A single infusion of engineered long-lived and multifunctional T cells confers durable remission of asthma in mice.

Asthma, the most prevalent respiratory disease, affects more than 300 million people and causes more than 250,000 deaths annually. Type 2-high asthma is characterized by interleukin (IL)-5-driven eosinophilia, along with airway inflammation and remodeling caused by IL-4 and IL-13. Here we utilize IL-5 as the targeting domain and deplete BCOR and ZC3H12A to engineer long-lived chimeric antigen receptor (CAR) T cells that can eradicate eosinophils. We call these cells immortal-like and functional IL-5 CAR T cells (5TIF) cells. 5TIF cells were further modified to secrete an IL-4 mutein that blocks IL-4 and IL-13 signaling, designated as 5TIF4 cells. In asthma models, a single infusion of 5TIF4 cells in fully immunocompetent mice, without any conditioning regimen, led to sustained repression of lung inflammation and alleviation of asthmatic symptoms. These data show that asthma, a common chronic disease, can be pushed into long-term remission with a single dose of long-lived CAR T cells.

The basic immunology of asthma.

In many asthmatics, chronic airway inflammation is driven by IL-4-, IL-5-, and IL-13-producing Th2 cells or ILC2s. Type 2 cytokines promote hallmark features of the disease such as eosinophilia, mucus hypersecretion, bronchial hyperresponsiveness (BHR), IgE production, and susceptibility to exacerbations. However, only half the asthmatics have this "type 2-high" signature, and "type 2-low" asthma is more associated with obesity, presence of neutrophils, and unresponsiveness to corticosteroids, the mainstay asthma therapy. Here, we review the underlying immunological basis of various asthma endotypes by discussing results obtained from animal studies as well as results generated in clinical studies targeting specific immune pathways.

An Allosteric Anti-tryptase Antibody for the Treatment of Mast Cell-Mediated Severe Asthma.

Severe asthma patients with low type 2 inflammation derive less clinical benefit from therapies targeting type 2 cytokines and represent an unmet need. We show that mast cell tryptase is elevated in severe asthma patients independent of type 2 biomarker status. Active ß-tryptase allele count correlates with blood tryptase levels, and asthma patients carrying more active alleles benefit less from anti-IgE treatment. We generated a noncompetitive inhibitory antibody against human ß-tryptase, which dissociates active tetramers into inactive monomers. A 2.15 Å crystal structure of a ß-tryptase/antibody complex coupled with biochemical studies reveal the molecular basis for allosteric destabilization of small and large interfaces required for tetramerization. This anti-tryptase antibody potently blocks tryptase enzymatic activity in a humanized mouse model, reducing IgE-mediated systemic anaphylaxis, and inhibits airway tryptase in Ascaris-sensitized cynomolgus monkeys with favorable pharmacokinetics. These data provide a foundation for developing anti-tryptase as a clinical therapy for severe asthma.

A gammaherpesvirus provides protection against allergic asthma by inducing the replacement of resident alveolar macrophages with regulatory monocytes.

The hygiene hypothesis postulates that the recent increase in allergic diseases such as asthma and hay fever observed in Western countries is linked to reduced exposure to childhood infections. Here we investigated how infection with a gammaherpesvirus affected the subsequent development of allergic asthma. We found that murid herpesvirus 4 (MuHV-4) inhibited the development of house dust mite (HDM)-induced experimental asthma by modulating lung innate immune cells. Specifically, infection with MuHV-4 caused the replacement of resident alveolar macrophages (AMs) by monocytes with regulatory functions. Monocyte-derived AMs blocked the ability of dendritic cells to trigger a HDM-specific response by the TH2 subset of helper T cells. Our results indicate that replacement of embryonic AMs by regulatory monocytes is a major mechanism underlying the long-term training of lung immunity after infection.

Early Diagnosis and Treatment of COPD and Asthma - A Randomized, Controlled Trial.

BACKGROUND: Many persons with chronic obstructive pulmonary disease (COPD) or asthma have not received a diagnosis, so their respiratory symptoms remain largely untreated. METHODS: We used a case-finding method to identify adults in the community with respiratory symptoms without diagnosed lung disease. Participants who were found to have undiagnosed COPD or asthma on spirometry were enrolled in a multicenter, randomized, controlled trial to determine whether early diagnosis and treatment reduces health care utilization for respiratory illness and improves health outcomes. Participants were assigned to receive the intervention (evaluation by a pulmonologist and an asthma-COPD educator who were instructed to initiate guideline-based care) or usual care by their primary care practitioner. The primary outcome was the annualized rate of participant-initiated health care utilization for respiratory illness. Secondary outcomes included changes from baseline to 1 year in disease-specific quality of life, as assessed with the St. George Respiratory Questionnaire (SGRQ; scores range from 0 to 100, with lower scores indicating better health status); symptom burden, as assessed with the COPD Assessment Test (CAT; scores range from 0 to 40, with lower scores indicating better health status); and forced expiratory volume in 1 second (FEV1). RESULTS: Of 38,353 persons interviewed, 595 were found to have undiagnosed COPD or asthma and 508 underwent randomization: 253 were assigned to the intervention group and 255 to the usual-care group. The annualized rate of a primary-outcome event was lower in the intervention group than in the usual-care group (0.53 vs. 1.12 events per person-year; incidence rate ratio, 0.48; 95% confidence interval [CI], 0.36 to 0.63; P<0.001). At 12 months, the SGRQ score was lower than the baseline score by 10.2 points in the intervention group and by 6.8 points in the usual-care group (difference, -3.5 points; 95% CI, -6.0 to -0.9), and the CAT score was lower than the baseline score by 3.8 points and 2.6 points, respectively (difference, -1.3 points; 95% CI, -2.4 to -0.1). The FEV1 increased by 119 ml in the intervention group and by 22 ml in the usual-care group (difference, 94 ml; 95% CI, 50 to 138). The incidence of adverse events was similar in the trial groups. CONCLUSIONS: In this trial in which a strategy was used to identify adults in the community with undiagnosed asthma or COPD, those who received pulmonologist-directed treatment had less subsequent health care utilization for respiratory illness than those who received usual care. (Funded by Canadian Institutes of Health Research; UCAP ClinicalTrials.gov number, NCT03148210.).

Impact of socioeconomic factors on allergic diseases.

Allergic and immunologic conditions, including asthma, food allergy, atopic dermatitis, and allergic rhinitis, are among the most common chronic conditions in children and adolescents that often last into adulthood. Although rare, inborn errors of immunity are life-altering and potentially fatal if unrecognized or untreated. Thus, allergic and immunologic conditions are both medical and public health issues that are profoundly affected by socioeconomic factors. Recently, studies have highlighted societal issues to evaluate factors at multiple levels that contribute to health inequities and the potential steps toward closing those gaps. Socioeconomic disparities can influence all aspects of care, including health care access and quality, diagnosis, management, education, and disease prevalence and outcomes. Ongoing research, engagement, and deliberate investment of resources by relevant stakeholders and advocacy approaches are needed to identify and address the impact of socioeconomics on health care disparities and outcomes among patients with allergic and immunologic diseases.

Asthma Pathogenesis: Phenotypes, Therapies, and Gaps: Summary of the Aspen Lung Conference 2023.

Although substantial progress has been made in our understanding of asthma pathogenesis and phenotypes over the nearly 60-year history of the Aspen Lung Conferences on asthma, many ongoing challenges exist in our understanding of the clinical and molecular heterogeneity of the disease and an individual patient's response to therapy. This report summarizes the proceedings of the 2023 Aspen Lung Conference, which was organized to review the clinical and molecular heterogeneity of asthma and to better understand the impact of genetic, environmental, cellular, and molecular influences on disease susceptibility, heterogeneity, and severity. The goals of the conference were to review new information about asthma phenotypes, cellular processes, and cellular signatures underlying disease heterogeneity and treatment response. The report concludes with ongoing gaps in our understanding of asthma pathobiology and provides some recommendations for future research to better understand the clinical and basic mechanisms underlying disease heterogeneity in asthma and to advance the development of new treatments for this growing public health problem.

Association between care experience and mental health hospitalisation among children in Scotland, with a focus on chronic conditions (CHiCS): a population-wide longitudinal study using administrative data.

BACKGROUND: Chronic conditions in children are associated with an increased risk of mental health problems. However, not much is known about the nature of this association among care experienced children. We explore the association between three chronic conditions (epilepsy, asthma, and diabetes) and mental health hospitalisation in children with or without care experience. METHODS: The Children's Health in Care in Scotland (CHiCS) is a population-wide longitudinal study that links health and social care data for 13 830 care-experienced children (6274 [45%] female, 7556 [55%] male) and 649 771 general population children (319 438 [49%] female, 330 333 [51%] male). Hospitalisations were followed up from birth between 1990 and 2004, up to July 31, 2016 (when children were aged 12-27 years). We used Cox proportional hazards models with age as timescale to estimate hazard ratios (HR) and 95% CIs for first mental health hospitalisation separately among care-experienced children and general population children. FINDINGS: Among general population children, 3152 (0·49%) children had epilepsy, 94 700 (14·57%) had asthma, and 5501 (0·85%) had diabetes. In comparison, among care-experienced children, 160 (1·16%) children had epilepsy, 2242 (16·21%) had asthma, and 142 (1·03%) had diabetes. Care-experienced children were more likely to have mental health hospitalisations than general population children, with 701 cases (5·1%) versus 5225 cases (0·8%), respectively. Among general population children, out of all three chronic conditions, epilepsy showed the highest risk (HR 2·61, 95% CI 2·20-3·09) for first mental health hospitalisation, followed by diabetes (1·93, 1·62-2·31), and asthma (1·25, 1·16-1·34). Among care-experienced children, asthma showed an HR of 1·43 (1·17-1·74) for first mental health hospitalisation, whereas epilepsy (1·33, 0·70-2·52) and diabetes (1·71, 0·96-3·05) had no association with first mental health hospitalisation in this subgroup. INTERPRETATION: The study highlights the associations between chronic conditions and risk of mental health hospitalisation among children with or without care experience. One limitation of the study is the small number of care experienced children with a chronic condition and mental health hospitalisation, which might have contributed to the lack of association found among care-experienced children between epilepsy and mental health, and diabetes and mental health. Nevertheless, one of its strengths is contributing to the limited knowledge regarding this association. FUNDING: Economic and Social Research Council, Medical Research Council, Scottish Government Chief Scientist Office.

Genetic and T2 biomarkers linked to the efficacy of HDM sublingual immunotherapy in asthma.

BACKGROUND: Hypersensitivity to house dust mite (HDM) allergens is a common cause of allergic asthma symptoms and can be effectively treated with allergy immunotherapy (AIT). OBJECTIVE: To investigate whether genetic and type 2 (T2) inflammatory biomarkers correlate with disease severity in subjects with allergic asthma, and whether this can be modified by AIT. METHODS: MITRA (NCT01433523) was a phase III, randomised, double-blind, placebo-controlled trial of HDM sublingual immunotherapy (SLIT)-tablets in adults with HDM allergic asthma. Post hoc analyses of the study population (N=742) evaluated associations between T2 inflammatory (blood eosinophils, eosinophil cationic protein (ECP), total IgE and tryptase) and genetic (single-nucleotide polymorphisms, SNP) biomarkers (n=582) for the primary study endpoint (time to first moderate/severe asthma exacerbation). SNP associations were verified in HDM-positive subgroup from an independent 3-year Severe Asthma Research Programme (SARP3) subject cohort. RESULTS: An increased asthma exacerbation risk in subjects homozygous for SNP rs7216389 (chromosomal locus 17q12-21) was reduced (p=0.037) by treatment with HDM SLIT (HR=0.37 (95% CI 0.22 to 0.64), p<0.001). The associations between exacerbation risk and 17q12-21 SNPs were replicated in the SARP3 HDM-positive subgroup. High levels of T2 biomarkers were associated with increased risk of asthma exacerbations in the placebo group. HDM SLIT-tablet treatment reduced this risk (blood eosinophils: HR=0.50 (95% CI 0.30 to 0.85); ECP: HR=0.45 (95% CI 0.29 to 0.87); tryptase: HR=0.45 (95% CI 0.25 to 0.80)). The treatment effect was higher (p=0.006) for subjects with a higher number of elevated T2 biomarkers. CONCLUSIONS: HDM SLIT-tablet AIT is efficacious in HDM-sensitised asthma subjects with a genetic asthma predisposition and/or an underlying T2 endotype. TRIAL REGISTRATION NUMBER: NCT01433523.

Mesenchymal stromal cells and their small extracellular vesicles in allergic diseases: From immunomodulation to therapy.

Mesenchymal stromal cells (MSCs) have long been considered a potential tool for treatment of allergic inflammatory diseases, owing to their immunomodulatory characteristics. In recent decades, the medical utility of MSCs has been evaluated both in vitro and in vivo, providing a foundation for therapeutic applications. However, the existing limitations of MSC therapy indicate the necessity for novel therapies. Notably, small extracellular vesicles (sEV) derived from MSCs have emerged rapidly as candidates instead of their parental cells. The acquisition of abundant and scalable MSC-sEV is an obstacle for clinical applications. The potential application of MSC-sEV in allergic diseases has attracted increasing attention from researchers. By carrying biological microRNAs or active proteins, MSC-sEV can modulate the function of various innate and adaptive immune cells. In this review, we summarise the recent advances in the immunomodulatory properties of MSCs in allergic diseases, the cellular sources of MSC-sEV, and the methods for obtaining high-quality human MSC-sEV. In addition, we discuss the immunoregulatory capacity of MSCs and MSC-sEV for the treatment of asthma, atopic dermatitis, and allergic rhinitis, with a special emphasis on their immunoregulatory effects and the underlying mechanisms of immune cell modulation.

Racial differences in length of stay and readmission for asthma in the all of us research program.

BACKGROUND: This study addresses the limited research on racial disparities in asthma hospitalization outcomes, specifically length of stay (LOS) and readmission, across the U.S. METHODS: We analyzed in-patient and emergency department visits from the All of Us Research Program, identifying various risk factors (demographic, comorbid, temporal, and place-based) associated with asthma LOS and 30-day readmission using Bayesian mixed-effects models. RESULTS: Of 17,233 patients (48.0% White, 30.7% Black, 19.7% Hispanic/Latino, 1.3% Asian, and 0.3% Middle Eastern and North African) with 82,188 asthma visits, Black participants had 20% shorter LOS and 12% higher odds of readmission, compared to White participants in multivariate analyses. Public-insured patients had 14% longer LOS and 39% higher readmission odds than commercially insured patients. Weekend admissions resulted in a 12% shorter LOS but 10% higher readmission odds. Asthmatics with chronic diseases had a longer LOS (range: 6-39%) and higher readmission odds (range: 9-32%) except for those with allergic rhinitis, who had a 23% shorter LOS. CONCLUSIONS: A comprehensive understanding of the factors influencing asthma hospitalization, in conjunction with diverse datasets and clinical-community partnerships, can help physicians and policymakers to systematically address racial disparities, healthcare utilization and equitable outcomes in asthma care.

Beyond CAR-T: The rise of CAR-NK cell therapy in asthma immunotherapy.

Asthma poses a major public health burden. While existing asthma drugs manage symptoms for many, some patients remain resistant. The lack of a cure, especially for severe asthma, compels exploration of novel therapies. Cancer immunotherapy successes with CAR-T cells suggest its potential for asthma treatment. Researchers are exploring various approaches for allergic diseases including membrane-bound IgE, IL-5, PD-L2, and CTLA-4 for asthma, and Dectin-1 for fungal asthma. NK cells offer several advantages over T cells for CAR-based immunotherapy. They offer key benefits: (1) HLA compatibility, meaning they can be used in a wider range of patients without the need for matching tissue types. (2) Minimal side effects (CRS and GVHD) due to their limited persistence and cytokine profile. (3) Scalability for "off-the-shelf" production from various sources. Several strategies have been introduced that highlight the superiority and challenges of CAR-NK cell therapy for asthma treatment including IL-10, IFN-γ, ADCC, perforin-granzyme, FASL, KIR, NCRs (NKP46), DAP, DNAM-1, TGF-ß, TNF-α, CCL, NKG2A, TF, and EGFR. Furthermore, we advocate for incorporating AI for CAR design optimization and CRISPR-Cas9 gene editing technology for precise gene manipulation to generate highly effective CAR constructs. This review will delve into the evolution and production of CAR designs, explore pre-clinical and clinical studies of CAR-based therapies in asthma, analyze strategies to optimize CAR-NK cell function, conduct a comparative analysis of CAR-T and CAR-NK cell therapy with their respective challenges, and finally present established novel CAR designs with promising potential for asthma treatment.

Objective monitoring tools for improved management of childhood asthma.

Asthma is a common chronic disease amongst children. Epidemiological studies showed that the mortality rate of asthma in children is still high worldwide. Asthma control is therefore essential to minimize asthma exacerbations, which can be fatal if the condition is poorly controlled. Frequent monitoring could help to detect asthma progression and ensure treatment effectiveness. Although subjective asthma monitoring tools are available, the results vary as they rely on patients' self-perception. Emerging evidence suggests several objective tools could have the potential for monitoring purposes. However, there is no consensus to standardise the use of objective monitoring tools. In this review, we start with the prevalence and severity of childhood asthma worldwide. Then, we detail the latest available objective monitoring tools, focusing on their effectiveness in paediatric asthma management. Publications of spirometry, fractional exhaled nitric oxide (FeNO), hyperresponsiveness tests and electronic monitoring devices (EMDs) between 2016 and 2023 were included. The potential advantages and limitations of each tool were also discussed. Overall, this review provides a summary for researchers dedicated to further improving objective paediatric asthma monitoring and provides insights for clinicians to incorporate different objective monitoring tools in clinical practices.

Digitally-enabled, person-centred care (PCC) in allergen immunotherapy: An ARIA-EAACI Position Paper.

In rhinitis and asthma, several mHealth apps have been developed but only a few have been validated. However, these apps have a high potential for improving person-centred care (PCC), especially in allergen immunotherapy (AIT). They can provide support in AIT initiation by selecting the appropriate patient and allergen shared decision-making. They can also help in (i) the evaluation of (early) efficacy, (ii) early and late stopping rules and (iii) the evaluation of (carried-over) efficacy after cessation of the treatment course. Future perspectives have been formulated in the first report of a joint task force (TF)-Allergic Rhinitis and Its Impact on Asthma (ARIA) and the European Academy of Allergy and Clinical Immunology (EAACI)-on digital biomarkers. The TF on AIT now aims to (i) outline the potential of the clinical applications of mHealth solutions, (ii) express their current limitations, (iii) make proposals regarding further developments for both clinical practice and scientific purpose and (iv) suggest which of the tools might best comply with the purpose of digitally-enabled PCC in AIT.

Biologics (mepolizumab and omalizumab) induced remission in severe asthma patients.

BACKGROUND: Asthma remission has emerged as a potential treatment goal. This study evaluated the effectiveness of two biologics (mepolizumab/omalizumab) in achieving asthma remission. METHODS: This observational study included 453 severe asthma patients (41% male; mean age ± SD 55.7 ± 14.7 years) from two real-world drug registries: the Australian Mepolizumab Registry and the Australian Xolair Registry. The composite outcome clinical remission was defined as zero exacerbations and zero oral corticosteroids during the previous 6 months assessed at 12 months and 5-item Asthma Control Questionnaire (ACQ-5) ≤1 at 12 months. We also assessed clinical remission plus optimization (post-bronchodilator FEV1 ≥80%) or stabilization (post-bronchodilator FEV1 not greater than 5% decline from baseline) of lung function at 12 months. Sensitivity analyses explored various cut-offs of ACQ-5/FEV1 scores. The predictors of clinical remission were identified. RESULTS: 29.3% (73/249) of AMR and 22.8% (37/162) of AXR cohort met the criteria for clinical remission. When lung function criteria were added, the remission rates were reduced to 25.2% and 19.1%, respectively. Sensitivity analyses identified that the remission rate ranged between 18.1% and 34.9% in the AMR cohort and 10.6% and 27.2% in the AXR cohort. Better lung function, lower body mass index, mild disease and absence of comorbidities such as obesity, depression and osteoporosis predicted the odds of achieving clinical remission. CONCLUSION: Biologic treatment with mepolizumab or omalizumab for severe asthma-induced asthma remission in a subgroup of patients. Remission on treatment may be an achievable treatment target and future studies should consider remission as an outcome measure.

Telemedicine with special focus on allergic diseases and asthma-Status 2022: An EAACI position paper.

Efficacious, effective and efficient communication between healthcare professionals (HCP) and patients is essential to achieve a successful therapeutic alliance. Telemedicine (TM) has been used for decades but during the COVID-19 pandemic its use has become widespread. This position paper aims to describe the terminology and most important forms of TM among HCP and patients and review the existing studies on the uses of TM for asthma and allergy. Besides, the advantages and risks of TM are discussed, concluding that TM application reduces costs and time for both, HCP and patients, but cannot completely replace face-to-face visits for physical examinations and certain tests that are critical in asthma and allergy. From an ethical point of view, it is important to identify those involved in the TM process, ensure confidentiality and use communication channels that fully guarantee the security of the information. Unmet needs and directions for the future regarding implementation, data protection, privacy regulations, methodology and efficacy are described.

Resting state functional connectivity changes following mindfulness-based stress reduction predict improvements in disease control for patients with asthma.

BACKGROUND: The staggering morbidity associated with chronic inflammatory diseases can be reduced by psychological interventions, including Mindfulness-Based Stress Reduction (MBSR). Proposed mechanisms for MBSR's beneficial effects include changes in salience network function. Salience network perturbations are also associated with chronic inflammation, including airway inflammation in asthma, a chronic inflammatory disease affecting approximately 10% of the population. However, no studies have examined whether MBSR-related improvements in disease control are related to changes in salience network function. METHODS: Adults with asthma were randomized to 8 weeks of MBSR or a waitlist control group. Resting state functional connectivity was measured using fMRI before randomization, immediately post-intervention, and 4 months post-intervention. Using key salience network regions as seeds, we calculated group differences in change in functional connectivity over time and examined whether functional connectivity changes were associated with increased mindfulness, improved asthma control, and decreased inflammatory biomarkers. RESULTS: The MBSR group showed greater increases in functional connectivity between salience network regions relative to the waitlist group. Improvements in asthma control correlated with increased functional connectivity between the salience network and regions important for attention control and emotion regulation. Improvements in inflammatory biomarkers were related to decreased functional connectivity between the salience network and other networks. CONCLUSIONS: Increased resting salience network coherence and connectivity with networks that subserve attention and emotion regulation may contribute to the benefits of MBSR for patients with asthma. Understanding the neural underpinnings of MBSR-related benefits in patients is a critical step towards optimizing brain-targeted interventions for chronic inflammatory disease management.

An insight into biosensing platforms used for the diagnosis of various lung diseases: A review.

Many of the infectious diseases are ubiquitous in nature and pose a threat to global and public health. The original cause for such type of serious maladies can be summarized as the scarcity of appropriate analysis and treatment methods. Pulmonary diseases are considered one of the life-threatening lung diseases that affect millions of people globally. It consists of several types, namely, asthma, lung cancer, tuberculosis, chronic obstructive pulmonary disease, and several respiratory-related infections. This is due to the limited access to well-equipped healthcare facilities for early disease diagnosis. This needs the availability of processes and technologies that can help to stop this harmful disease-diagnosing practice. Various approaches for diagnosing various lung diseases have been developed over time, namely, autopsy, chest X-rays, low-dose CT scans, and so forth. The need of the hour is to develop a rapid, simple, portable, and low-cost method for the diagnosis of pulmonary diseases. So nowadays, biosensors have been becoming one of the highest priority research areas as a potentially useful tool for the early diagnosis and detection of many pulmonary lung diseases. In this review article, various types of biosensors and their applications in the diagnosis of lung-related disorders are expansively explained.

Remission in asthma.

PURPOSE OF REVIEW: To review the current concepts of remission in asthma. RECENT FINDINGS: Until 2023, asthma guidelines have been promoting the concept of disease control, recommending the step-wise addition of drugs until the best possible disease control is achieved. With the advent of highly effective, anti-inflammatory disease-modifying antiasthmatic drugs (DMAADs), treatment goals of asthma have changed. Several national guidelines have now announced remission as a general treatment goal in asthma. Currently, all guidelines agree that asthma remission is defined by the presence of at least three characteristics over a period of at least one 1 year: absence of exacerbations, no systemic corticosteroid use for the treatment of asthma and minimal asthma-related symptoms. In the future, a generally accepted, evidence-based and easy-to-use definition of remission will be needed for daily clinical practice. It is clear, however, that precise phenotyping (including measurement of biomarkers) is an essential prerequisite to achieve clinical remission in each individual patient. SUMMARY: Remission has been included as the treatment goal in asthma in several national guidelines, reflecting the paradigm shift in asthma, from short-term symptom control to long-term symptom prevention. An international consensus on the criteria for asthma remission is expected in the near future.

Obesity-related asthma: new insights leading to a different approach.

PURPOSE OF REVIEW: Obesity is a growing global health threat that significantly contributes to the burden of asthma by increasing the risk of developing asthma and exerting a distinct effect on lung function and inflammation. The treatment of obesity-related asthma is hindered by a poor response to standard asthma treatments, leading to worse asthma control. Weight loss strategies have a significant effect on asthma symptoms but are not feasible for a large proportion of patients, underscoring the need for a better understanding of the pathophysiology and the development of additional treatment options. RECENT FINDINGS: Recent literature focusing on pathophysiology particularly delved into nontype 2 inflammatory mechanisms, associations with the metabolic syndrome and small airway impairment. Additionally, several new treatment options are currently investigated, including biologics, weight reduction interventions, and novel antiobesity drugs. SUMMARY: Obesity-related asthma is a highly prevalent asthma phenotype for which weight loss strategies currently stand as the most specific treatment. Furthermore, novel pharmacological interventions aiming at metabolic processes are on the way.