects were included (11 MRs; 36 DRs). FEV₁ % predicted did not differ between MR and DR at baseline, but DR had lower median PC₂₀M (0.84 (range 0.07–7.51) vs. MR (2.15 (0.53–11.29)); p = 0.036). During the LAR, DRs had higher IOS values than MRs. For IOS parameters (but not for FEV₁), the maximal % change from baseline following M and HDM challenge were correlated. PC₂₀M was inversely correlated with the % change in FEV₁ and the % change in Xrs5 during the LAR (r= −0.443; p = 0.0018 and r= −0.389; p = 0.0075, respectively). Conclusions: During HDM-induced LAR, changes in small airway physiology can be non-invasively detected with IOS and are associated with increased airway hyperresponsiveness and changes in small airway physiology during methacholine challenge. DRs have a small airways phenotype, which reflects a more advanced airway disease.