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1.
Respir Physiol Neurobiol ; 308: 103983, 2022 Nov 04.
Article in English | MEDLINE | ID: covidwho-2095959

ABSTRACT

PURPOSE: We investigated abnormalities and recovery in respiratory function after COVID-19 infection in an unvaccinated elite athlete population. METHODS: Measurements included maximal inspiratory pressure (MIP), maximal expiratory pressure (MEP), forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), and peak expiratory flow (PEF). RESULTS: The most frequent reported symptoms were fatigue with 80% and muscle/joint pain and headache with 50%, whereas only 10% reported dyspnoea and 30% cough. During follow-up, MIP was up to 13% and MEP up to 8% lower following COVID-19 infection. Likewise, FEV1 was up to 2% and FVC up to 5% lower. While MEP and FEV1 rapidly normalised, MIP and FVC still remained abnormal after 52 days of COVID-19 infection, thereby leading to a restrictive ventilatory pattern. PEF seemed unaffected during follow-up. CONCLUSIONS: COVID-19 decreases respiratory function in unvaccinated athletes despite reporting few respiratory symptoms and having mild disease. An initiative aimed at reducing the long-term adverse effects following COVID-19 infection seems warranted, which perhaps may be avoided through vaccination.

2.
Archives of Disease in Childhood ; 107(Supplement 2):A241, 2022.
Article in English | EMBASE | ID: covidwho-2064030

ABSTRACT

Aims During the COVID-19 pandemic, home spirometry became essential for continued monitoring of cystic fibrosis patients, however, the clinical effectiveness was unknown.The aims of this study were to assess the success rate of testing patients at home and to compare the results to the gold standard testing (in lab spirometry). Methods 147 home spirometry devices (Air Next, NuvoAir, USA) were given out to cystic fibrosis patients (M:F 67:80;mean age 11.8 [4.7 - 17.3]) who had previous experience of spirometry and deemed to be competent to perform spirometry at home. Patients were asked to perform 4 tests in the first month, then 1 test per month unless clinically requested. When Lab spirometry resumed, 28 (M:F 12:16;mean age 13.1 [8.0-17.0]) patients tested on NuvoAir within 5 days (mean 0.7 days (1.0)) of Lab spirometry (Vyntus Spiro, Vyaire Medical, USA). Correlation between spirometry indices were analysed using linear regression. Results 142 patients (96.6%) successfully onboarded onto the NuvoAir platform. Between July 2020 and Jan 2022, 1854 tests were performed, with 1711 (92.3%) tests over-read to be valid. 54 patients (36.7%) performed >=15 tests requested. FEV1 (R2 = 0.93, p = <0.00), Ratio (R2 = 0.70, p = <0.00), FVC (R2 = 0.91, p = <0.00), MMEF (R2 = 0.87, p = <0.00) and PEF (R2 = 0.88, p = <0.00) all showed significant correlation between Lab spirometry and Home spirometry. Conclusion Our results show that home spirometry is well adopted by cystic fibrosis patients, however, continual encouragement may be required. We have also shown that valid spirometry loops can be performed by cystic fibrosis patients on this device. There is also close agreement between this home spirometry device and the gold standard of lab spirometry and therefore, results can be deemed valid and reliable.

3.
American Journal of Transplantation ; 22(Supplement 3):720, 2022.
Article in English | EMBASE | ID: covidwho-2063497

ABSTRACT

Purpose: Liver transplant recipients have a high risk of developing postoperative pulmonary complications. Pulmonary function tests (PFTs) are expensive and often incapable of predicting patients at risk or improving patient outcomes, thus a single-center implemented specific criteria to determine when a PFT is administered for the evaluation of patients for liver transplantation. The protocol recommends a PFT for patients with a history of chronic lung disease, recurrent pneumonia prior to transplant, symptomatic COVID-19 requiring hospitalization, tobacco abuse, alpha-1 antitrypsin positivity, or oxygen dependency. Method(s): We conducted a retrospective cohort study of consecutive adult patients (age greater than 18 years) who underwent deceased donor liver transplantation from January 1, 2020, to June 30, 2021. We analyzed results from pre-protocol (PRE) and post-protocol (POST) implementation. Result(s): There were a total of 215 patients in the study, 186 PRE and 29 POST protocol implementation. In the PRE group, 168 (90%) patients received PFTs compared to 12 (41%) in the POST group, p<0.001). There was no difference between the PRE and POST groups based on age in years (56 vs 55, p=0.713), male gender (65% vs 662%, p=0.83), White race (80% vs 86%, p=0.15), BMI (34 vs 28, p=0.107), or cold ischemic time in hours (5.7 vs 6, p=0.252). There was no difference in FVC (3.3 vs 3.0, p=0.84), FEV1 (2.6 vs 2.2, p=0.87), FEV1/FVC% (76.9 vs 74.4, p=0.47) and DLCO (16.4 vs 13.8, p=0.11). The postoperative variables were the same for both groups with time to extubation hours (25 vs 31, p=0.26), ICU length of stay days (8 vs 10, p=0.12), and transplant admission length of stay days (14.4 vs 17.4, p=0.36). Lastly, there was no difference between PRE and POST graft survival (p=0.69) or patient survival (p=0.08). Conclusion(s): This study demonstrates the successful implementation of a PFT protocol with a cost savings of roughly $38,000 in just three months with no impact on patient outcomes. Further research is indicated for broad-scale implementation.

4.
American Journal of Transplantation ; 22(Supplement 3):993, 2022.
Article in English | EMBASE | ID: covidwho-2063460

ABSTRACT

Purpose: Limited data exists on CT chest abnormalities during acute Coronavirus disease 2019 (COVID-19) infection and associated post-illness loss of lung function among lung transplant (LT) patients. Method(s): The institutional database was interrogated for any LT patient diagnosed with COVID-19 during a one-year period (March 2020 to Feb 2021;n=54). 44 patients with acute COVID-19 were alive at 3-month follow up (COVID-survivors: 81.5%). Of the survivors, 34 had a CT chest during the first two weeks of acute illness. A validated CT score was used to quantify the parenchymal abnormalities due to COVID-19. Each lung was divided into 10 separate regions which were scored 0-2 based on the severity and extent of parenchymal opacification (maximum score per lung=20). To avoid confounding from underlying lung disease, only the allograph was assessed in single LT. The average score of both lungs was calculated in bilateral LT. The primary outcome measure was sustained decline of FEV1 or FVC >10% from pre-infection spirometry. Result(s): Abnormal CT score and lung opacities on CT chest were nearly ubiquitous during acute COVID-19 illness (>0;36/37, 97.3%, median score with IDR: 7.25, 4.625-10.125). The lower lobes (LL) were more affected by COVID-19 than the upper and middle lobes (UML) (median CT score in LL: 4, 2.75-6 vs 3.5, 1.25-5 in UML). A >10% decline in FEV1 or FVC was common after COVID-19 pneumonia (38.2%). The overall CT score correlated with amount of lung function loss (r=0.36, p=0.03) although the association was modest and limited to regions reflecting the UML. On ROC curve, CT score was modestly predictive of lung function decline (Fig 1). CT score from UML had the highest area under the curve (78.2%, 61.1-95.4%;p=0.006) with a score of 4.5 being the best cut-off (sensitivity 71%, specificity 85% for post-COVID lung function loss >10%). An UML CT score >4.5 was strongly associated with respiratory failure during acute illness (69% vs 24%;OR: 7.2, 1.5-33.8;p=0.01) and lung function decline >10% (77% vs 19%;OR: 14.2, 2.6-76.7;p=0.001). Conclusion(s): The CT score during acute COVID-19 infection provides prognostic information regarding loss of lung function among LT patients who survive COVID-19. Parenchymal abnormalities in the UML best predict subsequent lung function loss.

5.
Cardiology in the Young ; 32(Supplement 2):S248, 2022.
Article in English | EMBASE | ID: covidwho-2062092

ABSTRACT

Background and Aim: Coronavirus infection (COVID-19) in paedi-atric population has a generally mild course. In Spain, patients under 15 years old have accounted only for 0,4% of hospital admis-sions and 0,7% of intensive care admissions. However, in May 2020, cases of children with a systemic inflammatory syndrome related to a recent COVID-19 infection were described. In severe forms, left ventricular systolic dysfunction, mitral regurgitation, pericardial effusion and coronary artery dilatation or aneurysms have been described. The aim of this study is to describe the results obtained in cardiopulmonary exercise test (CPET) in previously healthy patients with PIMS. Method(s): Prospective study of PIMS patients who performed CPET. Godfrey ramp protocol recommended by European Society of Cardiology (ESC) was used in all cases. Measured var-iables, expressed by predicted values, were: forced vital capacity (FVC), forced expiratory volume (FEV1), ratio of minute venti-lation to carbon dioxide production (VE/VO2 slope), maximal oxygen consumption (VO2 max), oxygen uptake efficiency slope (OUES), oxygen pulse (O2 pulse) and maximum heart rate (HR). Result(s): Eight patients (75% boys) aged 5-14 years (median 10,5 years) performed CPET reaching a mean peak load of 105,87 W (median 112,5 W and mean load per kg of weight 2,34 W/kg). Only 1 patient (12,5%) presented basal spirometric disturb-ances in context of asthma without chronic treatment. Obtained mean respiratory parameters were: FVC 97,88%, FEV1 92,7%, Tiffeneau 83% and VECO2p 32,47. Oxygen satu-ration before and after CPET was greater than 95% in 100% of patients. In 6 patients (75%) the V02max and oxygen pulse was greater than 80% of predicted value (100% of patients reached at least 40% of V02 max at anaerobic threshold). Obtained mean cardiovascular parameters were: VO2 max 1624mL/min (median 1655 ml/min and V02 per kg of weight 36,9 ml/kg), pulse oxygen 9 ml and OUES 1,92. Conclusion(s): PIMS may cause severe cardiac disturbances justifying cardiological monitoring of these patients. CPET allows to assess functional capacity of these children after the disease. In our serie, most of patients had a good functional capacity (75%). Studies with more patients are needed to make extended conclusions.

6.
Cardiology in the Young ; 32(Supplement 2):S242, 2022.
Article in English | EMBASE | ID: covidwho-2062090

ABSTRACT

Background and Aim: Since December 2019 the novel coronavirus disease 2019 (COVID-19) has been burdening all health systems worldwide. However, cardiopulmonary repercussions in paediat-ric patients with congenital heart disease (CHD) are unknown. The aim of this study is to compare changes in cardiopulmonary exercise test (CPET) in this patients before and after COVID-19. Method(s): Prospective observational study was lead comparing CPET results after COVID-19 in paediatric patients with stable CHD who had a previous routine CPET. All underwent for stand-ardised CPET, using Godfrey ramp protocol as recommended by the European Society of Cardiology (ESC). Measured variables, expressed by predicted values, were: forced vital capacity (FVC), forced expiratory volume (FEV1), ratio of minute venti-lation to carbon dioxide production (VE/VO2 slope), peak oxy-gen consumption (peak VO2), oxygen uptake efficiency slope (OUES), oxygen pulse (O2 pulse) and peak heart rate (pHR). Wilcoxon test was used to compare continuous variables for related samples. Result(s): Ten patients (6 boys, 60%;mean age 11,4 +/- 2,4 years) with hemodynamically stable CHD (3 Tetralogy of Fallot, 30%;2 trans-position of the great arteries, 20%;2 dilated cardiomyopathy, 20%;2 Kawasaki disease, 20%;1 cardiac tumor, 10%) were selected to repeat a post-COVID CPET. All of them had mild COVID and could follow ambulatory treatment. Comparing before/post COVID tests, there were no significantly changes in predicted res-piratory parameters: FVC (90,6 +/- 7,4 vs 98,1 +/- 23,9%;p = 0,799), FEV1 (89,5 +/- 13,8 vs 94,5 +/- 8,8%;p = 0,475), VE/CO2 slope (31,6 +/- 3,7 vs 30,6 +/- 3,9degree, p = 0,203). In the same way, no significantly changes were seen in cardiovascular predicted parameters: oxygen pulse (97,3 +/- 19,2 vs 98,5 +/- 17,4%, p = 0,798), peak VO2 (82,4 +/- 19,4 vs 76,8 +/- 13,7;p = 0,123) and OUES (1,79 +/- 0,4 vs 2,01 +/- 0,6;p = 0,066). Respect peak VO2, there was a non-significant slightly decrease in post-COVID test (82,4 +/- 19,4 vs 76,8 +/- 13,7;p = 0,123). Conclusion(s): In our series, post-COVID CPET results showed that paediatric patients with hemodynamically stable CHD had no impairment in their functional capacity in relation to Sars-CoV-2 disease. Contrary to adults with previous cardiovascular disease, children should have mild infections without sequelae in cardio-pulmonary function.

7.
Chest ; 162(4):A2562-A2563, 2022.
Article in English | EMBASE | ID: covidwho-2060964

ABSTRACT

SESSION TITLE: COVID-19 Infections: Issues During and After Hospitalization SESSION TYPE: Original Investigations PRESENTED ON: 10/17/2022 01:30 pm - 02:30 pm PURPOSE: It has been established that recipients of solid organ transplants have worse outcomes compared to the general population from COVID-19 infections. We sought to determine the course and outcomes of lung transplant recipients (LTR) with COVID-19 infections based on vaccination status and treatments. METHODS: We performed a retrospective study of all LTR from Inova Fairfax Hospital with COVID-19 infections. Infection was confirmed based on symptoms and testing from an urgent care, hospital, or home kit. Patients with presumed but unconfirmed COVID-19 infections were excluded. The study timeframe was the two-year period: 3/1/2020 - 2/28/2022. Data collected included patient demographics, transplant type, immunosuppression, immunization status, episodes of rejection, donor derived cell-free DNA (dd-cfDNA) values (where available), spirometric data, outpatient/inpatient treatments, hospitalization data, and outcomes including death, infections, and other complications. The severity of illness was based on the 8-point ordinal scale. RESULTS: There were 45 LTR who tested positive during the study period;22 male and 23 female, average age of 57 and mean time from transplant of 4 years. 11 of the patients were unvaccinated (UV), 2 partially vaccinated (PV), 11 vaccinated non-boosted (VNB), and 21 vaccinated and boosted (VB). In total, 34 (76%) LTR required hospitalization. Of those hospitalized: 7 UV, 1 PV, 11 VNB, and 15 FV. In addition, 7 of those hospitalized required intubation with only 1/7 surviving to discharge. Overall, 8/45 (17.8%) patients died from COVID-19: 3 UV, 1PV, 1 VNB, 3VB. Infectious complications included 3 cases of PCP, 1 empyema, and 1 reactivation of CMV. For individuals who had spirometry at least 2 weeks after diagnosis (n =25), FVC decreased in 17 LTR by an average of 0.17 L, the FEV1 decreased in 14 LTR by an average of 0.14 L. On repeat spirometry testing (n=14), FVC further decreased in 9 LTR by 0.25 L and the FEV1 further decreased in 7 LTR by 0.13 L. CONCLUSIONS: A large proportion of LTR with COVID-19 infections require hospitalization (76%) with a high associated mortality rate and a sustained lung function decline seen in many who survive. The high mortality was independent of vaccination status, likely reflecting the inability of LTR to mount an immune response. A high index of suspicion and monitoring for superimposed infections, especially PCP, appears prudent. The sustained decline in lung function raises the notion of COVID-19 as a precipitating factor for chronic lung allograft dysfunction (CLAD). CLINICAL IMPLICATIONS: LTR who contract COVID-19 infection represent a high-risk population, even in those fully vaccinated, with potential for hospitalization, death, loss of lung function, and infectious complications. In this population, new algorithms for immunosuppression, monitoring and treatments may help to improve outcomes. DISCLOSURES: No relevant relationships by Shambhu Aryal No relevant relationships by A. Whitney Brown, value=Honoraria Removed 04/03/2022 by A. Whitney Brown No relevant relationships by A. Whitney Brown, value=Honoraria Removed 04/03/2022 by A. Whitney Brown No relevant relationships by A. Whitney Brown, value=Consulting fee Removed 04/03/2022 by A. Whitney Brown No relevant relationships by Jessica Chun No relevant relationships by Meg Fregoso No relevant relationships by Vikramjit Khangoora Advisory Committee Member relationship with Boehringer Ingelheim Please note: 2019-2021 Added 04/03/2022 by Christopher King, value=Consulting fee Advisory Committee Member relationship with Actelion Please note: 2019-2022 Added 04/03/2022 by Christopher King, value=Consulting fee Advisory Committee Member relationship with United Therapeutics Please note: 2019-2022 Added 04/03/2022 by Christopher King, value=Consulting fee Speaker/Speaker's Bureau relationship with Actelion Please note: 2019-2022 Added 04/0 /2022 by Christopher King, value=Consulting fee Speaker/Speaker's Bureau relationship with United Therapeutics Please note: 2020-22 Added 04/03/2022 by Christopher King, value=Consulting fee Consultant relationship with Veracyte Please note: $1001 - $5000 by Steven Nathan, value=Honoraria Removed 03/29/2022 by Steven Nathan Consultant relationship with United Therapeutics Please note: $5001 - $20000 by Steven Nathan, value=Consulting fee Consultant relationship with Bellerophon Please note: $5001 - $20000 by Steven Nathan, value=Consulting fee Speaker/Speaker's Bureau relationship with Roche-Genentech Please note: $5001 - $20000 by Steven Nathan, value=Honoraria Speaker/Speaker's Bureau relationship with Boerhinger-Ingelheim Please note: $20001 - $100000 by Steven Nathan, value=Honoraria No relevant relationships by Alan Nyquist No relevant relationships by Michelle Schreffler Speaker/Speaker's Bureau relationship with United Therapeutics Please note: 2020-2022 Added 04/01/2022 by Oksana Shlobin, value=Consulting fee Speaker/Speaker's Bureau relationship with Bayer Please note: 2020-2022 Added 04/01/2022 by Oksana Shlobin, value=Honoraria Speaker/Speaker's Bureau relationship with Janssen&Janssen Please note: 2020-2022 Added 04/01/2022 by Oksana Shlobin, value=Honoraria Consultant relationship with Altavant Please note: 2020-2022 Added 04/01/2022 by Oksana Shlobin, value=Consulting fee Consultant relationship with Acceleron Please note: 2020-2022 Added 04/01/2022 by Oksana Shlobin, value=Honoraria Consultant relationship with United Therapeutics Please note: 2020-2022 Added 04/01/2022 by Oksana Shlobin, value=Honoraria No relevant relationships by Anju Singhal No relevant relationships by Christopher Thomas

8.
Chest ; 162(4):A2560, 2022.
Article in English | EMBASE | ID: covidwho-2060963

ABSTRACT

SESSION TITLE: Lung Transplantation: New Issues in 2022 SESSION TYPE: Rapid Fire Original Inv PRESENTED ON: 10/19/2022 11:15 am - 12:15 pm PURPOSE: Currently the sequelae of COVID pneumonia in lung transplant recipients (LTR) is poorly described and the long-term effects are largely unknown. LTRs encompass a unique patient population with anatomic and immunological changes that pose a huge challenge in the management of COVID pneumonia compared to the general population. This project looks to further delineate risk factors, prognostication, and long-term sequelae of COVID pneumonia in LTRs. METHODS: A retrospective analysis was performed in a single large lung transplant center in Chicago from January 2020 to June 2021. Impact of COVID-19 based on patient demographics, management strategies, level of care, mortality, and pre- and post-COVID spirometry changes were analyzed based on follow-up visits after infection in survivors. RESULTS: There was an overall mortality of 21% with 68% requiring hospital admission. Of the patients admitted, there was a 62% mortality risk associated with ICU admission. Pre-existing chronic lung allograft dysfunction (CLAD) was present in 10 patients of which 50% were admitted to the ICU. Baseline FEV1 was 1.95 L with an average post covid FEV1 of 1.89 L (3.7% decline) for survivors. Pre-existing CLAD, lower baseline FEV1, and increased time since transplant were predictors of ICU admission. CONCLUSIONS: COVID-19 continues to remain a dangerous, life-threatening disease, particularly for LTRs. While there were no patients that developed CLAD post infection, there was an overall decrease in lung function. The long term trajectory of graft function post-covid remains unclear, however pre-existing allograft dysfunction appears to provide prognostic value. CLINICAL IMPLICATIONS: Further study needs to be done on COVID-19 and the long-term implications of allograft function in the LTR population. DISCLOSURES: Speaker/Speaker's Bureau relationship with boehringer ingelheim Please note: $5001 - $20000 by Brad Bemiss, value=Travel and payment for lecture No relevant relationships by Timothy O'Connor No relevant relationships by Love Patel

9.
Chest ; 162(4):A2559, 2022.
Article in English | EMBASE | ID: covidwho-2060962

ABSTRACT

SESSION TITLE: Lung Transplantation: New Issues in 2022 SESSION TYPE: Rapid Fire Original Inv PRESENTED ON: 10/19/2022 11:15 am - 12:15 pm PURPOSE: Donor-derived cell-free DNA (dd-cfDNA) is a promising plasma analyte for surveillance of rejection and lung transplant (LT) injury. Herein we report our preliminary real-world experiences in concert with standard of practice (SOP) assessments. METHODS: We performed a prospective, cross-sectional, cohort study of a clinically available dd-cfDNA test (the Prospera™ test, Natera, Inc.) combined with SOP clinical assessments − spirometry, fiberoptic bronchoscopy (FOB), donor-specific HLA antibodies (DSA). Single LT dd-cfDNA results were corrected (2X) for lung mass before analysis. Clinical-pathologic cohorts were assigned based on ISHLT guidelines for acute cellular rejection (ACR), uncomplicated chronic lung allograft dysfunction (U-CLAD), and either CoVid-19 or Non-CoVid-19 allograft infection. We also compared median dd-cfDNA fractions between patients experiencing allograft dysfunction (AD) (defined by ΔFEV1≥ -10%) vs stability (STA) and stratified by DSA status. Groups were analyzed by Mann-Whitney (p<0.05) and data expressed as median with 25-75% interquartile range (IQR). RESULTS: A total of 54 plasma samples from 42 unique LT recipients (Single=6, Double=36) were collected at Spectrum Health between November 2021 and February 2022. Primary diagnoses included chronic obstructive pulmonary disease (n=7), interstitial lung disease (n=31), CoVid-19 related ARDS (n=2), CF (n=1) and PAH (n=1). Matching histopathology was available for 68% of dd-cfDNA samples. dd-cfDNA fraction trended 2-fold higher in patient with ACR (1.59%, IQR: 0.09-3.57;n=3) and U-CLAD (1.88%, IQR: 0.88-3.32;n=4) than STA (0.86%, IQR: 0.21-1.62;n=14) patients. Patients with CoVid-19 had significantly higher dd-cfDNA fraction (6.91%, IQR: 2.41-9.77;n=4) than both STA (p=0.035) and NON-CoVid-19 infection cohorts (p=0.049). Although no antibody-mediated rejection (AMR) events were observed, dd-cfDNA fraction was significantly elevated in DSA(+) patients (2.75%, IQR: 1.72-6.25;n=8, class I (4) and II (4)) vs DSA(-) (1.035%, 0.04-1.64;n=46) cohorts (p=0.011). A trend was noted with elevated dd-cfDNA with AD (1.58%, IQR: 0.74-3.62;n=17) vs AS (1.05%, 0.66-1.79;n=37) (p=0.29). CONCLUSIONS: Our preliminary experience is consistent with prior studies, suggesting elevated dd-cfDNA fraction during LT allograft rejection and specific types of infection, in particular, CoVid-19. Of interest, dd-cfDNA detected potential occult molecular injury associated with anti-HLA DSA. CLINICAL IMPLICATIONS: dd-cfDNA fraction assessment after LT represents a valuable clinical tool for clinical surveillance of organ transplant health. DISCLOSURES: Employee relationship with Veracyte, Inc Please note: 2 years by Sangeeta Bhorade, value=Salary Removed 04/03/2022 by Sangeeta Bhorade Employee relationship with Natera Inc Please note: 2/22/22- present Added 04/03/2022 by Sangeeta Bhorade, value=Salary Employee relationship with Natera Please note: 05/2021-present Added 04/04/2022 by Kathryn Crabtree, value=Salary research relationship with United Therapeutics Please note: 2016- ongoing by Reda Girgis, value=Grant/Research research relationship with Pfizer Please note: 2014-2020 by Reda Girgis, value=Grant/Research Speaker/Speaker's Bureau relationship with Boehringher Ingelheim Please note: 2016-ongoing by Reda Girgis, value=Honoraria Speaker/Speaker's Bureau relationship with Genentech Please note: 2016-ongoing by Reda Girgis, value=Honoraria no disclosure on file for Cameron Lawson;No relevant relationships by Edward Murphy Employee relationship with Natera, Inc. Please note: 2020- present by David Ross, value=Salary

10.
Chest ; 162(4):A2474, 2022.
Article in English | EMBASE | ID: covidwho-2060949

ABSTRACT

SESSION TITLE: Unique Uses of Pulmonary Function Tests SESSION TYPE: Rapid Fire Original Inv PRESENTED ON: 10/19/2022 11:15 am - 12:15 pm PURPOSE: Prevention of asthma exacerbations can be done through adequate self management at home. This study aimed to evaluate the feasibility and safety of a portable spirometer for unsupervised home spirometry measurements among patients with asthma. METHODS: A single center, prospective, single-arm, open study recruited 25 patients with moderate or severe asthma. After a 45 min video training session by a respiratory therapist, patients performed daily spirometry at home with the Spirobank Smart MIR mobile spirometry system that was bluetooth connected to the KevaTalk app. Each spirometry examination was recorded and evaluated according to the ATS/ERS acceptability and repeatability criteria. Patients had to perform at least three technically acceptable maneuvers with the KevaTalk app guiding them if they had a good or bad blow. The best value of the three maneuvers were used for subsequent analyses. Patients also entered their daily check ins and symptoms via the KevaTalk Asthma app, tracked their controller and rescue medication use, filled up ATAQ questionnaires as well as were reminded of their action plans. Data obtained from spirometry was reviewed by nurses and pulmonologist and the Keva365 remote monitoring platform prompted alerts based on patient checkins, use of medication and PEF values in the red or yellow zone. Any escalations based on nurse review were reported to the office. RESULTS: Mean age of the patients was 57 years. 1155 spirometry sessions were completed over the duration of 9 months of the study. Data for FEV1, FEV6, PEF FEV1/FVC, as well as the Best Predicted and LLN values was reviewed daily for patients. Flow volume loops during the sessions were reviewed to identify if the home spirometry was done correctly and retraining was provided if needed. The reported values were tracked over the duration the patient was enrolled in the Keva program. 60.9% of patients were found to have peak flows in their respective red zones at least once and 87% were found to have peak flows in their yellow zone at least once, during the course of the study. If 3 consecutive values were in the yellow or red zone along with worsening of symptoms, the physician's office was informed for further course of action. CONCLUSIONS: The COVID-19 pandemic led to paucity of in office spirometry and face-to-face visits for asthmatic patients. Increasing the availability of spirometry with handheld devices along with a remote monitoring platform is useful for improving asthma control and reducing the risk of asthma-related hospital admissions and deaths. CLINICAL IMPLICATIONS: Remote objective spirometry yields clinically meaningful information that helps with asthma patient management and prevent an exacerbation from becoming worse. DISCLOSURES: No relevant relationships by Karim Anis No relevant relationships by Varada Divgi No relevant relationships by Jyotsna Mehta No relevant relationships by Shail Mehta No relevant relationships by Denzil Reid

11.
Chest ; 162(4):A2281, 2022.
Article in English | EMBASE | ID: covidwho-2060930

ABSTRACT

SESSION TITLE: Impact of Health Disparities and Differences SESSION TYPE: Rapid Fire Original Inv PRESENTED ON: 10/19/2022 11:15 am - 12:15 pm PURPOSE: To address rural healthcare disparities by providing access to home based pulmonary rehabilitation (HBPR) program for eligible veterans at the Salem Veterans Affairs Medical Center (VAMC) who reside in remote areas or those with barriers of long travel time and transportation hardship. METHODS: The Pulmonary Section at the Salem VAMC received a grant from the Office of Rural Health to establish HBPR program for eligible veterans. Its goal was to improve quality of life and potentially reduce COPD hospitalizations and exacerbations (AECOPD). Under the direction of pulmonologists, the program was run by an exercise physiologist (EP). Referrals were received from inpatient and outpatient providers. After an initial in-person evaluation, weekly telehealth meetings (telephone, video) occurred over 12 weeks. Veterans were provided with the equipment, and an individualized targeted exercise program along with education and counseling on tobacco cessation, nutrition, oxygen compliance, stress management, medication adherence. Follow up appointments were scheduled at 3, 6 and 12 months post completion. RESULTS: Between September 2020 and January 2022, 312 consults were received, 206 consults were scheduled and 175 veterans enrolled. To date, 100 have completed the program with 24 ongoing. 30% declined service, citing: comorbidities, physical debility, difficulty remembering scheduled appointments, lack of motivation, social reasons, worsening health status. Mean age was 71, male predominance (95%). Referral diagnoses included: COPD (86%), chronic hypoxic respiratory failure (55%), COVID-19 (11%), Interstital Lung Diseases (10%). Mean FEV1 was 57% predicted, mean MMRC Dyspnea Scale 2.5, mean BODE score 5. 20% of enrolled veterans were active smokers, 72% were former smokers. 6 minute walk test increased from 156 meters on enrollment to 216 meters on completion. 45 veterans required hospitalization for pulmonary issues during their participation in the program. EP identified on weekly appointments 20 AECOPD that were treated as outpatient, 1 spontaneous pneumothorax that led to hospitalization, and facilitated the refill of inhalers or adjustment of medical regimen. Patient satisfaction score, including perception of benefit post completion was 29.4/30. CONCLUSIONS: HBPR at the Salem VAMC provided access to eligible veterans, overcoming barriers of rurality, transportation hardship and lack of nearby conventional programs. It also offered off business hours PR to veterans who continue to work. It allowed decrease in community care referrals thus establishing useful and cost effective service. CLINICAL IMPLICATIONS: Pulmonary Rehabilitation has been shown to reduce morbidity, improve functional status and have mortality benefit. Healthcare discrepancies and disparities have been a major obstacle for enrollment. HBPR would address these issues and contribute to decreased health service utilization and costs. DISCLOSURES: No relevant relationships by Nathalie Abi Hatem No relevant relationships by Brittany Frost No relevant relationships by Mitchell Horowitz No relevant relationships by Deepa Lala

12.
Chest ; 162(4):A2264, 2022.
Article in English | EMBASE | ID: covidwho-2060926

ABSTRACT

SESSION TITLE: Post-COVID-19 Outcomes SESSION TYPE: Rapid Fire Original Inv PRESENTED ON: 10/19/2022 11:15 am - 12:15 pm PURPOSE: Alterations in lung function may occur in patients with HIV and who were infected with SARSCoV2. In order to describe this characteristics we created the following groups: Group (1) HIV (+) SARS-COV-2 (+), Group (2) HIV (+) SARS-COV-2 (-), Group (3) HIV (-) SARS-COV2 (+), Group (4) HIV (-) SARS-COV-2 (-). METHODS: In this prospective, longitudinal cohort we included patients with infection with SARS-CoV-2 ( RT- PCR test o Antigen Testing positive) who agreed to participate in the study. Spirometry, diffusing capacity of carbon monoxide (DLCO), body plethysmography, and 6-minute walk test (6MWT) were performed to assess lung function 3 to 6 months after SARS-CoV2 infection, clinical and laboratory characteristics were assesed. We performed descriptive statistics including means and standar deviations for normally distributed continous variables, medians and interquartile ranges for non-parametric distributions, and proportions for categorical variables. The comparisons between groups were made using Fisher´s exact test and Mann-Whitney U for categorical and continous variables respectively. RESULTS: During the between April 2021-February 2022, a total of 104 patients were included. Group (1)44 patients (14 were hospitalized), Group (2)19 patients, Group (3)26 patients (16 were hospitalized), Group (4)15 patients. Hypertension was higher in the Group HIV (-) SARS-COV-2 (+). We didn´t find differences in lung pulmonary function (Spirometry, DLCO, body plethysmography or 6MWT between groups). Spirometry results: FEV1/FVC % Predicted Group 1: 58.0 [25.5, 74.0], Group 2:42.5 [19.5, 65.5], Group 3: 55.0 [38.5, 80.5], Group 4: 35.0 [19.0, 68.5], HIV(+)/HIV(-) p-value: 0.43. DLCO% predicted Group 1: 82.7 [71.5, 90.0], Group 2: 86.7 [76.8, 96.3], Group 3: 85.6 [76.8, 91.6], Group 4: 88.3 [85.7, 98.6], p: 0.199. Total lung capacity (TLC) % of predicted, Group 1: 101 [88.8, 109], Group 2: 99.5 [97.0, 112], Group 3: 102 [94.3, 112], Group 4: 111 [103, 115], p: 0.105. 6MWT: Group 1: 566 [529, 604], Group 2: 595 [548, 622], Group 3: 548 [493, 604], Group 4: 593 [547, 630], p: 0.702. CONCLUSIONS: To our knowledge, this is the first study to characterize pulmonary function in ill COVID-19 survivors with HIV. Our results suggest not difference between the lung function tests performed in patients coinfected with HIV and SARS-CoV 2 compared to patients infected with SARS-CoV2 HIV (-). Limitations, not pre-testing pulmonary function. Inclusion of a greater number of HIV (-) patients who required hospitalization. CLINICAL IMPLICATIONS: Beyond the effects of SARS-CoV2 on HIV outcomes, it is essential to examine whether HIV has an impact on susceptibility to COVID-19 or if it will generate changes that lead to increased sequelae in these patients. It is well known that patients with HIV may be at increased risk of lung function test abnormalities due to the infection itself, as well as some additional exposures. DISCLOSURES: No relevant relationships by Olivia Briceño No relevant relationships by GUSTAVO CASAS no disclosure on file for Mauricio Gonzalez Navarro;No relevant relationships by Alejandro Juárez Díaz No relevant relationships by William C. Lara-Vazquez No relevant relationships by María Isabel León Rodríguez No relevant relationships by JOSE CHRISTIAN RODRIGUEZ HERNANDEZ No relevant relationships by Gonzalo Salgado

13.
Chest ; 162(4):A2190, 2022.
Article in English | EMBASE | ID: covidwho-2060909

ABSTRACT

SESSION TITLE: Issues After COVID-19 Vaccination Case Posters SESSION TYPE: Case Report Posters PRESENTED ON: 10/19/2022 12:45 pm - 01:45 pm INTRODUCTION: Eosinophilia is the most commonly reported adverse event following administration of the Pfizer/BioNTech vaccine, accounting for 237 of 372 events (63.7%). Eosinophilic pneumonia has been described noted in 3 of all reported cases. CASE PRESENTATION: We present the case of a 73 year-old male presented to his PCP with a 3 week history of nonproductive cough and wheezing. He completed a 2-shot series of BNT162b2 mRNA (Pfizer/BioNTech) COVID vaccine 1 week prior to symptom onset. He had no history of respiratory symptoms, smoking, sick contacts, recent travel, chemical or biological exposures. On presentation, he was afebrile, tachycardic and required 3LPM supplemental oxygen to maintain peripheral oxygen saturation (SpO2) above 94%. Laboratory findings noted leukocytosis (13,200/mL) and eosinophilia at 5% (Absolute Eosinophil Count (AEC): 580 cells/L). Respiratory viral panel, procalcitonin, ESR and D-dimer were negative. Chest CT scan was unremarkable. He was treated with azithromycin, prednisone and inhaled bronchodilators with improvement in hypoxia. 2 weeks later, he reported intermittent dyspnea during a pulmonary clinic visit. Pulmonary function testing was normal (FEV1/FVC: 76%;FVC: 3.67L (90% predicted);FEV1: 2.80L (88% predicted). IgE level was normal and eosinophilia had resolved. 6 months after initial symptom onset, the patient received his third BNT162b2 mRNA vaccine dose. 2 weeks after vaccination, he presented to the ED with severe dyspnea, wheezing and cough with yellow sputum. He also noted a new itchy, erythematous bilateral forearm rash and painless oral ulcers. On exam, he was afebrile, tachypneic with SpO2 of 93% on 4LPM supplemental oxygen and audibly wheezing with a prolonged expiratory phase. Laboratory studies noted elevated creatinine and leukocytosis (23,100/mL) with marked eosinophilia (29.5 %, AEC: 6814 cells/L). Chest CT scan revealed a 2 cm rounded ground-glass opacity in the right upper lobe. (Figure 1.) Further workup revealed a weakly positive antihistone antibody (1:4 titer). IgE, ANA, ANCA, SS-A/B, anti-CCP, and complement levels were normal. Intravenous methylprednisolone treatment was initiated with rapid improvement in dyspnea, eosinophilia and renal function. A transbronchial biopsy (Figure 2.) of the RUL lung lesion revealed organizing pneumonia with mixed inflammatory infiltrate. Bronchoalveolar lavage analysis revealed elevated WBC (432 cells/L) with neutrophilic predominance (85%). Patient was discharged home on a prednisone taper with resolution of symptoms. DISCUSSION: Subsequent allergy work up did not indicate any apparent etiology of hypereosinophilia. Testing for strongyloides, coccidiosis and aspergillosis were also negative. A final diagnosis of BNT162b2 mRNA vaccine related pulmonary eosinophilia was made. CONCLUSIONS: Additional study is warranted into eosinophilic disease associated with the BNT162b2 mRNA vaccine. Reference #1: 1. United States Department of Health and Human Services (DHHS), Public Health Service (PHS), Centers for Disease Control (CDC) / Food and Drug Administration (FDA), Vaccine Adverse Event Reporting System (VAERS) 1990 - 03/11/2022, CDC WONDER On-line Database. Accessed at http://wonder.cdc.gov/vaers.html on Mar 11, 2022 1:18:37 PM DISCLOSURES: No relevant relationships by Matthew Haltom No relevant relationships by Nikky Keer No relevant relationships by Thekrayat Khader No relevant relationships by Muthiah Muthiah

14.
Chest ; 162(4):A2006-A2007, 2022.
Article in English | EMBASE | ID: covidwho-2060886

ABSTRACT

SESSION TITLE: Occupational and Environmental Lung Disease Case Posters SESSION TYPE: Case Report Posters PRESENTED ON: 10/17/2022 12:15 pm - 01:15 pm INTRODUCTION: We describe a case of acute progression of chronic hypersensitivity pneumonitis (HP) in an adult, previously misdiagnosed as COPD for 13 years due to severe emphysematous changes seen on imaging. He was also found to have acutely worsened disease as a result of Covid-19. CASE PRESENTATION: A 64-year-old male presented to the pulmonary clinic with dyspnea on minimal exertion. He reported respiratory complaints for 13 years, treated with 2 L/min of oxygen overnight, and budesonide-formoterol and tiotropium inhalers. These complaints were previously associated with brief occupational mold exposure and possible COPD. His respiratory distress worsened one year ago when he was hospitalized for Covid-19. On discharge, his oxygen requirement had increased to 6 L/min. CT chest showed air-trapping in the mid-zones bilaterally, mosaic attenuation, and peri-bronchial thickening. PFTs showed an FEV1 33% and FVC 55% of predicted, consistent with severe obstruction and reduction in lung volume. As the patient was a lifetime non-smoker, alternative diagnoses were pursued. Alpha-1 antitrypsin levels and immunologic testing, including scleroderma and myositis panels, were within normal limits. Positive findings included CCP IgG/IgA antibodies at 96 units and HP panel positive for pigeon serum antibodies. Prompted by this testing, the patient revealed that he had parakeets in his home for the past 15 years. He also reported significant symptom improvement on occasions that he took a course of steroids. Based on these findings, a diagnosis of chronic fibrotic hypersensitivity pneumonitis with bronchiolitis obliterans was considered. The patient's severe airflow obstruction and respiratory failure precluded surgical lung biopsy. Empiric management was initiated with 30 mg of prednisone daily with a slow taper and instruction to eliminate exposure to exotic birds. DISCUSSION: HP is commonly caused by inhalation of and sensitization to an aerosolized environmental antigen;a common subtype is bird fancier's lung due to repetitive exposure of avian antigen. Continuous antigen exposure increases the risk for development of fibrosis, which was also seen in our patient. The most commonly described radiologic findings in HP are ground-glass opacities, ill-defined centrilobular nodules, and focal areas of air trapping resulting in mosaic attenuation and fibrosis. More than 20% lymphocytosis on bronchoalveolar lavage is also a sensitive tool in detecting alveolitis. The relationship between Covid-19 and disease progression in HP is not well studied. CONCLUSIONS: Chronic hypersensitivity pneumonitis from avian antigens, or Bird fancier's lung, can present with severe emphysematous changes on CT imaging, along with obstructive pattern of PFTs. This should be an important differential, especially in patients who are non-smokers. Covid-19 causes disease progression in HP, this relationship needs to be further explored. Reference #1: Funke M., Fellrath J.-M. Hypersensitivity pneumonitis secondary to lovebirds: a new cause of bird fancier's disease. Eur. Respir. J. 2008;32:517–521. DOI: 10.1183/09031936.00108507 Reference #2: Pereira C., Gimenez A., Kuranishi L., Storrer K. Chronic hypersensitivity pneumonitis. J. Asthma Allergy. 2016;9:171–181. DOI: 10.2147/JAA.S81540 Reference #3: C.S. Glazer, C.S. Rose, D.A. Lynch Clinical and radiologic manifestations of hypersensitivity pneumonitis J. Thorac. Imag., 17 (4) (2002), pp. 261-272. DOI: 10.1097/00005382-200210000-00003 Morell F, Roger A, Reyes L, Cruz MJ, Murio C, Muñoz X Bird fancier's lung: a series of 86 patients. Medicine (Baltimore). 2008;87(2):110-130. DOI: 10.1097/MD.0b013e31816d1dda DISCLOSURES: No relevant relationships by Momina Amjad No relevant relationships by Amit Chopra No relevant relationships by Rafeh Safdar

15.
Chest ; 162(4):A2002, 2022.
Article in English | EMBASE | ID: covidwho-2060885

ABSTRACT

SESSION TITLE: Occupational and Environmental Lung Disease Case Posters SESSION TYPE: Case Report Posters PRESENTED ON: 10/17/2022 12:15 pm - 01:15 pm INTRODUCTION: Hypersensitivity Pneumonitis (HP) one of the most common interstitial lung diseases (ILD) and is caused by an allergic reaction to an inciting agent in the airway of a susceptible individual1. The diagnosis is challenging as many of the classic symptoms, dyspnea and fatigue, are nonspecific. An accurate diagnosis involves careful history taking, physical exam, pulmonary function tests (PFTs), chest computed tomography (CT) imaging, and lung biopsy. CASE PRESENTATION: Patient is a 51 year old female with no PMH presents to clinic with worsening dyspnea and nonproductive cough. Symptoms began 6 months ago. She could not identify any triggers and was prescribed steroids and antibiotics with minimal relief. The patient has never smoked, denies drug use but had two pigeons. During the COVID pandemic she admitted to staying indoors more often and was not nearly as active outdoors as before. She denied fevers, chills, night sweats and weight loss. CXR showed no focal infiltrates, sharp costophrenic angels with no evidence of acute pathology. PFT's showed FVC pre 1.78, FVE1 pre 1.35, FVE1 % predicted pre 48%, FEV1/FVC pre 76%, TLC pre 3.23, VC pre 2.06 and a DLCO pre 10.98 with her LLN of 16.59. FVC post 1.91, FEV1 post 1.57, FVE1 % predicted post 58%, FEV1/FVC post 82% (Fig 1). She had positive pigeon serum antibodies. CT chest showed faint diffuse ground glass opacities bilaterally with mild mosaic attenuation reflecting HP (Figs 2, 3). The patient was diagnosed with HP, started on steroids and surrendered her pigeons with resolution of her symptoms. DISCUSSION: Diagnosis of HP is challenging as the classic symptoms of dyspnea and fatigue can be nonspecific. Physicians should be aware about increasing exposures to home antigens during the COVID pandemic in patients who have been indoors for prolonged periods of time. PFTs show a restrictive pattern and DLCO impairment. CT show the presence of centrilobular nodules, ground-glass opacities, mosaic attenuation/perfusion and air trapping and in longstanding disease there can be honeycombing and traction bronchiectasis2. Mainstay treatment is antigen avoidance and corticosteroids. Identification and complete avoidance of the antigen is the mainstay of treatment. Antigen avoidance is critically stressed as repeated exposures can result in HP progression and avoidance of the antigen is associated with improved lung function1. Corticosteroid initiation in progressive patients resulted in a reversal with an improvement of lung function3. Corticosteroids are often used in non-fibrotic HP however its efficacy remains unclear as long term prognosis has never been studied1. CONCLUSIONS: Physicians should recognize that prolonged time indoors, that have been exacerbated during the COVID19 pandemic, can increase the time patients are exposed to home antigens thus a prompt diagnosis and strict avoidance of the antigen is required to prevent irreversible damage. Reference #1: Maria Laura Alberti, "Hypersensitivity Pneumonitis: Diagnostic and Therapeutic Challenges". Frontiers in Medicine, Front. Med., 23 September 2021 ;https://doi.org/10.3389/fmed.2021.718299 Reference #2: Zompatori M, Calabrò E, Chetta A, Chiari G, Marangio E, Olivieri D. Chronic hypersensitivity pneumonitis or idiopathic pulmonary fibrosis? Diagnostic role of high resolution Computed Tomography (HRCT). Radiol Med. 2003 Sep;106(3):135-46. English, Italian. PMID: 14612834 Reference #3: De Sadeleer LJ, Hermans F, De Dycker E, Yserbyt J, Verschakelen JA, Verbeken EK, Verleden GM, Wuyts WA. Effects of Corticosteroid Treatment and Antigen Avoidance in a Large Hypersensitivity Pneumonitis Cohort: A Single-Centre Cohort Study. J Clin Med. 2018 Dec 21;8(1):14. doi: 10.3390/jcm8010014. PMID: 30577667;PMCID: PMC6352061. DISCLOSURES: No relevant relationships by Aryeh Bernstein No relevant relationships by Thai Donenfeld No relevant relationships by Lourdes Marie F aminiano

16.
Chest ; 162(4):A1778, 2022.
Article in English | EMBASE | ID: covidwho-2060860

ABSTRACT

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

17.
Chest ; 162(4):A1289-A1290, 2022.
Article in English | EMBASE | ID: covidwho-2060797

ABSTRACT

SESSION TITLE: COVID-19 Case Report Posters 2 SESSION TYPE: Case Report Posters PRESENTED ON: 10/19/2022 12:45 pm - 01:45 pm INTRODUCTION: Much has been learned about the immune dysregulation and release of pro-inflammatory cytokines since the emergence of the COVID-19 pandemic.1 Patients with interstitial lung disease are often on immunosuppressive agents, such as rituximab, which is a B-cell depleting agent. There has been a large retrospective cohort study showing that rituximab therapy was the only immunosuppressive medication with a trend towards in-hospital death.2 We present a case of COVID-19 in a patient on rituximab with ANCA vasculitis. CASE PRESENTATION: A 51-year-old male, never smoker, with ANCA positive vasculitis (positive MPO and PR3) and interstitial lung disease (on 4-5L of oxygen) presented to the hospital with nausea and fever for 2 days and was found to have a positive SARS-CoV-2 PCR. At the time of presentation, he was on rituximab 1000 mg x 2 doses every 6 months with last infusion one month prior to presentation, azathioprine 150 mg daily, prednisone 15 mg daily, nintedanib 100 mg BID, and IVIG monthly. Spirometry showed FVC of 1.60L/37% predicted and an FEV1 1.28L/39% predicted. Patient had 2 COVID vaccinations and one booster (all Pfizer mRNA), the latter 3 months prior to presentation. On admission, he was saturating at 55% on 4L and placed on 15L non-rebreather;he was afebrile, normotensive, and with a pulse of 110 BPM. Exam was notable for a cough, wheezing, and tachypnea. Lab work was notable for positive SARS-COV-2 PCR, a total white blood cell count of 5.3x103 uL, and a normal hemoglobin and platelet count. He had a CO2 of 34, normal creatinine, and no transaminitis. Lactate dehydrogenase (LDH) was elevated at 318 U/L, and lactate was elevated at 3.5 mmol/L. His chest x-ray on admission demonstrated patchy filling opacities and low lung volumes. He received dexamethasone, remdesivir, and the monoclonal antibodies casirivimab and imdevimab (REGEN-COV) on the first day of admission. Patient also received his monthly IVIG dose inpatient. After a week, he was weaned back to his home oxygen and symptomatically back to baseline. Most recent PFTs on the same outpatient immunosuppressive regimen as prior to admission are unchanged. Patient received two doses of preventative monoclonal antibodies (EVUSHELD) 3 months after admission. DISCUSSION: Here we discuss a case of a patient with severe COVID-19 pneumonia requiring inpatient hospitalization despite three COVID mRNA vaccinations, likely secondary to difficulty in mounting an immune response to the vaccinations given his use of immunosuppressive medications. This is also an example of the early use of monoclonal antibodies in an inpatient with long term preservation of his underlying lung function.3 CONCLUSIONS: We recommend counseling and close observation of patients on rituximab due to risk of severe COVID-19 infection as well the use of preventative monoclonal antibodies (EVUSHELD). Reference #1: Jamal M, Bangash HI, Habiba M, Lei Y, Xie T, Sun J, Wei Z, Hong Z, Shao L, Zhang Q. Immune dysregulation and system pathology in COVID-19. Virulence. 2021 Dec;12(1):918-936. doi: 10.1080/21505594.2021.1898790. PMID: 33757410;PMCID: PMC7993139. Reference #2: Andersen, K. M., Bates, B. A., Rashidi, E. S., Olex, A. L., Mannon, R. B., Patel, R. C., Singh, J., Sun, J., Auwaerter, P. G., Ng, D. K., Segal, J. B., Garibaldi, B. T., Mehta, H. B., Alexander, G. C., Haendel, M. A., & Chute, C. G. (2022). Long-term use of immunosuppressive medicines and in-hospital COVID-19 outcomes: A retrospective cohort study using data from the National COVID Cohort Collaborative. The Lancet Rheumatology, 4(1), e33–e41. https://doi.org/10.1016/S2665-9913(21)00325-8 Reference #3: Weinreich, D. M., Sivapalasingam, S., Norton, T., Ali, S., Gao, H., Bhore, R., Xiao, J., Hooper, A. T., Hamilton, J. D., Musser, B. J., Rofail, D., Hussein, M., Im, J., Atmodjo, D. Y., Perry, C., Pan, C., Mahmood, A., Hosain, R., Davis, J. D., Yancopoulos, G. D. (2021). Regen-cov antibody combination and outcomes in outpatients with covid-19. New England Journal of Medicine, 385(23), e81. https://doi.org/10.1056/NEJMoa2108163 DISCLOSURES: Advisory Committee Member relationship with Genentech Please note: 2019-2022 Added 06/06/2022 by Ayodeji Adegunsoye, value=Consulting fee Advisory Committee Member relationship with Boehringer Ingelheim Please note: 2018-2022 Added 06/06/2022 by Ayodeji Adegunsoye, value=Consulting fee Speaker/Speaker's Bureau relationship with Boehringer Ingelheim Please note: 2018-2022 Added 06/06/2022 by Ayodeji Adegunsoye, value=Honoraria Consultant relationship with Genentech Please note: 2018-2020 by Ayodeji Adegunsoye, value=Consulting fee Removed 06/06/2022 by Ayodeji Adegunsoye No relevant relationships by Cathryn Lee No relevant relationships by Kavitha Selvan PI relationship with Boehringer-Ingelheim Please note: >$100000 by Mary Strek, value=Grant/Research Support PI relationship with Galapagos Please note: $70,000-100,00 by Mary Strek, value=Grant/Research Support Endpoint Adjudication Committee Member relationship with Fibrogen Please note: $1-$1000 by Mary Strek, value=Honoraria No relevant relationships by Rachel Strykowski

18.
Chest ; 162(4):A638, 2022.
Article in English | EMBASE | ID: covidwho-2060654

ABSTRACT

SESSION TITLE: Unique Uses of Pulmonary Function Tests SESSION TYPE: Rapid Fire Original Inv PRESENTED ON: 10/19/2022 11:15 am - 12:15 pm PURPOSE: Coronavirus disease 2019 (COVID-19) is a highly transmissible respiratory disease that causes global pandemic. It is known to cause impairment of lung function leading to morbidity and mortality. Long term data for lung function tests in these populations is still limited. METHODS: A retrospective chart review of patients with COVID-19 pneumonia who had initial and follow up spirometry tests from August 2020 to December 2021 in a pulmonary clinic in Corpus Christi, Texas was performed. Baseline characteristic and spirometry parameters including age, gender, race, body mass index, comorbidities, pre/post bronchodilator FEV1, FVC, lung volume, DLCO and 6-minute walk test were collected. T test analysis was performed to compare the data between initial and follow up pulmonary function tests. RESULTS: A total of 29 patients were enrolled.The mean COVID diagnosis to PFT interval was 126 days. Mean follow up duration was 309 days. Mean (SD) age was 58 (10) years. Forty-eight percent of the participants were male gender. Majority of our participants were hispanic (72%) followed by caucasian (21%) and others (7%). Average BMI (SD) was 34.6 (7.5) kg/m². Restrictive lung defect pattern was found in 55.2% on initial pulmonary function test in the clinic which dropped to 41.4% in the follow up test with supportive management. Initial and follow up prebronchodilator percent predicted mean(SD) of FVC were 65 (20) and 72 (20) respectively with a mean difference of 6.3 (p=0.002, 95% CI 2.54-10.10). Initial and follow up prebronchodilator percent predicted mean(SD) of FEV1 were 71 (23) and 78 (21) respectively with a mean difference of 6.7 (p=0.003, 95% CI 2.46-10.90). Moreover, mean(SD) of DLCO and TLC showed significant improvement during follow-up visit [DLCO-69 (24) and 77 (20), mean difference of 7.6 (p=0.016, 95% CI 1.58-13.59), TLC-64 (17) and 71 (14) respectively, mean difference of 7(p=0.005, 95%CI 2.32-11.76)]. CONCLUSIONS: We found improvement of many parameters of pulmonary function test in post COVID-19 patients during follow-up with supportive care. CLINICAL IMPLICATIONS: Regular follow up can be a useful tool to understand the prognosis of post COVID-19 pneumonia sequelae. DISCLOSURES: No relevant relationships by Asad Chohan No relevant relationships by Saiara Choudhury No relevant relationships by Pahnwat Taweesedt No relevant relationships by Abhay Vakil

19.
Chest ; 162(4):A346, 2022.
Article in English | EMBASE | ID: covidwho-2060570

ABSTRACT

SESSION TITLE: Long COVID: It Can Take Your Breath Away SESSION TYPE: Original Investigations PRESENTED ON: 10/16/2022 10:30 am - 11:30 am PURPOSE: Post-acute sequelae of COVID-19 (PASC) infection is an area of active research, and much remains unknown about the trajectory of respiratory system recovery. While chronic dyspnea is a commonly reported PASC symptom, it is unclear how objective lung function metrics change over time. In this study, we sought to in lung function in PASC by comparing serial pulmonary function tests (PFTs) after COVID-19 infection. METHODS: Patients with prior COVID-19 infection and at least two PFTs after acute infection were identified retrospectively from our COVID-19 recovery clinic at a tertiary care center in Chicago, Illinois. PFT data and other clinical information were ed from the electronic medical record. Using a matched paired t-test, the differences between forced expiratory volume at one second (FEV1), forced vital capacity (FVC), total lung capacity (TLC), and diffusion capacity of carbon monoxide (DLCO) were compared over time. RESULTS: There were 32 patients who underwent pulmonary function testing twice after COVID-19 illness from 2020-2022, with a mean age of 56 years. The majority of the cohort were female (59%) and white (56%). 16 patients (50%) had required hospitalization for their acute COVID-19 illness, and 7 (22%) had required ICU level of care. The mean time from illness onset to first PFT was 207 days, and the mean time between the first and second PFT was 204 days. There was a statistically significant increase in FVC (2.2%, p=0.01), TLC (2.2%, p=0.01), and DLCO (2.43 mL/min/mmHg), but not in FEV1. Rate of change was calculated for each patient by dividing the difference for each parameter by the time (in years) between PFTs. TLC improved most rapidly (median 10.9% per year, IQR 0-24), followed by DLCO (median 6.6% per year, IQR -1 – 19.4). FEV1 increased by 3.9% per year (IQR -12.5 – 22), and FVC increased by 5.1% per year (IQR -4.5 – 22.7). Rate of change was calculated for each patient by dividing the difference for each parameter by the time (in years) between PFTs. TLC improved most rapidly (median 10.9% per year, IQR 0-24), followed by DLCO (median 6.6% per year, IQR -1 – 19.4). FEV1 increased by 3.9% per year (IQR -12.5 – 22), and FVC increased by 5.1% per year (IQR -4.5 – 22.7). CONCLUSIONS: There was an improvement in lung function metrics in our PASC cohort. This data describes the rate of improvement for each parameter, which may be helpful in prognostication and counselling patients about expected recovery times. CLINICAL IMPLICATIONS: A large number of patients with PASC experience chronic dyspnea and have persistent radiographic changes and/or abnormal pulmonary function testing. Our data suggests that for patients with abnormal PFTs, there is gradual improvement over time. With the burden of COVID-19 illness worldwide, it is crucial that we can accurately risk stratify those at high risk for persistent symptoms as well as understand the trajectory of recovery. DISCLOSURES: no disclosure submitted for Joseph Bailey;No relevant relationships by Amy Ludwig No relevant relationships by Marc Sala

20.
Chest ; 162(4):A1-A5, 2022.
Article in English | EMBASE | ID: covidwho-2060532

ABSTRACT

SESSION TITLE: Imaging Across the Care Spectrum SESSION TYPE: Rapid Fire Original Inv PRESENTED ON: 10/19/2022 11:15 am - 12:15 pm PURPOSE: Eosinophilic airway inflammation and mucus plugs are common in asthma patients. Eosinophil depletion may reduce mucus plugging and improve airway patency and airflow distribution. This study will investigate the short-term benefits of sustained depletion of airway eosinophils by benralizumab, an anti-IL-5Rα monoclonal antibody, on airway structure and dynamics using functional respiratory imaging (FRI) in adults with severe eosinophilic asthma (SEA). METHODS: A multicenter, single-arm, open-label, phase 4 study enrolling approximately 138 patients. Screening will be followed by a run-in period of up to 21 days, before administration of subcutaneous benralizumab 30 mg at Weeks 0, 4 and 8, final assessment at Week 13, and a 2-week follow-up period. RESULTS: Key inclusion criteria: age 18-70 years with diagnosed SEA inadequately controlled by high-dose inhaled corticosteroid and long-acting β2-agonist (ICS-LABA) treatment +- oral corticosteroids (OCS) or other asthma controllers;documented post-bronchodilator (BD) reversibility;≥2 exacerbations in prior 12 months;baseline peripheral blood eosinophil count ≥300/μL (≥150 cells/μL if OCS-dependent);pre-BD forced vital capacity (FVC) <65% predicted, pre-BD FEV1 <80% predicted and Asthma Control Questionnaire (ACQ-6) ≥1.5. Key exclusion criteria: exacerbation/pulmonary infection 6 weeks pre-screening;smokers or ex-smokers who stopped smoking ≤12 months pre-screening and/or history of >10 pack-years;positive for COVID-19 at or ≤6 weeks before screening, or severe COVID-19 at any time.The primary endpoint is mean change from baseline in specific airway volume measured at total lung capacity. Secondary objectives include change from baseline in airway dynamics (lung, airway and blood vessel volumes, airflow distribution, airway resistance, air trapping, ventilation/perfusion mapping) and mucus plug scores, and correlations with conventional lung function measurements (FVC, FEV1) at baseline and Week 13. FRI will be via computed tomography scans assessed using computer modelling. Exploratory objectives include: relationships between airway dynamics and patient-reported outcomes (PROs) such as the Asthma Impairment and Risk Questionnaire (AIRQ), ACQ-6, and St George's Respiratory Questionnaire (SGRQ) at baseline, from baseline to Week 13, and change from baseline in Central/Peripheral (C/P) lung deposition ratio of inhaled drugs. Safety and tolerability will also be assessed. CONCLUSIONS: This study will advance understanding of the eosinophil-depletion effects of benralizumab on airway structure, dynamics, and mucus plugs and could provide additional useful insights into the relationship of PROs with changes in airway dynamics and structure. CLINICAL IMPLICATIONS: Our results may help further characterize physiologic changes resulting from eosinophil depletion with benralizumab and better delineate the impact of changes in lung function and structure on PROs. DISCLOSURES: stockholder relationship with AstraZeneca Please note: 2 years Added 03/31/2022 by Donna Carstens, value=Salary No relevant relationships by Wilfried De Backer Employee relationship with AstraZeneca LP Please note: Since 2014 by Eduardo Genofre, value=Salary Shareholder relationship with AstraZeneca LP Please note: Since 2014 by Eduardo Genofre, value=LTIs Employee relationship with FLUIDDA Inc Please note: Aug 2021 - Present Added 04/12/2022 by Patrick Muchmore, value=Salary Advisory Committee Member relationship with AstraZeneca Please note: 24 months Added 03/29/2022 by Reynold Panettieri, value=Grant/Research Support Removed 03/29/2022 by Reynold Panettieri Consultant relationship with AstraZeneca Please note: 24 months Added 03/29/2022 by Reynold Panettieri, value=Honoraria Removed 03/29/2022 by Reynold Panettieri Speaker/Speaker's Bureau relationship with AstraZeneca Please note: 24 months by Reynold Panettieri, value=Honoraria Removed 03/29/20 2 by Reynold Panettieri Advisory Committee Member relationship with RIFM Please note: 24 months by Reynold Panettieri, value=Grant/Research Support Removed 03/29/2022 by Reynold Panettieri Consultant relationship with RIFM Please note: 24 months by Reynold Panettieri, value=Honoraria Removed 03/29/2022 by Reynold Panettieri Advisory Committee Member relationship with Equillium Please note: 24 months Added 03/29/2022 by Reynold Panettieri, value=Grant/Research Support Removed 03/29/2022 by Reynold Panettieri Advisory Committee Member relationship with Equillium Please note: 24 months by Reynold Panettieri, value=Honoraria Removed 03/29/2022 by Reynold Panettieri Advisory Committee Member relationship with Genetech Please note: 24 months Added 03/29/2022 by Reynold Panettieri, value=Grant/Research Support Removed 03/29/2022 by Reynold Panettieri Speaker/Speaker's Bureau relationship with Genetech Please note: 24 months by Reynold Panettieri, value=Honoraria Removed 03/29/2022 by Reynold Panettieri Speaker/Speaker's Bureau relationship with Sanofi/Regeneron Please note: 24 months by Reynold Panettieri, value=Honoraria Removed 03/29/2022 by Reynold Panettieri Consultant relationship with Bayer Please note: 24 months by Reynold Panettieri, value=Honoraria Advisory Committee Member relationship with Theravance Please note: 24 months by Reynold Panettieri, value=Grant/Research Support Advisory Committee Member relationship with Novartis Please note: 24 months Added 03/29/2022 by Reynold Panettieri, value=Grant/Research Support Removed 03/29/2022 by Reynold Panettieri Contracted Research relationship with Optikira Please note: 24 months by Reynold Panettieri, value=Grant/Research Support Removed 03/29/2022 by Reynold Panettieri Advisory Committee Member relationship with Medimmune Please note: 24 months Added 03/29/2022 by Reynold Panettieri, value=Grant/Research Support Removed 03/29/2022 by Reynold Panettieri Contracted Research relationship with Maven Please note: 24 months by Reynold Panettieri, value=Grant/Research Support Removed 03/29/2022 by Reynold Panettieri Contracted Research relationship with Evelobio Please note: 24 months by Reynold Panettieri, value=Grant/Research Support Contracted Research relationship with Johnson & Johnson Please note: 24 months by Reynold Panettieri, value=Grant/Research Support Advisory Committee Member relationship with AstraZeneca;RIFM;Equillium;Genentech;Thervance Please note: 24 months by Reynold Panettieri, value=Honoraria Removed 03/29/2022 by Reynold Panettieri Consultant relationship with AstraZeneca;RIFM;Equillium;Bayer Please note: 24 months by Reynold Panettieri, value=Honoraria Removed 03/29/2022 by Reynold Panettieri Speaker/Speaker's Bureau relationship with AstraZeneca;Sanofi/Regeneron;Genentech Please note: 24 months by Reynold Panettieri, value=Honoraria Removed 03/29/2022 by Reynold Panettieri Research grant recipient relationship with Novartis;Optikira;Medimmune;Maven;Evelobio Please note: 24 months by Reynold Panettieri, value=Grant/Research Support Removed 03/29/2022 by Reynold Panettieri Research grant recipient relationship with Johnson & Johnson;AstraZeneca;RIFM;Equillium;Genentech Please note: 24 months by Reynold Panettieri, value=Grant/Research Support Removed 03/29/2022 by Reynold Panettieri Research grant recipient relationship with Theravance Please note: 24 months by Reynold Panettieri, value=Grant/Research Support Advisory Committee Member relationship with AstraZeneca Please note: $1001 - $5000 by Reynold Panettieri, value=Consulting fee Removed 03/29/2022 by Reynold Panettieri Principal Investigator relationship with AstraZeneca Please note: $20001 - $100000 by Reynold Panettieri, value=Grant/Research Support Removed 03/29/2022 by Reynold Panettieri Speaker/Speaker's Bureau relationship with AstraZeneca Please note: $1001 - $5000 by Reynold Panettieri, value=Honoraria Removed 03/29/2022 by Reynold Panettieri Advisory Committee Member relationship with MedImmune Please note: $1001 - $5000 by Reynold Panettieri, value=Consulting fee Removed 0 /29/2022 by Reynold Panettieri Principal Investigator relationship with MedImmune Please note: $20001 - $100000 by Reynold Panettieri, value=Grant/Research Support Removed 03/29/2022 by Reynold Panettieri Advisory Committee Member relationship with Reseaerch Institute for Fragrance Materials Please note: $1001 - $5000 by Reynold Panettieri, value=Consulting fee Removed 03/29/2022 by Reynold Panettieri Principal Investigator relationship with Reseaerch Institute for Fragrance Materials Please note: $20001 - $100000 by Reynold Panettieri, value=Grant/Research Support Removed 03/29/2022 by Reynold Panettieri Advisory Committee Member relationship with Equillium Please note: $1001 - $5000 by Reynold Panettieri, value=Consulting fee Removed 03/29/2022 by Reynold Panettieri Principal Investigator relationship with Equillium Please note: $20001 - $100000 by Reynold Panettieri, value=Grant/Research Support Removed 03/29/2022 by Reynold Panettieri Advisory Committee Member relationship with Theravance Please note: $1001 - $5000 by Reynold Panettieri, value=Consulting fee Removed 03/29/2022 by Reynold Panettieri Advisory Committee Member relationship with Avillion Please note: $1001 - $5000 by Reynold Panettieri, value=Consulting fee Speaker/Speaker's Bureau relationship with Sanofi/Regeneron Please note: $1001 - $5000 by Reynold Panettieri, value=Honoraria Removed 03/29/2022 by Reynold Panettieri Speaker/Speaker's Bureau relationship with Genentech Please note: $1001 - $5000 by Reynold Panettieri, value=Honoraria Removed 03/29/2022 by Reynold Panettieri Principal Investigator relationship with Genentech Please note: $20001 - $100000 by Reynold Panettieri, value=Grant/Research Support Removed 03/29/2022 by Reynold Panettieri Principal Investigator relationshipwith OncoArendi Please note: $20001 - $100000 by Reynold Panettieri, value=Grant/Research Support Principal Investigator relationship with Metera Please note: $20001 - $100000 by Reynold Panettieri, value=Grant/Research Support Removed 03/29/2022 by Reynold Panettieri Consultant relationship with TEVA Please note: 24 months Added 03/29/2022 by Reynold Panettieri, value=Honoraria Removed 03/29/2022 by Reynold Panettieri Consultant relationship with AstraZeneca Please note: 24 months Added 03/29/2022 by Reynold Panettieri, value=Honoraria Advisory Committee Member relationship with AstraZeneca Please note: 24 months Added 03/29/2022 by Reynold Panettieri, value=Honoraria Speaker/Speaker's Bureau relationship with AstraZeneca Please note: 24 months Added 03/29/2022 by Reynold Panettieri, value=Honoraria Principal Investigator relationship with AstraZeneca Please note: 24 months Added 03/29/2022 by Reynold Panettieri, value=Grant/Research Support Consultant relationship with RIFM Please note: 24 months Added 03/29/2022 by Reynold Panettieri, value=Honoraria Advisory Committee Member relationship with RIFM Please note: 24 months Added 03/29/2022 by Reynold Panettieri, value=Honoraria Principal Investigator relationship with RIFM Please note: 24 months Added 03/29/2022 by Reynold Panettieri, value=Grant/Research Support Advisory Committee Member relationship with Genentech Please note: 24 months Added 03/29/2022 by Reynold Panettieri, value=Honoraria Principal Investigator relationship with Genentech Please note: 24 months Added 03/29/2022 by Reynold Panettieri, value=Grant/Research Support Consultant relationship with TEVA Please note: 24 months Added 03/29/2022 by Reynold Panettieri, value=Honoraria Principal Investigator relationship with TEVA Please note: 24 months Added 03/29/2022 by Reynold Panettieri, value=Grant/Research Support Principal Investigator relationship with Equillium Please note: 24 months Added 03/29/2022 by Reynold Panettieri, value=Grant/Research Support Principal Investigator relationship with Novartis Please note: 24 months Added 03/29/2022 by Reynold Panettieri, value=Grant/Research Support Principal Investigator relationship with Medimmune Please note: 24 months Added 03/29/2022 by Reynold Panettieri, value=Grant/Research Support Principal Investigator r lationship with Origo Please note: 24 months Added 03/29/2022 by Reynold Panettieri, value=Grant/Research Support Principal Investigator relationship with ACTIV-1 Please note: 24 months Added 03/29/2022 by Reynold Panettieri, value=Grant/Research Support Principal Investigator relationship with Janssen Please note: 24 months Added 03/29/2022 by Reynold Panettieri, value=Grant/Research Support Principal Investigator relationship with Vault Health Please note: 24 months Added 03/29/2022 by Reynold Panettieri, value=Grant/Research Support Speaker/Speaker's Bureau relationship with Sanofi Please note: 24 months Added 03/29/2022 by Reynold Panettieri, value=Honoraria Speaker/Speaker's Bureau relationship with Merck & Co Please note: 24 months Added 03/29/2022 by Reynold Panettieri, value=Honoraria Employee No relevant relationships by Vivian Shih Shareholder relationship with AstraZeneca Please note: >5 years by Frank Trudo, value=Shares

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