Substitution with Low-Osmolar Iodinated Contrast Agent to Minimize Recurrent Immediate Hypersensitivity Reaction.

Background The recurrence of hypersensitivity reaction (HSR) to low-osmolar iodinated contrast media (LOCM) remains challenging despite premedication and substitution of the LOCM. Purpose To determine the optimal practical preventive strategy for LOCM substitution in patients with a history of prior immediate HSR to LOCM. Materials and Methods In a retrospective study, patients with an immediate HSR to LOCM before February 2020 and who underwent subsequent exposure to LOCM until March 2021 were enrolled in five tertiary referral hospitals in South Korea. The association of recurrence of an HSR after subsequent LOCM exposures was assessed using multivariate general estimating equation analysis according to age, sex, the severity of the index HSR, premedication, and substituting LOCM based on common carbamoyl side chains, including the N-(2,3-dihydroxypropyl)-carbamoyl and N-(2,3-dihydroxypropyl)-N-methyl-carbamoyl moieties. Results The evaluation included 3800 subsequent LOCM exposures in 1066 patients (mean age, 56.2 years ± 13.5 [SD]; 567 [53%] female and 499 [47%] male patients). The general estimating equation analysis, using 1:1 propensity score matched data for age, sex, HSR severity, and LOCM selection, showed that premedication with corticosteroids significantly reduced recurrent HSR (odds ratio [OR], 0.72; 95% CI: 0.52, 1.00; P = .049). The change to another LOCM with a common side chain had a similar recurrence rate as using the same LOCM (OR, 0.98; 95% CI: 0.64, 1.50; P = .93), whereas the use of a different LOCM without a common side chain significantly lowered HSR recurrence (OR, 0.51; 95% CI: 0.37, 0.69; P < .001) in multivariate general estimating equation analysis. Substitution of an LOCM without a common side chain was effective regardless of the index HSR severity but was more pronounced in moderate-to-severe reactions (OR, 0.30; 95% CI: 0.16, 0.55; P < .001). Conclusion For patients with a previous immediate HSR of any severity to LOCM, alternative LOCM without a common carbamoyl side chain reduced recurrent HSR during subsequent exposures. © RSNA, 2023 Supplemental material is available for this article. See also the editorial by McDonald in this issue.

Classical monocyte-derived macrophages as therapeutic targets of umbilical cord mesenchymal stem cells: comparison of intratracheal and intravenous administration in a mouse model of pulmonary fibrosis.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a progressive fibrotic lung disease that has no cure. Although mesenchymal stem cells (MSCs) have been reported to ameliorate lung inflammation and fibrosis in mouse models, their mechanisms of action remain unknown. Therefore, we aimed to determine the changes in various immune cells, especially macrophages and monocytes, involved in the effects of MSC treatment on pulmonary fibrosis. METHODS: We collected and analyzed explanted lung tissues and blood from patients with IPF who underwent lung transplantation. After establishing a pulmonary fibrosis model via the intratracheal administration of bleomycin (BLM) to 8-week-old mice, MSCs derived from human umbilical cords were administered intravenously or intratracheally on day 10 and the lungs were immunologically analyzed on days 14 and 21. Flow cytometry was performed to analyze the immune cell characteristics, and gene expression levels were examined using quantitative reverse transcription-polymerase chain reaction. RESULTS: In the histological analysis of explanted human lung tissues, the terminally fibrotic areas contained a larger number of macrophages and monocytes than the early fibrotic areas of the lungs. When human monocyte-derived macrophages (MoMs) were stimulated with interleukin-13 in vitro, the expression of type 2 macrophage (M2) markers was more prominent in MoMs from the classical monocyte subset than in those from intermediate or non-classical monocyte subsets, and MSCs suppressed M2 marker expression independent of MoM subsets. In the mouse model, the increased number of inflammatory cells in the bronchoalveolar lavage fluid and the degree of lung fibrosis observed in BLM-treated mice were significantly reduced by MSC treatment, which tended to be more prominent with intravenous administration than intratracheal administration. Both M1 and M2 MoMs were upregulated in BLM-treated mice. The M2c subset of M2 MoMs was significantly reduced by MSC treatment. Among M2 MoMs, M2 MoMs derived from Ly6C+ monocytes were most effectively regulated by the intravenous administration, not intratracheal administration, of MSCs. CONCLUSIONS: Inflammatory classical monocytes may play a role in lung fibrosis in human IPF and BLM-induced pulmonary fibrosis. Intravenous rather than intratracheal administration of MSCs may ameliorate pulmonary fibrosis by inhibiting monocyte differentiation into M2 macrophages.

Neuromuscular blocking agent re-exposure in a retrospective cohort with neuromuscular blocking agent-associated anaphylaxis.

BACKGROUND: Neuromuscular blocking agents (NMBAs) are one of the most common causes of perioperative anaphylaxis. Although skin test positivity may help identify reactive NMBAs, it is unclear whether skin test negativity can guarantee the safety of systemically administered NMBAs. OBJECTIVE: This study aimed to evaluate the real-world safety of alternative NMBAs screened using skin tests in patients with suspected NMBA-induced anaphylaxis. METHODS: A retrospective cohort of suspected NMBA-induced anaphylaxis were recruited among patients at Seoul National University Hospital from June 2009 to May 2021, and their characteristics and outcomes were assessed. RESULTS: A total of 47 cases (0.017%) of suspected anaphylaxis occurred in 282,707 patients who received NMBAs. Cardiovascular manifestations were observed in 95.7%, whereas cutaneous findings were observed in 59.6%. Whereas 83% had a history of undergoing general anesthesia, 17% had no history of NMBA use. In skin tests, the overall positivity to any NMBA was 94.6% (81.1% to culprit NMBAs) and the cross-reactivity was 75.7%, which is related to the chemical structural similarity among NMBAs; the cross-reactivity and chemical structure similarity of rocuronium were 85.3% and 0.814, respectively, with vecuronium; this is in contrast to 50% and 0.015 with cisatracurium and 12.5% and 0.208 with succinylcholine. There were 15 patients who underwent subsequent surgery with a skin test-negative NMBA; whereas 80.0% (12/15) safely completed surgery, 20.0% (3/15) experienced hypotension. CONCLUSION: Similarities in chemical structure may contribute to the cross-reactivity of NMBAs in skin tests. Despite the high negative predictability of skin tests for suspected NMBA-induced anaphylaxis, the potential risk of recurrent anaphylaxis has not been eliminated.

A unique population of neutrophils generated by air pollutant-induced lung damage exacerbates airway inflammation.

BACKGROUND: Diesel exhaust particles (DEPs) are the main component of traffic-related air pollution and have been implicated in the pathogenesis and exacerbation of asthma. However, the mechanism by which DEP exposure aggravates asthma symptoms remains unclear. OBJECTIVE: This study aimed to identify a key cellular player of air pollutant-induced asthma exacerbation and development. METHODS: We examined the distribution of innate immune cells in the murine models of asthma induced by house dust mite and DEP. Changes in immune cell profiles caused by DEP exposure were confirmed by flow cytometry and RNA-Seq analysis. The roles of sialic acid-binding, Ig-like lectin F (SiglecF)-positive neutrophils were further evaluated by adoptive transfer experiment and in vitro functional studies. RESULTS: DEP exposure induced a unique population of lung granulocytes that coexpressed Ly6G and SiglecF. These cells differed phenotypically, morphologically, functionally, and transcriptionally from other SiglecF-expressing cells in the lungs. Our findings with murine models suggest that intratracheal challenge with DEPs induces the local release of adenosine triphosphate, which is a damage-associated molecular pattern signal. Adenosine triphosphate promotes the expression of SiglecF on neutrophils, and these SiglecF+ neutrophils worsen type 2 and 3 airway inflammation by producing high levels of cysteinyl leukotrienes and neutrophil extracellular traps. We also found Siglec8- (which corresponds to murine SiglecF) expressing neutrophils, and we found it in patients with asthma-chronic obstructive pulmonary disease overlap. CONCLUSION: The SiglecF+ neutrophil is a novel and critical player in airway inflammation and targeting this population could reverse or ameliorate asthma.

Allergic-like Hypersensitivity Reactions to Gadolinium-based Contrast Agents: An 8-year Cohort Study of 154 539 Patients.

Background With the widespread use of gadolinium-based contrast agents (GBCAs), the incidence of allergic-like hypersensitivity reactions (HSRs) to GBCAs is increasing. Research on the incidence and risk factors for HSRs to GBCAs is needed for their safe use. Purpose To determine the incidence of acute and delayed reactions to GBCAs and to discuss the risk factors and strategies for the prevention of HSRs to GBCAs. Materials and Methods All cases of HSRs to contrast media that occurred at the Seoul National University Hospital from July 1, 2012, to June 30, 2020, were assessed. Information including age, sex, GBCA type, onset, and severity of HSRs was retrospectively analyzed. Results Among the 331070 cases of GBCA exposure in 154539 patients, 1304 cases of HSRs (0.4%) were reported. Acute HSRs accounted for 1178 cases (0.4%), while 126 cases (0.04%) were delayed HSRs. While both premedication (odds ratio [OR] = 0.7, P = .041) and changing the type of GBCA (OR = 0.2, P < .001) showed preventative effects in patients with a history of acute HSRs, only premedication (OR = 0.2, P = .016) significantly reduced the incidence of HSRs in patients with a history of delayed reactions. The risk of an HSR to GBCA was higher in those with a history of an HSR to iodinated contrast media (OR = 4.6, P < .001). Conclusion The rate of hypersensitivity reactions (HSRs) to gadolinium-based contrast agents (GBCAs) was 0.4%. The absence of premedication, repeated exposures to the culprit GBCA, and a history of HSRs to iodinated contrast media and GBCAs were risk factors for HSRs to GBCAs. © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Kallmes and McDonald in this issue.

Effect of Acinetobacter lwoffii on the modulation of macrophage activation and asthmatic inflammation.

BACKGROUND: Although lung macrophages are directly exposed to external stimuli, their exact immunologic roles in asthma are still largely unknown. The aim of this study was to investigate the anti-asthmatic effect of Acinetobacter lwoffii in terms of lung macrophage modulation. METHODS: Six-week-old female BALB/c mice were sensitized and challenged with ovalbumin (OVA) with or without intranasal administration of A. lwoffii during the sensitization period. Airway hyperresponsiveness and inflammation were evaluated. Using flow cytometry, macrophages were subclassified according to their activation status. In the in vitro study, a murine alveolar macrophage cell line (MH-S) treated with or without A. lwoffii before IL-13 stimulation were analysed by quantitative RT-PCR. RESULTS: In a murine asthma model, the number of inflammatory cells, including macrophages and eosinophils, decreased in mice treated with A. lwoffii (A. lwoffii/OVA group) compared with untreated mice (OVA group). The enhanced expression of MHCII in macrophages in the OVA group was decreased by A. lwoffii treatment. M2 macrophage subtypes were significantly altered. A. lwoffii treatment decreased CD11b+ M2a and CD11b+ M2c macrophages, which showed strong positive correlations with Th2 cells, ILC2 and eosinophils. In contrast, CD11b+ M2b macrophages were significantly increased by A. lwoffii treatment and showed strong positive correlations with ILC1 and ILC3. In vitro, A. lwoffii down-regulated the expression of M2 markers related but up-regulated those related to M2b macrophages. CONCLUSIONS AND CLINICAL RELEVANCE: Intranasal A. lwoffii exposure suppresses asthma development by suppressing the type 2 response via modulating lung macrophage activation, shifting M2a and M2c macrophages to M2b macrophages.

Peripheral blood transcriptomic clusters uncovered immune phenotypes of asthma.

BACKGROUND: Transcriptomic analysis has been used to elucidate the complex pathogenesis of heterogeneous disease and may also contribute to identify potential therapeutic targets by delineating the hub genes. This study aimed to investigate whether blood transcriptomic clustering can distinguish clinical and immune phenotypes of asthmatics, and microbiome in asthmatics. METHODS: Transcriptomic expression of peripheral blood mononuclear cells (PBMCs) from 47 asthmatics and 21 non-asthmatics was measured using RNA sequencing. A hierarchical clustering algorithm was used to classify asthmatics. Differentially expressed genes, clinical phenotypes, immune phenotypes, and microbiome of each transcriptomic cluster were assessed. RESULTS: In asthmatics, three distinct transcriptomic clusters with numerously different transcriptomic expressions were identified. The proportion of severe asthmatics was highest in cluster 3 as 73.3%, followed by cluster 2 (45.5%) and cluster 1 (28.6%). While cluster 1 represented clinically non-severe T2 asthma, cluster 3 tended to include severe non-T2 asthma. Cluster 2 had features of both T2 and non-T2 asthmatics characterized by the highest serum IgE level and neutrophil-dominant sputum cell population. Compared to non-asthmatics, cluster 1 showed higher CCL23 and IL1RL1 expression while the expression of TREML4 was suppressed in cluster 3. CTSD and ALDH2 showed a significant positive linear relationship across three clusters in the order of cluster 1 to 3. No significant differences in the diversities of lung and gut microbiomes were observed among transcriptomic clusters of asthmatics and non-asthmatics. However, our study has limitations in that small sample size data were analyzed with unmeasured confounding factors and causal relationships or function pathways were not verified. CONCLUSIONS: Genetic clustering based on the blood transcriptome may provide novel immunological insight, which can be biomarkers of asthma immune phenotypes. Trial registration Retrospectively registered.

The international WAO/EAACI guideline for the management of hereditary angioedema-The 2021 revision and update.

Hereditary angioedema (HAE) is a rare and disabling disease for which early diagnosis and effective therapy are critical. This revision and update of the global WAO/EAACI guideline on the diagnosis and management of HAE provides up-to-date guidance for the management of HAE. For this update and revision of the guideline, an international panel of experts reviewed the existing evidence, developed 28 recommendations, and established consensus by an online DELPHI process. The goal of these recommendations and guideline is to help physicians and their patients in making rational decisions in the management of HAE with deficient C1 inhibitor (type 1) and HAE with dysfunctional C1 inhibitor (type 2), by providing guidance on common and important clinical issues, such as: (1) How should HAE be diagnosed? (2) When should HAE patients receive prophylactic on top of on-demand treatment and what treatments should be used? (3) What are the goals of treatment? (4) Should HAE management be different for special HAE patient groups such as children or pregnant/breast-feeding women? and (5) How should HAE patients monitor their disease activity, impact, and control? It is also the intention of this guideline to help establish global standards for the management of HAE and to encourage and facilitate the use of recommended diagnostics and therapies for all patients.

Epidemiology and evaluation of adverse drug reactions in a Korean hospital database for spontaneous reports in the period 2009 to 2018.

OBJECTIVE: To evaluate the epidemiology of adverse drug reactions (ADRs) in the Korean population and to identify their characteristics and factors affecting their severity. MATERIALS AND METHODS: The analysis was based on the ADRs reported to the Seoul National University Hospital between 2009 and 2018. Statistical assessment (SPSS Statistics 25) included frequency analysis and the χ2-test. Risk factors were assessed using logistic regression analysis. Results were considered significant at p < 0.05. RESULTS: A total of 44,122 cases were analyzed of which 24,801 (56.2%) cases concerned females and 19,321 (43.8%) males. A total of 47% of cases involved persons aged between 50 and 79 years. Antineoplastic agents, immunomodulating agents, and systemically administered anti-infective agents accounted for 57.6% of all drugs reported. Gastro-intestinal system disorders accounted for the largest proportion (25.8%) of adverse drug reactions reported. A total of 3,429 (7.8%) ADRs were reported as being in the category severe. Multivariate analysis showed that the risk of an ADR being reported as severe is higher in males than in females (OR = 1.25, 95% CI: 1.16 - 1.35), and higher in those aged 0 - 4 years (OR = 1.74, 95% CI: 1.46 - 2.08), in those aged 5 - 19 years (OR = 1.19, 95% CI: 1.07 - 1.31), and in those aged 65 years and over (OR = 1.26, 95% CI: 1.16 - 1.37), compared to those aged 20 - 64 years. DISCUSSION AND CONCLUSION: From a public health perspective, ADRs are important because they are preventable. Important determinants, such as differences in specific age groups and drug classes, for the occurrence of ADRs and the occurrence of severe ADRs in particular, were identified. These determinants need to be carefully monitored in both private medical practices, clinics and hospitals. This monitoring of specific groups will involve close attention factors associated with gender, age group, and drug classes.

Lung virome: New potential biomarkers for asthma severity and exacerbation.

BACKGROUND: Although some respiratory virus infections are known to contribute to the development and exacerbation of asthma, commensal viromes in airway have not been extensively studied due to technical challenges. OBJECTIVES: This study investigated the characteristics of the virome in asthmatic airways. METHODS: Both the bacteriome and virome profiles in sputum from 12 healthy individuals, 15 patients with nonsevere asthma, and 15 patients with severe asthma were analyzed and assessed for the association with clinical characteristics such as severity, exacerbation, Asthma Control Test (ACT), and lung function. RESULTS: While analysis of the 16S ribosomal RNA bacteriome in the airway showed no differences, clear contrasts in the diversity and composition of airway viromes were observed between healthy controls and patients with asthma. Herpesviruses were the most abundant type of virus in the asthma group (44.6 ± 4.6%), mainly with cytomegalovirus (CMV) and EBV accounting for 24.5 ± 3.3% and 16.9 ± 3.5%, respectively, in contrast to those in the healthy controls (5.4 ± 2.5% and 7.1 ± 3.0%, respectively). CMV and EBV were more abundant in patients with asthma who experienced exacerbation, and their abundance showed correlation with more severe asthma, lower ACT score, and lower lung function. On the contrary, bacteriophage that is abundant in healthy controls was severely reduced in patients with asthma in the order of nonsevere and severe asthma and presented significant positive correlation with ACT and FEV1/forced vital capacity. CONCLUSIONS: Lung viromes, especially, CMV, EBV, and bacteriophage may be potential biomarkers of asthma severity and exacerbation.

Practice parameters for diagnosing and managing iodinated contrast media hypersensitivity.

Immediate and nonimmediate hypersensitivity reactions to iodinated contrast media (ICM) have been reported to occur in a frequency of about 0.5%-3% of patients receiving nonionic ICM. The diagnosis and management of these patients vary among guidelines published by various national and international scientific societies, with recommendations ranging from avoidance or premedication to drug provocation test. This position paper aims to give recommendations for the management of patients with ICM hypersensitivity reactions and analyze controversies in this area. Skin tests are recommended as the initial step for diagnosing patients with immediate and nonimmediate hypersensitivity reactions; besides, they may also help guide on tolerability of alternatives. Re-exposition or drug provocation test should only be done with skin test-negative ICMs. The decision for performing either re-exposition or drug provocation test needs to be taken based on a risk-benefit analysis. The role of in vitro tests for diagnosis and pretreatment for preventing reactions remains controversial.

Transglutaminase 2 mediates lung inflammation and remodeling by transforming growth factor beta 1 via alveolar macrophage modulation.

Transforming growth factor beta 1 (TGF-ß1) induces pulmonary fibrosis by enhancing epithelial apoptosis and affects the enzymatic activity of transglutaminase 2 (TG2). The aim of this study was to determine the role of TG2 in TGF-ß1-induced lung remodeling and alveolar macrophage modulation. We characterized the in vivo effects of TGF-ß1 and TG2 on lung inflammation, fibrosis, and macrophage activity using transgenic C57BL/6 mice with wild and null TG2 loci. The effect of TG2 inhibition on in vitro TGF-ß1-stimulated alveolar macrophages was assessed through mRNA analysis. TG2 was remarkably upregulated in the lungs of TGF-ß1 transgenic (TGF-ß1 Tg) mice, especially in alveolar macrophages and epithelial cells. In the absence of TG2, TGF-ß1-induced inflammation was suppressed, decreasing the number of macrophages in the bronchoalveolar lavage fluid. In addition, the alveolar destruction and peribronchial fibrosis induced by TGF-ß1 overexpression were significantly reduced, which correlated with decreases in the expression of fibroblast growth factor and matrix metallopeptidase 12, respectively. However, TG2 deficiency did not compromise the phagocytic activity of alveolar macrophages in TGF-ß1 Tg mice. At the same time, TG2 contributed to the regulation of TGF-ß1-induced macrophage activation. Inhibition of TG2 did not affect the TGF-ß1-induced expression of CD86, an M1 marker, in macrophages, but it did reverse the TGF-ß1-induced expression of CD206. This result suggests that TG2 mediates TGF-ß1-induced M2-like polarization but does not contribute to TGF-ß1-induced M1 polarization. In conclusion, TG2 regulates macrophage modulation and plays an important role in TGF-ß1-induced lung inflammation, destruction, and fibrosis.

The Use of Contrast Agents in Interventional Pain Procedures: A Multispecialty and Multisociety Practice Advisory on Nephrogenic Systemic Fibrosis, Gadolinium Deposition in the Brain, Encephalopathy After Unintentional Intrathecal Gadolinium Injection, and Hypersensitivity Reactions.

This Practice Advisory presents a comprehensive and evidence-based set of position statements and recommendations for the use of contrast media in interventional pain procedures. The advisory was established by an international panel of experts under the auspices of 11 multinational and multispecialty organizations based on a comprehensive review of the literature up to December 31, 2019. The advisory discusses the risks of using gadolinium-based contrast agents. These include nephrogenic systemic fibrosis, gadolinium brain deposition/retention, and encephalopathy and death after an unintentional intrathecal gadolinium injection. The advisory provides recommendations on the selection of a specific gadolinium-based contrast agent in patients with renal insufficiency, those who had multiple gadolinium-enhanced magnetic resonance imaging examinations, and in cases of paraspinal injections. Additionally, recommendations are made for patients who have a history of mild, moderate, or severe hypersensitivity reactions to contrast medium.

Aggravation of asthmatic inflammation by chlorine exposure via innate lymphoid cells and CD11cintermediate macrophages.

BACKGROUND: Chlorine is widely used in daily life as disinfectant. However, chronic exposure to chlorine products aggravates allergic TH 2 inflammation and airway hyperresponsiveness (AHR). Innate lymphoid cells (ILCs) in airways contribute to the inception of asthma in association with virus infection, pollution, and excess of nutrient, but it is not known whether chronic chlorine exposure can activate innate immune cells. The aim of this study was to evaluate the impact of chlorine inhalation on the innate immunity such as ILCs and macrophages in relation with the development of asthma by using murine ovalbumin (OVA) sensitization/challenge model. METHODS: Six-week-old female BALB/c mice were sensitized and challenged with OVA in the presence and absence of chronic low-dose chlorine exposure by inhalation of naturally vaporized gas of 5% sodium hypochlorite solution. AHR, airway inflammatory cells, from BALF and the population of ILCs and macrophages in the lung were evaluated. RESULTS: The mice exposed to chlorine with OVA (Cl + OVA group) showed enhanced AHR and eosinophilic inflammation compared to OVA-treated mice (OVA group). The population of TH 2 cells, ILC2s, and ILC3s increased in Cl + OVA group compared with OVA group. CD11cint macrophages also remarkably increased in Cl + OVA group compared with OVA group. The deletion of macrophages by clodronate resulted in reduction of ILC2s and ILC3s population which was restored by adoptive transfer of CD11cint macrophages. CONCLUSIONS: Chronic chlorine inhalation contributes to the exacerbation of airway inflammation in asthmatic airway by mobilizing pro-inflammatory macrophage into the lung as well as stimulating group 2 and 3 ILCs.

Analysis of Innate and Adaptive Immunological Characteristics in Patients with IgG4-Related Disease.

BACKGROUND: Immunoglobulin G4-related disease (IgG4-RD) is a systemic immunological disorder characterized by fibro-inflammatory conditions; however, the pathobiology of IgG4-RD has not been fully identified. OBJECTIVE: This study aimed to analyze systemic differences of innate and adaptive immune cells from healthy controls and patients with IgG4-RD. METHODS: Healthy controls (n = 9) and IgG4-RD patients (n = 7) were recruited with informed consent. Peripheral blood was collected from healthy controls and IgG4-RD patients, and three blood samples from IgG4-RD patients were re-collected two months after the last rituximab (RTX) treatment. The various immune cells and cytokine productions were measured by flow cytometry. RESULTS: Blood CD14+ monocytes and steady-state follicular helper T cells were increased in patients with IgG4-RD. However, there were no changes in other immune cell populations, including B cells, CD4 T cells, CD8 T cells, and innate lymphoid cells. Also, the TGF-ß-producing CD14+ monocytes were significantly augmented in patients with IgG4-RD. Two months after RTX treatment, total B cells (CD19+) were depleted; however, the expressions of TGF-ß from CD14+ monocytes remained unchanged. CONCLUSION: These findings showed that IgG4-RD is related to the increment of CD14+ monocytes. Besides, controlling increased TGF-ß-producing CD14+ monocytes with RTX treatment might be a conducive way to regulate IgG4-RD.

Correction to: Immediate and delayed hypersensitivity after intra-arterial injection of iodinated contrast media: a prospective study in patients with coronary angiography.

The original version of this article, published on 01 April 2019, unfortunately contained a mistake. The presentation of Fig. 1 was incorrect. The corrected figure is given below.

Innate immune crosstalk in asthmatic airways: Innate lymphoid cells coordinate polarization of lung macrophages.

BACKGROUND: Recent studies have emphasized the role of innate lymphoid cells (ILCs) in the development of asthma. The involvement of group 2 innate lymphoid cells (ILC2s) in asthma is well studied: however, the participation of other types of ILCs in the development of asthma remains unclear. OBJECTIVE: This study aims to understand the role of various ILCs in patients with asthma, especially their effect on macrophage polarization. METHODS: Each subset of ILCs and macrophages in induced sputum from 51 steroid-naive patients with asthma and 18 healthy donors was analyzed by using flow cytometry. Alveolar macrophages (AM) were sorted and cocultured with each subset of ILCs to determine whether the polarization of macrophages could be regulated by ILCs. RESULTS: In addition to ILC2s, numbers of group 1 innate lymphoid cells (ILC1s) and group 3 innate lymphoid cells (ILC3s) were increased in induced sputum from asthmatic patients when compared with those in healthy control subjects. The dominance of macrophages in induced sputum was more prominent in asthmatic patients than in healthy control subjects. A positive correlation between numbers of ILC2s and numbers of M2 macrophages and those of ILC1s/ILC3s and M1 macrophages was observed. Coculture of ILC2s with AMs induced expression of M2 macrophage-related genes, whereas coculture of ILC1s and ILC3s with AMs induced expression of M1 macrophage-related genes through cytokine secretion, as well as cell-cell contact. According to the inflammatory signature, patients with eosinophilic asthma have more ILC2s and M2 macrophages, and those with noneosinophilic asthma have an M1 macrophage-dominant profile. CONCLUSION: A different subset of ILCs regulates macrophage polarization, contributing to developing the distinct phenotype of asthma.

Prevalence of Toxocariasis and Its Risk Factors in Patients with Eosinophilia in Korea.

Eosinophilia occurs commonly in many diseases including allergic diseases and helminthic infections. Toxocariasis has been suggested as one cause of eosinophilia. The present study was undertaken to examine the prevalence of toxocariasis in patients with eosinophilia and to identify the risk factors for toxocariasis. This prospective cohort study recruited a total of 81 patients with eosinophilia (34 males and 47 females) who visited the outpatient clinic at Seoul National University Hospital from January 2017 to February 2018 and agreed to participate in this study. The prevalence of toxocariasis was examined by T. canis-specific ELISA, and the various risk factors for toxocariasis were evaluated by a questionnaire survey. Among 81 patients with eosinophilia, 18 were positive for anti-T. canis antibodies (22.2%); 88.9% were male (16/18) and 11.1% were female (2/18). Multivariate statistical analysis revealed that males (OR 21.876, 95% CI: 1.667-287.144) with a history of consuming the raw meat or livers of animals (OR 5.899, 95% CI: 1.004-34.669) and a heavy alcohol-drinking habit (OR 8.767, 95% CI: 1.018-75.497) were at higher risk of toxocariasis in patients with eosinophilia. Toxocariasis should be considered a potential cause of eosinophilia when the patient has a history of eating the raw meat or livers of animals in Korea. A single course of albendazole is recommended to reduce the migration of Toxocara larvae in serologically positive cases with eosinophilia.

Hypersensitivity Reactions to Iodinated Contrast Media: A Multicenter Study of 196 081 Patients.

Background Multicenter studies may be required for establishing guidelines for safe usage of iodinated contrast media (ICM). Purpose To identify the prevalence, patterns, risk factors, and preventive measures for ICM-related hypersensitivity reactions (HSRs). Materials and Methods Between March 2017 and October 2017, a total of 196 081 patients who underwent ICM administration were enrolled from seven participating institutions. The occurrence of HSRs and baseline patient information were recorded. χ2 and Student t test were performed, and logistic regression analyses were used to identify risk factors that predict occurrence and recurrence of HSR. Results Among 196 081 patients (mean age ± standard deviation, 59.1 years ± 16.0; 105 014 men and 91 067 women) who underwent ICM administration, the overall prevalence of HSRs was 0.73% (1433 of 196 081), and severe reactions occurred in 0.01% (17 of 196 081). Conditional logistic regression for patients with HSR (n = 1433) and a control group (1:1 matched group for age, sex, ICM product, and institution) demonstrated that a patient's previous individual history of an ICM-related HSR (adjusted odds ratio [OR], 198.8; P < .001), hyperthyroidism (adjusted OR, 3.6; P = .04), drug allergy (adjusted OR, 3.5; P < .001), and other allergic diseases (adjusted OR, 6.8; P < .001) and a family history of ICM-related HSRs (adjusted OR, 14.0; P = .01) were predictors of HSR occurrence. Logistic regression analysis showed that use of premedication with antihistamine (OR, 0.5; P = .01) and change in the generic profile of ICM (OR, 0.5; P < .001) were preventive against recurrent HSR. Conclusion Family history as well as previous individual history of hypersensitivity reactions (HSRs) to iodinated contrast media (ICM) were risk factors for HSR occurrence, suggesting a potential genetic predisposition. A change in the culprit ICM and premedication with antihistamine are useful for reducing the recurrence of HSRs. © RSNA, 2019 Online supplemental material is available for this article.

Duration of Observation for Detecting a Biphasic Reaction in Anaphylaxis: A Meta-Analysis.

BACKGROUND: We conducted a meta-analysis to determine a practical observation time for detecting a biphasic reaction after resolution of the initial anaphylactic reaction. METHODS: A systematic literature search identified studies on adult patients with anaphylaxis and a subsequent biphasic reaction due to various causes that contained sufficient data to extract outcomes. The outcomes were pooled using a random-effects model. RESULTS: Twelve studies with a total of 2,890 adult patients with anaphylaxis and 143 patients with a biphasic reaction were included. In terms of the pooled negative predictive value, 1 h of observation achieved a 95.0% negative predictive value and ≥6 h of observation provided a 97.3% negative predictive value (95% CI: 95.0-98.5). The negative predictive value for a biphasic reaction increased with a longer observation time after initial anaphylaxis, and the increasing trend slowed down from 6 h of observation time. The pooled additional incidence rates of biphasic reactions per 100 person-hours after 1- and 4-h observations were 0.45 (95% CI: 0.20-1.04) and 0.41 (95% CI: 0.19-0.87), respectively. After > 8-12 h of postanaphylactic observation, the negative predictive value reached > 98%, while the additional incidence per 100 person-hours was < 0.10. CONCLUSIONS: An observation time of ≥6 h after resolution of an initial anaphylaxis symptom can exclude recurrence of a secondary reaction in > 95% of patients. Although longer observation periods resulted in the detection of more biphasic reactions, 6-12 h of observation time would be practical, supporting current relevant guidelines.