Structural Lung Disease and Clinical Phenotype in Bronchiectasis Patients: The EMBARC CT Study.

Rationale: Chest computed tomography (CT) scans are essential to diagnose and monitor bronchiectasis (BE). To date, few quantitative data are available about the nature and extent of structural lung abnormalities (SLAs) on CT scans of patients with BE. Objectives: To investigate SLAs on CT scans of patients with BE and the relationship of SLAs to clinical features using the EMBARC (European Multicenter Bronchiectasis Audit and Research Collaboration) registry. Methods: CT scans from patients with BE included in the EMBARC registry were analyzed using the validated Bronchiectasis Scoring Technique for CT (BEST-CT). The subscores of this instrument are expressed as percentages of total lung volume. The items scored are atelectasis/consolidation, BE with and without mucus plugging (MP), airway wall thickening, MP, ground-glass opacities, bullae, airways, and parenchyma. Four composite scores were calculated: total BE (i.e., BE with and without MP), total MP (i.e., BE with MP plus MP alone), total inflammatory changes (i.e., atelectasis/consolidation plus total MP plus ground-glass opacities), and total disease (i.e., all items but airways and parenchyma). Measurements and Main Results: CT scans of 524 patients with BE were analyzed. Mean subscores were 4.6 (range, 2.3-7.7) for total BE, 4.2 (1.2-8.1) for total MP, 8.3 (3.5-16.7) for total inflammatory changes, and 14.9 (9.1-25.9) for total disease. BE associated with primary ciliary dyskinesia was associated with more SLAs, whereas chronic obstructive pulmonary disease was associated with fewer SLAs. Lower FEV1, longer disease duration, Pseudomonas aeruginosa and nontuberculous mycobacterial infections, and severe exacerbations were all independently associated with worse SLAs. Conclusions: The type and extent of SLAs in patients with BE are highly heterogeneous. Strong relationships between radiological disease and clinical features suggest that CT analysis may be a useful tool for clinical phenotyping.

A Bispecific Monoclonal Antibody Targeting Psl and PcrV Enhances Neutrophil-Mediated Killing of Pseudomonas aeruginosa in Patients with Bronchiectasis.

Rationale: Pseudomonas aeruginosa infection is associated with worse outcomes in bronchiectasis. Impaired neutrophil antimicrobial responses contribute to bacterial persistence. Gremubamab is a bivalent, bispecific monoclonal antibody targeting Psl exopolysaccharide and the type 3 secretion system component PcrV. Objectives: This study evaluated the efficacy of gremubamab to enhance killing of P. aeruginosa by neutrophils from patients with bronchiectasis and to prevent P. aeruginosa-associated cytotoxicity. Methods: P. aeruginosa isolates from a global bronchiectasis cohort (n = 100) underwent whole-genome sequencing to determine target prevalence. Functional activity of gremubamab against selected isolates was tested in vitro and in vivo. Patients with bronchiectasis (n = 11) and control subjects (n = 10) were enrolled, and the effect of gremubamab in peripheral blood neutrophil opsonophagocytic killing (OPK) assays against P. aeruginosa was evaluated. Serum antibody titers to Psl and PcrV were determined (n = 30; 19 chronic P. aeruginosa infection, 11 no known P. aeruginosa infection), as was the effect of gremubamab treatment in OPK and anti-cytotoxic activity assays. Measurements and Main Results: Psl and PcrV were conserved in isolates from chronically infected patients with bronchiectasis. Seventy-three of 100 isolates had a full psl locus, and 99 of 100 contained the pcrV gene, with 20 distinct full-length PcrV protein subtypes identified. PcrV subtypes were successfully bound by gremubamab and the monoclonal antibody-mediated potent protective activity against tested isolates. Gremubamab increased bronchiectasis patient neutrophil-mediated OPK (+34.6 ± 8.1%) and phagocytosis (+70.0 ± 48.8%), similar to effects observed in neutrophils from control subjects (OPK, +30.1 ± 7.6%). No evidence of competition between gremubamab and endogenous antibodies was found, with protection against P. aeruginosa-induced cytotoxicity and enhanced OPK demonstrated with and without addition of patient serum. Conclusions: Gremubamab enhanced bronchiectasis patient neutrophil phagocytosis and killing of P. aeruginosa and reduced virulence.

The Association between Bronchiectasis and Chronic Obstructive Pulmonary Disease: Data from the European Bronchiectasis Registry (EMBARC).

Rationale: COPD and bronchiectasis are commonly reported together. Studies report varying impacts of co-diagnosis on outcomes, which may be related to different definitions of disease used across studies. Objectives: To investigate the prevalence of chronic obstructive pulmonary disease (COPD) associated with bronchiectasis and its relationship with clinical outcomes. We further investigated the impact of implementing the standardized ROSE criteria (radiological bronchiectasis [R], obstruction [FEV1/FVC ratio <0.7; O], symptoms [S], and exposure [⩾10 pack-years of smoking; E]), an objective definition of the association of bronchiectasis with COPD. Methods: Analysis of the EMBARC (European Bronchiectasis Registry), a prospective observational study of patients with computed tomography-confirmed bronchiectasis from 28 countries. The ROSE criteria were used to objectively define the association of bronchiectasis with COPD. Key outcomes during a maximum of 5 years of follow-up were exacerbations, hospitalization, and mortality. Measurements and Main Results: A total of 16,730 patients with bronchiectasis were included; 4,336 had a clinician-assigned codiagnosis of COPD, and these patients had more exacerbations, worse quality of life, and higher severity scores. We observed marked overdiagnosis of COPD: 22.2% of patients with a diagnosis of COPD did not have airflow obstruction and 31.9% did not have a history of ⩾10 pack-years of smoking. Therefore, 2,157 patients (55.4%) met the ROSE criteria for COPD. Compared with patients without COPD, patients who met the ROSE criteria had increased risks of exacerbations and exacerbations resulting in hospitalization during follow-up (incidence rate ratio, 1.25; 95% confidence interval, 1.15-1.35; vs. incidence rate ratio, 1.69; 95% confidence interval, 1.51-1.90, respectively). Conclusions: The label of COPD is often applied to patients with bronchiectasis who do not have objective evidence of airflow obstruction or a smoking history. Patients with a clinical label of COPD have worse clinical outcomes.

Bronchiectasis and asthma: Data from the European Bronchiectasis Registry (EMBARC).

BACKGROUND: Asthma is commonly reported in patients with a diagnosis of bronchiectasis. OBJECTIVE: The aim of this study was to evaluate whether patients with bronchiectasis and asthma (BE+A) had a different clinical phenotype and different outcomes compared with patients with bronchiectasis without concomitant asthma. METHODS: A prospective observational pan-European registry (European Multicentre Bronchiectasis Audit and Research Collaboration) enrolled patients across 28 countries. Adult patients with computed tomography-confirmed bronchiectasis were reviewed at baseline and annual follow-up visits using an electronic case report form. Asthma was diagnosed by the local investigator. Follow-up data were used to explore differences in exacerbation frequency between groups using a negative binomial regression model. Survival analysis used Cox proportional hazards regression. RESULTS: Of 16,963 patients with bronchiectasis included for analysis, 5,267 (31.0%) had investigator-reported asthma. Patients with BE+A were younger, were more likely to be female and never smokers, and had a higher body mass index than patients with bronchiectasis without asthma. BE+A was associated with a higher prevalence of rhinosinusitis and nasal polyps as well as eosinophilia and Aspergillus sensitization. BE+A had similar microbiology but significantly lower severity of disease using the bronchiectasis severity index. Patients with BE+A were at increased risk of exacerbation after adjustment for disease severity and multiple confounders. Inhaled corticosteroid (ICS) use was associated with reduced mortality in patients with BE+A (adjusted hazard ratio 0.78, 95% CI 0.63-0.95) and reduced risk of hospitalization (rate ratio 0.67, 95% CI 0.67-0.86) compared with control subjects without asthma and not receiving ICSs. CONCLUSIONS: BE+A was common and was associated with an increased risk of exacerbations and improved outcomes with ICS use. Unexpectedly we identified significantly lower mortality in patients with BE+A.

Objective sputum colour assessment and clinical outcomes in bronchiectasis: data from the European Bronchiectasis Registry (EMBARC).

BACKGROUND: A validated 4-point sputum colour chart can be used to objectively evaluate the levels of airway inflammation in bronchiectasis patients. In the European Bronchiectasis Registry (EMBARC), we tested whether sputum colour would be associated with disease severity and clinical outcomes. METHODS: We used a prospective, observational registry of adults with bronchiectasis conducted in 31 countries. Patients who did not produce spontaneous sputum were excluded from the analysis. The Murray sputum colour chart was used at baseline and at follow-up visits. Key outcomes were frequency of exacerbations, hospitalisations for severe exacerbations and mortality during up to 5-year follow-up. RESULTS: 13 484 patients were included in the analysis. More purulent sputum was associated with lower forced expiratory volume in 1 s (FEV1), worse quality of life, greater bacterial infection and a higher bronchiectasis severity index. Sputum colour was strongly associated with the risk of future exacerbations during follow-up. Compared to patients with mucoid sputum (reference group), patients with mucopurulent sputum experienced significantly more exacerbations (incident rate ratio (IRR) 1.29, 95% CI 1.22-1.38; p<0.0001), while the rates were even higher for patients with purulent (IRR 1.55, 95% CI 1.44-1.67; p<0.0001) and severely purulent sputum (IRR 1.91, 95% CI 1.52-2.39; p<0.0001). Hospitalisations for severe exacerbations were also associated with increasing sputum colour with rate ratios, compared to patients with mucoid sputum, of 1.41 (95% CI 1.29-1.56; p<0.0001), 1.98 (95% CI 1.77-2.21; p<0.0001) and 3.05 (95% CI 2.25-4.14; p<0.0001) for mucopurulent, purulent and severely purulent sputum, respectively. Mortality was significantly increased with increasing sputum purulence, hazard ratio 1.12 (95% CI 1.01-1.24; p=0.027), for each increment in sputum purulence. CONCLUSION: Sputum colour is a simple marker of disease severity and future risk of exacerbations, severe exacerbations and mortality in patients with bronchiectasis.

Airway clearance management in people with bronchiectasis: data from the European Bronchiectasis Registry (EMBARC).

BACKGROUND: International guidelines recommend airway clearance management as one of the important pillars of bronchiectasis treatment. However, the extent to which airway clearance is used for people with bronchiectasis in Europe is unclear. The aim of the study was to identify the use of airway clearance management in patients with bronchiectasis across different countries and factors influencing airway clearance use. METHODS: This was a prospective observational study using data from the European Multicentre Bronchiectasis Audit and Research Collaboration (EMBARC) Registry between January 2015 and April 2022. Prespecified options for airway clearance management were recorded, including airway clearance techniques, devices and use of mucoactive drugs. RESULTS: 16 723 people with bronchiectasis from 28 countries were included in the study. The mean age was 67 years (interquartile range 57-74 years, range 18-100 years) and 61% were female. 72% of the participants reported daily sputum expectoration and 52% (95% CI 51-53%) of all participants reported using regular airway clearance management. Active cycle of breathing technique was used by 28% of the participants and airway clearance devices by 16% of participants. The frequency of airway clearance management and techniques used varied significantly between different countries. Participants who used airway clearance management had greater disease severity and worse symptoms, including a higher daily sputum volume, compared to those who did not use it regularly. Mucoactive drugs were also more likely to be used in participants with more severe disease. Access to specialist respiratory physiotherapy was low throughout Europe, but particularly low in Eastern Europe. CONCLUSIONS: Only a half of people with bronchiectasis in Europe use airway clearance management. Use of and access to devices, mucoactive drugs and specialist chest physiotherapy appears to be limited in many European countries.

Effect of Ginger Root Powder on Gastrointestinal Bacteria Composition, Gastrointestinal Symptoms, Mental Health, Fatigue, and Quality of Life: A Double-Blind Placebo-Controlled Trial.

BACKGROUND: Despite compositional alterations in gastrointestinal microbiota being purported to underpin some of the therapeutic effects of ginger, the effect of a standardized ginger supplement on gut microbiota has not been tested in humans. OBJECTIVES: To determine the effect of a standardized ginger (Zingiber officinale) root powder, compared to placebo, on gastrointestinal bacteria and associated outcomes in healthy adults. METHODS: A randomized double-blind placebo-controlled trial allocated participants aged 18 to 30 y to ginger or microcrystalline cellulose (MCC) placebo. The intervention comprised 1.2 g/d of ginger (4 capsules per day totaling 84 mg/d of active gingerols/shogaols) for 14 d following a 1-wk run-in period. Primary outcomes were gastrointestinal community composition, alpha and beta diversity, and differential abundance, measured using 16S rRNA gene sequencing of fecal samples. Secondary outcomes were gastrointestinal symptoms, bowel function, depression, anxiety, stress, fatigue, quality of life, and adverse events. RESULTS: Fifty-one participants were enrolled and analyzed (71% female; mean age 25 ± 3 y; ginger: n = 29, placebo: n = 22). There was a greater increase in relative abundance of phylum, Actinobacteria, observed following ginger supplementation compared to placebo (U: 145.0; z: -2.1; P = 0.033). Ginger was associated with a greater abundance of the genera Parabacteroides, Bacillus, Ruminococcaceae incertae sedis, unclassified Bacilli, families Defluviitaleaceae, Morganellaceae, and Bacillaceae as well as lower abundance of the genus Blautia and family Sphingomonadaceae (P < 0.05). An improvement in indigestion symptoms was observed with ginger supplementation (U: 196.0; z: -2.4; P = 0.015). No differences between ginger and placebo groups were found for alpha and beta diversity or other secondary outcomes. No moderate or severe adverse events were reported. CONCLUSIONS: Supplementation with ginger root powder was safe and altered aspects of gastrointestinal bacteria composition; however, it did not change alpha- or beta diversity, bowel function, gastrointestinal symptoms, mood, or quality of life in healthy adults. These results provide further understanding regarding the mechanisms of action of ginger supplementation. This trial was registered in the Australia New Zealand Clinical Trials Registry as ACTRN12620000302954p and the Therapeutic Goods Administration as CT-2020-CTN-00380-1.

Heterogeneity of treatment response in bronchiectasis clinical trials.

BACKGROUND: Recent randomised clinical trials in bronchiectasis have failed to reach their primary end-points, suggesting a need to reassess how we measure treatment response. Exacerbations, quality of life (QoL) and lung function are the most common end-points evaluated in bronchiectasis clinical trials. We aimed to determine the relationship between responses in terms of reduced exacerbations, improved symptoms and lung function in bronchiectasis. METHODS: We evaluated treatment response in three randomised clinical trials that evaluated mucoactive therapy (inhaled mannitol), an oral anti-inflammatory/antibiotic (azithromycin) and an inhaled antibiotic (aztreonam). Treatment response was defined by an absence of exacerbations during follow-up, an improvement of QoL above the minimum clinically important difference and an improvement in forced expiratory volume in 1 s (FEV1) of ≥100 mL from baseline. RESULTS: Cumulatively the three trials included 984 patients. Changes in FEV1, QoL and exacerbations were heterogeneous in all trials analysed. Improvements in QoL were not correlated to changes in FEV1 in the azithromycin and aztreonam trials (r= -0.17, p=0.1 and r=0.04, p=0.4, respectively) and weakly correlated in the mannitol trial (r=0.22, p<0.0001). An important placebo effect was observed in all trials, especially regarding improvements in QoL. Clinical meaningful lung function improvements were rare across all trials evaluated, suggesting that FEV1 is not a responsive measure in bronchiectasis. CONCLUSIONS: Improvements in lung function, symptoms and exacerbation frequency are dissociated in bronchiectasis. FEV1 is poorly responsive and poorly correlated with other key outcome measures. Clinical parameters are poorly predictive of treatment response, suggesting the need to develop biomarkers to identify responders.

Benefits of supportive strategies for carers of people with high-grade glioma: a systematic review : Strategies for addressing the needs of high-grade glioma carers.

PURPOSE: To systematically review and examine current evidence for the carer-reported benefits of supportive care strategies for carers of adults with high-grade glioma (HGG). METHODS: Four databases (CINAHL, EMBASE, PubMed, PsycINFO) were searched for articles published between January 2005 and April 2022 that assessed strategies for addressing the supportive care needs of carers of adults with HGG (WHO grade 3-4). Study selection and critical appraisal were conducted independently by three authors (DJ/MC, 2021; DJ/RJ 2022). Data extraction was conducted by one author (DJ) and checked by a second author (RJ). Results were synthesised narratively. RESULTS: Twenty-one studies involving 1377 caregivers were included, targeting the carer directly (n = 10), the patient-carer dyad (n = 3), or focused on people with HGG + / - their carers (n = 8). A paucity of high-quality evidence exists for effective and comprehensive support directly addressing outcomes for carers of adults with HGG. Strategies that demonstrated some benefits included those that built carer knowledge or provided emotional support, delivered by health professionals or through peer support. Supportive and early palliative care programmes have potential to reduce unmet carer needs while providing ongoing carer support. CONCLUSION: Strategies incorporating an educational component, emotional support, and a regular needs assessment with corresponding tailored support are most valued by carers. Future practice development research should adopt a value-based approach and exceed evaluation of efficacy outcomes to incorporate evaluation of the experience of patients, carers, and staff, as well as costs.

Essential elements of optimal dietary and exercise referral practices for cancer survivors: expert consensus for medical and nursing health professionals.

PURPOSE: To develop and establish expert consensus on essential elements of optimal dietary and exercise referral practices for cancer survivors. METHODS: A four-round modified, Delphi method (face-to-face and electronic). In round 1, initial statements were drafted based on Cancer Australia's Principles of Cancer Survivorship and input from key stakeholders through a cancer preconference workshop. In round 2, the initial statements were distributed to a panel (round 1 participants) to establish consensus by rating the importance of each statement using a five-point Likert scale. Statements that required significant changes in wording were redistributed to panel members in round 3 for voting. Round 4 was for consumers, requiring them to rate their level of agreement of final statements. RESULTS: In total, 82 stakeholders participated in round 1. Response rates for survey rounds 2 and 3 were 59% (n = 54) and 39% (n = 36). Panel members included nurses (22%), dietitians (19%), exercise professionals (16%), medical practitioners (8%), and consumers (4%). The mean "importance" rating for all essential elements was 4.28 or higher (i.e., fairly important, or very important). Round 4's consumer-only engagement received responses from 58 consumers. Overall, 24 elements reached consensus following some revised wording, including the development of three new statements based on panel feedback. CONCLUSION: Our developed essential elements of optimal dietary and exercise referral practices can help provide guidance to medical and nursing health professionals relevant to dietary and exercise referral practices. Future research should conduct an implementation intervention and evaluation of these essential elements to optimise dietary and exercise care in cancer survivors.

Validation of the Bronchiectasis Impact Measure (BIM): a novel patient-reported outcome measure.

INTRODUCTION: Existing quality-of-life and symptom tools used in bronchiectasis trials are either not disease specific or are complex and have not been consistently responsive. We developed a simple patient-reported visual analogue outcome measure, the Bronchiectasis Impact Measure (BIM), for use in clinical research, including clinical trials. METHODS: Patients with bronchiectasis attending a tertiary referral clinic in the east of Scotland were invited to complete the BIM questionnaire and the quality-of-life bronchiectasis questionnaire at baseline with repeat questionnaires after 2 weeks and 6 months. We assessed internal consistency, test-retest reliability, construct validity and responsiveness by evaluating change during an acute exacerbation. RESULTS: 173 patients were included. The eight domains (cough, sputum, breathlessness, tiredness, activity, general health, control, exacerbations) showed excellent internal consistency (Cronbach's α 0.93). The intraclass correlation coefficient demonstrated excellent reliability over a 2-week period: cough (0.79, 95% CI 0.70-0.85), sputum (0.86, 95% CI 0.80-0.90), dyspnoea (0.82, 95% CI 0.74-0.87), tiredness (0.88, 95% CI 0.82-0.91), activity (0.84, 95% CI 0.77-0.89), general health (0.81, 95% CI 0.74-0.87), control (0.83, 95% CI 0.75-0.88) and exacerbation (0.71, 95% CI 0.60-0.79). Domains correlated strongly with bronchiectasis severity and exacerbation history. Both distribution and patient-based methods estimated the minimal clinically important difference for each domain as 1.5 points on a 10-point scale. Statistically significant changes in all BIM domains were observed during an acute exacerbation. CONCLUSION: The BIM is a simple patient-reported outcome. This study validates the internal consistency, reliability, construct validity and response of the tool at acute exacerbation. Further validation of the tool is now required.

Management of hospitalised adults with coronavirus disease 2019 (COVID-19): a European Respiratory Society living guideline.

INTRODUCTION: Hospitalised patients with coronavirus disease 2019 (COVID-19) as a result of SARS-CoV-2 infection have a high mortality rate and frequently require noninvasive respiratory support or invasive ventilation. Optimising and standardising management through evidence-based guidelines may improve quality of care and therefore patient outcomes. METHODS: A task force from the European Respiratory Society and endorsed by the Chinese Thoracic Society identified priority interventions (pharmacological and non-pharmacological) for the initial version of this "living guideline" using the PICO (population, intervention, comparator, outcome) format. The GRADE approach was used for assessing the quality of evidence and strength of recommendations. Systematic literature reviews were performed, and data pooled by meta-analysis where possible. Evidence tables were presented and evidence to decision frameworks were used to formulate recommendations. RESULTS: Based on the available evidence at the time of guideline development (20 February, 2021), the panel makes a strong recommendation in favour of the use of systemic corticosteroids in patients requiring supplementary oxygen or ventilatory support, and for the use of anticoagulation in hospitalised patients. The panel makes a conditional recommendation for interleukin (IL)-6 receptor antagonist monoclonal antibody treatment and high-flow nasal oxygen or continuous positive airway pressure in patients with hypoxaemic respiratory failure. The panel make strong recommendations against the use of hydroxychloroquine and lopinavir-ritonavir. Conditional recommendations are made against the use of azithromycin, hydroxychloroquine combined with azithromycin, colchicine, and remdesivir, in the latter case specifically in patients requiring invasive mechanical ventilation. No recommendation was made for remdesivir in patients requiring supplemental oxygen. Further recommendations for research are made. CONCLUSION: The evidence base for management of COVID-19 now supports strong recommendations in favour and against specific interventions. These guidelines will be regularly updated as further evidence becomes available.

Inhaled aztreonam improves symptoms of cough and sputum production in patients with bronchiectasis: a post hoc analysis of the AIR-BX studies.

INTRODUCTION: Inhaled antibiotics may improve symptom scores, but it is not known which specific symptoms improve with therapy. Item-level analysis of questionnaire data may allow us to identify which specific symptoms respond best to treatment. METHODS: Post hoc analysis of the AIR-BX1 studies and two trials of inhaled aztreonam versus placebo in bronchiectasis. Individual items from the quality of life bronchiectasis (QOL-B) respiratory symptom scale, were extracted as representing severity of nine distinct symptoms. Generalised linear models were used to evaluate changes in symptoms with treatment versus placebo from baseline to end of first on-treatment cycle and mixed models were used to evaluate changes across the full 16-week trial. RESULTS: Aztreonam improved cough (difference 0.22, 95% CI 0.08-0.37; p=0.002), sputum production (0.30, 95% CI 0.15-0.44; p<0.0001) and sputum colour (0.29, 95% CI 0.15-0.43; p<0.0001) versus placebo equating to a 20% improvement in cough and 25% improvement in sputum production and colour. Similar results were observed for cough, sputum production and sputum purulence across the trial duration (all p<0.05). Patients with higher sputum production and sputum colour scores had a greater response on the overall QOL-B (difference 4.82, 95% CI 1.12-8.53; p=0.011 for sputum production and 5.02, 95% CI 1.19-8.86; p=0.01 for sputum colour). In contrast, treating patients who had lower levels of bronchitic symptoms resulted in shorter time to next exacerbation (hazard ratio 1.83, 95% CI 1.02-3.28; p=0.042). CONCLUSION: Baseline bronchitic symptoms predict response to inhaled aztreonam in bronchiectasis. More sensitive tools to measure bronchitic symptoms may be useful to better identify inhaled antibiotic responders and to evaluate patient response to treatment.

Development and initial validation of the bronchiectasis exacerbation and symptom tool (BEST).

BACKGROUND: Recurrent bronchiectasis exacerbations are related to deterioration of lung function, progression of the disease, impairment of quality of life, and to an increased mortality. Improved detection of exacerbations has been accomplished in chronic obstructive pulmonary disease through the use of patient completed diaries. These tools may enhance exacerbation reporting and identification. The aim of this study was to develop a novel symptom diary for bronchiectasis symptom burden and detection of exacerbations, named the BEST diary. METHODS: Prospective observational study of patients with bronchiectasis conducted at Ninewells Hospital, Dundee. We included patients with confirmed bronchiectasis by computed tomography, who were symptomatic and had at least 1 documented exacerbation of bronchiectasis in the previous 12 months to participate. Symptoms were recorded daily in a diary incorporating cough, sputum volume, sputum colour, dyspnoea, fatigue and systemic disturbance scored from 0 to 26. RESULTS: Twenty-one patients were included in the study. We identified 29 reported (treated exacerbations) and 23 unreported (untreated) exacerbations over 6-month follow-up. The BEST diary score showed a good correlation with the established and validated questionnaires and measures of health status (COPD Assessment Test, r = 0.61, p = 0.0037, Leicester Cough Questionnaire, r = - 0.52,p = 0.0015, St Georges Respiratory Questionnaire, r = 0.61,p < 0.0001 and 6 min walk test, r = - 0.46,p = 0.037). The mean BEST score at baseline was 7.1 points (SD 2.2). The peak symptom score during exacerbation was a mean of 16.4 (3.1), and the change from baseline to exacerbation was a mean of 9.1 points (SD 2.5). Mean duration of exacerbations based on time for a return to baseline symptoms was 15.3 days (SD 5.7). A minimum clinically important difference of 4 points is proposed. CONCLUSIONS: The BEST symptom diary has shown concurrent validity with current health questionnaires and is responsive at onset and recovery from exacerbation. The BEST diary may be useful to detect and characterise exacerbations in bronchiectasis clinical trials.

Blood neutrophil counts are associated with exacerbation frequency and mortality in COPD.

BACKGROUND: Identifying patients with COPD at increased risk of poor outcomes is challenging due to disease heterogeneity. Potential biomarkers need to be readily available in real-life clinical practice. Blood eosinophil counts are widely studied but few studies have examined the prognostic value of blood neutrophil counts (BNC). METHODS: In a large population-based COPD registry in the East of Scotland (TARDIS: Tayside Allergic and Respiratory Disease Information System), BNC were compared to measures of disease severity and mortality for up to 15 years follow-up. Potential mechanisms of disease modification by BNC were explored in a nested microbiome substudy. RESULTS: 178,120 neutrophil counts were obtained from 7220 people (mean follow up 9 years) during stable disease periods. Median BNC was 5200cells/µL (IQR 4000-7000cells/µL). Mortality rates among the 34% of patients with elevated BNCs (defined as 6000-15000cells/µL) at the study start were 80% higher (14.0/100 person years v 7.8/100py, P < 0.001) than those with BNC in the normal range (2000-6000cells/µL). People with elevated BNC were more likely to be classified as GOLD D (46% v 33% P < 0.001), have more exacerbations (mean 2.3 v 1.3/year, P < 0.001), and were more likely to have severe exacerbations (13% vs. 5%, P < 0.001) in the following year. Eosinophil counts were much less predictive of these outcomes. In a sub-cohort (N = 276), patients with elevated BNC had increased relative abundance of Proteobacteria and reduced microbiome diversity. CONCLUSION: High BNC may provide a useful indicator of risk of exacerbations and mortality in COPD patients.

Supportive care and unmet needs in patients with melanoma: a mixed-methods systematic review.

PURPOSE: Understanding the supportive care and unmet care needs of patients with melanoma is essential for informing the development or evaluation of supportive care services and interventions for patients with melanoma. METHODS: Three electronic databases (CINAHL, Medline and PsycINFO) were searched from 2000 to November 2019 to identify eligible quantitative and qualitative studies. The quality of evidence was assessed using the Mixed Methods Appraisal Tool. RESULTS: Fourteen studies (10 quantitative, three qualitative and one mixed-methods) were included. Informational care and unmet needs were the most commonly reported in patients with melanoma, followed by psychological, then social and physical. Findings were consistent between quantitative and qualitative studies; however, findings from qualitative data complimented those from quantitative data by providing more depth and insight into the prevalence, effects and associations of the different care needs. Patients' care and unmet needs were found to also be present all throughout their cancer journey and vary according to the stage throughout. CONCLUSION: Melanoma-specific care and unmet care needs were identified most commonly in the informational domain, followed by psychological, social and physical domains. Oncology practitioners should consider enhancing their supportive care interventions throughout the journey of patient with melanoma to reduce or address their unmet needs. The results of this mixed-methods systematic review warrant further research using robust study designs, melanoma-specific validated outcome measures and complete reporting of data in terms of disease stage.

Advances and future directions in the use of mobile health in supportive cancer care: proceedings of the 2019 MASCC Annual Meeting symposium.

PURPOSE: The role of mobile health (mHealth) technology in cancer care has evolved alongside the rapid development in digital technology. Its use can come with significant potential benefits; however, such use may also be associated with risks. This paper summarizes the latest developments around mHealth use in cancer care presented by a panel of experts at the 2019 Annual Meeting of the Multinational Association of Supportive Care in Cancer. METHODS: Through lectures, case studies, and panel discussions, speakers and participants (including cancer specialist doctors, nurses, and allied health professionals) evaluated current and emerging mHealth methods for supportive care in cancer survivorship. Focus areas and special considerations were agreed upon by consensus. RESULTS: Three focus areas for the use of mHealth in cancer care were identified: activation and support of self-management, exercise oncology, and enablement of survivorship care delivery. In addition to these focus areas, two special considerations were highlighted: technology-enhanced supportive cancer care for disparate populations, and ethical considerations relevant to the use of technology in supportive care. CONCLUSION: mHealth has the potential to revolutionize and transform cancer care delivery. Future research should guide further advances in the use of technology in supportive cancer care and carefully explore the safety, efficacy, cost-effectiveness, and implementation of interventions delivered through mHealth platforms.

A systematic review, meta-analysis and meta-regression of the prevalence of protein-energy malnutrition: associations with geographical region and sex.

Background: protein-energy malnutrition is a major health concern in home-dwelling older adults, particularly in the context of an ageing population. Therefore, a systematic review and meta-analysis was undertaken to determine the prevalence of malnutrition among older adults living independently in the community according to geographical region, sampling frame, rurality and sex. Methods: six electronic databases were searched until September 2016. Original research studies which used the Mini Nutritional Assessment, Patient-Generated Subjective Global Assessment or Subjective Global Assessment to determine nutrition status in community samples with a mean age of ≥65 years were critically appraised and pooled using meta-analysis. Meta-regression was used to explore predictors of malnutrition prevalence in pooled statistics with high heterogeneity. Results: 111 studies from 38 countries (n = 69,702 participants) were included. The pooled prevalence of malnutrition in the older community setting ranged from 0.8% (95% CI: 0.2-1.7%) in Northern Europe to 24.6% (95% CI: 0.0-67.9%) in South-East Asia. Of all sampling frames, participants receiving homecare services had the highest prevalence at 14.6% (95% CI: 9.9-20.0%). Malnutrition prevalence in rural communities (9.9%; 95% CI: 4.5-16.8%) was double that in urban communities (5.7%; 95% CI: 4.2-7.3%) and higher among females than males (odds ratio = 1.45 [95% CI: 1.27-1.66]; P < 0.00001). Conclusions: the results of this review provide strategic insight to develop public and community health priorities for preventing malnutrition and associated poor health outcomes.

Pulmonary rehabilitation after exacerbation of bronchiectasis: a pilot randomized controlled trial.

BACKGROUND: Pulmonary rehabilitation improves exercise capacity and reduces risk of future exacerbation in COPD when performed after an exacerbation. There have been no previous studies of post-exacerbation rehabilitation in bronchiectasis. METHODS: Parallel group randomized controlled trial compared pulmonary rehabilitation (PR) to standard care (SC) in patients followed an antibiotic treated exacerbation of bronchiectasis. Patients were randomized following a 14 day course of antibiotics was completed. The primary outcome was 6-min walk distance (6 MW) at 8 weeks. Secondary outcomes were time to the next exacerbation, St.Georges Respiratory Questionnaire, COPD CAT score, Leicester cough questionnaire (LCQ) and FEV1 at 8 and 12 weeks post exacerbation. RESULTS: Forty eight patients were enrolled but only 27 had exacerbations within 12 months of enrolment. Nine patients received pulmonary rehabilitation and 18 received standard care. The 6 MW improved significantly from post-exacerbation to 8 weeks in both groups, with no significant difference between PR and SC- mean difference of 11 m (95% CI -34.3 to 56.3,p = 0.6). Time to the next exacerbation was not significantly different hazard ratio 0.83 (0.31-2.19, p = 0.7). No significant differences were seen between groups in terms of LCQ, CAT, FEV1 or SGRQ between groups. An analysis of probability based on the patients enrolled suggested > 1000 subjects are likely be required to have an > 80% probability of observing a statistically significant difference between PR and SC and any such differences would be likely to be too small to be clinically relevant. CONCLUSIONS: This pilot study identified no significant benefits associated with pulmonary rehabilitation after exacerbations of bronchiectasis. TRIAL REGISTRATION: NCT02179983, registered on Clinicaltrials.gov 29th June 2014.