Table 1.

Proposed diagnostic features of asthma and COPD overlap (ACO).

Study	Major Criteria	Minor Criteria	Diagnosis
Gibson, 2009 [3]	▪Clinical symptoms of chronic airway disease, FEV1/FVC < 70% ▪FEV1 <80% ▪Bronchial hyper-responsiveness defined as a PD15 < 12 mL (provocative dose of hypertonic saline that induces a 15% fall in FEV1)		3 major criteria
Soler-Cataluna, 2011 [11]	COPD plus: ▪Positive bronchodilator test defined by increase in FEV1 ≥ 15% and ≥400 mL ▪Sputum eosinophilia ▪History of asthma	COPD plus: ▪High total serum IgE ▪History of atopy ▪Positive bronchodilator test, i.e., increase in FEV1 ≥ 12% and ≥200 mL over baseline on ≥2 occasions	2 major criteria OR 1 major criterion AND 2 minor criteria
Koblizek, 2013 [12]	COPD plus: ▪Positive bronchodilator test defined by increase in FEV1 > 15% and >400 mL ▪Methacholine challenge test positivity ▪FENO ≥ 45 to 50 ppb and/or sputum eosinophils > 3% ▪History of asthma	COPD plus: ▪Mildly positive bronchodilator test, i.e., increase in FEV1 >12% and >200 mL ▪Elevated IgE ▪History of atopy	2 major criteria OR 1 major criterion AND 2 minor criteria
GINA/GOLD Criteria, 2014 [10]	More likely COPD if: ▪Onset age > 40 years ▪Persistence of symptoms ▪Daily symptoms with exertional dyspnea and good/bad days ▪Chronic cough and sputum precede onset of dyspnea, unrelated to triggers ▪Documented persistent airflow limitation (post-bronchodilator FEV1/FVC <70%) ▪Lung function abnormal between symptoms ▪Previous physician diagnosis of COPD, chronic bronchitis or emphysema ▪Heavy exposure to a risk factor (tobacco smoke, biomass fuel) ▪Symptoms slowly worsening over time (progressive course over years) ▪Rapid-acting bronchodilator treatment provides only limited relief ▪Chest radiograph with features of severe hyperinflation	More likely asthma if: ▪Onset age < 20 years ▪Variation in symptoms within short periods ▪Worsening of symptoms at night/early morning ▪Symptoms triggered by exercise, emotions/laughter, dust, or allergens’ exposure ▪Documented airflow limitation variability (peak flow, spirometry) ▪Lung function normal between symptoms ▪Prior physician diagnosis of asthma ▪Family history of asthma or atopy/eczema ▪No worsening of symptoms over time (symptoms vary either seasonally or from year to year) ▪May improve spontaneously or have an immediate response to bronchodilators or to inhaled steroids over weeks ▪Normal chest radiograph	If ≥3 items are present for either asthma or COPD, the patient is likely to have that disease A similar number of items for asthma and COPD is suggestive for ACO
Cosio, 2016 [13]	COPD plus: ▪History of asthma ▪Bronchodilator response to salbutamol > 15% and 400 mL	COPD plus: ▪IgE > 100 IU ▪History of atopy ▪Two separated bronchodilator responses to salbutamol > 12% and 200 mL ▪Blood eosinophils >5%	1 major criterion OR 2 minor criteria
Sin, 2016 [14]	COPD plus: ▪FEV1/FVC < 0.7 or LLN in patients ≥ 40 years of age ▪≥10 pack years of tobacco smoking OR equivalent indoor or outdoor air pollution exposure ▪Documented history of asthma before 40 years of age OR bronchodilator reversibility >400 mL in FEV1	COPD plus: ▪Documented history of atopy or allergic rhinitis ▪Bronchodilator reversibility of FEV1 ≥ 200 mL and 12% from baseline on ≥2 visits ▪Peripheral blood eosinophil count of ≥300 cells/mL	3 major criteria AND 1 minor criterion
Cataldo, 2017 [15]	ACO in a COPD patient: ▪High degree of variability in airway obstruction over time: FEV1 variation ≥ 400 mL ▪High degree of response to bronchodilators: >200 mL and 12% above baseline	ACO in a COPD patient: ▪Personal or family history of atopy and/or IgE sensitivity to one or more airborne allergens ▪Elevated blood or sputum eosinophils or increased FENO ▪Asthma diagnosed before the age of 40 ▪Symptoms’ variability ▪Age (in favor of asthma)	2 major criteria AND 1 minor criterion
	ACO in an asthma patient: ▪Persistence over time of airflow obstruction (FEV1/FVC <0.7 or <LLN) ▪Exposure to noxious particles or gases, with ≥10 pack years for smokers	ACO in an asthma patient: ▪Lack of response on acute bronchodilator tests ▪Reduced lung diffusion capacity ▪Little variability in airway obstruction ▪Age in favor of COPD (>40 years) ▪Presence of emphysema on chest CT scan
Miravittles, 2017 [16]	▪Age > 35 years ▪Postbronchodilator FEV1/FVC < 70% ▪≥10 pack years tobacco smoke	▪Current diagnosis of asthma ▪No current diagnosis of asthma but a bronchodilator response to albuterol ≥ 15% and 400 mL and/or blood eosinophils ≥ 300 cells/microL	3 major criteria AND 1 minor criterion

ACO: asthma COPD overlap; COPD: chronic obstructive pulmonary disease; IgE: immunoglobulin E; FE_NO: fraction of exhaled nitric oxide; ppb: parts per billion; FEV₁: forced expiratory volume in one second; FVC: forced vital capacity; IU: international units; LLN: lower limit of normal; PD15: provocative dose.