VA Outlines Stepwise Treatment for Asthma-COPD Overlap Syndrome

Treatment Recommendations

The critical first step in the treatment of any patient with COPD or ACOS is to stop smoking or vaping nicotine and marijuana, the authors said. While smoking cessation is notoriously difficult for many patients, a number of products and medications can help, including nicotine gums and patches, nortriptyline, bupropion, cytosine and varenicline.

Patients with ACOS also should receive annual influenza vaccines and the 13- and 23-valent pneumococcal vaccines.

As for pharmacotherapies, inhalers are the first step for patients with asthma, COPD or ACOS.

The algorithm presented by the authors recommends starting patients with ACOS on a short-acting beta2 receptor agonist or a short-acting muscarinic receptor antagonist. These short-acting bronchodilators are used as rescue medications.

SABAs include albuterol and levalbuterol, which may be administered by metered dose inhaler or nebulizer. Ipratropium is the most common SAMA and comes in both nebulizer and inhaler forms. Some bronchodilators combine a SABA and SAMA, albuterol and ipratropium.

Patients with ACOS with Type 2 inflammatory activation then proceed to inhaled corticosteroids, if occasional use of a rescue inhaler is insufficient. Inhaled corticosteroids reduce inflammation by binding to glucocorticoid receptors. Drugs in this class include beclomethasone, budesonide, fluticasone and mometasone. They may be delivered by metered dose inhaler/hydrofluoroalkane inhaler, dry powder inhaler, or nebulizer.

Those with other types of ACOS may move to a long-acting muscarinic receptor or long-acting beta2 receptor agonist. LABAs stimulate bronchodilation by acting on the beta2 receptors, while LAMAs address the cholinergic pathway.

LAMAs include aclidinium, glycopyrrolate, tiotropium and umeclidinium. The drugs are delivered using specialized inhalers, the Respimat for tiotropium and glycopyrrolate, Pressair for aclidinium and Ellipta for umeclidinium. LABAs (indacaterol, arformoterol, formoterol, salmeterol and olodaterol) are administered via metered dose inhaler, nebulizer, or the Discus, Ellipta or Respimat inhalers.

“Treatment can be customized for each patient, because [ACOS] is not one disease,” Albertson said.

If those drugs do not provide sufficient symptom relief and control of exacerbations, combining an ICS with a LAMA or LABA is the next step, followed by triple therapy with ICS, LABA and LAMA. Combinations of LAMA/LABA delivered in single inhalers include umeclidinium/vilanterol, olodaterol/tiotropium, indacaterol/glycopyrrolate, and glycopyrrolate/formoterol.

Using the three types of medication—ICS, LABA, and LAMA—together provides better control for patients by targeting multiple pathways to keep the airways open. A recent study presented at the Western Society of Allergy, Asthma, and Immunology 2020 Annual Scientific Session in Hawaii found that adding the LAMA tiotropium bromide to ICS and LABA therapy led to fewer asthma-related exacerbations than simply increasing the dose of ICS and LABA.⁴

Patients with severe ACOS often prove refractory to inhaled corticosteroids and need additional medications. Options to try include phosphodiesterase inhibitors, chronic macrolides and leukotriene receptor antagonists or leukotriene synthesis inhibitors.

“In the clinical treatment of the ACOS patient, the phenotypical manifestations of that patient should drive the next pharmacological steps,” the authors wrote.

Those with evidence of Type 2 inflammatory pathway activation, atopic disease of the airways with elevated sputum or blood eosinophils and elevated IgE may benefit from immunotherapy or immunomodulating monoclonal antibody therapy, according to the algorithm.

“Patients with evidence of more Type 2 inflammation the ones most likely to respond” to these newer therapies, Albertson noted.

The VA/DoD Clinical Practice Guideline for the Primary Care Management of Asthma urges primary care practitioners to consult a pulmonologist or allergist before recommending any of the five U.S. Food and Drug Administration-approved biologic agents for asthma or ACOS—omalizumab, mepolizumab, benralizumab, reslizumab and dupilumab. Patients needing these medications should be referred to specialty care.

Based on the algorithm, non-Type 2 inflammation patients may be better served by trying medications used to reduce exacerbations in COPD patients such as roflumilast, theophylline or macrolide antibiotics.

The VA/DoD guidelines caution that patients on theophylline require routine monitoring of serum levels and should be managed by a specialist as it is associated with a number of potentially severe adverse reactions including arrhythmias, delirium, seizures, and death.

1. Rivera AC, Powell TM, Boyko EJ, et al. New-Onset Asthma and Combat Deployment: Findings From the Millennium Cohort Study. Am J Epidemiol. 2018;187(10):2136‐2144. doi:10.1093/aje/kwy112.
2. Global Initiative for Asthma/Global Initiative for Chronic Obstructive Lung Disease. Diagnosis of Diseases of Chronic Airflow Limitation: Asthma, COPD and Asthma-COPD Overlap Syndrome (ACOS). 2015.
3. Albertson TE, Chenoweth JA, Pearson SJ, Murin S. The Pharmacological Management of Asthma-Chronic Obstructive Pulmonary Disease Overlap Syndrome (ACOS). Expert Opin Pharmacother. 2020 Feb;21(2):213-231.
4. Chipps B, Mosnaim G, Mathur SK, Shaikh A, Khoury S, Gopalan G, Palli SR, Lamerato L, Casciano J, Dotiwala Z, Settipane R. Add-on tiotropium versus step-up inhaled corticosteroid plus long-acting beta-2-agonist in real-world patients with asthma. Allergy and Asthma Proceedings. 2020 May 15. DOI: 10.2500/aap.2020.41.200036.

Differential Diagnosis Asthma vs COPD

Sources: American Academy of Family Physicians. COPD and Asthma: Differential Diagnosis. 1 April 2017; Ray E and Kelly C. The overlap between asthma and COPD: a case study. Independent Nurse. 16 Oct 2019;2019(10).