Journal of Allergy and Clinical Immunology-In Practice最新文献

Clinical implications: We present the case of a girl with CRIA syndrome treated with sirolimus with significant reduction in the number of days with fever, the total dose of glucocorticoids used and the inflammatory markers levels, together with a reduction in the double negative T-cells and control of PI3K/mTor Activity. We propose sirolimus as a valid therapeutic choice in patients with CRIA syndrome.

Chronic cough is among the most common symptoms prompting medical care. Cough variant asthma (CVA) is an asthma subset where cough is the primary symptom, without wheezing, chest tightness, or dyspnea. It is an important cause of chronic cough, estimated to account for 25% to 42% of cases, but likely underdiagnosed due to delayed recognition and pitfalls of diagnostic testing. Early recognition and treatment can reduce morbidity and delay its progression to more typical asthma. This review details the clinical characteristics, diagnosis, pathophysiology, and treatment of CVA and contrasts it with classic asthma (CA) and other causes of chronic cough.

Cough reflex hypersensitivity is emerging as a key treatable trait in chronic cough and other cough-associated respiratory conditions. This review examines the neurological basis of cough, highlighting the complex interplay between peripheral and central mechanisms. The concept of cough hypersensitivity aims to address unmet clinical needs by recognizing chronic cough as a distinct disorder rather than merely a symptom. Evidence from clinical trials supports cough hypersensitivity as a treatable trait in chronic cough, with opiates, gabapentinoids, and novel P2X3 antagonists showing efficacy. Cough hypersensitivity is also relevant in conditions presenting with persistent cough, like asthma, bronchiectasis, and idiopathic pulmonary fibrosis, though more research is needed. Recognizing cough reflex hypersensitivity as a treatable trait offers new avenues for management, particularly for patients with persistent cough despite etiology-targeted therapies. We propose redefining chronic cough as a distinct disease entity in which cough hypersensitivity is a common feature and key therapeutic target, potentially leading to better patient care and the development of novel therapies.

Chronic cough remains a significant clinical challenge, affecting approximately 10% of the population and leading to significant impairment in psychological, social and physical quality of life. In recent years, efforts have intensified to elucidate the mechanisms underlying chronic cough and to focus on investigating and treating refractory chronic cough (RCC). A 'treatable trait' approach, which focuses on identifying and addressing the specific associated causes of chronic cough, has gained traction. In some patients, refractory chronic cough is likely driven by a neuropathic mechanism due to dysregulation of the neuronal pathways involved in the cough reflex, often clinically described as cough hypersensitivity syndrome. While the initial treatment of underlying conditions remains central to managing treatable traits, the therapeutic options for RCC have expanded to include targeting cough hypersensitivity. First-line treatments now include neuromodulators and speech therapy with one P2X3 receptor antagonist (gefapixant) recently licensed in the EU, UK and Japan. Despite these advances, patient responses remain variable, underscoring the ongoing need for research into the pathophysiology and treatment of RCC. This article reviews current investigations and management options in treating chronic cough and RCC.

Background: Tezepelumab has shown promising efficacy for adult patients with severe asthma since its approval. However, the post-marketing safety evaluation of tezepelumab is currently lacking.

Objective: The present study aims to investigate the post-marketing safety of tezepelumab based on the FDA Adverse Event Reporting System (FAERS) database.

Methods: Adverse events (AEs) reports from January 2022 to December 2023 were extracted from the FAERS database. Disproportionality analysis by reporting odds ratio (ROR) and empirical Bayesian geometric mean (EBGM) was performed to detect potential AEs related to tezepelumab. Clinical characteristics and time to onset of AEs were also assessed.

Results: A total of 1,699 tezepelumab-related AE reports were identified during the study period. Thirty tezepelumab-related AE signals were detected by simultaneously applying the two algorithms. At the system organ class (SOC) level, the most common SOC related to tezepelumab was respiratory, thoracic and mediastinal disorders. At the preferred term (PT) level, common AEs including arthralgia and back pain were detected which were also documented in the label of tezepelumab and clinical trials. New unexpected AEs such as chest pain and myalgia were also identified. The median time to onset of tezepelumab-related AEs was 7.5 days, and the majority of AEs occurred within the first 1 month after tezepelumab initiation.

Conclusion: The present study presents a comprehensive evaluation of the post-marketing safety of tezepelumab in the real-world setting. Our findings will provide valuable evidence for future clinical studies and management of safety issues of tezepelumab.

Background: Patients with mastocytosis (MC) have an increased risk of severe anaphylaxis. They report hypersensitivity reactions to drugs and food, but causality often remains questionable. Most allergy centers avoid oral challenge tests (OCT) in MC patients.

Objective: To determine the safety of food and drug OCT in patients with MC.

Methods: To retrospectively evaluate the safety and outcome of challenges to drugs and food including food additives, out of 126 adult MC inpatients, 83 patients had a suspicion of food or drug hypersensitivity and 445 OCTs were performed. History, clinical data and allergy test results highlighting OCTs were analyzed.

Results: Only 10 of 445 OCTs (2.2%) in 9 patients resulted in anaphylaxis. Drugs elicited reactions in 4/170 (2.4 %) patients: two patients to acetylsalicylic acid (2/39 tested patients, 5.1%), one to tramadol (1/12, 8.3%) and one to flurbiprofen (1/1). Anaphylaxis to food was recorded in 6/275 OCTs (2.2%); two out of 48 (4.1%) to α-gal, two to other foods and two to sulfites. Flushing or diarrhea occurred to histamine in 5/48 (10.4%), but also in 5/50 (10.0%) placebo challenges strongly questioning its relevance. Patients with proven anaphylaxis had more bone marrow MC and higher basal serum tryptase (71.3 vs. 44.3ug/l; p<0.05).

Conclusions: Challenge-confirmed food and drug anaphylaxis was rare in MC patients. Results have to be interpreted cautiously as placebo reactions did occur. Severe anaphylaxis was seldom, but may occur and should be met by emergency preparedness.

Cow's milk allergy (CMA) is one of the most common food allergies in early childhood. CMA has varied presentations and multiple facets. A detailed clinical history is key for classification. In IgE-mediated CMA skin prick testing and serum specific IgE testing are useful in the diagnosis, but an oral food challenge (OFC) may still be necessary if there is doubt or to assess tolerance. Non-IgE-mediated CMA presentations include food protein-induced allergic proctocolitis (FPIAP), food protein-induced enterocolitis syndrome (FPIES), and eosinophilic esophagitis (EoE). The diagnosis of FPIAP and FPIES is based on the clinical history. An esophageal biopsy is required for the diagnosis of EoE. Atopy patch testing, IgG or IgG4 testing are not helpful in any CMA evaluation. Children with CMA (except those with FPIAP) are at risk for poor growth and a nutritional evaluation should be part of routine care. Extensively hydrolyzed formulas are the recommended first choice alternative formula for CMA. For IgE-mediated CMA, alternative approaches to traditional strict avoidance include oral immunotherapy (OIT) and omalizumab (both as monotherapy and as an adjunct to OIT). Multiple international guidelines have addressed evaluation and management of CMA providing key information, support and guidance for clinicians in daily practice.

Background: Mepolizumab can induce an early response and clinical remission in people with severe eosinophilic asthma (SEA).

Objective: We questioned whether early response to mepolizumab could predict future asthma remission, and sought to identify the best predictor of treatment response to mepolizumab for achieving remission.

Methods: The Australian Mepolizumab Registry was used to investigate the early response to mepolizumab at 3 and 6 months and relate this to clinical remission at 12 months. Treatment response was assessed using the Asthma Control Questionnaire (ACQ)-5, oral corticosteroid (OCS) dose, exacerbation frequency, and post-bronchodilator FEV₁. Clinical remission, assessed at 12 months, was defined as ACQ-5 ≤1.0 at 12 months, no exacerbations in the previous 6 months, and no OCS use for asthma in the previous 6 months. We estimated the optimism-corrected area under the curve (AUC) for internal validation.

Results: We analyzed 255 participants with SEA. Seventy-eight (30.6%) participants achieved clinical remission at 12 months. A prediction model including ACQ-5 score, exacerbation frequency, OCS dose, and post-bronchodilator FEV₁ at 6 months was more predictive of achieving remission than measures at 3 months. ACQ-5 score at 6 months had the highest optimism-corrected AUC of 0.778 [95% CI: 0.719-0.833]. ACQ-5 score <1.5 at 6 months had a sensitivity of 85.9% for achieving clinical remission, while ACQ-5 score <0.75 had a specificity of 84.7%.

Conclusion: ACQ-5 score at 6 months was the best predictor of achieving clinical remission at 12 months in people with SEA treated with mepolizumab. These results can be used to design a treat-to-target paradigm for asthma, where treatment response is assessed at 6 months to predict clinical remission.