endotype

INTRODUCTION: Recurrent wheezing disorders including asthma are complex and heterogeneous diseases that affect up to 30% of all children, contributing to a major burden on children, their families, and global healthcare systems. It is now recognized that a dysfunctional airway epithelium plays a central role in the pathogenesis of recurrent wheeze, although the underlying mechanisms are still not fully understood. This prospective birth cohort aims to bridge this knowledge gap by investigating the influence of intrinsic epithelial dysfunction on the risk for developing respiratory disorders and the modulation of this risk by maternal morbidities, in utero exposures, and respiratory exposures in the first year of life...

There are multiple mechanisms underlying obstructive sleep apnea (OSA) development. However, how classic OSA risk factors such as body mass index (BMI) and sex portend to OSA development have not been fully described. Thus, we sought to evaluate how obesity leads to OSA, and assess how these mechanisms differ between men and women. Methods The San Diego Multi-Outcome OSA Endophenotype (SNOOzzzE) cohort includes 3,319 consecutive adults who underwent a clinical in-laboratory polysomnography at the UCSD sleep clinic between 1/2017-12/2019...

PURPOSE OF REVIEW: Eosinophilic esophagitis is a chronic and commonly evolving condition leading to relevant and potentially irreversible burden in terms of tissue damage and related functional impairment, thus significantly impacting on quality of life. The aim of the present review is to summarize the recent advances in terms of diagnostic work-up and pharmacological and nonpharmacological management of the disease, under the broader perspective of type 2 inflammation. RECENT FINDINGS: Two major novelties have prompted an innovative approach to EoE...

PURPOSE: Immune-related cutaneous adverse events (ircAEs) occur in ≥50% of patients treated with checkpoint inhibitors (CPI), but mechanisms are poorly understood. EXPERIMENTAL DESIGN: Phenotyping/biomarker analyses were conducted in 200 patients on CPIs (139 with ircAEs, 61 without, control) to characterize their clinical presentation and immunologic endotypes. Cytokines were evaluated in skin biopsies, skin tape strip (STS) extracts and plasma using real-time PCR and Meso Scale Discovery multiplex cytokine assays...

UNLABELLED: A 34-year-old man with a history of Kawasaki disease had been experiencing chest pain at rest since middle school. Multidetector-row computed tomography showed no aneurysm formation; however, the right coronary artery had an anomalous origin with moderate stenosis. Invasive coronary angiography revealed moderate right coronary artery stenosis with a fractional flow reserve of 0.97. Finally, with a positive acetylcholine provocation test and elevated index of microvascular resistance, the patient was diagnosed with microvascular and epicardial vasospastic angina in the endotypes of ischemia with nonobstructive coronary arteries...

Background Infants with frequent viral and bacterial respiratory infections exhibit compromised immunity to routine immunisations. They are also more likely to develop chronic respiratory diseases in later childhood. This study investigated the feasibility of epigenetic profiling to reveal endotype-specific molecular pathways with potential for early identification and immuno-modulation. Peripharal immune cells from respiratory infection allergy/asthma prone (IAP) infants were retrospectively selected for genome-wide DNA methylation and single nucleotide polymorphism analysis...

The acute respiratory distress syndrome (ARDS) is a heterogeneous syndrome characterized by distinct etiologies and complicated pathobiological mechanism. It is difficult to discriminate patients with unique biological features or individual response to specific therapy by traditional definition and subgrouping. Unfortunately, there are few clinical evidences supporting effective drug therapy to ARDS. The sub-phenotype or endotype of ARDS is related to potential mechanism of the syndrome, and is critical to personalized treatment of ARDS...

Although substantial progress has been made in our understanding of asthma pathogenesis and phenotypes over the 60-year history of 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 application of microbiome-based therapies in various areas of human disease has recently increased. In chronic respiratory disease, microbiome-based clinical applications are considered compelling options due to the limitations of current treatments. The lung microbiome is ecologically dynamic and affected by various conditions, and dysbiosis is associated with disease severity, exacerbation, and phenotype as well as with chronic respiratory disease endotype. However, it is not easy to directly modulate the lung microbiome...

Inhaled corticosteroid (ICS) is a mainstay treatment for controlling asthma and preventing exacerbations in patients with persistent asthma. Many types of ICS drugs are used, either alone or in combination with other controller medications. Despite the widespread use of ICSs, asthma control remains suboptimal in many people with asthma. Suboptimal control leads to recurrent exacerbations, causes frequent ER visits and inpatient stays, and is due to multiple factors. One such factor is the inappropriate ICS choice for the patient...

Casein (CN) is the primary allergenic protein in cow's milk, contributing to the worldwide escalating prevalence of food allergies. However, there remains limited knowledge regarding the effect of structural modifications on CN allergenicity. Herein, we prepared three modified CNs (mCN), including sodium dodecyl sulfate and dithiothreitol-induced linear CN (LCN), transglutaminase-cross-linked CN (TCN), and glucose-glycated CN (GCN). The electrophoresis results indicated widespread protein aggregation among mCN, causing variations in their molecular weights...

INTRODUCTION: Two distinct chronic spontaneous urticaria (CSU) endotypes, IgE-mediated autoallergic and IgG-mediated autoimmune, were defined based on the response patterns to omalizumab. However, the coexistence of IgE and IgG autoantibodies in a subset of patients might complicate the prediction of the treatment outcomes. This study aimed to evaluate the effectiveness and safety of omalizumab in CSU patients, focusing on the factors predicting the response patterns. METHODS: This was a retrospective cross-sectional single-center study investigating CSU patients treated with omalizumab for at least 6 months between September 2015 and February 2023...

BACKGROUND: Chronic Obstructive Pulmonary Disease (COPD) is a heterogeneous condition. We hypothesized that the unbiased integration of different COPD lung omics using a novel multi-layer approach may unravel mechanisms associated with clinical characteristics. METHODS: We profiled mRNA, miRNA and methylome in lung tissue samples from 135 former smokers with COPD. For each omic (layer) we built a patient network based on molecular similarity. The three networks were used to build a multi-layer network, and optimization of multiplex-modularity was employed to identify patient communities across the three distinct layers...

Two recent articles by the same research group documented that patients with severe eosinophilic asthma exhibit an increased proportion of a subtype of eosinophils, namely CD62Llow inflammatory eosinophils (iEos) and identified an intriguing correlation between such iEos and asthma control scores. Moreover, CD62Llow iEos were reduced after treatment with the anti-IL-5 monoclonal antibody mepolizumab. In the future, we believe that eosinophil subtypes could represent a useful biomarker in severe eosinophilic asthma, helping clinicians characterize patient endotypes and monitoring the response to biological drugs...

Atopic dermatitis (AD) is the most common form of chronic skin inflammation with diverse clinical variants. Historically, various AD phenotypes have been grouped together without considering their heterogeneity. This approach has resulted in a lack of phenotype- and endotype-adapted therapeutic strategies. Comprehensive insights into AD pathogenesis have enabled precise medicinal approach for AD. These efforts aimed to redefine the endophenotype of AD and develop various biomarkers for diverse purposes. Among these endeavours, efforts are underway to elucidate the mechanisms (and related biomarkers) that lead to the emergence and progression of atopic diseases originating from AD (e...

INTRODUCTION: Systemic lupus erythematosus with antiphospholipid syndrome (SLE-APS) represents a challenging SLE endotype whose molecular basis remains unknown. METHODS: We analysed whole-blood RNA-sequencing data from 299 patients with SLE (108 SLE-antiphospholipid antibodies (aPL)-positive, including 67 SLE-APS; 191 SLE-aPL-negative) and 72 matched healthy controls (HC). Pathway enrichment analysis, unsupervised weighted gene coexpression network analysis and machine learning were applied to distinguish disease endotypes...

IntroductionThere is an urgent, persistent, need for better biomarkers in clinical drug development. More informative biomarkers can increase the likelihood of drug advancement or approval, and implementing biomarkers increases the success rate in drug development. Biomarkers may guide decisions and allow resources to be directed to the projects most likely to succeed. However, biomarkers that are validated to high standards are needed, reflecting biological and pathological processes accurately. Such biomarkers are needed to develop treatments faster, and to improve and guide clinical trial design by selecting and de-selecting patients...

Obstructive sleep apnea (OSA) is the frequent occurrence of apnea and/or hypopnea during sleep, leading to intermittent hypoxia, hypercapnia, and disruption of sleep architecture, further resulting in multisystem damage. The pathophysiological mechanisms include abnormal anatomical structure, low arousal threshold, high loop gain, and poor muscle reactivity, etc . As there are individual differences in the underlying mechanisms of OSA (i.e. endotypes), the effectiveness of treatment and prognosis may also vary according to these characteristics...

INTRODUCTION: Trauma-related deaths and post-traumatic sequelae are a global health concern, necessitating a deeper understanding of the pathophysiology to advance trauma therapy. Proteomics offers insights into identifying and analyzing plasma proteins associated with trauma and inflammatory conditions; however, current proteomic methods have limitations in accurately measuring low-abundance plasma proteins. This study compared plasma proteomics profiles of patients from different acute trauma subgroups to identify new therapeutic targets and devise better strategies for personalized medicine...

Obstructive sleep apnea (OSA) affects almost a billion people worldwide and is associated with a myriad of adverse health outcomes. Among the most prevalent and morbid are cardiovascular diseases (CVDs). Nonetheless, randomized controlled trials (RCTs) of OSA treatment have failed to show improvements in CVD outcomes. A major limitation in our field is the lack of precision in defining OSA and specifically subgroups with the potential to benefit from therapy. Further, this has called into question the validity of using the time-honored apnea-hypopnea index as the ultimate defining criteria for OSA...