There is general agreement that chronic obstructive pulmonary disease. (COPD) is a global epidemic affecting both developed and, particularly, developing countries.
Despite access to the most up-to-date medicine currently available. We all also agree that its management is inadequate in at least two ways; people still smoke cigarettes and, for those who already have COPD, current treatment is inadequate. Patients still suffer and die of COPD.
None of our therapies have substantially decreased its mortality or progression in this disease.
Although effective therapies are available for asthma, the disease in many patients is not adequately controlled.
The asthma–COPD overlap syndrome combines the suffering and mortality of both disorders and may require combined therapy.
From this Perspective we focus on the drugs currently being developed to address these unmet needs.
The same drug classes are often in development for severe asthma and COPD in parallel, as there are many shared mechanisms of chronic inflammation.
Additionally in asthma, the greatest need, apart from improving adherence, is the need for therapies that address patients who have severe disease despite using current therapies.
In COPD the greatest needs are for treatments that address smoking cessation and the underlying progressive disease process that can continue to damage the airways and parenchyma long after smoking cessation.
Types of Therapies
Although short-acting inhaled bronchodilators (such as albuterol and ipratropium) are still used as rescue therapy, the major development has been in the introduction of long-acting inhaled β2-agonists (LABAs) and long-acting muscarinic antagonists (LAMAs), with several new products and LABA–LAMA combinations now on the market and in clinical development.
Fixed combinations of ICS–LABA–LAMA are now in development for COPD and severe asthma. One of the first triple inhalers with beclomethasone dipropionate–formoterol–glycopyrrolate twice daily shows a clinical advantage over the ICS–LABA combination in patients with COPD.
Muscarinic antagonist–β2 agonists (MABAs), combining two pharmacophores by an inactive spine, are also in development.
A major problem is that it is difficult to balance the LABA and LAMA activities. So that most MABAs tend to have a predominance of either LABA or LAMA activity.
MABAs combined with an ICS are also in development as functional triple combinations.
Several ICSs for twice-daily administration are now on the market and a once-daily ICS, fluticasone furoate, has been introduced in combination with vilanterol. There has been a search for safer corticosteroids and several nonsteroidal selective glucocorticoid receptor agonists (SEGRAs).
The discovery that the bronchodilator and antiinflammatory effects of theophylline are mediated mainly through inhibition of phosphodiesterases (PDEs), which include 11 major families of enzyme, each of which may have several isoforms, led to the development of selective PDE inhibitors in the hope that efficacy may be enhanced and side effects reduced.