Baseline Characteristics and Maintenance Therapy Choice on Symptom Control, Reliever Use, Exacerbation Risk in Moderate-Severe Asthma: A Clinical Modelling and Simulation Study.

INTRODUCTION: Although some factors associated with asthma symptom deterioration and risk of exacerbation have been identified, these are not yet fully characterised. We conducted a clinical modelling and simulation study to understand baseline factors affecting symptom control, reliever use and exacerbation risk in patients with moderate-severe asthma during follow-up on regularly dosed inhaled corticosteroid (ICS) monotherapy, or ICS/long-acting beta2-agonist (LABA) combination therapy. METHODS: Individual patient data from randomised clinical trials (undertaken between 2001 and 2019) were used to model the time course of symptoms (n = 7593), patterns of reliever medication use (n = 3768) and time-to-first exacerbation (n = 6763), considering patient-specific and extrinsic factors, including treatment. Model validation used standard graphical and statistical criteria. Change in symptom control scores (Asthma Control Questionnaire 5 [ACQ-5]), reduction in reliever use and annualised exacerbation rate were then simulated in patient cohorts with different baseline characteristics and treatment settings. RESULTS: Being a smoker, having higher baseline ACQ-5 and body mass index affected symptom control scores, reliever use and exacerbation risk (p < 0.01). In addition, low forced expiratory volume in 1 s percent predicted, female sex, season and previous exacerbations were found to contribute to a further increase in exacerbation risk (p < 0.01), whereas long asthma history was associated with more frequent reliever use (p < 0.01). These effects were independent from the underlying maintenance therapy. In different scenarios, fluticasone furoate (FF)/vilanterol was associated with greater reductions in reliever use and exacerbation rates compared with FF or fluticasone propionate (FP) alone or budesonide/formoterol, independently from other factors (p < 0.01). CONCLUSIONS: This study provided further insight into the effects of individual baseline characteristics on treatment response and highlighted significant differences in the performance of ICS/LABA combination therapy on symptom control, reliever use and exacerbation risk. These factors should be incorporated into clinical practice as the basis for tailored management of patients with moderate-severe asthma.

In this study we quantified how individual baseline patient characteristics at the start of treatment influence the response to regular maintenance medication. Specifically, using computer modelling and simulations based on data from individual patients enrolled into clinical trials in moderate­severe asthma, we predicted how much reliever inhaler they need, how well they rate their asthma control, and how likely an asthma attack (exacerbation) is to occur within the next 12 months. Simulation scenarios were then implemented to evaluate opportunities to improve and personalise real-life management of patients in clinical practice. Considering symptom control level, reliever use and other patient-specific factors at the start of treatment, we assessed how well maintenance therapy with inhaled corticosteroids/bronchodilators contributes to symptom improvement and/or reduction in the risk of asthma attacks. These scenarios show that current smokers, people with higher asthma symptom scores, who are obese, and have a longer history of asthma tend to use their reliever inhalers more often. Moreover, this was linked to a higher risk of having an asthma attack and worse symptom control. This pattern appears to compensate in most cases for the effect of the same baseline factors on symptom control. Switching patients who are not responding well to initial treatment with the inhaled corticosteroid, fluticasone propionate, to fluticasone furoate/vilanterol resulted in a significantly greater reduction in reliever inhaler use and risk of asthma attack, compared with those switched to budesonide/formoterol. These findings highlight the importance of tailored choices for optimal management of patients with moderate­severe asthma.

Biologics in T2 Severe Asthma: Unveiling Different Effectiveness by Real-World Indirect Comparison.

Background: Indirect comparison among biologics in severe asthma (SA) is a challenging but desirable goal for clinicians in real life. The aim of the study is to define characteristics of a biologic-treated T2-driven-SA population and to evaluate the effectiveness of biologic treatments in a real-world setting by variation in intra/inter-biologic parameters in an up to 4-year follow-up. Methods: Demographic, clinical, functional, and biological characteristics were evaluated retrospectively in 104 patients recruited until July 2022 at baseline (T0) and over a maximum of 4 years (T4) of biologic therapy (omalizumab/OmaG = 41, from T0 to T4, mepolizumab/MepoG = 26, from T0 to T4, benralizumab/BenraG = 18, from T0 to T2, and dupilumab/DupiG = 19, from T0 to T1). Variations of parameters using means of paired Delta were assessed. Results: At baseline, patients had high prevalence of T2-driven comorbidities, low asthma control test (ACT mean 17.65 ± 4.41), impaired pulmonary function (FEV1 65 ± 18 %pred), frequent exacerbations/year (AEs 3.5 ± 3), and OCS dependence (60%). DupiG had lower T2 biomarkers/comorbidities and AEs, and worse FEV1 (57 ± 19 %pred) compared to other biologics (p < 0.05). All biologics improved ACT, FEV1%, FVC%, AEs rate, and OCS use. FEV1% improved in MepoG and BenraG over the minimal clinically important difference and was sustained over 4 years in OmaG and MepoG. A significant RV reduction in OmaG (T4) and DupiG (T1), and BenraG normalization (T2) of airflow limitation were found. We observed through inter-biologic parameters pair delta variation comparison a significant nocturnal awakenings reduction in BenraG vs. OmaG/MepoG, and neutrophils reduction in BenraG/DupiG vs. OmaG. Conclusions: Indirect comparison among biologics unveils clinical and functional improvements that may mark a different effectiveness. These results may highlight the preference of a single biologic compared to another with regard to specific treatable traits.

Impact of comorbidities on EQ-5D quality-of-life index in severe asthma.

Background: Severe asthma pathology encompasses a wide range of pulmonary and extrapulmonary treatable traits with a high prevalence of comorbidities. Although asthma-specific health-related quality-of-life measures are most sensitive to changes in asthma control, generic measures, such as EQ-5D-5L (EuroQol 5-Dimension 5-Level questionnaire), are potentially better for capturing the impact of comorbidities. Objective: We sought to examine the impact of pulmonary and extrapulmonary treatable traits on quality of life at initial severe asthma assessment, and to compare the characteristics of those patients whose quality of life does and does not improve during follow-up at severe asthma centers. Methods: Patients' characteristics at baseline assessment within the UK Severe Asthma Registry were compared by EQ-5D-5L utility index quartile. Patients with follow-up review data were stratified by change in EQ-5D-5L utility index from baseline to follow-up, and characteristics similarly examined. Results: Patients in the quartiles with worst dysutility at baseline were observed to exhibit more treatable traits and in particular extrapulmonary traits associated with cumulative systemic corticosteroids, including obesity, anxiety/depression, and osteoporosis. In those patients whose quality of life improved over follow-up, a reduction in exacerbations, uncontrolled symptoms, and requirement for maintenance oral corticosteroids were observed. Conclusions: Both pulmonary and extrapulmonary treatable traits are important determinants of quality of life in severe asthma. Comorbidities associated with cumulative systemic corticosteroid exposure are particularly associated with worse quality of life, emphasizing the importance of early identification and management of severe asthma before comorbidities develop.

Contemporary Concise Review 2023: Asthma.

Asthma research and management needs to meet the priorities of the end user-patients, carers and clinicians. A better understanding of the natural history of asthma and the progression of disease has highlighted the importance of early identification of patients with asthma and the potential role of early intervention. Management of mild asthma requires a consistent approach with the same detail and consideration used when managing severe disease. Evidence around treatable traits approaches continues to evolve, supporting the role of a personalized medicine in asthma. Oral corticosteroid (OCS) stewardship continues to be an urgent issue in asthma management. Strategies to taper OCS doses and the implementation of biologic therapies for their steroid sparing benefits will be important steps to address this problem. The concept of remission in asthma provides an ambitious target and treatment outcome.

Understanding Breathlessness Burden and Psychophysiological Correlates in Asthma.

BACKGROUND: Breathlessness is a disabling symptom, with complexity that is often under-recognized and undertreated in asthma. OBJECTIVE: To highlight the burden of breathlessness in people with severe compared with mild-to-moderate asthma and identify psychophysiological correlates of breathlessness. METHODS: This was a cross-sectional study of people with mild-to-severe asthma, who attended 2 in-person visits to complete a multidimensional assessment. The proportion of people with mild-to-moderate versus severe asthma who reported physically limiting breathlessness (modified Medical Research Council [mMRC] dyspnea score ≥2) was compared. Psychophysiological factors associated with breathlessness in people with asthma were identified via a directed acyclic graph and explored with multivariate logistic regression to predict breathlessness. RESULTS: A total of 144 participants were included, of whom, 74 (51%) had mild-to-moderate asthma and 70 (49%) severe asthma. Participants were predominantly female (n = 103, 72%) with a median (quartile 1, quartile 3) age of 63.4 (50.5, 69.5) years and body mass index (BMI) of 31.3 (26.2, 36.0) kg/m2. The proportion of people reporting mMRC ≥2 was significantly higher in those with severe- (n = 37, 53%) than those with mild-to-moderate (n = 21, 31%) asthma (P = .013). Dyspnoea-12 Total (8.00 [4.75, 17.00] vs 5.00 [2.00, 11.00], P = .037) score was also significantly higher in the severe asthma group. Significant predictors of physically limiting breathlessness were BMI, asthma control, exercise capacity, and hyperventilation symptoms. Airflow limitation and type 2 inflammation were poor breathlessness predictors. CONCLUSIONS: Over half of people with severe asthma experience physically limiting breathlessness despite treatment. Targeting psychophysiological factors, or traits, associated with breathlessness may help relieve this distressing symptom, which is of high priority to people with asthma.

A Simulation Study of the Effect of Clinical Characteristics and Treatment Choice on Reliever Medication Use, Symptom Control and Exacerbation Risk in Moderate-Severe Asthma.

INTRODUCTION: The relationship between immediate symptom control, reliever medication use and exacerbation risk on treatment response and factors that modify it have not been assessed in an integrated manner. Here we apply simulation scenarios to evaluate the effect of individual baseline characteristics on treatment response in patients with moderate-severe asthma on regular maintenance dosing monotherapy with fluticasone propionate (FP) or combination therapy with fluticasone propionate/salmeterol (FP/SAL) or budesonide/formoterol (BUD/FOR). METHODS: Reduction in reliever medication use (puffs/24 h), change in symptom control scores (ACQ-5), and annualised exacerbation rate over 12 months were simulated in a cohort of patients with different baseline characteristics (e.g. time since diagnosis, asthma control questionnaire (ACQ-5) symptom score, smoking status, body mass index (BMI) and sex) using drug-disease models derived from large phase III/IV clinical studies. RESULTS: Simulation scenarios show that being a smoker, having higher baseline ACQ-5 and BMI, and long asthma history is associated with increased reliever medication use (p < 0.01). This increase correlates with a higher exacerbation risk and higher ACQ-5 scores over the course of treatment, irrespective of the underlying maintenance therapy. Switching non-responders to ICS monotherapy to combination therapy after 3 months resulted in immediate reduction in reliever medication use (i.e. 1.3 vs. 1.0 puffs/24 h for FP/SAL and BUD/FOR, respectively). In addition, switching patients with ACQ-5 > 1.5 at baseline to FP/SAL resulted in 34% less exacerbations than those receiving regular dosing BUD/FOR (p < 0.01). CONCLUSIONS: We have identified baseline characteristics of patients with moderate to severe asthma that are associated with greater reliever medication use, poor symptom control and higher exacerbation risk. Moreover, the effects of different inhaled corticosteroid (ICS)/long-acting beta agonist (LABA) combinations vary significantly when considering long-term treatment performance. These factors should be considered in clinical practice as a basis for personalised management of patients with moderate-severe asthma symptoms.

In this study we looked at how different factors affect the response to asthma treatment in people with moderate to severe asthma who are taking regular medication. Specifically, we wanted to quantify how much asthma duration, differences in the degree of symptom control and lung function, as well as smoking habit, body weight, and sex influence how well someone responds to regular maintenance therapy. Using computer simulations based on models obtained from data in a large patient population with moderate­severe asthma, we explored scenarios that reflect real-life management of patients undergoing treatment with inhaled corticosteroids alone or in combination with long-acting beta agonists over a 12-month period. We looked at how much reliever inhaler they use, how well they rate their asthma control, and how often they have asthma attacks. By considering these results together, we evaluated how well the treatments work on ongoing symptoms and/or reduce the risk of future asthma attacks. Our simulations showed that smokers, people with higher asthma symptom scores, who are obese, and have a longer history of asthma tend to use their reliever inhalers more often. This was linked to a higher risk of having asthma attacks and worse symptom control. Switching those patients who do not respond well to their initial treatment with corticosteroid to combination therapy reduced how much reliever inhaler they need. Also, the effects of fluticasone propionate/salmeterol combination therapy were greater than budesonide/formoterol. In conclusion, our study found that certain patient characteristics can predict how well someone responds to asthma treatment.

Treatable traits and exacerbation risk in patients with uncontrolled asthma prescribed GINA step 1-3 treatment: A nationwide asthma cohort study.

BACKGROUND AND OBJECTIVE: Uncontrolled asthma in patients treated for mild/moderate disease could be caused by non-pulmonary treatable traits (TTs) that affect asthma control negatively. We aimed to identify demographic characteristics, behavioural (smoking) and extrapulmonary (obesity, comorbidities) TTs and the risk for future exacerbations among patients with uncontrolled asthma prescribed step 1-3 treatment according to the Global Initiative for Asthma (GINA). METHODS: Twenty-eight thousand five hundred eighty-four asthma patients (≥18 y) with a registration in the Swedish National Airway Register between 2017 and 2019 were included (index-date). The database was linked to other national registers to obtain information on prescribed drugs 2-years pre-index and exacerbations 1-year post-index. Asthma treatment was classified into step 1-3 or 4-5, and uncontrolled asthma was defined based on symptom control, exacerbations and lung function. RESULTS: GINA step 1-3 included 17,318 patients, of which 9586 (55%) were uncontrolled (UCA 1-3). In adjusted analyses, UCA 1-3 was associated with female sex (OR 1.34, 95% CI 1.27-1.41), older age (1.00, 1.00-1.00), primary education (1.30, 1.20-1.40) and secondary education (1.19, 1.12-1.26), and TTs such as smoking (1.25, 1.15-1.36), obesity (1.23, 1.15-1.32), cardiovascular disease (1.12, 1.06-1.20) and depression/anxiety (1.13, 1.06-1.21). Furthermore, UCA 1-3 was associated with future exacerbations; oral corticosteroids (1.90, 1.74-2.09) and asthma hospitalization (2.55, 2.17-3.00), respectively, also when adjusted for treatment step 4-5. CONCLUSION: Over 50% of patients treated for mild/moderate asthma had an uncontrolled disease. Assessing and managing of TTs such as smoking, obesity and comorbidities should be conducted in a holistic manner, as these patients have an increased risk for future exacerbations.

First Report of the Prevalence at Baseline and after 1-Year Follow-Up of Treatable Traits in Interstitial Lung Diseases.

Different factors, not limited to the lung, influence the progression of ILDs. A "treatable trait" strategy was recently proposed for ILD patients as a precision model of care to improve outcomes. However, no data have been published so far on the prevalence of TTs in ILD. A prospective, observational, cohort study was conducted within the ILD Program at the IRCCS Humanitas Research Hospital (Milan, Italy) between November 2021 and November 2023. TTs were selected according to recent literature and assigned during multidisciplinary discussion (MDD) to one of the following categories: pulmonary, etiological, comorbidities, and lifestyle. Patients were further divided into four groups according to their post-MDD diagnosis: idiopathic ILD, sarcoidosis, connective tissue disease-ILD, and other ILD. The primary study outcome was the prevalence of each TT in the study population. A total of 116 patients with ILD [63.9% male; median (IQR) age: 69 (54-78) years] were included in the study. All the TTs identified in the literature were found in our cohort, except for intractable chronic cough. We also recognized differences in TTs across the ILD groups, with less TTs in patients with sarcoidosis. This analysis provides the first ancillary characterization of TTs in ILD patients in a real setting to date.

Treatable Traits in Pregnant Women with Asthma.

BACKGROUND: Asthma is the most common chronic respiratory disease in pregnancy, affecting approximately 8-10% of pregnant women. Uncontrolled asthma is associated with adverse perinatal outcomes, including low birth weight, preterm birth, and maternal complications such as pre-eclampsia. SUMMARY: A current approach to the management of chronic airway diseases is based on targeting treatable traits. The aim of this review was to define treatable traits in pregnant women with asthma based on recent literature and to determine personalized treatment options according to these traits. Traits addressed in this review that may improve asthma control and pregnancy outcomes are fractional exhaled nitric oxide-based asthma monitoring and treatment, medication adherence and inhalation technique, impaired lung function, smoking cessation and comorbidity including psychological conditions (depression and anxiety), obesity, rhinitis, gastroesophageal reflux disease, chronic rhinosinusitis with or without nasal polyps, and sleep apnea. KEY MESSAGES: All the treatable traits discussed have the potential to improve asthma control and pregnancy outcomes in pregnant women with asthma. Further research is needed to determine which management approaches are best to improve asthma control during pregnancy, to identify other relevant treatable traits, and to determine whether the treatable trait approach is feasible and beneficial in pregnant women with asthma.

Clinical Benefits of Targeting Treatable Traits in Asthma and Chronic Obstructive Pulmonary Disease.

Asthma and chronic obstructive pulmonary disease (COPD) have long been debated regarding their similarities and differences in clinical presentation and pathology. There has also been a discussion about how common therapeutics should be used differently for each disease. Traditionally, a "one size fits all" stepwise treatment has been chosen based on the severity of each case after categorizing the diseases, such as asthma or COPD. However, recently, the need for a precise approach for the treatment of individual patients beyond the disease category has been emphasized, especially in severe cases. To achieve precise personalized therapy, it has become necessary to focus on the individual phenotypes and underlying causal molecular mechanisms (endotypes) and to identify key therapeutic targets, which are called treatable traits. This review discusses the evidence for the importance of identifying treatable traits and therapeutic strategies based on the broader perspective of chronic obstructive airway disease rather than on individual diseases such as asthma or COPD.

Common Pathogeneses Underlying Asthma and Chronic Obstructive Pulmonary Disease -Insights from Genetic Studies.

Neither asthma nor chronic obstructive pulmonary disease (COPD) is a single disease consisting of a uniform pathogenesis; rather, they are both syndromes that result from a variety of basic distinct pathogeneses. Many of the basic pathogeneses overlap between the two diseases, and multiple basic pathogeneses are simultaneously involved at varying proportions in individual patients. The specific combination of different basic pathogeneses in each patient determines the phenotype of the patient, and it varies widely from patient to patient. For example, type 2 airway inflammation and neutrophilic airway inflammation may coexist in the same patient, and quite a few patients have clinical characteristics of both asthma and COPD. Even in the same patient, the contribution of each pathogenesis is expected to differ at different life stages (eg, childhood, adolescence, middle age, and older), during different seasons (eg, high seasons for hay fever and rhinovirus infection), and depending on the nature of treatments. This review describes several basic pathogeneses commonly involved in both asthma and COPD, including chronic non-type 2 inflammation, type 2 inflammation, viral infections, and lung development. Understanding of the basic molecular pathogeneses in individual patients, rather than the use of clinical diagnosis, such as asthma, COPD, or even asthma COPD overlap, will enable us to better deal with the diversity seen in disease states, and lead to optimal treatment practices tailored for each patient with less disease burden, such as drug-induced side effects, and improved prognosis. Furthermore, we can expect to focus on these molecular pathways as new drug discovery targets.

The pharmacological management of asthma in adults: 2023 update.

INTRODUCTION: The pharmacotherapy of asthma is a dynamic process that changes as our knowledge of the underlying pathophysiology and treatment of this disease continues to evolve. This implies the need for continuous revision of the recommendations of asthma guidelines and strategies. AREAS COVERED: This review summarizes the latest key practical information on the pharmacological management of asthma in adults. We provide the background to the 2023 update of the GINA strategy report, focusing on changes and discussing areas of uncertainty. We review current and emerging pharmacotherapy for uncontrolled asthma, including synthetic agents and new biologics, and provide expert perspectives and opinions on the treatment of uncontrolled asthma. EXPERT OPINION: The current pharmacological treatment of asthma, based on a step-by-step, control-based approach, with ICSs, LABAs and LAMAs being the mainstay generally provides good symptom control. Biologic therapies are often effective in treating T2high severe asthma. However, there is still room for improvement, such as the discovery of new molecules that specifically target chronic inflammation and, most importantly, the ability to provide solutions to the various areas of uncertainty that still exist. Also finding solutions to improve the accessibility and affordability of rescue ICS in resource-constrained settings is critical.

Treatable traits in advanced emphysema patients eligible for bronchoscopic lung volume reduction with endobronchial valves.

INTRODUCTION: Patients with advanced emphysema eligible for bronchoscopic lung volume reduction (BLVR) using endobronchial valves (EBV) are characterized by severe static lung hyperinflation, which can be considered a treatable trait. Other treatable traits (TTs), which are assumed to be present in this highly selected patient group, have not been studied in detail nor how they may affect health-related quality of life (HRQL). AIMS: We aimed to evaluate a spectrum of TTs in COPD patients eligible for EBV treatment and their association with HRQL. METHODS: The SoLVE study (NCT03474471) was a prospective multicenter randomized controlled trial to examine the impact of pulmonary rehabilitation in COPD patients receiving EBV. The presence/absence of 16 TTs was based on pre-defined thresholds. HRQL was assessed with the St. George's Respiratory Questionnaire (SGRQ). Subjects were stratified into two groups, using the median split method, into higher or lower SGRQ total score. Logistic regression assessed the odds ratio (OR) of having a higher SGRQ total score per TT. RESULTS: Ninety-seven subjects were included, the mean number of TTs per patient was 8.1 ± 2.5. Low physical activity (95%), poor exercise capacity (94%) and severe fatigue (75%) were the most prevalent TTs. The sum of TTs present in a subject was associated with the SGRQ total score (r = 0.53; p < 0.001). Severe fatigue, depression, and anxiety were predictors of having a higher SGRQ total score. CONCLUSIONS: A high prevalence and co-occurrence of multiple TTs were identified in emphysema patients eligible for EBV. Patients with a higher number of TTs were more likely to have worse HRQL.

Treatable Traits in Asthma: The Importance of Extrapulmonary Traits-GERD, CRSwNP, Atopic Dermatitis, and Depression/Anxiety.

Treatable traits is a personalized medicine approach to the management of airway disease. Assessing traits within the 3 domains of pulmonary, extrapulmonary, and behavioral/lifestyle/risk factor traits, and applying targeted treatments to effectively manage these traits, enables a holistic and personalized approach to care. Asthma is a heterogeneous and complex airway disease that is frequently complicated by several extrapulmonary traits that impact asthma outcomes and predict future outcomes. We propose that the identification of extrapulmonary and behavioral risk factor traits and the implementation of targeted therapy will lead to improved management of people with asthma. Furthermore, many extrapulmonary traits present as "connected comorbidities"; that is, they coexist with asthma, have an impact on asthma, and effective treatment improves both asthma and the comorbidity or the comorbidities may share a similar mechanism. In this review, we explore this concept and look at atopic dermatitis, chronic rhinosinusitis with nasal polyps, gastroesophageal reflux disease, anxiety, and depression as treatable traits of asthma and how these can be managed using this approach.

Systematic literature review of traits and outcomes reported in randomised controlled trials of asthma with regular dosing of inhaled corticosteroids with short-acting ß2-agonist reliever, as-needed ICS/formoterol, or ICS/formoterol maintenance and reliever therapy.

INTRODUCTION: Asthma treatments based solely on diagnostic label do not benefit patients equally. To identify patient traits that may be associated with improved treatment response to regular inhaled corticosteroid (ICSs) dosing with short-acting ß2-agonist reliever or ICS/formoterol-containing therapy, a systematic literature review (SLR) was conducted. METHODS: Searches of databases including MEDLINE and Embase identified randomised controlled trials (RCTs) of patients with asthma, aged ≥12 years, published 1998-2022, containing ≥1 regular ICS dosing or ICS/formoterol-containing treatment arm, and reporting patient traits and outcomes of interest. Relevant data was extracted and underwent a feasibility assessment to determine suitability for meta-analysis. RESULTS: The SLR identified 39 RCTs of 72,740 patients and 90 treatment arms, reporting 11 traits and 11 outcomes. Five patient traits (age, body mass index, FEV1, smoking history, asthma control) and five outcomes (exacerbation rate, lung function, asthma control, adherence, time to first exacerbation) were deemed feasible for inclusion in meta-analyses due to sufficient comparable reporting. Subgroups of clinical outcomes stratified by levels of patient traits were reported in 16 RCTs. CONCLUSION: A systematic review of studies of regular ICS dosing with SABA or ICS/formoterol-containing treatment strategies in asthma identified consistent reporting of five traits and outcomes, allowing exploration of associations with treatment response. Conversely, many other traits and outcomes, although being potentially relevant, were inconsistently reported and limited subgroup reporting meant analyses of treatment response for subgroups of traits was not possible. We recommend more consistent measurement and reporting of clinically relevant patient traits and outcomes in respiratory RCTs.

Treatable traits models of care.

Treatable traits is a personalized approach to the management of respiratory disease. The approach involves a multidimensional assessment to understand the traits present in individual patients. Traits are phenotypic and endotypic characteristics that can be identified, are clinically relevant and can be successfully treated by therapy to improve clinical outcomes. Identification of traits is followed by individualized and targeted treatment to those traits. First proposed for the management of asthma and chronic obstructive pulmonary disease (COPD) the approach is recommended in many other areas of respiratory and now immunology medicine. Models of care for treatable traits have been proposed in different diseases and health care setting. In asthma and COPD traits are identified in three domains including pulmonary, extrapulmonary and behavioural/lifestyle/risk-factors. In bronchiectasis and interstitial lung disease, a fourth domain of aetiological traits has been proposed. As the core of treatable traits is personalized and individualized medicine; there are several key aspects to treatable traits models of care that should be considered in the delivery of care. These include person centredness, consideration of patients' values, needs and preferences, health literacy and engagement. We review the models of care that have been proposed and provide guidance on the engagement of patients in this approach to care.