Treatment options for moderate-to-very severe chronic obstructive pulmonary disease

ABSTRACT

Introduction: The appropriate drug management of COPD is still based on the use of bronchodilators, possibly associated with an anti-inflammatory agent. However, there are still fundamental questions that require clarification to optimise their use and major unmet clinical needs that must be addressed.

Areas covered: The advances obtained with the pharmacological options currently consolidated and the different approaches that are often used in an attempt to respond to unmet therapeutic needs are reviewed

Expert opinion: In view of the unsatisfactory status of current treatments for COPD, there is an urgent need for alternative and more effective therapeutic approaches that will help to relieve patient symptoms and affect the natural course of COPD, inhibiting chronic inflammation and reversing the disease process or preventing its progression. However, new pharmacologic options have proved difficult to develop. Therefore, it is mandatory to optimize the use of the treatment options at our disposal. However, there are still fundamental questions regarding their use, including the step-up and step-down pharmacological approach, that require clarification to optimise the use of these drugs. It is likely that phenotyping COPD patients would help in identifying the right treatment for each COPD patient and improve the effectiveness of therapies.

KEYWORDS:

• Chronic obstructive pulmonary disease
• unmet needs
• COPD phenotypes
• treatment guidelines
• therapeutic options

Article highlights

• The appropriate drug management of COPD has been specified exhaustively in many national and international treatment guidelines or expert recommendations. It is still based on the use of bronchodilators (β₂-agonists and muscarinic receptor antagonists), possibly associated with an anti-inflammatory agent, especially an ICS. However, there are still fundamental questions that require clarification to optimize their use.

• Use of mucolytic agents, mainly NAC, and immunoregulators, mainly bacterial lysates, as add-on therapy, can be helpful in reducing the risk of AECOPDs. Use of continuous prophylactic antibiotics results in a clinically significant benefit in reducing exacerbations in COPD patients. However, because of concerns about antibiotic resistance and specific adverse effects, consideration of prophylactic antibiotic use should be mindful of the balance between benefits to individual patients and the potential harms to society created by antibiotic overuse.

• Drugs that are used for cardiovascular disease, such as statins, ACE inhibitors, and AT1-receptor blockers, and β-blockers may be useful in COPD because they improve survival and reduce the risk of AECOPD with or without hospitalization in patients with COPD. However, prospective interventional trials that should answer the important question as to whether the successful treatment of cardiovascular diseases associated with COPD also positively affects the course of the lung disease are now mandatory.

• COPD is particularly in need of a personalized medicine strategy because it is a very heterogeneous morbid condition. Therefore, it is important to group patients in phenotypes because subjects included in the same phenotype are expected to have similar disease, progression of disease, and response to treatments. Phenotyping COPD patients would be very useful to identify the right treatment for each COPD patient, and at the same time, improve the effectiveness of therapies, avoid treatments not indicated, and reduce adverse effects. The clinical importance of phenotypes is changing the paradigm of COPD management from evidence-based to personalized medicine. However, the personalized pharmacological strategy of COPD has still to be validated in future clinical studies. Nonetheless, we have some useful information that is allowing us to make better use of the treatment options at our disposal.

• In view of the unsatisfactory status of current treatments for COPD, there is an urgent need for alternative and more effective therapeutic approaches that not only will help relieve patient symptoms but will also affect the natural course of the disease, inhibiting chronic inflammation and reversing the disease process or preventing its progression. Whilst significant advances in our understanding of the cellular and molecular mechanisms involved in the pathogenesis of COPD have allowed for the identification of novel therapeutic targets, only few new pharmaceutical agents have been developed for clinical treatment and none of them can be considered truly innovative.

Declaration of interest

M Cazzola has participated as a lecturer, speaker, and advisor in scientific meetings and courses under the sponsorship of Almirall, AstraZeneca, Biofutura, Boehringer Ingelheim, Chiesi Farmaceutici, GlaxoSmithKline, Menarini Group, Lallemand, Mundipharma, Novartis, Pfizer, Verona Pharma, and Zambon. He is or has been a consultant to Chiesi Farmaceutici, Lallemand, Novartis, Verona Pharma, and Zambon. P Rogliani participated as a lecturer, speaker, and advisor in scientific meetings and courses under the sponsorship of Almirall, AstraZeneca, Biofutura, Boehringer Ingelheim, Chiesi Farmaceutici, GlaxoSmithKline, Menarini Group, Mundipharma and Novartis. M G Matera participated as a lecturer, speaker, and advisor in scientific meetings and courses under the sponsorship of Almirall, AstraZeneca, Boehringer Ingelheim, Chiesi Farmaceutici, GlaxoSmithKline, and Novartis. She has been a consultant to Chiesi Farmaceutici. The Department of Systems Medicine of the University of Rome Tor Vergata has been funded by Almirall, Boehringer Ingelheim, Novartis, and Zambon to conduct research in the respiratory field. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.