Tiotropium treatment for bronchiectasis: a randomised, placebo-controlled, crossover trial.

BACKGROUND: Tiotropium via the HandiHaler device is an established long-acting, anticholinergic bronchodilator that prevents exacerbations and improves lung function in patients with chronic obstructive pulmonary disease. We hypothesised that tiotropium would reduce pulmonary exacerbations and improve lung function in patients with stable bronchiectasis and airflow limitation, and assessed the effect of tiotropium on these outcomes. METHODS: In a randomised, double-blind, two-period crossover trial, we recruited adult patients from three hospitals in New Zealand. Patients were excluded if they had a smoking history of >20 pack-years. Patients were assigned to either the tiotropium-placebo or placebo-tiotropium sequence in a 1:1 ratio, using randomly permuted blocks stratified by centre. Participants and investigators were masked to treatment allocation. Eligible patients received tiotropium 18 µg via HandiHaler daily for 6 months followed by 6 months of placebo, or vice versa, with a washout period of 4 weeks. The primary end-point was rate of event-based exacerbations during the 6-month period. Primary analyses were carried out in an intention-to-treat set. RESULTS: 90 patients were randomly assigned and 85 completed both treatment cycles. The rate of exacerbations was 2.17 per year under the tiotropium treatment and 2.27 per year under placebo (rate ratio 0.96, 95% CI 0.72-1.27; p=0.77). Tiotropium, compared with placebo, improved forced expiratory volume in 1 s by 58 mL (95% CI 23-92 mL; p=0.002). Adverse events were similar under both treatments. CONCLUSIONS: Tiotropium via HandiHaler over 6 months significantly improved lung function but not frequency of exacerbations. Further research is required to understand the clinical context and significance of these findings.

Ethnicity, socioeconomic status and the severity and course of non-cystic fibrosis bronchiectasis.

BACKGROUND AND AIMS: This study evaluated whether there are ethnic factors which affect the severity and progression of bronchiectasis in our adult multi-ethnic population in Auckland, New Zealand. METHODS: Clinical records were reviewed from patients attending the outpatient facilities of our institution between 2007 and 2010. Data collected included demographics, clinical features, smoking status, self-reported ethnicity, socioeconomic status (NZDep), pulmonary function and sputum microbiology. RESULTS: A total of 437 patients was identified: median age 65 years, 66% female, mean forced expiratory volume in the first second (FEV1 ) 62.4% predicted, and 10.5% of patients had recurrent growth of Pseudomonas aeruginosa. Patients of Maori and Pacific ethnicity were overrepresented compared to the institution population catchment and had more severe impairment of lung function: mean % predicted FEV1 for Pacific 52.0, Maori 58.6, European 68.6, Asian 64.2 (P < 0.0001). This was independent of socioeconomic status. However, no overall decline was seen in serial lung function measurements, either across the whole cohort or in any particular ethnic group. CONCLUSIONS: Patients of Maori and Pacific ethnicity are both overrepresented and have more severe bronchiectasis in this cohort, independent of socioeconomic status. Ethnicity did not predict decline in pulmonary function. Further studies into genetic predisposition to bronchiectasis in Maori or Pacific people may be warranted.

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.

Nasal levels of nitric oxide as an outcome variable in allergic upper respiratory tract disease: Influence of atopy and hayfever on nNO.

BACKGROUND: The role of nasal levels of nitric oxide (nNO) as noninvasive marker of inflammation and as an outcome variable in allergic upper respiratory tract disease has not been defined. Our aim is to determine in patients with perennial allergic rhinitis (i) whether nNO is elevated, (ii) whether increased nNO is correlated with upper respiratory tract symptoms (discrimination), and (iii) whether changes in symptom scores are associated with changes in nNO levels (responsiveness). METHODS: Subjects (n = 38) with perennial rhinitis were studied weekly for 3 weeks. At each visit they completed a validated symptom questionnaire and had expired NO and nNO measured. RESULTS: Nasal NO levels were higher in those allergic to house-dust mite and cat. Nasal NO levels in subjects with perennial rhinitis were not elevated compared with non-atopic asymptomatic subjects. The intra-week reproducibility of nNO measurements was poor. There was no relationship between the symptom scores and nasal NO levels (discrimination). When analysis was confined to nasal symptoms, a weak but negative correlation was identified. Changes in symptom scores from week to week were not correlated with changes in nNO levels (responsiveness). CONCLUSIONS: Nasal NO levels were not elevated in subjects with perennial rhinitis, and nNO levels were neither discriminatory nor responsive. The measurement of nNO therefore appears not to be a useful marker of disease activity in subjects with allergic rhinitis.

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.