Pulmonary artery enlargement and cystic fibrosis pulmonary exacerbations: a cohort study

Wells, J. Michael, Farris, Roopan F., Gosdin, Taylor A., Dransfield, Mark T., Wood, Michelle E., Bell, Scott C. and Rowe, Steven M. (2016) Pulmonary artery enlargement and cystic fibrosis pulmonary exacerbations: a cohort study. Lancet Respiratory Medicine, 4 8: 636-645. doi:10.1016/S2213-2600(16)30105-9


Author Wells, J. Michael
Farris, Roopan F.
Gosdin, Taylor A.
Dransfield, Mark T.
Wood, Michelle E.
Bell, Scott C.
Rowe, Steven M.
Title Pulmonary artery enlargement and cystic fibrosis pulmonary exacerbations: a cohort study
Journal name Lancet Respiratory Medicine   Check publisher's open access policy
ISSN 2213-2600
2213-2619
Publication date 2016-08-01
Sub-type Article (original research)
DOI 10.1016/S2213-2600(16)30105-9
Open Access Status Not yet assessed
Volume 4
Issue 8
Start page 636
End page 645
Total pages 10
Place of publication London, United Kingdom
Publisher The Lancet Publishing Group
Language eng
Abstract Acute pulmonary exacerbations are associated with progressive lung function decline and increased mortality in cystic fibrosis. The role of pulmonary vascular disease in pulmonary exacerbations is unknown. We aimed to assess the association between pulmonary artery enlargement (defined as pulmonary artery diameter to ascending aorta diameter [PA:A] ratio >1), a marker of pulmonary vascular disease, and exacerbations.
Formatted abstract
Background: Acute pulmonary exacerbations are associated with progressive lung function decline and increased mortality in cystic fibrosis. The role of pulmonary vascular disease in pulmonary exacerbations is unknown. We aimed to assess the association between pulmonary artery enlargement (defined as pulmonary artery diameter to ascending aorta diameter [PA:A] ratio >1), a marker of pulmonary vascular disease, and exacerbations.

Methods: In this cohort study, we used clinical, CT imaging, and prospective exacerbation data from a previous prospective clinical trial (derivation cohort) and from The Prince Charles Hospital (TPCH; Brisbane, QLD, Australia) cystic fibrosis registry (validation cohort). In our derivation cohort, we included adults aged 18 years or older with cystic fibrosis and at least one CFTR nonsense mutation, who were enrolled in the trial between Sept 8, 2009, and Nov 30, 2010, randomly assigned to receive placebo, and had baseline CT imaging. Our validation cohort included adult patients with cystic fibrosis who had CT imaging performed between Jan 1, 2002, and Dec 31, 2014. We measured the PA:A ratio at the level of the pulmonary artery bifurcation on CT scans. Patients in each cohort were separated into two groups on the basis of PA:A ratio (>1 or ≤1) and were followed up for 1 year in the derivation cohort and 2 years in the validation cohort. The primary endpoint was the development of one or more acute pulmonary exacerbations during follow-up. We used linear and logistic regression models to determine associations between clinical factors, the PA:A ratio, and pulmonary exacerbations. We used Cox regression to determine the time to first exacerbation in the validation cohort.

Findings: 37 (50%) of 74 patients in the derivation cohort and 89 (47%) of 190 patients in the validation cohort had enlarged pulmonary arteries (PA:A>1). 50 (68%) patients in the derivation cohort had one or more exacerbations at 1 year and 133 (70%) patients in the validation cohort had one or more exacerbations at 2 years. At baseline, patients with pulmonary artery enlargement were younger than those without enlargement in both cohorts and had elevated sweat chloride concentrations in the derivation cohort (100·5 mmol/L [SD 10·9] vs 90·4 mmol/L [19·9]; difference 10·1 mmol/L [95% CI 2·5–17·7], p=0·017). Pulmonary artery enlargement was associated with exacerbations in the derivation cohort (odds ratio 3·49 [95% CI 1·18–10·3], p=0·023) when adjusted for sex, body-mass index (BMI), forced expiratory volume in 1 s (FEV1), and PA:A greater than 1, and in the validation cohort (2·41 [1·06–5·52], p=0·037) when adjusted for sex, BMI, chronic Pseudomonas aeruginosa infection, FEV1/FVC (forced vital capacity), PA:A greater than 1, and previous exacerbation. The time to first exacerbation was shorter in patients with enlarged pulmonary arteries than in those with normal-sized pulmonary arteries in the validation cohort (hazard ratio 1·66 [95% CI 1·18–2·34], p=0·0038) in unadjusted analysis, but not when adjusted for sex, BMI, exacerbations within 1 year before index CT scan, FEV1/FVC, and chronic P aeruginosa infection (1·14 [0·80–1·62], p=0·82).

Interpretation: Pulmonary artery enlargement is prevalent in adult patients with cystic fibrosis and was associated with acute pulmonary exacerbation risk in two well characterised cohorts. The PA:A ratio could be a predictive marker in cystic fibrosis.
Q-Index Code C1
Q-Index Status Provisional Code
Grant ID K08 HL123940
P30 DK072482
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
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