Pulmonary exacerbation in adults with bronchiectasis: a consensus definition for clinical research

Abstract

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.

The Roles of Bacteria and Viruses in Bronchiectasis Exacerbation: A Prospective Study

“…AEs were defined as significant deterioration (>48 h) of ≥3 symptoms, including cough frequency, sputum volume and/or consistency, sputum purulence, breathlessness and/or exercise tolerance, fatigue and/or malaise, hemoptysis, which required immediate changes in treatment. 23 Treatment decisions were made before all testing results became available.…”

Bronchiectasis: Treatment decisions for pulmonary exacerbations and their prevention

“…While exacerbations are considered to occur with a change in, or development of new, symptoms, a standard definition has been difficult to ascertain with some studies giving weight to differing parameters, or major and minor criteria, with the majority also requiring that the episode received antibiotic treatment. A recent systematic review identified 50 trials with 20 different definitions . This international consensus of experienced clinicians proposed that the definition includes: (i) 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 (ii) a clinician determines that a change in bronchiectasis treatment is required.…”

“…Notably, measurements of lung function were not included in the definition as they are rarely helpful in confirming an episode of exacerbation in patients with bronchiectasis. In the consensus process, neither laboratory findings nor chest X‐ray changes reached a sufficient threshold of support to be included . It is recognized that the ‘change of treatment’ will most likely be the initiation of antibiotics (oral, systemic or inhaled), but other possible changes could be the commencement of oral corticosteroids, mucolytics or change in airway clearance technique.…”

RESPIRE: breathing new life into bronchiectasis

“…Frequency of exacerbations is the most clinically meaningful end-point in evaluating a long-term treatment that aims to reduce exacerbations [6]. When a meta-analysis for frequency of exacerbation results are pooled from both the 14-and 28-day arms, a reasonable approach as the studies illustrate minimal difference in drug effectiveness between them, the data looks promising and heterogeneity modest ( figure 1).…”