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INTRODUCTION: Cryptogenic organizing pneumonia (COP) accounts for 5% of all ILD cases. Due to a low incidence rate of 1 case per 100,000 persons per annum, it is often misdiagnosed as bacterial pneumonia, but when timely managed, it has an excellent prognosis. We discuss Methamphetamine, a commonly abused stimulant that has unfortunately not yet garnered enough notoriety as a respiratory toxidrome for causing inhalation injury, potentially leading to fulminant COP. DESCRIPTION: A 44-year-old male presented to ED with fevers, cough, and dyspnea gradually worsening over the past two weeks. Of note, he smoked ten cigarettes/day and relapsed to methamphetamines inhalation, the latest use being two weeks prior. On physical exam, oxygen saturation was 70% on RA and had significant bilateral inspiratory crackles. The respiratory Viral Panel, including COVID-19, was negative. Drug screens were negative. Chest X-Ray and CTA showed bilateral ground glass opacities concerning multifocal pneumonia but no pulmonary embolism. Broadspectrum antibiotics were started. For worsening Acute Hypoxemic Respiratory failure (AHRF) on Day 3, he underwent intubation and mechanical ventilation. Further workup for infectious etiologies like S. pneumoniae and Legionella, HIV-1, and sputum and blood cultures were all negative. Initial autoimmune and connective tissue disease workup was within normal limits. Bronchoalveolar lavage (BAL) analysis did not yield an infectious, inflammatory, or neoplastic source. On day 7, he underwent an open lung biopsy which confirmed COP, with histological features of toxic injury. IV glucocorticoids were started, with gradual improvement noticed in AHRF. DISCUSSION: Respiratory failure within 30 days of hospitalization is the most common cause of mortality in fulminant COP.If a patient's history suggests exposure to inhaled amphetamine and have no response to antibiotics for supposed pneumonia, physicians should consider COP to make a timely diagnosis and initiate glucocorticoid treatment to warrant rapid clinical improvement, often seen as early as 72 hours, and prevent future relapses.With Substance use continuing to be a major healthcare problem, now more than ever, healthcare providers must be familiar with respiratory toxidrome to provide timely diagnosis and treatment.
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SESSION TITLE: Pulmonary Manifestations of Systemic Disease Case Posters SESSION TYPE: Case Report Posters PRESENTED ON: 10/19/2022 12:45 pm - 01:45 pm INTRODUCTION: Organizing pneumonia (OP) is a form of interstitial lung disease with a distinct histopathological pattern where bronchioles and alveoli become inflamed. It is associated with many clinical conditions including infections and connective tissue disease. OP has also been seen in patients with hematologic malignancies, however, primary pulmonary presentation of chronic lymphocytic leukemia (CLL) is uncommon. We present a rare case of OP as an initial presentation of CLL. CASE PRESENTATION: A 62 year-old male with a sixty pack year smoking history and COVID-19 infection one month ago presents with complaints of worsening dyspnea, headaches, productive cough, and congestion of 10 days duration. Patient is unvaccinated and did not require hospitalization for his COVID-19 infection. His vital signs on admission were significant for tachypnea with respiratory rate of 35 and hypoxia with oxygen saturation of 84% on room air. He initially required oxygen supplementation via non-rebreather mask to maintain oxygen saturation >88%. A chest tomography (CT) scan was completed and revealed bilateral dense consolidations with ground-glass opacities and air bronchograms consistent with OP. The scan was also significant for bulky mediastinal lymphadenopathy. The patient denied any personal or family history of autoimmune disease, occupational exposures, and recent travel. Evaluation for infection and for underlying connective tissue disease was unremarkable. He was started on broad spectrum antibiotics and high dose steroids. Due to fluctuating lymphocytosis, bulky lymphadenopathy, and negative infectious workup despite clinical improvement, he underwent a bronchoscopy with endobronchial ultrasound guided transbronchial needle aspiration of lymph nodes. Immunohistochemical (IHC) stains of these samples were compatible with CLL. Additionally, peripheral blood flow cytometry was also diagnostic of CLL. Oncology was consulted for further evaluation and treatment of CLL. The patient's respiratory symptoms improved and oxygen requirements decreased with steroid treatment and he was discharged home. DISCUSSION: OP occurring in patients with hematologic malignancies has multiple etiologies. Most case reports describe patients with previous exposure to chemotherapy, radiotherapy, or bone marrow transplant. However, our patient had no such exposure history and no prior diagnosis of a hematologic malignancy. Infectious and autoimmune etiology were considered, but serologic evaluation was unremarkable. Flow cytometric analysis of lymph node tissue along with lymphocytic bronchoalveolar lavage was consistent with initial diagnosis of CLL. CONCLUSIONS: Despite the low incidence, hematologic malignancy should be considered as a differential diagnosis in all patients who present with organizing pneumonia. Prednisone therapy for 6-12 month duration has been shown to reduce respiratory symptoms and may improve survival. Reference #1: Craig E. Daniels, Jeffrey L. Myers, James P. Utz, Svetomir N. Markovic, Jay H. Ryu. Organizing pneumonia in patients with hematologic malignancies: A steroid-responsive lesion. Respiratory Medicine, 101 (1) (2007), pp. 162-168. Reference #2: M. Mokhtari, P.B. Bach, P.A. Tietjen, D.E. Stover. Bronchiolitis obliterans organizing pneumonia in cancer: a case series. Respiratory Medicine, 96 (4) (2002), pp. 280-286. DISCLOSURES: no disclosure on file for Guillermo Garrido;No relevant relationships by Anita Gopalakrishnan No relevant relationships by Rameez Rao No relevant relationships by Mohammad Salimian
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SESSION TITLE: Pulmonary Involvement in Critical Care Case Posters SESSION TYPE: Case Report Posters PRESENTED ON: 10/17/2022 12:15 pm - 01:15 pm INTRODUCTION: Cryptogenic organizing pneumonia (COP), also known as bronchiolitis obliterans organizing pneumonia (BOOP), is one of the idiopathic interstitial lung diseases that affects the alveolar epithelium and surrounding interstitium. Its diagnosis is usually delayed due to similar clinical presentation as other illnesses (e.g. pneumonia) [1]. CASE PRESENTATION: A 65-year-old male presented with rapidly progressive respiratory failure. Computed tomography (CT) of chest showed multifocal ground glass opacities. He had suboptimal response to antibiotics and had to be intubated on day 9 due to worsening respiratory failure. Bronchoscopy with bronchoalveolar lavage was performed, cytology of which revealed severe acute inflammation and mononuclear infiltration. Decision was made to perform open lung biopsy which showed polypoid plugs of organizing fibroblasts and myofibroblasts in the distal airways and alveoli with focal hyaline membrane and alveolar damage, consistent with acute onset fulminant COP. As expected, the patient responded fairly well to high-dose corticosteroids and was extubated on day 9 of intubation. DISCUSSION: Even though it is very rare, COP should be kept in differentials especially when initial interventions fail (as in our patient). There is no single laboratory study or intervention to diagnose this condition. Hence it is imperative to rule out other causes of similar presentation like pneumonia (using cultures, urine antigen testing, and viral polymerase chain reaction tests). The clinical picture is combined with supportive evidence like elevated erythrocyte sedimentation rate, leukocytosis, imaging findings, and bronchoscopic and histopathology evaluation [2]. Once diagnosed, it is important to rule out any associated CTD, for it can change management and prevent additional complications. The majority of patients with COP exhibit rapid response to glucocorticoid treatment. For fulminant disease, intravenous glucocorticoids (e.g. methylprednisolone 125-250 mg every six hours) should be initiated based on the clinical experience and case reports [3]. CONCLUSIONS: Diagnoses of interstitial lung diseases should be pursued in a systemic fashion from more common to less common. However, anchoring to common diagnoses should be avoided to negate delay in diagnoses and allow timely management. If initial workup is unrevealing, bronchoscopy and open lung biopsies should be performed while the patient is stable enough to undergo the interventions to avoid antibiotic resistance, morbidity and mortality associated with rapidly progressive noninfectious illnesses like fulminant COP. Reference #1: Drakopanagiotakis F, Polychronopoulos V, Judson MA. Organizing pneumonia. The American journal of the medical sciences. 2008 Jan 1;335(1):34-9. Reference #2: Cordier JF. Cryptogenic organising pneumonia. European Respiratory Journal. 2006 Aug 1;28(2):422-46. Reference #3: Nizami IY, Kissner DG, Visscher DW, Dubaybo BA. Idiopathic bronchiolitis obliterans with organizing pneumonia: an acute and life-threatening syndrome. Chest. 1995 Jul 1;108(1):271-7 DISCLOSURES: No relevant relationships by Fareeha Abid No relevant relationships by Vipin Garg No relevant relationships by Qirat Jawed No relevant relationships by Asnia Latif No relevant relationships by Ahmed Mowafy No relevant relationships by Muniba Naqi No relevant relationships by Muhammad Atif Masood Noori No relevant relationships by Hasham Saeed
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SESSION TITLE: Rare Pulmonary Infections SESSION TYPE: Rapid Fire Case Reports PRESENTED ON: 10/18/2022 01:35 pm - 02:35 pm INTRODUCTION: Castleman's Disease (CD) includes a group of rare and heterogenous lymphoproliferative disorders that share characteristic histopathological features. The etiology of CD is unknown. The condition results in episodic regional lymphadenopathy. Symptoms are driven by episodic cytokine excess. Clinical presentation can include fevers, night sweats, weight loss and fatigue. Life expectancy is not affected, however patients are at risk of developing various other conditions including amyloidosis, cryptogenic organizing pneumonia and lymphoma. COVID-19 is known to have periods of cytokine excess. In severe instances in can lead to cytokine storm, characterized by bilateral pulmonary infiltrates, worsening hypoxemia, and organ failure. We present the case of a 48 year-old female with CD who endured prolonged COVID-19 and cytokine storm. CASE PRESENTATION: A 48-year-old female with CD presented to the emergency department for shortness of breath. Six months prior to admission she had received one dose of the mRNA-1273 (Moderna) vaccine against SARS-CoV-2. Unfortunately, she contracted COVID-19 prior to the second dose. At that time she was hospitalized at a separate institution for COVID-19 and hypoxemia. The patient was treated with systemic glucocorticoids and remdesivir, and subsequently discharged home on supplemental oxygen via nasal cannula at 2 l/min. Unfortunately her respiratory status progressively declined over the following two months. During this time PCR testing for SARS-CoV-2 was positive on multiple occasions. She subsequently presented to our ER for dyspnea and hypoxemia. She once again tested positive by PCR. Inflammatory markers including fibrin degradation products, c-reactive protein and fibrinogen were severely elevated. Chest radiograph revealed bilateral infiltrates. The patient was placed on high flow oxygen and admitted to the ICU. Treatment was initiated with remdesivir, systemic glucocorticoids, and tocilizumab. Unfortunately, she continued to decline and was eventually placed on mechanical ventilation. The patient was then transferred to another institution for evaluation of extracorporeal membrane oxygenation. DISCUSSION: Both CD and COVID-19 are characterized by cytokine excess. Our patient with CD presented with persistent COVID-19. She remained symptomatic for close to six months. Her course was waxing and waning for the first few months and then progressively declined. Multiple PCR tests for SARS-CoV-2 were positive during this interval. We postulate that the proclivity of CD to cytokine excess had a synergistic effect on the inflammatory components of COVID-19 infection. This may have contributed to the protracted infection. CONCLUSIONS: More research is needed in patients with lymphoproliferative disorders and the impact of COVID-19 infection on their outcomes. Reference #1: Van Rhee, Frits, et al. "International, Evidence-Based Consensus Treatment Guidelines for Idiopathic Multicentric Castleman Disease.” American Society of Hematology, American Society of Hematology, 15 Nov. 2018, https://ashpublications.org/blood/article/132/20/2115/39506/International-evidence-based-consensus-treatment. Reference #2: "Castleman Disease: Symptoms, Causes, Treatments and Tests.” Cleveland Clinic, https://my.clevelandclinic.org/health/diseases/17920-castleman-disease. Reference #3: "Castleman Disease.” NORD (National Organization for Rare Disorders), 10 July 2017, https://rarediseases.org/rare-diseases/castlemans-disease/. DISCLOSURES: No relevant relationships by Wajahat Khan No relevant relationships by Nashwa Yosry
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SESSION TITLE: COVID-19 Case Report Posters 1 SESSION TYPE: Case Report Posters PRESENTED ON: 10/17/2022 12:15 pm - 01:15 pm INTRODUCTION: Persistent acute symptoms of coronavirus disease 2019 (Covid-19) have been previously described in patients receiving immunosuppression, and have additionally been associated with the development of new variants of the SARS-CoV-2 virus. Here follows a report of a similar case which eventually responded to treatment with antiviral and monoclonal antibody therapies. CASE PRESENTATION: The patient is a 51 year old male with a past medical history of bilateral optic neuritis (treated with rituximab), polysubstance use disorder, bipolar disorder, and hypertension. He initially presented to the emergency department in January 2022 with symptoms of shortness of breath, cough, and worsening fatigue over the preceding 3-4 weeks. On presentation he required intubation for hypoxia. A PCR test for SARS-CoV-2 returned positive and he was initiated on treatment with intravenous dexamethasone and antibiotics for presumed community acquired pneumonia. He was extubated 4 days later, but remained hospitalized for a further 6 weeks due to recurrent fevers and a persistent supplemental oxygen requirement. Due to concern for viral-induced cryptogenic organizing pneumonia he was started on high-dose intravenous steroids. However, he developed escalating oxygen requirements resulting in a second intubation to facilitate bronchoscopy, results of which were non-diagnostic. Serum testing for SARS COV2 IgG antibody, 10 weeks after the initial onset of his symptoms, returned negative, therefore he was then treated with a 5 day course of remdesivir, as well as monoclonal antibody therapy with casirivimab-imdevimab. He additionally underwent a VATS lung biopsy for definitive tissue diagnosis, which revealed interstitial inflammation with patchy fibroblastic linear nodules, consistent with diffuse alveolar damage. He was extubated and had improvement in his oxygen requirements and respiratory function, and was planned for discharge to pulmonary rehabilitation almost 3 months after his initial presentation. DISCUSSION: Patients receiving immunosuppression remain at risk for persistent symptoms, prolonged hospitalization, and increased morbidity and mortality, when infected with SARS-CoV-2. Notably, the patient described here had received only 2 doses of an FDA-approved COVID-19 vaccine at the time of his infection, and was being treated with rituximab for optic neuritis, with his last infusion being approximately one month before the onset of his symptoms. Such prolonged, symptomatic infection from SARS-CoV-2 remains a clinical concern, especially due to its association with the development of new viral variants, and further research into appropriate treatment for these patients continues to be investigated. CONCLUSIONS: This case demonstrates an immunocompromised patient with persistent symptoms of Covid-19 who eventually responded to treatment with the antiviral remdesivir, as well as monoclonal antibodies. Reference #1: Choi B, Choudhary MC, Regan J, et al. Persistence and evolution of SARS-CoV-2 in an immunocompromised host. N Engl J Med 2020;383:2291-2293. DISCLOSURES: No relevant relationships by Vivek Sinanan
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SESSION TITLE: Critical Diffuse Lung Disease Cases 2 SESSION TYPE: Case Report Posters PRESENTED ON: 10/19/2022 12:45 pm - 01:45 pm INTRODUCTION: Recurrent episodes of community acquired pneumonia (CAP) have been shown to be common in elderly patients. Cryptogenic organizing pneumonia (COP) is an interstitial lung disease that is often mistaken for pneumonia, especially in the older population. Here, we present a 100-year-old woman diagnosed with COP after multiple failed courses of antibiotics for CAP. CASE PRESENTATION: A 100-year-old female with a history of cardiomyopathy, pulmonary hypertension, and autoimmune hemolytic anemia previously on prednisone, who presented with shortness of breath and non-productive cough. CT of the chest showed dense left upper and lower lobe consolidations. She was admitted 2 months prior with similar symptoms and found to have extensive right sided consolidations with concerns of CAP. She was treated with antibiotics without resolution of her symptoms. CXR from two years prior revealed right upper and right lower lobe consolidations. This admission, she was started on antibiotics with no improvement and required supplemental oxygen. She had no leukocytosis. COVID-19 testing was negative and she was unable to produce any sputum for culture. The patient declined bronchoscopy. She was seen by speech and swallow with no concern for aspiration. Prednisone was started empirically for COP and the patient experienced rapid improvement in symptoms and oxygenation. Ultimately, she was discharged on 20 mg of prednisone daily as well as Bactrim for PCP prophylaxis. She continued a slow taper as an outpatient with overall improvement in her clinical symptoms. Serial CT scans demonstrate complete resolution of the infiltrates with no recurrence or new infiltrates. DISCUSSION: Cryptogenic organizing pneumonia is a rare interstitial lung disease known to affect bronchioles and alveoli. Its etiology is unclear and symptoms often mimic other types of infectious pneumonia leading to frequent mis-diagnosis. The average age of onset is typically 50-60. Establishing this diagnosis can be difficult due to the non-specific symptomatology of dry cough and dyspnea. Bronchoscopy with lavage and transbronchial biopsies can be performed to rule out infectious and non-infectious etiologies but is not necessary for diagnosis. The most common radiographic pattern is multifocal asymmetrical parenchymal consolidations with air bronchograms that tend to migrate and appear in different sites over time. Less common presentations include ground glass opacities, nodular densities, and progressive fibrotic patterns. Steroids with a slow taper as outpatient are mainstay of therapy and the majority of patients respond with symptom and radiographic improvement. CONCLUSIONS: While elderly patients are particularly susceptible to recurrent CAP, the diagnosis of COP should be considered part of the differential diagnosis in those with recurrent unexplained consolidations on chest radiography without an infectious etiology. Reference #1: Hedlund J, Kalin M, Ortqvist A. Recurrence of pneumonia in middle-aged and elderly adults after hospital-treated pneumonia: aetiology and predisposing conditions. Scand J Infect Dis. 1997;29(4):387-92. doi: 10.3109/00365549709011836. PMID: 9360255. Reference #2: Tiralongo F, Palermo M, Distefano G, et al. Cryptogenic Organizing Pneumonia: Evolution of Morphological Patterns Assessed by HRCT. Diagnostics (Basel). 2020;10(5):262. Published 2020 Apr 29. doi:10.3390/diagnostics10050262 Reference #3: Lee JW, Lee KS, Lee HY, Chung MP, Yi CA, Kim TS, Chung MJ. Cryptogenic organizing pneumonia: serial high-resolution CT findings in 22 patients. AJR Am J Roentgenol. 2010 Oct;195(4):916-22. doi: 10.2214/AJR.09.3940. PMID: 20858818. DISCLOSURES: No relevant relationships by Vincent Chan No relevant relationships by Mackenzie Kramer No relevant relationships by John Madara No relevant relationships by Stephanie Tzarnas No relevant relationships by Laura Walters
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Introduction: Mycoplasma pneumoniae is a respiratory tract pathogen that most commonly causes acute bronchitis. Pneumonia is a less common manifestation. Herein we describe a patient who presented with COVID19 like symptoms after exposure but was later found to have Mycoplasma with cryptogenic organizing pneumonia (COP). Case Description: A 63-year-old lady presented to the emergency department with a cough with minimal sputum production and dyspnea for one week and a generalized itchy rash for four days. She had a recent travel history, exposure to a COVID-19 patient, and was unvaccinated against COVID-19. On admission, vitals were normal except for a heart rate of 121/min. On examination, she had a maculopapular rash involving the face, neck, back, palms, and soles (Fig A and B). Labs were significant for total leukocyte count of 12.9 X 103/ mm3, D-dimer of 1125 ng/mL which increased to 1635ng/mL in 24 hours, erythrocyte sedimentation rate of 38mm/h, and C-reactive peptide of 101.5mg/L. Chest x-ray revealed bilateral opacities worse on the right (Fig C). A CT pulmonary angiogram was negative for PE but showed bilateral peripheral opacities greater on the right side, suggesting COVID19 as the etiology (Fig D). But COVID19 PCR was negative. Due to the presence of diffuse rash, mycoplasma IgG antibodies were checked which were positive. During the hospital course, she became hypoxic requiring nasal cannula oxygenation. The patient underwent bronchoalveolar lavage (BAL) with transbronchial lung biopsy (TBLB) which revealed 60% eosinophils with COP. She was treated with IV methylprednisolone, IV ceftriaxone, and doxycycline. Her respiratory symptoms got better, and the rash significantly improved with residual hyperpigmentation. The patient was discharged on tapering doses of steroids and levofloxacin to complete 14 days of antibiotics. Discussion: Mycoplasma pneumoniae is known to cause atypical pneumonia most commonly in young children than in adolescents and adults. COP is rarely seen with it. Common dermatological manifestations include erythematous maculopapular rash, erythema multiforme. Our patient was an elderly female who presented with classic maculopapular rash and respiratory symptoms. The presence of rash and hypoxia prompted us to get BAL with TBLB which led to the diagnosis of COP and early initiation of steroids. Although open lung biopsy is considered the best approach for diagnosis, BAL with TBLB has a positive predictive value of around 95%. Symptomatic improvement in such patients is quite impressive with steroids with complete recovery in most of the patients. (Table Presented).
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Introduction: Antisynthetase syndrome(ASS) is a rare autoimmune disease characterized by myositis, arthritis, cutaneous findings and interstitial lung disease (ILD). In 15-30% cases of ASS, ILD can be the presenting feature making this a very challenging diagnosis to make, especially during the COVID 19 pandemic. We present a unique case of ILD as presenting feature of ASS. Case: A 31 yr old female, never smoker, with asthma and obesity was referred to the pulmonary clinic for dyspnea of 2 months. Dyspnea was on exertion, associated with cough and pleuritic chest pain. Oxygen saturation on exam was 91% at rest and 86% on exertion. PCR and antibodies for COVID was negative. CXR showed bilateral infiltrates. She was treated with several courses of antibiotics and steroids. Her symptoms improved with steroids yet returned when course completed. Chest CT revealed bilateral parenchyma opacities with sparing of the lung apices. This was repeated 3 months after her course of antibiotics and steroids which revealed worsening of ground glass opacities, now diffuse with areas of organizing pneumonia. Bronchoalveolar lavage showed alveolar macrophages with a mixture of acute and chronic inflammatory cells. PFTs revealed severe restrictive lung disease. Infectious work up including bacterial, viral and fungal causes was negative. Complete blood count with differential was normal. B-type natriuretic peptide, creatine kinase, liver function test, basic metabolic panel, HIV and fungal serologies were unrevealing. A rheumatologic work up revealed elevated ESR (48), CRP (6.9), aldolase (48) with positive anti OJ antibodies. She underwent VATs with wedge lung biopsy which revealed cellular non specific interstitial pneumonia (NSIP). She was diagnosed with ASS and started on a gradual taper of high dose steroids and steroid sparing agent Mycophenolate Mofetil. With time her respiratory symptoms improved and she no longer required supplemental oxygen. She was enrolled in pulmonary rehabilitation and encouraged to loose weight as her BMI of 55 could preclude lung transplantation if needed. Discussion: ASS is a rare autoimmune connective tissue disorder characterized by myositis, polyarthritis, cutaneous findings and ILD. It occurs more commonly in women with average age of onset in 50s. ILD has been reported in 69-100% with NSIP being most common followed by cryptogenic organizing pneumonia and UIP. Treatment consists of steroids, with or without a steroid-sparing agent. Timely diagnosis of ASS is imperative for patients presenting with ILD as delay can lead to progression of ILD which serves as a predictor for morbidity and mortality. (Figure Presented).
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Pneumonia is one of the most common pathologies seen in the inpatient setting. The rapid response to treat febrile patients with infiltrates on chest x-ray has reduced hospital length of stay and hospital costs. However, the automatic reaction to treat all infiltrates and opacities seen on a chest x-ray as pneumonia can be costly. This report presents the case of a patient suspected initially of having pneumonia, who was unresponsive to broad-spectrum antibiotics. A 58-year-old woman presented with dyspnea on exertion and a nonproductive cough. Her chest x-ray showed dense right-sided coalescent opacities encompassing the entirety of the right lung. Flexible bronchoscopy biopsy specimens revealed the cause to be cryptogenic organizing pneumonia. This case highlights the diverse set of pulmonary pathologies that can mimic pneumonia and should be suspected in cases of antibiotic-resistant suspected pneumonia patients.
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Case Report Purpose of Study Interstitial lung disease (ILD) is a group of pulmonary disorders that cause varying degrees of inflammation and fibrosis of pulmonary architecture. The diagnosis requires good clinical history, examination, appropriate workup, and a high degree of suspicion. This case report draws attention toward a unique case of cryptogenic organizing pneumonia after mold exposure. Methods Used Not applicable. Summary of Results A 36-year-old nonsmoker male with no comorbidities presented with worsening shortness of breath after cleaning a walk-in cooler room contaminated with mold. He was seen at multiple facilities for presumed diagnosis of COVID-19 despite being vaccinated and 4 negative COVID-19 results. He was discharged with 2 liters of supplemental home oxygen and a 7-day course of Levofloxacin, with no resolution of symptoms. The patient presented to our hospital 2 months after initial onset of symptoms. On examination, the patient had bronchial breath sounds with fine crepitations, egophony, and increased vocal resonance. Chest x-ray revealed bilateral airspace consolidation with scattered ground-glass opacities in the apices. Computed Tomography (CT) of the thorax showed peripheral upper lobe ground-glass opacities with interstitial thickening in a 'crazy-paving' pattern. A chest CT angiogram showed patchy ground-glass pulmonary infiltrates with peripheral predominance consistent with severe COVID pneumonia. PCR for SARS-CoV-2 was negative. The patient's oxygen demand increased progressively from 4L on nasal cannula to 40L on high flow nasal cannula to maintain an oxygen saturation of 90%. Labs showed normal leukocyte count, ESR, ALT, and AST with a mildly elevated CRP. Workup for infectious etiology was negative for S. pneumoniae, legionella, coccidioides, HIV, hepatitis panel, Quanti- FERON gold and blood culture. Autoimmune workup was negative for ANA, RF, CCP, ANCA, anti-centromere Antibody, anti-ds DNA. The patient underwent a bronchoalveolar lavage with culture negative for acid fast bacilli, fungi, and P. jirovecii. Bronchoscopic biopsy was subsequently performed and revealed lung parenchyma with foci of mild chronic inflammation with focal fibroblastic proliferation and fibrosis, suggestive of an organizing pneumonia. The patient was started on steroids 1 mg/kg resulting in significant clinical improvement requiring only 3L on nasal cannula on day 5 of treatment. He was then discharged with high dose steroid therapy for 3 months. Conclusions The prognosis and treatment of ILD depends on accurate diagnosis and its subtype. Hence appropriate workup is essential to guide therapy. In the setting of the current pandemic, relatively uncommon causes of ILD like cryptogenic organizing pneumonia may go undiagnosed due to the unconscious bias among health care providers resulting in delayed treatment. This report highlights the importance of considering alternative diagnosis when a disease does not follow an expected course.
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Patients with SARS-CoV-2 may be affected by the acute respiratory distress syndrome (ARDS), which has been associated with high mortality rate. As no specific drugs are available for ARDS, mesenchymal stem cells (MSC) seems to be a promising cell therapy due to immunomodulatory effects on reducing and healing inflammation-induced lung and other tissue injuries. The goal of this Phase I clinical trial was to explore the safety and efficacy of bone marrow-derived MSC (BM-MSC) infusions in patients with COVID-19 ARDS. The inclusions criteria were age between 18 to 70 years and PaO2/FiO2≤200mmHg. The BM-MSC infusions were as follow: one to 3 infusions intravenous doses of BM-MSC of 1x10 6 cells/kg;each dose could be administered with an interval between 3 to 7 days. The primary endpoint was safety (adverse events) within 6 hours;cardiac arrest or death within 24 hours post-infusion. The secondary endpoint includes patient survival at 30 days after the first infusion. Six patients were included in the trial and treated with at least one infusion of BM-MSC. The median age was 60,3 years (54 to 69), 5 were male. The median time between the worsening of respiratory distress and the BM-MSC infusion was 10 days (3 to 31 days). The median of PaO2/FiO2 before infusion was 151.86 (127.80-164.44) and median PaCO2 was 63,85 (39 to 117). One patient was treated with 3 MSC doses, two patients with 2 doses and 3 patients one dose. No serious adverse effects were observed within 24 hours post-infusion;only one death was observed following 30 days of cell administration. None of them showed adverse events during BM-MSC infusion. Only one patient showed signs of pulmonary infection one week after first BM-MSC infusion. This patient was at increased risk for infection due to prolonged intubation and a high dose of corticosteroid. Therefore, it was not possible to conclude its association with BM-MSC treatment. Only two patients showed clinical improvement after BM-MSC infusion. Patient 1 had BM-MSC infusion 72 hours after worsening of respiratory parameters, and thorax CT suggested the hypothesis of cryptogenic organizing pneumonia, which led to decision of using methylprednisolone 125mg I.V. for 3 days and carry on with MSC infusion. We observed a decrease in CRP levels from 126 to 67 mg/dL on day 1 after the first infusion, and PaO2/FiO2 ratio improved from 155 to 297 mmHg on day 5. He received the second dose within 7 days interval and by day 11 of the first infusion a new thorax TC showed complete resolution of alveolar consolidation areas in both lungs (Figure 1A and 1B). Patient 2 had BM-MSC administration 11 days after respiratory worsening and also presented improvement of PaO2/FiO2 ratio (148 to 215 mmHg after 2 days of infusion) and had thorax CT images suggesting cryptogenic organizing pneumonia with administration of methylprednisolone 250mg I.V. Nevertheless, the second dose was not administered due to ventilator-associated pneumonia and urinary infection. Four patients showed a non-sustained increase of PaO2/FiO2 ratio, with higher median PCO2 levels of 69,3 mmHg (range, 61,2 to 117) comparing to 39 and 47,3 mmHg of patients 1 and 2, respectively. PCO2 parameter could be a marker to indicate a worse response to MSC treatment, since it could point out chronic phases of COVID-19 disease. The patients died due to COVID-19 complications. No difference in inflammatory markers, such as interleukin 6, C-protein reactive test, procalcitonin, ferritin was observed before and after treatment. Inclusion criteria did not defined interval between respiratory worsening and first BM-MSC infusion. Four patients had chronic phase of COVID-19 without inflammatory markers and hypercapnia. It could be related to severity of pulmonary disease, such as reported in chronic obstructive pulmonary disease. Two patients were discharged after MSC treatment and they received methylprednisolone to treat cryptogenic organizing pneumonia. There are only a few clinical trials and observational studies evaluating the use of high-dose of glucocorticoid for severe COVID-19 pneumonia. Therefore, it is not possible to conclude that use of glucocorticoid has contributed to favorable outcomes. In conclusion, BM-MSC showed to be a secure therapeutic option for severe COVID-19 pneumonia, possibly with superior benefit in acute phases and lower PCO2 levels. Further studies involving a large cohort or randomized controlled trials are warranted. [Formula presented] Disclosures: No relevant conflicts of interest to declare.