Hypersensitivity Reactions to Taxanes: A Multicenter Study for Outcomes and Safety of Rapid Drug Desensitization.

PURPOSE: Taxanes can cause hypersensitivity reactions (HSRs), which pose a significant challenge in the treatment of malignancies. Patients who are eligible for rapid drug desensitization (RDD) can continue treatment; however, some patients experience breakthrough reactions (BTRs). Data about risk factors for BTRs during RDDs in patients with HSRs to taxanes are limited. METHODS: This was a multicenter, retrospective study of patients with immediate-HSRs to taxanes. Initial HSRs were classified as grade 1, 2, or 3 based on severity. Prick/intradermal skin tests were performed with implicated taxanes. A 12-step protocol was used during RDD. RESULTS: The study comprised 75 patients (F/M: 63/12, mean age 49.92 ± 11.72 years, 43 HSRs to paclitaxel, 32 HSRs to docetaxel). The majority of reactions (86.7%) occurred during the first or second exposure. The prevalence of drug allergy history was higher in patients with paclitaxel HSR than in those with docetaxel HSR, although it was not statistically significant (23.3% vs. 6.3%). The initial HSRs were mostly grade 2 (n = 50, 66.7%) or grade 3 (n = 22, 29.3%). Skin tests with implicated taxanes were done on 48 patients, and the rate of positive response in patients with grade 1, 2, and 3 initial HSRs were 50%, 17.6%, and 16.7%, respectively. . A total of 255 RDDs were completely performed, although BTRs occurred in 27 (grade 1, 55.6%; grade 2, 40.7%; grade 3, 3.7%). There were no statistically significant correlations between the risk of BTR and age, drug cycle, gender, positivity of skin test or atopy. The step reduction was successfully done on 9 eligible patients with mild or moderate HSRs during the 12-step RDDs. CONCLUSIONS: Our experience demonstrates a 100% success rate in completing the 255 RDDs for taxanes, affirming the safety and efficacy of the RDD within the study population.

Comparison of 300 mg versus 600 mg daily maintenance doses of aspirin treatment after desensitization in N-ERD: A three-year multicentre experience.

Background: Aspirin treatment after desensitization (ATAD) is effective in preventing nasal polyps recurrence as well as respiratory symptoms in patients with nonsteroidal anti-inflammatory drug (NSAID)-exacerbated respiratory diseases (N-ERD). However, there is no consensus on effective daily maintenance doses in ATAD. Therefore, we aimed to compare the effects of two different maintenance doses of aspirin on clinical outcomes for 1-3 years of ATAD. Methods: This was a retrospective, multicenter study that involved four tertiary centers. The maintenance doses of daily aspirin were 300 mg in one center and 600 mg in the remaining three. The data of patients who were on ATAD for 1-3 years were included. Study outcomes (nasal surgeries, sinusitis, asthma attacks, hospitalization, oral corticosteroid use, and medication uses) were assessed in a standardized way and recorded from case files. Results: The study initially included 125 subjects, 38 and 87 were receiving 300 and 600 mg daily aspirin for ATAD, respectively. Number of nasal polyp surgeries decreased after 1 -3 years compared with before ATAD in both groups (group 1, baseline: 0.44 ± 0.07 versus first year: 0.08 ± 0.05; p < 0.001 and baseline: 0.44 ± 0.07 versus 3rd year: 0.01 ± 0.01; p < 0.001; and group 2, baseline 0.42 ± 0.03 versus first year: 0.02 ± 0.02; p < 0.001 and baseline: 0.42 ± 0.03 versus 3rd year: 0.07 ± 0.03; p < 0.001). Conclusion: Given the comparable effects of 300 mg and 600 mg aspirin daily as maintenance treatment of ATAD on both asthma and sinonasal outcomes in N-ERD, our results suggest using 300 mg of aspirin daily in ATAD owing to its better safety profile.

Hypersensitivity reactions to biologicals: An EAACI position paper.

Biologicals are crucial targeted therapeutic agents in oncological, immunological, and inflammatory diseases, and their use in clinical practice is broadening. In recent years, the spread of Personalized Precision Medicine has facilitated a proliferation of new treatment options, especially biologicals. Consequently, biologicals are now among the drugs that most frequently cause hypersensitivity reactions (HSRs). Patients can develop HSRs to these agents during the first-lifetime exposure or after repeated exposure, and these HSRs can be potentially life-threatening or limit therapeutic options. Despite the relatively high prevalence, the underlying mechanisms of these HSRs remain obscure, and the optimal management pathways are still a matter of discussion. In this Position Paper, the authors will provide evidence-based recommendations for diagnosing and managing HSRs to biologicals. Additionally, the document defines unmet needs as an opportunity to shape future research.

The effects of mold sensitivity on the clinical characteristics of adult asthmatic patients.

INTRODUCTION: The effects of mold sensitivity on the development and course of asthma have been researched previously, although study results vary. We sought to evaluate the characteristics of our mold-sensitive patients in comparison with those of other adult asthmatic patients. MATERIALS AND METHODS: Data were collected retrospectively from adult asthmatic patients who underwent regular follow-ups at our tertiary care outpatient clinic for immunology and allergic diseases. Patients were grouped and compared according to three categories of aeroallergen sensitivity status determined via a skin prick test. The study variables were demographic data, asth-ma-onset age, comorbid conditions, asthma-related emergency department visits and hospitalizations, systemic corticosteroid burst, asthma control assessment tests, and pulmonary function tests. RESULTS: In total, 242 patients' data were evaluated. Their mean age was 48.6 ± 15.4 years, with female predominance (81.4%). Mold-sensitive asthmatics composed 34.7%, while the aeroallergen-sensitive group without molds (33.1%) and the non-sensitized group (32.2%) composed the rest. The mold-sensitive group had a higher rate of polysensitization (92.8%) than the sensitized group without molds. In multinomial logistic regression analysis, mold sensitivity was positively associated with shorter asthma duration, absence of sinonasal polyposis, presence of allergic rhinitis, and generally well-controlled asthma compared to the non-sensitized group. Also, mold sensitivity was positively associated with shorter asthma duration, drug allergy, and absence of systemic corticosteroid bursts compared to the sensitized group without molds in logistic regression analysis. CONCLUSION: Our mold-sensitive asthmatic patients demonstrated better asthma symptom control. It should be considered that mold sensitization in adult asthmatics is not always a poor prognostic factor.

Role of Skin Tests in the Diagnosis of Immediate Hypersensitivity Reactions to Taxanes: Results of a Multicenter Study.

BACKGROUND: Immediate hypersensitivity reactions (HSRs) to taxanes have been increasing in recent years, but the importance of skin tests in allergological workup has not been established. OBJECTIVE: In our study we tried to evaluate the role of prick and intradermal tests in the diagnosis of HSRs to paclitaxel and docetaxel. METHODS: In this multicenter prospective study, we enrolled patients with immediate HSRs to the aforesaid agents. Skin tests were performed on these subjects and if results were negative, intradermal tests with the culprit drug were conducted. Patients with grade 1 reactions subsequently underwent graded challenge; in cases of grade 2 or 3 reactions and/or positive test results, the culprit drug was administered with a desensitization schedule. Skin tests were also performed in 30 control subjects exposed to the taxanes without HSRs. RESULTS: A total of 84 patients (63 with HSRs to paclitaxel and 21 to docetaxel) were recruited in the period July 2015 to July 2017 by 8 centers; 58 patients (69%) developed grade 2 or 3 reactions. Prick test results were negative in all the cases, whereas intradermal test results were positive in 14 patients (10 with paclitaxel [15.9%] and 4 with docetaxel [19%]). The positivity of skin tests significantly correlated with grade 3 reactions and cutaneous involvement during HSRs. Graded challenge was performed in 16 patients without problems and 58 subjects underwent desensitization, which was well tolerated in all but 2 cases. In the control group, skin test results were negative in all the patients. CONCLUSIONS: Skin tests for taxanes seem useful and can be performed in the allergological workup of subjects with HSRs to these agents, especially in cases of severe reactions with cutaneous involvement.

The prevalence of obstructive sleep apnea in patients with difficult-to-treat asthma.

OBJECTIVES: Obstructive sleep apnea (OSA) occurs more commonly in asthma patients than in the general population and can complicate asthma management. The aim of this study was to evaluate the presence of OSA in patients with difficult-to-treat asthma (DTA) and to investigate the sleep quality in these patients. METHODS: Patients with DTA were recruited from the adult allergy clinic of a tertiary care hospital. After completing the Sleep Questionnaire and Epworth Sleepiness Scale, all participants underwent overnight polysomnography. The demographic and asthma severity assessments included the following measures: the age at diagnosis, duration of illness, smoking and atopy status, results of pulmonary function tests, number of asthma control medications used, and number of hospitalizations and emergency room visits because of asthma and analgesic hypersensitivity according to apnea-hypopnea index (AHI) scores. RESULTS: We analyzed 47 (M:9/F:38) DTA patients with a mean age of 48.74±9.45 years. The mean duration of asthma was 9.17±6.5 years. Twenty-four (51.1%) patients were atopic. The analgesic hypersensitivity rate was 27.7%. Fourteen patients (29.8%) were former smokers and 2 patients were current smokers. Sleep quality was impaired in all patients. Thirty-five patients (74.5%) had OSA, 11 of whom had mild OSA, and 24 patients had moderate-severe OSA. The presence of OSA was not statistically correlated with asthma characteristics. CONCLUSION: The study showed that there is a remarkably high prevalence of OSA in DTA. Although no statistically significant relationship between the presence of OSA and clinical asthma characteristics was identified, all DTA patients should be assessed for OSA.

Does gender affect asthma control in adult asthmatics?

Several studies have shown gender differences in prevalence of asthma but there is little information about asthma control. In this study, we aimed to evaluate the effect of gender on asthma control in adult asthmatics. Medical records of 242 patients older than 18 years of age who regularly visited the allergy unit were evaluated. Standardized asthma questionnaires like the asthma control test (ACT) were performed. ACT scores, clinical characteristics, and demographic data such as smoking status, education, duration and severity of asthma, atopic status, family history of asthma, analgesic hypersensitivity, number of emergency visits, and hospitalization in the previous year were compared based on gender. In this study, 77.3% of the patients were female. Mean age, body mass index, and duration of asthma were 39.0 ± 0.7, 27.3 ± 0.3, and 6.6 ± 0.4 years, respectively. Of the total, 14.9% of the patients were smokers. Also, 55.8% of them were graduated from middle school, 22.7% from high school, and 14% from university. Atopy rate was 57%. Analgesic hypersensitivity was found in 18.6% of them. There was 30.2% family history of asthma. The asthma severity was mild in 45.5%, moderate in 40.9%, and severe in 13.6% of the patients. One-third of the patients were admitted to emergency room; 1/10th were hospitalized due to asthma in the previous year. ACT scores indicated complete control in 67.8%, partial control in 17.8%, and uncontrolled asthma in 14.5%. Comparing the results of males with females having asthma, there was no statistically significant difference between the two gender according to ACT scores and clinical characteristics. Finally, the results conclude that there was no effect of gender on asthma control assessed with standardized questionnaire in adult asthmatics.

Prevalence of asthmatic smokers: Turkish experience (PASTE Study).

BACKGROUND: Although both asthma and smoking are major health problems worldwide, smokers are often excluded from asthma studies. OBJECTIVES: It was aimed to verify the prevalence of asthmatic smokers in Turkey and assess the effects of smoking based on clinical parameters, exacerbations and hospitalizations because of lack of national data about the prevalence of smoking among asthmatics. METHODS: The study protocol was comprised of a retrospective questionnaire. The asthmatic patients were followed in the outpatient clinics of 18 tertiary hospitals selected from seven different geographical regions in Turkey. We evaluated demographic data, smoking habits, asthma-related diseases, respiratory function and emergency visits. RESULTS: The study population included 1385 patients (M/F: 343/1042), and the mean age was 45.1 ± 14.0 years. Current and former smoking prevalence was 11.4% and 15.1%, respectively. Smoker rates were higher in males and younger asthmatics compared with females and older asthmatics (P < 0.01 and P < 0.05, respectively). Smoking history ranged from 0.20 to 90 pack-years (the mean was 12.9), and smokers had a higher level of education compared with nonsmokers (P < 0.01). Socioeconomically, the most developed region had the highest rate of smoker asthmatics (33.9%; P = 0.014). There was an increase in the number of exacerbations in smoker asthmatics during the previous year, but it was not statistically significant (P > 0.05). CONCLUSION: We showed that the smoking prevalence in Turkey was lower in asthmatics (11.4%) compared with the general population (44.5%). Nevertheless, every effort should be made to encourage asthmatics to stop smoking because smoking is a modifiable risk factor for adverse asthma health outcomes.

Allopurinol desensitization with A 2 weeks modified protocol in an elderly patients with multiple comorbidities: a case report.

BACKGROUND: Allopurinol is an effective urate-lowering drug that is well tolerated by the majority of patients. Patients with chronic renal insufficiency have an increased risk of hypersensitivity reactions with allopurinol. CASE PRESENTATION: 75 year old male patient with gout, renal insufficiency, history of metastatic colorectal carcinoma status post-resection was referred to Allergy clinic for a maculopapular eruption that developed 1 week after initiating therapy with allopurinol. The rash resolved with discontinuation of allopurinol. However, his serum urate level rose to 19.9 mg/dl. We initially proposed a slow 4 week oral allopurinol desensitization. The treating nephrologist felt it was critical to lower urate more rapidly. As a result, we modified the dose and standard 4 week protocol down to 2 weeks. A suspension of allopurinol was prepared by the allergy nurse practitioner with a 300 mg allopurinol tablet. The sensitization protocol was modified as a starting dose of 0.3 mg escalating to a final dose of 300 mg/day in 2 weeks. There was no reaction during or after the desensitization. The patient's urate level normalized (6.3 mg/dl) and has continued on 300 mg allopurinol daily without reaction. CONCLUSION: A 2 week modified allopurinol desensitization protocol is a safe alternative for elderly patients with multiple comorbidities.

Two cases of tracheal disease misdiagnosed as difficult-to-treat asthma.

Initial management of patients with difficult-to-treat asthma must begin with confirmation of the diagnosis. We present 2 cases of tracheal disease misdiagnosed as difficult-to-treat asthma. After systemic evaluation, tracheomalacia and tracheobronchial narrowing due to diffuse calcification of the cartilaginous rings were found as mimicking asthma.

Predicting outcomes of oral aspirin challenges in patients with asthma, nasal polyps, and chronic sinusitis.

BACKGROUND: A definitive diagnosis of aspirin-exacerbated respiratory disease (AERD) requires a positive oral aspirin challenge (OAC), but predicting which patients will have positive challenges is often difficult. OBJECTIVE: To analyze information about historical aspirin- and nonsteroidal anti-inflammatory drug (NSAID)-associated respiratory reactions and clinical characteristics as potential markers to predict positive OACs. METHODS: A total of 243 patients underwent OACs. Data related to previous reactions and clinical characteristics of patients were correlated with the result of the OACs. RESULTS: Without prior exposure to aspirin or NSAIDs, the chance of a positive OAC was 5 in 12 (42%) but was 198 in 231 (86%) for those with a history of aspirin- and NSAID-associated asthma attacks. Sex, atopy, number of sinus infections per year, and number of sinus surgical procedures were not associated with positive OACs. Patients with 2 or more prior aspirin- and NSAID-associated respiratory reactions had an 89% chance of having a positive OAC vs single reactors (80%; P = .04). Mild or moderate prior reactions were associated with 84% or 80% positive OACs, whereas 100% of the 45 patients with severe prior reactions had positive OACs (P = .007). Except for hospitalizations, treatment locations of prior reactions (home or emergency department) did not seem to make any difference. Logistic regression identified age, sense of smell, and multiple prior reactions as independent risk factors associated with positive OACs. CONCLUSIONS: Age younger than 40 years, poor sense of smell, multiple prior respiratory reactions, and severe prior asthmatic reactions associated with aspirin and NSAIDs significantly increased the chances of a positive OAC.

Endobronchial metastases: a clinicopathological analysis.

OBJECTIVE: It is important to distinguish endobronchial metastases (EBM) from both primary lung cancers and benign lesions, as treatment will differ. The clinicopathological characteristics of EBM cases were documented to see whether any distinguishing features exist. METHODOLOGY: Histological cases diagnosed as EBM in the pathology laboratory of a tertiary hospital were re-evaluated. Symptoms, primary tumour sites, recurrence interval, radiological and bronchoscopic features, and histopathological properties were assessed. RESULTS: There were 18 cases (eight female, 10 male) with EBM. All were diagnosed by bronchoscopic bronchial biopsy. The primary tumour sites were: colorectal (4), breast (3), renal (3), lymphoma (3), rhabdomyosarcoma (2), bladder (1), thyroid (1) and malignant melanoma (1). The mean time from the diagnosis of the primary tumour to their presentation was 3.89+/-1.09 (range, 0--19) years. In five patients, EBM was diagnosed synchronously with their extra pulmonary primary tumour. Two had other metastatic sites. Haemoptysis and cough were the more common symptoms. Interestingly, three patients were asymptomatic. There was no predilection for a particular airway segment to be involved but a predilection for the upper lobe existed. Endoscopic appearance was polypoid in 10 cases and mucosal infiltration in the remainder. Histopathological examination revealed epithelial tissue at the surface of the tumour in nine cases and four of these were metaplastic. In all but one there was inflammation, mainly lymphocytic. Necrosis was present in 10 cases and bleeding was seen in four. There were no statistically significant differences between the level of lymphocytic inflammation and other clinicopathological parameters. CONCLUSION: EBM is a rare condition that can be synchronous or occur late. Surprisingly, it can be asymptomatic. It is usually found in the upper lobes. Lymphocytic inflammation is a common histopathological finding. There is need for further studies to clarify the clinical importance of EBM.