Understanding breathlessness burden and psychophysiological correlates in asthma.

BACKGROUND: Breathlessness is a disabling symptom, with complexity that is often under recognised and under treated 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 two 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] dyspnoea 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: 144 participants were included, of which, 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%) compared with mild-to-moderate (n=21, 31%) asthma (p=0.013). Dyspnoea-12 Total (8.00 [4.75, 17.00] versus 5.00 [2.00, 11.00], p=0.037) 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. CONCLUSION: 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.

The illness burden of severe asthma contrasted to people with mild-to-moderate asthma: a qualitative study.

Background: Disabling symptoms of asthma including breathlessness, cough, wheeze and chest tightness largely impact quality of life; however, how these symptoms impact people with asthma of different severity levels remains unknown. This study aimed to compare and characterise patients' symptom experience and the burden caused, their quality of life, and the medication preferences of people with severe asthma against those of people with mild-to-moderate asthma. Methods: This was a multisite qualitative study involving two focus groups and semistructured interviews of adults with severe asthma undertaken in Australia and UK. Interviews were also undertaken in people with mild-to-moderate asthma. Audio recordings were transcribed and analysed thematically. Results: Participants in both severe asthma and mild-to-moderate asthma groups had a mean±sd age of 57±12 years. Between the severe asthma and mild-to-moderate asthma groups, 62% of participants were female and 86% lived with family. Themes were identified: 1) what is asthma and most bothersome symptoms: both groups reported breathlessness as the most bothersome symptom; 2) impacts on life: disease-related impact differed as people with severe asthma reported significant burden in their quality of life, which encompassed emotional, physical, social and financial wellbeing; and 3) personalised and responsive care: severe asthma interviewees preferred injectable biological therapy as a mode of treatment administration. Conclusions: People with asthma are burdened by breathlessness and cough and other disabling symptoms resulting in impaired quality of life. Understanding the experiences of people with asthma of different severities can improve the patient-clinician partnership.

Bacterial interactome disturbance in chronic obstructive pulmonary disease clinical stability and exacerbations.

RATIONALE: Our understanding of airway dysbiosis in chronic obstructive pulmonary disease (COPD) remains incomplete, which may be improved by unraveling the complexity in microbial interactome. OBJECTIVES: To characterize reproducible features of airway bacterial interactome in COPD at clinical stability and during exacerbation, and evaluate their associations with disease phenotypes. METHODS: We performed weighted ensemble-based co-occurrence network analysis of 1742 sputum microbiomes from published and new microbiome datasets, comprising two case-control studies of stable COPD versus healthy control, two studies of COPD stability versus exacerbation, and one study with exacerbation-recovery time series data. RESULTS: Patients with COPD had reproducibly lower degree of negative bacterial interactions, i.e. total number of negative interactions as a proportion of total interactions, in their airway microbiome compared with healthy controls. Evaluation of the Haemophilus interactome showed that the antagonistic interaction networks of this established pathogen rather than its abundance consistently changed in COPD. Interactome dynamic analysis revealed reproducibly reduced antagonistic interactions but not diversity loss during COPD exacerbation, which recovered after treatment. In phenotypic analysis, unsupervised network clustering showed that loss of antagonistic interactions was associated with worse clinical symptoms (dyspnea), poorer lung function, exaggerated neutrophilic inflammation, and higher exacerbation risk. Furthermore, the frequent exacerbators (≥ 2 exacerbations per year) had significantly reduced antagonistic bacterial interactions while exhibiting subtle compositional changes in their airway microbiota. CONCLUSIONS: Bacterial interactome disturbance characterized by reduced antagonistic interactions, rather than change in pathogen abundance or diversity, is a reproducible feature of airway dysbiosis in COPD clinical stability and exacerbations, which suggests that we may target interactome rather than pathogen alone for disease treatment.

Landscape fire smoke airway exposure impairs respiratory and cardiac function and worsens experimental asthma.

BACKGROUND: Millions of people are exposed to landscape fire smoke (LFS) globally, and inhalation of LFS particulate matter (PM) is associated with poor respiratory and cardiovascular outcomes. However, how LFS affects respiratory and cardiovascular function is less well understood. OBJECTIVE: We aimed to characterize the pathophysiologic effects of representative LFS airway exposure on respiratory and cardiac function and on asthma outcomes. METHODS: LFS was generated using a customized combustion chamber. In 8-week-old female BALB/c mice, low (25 µg/m3, 24-hour equivalent) or moderate (100 µg/m3, 24-hour equivalent) concentrations of LFS PM (10 µm and below [PM10]) were administered daily for 3 (short-term) and 14 (long-term) days in the presence and absence of experimental asthma. Lung inflammation, gene expression, structural changes, and lung function were assessed. In 8-week-old male C57BL/6 mice, low concentrations of LFS PM10 were administered for 3 days. Cardiac function and gene expression were assessed. RESULTS: Short- and long-term LFS PM10 airway exposure increased airway hyperresponsiveness and induced steroid insensitivity in experimental asthma, independent of significant changes in airway inflammation. Long-term LFS PM10 airway exposure also decreased gas diffusion. Short-term LFS PM10 airway exposure decreased cardiac function and expression of gene changes relating to oxidative stress and cardiovascular pathologies. CONCLUSIONS: We characterized significant detrimental effects of physiologically relevant concentrations and durations of LFS PM10 airway exposure on lung and heart function. Our study provides a platform for assessment of mechanisms that underpin LFS PM10 airway exposure on respiratory and cardiovascular disease outcomes.

Azithromycin Induced Asthma Remission in Adults With Persistent Uncontrolled Asthma: A Secondary Analysis of a Randomized, Double-Blind, Placebo-Controlled Trial.

BACKGROUND: Asthma remission is a potential treatment goal. RESEARCH QUESTION: Does adding azithromycin to standard therapy in patients with persistent uncontrolled asthma induce remission compared with placebo? STUDY DESIGN AND METHODS: This secondary analysis used data from the AMAZES clinical trial-a double-blind placebo-controlled trial that evaluated the safety and efficacy of azithromycin on asthma exacerbations. The primary remission definition (referred to as clinical remission) was zero exacerbations and zero oral corticosteroids during the previous 6 months evaluated at 12 months and a 5-item Asthma Control Questionnaire score ≤ 1 at 12 months. Secondary remission definitions included clinical remission plus lung function criteria (postbronchodilator FEV1 ≥ 80% or postbronchodilator FEV1 ≤ 5% decline from baseline) and complete remission (sputum eosinophil count < 3% plus the aforementioned criteria). Sensitivity analyses explored the robustness of primary and secondary remission definitions. The predictors of clinical remission were identified. RESULTS: A total of 335 participants (41.5% male; median age, 61.01 years; quartile 1-3, 51.03-68.73) who completed the 12-month treatment period were included in the analysis. Twelve months of treatment with azithromycin induced asthma remission in a subgroup of patients, and a significantly higher proportion in the azithromycin arm achieved both clinical remission (50.6% vs 38.9%; P = .032) and clinical remission plus lung function criteria (50.8% vs 37.1%; P = .029) compared with placebo, respectively. In addition, a higher proportion of the azithromycin group achieved complete remission (23% vs 13.7%; P = .058). Sensitivity analyses supported these findings. Baseline factors (eg, better asthma-related quality of life, absence of oral corticosteroid burst in the previous year) predicted the odds of achieving clinical remission. Azithromycin induced remission in both eosinophilic and noneosinophilic asthma. INTERPRETATION: Adults with persistent symptomatic asthma achieved a higher remission rate when treated with azithromycin. Remission on treatment may be an achievable treatment target in moderate/severe asthma, and future studies should consider remission as an outcome measure.

Core Function in Adults With Severe Asthma and Its Relationship With Breathing Symptoms.

BACKGROUND: People with asthma may have skeletal muscle dysfunction but data describing core function in severe asthma are limited. OBJECTIVE: To compare core function between people with severe asthma and healthy controls and to determine the difference between males and females. Furthermore, we aimed to investigate the association between core function and breathing symptoms. METHOD: Adults with a diagnosis of severe asthma and healthy controls undertook an assessment that included 3 core function tests: partial sit-up, Biering-Sorensen, and side bridge. Breathing symptoms were assessed by the modified Medical Research Council dyspnea scale, modified Borg scale, and Nijmegen questionnaire. RESULTS: People with severe asthma (n = 136) (38% male, age median [Q1-Q3] 59 y [45-68], body mass index 30 kg/m2 [26-37]) were compared with 66 people without respiratory disease (47% male, age 55 y [34-65], body mass index 25 kg/m2 [22-28]). There was no difference between groups in the partial sit-up (P = .09). However, participants with severe asthma performed worse with the Biering-Sorensen (P < .001), and the left and right side bridge test (P < .001 for both) than the healthy comparison group. Similar results were found when comparing males and females separately. Males with severe asthma had increased function compared with their female counterparts in the left side bridge test. Core function tests correlated with the breathing symptom measures, the modified Medical Research Council, modified Borg scale, and Nijmegen questionnaire (-0.51 > r > -0.19; P ≤ .03). CONCLUSIONS: Adults with severe asthma have worse core function than their control counterparts, independent of sex. Furthermore, as core function decreases, breathing symptoms increase.

Personal strategies to reduce the effects of landscape fire smoke on asthma-related outcomes: a protocol for systematic review and meta-analysis.

INTRODUCTION: Landscape fire smoke (LFS) contains several hazardous air pollutants that are known to be detrimental to human health. People with asthma are more vulnerable to the health impact of LFS than general populations. The aim of this review is to investigate the effectiveness of personal strategies to reduce the effect of LFS on asthma-related outcomes. METHODS AND ANALYSIS: We will electronically search databases such as Medline, Embase, CINAHL and Cochrane Clinical Trials Register to identify eligible articles for the review. Screening of search results and data extraction from included studies will be completed by two independent reviewers. The risk of bias (RoB 2) will be assessed using the Risk of Bias Assessment Tool for Non-Randomised Studies for observational studies, the Cochrane Collaboration tool for assessing the RoB 2 for randomised controlled trials (RCTs) and the Risk Of Bias In Nonrandomized Studies of Interventions tool for non-RCTs. A random-effect meta-analysis will be performed to determine the pooled summary of findings of the included studies. If meta-analysis is not possible, we will conduct a narrative synthesis. Findings will be reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. ETHICS AND DISSEMINATION: This study will synthesise the available evidence obtained from published studies and as such, no ethical approval is required. The review will be disseminated through peer-reviewed publications and conference presentations. PROSPERO REGISTRATION NUMBER: CRD42022341120.

Living With Asthma and Vocal Cord Dysfunction/Inducible Laryngeal Obstruction: "I Just Can't Get Air In".

BACKGROUND: Asthma and vocal cord dysfunction (VCD), also known as inducible laryngeal obstruction (ILO), may coexist, resulting in worse outcomes for patients. The experience of people with VCD/ILO and coexisting asthma is unknown. OBJECTIVE: We sought to determine whether coexistent VCD/ILO and asthma have deleterious impacts on quality of life. METHODS: We undertook a descriptive qualitative study using one-to-one semistructured interviews with 30 purposively recruited adult participants with a prior confirmed doctor asthma diagnosis and laryngoscopy-confirmed VCD/ILO. A thematic and content analysis was conducted to explore the data. RESULTS: Participants were mostly female (63%), mean ± SD age 63 ± 12 years. Four themes were identified: trapped voice, altered life, knowledge about VCD/ILO, and looking for solutions. Participants reported their voice being trapped in their throat or the voice being suddenly cut off when talking or singing. Self-reported VCD/ILO symptoms including throat tightness and breathlessness were highlighted by participants. The second theme described how patients struggle to communicate or tended to shorten conversations. Insufficient knowledge and existing confusion regarding whether asthma was causing the breathlessness was described in the third theme. Looking for solutions depicted participants' diagnostic journey and how they sought an explanation for the symptoms. CONCLUSIONS: People with asthma and coexisting VCD/ILO experience a substantial burden affecting the quality of life. These data describe the impact on patients with coexisting conditions and should be used to increase clinician awareness of the experience of VCD/ILO from patients' perspectives to support a personalized approach to care.

From treatable traits to GETomics in airway disease: moving towards clinical practice.

The treatable traits approach represents a strategy for patient management. It is based on the identification of characteristics susceptible to treatments or predictive of treatment response in each individual patient. With the objective of accelerating progress in research and clinical practice relating to such a treatable traits approach, the Portraits event was convened in Barcelona, Spain, in November 2022. Here, while reporting the key concepts that emerged from the discussions during the meeting, we review the current state of the art related to treatable traits and chronic respiratory diseases management, and we describe the possible actions that clinicians can take in clinical practice to implement the treatable traits framework. Furthermore, we explore the new concept of GETomics and the new models of research in the field of COPD.

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.

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.

Biologics (mepolizumab and omalizumab) induced remission in severe asthma patients.

BACKGROUND: Asthma remission has emerged as a potential treatment goal. This study evaluated the effectiveness of two biologics (mepolizumab/omalizumab) in achieving asthma remission. METHODS: This observational study included 453 severe asthma patients (41% male; mean age ± SD 55.7 ± 14.7 years) from two real-world drug registries: the Australian Mepolizumab Registry and the Australian Xolair Registry. The composite outcome clinical remission was defined as zero exacerbations and zero oral corticosteroids during the previous 6 months assessed at 12 months and 5-item Asthma Control Questionnaire (ACQ-5) ≤1 at 12 months. We also assessed clinical remission plus optimization (post-bronchodilator FEV1 ≥80%) or stabilization (post-bronchodilator FEV1 not greater than 5% decline from baseline) of lung function at 12 months. Sensitivity analyses explored various cut-offs of ACQ-5/FEV1 scores. The predictors of clinical remission were identified. RESULTS: 29.3% (73/249) of AMR and 22.8% (37/162) of AXR cohort met the criteria for clinical remission. When lung function criteria were added, the remission rates were reduced to 25.2% and 19.1%, respectively. Sensitivity analyses identified that the remission rate ranged between 18.1% and 34.9% in the AMR cohort and 10.6% and 27.2% in the AXR cohort. Better lung function, lower body mass index, mild disease and absence of comorbidities such as obesity, depression and osteoporosis predicted the odds of achieving clinical remission. CONCLUSION: Biologic treatment with mepolizumab or omalizumab for severe asthma-induced asthma remission in a subgroup of patients. Remission on treatment may be an achievable treatment target and future studies should consider remission as an outcome measure.

Ventilation Heterogeneity Is a Treatable Trait in Severe Asthma.

BACKGROUND: Ventilation heterogeneity (VH) is a feature of asthma and indicates small airway disease. Nuclear imaging methods assess VH, which can facilitate clinical diagnosis and further our understanding of disease aetiology. OBJECTIVE: We sought to assess VH in severe eosinophilic asthma (SEA) using ventilation/perfusion single-photon emission computed tomography (V/P SPECT), and to assess its use as an objective test of the effect of biologic treatment for ventilation defects in SEA. METHODS: Adults (≥18 y) with severe asthma were recruited to participate in a cross-sectional observational study. Participants underwent a clinical assessment and V/P SPECT CT using Technegas as the ventilation agent. Measures were repeated for a nested before-after treatment study in people with SEA commencing biologics. RESULTS: A total of 62 participants with severe asthma were recruited. From this, 38 participants with SEA were included in the before-after study. The VH was associated with clinical variables such as lung function impairment and significantly improved after monoclonal antibody treatment in the severe asthma group. The changes in VH correlated with change in post bronchodilator forced expiratory volume in 1 second (FEV1) %predicted (r = -0.503; P = .001) and post bronchodilator FEV1/FVC (forced vital capacity) (r = -0.415; P = .01). CONCLUSIONS: The VH is clinically significant, measurable, and treatable, which establishes VH as a treatable trait in severe asthma.

Treatable traits in asthma during pregnancy: a call for a shift towards a precision-based management approach.

Asthma is the most common chronic medical condition in pregnancy. Asthma exacerbations in pregnancy are unpredictable, and are associated with adverse maternal and fetal perinatal outcomes such as preterm birth and low birthweight. Goals of asthma management in pregnancy are to establish effective asthma control and prevent exacerbations. Optimising the management of asthma in pregnancy is an important goal of practice and future research.Treatable traits is a precision medicine paradigm proposed for the management of airways diseases, which holistically addresses the complexity and heterogeneity of airways disease. It is an individualised treatment approach that aims to improve outcomes. This makes treatable traits well suited for pregnant women with asthma, who have a high prevalence of obesity, mental health conditions, poor symptom perception and suboptimal asthma management skills including low treatment adherence. These traits are measurable and treatable. In this review, we explore current knowledge on the burden of asthma, maternal and perinatal consequences of asthma during pregnancy, the treatable traits paradigm, the prevalence of treatable traits in pregnant women with asthma, and consider how the treatable traits paradigm can be integrated into the management of asthma in pregnancy.

Healthcare Professionals' Perspectives of Nonsurgical Care of Older Inpatients with Class II or III Obesity and Comorbidities: A Qualitative Study.

Background: Older people with Class II or III obesity and comorbidities experience complex care needs with frequent hospital admissions. In 2019/20 the National Health Service in England reported a 17% increase in hospital admissions of patients with obesity compared to 2018/19. Gaps in care for this population have been identified. Purpose: The purpose of this study was to understand the experiences and perspectives of healthcare professionals delivering non-surgical care to older people with Classes II or III obesity admitted to a tertiary care hospital. Methods: Healthcare professionals delivering non-surgical care to older people admitted with Class II or III obesity with comorbidities were recruited from an Australian tertiary referral hospital. Qualitative semi-structured interviews were conducted with 24 healthcare professionals from seven disciplines between August and December 2019. The interviews were audio-recorded, transcribed, and reviewed by participants for accuracy. Thematic inductive data analysis was deductively mapped to the Theoretical Domains Framework (TDF). Results: Four major themes of Barriers, Facilitators, Current Practice, and Recommendations and 11 subthemes were identified and mapped to nine domains in the TDF. The Barriers subtheme identified perceived patient related factors, health system issues, and provider issues, while the Facilitators subtheme included a patient centred approach, knowledge, and resources in the subacute setting. The major Current Practice theme explored factors influencing clinical management, and the Recommendations subthemes included engaging patients, access to quality care, education and support, and obesity as a chronic disease. Conclusion: This novel application of the TDF provided broad insights related to the barriers and facilitators in delivering non-surgical care to this hospital population, from the perspective of healthcare professionals. Understanding how these barriers interact can provide strategies to influence behaviour change and assist in the development of a holistic multidisciplinary model of care.

Asthma and landscape fire smoke: A Thoracic Society of Australia and New Zealand position statement.

Landscape fires are increasing in frequency and severity globally. In Australia, extreme bushfires cause a large and increasing health and socioeconomic burden for communities and governments. People with asthma are particularly vulnerable to the effects of landscape fire smoke (LFS) exposure. Here, we present a position statement from the Thoracic Society of Australia and New Zealand. Within this statement we provide a review of the impact of LFS on adults and children with asthma, highlighting the greater impact of LFS on vulnerable groups, particularly older people, pregnant women and Aboriginal and Torres Strait Islander peoples. We also highlight the development of asthma on the background of risk factors (smoking, occupation and atopy). Within this document we present advice for asthma management, smoke mitigation strategies and access to air quality information, that should be implemented during periods of LFS. We promote clinician awareness, and the implementation of public health messaging and preparation, especially for people with asthma.

Key Considerations When Addressing Physical Inactivity and Sedentary Behaviour in People with Asthma.

People with asthma tend to be less physically active and more sedentary than people without asthma. This narrative review aimed to present key considerations when addressing physical inactivity and sedentary behaviour in people with asthma by identifying barriers and facilitators, determinants and correlates, and intervention approaches. Using a search strategy, electronic databases were searched for relevant studies. Data extracted from studies were qualitatively synthesised. A total of 26 studies were included in the review. Six studies reported asthma symptoms as a barrier to physical activity, while four studies reported having a supportive network as a physical activity facilitator. Across studies, physical activity correlates/determinants were pulmonary function, exercise capacity, body mass index, dyspnoea, psychological health, and asthma control. Interventions that effectively improved physical activity in the short term were a step-based prescription programme, a weight loss programme incorporating aerobic and resistance training, and a weight loss lifestyle intervention, while a high-intensity interval training pulmonary rehabilitation program was effective in the long term. The collective findings suggest that a personalised physical activity programme incorporating different strategies is needed. There was minimal evidence to provide recommendations to optimise sedentary behaviour in asthma, and more research is needed on the topic.

Treatable traits, combination inhaler therapy and the future of asthma management.

The landscape of asthma has considerably changed in the last decade. Effective medications and inhaler devices have been developed and integrated into the asthma pharmacopoeia, but unfortunately, the proportion of uncontrolled patients remains unacceptably high. This is now recognized to be mainly due to the inappropriate use of medications or inhaler devices, heterogeneity of the disease or other factors contributing to the disease. Currently, inhaled corticosteroids (ICS), with or without long-acting beta agonists (LABA), are the cornerstone of asthma management, and recently international guidelines recognized the importance of combination inhaler therapy (ICS/LABA) even in mild asthma. In future, ultra-long-acting personalized medications and smart inhalers will complement combination inhaler therapy in order to effectively addresses issues such as adherence, inhaler technique and polypharmacy (both of drugs and devices). Asthma is now acknowledged as a multifaceted cluster of disorders and the treatment model has evolved from one-size-fits-all to precision medicine approaches such as treatable traits (TTs, defined as measurable and treatable clinically important factors) which encourages the quality use of medications and identification and management of all underlying behavioural and biological treatable risk factors. TT requires research and validation in a clinical context and the implementation strategies and efficacy in various settings (primary/secondary/tertiary care, low-middle income countries) and populations (mild/moderate/severe asthma) are currently evolving. Combination inhaler therapy and the TTs approach are complementary treatment approaches. This review examines the current status of personalized medicine and combination inhaler therapy, and describes futuristic views for these two strategies.

Diagnosis of vocal cord dysfunction/inducible laryngeal obstruction: An International Delphi Consensus Study.

BACKGROUND: Vocal cord dysfunction/inducible laryngeal obstruction (VCD/ILO) is characterized by breathing difficulties in association with excessive supraglottic or glottic laryngeal narrowing. The condition is common and can occur independently; however, it may also be comorbid with other disorders or mimic them. Presentations span multiple specialties and misdiagnosis or delayed diagnosis is commonplace. Group-consensus methods can efficiently generate internationally accepted diagnostic criteria and descriptions to increase clinical recognition, enhance clinical service availability, and catalyze research. OBJECTIVES: We sought to establish consensus-based diagnostic criteria and methods for VCD/ILO. METHODS: We performed a modified 2-round Delphi study between December 7, 2021, and March 14, 2022. The study was registered at ANZCTR (Australian New Zealand Clinical Trials Registry; ACTRN12621001520820p). In round 1, experts provided open-ended statements that were categorized, deduplicated, and amended for clarity. These were presented to experts for agreement ranking in round 2, with consensus defined as ≥70% agreement. RESULTS: Both rounds were completed by 47 international experts. In round 1, 1102 qualitative responses were received. Of the 200 statements presented to experts across 2 rounds, 130 (65%) reached consensus. Results were discussed at 2 international subject-specific conferences in June 2022. Experts agreed on a diagnostic definition for VCD/ILO and endorsed the concept of VCD/ILO phenotypes and clinical descriptions. The panel agreed that laryngoscopy with provocation is the gold standard for diagnosis and that ≥50% laryngeal closure on inspiration or Maat grade ≥2 define abnormal laryngeal closure indicative of VCD/ILO. CONCLUSIONS: This Delphi study reached consensus on multiple aspects of VCD/ILO diagnosis and can inform clinical practice and facilitate research.