Treatable Traits in COPD – A Proposed Approach

Figures & data

Figure 1 Definition of therapeutic goals and treatable traits. The numbers and letters are for illustrative purposes only.

Table 1 Treatable Traits to Be Addressed in the First Phase

Treatable Trait	Trait Identification Marker	Therapeutic Options
Pulmonary
Airflow limitation	Post-bronchodilator FEV1/FVC < 0.7 or LLN	Bronchodilators, pulmonary rehabilitation
Exercise intolerance	6MWD (distance <350m), mMRC ≥ 2	Exercise, Pulmonary Rehabilitation
Chronic bronchitis	Cough and sputum for at least 3 months, for 2 years	Smoking cessation, mucolytics
Eosinophilic airway inflammation	Blood eosinophil count	Inhaled corticosteroids
Alpha-1 antitrypsin deficiency	Alpha-1 antitrypsin levels	Proceed to the second phase
Extrapulmonary
Nutritional state
Obesity	BMI > 30	Physical activity
Malnutrition	BMI < 20	Supplements
Behavioral
Low physical activity and sedentary lifestyle	Self-reported	Exercise plan
Smoking and other environmental exposures	Self-reported or exhaled concentration of CO ≥ 10 ppm	Cessation support, nicotine replacement therapy, varenicline, bupropion. Avoid other environmental exposures.
Poor inhalation technique	Direct observation, training devices	Education
Nonadherence to therapeutics	Prescription refill rate, chipped inhalers, self-report	Education, self-management support
Poor family/social support	Self-report, assessment of familial context	Family therapy; self-management support
Inhaler device polypharmacy	Self-report	Therapy re-evaluation

Abbreviations: BMI, body mass index; FEV₁, forced expiratory volume in the first second; FVC, forced vital capacity; LLN, lower limit of normal; mMRC, modified Medical Research Council dyspnoea scale; 6MWD, 6-minute walking distance.

Table 2 Treatable Traits to Be Addressed in the Second Phase

Treatable Trait	Trait Identification Marker	Therapeutic Options
Pulmonary
Chronic bronchitis	Cough and sputum for at least 3 months, for 2 years	Smoking cessation; mucolytics, macrolides, PDE-4 inhibitors
Chronic respiratory failure
Arterial hypoxemia	PaO2< 55 mmHg	Long-term oxygen therapy
Arterial hypercapnia	PaCO2 > 45 mm Hg	Non-invasive ventilation, lung transplant
Chronic bronchial infection	Sputum culture, quantitative PCR	Antibiotics
Bronchiectasis	Chest computed tomography	Drainage, macrolides, nebulized antibiotics, surgery, vaccination
Eosinophilic airway inflammation	Blood eosinophil count, FeNO	Inhaled corticosteroids, biologic therapy
Emphysema	Chest computer tomography, DLCO	Lung volume reduction surgery, Bronchoscopic lung volume reduction, Lung transplant
Lung hyperinflation	Decreased IC/TLC	Bronchodilators, pulmonary rehabilitation, bronchoscopic lung volume reduction, lung volume reduction surgery.
Pulmonary hypertension	BNP, Doppler echocardiography, right heart catheterization	Oxygen/NIV/Lung transplant
Alpha-1 antitrypsin deficiency	Alpha-1-antitrypsin levels, phenotype, genotype	α1-antitrypsin replacement
Exercise-induced oxygen desaturation	Desaturation ≥ 4% on SpO2 and minimum SpO2 < 90% during 6MWD test	Ambulatory oxygen therapy if demonstrated clinical benefit
Extrapulmonary
Deconditioning	6 MWD, Cardio-pulmonary exercise testing	Exercise, pulmonary rehabilitation
Comorbidities
Cardiovascular disease	BNP, Electrocardiogram, Doppler echocardiography	ACE inhibitors, diuretics, β blockers
Anxiety and depression	Questionnaires, psychological or psychiatric assessment	Cognitive behavioral therapy, pharmacotherapy
Obstructive sleep apnea	Questionnaires, polysomnography	Continuous positive airway pressure; weight loss, mandibular advancement splint
Osteoporosis	Low BMD (T-score ≤−2.5)	Smoking cessation, Diet, Exercise, Calcium, Vitamin D, Bisphosphonates
Systemic Inflammation	High sensitivity C-Reactive Protein	Statins
Gastro-esophageal reflux	Gastrointestinal endoscopy, pH monitoring	Proton pump inhibitors, H2 antagonists; surgery

Abbreviations: ACE, angiotensin-converting enzyme; BMD, bone mineral density; BNP, brain natriuretic peptide; DLCO, diffusing capacity for carbon monoxide; FeNO, fractional exhaled nitric oxide; IC, inspiratory capacity; NIV, non-invasive ventilation; PaO2, partial pressure of oxygen; PaCO2, partial pressure of carbon dioxide; PDE-4, phosphodiesterase type 4; SpO2, peripheral oxygen saturation; TLC, total lung capacity; 6MWD, six-minute walking distance.

Figure 2 Algorithm for COPD management based on the treatable traits strategy.

Abbreviations: CAT, COPD assessment test; COPD, chronic obstructive pulmonary disease; FEV₁, forced expiratory volume; mMRC, modified Medical Research Council dyspnea scale; TTs, treatable traits.

Table 3 Treatable Traits Associated with Increased Risk of Exacerbation*

Pulmonary

Eosinophilic airway inflammation^Citation30

Bronchiectasis^Citation118

Chronic bronchial infection^Citation80

Airflow limitation^Citation96,Citation120

Lung hyperinflation^Citation72,Citation75

Chronic bronchitis^Citation121,Citation122

Extrapulmonary

Obstructive sleep apnea^Citation123^–^Citation125

Cardiovascular disease^Citation59

Anxiety/ Depression^Citation126

Persistent systemic inflammation^Citation80

Cachexia^Citation127

Exercise intolerance^Citation128

Physical inactivity^Citation129,Citation130

Behavioral

Poor inhalation technique^Citation131,Citation132

Smoking and other environmental exposures^Citation133

Non-adherence^Citation134

Poor family/social support^Citation135

Note: *Treat identification markers and therapeutic options for each treatable trait are listed in Tables 1 and 2.

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