A longitudinal study characterising a large adult primary ciliary dyskinesia population

Abstract

Primary ciliary dyskinesia (PCD) in adults has not been well described. In this retrospective observational study we aimed to characterise a large adult population and identify features associated with disease progression.We retrospectively analysed 151 adult patients at a single tertiary centre at baseline and longitudinally for a median of 7 years.We found significant variation in age at diagnosis (median 23.5 years; range <1-72 years). Older age at diagnosis was associated with impaired baseline forced expiratory volume in 1 s (FEV1) (r= -0.30, p=0.01) and increased Pseudomonas aeruginosa colonisation (difference in medians 17 years (95% CI 4.5-20 years); p=0.002). Lung function decline was estimated at FEV1 decline of 0.49% predicted per year. Lung function decline was associated with ciliary ultrastructure, with microtubular defect patients having the greatest decline (p=0.04). High-resolution computed tomography (HRCT) scores of severity of bronchial wall dilatation (p<0.001) and extent of bronchiectasis (p=0.03) additionally showed evidence of modifying FEV1 decline with age.Our study reveals that a large proportion of adult PCD patients are diagnosed late, with impaired FEV1 and increased P. aeruginosa colonisation. Increased disease burden on HRCT and ciliary ultrastructure may predict progressive lung function decline. This study characterises a large adult PCD population, identifies features associated with disease progression and highlights the need for prospective trials to determine whether early diagnosis of high-risk subgroups alongside optimal management can modify disease progression.

Lung structure and function similarities between primary ciliary dyskinesia and mild cystic fibrosis: a pilot study

“…Despite counterintuitive, the lack of association between early PCD diagnosis and better pulmonary outcomes, strongly suggested by our results, has been highlighted previously [31, 32]. Furthermore, a recent longitudinal study of adult PCD subjects has confirmed that, even though negatively associated with baseline FEV 1 , age at diagnosis does not correlate with longitudinal functional measurements, thus raising doubts on the real impact of optimal management at an early stage on the subsequent disease progression [33]. These studies did not correlate chest CT scores with age at diagnosis, but it is reasonable to hypothesize that, likewise functional impairment, also structural abnormalities are poorly affected by it.…”

Primary Ciliary Dyskinesia: An Update on Clinical Aspects, Genetics, Diagnosis, and Future Treatment Strategies

“…Information on PCD disease progression is still incomplete, even though the mortality data are hard to interpret, as they are not age standardized. A recent retrospective study of 151 PCD adults with a median age of 35 years longitudinally followed for 7 years found an incidence of all-cause mortality of nearly 5%, and a respiratory mortality of 3.3% (62). Authors showed that older age at diagnosis was associated with impaired baseline FEV 1 and increased P. aeruginosa colonization.…”

Primary ciliary dyskinesia: the patients grow up

“…Models of transitional care for cystic fibrosis might inform PCD care; the need for collaborative working between paediatric and adult clinics is essential to enable longitudinal understanding of the patient "from cradle to grave". The article by SHAH et al [1], although describing a population that originated from the paediatric service in the same hospital, does not draw on health status in childhood. The earliest information presented in the article dates from the time of transfer to adult services.…”

“…The North American Disorders of Mucociliary Clearance Consortium reported half of the patients initially labelled as "PCD" were de-diagnosed after extensive testing [31]; conversely, we are aware of patients whose investigations had previously "excluded a diagnosis" where that decision has been overturned. In the study described by SHAH et al [1], nNO had been measured in only two-thirds of the patients (64%), although it is a noninvasive and affordable test.…”

“…Inconclusive and positive samples are reanalysed following culture of ciliated cells. Figure 1 of the article by SHAH et al [1] suggests that this algorithm might only have been applied to newly diagnosed patients rather than reviewing diagnostic certainty periodically in the light of new developments in diagnostic testing. This is important given the lack of a gold standard diagnostic test and an evolving understanding of the diversity of the PCD phenotypes.…”