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.
Asthma phenotyping and endotyping are constantly evolving. Currently, several biologic agents have been developed towards a personalized approach to asthma management. This review will focus on different eosinophilic phenotypes and Th2-associated endotypes with eosinophilic inflammation. Additionally, airway remodeling is analyzed as a key feature of asthmatic eosinophilic endotypes. In addition, evidence of biomarkers is examined with a predictive value to identify patients with severe, uncontrolled asthma who may benefit from new treatment options. Finally, there will be a discussion on the results from clinical trials regarding severe eosinophilic asthma and how the inhibition of the eosinophilic pathway by targeted treatments has led to the reduction of recurrent exacerbations.
Asthma is a heterogeneous disease usually characterized by chronic airway inflammation, in which several phenotypes have been described, related to the age of onset, symptoms, inflammatory characteristics and treatment response. The identification of the inflammatory phenotype in asthma is very useful, since it allows for both the recognition of the asthmatic triggering factor as well as the optimization of treatment The paucigranulocytic phenotype of asthma (PGA) is characterized by sputum eosinophil levels <1–3% and sputum neutrophil levels < 60%. The precise characteristics and the pathobiology of PGA are not fully understood, and, in some cases, it seems to represent a previous eosinophilic phenotype with a good response to anti-inflammatory treatment. However, many patients with PGA remain uncontrolled and experience asthmatic symptoms and exacerbations, irrespective of the low grade of airway inflammation. This observation leads to the hypothesis that PGA might also be either a special phenotype driven by different kinds of cells, such as macrophages or mast cells, or a non-inflammatory phenotype with a low grade of eosinophilic inflammation. In this review, we aim to describe the special characteristics of PGA and the potential therapeutic interventions that could be offered to these patients.
Background : Anxiety and depression are common psychological disturbances among asthmatic patients. The aim of the present study is the assessment of anxiety and depression in asthmatic patients and their correlation with symptoms control level and number of exacerbations per year. Methods : One hundred patients with asthma diagnosis, according to the Global Initiative for Asthma (GINA), aged > 18 years old, having a stable disease, were included. Emotional status was evaluated using the Hospital Anxiety Depression Scale (HADS). Patients were followed up for a year to assess the number and severity of exacerbations. Results : Most of our patients were female (58%), middle-aged (mean = 54 ± 13), and married (81%), with low frequency of smoking habits (smokers, ex-smokers and non-smokers were 26%, 30% and 37%, respectively) and low levels of both anxiety and depression [median (interquartile range (IQR)) = 4(2) and median (IQR) = 4(2), respectively]. At the low and moderate level of the depression subscale, female patients experienced asthma exacerbations more frequently compared to male patients (adjusted Incidence Rate Ratio (aIRR) = 4.30; 95% Confidence Interval (CI): 1.94–9.53 and aIRR = 1.82; 95% CI: 1.07–3.13, respectively). Conclusions. Clinicians should evaluate asthma patients for depression, as gender differentially influences outcomes among those with low and moderate levels of depression, with female asthmatics presenting more frequent exacerbations.
Long-acting muscarinic antagonists (LAMAs) are a class of inhalers that has recently been included as add-on therapy in the GINA guidelines, either in a single inhaler device with inhaled corticosteroids plus long-acting β2-agonists (ICS + LABA) (closed triple inhaler therapy) or in a separate one (open triple inhaler therapy). This review summarizes the existing evidence on the addition of LAMAs in patients with persistently uncontrolled asthma despite ICS + LABA treatment based on clinical efficacy in the reduction of asthma symptoms and exacerbations, the improvement in lung function, and its safety profile.
Lung cancer is a substantial global burden for patients, healthcare professionals and healthcare systems. Multiple scientific international and national initiatives are tackling the various problems associated with this disease, which is currently the leading cause of cancer-related mortality worldwide. During the European Respiratory Society International Congress 2018 in Paris, France, lung cancer experts gathered to present the most recent aspects of lung cancer care, and discuss the need for joint initiatives and an international lung cancer alliance, aiming to provide high quality, accessible health care. The US experience and American Lung Association/American Thoracic Society implementation guide on lung cancer screening programmes, the key features of optimising and implementing such programmes, the challenges of treatment in the subset of patients where lung cancer is combined with interstitial lung disease, and novel lung cancer biomarkers and immunotherapy were among the most anticipated issues covered during the congress.