The asthma–COPD overlap syndrome: do we really need another syndrome in the already complex matrix of airway disease?

Figures & data

Figure 1 Prevalence of overlapping asthma and COPD in studies of varying designs in a cluster analysis (following a systematic literature search).

Notes: A systematic literature review of cluster analyses of asthma and COPD was performed. Articles from 2009 to September 1, 2014, dealing with prevalence, morbidity, and treatment of asthma–COPD overlap, were identified and reviewed. The prevalence of overlapping asthma and COPD was reported in epidemiological studies (•), studies in severe asthma (■), studies in adult asthma (▼), and studies in COPD (▲). Reproduced from Thorax, Gibson PG, McDonald VM. 70(7), 683–691. Copyright 2015. With permission from BMJ Publishing Group Ltd.¹⁰

Figure 2 Pathophysiology of asthma, COPD, and overlap.

Notes: Data taken from Postma et al²⁵ and Barnes et al.²⁷
Abbreviations: TGFβ, tumor growth factor β; T_H1, T-helper 1; T_C1, type 1 cytotoxic T cells.

Table 1 Inflammatory biomarkers in the diagnosis of asthma and COPD

	Asthma	COPD
Test for atopy (specific IgE and/or skin prick tests)	Modestly increases probability of asthma; not relevant in nonatopic asthma	Conforms to background prevalence; does not rule out COPD
FeNO	A high level (>50 ppb) in non-smokers supports a diagnosis of eosinophilic airway inflammation	Usually normal
	Lower in smoking asthmatics	Low in current smokers
Blood eosinophilia	Supports asthma diagnosis	May be present during exacerbations
Sputum inflammatory cell analysis	Role in differential diagnosis is not established in large populations

Note: Reproduced after permission from the Global Strategy for Diagnosis, Management and Prevention of COPD 2016 ©.¹⁵

Abbreviations: FeNO, fractional exhaled nitric oxide; IgE, immunoglobulin E.

Table 2 Major and minor criteria for the identification of the mixed COPD/asthma phenotype

Major criteriaa	Minor criteriaa
Very positive bronchodilator test (increase of FEV1 ≥15% and ≥400 mL over baseline)	High total IgE
Eosinophilia in sputum	Personal history of atopy
Personal history of asthma	Positive bronchodilator test (increase
(before the age of 40 years)	in FEV1 ≥12% and ≥200 mL over baseline) on two or more occasions

Notes: Adapted from Archivos de Bronconeumologica, 48(9): Soler-Cataluña JJ, et al; Consensus Document on the Overlap Phenotype COPD-Asthma in COPD, 331–337, Copyright (2012), with permission from Elsevier.⁷

a Two major criteria, or one major and two or more minor are strongly indicative of overlapping asthma and COPD.

Abbreviations: FEV₁, forced expiratory volume in 1 second; FVC, forced vital capacity; IgE, immunoglobulin E.

Table 3 Potential pharmacological and nonpharmacological treatment options in patients with asthma–COPD overlap

	Comments
Pharmacological
ICS	Limited supporting evidence; recommended in opinion-led guidelines, as required; ICS monotherapy is not indicated in patients with COPD
Long-acting bronchodilators (LABA and/or LAMA)	Limited supporting evidence; recommended in opinion-led guidelines, as required; LABA monotherapy is not indicated in patients with asthma
ICS/LABA	Limited supporting evidence; recommended in opinion-led guidelines, as required
ICS/LABA/LAMA	Limited supporting evidence; recommended in opinion-led guidelines, as required
Other (eg, biologicals, theophylline, LTRA, phosphodiesterase 4 inhibitors, macrolides; anti-leukotrienes, MABA, p38 MAPK inhibitors; 5-lipoxygenase inhibitor)	Very limited data in patients with overlapping asthma and COPD; some are still in development; none are approved in opinion-led guidelines
Vaccination	Recommended in opinion-led guidelines
Nonpharmacological
Smoking cessation advice and treatment	Recommended in opinion-led guidelines
Pulmonary rehabilitation	Recommended in opinion-led guidelines, as required; effective in patients with COPD
Bronchial thermoplasty	No known evidence available in patients with overlapping asthma and COPD
Treatment of comorbidities	Recommended in opinion-led guidelines, although limited evidence available regarding the impact of comorbidities on disease outcomes and treatment choice

Note: Data taken from Louie et al.⁶⁹

Abbreviations: ICS, inhaled corticosteroid; LABA, long-acting beta agonist; LAMA, long-acting muscarinic antagonist; LTRA, leukotriene receptor antagonists; MABA, dual pharmacophore with long-acting muscarinic antagonist and β2 agonist pharmacology; MAPK, mitogen-activated protein kinase.

Figure 3 Proposed algorithmic approach for patients with overlapping clinical characteristics of asthma and COPD.

Abbreviation: ICS, inhaled corticosteroid.

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