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Review
. 2018 Sep 28:13:3003-3009.
doi: 10.2147/COPD.S177333. eCollection 2018.

Current appraisal of single inhaler triple therapy in COPD

Brian Lipworth  1 , Chris RuiWen Kuo  1 , Sunny Jabbal  1
Affiliations
Review

Current appraisal of single inhaler triple therapy in COPD

Brian Lipworth et al. Int J Chron Obstruct Pulmon Dis. .

Abstract

A single inhaler containing inhaled corticosteroid (ICS)/long-acting beta-agonist (LABA)/long-acting muscarinic antagonist (LAMA) is a more convenient way of delivering triple therapy in patients with COPD. Single triple therapy has been shown to be superior at reducing exacerbations and improving quality of life compared to LABA/LAMA, especially in patients with a prior history of frequent exacerbations and blood eosinophilia, who have ICS responsive disease. The corollary is that patients with infrequent exacerbations who are noneosinophilic may be safely de-escalated from triple therapy to LABA/LAMA without loss of control. Pointedly, there is a substantially increased risk of pneumonia associated with the triple therapy containing fluticasone furoate but not beclometasone dipropionate or budesonide. Since triple therapy is also better than ICS/LABA at reducing exacerbations and improving lung function, symptoms, and quality of life, this brings into question the rationale for using ICS/LABA. Hence, we propose a simplified pragmatic decision process based on symptoms, prior to exacerbation history, and blood eosinophils to select which patients should be given a single triple inhaler or LABA/LAMA. Differences in patient preference of inhaler device, formulations and drugs will also determine which triple inhaler prescribers elect to use.

Keywords: COPD; exacerbation; inhaled corticosteroid; long-acting beta-agonist; long-acting muscarinic antagonist; lung function.

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Conflict of interest statement

Disclosure Dr Lipworth reports grants and personal fees from AZ, personal fees and other from Teva, personal fees from Novartis, nonfinancial support from GSK, grants and personal fees from Chiesi, grants and personal fees from Boerhinger, during the conduct of the study; grants and personal fees from Meda/Mylan, grants from Janssen, grants from Roche, personal fees from Lupin, grants and personal fees from Boerhinger Ingelheim, grants and personal fees from Chiesi, personal fees from Cipla, personal fees from Sandoz, personal fees from Dr Reddys, grants and personal fees from Sanofi, personal fees from Circassia, outside the submitted work. Dr Kuo reports personal fees and nonfinancial support from Pfizer, outside the submitted work. Dr Jabbal reports personal fees and nonfinancial support from Chiesi Pharma, personal fees and nonfinancial support from Pfizer, nonfinancial support and other from Napp, personal fees and nonfinancial support from AstraZeneca, nonfinancial support from Teva, personal fees and nonfinancial support from Mylan, personal fees from Boehringer Ingelheim, outside the submitted work. The authors report no other conflicts of interest in this work.

Figures

Figure 1
Figure 1
Schematic to show effects of inhaled corticosteroid (ICS) moiety of single triple inhaler therapy in COPD. Notes: (A, B) The benefit is shown as attenuation of bronchial mucosal eosinophilic inflammation resulting in reduced exacerbations; (B, C) risk depicted as impaired mucociliary function with mucus retention and altered microbiome following initial viral infection, along with prolonged bronchial/alveolar ICS retention and resulting local immunosuppression, in turn producing consolidation (pneumonia).
Figure 2
Figure 2
Duration of lung retention with inhaled corticosteroids due to relative lipophilicity, which in turn determines pneumonia risk in COPD. Note: Fluticasone furoate (FF), fluticasone propionate (FP), budesonide (BUD), and beclometasone dipropionate (BDP: via its active metabolite 17-BMP) – schematically depicted to reflect their respective kinetic terminal elimination half lives (FF.FP.BUD/BDP). Abbreviation: 17-BMP, 17-beclometasone monopropionate.
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