Changes in physiological, functional and structural markers of cystic fibrosis lung disease with treatment of a pulmonary exacerbation.

BACKGROUND: Clinical trials in cystic fibrosis (CF) have been hindered by the paucity of well characterised and clinically relevant outcome measures. AIM: To evaluate a range of conventional and novel biomarkers of CF lung disease in a multicentre setting as a contributing study in selecting outcome assays for a clinical trial of CFTR gene therapy. METHODS: A multicentre observational study of adult and paediatric patients with CF (>10 years) treated for a physician-defined exacerbation of CF pulmonary symptoms. Measurements were performed at commencement and immediately after a course of intravenous antibiotics. Disease activity was assessed using 46 assays across five key domains: symptoms, lung physiology, structural changes on CT, pulmonary and systemic inflammatory markers. RESULTS: Statistically significant improvements were seen in forced expiratory volume in 1 s (p<0.001, n=32), lung clearance index (p<0.01, n=32), symptoms (p<0.0001, n=37), CT scores for airway wall thickness (p<0.01, n=31), air trapping (p<0.01, n=30) and large mucus plugs (p=0.0001, n=31), serum C-reactive protein (p<0.0001, n=34), serum interleukin-6 (p<0.0001, n=33) and serum calprotectin (p<0.0001, n=31). DISCUSSION: We identify the key biomarkers of inflammation, imaging and physiology that alter alongside symptomatic improvement following treatment of an acute CF exacerbation. These data, in parallel with our study of biomarkers in patients with stable CF, provide important guidance in choosing optimal biomarkers for novel therapies. Further, they highlight that such acute therapy predominantly improves large airway parameters and systemic inflammation, but has less effect on airway inflammation.

Pulmonary hypertension in patients with bronchiectasis: prognostic significance of CT signs.

OBJECTIVE: The purpose of this study was to evaluate the association between pulmonary hypertension estimated with CT and outcome among patients with bronchiectasis. MATERIALS AND METHODS: The cases of 91 patients with bronchiectasis were studied. CT signs of pulmonary hypertension examined were main pulmonary artery diameter, right and left main pulmonary artery diameters, and the ratio between the diameters of the main pulmonary artery and the ascending aorta. CT scans were scored for extent of bronchiectasis and presence of bronchial dilatation, bronchial wall thickening, mucous plugging, mosaicism, and emphysema. Univariate, bivariate, and multivariate Cox proportional hazards models were used to test the influence of CT signs on mortality. RESULTS: Average right and left main pulmonary artery diameter was the best predictor of mortality (hazard ratio, 1.24; 95% CI, 1.13-1.35; p < 0.0001) and was associated with outcome independent of CT signs of bronchiectasis. CONCLUSION: Pulmonary hypertension, reflected by pulmonary arterial enlargement on CT scans, is a highly significant prognostic indicator in the evaluation of patients with bronchiectasis.

Detection of pulmonary hypertension with multidetector CT and echocardiography alone and in combination.

PURPOSE: To test the reliability of potentially new computed tomographic (CT) indicators of pulmonary hypertension (PH) and to establish whether a combination of CT and echocardiographic measurements was more predictive of PH than either test alone. MATERIALS AND METHODS: The institutional review board approved this retrospective study; patient consent was not required. Seventy-seven patients undergoing right-sided heart catheterization were examined. CT diameters of the main pulmonary artery, ascending aorta, and thoracic vertebra and cross-sectional area of the main pulmonary artery were measured. Segmental and subsegmental arterial diameters were recorded, and segmental artery size was compared with adjacent bronchus size by using a semiquantitative scoring system. The relationship between CT measurements and mean pulmonary arterial pressure (mPAP) was tested with linear regression. Multivariate regression was used to establish a composite index of mPAP by using CT markers of PH with echocardiography-derived right ventricular systolic pressure (RVSP). Post hoc logistic regression and receiver operating characteristic curve analysis were performed to test the diagnostic ability of the CT-echocardiography composite. RESULTS: The ratios of the diameter of the main pulmonary artery to the diameter of the ascending aorta (R(2) = 0.45; P < .001) and of the cross-sectional area of the pulmonary artery to the diameter of the ascending aorta (R(2) = 0.45; P < .001) correlated equally with mPAP. The ratio of the diameter of the main pulmonary artery to the diameter of the thoracic vertebra, the segmental arterial diameter, and the segmental artery-to-bronchus ratio were related to mPAP but did not strengthen correlations compared with the ratio of the diameter of the main pulmonary artery to the diameter of the ascending aorta alone. A composite index of the ratio of the diameter of the main pulmonary artery to the diameter of the ascending aorta and echocardiography-derived RVSP was more strongly related (R(2) = 0.55) to mPAP and was more significantly predictive of PH than either measure alone. CONCLUSION: A combination of CT and echocardiographic markers of PH is more closely related to mPAP than either test in isolation.

The effect of diffuse pulmonary fibrosis on the reliability of CT signs of pulmonary hypertension.

PURPOSE: To determine whether pulmonary artery (PA) dilatation is a reliable indicator of pulmonary hypertension (PH) in patients with pulmonary fibrosis. MATERIALS AND METHODS: This study had institutional review board approval. Patient consent was not required. Seventy-seven patients (39 men, 38 women) who underwent right heart catheterization were studied. The study population was divided into 30 patients with pulmonary fibrosis (group A), and 47 without (group B). The main PA diameter (dPA) and ascending aorta diameter (dAA) were measured by using computed tomography (CT), and the extent of fibrosis was recorded in group A. The dPA and the dPA/dAA ratio were correlated (Spearman rank) with mean PA pressure (mPAP) and pulmonary vascular resistance index (PVRi). The relationship between dPA and pulmonary fibrosis extent and total lung capacity (TLC) was examined by using multivariate linear regression. RESULTS: There were strong correlations between dPA and both mPAP (r = 0.67, P < .0001) and PVRi (r = 0.78, P < .0001) in group B. In contrast, there were no significant correlations in group A (r = 0.23, P = .22 for mPAP and r = 0.23, P = .28 for PVRi). The dPA/dAA ratio had similar relationships to dPA alone in group B (r = 0.72, P < .0001 for mPAP and r = 0.71, P < .0001 for PVRi), but significantly strengthened the correlations in group A (r = 0.54, P < .005 for mPAP and r = 0.48, P = .04 for PVRi). PA dilatation occurred in group A in the absence of significant PH, and was unrelated to CT fibrosis score or TLC. CONCLUSION: PA dilatation occurs in the absence of PH in patients with pulmonary fibrosis and is therefore an unreliable sign of PH in these patients.

What is the value of magnetic resonance venography in children before renal transplantation?

Radiological evaluation before renal transplantation includes imaging of vascular anatomy, as thrombosis, narrowing and anomalies of the inferior vena cava (IVC) and/or iliac veins (IV) can influence the surgical technique. Most cases only require investigation with Doppler vessel ultrasonography (US), with magnetic resonance venography (MRV) reserved to clarify US findings and investigate high-risk patients. The purpose of this study was to compare these modalities in evaluating IVC and IV and correlate imaging and operative findings of patients at RTx surgery. Twenty-nine children, 21 (72%) of whom had subsequent RTx surgery, were investigated over 5 years with correlation of US and MRV in 62% (18 of 29). Technically difficult US examinations needing MRV for clarification occurred in six (21%), and normal US with anatomical variations on MRV was seen in three (10%). The anatomical variations consisted of left-sided IVC, aberrant right common femoral vein and a left IV partly draining into the azygos and renal veins. US is an excellent screening tool for evaluating vascular anatomy patency in children. MRV infrequently contributes beneficial information, is difficult to justify as a screening tool, and due to the risks of gadolinium in uraemia, should only be used on an individual patient basis.