Asthma-COPD Overlap - Effectiveness of Long-Acting Muscarinic Antagonists

Introduction:

Asthma and chronic obstructive pulmonary disease (COPD) lead to around 15 % to 25 % of airway obstruction cases. Both disorders are considerably different but share a significant amount of clinical features. Over the past few years, considerable interest has been expressed in the group of patients who have overlapping characteristics of both diseases. Previously it was described as asthma-COPD overlap syndrome. The term “syndrome” is no longer used because it does not represent a separate disease entity but is a spectrum of overlapping features of both asthma and chronic pulmonary obstructive disease.

What Is Asthma and Chronic Obstructive Pulmonary Disease?

Asthma is a disease in which the airway becomes narrow and swells up. It may lead to the production of extra mucus, which makes breathing difficult and causes coughing. In addition, a whistling sound is produced while breathing, and shortness of breath is present.

Chronic pulmonary obstructive disease (COPD) is a chronic inflammatory lung disease that leads to obstructed airflow from the lungs. Clinical features include breathing difficulty, cough, mucus production, and wheezing.

A long-acting muscarinic antagonist significantly increases lung function in patients with overlapping asthma and chronic obstructive pulmonary disease (COPD). A long-acting muscarinic antagonist forms the basis of COPD and plays a significant role in asthma. As the symptoms of asthma-COPD overlap are more severe than those of asthma or COPD alone, the long-acting muscarinic antagonist is sometimes prescribed. However, the therapeutic benefit of long-acting muscarinic antagonists in asthma-COPD overlap syndrome has not yet been confirmed.

What Are the Types of Asthma-COPD Syndrome?

The asthma-COPD involves an airflow obstruction that cannot be reversed completely. The asthma-COPD syndrome can be of two types depending on the following factors:

1. Asthma with partially reversible airflow obstruction with or without emphysema and reduced carbon monoxide diffusing capacity.

2. Chronic obstructive pulmonary disease with emphysema accompanied by reversible or partially reversible airflow obstruction, with or without environmental allergies or reduced carbon monoxide diffusing capacity.

What Are Long-Acting Muscarinic Antagonists?

Long-acting muscarinic receptor antagonists cause airflow obstruction by counteracting the parasympathetic bronchoconstriction effects within the airways. For many years, Tiotropium (HandiHaler, Respimat) has been an essential long-acting muscarinic antagonist for chronic obstructive pulmonary disease (COPD) management. In recent years, new agents have been developed and introduced into clinical practice, that includes:

• Aclidinium bromide.

• Glycopyrronium bromide.

• Tiotropium.

• Umeclidinium bromide.

Aclidinium: Aclidinium is administered twice daily. It results in marginal improvements in quality of life and reduces the number of patients with exacerbations requiring hospitalization. Aclidinium has also proved to reduce the rate of moderate to severe exacerbations.

Glycopyrronium: It is administered once daily. It has shown significant improvement in spirometry and a reduction in the rate of moderate to severe exacerbations, but no difference in the quality of life is noticed.

Tiotropium: It is administered once daily. Tiotropium results in improved quality of life and reduced exacerbation rates. Compared to Ipratropium, Tiotropium had beneficial effects on quality of life, dyspnoea, and exacerbation rates.

Umeclidinium: It is administered once daily. Umeclidinium significantly improves lung function, dyspnoea, and quality of life and shows better improvement than Tiotropium, but there were no significant differences between Umeclidinium and Tiotropium for dyspnoea.

Adverse effects of these long-term muscarinic antagonists include:

• Dry mouth.

• Constipation.

• Urinary retention.

The long-term muscarinic antagonists are advantageous in terms of onset of action, symptom control, and safety. In addition, a number of long-term muscarinic antagonists are being developed for combination treatments with long-acting β2-agonists (LABAs) or inhaled glucocorticosteroids, potentially essential treatment options for patients who require combination therapy to produce an optimal therapeutic response as the disease progresses.

What Are the Risks and Complications Associated With Asthma-COPD Syndrome?

The patients with asthma-COPD overlap experience life-threatening complications compared to asthma and chronic obstructive pulmonary disease alone. Risk factors for this disease include smoking and atopy in the younger population with chronic pulmonary obstructive disease. For the development of an effective treatment plan, it is essential to identify the relevant organism and start antibiotic therapy accordingly. In addition, it is necessary to evaluate the effect on the functioning of the lungs, acute exacerbations, and mortality rate. It is difficult to differentiate between asthma and chronic obstructive pulmonary disease in the clinical setting due to their overlying features.

What Are the Goals of the Treatment?

The goal of the treatment in asthma-COPD syndrome is to reduce the symptoms and risks of impairment, including acute exacerbations, decreased lung functions, and adverse effects of drug treatment. In addition, the target of the therapy is to disturb the pathobiology that causes asthma, chronic obstructive pulmonary disease, and asthma-COPD overlap syndrome. The ultimate goal of the treatment is to improve smooth muscle dysfunction and reduce airway inflammation.

What Is the Role of Long-Acting Muscarinic Antagonists in Asthma-COPD Overlap Treatment?

The targeted drug includes receptors of the parasympathetic and sympathetic nervous systems that end in the tracheobronchial tree, hypertrophied bronchial smooth muscles, the complex cytokine network activated by infections, and cellular and humoral processes, among others that contribute to airway inflammation and smooth muscle bronchoconstriction. The long-acting muscarinic antagonists aim to treat mucociliary dysfunction, chronic infections with advanced immunosenescence, and pulmonary emphysema. The patient's drug therapies should be based on the pathophysiology of the involved microorganism. Drugs for treating the asthma-COPD syndrome can be divided into:

• Narrow spectrum (specific for asthma or chronic obstructive pulmonary disease). Examples of narrow-spectrum drugs include leukotriene receptor antagonists (LTRAs) and monoclonal antibodies, like Omalizumab, for the treatment of asthma.

• Broad-spectrum (effective for both asthma and chronic pulmonary obstructive disease). Broad-spectrum drugs may include bronchodilators, corticosteroids, Theophylline, and antibiotics, which have ‘dual efficacy’ and can treat asthma and chronic pulmonary obstructive disease (COPD).

Conclusion:

Asthma-chronic obstructive pulmonary disease (COPD) overlap syndrome is not adequately recognized as this condition has not gained much attention during clinical trials. Morbidity from asthma-COPD syndrome can lead to coughing, wheezing, mucus production, shortness of breath on exertion, and adverse effects of drug treatments. In addition, mortality can result from frequent exacerbations and complications, including acute respiratory failure. To prevent these complications, the patient is advised to quit smoking (in the case of a regular smoker) to help decrease the risk of lung cancer and other heart diseases. Furthermore, regular vaccination against pneumococcal pneumonia can also prevent some infections.

The cases of this syndrome have not been appropriately studied due to strict inclusion and exclusion criteria that exclude asthma patients from chronic pulmonary obstructive disease patients from asthma studies.