What pulmonologists think about the asthma–COPD overlap syndrome

Figures & data

Table 1 Responses to the questionnaire about ACOS administered before the debate

Epidemiology	n (%)
Of all the patients you see, give an approximation of the percentage with ACOS (mean [SD])	12.6 (7.0)
Do some patients have a mixed asthma–COPD phenotype? Yes	22 (84.6)
Diagnosis
Are the diagnostic criteria of ACOS well defined? Yes	5 (19.2)
Regarding the debate on the possible coexistence of asthma and COPD in the same patient, do you think it is:
Unnecessary. They do not coexist.	0
Inadmissible. This is an academic more than a practical question. In the end, the patients receive the same treatment.	1 (3.8)
Futile. The opinions among professionals are very conflicting, irreconcilable.	1 (3.8)
Admissible, but it is not well defined.	8 (30.8)
Essential. The experts should reach some agreement. It could have specific future therapeutic consequences.	16 (61.5)
In your opinion, the combination of criteria of asthma and COPD in the same patient is:
A specific phenotype of a disease. These are patients with COPD who have a history and criteria of allergic asthma.	8 (30.8)
A coincidence of the two diseases in the same patient. It is the overlapping of two prevalent diseases, not the phenotype of one of these diseases.	14 (53.8)
An invention. This does not exist. One disease always predominates another. The other characteristics act as diagnostic confounders.	2 (7.7)
None of the above.	2 (7.7)
What is your opinion of the ACOS criteria of the Spanish consensus? (multiple choice: more than one answer allowed)
They are adequate.	1 (3.8)
They are too complex.	9 (34.6)
They should be validated.	20 (76.9)
They are incomplete.	7 (26.9)
They are too many.	2 (7.7)
To what degree do you agree with the definition and diagnostic criteria of ACOS drawn up in the Spanish consensus?
I fully agree.	0
Partially, but in the main I agree.	9 (34.6)
Mid-position between agreement and disagreement.	8 (30.8)
Partially, but in the main I disagree.	6 (23.1)
I completely disagree.	3 (11.5)
I have no definite opinion.	0
Should there be main, major, and minor diagnostic criteria for ACOS?
Yes.	9 (34.6)
No.	5 (19.2)
I don’t know.	12 (46.2)
Which of the following criteria of ACOS do you consider to be adequate? (multiple choice: more than one answer allowed)
Very positive bronchodilator test.	13 (50.0)
At least two positive bronchodilator tests.	9 (34.6)
Elevated IgE.	11 (42.3)
History of atopy.	14 (53.8)
Previous history of asthma.	23 (88.5)
History of smoking.	19 (73.1)
Postbronchodilator FEV1/FVC <0.7	18 (69.2)
Elevated FENO.	14 (53.8)
Eosinophilia in sputum.	12 (46.2)
Eosinophilia in blood.	11 (42.3)
The diagnostic evaluation of the asthma component of ACOS in the Spanish consensus is:
Perfect, and well adjusted to the phenotype.	0
Partial, but sufficient for clinical practice.	7 (26.9)
Insufficient, since it does not include patients with nonallergic asthma.	15 (57.7)
Inadmissible, as there is no such phenotype.	3 (11.5)
Diagnostic evaluation of the asthma component of ACOS in the Spanish consensus should be:
Eliminated. There is no mixed asthma–COPD phenotype.	1 (3.8)
Redefined in depth, including patients with nonallergic asthma.	16 (61.5)
Partially modified, perhaps being simplified.	9 (34.6)
Fully maintained as defined by the consensus of experts.	0
The role of smoking in the pathogenesis of the combination of asthma and COPD in the same patient:
Is irrelevant. The symptoms and pulmonary function are important.	0
Is overevaluated. These patients may exist without having previously smoked. Requiring the presence of smoking undeservedly excludes patients with the syndrome.	3 (11.5)
Important, since it actually involves smoker or ex-smoker asthma patients.	18 (69.2)
Is essential. This phenomenon cannot exist without its presence or history.	5 (19.2)
Do you think the ACOS criteria of the Spanish consensus have contributed to the diffusion of the mixed asthma–COPD phenotype? Yes	21 (80.8)
Can ACOS change over time?
Yes.	14 (53.8)
No.	4 (15.4)
I don’t know.	8 (30.8)
Treatment
Does ACOS require differentiated treatment? Yes	23 (88.5)
From the following, select the first choice of pharmacological treatment for a patient with severe poorly controlled asthma and chronic airflow obstruction.
Combination of LABA/ICS + montelukast.	6 (23.1)
Combination of LABA/ICS + LAMA.	16 (61.5)
Combination of LABA/ICS + theophylline.	1 (3.8)
Combination of LABA/ICS + omalizumab.	3 (11.5)
From the following, select the first choice of pharmacological treatment for a patient with very severe ACOS.
Combination of LABA/ICS + montelukast.	1 (3.8)
Combination of LABA/ICS + LAMA.	25 (96.2)
Combination of LABA/ICS + theophylline.	0
Combination of LABA/ICS + roflumilast.	0
The commercial impact of the new bronchodilators for COPD and the greater risk of respiratory infections associated with inhaled steroids may make anti-inflammatory treatment in ACOS patients:
Absolutely underused, particularly in primary care.	1 (3.8)
Less used than it should be on being consigned to the characteristic treatment of COPD.	12 (46.2)
Minor. There is a great tradition of prescribing LABA + ICS in severe COPD.	8 (30.8)
Null. ICS continue to be the treatment of choice in asthma as well as ACOS.	5 (19.2)
Therapeutic management by specialties (pulmonology/primary care)
Should the criteria of ACOS be different for pulmonology and primary care?
Yes.	3 (11.5)
No.	19 (73.1)
I don’t know.	4 (15.4)
Appropriate diagnostic and therapeutic evaluation of patients with ACOS should:
Always be done by a primary care physician.	0
Always be done by a pulmonologist.	7 (26.9)
Be done according to the severity of the patient, with mild cases evaluated by primary care physicians and severe cases by pulmonologists.	6 (23.1)
Be done according to the quality of care and resources available in primary care of a determined health care area. If these are low, it should be done by a pulmonologist.	13 (50.0)
I don’t know.	0

Abbreviations: ACOS, asthma–COPD overlap syndrome; SD, standard deviation; FEV₁, forced expiratory volume in 1 second; FVC, forced vital capacity; FENO, fraction of exhaled nitric oxide in exhaled air; LABA, long-acting β₂-agonist; ICS, inhaled corticosteroids; LAMA, long-acting muscarinic antagonist.

Figure 1 Criteria preferred by the participants for the diagnosis of asthma–COPD overlap syndrome.

Abbreviations: FEV₁, forced expiratory volume in 1 second; FVC, forced vital capacity; FENO, fraction of nitric oxide in exhaled air.

Table 2 Classification of the importance of the criteria and applicability in specialized and primary care

	Very important criteria	Important criteria	Less important criteria
Specialized care
Very applicable	Very positive bronchodilator test (increase in FEV1 ≥15% and ≥400 mL compared to basal value) Previous history of asthma before 40 years of age	Positive bronchodilator test on two or more occasions Blood eosinophilia	Positive bronchodilator test Family history of atopy and/or asthma
Quite applicable	Elevated FeNO	Total IgE Positive methacholine test History of atopy Rhinitis of any type	Positive skin tests
Not very applicable	Eosinophilia in sputum Positive oral corticosteroid test		Increased or seasonal variability of symptoms Variability of peak flow >20%
Primary care
Very applicable	Previous history of asthma before 40 years of age	Eosinophilia in blood
Quite applicable	Very positive bronchodilator test	Rhinitis of any type Elevated total IgE Personal history of atopy	Family history of asthma and/or atopy
Not very applicable	Eosinophilia in sputum Elevated FeNO Positive oral corticosteroid test	Positive bronchodilator test on two or more occasions Positive methacholine test	Increased or seasonal variability of symptoms Positive skin tests Variability in peak flow >20% Positive bronchodilator test

Notes: The “very applicable” criteria were considered as such by more than 65% of the panel. The “quite applicable” criteria were considered as such by 50%–65%, and the “not very applicable” were considered as such by less than 50% of the panel. Very positive bronchodilator test means an increase in FEV₁≥15% and ≥400 mL compared to basal value. Positive bronchodilator test means an increase in FEV₁ ≥12% and ≥200 mL compared to basal value.

Abbreviations: FEV₁, forced expiratory volume in 1 second; FENO, fraction of nitric oxide in exhaled air.

Table 3 Case scenarios of patients and suggested diagnosis and treatment

Case definition	Diagnosis	Treatment
		First choice	Second choice
Case 1: A 62-year-old woman, smoker of 14 pack-years up to 10 years ago. She consulted for breathlessness with little effort. She had a history of frequent bronchitis during childhood and youth with unknown diagnosis. She did not report recent episodes of bronchitis or the use of antibiotics. Postbronchodilator spirometry: FEV1 (%) =67%; FEV1/FVC =0.61. Positive bronchodilator test with +14% and 320 mL increase in FEV1.	Asthma (or ACOS)	LABA/ICS	LABA/ICS + LAMA
Case 2: A 71-year-old man, smoker of one pack/day and accumulated consumption of 44 pack-years. He had a history of cough with daily expectoration since many months ago. A history of diagnosis of asthma at 21 years of age. He followed irregular treatment with theophyllines and salbutamol until the age of 45. He reported frequent exacerbations with an increase in dyspnea and mucopurulent expectoration treated with oral corticosteroids and antibiotics. He had never required hospitalization. Postbronchodilator spirometry: FEV1(%) =41%; FEV1/FVC =0.52. Negative bronchodilator test with +10% and 180 mL increase in FEV1.	ACOS (or COPD)	LABA/ICS ± LAMA	LABA/ICS + LAMA ± PDE4 inhibitor
Case 3: A 68-year-old man, smoker of ten cigarettes/day (accumulated consumption of 20 pack-years) who consulted for an acute episode of 2 days of evolution of an increase in dyspnea with purulent expectoration, without fever. He had not taken any treatment for his respiratory disease. In the stable phase, he presented with dyspnea with intermediate effort (he did not climb stairs) and spirometry results from 3 months previously with postbronchodilator values FEV1(%) =63%, FEV1/FVC =0.68, and positive postbronchodilator test with increase in FEV1 of 14% and 312 mL.	ACOS (or asthma)	LABA/ICS ± antibiotic	LABA/ICS + LAMA

Abbreviations: FEV₁, forced expiratory volume in 1 second; FVC, forced vital capacity; ACOS, asthma–COPD overlap syndrome; LABA, long-acting β₂-agonist; ICS, inhaled corticosteroids; LAMA, long-acting muscarinic antagonist.