Azithromycin for prevention of exacerbations in non-cystic fibrosis bronchiectasis (EMBRACE): a randomised, double-blind, placebo-controlled trial.

BACKGROUND: Azithromycin is a macrolide antibiotic with anti-inflammatory and immunomodulatory properties. We tested the hypothesis that azithromycin would decrease the frequency of exacerbations, increase lung function, and improve health-related quality of life in patients with non-cystic fibrosis bronchiectasis. METHODS: We undertook a randomised, double-blind, placebo-controlled trial at three centres in New Zealand. Between Feb 12, 2008, and Oct 15, 2009, we enrolled patients who were 18 years or older, had had at least one pulmonary exacerbation requiring antibiotic treatment in the past year, and had a diagnosis of bronchiectasis defined by high-resolution CT scan. We randomly assigned patients to receive 500 mg azithromycin or placebo three times a week for 6 months in a 1:1 ratio, with a permuted block size of six and sequential assignment stratified by centre. Participants, research assistants, and investigators were masked to treatment allocation. The coprimary endpoints were rate of event-based exacerbations in the 6-month treatment period, change in forced expiratory volume in 1 s (FEV(1)) before bronchodilation, and change in total score on St George's respiratory questionnaire (SGRQ). Analyses were by intention to treat. This study is registered with the Australian New Zealand Clinical Trials Registry, number ACTRN12607000641493. FINDINGS: 71 patients were in the azithromycin group and 70 in the placebo group. The rate of event-based exacerbations was 0·59 per patient in the azithromycin group and 1·57 per patient in the placebo group in the 6-month treatment period (rate ratio 0·38, 95% CI 0·26-0·54; p<0·0001). Prebronchodilator FEV(1) did not change from baseline in the azithromycin group and decreased by 0·04 L in the placebo group, but the difference was not significant (0·04 L, 95% CI -0·03 to 0·12; p=0·251). Additionally, change in SGRQ total score did not differ between the azithromycin (-5·17 units) and placebo groups (-1·92 units; difference -3·25, 95% CI -7·21 to 0·72; p=0·108). INTERPRETATION: Azithromycin is a new option for prevention of exacerbations in patients with non-cystic fibrosis bronchiectasis with a history of at least one exacerbation in the past year. FUNDING: Health Research Council of New Zealand and Auckland District Health Board Charitable Trust.

Does early pulmonary rehabilitation reduce acute health-care utilization in COPD patients admitted with an exacerbation? A randomized controlled study.

BACKGROUND AND OBJECTIVE: In COPD, hospital admissions and readmissions account for the majority of health-care costs. The aim of this prospective randomized controlled study was to determine if early pulmonary rehabilitation, commenced as an inpatient and continued after discharge, reduced acute health-care utilization. METHODS: Consecutive COPD patients (n = 397), admitted with an exacerbation, were screened: 228 satisfied the eligibility criteria, of whom 97 consented to randomization to rehabilitation or usual care. Both intention-to-treat and per-protocol analyses are reported with adherence being defined a priori as participation in at least 75% of rehabilitation sessions. RESULTS: The participants were elderly with severe impairment of pulmonary function, poor health-related quality of life and high COPD-related morbidity. The rehabilitation group demonstrated a 23% (95% CI: 11-36%) risk of readmission at 3 months, with attendees having a 16% (95% CI: 0-32%) risk compared with 32% (95% CI: 19-45%) for usual care. These differences were not significant. There were a total of 79 COPD-related readmission days (1.7 per patient, 95% CI: 0.6-2.7, P = 0.19) in the rehabilitation group, compared with 25 (1.3 per patient, 95% CI: 0-3.1, P = 0.17) for the attendees and 209 (4.2 per patient, 95% CI: 1.7-6.7) for usual care. The BMI, airflow obstruction, dyspnoea and exercise capacity index showed a non-significant trend to greater improvement among attendees compared with those receiving usual care (5.5 (2.3) and 5.6 (2.7) at baseline, improving to 3.7 (1.9) and 4.5 (2.5), respectively, at 3 months). No adverse effects were identified. CONCLUSIONS: Early inpatient-outpatient rehabilitation for COPD patients admitted with an exacerbation was feasible and safe, and was associated with a non-significant trend towards reduced acute health-care utilization.

Home overnight pulse oximetry in patients with COPD: more than one recording may be needed.

STUDY OBJECTIVES: Home overnight pulse oximetry (OPO) is used to assess nocturnal desaturation in patients with COPD, but the current practice of relying on one recording has not been studied. We assessed the variability of nocturnal desaturation in patients with COPD between nights, as measured by home OPO. DESIGN: Study subjects attended for clinical evaluation, spirometry, and arterial blood gas analysis. OPO was prospectively completed at home on 2 consecutive nights (study night 1 [N1] and study night 2 [N2]) and repeated at 3 weeks (study night 3 [N3]). SETTING: Respiratory Services, Green Lane Hospital, Auckland, New Zealand. PATIENTS: Twenty-six patients with clinically stable COPD (mean age, 69.3 years [SD, 6.9]; FEV(1), 28.6% predicted [SD, 10.6]; PO(2), 71.3 mm Hg [SD, 9.8]). Patients with asthma or clinical evidence of obstructive sleep apnea were excluded. MEASUREMENTS AND RESULTS: Mean nocturnal saturation (MNS) and time spent with saturation below 90% (TB90%) were calculated for N1, N2, and N3. Group mean recording length, MNS, and TB90% were similar for each night. Little variation in MNS was seen between nights (N1 and N2 mean difference, 1.31%; N2 and N3, 1.26%; N1 and N3, 1.25%). Larger variation was seen between nights for TB90% (N1 and N2 mean difference, 17.46%; N2 and N3, 9.95%; N1 and N3, 14.05%). No factors were identified that predicted increased variability of TB90%. Using the current definition of "significant nocturnal desaturation" (TB90% > or = 30% of the night), 9 of 26 patients (34.6%) changed category between "desaturator" and "nondesaturator" from N1 to N2. CONCLUSION: Nocturnal desaturation in patients with COPD exhibits considerable night-to-night variability when measured by home OPO. A single home OPO recording may be insufficient for accurate assessment of nocturnal desaturation.

Pleurodesis practice for malignant pleural effusions in five English-speaking countries: survey of pulmonologists.

BACKGROUND: Pleurodesis is important in the management of malignant pleural effusions, but no consensus exists on the optimal agent or methods of pleurodesis. How pleurodesis is practiced worldwide has not been studied. OBJECTIVES: To identify variations in the clinical practice of pleurodesis in major English-speaking countries, and to quantify the experience of pulmonologists on the effectiveness and adverse effects of different pleurodesis agents worldwide. METHODS: Eight hundred fifty-nine pulmonologists practicing in the United States, United Kingdom, Canada, Australia, and New Zealand participated in a Web-based survey. RESULTS: The respondents collectively perform > 8,300 pleurodesis annually. Talc was the preferred agent by most respondents (slurry, 56%; poudrage, 12%), followed by tetracycline derivatives (26%), and bleomycin (7%). Differences were seen in pleurodesis practice patterns among practitioners among and within the surveyed countries. Physicians' overall satisfaction with the available pleurodesis agents was modest (5.0 out of 8), and the reported success rate averaged only 66%. Talc (both poudrage and slurry) was perceived as significantly more effective, but was associated with significantly more pain, nausea, and fever (p < 0.05). Respiratory failure occurred more commonly with talc poudrage than with other agents (p < 0.05), and had been observed by 70% and 54% of physicians who used talc poudrage and slurry, respectively. CONCLUSIONS: Significant variations exist in how pleurodesis is performed worldwide. Pleurodesis agents currently available are perceived as suboptimal. Talc poudrage and slurry were perceived to be more effective, but were associated with more complications, including respiratory failure.

Allergic bronchopulmonary aspergillosis in a lung transplant patient successfully treated with nebulized amphotericin.

A case of allergic bronchopulmonary Aspergillosis (ABPA) complicating lung transplantation for cystic fibrosis is described. Control of ABPA was only achieved with 20 mg of prednisone and 600 mg of itraconazole per day. However, a prompt clinical and physiologic response was observed when nebulized amphotericin was introduced, which allowed prednisone to be reduced to 7.5 mg per day and, in time, all anti-fungal therapy to be withdrawn.

Six-minute walk, maximal exercise tests: reproducibility in fibrotic interstitial pneumonia.

Resting pulmonary function and exercise variables are widely used to stage and monitor idiopathic interstitial pneumonia (IIP). However, the variability of exercise data (maximal exercise and the 6-minute walk test) has not been evaluated definitively. We have prospectively quantified the reproducibility of resting and exercise functional data in fibrotic IIP (idiopathic pulmonary fibrosis, fibrotic nonspecific interstitial pneumonia) and have evaluated interrelationships between variables. Thirty consecutive patients with fibrotic IIP underwent serial resting pulmonary function tests, 6-minute walk (n = 29), and maximal exercise (n = 24) at an interval of 1 week, with all testing performed in accordance with American Thoracic Society standards. Within-subject reproducibility was excellent for 6-minute walk distance (SD/mean = 4.2%) and clinically acceptable for resting pulmonary function indices and VO(2)max on maximal exercise testing. However, the amplitude of oxygen desaturation at the end of exercise was poorly reproducible in both 6-minute walk and maximal exercise testing (SD/mean > 25%). There was a highly significant relationship between VO2max on maximal exercise testing and 6-minute walk distance (r(s) = 0.78, p < 0.0001). In fibrotic IIP, the excellent reproducibility of the 6-minute walk distance is a major advantage in routine staging and monitoring, whereas maximal exercise variables are poorly reproducible.