Investigational beta-2 adrenergic agonists for the treatment of chronic obstructive pulmonary disease.

INTRODUCTION: Long-acting bronchodilators are pivotal in the therapeutic management of COPD patients with moderate-to-severe airflow obstruction. New ultra-long-acting ß2-agnoists (ultra-LABAs) have been developed, some of which have been licensed for use as monotherapy and/or in combination with other bronchodilators or inhaled corticosteroids, for use in COPD patients with persistent symptoms and worsening airflow limitation. These new agents are faster in onset and have a prolonged duration of action, with a similar safety profile to the traditional twice-daily bronchodilators which may have an impact on patient concordance. Areas covered: A number of these ultra-LABAs are still under development and bi-functional hybrid molecules containing regions functioning as ß2-agonists, and as muscarinic agonists (MABAs) has been developed. This review summarizes these (excluding the licensed ultra-LABAs) with attention on phase II studies data available to-date on their pharmacological profiles, clinical efficacy and safety, and future perspectives. Expert opinion: Despite all the new agents' available, the challenges that persist include any differences in efficacy and safety between the various possible LAMA/LABA combinations, relative advantages of MABAs over fixed-dose LAMA/LABAs, and the impact of these new molecules in terms of long term safety, especially in certain populations in co-morbidities frequently associated with COPD.

Vilanterol trifenatate for the treatment of COPD.

INTRODUCTION: Currently the treatment of chronic obstructive pulmonary disease (COPD) has limited effectiveness and there is a need to develop new drugs. International guidelines recommend the use of long-acting bronchodilators (ß2 agonists and anti-cholinergics/muscarinics), inhaled steroids and associations between these drugs in the maintenance treatment of moderate-to-severe COPD. AREA COVERED: Vilanterol trifenate is a new once-daily highly selective ß2-agonist available in USA and Europe in association with umeclidinium bromide (a long-acting anti-muscarnic agent) and fluticasone furoate (an inhaled corticosteroid) for the once-daily maintenance treatment of COPD. Vilanterol combined in fixed-dose treatments has been tested in numerous clinical trials involving thousands of patients. Expert commentary: These new once-daily formulations have the potential to improve compliance to long-term inhaled therapy. This paper will review the clinical and experimental data regarding vilanterol use in the regular treatment of COPD as well as provide a critical discussion of possible future treatment settings.

Pneumothorax: a tale of pain or spontaneity.

Pneumothoraces may be due a variety of aetiologies. Here we present two different cases: one with a unilateral pneumothorax due an iatrogenic medical procedure and another of idiopathic spontaneous bilateral nature. Although both cases were initially managed conservatively, the latter case required surgical intervention. We also conduct a literature review of the aetiology and management of pneumothoraces.

Biologic and pharmacologic therapies in clinical development for the inflammatory response in COPD.

Chronic obstructive pulmonary disease (COPD) is a progressive and debilitating condition with declining lung function associated with airway inflammation, mucus hypersecretion and remodeling. Inflammatory cells contribute to the disease processes via the production of proteases, fibrotic or mitogenic growth factors, cytokines, chemokines and their receptors. Particularly newer agents that treat the underlying inflammation and remodeling. Here, we briefly review current understanding of the inflammatory mechanisms involved in the pathogenesis of COPD. This understanding has enabled the identification of several therapeutic targets that might have great potential for the development of novel anti-inflammatory and anti-remodeling biologic therapies with considerable clinical advantage for COPD. Some of these molecules have been assessed, and others are in the early stages of being assessed. This article gives an up-to-date summary of these novel therapies and their status of clinical development in targeting the various inflammatory pathways of COPD.