Professor Vanessa McDonald

We have presented Lucy, a 42-year-old female with asthma, who was recently admitted to hospital with an acute exacerbation of her asthma. Currently, she has ongoing poor symptom control despite being prescribed a combination high-dose ICS/LABA. An assessment of her asthma management skills and knowledge indicates that there are a number of areas that require addressing. Asthma education will be integral to Lucy¿s management of her asthma.

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.

Interstitial lung disease (ILD) is a diverse group of inflammatory and fibrotic lung conditions causing significant morbidity and mortality. A multitude of factors beyond the lungs influence symptoms, health-related quality of life, disease progression and survival in patients with ILD. Despite an increasing emphasis on multidisciplinary management in ILD, the absence of a framework for assessment and delivery of comprehensive patient care poses challenges in clinical practice. The treatable traits approach is a precision medicine care model that operates on the premise of individualised multidimensional assessment for distinct traits that can be targeted by specific interventions. The potential utility of this approach has been described in airway diseases, but has not been adequately considered in ILD. Given the similar disease heterogeneity and complexity between ILD and airway diseases, we explore the concept and potential application of the treatable traits approach in ILD. A framework of aetiological, pulmonary, extrapulmonary and behavioural and lifestyle treatable traits relevant to clinical care and outcomes for patients with ILD is proposed. We further describe key research directions to evaluate the application of the treatable traits approach towards advancing patient care and health outcomes in ILD.

Background: The management of obstructive airway diseases (OADs) is complex. The treatable traits (TTs) approach may be an effective strategy for managing OADs. Objective: To determine the effectiveness of interventions targeting TTs for managing OADs. Methods: Ovid Embase, Medline, CENTRAL, and CINAHL Plus were searched from inception to March 9, 2022. Studies of interventions targeting at least 1 TT from pulmonary, extrapulmonary, and behavioral/lifestyle domains were included. Two reviewers independently extracted relevant data and performed risk-of-bias assessments. Meta-analyses were performed using random-effects models. Subgroup and sensitivity analyses were carried out to explore heterogeneity and to determine the effects of outlying studies. Results: Eleven studies that used the TTs approach for OAD management were identified. Traits targeted within each study ranged from 13 to 36. Seven controlled trials were included in meta-analyses. TT interventions were effective at improving health-related quality of life (mean difference [MD] = -6.96, 95% CI: -9.92 to -4.01), hospitalizations (odds ratio [OR] = 0.52, 95% CI: 0.39 to 0.69), all-cause-1-year mortality (OR = 0.65, 95% CI: 0.45 to 0.95), dyspnea score (MD = -0.29, 95% CI: -0.46 to -0.12), anxiety (MD = -1.61, 95% CI: -2.92 to -0.30), and depression (MD = -2.00, 95% CI: -3.53 to -0.47). Conclusion: Characterizing TTs and targeted interventions can improve outcomes in OADs, which offer a promising model of care for OADs.

Background: Identification of eosinophilic asthma (EA) using sputum analysis is important for disease monitoring and individualized treatment. But it is laborious and technically demanding. We aimed to develop and validate an effective model to predict EA with multidimensional assessment (MDA). Methods: The asthma patients who underwent a successful sputum induction cytological analysis were consecutively recruited from March 2014 to January 2021. The variables assessed by MDA were screened by least absolute shrinkage and selection operator (LASSO) and logistic regression to develop a nomogram and an online web calculator. Validation was performed internally by a bootstrap sampling method and externally in the validation cohort. Diagnostic accuracy of the model in different asthma subgroups were also investigated. Results: In total of 304 patients in the training cohort and 95 patients in the validation cohort were enrolled. Five variables were identified in the EA prediction model: gender, nasal polyp, blood eosinophils, blood basophils and FeNO. The C-index of the model was 0.86 (95% CI: 0.81¿0.90) in the training cohort and 0.84 (95% CI: 0.72¿0.89) in the validation cohort. The calibration curve showed good agreement between the prediction and actual observation. The decision curve analysis (DCA) also demonstrated that the EA prediction model was clinically beneficial. An online publicly available web calculator was constructed (https://asthmaresearcherlimin.shinyapps.io/DynNomapp/). Conclusion: We developed and validated a multivariable model based on MDA to help the diagnosis of EA, which has good diagnostic performance and clinical practicability. This practical tool may be a useful alternative for predicting EA in the clinic.

Background: Little is known about the physical and mental health impact of exposure to landscape fire smoke in women with asthma. This study examined the health impacts and information-seeking behaviours of women with asthma exposed to the 2019/2020 Australian fires, including women who were pregnant. Methods: Women with asthma were recruited from the Breathing for Life Trial in Australia. Following the landscape fire exposure period, self-reported data were collected regarding symptoms (respiratory and non-respiratory), asthma exacerbations, wellbeing, quality of life, information seeking, and landscape fire smoke exposure mitigation strategies. Participants¿ primary residential location and fixed site monitoring was used to geolocate and estimate exposure to landscape fire-related fine Particulate Matter (PM2.5). Results: The survey was completed by 81 pregnant, 70 breastfeeding and 232 non-pregnant and non-breastfeeding women with asthma. Participants had a median daily average of 17 µg/m3 PM2.5 and 105 µg/m3 peak PM2.5 exposure over the fire period (October 2019 to February 2020). Over 80% of participants reported non-respiratory and respiratory symptoms during the fire period and 41% reported persistent symptoms. Over 82% reported asthma symptoms and exacerbations of asthma during the fire period. Half the participants sought advice from a health professional for their symptoms. Most (97%) kept windows/doors shut when inside and 94% stayed indoors to minimise exposure to landscape fire smoke. Over two in five (43%) participants reported that their capacity to participate in usual activities was reduced due to prolonged smoke exposure during the fire period. Participants reported greater anxiety during the fire period than after the fire period (mean (SD) = 53(13) versus 39 (13); p < 0.001). Two in five (38%) pregnant participants reported having concerns about the effect of fire events on their pregnancy. Conclusion: Prolonged landscape fire smoke exposure during the 2019/2020 Australian fire period had a significant impact on the health and wellbeing of women with asthma, including pregnant women with asthma. This was despite most women taking actions to minimise exposure to landscape fire smoke. Effective and consistent public health messaging is needed during landscape fire events to guard the health of women with asthma.

Background: Asthma is a respiratory disease characterised by variable airflow limitation and the presence of respiratory symptoms including wheeze, chest tightness, cough and/or dyspnoea. Exercise training is beneficial for people with asthma; however, the response to conventional models of pulmonary rehabilitation is less clear. Objectives: To evaluate, in adults with asthma, the effectiveness of pulmonary rehabilitation compared to usual care on exercise performance, asthma control, and quality of life (co-primary outcomes), incidence of severe asthma exacerbations/hospitalisations, mental health, muscle strength, physical activity levels, inflammatory biomarkers, and adverse events. Search methods: We identified studies from the Cochrane Airways Trials Register, Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, ClinicalTrials.gov, and the World Health Organization International Clinical Trials Registry Platform, from their inception to May 2021, as well as the reference lists of all primary studies and review articles. Selection criteria: We included randomised controlled trials in which pulmonary rehabilitation was compared to usual care in adults with asthma. Pulmonary rehabilitation must have included a minimum of four weeks (or eight sessions) aerobic training and education or self-management. Co-interventions were permitted; however, exercise training alone was not. Data collection and analysis: Following the use of Cochrane's Screen4Me workflow, two review authors independently screened and selected trials for inclusion, extracted study characteristics and outcome data, and assessed risk of bias using the Cochrane risk of bias tool. We contacted study authors to retrieve missing data. We calculated between-group effects via mean differences (MD) or standardised mean differences (SMD) using a random-effects model. We evaluated the certainty of evidence using GRADE methodology. Main results: We included 10 studies involving 894 participants (range 24 to 412 participants (n = 2 studies involving n > 100, one contributing to meta-analysis), mean age range 27 to 54 years). We identified one ongoing study and three studies awaiting classification. One study was synthesised narratively, and another involved participants specifically with asthma-COPD overlap. Most programmes were outpatient-based, lasting from three to four weeks (inpatient) or eight to 12 weeks (outpatient).¿Education or self-management components included breathing retraining and relaxation, nutritional advice and psychological counselling. One programme was specifically tailored for people with severe asthma. Pulmonary rehabilitation compared to usual care may increase maximal oxygen uptake (VO2 max) after programme completion, but the evidence is very uncertain for data derived using mL/kg/min (MD between groups of 3.63 mL/kg/min, 95% confidence interval (CI) 1.48 to 5.77; 3 studies; n = 129) and uncertain for data derived from % predicted VO2 max (MD 14.88%, 95% CI 9.66 to 20.1%; 2 studies; n = 60). The evidence is very uncertain about the effects of pulmonary rehabilitation¿compared to usual care on incremental shuttle walk test distance (MD between groups 74.0 metres, 95% CI 26.4 to 121.4; 1 study; n = 30).¿Pulmonary rehabilitation may have little to no effect on VO2max¿at longer-term follow up (9 to 12 months), but the evidence is very uncertain (MD -0.69 mL/kg/min, 95% CI -4.79 to 3.42; I2 = 49%;¿3 studies; n = 66). Pulmonary rehabilitation likely improves functional exercise capacity as measured by 6-minute walk distance, with MD between groups after programme completion of 79.8 metres (95% CI 66.5 to 93.1; 5 studies; n = 529; moderate certainty evidence). This magnitude of mean change exceeds the minimally clinically important difference (MCID) threshold for people with chronic respiratory disease. The evidence is very uncertain about the longer-term effects one year after pulmonary rehabilitation for this outcom...

Background and objective: Exercise capacity is associated with health-related quality of life and symptom control in severe asthma. Thus, interventions targeting exercise capacity are likely to be beneficial. However, clinical and biological factors impacting exercise capacity in severe asthma are sparsely investigated. We aimed to describe the association of selected clinical and biological factors with 6-min walk distance (6MWD) in adults with severe asthma and investigate the impact of sex on these outcomes. Methods: A cross-sectional study in adults with severe asthma was conducted. Exercise capacity was measured by 6-min walk test, and association between 6MWD and predictors were evaluated using multiple linear regression. Results: A total of 137 patients (females, 85; median age, 59 years) were recruited. Overall, asthma control (-15.2 m, 95% CI -22.6 to -7.7; p¿=¿0.0001) and BMI (-3.2¿m, 95% CI -5.1 to -1.3; p¿=¿0.001) were significantly associated with exercise capacity (adjusted variance, adj. R2¿=¿0.425). In females, 5-item Asthma Control Questionnaire (ACQ-5; p¿=¿0.005) and BMI (p¿< 0.001) were significantly associated with 6MWD (adj. R2¿=¿0.423). In males, a 0.5-point increase in ACQ-5 was associated with a decrease in 6MWD by 10.2¿m (95% CI -22.8 to 2.4; p¿=¿0.11), but no clinical nor biological factors reached statistical significance (adj. R2¿=¿0.393). Conclusion: Asthma symptoms and BMI were associated with exercise capacity in the overall population. Optimizing these factors may enhance the ability of patients to improve their exercise capacity and gain the associated positive health outcomes, but further studies are warranted.

Background Whilst multidimensional assessment enables the detection of treatable traits in severe asthma and has the potential to improve patient outcomes, healthcare disparities exist, and little is known about the factors influencing optimal management in severe asthma. This study aimed to explore perceived barriers, and enablers to implementing personalised care in severe asthma, from the healthcare professionals¿ perspective. Methods A descriptive, qualitative study involving a single focus group (n = 7) and semi-structured interviews (n = 33) with multidisciplinary healthcare professionals involved in severe asthma care was conducted. A hybrid thematic and content analysis was undertaken to identify themes, which were then deductively mapped to the Theoretical Domains Framework (TDF). Results Overall, three emergent themes were identified: (1) Barriers- (2) Enablers- to optimal management; (3) Desired model of care. Across all TDF domains, 6 constructs influenced development and implementation of optimal care: (1) belief about consequences, (2) environmental context and resources, (3) belief about capabilities, (4) social/professional role and identity, (5) goals and (6) knowledge. Conclusion Implementation of personalised care in severe asthma is complex and non-linear. The use of a theory-based approach effectively demonstrated how a variety of behaviours could be targeted to optimise and promote personalised care in different clinical setting.

Introduction: Chronic obstructive pulmonary disease (COPD) is a treatable and preventable disease characterised by persistent respiratory symptoms and chronic airflow limitation on spirometry. COPD is highly prevalent and is associated with exacerbations and comorbid conditions. ¿COPD-X¿ provides quarterly updates in COPD care and is published by the Lung Foundation Australia and the Thoracic Society of Australia and New Zealand. Main recommendations: The COPD-X guidelines (version 2.65) encompass 26 recommendations addressing: case finding and confirming diagnosis; optimising function; preventing deterioration; developing a plan of care; and managing an exacerbation. Changes in management as a result of these guidelines: Both non-pharmacological and pharmacological strategies are included within these recommendations, reflecting the importance of a holistic approach to clinical care for people living with COPD to delay disease progression, optimise quality of life and ensure best practice care in the community and hospital settings when managing exacerbations. Several of the new recommendations, if put into practice in the appropriate circumstances, and notwithstanding known variations in the social determinants of health, could improve quality of life and reduce exacerbations, hospitalisations and mortality for people living with COPD.

Background: Hospitalization due to acute asthma exacerbation (AE) is a highly detrimental situation requiring critical management to prevent further deterioration, including mechanical ventilation, intensive care unit (ICU) admission, and death. However, patients hospitalized for AEs are highly heterogeneous and remain largely unexplored. Objective: To identify clinical and inflammatory phenotypes of AE requiring hospitalization associated with in-hospital outcomes. Methods: We performed a hierarchical cluster analysis of 825 consecutively recruited patients hospitalized for AEs. Logistic regressions were conducted to quantify the independent associations of the identified phenotypes with in-hospital outcomes. Decision tree analysis was developed to predict cluster assignment. Results: We identified 3 clusters of patients, which had significantly different characteristics associated with in-hospital adverse outcomes. Cluster 1 (n = 526, 63.8%) was a late-onset phenotype, cluster 2 (n = 97, 11.8%) was an early-onset phenotype, and cluster 3 (n = 202, 24.5%) was a phenotype with fewer eosinophils and more comorbidities. Clusters 2 and 3 had an elevated risk of death (relative ratio [RRadj], 18.10 and 19.17, respectively) and mechanical ventilation (RRadj, 2.56 and 5.71, respectively) than did cluster 1. Individuals in cluster 3 had an extended length of hospital stay (11 days), increased hospitalization direct costs (13,481.57 Chinese Yuan), and a higher risk of ICU admission (RRadj, 2.14) than individuals in clusters 1 and 2. The decision tree assigned 90.8% of the participants correctly. Conclusions: We identified 3 phenotypes with differential clinical and inflammatory characteristics associated with in-hospital adverse outcomes. These new phenotypes might have important and clinically relevant implications for the management of patients hospitalized for AEs.

Background: Physical inactivity is common in severe asthma and associated with poor health outcomes. New approaches are needed to address physical inactivity in this group. Objective: To examine whether yoga and mindfulness improves health-related quality of life (HRQoL) compared with a minimal active control group and collect feasibility data to inform future studies. Methods: Over 12-weeks, adults with severe asthma were recruited. Participants were randomised 2:1 to parallel yoga or control groups. All participants received an activity tracker. The yoga group received tailored group classes twice a week for 16-weeks with a qualified yoga instructor. The control group set activity goals with a research officer and received eight progress calls. Outcomes were assessed at 16-weeks. Primary outcome was St George¿s Respiratory Questionnaire (SGRQ). Secondary outcomes included asthma control, physical activity, breathlessness, and inflammation. Face-to-face qualitative interviews were conducted to determine acceptability. Results: There were 15 participants randomised to yoga (mean 67¿years; 60% female) and 9 to control (68¿years; 56% female). Planned comparisons indicated the yoga group had greater SGRQ improvement than the control group. There was little change in secondary outcomes. Moderate-vigorous activity increased substantially in the control group. Participants found the intervention acceptable; key barriers and facilitators were social connection, the setting, addressing breathing and asthma symptoms, changing their mindset, and the intersection of different elements. Conclusion: A yoga and mindfulness intervention was feasible, acceptable to patients and improved HRQoL. The findings will inform design of much needed future research into physical activity interventions for severe asthma. World Health Organization International Clinical Trials Registry Platform The study was registered under the Australian New Zealand Clinical Trials Registry (ANZCTR) on the 26th of November 2018, Trial ID ACTRN12618001914257.

Asthma and chronic obstructive pulmonary disease (COPD) are two prevalent chronic airways diseases. Both are complex and heterogeneous. Traditionally, clinical guidelines have advocated a stepwise approach to pharmacotherapy of asthma and COPD, but there is increasing realization that both require a more personalized and precise management approach. To this end, a management strategy based on the so-called Treatable Traits has been proposed. Emerging evidence suggests that this model improves relevant outcomes in patients with chronic airway diseases but further research is needed to guide implementation. This review discusses the challenges, opportunities, and hurdles that its implementation will have to face.

Purpose: Systemic inflammatory biomarkers can improve diagnosis and assessment of chronic obstructive pulmonary disease (COPD) and asthma. We aimed to validate an airway disease biomarker panel of 4 systemic inflammatory biomarkers, a2-macroglobulin, ceruloplasmin, haptoglobin and hemopexin, to establish their relationship to airway disease diagnosis and inflammatory phenotypes and to identify an optimized biomarker panel for disease differentiation. Methods: Participants with COPD or asthma were classified by inflammatory phenotypes. Immunoassay methods were used to measure levels of validation biomarkers in the sera of participants with disease and non-respiratory disease controls. Markers were analyzed individually and in combination for disease differentiation and compared to established biomarkers (C-reactive protein, interleukin-6, and white blood cell/blood eosinophil count). Results: The study population comprised of 141 COPD, 127 severe asthma, 54 mild-moderate asthma and 71 control participants. Significant differences in ceruloplasmin, haptoglobin and hemopexin levels between disease groups and between systemic inflammatory phenotypes were observed. However, no differences were found between airway inflammatory phenotypes. Hemopexin was the best performing individual biomarker and could diagnose COPD versus control participants (area under the curve [AUC], 98.3%; 95% confidence interval [CI], 96.7%-99.9%) and differentiate COPD from asthmatic participants (AUC, 97.0%; 95% CI, 95.4%-98.6%), outperforming established biomarkers. A biomarker panel, including hemopexin, haptoglobin and other established biomarkers, could diagnose asthma versus control participants (AUC, 87.5%; 95% CI, 82.8%-92.2%). Conclusions: Hemopexin can be a novel biomarker with superior diagnostic ability in differentiating COPD and asthma. We propose an anti-inflammatory axis between the airways and systemic circulation, in which hemopexin is a protective component in airway disease.

Monoclonal antibody therapies are effective for many but not all people with severe asthma. Precision medicine guides treatment selection using biomarkers to select patients most likely to respond according to their inflammatory endotypes. However, when assessing response to treatment, greater precision is required. We report a case series describing treatment response to mepolizumab in four severe asthma patients, assessed by traditional methods and with objective ventilation/perfusion single photon emission computed tomography (V-P SPECT). In this series, patients with severe asthma received mepolizumab treatment with clinical outcomes recorded at commencement and at approximately 16 weeks post-treatment initiation. V-P SPECT imaging was performed before and after treatment to determine ventilation heterogeneity and perfusion, and its ability to assess treatment responsiveness. V-P SPECT shows promise as an objective measure to assess lung ventilation and perfusion to observe and assess responsiveness to mepolizumab. With quantification, this measure may allow better precision in determining treatment improvements.

Background: Clinicians are increasingly recognizing severe asthma patients in whom biologics and other add-on therapies lead to dramatic improvement. Currently, there is no agreed-upon super-responder (SR) definition. Objective: To survey severe asthma experts using a modified Delphi process, to develop an international consensus-based definition of a severe asthma SR. Methods: The Delphi panel was composed of 81 participants (94% specialist pulmonologists or allergists) from 24 countries and consisted of three iterative online voting rounds. Consensus on individual items, whether acceptance or rejection, required at least 70% agreement by panel members. Results: Consensus was achieved that the SR definition should be based on improvement across three or more domains assessed over 12 months. Major SR criteria included exacerbation elimination, a large improvement in asthma control (two or more times the minimal clinically important difference), and cessation of maintenance of oral steroids (or weaning to adrenal insufficiency). Minor SR criteria were composed of a 75% exacerbation reduction, having well-controlled asthma, and 500 mL or greater improvement in FEV1. The SR definition requires improvement in at least two major criteria. In the future, the SR definition should be expanded to incorporate quality of life measures, although current tools can be difficult to implement in a clinical setting and further research is needed. Conclusions: This international consensus-based definition of severe asthma SRs is an important prerequisite for better understanding SR prevalence, predictive factors, and the mechanisms involved. Further research is needed to understand the patient's perspective and to measure quality of life more precisely in SRs.

Background: A strategy based on the assessment and management of treatable traits (TTs) has been proposed as a new paradigm in airway disease. There is a potentially long list of TTs with likely different clinical impact. Objective: To identify TTs most strongly associated with poorer health-related quality of life (HRQOL) and treatments that most substantially improved HRQOL. Methods: We pooled data from 2 parallel-group clinical trials of multidimensional assessment and individualized management targeted to TTs versus usual care in patients with chronic obstructive pulmonary disease or severe asthma (intervention N = 45; control N = 46). Following multidimensional assessment, 22 TTs were identified and the intervention group received treatments tailored to their identified TT. We used Bayesian Model Averaging to examine associations between TTs and HRQOL (St George's Respiratory Questionnaire) at baseline, as well as between each TT treatment and the observed change in HRQOL postintervention. Results: TTs most substantially associated with poorer baseline HRQOL were frequent chest infections, breathing pattern disorder, inadequate inhaler technique, systemic inflammation (C-reactive protein >3 mg/L), and depression. In both trials, TT treatment led to a large, significant improvement in HRQOL compared with usual care (Cohen's d = 1.19; P < .001). Receiving a statin for systemic inflammation and oral corticosteroid for eosinophilic airway inflammation was associated with the largest HRQOL improvements. Treatments for exercise intolerance, anxiety, and obesity were associated with smaller improvements in HRQOL. Conclusions: This study contributes to identifying clinically impactful TTs by showing that TTs across pulmonary, extrapulmonary, and behavioral domains were associated with HRQOL impairment and treatment response.

Background: People with severe asthma experience frequent life-threatening acute asthma events. A Lancet commission recently highlighted that terms ¿exacerbations¿ and ¿flare-ups¿ are seen to trivialize these episodes and recommended use of the term ¿attacks.¿ Clinicians however, preferentially use the term ¿exacerbation¿ and some guidelines recommend the use of ¿exacerbation¿ with patients. Objective: This descriptive qualitative study aimed to understand the patient¿s experience and perspectives of these events and language used to describe them. Methods: Semi-structured one-on-one interviews were conducted in Australia and the UK in 18 people with severe asthma and 10 with mild-moderate asthma regarding their usage and preferences for such terminologies. Additionally, nine people with severe asthma participated in two focus groups in which use of preferred terminology was explored. Results: Mean age of participants was 57 ± 14.03 yr and 65% were female. A total 67 quotes were recorded in which 16 participants with severe asthma spontaneously used either the term ¿attack,¿ ¿flare-up¿ and/or ¿exacerbation.¿ Of these quotes, all 16 participants used ¿attack,¿ one used all three terms and two used both ¿exacerbation¿ and ¿attack.¿ The term ¿attack¿ was used to describe frightening events having major impacts on participant¿s lives, whereas ¿exacerbation¿ and ¿flare-up¿ were used to refer to both severe and mild, transient asthma-related events. Conclusion: Usage of the term ¿attack¿ was preferred by patients with severe asthma. Adoption of this language may assist in patient-clinician communication and disease management and outcomes. Wider stakeholder engagement is needed to confirm this suggestion. AbbreviationsFEV1 forced expiratory volume in 1 secondATS American Thoracic SocietyERS European Respiratory SocietyACQ Asthma Control QuestionnaireICS inhaled corticosteroidsOCS oral corticosteroidsBTS British Thoracic SocietySIGN Scottish Intercollegiate Guidelines NetworkWAP written action plan.

Background: Data on treatable traits (TTs) in different populations are limited. Objective: To assess TTs in elderly patients with asthma and compare them to younger patients, to evaluate the association of TTs with future exacerbations, and to develop an exacerbation prediction model. Methods: We consecutively recruited 521 participants at West China Hospital, Sichuan University based on the Australasian Severe Asthma Network, classified as elderly (n = 62) and nonelderly (n = 459). Participants underwent a multidimensional assessment to characterize the TTs and were then followed up for 12 months. TTs and their relationship with future exacerbations were described. Based on the TTs and asthma control levels, an exacerbation prediction model was developed, and the overall performance was externally validated in an independent cohort. Results: A total of 38 TTs were assessed. Elderly patients with asthma had more chronic metabolic diseases, fixed airflow limitation, emphysema, and neutrophilic inflammation, whereas nonelderly patients with asthma exhibited more allergic characteristics and psychiatric diseases. Nine traits were associated with increased future exacerbations, of which exacerbation prone, upper respiratory infection¿induced asthma attack, cardiovascular disease, diabetes, and depression were the strongest. A model including exacerbation prone, psychiatric disease, cardiovascular disease, upper respiratory infection¿induced asthma attack, noneosinophilic inflammation, cachexia, food allergy, and asthma control was developed to predict exacerbation risk and showed good performance. Conclusions: TTs can be systematically assessed in elderly patients with asthma, some of which are associated with future exacerbations, proving their clinical utility of evaluating them. A model based on TTs can be used to predict exacerbation risk in people with asthma.

Background and objective: Severe asthma is responsible for a disproportionate burden of illness and healthcare costs spent on asthma. This study analyses sputum transcriptomics to investigate the mechanisms and novel treatment targets of severe asthma. Methods: Induced sputum samples were collected in a cross-sectional study from participants with severe asthma (n = 12, defined as per GINA criteria), non-severe uncontrolled (n = 21) and controlled asthma (n = 21) and healthy controls (n = 15). Sputum RNA was extracted and transcriptomic profiles were generated (Illumina HumanRef-8 V2) and analysed (GeneSpring). Sputum protein lysates were analysed for p38 activation in a validation study (n = 24 asthma, n = 8 healthy) by western blotting. Results: There were 2166 genes differentially expressed between the four groups. In severe asthma, the expression of 1875, 1308 and 563 genes was altered compared to healthy controls, controlled and uncontrolled asthma, respectively. Of the 1875 genes significantly different to healthy controls, 123 were >2-fold change from which four networks were identified. Thirty genes (>2-fold change) were significantly different in severe asthma compared to both controlled asthma and healthy controls. There was enrichment of genes in the p38 signalling pathway that were associated with severe asthma. Phosphorylation of p38 was increased in a subset of severe asthma samples, correlating with neutrophilic airway inflammation. Conclusion: Severe asthma is associated with substantial differences in sputum gene expression that underlie unique cellular mechanisms. The p38 signalling pathway may be important in the pathogenesis of severe asthma, and future investigations into p38 inhibition are warranted as a ¿non-Th2¿ therapeutic option.

Rationale & Objective: More than 50% of hemodialysis patients experience sleep disturbance and most have coexisting sleep apnea. However, how sleep apnea affects sleep and the overall experience of patients with chronic kidney disease treated by hemodialysis has not been evaluated. Study Design: A mixed-methods design, incorporating cross-sectional observational and descriptive qualitative methodologies. Setting & Participants: Patients receiving maintenance hemodialysis in Newcastle, New South Wales, Australia, with newly diagnosed sleep apnea (apnea-hypopnea index = 5 per hour). Assessments: In-laboratory polysomnography to assess sleep apnea and objective sleep parameters. Epworth Sleepiness Scale to assess daytime symptoms. A semi-structured qualitative interview to explore patient experience. Analytical Approach: Descriptive and iterative thematic analysis. Results: We analyzed 36 patients with newly diagnosed sleep apnea and interviewed 26 (mean age, 62 years, median apnea-hypopnea index, 32 per hour). Severity of sleep apnea did not affect patients¿ sleep duration, sleep efficiency, or self-reported Epworth Sleepiness Scale score. From the qualitative interviews, 4 themes emerged: ¿broken sleep¿ related to short sleep duration, with waking and dozing off a common sleep cycle, caused by uncontrolled pain and dialysis. Many participants reported regularly ¿feeling unrefreshed¿ on waking. ¿Impact of sleep disturbance¿ included reduced physical, mental, and self-management capacity. Finally, interviewees described the need to use strategies to ¿soldier on¿ with symptoms. Limitations: Participants¿ views are only transferrable to hemodialysis patients with sleep apnea. Conclusions: Our findings suggest that severity of sleep apnea does not affect sleep time or patient-reported daytime sleepiness; however, hemodialysis patients with sleep apnea report disturbed and unrefreshed sleep and the debilitating effects of sleep disturbance is profound. Broken and unrefreshed sleep were the dominant symptoms of sleep apnea and should be assessed routinely to identify patients with sleep apnea and improve quality of life in patients with chronic kidney disease treated with hemodialysis.

Asthma is a common disease affecting approximately 300 million people worldwide, across all age ranges. Despite advances in asthma outcomes of the last few decades, there remains room for improvement in asthma management and for patient outcomes, particularly in older patients. The heterogeneity of asthma is now well recognized, and is known to complicate response to treatment and patient behavior and impact health outcomes. Asthma and its heterogeneity change according to age. Asthma affects people differently across the life span. In adults, prevalence is highest among those in middle age; however, mortality is greater in the older age group. In this clinical commentary, we describe how age impacts asthma prevalence and incidence, outcomes, disease expression, and approach to management in adulthood and in older patients.

Background: The 6 gene expression signature (6GS) predicts in¿ammatory phenotype, exacerbation risk, and corticosteroid responsiveness in asthma. In COPD, patterns of airway in¿ammation are similar, suggesting the 6GS may be useful. This study determines the diagnostic and prognostic ability of 6GS in predicting in¿ammatory phenotypes and exacerbation risk in COPD. Methods: We performed 2 studies: a cross-sectional phenotype prediction study in stable COPD (total N=132; n=34 eosinophilic (E)-COPD, n=42 neutrophilic (N)-COPD, n=39 paucigranulocytic (PG)-COPD, n=17 mixed-granulocytic (MG)-COPD) that assessed 6GS ability to discriminate phenotypes (eosinophilia=3%; neutrophilia=61%); and a prospective cohort study (total n=54, n=8 E-COPD; n=18 N-COPD; n=20 PG-COPD; n=8 MG-COPD, n=21 exacerbation prone (=2/year)) that investigated phenotype and exacerbation prediction utility. 6GS was measured by qPCR and evaluated using multiple logistic regression and area under the curve (AUC). Short-term reproducibility (intra-class correlation) and phenotyping method agreement (¿ statistic) were assessed. Results: In the phenotype prediction study, 6GS could accurately identify and discriminate patients with E-COPD from N-COPD (AUC=96.4%; p<0.0001), PG-COPD (AUC=88.2%; p<0.0001) or MG-COPD (AUC=86.2%; p=0.0001), as well as N-COPD from PG-COPD (AUC=83.6%; p<0.0001) or MG-COPD (AUC=87.4%; p<0.0001) and was reproducible. In the prospective cohort study, 6GS had substantial agreement for neutrophilic in¿ammation (82%, ¿=0.63,p<0.001)and moderate agreement foreosinophilici n¿ammation(78%, ¿=0.42,p<0.001). 6GS could signi¿cantly discriminate exacerbationprone patients (AUC=77.2%; p=0.034). Higher IL1B levels were associated with poorer lung function and increased COPD severity. Conclusion: 6GS can signi¿cantly and reproducibly discriminate COPD in¿ammatory phenotypes and predict exacerbation prone patients and may become a useful molecular diagnostic tool assisting COPD management..

Background: Severe asthma and bronchiectasis are heterogeneous diseases that contribute to disability beyond the pulmonary system. The magnitude of the impact that these extrapulmonary features has on health-related quality of life (HRQoL) is unknown. Methods: We analysed the cross-sectional relationships between HRQoL (St. George's Respiratory Questionnaire; SGRQ) and extrapulmonary characteristics, including physical activity (steps/day), anxiety and depression, isometric leg strength, systemic inflammation, and several comorbidities in adults with severe asthma (n = 70) and bronchiectasis (n = 61). Results: Participants with severe asthma and bronchiectasis had similar SGRQ total scores (mean scores 43.7 and 37.8 for severe asthma and bronchiectasis; p > 0.05), and similar pulmonary and extrapulmonary characteristics. The associations between extrapulmonary variables and HRQoL did not differ according to diagnosis (all interactions p > 0.05). Greater anxiety and depressive symptoms, fewer steps/day and greater systemic inflammation were statistically associated with poorer HRQoL in both diseases (p < 0.05). Lower isometric leg strength in severe asthma, and greater Charlson Comorbidity Index in bronchiectasis were also associated with poorer HRQoL (p < 0.05). In the multivariable regression model performed in the combined disease groups, anxiety and depression, steps/day, systemic inflammation and isometric leg strength remained independently associated with HRQoL. Associations between extrapulmonary characteristics and SGRQ domains were stronger for the activity and impact domains, than symptoms. Conclusion: In severe asthma and bronchiectasis, extrapulmonary features including physical activity and leg strength have a significant impact on HRQoL, especially within the activity and impact domains. These features should be considered as part of the assessment of these conditions, and they may represent additional treatment targets to improve HRQoL.

Background: Dysfunction of the bronchial epithelium plays an important role in asthma; however, its measurement is challenging. Columnar epithelial cells are often quantified, yet rarely analysed, in induced sputum studies. Objective: We aimed to test whether sputum columnar epithelial cell proportion and count are altered in asthma, and whether they are associated with clinical and inflammatory variables. We aimed to test whether sputum-based measures could provide a relatively non-invasive means through which to monitor airway epithelial activation status. Methods: We examined the relationship of sputum columnar epithelial cells with clinical and inflammatory variables of asthma in a large retrospective cross-sectional cohort (901 participants with asthma and 138 healthy controls). In further studies, we used flow cytometry, microarray, qPCR and ELISA to characterize sputum columnar epithelial cells and their products. Results: Multivariate analysis and generation of 90th centile cut-offs (=11% or =18.1¿×¿104/mL) to identify columnar epithelial cell ¿high¿ asthma revealed a significant relationship between elevated sputum columnar cells and male gender, severe asthma and non-neutrophilic airway inflammation. Flow cytometry showed viable columnar epithelial cells were present in all sputum samples tested. An epithelial gene signature (SCGB3A1, LDLRAD1, FOXJ1, DNALI1, CFAP157, CFAP53) was detected in columnar epithelial cell-high sputum. CLCA1 mRNA and periostin protein, previously identified biomarkers of IL-13-mediated epithelial activation, were elevated in columnar epithelial cell-high sputum samples, but only when accompanied by eosinophilia. Conclusions & clinical relevance: Sputum columnar epithelial cells are related to important clinical and inflammatory variables in asthma. Measurement of epithelial biomarkers in sputum samples could allow non-invasive assessment of altered bronchial epithelium status in asthma.

Introduction The evidence that teaching self-management techniques to children and young people with asthma in schools is effective has not, to date, been the subject of systematic review. Methods We conducted a systematic review of intervention studies. Studies were eligible if they employed a randomised parallel-group design and were published in English from 1995 onwards. Participants included children with asthma aged 5-18 years who participated within their own school environment. Searches were conducted on the Cochrane Airways Group Specialised Register. Quantitative data were combined using random-effects meta-analyses. Results Thirty-three outcome evaluation studies were included. School-based interventions were effective in reducing the frequency of emergency department visits (OR 0.70, 95% CI 0.53 to 0.92; studies=13), and moderately effective in reducing levels of hospitalisations (standardised mean differences [SMD] â '0.19, 95% CI â '0.35 to â '0.04; studies=6). A meta-analysis of three studies suggest that the intervention approach could reduce the number of days of restricted activity (SMD â '0.30, 95% CI â '0.41 to â '0.18; studies=3). However, there was uncertainty as to whether school-based self-management interventions impacted on reducing absences from school. Conclusions Self-management interventions for children with asthma delivered in schools reduce the number of acute episodes of healthcare usage. We conclude that the school environment is an important space for delivering interventions to improve children's health.

Background and objective: A new taxonomic and management approach, termed treatable traits, has been proposed for airway diseases including severe asthma. This study examined whether treatable traits could be identified using registry data and whether particular treatable traits were associated with future exacerbation risk. Methods: The Australasian Severe Asthma Web-Based Database (SAWD) enrolled 434 participants with severe asthma and a comparison group of 102 participants with non-severe asthma. Published treatable traits were mapped to registry data fields and their prevalence was described. Participants were characterized at baseline and every 6 months for 24 months. Results: In SAWD, 24 treatable traits were identified in three domains: pulmonary, extrapulmonary and behavioural/risk factors. Patients with severe asthma expressed more pulmonary and extrapulmonary treatable traits than non-severe asthma. Allergic sensitization, upper-airway disease, airflow limitation, eosinophilic inflammation and frequent exacerbations were common in severe asthma. Ten traits predicted exacerbation risk; among the strongest were being prone to exacerbations, depression, inhaler device polypharmacy, vocal cord dysfunction and obstructive sleep apnoea. Conclusion: Treatable traits can be assessed using a severe asthma registry. In severe asthma, patients express more treatable traits than non-severe asthma. Traits may be associated with future asthma exacerbation risk demonstrating the clinical utility of assessing treatable traits.

Background and objective: Physical activity (PA) in obstructive airway diseases (OAD) is likely to be impaired but this has not been extensively studied outside of chronic obstructive pulmonary disease (COPD). We describe PA levels in severe asthma and bronchiectasis compared to moderate¿severe COPD and to controls, and tested the cross-sectional associations of PA (steps/day) with shared disease characteristics in the OAD group. Methods: Adults with OAD (severe asthma = 62, COPD = 67, bronchiectasis = 60) and controls (n = 63) underwent a multidimensional assessment, including device-measured PA levels. Results: The OAD group included 189 participants (58.7% females), with median (interquartile range) age of 67 (58¿72) years and mean forced expiratory volume in the first second (FEV 1 ) % predicted of 69.4%. Demographic characteristics differed between groups. Compared to controls (52.4% females, aged 55 (34¿64) years, median 7640 steps/day), those with severe asthma, bronchiectasis and COPD accumulated less steps/day: median difference of -2255, -2289, and -4782, respectively (P = 0.001). Compared to COPD, severe asthma and bronchiectasis participants accumulated more steps/day: median difference of 2375 and 2341, respectively (P = 0.001). No significant differences were found between the severe asthma and bronchiectasis group. Exercise capacity, FEV 1 % predicted, dyspnoea and systemic inflammation differed between groups, but were each significantly associated with steps/day in OAD. In the multivariable model adjusted for all disease characteristics, exercise capacity and FEV 1 % predicted remained significantly associated. Conclusion: PA impairment is common in OAD. The activity level was associated with shared characteristics of these diseases. Interventions to improve PA should be multifactorial and consider the level of impairment and the associated characteristics.

Living well with severe asthma can be challenging. People with severe asthma can be refractory to treatment, can experience poor symptom control and are at a heightened risk of death. Patients experience symptoms of shortness of breath, chest tightness, cough and wheeze. These symptoms influence many aspects of an individual¿s life, resulting in emotional, financial, functional and medication-related burdens that negatively impact quality of life. Quality of life is known to be influenced by individual levels of satisfaction that stem from real-life treatment experiences. This experience is portrayed through the lens of the patient, which is commonly referred to as the patient perspective. The patient perspective is only one element of the patient experience. It influences health status, which, in severe asthma, is commonly assessed using validated health-related quality of life measures. A positive patient perspective may be achieved with implementation of management strategies tailored to individual needs. Management strategies developed in partnership between the patient, the severe asthma multidisciplinary team and the general practitioner may minimise disease-related impairment, allowing patients to live well with severe asthma.

Severe asthma leads to debilitating symptoms for patients and excessive socioeconomic burden for the community. Comprehensive models of care are required to address complex issues, risk factors and comorbidities in patients with severe asthma, and to identify patients most appropriate for specialised treatments. Dedicated severe asthma services improve asthma control, reduce asthma exacerbations and hospital admissions, and improve quality of life. Currently, diverse models of care exist for managing severe asthma across Australia. Most referrals to severe asthma services are from respiratory physicians seeking a second opinion or from primary care for poorly controlled asthma. Despite benefits of specialised severe asthma services, many patients are not referred and resources are limited, often resulting in long waiting times. Patient referral is often unstructured and there are considerable variations in the management of severe asthma with limited access to other health care professionals such as speech pathologists and dieticians, and restricted scope to optimise patient work-up before referral. Ongoing communication between the specialist and referring clinician is essential for continuity of care but is often lacking. Referral pathways can be optimised by developing referral criteria and guidelines to triage patients with severe asthma and to improve resource efficiency. Additional education and tools for assessing and managing severe asthma are needed, and mechanisms should be developed for involving primary care in the management of stabilised patients. Strategies to increase patient access to multidisciplinary services are recommended.

Background: Physical inactivity and high sedentary time are associated with adverse health outcomes in several diseases. However, their impact in asthma is less clear. Objective: We aimed to synthesize the literature characterizing physical activity and sedentary time in adults with asthma, to estimate activity levels using meta-analysis, and to evaluate associations between physical activity and sedentary time and the clinical and physiological characteristics of asthma. Methods: Articles written in English and addressing the measurement of physical activity or sedentary time in adults =18 years old with asthma were identified using 4 electronic databases. Meta-analysis was used to estimate steps/day in applicable studies. Results: There were 42 studies that met the inclusion criteria. Physical activity in asthma was lower compared with controls. The pooled mean (95% confidence interval) steps/day for people with asthma was 8390 (7361, 9419). Physical activity tended to be lower in females compared with males, and in older people with asthma compared with their younger counterparts. Higher levels of physical activity were associated with better measures of lung function, disease control, health status, and health care use. Measures of sedentary time were scarce, and indicated a similar engagement in this behavior between participants with asthma and controls. High sedentary time was associated with higher health care use, and poorer lung function, asthma control, and exercise capacity. Conclusions: People with asthma engage in lower levels of physical activity compared with controls. Higher levels of physical activity may positively impact on asthma clinical outcomes. Sedentary time should be more widely assessed.

Background: Asthma is often suboptimally controlled, in part due to patients' disease knowledge. Understanding patients' knowledge, prior to education may help in individualizing content. However, there are no well validated or internationally relevant patient asthma knowledge questionnaires available. Objective: To translate and validate the rigorously validated Questionnaire de connaissances sur l'asthme destiné aux patients adultes (QCA-PA) based on key points related to asthma knowledge and self-management accordingly to the Global Initiative for Asthma report. Methods: Based on Vallerand's methodology, a preliminary version of the ¿Patient-completed Asthma Knowledge Questionnaire¿ (PAKQ) was back-translated and evaluated by an expert committee. A sample of 20 individuals with asthma pretested the questionnaire, after which 62 adults were recruited. Sociodemographic data were collected and the PAKQ together with a comparator questionnaire (Consumer Questionnaire (CQ)) were completed. Fourteen days after the first visit, participants returned to recomplete both questionnaires; half were randomly selected to receive a one-on-one asthma education session and again completed both questionnaires immediately after education, and at 10 days follow-up. Results: The PAKQ showed good internal consistency (KR-20 = 0.77). Moderate correlation with CQ (r = 0.596, p = 0.01) attested to its concurrent validity. Confirmatory factor analyses confirmed a single factor structure. A repeated measures ANOVA showed its reproducibility (n = 21:F(1)= 3.578, p = 0.07, ¿p2= 0.152) and responsiveness (n = 21:F(1)= 26.041, P < 0.05, ¿p2= 0.566). Conclusion: The PAKQ is a valid asthma knowledge questionnaire which is based on international asthma recommendations and could help healthcare professionals in individualizing educational interventions for people with asthma.

Sleep disturbance is one of the most common dialysis-related symptoms reported by hemodialysis patients. Poor sleep confers significant physical and psychological burden on patients with kidney disease and is associated with reduced quality of life and survival. More recent evidence also indicates that sleep-disordered breathing may be a risk factor for kidney injury.

Asthma is a chronic respiratory disease characterized by respiratory symptoms, airway inflammation, airway obstruction and airway hyper-responsiveness. Asthma is common and directly affects 10% of Australians, 1¿5% of adults in Asia and 300 million people worldwide. It is a heterogeneous disorder with many clinical, molecular, biological and pathophysiological phenotypes. Current management strategies successfully treat the majority of patients with asthma who have access to them. However, there is a subset of an estimated 5¿10% of patients with asthma who have severe disease and are disproportionately impacted by symptoms, exacerbations and overall illness burden. The care required for this relatively small proportion of patients is also significant and has a major impact on the healthcare system. A number of new therapies that hold promise for severe asthma are currently in clinical trials or are entering the Australian and international market. However, recognition of severe asthma in clinical practice is variable, and there is little consensus on the best models of care or how to integrate emerging and often costly therapies into current practice. In this article, we report on roundtable discussions held with severe asthma experts from around Australia, and make recommendations about approaches for better patient diagnosis and assessment. We assess current models of care for patient management and discuss how approaches may be optimized to improve patient outcomes. Finally, we propose mechanisms to assess new therapies and how to best integrate these approaches into future treatment.

Background and objective: The aim of the Pulmonary Rehabilitation Guidelines (Guidelines) is to provide evidence-based recommendations for the practice of pulmonary rehabilitation (PR) specific to Australian and New Zealand healthcare contexts. Methods: The Guideline methodology adhered to the Appraisal of Guidelines for Research and Evaluation (AGREE) II criteria. Nine key questions were constructed in accordance with the PICO (Population, Intervention, Comparator, Outcome) format and reviewed by a COPD consumer group for appropriateness. Systematic reviews were undertaken for each question and recommendations made with the strength of each recommendation based on the GRADE (Gradings of Recommendations, Assessment, Development and Evaluation) criteria. The Guidelines were externally reviewed by a panel of experts. Results: The Guideline panel recommended that patients with mild-to-severe COPD should undergo PR to improve quality of life and exercise capacity and to reduce hospital admissions; that PR could be offered in hospital gyms, community centres or at home and could be provided irrespective of the availability of a structured education programme; that PR should be offered to patients with bronchiectasis, interstitial lung disease and pulmonary hypertension, with the latter in specialized centres. The Guideline panel was unable to make recommendations relating to PR programme length beyond 8 weeks, the optimal model for maintenance after PR, or the use of supplemental oxygen during exercise training. The strength of each recommendation and the quality of the evidence are presented in the summary. Conclusion: The Australian and New Zealand Pulmonary Rehabilitation Guidelines present an evaluation of the evidence for nine PICO questions, with recommendations to provide guidance for clinicians and policymakers.

Severe asthma is a complex heterogeneous disease that is refractory to standard treatment and is complicated by multiple comorbidities and risk factors. In mild to moderate asthma, the burden of disease can be minimised by inhaled corticosteroids, bronchodilators and self-management education. In severe asthma, however, management is more complex. When patients with asthma continue to experience symptoms and exacerbations despite optimal management, severe refractory asthma (SRA) should be suspected and confirmed, and other aetiologies ruled out. Once a diagnosis of SRA is established, patients should undergo a systematic and multidimensional assessment to identify inflammatory endotypes, risk factors and comorbidities, with targeted and individualised management initiated. We describe a practical approach to assessment and management of patients with SRA.

Background: Exacerbations of asthma and COPD are a major cause of morbidity and mortality and are responsible for significant health care costs. This study further investigates interleukin (IL)-1 pathway activation and its relationship with exacerbations of asthma and COPD. Methods: In this prospective cohort study, 95 participants with stable asthma (n=35) or COPD (n=60) were recruited and exacerbations recorded over the following 12 months. Gene expressions of IL-1 pathway biomarkers, including the IL-1 receptors (IL1R1, IL1R2, and IL1RN), and signaling molecules (IRAK2, IRAK3, and PELI1), were measured in sputum using real-time quantitative polymerase chain reaction. Mediators were compared between the frequent (2 exacerbations in the 12 months) and infrequent exacerbators, and the predictive relationships investigated using receiver operating characteristic curves and area under the curve (AUC) values. Results: Of the 95 participants, 89 completed the exacerbation follow-up, where 30 participants (n=22 COPD, n=8 asthma) had two or more exacerbations. At the baseline visit, expressions of IRAK2, IRAK3, PELI1, and IL1R1 were elevated in participants with frequent exacerbations of both asthma and COPD combined and separately. In the combined population, sputum gene expression of IRAK3 (AUC=75.4%; P,0.001) was the best predictor of future frequent exacerbations, followed by IL1R1 (AUC=72.8%; P,0.001), PELI1 (AUC=71.2%; P,0.001), and IRAK2 (AUC=68.6; P=0.004). High IL-1 pathway gene expression was associated with frequent prior year exacerbations and correlated with the number and severity of exacerbations. Conclusion: The upregulation of IL-1 pathway mediators is associated with frequent exacerbations of obstructive airway disease. Further studies should investigate these mediators as both potential diagnostic biomarkers predicting at-risk patients and novel treatment targets.

Background Asthma and COPD are common airway diseases. Individuals with overlapping asthma and COPD experience increased health impairment and severe disease exacerbations. Efficacious treatment options are required for this population. Omalizumab (anti-IgE) therapy is effective in patients with severe persistent asthma, but limited data are available on efficacy in populations with overlapping asthma and COPD. Methods Data from the Australian Xolair Registry were used to compare treatment responses in individuals with asthma-COPD overlap with responses in patients with severe asthma alone. Participants were assessed at baseline and after 6¿months of omalizumab treatment. We used several different definitions of asthma-COPD overlap. First, we compared participants with a previous physician diagnosis of COPD to participants with no COPD diagnosis. We then made¿comparisons based on baseline lung function, comparing participants with an FEV1 <¿80%¿predicted to those with an FEV1 > 80%¿predicted after bronchodilator use. In the population with an FEV1< 80%, analysis was further stratified based on smoking history. Results Omalizumab treatment markedly improved asthma control and health-related quality of life in all populations assessed based on the Asthma Control Questionnaire and Asthma Quality of Life Questionnaire scores. Omalizumab treatment did not improve lung function (FEV1, FVC, or FEV1/FVC ratio) in populations that were enriched for asthma-COPD overlap (diagnosis of COPD or FEV1¿< 80%/ever smokers). Conclusions Our study suggests that omalizumab improves asthma control and health-related quality of life in individuals with severe allergic asthma and overlapping COPD. These findings provide real-world efficacy data for this patient population and suggest that omalizumab is useful in the management of severe asthma with COPD overlap.

Introduction: Chronic obstructive pulmonary disease (COPD) is characterised by persistent respiratory symptoms and chronic airflow limitation, and is associated with exacerbations and comorbidities. Advances in the management of COPD are updated quarterly in the national COPD guidelines, the COPD-X plan, published by Lung Foundation Australia in conjunction with the Thoracic Society of Australia and New Zealand and available at http://copdx.org.au. Main recommendations: · Spirometry detects persistent airflow limitation (post-bronchodilator FEV1/FVC < 0.7) and must be used to confirm the diagnosis. · Non-pharmacological and pharmacological therapies should be considered as they optimise function (ie, improve symptoms and quality of life) and prevent deterioration (ie, prevent exacerbations and reduce decline). · Pulmonary rehabilitation and regular exercise are highly beneficial and should be provided to all symptomatic COPD patients. · Short- and long-acting inhaled bronchodilators and, in more severe disease, anti-inflammatory agents (inhaled cortico-steroids) should be considered in a stepwise approach. · Given the wide range of inhaler devices available, inhaler technique and adherence should be checked regularly. · Smoking cessation is essential, and influenza and pneumococcal vaccinations reduce the risk of exacerbations. · A plan of care should be developed with the multidisciplinary team. COPD action plans reduce hospitalisations and are recommended as part of COPD self-management. · Exacerbations should be managed promptly with bronchodilators, corticosteroids and antibiotics as appropriate to prevent hospital admission and delay COPD progression. · Comorbidities of COPD require identification and appropriate management. · Supportive, palliative and end-of-life care are beneficial for patients with advanced disease. · Education of patients, carers and clinicians, and a strong partnership between primary and tertiary care, facilitate evidence-based management of COPD. Changes in management as result of the guideline: Spirometry remains the gold standard for diagnosing airflow obstruction and COPD. Non-pharmacological and pharmacological treatment should be used in a stepwise fashion to control symptoms and reduce exacerbation risk.

Background: COPD patients are often prescribed multiple medications for their respiratory disease and comorbidities. This can lead to complex medication regimens resulting in poor adherence, medication errors, and drug-drug interactions. The relationship between clinical outcomes and medication burden beyond medication count in COPD is largely unknown. Objectives: The aim of this study was to explore the relationships of medication burden in COPD with clinical outcomes, comorbidities, and multidimensional indices. Methods: In a cross-sectional study, COPD patients (n=222) were assessed for demographic information, comorbidities, medication use, and clinical outcomes. Complexity of medication regimens was quantified using the validated medication regimen complexity index (MRCI). Results: Participants (58.6% males) had a mean (SD) age of 69.1 (8.3) years with a postbronchodilator forced expiratory volume in 1 second % predicted of 56.5 (20.4) and a median of five comorbidities. The median (q1, q3) total MRCI score was 24 (18.5, 31). COPD-specific medication regimens were more complex than those of non-COPD medications (median MRCI: 14.5 versus 9, respectively; P<0.0001). Complex dosage formulations contributed the most to higher MRCI scores of COPD-specific medications while dosing frequency primarily drove the complexity associated with non-COPD medications. Participants in Global Initiative for Chronic Obstructive Lung Disease quadrant D had the highest median MRCI score for COPD medications (15.5) compared to those in quadrants A (13.5; P=0.0001) and B (12.5; P<0.0001). Increased complexity of COPD-specific treatments showed significant but weak correlations with lower lung function and 6-minute walk distance, higher St George¿s Respiratory Questionnaire and COPD assessment test scores, and higher number of prior year COPD exacerbations and hospitalizations. Comorbid cardiovascular, gastrointestinal, or metabolic diseases individually contributed to higher total MRCI scores and/or medication counts for all medications. Charlson Comorbidity Index and COPD-specific comorbidity test showed the highest degree of correlation with total MRCI score (¿=0.289 and ¿=0.326; P<0.0001, respectively). Conclusion: In COPD patients, complex medication regimens are associated with disease severity and specific class of comorbidities.

The management of severe asthma is complex. Multidimensional assessment (MDA) of specific traits has been proposed as an effective strategy to manage severe asthma, although it is supported by few prospective studies. We aimed to systematically review the literature published on MDA in severe asthma, to identify the traits included in MDA and to determine the effect of MDA on asthma-related outcomes. We identified 26 studies and classified these based on study type (cohort/cross-sectional studies; experimental/outcome studies; and severe asthma disease registries). Study type determined the comprehensiveness of the assessment. Assessed traits were classified into three domains (airways, co-morbidities and risk factors). The airway domain had the largest number of traits assessed (mean ± SD = 4.2 ± 1.7) compared with co-morbidities (3.6 ± 2.2) and risk factors (3.9 ± 2.1). Bronchodilator reversibility and airflow limitation were assessed in 92% of studies, whereas airway inflammation was only assessed in 50%. Commonly assessed co-morbidities were psychological dysfunction, sinusitis (both 73%) and gastro-oesophageal reflux disease (GORD; 69%). Atopic and smoking statuses were the most commonly assessed risk factors (85% and 86%, respectively). There were six outcome studies, of which five concluded that MDA is effective at improving asthma-related outcomes. Among these studies, significantly more traits were assessed than treated. MDA studies have assessed a variety of different traits and have shown evidence of improved outcomes. This promising model of care requires more research to inform which traits should be assessed, which traits should be treated and what effect MDA has on patient outcomes.

Mast cells are a resident inflammatory cell of the airways, involved in both the innate and adaptive immune response. The relationship between mast cells and inflammatory phenotypes and treatment response of asthma is not clear. Clinical characteristics of subjects with stable asthma (n=55), inflammatory cell counts and gene expression microarrays in induced sputum were analysed. Sputum mast cell subtypes were determined by molecular phenotyping based on expression of mast cell biomarkers (tryptase (TPSAB1), chymase (CMA1) and carboxypeptidase A3 (CPA3)). Effects of mast cell subtypes on steroid response were observed in a prospective cohort study (n=50). MCT (n=18) and MCT/CPA3 (mRNA expression of TPSAB1 and CPA3; n=29) subtypes were identified, as well as a group without mast cell gene expression (n=8). The MCT/CPA3 subtype had elevated exhaled nitric oxide fraction, sputum eosinophils, bronchial sensitivity and reactivity, and poorer asthma control. This was accompanied by upregulation of 13 genes. Multivariable logistic regression identified CPA3 (OR 1.21, p=0.004) rather than TPSAB1 (OR 0.92, p=0.502) as a determinant of eosinophilic asthma. The MCT/CPA3 subtype had a better clinical response and reduced signature gene expression with corticosteroid treatment. Sputum mast cell subtypes of asthma can be defined by a molecular phenotyping approach. The MCT/CPA3 subtype demonstrated increased bronchial sensitivity and reactivity, and signature gene expression, which was associated with airway eosinophilia and greater corticosteroid responsiveness.

Background and objective Chronic obstructive pulmonary disease (COPD) is characterized by progressive airflow limitation and inflammation. Airway bacterial colonization is increased in COPD; however, the role of potentially pathogenic and non-pathogenic bacteria in the pathogenesis of disease is unclear. This study characterized the presence of bacteria in a well-characterized cohort of adults with COPD and healthy controls. Methods Adults with COPD (n = 70) and healthy controls (n = 51) underwent clinical assessment and sputum induction. Sputum was dispersed, and total and differential cell counts were performed. Bacteria were cultured, identified and enumerated. Supernatants were assessed for neutrophil elastase (NE) and IL-1ß. Common respiratory pathogens were also determined using real-time PCR. Results Participants with COPD had a typical neutrophilic inflammatory profile. The total load of bacteria was increased in COPD and was associated with poorer respiratory health status, as measured by the St George's Respiratory Questionnaire (Spearman's r = 0.336, P = 0.013). Significantly lower levels of culturable Bacillus species were identified compared with healthy controls. PCR analyses revealed increased rates of detection of potentially pathogenic bacteria with Haemophilus influenzae detection associated with higher sputum levels of NE and IL-1ß, while Streptococcus pneumoniae was more common in male ex-smokers with emphysema and a deficit in diffusion capacity. Conclusion Non-pathogenic and pathogenic bacteria were altered in the sputum of patients with COPD. These observations highlight the potential to identify treatment and management strategies that both target specific bacterial pathogens and restore the microbial balance, which may lead to reductions in inflammation and subsequent improvements in lung health.

Background: Severe asthma is a high impact disease. Omalizumab targets the allergic inflammatory pathway; however, effectiveness data in a population with significant comorbidities are limited. Aims: To describe severe allergic asthma, omalizumab treatment outcomes and predictors of response among the Australian Xolair Registry participants. Methods: A web-based post-marketing surveillance registry was established to characterise the use, effectiveness and adverse effects of omalizumab (Xolair) for severe allergic asthma. Results: Participants (n = 192) (mean age 51 years, 118 female) with severe allergic asthma from 21 clinics in Australia were assessed, and 180 received omalizumab therapy. They had poor asthma control (Asthma Control Questionnaire, ACQ-5, mean score 3.56) and significant quality of life impairment (Asthma-related Quality of Life Questionnaire score 3.57), and 52% were using daily oral corticosteroid (OCS). Overall, 95% had one or more comorbidities (rhinitis 48%, obesity 45%, cardiovascular disease 23%). The omalizumab responder rate, assessed by an improvement of at least 0.5 in ACQ-5, was high at 83%. OCS use was significantly reduced. The response in participants with comorbid obesity and cardiovascular disease was similar to those without these conditions. Baseline ACQ-5 = 2.0 (P = 0.002) and older age (P = 0.05) predicted the magnitude of change in ACQ-5 in response to omalizumab. Drug-related adverse events included anaphylactoid reactions (n = 4), headache (n = 2) and chest pains (n = 1). Conclusion: Australian patients with severe allergic asthma report a high disease burden and have extensive comorbidity. Symptomatic response to omalizumab was high despite significant comorbid disease. Omalizumab is an effective targeted therapy for severe allergic asthma with comorbidity in a real-life setting.

Oxygen is a commonly used drug in the clinical setting and like other drugs its use must be considered carefully. This is particularly true for those patients who are at risk of type II respiratory failure in whom the risk of hypercapnia is well established. In recent times, several international bodies have advocated for the prescription of oxygen therapy in an attempt to reduce this risk in vulnerable patient groups. Despite this guidance, published data have demonstrated that there has been poor uptake of these recommendations. Multiple interventions have been tested to improve concordance, and while some of these interventions show promise, the sustainability of these interventions are less convincing. In this review, we summarize data that have been published on the prevalence of oxygen prescription and the accurate and appropriate administration of this drug therapy. We also identify strategies that have shown promise in facilitating changes to oxygen prescription and delivery practice. There is a clear need to investigate the barriers, facilitators, and attitudes of clinicians in relation to the prescription of oxygen therapy in acute care. Interventions based on these findings then need to be designed and tested to facilitate the application of evidence-based guidelines to support sustained changes in practice, and ultimately improve patient care.

Background and objective Neutrophil extracellular traps (NETs) are web-like structures comprising DNA and antimicrobial proteins, expelled from neutrophils during NETosis. Persistence of NETs can be pro-inflammatory, yet their role in respiratory disease remains unclear. This study aimed to investigate the presence of NETs in sputum from patients with asthma and COPD, and the relationship of NETs with inflammatory phenotype and disease severity. Methods Induced sputum was collected from healthy controls, asthma and COPD patients. Extracellular DNA (eDNA) was quantified by PicoGreen. LL-37, a-defensins1-3, NE, IL-1ß and CXCL8 were quantified by ELISA. PAD4 and NLRP3 gene expression was performed using qPCR. NETs were imaged in sputum smears using immunofluorescence microscopy. Results Sputum eDNA and NET neutrophil antimicrobial proteins were significantly elevated in asthma and COPD compared with healthy controls. Levels of eDNA and NET components were significantly higher in neutrophilic versus non-neutrophilic asthma and COPD. NETs were clearly visualized in sputum smears. PAD4 mRNA was upregulated in neutrophilic COPD. The level of eDNA was higher in severe asthma. High eDNA levels were associated with heightened innate immune responses, including elevated CXCL8 and IL-1ß, and NLRP3 gene expression in both COPD and asthma. Antimicrobial proteins and eDNA were positively correlated with airway neutrophils, and negatively correlated with lung function and symptoms. Conclusion NETs are present in the airways of subjects with asthma and COPD. Accumulation of excessive NETs was associated with activation of innate immune responses contributing to disease pathogenesis in chronic airway disease.

Background: Omalizumab (Xolair) dosing in severe allergic asthma is based on serum IgE and bodyweight. In Australia, patients eligible for omalizumab but exceeding recommended ranges for IgE (30¿1500 IU/mL) and bodyweight (30¿150 kg) may still receive a ceiling dose of 750 mg/4 weeks. About 62% of patients receiving government-subsidized omalizumab are enrolled in the Australian Xolair Registry (AXR). Objectives: To determine whether AXR participants above the recommended dosing ranges benefit from omalizumab and to compare their response to within-range participants. Methods: Data were stratified according to dose range status (above-range or within-range). Further sub-analyses were conducted according to the reason for being above the dosing range (IgE only vs. IgE and weight). Results: Data for 179 participants were analysed. About 55 (31%) were above recommended dosing criteria; other characteristics were similar to within-range participants. Above-range participants had higher baseline IgE [812 (IQR 632, 1747) IU/mL vs. 209 (IQR 134, 306) IU/mL] and received higher doses of omalizumab [750 (IQR 650, 750) mg] compared to within-range participants [450 (IQR, 300, 600) mg]. At 6 months, improvements in Juniper 5-item Asthma Control Questionnaire (ACQ-5, 3.61 down to 2.01 for above-range, 3.47 down to 1.93 for within-range, P < 0.0001 for both) and Asthma Quality of Life Questionnaire (AQLQ mean score (3.22 up to 4.41 for above-range, 3.71 up to 4.88 for within-range, P < 0.0001) were observed in both groups. Forced expiratory volume in one second (FEV1) improved among above-range participants. There was no difference in response between above-range and within-range participants. Above-range participants due to either IgE alone or IgE and weight had similar improvements in ACQ-5, AQLQ and FEV1. Conclusions and Clinical Relevance: Patients with severe allergic asthma above recommended dosing criteria for omalizumab have significantly improved symptom control, quality of life and lung function to a similar degree to within-range participants, achieved without dose escalation above 750 mg.

Introduction: Sputum eosinophilia occurs in approximately one-third of stable chronic obstructive pulmonary disease (COPD) patients and can predict exacerbation risk and response to corticosteroid treatments. Sputum induction, however, requires expertise, may not always be successful, and does not provide point-of-care results. Easily applicable diagnostic markers that can predict sputum eosinophilia in stable COPD patients have the potential to progress COPD management. This study investigated the correlation and predictive relationship between peripheral blood and sputum eosinophils. It also examined the repeatability of blood eosinophil counts. Methods: Stable COPD patients (n=141) were classified as eosinophilic or noneosinophilic based on their sputum cell counts (=3%), and a cross-sectional analysis was conducted comparing their demographics, clinical characteristics, and blood cell counts. Receiver operating characteristic curve analysis was used to assess the predictive ability of blood eosinophils for sputum eosinophilia. Intraclass correlation coefficient was used to examine the repeatability of blood eosinophil counts. Results: Blood eosinophil counts were significantly higher in patients with sputum eosinophilia (n=45) compared to those without (0.3×109/L vs 0.15×109/L; P<0.0001). Blood eosinophils correlated with both the percentage (¿=0.535; P<0.0001) and number of sputum eosinophils (¿=0.473; P<0.0001). Absolute blood eosinophil count was predictive of sputum eosinophilia (area under the curve =0.76, 95% confidence interval [CI] =0.67¿0.84; P<0.0001). At a threshold of =0.3×109/L (specificity =76%, sensitivity =60%, and positive likelihood ratio =2.5), peripheral blood eosinophil counts enabled identification of the presence or absence of sputum eosinophilia in 71% of the cases. A threshold of =0.4×109/L had similar classifying ability but better specificity (91.7%) and higher positive likelihood ratio (3.7). In contrast, =0.2×109/L offered a better sensitivity (91.1%) for ruling out sputum eosinophilia. There was a good agreement between two measurements of blood eosinophil count over a median of 28 days (intraclass correlation coefficient =0.8; 95% CI =0.66¿0.88; P<0.0001). Conclusion: Peripheral blood eosinophil counts can help identify the presence or absence of sputum eosinophilia in stable COPD patients with a reasonable degree of accuracy.

Background and objective: Obesity is an established risk factor for poor health outcomes, but paradoxically in chronic obstructive pulmonary disease (COPD), it is associated with improved survival and lung function. A major evidence gap exisits to inform treatment recommendations for patients with COPD who are obese. We aimed to determine the effect of weight reduction involving a low-energy diet utilizing a partial meal replacement plan, coupled with resistance exercise training in obese COPD patients. Methods: In a proof of concept before¿after clinical trial, obese (body mass index =30 kg/m2) COPD patients received a 12 week weight reduction programme involving meal replacements, dietary counselling by a dietitian and resistance exercise training prescribed and supervised by a physiotherapist. Patients were reviewed face to face by the dietitian and physiotherapist every 2 weeks for counselling. Results: Twenty-eight participants completed the intervention. Mean (standard deviation) body mass index was 36.3 kg/m2 (4.6) at baseline and reduced by 2.4 kg/m2 ((1.1) P < 0.0001) after the intervention. Importantly, skeletal muscle mass was maintained. Clinical outcomes improved with weight loss including exercise capacity, health status, dyspnea, strength and functional outcomes. There was also a significant reduction in the body mass index, obstruction, dyspnea and exercise score (BODE). Systemic inflammation measured by C-reactive protein however did not change. Conclusion: In obese COPD patients, dietary energy restriction coupled with resistance exercise training results in clinically significant improvements in body mass index, exercise tolerance and health status, whilst preserving skeletal muscle mass. This novel study provides a framework for development of guidelines for the management of obese COPD patients and in guiding future research.

This is the protocol for a review and there is no abstract. The objectives are as follows: This review has two primary objectives. To assess the effects of school-based interventions for improvement of asthma self management on children's outcomes. To identify the processes and methods that are aligned with effective and non-effective interventions.

Background: The overlap between asthma and COPD is increasingly recognised. This review examines the new insights, treatment and remaining knowledge gaps for asthma-COPD overlap. Method: A systematic literature review of cluster analyses of asthma and COPD was performed. Articles from 2009 to the present dealing with prevalence, morbidity and treatment of asthma-COPD overlap were identified and reviewed. Results: Asthma-COPD overlap was consistently recognised in studies using a variety of different study designs and sampling. The prevalence was approximately 20% in patients with obstructive airways diseases. Asthma-COPD overlap was associated with increased morbidity and possibly an increased mortality and comorbidity. There was evidence of a heterogeneous pattern of airway inflammation that included eosinophilic (in adult asthma), neutrophilic or mixed patterns (in severe asthma and COPD). Systemic inflammation was present in asthma-COPD overlap and resembled that of COPD. Within asthma-COPD overlap, there is evidence of different subgroups, and recognition using bronchodilator responsiveness has not been successful. Guidelines generally recommend a serial approach to assessment, with treatment recommendations dominated by an asthma paradigm. Research is needed into key clinical features that impact outcome, mechanisms and treatment approaches in asthma-COPD overlap. Identifying and treating disease components by multidimensional assessment shows promise. Conclusions: Asthma-COPD overlap has drawn attention to the significant heterogeneity that exists within obstructive airway diseases. It should be replaced by novel approaches that identify and manage the components of this heterogeneity, such as multidimensional assessment and treatment. Future research is needed to test these novel and personalised approaches.

This is the protocol for a review and there is no abstract. The objectives are as follows: To assess the effect of asthma self-management education interventions delivered in mainstream school settings on asthma morbidity.

Adult-onset asthma and chronic obstructive pulmonary disease (COPD) are major public health burdens. This review presents a comprehensive synopsis of their epidemiology, pathophysiology, and clinical presentations; describes how they can be distinguished; and considers both established and proposed new approaches to their management. Both adult-onset asthma and COPD are complex diseases arising from gene¿environment interactions. Early life exposures such as childhood infections, smoke, obesity, and allergy influence adult-onset asthma. While the established environmental risk factors for COPD are adult tobacco and biomass smoke, there is emerging evidence that some childhood exposures such as maternal smoking and infections may cause COPD. Asthma has been characterized predominantly by Type 2 helper T cell (Th2) cytokine-mediated eosinophilic airway inflammation associated with airway hyperresponsiveness. In established COPD, the inflammatory cell infiltrate in small airways comprises predominantly neutrophils and cytotoxic T cells (CD8 positive lymphocytes). Parenchymal destruction (emphysema) in COPD is associated with loss of lung tissue elasticity, and small airways collapse during exhalation. The precise definition of chronic airflow limitation is affected by age; a fixed cut-off of forced expiratory volume in 1 second/forced vital capacity leads to overdiagnosis of COPD in the elderly. Traditional approaches to distinguishing between asthma and COPD have highlighted age of onset, variability of symptoms, reversibility of airflow limitation, and atopy. Each of these is associated with error due to overlap and convergence of clinical characteristics. The management of chronic stable asthma and COPD is similarly convergent. New approaches to the management of obstructive airway diseases in adults have been proposed based on inflammometry and also multidimensional assessment, which focuses on the four domains of the airways, comorbidity, self-management, and risk factors. Short-acting beta-agonists provide effective symptom relief in airway diseases. Inhalers combining a long-acting beta-agonist and corticosteroid are now widely used for both asthma and COPD. Written action plans are a cornerstone of asthma management although evidence for self-management in COPD is less compelling. The current management of chronic asthma in adults is based on achieving and maintaining control through step-up and step-down approaches, but further trials of back-titration in COPD are required before a similar approach can be endorsed. Long-acting inhaled anticholinergic medications are particularly useful in COPD. Other distinctive features of management include pulmonary rehabilitation, home oxygen, and end of life care.

Background: The progression of obstructive airway diseases (OADs) including asthma, chronic obstructive pulmonary disease (COPD) and asthma-COPD overlap syndrome in older adults is not well understood. Objective: To examine the prognosis of OADs and to identify potential determinants for longitudinal changes in clinical outcomes. Methods: We consecutively recruited 99 older adults (>55 years) with OADs who underwent a multidimensional assessment at baseline and 4 years which involved spirometry, 6-min walk distance (6MWD), assessments of health status (Saint George's Respiratory Questionnaire, SGRQ), comorbidity, and serum and sputum biomarkers. All-cause mortality and respiratory hospitalisation during the follow-up period were recorded. Clinical outcomes were compared between basal and final visits, and changes in clinical outcomes were compared among asthma, COPD and asthma-COPD overlap groups. Associations between clinical parameters, biomarkers and prognosis were examined. Results: After a median follow-up of 4.2 years, outcome data were available for 75 (75.8%) patients. There were 16 (16.2%) deaths. The BODE index predicted all-cause mortality in older people with OADs. While spirometry, 6MWD and SGRQ deteriorated significantly over the 4 years, there was significant heterogeneity in the longitudinal changes in these clinical outcomes. Participants with COPD had a significant decline in FEV1 (p = 0.003), SGRQ (p = 0.030) and 6MWD [decline of 75.5 (93.4) m, p = 0.024]. The change in 6MWD was lower in the asthma-COPD overlap group. Airflow reversibility was associated with a reduced decline in 6MWD. Conclusion: COPD patients had a poor prognosis compared with asthma and asthma-COPD overlap patients. The BODE index is a useful prognostic indicator in older adults with OADs. Both airway disease diagnosis and BODE index warrant specific attention in clinical practice. © 2013 S. Karger AG, Basel.

Background: Severe asthma and chronic obstructive pulmonary disease (COPD) are chronic inflammatory airway diseases in which the mechanisms are not fully understood. A disintegrin and metalloproteinase domain 8 (ADAM8) is an enzyme expressed on most leucocytes and may be important for facilitating leucocyte migration in respiratory disease. Objective: To investigate ADAM8 mRNA and protein expression in asthma and COPD and its relationship between asthma severity and inflammatory phenotypes. Methods: Induced sputum was collected from 113 subjects with asthma (severe n = 31, uncontrolled n = 39 and controlled n = 35), 20 subjects with COPD and 21 healthy controls. Sputum ADAM8 mRNA expression was measured by qPCR, and soluble ADAM8 (sADAM8) protein was measured in the sputum supernatant by validated ELISA. Results: ADAM8 mRNA correlated with ADAM8 protein levels (r = 0.27, P < 0.01). ADAM8 mRNA (P = 0.004) and sADAM8 protein (P = 0.014) levels were significantly higher in both asthma and COPD compared with healthy controls. ADAM8 mRNA (P = 0.035) and sADAM8 protein (P = 0.002) levels were significantly higher in severe asthma compared with controlled asthma. Total inflammatory cell count (P < 0.01) and neutrophils (P < 0.01) were also elevated in severe asthmatic sputum. Although ADAM8 mRNA was significantly higher in eosinophilic and neutrophilic asthma (P < 0.001), sADAM8 did not differ between asthma inflammatory phenotypes. ADAM8 expression positively correlated with sputum total cell count and sputum neutrophils. Conclusions and Clinical Relevance: ADAM8 expression is increased in both severe asthma and COPD and associated with sputum total cell count and neutrophils. ADAM8 may facilitate neutrophil migration to the airways in severe asthma and COPD. © 2013 John Wiley & Sons Ltd.

Purpose: The role of systemic inflammation on asthma-COPD overlap syndrome is unknown. This study aimed to examine systemic inflammation in asthma-COPD overlap syndrome, and to identify associations between clinical characteristics and inflammatory mediators in asthma-COPD overlap syndrome. Methods: In 108 adults older than 55 years comprising healthy controls (n=29), asthma (n=16), COPD (n=21) and asthma-COPD overlap syndrome (n=42), serum high sensitivity C-reactive protein and Interleukin 6 (IL-6) were assayed. Spirometry, induced sputum, quality of life, comorbidities and medications were assessed, and their associations with asthma-COPD overlap syndrome were analyzed using logistic regression. Associations between systemic inflammatory mediators and clinical characteristics were tested in multivariate linear regression models. Results: Patients with asthma-COPD overlap syndrome had significantly elevated IL-6 levels compared with healthy controls and asthmatics. Age, comorbidity index and IL-6 level were independently associated with asthma-COPD overlap syndrome. FEV1% predicted was inversely associated with IL-6 level, and cardiovascular disease was associated with an increased IL-6 level. Systemic markers were not associated with airway inflammation. Conclusions: Systemic inflammation is commonly present in asthma-COPD overlap syndrome, and asthma-COPD overlap syndrome resembled COPD in terms of systemic inflammation. IL-6 is a pivotal inflammatory mediator that may be involved in airflow obstruction and cardiovascular disease and may be an independent treatment target. © Copyright The Korean Academy of Asthma, Allergy and Clinical Immunology.

© 2015 The Japanese Respiratory Society. Patients with chronic obstructive pulmonary diseases (COPD) often experience comorbid conditions. The most common comorbidities that have been associated with COPD include cardiovascular diseases, lung cancer, metabolic disorder, osteoporosis, anxiety and depression, skeletal muscle dysfunction, cachexia, gastrointestinal diseases, and other respiratory conditions. Not only are comorbidities common but they also considerably influence disease prognosis and patients' health status, and are associated with poor clinical outcomes. However, perusal of literature indicates that little has been done so far to effectively assess, manage, and treat comorbidities in patients with COPD. The aim of this review is to comprehensively narrate the comorbid conditions that often coexist with COPD, along with their reported prevalence and their significant impacts in the disease management of COPD. A perspective on integrated disease management approaches for COPD is also discussed.

Objectives: Outcome assessment is an important part of the management of airways disease, yet older adults may have difficulty with the burden of testing. This study evaluated the patient perception of tests used for the assessment of airways disease in older people. Data Source: Older adults (>55 years) with obstructive airway disease and healthy controls (N=56) underwent inhaler technique assessment, skin allergy testing, venepuncture, fractional exhaled nitric oxide (FENO) and gas diffusion measurement, exercise testing, sputum induction, and questionnaire assessment. They then completed an assessment burden questionnaire across five domains: difficulty, discomfort, pain, symptoms and test duration. Results: Test perception was generally favourable. Induced sputum had the greatest test burden perceived as being more difficult (mean 0.83, P=0.001), associated with more discomfort (mean 1.3, P<0.001), more painful (0.46, P=0.019), longer test duration (0.84, P<0.001) and worsening symptoms (0.55, P=0.001) than the questionnaires. FENO had a more favourable assessment but was assessed to be difficult to perform. Inhaler technique received the most favourable assessment. Conclusions: Older adults hold favourable perceptions to a range of tests that they might encounter in the course of their care for airway disease. The newer tests of sputum induction and FENO have some observed difficulties, in particular sputum induction. The results of this study can inform current practice by including details of the test and its associated adverse effects when conducting the test, as well as providing clear explanations of the utility of tests and how the results might aid in patient care. © 2013 John Wiley & Sons Ltd.

Background: COPD and asthma in older people are complex conditions associated with multiple clinical problems. The relative importance of these problems to both patients and physicians and the level of agreement between them is largely unknown. Methods: Older people with asthma and COPD underwent a multidimensional assessment to characterise the prevalence of clinical problems. Each individual's problems were then summarised and presented separately to the patient and physician to rate problem importance. Problems were scored using a 5-point Likert scale from unimportant to very important. Results: The highest-rated problems were dyspnoea, activity limitation and airway inflammation, and these areas had good patientphysician concordance. Poor concordance was found for inhaler technique adequacy, airflow obstruction and obesity. Good concordance was found for written action plans, but this was less important to both patients and physicians. Conclusions: In asthma and COPD, patients and their physicians agree about the importance of managing activity limitation, dyspnoea, and airway inflammation. Other areas of management had little concordance or were viewed as less important. Self-management skills were not rated as important by patients and this may hinder successful management. Eliciting problems and addressing their importance to treatment goals may improve care in COPD and asthma. © 2011 Primary Care Respiratory Society UK. All rights reserved.