QVA149 (indacaterol/glycopyrronium) for the treatment of chronic obstructive pulmonary disease

Introduction: The combination of two bronchodilators with different mechanisms of action to treat patients with chronic obstructive pulmonary disease (COPD) is an established medical practice, but the dissimilarities in the onset and duration of action of long-acting β₂-agonists (LABA) and long-acting muscarinic agents (LAMA) and differences in the devices used for the delivery of these drugs make free combinations uncomfortable and unpredictable, especially if focused on adherence to prescribed treatment. Therefore, there is the need for fixed-dose combinations (FDCs) of bronchodilators in a single inhaler.

Areas covered: The results of the pivotal Phase III IGNITE and EXPEDITION programs show that QVA149 (indacaterol/glycopyrronium FDC) is able to elicit a significant improvement in lung function and patient-reported outcomes, including breathlessness and rescue medication use, reduced rates of COPD exacerbations and health-related quality of life when compared with current standard of care. Moreover, QVA149 is generally well tolerated, with most adverse events being of mild-to-moderate severity.

Expert opinion: Given that the LABA/LAMA coformulation is the most powerful bronchodilator available, QVA149, which has been the first LABA/LAMA FDC to be developed, should be considered central in the maintenance treatment of COPD, and could be a potential option for improving lung function and health status in maintenance-naïve patients.     

Indacaterol for the treatment of chronic obstructive pulmonary disease

Introduction: The need for a rapid onset of action and a long duration of the broncholytic effect is the likely reason for the development of new long-acting β2-agonists (LABAs) that are fast acting and have true 24 h duration of action. Indacaterol is the archetype of once-daily LABAs and already marketed as a maintenance therapy in patients with moderate to severe chronic obstructive pulmonary disease (COPD).

Areas covered: Meta-analyses of published data or pooled analyses of primary data provide good insight into the clinical role of indacaterol in COPD.

Expert opinion: The choice of the once-daily bronchodilator to start treatment in a patient with COPD mainly depends on the outcome of interest. Indacaterol is more effective than tiotropium if we consider symptoms or health-related quality of life as the primary outcome. Moreover, in symptomatic patient indacaterol should be preferred to tiotropium because of its rapid onset of action. By contrast, tiotropium appears to be more effective than indacaterol if exacerbations are the expected primary outcome. However, as indacaterol/glycopyrronium fixed-dose combination (QVA149) shows superior efficacy compared to glycopyrronium and tiotropium in patients with moderate to severe COPD, a fundamental question regarding the use of indacaterol that requires clarification is whether it is preferable to start immediately with QVA149 rather than using indacaterol alone.     

Evaluation of DNA damage by the alkaline comet assay of the olfactory and respiratory epithelia of dogs from the city of São Paulo,Brazil

Animals kept as pets may be considered sentinels for environmental factors to which humans could be exposed. Olfactory and respiratory epithelia are directly subjected to airborne factors, which could cause DNA lesions, and the alkaline comet assay is considered a reliable tool for the assessment of DNA damage. The objective of this work is to evaluate the extent of DNA damage by the comet assay of the olfactory and respiratory epithelia of dogs from different regions of the city of São Paulo, Brazil. Thirty-three clinically healthy dogs, aged 5 years or more, were used in the study, with 7 from the North region of São Paulo, 7 from the South region, 3 dogs from the East region, and 16 dogs from the West city region. Three dogs younger than 6 months were used as controls. DNA damage was analyzed by the alkaline comet assay. We observed no difference in histopathological analysis of olfactory and respiratory epithelia between dogs from different regions of São Paulo. Dogs older than 5 years presented significantly higher comet length in both olfactory and respiratory epithelia, when compared with controls, indicating DNA damage. When separated by regions, olfactory and respiratory epithelia presented similar DNA damage in dogs from different regions of São Paulo, corroborating with similar levels of particulate matter index (PM10) in all regions of the city. In this study, we report for the first time that the comet assay can be used to quantify the extent of DNA damage in dog olfactory and respiratory epithelia, and that comet length (DNA damage) increases with age, probably due to environmental factors. Air pollution, as measured by PM10, can be responsible for this DNA damage.     

Targeting systemic inflammation: novel therapies for the treatment of chronic obstructive pulmonary disease

The increasing evidence that inflammation in the lungs leads to the structural changes observed in chronic obstructive pulmonary disease, whereas extrapulmonary symptoms and comorbidities may be systemic manifestations of these inflammatory processes, highlights an urgent need to discover novel, effective anti-inflammatory treatments for this disease. Some studies are suggesting that, by decreasing dynamic hyperinflation, bronchodilators might reduce systemic inflammation; inhaled corticosteroids and their combination with long-acting beta2-agonists might contribute to this goal. Even so, the opinion that suppression of the inflammatory response might improve systemic complications is stimulating a search for novel anti-inflammatory therapies. Many drugs include those that inhibit the recruitment and activation of inflammatory cells and/or antagonise their products. However, many of these therapeutic strategies are not specific for neutrophilic inflammation because they affect other cell types, thus, it is difficult to interpret whether any clinical benefit observed is a result of a reduction in airway neutrophils. In any case, there is some evidence that drugs used to treat a co-morbid condition, such as statins, angiotensin converting enzyme (ACE) inhibitors and angiontensin II type 1 (AT1) receptor blockers as well as glycosaminoglycans and peroxisome proliferator-activated receptor (PPAR) agonists, might benefit chronic obstructive pulmonary disease patients because they deal with the extrapulmonary, systemic component of chronic obstructive pulmonary disease.