Tam Eaton

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 Georges 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.

Serious complications with talc slurry pleurodesis

Objective: Talc is a highly efficacious and commonly employed agent for chemical pleurodesis, which has generally been felt to be well tolerated. However, increasing reports of adult respiratory distress syndrome (ARDS) have heightened safety concerns. A recent case of ARDS prompted us to review our experience with talc pleurodesis.

Isolated nocturnal desaturation in COPD: prevalence and impact on quality of life and sleep

Background and aims: The clinical impact of nocturnal desaturation on health related quality of life (HRQL) and sleep in chronic obstructive pulmonary disease (COPD) has been little studied. The aim of this study was to evaluate the prevalence and clinical impact of nocturnal desaturation in a typical outpatient population with COPD. Patients and methods: Between 2002 and 2005, consecutive patients with COPD attending outpatient services at the study centre underwent resting oximetry if they were not on domiciliary oxygen therapy. If their resting saturations were less than 95%, overnight pulse oximetry was performed. Significant nocturnal desaturation was defined as spending more than 30% of at least one of two nights with a saturation of less than 90%. The Chronic Respiratory Questionnaire (CRQ) and Short Form 36 (SF36) were used to assess HRQL, and the Pittsburgh Sleep Quality Index (PSQI), Epworth Sleepiness Score (ESS) and Functional Outcomes of Sleep (FOSQ) questionnaires were used to assess sleep quality and daytime function. Results: Of 1104 patients, 803 underwent resting oximetry and 79 had resting oxygen saturations of less than 95%. Of these, 59 agreed to undergo overnight oximetry (mean age 70 years, forced expiratory volume in 1 s 37.2% predicted, resting Po2 on air 8.9 kPa). Significant nocturnal desaturation was seen in 29 (49.2%) of the 59 subjects. Assuming the less hypoxic patients do not have nocturnal desaturation, the prevalence of nocturnal desaturation in the whole clinic population could be estimated at 4.8%. There were no significant differences in CRQ, SF36, PSQI, ESS or FOSQ scores for desaturators compared with non-desaturators. Conclusion: Significant nocturnal desaturation was common in patients with COPD with resting saturations of less than 95%, but was estimated to have a prevalence of less than 5% in the whole outpatient population. Nocturnal desaturation was not associated with impairment of HRQL, sleep quality or daytime function.

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.

Management of solitary pulmonary nodules: how do thoracic computed tomography and guided fine needle biopsy influence clinical decisions?

Background: Computed tomography (CT) and fine needle guided biopsy (FNB) are often used in the assessment of patients with lung nodules. The influence of these techniques on clinical decision making has not been quantified, especially for small solitary pulmonary nodules (SPN) where the probability of malignancy is lower. A study was undertaken to determine the effect of CT and FNB derived information on clinical decision making in patients with a solitary pulmonary nodule < 3 cm in diameter on initial chest radiography. Methods: Clinical, physiological, and outcome data on 114 patients with an SPN < 3 cm who had subsequent thoracic CT and FNB were extracted from the records of a specialist cardiorespiratory hospital in Auckland, New Zealand. Chest radiographs and CT scans were reported according to specified criteria by a thoracic radiologist. Computer generated summary sheets were used to present cases to each of six clinicians. Each case was presented three times: (1) with clinical data and chest radiograph only; (2) with the addition of the CT report; and (3) with all data including the result of the FNB. Clinicians were asked to specify their management on each occasion and to estimate the probability of the lesion being malignant. Reproducibility was assessed by re-evaluating 24 cases 1 month later. Results: 33 (29%) nodules were benign, 35 (31%) nodules (malignant) were resected with negative node sampling, and 46 (40%) had a non-curative outcome (radiotherapy, incomplete resection, refused therapy). Intra-clinician decision making was consistent for all three levels of clinical data (median κ values 0.79–0.89). Agreement between clinicians on the need for surgery was lowest with chest radiography alone (κ=0.33), rose with CT information (κ=0.44), and increased further with the addition of the FNB data (κ=0.57). The proportion of successful decisions on surgical intervention (against the known outcome) increased with the addition of CT reports and further with FNB reports (p=0.006, Friedmans test). The major benefit of the information added by CT and FNB reports was a reduction in unnecessary surgery, especially when the clinical perception of pre-test probability of malignancy was intermediate (31–70%). FNB data contributed most to the benefit (p<0.001). The addition of CT and FNB was cost efficient and can be applied specifically to patients with a low or intermediate probability of malignancy. Conclusion: Both CT and FNB make cost effective contributions to the clinical management of SPN < 3 cm in diameter by reducing unnecessary operations and increasing agreement between physicians on the need for surgery.

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.

Overnight prescription of oxygen in long term oxygen therapy: time to reconsider the guidelines?

Background: Guidelines for long term oxygen therapy (LTOT) recommend increasing oxygen flow by 1 l/min overnight. A study was undertaken in patients with COPD on LTOT to determine the prevalence of overnight desaturation if the usual oxygen flow rate is not increased at night, whether resting oxygen saturation predicts overnight desaturation, and whether overnight desaturation correlates with health related quality of life (HRQL) and sleep quality. Methods: A cross sectional prospective study was performed on consecutive patients with COPD on LTOT attending our regional outpatient oxygen service. All patients fulfilled standard criteria for LTOT, had been established on LTOT at a flow to achieve resting oxygen saturations >90%, but had not been instructed to increase oxygen flow overnight. Overnight desaturation was defined as <90% for ⩾30% of the night on either of two consecutive nights. HRQL was evaluated with the SF-36 Health Survey Questionnaire, Chronic Respiratory Questionnaire, and the Pittsburgh Sleep Quality Index. Results: Thirty eight patients (63% men) of mean (SD) age 73.5 (8.04) years and mean (SD) forced expiratory volume in 1 second 0.77 (0.35) l were evaluated. Overnight desaturation occurred in six (16%; 95% CI 4 to 27). Desaturators had mean (SD) resting oxygen saturation on room air of 88 (4.2)% compared with 90 (4.1)% in non-desaturators (p = 0.15), and corrected saturations of 93 (2.0)% versus 94 (2.0)% (p = 0.18). HRQL and sleep quality were poor but did not differ between desaturators and non-desaturators. Conclusions: Most patients did not exhibit overnight desaturation despite not increasing their LTOT prescription overnight. These results challenge the recommendation of routinely increasing overnight oxygen flow in patients receiving LTOT.

Comparative clinical and physiological features of Maori, Pacific Islanders and Europeans with sleep related breathing disorders

Abstract