Asthma Immunology Research Articles

Immunologic aspects of asthma: from molecular mechanisms to disease pathophysiology and clinical translation.

In the present review, we focused on recent translational and clinical discoveries in asthma immunology, facilitating phenotyping and stratified or personalized interventions for patients with this condition. The immune processes behind chronic inflammation in asthma exhibit marked heterogeneity, with diverse phenotypes defining discernible features and endotypes illuminating the underlying molecular mechanisms. In particular, two primary endotypes of asthma have been identified: "type 2-high," characterized by increased eosinophil levels in the airways and sputum of patients, and "type 2-low," distinguished by increased neutrophils or a pauci-granulocytic profile. Our review encompasses significant advances in both innate and adaptive immunities, with emphasis on the key cellular and molecular mediators, and delves into innovative biological and targeted therapies for all the asthma endotypes. Recognizing that the immunopathology of asthma is dynamic and continuous, exhibiting spatial and temporal variabilities, is the central theme of this review. This complexity is underscored through the innumerable interactions involved, rather than being driven by a single predominant factor. Integrated efforts to improve our understanding of the pathophysiological characteristics of asthma indicate a trend toward an approach based on disease biology, encompassing the combined examination of the clinical, cellular, and molecular dimensions of the disease to more accurately correlate clinical traits with specific disease mechanisms.

Anatomical and histopathological approaches to asthma phenotyping

Asthma is typically characterized by variable respiratory symptoms and airflow limitation. Along with the pathophysiology and symptoms are immunological and inflammatory processes. The last decades research has revealed that the immunology of asthma is highly heterogeneous. This has clinical consequences and identification of immunological phenotypes is currently used to guide biological treatment. The focus of this review is on another dimension of asthma diversity, namely anatomical heterogeneity. Immunopathological alterations may go beyond the central airways to also involve the distal airways, the alveolar parenchyma, and pulmonary vessels. Also, extrapulmonary tissues are affected. The anatomical distribution of inflammation in asthma has remained relatively poorly discussed despite its potential implication on both clinical presentation and response to treatment. There is today evidence that a significant proportion of the asthma patients has small airway disease with type 2 immunity, eosinophilia and smooth muscle infiltration of mast cells. The small airways in asthma are also subjected to remodelling, constriction, and luminal plugging, events that are likely to contribute to the elevated distal airway resistance seen in some patients. In cases when the inflammation extends into the alveolar parenchyma alveolar FCER1-high mast cells, eosinophilia, type 2 immunity and activated alveolar macrophages, together with modest interstitial remodelling, create a complex immunopathological picture. Importantly, the distal lung inflammation in asthma can be pharmacologically targeted by use of inhalers with more distal drug deposition. Biological treatments, which are readily distributed to the distal lung, may also be beneficial in eligible patients with more severe and anatomically widespread disease.

Clinical guidance for the use of dupilumab in eosinophilic esophagitis: A yardstick

The Joint Task Force for the American Academy of Allergy Asthma Immunology and American College of Allergy Asthma Immunology and the American Gastroenterology Association recently published guidelines for the management of eosinophilic esophagitis (EoE). Because the guideline was published, dupilumab became the first and only medication to gain regulatory approval for the treatment of EoE. This expert opinion document provides a framework for how the clinician can consider using dupilumab in the treatment strategy for patients with EoE.

Editorial introductions.

Editorial introductions.

Microbiome, Metabolism, and Immunoregulation of Asthma: An American Thoracic Society and National Institute of Allergy and Infectious Diseases Workshop Report.

This report presents the proceedings from a workshop titled “Microbiome, Metabolism and Immunoregulation of Asthma” that was held virtually May 13 and 14, 2021. The workshop was jointly sponsored by the American Thoracic Society (Assembly on Allergy, Immunology, and Inflammation) and the National Institute of Allergy and Infectious Diseases. It convened an interdisciplinary group of experts with backgrounds in asthma immunology, microbiome science, metabolomics, computational biology, and translational pulmonary research. The main purpose was to identify key scientific gaps and needs to further advance research on microbial and metabolic mechanisms that may contribute to variable immune responses and disease heterogeneity in asthma. Discussions were structured around several topics, including 1) immune and microbial mechanisms of asthma pathogenesis in murine models, 2) the role of microbes in pediatric asthma exacerbations, 3) dysregulated metabolic pathways in asthma associated with obesity, 4) metabolism effects on macrophage function in adipose tissue and the lungs, 5) computational approaches to dissect microbiome–metabolite links, and 6) potential confounders of microbiome–disease associations in human studies. This report summarizes the major points of discussion, which included identification of specific knowledge gaps, challenges, and suggested directions for future research. These include questions surrounding mechanisms by which microbiota and metabolites shape host health versus an allergic or asthmatic state; direct and indirect influences of other biological factors, exposures, and comorbidities on these interactions; and ongoing technical and analytical gaps for clinical translation.

Biologics in Asthma: A Molecular Perspective to Precision Medicine.

Recent developments in therapeutic strategies have provided alternatives to corticosteroids as the cornerstone treatment for managing airway inflammation in asthma. The past two decades have witnessed a tremendous boost in the development of anti-cytokine monoclonal antibody (mAb) therapies for the management of severe asthma. Novel biologics that target eosinophilic inflammation (or type 2, T2 inflammation) have been the most successful at treating asthma symptoms, though there are a few in the drug development pipeline for treating non-eosinophilic or T2-low asthma. There has been significant improvement in clinical outcomes for asthmatics treated with currently available monoclonal antibodies (mAbs), including anti-immunoglobulin (Ig) E, anti-interleukin (IL)-4 receptor α subunit, anti-IL-5, anti-IL-5Rα, anti-IL-6, anti-IL-33, and anti-thymic stromal lymphopoietin (TSLP). Despite these initiatives in precision medicine for asthma therapy, a significant disease burden remains, as evident from modest reduction of exacerbation rates, i.e., approximately 40–60%. There are numerous studies that highlight predictors of good responses to these biologics, but few have focused on those who fail to respond adequately despite targeted treatment. Phenotyping asthmatics based on blood eosinophils is proving to be inadequate for choosing the right drug for the right patient. It is therefore pertinent to understand the underlying immunology, and perhaps, carry out immune endotyping of patients before prescribing appropriate drugs. This review summarizes the immunology of asthma, the cytokines or receptors currently targeted, the possible mechanisms of sub-optimal responses, and the importance of determining the immune make-up of individual patients prior to prescribing mAb therapy, in the age of precision medicine for asthma.

Editorial introductions.

Editorial introductions.

The evolving nature of asthma and contemporary management of this respiratory disorder

wheezing and increased airway responsiveness to a variety of environmental stimuli. The definition of asthma involves various phenotypes and endotypes.The immunopathogenesis of asthma involves many immune cell sand involves the airway epithelium as well as both innate and adaptive components of the immune system. Understanding the Immunology of asthma is essential in its treatment.Asthma is a rising significant global public health burden. The annual prevalence of severe asthma episodes is estimated from 1% to 21% for adults and over 20% for children aged 6–7 years. The prevalence of asthma varies widely around the world, ranging from 0.2% to 21.0% in adults and from 2.8% to 37.6% in 6- to 7-year-old children. The development of novel asthma phenotyping & endo typing plus better classification of patients using machine learning and big data have markedly improved asthma treatment outcomes in both children and Adults.Several research groups have developed cluster analyses of phenotypes and endo-types in severe asthma. These clusters support the importance of disease heterogeneity in asthma and suggest differences in pathophysiologic mechanisms that define these clusters.Biomarkers of asthma include Serum Immunoglobulin, Fractional excretion of nitric oxide and blood eosinophils amongst others. There are five food and drug administration approved biologicals for the treatment of severe asthma.

The Role of Neutrophils in the Pathophysiology of Asthma in Humans and Horses.

Asthma is a common and debilitating chronic airway disease that affects people and horses of all ages worldwide. While asthma in humans most commonly involves an excessive type 2 immune response and eosinophilic inflammation, neutrophils have also been recognized as key players in the pathophysiology of asthma, including in thesevere asthma phenotype where neutrophilic inflammation predominates. Severe equine asthma syndrome (sEAS) features prominent neutrophilic inflammation and has been increasingly used as a naturally occurring animal model for the study of human neutrophilic asthma. This comparative review examines the recent literature in order to explore the role of neutrophil inflammatory functions in the pathophysiology and immunology of asthma in humans and horses.

Epithelial Barrier Dysfunction in Type 2 Inflammatory Diseases

This satellite symposium took place during the 49th annual meeting of the European Society for Dermatological Research (ESDR). Prof Dávila began the symposium by describing the immunology behind Type 2 inflammation as a complex interaction between environmental factors, immune response, and barrier dysfunction. He explained that the principal cells participating in innate Type 2 immunity are Type 2 innate lymphoid cells (ILC2), eosinophils, basophils, and mast cells, and that Th2 lymphocytes, dendritic cells (DC), and their main cytokines (IL-4, IL-5, and IL-13) comprise the adaptive arm of the Type 2 immune response and are essential in IgE-mediated reactions. Prof Seneschal followed by explaining that Type 2 inflammation in atopic dermatitis (AD) is a combination of immune and epidermal barrier components influenced by genetic and environmental factors. Epidermal barrier proteins are expressed in lower levels in AD, and other proteins are also dysregulated, disrupting tight junctions. Both lesional and nonlesional skin in patients with AD show epithelial barrier dysfunction, and inflammation can lead to a vicious cycle of itching and damage. Prof Dahlén concluded the meeting by explaining that airway inflammation is one of the major factors involved in Type 2 asthma, and this can be driven by an allergic route, involving mast cells, or a nonallergic route, involving ILC2. Inflammatory cytokines also increase mucus production, one of the main causes of asthma-related death. Recent studies of asthma immunology have suggested that ILC2 are subject to feedback modulation by prostaglandin D2 (PGD2), and that both IL-4 and IL-13 are involved in hyper-responsiveness in asthmatic lung tissue.

Editorial introductions

Editorial introductions

Microbial Insights into Asthmatic Immunopathology. A Forward-Looking Synthesis and Commentary.

Asthma is an aberrant inflammatory condition of the airways affecting approximately 1 in 10 children in affluent countries. An increasing body of evidence suggests that microbial exposures during a "critical window" of development in early life play a central role in determining future asthma susceptibility. However, like the disease itself, considerable heterogeneity exists among studies in which researchers have investigated the associations between particular microbial taxa and asthma immunology. As our understanding of asthmatic pathology evolves to enable clearer definition of asthma endotypes, it will be important to consider the impact of various environmental factors on each endotype. Given the strong evidence in support of the hypothesis that early-life microbial exposures predict later disease states such as asthma, consideration of these endotypes when establishing experimental outcomes in epidemiological studies could allow for increased precision when determining exposure-outcome associations and engaging in more focused follow-up mechanistic investigations.

Pulmonologist perspectives regarding diagnosis and management of primary immunodeficiency diseases.

The time from symptom onset to diagnosis for patients with primary immunodeficiency diseases (PIDD) is an average of 12 years, but prompt diagnosis and treatment can promote best outcomes. Because the manifestations of PIDD are often sinopulmonary in nature, patients with undiagnosed PIDD are frequently referred to pulmonologists. This study sought to identify opportunities among these specialists to improve diagnosis and clinical management of patients with PIDD. A survey was sent to American Medical Association and American Osteopathic Association members whose specialty was pulmonology. Responses were compared with those from a historical survey of 71 subspecialist immunologists (American Academy of Allergy, Asthma Immunology members who devoted 10% of their practice to patients with PIDD). The surveys were returned by 485 pulmonologists, 49% of whom had diagnosed at least one patient with PIDD. In comparison with subspecialist immunologists, fewer pulmonologists were aware of the professional PIDD diagnosis and management guidelines and fewer followed up patients with various PIDDs. Pulmonologists and subspecialist immunologists also differed in the practice of prescribing prophylactic antibiotics and immunoglobulin replacement and in avoiding live viral vaccines. Differences in the diagnosis and treatment of patients with PIDD between these two groups of specialists revealed areas in which PIDD-focused educational initiatives may be helpful for pulmonologists.

The immunology of asthma.

Asthma is a common disease that affects 300 million people worldwide. Given the large number of eosinophils in the airways of people with mild asthma, and verified by data from murine models, asthma was long considered the hallmark T helper type 2 (TH2) disease of the airways. It is now known that some asthmatic inflammation is neutrophilic, controlled by the TH17 subset of helper T cells, and that some eosinophilic inflammation is controlled by type 2 innate lymphoid cells (ILC2 cells) acting together with basophils. Here we discuss results from in-depth molecular studies of mouse models in light of the results from the first clinical trials targeting key cytokines in humans and describe the extraordinary heterogeneity of asthma.

Beyond the guidelines: Fatal and near-fatal asthma

While asthma is extremely common, fatal and near fatal asthma is rare and often preventable if there is early recognition of symptom progression and appropriate intervention. In the past decade, asthma mortality has progressively declined in association with the widespread use of inhaled corticosteroids and asthma care plans. Management of life threatening asthma requires patient education to ensure the proper use of medications and to enable the patient to recognize when additional therapy for poorly controlled asthma is required. There is some evidence that suggests that the overly aggressive use of asthma medications when treating a severe exacerbation may contribute to morbidity. Because of the risks of air trapping and barotrauma associated with partial airway obstruction, it is best to avoid mechanical ventilation if possible but when this is used, low tidal volumes, longer exhalation times, and permissive hypercarbia can minimize these risks. There is the promise that a better understanding of asthma immunology and severe asthma "phenotypes" will lead to better prevention and therapy.

Immunobiology of Asthma

Asthma is characterized by chronic inflammation of the airways in which there is an overabundance of eosinophils, mast cells, and activated T helper lymphocytes. These inflammatory cells release mediators that then trigger bronchoconstriction, mucus secretion, and remodeling. The inflammatory mediators that drive this process include cytokines, chemokines, growth factors, lipid mediators, immunoglobulins, and histamine. The inflammation in allergic asthma can be difficult to control. This is mainly due to the development of an adaptive immunity to an allergen, leading to immunological memory. This leads to recall reactions to the allergen, causing persistent inflammation and damage to the airways. Generally, in asthma inflammation is directed by Th2 cytokines, which can act by positive feedback mechanisms to promote the production of more inflammatory mediators including other cytokines and chemokines. This review discusses the role of cytokines and chemokines in the immunobiology of asthma and attempts to relate their expression to morphological and functional abnormalities in the lungs of asthmatic subjects. We also discuss new concepts in asthma immunology, in particular the role of cytokines in airway remodeling and the interaction between cytokines and infection.

Immunology of asthma and chronic obstructive pulmonary disease

Asthma and chronic obstructive pulmonary disease (COPD) are both obstructive airway diseases that involve chronic inflammation of the respiratory tract, but the type of inflammation is markedly different between these diseases, with different patterns of inflammatory cells and mediators being involved. As described in this Review, these inflammatory profiles are largely determined by the involvement of different immune cells, which orchestrate the recruitment and activation of inflammatory cells that drive the distinct patterns of structural changes in these diseases. However, it is now becoming clear that the distinction between these diseases becomes blurred in patients with severe asthma, in asthmatic subjects who smoke and during acute exacerbations. This has important implications for the development of new therapies.

MEAAAIC 2009 -The First Middle East-Asia Allergy Asthma Immunology Congress

MEAAAIC 2009 -The First Middle East-Asia Allergy Asthma Immunology Congress

Asthma: new developments concerning immune mechanisms, diagnosis and treatment

This brief review discusses how recent research may modify our understanding of the immunology of asthma. Consideration is given to the possible impact that these observations may have upon diagnostic and therapeutic strategies. New studies indicate that current conceptions regarding the balance between Th1 and Th2 systems may need modification. The relationship between infection and the development of asthma in children has proven to be much more complex than originally suggested by the 'hygiene hypothesis'. In addition, important genetic differences have been found in the response of asthmatic patients to therapeutic agents. Greater insight into the mechanisms responsible for asthma and the introduction of new drugs will depend in part upon the development of reliable and simple methods for detecting airway inflammation. As the immunologic aspects of asthma are dissected, we can expect that many more potential targets for treatment will be discovered, but treatment may have to be individualized for genetic differences between different individuals.

Immunology of Asthma & Immunotherapy

Clinical & Experimental AllergyVolume 36, Issue 10 p. 1334-1338 Immunology of Asthma & Immunotherapy First published: 02 October 2006 https://doi.org/10.1111/j.1365-2222.2006.02583_8.xRead the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat Volume36, Issue10October 2006Pages 1334-1338 RelatedInformation