There is renewed interest in non-cystic fibrosis bronchiectasis, which is a cause of significant morbidity in adults and can be diagnosed by high-resolution chest computed tomography scan. No longer mainly a complication after pulmonary infection with Mycobacterium tuberculosis, diverse disease processes and mechanisms have been demonstrated to result in the chronic cough, purulent sputum production, and airway dilation that characterize this disease. Improved understanding of the role of mucus stasis in causing bacterial colonization has led to increased emphasis on the use of therapies that enhance airway clearance. Inhalational antibiotics reduce the bacterial burden associated with a worse outcome. Low-dose, chronic macrolide therapy has been shown to decrease exacerbation frequency and airway inflammation. For the first time, a number of therapies for non-cystic fibrosis bronchiectasis are undergoing testing in clinical research trials designed specifically for this population. This concise clinical review focuses on the major etiologies, diagnostic testing, microbiology, and management of patients with adult non-cystic fibrosis bronchiectasis. Systematic evaluation identifies a specific cause in the majority of patients and may affect subsequent treatment. We outline current therapies and review the data that support their use.

We employed a retrospective cohort design to estimate the prevalence and economic burden of bronchiectasis. Data were obtained from the health-care claims processing systems of more than 30 US health plans (with a combined total of 5.6 million covered lives) and spanned the period January 1, 1999, to December 31, 2001. Study subjects consisted of all persons who were aged Ն18 years in 2001 and had diagnoses of bronchiectasis between 1999 and 2001; those with diagnoses of cystic fibrosis were excluded. For purposes of comparison, a cohort of persons without diagnoses of bronchiectasis was randomly selected and matched on age, sex, geographic region, and comorbid conditions. Prevalence of bronchiectasis ranged from 4.2 per 100,000 persons aged 18 -34 years to 271.8 per 100,000 among those aged Ն75 years. Prevalence was higher among women than men at all ages. Persons with bronchiectasis averaged 2.0 (95% confidence interval 1.7-2.3) additional days in hospital, 6.1 (6.0 -6.1) additional outpatient encounters, and 27.2 (25.0 -29.1) more days of antibiotic therapy than those without the disorder in 2001; average total medical-care expenditures were $5681 ($4862-$6593) higher for bronchiectasis patients. Our findings suggest that over 110,000 persons in the United States may be receiving treatment for bronchiectasis, resulting in additional medical-care expenditures of $630 million annually.

There is a need for a clear definition of exacerbations used in clinical trials in patients with bronchiectasis. An expert conference was convened to develop a consensus definition of an exacerbation for use in clinical research.A systematic review of exacerbation definitions used in clinical trials from January 2000 until December 2015 and involving adults with bronchiectasis was conducted. A Delphi process followed by a round-table meeting involving bronchiectasis experts was organised to reach a consensus definition. These experts came from Europe (representing the European Multicentre Bronchiectasis Research Collaboration), North America (representing the US Bronchiectasis Research Registry/COPD Foundation), Australasia and South Africa.The definition was unanimously approved by the working group as: a person with bronchiectasis with a deterioration in three or more of the following key symptoms for at least 48 h: cough; sputum volume and/or consistency; sputum purulence; breathlessness and/or exercise tolerance; fatigue and/or malaise; haemoptysis AND a clinician determines that a change in bronchiectasis treatment is required.The working group proposes the use of this consensus-based definition for bronchiectasis exacerbation in future clinical research involving adults with bronchiectasis.

Rationale: Primary graft dysfunction is a severe acute lung injury syndrome after lung transplantation. Long-term outcomes of subjects with primary graft dysfunction have not been studied. Objectives: We sought to test the relationship of primary graft dysfunction with both short-and long-term mortality using a large registry. Methods: We used data collected on 5,262 patients in the United Network for Organ Sharing/International Society of Heart and Lung Transplantation registry between 1994 and 2000. We assessed outcomes in all subjects; to assess potential bias from the effects of early mortality, we also evaluated subjects who survived at least 1 year, using Cox proportional hazards models with time-varying covariates. Main Results: The overall incidence of primary graft dysfunction was 10.2% (95% confidence intervals [CI], 9.2, 10.9). The incidence did not vary by year over the period of observation (p ϭ 0.22). All-cause mortality at 30 days was 42.1% for primary graft dysfunction versus 6.1% in patients without graft dysfunction (relative risk ϭ 6.95; 95% CI, 5.98, 8.08; p Ͻ 0.001); among subjects who died by 30 days, 43.6% had primary graft dysfunction. Among patients surviving at least 1 year, those who had primary graft dysfunction had significantly worse survival over ensuing years (hazard ratio, 1.35; 95% CI, 1.07, 1.70; p ϭ 0.011). Adjustment for clinical variables including bronchiolitis obliterans syndrome did not change this relationship. Conclusion: Primary graft dysfunction contributes to nearly half of the short-term mortality after lung transplantation. Survivors of primary graft dysfunction have increased risk of death extending beyond the first post-transplant year.Keywords: acute lung injury; lung transplantation; outcomes; primary graft dysfunction; reperfusion injury Primary graft dysfunction (PGD), also known as primary graft failure, is a form of lung allograft ischemia-reperfusion injury (1, 2). Occurring in the first hours to days after transplantation, the clinical course and pathophysiology of the most severe forms are most similar to the acute respiratory distress syndrome (1,3,4). With an incidence reported between 10 and 25%, and a high mortality (5), PGD represents the leading cause of early death after transplantation (1, 2, 5-8).However, the long-term outcomes of PGD have not been (Received in original form September 20, 2004; accepted in final form March 3, 2005) Supported by grants NHLBI K23 HL04243 and the Craig and Elaine Dobbin Pulmonary Research Fund.Correspondence and requests for reprints should be addressed to

Rationale Bronchiectasis is characterised by excessive production of mucus and pulmonary exacerbations. Inhaled osmotic agents may enhance mucociliary clearance, but few long-term clinical trials have been conducted. Objectives To determine the impact of inhaled mannitol on exacerbation rates in patients with non-cystic fibrosis (CF) bronchiectasis. Secondary endpoints included time to first exacerbation, duration of exacerbations, antibiotic use for exacerbations and quality of life (QOL) (St George's Respiratory Questionnaire, SGRQ). Methods Patients with non-CF bronchiectasis and a history of chronic excess production of sputum and ≥2 pulmonary exacerbations in the previous 12 months were randomised (1:1) to 52 weeks treatment with inhaled mannitol 400 mg or low-dose mannitol control twice a day. Patients were 18-85 years of age, baseline FEV 1 ≥40% and ≤85% predicted and a baseline SGRQ score ≥30. Main results 461 patients (233 in the mannitol and 228 in the control arm) were treated. Baseline demographics were similar in the two arms. The exacerbation rate was not significantly reduced on mannitol (rate ratio 0.92, p=0.31). However, time to first exacerbation was increased on mannitol (HR 0.78, p=0.022). SGRQ score was improved on mannitol compared with low-dose mannitol control (−2.4 units, p=0.046). Adverse events were similar between groups. Conclusions Mannitol 400 mg inhaled twice daily for 12 months in patients with clinically significant bronchiectasis did not significantly reduce exacerbation rates. There were statistically significant improvements in time to first exacerbation and QOL. Mannitol therapy was safe and well tolerated. Trial registration number NCT00669331.