COVID-19 susceptibility and clinical outcomes in autoimmune inflammatory rheumatic diseases (AIRDs): a systematic review and meta-analysis.

OBJECTIVE: This meta-analysis aims to assess the susceptibility to and clinical outcomes of COVID-19 in autoimmune inflammatory rheumatic disease (AIRD) and following AIRD drug use. MATERIALS AND METHODS: We included observational and case-controlled studies assessing susceptibility and clinical outcomes of COVID-19 in patients with AIRD as well as the clinical outcomes of COVID-19 with or without use of steroids and conventional synthetic disease-modifying antirheumatic drugs (csDMARDs). RESULTS: Meta-analysis including three studies showed that patients with AIRD are not more susceptible to COVID-19 compared to patients without AIRD or the general population (OR: 1.11, 95% CI: 0.58 to 2.14). Incidence of severe outcomes of COVID-19 (OR: 1.34, 95% CI: 0.76 to 2.35) and COVID-19 related death (OR: 1.21, 95% CI: 0.68 to 2.16) also did not show significant difference. The clinical outcomes of COVID-19 among AIRD patients with and without csDMARD or steroid showed that both use of steroid (OR: 1.69, 95% CI: 0.96 to 2.98) or csDMARD (OR: 1.35, 95% CI: 0.63 to 3.08) had no effect on clinical outcomes of COVID-19. CONCLUSIONS: AIRD does not increase susceptibility to COVID-19, not affecting the clinical outcome of COVID-19. Similarly, the use of steroids or csDMARDs for AIRD does not worsen the clinical outcome.

Prevalence of allergic diseases among Korean adolescents during the COVID-19 pandemic: comparison with pre-COVID-19 11-year trends.

OBJECTIVE: During the coronavirus disease 2019 (COVID-19) pandemic, emergency department utilization and hospitalization rates for allergic diseases declined and the severity of allergies among admitted patients was low. This study aimed to determine the prevalence of allergic diseases among adolescents and the changes in trend during the COVID-19 pandemic compared with those during the preceding 11 years. SUBJECTS AND METHODS: We analyzed data from the nationwide web-based self-report Korea Youth Risk Behavior Survey. From 2009 to 2020, adolescents aged 13-18 years participated in the survey. The survey period was divided into pre-pandemic Periods I (2009-2011), II (2012-2014), III (2015-2017), and IV (2018-2019) and the pandemic period (Period V, 2020). The current prevalence of asthma, allergic rhinitis, atopic dermatitis, allergic morbidity (having at least one of the three conditions) and changes in the prevalence before and during the COVID-19 pandemic were analyzed. RESULTS: Data of 787,043 participants were analyzed after weighting the study population (mean age, 15.1 years; males, 52.3%). The prevalence of asthma, allergic rhinitis, atopic dermatitis, and allergic morbidity was 2.1%, 18.4%, 6.8%, and 23.6%, respectively. The prevalence of allergic morbidity increased between Periods I and IV but declined significantly from Periods IV to V. From Periods I to IV, the prevalence of asthma decreased, the prevalence of allergic rhinitis increased, and the prevalence of atopic dermatitis remained unchanged. During Period V, the prevalence of all three conditions decreased. CONCLUSIONS: It is necessary to update management measures and develop relevant policies in response to the altered prevalence of allergic diseases since the outbreak of COVID-19.

A multicenter study on anaphylaxis caused by peanut, tree nuts, and seeds in children and adolescents.

Peanut (PN) and tree nuts (TNs) are common causes of anaphylaxis in Western countries, but no information is available in Korea. To feature clinical characteristics of anaphylaxis caused by PN, TNs, and seeds, a retrospective medical record review was performed in 14 university hospitals in Korea (2009-2013). One hundred and twenty-six cases were identified, with the mean age of 4.9 years. PN, walnut (WN), and pine nut accounted for 32.5%, 41.3%, and 7.1%, respectively. The median values of specific IgE (sIgE) to PN, WN, and pine nut were 10.50, 8.74, and 4.61 kUA /l, respectively. Among 50 cases managed in the emergency department, 52.0% were treated with epinephrine, 66.0% with steroid, 94.0% with antihistamines, 36.0% with oxygen, and 48.0% with bronchodilator. In conclusion, WN, PN, and pine nut were the three most common triggers of anaphylaxis in Korean children, and anaphylaxis could occur at remarkably low levels of sIgE.

Serum periostin levels correlate with airway hyper-responsiveness to methacholine and mannitol in children with asthma.

BACKGROUND: Periostin is a matricellular protein, and its synthesis in airway epithelial cells and lung fibroblasts is induced by interleukin (IL)-4 and IL-13. The significance of periostin as a biomarker of TH 2-induced airway inflammation, and (importantly) as a measure of the response to TH 2-targeted therapy, has recently been emphasized. We explored the relationship between periostin and airway hyperresponsiveness (AHR) in asthmatic children. METHODS: The study included 83 children aged 6-15 years in an asthmatic group (n = 54) and healthy controls (n = 29). We measured the periostin levels in serum and performed methacholine and mannitol provocation challenges. The responses to mannitol were expressed as the provocative dose causing a 15% fall in the FEV1 (the PD15 dose). RESULTS: Of the 54 subjects with asthma, all had positive methacholine bronchial provocation test (BPT) results and 38 had positive mannitol BPT results. Children with asthma had significantly higher periostin levels than controls [76.0 (65.0-91.8) vs 71.0 (57.5-80.0) ng/mL; P = 0.017]. Periostin levels were significantly correlated with both the methacholine PC20 and mannitol PD15 values. CONCLUSION: Serum levels of periostin, a new biomarker induced by IL-13, were higher in asthmatic children, and were associated with AHR to methacholine and mannitol.

Bronchial hyperresponsiveness to methacholine and adenosine 5'-monophosphate, and the presence and degree of atopy in young children with asthma.

BACKGROUND: Bronchial hyperresponsiveness (BHR) is a characteristic feature of asthma, and is usually measured by bronchial challenges using direct or indirect stimuli. The relationship between atopy and BHR remains to be clarified, particularly in a population selected for asthma. Furthermore, data for young children are limited, although asthma frequently occurs in early childhood. OBJECTIVE: The aim of this study was to investigate methacholine (direct stimulus) and adenosine 5'-monophosphate (AMP) (indirect stimulus) responsiveness according to the presence and degree of atopy in young children with asthma. METHODS: A retrospective analysis of data from 122 preschool children (median age [range]: 5.3 years [4.0-6.8]) presenting with the diagnosis of asthma was performed. These children were characterized by skin-prick tests (SPTs) and bronchial challenges with methacholine and AMP, using a modified auscultation method. The end-point concentration, resulting in audible wheezing and/or oxygen desaturation, was determined for each challenge. Atopy was defined by at least one positive reaction to SPTs, and its degree was assessed using serum total IgE levels, number of positive SPTs, and atopic scores (sum of graded weal size). RESULTS: Atopic patients (n=97) had a significantly lower AMP end-point concentration than non-atopic patients (n=25), whereas the methacholine end-point concentration was not different between the two groups. Among the atopic patients, there was no association between the methacholine end-point concentration and any of the atopy parameters. By contrast, a significant association was found between the AMP end-point concentration and the degree of atopy reflected in serum total IgE and atopic scores (χ² test for trend, P=0.001, 0.003, respectively). CONCLUSION AND CLINICAL RELEVANCE: Young children with atopic asthma had a significantly greater AMP responsiveness than those with non-atopic asthma, whereas methacholine responsiveness was not significantly different between the two groups. The degree of atopy appeared to be an important factor in AMP responsiveness, but not in methacholine responsiveness, and thus might be a marker of airway inflammation in asthma.

Bronchial hyperresponsiveness to methacholine/AMP and the bronchodilator response in asthmatic children.

Bronchodilator response (BDR) is assessed to estimate the reversibility of airflow obstruction. Bronchial hyperresponsiveness (BHR) is a characteristic feature of asthma and is usually measured by means of bronchial challenges using direct or indirect stimuli. The aim of the present study was to compare BHR to methacholine (direct) and that to adenosine 5'-monophosphate (AMP) (indirect) with regard to their relationships to BDR in asthmatic children. Methacholine and AMP challenge tests were performed on 138 children with mild-to-moderate asthma, and the provocative concentration causing a 20% decline in forced expiratory volume in 1 s (FEV1) (PC20) was determined for each challenge. BDR was calculated as the change in FEV(1), expressed as a percentage of the initial value, after inhalation of 400 µg salbutamol. Methacholine PC20 correlated significantly but weakly with BDR (r = -0.254; p = 0.003). However, there was a significant and strong correlation between AMP PC20 and BDR (r = -0.489; p = 0.000). For AMP PC20, the relationship was closer than for methacholine PC20 (p = 0.024 for comparison between correlation coefficients). The same figures were observed when BDR was expressed as a percentage of the predicted value. A stronger correlation of BDR with AMP PC20 than with methacholine PC20 suggests that BDR may be better reflected by BHR as assessed by AMP challenge than by methacholine challenge.

Relationship between chondrocyte apoptosis and matrix depletion in human articular cartilage.

OBJECTIVE: Chondrocyte apoptosis has been described in studies of the pathogenesis of various arthritides. Since matrix degradation is important in the pathology of arthritis, we investigated the effect of matrix depletion on chondrocyte apoptosis. METHODS: Consecutive 1 mm sections of child's rib cartilage were cultured under 4 sets of conditions: (1) control; and treatment with (2) hyaluronidase, (3) collagenase, (4) hyaluronidase/collagenase alternately. Sections were harvested on Days 5, 8, and 11, and the proportion of apoptotic cells was measured by propidium iodide staining and flow cytometry. Changes of Fas and Fas ligand expression were verified by immunohistochemistry and Western blot. RESULTS: Collagenase treatment led to an increase of apoptosis, which began on Day 8, whereas hyaluronidase treatment had no effect on chondrocyte viability up to Day 11. Alternating hyaluronidase and collagenase treatment induced chondrocyte death earlier, but the difference in apoptotic rate was not significant on Days 8 or 11 compared to collagenase treatment alone. Immunohistochemistry showed the expression of Fas ligand in all enzymatically treated specimens. Expression of Fas receptor was ubiquitous in both control and treated specimens. CONCLUSION: The collagen framework is important in the maintenance of chondrocyte survival in human cartilage. Upregulation of Fas ligand in matrix depleted specimens suggested that the Fas pathway may have a role in apoptosis induced by matrix depletion.