Inhibition of tyrosine kinase Fgr prevents radiation-induced pulmonary fibrosis (RIPF)
Amitava MukherjeeMichael W. EpperlyRenee FisherWen‐Chi HouDonna ShieldsM. Saiful HuqPhillip M. PiferRia MulherkarT.J. WilhiteHong WangPeter WipfJoel S. Greenberger
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Abstract Cellular senescence is involved in the development of pulmonary fibrosis as well as in lung tissue repair and regeneration. Therefore, a strategy of removal of senescent cells by senolytic drugs may not produce the desired therapeutic result. Previously we reported that tyrosine kinase Fgr is upregulated in ionizing irradiation-induced senescent cells. Inhibition of Fgr reduces the production of profibrotic proteins by radiation-induced senescent cells in vitro; however, a mechanistic relationship between senescent cells and radiation-induced pulmonary fibrosis (RIPF) has not been established. We now report that senescent cells from the lungs of mice with RIPF, release profibrotic proteins for target cells and secrete chemotactic proteins for marrow cells. The Fgr inhibitor TL02-59, reduces this release of profibrotic chemokines from the lungs of RIPF mice, without reducing numbers of senescent cells. In vitro studies demonstrated that TL02-59 abrogates the upregulation of profibrotic genes in target cells in transwell cultures. Also, protein arrays using lung fibroblasts demonstrated that TL02-59 inhibits the production of chemokines involved in the migration of macrophages to the lung. In thoracic-irradiated mice, TL02-59 prevents RIPF, significantly reduces levels of expression of fibrotic gene products, and significantly reduces the recruitment of CD11b+ macrophages to the lungs. Bronchoalveolar lavage (BAL) cells from RIPF mice show increased Fgr and other senescent cell markers including p16. In human idiopathic pulmonary fibrosis (IPF) and in RIPF, Fgr, and other senescent cell biomarkers are increased. In both mouse and human RIPF, there is an accumulation of Fgr-positive proinflammatory CD11b+ macrophages in the lungs. Thus, elevated levels of Fgr in lung senescent cells upregulate profibrotic gene products, and chemokines that might be responsible for macrophage infiltration into lungs. The detection of Fgr in senescent cells that are obtained from BAL during the development of RIPF may help predict the onset and facilitate the delivery of medical countermeasures.Keywords:
Proinflammatory cytokine
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.
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Bronchoalveolar lavage; Methods; Distal bronchoalveolar lavage; Common bronchoalveolar lavage
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Abstract Objectives The study was to explore the influence of microRNA (miR)-345-3p on proinflammatory cytokines in patients with rheumatoid arthritis (RA). Methods A total of 32 RA patients and 32 healthy patients were enrolled. Proinflammatory factors in patients’ serum were detected by ELISA, and miR-345-3p was detected by RT-qPCR. The correlation between miR-345-3p expression and proinflammatory factors in RA patients was analyzed. The diagnostic value of miR-345-3p and proinflammatory factors in RA patients was analyzed by receiver operating curve diagnosis. The predictive value of miR-345-3p levels and proinflammatory factors in RA patients was analyzed by multivariate Cox regression. HFLS-RA and HFLS cells were cultured, in which miR-345-3p and proinflammatory cytokines were detected by RT-qPCR. Cell proliferation and apoptosis were determined by CCK-8 and flow cytometry, respectively. Results MiR-345-3p was lowly expressed in the serum of RA patients. MiR-345-3p and proinflammatory factors were of diagnostic and predictive values in RA. Elevated miR-345-3p restrained the production of proinflammatory factors of HFLS-RA cells, improved cell proliferation, and reduced apoptosis. Conclusion MiR-345-3p is a potential biomarker and ameliorates RA by reducing the release of proinflammatory cytokines.
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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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Objective: To take the opportunity of a bronchoalveolar lavage to challenge the transpulmonary thermodilution for detecting the time course of changes in extravascular lung water. Design: Observational study. Setting: Medical ICU. Patients: Mechanically ventilated patients in whom a bronchoalveolar lavage by bronchoscopy was performed. Intervention: Transpulmonary thermodilution before and after bronchoalveolar lavage. Measurements and Main Results: Before and at different times after bronchoalveolar lavage, transpulmonary thermodilution was performed to record the value of indexed extravascular lung water. For each measurement, the values of three thermodilution measurements were averaged at the following steps: before bronchoalveolar lavage, after bronchoalveolar lavage, and 1 hour, 2 hours, 4 hours, and 6 hours after bronchoalveolar lavage. The amount of saline infusion left in the lungs after bronchoalveolar lavage was also recorded. Twenty-five patients with suspicion of pneumonia were included. Twenty-eight bronchoalveolar lavages were finally analyzed. On average, 200 mL (180–200 mL) of saline were injected and 130 mL (100–160 mL) were left in the lungs. Between before and immediately after bronchoalveolar lavage, indexed extravascular lung water significantly increased from 12 ± 4 to 15 ± 5 mL/kg, respectively, representing a 169 ± 166 mL increase in nonindexed extravascular lung water. After bronchoalveolar lavage, the value of indexed extravascular lung water was significantly different from the baseline value until 2 hours after bronchoalveolar lavage and became similar to the baseline value thereafter. Conclusions: Transpulmonary thermodilution enabled to detect small short-term changes of indexed extravascular lung water secondary to bronchoalveolar lavage.
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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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