Clinimetric Properties of Outcome Measures in Bronchiectasis.

Rationale: There is a lack of outcome measures with robust clinimetric properties in bronchiectasis. Objectives: To determine the clinimetric properties (reliability over 1 year during clinical stability and responsiveness over the course of antibiotics for pulmonary exacerbation) of objective and patient-reported outcome measures. Methods: This multicenter cohort study included adults with bronchiectasis from seven hospitals in the United Kingdom. Participants attended four visits, 4 months apart over 1 year while clinically stable and at the beginning and end of exacerbation and completed lung function (spirometry and multiple breath washout), provided a blood sample for C-reactive protein (CRP) measurement, and completed health-related quality of life (HRQoL) questionnaires (Quality of Life-Bronchiectasis, St. George's Respiratory Questionnaire, and EuroQoL 5-Dimensions 5-Levels). Results: Participants (n = 132) had a mean (standard deviation) age of 66 (11) years, and 64% were female. Lung function parameters (forced expiratory volume in one second [FEV1], standard lung clearance index [LCI2.5]) were reliable over time [coefficient of variation (CV): <10%]). Regarding responsiveness, FEV1 demonstrated better properties than LCI2.5; therefore, a clear justification for the use of LCI2.5 in future trials is needed. CRP was less reliable (CV > 20%) over time than FEV1 and LCI2.5, and whereas CRP had a large mean change between the start and end of an exacerbation, this may have been driven by a small number of patients having a large change in CRP. Reliability of HRQoL questionnaires and questionnaire domains ranged from acceptable (CV: 20-30%) to good (CV: 10-20%), and HRQoL were responsive to treatment of exacerbations. Considering the specific questionnaire domain relevant to the intervention and its associated clinimetric properties is important. Additional statistics will support future power and/or sample size analysis. Conclusions: This information on the clinimetric properties of lung function parameters, CRP, and HRQoL parameters should be used to inform the choice of outcome measures used in future bronchiectasis trials.

Multiple-Breath Washout Outcome Measures in Adults with Bronchiectasis.

Rationale: Lung clearance index (LCI) has good intravisit repeatability with better sensitivity in detecting lung disease on computed tomography scan compared with forced expiratory volume in 1 second (FEV1) in adults with bronchiectasis. Alternative multiple-breath washout parameters have not been systematically studied in bronchiectasis. Objectives: To determine the validity, repeatability, sensitivity, specificity, and feasibility of standard LCI (LCI2.5), shortened LCI (LCI5.0), ventilation heterogeneity arising within proximal conducting airways (ScondVT), and ventilation heterogeneity arising within the acinar airways (SacinVT) in a cross-sectional observational cohort of adults with bronchiectasis. Methods: Cross-sectional multiple-breath nitrogen washout data (Exhalyzer D; Eco Medics AG) from 132 patients with bronchiectasis across five United Kingdom centers (BronchUK Clinimetrics study) and 88 healthy control subjects were analyzed. Results: Within-test repeatability (mean coefficient of variation) was <5% for both LCI2.5 and LCI5.0 in patients with bronchiectasis, and there was no difference in mean coefficient of variation for LCI2.5 and LCI5.0 in patients with bronchiectasis compared with healthy volunteers. Moderate-strength correlations were seen between FEV1 and LCI2.5 (r = -0.54), LCI5.0 (r = -0.53), ScondVT (r = -0.35), and SacinVT (r = -0.38) z-scores. The proportion of subjects with abnormal multiple-breath washout (z-score > 2) but in normal FEV1 (z-score < -2) was 42% (LCI2.5) and 36% (LCI5.0). Overall results from the receiver operating characteristic curve analysis indicated that LCI2.5 had the greatest combined sensitivity and specificity to discriminate between bronchiectasis and control subjects, followed by LCI5.0, FEV1, and ScondVT z-scores. There was a 57% time saving with LCI5.0. Conclusions: LCI2.5 and LCI5.0 had good within-test repeatability and superior sensitivity compared with spirometry measures in differentiating between health and bronchiectasis disease. LCI5.0 is quicker and more feasible than LCI2.5. Clinical trial registered with www.clinicaltrials.gov (NCT02468271).

BronchUK: protocol for an observational cohort study and biobank in bronchiectasis.

Bronchiectasis has been a largely overlooked disease area in respiratory medicine. This is reflected by a shortage of large-scale studies and lack of approved therapies, in turn leading to a variation of treatment across centres. BronchUK (Bronchiectasis Observational Cohort and Biobank UK) is a multicentre, prospective, observational cohort study working collaboratively with the European Multicentre Bronchiectasis Audit and Research Collaboration project. The inclusion criteria for patients entering the study are a clinical history consistent with bronchiectasis and computed tomography demonstrating bronchiectasis. Main exclusion criteria are 1) patients unable to provide informed consent, 2) bronchiectasis due to known cystic fibrosis or where bronchiectasis is not the main or co-dominant respiratory disease, 3) age <18 years, and 4) prior lung transplantation for bronchiectasis. The study is aligned to standard UK National Health Service (NHS) practice with an aim to recruit a minimum of 1500 patients from across at least nine secondary care centres. Patient data collected at baseline includes demographics, aetiology testing, comorbidities, lung function, radiology, treatments, microbiology and quality of life. Patients are followed up annually for a maximum of 5 years and, where able, blood and/or sputa samples are collected and stored in a central biobank. BronchUK aims to collect robust longitudinal data that can be used for analysis into current NHS practice and patient outcomes, and to become an integral resource to better inform future interventional studies in bronchiectasis.

Psychometrics of health-related quality of life questionnaires in bronchiectasis: a systematic review and meta-analysis.

INTRODUCTION: Understanding the psychometric properties of health-related quality of life (HRQoL) questionnaires can help inform selection in clinical trials. Our objective was to assess the psychometric properties of HRQoL questionnaires in bronchiectasis using a systematic review and meta-analysis of the literature. METHODS: A literature search was conducted. HRQoL questionnaires were assessed for psychometric properties (reliability, validity, minimal clinically important difference (MCID) and floor/ceiling effects). Meta-analyses assessed the associations of HRQoL with clinical measures and responsiveness of HRQoL in clinical trials. RESULTS: 166 studies and 12 HRQoL questionnaires were included. The Bronchiectasis Health Questionnaire (BHQ), Leicester Cough Questionnaire (LCQ), Chronic Obstructive Pulmonary Disease (COPD) Assessment Test (CAT) and Medical Outcomes Study 36-item Short-Form Health Survey (SF-36) had good internal consistency in all domains reported (Cronbach's α≥0.7) across all studies, and the Quality of Life-Bronchiectasis (QOL-B), St George's Respiratory Questionnaire (SGRQ), Chronic Respiratory Disease Questionnaire (CRDQ) and Seattle Obstructive Lung Disease Questionnaire (SOLQ) had good internal consistency in all domains in the majority of (but not all) studies. BHQ, SGRQ, LCQ and CAT had good test-retest reliability in all domains reported (intraclass correlation coefficient ≥0.7) across all studies, and QOL-B, CRDQ and SOLQ had good test-retest reliability in all domains in the majority of (but not all) studies. HRQoL questionnaires were able to discriminate between demographics, important markers of clinical status, disease severity, exacerbations and bacteriology. For HRQoL responsiveness, there was a difference between the treatment and placebo effect. CONCLUSIONS: SGRQ was the most widely used HRQoL questionnaire in bronchiectasis studies and it had good psychometric properties; however, good psychometric data are emerging on the bronchiectasis-specific HRQoL questionnaires QOL-B and BHQ. Future studies should focus on the medium- to long-term test-retest reliability, responsiveness and MCID in these HRQoL questionnaires which show potential in bronchiectasis.

Composition of airway bacterial community correlates with chest HRCT in adults with bronchiectasis.

BACKGROUND AND OBJECTIVE: In bronchiectasis (BE) not caused by cystic fibrosis, chronic, polymicrobial airway infection contributes to the underlying pathogenesis of disease. There is little information on whether bacterial community composition relates to clinical status. We determined the relationship between bacterial community composition, chest high-resolution computed tomography (HRCT) scores and clinical markers in BE. METHODS: A subgroup of BE patients from a previous cross-sectional study were analysed. Spontaneously expectorated sputum was analysed using culture-independent sequencing on the Roche 454-FLX platform covering the V1-V3 region of the 16S rRNA marker gene. Chest HRCT scans, multiple breath washout, spirometry and blood inflammatory markers were collected. Spearman's rank (r) correlation coefficient was used to assess relationships. RESULTS: Data from 21 patients were analysed (mean (SD) age: 64.0 (7.7); female : male 14:7; mean (SD) forced expiratory volume in 1 s (FEV1 ): 76.5 (17.2)). All bacterial community composition metrics (bacterial richness, diversity, evenness and dominance) correlated with percentage BE score, with more severe HRCT abnormality relating to lower bacterial richness, evenness and diversity (range r = -0.47 to -0.66; P < 0.05). Inflammation (C-reactive protein and white cell count) was greater in patients with lower diversity and richness (range r = -0.44 to -0.47; P < 0.05). Bacterial community characteristics did not correlate with lung function. CONCLUSION: This is the first study to indicate a relationship between bacterial community characteristics by 16S rRNA marker gene sequencing, structural damage as determined by chest HRCT and clinical measures in BE. The association between loss of diversity and chest HRCT severity suggests that bacterial dominance with pathogenic bacteria may contribute to disease pathology.

Airway clearance, mucoactive therapies and pulmonary rehabilitation in bronchiectasis.

This paper aims to provide physiological rationale for airway clearance, mucoactive therapy and pulmonary rehabilitation (PR) (or exercise interventions) in bronchiectasis. There is increasing emphasis on the role of airway clearance techniques (ACT) in the management of bronchiectasis. No single ACT has currently shown superior effect over another. Given the large range of different techniques available, consideration of the physiological effects underpinning a technique including expiratory flow, ventilation and oscillation, is essential to effectively personalize ACT. Key clinical trials of mucoactives in bronchiectasis are underway and will provide clarity on the role of these agents in the management of patients with bronchiectasis. Prescription of mucoactive therapies should be done in conjunction with ACT and therefore the mechanism of action of mucoactive drugs and their timing with ACT should be taken into consideration. PR and/or exercise training are recommended in all current bronchiectasis guidelines. There is a clear physiological rationale that muscle weakness and physical inactivity may play a role in disease progression as well as impacting health-related quality of life, frequency of pulmonary exacerbations and ability to mobilize sputum. However, there are residual unanswered questions surrounding the delivery and accessibility to PR. This review summarizes the physiological principles and supporting evidence for airway clearance, mucoactive medication and PR, which are key components in the management of bronchiectasis.

Quality control for multiple breath washout tests in multicentre bronchiectasis studies: Experiences from the BRONCH-UK clinimetrics study.

INTRODUCTION: Multiple Breath Washout (MBW) to measure Lung Clearance Index (LCI) is increasingly being used as a secondary endpoint in multicentre bronchiectasis studies. LCI data quality control or "over-reading" is resource intensive and the impact is unclear. OBJECTIVES: To assess the proportion of MBW tests deemed unacceptable with over-reading, and to assess the change in LCI (number of turnovers), LCI coefficient of variation (CV%) and tidal volume (VT) CV% results after over-reading. METHODS: Data were analysed from 250 MBW tests (from 98 adult bronchiectasis patients) collected as part of the Bronch-UK Clinimetrics study in 5 UK centres. Each MBW test was over-read centrally using pre-defined criteria. MBW tests with <2 technically valid and repeatable trials were deemed unacceptable to include in analysis. In accepted tests, values for LCI, LCI CV% and VT CV% before and after over-reading, were compared. RESULTS: Insufficient data was collected in 10/250 tests. With over-reading, 30/240 (12%) were deemed unacceptable to include in analysis. In those accepted tests, overall the change in LCI, LCI CV% and VT CV% with over-reading was not statistically significant. When MBW new sites were compared to MBW expert sites, the change in LCI with over-reading was significantly greater in MBW new sites (p = 0.047). Data suggests that over-reading could be important up to at least 12 months post initiation of MBW activity. CONCLUSION: MBW over-reading was important in this study as 12% of tests were considered unacceptable. Over-reading improved test result accuracy in sites new to MBW.

Non-invasive ventilation for cystic fibrosis.

BACKGROUND: Non-invasive ventilation may be a means to temporarily reverse or slow the progression of respiratory failure in cystic fibrosis by providing ventilatory support and avoiding tracheal intubation. Using non-invasive ventilation, in the appropriate situation or individuals, can improve lung mechanics through increasing airflow and gas exchange and decreasing the work of breathing. Non-invasive ventilation thus acts as an external respiratory muscle. This is an update of a previously published review. OBJECTIVES: To compare the effect of non-invasive ventilation versus no non-invasive ventilation in people with cystic fibrosis for airway clearance, during sleep and during exercise. SEARCH METHODS: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register comprising references identified from comprehensive electronic database searches, handsearching relevant journals and abstract books of conference proceedings. We searched the reference lists of each trial for additional publications possibly containing other trials.Most recent search: 08 August 2016. SELECTION CRITERIA: Randomised controlled trials comparing a form of pressure preset or volume preset non-invasive ventilation to no non-invasive ventilation used for airway clearance or during sleep or exercise in people with acute or chronic respiratory failure in cystic fibrosis. DATA COLLECTION AND ANALYSIS: Three reviewers independently assessed trials for inclusion criteria and methodological quality, and extracted data. MAIN RESULTS: Ten trials met the inclusion criteria with a total of 191 participants. Seven trials evaluated single treatment sessions, one evaluated a two-week intervention, one evaluated a six-week intervention and one a three-month intervention. It is only possible to blind trials of airway clearance and overnight ventilatory support to the outcome assessors. In most of the trials we judged there was an unclear risk of bias with regards to blinding due to inadequate descriptions. The six-week trial was the only one judged to have a low risk of bias for all other domains. One single intervention trial had a low risk of bias for the randomisation procedure with the remaining trials judged to have an unclear risk of bias. Most trials had a low risk of bias with regard to incomplete outcome data and selective reporting.Six trials (151 participants) evaluated non-invasive ventilation for airway clearance compared with an alternative chest physiotherapy method such as the active cycle of breathing techniques or positive expiratory pressure. Three trials used nasal masks, one used a nasal mask or mouthpiece and one trial used a face mask and in one trial it is unclear. Three of the trials reported on one of the review's primary outcome measures (quality of life). Results for the reviews secondary outcomes showed that airway clearance may be easier with non-invasive ventilation and people with cystic fibrosis may prefer it. We were unable to find any evidence that non-invasive ventilation increases sputum expectoration, but it did improve some lung function parameters.Three trials (27 participants) evaluated non-invasive ventilation for overnight ventilatory support compared to oxygen or room air using nasal masks (two trials) and nasal masks or full face masks (one trial). Trials reported on two of the review's primary outcomes (quality of life and symptoms of sleep-disordered breathing). Results for the reviews secondary outcome measures showed that they measured lung function, gas exchange, adherence to treatment and preference, and nocturnal transcutaneous carbon dioxide. Due to the small numbers of participants and statistical issues, there were discrepancies in the results between the RevMan and the original trial analyses. No clear differences were found between non-invasive ventilation compared with oxygen or room air except for exercise performance, which significantly improved with non-invasive ventilation compared to room air over six weeks.One trial (13 participants) evaluated non-invasive ventilation on exercise capacity (interface used was unclear) and did not reported on any of the review's primary outcomes. The trial found no clear differences between non-invasive ventilation compared to no non-invasive ventilation for any of our outcomes.Three trials reported on adverse effects. One trial, evaluating non-invasive ventilation for airway clearance, reported that a participant withdrew at the start of the trial due to pain on respiratory muscle testing. One trial evaluating non-invasive ventilation for overnight support reported that one participant could not tolerate an increase in inspiratory positive airway pressure. A second trial evaluating non-invasive ventilation in this setting reported that one participant did not tolerate the non-invasive ventilation mask, one participant developed a pneumothorax when breathing room air and two participants experienced aerophagia which resolved when inspiratory positive airway pressure was decreased. AUTHORS' CONCLUSIONS: Non-invasive ventilation may be a useful adjunct to other airway clearance techniques, particularly in people with cystic fibrosis who have difficulty expectorating sputum. Non-invasive ventilation, used in addition to oxygen, may improve gas exchange during sleep to a greater extent than oxygen therapy alone in moderate to severe disease. The effect of NIV on exercise is unclear. These benefits of non-invasive ventilation have largely been demonstrated in single treatment sessions with small numbers of participants. The impact of this therapy on pulmonary exacerbations and disease progression remain unclear. There is a need for long-term randomised controlled trials which are adequately powered to determine the clinical effects of non-invasive ventilation in cystic fibrosis airway clearance and exercise.

Timing of hypertonic saline and airway clearance techniques in adults with cystic fibrosis during pulmonary exacerbation: pilot data from a randomised crossover study.

BACKGROUND: Streamlining the timing of treatments in cystic fibrosis (CF) is important to optimise adherence while ensuring efficacy. The optimal timing of treatment with hypertonic saline (HTS) and airway clearance techniques (ACT) is unknown. OBJECTIVES: This study hypothesised that HTS before ACT would be more effective than HTS during ACT as measured by Lung Clearance Index (LCI). METHODS: Adults with CF providing written informed consent were randomised to a crossover trial of HTS before ACT or HTS during ACT on consecutive days. ACT treatment consisted of Acapella Duet. Patients completed LCI and spirometry at baseline and 90 min post treatment. Mean difference (MD) and 95% CIs were reported. RESULTS: 13 subjects completed the study (mean (SD) age 33 (12) years, forced expiratory volume in 1second % (FEV1%) predicted 51% (22), LCI (no. turnovers) 14 (4)). Comparing the two treatments (HTS before ACT vs HTS during ACT), the change from baseline to 90 min post treatment in LCI (MD (95% CI) -0.02 (-0.63 to 0.59)) and FEV1% predicted (MD (95% CI) -0.25 (-2.50 to 1.99)) was not significant. There was no difference in sputum weight (MD (95% CI) -3.0 (-14.9 to 8.9)), patient perceived ease of clearance (MD (95% CI) 0.4 (-0.6 to 1.3) or satisfaction (MD (95% CI) 0.4 (-0.6 to 1.5)). The time taken for HTS during ACT was significantly shorter (MD (95% CI) 14.7 (9.8 to 19.6)). CONCLUSIONS: In this pilot study, HTS before ACT was no more effective than HTS during ACT as measured by LCI. TRIAL REGISTRATION NUMBER: NCT01753869; Pre-results.

Lung Clearance Index in Adults and Children With Cystic Fibrosis.

BACKGROUND: Lung clearance index (LCI) has good clinimetric properties and an acceptable feasibility profile as a surrogate end point in cystic fibrosis (CF). Although most studies to date have been in children, increasing numbers of adults with CF also have normal spirometric findings. Further study of LCI as an end point in adults with CF is required. Therefore, the purpose of this study was to determine the clinimetric properties of LCI across the age range of people with CF. METHODS: Clinically stable adults and children with CF and age-matched healthy control subjects were recruited. RESULTS: LCI and spirometry data for 110 subjects with CF and 61 control subjects were collected at a stable visit. The CF Questionnaire-Revised (CFQ-R) was completed by 80 of 110 subjects with CF. Fifty-six subjects with CF completed a second stable visit. The LCI coefficient of variation percent was 4.1% in adults and 6.3% in children with CF. The coefficient of repeatability of LCI was 1.2 in adults and 1.3 in children. In both adults and children, LCI (area under the receiving operator characteristic curve [AUCROC] = 0.93 and 0.84, respectively) had greater combined sensitivity and specificity to discriminate between people with CF and control subjects when compared with FEV1 (AUCROC = 0.88 and 0.60, respectively) and forced expiratory flow at 25% to 75% of the curve (AUCROC = 0.87 and 0.68, respectively). LCI correlated significantly with the CFQ-R treatment burden in adults (r = -0.37; P < .01) and children (r = -0.50; P < .01). Washout tests were successful in 90% of subjects with CF and were perceived as comfortable and easy to perform in both adults and children. CONCLUSIONS: These data support the use of LCI as a surrogate outcome measure in CF clinical trials in adults as well as in children.

Definitive activation of endogenous antitumor immunity by repetitive cycles of cyclophosphamide with interspersed Toll-like receptor agonists.

Many cancers both evoke and subvert endogenous anti-tumor immunity. However, immunosuppression can be therapeutically reversed in subsets of cancer patients by treatments such as checkpoint inhibitors or Toll-like receptor agonists (TLRa). Moreover, chemotherapy can leukodeplete immunosuppressive host elements, including myeloid-derived suppressor cells (MDSCs) and regulatory T-cells (Tregs). We hypothesized that chemotherapy-induced leukodepletion could be immunopotentiated by co-administering TLRa to emulate a life-threatening infection. Combining CpG (ODN 1826) or CpG+poly(I:C) with cyclophosphamide (CY) resulted in uniquely well-tolerated therapeutic synergy, permanently eradicating advanced mouse tumors including 4T1 (breast), Panc02 (pancreas) and CT26 (colorectal). Definitive treatment required endogenous CD8+ and CD4+ IFNγ-producing T-cells. Tumor-specific IFNγ-producing T-cells persisted during CY-induced leukopenia, whereas Tregs were progressively eliminated, especially intratumorally. Spleen-associated MDSCs were cyclically depleted by CY+TLRa treatment, with residual monocytic MDSCs requiring only continued exposure to CpG or CpG+IFNγ to effectively attack malignant cells while sparing non-transformed cells. Such tumor destruction occurred despite upregulated tumor expression of Programmed Death Ligand-1, but could be blocked by clodronate-loaded liposomes to deplete phagocytic cells or by nitric oxide synthase inhibitors. CY+TLRa also induced tumoricidal myeloid cells in naive mice, indicating that CY+TLRa's immunomodulatory impacts occurred in the complete absence of tumor-bearing, and that tumor-induced MDSCs were not an essential source of tumoricidal myeloid precursors. Repetitive CY+TLRa can therefore modulate endogenous immunity to eradicate advanced tumors without vaccinations or adoptive T-cell therapy. Human blood monocytes could be rendered similarly tumoricidal during in vitro activation with TLRa+IFNγ, underscoring the potential therapeutic relevance of these mouse tumor studies to cancer patients.

MUC1 Vaccines, Comprised of Glycosylated or Non-Glycosylated Peptides or Tumor-Derived MUC1, Can Circumvent Immunoediting to Control Tumor Growth in MUC1 Transgenic Mice.

It remains challenging to produce decisive vaccines against MUC1, a tumor-associated antigen widely expressed by pancreas, breast and other tumors. Employing clinically relevant mouse models, we ruled out such causes as irreversible T-cell tolerance, inadequate avidity, and failure of T-cells to recognize aberrantly glycosylated tumor MUC1. Instead, every tested MUC1 preparation, even non-glycosylated synthetic 9mer peptides, induced interferon gamma-producing CD4(+) and CD8(+) T-cells that recognized glycosylated variants including tumor-associated MUC1. Vaccination with synthetic peptides conferred protection as long as vaccination was repeated post tumor challenge. Failure to revaccinate post challenge was associated with down-regulated tumor MUC1 and MHC molecules. Surprisingly, direct admixture of MUC1-expressing tumor with MUC1-hyperimmune T-cells could not prevent tumor outgrowth or MUC1 immunoediting, whereas ex vivo activation of the hyperimmune T-cells prior to tumor admixture rendered them curative. Therefore, surrogate T-cell preactivation outside the tumor bed, either in culture or by repetitive vaccination, can overcome tumor escape.

Applying the Transtheoretical Model to Physical Activity Behavior in Individuals With Non-Cystic Fibrosis Bronchiectasis.

BACKGROUND: The transtheoretical model has been successful in promoting health behavior change in general and clinical populations. However, there is little knowledge about the application of the transtheoretical model to explain physical activity behavior in individuals with non-cystic fibrosis bronchiectasis. The aim was to examine patterns of (1) physical activity and (2) mediators of behavior change (self-efficacy, decisional balance, and processes of change) across stages of change in individuals with non-cystic fibrosis bronchiectasis. METHODS: Fifty-five subjects with non-cystic fibrosis bronchiectasis (mean age ± SD = 63 ± 10 y) had physical activity assessed over 7 d using an accelerometer. Each component of the transtheoretical model was assessed using validated questionnaires. Subjects were divided into groups depending on stage of change: Group 1 (pre-contemplation and contemplation; n = 10), Group 2 (preparation; n = 20), and Group 3 (action and maintenance; n = 25). Statistical analyses included one-way analysis of variance and Tukey-Kramer post hoc tests. RESULTS: Physical activity variables were significantly (P < .05) higher in Group 3 (action and maintenance) compared with Group 2 (preparation) and Group 1 (pre-contemplation and contemplation). For self-efficacy, there were no significant differences between groups for mean scores (P = .14). Decisional balance cons (barriers to being physically active) were significantly lower in Group 3 versus Group 2 (P = .032). For processes of change, substituting alternatives (substituting inactive options for active options) was significantly higher in Group 3 versus Group 1 (P = .01), and enlisting social support (seeking out social support to increase and maintain physical activity) was significantly lower in Group 3 versus Group 2 (P = .038). CONCLUSIONS: The pattern of physical activity across stages of change is consistent with the theoretical predictions of the transtheoretical model. Constructs of the transtheoretical model that appear to be important at different stages of change include decisional balance cons, substituting alternatives, and enlisting social support. This study provides support to explore transtheoretical model-based physical activity interventions in individuals with non-cystic fibrosis bronchiectasis. (ClinicalTrials.gov registration NCT01569009.).

Interventions for enhancing adherence to treatment in adults with bronchiectasis.

BACKGROUND: Bronchiectasis is characterised by a widening of the airways, leading to excess mucus production and recurrent infection. It is more prevalent in women and those in middle age. Many patients with bronchiectasis do not adhere to treatments (medications, exercise and airway clearance) prescribed for their condition. The best methods to change these adherence behaviours have not been identified. OBJECTIVES: To assess the effects of interventions to enhance adherence to any aspect of treatment in adults with bronchiectasis in terms of adherence and health outcomes, such as pulmonary exacerbations, health-related quality of life and healthcare costs. SEARCH METHODS: We searched the Cochrane Airways Group Specialised Register (CAGR), which contains trial reports identified through systematic searches of CENTRAL, MEDLINE, EMBASE, CINAHL, AMED and PsycINFO, from inception to October 2015. SELECTION CRITERIA: We planned to include randomised controlled trials (RCTs) of adults with bronchiectasis that compared any intervention aimed at enhancing adherence versus no intervention, usual care or another adherence intervention. We excluded studies of those who had bronchiectasis due to cystic fibrosis. DATA COLLECTION AND ANALYSIS: Two review authors (AMcC and ET) independently screened titles, abstracts and full-texts of identified studies. MAIN RESULTS: Searches retrieved 36 studies reported in 37 articles; no eligible studies were identified. AUTHORS' CONCLUSIONS: We did not identify any studies that assessed the effect of interventions to enhance adherence to treatment in bronchiectasis. Adequately powered, well-designed trials of adherence interventions for bronchiectasis are needed.

Defining the content and delivery of an intervention to Change AdhereNce to treatment in BonchiEctasis (CAN-BE): a qualitative approach incorporating the Theoretical Domains Framework, behavioural change techniques and stakeholder expert panels.

BACKGROUND: Low patient adherence to treatment is associated with poorer health outcomes in bronchiectasis. We sought to use the Theoretical Domains Framework (TDF) (a framework derived from 33 psychological theories) and behavioural change techniques (BCTs) to define the content of an intervention to change patients' adherence in bronchiectasis (Stage 1 and 2) and stakeholder expert panels to define its delivery (Stage 3). METHODS: We conducted semi-structured interviews with patients with bronchiectasis about barriers and motivators to adherence to treatment and focus groups or interviews with bronchiectasis healthcare professionals (HCPs) about their ability to change patients' adherence to treatment. We coded these data to the 12 domain TDF to identify relevant domains for patients and HCPs (Stage 1). Three researchers independently mapped relevant domains for patients and HCPs to a list of 35 BCTs to identify two lists (patient and HCP) of potential BCTs for inclusion (Stage 2). We presented these lists to three expert panels (two with patients and one with HCPs/academics from across the UK). We asked panels who the intervention should target, who should deliver it, at what intensity, in what format and setting, and using which outcome measures (Stage 3). RESULTS: Eight TDF domains were perceived to influence patients' and HCPs' behaviours: Knowledge, Skills, Beliefs about capability, Beliefs about consequences, Motivation, Social influences, Behavioural regulation and Nature of behaviours (Stage 1). Twelve BCTs common to patients and HCPs were included in the intervention: Monitoring, Self-monitoring, Feedback, Action planning, Problem solving, Persuasive communication, Goal/target specified:behaviour/outcome, Information regarding behaviour/outcome, Role play, Social support and Cognitive restructuring (Stage 2). Participants thought that an individualised combination of these BCTs should be delivered to all patients, by a member of staff, over several one-to-one and/or group visits in secondary care. Efficacy should be measured using pulmonary exacerbations, hospital admissions and quality of life (Stage 3). CONCLUSIONS: Twelve BCTs form the intervention content. An individualised selection from these 12 BCTs will be delivered to all patients over several face-to-face visits in secondary care. Future research should focus on developing physical materials to aid delivery of the intervention prior to feasibility and pilot testing. If effective, this intervention may improve adherence and health outcomes for those with bronchiectasis in the future.

Predictors of adherence to treatment in bronchiectasis.

OBJECTIVES: We aimed to determine if beliefs about treatment, clinical factors and quality of life predicted adherence to treatment in patients with bronchiectasis. METHODS: We recruited participants with confirmed bronchiectasis to a one-year study. We calculated adherence to treatment using medication possession ratios and self-report. Baseline Beliefs about Medicines, clinical, demographic and Quality of Life Questionnaire-Bronchiectasis data were collected. We used logistic regression to determine predictors of adherence to treatment during the subsequent year. RESULTS: Seventy-five participants were recruited. Beliefs about harm, age and total number of prescribed medications were predictors of adherence to inhaled antibiotics. Concerns about medication, age and Quality of Life Questionnaire-Bronchiectasis Treatment Burden were predictors of adherence to other respiratory medicines. Beliefs about necessity of airway clearance and age were predictors of adherence to airway clearance. CONCLUSION: Beliefs about treatment, age, number of prescribed medications and perceived treatment burden predicted subsequent adherence in bronchiectasis, thereby, providing potential targets for future interventions in this population. Clinicians can use these data to identify patients with bronchiectasis who might be at risk of non-adherence i.e. those who are younger, have concerns about medications, who do not think airway clearance is necessary or who are prescribed numerous medications.

Linear synthesis and immunological properties of a fully synthetic vaccine candidate containing a sialylated MUC1 glycopeptide.

A strategy for the linear synthesis of a sialylated glycolipopeptide cancer vaccine candidate has been developed using a strategically designed sialyl-Tn building block and microwave-assisted solid-phase peptide synthesis. The glycolipopeptide elicited potent humoral and cellular immune responses. T-cells primed by such a vaccine candidate could be restimulated by tumor-associated MUC1.

Reduced bacterial colony count of anaerobic bacteria is associated with a worsening in lung clearance index and inflammation in cystic fibrosis.

Anaerobic bacteria have been identified in abundance in the airways of cystic fibrosis (CF) subjects. The impact their presence and abundance has on lung function and inflammation is unclear. The aim of this study was to investigate the relationship between the colony count of aerobic and anaerobic bacteria, lung clearance index (LCI), spirometry and C-Reactive Protein (CRP) in patients with CF. Sputum and blood were collected from CF patients at a single cross-sectional visit when clinically stable. Community composition and bacterial colony counts were analysed using extended aerobic and anaerobic culture. Patients completed spirometry and a multiple breath washout (MBW) test to obtain LCI. An inverse correlation between colony count of aerobic bacteria (n = 41, r = -0.35; p = 0.02), anaerobic bacteria (n = 41, r = -0.44, p = 0.004) and LCI was observed. There was an inverse correlation between colony count of anaerobic bacteria and CRP (n = 25, r = -0.44, p = 0.03) only. The results of this study demonstrate that a lower colony count of aerobic and anaerobic bacteria correlated with a worse LCI. A lower colony count of anaerobic bacteria also correlated with higher CRP levels. These results indicate that lower abundance of aerobic and anaerobic bacteria may reflect microbiota disruption and disease progression in the CF lung.

Sedentary behaviour and physical activity in bronchiectasis: a cross-sectional study.

BACKGROUND: The impact of bronchiectasis on sedentary behaviour and physical activity is unknown. It is important to explore this to identify the need for physical activity interventions and how to tailor interventions to this patient population. We aimed to explore the patterns and correlates of sedentary behaviour and physical activity in bronchiectasis. METHODS: Physical activity was assessed in 63 patients with bronchiectasis using an ActiGraph GT3X+ accelerometer over seven days. Patients completed: questionnaires on health-related quality-of-life and attitudes to physical activity (questions based on an adaption of the transtheoretical model (TTM) of behaviour change); spirometry; and the modified shuttle test (MST). Multiple linear regression analysis using forward selection based on likelihood ratio statistics explored the correlates of sedentary behaviour and physical activity dimensions. Between-group analysis using independent sample t-tests were used to explore differences for selected variables. RESULTS: Fifty-five patients had complete datasets. Average daily time, mean(standard deviation) spent in sedentary behaviour was 634(77)mins, light-lifestyle physical activity was 207(63)mins and moderate-vigorous physical activity (MVPA) was 25(20)mins. Only 11% of patients met recommended guidelines. Forced expiratory volume in one-second percentage predicted (FEV1% predicted) and disease severity were not correlates of sedentary behaviour or physical activity. For sedentary behaviour, decisional balance 'pros' score was the only correlate. Performance on the MST was the strongest correlate of physical activity. In addition to the MST, there were other important correlate variables for MVPA accumulated in ≥10-minute bouts (QOL-B Social Functioning) and for activity energy expenditure (Body Mass Index and QOL-B Respiratory Symptoms). CONCLUSIONS: Patients with bronchiectasis demonstrated a largely inactive lifestyle and few met the recommended physical activity guidelines. Exercise capacity was the strongest correlate of physical activity, and dimensions of the QOL-B were also important. FEV1% predicted and disease severity were not correlates of sedentary behaviour or physical activity. The inclusion of a range of physical activity dimensions could facilitate in-depth exploration of patterns of physical activity. This study demonstrates the need for interventions targeted at reducing sedentary behaviour and increasing physical activity, and provides information to tailor interventions to the bronchiectasis population. TRIAL REGISTRATION: NCT01569009 ("Physical Activity in Bronchiectasis").