Angiogenic cytokines in patients with idiopathic interstitial pneumonia.

BACKGROUND: Angiogenesis has been implicated in the pathogenesis of idiopathic interstitial pneumonia (IIP). The aim of this study was to examine the relationship between plasma concentrations of the angiogenic cytokines interleukin 8 (IL-8), vascular endothelial growth factor (VEGF), and endothelin-1 (ET-1) and clinical parameters of disease progression over a 6 month period to identify potential aetiological mediators and prognostic markers of disease activity in patients with IIP. METHODS: Forty nine patients with IIP (40 men) were recruited to the study. Plasma cytokine measurements, pulmonary function tests, and high resolution computed tomography (HRCT) scans were performed on recruitment and after 6 months. Plasma cytokine measurements were also performed in 15 healthy volunteers for control purposes. RESULTS: Patients with IIP had significantly higher median (IQR) baseline concentrations of IL-8 and ET-1 than controls (155 (77-303) pg/ml v 31 (0-100) pg/ml, p<0.001) and (1.21 (0.91-1.88) pg/ml v 0.84 (0.67-1.13) pg/ml, p<0.01), respectively. Baseline concentrations of IL-8, ET-1, and VEGF were significantly related to the baseline HRCT fibrosis score (r = 0.42, p<0.005; r = 0.39, p<0.01; and r = 0.42, p<0.005, respectively). Patients with IIP who developed progressive disease had significantly higher baseline levels of IL-8 (345 (270-497) pg/ml v 121 (73-266) pg/ml, p = 0.001) and VEGF (1048 (666-2149) pg/ml v 658 (438-837) pg/ml, p = 0.019). Over 6 months the change in VEGF was significantly related to the change in HRCT fibrosis score (r = 0.565, p = 0.035) and negatively related to the change in forced vital capacity (r = -0.353, p = 0.035).

A prospective study of change in bone mineral density over one year in adults with cystic fibrosis.

BACKGROUND: Low bone mineral density (BMD) is prevalent in adults with cystic fibrosis. To identify appropriate therapeutic strategies and the optimal time for intervention, it is necessary to document the natural history of cystic fibrosis related low BMD. METHODS: 114 adults with cystic fibrosis underwent bone densitometry a median (25-75% interquartile range) of 12 (12-13) months after initial assessment of bone density. BMD was measured in the lumbar spine, femoral neck, total hip, and distal forearm on recruitment to the trial and at follow up. RESULTS: In patients or=25 years of age (n=59, mean (SD) age 30.3 (5.4) years) in whom no annual change in BMD would normally be expected, BMD decreased by 1.9% (95% CI -2.9 to -0.8) per year in the femoral neck (p<0.001), by 1.5% (95% CI -2.4 to -0.6) per year in the total hip (p=0.001), and by 0.8% (95% CI -1.5 to -0.1) per year in the distal forearm (p=0.026). There was no significant annual change in lumbar spine BMD in either patient cohort. CONCLUSIONS: Reduced rates of bone accretion and accelerated rates of bone loss explain the high prevalence of low BMD in adults with cystic fibrosis.

Pulmonary (99m)Tc-DTPA aerosol clearance and survival in usual interstitial pneumonia (UIP).

BACKGROUND: Clearance of inhaled technetium 99m-labelled diethylenetriamine penta-acetic acid ((99m)Tc-DTPA) from the lungs is a potential indicator of disease progression in patients with idiopathic pulmonary fibrosis (IPF). METHODS: We prospectively analysed the usefulness of this technique for predicting survival in 106 non-smoking patients with usual interstitial pneumonia (UIP) pattern IPF diagnosed by high resolution CT (HRCT) scanning or histological examination (M/F 65/41, mean (SD) age 61 (11) years). DTPA clearance was analysed according to both mono-exponential and bi-exponential models. Half times for the fast (t(0.5)F) and slow (t(0.5)S) components of clearance, the percentage contribution of the fast component (fF), and half time for mono-exponential approximation to the early part of the clearance curve (t(0.5)) were calculated. RESULTS: The patients had substantially faster t(0.5) (mean 23.9 (9.6) minutes) than normal values (>45 minutes). Thirty seven patients (35%) died during follow up (median 15 months). Univariate Cox regression analysis identified significant predictors of survival as age, forced expiratory volume in 1 second (FEV(1)), forced vital capacity (FVC), total lung capacity (TLC), % predicted TLC, carbon monoxide transfer factor (TLCO), % predicted TLCO, arterial oxygen tension (PaO(2)), oxygen saturation, t(0.5)F, and HRCT fibrosis score. Multiple stepwise Cox regression analysis identified t(0.5)F (p=0.03, hazard ratio 0.747, 95% CI 0.578 to 0.964), % predicted TLC (p=0.02, hazard ratio 0.976, 95% CI 0.956 to 0.995), % predicted TLCO (p=0.003, hazard ratio 0.960, 95% CI 0.935 to 0.986), and age (p=0.003, hazard ratio 1.062, 95% CI 1.021 to 1.104) as independent predictors of survival. CONCLUSION: These data suggest that (99m)Tc-DTPA clearance t(0.5)F measurement may predict survival in patients with UIP pattern IPF.

Pulmonary function in idiopathic pulmonary fibrosis and referral for lung transplantation.

Of patients awaiting lung transplantation, the death rates are highest in those with idiopathic pulmonary fibrosis (IPF), suggesting that many IPF patients are referred late for transplantation. Therefore this study was undertaken to evaluate baseline pulmonary function test (PFT) and high-resolution computed tomography (HRCT) fibrosis scores, and the relationship to survival in IPF patients younger than 65 yr of age. A total of 115 patients with usual interstitial pneumonia (UIP) were studied. At presentation to a tertiary referral center, PFT and HRCT data were collected and analyzed for prognostic significance: the primary outcome measure was patient death. Based on the length of the waiting list for transplantation, prediction of 2-yr survival was examined. DL(CO) percent predicted and HRCT-fibrosis score were found to be independent predictors of survival and in combination gave the best prognostic prediction. The optimal points on the receiver operating characteristic (ROC) curves for discriminating between survivors and nonsurvivors corresponded to 39% DL(CO) percent predicted, and to a HRCT-fibrosis score of 2.25. The combination of these parameters yielded an optimal point with a specificity and a sensitivity of 84% and 82%, respectively. A model based on a combination of DL(CO) percent predicted and HRCT-fibrosis score may optimize the timing of referral for transplantation.

Effect of intravenous pamidronate on bone mineral density in adults with cystic fibrosis.

BACKGROUND: Low bone mineral density (BMD) is prevalent in adults with cystic fibrosis. The aim of this study was to assess the effect of intravenous pamidronate on BMD in these subjects. METHODS: Patients were invited to participate if they had a BMD Z score of -2 or less in the lumbar spine, proximal femur, or distal forearm. Patients were randomised to receive either 30 mg intravenous pamidronate every 3 months + 1 g calcium daily (pamidronate group) or 1 g calcium daily (control group). All pancreatic insufficient patients were prescribed oral vitamin D supplements. RESULTS: After 6 months of treatment the pamidronate group (n=13) showed a significant increase in absolute BMD compared with the control group (n=15) in the lumbar spine (mean difference 5.8% (CI 2.7% to 8.9%)) and total hip (mean difference 3.0% (CI 0.3% to 5.6%)). However, the pamidronate group showed a reduction in BMD compared with the control group in the distal forearm (mean difference -1.7% (CI -3.7% to 0.3%)). The use of pamidronate was associated with a high incidence of bone pain in non-corticosteroid treated individuals. CONCLUSION: Intravenous pamidronate increases axial BMD in adults with cystic fibrosis, but the high incidence of bone pain associated with this treatment might limit its use.

Low bone mineral density in adults with cystic fibrosis.

BACKGROUND: Patients with cystic fibrosis have several risk factors for the development of low bone mineral density (BMD). To identify the prevalence and clinical correlates of low BMD in adult patients with cystic fibrosis, densitometry was performed in 151 patients (83 men) aged 15-52 years. METHODS: BMD was measured in the lumbar spine (L1-4) using dual energy x ray absorptiometry (DXA) and quantitative computed tomography (QCT). It was also measured in the proximal femur (total hip and femoral neck) using DXA, and in the distal and ultra distal forearm using single energy x ray absorptiometry (SXA). Biochemical markers of bone turnover, vitamin D levels, parathyroid hormone levels, and a variety of anthropometric variables were also assessed. RESULTS: The mean (SD) BMD Z score was -0.73 (0.85) in the distal forearm, -0.31 (0.92) in the ultra distal forearm, -1.21 (1. 18) in the lumbar spine using DXA, -0.56 (1.36) in the lumbar spine using QCT, -1.25 (1.30) in the femoral neck, and -1.01 (1.14) in the total hip. 34% of patients had a BMD Z score of -2 or less at one or more skeletal sites. Body mass index (0.527, p = 0.01), percentage predicted forced expiratory volume in one second (0.388, p = 0.01), and physical activity (0.249, p = 0.05) were positively related to the mean BMD Z score. Levels of C reactive protein (-0.328, p = 0. 01), parathyroid hormone (-0.311, p = 0.01) and biochemical markers of bone turnover (osteocalcin -0.261 and bone specific alkaline phosphatase -0.249, p = 0.05) were negatively related to the mean BMD Z score. Vitamin D insufficiency (25-hydroxyvitamin D <15 ng/ml) was prevalent (53/139 patients, 38%) despite supplementation with 900 IU vitamin D per day. CONCLUSIONS: Low bone density is prevalent in adult patients with cystic fibrosis. Current levels of vitamin D supplementation appear to be inadequate.

Domiciliary radiography: an important service?

General practitioners' (GP) perceptions, comparative costs and potential influence on patient management of a domiciliary radiography service were reviewed. A postal questionnaire was sent to 159 local GPs, 130 of whom responded. Seventy-one per cent of respondents had requested domiciliary radiography in the previous year and 79% felt loss of the service could potentially be detrimental. Although 98% recognized that a chest X-ray was a suitable domiciliary radiography examination, 6% thought that a barium swallow could be adequately carried out with domiciliary equipment. Forty-nine per cent perceived a need for a domiciliary ultrasound service. Sixty-three per cent believed that domiciliary radiography was cheaper than return ambulance transport with departmental examination, although estimates showed a domiciliary visit to cost 82 pounds versus 60 pounds for a departmental visit. A retrospective review of 50 consecutive domiciliary radiography examinations showed that elderly and immobile patients were imaged most frequently. Malignancy was diagnosed in 14%, infection in 26% and a fracture in 14%. Overall there was an anticipated management change in 50% of patients.

Abdominal radiography in suspected 'body packers'.

Drug smuggling by intra-abdominal concealment is now a world-wide problem. This paper describes the establishment of a plain radiography service to assist customs officers of Manchester International Airport (MIA) in their work. Over a 2 1/2 year period, 158 suspected 'body packers' were radiographed, resulting in nine positive detections. The existence of the service has resulted in the apparent abandonment of MIA as a port of entry by an organized group of cocaine smugglers. Practical and ethical problems are described. This service is felt to be essential by the customs officers and a valuable service to society by the radiologists and hospital authorities concerned.