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Small-airway disease in asthma: pharmacological considerations

imagePurpose of review: To review the pharmacological considerations and rationale for treating small-airway disease in asthma via the inhaled and systemic route, and to also directly address the comparison between small vs. large aerosol particles in the management of asthmatic patients. Recent findings: Airway inflammation in patients with asthma is predominantly present within the small airways and this region is the main contributor to airflow limitation. Assessing small-airway dysfunction has advanced in the last decade, allowing us to compare this region in disease to health and also in response to treatment. Recent pharmaceutical developments have led to inhaler devices with smaller aerosols and systemic biologic treatments, enabling therapeutic drug delivery to the distal lung regions. The question therefore is does targeting the small airways directly translate into health benefits for asthmatic patients with respect to an improvement in their disease control and quality of life? Summary: Studies now show that treating the peripheral airways with smaller drug particle aerosols certainly achieve comparable efficacy (and some studies show superiority) compared with large particles, a reduction in the daily inhaled corticosteroid dose, and greater asthma control and quality of life in real-life studies. Hence, the small airways should not be neglected when choosing the optimal asthma therapy.

Managing severe asthma in adults: lessons from the ERS/ATS guidelines

imagePurpose of review: To review the latest guidelines on severe asthma. Recent findings: An updated definition of severe asthma is provided together with the evaluation steps necessary to reach a diagnosis of severe asthma. The importance of phenotyping is emphasized, and recommendations are provided for therapies specifically directed for severe asthma. Summary: Severe asthma is widely recognized as a major unmet need. It is defined as asthma that requires treatment with high-dose inhaled corticosteroids and a second controller and/or systemic corticosteroid to prevent it from becoming ‘uncontrolled’ or that remains ‘uncontrolled’ despite this therapy. Severe asthma is a heterogeneous condition that consists of phenotypes such as eosinophilic asthma. More phenotypes need to be defined. Evaluation of the patient referred to as having severe or difficult-to-control asthma must take into account adherence to treatment, comorbidities and associated factors including side effects from therapies. These need to be addressed. Recommendations on the use of sputum eosinophil count and exhaled nitric oxide to guide therapy are presented. Treatment with anti-IgE antibody, methotrexate, macrolide antibiotics, antifungal agents and bronchial thermoplasty is reviewed and recommendations made. Research efforts into phenotyping of severe asthma will provide both biomarker-driven approaches and newer effective therapies to severe asthma management.

The asthma–chronic obstructive pulmonary disease overlap syndrome (ACOS): opportunities and challenges

imagePurpose of review: Some individuals share characteristics of asthma and chronic obstructive pulmonary disease (COPD). The asthma–COPD overlap syndrome (ACOS) has been defined as symptoms of increased variability of airflow in association with an incompletely reversible airflow obstruction. In this review, we present the latest findings in the diagnosis, characterization and management of ACOS.

Recent findings: Around 15–20% of COPD patients may have an ACOS. Patients with ACOS are characterized by increased reversibility of airflow obstruction, eosinophilic bronchial and systemic inflammation, and increased response to inhaled corticosteroids, compared with the remaining patients with COPD. Patients with ACOS have more frequent exacerbations, more wheezing and dyspnoea, but similar cough and sputum production compared with COPD.

Summary: The relevance of the ACOS is to identify patients with COPD who may have underlying eosinophilic inflammation that responds to inhaled corticosteroids. So far, the previous diagnosis of asthma in a patient with COPD is the more reliable criterion for ACOS. Ongoing studies will clarify if concentrations of blood eosinophils may be useful to identify this subgroup of patients with COPD. If this is the case, the interest of ACOS may shift to that of eosinophilic COPD, which is easier to diagnose and has clear therapeutic implications.

The revised 2014 GINA strategy report: opportunities for change

Purpose of review: This document reviews a major revision of the Global Initiative for Asthma (GINA) Strategy for Asthma Management and Prevention that was published in 2014. The report aimed not only to update evidence-based recommendations for asthma diagnosis and management but also to innovate through a new format and layout to make its recommendations more clinically relevant and easier to implement.

Recent findings: The GINA 2014 report includes a new definition of asthma that recognizes the heterogeneity of the disease and its phenotypes, and a new chapter about the asthma–chronic obstructive pulmonary disease (COPD) overlap syndrome. Among key messages, the report stresses that therapeutic decisions should be based not only on assessment of symptoms but also on risk factors for exacerbations, side effects of therapy and development of fixed airflow limitation. Asthma management includes not only medications but also nonpharmacological therapies and strategies, in a coordinated and personalized approach to individual patient care. On the basis of evidence about how to achieve behaviour change by health professionals, the recommendations are presented in a user-friendly format, with numerous tables, algorithms and flow-charts facilitating implementation. Background supporting material has been gathered online.

Summary: The GINA 2014 report provides updated and more easily implementable recommendations on optimal asthma management.

Role of anticholinergics in asthma management: recent evidence and future needs

imagePurpose of review: Anticholinergic antimuscarinic bronchodilators play a major role in the treatment of chronic obstructive pulmonary disease, but their role in asthma has long been limited to acute management. More recently, the role of long-acting antimuscarinic bronchodilators (LAMAs) in chronic asthma management has been explored. This review will examine the pharmacological rationale for use of inhaled anticholinergics in the treatment of asthma, and provide an overview of the current literature supporting this use, as well as describe future research needs in this area.

Recent findings: Short-acting anticholinergic bronchodilators have a role as add-on agents in the treatment of acute asthma. Preliminary clinical studies suggest that inhaled LAMAs may be comparable to long-acting beta2-agonists (LABAs) as an add-on therapy in patients not controlled by inhaled corticosteroids (ICS) alone, and may also have added benefit in patients not controlled on combined ICS–LABA. Mechanistic studies suggest that apart from their bronchodilator activity, LAMAs may have anti-inflammatory and antiremodeling influences on the airways. Further research is needed to clarify the clinical relevance of these experimental observations.

Summary: Accumulating evidence supports the use of inhaled LAMAs as an add-on therapy in patients with asthma, who remain symptomatic despite guideline-based therapy with ICS with or without LABAs. Further studies are warranted to help define mechanisms of action of LAMAs, apart from their role as bronchodilators, and determine how these other actions impact asthma outcomes over time. Furthermore, future studies need to examine the long-term efficacy and safety of LAMAs in asthma and identify a subgroup of patients who would benefit from such therapies to facilitate early, personalized therapy.

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