Acute Adverse Events After Iodinated Contrast Agent Administration of 359,977 Injections: A Single-Center Retrospective Study.

OBJECTIVE: To assess the effects of patient variables, examination variables, and seasonality on allergic-like and physiologic reactions to iodinated contrast material (ICM). PATIENTS AND METHODS: All ICM-enhanced computed tomography (CT) examinations performed from June 1, 2009, to May 9, 2017, at our institution were included. Reactions were identified and categorized as allergic-like or physiologic and mild, moderate, or severe. The effect of patient and examination variables on reactions was evaluated by logistic regression models. RESULTS: A total of 359,977 CT examinations performed on 176,886 unique patients were included. A total of 1150 allergic-like reactions (0.32%; 19 severe [0.005%]) and 679 physiologic reactions (0.19%; 3 severe [0.0008%]) occurred. On multivariable analysis, iopromide had higher rates of reactions compared with iohexol (allergic-like reactions: odds ratio [OR], 3.07 [95% CI, 2.37 to 3.98], P<.0001; physiologic reactions: OR, 2.60 [1.92 to 3.52], P<.0001). Non-White patients had higher rates of reactions compared with White patients (allergic-like reactions: OR, 1.77 [1.36-2.30], P<.0001; physiologic reactions: OR, 1.76 [1.27-2.42], P=.0006). Patient age, sex, prior ICM reaction, ICM dose, CT location, and CT type were also significantly associated with reactions. No significant seasonality trend was observed (P=.07 and .80). CONCLUSION: Non-White patients and patients administered iopromide had higher rates of acute reactions compared with White patients and patients administered iohexol. Younger patients (<50 years vs 51 to 60 years), female sex, history of ICM allergy or other allergies, ICM dose, and contrast-enhanced CT location and type also correlated with higher acute reaction rates.

Development of a machine learning algorithm based on administrative claims data for identification of ED anaphylaxis patient visits.

Background: Epidemiologic studies of anaphylaxis commonly rely on International Classification of Diseases (ICD) codes to identify anaphylaxis cases, which may lead to suboptimal epidemiologic classification. Objective: We sought to develop and assess the accuracy of a machine learning algorithm using ICD codes and other administrative data compared with ICD code-only algorithms to identify emergency department (ED) anaphylaxis visits. Methods: We conducted a retrospective review of ED visits from January 2013 to September 2017. Potential ED anaphylaxis visits were identified using 3 methods: anaphylaxis ICD diagnostic codes (method 1), ICD symptom-based codes with or without a code indicating an allergic trigger (method 2), and ICD codes indicating a potential allergic reaction only (method 3). A machine learning algorithm was developed from administrative data, and test characteristics were compared with ICD code-only algorithms. Results: A total of 699 of 2191 (31.9%) potential ED anaphylaxis visits were classified as anaphylaxis. The sensitivity and specificity of method 1 were 49.1% and 87.5%, respectively. Method 1 used in combination with method 2 resulted in a sensitivity of 53.9% and a specificity of 68.7%. Method 1 used in combination with method 3 resulted in a sensitivity of 98.4% and a specificity of 15.1%. The sensitivity and specificity of the machine learning algorithm were 87.3% and 79.1%, respectively. Conclusions: ICD coding alone demonstrated poor sensitivity in identifying cases of anaphylaxis, with venom-related anaphylaxis missing 96% of cases. The machine learning algorithm resulted in a better balance of sensitivity and specificity and improves upon previous strategies to identify ED anaphylaxis visits.

Clinical Follow-up in Patients With Moderate or Severe Allergic-Like Reactions to Iodinated Contrast Material.

OBJECTIVE: To examine follow-up care in patients with a history of acute allergic-like reaction to iodinated contrast material (ICM), including subsequent imaging management, allergy consultation, and repeat ICM exposure and reactions. METHODS: All patients who had a moderate or severe acute allergic-like reaction to ICM after contrast-enhanced CT (CECT) examination from June 1, 2009, to January 1, 2022, at our institution were included. Chart review was performed to determine (1) whether subsequent imaging was not performed or was altered in these patients, (2) whether the patient underwent a subsequent CECT examination, and (3) whether the patient had an allergist consultation. RESULTS: A total of 251 patients were identified. One-third of patients (90 of 251, 36%) had at least one change to their subsequent imaging management due to their reaction, including performing an unenhanced CT (62 of 251, 25%) or MRI (22 of 251, 8.8%) instead of a CECT or not performing a CECT when otherwise clinically indicated (20 of 251, 8.0%). Patients with a prior severe reaction were more likely to have a change in management than patients with a prior moderate reaction (severe: 22 of 32 [69%] versus moderate: 68 of 219 [31%], P < .0001). Only 17 patients (6.8%) had an allergy consult for their ICM reaction. A total of 90 patients underwent 274 subsequent CECT examinations. Repeat allergic-like reactions were observed in one quarter of patients (24 of 90, 27%) and a tenth of CECT examinations (29 of 274, 11%). DISCUSSION: One-third of patients with a history of a moderate or severe allergic-like reaction to ICM had their subsequent imaging care modified due to their reaction.

Aspirin-Exacerbated Respiratory Disease and the Unified Airway: A Contemporary Review.

Aspirin-exacerbated respiratory disease (AERD) is characterized by abnormal arachidonic acid metabolism leading to chronic rhinosinusitis with nasal polyposis (CRSwNP), asthma, and upper and/or lower respiratory symptoms after ingestion of cyclooxygenase-1 inhibiting nonsteroidal antiinflammatory drugs. Diagnosis is clinical and may involve an aspirin challenge. Inflammatory biomarkers may be useful for diagnosis and treatment monitoring. Conventional medical management for asthma and CRSwNP is often inadequate. Endoscopic sinus surgery followed by continued medical management with or without aspirin desensitization frequently improves symptoms and objective disease measures. Biological agents targeting eosinophilic inflammation are promising alternatives to conventional management.

Topical corticosteroids for chronic rhinosinusitis with nasal polyposis: GRADE systematic review and network meta-analysis.

BACKGROUND: Chronic rhinosinusitis with nasal polyposis (CRSwNP) is associated with a significant disease burden. The optimal use of and administration route for intranasal corticosteroids (INCS) when managing CRSwNP are unclear. OBJECTIVE: We systematically synthesized the evidence addressing INCS for CRSwNP. METHODS: We searched studies archived in Medline, Embase, and Central from database inception until September 1, 2021, for randomized controlled trials comparing INCS using any delivery method to placebo or other INCS administration types. Paired reviewers screened records, abstracted data, and rated risk of bias (CLARITY revision of Cochrane Risk of Bias version 1 tool) independently and in duplicate. We synthesized the evidence for each outcome using random effects network meta-analyses. We critically appraised the evidence following the GRADE (Grades of Recommendation Assessment, Development, and Evaluation) approach. RESULTS: We analyzed 61 randomized controlled trials (7176 participants, 8 interventions). Sinusitis-related quality of life might improve with INCS rinse (mean difference [MD] -6.83, 95% confidence interval [CI] -11.94 to -1.71) and exhalation delivery system (EDS) (MD -7.86, 95% CI -14.64 to -1.08) compared to placebo (both low certainty evidence). Nasal obstruction symptoms are likely improved when receiving INCS via stent/dressing (MD -0.31, 95% CI -0.54 to -0.08), spray (MD -0.51, 95% CI -0.61 to -0.41), and EDS (MD -0.35, 95% CI -0.51 to -0.18) (all moderate to high certainty) compared to placebo. We found no important differences in adverse effects among interventions (moderate certainty for INCS spray, very low to low certainty for others). CONCLUSIONS: Multiple delivery forms of INCS are viable therapeutic options for CRSwNP, resulting in improvement of patient-important outcomes. INCS via stent, spray, and EDS appear to be beneficial across the widest range of considered outcomes.

Recommendations for daytime, evening, and nighttime indoor light exposure to best support physiology, sleep, and wakefulness in healthy adults.

Ocular light exposure has important influences on human health and well-being through modulation of circadian rhythms and sleep, as well as neuroendocrine and cognitive functions. Prevailing patterns of light exposure do not optimally engage these actions for many individuals, but advances in our understanding of the underpinning mechanisms and emerging lighting technologies now present opportunities to adjust lighting to promote optimal physical and mental health and performance. A newly developed, international standard provides a SI-compliant way of quantifying the influence of light on the intrinsically photosensitive, melanopsin-expressing, retinal neurons that mediate these effects. The present report provides recommendations for lighting, based on an expert scientific consensus and expressed in an easily measured quantity (melanopic equivalent daylight illuminance (melaponic EDI)) defined within this standard. The recommendations are supported by detailed analysis of the sensitivity of human circadian, neuroendocrine, and alerting responses to ocular light and provide a straightforward framework to inform lighting design and practice.

Risk for Postmarket Black Box Warnings in FDA-Approved Monoclonal Antibodies.

OBJECTIVE: To estimate the potential risk for a future postmarket black box warning (BBW) of US Food and Drug Administration (FDA)-approved monoclonal antibodies (mAbs) because of the importance for medical clinicians to understand mAb risks and benefits, including unknown future risks, especially for recently approved mAbs. METHODS: The complete dates of the study were March 16, 2020, through May 12, 2021. We searched the FDALabel database online and reviewed the scientific literature to determine current and previous FDA-approved mAbs as of March 2020. The BBWs and initial FDA-issued safety warnings were identified. The BBWs were categorized as premarket or postmarket. For mAbs with specific postmarket BBWs, previous FDA labels were evaluated to identify the presence or absence of an initial corresponding specific FDA warning. RESULTS: In March 2020, a total of 83 mAbs had FDA approval; 33 had BBWs (27 premarket and 13 postmarket BBWs). Of these 33 mAbs, 55 individual specific BBWs existed (36 premarket and 19 postmarket specific warnings). On average, the specific BBWs occurred in the postmarket period at a rate of 3.4% (19/562) per year. Most (73.7%; 14/19) specific postmarket BBWs were preceded by an FDA warning in a median time of 3.61 (interquartile range, 1.36-5.78) years. Specific postmarket BBWs not preceded by a specific FDA product label warning occurred at an average rate of 0.9% (5/562) per year. CONCLUSION: Specific postmarket BBWs occurred in FDA-approved mAbs at a rate of 3.4% per year. Specific postmarket BBWs not preceded by a specific FDA product label warning had a rate of 0.9% per year.

Identification of 22 novel BTK gene variants in B cell deficiency with hypogammaglobulinemia.

X-linked agammaglobulinemia (XLA) is an inborn error of immunity caused by pathogenic variants in the BTK gene, resulting in impaired B cell differentiation and maturation. Over 900 variants have already been described in this gene, however, new pathogenic variants continue to be identified. In this report, we describe 22 novel variants in BTK, associated with B cell deficiency with hypo- or agammaglobulinemia in male patients or in asymptomatic female carriers. Genetic data was correlated with BTK protein expression by flow cytometry, and clinical and family history to obtain a comprehensive assessment of the clinico-pathologic significance of these new variants in the BTK gene. For one novel missense variant, p.Cys502Tyr, site-directed mutagenesis was performed to determine the impact of the sequence change on protein expression and stability. Genetic data should be correlated with protein and/or clinical and immunological data, whenever possible, to determine the clinical significance of the gene sequence alteration.

Pneumococcal serotype-specific cut-offs based on antibody responses to pneumococcal polysaccharide vaccination in healthy adults.

Antibody responses to pneumococcal polysaccharide vaccination are frequently used as a diagnostic tool for humoral immunodeficiencies, part of the larger collection of inborn errors of immunity. Currently, arbitrary criteria, such as a serotype specific titer of >/= 1.3 µg/mL is most often used as a cut-off for interpretation of pneumococcal antibody responses. The magnitude of the antibody response to each of the 23 serotypes in Pneumovax®, and serotype-specific cut-offs in healthy pneumococcal vaccine-naïve adults has not been previously characterized. IgG antibody concentrations were measured prospectively for 23 pneumococcal serotypes pre and 4-6 weeks post-Pneumovax® vaccination in 100 healthy adults, using a multiplex bead-based assay. Antibodies to 19 of 23 serotypes were informative for distinguishing subjects who responded to vaccination, and the serotype threshold was determined to be 9 of 19 serotypes, which characterized an antibody response to pneumococcal vaccination. While this study may facilitate classification of IgG serotype-specific antibody responses post-pneumococcal vaccination in adult patients undergoing diagnostic immunological evaluation for antibody immunodeficiencies or other relevant contexts, additional studies in healthy children and S. pneumoniae protein-conjugate-vaccinated healthy adults will need to be undertaken in the future.

Survey of Home-Use UV Disinfection Products†.

The COVID-19 pandemic provided a commercial opportunity for traders marketing a range of ultraviolet (UV) radiation products for home-use disinfection. Due to concerns about the efficacy of such products and the potential for harmful levels of UV exposure to people, a range of products were purchased from on-line trading platforms. Spectral irradiance measurements were carried out to determine whether the products could be effective against the SARS-CoV-2 virus and whether they were likely to exceed internationally agreed exposure limits. It was concluded that many of the devices were not effective and many of those that were potentially effective presented a risk to users.

In vitro Culture with Cytokines Provides a Tool to Assess the Effector Functions of ILC2s in Peripheral Blood in Asthma.

BACKGROUND: Group 2 innate lymphoid cells (ILC2s) play crucial roles in type 2 immunity and asthma development. While ILC2s are resident in mucosal tissues, they also circulate in peripheral blood. It remains controversial whether ILC2s are increased in the peripheral blood of patients with asthma. PURPOSE: The goal of this project was to study the effector functions of ILC2s in peripheral blood samples by in vitro culture with cytokines. PATIENTS AND METHODS: Peripheral blood mononuclear cells (PBMCs) were collected from 11 adult patients with mild asthma and 12 healthy control subjects. The number of peripheral blood ILC2s in PBMCs was analyzed by flow cytometry. PBMCs were cultured with IL-33 and IL-25 without any antigens, and the amounts of type 2 cytokines in cell-free supernatants were analyzed by ELISA. In selected experiments, production of cytokines by ILC2s was analyzed by intracellular cytokine staining and flow cytometry. RESULTS: In response to either IL-33 or IL-25 stimulation, PBMCs from patients with mild asthma produced larger amounts of IL-5 and IL-13 than PBMCs from healthy control subjects. However, ILC2 numbers or proportions were not significantly different between these two groups. Flow cytometric analysis confirmed production of IL-5 by ILCs when stimulated with IL-33. CONCLUSION: In vitro culture of PBMCs with a cocktail of cytokines, such as either IL-33 or IL-25 plus IL-2, may provide a valuable tool to assess the effector functions of ILC2s and may serve as a biomarker for human asthma.

Rhinitis 2020: A practice parameter update.

This comprehensive practice parameter for allergic rhinitis (AR) and nonallergic rhinitis (NAR) provides updated guidance on diagnosis, assessment, selection of monotherapy and combination pharmacologic options, and allergen immunotherapy for AR. Newer information about local AR is reviewed. Cough is emphasized as a common symptom in both AR and NAR. Food allergy testing is not recommended in the routine evaluation of rhinitis. Intranasal corticosteroids (INCS) remain the preferred monotherapy for persistent AR, but additional studies support the additive benefit of combination treatment with INCS and intranasal antihistamines in both AR and NAR. Either intranasal antihistamines or INCS may be offered as first-line monotherapy for NAR. Montelukast should only be used for AR if there has been an inadequate response or intolerance to alternative therapies. Depot parenteral corticosteroids are not recommended for treatment of AR due to potential risks. While intranasal decongestants generally should be limited to short-term use to prevent rebound congestion, in limited circumstances, patients receiving regimens that include an INCS may be offered, in addition, an intranasal decongestant for up to 4 weeks. Neither acupuncture nor herbal products have adequate studies to support their use for AR. Oral decongestants should be avoided during the first trimester of pregnancy. Recommendations for use of subcutaneous and sublingual tablet allergen immunotherapy in AR are provided. Algorithms based on a combination of evidence and expert opinion are provided to guide in the selection of pharmacologic options for intermittent and persistent AR and NAR.

In-Flight UV-A Exposure of Commercial Airline Pilots.

INTRODUCTION: Understanding UV exposure is essential for the assessment of its contribution to the occupational risk of pilots developing ocular and skin pathologies. The objective of this observational study was to measure the UV exposure of pilots flying between the United Kingdom and a range of destinations at three different seasons.METHODS: The in-flight UV exposure of pilots was measured on 322 Monarch Airlines short-haul flights on the Airbus A321-231 and Airbus A320-214 to 31 destinations, mostly in Europe, from 4 UK airports in September 2016-August 2017. The erythema effective and UV-A doses were compared with the ICNIRP guidance and typical recreational weekend exposure of UK office workers.RESULTS: The erythema effective radiant doses did not exceed 0.1 SED. For most of the flights, the UV-A exposure was also low. On 27 single sector flights, UV-A exposure could have exceeded the ICNIRP guidance if eye protection was not used.DISCUSSION: The UV exposure in a cockpit is mostly governed by the presence of direct sunlight and the duration of a flight. The average monthly exposures were low and significantly below weekend recreational exposures of UK office workers over a similar period. To assess the contribution of occupational UV exposure to the risk of developing sun-related ocular and cutaneous pathologies, it is important to consider the accumulative flight time, destinations, and UV attenuation of aircraft windshields. Additionally, leisure and recreational outdoor time needs to be considered before meaningful overall risk analysis can be undertaken.Baczynska KA, Brown S, Chorley AC, O'Hagan JB, Khazova M, Lyachev A, Wittlich M. In-flight UV-A exposure of commercial airline pilots. Aerosp Med Hum Perform. 2020; 91(6):501-510.

Minimally invasive biomarker studies in eosinophilic esophagitis: A systematic review.

BACKGROUND: Eosinophilic esophagitis (EoE) is a chronic, inflammatory disease of the esophagus that currently requires repeated endoscopic biopsies for diagnosis and monitoring because no reliable noninvasive markers have been identified. OBJECTIVE: To identify promising minimally invasive EoE biomarkers and remaining gaps in biomarker validation. METHODS: We performed a systematic review of EMBASE, Ovid MEDLINE, PubMed, and Web of Science from inception to June 6, 2017. Studies were included if patients met the 2007 consensus criteria for EoE diagnosis, a minimally invasive biomarker was assessed, and the study included at least 1 control for comparison. RESULTS: The search identified 2094 studies, with 234 reviewed at full-text level, and 49 included in the analysis (20 adult, 19 pediatric, 7 pediatric and adult, and 3 not stated). Most (26 of 49) were published after 2014. Thirty-five studies included healthy controls, 9 analyzed atopic controls, and 29 compared samples from patients with active and inactive EoE. Minimally invasive biomarkers were obtained from peripheral blood (n = 41 studies), sponge or string samples (n = 3), oral or throat swab secretions (n = 2), breath condensate (n = 2), stool (n = 2), and urine (n = 2). The most commonly reported biomarkers were peripheral blood eosinophils (n = 16), blood and string eosinophil granule proteins (n = 14), and eosinophil surface or intracellular markers (n = 12). EoE biomarkers distinguished active EoE from healthy controls in 23 studies, atopic controls in 2 studies, and inactive EoE controls in 20 studies. CONCLUSION: Several promising minimally invasive biomarkers for EoE have emerged; however, few are able to differentiate EoE from other atopic diseases.

Why and how to step down chronic asthma drugs.

Asthma is a common chronic airways disease. The goal of asthma management is to control symptoms while minimizing the side effects of treatment. Following a period of stable asthma, clinicians should consider stepping down treatment. This approach is recommended by current guidelines. Step-down has been studied for several types of asthma drug regimens, and certain approaches may have lower risk than others. Systematic reviews of multiple trials support the following specific step-down approaches: optimizing inhaled corticosteroid dosing when stepping down oral corticosteroid, reducing inhaled corticosteroid from a higher dose, lowering inhaled corticosteroid-long acting bronchodilator (ICS-LABA) dose while adding ICS-LABA on-demand, adding leukotriene receptor antagonist (LTRA) while lowering inhaled corticosteroid dose, and using allergen immunotherapy when reducing inhaled corticosteroid from a higher dose. Systematic reviews of multiple trials support an increased risk of asthma exacerbation for patients who completely stop taking inhaled corticosteroid or long acting bronchodilator. Strategies to implement step-down in practice include the use of risk prediction as well as tools to support shared decision making and communication about risk between clinicians and patients.

Urinary Leukotriene E4 to Determine Aspirin Intolerance in Asthma: A Systematic Review and Meta-Analysis.

BACKGROUND: Urinary leukotriene E4 (ULTE4) may be a biomarker that distinguishes aspirin-intolerant asthma from other asthma subtypes. OBJECTIVE: To estimate the diagnostic testing accuracy of ULTE4 as a marker of aspirin intolerance in patients with asthma using previously published studies. METHODS: We identified relevant clinical studies from a systematic review of English and non-English articles using MEDLINE, EMBASE, and CENTRAL (inception to February 10, 2015). Articles were screened at the abstract and full-text level by 2 independent reviewers. We included previously published studies that analyzed ULTE4 in human subjects with asthma characterized as having or not having aspirin intolerance on the basis of a specified definition: convincing history of aspirin intolerance, positive aspirin challenge, or both as the criterion standard. Individual-level data points from all included studies were obtained and analyzed. RESULTS: The search strategy identified 867 potential articles, of which 86 were reviewed at the full-text level and 10 met criteria for inclusion. The sensitivity, specificity, positive predictive value, and negative predictive values of ULTE4 to determine aspirin intolerance in subjects with asthma were 0.55, 0.82, 0.75, and 0.66 (Amersham-enzyme immunoassay); 0.76, 0.77, 0.70, and 0.78 (Cayman-enzyme immunoassay); 0.70, 0.81, 0.86, and 0.79 (mass spectrometry); and 0.81,0.79, 0.65, and 0.88 (radioimmunoassay) at optimal thresholds of 192, 510, 167 to 173, and 66 to 69 pg/mg Cr, respectively. The diagnostic odds ratio for each methodology was 6.0, 11.9, 10.5, and 19.1, respectively. CONCLUSIONS: ULTE4 is a marker for aspirin-intolerant asthma and could potentially be used as a clinical test to identify the risk of aspirin intolerance in subjects with asthma.

Prospective Validation of the NIAID/FAAN Criteria for Emergency Department Diagnosis of Anaphylaxis.

BACKGROUND: Anaphylaxis diagnostic criteria were proposed at the Second Symposium on the Definition and Management of Anaphylaxis. These criteria were 97% sensitive and 82% specific when retrospectively validated. OBJECTIVE: To prospectively evaluate the diagnostic accuracy of the National Institute of Allergy and Infectious Diseases/Food Allergy and Anaphylaxis Network (NIAID/FAAN) criteria for diagnosis of anaphylaxis in the emergency department (ED). METHODS: We conducted a prospective observational study of patients seen in our institution's ED from April 2010 to March 2013. Patients seeking care for an allergic reaction and possible anaphylaxis were enrolled. Patients and providers completed questionnaires regarding onset, trigger, and signs and symptoms. Records were reviewed independently and blindly by 2 board-certified allergist-immunologists, and their final diagnosis (anaphylaxis vs no anaphylaxis) was used as the reference standard. Two-by-two tables were built, and test characteristics were calculated. RESULTS: Among the 174 enrolled patients, 91 (52%) met the NIAID/FAAN criteria for anaphylaxis. The allergist-immunologists diagnosed 61 cases of anaphylaxis (35%), of which 58 (95%) also satisfied the NIAID/FAAN criteria. The interrater agreement between allergist-immunologists was substantial (κ = 0.7). Test characteristics (95% CIs) of the NIAID/FAAN criteria were as follows: sensitivity, 95.1% (85.4%-98.7%); specificity, 70.8% (61.4%-78.8%); positive predictive value, 63.7% (52.9%-73.4%); negative predictive value, 96.4% (89.1%-99.1%); positive likelihood ratio, 3.26; and negative likelihood ratio, 0.07. CONCLUSIONS: Prospectively, the NIAID/FAAN criteria continued to be highly sensitive (95%) but had lower specificity (71%) than on retrospective assessment. These criteria are likely to be useful for the diagnosis of anaphylaxis in the ED.