S68 A longitudinal study characterising a large adult primary ciliary dyskinesia cohort

Abstract

Adult Primary Ciliary Dyskinesia (PCD) has not been well characterised. Patients have varied radiological severity of disease and lung function impairment and limited data is available regarding prognosis. In this retrospective study we describe and characterise a large adult PCD cohort, and identify determinates of disease progression using longitudinal lung function data.We retrospectively analysed 151 adult patients at a single tertiary centre. Overall mortality was 4.6% over a 7-year median follow-up period. Lung function decline was estimated at 0.49%FEV1predicted/year. Older age at diagnosis showed moderate negative correlation with FEV1%predicted at diagnosis (r = -0.30; p = 0.01) and increased Pseudomonas aeruginosa colonisation (p < 0.01) but not longitudinal FEV1%predicted (β = 0.001; (95% CI:-0.35,0.35)). Within multivariate mixed models of FEV1 adjusting for ciliary ultrastructure, HRCT scoring of severity of bronchial wall dilatation (p < 0.01) and extent of bronchiectasis (p = 0.03) showed evidence of modifying the decline in FEV1 with age. Lung function decline additionally differed by ciliary ultrastructure (p = 0.04) with patients with microtubular defects having the greatest decline.Our study reveals a large proportion of adult PCD patients are diagnosed late with lower FEV1 and increased P. aeruginosa colonisation at diagnosis. Increased disease burden on HRCT and microtubular defects on ciliary ultrastructure predicts progressive lung function decline. This study highlights the need for early diagnosis alongside prospective multi-centre disease-specific trials to confirm triggers for lung function decline and identify potential novel therapeutic strategies.

International BEAT-PCD consensus statement for infection prevention and control for primary ciliary dyskinesia in collaboration with ERN-LUNG PCD Core Network and patient representatives

“…A total of 11 studies were retrieved from the literature search that concerned prevalence, clinical impact and management of P. aeruginosa infection in patients with PCD [5,6,9,11,[20][21][22][23][24][25][26].…”

“…Three observational studies both showed worse CT scan scores in patients with PCD chronically infected with P. aeruginosa compared to non-infected patients [6,11,20] whereas convincing impact of P. aeruginosa infection on lung function was not consistently found among four included studies [11,23,25] as only one study out of four showed decreased FEV 1 in P. aeruginosa infected patients.…”

“…• June K Marthin 1 • Jane S Lucas 2 • Mieke Boon 3 • Carmen Casaulta 4 • Suzanne Crowley 5 • Damien MS Destouches (Patient Representative) 6 • Ernst Eber 7 • Amparo Escribano 8 • Eric Haarman 9 • Claire Hogg 10 • Bernard Maitre 11 • Gemma Marsh 10 • Vendula Martinu 12 • Antonio Moreno-Galdó 13 • Huda Mussaffi 14 • Heymut Omran 15 • Petr Pohunek 12 • Bernhard Rindlisbacher (Patient Representative) 16 • Phil Robinson 17 • Deborah Snijders 18 • Woolf T Walker 2 • Panayiotis Yiallouros 19 • Helle Krogh Johansen 20,21 • Kim G Nielsen 1,21…”

“…Patients with PCD are frequently chronically infected with bacterial pathogens similar to CF [5] and in adult patients with PCD Pseudomonas aeruginosa infection have shown to be more prevalent than H. influenzae infection [6] which underlines that P. aeruginosa is a pathogen of great concern also in patients with PCD and that the airway microbiology of patients with PCD seems to mirror that of CF [7]. This has enabled the extrapolation of information from CF airway microbiology to PCD, including assumptions of the need for similar management of pulmonary infections ranging from use of intensive antibiotic therapy regimens to infection prevention and control, despite little evidence [8][9][10].…”

Review of the British Thoracic Society Winter Meeting 2015, 2–4 December, London, UK

“…Dr Shah reported data from 151 adult patients with primary ciliary dyskinesia at a tertiary referral centre in London. Risk factors for lung function decline in relation to severity of disease on high-resolution CT and ciliary ultrastructure, but interestingly were not associated with Pseudomonas aeruginosa colonisation 27 . P aeruginosa was more common in patients diagnosed late, as was lower lung function, emphasising the importance of picking up the disease early 28…”