Medication-induced Pulmonary Injury: A Scenario- and Pattern-based Approach to a Perplexing Problem

Abstract Background Sepsis is a common complication of severe wound injury and infection, with a very high mortality rate. The P2Y12 receptor inhibitor, cangrelor, is an antagonist anti-platelet drug. Methods In our study, we investigated the protective mechanisms of cangrelor in CLP-induced pulmonary injury in sepsis, using C57BL/6 mouse models. Results TdT-mediated dUTP Nick-End Labeling (TUNEL) and Masson staining showed that apoptosis and fibrosis in lungs were alleviated by cangrelor treatment. Cangrelor significantly promoted surface expression of CD40L on platelets and inhibited CLP-induced neutrophils in Bronchoalveolar lavage fluid (BALF) (p < 0.001). We also found that cangrelor decreased the inflammatory response in the CLP mouse model and inhibited the expression of inflammatory cytokines, IL-1β (p < 0.01), IL-6 (p < 0.05), and TNF-α (p < 0.001). Western blotting and RT-PCR showed that cangrelor inhibited the increased levels of G-protein-coupled receptor 17 (GPR17) induced by CLP (p < 0.001). Conclusion Our study indicated that cangrelor repressed the levels of GPR17, followed by a decrease in the inflammatory response and a rise of neutrophils in BALF, potentially reversing CLP-mediated pulmonary injury during sepsis.

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523 Retrospective Outcomes Analysis of Tracheostomy in Paediatric Burn Population

Journal of Burn Care & Research ◽

10.1093/jbcr/irab032.174 ◽

2021 ◽

Vol 42 (Supplement_1) ◽

pp. S108-S109

Author(s):

Nicholas Iglesias ◽

Anesh Prasai ◽

George Golovko ◽

Deepak K Ozhathil ◽

Steven E Wolf

Keyword(s):

Inhalation Injury ◽

Smoke Inhalation ◽

Research Network ◽

Burn Patients ◽

Pulmonary Injury ◽

Smoke Inhalation Injury ◽

Mortality And Morbidity ◽

Laryngeal Injury ◽

Icd 10 ◽

Potential Benefits

Abstract Introduction For decades, controversy has raged regarding the placement of tracheostomy in severe paediatric burns. Numerous variables including extent of smoke inhalation injury, % TBSA burned, age of the patient, and co-morbidities among others complicate reaching consensus. Furthermore, paediatric patients are particularly susceptible to complications including inadvertent loss of airway and long-term swallowing and other anatomic issues. Additionally, previous analysis of the efficacy of tracheostomy in paediatric burn patients appears to be hindered by a lack of nationwide analysis. The aim of this study was to explore the efficacy of tracheostomy in the general paediatric burn patient population. Methods De-identified patient data was obtained from the TriNetX Research Network database. Two cohorts were identified: paediatric burn patients with tracheostomy (cohort A) and paediatric burn patients without tracheostomy (cohort B). Burn patients were identified using the ICD-10 codes T20-T25 & T30-T32. Tracheostomy was identified using the ICD-10 codes 1005887, 1014613, 31600, 31601, 31603, 31604, 31610, and Z93.0. A total of 132 patients were identified in cohort A in 23 HCOs and 83,117 patients were identified in cohort B in 38 HCOs. Infection, hypovolemia, pulmonary injury, laryngeal injury, pneumonia, and death were compared between the cohorts. Results Cohort A had a mean age of 11 (SD=5) and Cohort B had a mean age of 9 (SD=5). Paediatric burn patients with tracheostomy had a higher risk for death, infection, hypovolemia, pulmonary injury, laryngeal injury, and pneumonia when compared to their non-tracheostomy counterparts. The risk ratios for these outcomes were 62.452, 4.713, 9.267, 26.483, 116.163, and 18.154, respectively. Conclusions The analysis of the longitudinal outcomes of pediatric burn patients with tracheostomy as compared to those without tracheostomy demonstrated the tracheostomy cohort suffered much worse mortality and morbidity across several metrics. The potential benefits of tracheostomy placement in pediatric burn patients should be weighed against these outcomes.

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Lipid peroxidation and lung ultrastructural changes in an experimental model of leukocyte-mediated pulmonary injury

Lung ◽

10.1007/bf02719671 ◽

1990 ◽

Vol 168 (1) ◽

pp. 35-42 ◽

Cited By ~ 5

Author(s):

Emma Borrelli ◽

PierPaolo Giomarelli ◽

Osvaldo Chiara ◽

Alessandro Casini ◽

Sandra Betti ◽

...

Keyword(s):

Lipid Peroxidation ◽

Experimental Model ◽

Ultrastructural Changes ◽

Pulmonary Injury

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Higher Human T-Lymphotropic Virus Type 1 Subtype C Proviral Loads Are Associated With Bronchiectasis in Indigenous Australians: Results of a Case-Control Study

Open Forum Infectious Diseases ◽

10.1093/ofid/ofu023 ◽

2014 ◽

Vol 1 (1) ◽

Cited By ~ 28

Author(s):

Lloyd Einsiedel ◽

Olivier Cassar ◽

Emma Goeman ◽

Tim Spelman ◽

Virginia Au ◽

...

Keyword(s):

Virus Type ◽

Geographic Origin ◽

Peripheral Blood Lymphocytes ◽

Indigenous Australians ◽

Pulmonary Injury ◽

Subtype C ◽

T Lymphotropic Virus ◽

Adjusted Risk ◽

Tract Infections

Abstract Background. We previously suggested that infection with the human T-lymphotropic virus type 1 (HTLV-1) subtype C is associated with bronchiectasis among Indigenous Australians. Bronchiectasis might therefore result from an HTLV-1-mediated inflammatory process that is typically associated with a high HTLV-1 proviral load (PVL). Human T-lymphotropic virus type 1 PVL have not been reported for Indigenous Australians. Methods. Thirty-six Indigenous adults admitted with bronchiectasis from June 1, 2008, to December 31, 2009 were prospectively recruited and matched by age, sex, and ethno-geographic origin to 36 controls. Case notes and chest high-resolution computed tomographs were reviewed, and pulmonary injury scores were calculated. A PVL assay for the HTLV-1c subtype that infects Indigenous Australians was developed and applied to this study. Clinical, radiological, and virological parameters were compared between groups and according to HTLV-1 serostatus. Results. Human T-lymphotropic virus type 1 infection was the main predictor of bronchiectasis in a multivariable model (adjusted risk ratio [aRR], 1.84; 95% confidence interval [CI], 1.19–2.84; P = .006). Moreover, the median HTLV-1c PVL (interquartile range) for cases was >100-fold that of controls (cases, 0.319 [0.007, 0.749]; controls, 0.003 [0.000, 0.051] per 100 peripheral blood lymphocytes; P = .007), and HTLV-1c PVL were closely correlated with radiologically determined pulmonary injury scores (Spearman's rho = 0.7457; P = .0000). Other predictors of bronchiectasis were positive Strongyloides serology (aRR, 1.69; 95% CI, 1.13–2.53) and childhood skin infections (aRR, 1.62; 95% CI, 1.07–2.44). Bronchiectasis was the major predictor of death (aRR, 2.71; 95% CI, 1.36–5.39; P = .004). Conclusions. These data strongly support an etiological association between HTLV-1 infection and bronchiectasis in a socially disadvantaged population at risk of recurrent lower respiratory tract infections.

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Adenosine A2A receptors induced on iNKT and NK cells reduce pulmonary inflammation and injury in mice with sickle cell disease

Blood ◽

10.1182/blood-2010-06-290643 ◽

2010 ◽

Vol 116 (23) ◽

pp. 5010-5020 ◽

Cited By ~ 98

Author(s):

Kori L. Wallace ◽

Joel Linden

Keyword(s):

Sickle Cell Disease ◽

Pulmonary Function ◽

Nk Cells ◽

Natural Killer ◽

Sickle Cell ◽

Pulmonary Injury ◽

Cell Disease ◽

Inkt Cells ◽

Adenosine A2a ◽

Hypoxia Reoxygenation

Abstract We showed previously that pulmonary function and arterial oxygen saturation in NY1DD mice with sickle cell disease (SCD) are improved by depletion of invariant natural killer T (iNKT) cells or blockade of their activation. Here we demonstrate that SCD causes a 9- and 6-fold induction of adenosine A2A receptor (A2AR) mRNA in mouse pulmonary iNKT and natural killer (NK) cells, respectively. Treating SCD mice with the A2AR agonist ATL146e produced a dose-dependent reversal of pulmonary dysfunction with maximal efficacy at 10 ng/kg/minute that peaked within 3 days and persisted throughout 7 days of continuous infusion. Crossing NY1DD mice with Rag1−/− mice reduced pulmonary injury that was restored by adoptive transfer of 106 purified iNKT cells. Reconstituted injury was reversed by ATL146e unless the adoptively transferred iNKT cells were pretreated with the A2AR alkylating antagonist, FSPTP (5-amino-7-[2-(4-fluorosulfonyl)phenylethyl]-2-(2-furyl)-pryazolo[4,3-ϵ]-1,2,4-triazolo[1,5-c]pyrimidine), which completely prevented pro-tection. In NY1DD mice exposed to hypoxia-reoxygenation, treatment with ATL146e at the start of reoxygenation prevented further lung injury. Together, these data indicate that activation of induced A2ARs on iNKT and NK cells in SCD mice is sufficient to improve baseline pulmonary function and prevent hypoxia-reoxygenation–induced exacerbation of pulmonary injury. A2A agonists have promise for treating diseases associated with iNKT or NK cell activation.

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