Background:Smoking is the most common etiology for lung cancer and smoking cessation does not eliminate the risk. Mucin (MUC)1 glycoprotein is aberrantly expressed in lung carcinomas and premalignant lung lesions. We explored whether a MUC1 vaccine might be effective in halting neoplastic development and progression in individuals at high risk for lung cancer. Methods:We conducted a multicenter trial of a MUC1 vaccine in current and former heavy smokers to evaluate immunogenicity and safety. Smoking history of ≥30 pack-years and CT chest showing either no nodules or nodules < 6 mm were inclusion criteria. A vaccine containing MUC1 peptide was administered at weeks 0, 2 and 10. Blood was collected pre-vaccine administration, 2 weeks after each vaccine, and at week 24. Immunogenicity (primary endpoint) and the presence of myeloid-derived suppressor cells (MDSC) and regulatory T cells (secondary endpoints) were assessed. Adverse events and toxicities were monitored. Results:Of 77 individuals screened, 50 were registered and 45 completed the study (27 current and 18 former smokers). The vaccine was well-tolerated. Four current (14.8%) and 2 former smokers (11.1%) developed anti-MUC1 IgG titers ≥2 fold higher at week 12 as compared with baseline, with an overall immune response rate of 13.3% (95% CI 5.1-26.8%). We found high circulating levels of immunosuppressive MDSCs in both current and former smokers. Conclusions:Administering a potentially preventive vaccine is feasible and safe in individuals at high risk for lung cancer. However, this cohort exhibited a high level of immune suppression, previously documented only in patients with advanced lung cancer. Nonetheless, a vaccine-induced immune response was noted in 13% of participants. Further work is required to refine participant selection, understand the factors driving immunosuppression, and counteract these factors to apply immunoprevention strategies in this high-risk population. Translational Relevance:Vaccines targeting antigens aberrantly expressed on lung cancers and their precursors offer the potential for a relatively non-invasive prevention strategy. Worldwide, lung cancer remains the most important cause of cancer-related mortality, and an immunoprevention approach, if successful, has the potential to save many lives by prevention of lung cancer. All epithelial tumors, including lung cancer, express high levels of abnormal mucin (MUC)1 and MUC1-based therapeutic vaccines can increase this immune response to aberrant expressed MUC1 to therapeutic levels.We conducted a multicenter trial to evaluate the immunogenicity and safety of a MUC1 preventive vaccine in individuals with a significant smoking history and at high risk of developing lung cancer. The MUC1 vaccine was safe and elicited an immune response in 13%, which was lower than anticipated. Unexpectedly, we observed a high level of immune suppression in this cohort of heavy smokers, which has been previously documented in individuals who already have lung cancer. Although immunoprevention strategies are promising for reducing the risk of lung cancer in current and former heavy smokers, the immune environment induced by smoking, and the factors that drive immunosuppression are crucial barriers that must be overcome by well-designed immunoprevention strategies for lung cancer.

Abstract Background: Smoking is the most common etiology for lung cancer. Smoking cessation, even when successful, does not eliminate risk of lung cancer. With inconsistent results of lung chemoprevention trials, an emerging area of interest is immunoprevention, in particular vaccines. MUC1 is a transmembrane glycoprotein aberrantly overexpressed in adenocarcinomas, including lung cancer. Abnormal MUC1 expression is also characteristic of premalignant lesions, including bronchial dysplasia and atypical adenomatous hyperplasia. This suggests that immunization with a MUC1 vaccine in the premalignant or high-risk setting, before the tumor and cytotoxic therapy could suppress the immune system, might be effective in inducing strong immunity and reducing cancer risk. Trial design: Leveraging the infrastructure of the NCI-funded Cancer Prevention Network (CPN) consortium, we are conducting a two-center pilot trial to evaluate co-primary endpoints: immunogenicity of the MUC1 peptide plus polyICLC adjuvant vaccine (assessed at 12 weeks) and safety (assessed at up to 24 weeks) in current and former smokers who are at high risk for lung cancer. 50 participants will be screened in order to have 40 evaluable participants for baseline and 12-week immunogenicity assessments. Eligibility: Smoking history of ≥30 pack-years and either current smoker (still smoking or quit < 1 year prior to pre-registration) or former smoker (quit 1-15 years prior to pre-registration); ages 55-80 years; ECOG performance status ≤1; CT scan of the chest done ≤ 6 months prior to pre-registration showing either negative findings (no nodules) or solid or part-solid nodules < 6 mm in size (consistent with < 1% probability of malignancy, Lung-RADs Version 1.0). Exclusion criteria are standard. Immunogenicity and safety: MUC1 peptide plus polyICLC adjuvant vaccine will be administered at week 0, 2 and 10. The primary endpoint is anti-MUC1 IgG titer that is ≥2 fold higher at week 12 compared to baseline. Based on previous studies of this vaccine, we expect that 40 evaluable participants will provide 96% power to detect immunogenicity response rate of 15% versus 40% using a 2-sided test of proportions with type I error rate of 0.05. AEs and toxicities will be monitored for up to 24 weeks from the first vaccine. Secondary Objectives: We will explore differences, if any, in vaccine immunogenicity in current vs. former smokers. Smoking induces chronic inflammation (hallmark of cancer) associated with immunosuppression. We will evaluate pre-vaccination levels of circulating myeloid derived suppressor cells (MDSC) and correlate with the response to the vaccine. We will explore the impact, if any, of this vaccine on the markers of inflammation (hsCRP, IL-6) and the effect of baseline levels of these markers on the ability to successfully vaccinate. We will also assess the relationship between COPD status and immune response in current versus former smokers. The trial is open to accrual. Citation Format: Olivera J. Finn, Julie Ward, Tami Krpata, Lisa Bengtson, John McKolanis, Sharon Kaufman, Colleen Akerley, April Felt, Karrie Fursa, Anne Holland, Nathan Foster, Andres Salazar, Malgorzata Wojtowicz, Eva Szabo, Paul Limburg, David Midthun, Arjun Pennathur. A pilot study of a MUC1 vaccine in current and former smokers at high risk for lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr CT222.

Background: Smoking is the most common etiology for lung cancer and smoking cessation does not eliminate the risk. An emerging area of interest for risk reduction is immunoprevention. MUC1 glycoprotein is aberrantly expressed in adenocarcinomas, including lung cancer and their premalignant lesions. MUC1 vaccine in the premalignant or high-risk setting may be effective in halting neoplastic development and progression. Trial design: Through the NCI-funded Cancer Prevention Network (CPN), we conducted a two-center pilot trial to evaluate immunogenicity of the MUC1 vaccine (assessed at 12 weeks), and safety (assessed at up to 24 weeks) in current and former heavy smokers. 87 participants were screened in order to have at least 40 evaluable for baseline and 12-week immunogenicity assessments. Smoking history of ≥30 pack-years and either current (still smoking or quit < 1 year prior to pre-registration) or former smoker (quit 1-15 years prior to pre-registration); ages 55-80 years; ECOG performance status ≤1; CT scan of the chest done ≤ 6 months prior to pre-registration showing either negative findings (no nodules) or solid or part-solid nodules < 6 mm in size (consistent with < 1% probability of malignancy, Lung-RADs Version 1.0). Exclusion criteria were standard for lung cancer screening. Methods: MUC1 peptide plus polyICLC adjuvant (Hiltonol) vaccine was given at week 0, 2 and 10. Blood was collected for safety tests and immune assays pre and 2 weeks post each vaccine, and at week 24. Anti-MUC1 IgG titer was evaluated by ELISA. Based on previous studies of this vaccine, 40 evaluable participants would provide 96% power to detect immune response rate of 15% versus 40%, using a 2-sided test of proportions with type I error rate of 0.05. PBMC were assayed for the presence of regulatory T cells (Treg) and myeloid derived suppressor cells (MDSC) (secondary endpoint). Circulating levels of inflammatory cytokines and hsCRP were evaluated using commercially available tests (exploratory endpoint). AEs and toxicities were monitored for up to 24 weeks from the first vaccine. Results: 87 individuals were screened and 50 registered. 45 completed the study, 26 current and 19 former smokers (time since last smoked: average 7.8 years; 11 months -13 years). The vaccine was well-tolerated with injection site reactions being the most common AE. Immune response to the vaccine was lower than expected, with 2 current and 2 former smokers developing anti-MUC1 IgG titers ≥2 fold higher at week 12 over baseline (10%). We found high circulating levels of MDSCs in PBMC of both current and former smokers and very low or no serum cytokines. Conclusions: A preventative vaccine trial was feasible in individuals at high risk for lung cancer. However, we discovered a high level of immune suppression, previously documented only in advanced lung cancer. Mitigating the development of lung cancer in heavy smokers through vaccine administration may be limited by related immunosuppression. Citation Format: Olivera J. Finn, Julie Ward, Tami Krpata, Samantha Fatis, John McKolanis, Jia Xue, Pamela Beatty, Camille Jacqueline, Sharon Kaufman, Colleen Akerley, April Felt, Karrie Fursa, Anne Holland, Liz S. Ambulay, Nathan Foster, Ryan McMurray, Carrie Strand, Andres M. Salazar, Lisa Bengtson, Eva Szabo, Paul Limburg, Malgorzata Wojtowicz, David E. Midthun, Arjun Pennathur. A pilot study of a MUC1 vaccine in current and former smokers at high risk for lung cancer. [abstract]. In: Proceedings of the AACR Special Conference: Precision Prevention, Early Detection, and Interception of Cancer; 2022 Nov 17-19; Austin, TX. Philadelphia (PA): AACR; Can Prev Res 2023;16(1 Suppl): Abstract nr PR002.

Background Chronic obstructive pulmonary disease (COPD) is a progressive chronic condition. Improvements in therapies have resulted in better patient outcomes. The use of technology such as telemonitoring as an additional intervention is aimed at enhancing care and reducing unnecessary acute hospital service use. The influence of verbal communication between health staff and patients to inform decision making regarding use of acute hospital services within telemonitoring studies has not been assessed. Method A systematic overview of published systematic reviews of COPD and telemonitoring was conducted using an a priori protocol to ascertain the impact of verbal communication in telemonitoring studies on health service outcomes such as emergency department attendances, hospitalisation and hospital length of stay. The search of the following electronic databases: Cochrane Library, Medline, Pubmed, CINAHL, Embase, TROVE, Australian Digital Thesis and Proquest International Dissertations and Theses was conducted in 2017 and updated in September 2019. Results Six systematic reviews were identified. All reviews involved home monitoring of COPD symptoms and biometric data. Included reviews reported 5–28 studies with sample sizes ranging from 310 to 2891 participants. Many studies reported in the systematic reviews were excluded as they were telephone support, cost effectiveness studies, and/or did not report the outcomes of interest for this overview. Irrespective of group assignment, verbal communication with the health or research team did not alter the emergency attendance or hospitalisation outcome. The length of stay was longer for those who were assigned home telemonitoring in the majority of studies. Conclusion This overview of telemonitoring for COPD had small sample sizes and a wide variety of included studies. Communication was not consistent in all included studies. Understanding the context of communication with study participants and the decision-making process for referring patients to various health services needs to be reported in future studies of telemonitoring and COPD.

School of Public Health & Preventive Medicine, Monash University, Melbourne, Australia; Shaare Zedek Medical Center and The Hebrew University Hadassah Medical School, Jerusalem, Israel; National Healthcare Group Polyclinics, Singapore; Centre For Medicine Use and Safety, Faculty of Pharmacy and Pharmaceutical Sciences, Monash University, Parkville, Australia; Southern Academic Primary Care Research Unit, Department of General Practice, Monash University, Notting Hill, Australia; Discipline of Physiotherapy, La Trobe University and Alfred Health, Melbourne, Australia; Faculty of Health Sciences & Medicine, Bond University, Gold Coast, Australia; School of Medicine and Public Health, University of Newcastle, Callaghan, Australia; The Nossal Institute For Global Health, University of Melbourne, Melbourne, Australia; Eastern Melbourne PHN (EMPHN), Box Hill, Australia; Lung Foundation Australia (LFA), Milton, Australia; Department of Infrastructure Engineering, The University of Melbourne, Melbourne, Australia Purpose: Many older adults with a history of smoking and asthma develop clinical features of both asthma and COPD, an entity sometimes called asthma-COPD overlap (ACO). Patients with ACO may be at higher risk of poor health outcomes than those with asthma or COPD alone. However, understanding of ACO is limited in the primary care setting and more information is needed to better inform patient management. We aimed to compare the characteristics of patients with ACO or COPD in Australian general practices. Patients and methods: Data were from the RADICALS (Review of Airway Dysfunction and Interdisciplinary Community-based care of Adult Long-term Smokers) trial, an intervention study of an interdisciplinary community-based model of care. Baseline demographic and clinical characteristics, preand post-bronchodilator spirometry, dyspnoea and St. George’s Respiratory Questionnaire scores were compared between 60 ACO patients and 212 with COPD alone. Results: Pre-bronchodilator Forced Expiratory Volume in 1 second (mean±SD 58.4±14.3 vs 67.5±20.1% predicted) and Forced Vital Capacity (mean 82.1±16.9 v 91.9±17.2% predicted) were significantly lower in the ACO group (p<0.001), but no difference was found in postbronchodilator spirometry. Demographic and clinical characteristics, dyspnoea, quality of life, comorbidities and treatment prescribed did not differ significantly between groups. Conclusion: This is the first study describing the clinical characteristics of ACO patients in Australian general practices. Our finding of lower pre-bronchodilator lung function in the ACO group compared to those with COPD reinforces the importance of spirometry in primary care to inform management. Trial registration: Australian New Zealand Clinical Trials Registry ACTRN12614001155684.

BACKGROUND: Exertional desaturation is an important predictor of mortality in patients with interstitial lung disease. We evaluated the prevalence of exertional desaturation in subjects with interstitial lung disease and determined its relationship with the prescription of ambulatory oxygen therapy. METHODS: Our retrospective analysis examined prospectively collected data from interstitial lung disease registries of 2 Melbourne hospitals: Alfred Health and Austin Health. All patients with baseline the 6-min walk tests on room air were included. We evaluated the prescription of ambulatory oxygen therapy, up to 3 months after 6-min walk tests, among those with exertional desaturation. RESULTS: Of the 400 subjects, 214 (54%) had exertional desaturation. The prevalence of desaturation increased with the severity of lung function impairment (FVC measurement: 33% for > 75% predicted, 69% for 50–75% predicted, 86% for < 50% predicted; diffusing capacity of the lung for carbon monoxide measurement: 20% for > 55% predicted, 64% for 36–55% predicted, 93% for ≤ 35% predicted, P < .001 for both severity classifications). There was no difference in the prevalence of exertional desaturation among common disease subtypes (P = .17). Among the desaturators, 14 (7%) had resting hypoxemia and all were prescribed long-term oxygen therapy. Of the remaining 200 with exertional desaturation only, 58 (29%) were prescribed ambulatory oxygen therapy. Multiple logistic regression showed independent associations between the ambulatory oxygen therapy prescription and shorter 6-min walk distance (P < .001) as well as worse FVC (% predicted, P = .037). CONCLUSIONS: Exertional desaturation is common in subjects with interstitial lung disease. More severely impaired exercise capacity and worse lung function are associated with the prescription of ambulatory oxygen therapy in interstitial lung disease.

Rationale: Domiciliary oxygen therapy (DOT) is commonly prescribed for patients with interstitial lung disease (ILD) and hypoxemia, although evidence supporting benefit is limited. Objectives: The aim of this study was to explore perspectives of respiratory physicians about DOT in patients with ILD. Methods: A qualitative study was undertaken with 26 respiratory physicians from Australia. Interviews were transcribed verbatim and coded independently by two investigators. Themes were established by consensus. Results: Physicians reported symptomatic relief as the main indication for prescribing DOT in ILD. Concerns were raised regarding the applicability of current clinical guidelines for DOT to ILD. Compared with patients with other lung diseases, there was a lower threshold for DOT prescription for patients with ILD. Physicians perceived that patients with ILD complied better with recommended DOT prescription. There was significant variation in infrastructure for oxygen assessment and prescription, patient support, and equipment provision among institutions and states. Various patients' attitudes and experiences toward DOT were reported, but most notable was physicians' perception of significant anxiety in most patients using DOT because of social stigma and concerns that DOT signified end-stage disease. Conclusions: Oxygen therapy was primarily prescribed for symptomatic management in patients with ILD. Education provision and supports regarding DOT varied significantly.

Rationale: Domiciliary oxygen therapy is commonly prescribed for patients with interstitial lung disease and hypoxemia, either at rest or during exertion, with the aim of improving symptoms and functional status.Objectives: This study aimed to explore perspectives of adults with interstitial lung disease about domiciliary oxygen therapy, comparing insights from patients using and not using oxygen therapy.Methods: A qualitative study using semistructured interviews was undertaken on 24 adults residing in and near Melbourne, Australia who had a diagnosis of interstitial lung disease and met the Thoracic Society of Australia and New Zealand guidelines for domiciliary oxygen therapy. Study subjects included individuals who were oxygen-naive (n = 12) and oxygen-experienced (n = 12). Interviews were transcribed verbatim and coded independently by two investigators in accordance with the grounded theory method of analysis. Themes were established by consensus.Results: Patients using domiciliary oxygen therapy described widespread variation in usage. Oxygen-naive patients expected oxygen therapy to relieve dyspnea, whereas oxygen-experienced patients emphasized the benefits of oxygen on other, non-dyspnearelated physical symptoms. Practical and psychosocial challenges of using oxygen therapy were raised by both groups of patients.Conclusions: This study highlights the different expectations and experiences of domiciliary oxygen therapy for adults with interstitial lung disease. It is important to understand and address patients' concerns about the use of oxygen therapy for these patients.

Chronic obstructive pulmonary disease (COPD) is a significant chronic disease, particularly in aging populations. Both the prevalence and mortality of COPD are increasing throughout the world [1], ...

Background People with bronchiectasis experience chronic cough and sputum production and require the prescription of airway clearance techniques (ACTs). A common type of ACT prescribed is positive expiratory pressure (PEP) therapy. A previous review has suggested that ACTs including PEP therapy are beneficial compared to no treatment in people with bronchiectasis. However, the efficacy of PEP therapy in a stable clinical state or during an acute exacerbation compared to other ACTs in bronchiectasis is unknown. Objectives The primary aim of this review was to determine the effects of PEP therapy compared with other ACTs on health-related quality of life (HRQOL), rate of acute exacerbations, and incidence of hospitalisation in individuals with stable or an acute exacerbation of bronchiectasis. Secondary aims included determining the effects of PEP therapy upon physiological outcomes and clinical signs and symptoms compared with other ACTs in individuals with stable or an acute exacerbation of bronchiectasis. Search methods We searched the Cochrane Airways Group Specialised Register of Trials, PEDro and clinical trials registries from inception to February 2017 and we handsearched relevant journals. Selection criteria Randomised controlled parallel and cross-over trials that compared PEP therapy versus other ACTs in participants with bronchiectasis. Data collection and analysis We used standard methodological procedures as outlined by Cochrane. Main results Nine studies involving 213 participants met the inclusion criteria, of which seven were cross-over in design. All studies included adults with bronchiectasis, with eight including participants in a stable clinical state and one including participants experiencing an acute exacerbation. Eight studies used oscillatory PEP therapy, using either a Flutter or Acapella device and one study used Minimal PEP therapy. The comparison intervention differed between studies. The methodological quality of studies was poor, with cross-over studies including suboptimal or no washout period, and a lack of blinding of participants, therapists or personnel for outcome measure assessment in most studies. Clinical heterogeneity between studies limited meta-analysis. Daily use of oscillatory PEP therapy for four weeks was associated with improved general health according to the Short-Form 36 questionnaire compared to the active cycle of breathing technique (ACBT). When applied for three sessions over one week, minimal PEP therapy resulted in similar improvement in cough-related quality of life as autogenic drainage (AD) and L'expiration Lente Totale Glotte Ouverte en Decubitus Lateral (ELTGOL). Oscillatory PEP therapy twice daily for four weeks had similar effects on diseasespecific HRQOL (MD -0.09, 95% CI -0.37 to 0.19; low-quality evidence). Data were not available to determine the incidence of hospitalisation or rate of exacerbation in clinically stable participants. Two studies of a single session comparison of oscillatory PEP therapy and gravity-assisted drainage (GAD) with ACBT had contrasting findings. One study found a similar sputum weight produced with both techniques (SMD 0.54g (-0.38 to 1.46; 20 participants); the other found greater sputum expectoration with GAD and ACBT (SMD 5.6 g (95% CI 2.91 to 8.29: 36 participants). There was no difference in sputum weight yielded between oscillatory PEP therapy and ACBT with GAD when applied daily for four weeks or during an acute exacerbation. Although a single session of oscillatory PEP therapy was associated with less sputum compared to AD (median difference 3.1 g (95% CI 1.5 to 4.8 g; one study, 31 participants), no difference between oscillatory PEP therapy and seated ACBT was evident. PEP therapy had a similar effect on dynamic and static measures of lung volumes and gas exchange as all other ACTs. A single session of oscillatory PEP therapy (Flutter) generated a similar level of fatigue as ACBT with GAD, but greater fatigue was noted with oscillatory PEP therapy compared to ACBT alone. The degree of breathlessness experienced with PEP therapy did not differ from other techniques. Among studies exploring adverse events, only one study reported nausea with use of oscillatory PEP therapy. Authors' conclusions PEP therapy appears to have similar effects on HRQOL, symptoms of breathlessness, sputum expectoration, and lung volumes compared to other ACTs when prescribed within a stable clinical state or during an acute exacerbation. The number of studies and the overall quality of the evidence were both low. In view of the chronic nature of bronchiectasis, additional information is needed to establish the long-term clinical effects of PEP therapy over other ACTs for outcomes that are important to people with bronchiectasis and on clinical parameters which impact on disease progression and patient morbidity in individuals with stable bronchiectasis. In addition, the role of PEP therapy during an acute exacerbation requires further exploration. This information is necessary to provide further guidance for prescription of PEP therapy for people with bronchiectasis.

The overwhelming majority of people with chronic obstructive pulmonary disease (COPD) have at least one coexisting medical condition often conceptualized as comorbidities'. These coexisting conditions vary in severity and impact; it is likely that for some patients, COPD is not their most important or severe condition. The concepts of multimorbidity and frailty may be useful to understand the broader needs of people with COPD undergoing pulmonary rehabilitation. Multimorbidity describes the coexistence of two or more chronic conditions, without reference to a primary condition. Best care for people with multimorbidity has been described as a shift from providing disease-focused to patient-centred care. Pulmonary rehabilitation is well placed to deliver such care as it focuses on optimizing function, encourages integration across care settings, values input from multidisciplinary teams and measures patient-important outcomes. When designing optimal pulmonary rehabilitation services for people with multimorbidity, the concept of frailty may be useful. Frailty focuses on impairments rather than medical conditions including impairments in mobility, strength, balance, cognition, nutrition, endurance, mood and physical activity. Emerging data suggest that frailty may be modifiable with pulmonary rehabilitation. The challenge for pulmonary rehabilitation clinicians is to broaden our perspective on the role and outcomes of pulmonary rehabilitation for people with multimorbidity.

Objectives: To investigate the effects of intensive acute hospital physiotherapy for patients with isolated hip fractures. Design, setting: Single-institution, prospective, randomised trial at a level 1 trauma centre in Melbourne, March 2014 January 2015.Participants: 92 patients aged 65 years or more with isolated hip fractures. Patients were excluded if the fracture was subtrochanteric or pathological, or if post-operative orders required the patient to be non-weight-bearing on the operated leg.Interventions: Randomisation to usual care physiotherapy (daily; control group) or intensive physiotherapy (three times daily; intervention group).Main outcome measures: Outcomes were assessed at post-operative Day 5, at discharge, and at 6 months. The primary outcome was the modified Iowa Level of Assistance (mILOA) score, with other outcome measures including Timed Up and Go test performance and hospital length of stay (LOS).Results: After controlling for sex, anaesthetic type and home setting, the between-group difference in Day 5 mILOA score favoured the intervention group (mean difference v control group, 2.7 points; P=0.04). Hospital LOS was also shorter for the intervention group (median, 24.4 days v 35.0 days; P=0.01). A Cox proportional hazard model that controlled for potential confounders indicated that the probability of discharge was greater for intervention group patients at all time points following surgery (P<0.001). Re-admission and complication rates and 6-month outcomes for the two groups were not significantly different.Conclusions: Intensive acute hospital physiotherapy is safe and reduces hospital LOS after an isolated hip fracture. This has the potential to improve bed flow, given the large numbers of inpatient beds occupied by this patient population.

The use of different 6-min walk distance (6MWD) reference equations probably results in different predicted 6MWD reference values. We wished to investigate the impact of several 6MWD reference equations for adults in patients with chronic obstructive pulmonary disease (COPD) and factors accountable for different 6MWD% predicted values. Twenty-two 6MWD reference equations were applied to a data set of 2757 patients with COPD. The predicted 6MWD reference value of Troosters and colleagues was used as the point of reference. Four out of 21 remaining equations resulted in comparable 6MWD% predicted, 16 equations resulted in significantly higher 6MWD% predicted and 1 equation resulted in a significantly lower 6MWD% predicted. Similar differences in 6MWD% predicted were observed after stratification by sex. Body mass index and global initiative for chronic obstructive lung disease (GOLD) stage classification demonstrated varying results within and between the groups; 9 out of 21 equations resulted in comparable 6MWD% predicted in underweight patients but only 1 equation demonstrated comparable result in obese. Eight equations in GOLD I, whilst 5 out of 21 equations in GOLD IV resulted in comparable 6MWD% predicted. Existing 6MWD reference equations will give varying results. The choice of 6MWD reference equation should consider the consistency of 6-min walk test operating procedures and at least be specific for the country/region of origin.

BACKGROUNDPeople with non-cystic fibrosis bronchiectasis commonly experience chronic cough and sputum production and these features may be associated with progressive decline in clinical status. Airway clearance techniques (ACTs) are often prescribed to facilitate expectoration of sputum from the lungs, but the efficacy of these techniques in a stable clinical state or during an acute exacerbation of bronchiectasis is unclear.OBJECTIVESPrimary: to determine the effects of ACTs on the rate of acute exacerbations, incidence of hospitalisation and health-related quality of life in individuals with acute and stable bronchiectasis.Secondary: to determine whether a) ACTs are safe for individuals with acute and stable bronchiectasis and b) ACTs have beneficial effects on physiology and symptoms in individuals with acute and stable bronchiectasis.SEARCH METHODSWe searched the Cochrane Airways Group Specialised Register of trials from inception to October 2012, PEDro in October 2012 and handsearched relevant journals.SELECTION CRITERIARandomised controlled parallel and cross-over trials that compared an ACT to no treatment, sham ACT or directed coughing in participants with bronchiectasis.DATA COLLECTION AND ANALYSISWe used standard methodological procedures expected by The Cochrane Collaboration.MAIN RESULTSFive studies involving 51 participants met the inclusion criteria of the review, all of which were cross-over design. Four studies were on adults with stable bronchiectasis, and the other study was on clinically stable children with bronchiectasis. Three studies were single treatment sessions, two were longer-term studies. The interventions varied and some control groups received a sham intervention while others were inactive. The methodological quality of the studies was variable and the studies were not able to blind participants and personal. Heterogeneity between studies precluded these data from meta-analysis and the review was therefore narrative.One study on 20 adults comparing an airway oscillatory device with no treatment found no significant difference in the number of exacerbations at 12 weeks (low-quality evidence). No data were available to assess the impact of ACTs on the time to exacerbation, duration of, incidence of hospitalisation or total number of hospitalised days. The same study reported clinically significant improvements in health-related quality of life in both disease-specific and cough-related measures. While based on a small number of participants and the data were skewed, the median difference in the change in total St George's Respiratory Questionnaire (SGRQ) score over three months in this study was 8.5 units (P value = 0.005 (Wilcoxon), low-quality evidence). Two studies reported mean increases in volume of sputum expectorated with airway oscillatory devices in the short term of 8.4 mL (95% CI 3.4 to 13.4 mL) and in the long term of 3 mL (P value = 0.02), with no significant effect on lung function. One study reported an immediate reduction in pulmonary hyperinflation in adults with non-positive expiratory pressure (PEP) ACTs (difference in functional residual capacity (FRC) of 19%, P value < 0.05) and with airway oscillatory devices (difference in FRC of 30%, P value < 0.05) compared to no ACTs. A similar decrease in pulmonary hyperinflation (difference in FRC of 6%) was found in children using an airway oscillatory device for 3 months compared to sham therapy. No studies reported on the effects of gas exchange, people's symptoms or antibiotic usage.AUTHORS' CONCLUSIONSACTs appear to be safe for individuals (adults and children) with stable bronchiectasis, where there may be improvements in sputum expectoration, selected measures of lung function and health-related quality of life. The role of these techniques in people with an acute exacerbation of bronchiectasis is unknown. In view of the chronic nature of bronchiectasis, more data are needed to establish the clinical value of ACTs over the short and long term on patient-important outcomes, including symptoms, on physiological outcomes which may clarify the rationale for each technique and on long-term parameters that impact on disease progression in individuals with stable bronchiectasis. This is necessary in order to provide further guidance of specific ACT prescription for people with bronchiectasis. It may also be important to establish the comparative effect of different types of ACTs in people with bronchiectasis.

Background Early, accurate prediction of discharge destination from the acute hospital assists individual patients and the wider hospital system. The Trauma Rehabilitation and Prediction Tool (TRaPT), developed using registry data, determines probability of inpatient rehabilitation discharge for patients with isolated lower limb fractures. Objective The aims of this study were: (1) to prospectively validatate the TRaPT, (2) to assess whether its performance could be improved by adding additional demographic data, and (3) to simplify it for use as a bedside tool. Design This was a cohort, measurement-focused study. Methods Patients with isolated lower limb fractures (N=114) who were admitted to a major trauma center in Melbourne, Australia, were included. The participants' TRaPT scores were calculated from admission data. Performance of the TRaPT score alone, and in combination with frailty, weight-bearing status, and home supports, was assessed using measures of discrimination and calibration. A simplified TRaPT was developed by rounding the coefficients of variables in the original model and grouping age into 8 categories. Simplified TRaPT performance measures, including specificity, sensitivity, and positive and negative predictive values, were evaluated. Results Prospective validation of the TRaPT showed excellent discrimination (C-statistic=0.90 [95% confidence interval=0.82, 0.97]), a sensitivity of 80%, and specificity of 94%. All participants able to weight bear were discharged directly home. Simplified TRaPT scores had a sensitivity of 80% and a specificity of 88%. Limitations Generalizability may be limited given the compensation system that exists in Australia, but the methods used will assist in designing a similar tool in any population. Conclusions The TRaPT accurately predicted discharge destination for 80% of patients and may form a useful aid for discharge decision making, with the simplified version facilitating its use as a bedside tool.

Background Water displacement is considered to be the gold standard for measuring foot volume; however, it is time-consuming and infrequently used in clinical practice. The objectives of this study were to determine whether a home-made water displacement device is a reliable and time-efficient method for determining foot volume. Methods Thirty participants with no foot pathologies were enrolled and had their foot volume measured in two home-made water volumetry devices (Preski and PreskiLite). The participants' foot volumes were measured on two occasions on each of two different days. Results All measurements were achieved in less than 90 seconds. Within-day reliability was high (intraclass correlation [ICC]=0.997–0.999) with the minimal detectable change (MDC) at the 90% confidence level (MDC 90 ) of less than 25 ml for both devices. Mean differences in volume displaced between days were small (range 0.6– -5.4 mls). For between-day measures on the same leg, the mean coefficient of variation ranged from 0.65–1 with associated ICCs of 0.989–0.997. The MDC 90 for between-day measures was 46 ml for the PreskiLite and 23 ml for the Preski. The difference in volume displaced between right and left legs was less than the MDC 90 for both devices. Conclusions A novel, home-made water volumetry device provides reliable measures of foot volume both within and between days. Measurements taken on the contralateral leg provide an adequate control. These portable devices provide rapid measurements and only one measurement is needed per day.