Your browser doesn't support javascript.
Show: 20 | 50 | 100
Results 1 - 20 de 21
Filter
1.
Prostaglandins Leukot Essent Fatty Acids ; 179: 102426, 2022 04.
Article in English | MEDLINE | ID: covidwho-1763934

ABSTRACT

Many current treatment options for lung inflammation and thrombosis come with unwanted side effects. The natural omega-3 fatty acids (O3FA) are generally anti-inflammatory and antithrombotic. O3FA are always administered orally and occasionally by intravenous (IV) infusion. The main goal of this study is to determine if O3FA administered by inhalation of a nebulized formulation mitigates LPS-induced acute lung inflammation in male Wistar rats. Inflammation was triggered by intraperitoneal injection of LPS once a day for 14 days. One hour post-injection, rats received nebulized treatments consisting of egg lecithin emulsified O3, Budesonide and Montelukast, and blends of O3 and Melatonin or Montelukast or Cannabidiol; O3 was in the form of free fatty acids for all groups except one group with ethyl esters. Lung histology and cytokines were determined in n = 3 rats per group at day 8 and day 15. All groups had alveolar histiocytosis severity scores half or less than that of the disease control (Cd) treated with LPS and saline only inhalation. IL-6, TNF-α, TGF-ß, and IL-10 were attenuated in all O3FA groups. IL-1ß was attenuated in most but not all O3 groups. O3 administered as ethyl ester was overall most effective in mitigating LPS effects. No evidence of lipid pneumonia or other chronic distress was observed. These preclinical data suggest that O3FA formulations should be further investigated as treatments in lung inflammation and thrombosis related lung disorders, including asthma, chronic obstructive pulmonary disease, lung cancer and acute respiratory distress such as COVID-19.


Subject(s)
COVID-19 , Fatty Acids, Omega-3 , Pneumonia , Pulmonary Disease, Chronic Obstructive , Animals , COVID-19/drug therapy , Docosahexaenoic Acids/pharmacology , Eicosapentaenoic Acid/pharmacology , Fatty Acids, Omega-3/therapeutic use , Lipopolysaccharides , Male , Pneumonia/chemically induced , Pneumonia/drug therapy , Rats , Rats, Wistar
3.
Int J Mol Sci ; 22(23)2021 Nov 27.
Article in English | MEDLINE | ID: covidwho-1560687

ABSTRACT

Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are severe respiratory disorders that are caused by aspiration, sepsis, trauma, and pneumonia. A clinical feature of ALI/ARDS is the acute onset of severe hypoxemia, and the mortality rate, which is estimated at 38-50%, remains high. Although prostaglandins (PGs) are detected in the bronchoalveolar lavage fluid of patients with ALI/ARDS, the role of PGF2α in ALI remains unclear. We aimed to clarify the role of PGF2α/PGF2α receptor (FP) signaling in acid-induced ALI using an FP receptor antagonist, AL8810. Intratracheal injection of hydrochloric acid (HCl) increased neutrophil migration into the lungs, leading to respiratory dysfunction. Pre-administration of AL8810 further increased these features. Moreover, pre-treatment with AL8810 enhanced the HCl-induced expression of pro-inflammatory cytokines and neutrophil migratory factors in the lungs. Administration of HCl decreased the gene expression of lung surfactant proteins, which was further reduced by co-administration of AL8810. Administration of AL8810 also increased lung edema and reduced mRNA expression of epithelial sodium channel in the lungs, indicating that AL8810 reduced fluid clearance. Furthermore, AL8810 also increased lipopolysaccharide-induced expression of adhesion molecules such as intracellular adhesion molecule-1 and E-selectin in human umbilical vein endothelial cells. These results indicate that inhibition of FP receptors by AL8810 exacerbated HCl-induced ALI.


Subject(s)
Acute Lung Injury/metabolism , Lung/drug effects , Pneumonia/metabolism , Receptors, Prostaglandin/antagonists & inhibitors , Respiratory Distress Syndrome/metabolism , Acute Lung Injury/chemically induced , Acute Lung Injury/pathology , Animals , Disease Models, Animal , Female , Hydrochloric Acid/toxicity , Lung/metabolism , Lung/pathology , Mice , Mice, Inbred C57BL , Pneumonia/chemically induced , Pneumonia/immunology , Pneumonia/pathology , Prostaglandins F/metabolism , Respiratory Distress Syndrome/chemically induced , Respiratory Distress Syndrome/pathology
4.
BMJ Case Rep ; 14(10)2021 Oct 28.
Article in English | MEDLINE | ID: covidwho-1495129

ABSTRACT

Rituximab (RTX) is a monoclonal anti-CD20 antibody used to treat non-Hodgkin's lymphoma. RTX-organising pneumonia (RTX-OP) is a rare complication following treatment with RTX. We report a 49-year-old woman, with CD5-negative B-cell lymphoproliferative disorder who developed high-grade fever, dyspnoea and dry cough 3 days after the first dose of RTX. She responded poorly to antibiotics and antifungal therapy. High-resolution CT (HRCT) of the chest revealed bilateral patchy ground-glass opacities with arcade-like signs suggestive of OP. She was pulsed with intravenous methylprednisolone and RTX was discontinued. She was able to be weaned off the non-invasive ventilation (NIV) support and was discharged with maintenance prednisolone 1 mg/kg and tapered over 6 weeks. A repeated HRCT of the chest at 6 weeks showed a total resolution of OP. This highlights the early occurrence at day 3 of RTX-OP following the first dose of RTX and the complete resolution with steroid therapy.


Subject(s)
Antineoplastic Agents , Pneumonia , B-Lymphocytes , Female , Humans , Middle Aged , Pneumonia/chemically induced , Pneumonia/drug therapy , Prednisolone , Rituximab/adverse effects , Treatment Outcome
5.
Int J Radiat Oncol Biol Phys ; 112(1): 197-211, 2022 01 01.
Article in English | MEDLINE | ID: covidwho-1469874

ABSTRACT

PURPOSE: Low-dose whole lung radiation therapy (LDLR) has been proposed as a treatment for patients with acute respiratory distress syndrome associated with SARS-CoV-2 infection, and clinical trials are underway. There is an urgent need for preclinical evidence to justify this approach and inform dose, scheduling, and mechanisms of action. METHODS AND MATERIALS: Female C57BL/6 mice were treated with intranasal bleomycin sulfate (7.5 or 11.25 units/kg, day 0) and then exposed to whole lung radiation therapy (0.5, 1.0, or 1.5 Gy, or sham; day 3). Bodyweight was measured daily, and lung tissue was harvested for histology and flow cytometry on day 10. Computed tomography lung imaging was performed before radiation (day 3) and pre-endpoint (day 10). RESULTS: Bleomycin caused pneumonitis of variable severity, which correlated with weight loss. LDLR at 1.0 Gy was associated with a significant increase in the proportion of mice recovering to 98% of initial bodyweight, and a proportion of these mice exhibited less severe histopathologic lung changes. Mice experiencing moderate initial weight loss were more likely to respond to LDLR than those experiencing severe initial weight loss. In addition, LDLR (1.0 Gy) significantly reduced bleomycin-induced increases in interstitial macrophages, CD103+ dendritic cells (DCs), and neutrophil-DC hybrids. Overall, bleomycin-treated mice exhibited significantly higher percentages of nonaerated lung in left than right lungs, and LDLR (1.0 Gy) limited further reductions in aerated lung volume in right but not left lungs. LDLR at 0.5 and 1.5 Gy did not improve bodyweight, flow cytometric, or radiologic readouts of bleomycin-induced pneumonitis. CONCLUSIONS: Our data support the concept that LDLR can ameliorate acute inflammatory lung injury, identify 1.0 Gy as the most effective dose, and provide evidence that it is more effective in the context of moderate than severe pneumonitis. Mechanistically, LDLR at 1.0 Gy significantly suppressed bleomycin-induced accumulation of pulmonary interstitial macrophages, CD103+ DCs, and neutrophil-DC hybrids.


Subject(s)
Pneumonia , Radiotherapy , Animals , Bleomycin , COVID-19/radiotherapy , Disease Models, Animal , Female , Humans , Lung/diagnostic imaging , Mice , Mice, Inbred C57BL , Pneumonia/chemically induced , Weight Loss
6.
Zhongguo Fei Ai Za Zhi ; 24(7): 519-525, 2021 Jul 20.
Article in Chinese | MEDLINE | ID: covidwho-1348716

ABSTRACT

BACKGROUND: Immune checkpoint inhibitor associated pneumonia (CIP) is a serious side effect of immune checkpoint inhibitors. There is a consensus on the treatment of acute phase of CIP, but the treatment of pulmonary interstitial fibrosis after the acute phase is still a clinical problem to be solved. METHODS: The diagnosis and treatment of a non-small cell lung cancer (NSCLC) patient with immune checkpoint inhibitor associated pneumonia in the Stereotactic Radiotherapy Department of Qingdao Central Hospital were retrospectively analyzed, and literatures were reviewed. RESULTS: A 70-year-old male patient was diagnosed with Poorly differentiated squamous cell carcinoma of left lung with mediastinal lymph node metastasis T3N3M0 stage IIIc, EGFR/ALK/ROS1/RAF negative, PD-L1 (22c3) immunohistochemistry negative. After the progression of first-line chemotherapy, the patient was diagnosed as immune checkpoint inhibitor associated pneumonia grade 3 during second-line monotherapy with Nivolumab. After initial high-dose glucocorticoid pulse therapy, the lung computed tomography (CT) imaging and clinical symptoms of the patients were partially relieved, and then pirfenidone (300 mg tid) was given orally for more than 11 months. During the treatment of pirfenidone, the CT imaging and clinical symptoms of the patients were significantly improved, and there were no other adverse reactions except grade 1 nausea. During this period, chemotherapy and Anlotinib was given concurrently with pirfenidone and showed good safety profile. CONCLUSIONS: This case report is the first report of pirfenidone in the treatment of CIP, which provides a new idea for the clinical practice and research of CIP treatment.


Subject(s)
Anti-Inflammatory Agents, Non-Steroidal , Carcinoma, Squamous Cell , Immune Checkpoint Inhibitors/adverse effects , Lung Neoplasms , Pneumonia , Pyridones , Aged , Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Antineoplastic Agents/therapeutic use , Carcinoma, Squamous Cell/diagnostic imaging , Carcinoma, Squamous Cell/drug therapy , Carcinoma, Squamous Cell/pathology , Glucocorticoids/therapeutic use , Humans , Immune Checkpoint Inhibitors/therapeutic use , Indoles/therapeutic use , Lung Neoplasms/diagnostic imaging , Lung Neoplasms/drug therapy , Lung Neoplasms/pathology , Male , Nivolumab/adverse effects , Nivolumab/therapeutic use , Pneumonia/chemically induced , Pneumonia/diagnostic imaging , Pneumonia/drug therapy , Programmed Cell Death 1 Receptor/antagonists & inhibitors , Protein Kinase Inhibitors/therapeutic use , Pyridones/therapeutic use , Quinolines/therapeutic use , Retrospective Studies
7.
Pharmacol Res ; 157: 104820, 2020 07.
Article in English | MEDLINE | ID: covidwho-1318923

ABSTRACT

The Coronavirus Disease 2019 (COVID-19) pandemic has become a huge threaten to global health, which raise urgent demand of developing efficient therapeutic strategy. The aim of the present study is to dissect the chemical composition and the pharmacological mechanism of Qingfei Paidu Decoction (QFPD), a clinically used Chinese medicine for treating COVID-19 patients in China. Through comprehensive analysis by liquid chromatography coupled with high resolution mass spectrometry (MS), a total of 129 compounds of QFPD were putatively identified. We also constructed molecular networking of mass spectrometry data to classify these compounds into 14 main clusters, in which exhibited specific patterns of flavonoids (45 %), glycosides (15 %), carboxylic acids (10 %), and saponins (5 %). The target network model of QFPD, established by predicting and collecting the targets of identified compounds, indicated a pivotal role of Ma Xing Shi Gan Decoction (MXSG) in the therapeutic efficacy of QFPD. Supportively, through transcriptomic analysis of gene expression after MXSG administration in rat model of LPS-induced pneumonia, the thrombin and Toll-like receptor (TLR) signaling pathway were suggested to be essential pathways for MXSG mediated anti-inflammatory effects. Besides, changes in content of major compounds in MXSG during decoction were found by the chemical analysis. We also validate that one major compound in MXSG, i.e. glycyrrhizic acid, inhibited TLR agonists induced IL-6 production in macrophage. In conclusion, the integration of in silico and experimental results indicated that the therapeutic effects of QFPD against COVID-19 may be attributed to the anti-inflammatory effects of MXSG, which supports the rationality of the compatibility of TCM.


Subject(s)
Betacoronavirus/drug effects , Coronavirus Infections/drug therapy , Drugs, Chinese Herbal/analysis , Drugs, Chinese Herbal/pharmacology , Drugs, Chinese Herbal/therapeutic use , Pneumonia, Viral/drug therapy , Animals , Anti-Inflammatory Agents/analysis , Anti-Inflammatory Agents/pharmacology , COVID-19 , Cells, Cultured , Computer Simulation , Coronavirus Infections/genetics , Gene Expression/drug effects , Glycyrrhizic Acid/pharmacology , Humans , Interleukin-6/metabolism , Lipopeptides/antagonists & inhibitors , Lipopeptides/pharmacology , Lipopolysaccharides , Male , Pandemics , Pneumonia/chemically induced , Pneumonia/metabolism , Pneumonia, Viral/genetics , Rats , SARS-CoV-2 , Signal Transduction/drug effects , Thrombin/metabolism , Toll-Like Receptors/metabolism
8.
BMJ Case Rep ; 14(7)2021 Jul 15.
Article in English | MEDLINE | ID: covidwho-1315798

ABSTRACT

Pembrolizumab is a selective anti-PD-L1 humanised monoclonal antibody approved by the Food and Drug Administration for treating multiple cancers, including cervical cancer, non-small cell lung cancer (NSCLC), renal cell carcinoma, bladder cancer, and squamous head and neck cancer. Pneumonitis is a rare but known complication of pembrolizumab treatment for NSCLC. The median time frame of its appearance is 2.8 months. However, we present a case of pneumonitis appearing within 48 hours. The patient presented with rapidly progressive respiratory failure, and imaging demonstrated diffuse bilateral patchy involvement of the upper lung lobe and pre-hilar regions, which likely indicate pneumonitis. Because of likely grade 3 pneumonitis, he was treated with steroids and showed immediate improvement of symptoms. Repeated CT imaging showed resolution of bilateral patchy infiltrates. He was discharged to the rehabilitation unit. Rapid recognition of pneumonitis as a side effect of pembrolizumab is important because early treatment can help prevent respiratory failure and possible death.


Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Pneumonia , Antibodies, Monoclonal, Humanized/adverse effects , Carcinoma, Non-Small-Cell Lung/drug therapy , Humans , Lung Neoplasms/drug therapy , Male , Pneumonia/chemically induced
9.
Br J Pharmacol ; 178(21): 4368-4388, 2021 11.
Article in English | MEDLINE | ID: covidwho-1301461

ABSTRACT

BACKGROUND AND PURPOSE: Acute lung injury (ALI), acute respiratory distress syndrome (ARDS) and pulmonary fibrosis remain major causes of morbidity, mortality and a healthcare burden in critically ill patient. There is an urgent need to identify factors causing susceptibility and for the design of new therapeutic agents. Here, we evaluate the effectiveness of the immunomodulatory neuropeptide cortistatin to regulate pulmonary inflammation and fibrosis in vivo. EXPERIMENTAL APPROACH: ALI/ARDS and pulmonary fibrosis were induced experimentally in wild-type and cortistatin-deficient mice by pulmonary infusion of the bacterial endotoxin LPS or the chemotherapeutic drug bleomycin, and the histopathological signs, pulmonary leukocyte infiltration and cytokines, and fibrotic markers were evaluated. KEY RESULTS: Partially deficient mice in cortistatin showed exacerbated pulmonary damage, pulmonary inflammation, alveolar oedema and fibrosis, and subsequent increased respiratory failure and mortality when challenged to LPS or bleomycin, even at low doses. Treatment with cortistatin reversed these aggravated phenotypes and protected from progression to severe ARDS and fibrosis, after high exposure to both injury agents. Moreover, cortistatin-deficient pulmonary macrophages and fibroblasts showed exaggerated ex vivo inflammatory and fibrotic responses, and treatment with cortistatin impaired their activation. Finally, the protective effects of cortistatin in ALI and pulmonary fibrosis were partially inhibited by specific antagonists for somatostatin and ghrelin receptors. CONCLUSION AND IMPLICATIONS: We identified cortistatin as an endogenous inhibitor of pulmonary inflammation and fibrosis. Deficiency in cortistatin could be a marker of poor prognosis in inflammatory/fibrotic pulmonary disorders. Cortistatin-based therapies could emerge as attractive candidates to treat severe ALI/ARDS, including SARS-CoV-2-associated ARDS.


Subject(s)
Inflammation , Neuropeptides , Pneumonia , Animals , Disease Models, Animal , Fibrosis , Inflammation/drug therapy , Inflammation/pathology , Lipopolysaccharides , Lung/pathology , Mice , Neuropeptides/pharmacology , Pneumonia/chemically induced , Pneumonia/drug therapy
11.
Oncology (Williston Park) ; 34(9): 370-376, 2020 09 15.
Article in English | MEDLINE | ID: covidwho-1231670

ABSTRACT

In an asymptomatic 77-yearold woman, former 55 packyears smoker, a routine X-ray showed a 45-mm superior left lobe lesion. A chest CT scan confirmed a 36-mm superior left lobe lesion and an aortic-pulmonary lymph node enlargement measuring 42 mm, suspicious for neoplasia. A PET-CT scan showed an elevated uptake in the primary lesion, in the aortic-pulmonary lymph node, and in the left hilar lymph node with a standardized uptake value - 40 and 4.3, respectively. CT-guided lung biopsy showed a lung squamous cell carcinoma. An endobronchial ultrasound-guided transbronchial needle aspiration for lymph-node staging was negative for lymph node spread. Brain MRI was negative. Final staging was determined to be a IIIA (T2bN2) squamous cell carcinoma of the lung.


Subject(s)
Antibodies, Monoclonal/therapeutic use , Antineoplastic Agents, Immunological/therapeutic use , Carcinoma, Squamous Cell/therapy , Coronavirus Infections/diagnosis , Lung Neoplasms/therapy , Pneumonia, Viral/diagnosis , Pneumonia/diagnosis , Aged , Antibodies, Monoclonal/adverse effects , Antineoplastic Agents, Immunological/adverse effects , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Betacoronavirus , COVID-19 , Carboplatin/administration & dosage , Carcinoma, Squamous Cell/diagnostic imaging , Chemoradiotherapy , Consolidation Chemotherapy , Diagnosis, Differential , Female , Humans , Lung/diagnostic imaging , Lung Neoplasms/diagnostic imaging , Paclitaxel/administration & dosage , Pandemics , Pneumonia/chemically induced , SARS-CoV-2
12.
J Immunother Cancer ; 9(4)2021 04.
Article in English | MEDLINE | ID: covidwho-1209683

ABSTRACT

The clinically indistinguishable overlap between pneumonitis caused due to immune checkpoint inhibition (ICI) and pneumonia associated with COVID-19 has posed considerable challenges for patients with cancer and oncologists alike. The cancer community continues to face the challenges that lay at the complex immunological intersection of immune-based cancer therapy and immune dysregulation that results from COVID-19. Is there compounded immune dysregulation that could lead to poor outcomes? Could ICIs, in fact, ameliorate SARS-CoV-2-driven T-cell exhaustion?A little more is known about the kinetics of the viral replication in immunocompromised patients now as compared with earlier during the pandemic. Working knowledge of the diagnostic and therapeutic nuances of SARS-CoV-2 infection in patients with active cancers, issues related to viability and replication potential of the virus, unclear role of corticosteroids among those with diminished or dysfunctional effector T-cell repertoire, and the type of immunotherapy with differential risk of pneumonitis will inform decision making related to immunotherapy choices and decision for ICI continuation in the era of COVID-19.


Subject(s)
COVID-19/immunology , Immune Checkpoint Inhibitors/therapeutic use , Immunotherapy/methods , Neoplasms/therapy , Pneumonia/immunology , SARS-CoV-2/immunology , Antineoplastic Agents, Immunological/adverse effects , Antineoplastic Agents, Immunological/therapeutic use , COVID-19/prevention & control , COVID-19/virology , COVID-19 Vaccines/immunology , COVID-19 Vaccines/therapeutic use , Diagnosis, Differential , Humans , Immune Checkpoint Inhibitors/adverse effects , Immunocompromised Host/immunology , Immunotherapy/adverse effects , Neoplasms/immunology , Pneumonia/chemically induced , Pneumonia/diagnosis , SARS-CoV-2/physiology , T-Lymphocytes/drug effects , T-Lymphocytes/immunology , T-Lymphocytes/metabolism
13.
J Med Case Rep ; 15(1): 41, 2021 Feb 01.
Article in English | MEDLINE | ID: covidwho-1058271

ABSTRACT

BACKGROUND: Pneumonitis belongs to the fatal toxicities of anti-PD-1/PD-L1 treatments. Its diagnosis is based on immunotherapeutic histories, clinical symptoms, and the computed tomography (CT) imaging. The radiological features were typically ground-glass opacities, similar to CT presentation of 2019 Novel Coronavirus (COVID-19) pneumonia. Thus, clinicians are cautious in differential diagnosis especially in COVID-19 epidemic areas. CASE PRESENTATION: Herein, we report a 67-year-old Han Chinese male patient presenting with dyspnea and normal body temperature on the 15th day of close contact with his son, who returned from Wuhan. He was diagnosed as advanced non-small cell lung cancer and developed pneumonitis post Sintilimab injection during COIVD-19 pandemic period. The chest CT indicated peripherally subpleural lattice opacities at the inferior right lung lobe and bilateral thoracic effusion. The swab samples were taken twice within 72 hours and real-time reverse-transcription polymerase-chain-reaction (RT-PCR) results were COVID-19 negative. The patient was thereafter treated with prednisolone and antibiotics for over 2 weeks. The suspicious lesion has almost absorbed according to CT imaging, consistent with prominently falling CRP level. The anti-PD-1 related pneumonitis mixed with bacterial infection was clinically diagnosed based on the laboratory and radiological evidences and good response to the prednisolone and antibiotics. CONCLUSION: The anti-PD-1 related pneumonitis and COVID-19 pneumonia possess similar clinical presentations and CT imaging features. Therefore, differential diagnosis depends on the epidemiological and immunotherapy histories, RT-PCR tests. The response to glucocorticoid is still controversial but helpful for the diagnosis.


Subject(s)
Antibodies, Monoclonal, Humanized/adverse effects , Antineoplastic Agents, Immunological/adverse effects , COVID-19/diagnosis , Lung Neoplasms/drug therapy , Aged , Diagnosis, Differential , Humans , Male , Medical History Taking , Pneumonia/chemically induced , Pneumonia/diagnosis , Programmed Cell Death 1 Receptor/antagonists & inhibitors , Reverse Transcriptase Polymerase Chain Reaction , SARS-CoV-2 , Tomography, X-Ray Computed
14.
Cell Death Dis ; 12(1): 53, 2021 01 07.
Article in English | MEDLINE | ID: covidwho-1015001

ABSTRACT

Interleukin-38 has recently been shown to have anti-inflammatory properties in lung inflammatory diseases. However, the effects of IL-38 in viral pneumonia remains unknown. In the present study, we demonstrate that circulating IL-38 concentrations together with IL-36α increased significantly in influenza and COVID-19 patients, and the level of IL-38 and IL-36α correlated negatively and positively with disease severity and inflammation, respectively. In the co-cultured human respiratory epithelial cells with macrophages to mimic lung microenvironment in vitro, IL-38 was able to alleviate inflammatory responses by inhibiting poly(I:C)-induced overproduction of pro-inflammatory cytokines and chemokines through intracellular STAT1, STAT3, p38 MAPK, ERK1/2, MEK, and NF-κB signaling pathways. Intriguingly, transcriptomic profiling revealed that IL-38 targeted genes were associated with the host innate immune response to virus. We also found that IL-38 counteracts the biological processes induced by IL-36α in the co-culture. Furthermore, the administration of recombinant IL-38 could mitigate poly I:C-induced lung injury, with reduced early accumulation of neutrophils and macrophages in bronchoalveolar lavage fluid, activation of lymphocytes, production of pro-inflammatory cytokines and chemokines and permeability of the alveolar-epithelial barrier. Taken together, our study indicates that IL-38 plays a crucial role in protection from exaggerated pulmonary inflammation during poly(I:C)-induced pneumonia, thereby providing the basis of a novel therapeutic target for respiratory viral infections.


Subject(s)
COVID-19/metabolism , Immunity, Innate/drug effects , Influenza, Human/metabolism , Interleukins/pharmacology , Pneumonia/prevention & control , Poly I-C/toxicity , Respiratory System/immunology , Animals , COVID-19/immunology , COVID-19/virology , Cytokines/metabolism , Epithelial Cells/immunology , Epithelial Cells/metabolism , Epithelial Cells/pathology , Humans , Influenza A virus/isolation & purification , Influenza, Human/immunology , Influenza, Human/virology , Interleukin-1/blood , Interleukins/blood , Male , Mice , Mice, Inbred C57BL , Pneumonia/chemically induced , Pneumonia/immunology , Pneumonia/pathology , Respiratory System/metabolism , Respiratory System/pathology , SARS-CoV-2/isolation & purification
15.
Expert Opin Drug Saf ; 20(6): 651-667, 2021 Jun.
Article in English | MEDLINE | ID: covidwho-1006304

ABSTRACT

Introduction: Immune checkpoint inhibitors (ICIs) achieved response rates around 20% in advanced non-small cell lung cancer (NSCLC) with 8% of patients becoming long-term survivors. Outcomes have improved with the addition of chemotherapy to immunotherapy or the combination of anti-PD(L)1 with anti-CTLA-4 agents.Areas covered: The incidence of immune-related adverse events (irAEs) in patients with NSCLC treated with ICIs varied across clinical trials and real-life studies. The onset of irAEs was 10 weeks. Toxic deaths from irAEs following anti-PD(L)1 administration resulted mainly from pneumonitis. Some irAEs such as rash and thyroiditis were probably associated with better clinical outcomes, though confounding biases exist. Investigations are on-going to determine ideal biomarkers to predict the occurrence, to screen for and to diagnose irAEs.Expert opinion: Prevention, anticipation, detection, treatment and careful monitoring are the five principles that characterize our management of irAEs. Distinguishing immune-induced pneumonitis from progression, pseudo progression, hyper progression, or other etiologies (COVID-19) can be particularly challenging in lung cancer due to the baseline vulnerable pulmonary function and thus requires caution and teamwork. We treat patients according to institutional and international guidelines and we only rechallenge them with ICIs after resolution of the AE and corticosteroid tapering.


Subject(s)
Carcinoma, Non-Small-Cell Lung/drug therapy , Exanthema/chemically induced , Immune Checkpoint Inhibitors/adverse effects , Lung Neoplasms/drug therapy , Pneumonia/chemically induced , Thyroiditis/chemically induced , Adrenal Cortex Hormones/therapeutic use , COVID-19/diagnosis , Diagnosis, Differential , Disease Progression , Drug-Related Side Effects and Adverse Reactions , Exanthema/drug therapy , Exanthema/immunology , Humans , Immune Checkpoint Inhibitors/therapeutic use , Pneumonia/diagnosis , Pneumonia/drug therapy , Pneumonia/immunology , Practice Guidelines as Topic , SARS-CoV-2 , Thyroiditis/drug therapy , Thyroiditis/immunology
17.
J Am Heart Assoc ; 9(18): e017368, 2020 09 15.
Article in English | MEDLINE | ID: covidwho-748837

ABSTRACT

E-cigarette or vaping product use-associated lung injury was recognized in the United States in the summer of 2019 and is typified by acute respiratory distress, shortness of breath, chest pain, cough, and fever, associated with vaping. It can mimic many of the manifestations of coronavirus disease 2019 (COVID-19). Some investigators have suggested that E-cigarette or vaping product use-associated lung injury was due to tetrahydrocannabinol or vitamin E acetate oil mixed with the electronic cigarette liquid. In experimental rodent studies initially designed to study the effect of electronic cigarette use on the cardiovascular system, we observed an E-cigarette or vaping product use-associated lung injury-like condition that occurred acutely after use of a nichrome heating element at high power, without the use of tetrahydrocannabinol, vitamin E, or nicotine. Lung lesions included thickening of the alveolar wall with foci of inflammation, red blood cell congestion, obliteration of alveolar spaces, and pneumonitis in some cases; bronchi showed accumulation of fibrin, inflammatory cells, and mucus plugs. Electronic cigarette users should be cautioned about the potential danger of operating electronic cigarette units at high settings; the possibility that certain heating elements may be deleterious; and that E-cigarette or vaping product use-associated lung injury may not be dependent upon tetrahydrocannabinol, vitamin E, or nicotine.


Subject(s)
Dronabinol/toxicity , E-Cigarette Vapor/toxicity , Electronic Nicotine Delivery Systems , Lung Injury/chemically induced , Lung/drug effects , Pneumonia/chemically induced , Vaping/adverse effects , Vitamin E/toxicity , Animals , Inhalation Exposure , Lung/pathology , Lung Injury/pathology , Models, Animal , Oils , Pneumonia/pathology , Rats , Risk Assessment
18.
Am J Case Rep ; 21: e927586, 2020 Aug 25.
Article in English | MEDLINE | ID: covidwho-729776

ABSTRACT

BACKGROUND Rifampicin-induced pneumonitis is an infrequent occurrence, with only a few cases reported in the literature. Furthermore, this condition constitutes a diagnostic challenge, particularly in the era of COVID-19 infection. Here, we report a case of rifampicin-induced pneumonitis with clinical, imaging, and histological features of acute respiratory distress syndrome (ARDS), which required severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) testing to exclude a diagnosis of coronavirus disease 2019 (COVID-19) pneumonia. CASE REPORT A 43-year-old man on anti-TB treatment for TB meningitis developed new-onset fever, fatigue, hypoxemic respiratory failure, and bilateral pulmonary opacities. His clinical, chest X-ray, and CT thorax findings of ARDS were similar to both rifampicin-induced pneumonitis and severe COVID-19 pneumonia. However, reverse transcription polymerase chain reaction (RT-PCR) testing from a nasopharyngeal swab and bronchoalveolar lavage (BAL) via the GeneXpert system was negative for SARS-CoV-2. A detailed workup, including lung biopsy, revealed drug-induced pneumonitis as the cause of his presentation. His pneumonitis improved after discontinuation of rifampicin and recurred following the rifampicin challenge. CONCLUSIONS This case highlights the importance of early, rapid, and accurate testing for SARS-CoV-2 during the COVID-19 pandemic for patients presenting with acute respiratory symptoms, so that accurate diagnosis and early patient management are not delayed for patients with treatable causes of acute and severe lung diseases. Timely identification of rifampicin-induced pneumonitis via a high clinical suspicion, detailed workup, and histopathological analysis is required to avoid permanent damage to the lungs.


Subject(s)
Coronavirus Infections/complications , Pneumonia, Viral/complications , Pneumonia/chemically induced , Rifampin/adverse effects , Tomography, X-Ray Computed/methods , Tuberculosis, Meningeal/drug therapy , Adult , Antibiotics, Antitubercular/adverse effects , Betacoronavirus , COVID-19 , Coronavirus Infections/epidemiology , Humans , Male , Pandemics , Pneumonia/diagnosis , Pneumonia, Viral/epidemiology , SARS-CoV-2 , Tuberculosis, Meningeal/complications
19.
J Immunother Cancer ; 8(2)2020 07.
Article in English | MEDLINE | ID: covidwho-662488

ABSTRACT

Pneumonitis is a rare but serious adverse event caused by cancer immunotherapy. The diagnosis between COVID-19-induced pneumonia and immunotherapy-induced pneumonitis may be challenging in the era of COVID-19 outbreak. Some clinical symptoms and radiological findings of pneumonitis can be attributed to the coronavirus infection as well as to an immune-related adverse event. Identifying the exact cause of a pneumonitis in patients on treatment with immunotherapy is crucial to promptly start the most appropriate treatment. The proper management of immune checkpoint inhibitors for the risk of pneumonia must take into account a series of parameters. Accurate attention should be payed to symptoms like cough, fever and dyspnea during immunotherapy.


Subject(s)
Antineoplastic Agents, Immunological/adverse effects , Coronavirus Infections/diagnosis , Neoplasms/drug therapy , Pneumonia, Viral/diagnosis , Pneumonia/chemically induced , Pneumonia/diagnosis , Betacoronavirus , COVID-19 , COVID-19 Testing , CTLA-4 Antigen/antagonists & inhibitors , Clinical Laboratory Techniques , Coronavirus Infections/immunology , Coronavirus Infections/therapy , Diagnosis, Differential , False Negative Reactions , Glucocorticoids/therapeutic use , Humans , Immunosuppressive Agents/therapeutic use , Lung/diagnostic imaging , Pandemics , Pneumonia/drug therapy , Pneumonia/immunology , Pneumonia, Viral/immunology , Pneumonia, Viral/therapy , Programmed Cell Death 1 Receptor/antagonists & inhibitors , Reverse Transcriptase Polymerase Chain Reaction , SARS-CoV-2 , Tomography, X-Ray Computed
20.
J Immunother Cancer ; 8(1)2020 06.
Article in English | MEDLINE | ID: covidwho-607910

ABSTRACT

Immune-related (IR)-pneumonitis is a rare and potentially fatal toxicity of anti-PD(L)1 immunotherapy. Expert guidelines for the diagnosis and management of IR-pneumonitis include multidisciplinary input from medical oncology, pulmonary medicine, infectious disease, and radiology specialists. Severe acute respiratory syndrome coronavirus 2 is a recently recognized respiratory virus that is responsible for causing the COVID-19 global pandemic. Symptoms and imaging findings from IR-pneumonitis and COVID-19 pneumonia can be similar, and early COVID-19 viral testing may yield false negative results, complicating the diagnosis and management of both entities. Herein, we present a set of multidisciplinary consensus recommendations for the diagnosis and management of IR-pneumonitis in the setting of COVID-19 including: (1) isolation procedures, (2) recommended imaging and interpretation, (3) adaptations to invasive testing, (4) adaptations to the management of IR-pneumonitis, (5) immunosuppression for steroid-refractory IR-pneumonitis, and (6) management of suspected concurrent IR-pneumonitis and COVID-19 infection. There is an emerging need for the adaptation of expert guidelines for IR-pneumonitis in the setting of the global COVID-19 pandemic. We propose a multidisciplinary consensus on this topic, in this position paper.


Subject(s)
Antineoplastic Agents, Immunological/adverse effects , Betacoronavirus/immunology , Coronavirus Infections/prevention & control , Pandemics/prevention & control , Pneumonia, Viral/prevention & control , Pneumonia/therapy , Practice Guidelines as Topic , B7-H1 Antigen/antagonists & inhibitors , B7-H1 Antigen/immunology , COVID-19 , Consensus , Coronavirus Infections/epidemiology , Coronavirus Infections/transmission , Coronavirus Infections/virology , Humans , Infectious Disease Medicine/standards , Interdisciplinary Communication , Lung/diagnostic imaging , Lung/drug effects , Lung/immunology , Medical Oncology/standards , Neoplasms/drug therapy , Neoplasms/immunology , Pneumonia/chemically induced , Pneumonia/diagnosis , Pneumonia/immunology , Pneumonia, Viral/epidemiology , Pneumonia, Viral/transmission , Pneumonia, Viral/virology , Pulmonary Medicine/standards , Radiology/standards , SARS-CoV-2 , United States/epidemiology
SELECTION OF CITATIONS
SEARCH DETAIL