Current Opinion in Allergy and Clinical Immunology最新文献

Purpose of review: Chronic rhinosinusitis (CRS) is a diverse condition, including different underlying pathophysiologies. Tailoring the treatment for CRS depends on the individual's specific endotype and phenotype rather than using a universal approach. The emergence of biologics in recent years has raised questions about the role of antibiotics, particularly doxycycline, in CRS management. Insights from existing research on the mechanisms and appropriate use of doxycycline therapy may guide physicians in selecting the right treatment target.

Recent findings: CRS with nasal polyps (CRSwNP) is frequently associated with type 2 inflammation and characterized by tissue remodeling process that can result in recalcitrant condition. Doxycycline therapy (100 mg daily) improves CRSwNP by exerting antitissue remodeling effects through matrix metalloproteinase inhibition. Doxycycline seems to provide benefits when used alongside adequate medicine treatment.

Summary: Current evidence on the use of doxycycline therapy is limited to a small number of high-quality studies. Further research is needed to explore the duration and factors of success of doxycycline in treating CRS. Like other antibiotics, doxycycline has limitations related to side effects and the potential for antibiotic resistance. Therefore, treatment decisions should be made with caution, especially when doxycycline is used in combination with other pharmacologic therapies.

Purpose of review: Inborn errors of immunity with atopic phenotypes (IEIwA) are a subgroup of IEI that may present with severe and/or multiple atopic clinical manifestations. Because of their specific clinical management and prognosis, it is important to distinguish IEIwA from multifactorial allergic diseases. We aimed to review the main clinical manifestations associated with IEIwA and summarize the available data regarding the precision medicine approach for these conditions.

Recent findings: IEIwA include more than 50 monogenic disorders marked by different immune dysregulation mechanisms such as alterations in cytokine signaling, T cell receptor function, mast cell activation, and skin barrier integrity. A critical role in diagnosis is played by advanced genetic testing. Emerging treatments include targeted monoclonal antibodies and small molecules, whereas hematopoietic stem cell transplantation (HSCT) is still a valid option for some specific disorders and may be curative also on atopic manifestations.

Summary: The recognition and accurate diagnosis of IEIwA are crucial for timely and appropriate therapeutic intervention. The diagnosis should be suspected according to the presence of 'red flags' at clinical evaluation stage, such as early-onset severe atopy, recurrent/atypical infections, and autoimmunity. The diagnostic confirmation requires genetic testing. Precision medicine approaches like biological therapies and HSCT seem to provide promising results. It is worth noting that clinical and translational research in the field of IEIwA is currently paving the way for a more thorough understanding of the molecular bases of common allergic diseases.

Purpose of review: To evaluate the effect of climate change on pollen allergenicity, lengthening of the pollen season, and the spread of invasive species such as ragweed. To assess evidence to determine whether these effects are impacting the prevalence of pollen food syndrome (PFS).

Recent findings: There is good evidence to demonstrate that markers of climate change, including rising temperatures and to some extent greenhouse gases, are responsible for a rise in the allergenicity of pollen and an increase in the duration of the pollen season, especially for trees. These changes are likely to be linked to the increase in the prevalence of seasonal allergic rhinitis (SAR), especially in children. Sensitization to pollen, especially tree pollen, is also a risk factor for the development of PFS. Thought to mainly affect adults, recent evidence suggests that there is a rise in the prevalence of PFS in children, linked to an increase in SAR.

Summary: Increasing SAR due to climate change could lead to a greater number of children and adults developing PFS. Although PFS is generally considered to be a mild condition, severe reactions can occur and there might be numerous plant food triggers, which can adversely affect dietary choice and nutritional intake.

Purpose of review: Ethical dilemmas are a common occurrence in the provision of care to individuals with food allergies. Thus, an understanding of medical ethics is essential for allergists/immunologists.

Recent findings: Despite the importance of medical ethics in the clinical practice of food allergy, there has been little published on this topic. Some international allergy societies have published ethical guidelines. Further investigation on medical ethics in food allergy is required.

Summary: This review describes key ethical principles in relation to food allergy testing, oral food challenges, and various management strategies, including avoidance, omalizumab and oral immunotherapy. This review demonstrates the necessity for education and research on medical ethics in food allergy.

Purpose of review: This review provides the current understanding on the mechanism, diagnosis, and treatment of aspirin exacerbated respiratory disease (AERD) with chronic rhinosinusitis (CRS).

Recent findings: Updates focus on the current understanding of type 2 inflammation as a disease driver, alterations in gene expression in nasal polyps, and use of biologics in treating aspirin exacerbated respiratory disease. Recent findings include altered expression of GATA binding protein 3 (GATA3), interleukin (IL)-4, IL-5, and IL-17 in nasal polyps supports the current understanding that type 2 inflammation predominantly drives the pathophysiology of AERD with CRS. From a clinical standpoint, biologics offer an effective treatment option to address type 2 inflammation. Biologics should not be favored over endoscopic sinus surgery and aspirin desensitization with daily aspirin therapy (unless contraindication are present) due to high associated cost and failure to achieve remission.

Summary: This review outlines the current approach for diagnosis and treatment of aspirin exacerbated respiratory disease with a focus on desensitization protocols, the importance of endoscopic sinus surgery, the role of biologics, and the use of leukotriene modulators.

Purpose of review: Chronic rhinosinusitis (CRS) is a heterogeneous condition, so personalized treatment based on each patient's pathophysiology is essential, rather than a one-size-fits-all approach. Drug therapy for CRS has evolved significantly in recent years with the introduction of biologics, necessitating a reconsideration of the role of low-dose and long-term administration of a 14-membered ring macrolide (macrolide therapy) in the treatment of CRS. Recent research on the mechanisms of macrolide therapy and its proper use may assist physicians in improving patients' quality of life and reducing disease burden.

Recent findings: A classification of the pathogenesis of CRS based on endotype has been proposed, with type 2 inflammation playing a particularly important role as a refractory factor. Macrolide therapy improves CRS via immunomodulatory and anti-inflammatory effects rather than antimicrobial action, and it is expected to be effective in patients with neutrophil-dominant inflammation.

Summary: Understanding the effectiveness and limitations of macrolide therapy is critical for making the best treatment decisions, especially when combined with surgery and other pharmacologic therapies. Therefore, selecting appropriate patients for macrolide therapy is critical for achieving adequate therapeutic efficacy.

Purpose of review: Aspirin-exacerbated respiratory disease (AERD), a syndrome characterized clinically by asthma, chronic rhinosinusitis with nasal polyposis, and respiratory reactions to aspirin and other cyclooxygenase-1 inhibitors, is an inflammatory condition of the respiratory tract that is often severe and challenging to treat. There have been several recent advances in our understanding of the underlying pathology of the disease. These have been paralleled by welcome advances in the availability of targeted treatment options for patients with AERD.

Recent findings: Spurred in part by results from trials of targeted biologic therapies, along with single cell genomics, there is now clear evidence that the chronic respiratory inflammation in AERD is driven by combination of local tissue factors. These include abnormalities in effector cell populations, with increased accumulation and activation of mast cells and plasma cells in the nasal polyp, along with notable epithelial barrier dysregulation. The key mediators now identified include high levels of both type 2 inflammatory cytokines (IL-4, IL-5, IL-13) and cytokines involved in broader inflammatory pathways (IL-33, TSLP, IL-6, oncostatin M), as well as the overproduction of cysteinyl leukotrienes, and the underproduction of prostaglandin E 2 .

Summary: This review covers the latest insights into the immunopathogenesis of and targeted treatment of AERD, including the roles of lipids, effector cells, and inflammatory cytokines, and discusses unanswered questions regarding its pathogenesis and potential future therapies.

Purpose of review: We review updated key literature on comparative meta-analyses and real-world effectiveness of asthma biologics, with a focus on predictors of response and clinical remission while highlighting ongoing knowledge gaps. We aim to provide insight into the many factors to consider when choosing a biologic to treat uncontrolled moderate to severe asthma.

Recent findings: Predictors of response included higher type 2 (T2) biomarkers, shorter duration of asthma, and presence of key T2-related comorbidities. There were outcome-related variations in predictors. Predictors of clinical remission included better controlled asthma, better lung function, and higher T2 biomarkers. Few real-world studies included those treated with tezepelumab, a clear knowledge gap.

Summary: Asthma biologics demonstrate clear real-world effectiveness. There have been significant strides in better understanding predictors of response or clinical remission to guide management, yet ongoing knowledge gaps and the heterogeneity of asthma preclude a simple algorithmic approach. Our tools for precision medicine include consideration of clinical phenotypes and shared decision making while striving to achieve clinical remission in all our patients with asthma.

Purpose of review: Mast cell activation is defined by activation of mast cells by varying stimuli with release of chemical mediators either through degranulation or release of de novo synthesized proteins or lipid mediators. Currently, tryptase measurement increase during symptomatic episodes is the most accepted biomarker measurement for mast cell activation. However, newer diagnostic tools including clinically available urinary mast cell mediators are noninvasive and can be more readily obtained compared to serum tryptase levels. This review will highlight biomarker measurement in the diagnosis of mast cell activation.

Recent findings: This review will highlight biomarker measurement in mast cell activation including serum tryptase and urinary mast cell mediators including N-methylhistamine, leukotriene E4, and 2,3-dinor-11beta-prostaglandin F2 alpha.

Summary: Urine mast cell mediators obtained at baseline and during symptom exacerbation are emerging biomarkers in the diagnosis of mast cell activation. Tryptase measurement and urinary mast cell mediator measurement are currently the most accepted biomarkers for mast cell activation. Further research is needed to establish new biomarkers for mast cell activation.