| 1. |
- Stolk, Jan, et al.
(författare)
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Randomised controlled trial for emphysema with a selective agonist of the gamma-type retinoic acid receptor
- 2012
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Ingår i: European Respiratory Journal. - : European Respiratory Society (ERS). - 1399-3003 .- 0903-1936. ; 40:2, s. 306-312
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Tidskriftsartikel (refereegranskat)abstract
- Palovarotene is an oral gamma-selective retinoid agonist. In animal emphysema models, palovarotene reduced inflammation, promoted structural repair and functional improvement. REPAIR (Retinoid treatment of Emphysema in Patients on the alpha(1)-antitrypsin International Registry), was an investigator-initiated, double-blind, placebo-controlled randomised study to assess the safety and efficacy of 5 mg.day(-1) palovarotene given for 1 year to 262 patients with severe alpha(1)-antitrypsin deficiency and emphysema confirmed by computed tomography. Change in volume-adjusted 15th percentile point lung density from baseline in 1 year was the primary endpoint; functional end-points were also regularly assessed. We randomly assigned 133 and 129 patients to placebo or palovarotene, respectively. Both groups were well matched for all baseline characteristics, including respiratory medications. 88% and 85% of patients completed 1 year of treatment with placebo and palovarotene, respectively. Palovarotene was generally well tolerated. In the study completers population, the placebo-corrected difference of lung density was -0.45 HU at week 28 (p=0.64) and -0.25 HU at week 52 (p=0.94). A nonsignificant treatment difference in most functional parameters of the lung in favour of the drug was observed over time suggesting potential pharmacological effects of palovarotene. Palovarotene 5 mg.day(-1) over 1 yr failed to show a significant benefit on lung density in moderate-to-severe emphysema secondary to severe alpha(1)-antitrypsin deficiency.
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| 2. |
- Bakker, M. Els, et al.
(författare)
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Assessment of Regional Progression of Pulmonary Emphysema With CT Densitometry
- 2008
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Ingår i: Chest. - : Elsevier BV. - 1931-3543 .- 0012-3692. ; 134:5, s. 931-937
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Tidskriftsartikel (refereegranskat)abstract
- Background: Lung densitometry is an effective method to assess overall progression of emphysema, but generally the location of the progression is not estimated. We hypothesized that progression of emphysema is the result of extension from affected areas toward less affected areas in the lung. To test this hypothesis, a method was developed to assess emphysema severity at different levels in the lungs in order to estimate regional changes. Methods: Fifty subjects with emphysema due to alpha(1)-antitrypsin deficiency (AATD) [AATD deficiency of phenotype PiZZ (PiZ) group] and 16 subjects with general emphysema (general emphysema without phenotype PiZZ [non-.PiZ] group) were scanned with CT at baseline and after 30 months. Densitometry was performed in 12 axial partitions of equal volumes. To indicate predominant location, craniocaudal locallity was defined as the slope in the plot of densities against partitions. Regional progression of emphysema was calculated after volume correction, and its slope identifies the area of predominant progression. The hypothesis was tested by investigating the correlation between predominant location and predominant progression. Results: As expected, the PiZ patients showed more basal emphysema than the non-PiZ group (craniocaudal locality, -40.0 g/L vs -6.2 g/L). Overall progression rate in PiZ patients was lower than in non-PiZ subjects. A significant correlation was found between craniocaudal locality and progression slope in PiZ subjects (R = 0.566, p < 0.001). In the non-PiZ group, no correlation was found. Conclusions: In the PiZ group, the more emphysema is distributed basally, the more progression was found in the basal area. This finding suggests that emphysema due to AATD spreads out from affected areas. (CHEST 2008; 134:931-937)
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| 3. |
- Stoel, Berend C., et al.
(författare)
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Eureka?
- 2011
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Ingår i: Radiology. - : Radiological Society of North America (RSNA). - 1527-1315 .- 0033-8419. ; 259:2, s. 610-611
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Tidskriftsartikel (refereegranskat)
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| 4. |
- Stolk, Jan, et al.
(författare)
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Progression parameters for emphysema: A clinical investigation
- 2007
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Ingår i: Respiratory Medicine. - : Elsevier BV. - 1532-3064 .- 0954-6111. ; 101:9, s. 1924-1930
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Tidskriftsartikel (refereegranskat)abstract
- In patients with airflow limitation caused by cigarette smoking, lung density measured by computed tomography is strongly correlated with quantitative pathology scores of emphysema, but the ability of lung densitometry to detect progression of emphysema is disputed. We assessed the sensitivity of lung densitometry as a parameter of disease progression of emphysema in comparison to FEV1 and gas transfer. At study baseline and after 30 months we measured computed tomography (CT)-derived lung density, spirometry and carbon monoxide diffusion coefficient in 144 patients with chronic obstructive pulmonary disease (COPD) in five different centers. Annual change in lung density was 1.31 g/L/year (CI 95%: -2.12 to -0.50 HU, p = 0.0015, 39.5 mL/year (CI 95%: -100.0-21.0 mL, p = 0.2) for FEV1, (-39.5 mL) and 24.3 mu mol/min/kPa/L/year for gas transfer (CI 95%: -61.0-12.5 mu mol/min/kPa/L/year, p = 0.2). Signal-to-noise ratio (mean change divided by standard error of the change) for the detection of annual change was 3.2 for lung densitometry, but 1.3 for both FEV1 and gas diffusion. We conclude that detection of progression of emphysema was found to be 2.5-fold more sensitive using lung densitometry than by using currently recommended lung function parameters. Our results support CT scan as an efficacious test for novel drugs for emphysema. (c) 2007 Published by Elsevier Ltd.
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