Pulmonary exacerbations in patients with primary ciliary dyskinesia: an expert consensus definition for use in clinical trials

Abstract

Pulmonary exacerbations are a cause of significant morbidity in patients with primary ciliary dyskinesia (PCD) and are frequently used as an outcome measure in clinical research into chronic lung diseases. So far, there has been no consensus on the definition of pulmonary exacerbations in PCD.30 multidisciplinary experts and patients developed a consensus definition for children and adults with PCD. Following a systematic review, the panel used a modified Delphi process with a combination of face-to-face meetings and e-surveys to develop a definition that can be used in research settings for children and adults with PCD.A pulmonary exacerbation was defined by the presence of three or more of the following seven items: 1) increased cough, 2) change in sputum volume and/or colour, 3) increased shortness of breath perceived by the patient or parent, 4) decision to start or change antibiotic treatment because of perceived pulmonary symptoms, 5) malaise, tiredness, fatigue or lethargy, 6) new or increased haemoptysis, and 7) temperature >38°C.The consensus panel proposed that the definition should be used for future clinical trials. The definition should be validated and the usability assessed during these studies.

Exacerbations and Pseudomonas aeruginosa colonization are associated with altered lung structure and function in primary ciliary dyskinesia

“…The exacerbations in PCD, defined as an acute increase in respiratory symptoms [14], are predictors of severity of disease and poor quality of life [10] and negatively impact on lung function, as bacterial infections are associated with morbidity and mortality in these patients [13]. It was reported that about 25% of children with PCD fail to recover to baseline lung function within 3 months following a pulmonary exacerbation treated with intravenous antibiotics and may never regain pre-exacerbation spirometry [15].…”

“…We considered the definition of exacerbation in PCD as indicated by expert consensus (14). As the median of exacerbations was 2 per year prior to the analysis in our patients, we classified patients in two groups: Low-EXAC: < 2/year and High-EXAC ≥2/year.…”

“…Exacerbations in children and adults with PCD, defined as an acute increase in respiratory symptoms [14], characterize the natural history of the disease.…”

Health related quality of life in adult primary Ciliary dyskinesia patients in Cyprus: development and validation of the Greek version of the QOL-PCD questionnaire

“…Lastly, this work did not examine the effect of pulmonary exacerbations on HRQoL in PCD as a formal definition for pulmonary exacerbation in PCD was not available at the beginning of this study. Since 2019, an expert consensus statement has been proposed for PCD [36] and future studies are expected to focus on the responsiveness of QOL-PCD to pulmonary exacerbations in PCD.…”

Ciliary functional analysis: Beating a path towards standardization

“…Primary ciliary dyskinesia (PCD) is an inherited heterogeneous motile ciliopathy, in which respiratory cilia are stationary, or beat in a dyskinetic manner, leading to significant sinopulmonary disease . Currently, there is no single gold standard test which will diagnose every patient with PCD, and international guidelines recommend a panel of a variety of tests to diagnose PCD .…”