Asthma is one of the most common respiratory disease that affects both children and adults worldwide, with diverse phenotypes and underlying pathogenetic mechanisms poorly understood. As technology in genome sequencing progressed, scientific efforts were made to explain and predict asthma’s complexity and heterogeneity, and genome-wide association studies (GWAS) quickly became the preferred study method. Several gene markers and loci associated with asthma susceptibility, atopic and childhood-onset asthma were identified during the last few decades. Markers near the ORMDL3/GSDMB genes were associated with childhood-onset asthma, interleukin (IL)33 and IL1RL1 SNPs were associated with atopic asthma, and the Thymic Stromal Lymphopoietin (TSLP) gene was identified as protective against the risk to TH2-asthma. The latest efforts and advances in identifying and decoding asthma susceptibility are focused on epigenetics, heritable characteristics that affect gene expression without altering DNA sequence, with DNA methylation being the most described mechanism. Other less studied epigenetic mechanisms include histone modifications and alterations of miR expression. Recent findings suggest that the DNA methylation pattern is tissue and cell-specific. Several studies attempt to describe DNA methylation of different types of cells and tissues of asthmatic patients that regulate airway remodeling, phagocytosis, and other lung functions in asthma. In this review, we attempt to briefly present the latest advancements in the field of genetics and mainly epigenetics concerning asthma susceptibility.

Severe asthma (SA) is a chronic lung disease characterized by recurring symptoms of reversible airflow obstruction, airway hyper-responsiveness (AHR), and inflammation that is resistant to currently employed treatments. The nucleotide-binding oligomerization domain-like Receptor Family Pyrin Domain Containing 3 (NLRP3) inflammasome is an intracellular sensor that detects microbial motifs and endogenous danger signals and represents a key component of innate immune responses in the airways. Assembly of the NLRP3 inflammasome leads to caspase 1-dependent release of the pro-inflammatory cytokines IL-1β and IL-18 as well as pyroptosis. Accumulating evidence proposes that NLRP3 activation is critically involved in asthma pathogenesis. In fact, although NLRP3 facilitates the clearance of pathogens in the airways, persistent NLRP3 activation by inhaled irritants and/or innocuous environmental allergens can lead to overt pulmonary inflammation and exacerbation of asthma manifestations. Notably, administration of NLRP3 inhibitors in asthma models restrains AHR and pulmonary inflammation. Here, we provide an overview of the pathophysiology of SA, present molecular mechanisms underlying aberrant inflammatory responses in the airways, summarize recent studies pertinent to the biology and functions of NLRP3, and discuss the role of NLRP3 in the pathogenesis of asthma. Finally, we contemplate the potential of targeting NLRP3 as a novel therapeutic approach for the management of SA.

Recent studies have associated osteopontin (OPN) with allergic inflammation; however, its role in human asthma remains unclear. The aim of this study was to measure OPN levels in the serum, bronchoalveolar lavage fluid (BALF) and bronchial tissue of healthy controls and asthmatics, identify cellular sources of OPN and examine possible correlations between OPN expression, disease severity and airway remodelling.Serum samples were obtained from 35 mild-to-moderate asthmatics, 19 severe asthmatics and 17 healthy controls in the steady state and in cases of exacerbation. Of these subjects, 29 asthmatics and nine controls underwent bronchoscopy with endobronchial biopsy and BALF collection. OPN expression was determined by ELISA and immunohistochemistry/immunofluorescence. Reticular basement membrane thickness and goblet cell hyperplasia were also determined.Serum and BALF OPN levels were significantly increased in all asthmatics in the steady state, whereas serum levels decreased during exacerbations. OPN was upregulated in the bronchial tissue of all patients, and expressed by epithelial, airway and vascular smooth muscle cells, myofibroblasts, T-lymphocytes and mast cells. OPN expression correlated with reticular basement membrane thickness and was more prominent in subepithelial inflammatory cells in severe compared to mild-to-moderate asthma.OPN expression is upregulated in human asthma and associated with remodelling changes, and its subepithelial expression correlates with disease severity.

B lymphocytes are characterized by a unique and highly specialized developmental pathway that is responsible for their vast phenotypic and function diversity. B cell development is strictly regulated to ensure sufficient specific humoral immunity while at the same time avoiding any errors that would compromise B cell functionality. The generation and maintenance of mature B cells from the constant flux of bone marrow progenitors is a complex process that is generally poorly understood, although great progress has been made in recent years. B cells have for long been considered mainly as antibody-producing cells and therefore believed to play an important role in the pathophysiology of allergic diseases, primarily through their ability to produce IgE antibodies. However, recent findings have revealed new aspects of their role in immune responses that place them again under the spotlight as important immune regulators, independent of antibody production. This review focuses on the developmental processes responsible for the numerous phenotypes and functions of the B-lymphocyte pool and the different aspects of effector B cell functionality in the context of allergy.