Patient information, education and self-management in bronchiectasis: facilitating improvements to optimise health outcomes

Background: Bronchiectasis is an incurable lung disease characterised by irreversible airway dilatation. It causes symptoms including chronic productive cough, dyspnoea, and recurrent respiratory infections often requiring hospital admission. Fatigue and reductions in quality of life are also reported in bronchiectasis. Patients often require multi-modal treatments that can be burdensome, leading to issues with adherence. In this article we review the provision of, and requirement for, education and information in bronchiectasis. Discussion: To date, little research has been undertaken to improve self-management in bronchiectasis in comparison to other chronic conditions, such as COPD, for which there has been a wealth of recent developments. Qualitative work has begun to establish that information deficit is one of the potential barriers to self-management, and that patients feel having credible information is fundamental when learning to live with and manage bronchiectasis. Emerging research offers some insights into ways of improving treatment adherence and approaches to self-management education; highlighting ways of addressing the specific unmet information needs of patients and their families who are living with bronchiectasis. Conclusions: We propose non-pharmacological recommendations to optimise patient self-management and symptom recognition; with the aim of facilitating measurable improvements in health outcomes for patients with bronchiectasis

Evaluation of a novel information resource for patients with bronchiectasis: study protocol for a randomised controlled trial

Background: There is currently little patient information on bronchiectasis, a chronic lung disease with rising prevalence. Previous work shows that patients and their families want more information, which could potentially improve their understanding and self-management. Using interviews and focus groups, we have co-developed a novel patient and carer information resource, aiming to meet their identified needs. The aims and objectives are: 1. To assess the potential impact of the information resource 2. To evaluate and refine the intervention 3. To establish the feasibility of carrying out a multi-centre randomised controlled trial to determine its effect on understanding, self-management and health outcomes. Methods/design: This is a feasibility study, with a single-centre, randomised controlled trial design, comparing use of a novel patient information resource to usual care in bronchiectasis. Additionally, patients and carers will be invited to focus groups to discuss their views on both the intervention itself and the trial process. The study duration for each participant will be 3 months from the study entry date. A total of 70 patients will be recruited to the study, and a minimum of 30 will be randomised to each arm. Ten participants (and their carers if applicable) will be invited to attend focus groups on completion of the study visits. Participants will be adults with bronchiectasis diagnosed as per national bronchiectasis guidelines. Once consented, participants will be randomised to the intervention or control arm using random permuted blocks to ensure treatment group numbers are evenly balanced. Randomisation will be web-based. Those randomised to the intervention will receive the information resource (website and booklet) and instructions on its use. Outcome measures (resource satisfaction, resource use and alternative information seeking, quality of life questionnaires, unscheduled healthcare visits, exacerbation frequency, bronchiectasis knowledge questionnaire and lung function tests) will be recorded at baseline, 2 weeks and 3 months. Discussion: All outcome measures will be used in assessing feasibility and acceptability of a future definitive trial. Feasibility outcomes include recruitment, retention and study scale form completion rates. Focus groups will strengthen qualitative data for resource refinement and to identify participant views on the trial process, which will also inform feasibility assessments. Questionnaires will also be used to evaluate and refine the resource

Critical care admission trends and outcomes in individuals with bronchiectasis in the UK

Background: There are limited data on admission trends and outcomes of individuals with bronchiectasis admitted to intensive care (ICU). Using national critical care data, we analysed admissions to ICU and estimated outcomes in terms of mortality in individuals with bronchiectasis and chronic obstructive pulmonary disease (COPD) admitted to ICU. Methods: Using data from the Intensive Care National Audit and Research Centre, admissions from bronchiectasis and COPD from 1 January 2009 to 31 December 2013 were extracted. Crude admission rates for bronchiectasis and COPD were calculated and Poisson regression was used to estimate unadjusted annual admission rate ratios. We investigated changes to length of stay on ICU, ICU mortality and in-hospital mortality during the study period. We also compared mortality rates in people with bronchiectasis and COPD aged 70 or above. Results: We found an annual increase of 8% (95% Confidence Interval [CI] 2-15) in the number of ICU admissions from bronchiectasis, whilst the yearly increase in ICU admissions from COPD was 1% (95% CI 0.3-2). ICU and in-hospital mortality was higher in individuals with bronchiectasis compared with those with COPD, especially in people aged 70 years or above. Conclusion: Admission to ICU in people with bronchiectasis are uncommon, but are increasing in frequency over time, and carries a substantial mortality rate. This needs to be considered allocating health care resources and planning respiratory services

Phase II study of a neutrophil elastase inhibitor (AZD9668) in patients with bronchiectasis

SummaryNeutrophil elastase (NE) activity is increased in bronchiectasis and may play a role in this condition. We wished to determine the effect of AZD9668, a selective oral inhibitor of NE.Efficacy and safety of AZD9668 60 mg twice daily over 4 weeks were evaluated in a randomised, double-blind, placebo-controlled, parallel-group, Phase II, signal-searching study in patients with bronchiectasis. Outcome measures included: waking and post-waking sputum neutrophil counts; lung function tests; 24-h sputum weight; BronkoTest® diary card data; St George's Respiratory Questionnaire for COPD patients (SGRQ-C); sputum NE activity; inflammatory biomarker levels; desmosine levels; adverse events, safety haematology and biochemistry. AZD9668 levels in plasma and sputum were measured to confirm exposure.Thirty-eight patients were randomised: 16 to placebo and 22 to AZD9668. There was no change in sputum neutrophils with AZD9668. Forced expiratory volume in 1 s improved by 100 mL in the AZD9668 group compared with placebo (p = 0.006). Significant changes (defined a priori as p < 0.1) in favour of AZD9668 were also seen in slow vital capacity, plasma interleukin-8, and post-waking sputum interleukin-6 and Regulated on Activation, Normal T-cell Expressed and Secreted levels. Non-significant changes in favour of AZD9668 were seen in other lung function tests, sputum weight and the SGRQ-C. AZD9668 was well tolerated.In this small signal-searching study, 4 weeks' treatment with AZD9668 improved lung function in patients with bronchiectasis and there were trends for reductions in sputum inflammatory biomarkers. Larger studies of longer duration would be needed to confirm the potential benefits of this agent in bronchiectasis.Registration: NCT00769119

Anti-bacterial antibody and T cell responses in Bronchiectasis are differentially associated with lung colonization and disease

Background: As a way to determine markers of infection or disease informing disease management, and to reveal disease-associated immune mechanisms, this study sought to measure antibody and T cell responses against key lung pathogens and to relate these to patients’ microbial colonization status, exacerbation history and lung function, in Bronchiectasis (BR) and Chronic Obstructive Pulmonary Disease (COPD). Methods: 119 patients with stable BR, 58 with COPD and 28 healthy volunteers were recruited and spirometry was performed. Bacterial lysates were used to measure specific antibody responses by ELISA and T cells by ELIspot. Cytokine secretion by lysate-stimulated T cells was measured by multiplex cytokine assay whilst activation phenotype was measured by flow cytometry. Results: Typical colonization profiles were observed in BR and COPD, dominated by P.aeruginosa, H.influenzae, S.pneumoniae and M.catarrhalis. Colonization frequency was greater in BR, showing association with increased antibody responses against P.aeruginosa compared to COPD and HV, and with sensitivity of 73% and specificity of 95%. Interferon-gamma T cell responses against P.aeruginosa and S.pneumoniae were reduced in BR and COPD, whilst reactive T cells in BR had similar markers of homing and senescence compared to healthy volunteers. Exacerbation frequency in BR was associated with increased antibodies against P. aeruginosa, M.catarrhalis and S.maltophilia. T cell responses against H.influenzae showed positive correlation with FEV1% (r=0.201, p=0.033) and negative correlation with Bronchiectasis Severity Index (r=-0.287, p=0.0035). Conclusion: Our findings suggest a difference in antibody and T cell immunity in BR, with antibody being a marker of exposure and disease in BR for P.aeruginosa, M.catarrhalis and H.influenzae, and T cells a marker of reduced disease for H.influenzae

Information and education provision in bronchiectasis: co-development and evaluation of a novel patient-driven resource in a digital era

‘Take home message’ Improvements in information for those living with bronchiectasis should use patient driven co-development processes

Bronchiectasis Information and Education: a randomised, controlled feasibility trial

Background: There has been comparatively little patient information about bronchiectasis, a chronic lung disease with rising prevalence. Patients want more information, which could improve their understanding and self-management. A novel information resource meeting identified needs has been co-developed in prior work. We sought to establish the feasibility of conducting a multi-centre randomised controlled trial to determine effect of the information resource on understanding, self-management and health outcomes. Methods/design: We conducted an unblinded, single-centre, randomised controlled feasibility trial with two parallel groups (1:1 ratio), comparing a novel patient information resource with usual care in adults with bronchiectasis. Integrated qualitative methods allowed further evaluation of the intervention and trial process. The setting was two teaching hospitals in North East England. Participants randomised to the intervention group received the information resource (website and booklet) and instructions on its use. Feasibility outcome measures included willingness to enter the trial, in addition to recruitment and retention rates. Secondary outcome measures (resource use and satisfaction, quality of life, unscheduled healthcare presentations, exacerbation frequency, bronchiectasis knowledge and lung function) were recorded at baseline, 2 weeks and 12 weeks. Results: Sixty-two participants were randomised (control group = 30; intervention group = 32). Thirty-eight (61%) were female, and the participants’ median age was 65 years (range 15–81). Median forced expiratory volume in 1 s percent predicted was 68% (range 10–120). Sixty-two of 124 (50%; 95% CI, 41–59%) of potentially eligible participants approached were recruited. Sixty (97%) of 62 participants completed the study (control group, 29 of 30 [97%]; 95% CI, 83–99%; 1 unrelated death; intervention group, 31 [97%] of 32; 95% CI, 84–99%; 1 withdrawal). In the intervention group, 27 (84%) of 32 reported using the information provided, and 25 (93%) of 27 of users found it useful, particularly the video content. Qualitative data analysis revealed acceptability of the trial and intervention. Web analytics recorded over 20,000 page views during the 16-month study period. Conclusion: The successful recruitment process, high retention rate and study form completion rates indicate that it appears feasible to conduct a full trial based on this study design. Worldwide demand for online access to the information resource was high

Galectin-9 Is a Possible Promoter of Immunopathology in Rheumatoid Arthritis by Activation of Peptidyl Arginine Deiminase 4 (PAD-4) in Granulocytes

The aetiology of rheumatoid arthritis (RA) is unknown, but citrullination of proteins is thought to be an initiating event. In addition, it is increasingly evident that the lung can be a potential site for the generation of autoimmune triggers before the development of joint disease. Here, we identified that serum levels of galectin-9 (Gal-9), a pleiotropic immunomodulatory protein, are elevated in RA patients, and are even further increased in patients with comorbid bronchiectasis, a lung disease caused by chronic inflammation. The serum concentrations of Gal-9 correlate with C-reactive protein levels and DAS-28 score. Gal-9 activated polymorphonuclear leukocytes (granulocytes) in vitro, which was characterized by increased cytokine secretion, migration, and survival. Further, granulocytes treated with Gal-9 upregulated expression of peptidyl arginine deiminase 4 (PAD-4), a key enzyme required for RA-associated citrullination of proteins. Correspondingly, treatment with Gal-9 triggered citrullination of intracellular granulocyte proteins that are known contributors to RA pathogenesis (i.e., myeloperoxidase, alpha-enolase, MMP-9, lactoferrin). In conclusion, this study identifies for the first time an immunomodulatory protein, Gal-9, that triggers activation of granulocytes leading to increased PAD-4 expression and generation of citrullinated autoantigens. This pathway may represent a potentially important mechanism for development of RA

Relationship between Symptoms, Exacerbations, and Treatment Response in Bronchiectasis

RATIONALE: Bronchiectasis guidelines regard treatment to prevent exacerbation and treatment of daily symptoms as separate objectives. OBJECTIVE: We hypothesized that patients with greater symptoms would be at higher risk of exacerbations and therefore a treatment aimed at reducing daily symptoms would also reduce exacerbations in highly symptomatic patients. METHODS: An observational cohort of 333 patients from the East of Scotland(2012-2016). Symptoms were either modelled as a continuous variable or patients were classified as high, moderate and low symptom burden(&gt;70, 40-70 and &lt;40 using the SGRQ symptom score). We hypothesised that exacerbation would be reduced in highly symptomatic patients. This was tested in a post-hoc analysis of a randomized trial of inhaled mannitol (N=461 patients) Measurement and Main Results: In the observational cohort daily symptoms were a significant predictor of future exacerbations (rate ratio [RR] 1.10, 95% confidence interval[CI] 1.03-1.17, P=0.005). Patients with high symptom scores had higher exacerbation rates (RR 1.74, 95% CI 1.12-2.72,P=0.01) over 12 months follow-up compared to those with lower symptoms. Inhaled mannitol treatment improved the time to first exacerbation (hazard ratio [HR] 0.56; 95% CI 0.40-0.77; P&lt;0.001) and the proportion of patients remaining exacerbation free for 12 months treatment was higher in the mannitol group (32.7% vs. 14.6%; RR 2.84, 95% CI 1.40-5.76; P=0.003) only in highly symptomatic patients. In contrast no benefit was evident in patients with lower symptom burden. CONCLUSIONS: Highly symptomatic patients are at increased risk of exacerbations, and exacerbation benefit with inhaled mannitol was only evident in patients with high symptom burden