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Hydrogen peroxide is a chemical commonly used as a household antiseptic for cleaning and disinfecting. No cases of acute hydrogen peroxide inhalation-induced lung injury are previously described. We present a case of acute chemical pneumonitis caused by mixing hydrogen peroxide in a nighttime continuous positive airway pressure device's humidifier used for obstructive sleep apnea to prevent COVID-19 infection. The patient endorsed mixing hydrogen peroxide with distilled water in his nighttime continuous positive airway pressure device's humidifier at a ratio of 1:3-1:2 for the previous week before admission based on a friend's advice in preventing COVID-19. The presenting chest X-ray showed new multifocal consolidations with interstitial markings and alveolar edema throughout both lungs. Chest computed tomography (CT) imaging demonstrated multifocal, bilateral, hazy consolidations with increased interstitial markings and bilateral pleural effusions. The patient was subsequently initiated on systemic glucocorticoid therapy, significantly improving hypoxemia and dyspnea. Inhalation of hydrogen peroxide may produce acute pneumonitis distinct from what has been described previously with chronic inhalation. Given this case, systemic glucocorticoid therapy may be considered a viable treatment option for acute hydrogen peroxide-associated inhalation lung injury causing pneumonitis.
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During current COVID-19 pandemic health care professionals as well as general communities all over the world have become much more aware about the importance of such basic physiological functions as breathing and the essential nature of intact respiratory system for our proper functioning and survival. Treatment of severe forms of respiratory failure puts enormous personal, material as well as financial strains on health care systems even in countries of the developed world. Since the beginning of COVID-19 pandemic scientists and physicians alike are putting vast efforts into developing effective treatment plans to fight this new disease, yet many times with dubious effect. With repurposing old drugs and development of new ones, concerns of potential lung toxicity as a side effect of medication use pose a serious concern. Currently there are several hundred medications known to us which can exert various toxic effects on the respiratory system. As such, in every day clinical practice it is extremely important to identify and minimize the chances of morbidity and mortality induced by medications used in treatment of pulmonary diseases as well as non-pulmonary illnesses. In most cases the diagnosis of drug induced pulmonary toxicity is done by exclusion after all other etiologies of lung compromise have been eliminated. Transbronchial or even open surgical lung biopsy is in many times only of limited value on changing the treatment strategy, however it frequently poses a significant risk of developing pre and post-operative complications. It has to be cautiously considered on individual basis after evaluating potential risks and benefits of the intervention. Apart from affecting the pulmonary parenchyma drugs can exert their toxic effects on pulmonary vascular system, pleura, mediastinal structures as well as on the neuromuscular system driving and executing the respiratory effort. In conclusion, prior to initiating any medication therapy it is paramount to estimate the potential risks and benefits on the pulmonary system and notify the patient in order to make an adequate informed decision regarding starting or declining specific medical intervention (Tab. 3, Ref. 45). Text in PDF www.lekarsky.herba.sk. (http://www.lekarsky.herba.sk.) © 2022, Lekarsky Obzor.All Rights Reserved.
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SESSION TITLE: Signs and Symptoms of Chest Disease Case Report Posters SESSION TYPE: Case Report Posters PRESENTED ON: 10/19/2022 12:45 pm - 01:45 pm INTRODUCTION: Vaping products have been rapidly gaining popularity, with studies showing increasing use, even among school-going children and adolescents. E-cigarette or Vaping Associated Lung Injury (EVALI) is defined as respiratory failure within 90 days of e-cigarette use with pulmonary infiltrates on imaging, in the absence of infectious or alternative causes of respiratory failure.[1] Vitamin E acetate, a thickening agent in THC containing e-cigarettes, is thought to be the main causative agent of EVALI and has been found in the bronchoalveolar lavage samples in almost all cases of EVALI.[2] However, diagnosing EVALI in this era of COVID -19 is a challenge due to striking similarities in clinical symptoms and imaging findings. CASE PRESENTATION: A 32-year-old male with anxiety and polysubstance abuse, presented with headache, cough, low-grade fevers and chills of 1 week. In the ED, he was febrile to 102 F and hypoxic to 89% on room air and was started on 3 liters of oxygen. Labs showed leukocytosis and elevated inflammatory markers. Urine toxicology was positive for THC. Chest X-ray showed bilateral interstitial opacities. CT angio of the chest showed bilateral ground glass opacities. Despite 2 negative PCR tests, suspicion for COVID was high and the patient was initially started on dexamethasone and other supplements, along with antibiotic coverage for a possible bacterial etiology. Despite this, respiratory symptoms and hypoxia continued to worsen. Infectious work up including blood, sputum cultures with AFB staining, urine streptococcus and legionella tested negative. The patient however now revealed the regular use of THC containing vape and procuring the THC oil from a new street vendor. This prompted us to suspect vaping induced chemical pneumonitis. He was restarted on steroid therapy with methylprednisolone and within 1 week, had symptomatic improvement and resolution of hypoxia. The patient was eventually discharged on prednisone taper over 7-10 days. DISCUSSION: Our patient was initially treated for COVID pneumonia despite repeated negative PCR tests, as findings were suggestive of SARS-COV-2 infection. Fortunately, the patient eventually revealed about regular use of THC-oil vapes, making us consider a diagnosis of vaping induced chemical pneumonitis. The mainstay of treatment is steroid therapy and cessation of e-cigarette use. The severity of the pandemic has led to a low threshold for suspecting COVID, causing increased anchoring and availability bias, and potentially under-diagnosing conditions like EVALI which resemble COVID infection.[3] CONCLUSIONS: While it is important to have a low threshold for suspecting COVID-19, considering other mimics of COVID is prudent for providing treatment in an appropriate and timely manner. Detailed inquiry of e-cigarette use, particularly THC-oil containing vapes, duration of use and source of procurement, goes a long way in diagnosing of EVALI. Reference #1: EVALI and the Pulmonary Toxicity of Electronic Cigarettes: A Review Lydia Winnicka, MD and Mangalore Amith Shenoy, MD PMCID: PMC7351931 PMID: 32246394 Reference #2: Clinical presentation, treatment, and short-term outcomes of lung injury associated with e-cigarettes or vaping: a prospective observational cohort study Denitza P Blagev 1, Dixie Harris 2, Angela C Dunn 3, David W Guidry 2, Colin K Grissom 4, Michael J Lanspa 5 PMID: 31711629 DOI: 10.1016/S0140-6736(19)32679-0 Reference #3: EVALI: A Mimicker of COVID-19 Mitchell M. Pitlick, MD,a Daenielle K. Lang, MD,a Anne M. Meehan, MBBCh, PhD,b and Christopher P. McCoy, MDb, PMCID: PMC8006188 PMID: 33817560 DISCLOSURES: No relevant relationships by Kaushik Darbha No relevant relationships by Rashmikant Doshi No relevant relationships by Ishan Sahu No relevant relationships by sara samad
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SESSION TITLE: Drug-Induced Lung Injury Pathology Case Posters SESSION TYPE: Case Report Posters PRESENTED ON: 10/19/2022 12:45 pm - 01:45 pm INTRODUCTION: The most dangerous complication of amiodarone use is amiodarone-induced pulmonary toxicity (AIPT) (1). AIPT has no pathognomonic findings & is therefore diagnosed based on clinical suspicion & exclusion of other possible pulmonary diseases (2) CASE PRESENTATION: A 91-year-old female with history of CHF & atrial fibrillation on amiodarone 200mg once daily for approximately 10 years, presented for worsening shortness of breath for 3 days. On admission vitals were stable & pulse oximetry revealed a SpO2 of 89% on room air which increased to 96% on 4 litres oxygen. Examination revealed decreased breath sounds at bases, bilateral rales right>left. No clinical signs of fluid overload. Chest x-ray (fig 1) showed increased bilateral airspace opacities and computed tomography (CT) of chest (fig 3) revealed diffuse airspace opacities, right > left. Initial lab work was within normal limits. She was admitted with a working diagnosis of acute hypoxemic respiratory failure due to community acquired pneumonia (CAP) versus COVID-19 pneumonia due to high suspicion based on her clinical picture. She received remdesvir, empiric antibiotics and amiodarone was discontinued. COVID-19 PCR was negative, patient did not spike fevers or had any leukocytosis & pneumonia workup was negative. Therefore we now considered AIPT. Gallium scan for AIPT revealed abnormal uptake involving lungs bilaterally consistent with AIPT. Patient was continued on dexamethasone, after which patient's oxygen requirement subsequently decreased & repeat chest x-ray (fig 2 ) showed a significant decrease in bilateral infiltrates on steroids. She was discharged home on 2 litres oxygen & prednisone taper for 4 months. DISCUSSION: The advent of the highly contagious SARS-CoV-2 has made it further essential to diagnose AIPT correctly & to differentiate between these two entities. They have similar & non-specific features which makes this an even a greater challenge. Our elderly patient on long-term amiodarone use represents an at-risk group for AIPT (1). Her clinical picture was non-specific, initially suggesting CAP versus COVID-19 pneumonia. In our case, the consistent gallium scan findings confirmed the diagnosis of AIPT & enabled prompt anti-inflammatory treatment along with cessation of amiodarone which resulted in improved prognosis & outcome. AIPT should be suspected in patients taking amiodarone who have new or worsening symptoms with an insidious onset &/or new infiltrates on chest x-ray. Greater parenchymal activity on gallium scintigraphy scanning & the presence of lung biopsy findings can help further confirm the diagnosis (1) CONCLUSIONS: In the era of the COVID-19 pandemic, it becomes even more challenging to diagnose and differentiate AIPT from SARS-CoV-2 pneumonia, which can have a similar presentation (3). Early recognition of AIPT is critical to prevent or minimize its potentially devastating pulmonary effects. Reference #1: Martin, W. J., & Howard, D. M. (1985). Amiodarone-induced lung toxicity: In vitro evidence for the direct toxicity of the drug. American Journal of Pathology, 120(3), 344–350. Reference #2: Benassi, F., Molardi, A., Righi, E. et al. ECMO for pulmonary rescue in an adult with amiodarone-induced toxicity. Heart Vessels 30, 410–415 (2015). Reference #3: Macera M, De Angelis G, Sagnelli C, Coppola N, Vanvitelli Covid-Group. Clinical Presentation of COVID-19: Case Series and Review of the Literature. Int J Environ Res Public Health. 2020 Jul 14;17(14):5062. DISCLOSURES: No relevant relationships by Nayaab Bakshi No relevant relationships by Navjot Kaur Grewal No relevant relationships by Talha Munir No relevant relationships by Anusha Singhania
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SESSION TITLE: Drug-Induced and Associated Critical Care Cases Posters 2 SESSION TYPE: Case Report Posters PRESENTED ON: 10/19/2022 12:45 pm - 01:45 pm INTRODUCTION: Lung toxicity due to antineoplastic therapy is reported with both cytotoxic and molecularly targeted agents [1]. We present one such case of lung injury induced by capecitabine. CASE PRESENTATION: A 79-year-old female with history of triple negative infiltrating duct carcinoma of the right breast (status post mastectomy and adjuvant chemotherapy with docetaxel and cyclophosphamide 3 years prior) presented to the hospital with dyspnea on exertion following her fourth cycle of capecitabine therapy for breast cancer recurrence. Patient developed nausea, vomiting, and malaise with cycles 1, 2, and 3 of capecitabine therapy with onset of severe dyspnea on exertion, cough, and hypoxia following cycle 4. Computed tomography (CT) scan of the chest on admission showed consolidative opacities in the right upper, right middle, and anterior right lower lobe along with smaller opacities in the left lung apex and small subcentimeter nodules;no pulmonary embolism. Antibiotics were given for a short duration for suspected pneumonia without improvement. Capecitabine was held on discharge. She presented again to the emergency room with worsening shortness of breath, diarrhea, fatigue, and dizziness. COVID test was negative. Chest x-ray redemonstrated patchy airspace disease involving the right apical, lateral, mid lower lung field. Oral steroids were recommended for suspected organizing pneumonia, but the patient refused due to concerns about side effects. Her hospital course was complicated by Clostridium difficile infection (treated with oral vancomycin) and left lower extremity deep venous thrombosis (treated with anticoagulation). Subsequently she followed up with pulmonology outpatient. Repeat imaging showed evolving infiltrates in the same areas with elevated aspergillus IgG level (18.0 mcg/ml) and IgE (178 kU/L) but negative galactomannan and sputum bacterial/fungal/acid fast cultures. Oral steroids were initiated with clinical and symptomatic improvement. DISCUSSION: Capecitabine is a prodrug of fluorouracil (antimetabolite). It is used as a chemotherapy agent in multiple types of cancer including breast cancer. Respiratory side effects include cough (<7%) and bronchitis (<5%). Lung injury/pneumonitis is a rare complication with only a few cases reported to date [2,3]. The timing of symptoms with chemotherapy administration and the negative infectious work-up supports capecitabine as the inciting etiology of lung injury. Withholding chemotherapy and starting systemic steroids were effective treatments in this case of chemotherapy induced lung toxicity. CONCLUSIONS: Capecitabine induced lung injury is a rare but important entity and should always be kept in mind while evaluating dyspnea in cancer patients. Reference #1: Capri G, Chang J, et al. An open-label expanded access study of lapatinib and capecitabine in patients with HER2-overexpressing locally advanced or metastatic breast cancer. Ann Oncol. 2010;21(3):474. Epub 2009 Oct 8. DOI: 10.1093/annonc/mdp373 Reference #2: C. J. Benthin, G. Allada. Capecitabine-Induced Lung Injury. American Journal of Respiratory and Critical Care Medicine 2016;193:A1653. Reference #3: Andrew K Chan, Bok A Choo, John Glaholm. Pulmonary toxicity with oxaliplatin and capecitabine/5-Fluorouracil chemotherapy: a case report and review of the literature. Onkologie. 2011;34(8-9):443-6. doi: 10.1159/000331133. Epub 2011 Aug 19. DISCLOSURES: No relevant relationships by William Karkowsky No relevant relationships by Chahat Puri No relevant relationships by Sahib Singh
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SESSION TITLE: Drug-Induced Lung Injury and Disease SESSION TYPE: Rapid Fire Case Reports PRESENTED ON: 10/18/2022 01:35 pm - 02:35 pm INTRODUCTION: Lomustine, a nitrosurea, inhibits DNA, RNA, and protein synthesis by carbamylation and alkylation, leading to cytotoxic effects 1, 3. Its concentration is high in the central nervous system (CNS) and therefore is commonly used for the management of CNS tumors including recurrent glioblastoma. While known side effects include pancytopenia, few pulmonary toxicities have been reported. This case is a rare example of lomustine induced pneumonitis. CASE PRESENTATION: A 54-year-old female with a history of glioblastoma, treated with a combination of surgical resection, radiation therapy, and temozolomide followed by stereotactic surgery and bevacizumab after disease recurrence, developed progressive dyspnea after initiating lomustine. She had received one dose of lomustine 90 mg/m2 two months prior to developing dyspnea upon exertion. At baseline, she was an active individual who played sports. A chest computed tomography (CT) scan preformed ten months prior was without any parenchymal abnormalities, and pulmonary function tests (PFTs) two months prior were normal with an adjusted DLCO of 15.4 mL/mmHg/min (88%). Repeat chest CT revealed diffuse ground glass opacities, and repeat PFTs showed a moderately impaired adjusted DLCO of 10.4 mL/mmHg/min (60%). Other lab evaluation, CBC, BNP, troponin, and COVID PCR, were negative. After receiving six weeks of steroids, there was resolution of CT findings, improvement of DLCO, and relief from symptoms. DISCUSSION: More common adverse effects of lomustine are GI discomfort and pancytopenia. It is less widely documented to cause pulmonary toxicity compared to its chemical relative carmustine 1, 3. This is perhaps due to decreased alkylation ability and penetration into the lung tissue by lomustine7. There have been few case reports revealing pneumonitis and pulmonary fibrosis. Lomustine induced pneumonitis induces acute parenchymal changes of the lung demonstrated by characteristic symptoms and imaging/biopsies abnormalities after initiation of a drug. 2 Findings include breathlessness, dyspnea upon exertion, cough, hypoxia, crackles upon lung auscultation. PFT's may show a restrictive pattern with decreased FEV1/FVC ratio and DLCO. Imaging may reveal diffuse groundglass opacities, traction bronchiectasis, interlobular septal thickening, and honeycombing. Bronchoscopy with lavage would rule out infection. Management involves discontinuation of culprit medication, immunosuppression, and supportive therapies to alleviate respiratory discomfort. Lack of treatment may produce complications of acute respiratory distress syndrome and fibrosis. CONCLUSIONS: Lomustine is an essential treatment drug for recurrent CNS tumors. Toxicities such as pneumonitis have been rarely demonstrated. Timely recognition of pneumonitis features is key to treat this complication, improve quality of life, and prevent permanent lung compromise. Reference #1: Dent RG. Fatal pulmonary toxic effects of lomustine. British medical journal. 1982;DOI:10.1136/thx.37.8.627 Reference #2: Skeoch S, Weatherley N, Swift AJ, Oldroyd A, Johns C, Hayton, C, et al. Drug-Induced Interstitial Lung Disease: A Systemic Review. Journal of Clinical Medicine. 2018;doi 10.3390/jcm7100356 Reference #3: Weiss RB, Issell BF. The nitrosureas: carmustine and lomustine. Cancer treatment reviews. 1982;https://doi.org/10.1016/S0305-7372(82)80043-1 DISCLOSURES: No relevant relationships by Sukhdeep Kaur No relevant relationships by Chelsea Kennedy-Snodgrass No relevant relationships by Sarun Thomas
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Purpose or Objective Evaluation of the incidence of pulmonary toxicities, especially pneumonitis, for patients treated in a real setting with concurrent chemoradiation (CRT) followed by adjuvant durvalumab for unresectable stage III non-small-cell lung cancer (NSCLC). Materials and Methods This study included retrospectively 84 patients with unresectable stage III NSCLC treated by CRT followed by durvalumab in 5 french centers from May 2017 to May 2021. Pneumonitis incidence was analysed with a distinction between immune pneumonitis, lung infection and radiation pneumonitis. A multivariate analysis was realized for radiation pneumonitis to find predictive factors. Overall survival (OS) and Progression Free Survival (PFS) were also evaluated. Results With a median follow-up of 23 months, grade 3-4 pneumonitis were as follows: 3.4% of radiation pneumonitis, 5.9% of immune pneumonitis and 13.4% of lung infections. . In multivariate analysis, age ≥ 68 years-old, cardiovascular history and use of docetaxel came out as predictive factors for radiation pneumonitis.Considering the entire population, median PFS was 28.9 months and the 2-year OS was 70.8%. Besides, among our population study, 31% of patients presented at least one or more exclusion or non-inclusion criteria according to initial PACIFIC protocol. But there was no difference between the patients who meet the PACIFIC criteria and the others, whether for toxicity or survivals. The beginning of the durvalumab consolidation within 14 days after ending CRT seemed to improve the PFS according to PACIFIC’s findings. Conclusion In our real-word study, incidence of grade 3-4 radiation pneumonitis and immune pneumonitis are similar to those in the PACIFIC trial. Incidence of lung infections was higher, probably because of the context of SARS-CoV-2 pandemic. Age ≥ 68 years-old, cardiovascular history and use of docetaxel were found to be predictive factors for radiation pneumonitis. Moreover, PFS and OS were excellent
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The evaluation of inhalation toxicity, drug safety and efficacy assessment, as well as the investigation of complex disease pathomechanisms, are increasingly relying on in vitro lung models. This is due to the progressive shift towards human-based systems for more predictive and translational research. While several cellular models are currently available for the upper airways, modelling the distal alveolar region poses several constraints that make the standardization of reliable alveolar in vitro models relatively difficult. In this work, we present a new and reproducible alveolar in vitro model, that combines a human derived immortalized alveolar epithelial cell line (AXiAEC) and organ-on-chip technology mimicking the lung alveolar biophysical environment (AXlung-on-chip). The latter mimics key features of the in vivo alveolar milieu: breathing-like 3D cyclic stretch (10% linear strain, 0.2 Hz frequency) and an ultrathin, porous and elastic membrane. AXiAECs cultured on-chip were characterized for their alveolar epithelial cell markers by gene and protein expression. Cell barrier properties were examined by TER (Transbarrier Electrical Resistance) measurement and tight junction formation. To establish a physiological model for the distal lung, AXiAECs were cultured for long-term at air-liquid interface (ALI) on-chip. To this end, different stages of alveolar damage including inflammation (via exposure to bacterial lipopolysaccharide) and the response to a profibrotic mediator (via exposure to Transforming growth factor ß1) were analyzed. In addition, the expression of relevant host cell factors involved in SARS-CoV-2 infection was investigated to evaluate its potential application for COVID-19 studies. This study shows that AXiAECs cultured on the AXlung-on-chip exhibit an enhanced in vivo-like alveolar character which is reflected into: 1) Alveolar type 1 (AT1) and 2 (AT2) cell specific phenotypes, 2) tight barrier formation (with TER above 1,000 Ω cm2) and 3) reproducible long-term preservation of alveolar characteristics in nearly physiological conditions (co-culture, breathing, ALI). To the best of our knowledge, this is the first time that a primary derived alveolar epithelial cell line on-chip representing both AT1 and AT2 characteristics is reported. This distal lung model thereby represents a valuable in vitro tool to study inhalation toxicity, test safety and efficacy of drug compounds and characterization of xenobiotics.
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Introduction: First synthesized in 1869, Hydroxyurea is known for its efficacy in treating myeloproliferative disorders, cervical cancer, and sickle cell disease. Usually well-tolerated, Hydroxyurea has numerous documented adverse effects, including bone marrow suppression, fevers, gastrointestinal upset, anorexia, and maculopapular rash. In addition, one rare side effect is interstitial pneumonitis, a potentially devastating complication if overlooked. We present one such case of Hydroxyurea-induced interstitial pneumonitis. Case Description: A 65-year-old man with a six-month diagnosis of Chronic Granulocytic Leukemia (CGL) on Hydroxyurea developed acute hypoxemic respiratory failure saturating 80% on room air with HR 102, RR 24, and increasing oxygen requirements (10 Lpm) after being admitted with complaints of worsening dyspnea, fatigue, and productive cough with yellow/green sputum. Physical examination was notable for cachexia, ill appearance, generalized weakness, hoarse voice, tachycardia, tachypnea, diffusely diminished breath sounds, and scattered rales on auscultation of lung fields. Initial imaging was notable for bilateral airspace disease and pulmonary opacities on chest radiography and bilateral pneumonia (concerning for COVID-19 pneumonia), mediastinal adenopathy, and splenomegaly on chest computed tomography. Initial laboratory results were notable for leukocytosis 62.5 th/uL, lactic acidosis 2.5 mmol/L, procalcitonin level 4.95 ng/mL, and negative COVID-19 PCR test. Prompt initiation of Vancomycin/Cefepime therapy ensued upon collection of blood cultures in light of possible sepsis. Flagyl, Valacyclovir, and Posaconazole were added to antimicrobial coverage, along with steroid therapy, due to minimal clinical improvement. Tachycardia with significant oxygen requirements alternating between BiPAP and heated high flow nasal cannula with FiO2 ranging from 70-85% persisted. Daily imaging also showed worsening airspace disease. Negative viral, bacterial, and fungal cultures led to subsequent discontinuation of Hydroxyurea therapy due to suspicion of medicationinduced pneumonitis. Three days after cessation of Hydroxyurea, the patient's oxygen requirements began to decrease and imaging revealed interval resolution of pneumonitic changes in the absence of antimicrobial therapy. The patient was later transitioned to Ruxolitinib for his underlying CGL prior to his discharge home without the need for home oxygen therapy. Discussion: Thought to be caused by hypersensitivity pneumonitis, pulmonary toxicity from Hydroxyurea can easily be misdiagnosed. Unfortunately, while much is known about the pancytopenic, gastrointestinal, and cutaneous side effects of Hydroxyurea, few cases in the literature highlight the potentially fatal interstitial pneumopathy caused by Hydroxyurea, first reported in 1999. Thus, this case serves as an additional contribution to the minutiae of literature detailing Hydroxyurea's adverse pulmonary side effect profile. (Figure Presented).
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INTRODUCTION: Osimertinib is a molecular targeted antineoplastic tyrosine kinase inhibitor that is primarily used in the treatment of non-small cell lung cancer (NSCLC). It has been associated with the development of interstitial lung disease/pneumonitis that requires discontinuation of the drug and occurs usually within the first 2-3 months of therapy. Approximately 3% of patients treated with osimertinib will experience lung toxicity. Acute fibrinous and organizing pneumonia (AFOP) is a rare form of interstitial pneumonitis that has been associated with drug toxicity but to our knowledge has not yet been described in association with osimertinib. Here we present one such case. DESCRIPTION: A 77 year old woman with a history of EGFR+ stage IIB adenocarcinoma presented with two weeks of shortness of breath, fevers, and dry cough. She had been started on osimertinib two months prior to presentation. On admission she was noted to be hypoxic with new oxygen requirement of 4L nasal cannula. CT chest showed bilateral ground glass opacities. She was started on empiric vancomycin and zosyn without improvement in symptoms. She underwent bronchoscopy on hospital day 3 with lung biopsy pathology showing AFOP. Infectious workup including bronchoalveolar lavage, blood, and sputum cultures, as well as respiratory viral panel and COVID-19 test was negative. Transthoracic echocardiogram showed normal cardiac function with an ejection fraction of 64%. Given these findings she was started on methylprednisolone 1 mg/kg for TKI-induced pneumonitis on day 5. Her oxygen requirements increased during hospitalization and on day 7 she acutely desaturated and was intubated. Repeat chest CT was negative for pulmonary embolism but showed interval worsening of infiltrates and consolidation at lung bases. Her methylprednisolone was increased to 2 mg/kg on day 10. Her pulmonary function improved and she was extubated to nasal cannula on day 12. DISCUSSION: Molecular targeted antineoplastic agents have been associated with lung toxicity, which can be severe and even fatal. To our knowledge this is the first known case of osimertinib-induced AFOP, which improved with discontinuation of the drug and initiation of high-dose methylprednisolone.
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Exposure to environmental toxicants such as Arsenic (As) can result in As-induced alterations in immune regulators. Consequently, people who are more prone to viral infections like influenza A or B, H1N1, SARS CoV (Severe Acute Respiratory Syndrome Coronavirus), and SARS CoV2 may develop a susceptibility to immune responses in their lungs because our previous reports delineated the ability of QIAPI 1®, a melanin precursor, to dissociate water molecules with simultaneous therapeutic efficacy against central nervous system (CNS) diseases, retinopathy, and As-induced renal toxicity. Considering the commonalitie of lung pathology of SARS CoV and As-induced toxicity, the aim of this study is to decipher the efficacy of QIAPI 1® against pentavalent As-induced lung toxicity by examining the pulmonary pathology. Hematoxylin & Eosin (H&E) staining was used for ascertaining the lung pathology in Wistar rat models. Animals were divided into 3 groups: control group, group treated with pentavalent As, and a group treated with pentavalent As and QIAPI 1®. There were no significant changes in lung histopathology in the control group as indicated by intact morphology. The As-treated group revealed damage to the histoarchitecture with pulmonary edema, interstitial fibrosis, diffuse alveolar damage, Bronchiolitis obliterans organizing pneumonia (BOOP)-lesions, formation of hyaline membrane, multinucleated giant pneumocytes, atypical pneumocytes, inflammatory cell infiltration, and interstitial edema. The group treated with As and QIAPI 1® significantly associated with mitigated histological signs of lung inflammation induced by Arsenic. Therefore, QIAPI 1® can be recommended as antagonistic to Asinduced lung toxicity. In conclusion, this model could be preferred as a hypothetical model to examine the efficacy of QIAPI 1® in SARS CoV2-induced pulmonary damage. Future studies are warranted to delineate the efficacy of QIAPI 1® against SARS CoV and SARS CoV2 lung pathology.
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Arsenic , COVID-19 , Influenza A Virus, H1N1 Subtype , Animals , Arsenic/toxicity , Humans , Lung , Rats , Rats, Wistar , SARS-CoV-2ABSTRACT
Objective: To analyze the distribution characteristics of syndrome of TCM of the patients with COVID-19 in Kunming, China. Methods: To classify and summarize the TCM syndrome types of COVID-19 patients via Cluster analysis combining with tongue image, chest CT and clinical expertise of 36 Covid-19 patients in Kunming. Results: In the 36 cases of Kunming region confirmed COVID-19 patients, 17 cases had fever (47.2%), 18 cases had cough (50%), 16 cases felt bitter taste in the mouth (44.4%), 18 cases felt dry throat (50.0%), 17 cases had poor appetite (47.2%), 15 cases had nausea (41.7%);12 cases had diarrhea (33.3%), 15 cases had insomnia (41.7%);12 cases had chest tightness (33.3%);3 cases had dyspnea (8.3%);6 cases had nasal congestion and running nose (16.7%);15 cases had fatigue (41.7%);6 cases had headache and body pain (16.7%);5 cases had red tongue (13.9%);18 cases had pale red tongue (50%);8 cases had tongue with red edge and tip (22.2%);3 cases had dark red tongue (8.3%);2 cases had cyanosis (5.6%);3 cases had swollen tongue (8.3%);18 cases had dentate tongue (50%);4 cases had yellow tongue coating (11.1%);5 cases had yellow sticky tongue coating (13.9%);12 cases had white sticky tongue coating (33.3%);6 cases had thin white tongue coating (16.7%);2 cases had no tongue coating (5.6%). The chest CT results showed that: There were five cases without lesions. The lesions were located in the upper lobe of one lung in 13 cases located in the lower lobe of one lung in seven cases, located in the upper middle lobe in three cases, located in the lower lobe in five cases, and in the upper middle and lower lobes of double lung in 13 cases. There were 14 cases of Shaoyang syndrome, 17 cases of wet Resistance Tir-juao Syndrome. According to the time of onset, the disease was followed by Shaoyang Syndrome (1 day), the Wet blocked tri-jiao Syndrome (3 days), epidemic poison retention lung syndrome and syndrome of flaring heat in qifen and yingfen (5 days), and dampness-toxicity lung-stagnation syndrome (6 days). Conclusion: The TCM syndromes of COVID-19 in Kunming are mainly the Wet Resistance Tri-Jiao Syndrome and Shaoyang syndrome, followed by dampness-toxicity lung-stagnation syndrome, epidemic poison retention lung and syndrome of flaring heat in qifen and yingfen.
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Interstitial lung disease is recognized as a group of diseases with a different etiopathogenesis characterized by chronic lung inflammation with the accumulation of inflammatory cells, lymphocytes and macrophages, and the consequent release of proinflammatory cytokines. Various degrees of pulmonary fibrosis can be associated with this inflammatory condition. Interstitial lung disease related to oncological drugs is a relevant problem in clinical practice. The etiopathogenetic mechanisms underlying this adverse event are not completely known but can be partly explained by the mechanism of action of the drug involved. Therefore, knowledge of the relevance of this potentially fatal adverse event supported by the reported safety data of pivotal studies becomes fundamental in the management of patients. The prompt diagnosis of drug-related pneumonia and the consequent differential diagnosis with other forms of pneumonia allow a rapid suspension of treatment and the establishment of an immunosuppressive treatment if necessary. In the context of the health emergency related to SARS CoV2 infection and COVID-19-related interstitial lung disease, such knowledge holds decisive relevance in the conscious choice of cancer treatments. Our intent was to describe the oncological drugs most correlated with this adverse event by reporting, where possible, the percentages of insurgency in pivotal studies to provide an overview and therefore promote greater awareness of this important toxicity related to oncological treatment.