What are the Treatable Traits

What are the Treatable Traits

Treatable traits are phenotypic or endotypic characteristics which can include comorbidities (such as anxiety, vocal cord dysfunction and reflux), risk factors (such as smoking and bone density) and self-management skills (such as adherence and inhaler technique). To be considered a trait each characteristic must be clinically relevant, identifiable and measurable using validated trait identification markers, and treatable. Treatable Traits are recognised within three domains: pulmonary traits, extrapulmonary traits and behavioural/risk-factors. With advances in research and knowledge, new traits are always being considered and added. 

Pulmonary traits

TraitTrait identification marker/diagnostic criteriaPossible treatmentsEvidence level I–IV #
Airway smooth muscle contractionBronchodilator reversibility, peak expiratory flow variability, airway hyperresponsivenessBronchodilators:
Maintenance: LABA/LAMA;
Rescue: SABA/SAMA/rapid-acting LABA
I
Systemic allergic inflammationElevated serum IgEAnti-IgE monoclonal antibody therapyI
DyspnoeaDyspnoea score ≥2, modified Medical Research Council scalePulmonary rehabilitation, breathing retrainingI
Emphysema (loss of elastic recoil)Chest CT, plethysmography, lung complianceSmoking cessation, lung volume reduction surgery, lung transplantation, α1-antitrypsin replacement if deficientI
Airway inflammation (eosinophilic)Sputum eosinophils ≥3% and/or FENO ≥30 ppb and/or blood eosinophils ≥0.3×109 cells·L−1Corticosteroids, anti-IL-5, -13, -4 monoclonal antibody therapyI-II
Pulmonary hypertensionDoppler echocardiography, brain natriuretic peptide, right heart catheterisationOxygen therapy, pulmonary vasodilator therapy, lung transplantationI-II
BronchiectasisHigh-resolution chest CTPhysiotherapy, mucociliary clearance techniques, macrolides, pulmonary rehabilitation, vaccinationI–II
Bacterial colonisationPresence of a recognised bacterial pathogen in sputum (sputum culture, quantitative PCR)Antibiotics and tailored antibiotic written action plan for infectionsII
Airway inflammation (neutrophilic)Sputum neutrophils ≥61%Macrolides, tetracyclines, roflumilastII
Cough reflex hypersensitivityCapsaicin challenge, cough counts, cough questionnaireSpeech pathology intervention, gabapentinII
Mucus hypersecretion/ Chronic BronchitisVolume ≥25 mL of mucus produced daily for the past week in the absence of an infection/ COPD assessment tool: CAT 1 (cough) and 2 (sputum) items scores ≥3Mucociliary clearance techniques with a physiotherapist, inhaled hypertonic saline, macrolidesII

Hypoxaemia

PaO2 ≤55 mmHg; PaO2 56–59 mmHg and evidence of complications of hypoxaemia (e.g. pulmonary hypertension, polycythaemia, right-sided heart failure)Domiciliary oxygen therapyII

 

LABA: long-acting β2-agonists; LAMA: long-acting muscarinic antagonist; SABA: short-acting β2-agonists; SAMA: short-acting muscarinic antagonist; IgE: immunoglobulin E; CT: computed tomography; IL: interleukin; PaO2: partial pressure of oxygen. #: National Health and Medical Research Council (NHMRC) level of evidence currently available for the management/treatment of each trait; : studies examining the effectiveness of different treatments in bronchiectasis in general, not specifically in chronic airways disease patients with coexisting bronchiectasis.

 

Extrapulmonary traits

TraitTrait identification marker/diagnostic criteriaPossible treatmentsEvidence level I–IV #
DepressionQuestionnaires (e.g. HADS depression domain score ≥8, GADS score >5), psychologist/liaison psychiatrist assessmentCBT, pharmacotherapyI
AnxietyQuestionnaires (e.g. HADS anxiety domain score ≥8), psychologist/liaison psychiatrist assessmentPharmacotherapy (i.e., anxiolytics/antidepressants), breathing retraining, CBTI
Dysfunctional breathingNijmegen Questionnaire Total score ≥23, B-PAT (breathing pattern assessment tool) score >4, breath holding time, manual assessment of respiratory motion (MARM)Breathing retrainingI
Physical inactivity and sedentary behaviourActigraphy, International Physical Activity QuestionnairePulmonary rehabilitation, physical activity, breaking bouts of sedentary activityI
Overweight/obesityOverweight: BMI 25–29.9 kg·m−2
Obesity: BMI ≥30 kg·m−2
Caloric restriction, exercise, bariatric surgery, pharmacotherapyI–II
DeconditioningCardiopulmonary exercise testing, 6MWTStructured exercise programme, rehabilitationI+, II
RhinosinusitisHistory and examination, imaging (sinus CT), Sino-Nasal Outcome Test (SNOT-22)Topical corticosteroids, leukotriene receptor antagonists, antihistamines, surgery, intranasal saline lavageII
VCDQuestionnaires (e.g. Pittsburgh ≥4), laryngoscopy, dynamic neck CT, inspiratory flow–volume curveSpeech pathology intervention, laryngeal botulinum toxin, gabapentin/pregabalin, psychology/psychiatryII
Systemic inflammationLeukocyte count >9×109 cells·L−1or high-sensitivity CRP >3 mg·L−1StatinsII
AnaemiaMales: Hb <140 g·L−1
Females: Hb <120 g·L−1
Haematinic (iron/B12) supplementationI+, IV
Cardiovascular diseaseDoppler echocardiography, Electrocardiogram, brain natriuretic peptidePharmacotherapy (β-blockers, diuretics, angiotensin-converting enzyme inhibitors), surgeryII
GORDQuestionnaires, gastrointestinal endoscopy, pH monitoringAnti-reflux lifestyle measures, antacids, proton pump inhibitors, fundoplication surgeryII
OSAQuestionnaires (i.e., STOP-Bang Questionnaire), polysomnographyCPAP, mandibular advancement splint, positional therapy, weight lossIII-2

 

HADS: hospital anxiety and depression scale; GADS: Goldberg Anxiety and Depression Scale; CBT: cognitive behavioural therapy; BMI: body mass index; 6MWT: 6-min walk test; VCD: vocal cord dysfunction; CRP: C-reactive protein; Hb: haemoglobin; GORD: gastro-oesophageal reflux disease; OSA: obstructive sleep apnoea; CPAP: continuous positive airway pressure. #: NHMRC level of evidence currently available for the management/treatment of each trait; : currently research only; +: evidence from the general population

 

Behaviour/risk-factor traits

TraitTrait identification marker/diagnostic criteriaPossible treatmentsEvidence level I–IV #
Suboptimal inhaler techniqueDirect observation and standardised assessment checklists, assessment via chipped inhalersEducation including demonstration and regular reassessmentI
Suboptimal adherencePrescription refill rates, self-reported use of <80% of prescribed medication, chipped inhalers, FENO suppression test, measurement of drug concentrationsSelf-management support, education, simplification of medication regime (i.e., reduce number of medications, frequency of doses and number of devices)I
SmokingSelf-reported current smoking, elevated exhaled carbon monoxide, urinary cotinineSmoking cessation counselling ± pharmacotherapyI
Side-effects of treatmentsPatient report, monitored withdrawalOptimisation of treatment, alternative therapy, change deviceI
Absence of a written action planPatient does not possess a written action plan, or reports not using the prescribed plan during exacerbationsIndividualised self-management education with a written action planI
Exercise intolerance<350 m on 6MWTPulmonary rehabilitationI
Decreased bone mineral density (osteoporosis)T-score ≤−2.5Pharmacotherapy based on osteoporosis guidelines, vitamin D supplementation, resistance trainingI, II
SarcopeniaAppendicular skeletal muscle mass index:
Males <7.26 kg·m−2
Females <5.45 kg·m−2
Diet (high protein), resistance trainingI, II

#: NHMRC level of evidence currently available for the management/treatment of each trait; : evidence from the general population.