Comorbid asthma in patients with chronic rhinosinusitis with nasal polyps: did dupilumab make a difference?

BACKGROUND: The clinical heterogeneity of chronic rhinosinusitis (CRS) and bronchial asthma is attributable to different underlying inflammatory profiles. However, the similarity between CRS with nasal polyps (CRSwNP) and type-2 asthma pathophysiology speculates that one biological therapy could affect both comorbidities. Despite dupilumab, a monoclonal antibody that targets IL-4α and IL-13 receptors, being used in patients with nasal polyps and severe asthma, real-life data about its efficacy in improving the quality of life and patient symptoms is still lacking. This study's primary objective was to evaluate dupilumab treatment's effect on the frequency of olfactory symptoms and health-related quality of life tests as measured by the Sino-nasal outcome test (SNOT-22) in patients with NP. The secondary objective was the effect of dupilumab on asthma symptom control as measured by the asthma control test (ACT). METHODS: A prospective study was conducted of 166 patients with CRSwNP, with or without asthma. The following variables were collected at baseline and after at least six months of continuous dupilumab therapy; SNOT-22, olfactory symptoms frequency, and ACT score. RESULTS: Asthma prevalence in patients with CRSwNP was high (59.63%), and being female with a history of frequent use of oral corticosteroid (OCS) courses and repeated unsuccessful nasal and para-nasal surgeries for polyposis increased the likelihood of having underlying asthma by 2, 1 and 4 times more, respectively. Additionally, being asthmatic required a longer duration of dupilumab treatment. However, both the health-related quality of life and olfactory symptoms improved equally in both groups. CONCLUSION: Even with associated comorbid asthma in patients with CRSwNP, treatment with dupilumab could improve the quality of life, olfactory symptoms, and asthma symptom control.

Nationwide study of rates of reinfection with SARS-CoV-2 among adults in Kuwait.

Background: Data are scarce on differences in the rates of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reinfection after the first infection. Aims: We examined nationwide data on SARS-CoV-2 reinfection in Kuwait according to four-time windows to reinfection: 29-45 days, 46-60 days, 61-90 days, and ≥ 91 days. Methods: This was a population-level retrospective cohort study conducted between 31 March 2020 and 31 March 2021. We reviewed evidence of second positive RT-PCR test results for those who had previously recovered from COVID-19 and tested negative. Results: Reinfection rates were: 0.52% for reinfection window 29-45 days, 0.36% for 45-60 days, 0.29% for 61-90 days, and 0.20% for ≥ 91 days. The mean age (standard deviation [SD]) of individuals with the shortest reinfection time interval (29-45 days) was significantly older than the mean age of all other groups - 43.3 years (SD 17.5) compared with: 39.0 years (SD 16.5), P = 0.037 for 46-60-day interval; 38.3 years (SD 16.5), P = 0.002 for 61-90-day interval; and 39.2 years (SD 14.4), P = 0.001 for ≥ 91-days interval. Conclusion: SARS-CoV-2 reinfection was uncommon among this adult population. Older age was associated with a shorter time to reinfection.

Lupus anticoagulant activity and thrombosis post COVID-19 vaccination.

Some reports have discussed the development of a new entity called vaccine-induced immune thrombotic thrombocytopenia after COVID-19 vaccination. In this case series, we are describing four patients who have developed lupus anticoagulant-associated venous thromboembolism after Pfizer mRNA COVID-19 vaccination. All were COVID-19 negative on admission. Three had developed thrombosis after the first dose and one after the second dose of vaccination. All of them had venous thrombosis. Three patients developed thrombosis 2 weeks after vaccination and the fourth patient had developed thrombosis after 3 weeks of vaccination. None of the patients had thrombocytopenia on or during admission as seen in the case of vaccine-induced immune thrombotic thrombocytopenia. All patients had positive lupus anticoagulant and negative anticardiolipin antibodies and antibeta2 glycoprotein I. All of them were stable on discharge and were treated with low molecular weight heparin followed by warfarin. We suggest the presence of a possible link between the development of antiphospholipid antibodies and COVID-19 vaccine that requires further assessment.

Isolated thrombosis after COVID-19 vaccination: case series.

BACKGROUND: Data regarding thrombosis after COVID-19 vaccination are scarce. METHODS: Clinical and laboratory data were collected from all patients who developed thrombosis within 4 weeks of receiving the Pfizer or Oxford/AstraZeneca vaccine. None had a COVID-19-positive swab. RESULTS: Seventeen patients were included, with average age of 48.8 years and equal proportion of females to males. Our data suggest that thrombosis occurred in 1 in 163,000 of all individuals who had received any dose of any type of COVID-19 vaccine: six (1 in 123,000) patients after the first dose of Oxford/AstraZeneca, none after the second dose of Oxford/AstraZeneca, four (1 in 257,000) patients after the first dose of the Pfizer vaccine, and seven (1 in 102,000) patients after the second dose of Pfizer vaccine. Three of 17 patients with thrombosis (17.6%) died. CONCLUSIONS: We believe this report to be one of the earliest in the literature to address the question of whether isolated thrombosis is a possible complication of COVID-19 vaccination.

Peanut Component Ara h 1 and 2 Sensitization in Patients with Food Allergy in Kuwait.

INTRODUCTION: There is limited knowledge on the sensitization patterns to peanut proteins and food allergy in the Middle East. The objective of this study is to analyze the relationship between sensitization patterns to peanut proteins and clinical symptoms in a group of patients with physician-diagnosed peanut allergy (PA) in Kuwait. METHODS: PA patients were evaluated by the skin prick test (SPT), serum total IgE, peanut-specific IgE (sIgE), and sIgE against Ara h 1-3, 8, and 9, and clinical data were collected. RESULTS: Sixty-nine patients were included. A positive correlation between peanut SPT and sIgE was detected for all 3 storage proteins (Ara h 1-3) in patients <6 years old and for Ara h 1 and 2 in older patients. ROC analysis of positive correlations showed that oral food challenge should be considered for definite diagnosis of PA only if the level of Ara h 2 is <22.25 KUA/L, with level of Ara h 2 ≥15.4 allowing the detection of systemic reactions with a sensitivity of 55.56%. Patients presenting with systemic reactions more frequently had positive Ara h 1 (88.9%) and Ara h 2 (83.3%), compared with 44.1% and 52.9% in those with local reaction (p = 0.0046 and p = 0.0378). The levels of Ara h 1 and 2 were also significantly higher in patients with systemic reactions compared to those with a local reaction, with those differences being especially relevant for Ara h 2 (15.9 vs. 0.4) (p = 0.0005). CONCLUSIONS: The pattern of sensitization to peanut proteins in the Middle East is similar to that of the Western world. Measurement of sIgE antibodies to Ara h 1, 2, and 3 is useful in the diagnosis of PA and in the investigation of reactions to raw and roasted peanuts.

Drug Allergy Profile From a National Drug Allergy Registry.

Background: Drug hypersensitivity reactions (DHRs) are among the most frequent reasons for consultation in allergy departments and are becoming more common due to increasing prevalence and case complexity. Objective: To describe the most common drugs associated with clinical reactions, diagnostic methods used, and outcomes of allergic evaluations of a national drug allergy registry over a 12-year period were used. Methods: An observational, prospective, patient's data registry-based study was conducted to analyze all referrals to the drug allergy outpatient clinics at Al-Rashed Allergy Center, Kuwait, between 2007 and 2019. Demographics, description of DHRs, and results of allergy tests to potential causative medications were reviewed. Diagnostic methods were focused mainly on skin tests (STs) and drug provocation test (DPT), when indicated. Results: We evaluated 1,553 patients with reported DHRs. The mean age of the population was 41.52 ± 16.93 years, and the study population consisted of 63.7% female patients. Hypersensitivity was finally confirmed in 645 (41.5%) of patients, probable in 199 (12.8%), and not confirmed/nonallergic in 709 (45.6%) patients. Anti-inflammatory drugs and analgesics contributed to 39.22% of all confirmed drug allergies, followed by antibiotics 38.1% (ß-lactam antibiotics (BLs) constituted 73.98% of all antibiotics and 28.21% of all drugs), anesthetics 1.8%, and radio-contrast media 0.31%. The majority of reactions were non-immediate 51.44%. The most commonly presenting symptoms among confirmed patients were urticaria 57.80%, angioedema 42.50%, respiratory symptoms 47.60%, and erythema 33.60%. Symptoms of anaphylaxis/anaphylactic shock were reported by 284 patients (44.00%) among confirmed cases. The most common method of diagnosis was a positive clinical history (54.4% in BLs and 90.45% in nonsteroidal anti-inflammatory drugs (NSAIDs). Among confirmed allergy to BLs, a positive ST was obtained in 31.9% of patients and positive DPT in 13.7%. Conclusion: NSAIDs and antibiotics, mainly BLs, are the most commonly implicated in confirmed allergy. In both confirmed and not confirmed/nonallergic cases, BLs are the most frequently involved DHRs which are mainly immediate, and the most commonly presenting symptoms were urticaria, angioedema, and respiratory symptoms. Diagnosis was confirmed mainly by a positive clinical history and when indicated, by positive STs or a DPT.

"Real-life" Efficacy and Safety Aspects of 4-Year Omalizumab Treatment for Asthma.

OBJECTIVE: To evaluate the long-term efficacy and safety of omalizumab in asthma in a real-life setting. SUBJECTS AND METHODS: This 4-year observational study included 65 patients treated with omalizumab during clinic visits; treatment response was rated as excellent, good, and partial based on a modified physician's Global Evaluation of Treatment Effectiveness (mGETE) scale of emergency room visits (ERV), hospitalization, use of oral corticosteroids, inhaled corticosteroid (ICS)/long-acting ß-agonist (LABA) dose, and short-acting ß-agonist rescue. The following tests were done: forced expiratory volume in 1 s (FEV1) and the asthma control test (ACT). Measurements were performed 1 month before therapy and at 16 weeks, 1 year, and 4 years of treatment. Statistical analyses were done using the Wilcoxon signed-rank test, Spearman rank correlation, and McNemar χ2 test. RESULTS: The dropout rate was 15 (18.5%): 8 nonresponders (10.0%); 2 patients died (2.5%), and 5 were lost to follow-up (6.25%). Treatment response was excellent in 35 (53.8%); good in 23 (35.4%), and partial in 7 patients (10.8%). The number of excellent responders increased from 35 (53.8%) at 16 weeks to 48 (73.8%) at the 4-year follow-up. The number of patients who did not require ERV improved from 0 to 59 (90.8%), and the lowest rate of hospitalization was 1 in year 4 (p < 0.001); patients who did not require courses of oral corticosteroids improved from 0 to 54 (83%). ICS/LABA dose significantly reduced from 65 (100%) to 25 (38.5%) after 4 years of treatment (p < 0.001); ACT scores significantly increased from 15 ± 3 at baseline to 23 ± 3 (p < 0.001) and FEV1 level from 55.6 ± 10.6 to 76.63 ± 10.34 at year 4. CONCLUSION: In this study, omalizumab therapy resulted in better asthma control, and was effective and well tolerated as an add-on therapy for patients with moderate-to-severe asthma.

Establishing a Safe Administration of ASA in Cardiovascular Patients with Nonsteroidal Anti-Inflammatory Drug Hypersensitivity with Skin and/or Respiratory Involvement.

BACKGROUND: A history of nonsteroidal anti-inflammatory drug (NSAID) hypersensitivity with cross-intolerance to several drugs is common in some patients with coronary artery disease. We present a series of patients with acute coronary syndrome undergoing ASA desensitization prior to a possible stent to evaluate the short- and long-term efficacy and safety. The aim was to evaluate the outcomes of an ASA desensitization protocol developed by our center based on the guidelines proposed by the EAACI drug allergy expert recommendations. METHODS: We developed a desensitization protocol that was based on both the patient characteristics and onset of reaction after NSAIDs, including premedication with a leukotriene antagonist and the H1-antagonist antihistamine. The clinical entities were NSAID-induced urticaria and/or angioedema in the absence of chronic spontaneous urticaria (NIUA) and NSAID-exacerbated respiratory disease (NERD). RESULTS: A total of 23 patients were challenged or desensitized with ASA: 19 NIUA and 4 NERD. All patients tolerated the protocol at the different times of 30, 45, 90, and 120 min. The dosages of oral ASA that were given included 10, 21, 41, 81, and 162 mg (cumulative dose 315 mg). One patient reacted during the procedure and 1 during follow-up. Symptoms were limited to the skin without manifestations in other organs. All patients tolerated the required dose of ASA within 30-120 min. Those requiring urgent catheterization were desensitized within 90 min. CONCLUSIONS: Our protocol addresses challenge or desensitization with the contribution of a specialist allergist. It provides an effective, dynamic, safe, and short administration of 81 mg or higher of ASA in patients with a history of NSAID hypersensitivity with skin involvement.

Drug allergy evaluation for betalactam hypersensitivity: Cross-reactivity with cephalosporines, carbapenems and negative predictive value.

BACKGROUND: There are no studies on cross-reactivity of betalactams among patients allergic to penicillin, or on the negative predictive value (NPV) of penicillin allergy evaluation from Arabian Gulf countries. OBJECTIVE: We aimed to assess the role and NPV of drug provocation test (DPT) for betalactam hypersensitivity reactions in patients referred for allergy evaluation in Kuwait. METHODS: Skin test (ST) was performed for all patients with a history of betalactam hypersensitivity, other than anaphylaxis. Patients with a negative ST were challenged with a DPT containing phenoxymethyl penicillin or the culprit drug. Patients with anaphylaxis or who tested positive to betalactams were then challenged with a DPT containing cefuroxime, meropenem or ceftriaxone. Patients who tested negative were contacted by phone to evaluate subsequent betalactam intake. RESULTS: A total of 214 patients were tested for betalactam hypersensitivity. We had 91(42.5%) positive cases. Among positives, there were 78 (85.7%) patients with an initial reaction to penicillin and 13 (14.3%) who reacted to cephalosporin. DPT with alternative betalactam was performed in fifty who tested positive for betalactam hypersensitivity and 45 (90%) tolerated alternative antibiotics. Phone calls to 113 (59.8%) patients with negative betalactam testing showed that among 40(35.4%) patients who were successfully contacted; 17 (15%) took betalactams and 23 (20%) did not. Among the 17 patients who took betalactams, our calculated NPV for penicillin testing range from 88.2 to 100%, as the 2 patients who reported a reaction refused confirmatory retesting. CONCLUSION: Carbapenems and cephalosporines can be safely given to penicillin allergic patients by means of skin testing and if negative, proceeding with a graded challenge. Our calculated NPV for penicillin testing is similar to other studies.

Penicillin allergy evaluation: experience from a drug allergy clinic in an Arabian Gulf Country, Kuwait.

BACKGROUND: Hypersensitivity to penicillin has been studied worldwide, but data regarding patterns of sensitization in Arabian Gulf countries are scarce. OBJECTIVE: To describe the patterns of penicillin hypersensitivity during a 6-year study in Kuwait in terms of demographics, type of the culprit drug, in vivo and in vitro allergy testing. METHODS: One hundred and twenty-four patients referred to the drug allergy clinic for penicillin allergy were fully evaluated by skin prick and intradermal testing. Drug provocation test was done on patients with negative results. RESULTS: A total of 124 patients were evaluated for penicillin allergy. Mean age was 37.8 (standard deviation, 12.7) years, range from 8 to 74 years. Thirty-nine male (31.5%) and 85 female patients (68.5%) were included. Diagnosis of penicillin allergy was confirmed in 46 patients (37.1%). Among the 44 confirmed allergic patients by skin evaluation we had 15 (34.1%) positive skin prick test, and 29 (65.9%) positive intradermal testing. Among patients with positive skin testing, 47.7% were positive to major determinant benzylpenicilloyl poly-L-lysine, 20.4% to minor determinant mixture, 50.0% to penicillin G and 40.9% to ampicillin; 13.6% of patients were positive to amoxicillin by skin prick test. One patient had a positive radioallergosorbent test and one had a positive challenge test. CONCLUSION: Penicillin allergy is a common problem with an incidence of about one third in our study subjects.

Hypersensitivity reactions to mAbs: 105 desensitizations in 23 patients, from evaluation to treatment.

BACKGROUND: Rapid desensitization, a procedure for graded drug administration, allows for the safe readministration of a medication after certain types of hypersensitivity reactions (HSRs) and is indicated in cases in which there are no reasonable therapeutic alternatives. The use of rapid desensitization for HSRs to mAbs has not been validated. OBJECTIVE: We sought to describe our experience with rapid desensitization to mAbs, including rituximab, infliximab, and trastuzumab. METHODS: One hundred five rapid desensitizations were performed in 23 patients with a standardized 12-step, 6-hour protocol. Our approach to patient evaluation before desensitization is described. The severity, characteristics, and timing of both initial HSRs and HSRs during desensitization were determined by means of retrospective review of medical records. After a reaction during desensitization, patient-specific protocol modifications were made before each subsequent desensitization. RESULTS: 104 of 105 desensitizations undertaken were successfully completed. We observed HSRs during 29% of desensitizations, including 27 mild reactions, 1 moderate reaction, and 2 severe reactions. Overall, reactions during desensitization were markedly less severe than initial HSRs, but reactions did recur in a minority of successive desensitizations. CONCLUSIONS: Rapid desensitization is a promising method for the delivery of monoclonal therapeutics after an HSR, but the possibility of a reaction remains with each desensitization.

A safe protocol for rapid desensitization in patients with cystic fibrosis and antibiotic hypersensitivity.

BACKGROUND: CF patients often demonstrate hypersensitivity to one or multiple antibiotics due to frequent and repeated exposures. Attempts at antibiotic desensitization in this population are historically complicated by higher reaction rates, failure to complete the procedure and consequent withholding of first-line therapy. This study evaluates the outcomes of a rapid desensitization protocol developed at our institution. METHODS: We retrospectively reviewed the medical records of 15 patients undergoing 52 rapid antibiotic desensitizations at Brigham and Women's Hospital and Children's Hospital Boston utilizing our protocol. RESULTS: Mean FEV1 % predicted was 44.1 (SD 16.5), with two patients at <30% and one patient desensitized during bilateral lung transplantation. Adverse reactions during desensitization occurred in 13.4%, and most were mild. 100% of patients completed the protocol and ultimately tolerated subsequent full-strength antibiotic courses. CONCLUSIONS: CF patients with antibiotic hypersensitivity can safely receive first-line antibiotics via our rapid desensitization protocol, including those with severe obstructive lung disease.