Biological- and imaging biomarkers of edema and fibrosis in a rat model of drug-induced interstitial lung disease (DIILD)
Irma Mahmutovic PerssonHanna Falk HåkanssonAnders ÖrbomPer‐Ola ÖnnervikJanne PerssonKarin von WachenfeldtLars Olsson
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Abstract:
A large number of systemically administered drugs have the potential to cause DIILD. We aim to characterize a model of DIILD in the rat and develop imaging biomarkers for detection and quantification of DIILD. Methods: Sprague-Dawley rats received one single dose of intratracheal bleomycin and were longitudinally imaged at day 0, 3, 7, 14, 21 and 28 post dosing, applying imaging techniques MRI and PET/CT. Bronchoalveolar lavage fluid (BALF) was analyzed for total protein and inflammatory cells. Lungs were taken for further analyses by histology, and stained for inflammation and collagen deposition. Results: Bleomycin induced significant increase in total protein concentration and total cell count in BALF, peaking at day3 (p>0.001) and day7 (p>0.001) compared to control, respectively. The lesion measured by MRI and the FDG-PET signal in the lungs of bleomycin challenged rats was significantly increased during day3-14, peaking at day7. Two subgroups of animals were identified as low- and high responders to bleomycin challenge, by their different change in total lung volume. Both groups showed signs of inflammation initially, while at later time points the low-responder group recovered towards control, and the high-responder group showed progressive fibrosis with significant increase of lesion volume (p<0.001), compared to control. Conclusion: Bleomycin-induced lung injury with MRI and PET readout in rats, is an adequate and translational animal model for DIILD studies. The scenario comprised different disease responses, with different fractions of inflammation and fibrosis. Thereby, this study improved the understanding biological- and imaging biomarkers in DIILD.Keywords:
Histology
Objective To assess whether distal bronchoalveolar lavage(DBAL) with plastic tubing allowed recovery of more fluid in comparison with common bronchoalveolar lavage(CBAL), and whether tubing had a favorable impact on operative procedure and complications. Methods A randomized study was performed in the hospital. Patients scheduled for BAL were randomly assigned to DBAL (n = 66) and CBAL (n = 56) group. Results In DBAL group,5.55% more fluid was recovered,9. 19% fewer technical failures,and 7.41% fewer complications were recorded. Conclusions Based on these results, we recommend performing DBAL using plastic tubing to replace CBAL.
Key words:
Bronchoalveolar lavage; Methods; Distal bronchoalveolar lavage; Common bronchoalveolar lavage
Therapeutic irrigation
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Pulmonary alveolar proteinosis
Parenchyma
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人膀胱癌の1つの治療体系の確立を目的として, 温水潅流法による温熱 (Hyperthermia) 療法 (42～43℃) の臨床的検討を行つた. 温熱単独, 温熱と bleomycin の併用療法, 温熱と放射線の併用療法, 温熱と放射線と bleomycin の3者併用療法の4通りの療法を受けた34例の膀胱癌 (移行上皮癌) 患者につき, 治療効果, 副作用, 生体免疫能におよぼす影響につき検討を行つた.温熱単独では6例中2例に, 温熱と bleomycin の併用では4例中1例に, 温熱と放射線の併用では9例中5例に, 温熱と放射線と bleomycin の3者の併用では15例中12例に, 腫瘍の明らかな縮小や消失の治療効果が認められた.副作用は膀胱刺激症状, 尿道痛が主なものであり, 重篤な副作用は認められなかつた.PHAや Con Aによるリンパ球幼若化能等を指標として生体免疫能におよぼす温熱療法の影響を検討した. 温熱と放射線の併用, および温熱と放射線と bleomycin の3者併用療法を受けた患者のこれら指標は, 治療の経過に伴つて抑制されたが, 放射線単独療法を受けた患者のそれとは差が認められなかつた.これらより, 膀胱癌の温熱療法に特に温熱と放射線と bleomycin の3者の併用療法は充分臨床応用が可能と考えられた.
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Bronchoalveolar lavage (BAL) is a well-established diagnostic tool for the assessment of pulmonary diseases in adults. How BAL contributes to the diagnostic process in childhood lung diseases is less clear. One of the problems in interpreting BAL findings in children is that there are few reference data for BAL fluid constituents in children. This report addresses some of the technical problems of bronchoalveolar lavage in children and summarizes current knowledge on cellular and noncellular bronchoalveolar lavage fluid components in children without lung disease.
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Objectives: To evaluate the yield of mini-bronchoalveolar lavage compared with that of directed bronchoalveolar lavage in critically ill patients with suspected coronavirus disease 2019–associated pulmonary aspergillosis. Design: A retrospective cohort study. Setting: The ICU of the Amsterdam University Medical Centers. Patients: Patients with confirmed coronavirus disease 2019 screened for coronavirus disease 2019–associated pulmonary aspergillosis. INTERVENTIONS: Mini-bronchoalveolar lavage and/or directed bronchoalveolar lavage. Measurements and Main Results: In total, 76 patients were included, 20 of whom underwent bronchoalveolar lavage, 40 mini-bronchoalveolar lavage, and 16 both mini-bronchoalveolar lavage and bronchoalveolar lavage. The percentage of samples with one or more positive Aspergillus detecting test (galactomannan, culture, polymerase chain reaction) did not differ significantly between bronchoalveolar lavage and mini-bronchoalveolar lavage (16.7% vs 21.4%). However, in mini-bronchoalveolar lavage samples, this was more frequently driven by a positive polymerase chain reaction than in bronchoalveolar lavage samples (17.9% vs 2.8%; p = 0.030). In 81% of patients (13/16) with both mini-bronchoalveolar lavage and bronchoalveolar lavage, the test results were in agreement. In 11 of 12 patients (92%) with first a negative mini-bronchoalveolar lavage, the subsequent bronchoalveolar lavage sample was also negative. Conclusions: We found a similar percentage of positive test results in mini-bronchoalveolar lavage and bronchoalveolar lavage samples in patients with suspected coronavirus disease 2019–associated pulmonary aspergillosis. Our findings indicate that mini-bronchoalveolar lavage could be a useful tool for coronavirus disease 2019–associated pulmonary aspergillosis screening in ICU patients.
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Examination of bronchoalveolar lavage fluid is a method based on obtaining biological material in the from of cells and fluid derived directly from the alveoli of the bronchi. Cytological and biochemical examination of the bronchoalveolar fluid enables to understand pathomechanisms of various interstitial and obstructive pulmonary diseases. Bronchoalveolar lavage (BAL) is a sensitive and safe diagnostic method, which becomes to be widely employed in the pneumonologic++ diagnosis.
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