Long-acting beta-agonists and their association with inhaled corticosteroids in COPD.

Curr Med Chem. 2013 Jan 28;

Authors: Fuso L, Mores N, Valente S, Malerba M, Montuschi P

Abstract
Inhaled bronchodilators, including beta2-agonists and antimuscaric receptor antagonists, are the mainstay of pharmacotherapy in chronic obstructive pulmonary disease (COPD). The short-acting beta(2)-agonists, including salbutamol, and fenoterol, have a rapid onset of action, a bronchodilating effect for 3-6 h and are used on demand. The long-acting beta(2)-agonists (LABAs), including salmeterol and formoterol, have 12-hour duration of action and are used with a twice-daily dosing regimen for long-term COPD treatment. Unlike salmeterol, formoterol has a rapid onset of action. Pharmacological characteristics required by novel inhaled LABAs include 24 h bronchodilator effect in vivo which would make them suitable for once daily administration (ultra-LABA), high potency and selectivity for beta2-adrenoceptors, rapid onset of action, low oral bioavailability (< 5%) after inhalation, and high systemic clearance. Indacaterol, which has been approved for long-term treatment of COPD in Europe and in the USA, has a 24-h duration of action and a once-daily dosing regimen. Newer ultra-LABAs, including olodaterol, vilanterol, milveterol, carmoterol, and abediterol, are in development. Combination with ICS (fluticasone/salmeterol, budesonide/formoterol) appears to provide an additional benefit over the monocomponent therapy, although the extent of this benefit is variable and often not clinically significant in all the endpoints assessed. In patients with COPD, treatment with ICS is associated with increased risk of pneumonia which should be carefully considered when assessing the risk/benefit ratio of ICS/LABA combinations. Subphenotyping of patients with COPD (e.g., frequent exacerbations, sputum eosinophilia, mixed asthma/COPD phenotype) might help identify those patients who are most likely to benefit from addition of ICS to bronchodilating treatment. Ultra-LABA/LAMA combination treatment is under development and is likely to become a standard pharmacological strategy for COPD. Dual-pharmacology inhaled muscarinic antagonist-beta2 agonist (MABA) molecules provide a new approach to the treatment of COPD.

PMID: 23409722 [PubMed - as supplied by publisher]

Related Articles

Cardiovascular Safety In Patients Receiving Roflumilast for the Treatment of Chronic Obstructive Pulmonary Disease.

Chest. 2013 Feb 14;

Authors: White WB, Cooke GE, Kowey PR, Calverley PM, Bredenbröker D, Goehring UM, Zhu H, Lakkis H, Mosberg H, Rowe P, Rabe KF

Abstract
ABSTRACT BACKGROUND Evaluation of CV safety for new therapies for COPD is important as there is a high prevalence of cardiac comorbidities in the COPD population. Hence, we evaluated the effects of roflumilast, a novel oral phosphodiesterase 4 (PDE-4) inhibitor developed for the treatment of prevention of COPD exacerbations on major adverse cardiovascular events (MACE). METHODS Intermediate- and long-term placebo-controlled clinical trials of roflumilast in COPD were pooled and assessed for potential CV events; studies comprised fourteen 12- to 52-week placebo-controlled trials in patients with moderate-to-very severe COPD. All deaths and serious non-fatal CV events were evaluated by an independent adjudication committee blinded to study and treatment. The MACE composite of CV death, non-fatal myocardial infarction, and stroke were analyzed according to treatment group. RESULTS There were 52 patients with MACE in 6,563 patients on roflumilast (14.3 per 1,000 patient-years) and 76 patients with MACE in 5,491 patients on placebo (22.3 per 1,000 patient-years); the MACE composite rate was significantly lower on roflumilast compared to placebo (hazard ratio vs. placebo: 0.65; 95% CI: 0.45-0.93; p = 0.019). CONCLUSIONS A lower rate of CV events was observed on roflumilast compared to placebo in patients with COPD, indicating the lack of a CV safety signal when treating patients with COPD. Potential CV benefits of roflumilast should be evaluated in future controlled clinical trials.

PMID: 23412642 [PubMed - as supplied by publisher]

Should all patients with COPD be exercise-trained?

J Appl Physiol. 2013 Feb 14;

Authors: Ribeiro F, Thériault ME, Debigare R, Maltais F

Abstract
Exercise training is one of the most powerful interventions to provide symptomatic relief in patients with COPD. The purpose of this mini-review is to discuss how exercise training can improve limb muscle dysfunction in this disease. Various exercise training strategies will be outlined, along with their beneficial effects and potential limitations. Strategies to optimize the gains achievable with exercise training will be presented. Whether exercise training may exert deleterious effects in some patients will also be discussed.

PMID: 23412902 [PubMed - as supplied by publisher]

Cytokines in chronic respiratory diseases.

F1000 Biol Rep. 2013;5:3

Authors: Atamas SP, Chapoval SP, Keegan AD

Abstract
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PMID: 23413371 [PubMed]