A Multicenter Randomized Controlled Trial of Zephyr Endobronchial Valve Treatment in Heterogeneous Emphysema (LIBERATE).

RATIONALE: This is the first multicenter randomized controlled trial to evaluate the effectiveness and safety of Zephyr Endobronchial Valve (EBV) in patients with little to no collateral ventilation out to 12 months. OBJECTIVES: To evaluate the effectiveness and safety of Zephyr EBV in heterogeneous emphysema with little to no collateral ventilation in the treated lobe. METHODS: Subjects were enrolled with a 2:1 randomization (EBV/standard of care [SoC]) at 24 sites. Primary outcome at 12 months was the ΔEBV-SoC of subjects with a post-bronchodilator FEV1 improvement from baseline of greater than or equal to 15%. Secondary endpoints included absolute changes in post-bronchodilator FEV1, 6-minute-walk distance, and St. George's Respiratory Questionnaire scores. MEASUREMENTS AND MAIN RESULTS: A total of 190 subjects (128 EBV and 62 SoC) were randomized. At 12 months, 47.7% EBV and 16.8% SoC subjects had a ΔFEV1 greater than or equal to 15% (P < 0.001). ΔEBV-SoC at 12 months was statistically and clinically significant: for FEV1, 0.106 L (P < 0.001); 6-minute-walk distance, +39.31 m (P = 0.002); and St. George's Respiratory Questionnaire, -7.05 points (P = 0.004). Significant ΔEBV-SoC were also observed in hyperinflation (residual volume, -522 ml; P < 0.001), modified Medical Research Council Dyspnea Scale (-0.8 points; P < 0.001), and the BODE (body mass index, airflow obstruction, dyspnea, and exercise capacity) index (-1.2 points). Pneumothorax was the most common serious adverse event in the treatment period (procedure to 45 d), in 34/128 (26.6%) of EBV subjects. Four deaths occurred in the EBV group during this phase, and one each in the EBV and SoC groups between 46 days and 12 months. CONCLUSIONS: Zephyr EBV provides clinically meaningful benefits in lung function, exercise tolerance, dyspnea, and quality of life out to at least 12 months, with an acceptable safety profile in patients with little or no collateral ventilation in the target lobe. Clinical trial registered with www.clinicaltrials.gov (NCT 01796392).

Clinical review: Endobronchial valve treatment for emphysema.

Breathlessness and impaired quality of life are prominent features in patients with severe emphysema even when conventional methods of treatment are optimal. Lung volume reduction using endobronchial management for emphysema has emerged as a new method to relieve symptoms and improve lung function tests in this group. The endobronchial valves (EBVs) are the most widely used treatment. This article outlines current criteria of patients' selection with literature review and evidence of efficacy. Complications of EBV insertion as well as current shortfalls of this method of treatment are also discussed.

Low Frequency Ventilation During Cardiopulmonary Bypass to Protect Postoperative Lung Function in Cardiac Valvular Surgery: The PROTECTION Phase II Randomized Trial.

BACKGROUND: Cardiac surgery with cardiopulmonary bypass (CPB) triggers pulmonary injury. In this trial we assessed the feasibility, safety, and efficacy of low frequency ventilation (LFV) during CPB in patients undergoing valvular surgery. METHODS AND RESULTS: Patients with severe mitral or aortic valve disease were randomized to either LFV or usual care. Primary outcomes included release of generic inflammatory and vascular biomarkers and the lung-specific biomarker sRAGE (soluble receptor for advance glycation end products) up to 24 hours postsurgery. Secondary outcomes included pulmonary function tests and 6-minute walking test up to 8 weeks postdischarge. Sixty-three patients were randomized (33 LFV versus 30 usual care). Mean age was 66.8 years and 30% were female. LFV was associated with changes of sRAGE (soluble receptor for advance glycation end products) levels (geometric mean ratio, 3.05; [95% CI, 1.13-8.24] 10 minutes post CPB, and 1.07 [95% CI, 0.64-1.79], 0.84 [95% CI, 0.55-1.27], 0.67 [95% CI, 0.42-1.07], and 0.62 [95% CI, 0.45-0.85] at 2, 6, 12, and 24 hours post CPB respectively). No changes were observed for any of the generic biomarkers. Respiratory index soon after surgery (mean difference, -0.61 [95% CI, -1.24 to 0.015] 10 minutes post end of CPB), forced expiratory volume after 1 second/forced vital capacity ratio (0.050 [95% CI, 0.007-0.093] at 6 to 8 weeks pos-surgery), Forced vital capacity alone (95% CI, -0.191 L [-0.394 to 0.012]) and 6-minute walking test score at discharge (63.2 m [95% CI, 12.9-113.6]) were better preserved in the LFV group. No other differences were noted. CONCLUSIONS: The use of LFV during CPB in patients undergoing valvular surgery was feasible and safe and was associated with changes in sRAGE levels along with better preserved lung function and walking performance. These observations warrant further investigation in larger future studies. REGISTRATION: URL: https://www.isrctn.com; Unique Identifier: ISRCTN75795633.

Factors associated with a shorter time until the next pulmonary exacerbation in adult patients with cystic fibrosis.

Time until the subsequent exacerbation (PEx) in cystic fibrosis (CF) is a significant health outcome and one of the significant end points in clinical trials. Risk factors associated with shorter time until the next exacerbation (TUNE) have not been reported. This is a prospective study. TUNE was the number of days from the end of intravenous (IV) antibiotic treatment of a PEx until the day of start of IV antibiotics for the following PEx. Factors assessed were age, gender, site of treatment, CF-related diabetes (CFRD), allergic bronchopulmonary aspergillosis (ABPA) and infection with Pseudomonas aeruginosa (PA). In addition, we examined parameters obtained at day 14 of treatment including forced expiratory volume in the first second (FEV1), body mass index, CF respiratory symptom score, C-reactive protein (CRP) and serum cytokines. A total of 170 exacerbations in 58 adult CF patients (27 female), mean (SD) age 25.8 (6.7) years were analysed. When analysing individual variables, patients with lower FEV1, greater symptom score and higher CRP at the end of exacerbation were associated with shorter TUNE. Patients with ABPA and CFRD had a shorter TUNE than those without. When applying multiple regression analysis, factors associated with shorter TUNE were older age and lower day-14 FEV1 values. Shorter periods until the following PEx are expected in older CF patients and those with lower FEV1 at the end of course of treatment. When these risk factors are present, there may be a justification to take therapeutic steps to increase the time until the following PEx.

Extending the course of intravenous antibiotics in adult patients with cystic fibrosis with acute pulmonary exacerbations.

Most severe pulmonary exacerbations (PExs) in adult patients with cystic fibrosis (CF) are treated with 2 week of intravenous (IV) antibiotics. At occasions, the treatment is extended. The morbidity and the cost of extending the treatment are considerable. Risk factors and the outcome of extending the course of treatment have not been formally investigated. This was a prospective study. Decision to extend the course of antibiotics was made in patients who were not deemed to have responded to the initial 14 days of treatment. Risk factors examined for extending the course were site of treatment (home or hospital), CF symptom score, body mass index (BMI), forced expiratory volume in the first second (FEV1) and C-reactive protein (CRP) at days 1 and 14 of the treatment. The following outcome measures were assessed for PExs requiring prolongation of treatment: FEV1, BMI, CF symptom score, CRP and number of days until the following PExs. PExs that were treated with 14 day course were used for comparison. Of all the PExs, 22.9% needed extension of treatment beyond day 14. Compared with PExs needing 14 days of antibiotics, CF symptom score, FEV1 and CRP at day 14 were worse in those who had to have the course extended. Extending the course of IV antibiotics to 21 days improved symptom score, but not any of the other outcome measures, including the number of days until the next PEx. Extending the course beyond 21 days did not result in improvement in any outcome measure. PExs in patients with worse lung disease and greater residual symptoms and lung inflammation at day 14 of antibiotic treatment were associated with the extension of the course of IV antibiotics. Prolonging the treatment to 21 days improved symptoms, but did not result in improvement in any other short-term or lung outcome measures.

Chronic obstructive pulmonary disease (COPD) and old age?

Chronic obstructive pulmonary disease (COPD) in old age is an increasing problem. Understanding the features of COPD in older patients is important in order to introduce effective interventions and to inform efforts for health resource allocation. Features of importance to old age include increased prevalence of COPD in non-smokers and rise in the rate of systemic comorbidities. In addition, acute exacerbations in older patients have poorer outcome, manifesting by increase in the rate of hospitalisation, greater length of stay, increase of the rate of re-hospitalisation and in mortality rate. Impaired cognitive functions as well as problems affecting hand joints make using inhaled medications less reliable which leads to further deterioration of outcome of care. Even for those who are competent in using inhalers, the evidence for their efficacy in older patients is not certain.

Endobronchial valves in the management of bronchial fistulae caused by bronchopulmonary aspergillosis.

Following an aggressive episode of bronchopulmonary aspergillosis, a 54-year-old man developed a symptomatic air leak via a tunnel between the left upper lobe and an extra chest wall cavity. Following the failure of several surgical procedures to close the tunnel, endobronchial valves normally used in management of emphysema were used to successfully treat the air leak.

Telemonitoring in chronic obstructive airway disease and adult patients with cystic fibrosis.

We compared the use of telemonitoring in patients with chronic obstructive pulmonary disease (COPD) and adult patients with cystic fibrosis (CF). Seventy patients (51 CF and 19 COPD) were enrolled in two studies of six months' duration. Patients used a personal data assistant (PDA) attached to a spirometer to score symptoms and to perform daily spirometry. Criteria for diagnosis of exacerbations of COPD and CF were pre-defined. When exacerbations were detected, patients were offered treatment according to a pre-designed protocol. Thirty-two (63%) CF patients and one (5%) COPD patient withdrew from the studies due to lack of adherence to daily recording. For those who remained in the study, COPD patients recorded more study days (139) than CF patients (113), P = 0.03. The median number of exacerbations detected during the study was greater in COPD than in CF patients, although this was not significant. The median number of device-detected exacerbations in the COPD group was significantly greater than in the CF group, P = 0.024. When compared to a parallel period in the previous year, the number of hospitalisations for COPD exacerbations was reduced, whereas the number of intravenous antibiotics in CF patients did not differ. Adherence to telemonitoring was much greater for COPD than CF patients and the results appear to be more favourable for COPD patients than for CF patients.

Real-time, once-daily monitoring of symptoms and FEV in cystic fibrosis patients--a feasibility study using a novel device.

BACKGROUND AND AIMS: We investigated feasibility and value of a real-time electronic monitoring system adapted for early detection of cystic fibrosis (CF) pulmonary exacerbations (P Exs). METHODS: This was a 6-month prospective study. Patients recorded once daily their symptom score and spirometry using an electronic diary. The data were sent daily to the research team in real time. P Ex was considered to be present when change in symptoms and lung function values met a preset criteria. Number of P Exs during the study was compared with a parallel period of the previous and of the following years. RESULTS: Only 19 patients (37.2%) completed recording that could be evaluated. A total of 53 P Exs were identified, 26 (49.0%) of which needed intravenous (IV) antibiotics. The number of total P Exs in the study year did not differ from the previous or the following year, but the number of courses of oral antibiotics was greater than those given during the previous year. CONCLUSION: Remote daily monitoring of symptoms and spirometry had a poor uptake among CF patients. For those who completed the study, this method early detected P Exs that were treated with oral antibiotics that might otherwise required IV antibiotics.

Home intravenous antibiotic treatment for acute pulmonary exacerbations in cystic fibrosis - Is it good for the patient?

There is a worldwide drive for the home management of chronic respiratory diseases. With the widespread use of home intravenous (IV) treatment for cystic fibrosis (CF) pulmonary exacerbations (PExs), evidence pointing to an inferior outcome of care for home-treated patients in comparison to hospital-treated patients is a cause of concern. Currently, patients who self-administer IV antibiotics at home are provided with equipment and instructions on the use of antibiotics. Policies vary; but in most UK centers, these patients are then followed up by the multidisciplinary team only on days 1, 7 and 14 of the treatment course. We aimed to review the current published literature in search for evidence for the value and the shortfalls of self-administered IV treatment at home for acute PExs in CF patients in comparison to conventional hospital treatment. We searched the electronic database system Medline for published papers regarding studies comparing home- and hospital-based IV antibiotic treatment for both adult and pediatric CF patients. Sixteen studies were identified and grouped into those that showed a similar outcome between home and hospital treatment and those that showed an inferior outcome for home management. Most studies were retrospective or inadequately powered to provide clear answers. Ideally, outcome of care for home treatment should be at least equal to outcome for hospital treatment. Extensive efforts should be made to standardize therapies preserving the advantages of home management and addressing the perceived reasons for an inferior outcome. Until further studies provide definitive answers, treatment at home should be reserved for adequately selected patients and individualized depending on the unique settings of each CF center and specific patients' requirements. There is great need for a prospective randomized controlled trial comparing home and hospital treatments in order to clarify this matter.