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BACKGROUND: Nonsteroidal anti-inflammatory drug (NSAID) exacerbated respiratory disease (N-ERD) consists of chronic rhinosinusitis with nasal polyposis (CRSwNP), asthma, and NSAID intolerance. Acetylsalicylic acid treatment after desensitization (ATAD) is a treatment option for uncontrolled N-ERD. OBJECTIVE: To evaluate peroral ATAD's long-term effectiveness on CRSwNP disease control. METHODS: The retrospective data (patient characteristics, sinus surgeries before ATAD, ATAD, follow-up data [20191) were collected from patient records of 171 patients with N-ERD (102 ATAD patients, 69 controls with CRSwNP-F N-ERD without ATAD) who underwent tertiary hospital consultation from 2001 to 2017. Outcome measurements were ATAD discontinuation, revision sinus surgery, and corticosteroid and antibiotic courses for airway infections during 2016-2019. Associations were analyzed by survival and nonparametric methods. RESULTS: The ATAD group had more tissue eosinophilia, symptoms, and sinus surgeries before ATAD than others. The ATAD discontinuation rate was 63%, independent of ATAD dose or duration, usually due to side effects. Compared with the N-ERD group without ATAD, ATAD (mean duration, 2.9 years) did not affect the revision endoscopic sinus surgery rate (P = .21, by the log-rank test) or the number of peroral corticosteroid courses per year (P > .05, by the Mann-Whitney U-test) during the follow-up (mean, 7.6 years) despite the dose or duration of ATAD. CONCLUSIONS: The discontinuation rate of ATAD was high (63%), and ATAD did not affect revision sinus surgery rate nor the need of peroral corticosteroids during follow-up. However, the remaining 37% of the ATAD group did continue the treatment, indicating that they may have benefited from ATAD. (C) 2020 American Academy of Allergy, Asthma & Immunology

Background About one-tenth of patients with difficult-to-treat chronic rhinosinusitis with nasal polyps (CRSwNP) have comorbid non-steroidal anti-inflammatory drug-exacerbated respiratory disease (NSAID-ERD). Dupilumab, a fully human monoclonal antibody that blocks the shared interleukin (IL)-4/IL-13 receptor component, is an approved add-on treatment in severe CRSwNP. This post hoc analysis evaluated dupilumab efficacy and safety in patients with CRSwNP with/without NSAID-ERD. Methods Data were pooled from the phase 3 SINUS-24 and SINUS-52 studies in adults with uncontrolled severe CRSwNP who received dupilumab 300 mg or placebo every 2 weeks. CRSwNP, nasal airflow, lung function, and asthma control outcomes at Week 24 were evaluated, and treatment-subgroup interactions were assessed for patients with and without NSAID-ERD. Results Of 724 patients, 204 (28.2%) had a diagnosis of NSAID-ERD. At Week 24, least squares mean treatment differences demonstrated significant improvements in nasal polyp score, nasal congestion (NC), Lund-Mackay computed tomography, 22-item Sinonasal Outcome Test (SNOT-22), Total Symptom Score (TSS), rhinosinusitis severity visual analog scale, peak nasal inspiratory flow (PNIF), six-item Asthma Control Questionnaire score, and improvement in smell with dupilumab versus placebo (all p < .0001) in patients with NSAID-ERD. Treatment comparisons demonstrated significantly greater improvements with dupilumab in patients with versus without NSAID-ERD for NC (p = .0044), SNOT-22 (p = .0313), TSS (p = .0425), and PNIF (p = .0123). Conclusions In patients with uncontrolled severe CRSwNP, dupilumab significantly improved objective measures and patient-reported symptoms to a greater extent in the presence of comorbid NSAID-ERD than without. Dupilumab was well tolerated in patients with/without NSAID-ERD.

Purpose Although genome-wide association studies (GWASs) represent the most powerful approach for identifying genes that influence asthma, to date, no studies have established genetic susceptibility to asthma in the Korean population. This study aimed to identify genetic variants associated with adult Korean asthmatics and compare them with the significant single nucleotide polymorphisms (SNPs) of UK asthmatics from the UK Biobank. Methods Patients were defined as having asthma if they were diagnosed by a doctor or taking medications for asthma. Controls were defined as individuals without asthma or chronic obstructive pulmonary disease. We performed quality control, genotype imputation, GWAS, and PrediXcan analyses. In the GWAS, a P value of < 5 × 10−8 was considered significant. We compared significant SNPs between Korean and UK patients with asthma. Results A total of 1,386 asthmatic patients and 5,205 controls were analyzed. The SNP rs1770, located near the human leukocyte antigen (HLA)-DQB1, was the most significant SNP (P = 4.5 × 10−10). In comparison with 24 SNPs in a GWAS of UK asthmatics, six SNPs were significant with the same odds ratio (OR) direction, including signals related to type 2 inflammation (e.g., IL1RL1, TSLP, and GATA3) and mucus plugging (e.g., MUC5AC). HLA-DQA1 showed an opposite OR direction. The HLA-DQB1 gene demonstrated significantly imputed mRNA expression in the lung tissue and whole blood. Conclusions The SNP rs1770 of HLA-DQB1 was the most significant in Korean asthmatics. Similarities and discrepancies were found in the genetic variants between Korean and UK asthmatics. GWAS of Korean asthmatics should be replicated and compared with those of GWAS of other ethnicities.

Asthma is a common disease, and although its clinical manifestations may be similar among patients, recent research discoveries have shown that it consists of several distinct clinical clusters or phenotypes, each with different underlying molecular pathways yielding different treatment responses. Based on these observations, an alternative approach - known as 'precision medicine' - has been proposed for the management of patients with severe asthma. Precision medicine advocates identification of treatable traits, linking them to therapeutic approaches targeting genetic, immunological, environmental, and/or lifestyle factors in individual patients. The main "goal" of this personalised approach is to enable choosing a treatment which will be more likely to produce a beneficial response in the individual patient rather than a 'one size fits all' approach. The aim of the present review is to discuss different ways of phenotyping asthma and to provide a rationale for treatment algorithms based on principles of precision medicine.

Asthma is a common disease, and although its clinical manifestations may be similar among patients, recent research discoveries have shown that it consists of several distinct clinical clusters or phenotypes, each with different underlying molecular pathways yielding different treatment responses. Based on these observations, an alternative approach - known as 'precision medicine' - has been proposed for the management of patients with severe asthma. Precision medicine advocates identification of treatable traits, linking them to therapeutic approaches targeting genetic, immunological, environmental, and/or lifestyle factors in individual patients. The main "goal" of this personalised approach is to enable choosing a treatment which will be more likely to produce a beneficial response in the individual patient rather than a 'one size fits all' approach. The aim of the present review is to discuss different ways of phenotyping asthma and to provide a rationale for treatment algorithms based on principles of precision medicine.

Drug hypersensitivity reactions (DHRs) are unpredictable, complex responses to medicines in predisposed individuals. They represent a major health problem owing to the number of patients affected and the severity of the clinical conditions they can induce. In addition to environmental factors, the underlying mechanisms of DHRs are also influenced by genetic factors, although considerable gaps remain in our knowledge. Therefore, further study of the genetics of DHRs is necessary to shed light on their underlying mechanisms. In this manuscript, we provide an update on the genetic basis of the most frequent types of DHRs, including those mediated by immunological and nonimmunological mechanisms. For the first group, we will focus on immediate reactions to beta-lactam antibiotics, which are associated mainly with the IgE pathway (IL13, IL4R, LGALS3, and NOD2) and antigen presentation (HLA-DRA), and nonimmediate reactions to allopurinol, anticonvulsants, antibiotics, and antiretrovirals, which are often associated with polymorphisms in the HLA system. For the second group, we will focus on nonsteroidal anti-inflammatory drugs, which are mostly associated with genetic variants in enzymes and receptors from the arachidonic acid pathway (eg, ALOX5, ALOX5AP PTGDR, and CYSLTR1). The information provided here will be of interest for medical practitioners from a range of disciplines who come across these reactions in their clinical practice, as well as for allergologists.