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.

Rapamycin Restores Different Patterns of Cytokine Expression to Dexamethasone Treatment on CD14++CD16+ Monocytes from Steroid-Resistant Asthma Patients.

OBJECTIVE: We aimed to investigate the differences in interleukin (IL)-10, IL-1ß, IL-6, and tumor necrosis factor (TNF)-α expression in lipopolysaccharide (LPS)-stimulated CD14++CD16+ monocytes obtained from asthmatics after dexamethasone or dexamethasone plus rapamycin treatments between clinical steroid responders (R) and non-responders (NR). METHODS: Cytokine expressions in LPS-stimulated CD14++CD16+ p-mammalian target of rapamycin (mTOR) monocytes from R and NR were determined using flow cytometry. RESULTS: IL-10high CD14++CD16+ p-mTOR population following LPS stimulation increased in the R group although decreased in the NR group with dexamethasone treatment. IL-1ßhigh population decreased in the R group although increased in the NR group. Rapamycin treatment after LPS and dexamethasone resulted in a significant increase in the IL-10high population and a significant decrease in the IL-1ßhigh population in the NR group. CONCLUSION: Dexamethasone treatment resulted in different patterns of change in cytokine expressions in LPS-stimulated CD14++CD16+ p-mTOR monocytes between the R and NR. mTOR inhibition can restore steroid responsiveness involving IL-10 and IL-1ß in CD14++CD16+ p-mTOR monocytes.

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.

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.

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.

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

OBJECTIVES: While hypersensitivity reactions (HSR) to intravenously administered iodinated contrast media (ICM) have been well studied, not much is known about HSR to intra-arterially administered ICM. METHODS: A prospective observational study was performed to evaluate coronary angiography (CAG)-induced ICM hypersensitivity in patients who underwent CAG using ICM including ioversol, a low-osmolar non-ionic monomer, and iodixanol, an iso-osmolar non-ionic dimer. The HSR were investigated through in-patient monitoring after CAG and telephone interview after discharge. RESULTS: A total of 714 patients were enrolled during the observation period, of whom 26 (3.6%) showed immediate HSR and 108 (15.1%) showed delayed HSR. With regard to severity, proportion of immediate HSR grades 1, 2, and 3 was 57.7%, 38.5%, and 3.8%, respectively, whereas that of delayed HSR grades 1, 2, and 3 was 85.2%, 13.9%, and 0.9%, respectively. Multivariate analysis revealed that previous intra-arterial exposure to ICM was an independent risk factor for immediate HSR (odds ratio (OR) 2.92, 95% confidence interval (CI) 1.22-6.96; p = 0.015). Iodixanol was a significant risk factor for delayed HSR (OR 1.61, 95% CI 1.07-2.43; p = 0.024) and correlated with a higher incidence of delayed HSR within 24-h post-ICM administration compared to ioversol. CONCLUSION: The incidence rate of immediate and delayed HSR in intra-arterially administered ICM was 3.6% and 15.1%, respectively. Previous exposure to intra-arterially administered contrast media was a significant risk factor for immediate HSR. Compared to ioversol, iodixanol was associated with relatively earlier and more frequent delayed HSR. KEY POINTS: • In this prospective study, the incidence of immediate and delayed hypersensitivity in intra-arterial injection of contrast media during coronary angiography was 3.6% and 15.1%, respectively. • Delayed hypersensitivity reactions were more common but less severe than immediate hypersensitivity reactions during coronary angiography. • Previous exposure to ICM via intra-arterial route was a significant risk factor for immediate hypersensitivity to intra-arterial contrast medium.

Favorable longitudinal change of lung function in patients with asthma-COPD overlap from a COPD cohort.

BACKGROUND: The recognition of asthma-chronic obstructive pulmonary disease (COPD) overlap (ACO) as a distinct phenotype of COPD or asthma has increased. Although ACO has worse clinical features than non-ACO COPD, limited information is available on long-term outcomes of lung function decline for ACO and non-ACO COPD. METHODS: COPD patients with at least 3 years of follow-up were selected from the Korean Obstructive Lung Disease cohort. ACO was defined based on 3 major criteria: 1) airflow limitation in individuals 40 years of age and older, 2) ≥10 pack-years of smoking history, and 3) a history of asthma or bronchodilator response of > 400 mL in forced expiratory volume in 1 s (FEV1) at baseline; and at least 1 minor criterion: 1) history of atopy or allergic rhinitis, 2) two separated bronchodilator responses of ≥12% and 200 mL in FEV1, or 3) peripheral blood eosinophils ≥300 cells/µL. Lung function decline was compared using a linear mixed effects model for longitudinal data with random intercept and random slope. RESULTS: Among 239 patients, 47 were diagnosed with ACO (19.7%). During the follow-up period, change in smoking status, use of inhaled corticosteroids (ICS) and long-acting ß2-agonists or ICS and at least 2 exacerbations per year were similar between patients with non-ACO COPD and ACO. Over a median follow-up duration of 5.8 years, patients with non-ACO COPD experienced a faster annual decline in pre-bronchodilator FEV1 than patients with ACO (- 29.3 ml/year vs. -13.9 ml/year, P = 0.042), which was persistent after adjustment for confounders affecting lung function decline. CONCLUSION: Patients with ACO showed favorable longitudinal changes in lung function compared to COPD patients over a median follow-up of 5.8 years.

Biphasic and protracted anaphylaxis to iodinated contrast media.

OBJECTIVES: To investigate the prevalence of biphasic and protracted anaphylaxis to iodinated contrast media (ICM), their risk factors and practical observation duration for detecting biphasic reaction. METHODS: 145 patients with ICM anaphylaxis from January 2005-February 2016 were retrospectively categorised into uniphasic, biphasic (anaphylaxis recurrence within 72 h after resolution of initial anaphylaxis) and protracted (anaphylaxis >5 h) reaction groups. Multivariate regression analyses of potential risk factors were performed. We calculated negative predictive value (NPV) for biphasic reactions and additional person-hours required to detect one case during post-anaphylaxis observation. RESULTS: Fifteen patients had biphasic reactions with secondary reactions with similar or milder severity and six had protracted reactions. Most significant risk factors were anaphylaxis duration >40 min for biphasic reactions (odds ratio (OR), 8.65 [95 % CI, 1.05-70.71]; P=0.044), and additional epinephrine administration within 1 h of initial dosing for protracted reactions (OR, 102.0 [95 % CI, 3.40-3057.25]; P=0.008). A 6-h post-anaphylaxis observation produced NPV of 96.4 %, while requiring a minimum of 65.5 additional person-hours to detect one additional case. CONCLUSION: Biphasic and protracted ICM anaphylaxis developed in 10.3 % and 4.1 %, respectively, with revealing risk factors. Six hours could be practical for post-anaphylaxis observation to detect biphasic reaction. KEY POINTS: • Incidence of biphasic anaphylaxis in iodinated contrast media anaphylaxis is 10.3 %. • Incidence of protracted anaphylaxis in iodinated contrast media anaphylaxis is 4.1 %. • Initial anaphylaxis >40 min can predict for biphasic anaphylaxis development. • A 6-h post-anaphylactic observation in ICM-related anaphylaxis seems practical.

Autophagy Primes Neutrophils for Neutrophil Extracellular Trap Formation during Sepsis.

RATIONALE: Neutrophils are key effectors in the host's immune response to sepsis. Excessive stimulation or dysregulated neutrophil functions are believed to be responsible for sepsis pathogenesis. However, the mechanisms regulating functional plasticity of neutrophils during sepsis have not been fully determined. OBJECTIVES: We investigated the role of autophagy in neutrophil functions during sepsis in patients with community-acquired pneumonia. METHODS: Neutrophils were isolated from patients with sepsis and stimulated with phorbol 12-myristate 13-acetate (PMA). The levels of reactive oxygen species generation, neutrophil extracellular trap (NET) formation, and granule release, and the autophagic status were evaluated. The effect of neutrophil autophagy augmentation was further evaluated in a mouse model of sepsis. MEASUREMENTS AND MAIN RESULTS: Neutrophils isolated from patients who survived sepsis showed an increase in autophagy induction, and were primed for NET formation in response to subsequent PMA stimulation. In contrast, neutrophils isolated from patients who did not survive sepsis showed dysregulated autophagy and a decreased response to PMA stimulation. The induction of autophagy primed healthy neutrophils for NET formation and vice versa. In a mouse model of sepsis, the augmentation of autophagy improved survival via a NET-dependent mechanism. CONCLUSIONS: These results indicate that neutrophil autophagy primes neutrophils for increased NET formation, which is important for proper neutrophil effector functions during sepsis. Our study provides important insights into the role of autophagy in neutrophils during sepsis.

Stratified premedication strategy for the prevention of contrast media hypersensitivity in high-risk patients.

BACKGROUND: Although the severity of hypersensitivity reactions to iodinated contrast media varies, it is well correlated with the severity of recurrent reactions; however, prophylaxis protocols are not severity-stratified. OBJECTIVE: To assess the outcomes of tailored prophylaxis according to the severity of hypersensitivity reactions to iodinated contrast media. METHODS: Our premedication protocols were stratified based on the severity of previous reactions: (1) 4 mg of chlorpheniramine for mild reactions, (2) adding 40 mg of methylprednisolone for moderate reactions, and (3) adding multiple doses of 40 mg of methylprednisolone for severe index reactions. Cases of reexposure in patients with a history of hypersensitivity reactions were routinely monitored and mandatorily recorded. RESULTS: Among a total of 850 patients who underwent enhanced computed tomography after severity-tailored prophylaxis, breakthrough reactions occurred in 17.1%, but most breakthrough reactions (89.0%) were mild and did not require medical treatment. Additional corticosteroid use did not reduce the breakthrough reaction rate in cases with a mild index reaction (16.8% vs 17.2%, P = .70). However, underpremedication with a single dose of corticosteroid revealed significantly higher rates of breakthrough reaction than did double doses of corticosteroid in cases with a severe index reaction (55.6% vs 17.4%, P = .02). Changing the iodinated contrast media resulted in an additional reduction of the breakthrough reaction rate overall (14.9% vs 32.1%, P = .001). CONCLUSION: In a total severity-based stratified prophylaxis regimens and changing iodinated contrast media can be considered in patients with a history of previous hypersensitivity reaction to iodinated contrast media to reduce the risk of breakthrough reactions.

Relationship of computed tomography-based measurements with symptom perception and quality of life in patients with severe asthma.

BACKGROUND: Symptom perception and quality of life (QOL) are important domains for properly managing severe asthma. This study aimed to assess the relationship between airway structural and parenchymal variables measured using chest computed tomography (CT) and subjective symptom perception and QOL in patients with severe asthma enrolled in the Korean Severe Asthma Registry. METHODS: This study used CT-based objective measurements, including airway wall thickness (WT), hydraulic diameter, functional small airway disease (fSAD), and emphysematous lung (Emph), to assess their association with subjective symptom (cough, dyspnea, wheezing, and sputum) perception measured using the visual analog scale, and QOL measured by the Severe Asthma Questionnaire (SAQ). RESULTS: A total of 94 patients with severe asthma were enrolled in this study. The WT and fSAD% were significantly positively associated with cough and dyspnea, respectively. For QOL, WT and Emph% showed significant negative associations with the SAQ. However, there was no significant association between lung function and symptom perception or between lung function and QOL. CONCLUSION: Overall, WT, fSAD%, and Emph% measured using chest CT were associated with subjective symptom perception and QOL in patients with severe asthma. This study provides a basis for clarifying the clinical correlates of imaging-derived metrics and for understanding the mechanisms of respiratory symptom perception.

A Critical Systematic Review for Inhaled Corticosteroids on Lung Cancer Incidence: Not Yet Concluded Story.

BACKGROUND: To systematically review studies on inhaled corticosteroids (ICS) and lung cancer incidence in chronic airway disease patients. METHODS: We conducted electronic bibliographic searches on OVID-MEDLINE, EM- BASE, and the Cochrane Database before May 2020 to identify relevant studies. Detailed data on the study population, exposure, and outcome domains were reviewed. RESULTS: Of 4,058 screened publications, 13 eligible studies in adults with chronic obstructive pulmonary disease (COPD) or asthma evaluated lung cancer incidence after ICS exposure. Pooled hazard ratio and odds ratio for developing lung cancer in ICS exposure were 0.81 (95% confidence interval, 0.64 to 1.02; I2=95.7%) from 10 studies and 1.02 (95% confidence interval 0.50 to 2.07; I2=94.7%) from three studies. Meta-regression failed to explain the substantial heterogeneity of pooled estimates. COPD and asthma were variously defined without spirometry in 11 studies. Regarding exposure assessment, three and 10 studies regarded ICS exposure as a time-dependent and fixed variable, respectively. Some studies assessed ICS use for the entire study period, whereas others assessed ICS use for 6 months to 2 years within or before study entry. Smoking was adjusted in four studies, and only four studies introduced 1 to 2 latency years in their main or subgroup analysis. CONCLUSION: Studies published to date on ICS and lung cancer incidence had heterogeneous study populations, exposures, and outcome assessments, limiting the generation of a pooled conclusion. The beneficial effect of ICS on lung cancer incidence has not yet been established, and understanding the heterogeneities will help future researchers to establish robust evidence on ICS and lung cancer incidence.

Chronic viral hepatitis accelerates lung function decline in smokers.

Although hepatitis B virus (HBV) and hepatitis C virus (HCV) are hepatotrophic viruses, they may affect pulmonary diseases. The purpose of this study was to assess whether chronic viral hepatitis (CVH) infection was associated with a rapid decline in lung function. Repeated measurements of lung function were obtained from a well-curated health check-up database. A case was defined as an individual positive for HBsAg or anti-HCV antibody. A control was randomly selected (from the same dataset) after 1:1 matching in terms of age, sex, height, the body mass index, and smoking status. Separate analyses of non-smokers and smokers were performed. A total of 701 cases were enrolled (586 with HBV and 115 with HCV). In cross-sectional analysis, both forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) decreased significantly only in smokers (smoking cases vs. smoking controls) (adjusted p = 6.6 × 10-5 and adjusted p = 2.2 × 10-3, respectively). In longitudinal analysis, smoking cases showed significantly greater FEV1 and FVC decline rates than did smoking controls (adjusted p = 8.5 × 10-3 and adjusted p = 1.2 × 10-5, respectively). Such associations were particularly high in smoking cases at intermediate-to-high risk of hepatic fibrosis, as evaluated by the non-invasive Fibrosis-4 index. In summary, CVH was associated with both decreased lung function and accelerated lung function decline in smokers. A non-invasive measurement of hepatic fibrosis may be useful in predicting rapid lung function decline in smokers with CVH.

Transcriptome analysis of sputum cells reveals two distinct molecular phenotypes of "asthma and chronic obstructive pulmonary disease overlap" in the elderly.

BACKGROUND: Little is known about the pathogenesis of asthma and chronic obstructive pulmonary disease (COPD) overlap (ACO). This study examined the molecular phenotypes of ACO in the elderly. METHODS: A genome-wide investigation of gene expression in sputum cells from the elderly with asthma, ACO, or COPD was performed using gene set variation analysis (GSVA) with predefined asthma- or COPD-specific gene signatures. We then performed a subsequent cluster analysis using enrichment scores (ESs) to identify molecular clusters in the elderly with ACO. Finally, a second GSVA was conducted with curated gene signatures to gain insight into the pathogenesis of ACO associated with the identified molecular clusters. RESULTS: Seventy elderly individuals were enrolled (17 with asthma, 41 with ACO, and 12 with COPD). Two distinct molecular clusters of ACO were identified. Clinically, ACO cluster 1 (N = 23) was characterized by male and smoker dominance, more obstructive lung function, and higher proportions of both neutrophil and eosinophil in induced sputum compared to ACO cluster 2 (N = 18). ACO cluster 1 had molecular features similar to both asthma and COPD, with mitochondria and peroxisome dysfunction as important mechanisms in the pathogenesis of these diseases. The molecular features of ACO cluster 2 differed from those of asthma and COPD, with enhanced innate immune reactions to microorganisms identified as being important in the pathogenesis of this form of ACO. CONCLUSION: Recognition of the unique biological pathways associated with the two distinct molecular phenotypes of ACO will deepen our understanding of ACO in the elderly.

Does the Use of Asthma-Controller Medication in Accordance with Guidelines Reduce the Incidence of Acute Exacerbations and Healthcare Costs?

BACKGROUND: In asthma, consistent control of chronic airway inflammation is crucial, and the use of asthma-controller medication has been emphasized. Our purpose in this study is to compare the incidence of acute exacerbation and healthcare costs related to the use of asthma-controller medication. METHODS: By using data collected by the National Health Insurance Review and Assessment Service, we compared one-year clinical outcomes and medical costs from July 2014 to June 2015 (follow-up period) between two groups of patients with asthma who received different prescriptions for recommended asthma-controller medication (inhaled corticosteroids or leukotriene receptor antagonists) at least once from July 2013 to June 2014 (assessment period). RESULTS: There were 51,757 patients who satisfied our inclusion criteria. Among them, 13,702 patients (26.5%) were prescribed a recommended asthma-controller medication during the assessment period. In patients using a recommended asthma-controller medication, the frequency of acute exacerbations decreased in the follow-up period, from 2.7% to 1.1%. The total medical costs of the controller group decreased during the follow-up period compared to the assessment period, from $3,772,692 to $1,985,475. Only 50.9% of patients in the controller group used healthcare services in the follow-up period, and the use of asthma-controller medication decreased in the follow-up period. CONCLUSION: Overall, patients using a recommended asthma-controller medication showed decreased acute exacerbation and reduced total healthcare cost by half.

Targeting Chitinase 1 and Chitinase 3-Like 1 as Novel Therapeutic Strategy of Pulmonary Fibrosis.

Chitinase 1 (CHIT1) and chitinase 3-like-1 (CHI3L1), two representative members of 18-Glycosyl hydrolases family, are significantly implicated in the pathogenesis of various human diseases characterized by inflammation and remodeling. Notably, dysregulated expression of CHIT1 and CHI3L1 was noted in the patients with pulmonary fibrosis and their levels were inversely correlated with clinical outcome of the patients. CHIT1 and CHI3L1, mainly expressed in alveolar macrophages, regulate profibrotic macrophage activation, fibroblast proliferation and myofibroblast transformation, and TGF-ß signaling and effector function. Although the mechanism or the pathways that CHIT1 and CHI3L1 use to regulate pulmonary fibrosis have not been fully understood yet, these studies identify CHIT1 and CHI3L1 as significant modulators of fibroproliferative responses leading to persistent and progressive pulmonary fibrosis. These studies suggest a possibility that CHIT1 and CHI3L1 could be reasonable therapeutic targets to intervene or reverse established pulmonary fibrosis. In this review, we will discuss specific roles and regulatory mechanisms of CHIT1 and CHI3L1 in profibrotic cell and tissue responses as novel therapeutic targets of pulmonary fibrosis.

Validation of Practical Pathway in Patients With Anaphylaxis to Low Osmolar Contrast Media: A Retrospective Cohort Study.

BACKGROUND: An optimal strategy for choosing safe alternative low osmolar contrast media (LOCM) has not yet been established in patients with a history of LOCM-induced anaphylaxis. OBJECTIVES: To validate the practical pathway in patients with anaphylaxis to LOCMs and to compare 2 different doses of challenge testing with skin test-negative LOCM. METHODS: A retrospective cohort study was performed in patients with LOCM-induced anaphylaxis. Patients were challenged with intravenous LOCMs showing negativity in the skin test according to 2 different protocols: low-dose and high-dose (maximum dose 10 and 30 mL, respectively). Challenge-negative LOCMs were selected for use during computed tomography scans, and patients received intravenous pretreatment with 4 mg chlorpheniramine and 40 mg methylprednisolone. RESULTS: Of the 110 challenge tests, there were 4 (3.6%) positive challenges. Among 106 enhanced computed tomography scans performed using challenge-negative LOCMs, breakthrough reactions occurred in 8 (7.6%). Breakthrough reaction rates were not statistically different between the 2 protocols (8.9% and 6.0% in the low-dose challenge and the high-dose challenge, respectively). Compared with the low-dose protocol, the number needed to test of the high-dose challenge test decreased 2.5-fold. Moreover, none of the patients in the high-dose challenge group incurred severe reactions during computed tomography scans with challenge-negative LOCM, whereas 80% of reactions were severe in the low-dose challenge group. CONCLUSIONS: We validated a pathway consisting of a battery of skin testing to LOCMs and challenge with skin test-negative LOCM in patients with LOCM-induced anaphylaxis.

Incidence and risk factors of late adverse reactions to low-osmolar contrast media: A prospective observational study of 10,540 exposures.

PURPOSE: To evaluate the incidence and risk factors of late adverse reactions (ARs) to non-ionic low-osmolar contrast media (LOCM). METHODS: The occurrence of late AR was monitored on day 1 and from day 7 to day 28 in all patients who received enhanced computed tomography using LOCM during a 5-week study period in a single tertiary hospital. Patients who experienced late AR were followed up for three years. RESULTS: Among the total 10,540 LOCM exposures, 315 ARs (3.0%) were reported; acute ARs occurred in 108 LOCM exposures (1.0%) and late ARs occurred in 207 LOCM exposures (2.0%) (90.9% within one week, 9.1% developed afterwards by day 20). Previous history of drug allergy (odds ratio [OR] = 4.59; 95% confidence interval [CI] 2.17-9.71) and allergic diseases (OR = 2.54; 95% CI 1.32-4.91) were risk factors of late ARs to LOCM. Although the recurrence rate was lowered with premedication from 8.5% to 1.7% (8/94 vs. 3/178; p = 0.016), LOCM change did not make difference compared to reuse of the culprit LOCM (2/38 vs. 9/234; p = 0.655). In patients with a history of late AR to LOCM, the risk of recurrent reactions decreased with longer time intervals between exposures (OR = 0.86; 95% CI: 0.77-0.97; p = 0.025) and with the use of antihistamine premedication (OR = 0.27; 95% CI: 0.06-0.99; p = 0.049). CONCLUSIONS: Late ARs to LOCM occurred mostly within one week. The use of premedication may be helpful in reducing the recurrence of late ARs.

Analysis of Breakthrough Reactions in 1,143 Desensitization Procedures in a Single Tertiary Hospital Using a One-Bag Desensitization Protocol.

Background: Drug desensitization is helpful for patients who have experienced significant hypersensitivity reactions (HSRs) to antineoplastic agents. One-bag desensitization protocols, attracting attention in recent years, need to be validated on their safety and efficacy in a large number. Methods: One-bag desensitization procedures conducted from 2018 to 2020 were analyzed; their outcomes and the risk factors for breakthrough reactions (BTRs) were assessed in desensitization procedures to major drug types (platins, taxanes, and monoclonal antibodies). Results: A total of 1,143 procedures of one-bag desensitization were performed in 228 patients with 99% completion rate. BTRs occurred in 26% of the total desensitization procedures-34% in platins, 12% in taxanes, and 18% in mAbs. BTR occurrence rate decreased along the desensitization process with 80% of BTRs occurring within the 6th desensitization attempts. Severe BTR occurred more frequently with severe initial HSRs (1% in mild to moderate initial HSRs vs. 16% in severe). Severe initial HSR was also a significant risk factor for moderate to severe BTR in platins (odds ratio 1.56, 95% confidence interval [CI] 1.06-2.29, p = 0.025). The use of steroid was also associated with lower occurrence of moderate to severe BTR (odds ratio 0.50, 95% CI 0.35-0.72, p < 0.001). Conclusion: Most patients with HSRs to antineoplastic agents can safely receive chemotherapy through a one-bag desensitization protocol. Further studies on each drug with larger sample size can help verify the risk factors of BTRs and evaluate the efficacy of steroid premedication in improving the safety of desensitization in high-risk patients.