Triple Therapy with Budesonide/Glycopyrrolate/Formoterol Fumarate Improves Inspiratory Capacity in Patients with Asthma-Chronic Obstructive Pulmonary Disease Overlap

Int J Chron Obstruct Pulmon Dis. 2020 Feb 5:15:269-277. doi: 10.2147/COPD.S231004. eCollection 2020.

Abstract

Purpose: Asthma-chronic obstructive pulmonary disease overlap (ACO), characterized by airway limitation, is an important condition with high incidence and mortality. Although some guidelines recommend triple therapy with inhaled corticosteroids/long-acting muscarinic antagonists/long-acting β2 agonists, this treatment approach is based on the extrapolation of data from studies of asthma or chronic obstructive pulmonary disease (COPD) alone.

Methods: A 12-week, randomized, open-label cross-over pilot study was conducted in 19 patients with ACO to investigate the effect of triple therapy with glycopyrrolate (GLY) 50 µg/day on budesonide/formoterol fumarate (BUD/FORM) 640/18 µg/day. The study period included a 4-week wash-out, 4-week run-in, and 4-week treatment period. Respiratory function tests, fractional exhaled nitric oxide (FeNO), a COPD assessment test (CAT) and an asthma control questionnaire (ACQ) were carried out 0, 4, and 8 weeks after randomization.

Results: A total of 19 patients with stable ACO (19 males and no females) with a mean age of 70.7 ± 7.6 years (± standard deviation, SD; range 55-83 years) participated in this study. All patients were ex-smokers with a smoking history of 63.1 ± 41.1 pack-years (± SD). Mean values for inspiratory capacity (IC), an index of hyperinflation of the lung that causes exertional dyspnea and reduced exercise, were 1.93 L (± 0.47 L) after the run-in, 1.85 L (± 0.51 L) after the BUD/FORM dual therapy period and 2.11 L (± 0.58 L) after the BUD/GLY/FORM triple therapy period. IC values after the BUD/GLY/FORM triple therapy were significantly higher than those after the run-in (p < 0.02). FeNO values, ACQ, and CAT scores were not significantly different among the run-in, wash-out, and triple-therapy periods.

Conclusion: The present pilot study showed that triple therapy with BUD/GLY/FORM results in an improvement in lung function parameters including IC, indicating the potential value of triple therapy as standard treatment for ACO.

Keywords: asthma-COPD overlap; budesonide; formoterol fumarate; glycopyrrolate; triple therapy.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Adrenergic beta-2 Receptor Agonists / administration & dosage*
  • Adrenergic beta-2 Receptor Agonists / adverse effects
  • Aged
  • Aged, 80 and over
  • Asthma-Chronic Obstructive Pulmonary Disease Overlap Syndrome / diagnosis
  • Asthma-Chronic Obstructive Pulmonary Disease Overlap Syndrome / drug therapy*
  • Asthma-Chronic Obstructive Pulmonary Disease Overlap Syndrome / physiopathology
  • Bronchodilator Agents / administration & dosage*
  • Bronchodilator Agents / adverse effects
  • Budesonide, Formoterol Fumarate Drug Combination / administration & dosage*
  • Budesonide, Formoterol Fumarate Drug Combination / adverse effects
  • Cross-Over Studies
  • Female
  • Glucocorticoids / administration & dosage*
  • Glucocorticoids / adverse effects
  • Glycopyrrolate / administration & dosage*
  • Glycopyrrolate / adverse effects
  • Humans
  • Inspiratory Capacity / drug effects*
  • Japan
  • Lung / drug effects*
  • Lung / physiopathology
  • Male
  • Middle Aged
  • Muscarinic Antagonists / administration & dosage*
  • Muscarinic Antagonists / adverse effects
  • Pilot Projects
  • Recovery of Function
  • Time Factors
  • Treatment Outcome

Substances

  • Adrenergic beta-2 Receptor Agonists
  • Bronchodilator Agents
  • Budesonide, Formoterol Fumarate Drug Combination
  • Glucocorticoids
  • Muscarinic Antagonists
  • Glycopyrrolate