COVID-19 severity in asthma patients: a multi-center matched cohort study.

OBJECTIVE: The evidence pertaining to the effects of asthma on Coronavirus disease 2019 outcomes has been unclear. To improve our understanding of the clinically important association of asthma and Coronavirus disease 2019. METHODS: A matched cohort study was performed using data from the Mass General Brigham Health Care System (Boston, MA). Adult (age ≥18 years) patients with confirmed Coronavirus disease 2019 and without chronic obstructive pulmonary disease, cystic fibrosis, or interstitial lung disease between March 4, 2020 and July 2, 2020 were analyzed. Up to five non-asthma comparators were matched to each asthma patient based on age (within 5 years), sex, and date of positive test (within 7 days). The primary outcomes were hospitalization, mechanical ventilation, and death, using multivariable Cox-proportional hazards models accounting for competing risk of death, when appropriate. Patients were followed for these outcomes from diagnosis of Coronavirus disease 2019 until July 2, 2020. RESULTS: Among 562 asthma patients, 199 (21%) were hospitalized, 15 (3%) received mechanical ventilation, and 7 (1%) died. Among the 2686 matched comparators, 487 (18%) were hospitalized, 107 (4%) received mechanical ventilation, and 69 (3%) died. The adjusted Hazard Ratios among asthma patients were 0.99 (95% Confidence Internal 0.80, 1.22) for hospitalization, 0.69 (95% Confidence Internal 0.36, 1.29) for mechanical ventilation, and 0.30 (95% Confidence Internal 0.11, 0.80) for death. CONCLUSIONS: In this matched cohort study from a large Boston-based healthcare system, asthma was associated with comparable risk of hospitalization and mechanical ventilation but a lower risk of mortality.

mRNA Vaccines to Prevent COVID-19 Disease and Reported Allergic Reactions: Current Evidence and Suggested Approach.

The U.S. Food and Drug Administration (FDA) has recently issued an Emergency Use Authorization (EUA) for 2 highly effective coronavirus disease 2019 (COVID-19) vaccines from Pfizer-BioNTech and Moderna. This has brought hope to millions of Americans in the midst of an ongoing global pandemic. The FDA EUA guidance for both vaccines is to not administer the vaccine to individuals with a known history of a severe allergic reaction (eg, anaphylaxis) to any component of the COVID-19 vaccine. The Centers for Disease Control and Prevention (CDC) additionally advises individuals with a history of an immediate allergic reaction to a vaccine or injectable or any history of anaphylaxis be observed for 30 minutes after COVID-19 vaccination. All other individuals should be observed for 15 minutes after COVID-19 vaccination. Staff at vaccine clinics must be able to identify and manage anaphylaxis. Post-FDA EUA, despite very strong safety signals in both phase 3 trials, reports of possible allergic reactions have raised public concern. To provide reassurance and support during widespread global vaccination, allergists must offer clear guidance to individuals based on the best information available, but also in accordance with the broader recommendations of regulatory agencies. This review summarizes vaccine allergy epidemiology and proposes drug and vaccine allergy expert opinion informed risk stratification for Allergy specialist use in conjunction with guidance of public health and regulatory authorities. The risk stratification schema guide care for (1) individuals with different allergy histories to safely receive their first mRNA COVID-19 vaccine and (2) individuals who develop a reaction to their first dose of mRNA COVID-19 vaccine.

Sex differences in academic rank in allergy/immunology.

BACKGROUND: Female physicians are significantly less likely than male physicians to be full professors, even after accounting for age, experience, specialty, and measures of research and clinical productivity. OBJECTIVE: We sought to evaluate sex differences in academic rank in the allergy and immunology workforce. METHODS: We used a cross-sectional physician data set containing the allergist's sex, age, years since residency, faculty appointment, authored publications, National Institutes of Health (NIH) funding, clinical trial investigation, and Medicare reimbursement to investigate sex differences in the academic allergy and immunology workforce using multilevel logistic regression models. RESULTS: Among 507 academic allergists (9.3% of practicing US allergists in 2014), 323 (63.7%) were men, and 184 (36.3%) were women. Female allergists were younger (47.9 vs 56.9 years, P < .001), had fewer total (12.5 vs 28.7, P < .001) and first/last author (8.0 vs 21.5, P < .001) average publications, were less likely to have NIH funding (13.0% vs 23.5%, P = .004), were less frequently a clinical trial investigator (10.3% vs 16.1%, P = .07), and generated less average annual Medicare revenue ($44,000 vs $23,000, P = .10). Of 152 (30.0%) full professors, 126 (82.9%) were male, and 26 (17.0%) were female. After multivariable adjustment, rates of full professorship among female and male allergists were not significantly different (absolute adjusted difference for female vs male allergists, 6.0%; 95% CI, -8.3% to 20.2%). CONCLUSIONS: Among allergists with US medical school faculty appointments, men and women were similarly likely to be full professors after accounting for factors influencing promotion. Underlying differences in research productivity and NIH funding not explained by age differences alone warrant additional investigation.

Mining social media data to assess the risk of skin and soft tissue infections from allergen immunotherapy.

BACKGROUND: Allergen immunotherapy (AIT) treatment for allergic rhinitis and asthma is used by 2.6 million Americans annually. Clinical and sterility testing studies identify no risk of contamination or infection from extracts prepared using recommended aseptic techniques, but regulatory concerns persist. Social media can be used to investigate rare adverse effects not captured by traditional studies. OBJECTIVE: We sought to investigate large social media databases for suggestion of AIT skin and soft tissue infection (SSTI) risk and compare this risk to a comparator procedure with a sterile pharmaceutical. METHODS: We analyzed US-restricted data from more than 10 common text-based social media platforms including Facebook, Twitter, and Reddit between 2012 and 2016. We used natural language processing (NLP) to identify posts related to AIT and, separately, influenza vaccination (comparator procedure). NLP was followed by manual review to identify posts suggesting a possible SSTI associated with either AIT or influenza vaccination. SSTI frequencies with 95% CIs were compared. RESULTS: We identified 25,126 AIT posts, which were matched by social media platform to 25,126 influenza vaccination-related posts. NLP identified 4088 (16.3%) AIT posts that required manual review, with 6 posts (0.02%; 95% CI, 0.005%-0.043%) indicative of possible AIT-related SSTI. NLP identified 2689 (10.7%) influenza posts that required manual review, with 7 posts (0.03%; 95% CI, 0.007%-0.048%) indicative of possible influenza vaccination-related SSTI. CONCLUSIONS: Social media data suggest that SSTI from AIT and influenza vaccination are equally rare events. Given that AIT's SSTI risk appears comparable to the risk using a sterile pharmaceutical based on social media data, current aseptic technique procedures seem safe.

The Cost of Penicillin Allergy Evaluation.

BACKGROUND: Unverified penicillin allergy leads to adverse downstream clinical and economic sequelae. Penicillin allergy evaluation can be used to identify true, IgE-mediated allergy. OBJECTIVE: To estimate the cost of penicillin allergy evaluation using time-driven activity-based costing (TDABC). METHODS: We implemented TDABC throughout the care pathway for 30 outpatients presenting for penicillin allergy evaluation. The base-case evaluation included penicillin skin testing and a 1-step amoxicillin drug challenge, performed by an allergist. We varied assumptions about the provider type, clinical setting, procedure type, and personnel timing. RESULTS: The base-case penicillin allergy evaluation costs $220 in 2016 US dollars: $98 for personnel, $119 for consumables, and $3 for space. In sensitivity analyses, lower cost estimates were achieved when only a drug challenge was performed (ie, no skin test, $84) and a nurse practitioner provider was used ($170). Adjusting for the probability of anaphylaxis did not result in a changed estimate ($220); although other analyses led to modest changes in the TDABC estimate ($214-$246), higher estimates were identified with changing to a low-demand practice setting ($268), a 50% increase in personnel times ($269), and including clinician documentation time ($288). In a least/most costly scenario analyses, the lowest TDABC estimate was $40 and the highest was $537. CONCLUSIONS: Using TDABC, penicillin allergy evaluation costs $220; even with varied assumptions adjusting for operational challenges, clinical setting, and expanded testing, penicillin allergy evaluation still costs only about $540. This modest investment may be offset for patients treated with costly alternative antibiotics that also may result in adverse consequences.

Utility of Risk Stratification for Paclitaxel Hypersensitivity Reactions.

BACKGROUND: Hypersensitivity reactions (HSRs) are a common impediment to paclitaxel therapy. Management strategies to guide care after a paclitaxel-induced HSR are needed. OBJECTIVE: The objective was to evaluate the utility and safety of risk stratification on the basis of severity of the initial HSR. METHODS: A risk stratification pathway was developed on the basis of a retrospective review of the management and outcome of 130 patients with paclitaxel-induced HSRs at Massachusetts General Hospital. This pathway was then studied prospectively in patients referred to Allergy/Immunology with paclitaxel-induced HSRs. RESULTS: The study population (n = 35) had a mean age of 56.1 ± 12 years and most were women (n = 33 [94%]). All 5 patients (15%) with grade 1 initial HSRs were successfully reexposed to paclitaxel, 1 patient at the standard infusion rate and 4 patients at 50% of the standard infusion rate. Thirty patients (85%) with grade 2 to 4 initial HSRs underwent initial paclitaxel desensitization based on the risk stratification pathway. No patients developed severe HSRs using the pathway. Eleven (31%) patients had HSRs that were mild to moderate in nature (grade 1, n = 4 [11%]; grade 2, n = 6 [17%]; grade 3, n = 1 [3%]) during their first desensitization. Sixteen (46%) of the 35 patients safely returned to the outpatient infusion setting for paclitaxel treatment at 50% of the standard infusion rate. Seven (20%) discontinued paclitaxel before the completion of the risk stratification pathway because of disease progression, completion of therapy, or death. CONCLUSIONS: A management strategy using the initial HSR severity for risk stratification allowed patients to receive paclitaxel safely.

Cardiovascular and cerebrovascular events among patients receiving omalizumab: Results from EXCELS, a prospective cohort study in moderate to severe asthma.

BACKGROUND: EXCELS, a postmarketing observational cohort study, was a commitment to the US Food and Drug Administration to assess the long-term safety of omalizumab in an observational setting, focusing predominantly on malignancies. OBJECTIVE: The aim of this study was to examine a potential association between omalizumab and cardiovascular (CV)/cerebrovascular (CBV) events in EXCELS. METHODS: Patients (≥12 years of age) with moderate to severe allergic asthma and who were being treated with omalizumab (n = 5007) or not (n = 2829) at baseline were followed up for ≤5 years. Analyses included overall CV/CBV events, but focused on the subset of arterial thromboembolic events (ATEs), comprising CV death, myocardial infarction, ischemic stroke, transient ischemic attack, and unstable angina. A prespecified analysis of the end point of ATE was conducted to control for available potential confounders. A blinded independent expert panel adjudicated all events. RESULTS: At baseline, the 2 cohorts had similar demographic characteristics, but severe asthma was more common in the omalizumab versus the non-omalizumab group (50% vs 23%). Omalizumab-treated patients had a higher rate of CV/CBV serious adverse events (13.4 per 1,000 person years [PYs]) than did non-omalizumab-treated patients (8.1 per 1,000 PYs). The ATE rates per 1,000 PYs were 6.66 (101 patients/15,160 PYs) in the omalizumab cohort and 4.64 (46 patients/9,904 PYs) in the non-omalizumab cohort. After control for available confounding factors, the hazard ratio was 1.32 (95% CI, 0.91-1.91). CONCLUSION: This observational study demonstrated a higher incidence rate of CV/CBV events in the omalizumab versus the non-omalizumab cohort. Differences in asthma severity between cohorts likely contributed to this imbalance, but some increase in risk cannot be excluded.

Immune-mediated reactions to vancomycin: A systematic case review and analysis.

BACKGROUND: Vancomycin is a broad-spectrum antibiotic whose use may be limited by adverse drug reactions (ADRs). Although vancomycin toxic effects are known, there are limited data on vancomycin hypersensitivity reactions (HSRs). OBJECTIVE: To understand the most commonly reported vancomycin HSRs through systematic case review. METHODS: We performed a literature search for English-language case reports and series from 1982 through 2015 (last search July 31, 2015) on Ovid MEDLINE and PubMed. The search included the subject heading vancomycin with the subheading adverse effects and separate text searches for vancomycin with a list of specified HSRs. References of identified articles were reviewed to find additional articles. Clinical data were collected and summarized. RESULTS: Of 201 identified articles, 84 were screened and 57 fully assessed; these 57 articles contained 71 vancomycin HSR cases that were included in analysis. Vancomycin HSRs were immediate (anaphylaxis, n = 7) and nonimmediate (n = 64). Nonimmediate HSRs included linear IgA bullous dermatosis (LABD, n = 34), drug rash eosinophilia and systemic symptoms (DRESS) syndrome (n = 16), acute interstitial nephritis (AIN, n = 8), and Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN, n = 6). Median times of vancomycin therapy before HSR onset was 7 days (interquartile range [IQR], 4-10 days) for LABD, 9 days (IQR, 9-22 days) for SJS/TEN, 21 days (IQR, 17-28 days) for DRESS syndrome, and 26 days (IQR, 7-29 days) for AIN. Overall, 11 patients (16%) died, and 4 (6%) had deaths attributed to the HSR. CONCLUSION: Vancomycin causes a variety of HSRs; the most commonly identified were nonimmediate HSRs, with LABD being most frequent. We observed a high frequency of HSR mortality. Further data are needed to understand the frequency and severity of vancomycin HSRs.

Utility of ICD-9-CM Codes for Identification of Allergic Drug Reactions.

BACKGROUND: The epidemiology of allergic drug reactions is poorly understood due, in large part, to difficulty in identifying true cases in population data sets. Use of International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes is a potentially valuable approach that requires formal evaluation. OBJECTIVE: To better understand the utility of ICD-9-CM codes for identification of allergic drug reactions, including the validation of specific codes by chart review. METHODS: We reviewed randomly sampled medical records of patients treated in the emergency department (ED) between January 1, 2001, and December 31, 2006, with ICD-9-CM codes for drug allergy and E codes (E930-949) for adverse drug reactions. RESULTS: During the 6-year period, 11,130 charts were identified by ICD-9-CM and E codes and 1,634 were reviewed. Allergic drug reactions were found in 444 (27%) of the reviewed ED visits. The codes that identified the highest percentage of true allergic drug reactions were dermatitis due to drug (693.0; 87%), adverse reaction to drug (995.2; 52%), and anaphylaxis (995.0; 38%). Patients with both an ICD-9-CM code and an E code had a high likelihood of having an allergic drug reaction (76%). Most allergic drug reactions were attributed to antibiotics (42%), intravenous contrast (7%), and nonsteroidal anti-inflammatory drugs (6%). The estimated frequency of allergic drug reactions increased from 0.49% of ED visits in 2001 to 0.94% in 2012. CONCLUSIONS: Specific ICD-9-CM and E codes can be used in combination to identify allergic drug reactions. Further study of these codes in the inpatient and outpatient settings is necessary to better understand the utility of diagnosis codes for improving epidemiologic research on drug allergy.

Risk-stratification protocol for carboplatin and oxaliplatin hypersensitivity: repeat skin testing to identify drug allergy.

BACKGROUND: Hypersensitivity reactions (HSRs) to platinum-based chemotherapies are increasingly being recognized. The authors developed a novel risk-stratification protocol that was used successfully in a small number of patients with carboplatin-induced HSRs. OBJECTIVE: To describe the utility of this protocol in a large number of patients with carboplatin- or oxaliplatin-induced HSRs. METHODS: A 5-year retrospective review of patients referred to Massachusetts General Hospital with carboplatin- or oxaliplatin-induced HSR was performed. Patients were managed using a risk-stratification protocol using 3 repeat skin tests (STs) with intervening desensitizations. If the repeat ST result remained negative 3 times, patients received subsequent infusions without desensitization. RESULTS: From 2008 to 2012, 142 patients (92 treated with carboplatin, 50 treated with oxaliplatin) completed 574 desensitizations. Most patients were women (84.5%, mean ± SD 58.1 ± 9.3 years). Patients with carboplatin-induced HSRs were classified as having positive (n = 32, 34.8%), negative (n = 38, 41.3%), or converted (n = 22, 23.9%) ST reactions when the initial negative ST reaction converted to positive at repeat ST. Of those with oxaliplatin-induced HSRs, 22 (44%) had positive, 25 (50%) had negative, and 3 (6%) had converted ST reactions. Of the patients with negative ST reactions, 17 with carboplatin-induced HSRs and 16 with oxaliplatin-induced HSRs safely completed 59 and 95 outpatient infusions, respectively, without desensitizations. For carboplatin and oxaliplatin, ST conversion was associated with an interval of at least 6 months from the HSR to the initial ST (carboplatin, P = .002; oxaliplatin, P = .045). CONCLUSION: This risk-stratification protocol for presumed carboplatin- and oxaliplatin-induced HSRs safely identifies false-negative ST reactions and nonallergic patients who can receive infusions without desensitizations. This leads to fewer unnecessary desensitizations and improved patient care.

Comprehensive allergy evaluation is useful in the subsequent care of patients with drug hypersensitivity reactions during anesthesia.

BACKGROUND: For patients with a history of drug hypersensitivity reaction (HSR) during anesthesia, strategies to minimize risk with subsequent anesthesia are unclear. Identification of the cause of HSR during anesthesia remains challenging. OBJECTIVE: To determine the success of a comprehensive allergy evaluation and management plan for patients with HSR during anesthesia, including identification of the causative agent and review of outcomes during subsequent anesthesia exposure. METHODS: We performed chart reviews of patients referred for the evaluation of HSR during anesthesia between 2003 and 2012. Data collection included patient characteristics, signs/symptoms of HSR during anesthesia, and subsequent outcomes. Patients underwent comprehensive allergy evaluation including skin testing for identifying potential culprit agents, and the results were used to provide recommendations for any subsequent anesthesia. RESULTS: Over the 10-year study period, 73 patients with HSR during anesthesia were referred for further evaluation. Thirteen patients (18%) had positive skin test results to a drug received during anesthesia. One patient with a positive skin test result was diagnosed with mastocytosis. The causative agents identified in these 13 patients included latex, ß-lactam antibiotics, neuromuscular blockers, tetracaine, odansetron, and fentanyl. On follow-up, 47 of the 73 patients (64%) subsequently underwent procedures requiring anesthesia. Using our recommendations from evaluation and testing, 45 of these 47 patients (96%) successfully tolerated subsequent anesthesia. The 2 patients who developed recurrent HSR during anesthesia were later diagnosed with mast cell disorders. CONCLUSIONS: Our comprehensive evaluation and management plan minimizes risk with subsequent anesthesia even when the cause of HSR could not be identified. Baseline tryptase levels may be helpful in this patient population to diagnose mast cell disorders.

Safety and outcomes of test doses for the evaluation of adverse drug reactions: a 5-year retrospective review.

BACKGROUND: Graded challenges are the criterion standard for evaluating adverse drug reactions (ADR). Evidence-based guidelines regarding the optimal number of steps for challenges are lacking. OBJECTIVE: To determine the safety and outcomes of 1- or 2-step test doses among patients with ADRs seen by the allergy/immunology consult service and to compare the outcomes of 1- or 2-step test doses with multistep challenges performed during the same time period. METHODS: We conducted a retrospective chart review of all 1- or 2-step test doses and multistep challenges at a single academic center between 2008 and 2013. Patient demographics, symptoms of initial ADRs, and outcomes of test doses and multistep challenges were reviewed. ADRs were classified by type and were graded by severity. Outcomes of 1- or 2-step test doses were compared with multistep challenges. RESULTS: We identified 456 patients who underwent 497 one- or 2-step test doses (mean age, 51 years; 67.5% female patients). The most common drugs that prompted test doses were ß-lactams (62%). The majority of patients (n = 444 [89%]) did not experience any ADRs during test doses. ADRs that occurred during test doses (n = 53 [11%]) were most commonly non-immune-mediated (45%) or IgE-mediated (32%), with grade 1 or 2 severity (100%). Forty-nine percent of ADRs during test doses did not receive any treatment. The ADR rate during multistep challenges (10/82 [12%]) was similar to test doses. CONCLUSION: One- or 2-step test doses were safe for evaluation of ADRs. Multistep challenges did not confer added safety. Furthermore, 1- or 2-step test doses did not raise concern for induction of tolerance.

Management of hypersensitivity reactions to Carboplatin and Paclitaxel in an outpatient oncology infusion center: a 5-year review.

BACKGROUND: A high incidence of hypersensitivity reactions (HSR) to carboplatin and Taxol is limiting the use of carboplatin and Taxol. OBJECTIVE: We conducted a 5-year study of all patients with HSR to carboplatin or Taxol to better understand the nature of infusion HSR and success or failure of management plans after the initial HSR. METHODS: We performed a retrospective chart review of all safety reports from the Massachusetts General Hospital outpatient chemotherapy infusion center between January 2006 and February 2011. All the patients with HSRs to carboplatin or Taxol were identified and included in the final analysis. We reviewed patient characteristics, clinical symptoms, timing, and treatment of the initial HSR, and determined if the patient was rechallenged despite an initial HSR. RESULTS: We identified 152 patients with HSR to carboplatin (n = 45) or Taxol (n = 107). Carboplatin HSR was less severe than Taxol HSR. When comparing the 2 groups, the patients with carboplatin HSRs more commonly described itchy palms and feet, generalized itch, and general urticaria and/or erythema, whereas patients with Taxol HSR more commonly described facial flushing, back pain, and chest or throat tightness (all P < .05). Among 40 patients with mild-to-moderate carboplatin HSRs, only 7 were rechallenged, and 100% tolerated rechallenge without desensitization. None of the patients with severe carboplatin HSRs (n = 5) were rechallenged. Most patients (75%) with Taxol HSRs were rechallenged, and 91% tolerated rechallenge without desensitization; the patients with a severe HSR to Taxol were less likely to be rechallenged. CONCLUSION: The clinical symptoms and timing of carboplatin HSR are distinct from Taxol HSR. Most patients with carboplatin HSR were not rechallenged, whereas most patients with Taxol HSR were successfully rechallenged.

Retrospective study of drug-induced anaphylaxis treated in the emergency department or hospital: patient characteristics, management, and 1-year follow-up.

BACKGROUND: Drugs are a common cause of anaphylaxis, which is potentially life threatening. OBJECTIVE: We sought to describe US patients with an emergency department (ED) visit or hospitalization for drug-induced anaphylaxis (DIA), including postdischarge follow-up care. METHODS: By using International Classification of Diseases, Ninth Revision codes in the MarketScan Database, we identified all patients with an ED visit and/or hospitalization for DIA between 2002 and 2008 (index date = initial ED visit and/or hospitalization). Inclusion required continuous full insurance coverage ≥1 year in the pre- and postindex period. We examined patient factors during the preindex period, characteristics of the index event, and outcomes during the postindex period. RESULTS: The cohort included 716 patients with an ED visit and/or hospitalization for DIA (mean age, 48 years; 71% women). Most patients (71%) were managed in the ED, and only 8% of the patients with DIA treated in the ED received epinephrine. For those admitted, patients were hospitalized for a median of 3 days, and 41% spent time in the intensive care unit. Cardiorespiratory failure occurred in 5% of the patients in the ED and 23% of the patients who were hospitalized. The patients with a concomitant allergic condition were more likely to see an allergist/immunologist than those without a concomitant allergic condition, but 82% did not receive any subsequent care with an allergist/immunologist in the 1 year after the ED visit and/or hospitalization for DIA. CONCLUSION: Drugs are a common, yet under-recognized, cause of anaphylaxis. Only a small number of patients with DIA received epinephrine in the ED or had subsequent care with an allergist/immunologist. These findings are novel and identify areas for improvement in the care of individuals with DIA.