Underlying Lung Disease Research Articles

Etiology of severe community-acquired pneumonia in immunocompromised patients

Objective: To analyze the etiology of severe community-acquired pneumonia (SCAP) in immunocompromised patients, and to investigate the relationship between underlying diseases and infectious microorganisms. Methods: A retrospective analysis was performed on SCAP in immunocompromised patients admitted to the Fourth Department of Respiratory and Critical Medicine (MICU) of China-Japan Friendship Hospital from January 1, 2017 to December 31, 2019. A total of 119 SCAP patients were finally enrolled, including 65 males (54.6%), with an average age of (59.3±14.5) years. The average of Sequential Organ Failure Assessment (SOFA) score was 6.7±3.6 and the acute physiology and chronic health evaluation (APACHE) Ⅱ score was 19.4±6.8. Sixty (50%) of these patients were finally improved and discharged. Long-term glucocorticoid treatment was the main risk factor for immunocompromise. The difference of pathogenic microorganisms between patients with and without structural lung diseases, and the influence of different pathogenic microorganisms on hospital mortality were calculated, respectively. P<0.05 was considered to be statistically significant. Results: In this study, 99 (83.2%) patients were identified to have positive etiological results, and the incidence of concurrent infection was 54.5%. The top three pathogens were Pneumocystis Jiroveci (55.6%), Cytomegalovirus (47.5%) and Aspergillus (23.2%). Staphylococcus aureus was the most common bacterium, followed by Pseudomonas aeruginosa and Klebsiella pneumoniae. The risk of Pneumocystis Jiroveci infection was significantly higher in patients without underlying lung diseases as compared to those with underlying lung diseases (64.3% vs. 44.2%, P = 0.046). The in-hospital mortality was not different among patients infected with different pathogens(all P>0.05), but was higher in those with mixed infections(56.7% vs. 33.9%, P=0.013). Conclusions: Pneumocystis Jiroveci and Cytomegalovirus were the most common pathogens in immunocompromised patients with severe community-acquired pneumonia, and the incidence of Pneumocystis Jiroveci was significantly higher in patients without underlying lung diseases.

PH Roundtable: Conundrums and Controversies in PH-ILD: To Treat or Not to Treat—Identifying Optimal Treatment Candidates

PH Roundtable: Conundrums and Controversies in PH-ILD: To Treat or Not to Treat—Identifying Optimal Treatment Candidates

VV ECMO for Treatment of Severe ARDS in CoVID-19 Patients at UNMC

Introduction: Veno-venous extracorporeal membrane oxygenation (VV ECMO) is an indicated treatment for severe acute respiratory distress syndrome (ARDS) refractory to conventional medical treatment. Severe ARDS is a common complication of CoVID-19 infection. Subsequently, the efficacy of VV ECMO in CoVID-19 severe ARDS patients must be investigated. ECMO is a resource-intensive treatment modality, meaning that its use must be reserved for patients with robust indications and paucity of contraindications. Methods: We performed retrospective chart review of three patients at the University of Nebraska Medical Center that were placed on VV ECMO secondary to severe ARDS from CoVID-19 infection. Results: All patients were male with a median age of 39 years. Two patients were of Hispanic descent, and the third was of Asian descent. No patients had underlying lung disease, and all patients had type II diabetes mellitus. Median time on mechanical ventilation prior to ECMO cannulation was six days. Median duration of ECMO treatment was 21 days with a range of 17 to 27 days. All patients were decannulated from ECMO during their hospital stay, and all patients survived to 60 days post-hospital discharge. Complications while on ECMO included GI bleeding in two patients, hematuria in one patient, necessitation of vasodilator and vasopressor support in all patients, AKI in two patients, secondary bacterial pneumonia in two patients, and blood cultures positive for gram-positive organisms in all patients. No patients suffered DVT or CVA. All patients required pRBC transfusion during ECMO treatment. Two patients were treated with remdesivir and one patient received baricitinib, a JAK-inhibitor. Conclusion: VV ECMO is a viable treatment for patients with severe ARDS secondary to CoVID-19 infection that have failed conventional therapy. Stringent adherence to inclusion and exclusion criteria is imperative. VV ECMO combined with lung protective ventilation strategies with a focus on minimizing driving pressure can provide life-saving treatment to patients with severe ARDS secondary to CoVID-19 infection

DIFFUSE ALVEOLAR HEMORRHAGE RESULTING FROM RIVAROXABAN USE: A RARE COMPLICATION IN A PATIENT WITHOUT PREDISPOSING CONDITIONS

TOPIC: Diffuse Lung Disease TYPE: Fellow Case Reports INTRODUCTION: Diffuse alveolar hemorrhage (DAH) is a rare complication of direct oral anticoagulant (DOAC) use with few reported cases in patients with predisposing conditions or underlying lung disease. DAH results from disruption of the alveolar-capillary interface. Infectious, autoimmune, and drug mediated conditions may lead to DAH. Rivaroxaban is a DOAC used to treat venous thromboembolism (VTE) and non-valvular atrial fibrillation (NVAF). We present a case of a patient who developed DAH one month after starting rivaroxaban. CASE PRESENTATION: A 43-year-old female with a past medical history of hyperlipidemia and tobacco use disorder presented with frank hemoptysis and shortness of breath. She was diagnosed with lower extremity deep vein thrombosis (DVT) and was started on rivaroxaban. Vitals were stable without hypoxia. Hemoglobin dropped from 14 to 7 g/dL (normal 12.3-15.3 g/dL) requiring 2 units of blood. Prothrombin Complex Concentrate was given. Computed tomography angiogram of the chest showed bilateral lung fields with patchy ground-glass opacities with peripheral sparing, without significant intra-lobular septal thickening and no pulmonary embolus. Infectious work up was negative. Rheumatological workup with anti-glomerular basement antibodies, anti-double stranded DNA antibodies, lupus anticoagulant, antinuclear antibody, rheumatoid factor, anti-neutrophilic cytoplasmic antibody, proteinase-3 antibody, myeloperoxidase antibody, C-reactive protein and erythrocyte sedimentation rate was negative. Bronchoscopy confirmed the diagnosis of DAH. Hemoptysis resolved after discontinuing rivaroxaban, repeat lower extremity dopplers were negative for DVT. She was discharged home without anticoagulation. DISCUSSION: DAH occurs from direct injury or inflammation of the pulmonary arterioles, venules, or alveolar septal capillaries causing bleeding into the lung. It presents with non specific symptoms including cough, chest pain, hemoptysis, and dyspnea. It is life threatening with fast clinical deterioration leading to respiratory failure. The underlying vascular injury of DAH is based on histological appearance and is divided into pulmonary capillaritis, bland pulmonary hemorrhage, and diffuse alveolar damage. The diagnosis is usually made clinically and supported with imaging and bronchoscopic findings. There are few cases of rivaroxaban induced DAH in the literature. The majority of the cases report patients with an underlying medical conditions such as autoimmune disease, lung cancer, interstitial lung disease and pulmonary hypertension, predisposing them to DAH. Our patient had no predisposing factors that put her at risk of developing DAH. CONCLUSIONS: Oral anticoagulants are a under-recognized cause of DAH with limited literature on the incidence of DAH with the use of these medications. This case illustrates that patients with no underlying risk factors can develop DAH with the use of rivaroxaban. REFERENCE #1: Collard HR, Schwarz MI. Diffuse alveolar hemorrhage. Clinics in Chest Medicine 2004; 25(3): 583-92. REFERENCE #2: Park MS. Diffuse alveolar hemorrhage. Tuberc Respir Dis (Seoul) 2013; 74(4): 151-62. REFERENCE #3: Chen A, Stecker E, Warden BA. Direct Oral Anticoagulant Use: A Practical Guide to Common Clinical Challenges. Journal of the American Heart Association 2020; 9(13): e017559 DISCLOSURES: No relevant relationships by Ahmad Alhajhusain, source=Web Response No relevant relationships by Stephanie Baltaji, source=Web Response No relevant relationships by Helene Rovnan, source=Web Response

PULMONARY ATRESIA WITH INTACT VENTRICULAR SEPTUM: NOT CLEARED FOR TAKEOFF

TOPIC: Pulmonary Vascular Disease TYPE: Fellow Case Reports INTRODUCTION: In patients with underlying lung disease, pulmonary evaluation is required prior to air travel due to hypoxic conditions in higher altitudes. We present a case of a young man aspiring to become a pilot, found to have a congenital cardiopulmonary defect of pulmonary atresia. CASE PRESENTATION: An 18 year old male with right pulmonary atresia and intact ventricular septum (PA-IVS) presented to the pulmonary clinic seeking medical clearance for flight training school, endorsing fatigue and dyspnea on exertion. Vitals signs and physical examination were benign without cardiac murmurs, peripheral edema, or cyanosis. Chest CT revealed absent right PA (pulmonary artery) with contrast reflux. A subsequent angiogram revealed blood flow from the right internal mammary artery to the right upper PA and from the celiac and inferior diaphragmatic artery to the right lower PA. Left and right cardiac catheterization showed normal pressures in the right atrium, right ventricle, and PA. Mean PA pressure was 14 mmHg, and wedge pressure was 6 mmHg. Left ventricular end diastolic pressure was 6 mmHg, with normal coronary artery and vein anatomy. Oxygen saturations were: SVC 86%, RA 82%, RV 81%, left PA 81%, and femoral artery 96%. Treadmill stress test was inconclusive due to early termination as the patient did not achieve 85% of maximum heart rate. Occupational medicine recommended HAST (high altitude simulation testing) in concordance with FAA regulations. Before HAST was performed, the patient opted out of his dream career of becoming a pilot. DISCUSSION: PA-IVS is a rare congenital heart disease accounting for < 1 % of total heart defects [2]. It is characterized by atresia of the RV outflow tract. The precise cause is unclear, but thought to be related to an insult during embryological development. PA-IVS can be classified into membranous and muscular forms with the former harboring a better long term prognosis. The muscular form is associated with abnormal connections between the RV and coronary artery. In our patient, left heart catheterization did not reveal abnormal coronary anatomy to suggest muscular PA-IVS.HAST is utilized in patients with cardiopulmonary defects to predict physiological response to hypobaric conditions at higher altitudes. The patient is asked to breathe a mixture of gases with an oxygen saturation of 15.1%, and simulates cabin pressures up to 2400 meters. The test is considered abnormal if there is evidence of hypoxemia (pAO2 < 50 mmHg), symptoms, and/or arrhythmias. We believe that our patient would have had an appropriate response to HAST due to a favorable form of PA-IVS and normal cardiopulmonary pressures and saturations. CONCLUSIONS: In adolescents with congenital cardiopulmonary defects a thorough workup including HAST is recommended prior to allowing exposure to a suboptimal environment. REFERENCE #1: Daubeney PE, Sharland GH, Keeton BR, et al. Pulmonary atresia with intact ventricular septum. Circulation 1998 (8(6): 562-566. REFERENCE #2: Ferencz C, Rubin JD, McCarter RJ, Brenner JI, Neill CA, Perry LW, Hepner SI, Downing JW. Congenital heart disease: prevalence at livebirth. The Baltimore-Washington Infant Study. Am J Epidemiol. 1985 Jan;121(1):31-6. DISCLOSURES: No relevant relationships by Moises Cossio, source=Web Response No relevant relationships by Domingo Franco-Palacios, source=Web Response No relevant relationships by Arjun Mahendra, source=Web Response No relevant relationships by Toribiong Uchel, source=Web Response

AN UNUSUAL CAUSE OF SECONDARY SPONTANEOUS PNEUMOTHORAX

TOPIC: Chest Infections TYPE: Medical Student/Resident Case Reports INTRODUCTION: Secondary spontaneous pneumothorax (SSP) is defined as a non-traumatic pneumothorax in patients with underlying lung disease. They are commonly seen in patients with conditions such as chronic obstructive pulmonary disease, cystic fibrosis, infection, and cancer. While it is widely recognized that tuberculosis (TB) can cause SSP, estimates suggest less than 1% of TB cases are complicated by SSP. This case describes a rare initial presentation of TB. CASE PRESENTATION: A 41-year-old woman from Mexico presented with acute onset sharp left-sided chest pain. She had been having pneumonia symptoms (cough, chills, sputum production) for four months and took several courses of oral antibiotics with no improvement. She had no prior episodes of pneumonia, tuberculosis or other infections, and had no sick contacts. On presentation, she was afebrile, tachycardic, tachypneic and mildly hypoxic with decreased breath sounds on the left. A chest radiograph showed a large left-sided pneumothorax, and a 14-French pigtail chest tube was placed. Computed tomography of the chest showed bronchiectasis and cystic changes with large cavitation. Sputum acid-fast bacilli staining as well as mycobacterium tuberculosis (MTB) polymerase chain reaction returned positive. She was diagnosed with secondary spontaneous pneumothorax, and RIPE therapy was initiated. The chest tube was connected to suction which produced a continuous air leak which improved when the tube was connected to water seal, raising concern for a bronchopleural fistula. The air leak persisted for 14 days, and thus she was evaluated by thoracic surgery who ultimately performed a lobectomy. DISCUSSION: This case illustrates an unusual initial presentation of tuberculosis – this patient had an SSP from underlying bronchiectasis as well as a bronchopleural fistula. Mycobacterial infections (classically, non-tuberculous mycobacterium) often complicate pre-existing bronchiectasis. MTB itself can cause bronchiectasis from longstanding tuberculous bronchitis, post-obstructive damage secondary to post-tuberculous bronchial wall stenosis, and extraluminal bronchial obstruction by enlarged tuberculous lymph nodes. This patient had no symptoms of longstanding lung disease, and a basic workup for other causes of bronchiectasis returned normal, leaving MTB as the most likely reason for her abnormal lung architecture. The acute onset SSP triggered her eventual presentation to the hospital. It is estimated that SSP complicates between 0.6% and 1.5% of cases of tuberculosis. In one series, patients with SSP from MTB were safely treated with pleural drainage for an average of 13 days (ranging from 4 - 54 days). 28% of patients required surgery for persistent air leak, as did this patient. CONCLUSIONS: SSP is a potentially fatal complication of MTB that typically responds well to pleural drainage and RIPE therapy. Surgery may be needed for continuous air leaks. REFERENCE #1: Freixinet JL, Caminero JA, Marchena J, Rodríguez PM, Casimiro JA, Hussein M. Spontaneous pneumothorax and tuberculosis: long-term follow-up. Eur Respir J. 2011;38(1):126-131. doi:10.1183/09031936.00128910 REFERENCE #2: Doucette K, Cooper R. Tuberculosis. In: Grippi MA, Elias JA, Fishman JA, Kotloff RM, Pack AI, Senior RM, Siegel MD. eds. Fishman's Pulmonary Diseases and Disorders, Fifth Edition. McGraw-Hill; Accessed April 22, 2021. https://accessmedicine.mhmedical.com/content.aspx?bookid=1344§ionid=81199723 REFERENCE #3: Burguete S, DeArmond DT, Soni NJ, Peters J. Pneumothorax. In: Grippi MA, Elias JA, Fishman JA, Kotloff RM, Pack AI, Senior RM, Siegel MD. eds. Fishman's Pulmonary Diseases and Disorders, Fifth Edition. McGraw-Hill; Accessed April 29, 2021. https://accessmedicine.mhmedical.com/content.aspx?bookid=1344§ionid=81193412 DISCLOSURES: No relevant relationships by Ethan Loftspring, source=Web Response No relevant relationships by Dharani Kumari Narendra, source=Web Response No relevant relationships by Divya Verma, source=Web Response

METHOTREXATE-INDUCED PNEUMONITIS

TOPIC: Lung Pathology TYPE: Fellow Case Reports INTRODUCTION: Methotrexate is an analogue of folic acid that inhibits cellular proliferation by inducing an intracellular deficiency of folate coenzymes. Lung toxicity, while rare, often occurs after weeks to months of low dose oral methotrexate therapy. CASE PRESENTATION: A 46 year old male with a history of T cell lymphoma status post chemotherapy on POMP maintenance therapy and pleurX catheter for malignant pleural effusion presented to the ED with fever for 4 days. Associated symptoms were dry cough, chills, and fatigue. He denied drug allergies.BP 153/84, HR 135, SpO2 98% on room air, and temperature 101.5F. WBC was 3.2 and COVID PCR was negative. Broad spectrum antibiotics were initiated. CT thorax showed upper lobe predominant ground-glass opacities suggestive of a multifocal pneumonia or drug reaction. He became hypoxic requiring 3L of oxygen and underwent bronchoscopy. Transbronchial biopsy revealed lung parenchyma with isolated giant cells and loosely formed granulomas consistent with hypersensitivity pneumonia. Left upper lobe broncho-alveolar lavage had lymphocytic predominance and elevated CD4:CD8 ratio (4.7), all supporting the diagnosis of methotrexate pneumonitis. Empiric treatment for PJP and Prednisone were started. Viral, bacterial, fungal studies and PJP stain were negative. Antibiotics were stopped and steroids were continued for 2 weeks. His symptoms improved and fevers subsided. As an outpatient, repeat CT thorax and PFTs were ordered and he continues to improve clinically. DISCUSSION: There is a set of criteria to establish the diagnosis. Major criteria includes: 1. hypersensitivity pneumonitis by histopathology without pathogenic organisms 2. imaging with diffuse ground-glass or consolidative opacities 3. negative blood cultures (if febrile) and initial sputum cultures (if produced). Minor criteria includes: 1. dyspnea for <8 weeks 2. nonproductive cough 3. SpO2< 90% on room air at initial evaluation 4. DLCO < 70% of predicted for age and 5. WBC < 15k. Methotrexate pneumonitis is definite if major criteria 1 or 2 and major criterion 3 are present with three of the five minor criteria and probable if major criteria 2 and 3 plus two of the five minor criteria are present (1). Our patient met all major criteria and four minor criteria. CONCLUSIONS: Although rare with a prevalence of 0.3-11.6% (1,3), methotrexate pneumonitis has a mortality rate of 13-17.6% (2,4). Patients should be advised about the possibility of lung toxicity. Some data suggests patients should be screened for lung disease prior to medication initiation (5) and clinicians should be cautious using the drug in patients with underlying lung disease (6). REFERENCE #1: Salehi, Mashal et al. "Methotrexate-induced Hypersensitivity Pneumonitis appearing after 30 years of use: a case report." Journal of medical case reports vol. 11,1 174. 28 Jun. 2017, doi:10.1186/s13256-017-1333-0 DISCLOSURES: No relevant relationships by Bianca Dominguez, source=Web Response No relevant relationships by Gurjot Garcha, source=Web Response No relevant relationships by Wael Nasser, source=Web Response No relevant relationships by Olatunji Otegbeye, source=Web Response

BULLOUS LUNG DISEASE FOLLOWING COVID-19 INFECTION

TOPIC: Chest Infections TYPE: Medical Student/Resident Case Reports INTRODUCTION: The ongoing coronavirus disease 2019 (COVID-19) pandemic has resulted in persistent pulmonary complications among survivors. As our understanding of post infectious pulmonary phenomena continues to evolve, it is clear there are multiple difference manifestations of pulmonary lung disease associated with severe acute respiratory syndrome coronavirus 2 (SARS CoV-2). Here we describe a case of bullous lung disease as a complication of COVID-19. CASE PRESENTATION: A 61-year-old gentleman without significant past medical history presented with worsening shortness of breath of two days duration. Three months prior to presentation he was hospitalized for acute hypoxemic respiratory failure due to COVID-19 requiring Bi-level Positive Airway Pressure which was complicated by pneumomediastinum and right-sided pneumothorax that required chemical pleurodesis. On this presentation, he was hypoxemic and CT scan of the chest showed extensive bullous lung disease (BLD) throughout the right lung with mediastinal shift, not noted on prior imaging. He denied family history of lung disease or connective tissue disease. Prior to COVID-19 infection he was an avid marathon-runner, worked as a civil engineer with no occupational exposures, and never smoked tobacco products, vaped electronic cigarettes, or used illicit drugs. Admission vitals were unremarkable and physical exam revealed decreased breath sounds on the right side. His laboratory data including repeat SARS CoV-2 nasal polymerase chain reaction, alpha-1 antitrypsin and angiotensin-converting enzyme levels were unrevealing. Cardiothoracic surgery was consulted and he successfully underwent Video-Assisted Thoracoscopic surgery with wedge resection of the right lower lobe and chemical pleurodesis. Pathology ruled out a loculated pneumothorax and confirmed the presence of bullae localized within the lung parenchyma. DISCUSSION: Bullous lung disease has been described secondary to cocaine, cigarette or marijuana smoking as well as Emphysema, Sarcoidosis, alpha1-antitrypsin deficiency, Marfan's syndrome, Ehlers-Danlos syndrome and inhaled fiberglass exposure. However, our patient did not have any family history of lung disease, occupational exposures or smoking history, and physical exam was not suggestive of either Marfan's or Ehlers-Danlos syndrome. Since there was no underlying lung disease prior to hospitalization, common etiologies of bullous lung disease were ruled out, and given temporal association with COVID-19 infection, we hypothesized that his lung disease was related to his infection. Although the relationship between bullous lung disease and COVID-19 has yet-to-be defined, case reports have described this emerging association. CONCLUSIONS: Further investigation in the development of chronic lung disease following COVID-19 infection is sorely needed given the growing population of COVID-19 survivors. REFERENCE #1: Berhane S, Tabor A, Sahu A, Singh A. Development of bullous lung disease in a patient with severe COVID-19 pneumonitis. BMJ Case Reports. 2020;13(10):e237455. REFERENCE #2: Sun R, Liu H, Wang X. Mediastinal Emphysema, Giant Bulla, and Pneumothorax Developed during the Course of COVID-19 Pneumonia. Korean J Radiol. 2020;21(5):541-544. REFERENCE #3: Goldberg C, Carey KE. Bullous lung disease. West J Emerg Med. 2013;14(5):450-451. doi:10.5811/westjem.2013.3.16276. DISCLOSURES: No relevant relationships by Kwesi Amoah, source=Web Response No relevant relationships by robert homer, source=Web Response No relevant relationships by Denyse Lutchmansingh, source=Web Response No relevant relationships by Prachi Pednekar, source=Web Response No relevant relationships by Changwan Ryu, source=Web Response

A CASE OF CHRONIC PULMONARY ASPERGILLOSIS AS THE INITIAL PRESENTATION FOR SARCOIDOSIS

TOPIC: Chest Infections TYPE: Medical Student/Resident Case Reports INTRODUCTION: Subacute invasive pulmonary aspergillosis is a locally invasive subacute form of chronic pulmonary aspergillosis (CPA) which typically involves the upper lobes of individuals with pre-existing lung disease or immunodeficiency. Patients with chronic fibrocystic sarcoidosis are prone to CPA. We described a case of sarcoidosis complicated with CPA which was diagnosed concomitantly. CASE PRESENTATION: A 34 year old male with no past medical history presented with hemoptysis for 3 days, associated with chronic productive cough, exertional dyspnea and skin rashes over his arms and face for the past year. Physical examination revealed multiple violaceous plaque over bilateral upper arms and face; reduced breath sounds over bilateral upper zones. CT Chest revealed bilateral upper lobes cavitations, left upper lobe mass-like consolidation, approximately 2.9 cm with air crescent sign. Laboratory tests were notable for lymphopenia, ESR 43 mm/h, CD4+ count 244, Aspergillus Ag 0.6, Aspergillus IgG positive, serum ACE 178 U/L, fungal culture from bronchial alveolar lavage (BAL) isolated Aspergillus species. ANCA, Histoplasma Ag, Cryptococcal Ag, HIV Ag-Ab, Quantiferon TB, Sputum acid fast smear were negative. Endobronchial ultrasound with fine needle aspiration (FNA) of subcarinal lymph nodes showed non-caseating granuloma. Skin biopsies of upper extremities skin lesions showed non-caseating granulomas without microorganisms seen. The patient was started on Voriconazole for 3 months duration and scheduled for outpatient follow up. DISCUSSION: Patients with sarcoidosis are predisposed to CPA due to underlying pulmonary involvement especially with fibrocystic sarcoidosis in addition to the mildly immunocompromised state, as evidenced by low CD4 count. The diagnosis of CPA was made based on symptomatology (chronic productive cough, dyspnea and hemoptysis), bilateral upper lobe cavitations on CT Chest, positive Aspergillus IgG and positive BAL culture for Aspergillus species. It was a challenge in making concomitant diagnosis of Sarcoidosis as it is a diagnosis of exclusion. Diagnosis of sarcoidosis cannot be made based on the non-caseating granulomas resulted from the FNA of the lymph nodes as aspergillosis can present with similar picture. The skin rash which appeared to be plaque sarcoidosis ultimately leads us to the diagnosis of sarcoidosis after confirmation of non-caseating granuloma on skin biopsy. CONCLUSIONS: Patients with CPA typically present with background risk factors of underlying lung disease. It is essential to have a high clinical suspicion for underlying undiagnosed disease processes especially when individuals presented with CPA without any obvious risk factors. CPA is a serious complication of sarcoidosis and is associated with high mortality and morbidity. Unfortunately, there is no consensus currently on how to best treat patients diagnosed with sarcoidosis and CPA. REFERENCE #1: Denning DW, Cadranel J, Beigelman-Aubry C, et al. Chronic pulmonary aspergillosis: rationale and clinical guidelines for diagnosis and management. Eur Respir J. 2016;47(1):45-68. doi:10.1183/13993003.00583-2015 REFERENCE #2: Alastruey-Izquierdo A, Cadranel J, Flick H, et al. Treatment of Chronic Pulmonary Aspergillosis: Current Standards and Future Perspectives. Respiration. 2018;96(2):159-170. doi:10.1159/000489474 REFERENCE #3: Denning DW, Pleuvry A, Cole DC. Global burden of chronic pulmonary aspergillosis complicating sarcoidosis. Eur Respir J. 2013;41(3):621-626. doi:10.1183/09031936.00226911 DISCLOSURES: No relevant relationships by Farahnaz Anwar, source=Web Response No relevant relationships by James Choi, source=Web Response No relevant relationships by Si Yuan Khor, source=Web Response No relevant relationships by Jason Liu Liu, source=Web Response No relevant relationships by Akhil Sharma, source=Web Response No relevant relationships by Enhua Wang, source=Web Response

CHARACTERISTICS AND PROCEDURAL OUTCOMES IN PATIENTS WITH PROLONGED AIR-LEAK UNDERGOING ENDOBRONCHIAL VALVES PLACEMENT (EBV): A RETROSPECTIVE CASE SERIES

TOPIC: Disorders of the Pleura TYPE: Original Investigations PURPOSE: Endobronchial valves (EBV)are FDA approved for bronchoscopic lung volume reduction in certain COPD patients. EBV has also emerged as a therapeutic option for patients with pneumothorax (PTX) and persistent air leak. Limited data is available about the characteristics of this patient population and their procedural outcomes. METHODS: We retrospectively reviewed all patients who underwent EBV placement for pneumothorax with prolonged airleak at a tertiary referral center over a 5-year period. Outcomes assessed included length of stay (LOS), need for repeated procedure or further surgical intervention, and resolution of airleak at discharge. RESULTS: Between 2015 and 2020, 36 patients underwent evaluation for EBV for PTX. Secondary spontaneous pneumothorax (SSP) was the primary diagnoses in 25/36 (70%) with COPD as the primary underlying lung disease in 20/25 (80%). Only 30% of patients had VATS with or without resection prior to EBV placement. Median LOS was 25 days with a median of 12 days from pneumothorax onset to EBV placement and 13.5 days between EBV placement and discharge. Early placement of EBV was significantly associated with shorter LOS (R2=0.68; p<0.001). A second bronchoscopy procedure was required during the same admission in 15/36 (41%) for either recurrence or continued air-leak with additional (28%) or replacing (17%) previously placed EBV. Primary Spontanous Pneumothorax (PSP) patients were the least likely to need repeat EBV procedures as compared to patient with SSP [0/4 (0%) vs. 13/25 (52%) respectively; p= 0.05]. Prior lobectomy (p=0.02), older age (p=0.03) and laterality of PTX were more likely to have a second procedure (left greater than right sided PTX (9/11 9 (81%) vs. 6/25 (24%); p=0.001). Median number of EBV placed was 3. Post lobectomy patients had a higher number of total valves compared to other patients (4.5 vs. 3.0 respectively; p=0.03), but none of those patients required an additional surgical intervention. Neither total number valves nor number of lobes targeted affected LOS, need for 2nd procedure, or the need for further surgical intervention after EBV placement. Following EBV, 25/36 patients (70%) had resolution of their airleak without subsequent surgical intervention, 7/36 (20%) required surgical intervention for persistent airleak post EBV placement and 5/36 (14%) patients were discharged with chest tube in place due to persistent airleak. CONCLUSIONS: EBV were effective in stopping airleak in the majority of patients with pneumothorax and persistent airleak. Early placement of EBV significantly correlated with shorter LOS. Further studies are needed to identify patient population who are at risk and would benefit the most from early EBV placement. CLINICAL IMPLICATIONS: EBV can effictively stop airleak and potentially reduce hospital length of stay in patients with pneumothorax and prolonged airleak. DISCLOSURES: No relevant relationships by Mamoon Al Ahmad, source=Web Response No relevant relationships by Yaser Dawod, source=Web Response No relevant relationships by Syed Nazeer Mahmood, source=Web Response No relevant relationships by Jessica Wang Memoli, source=Web Response

Mycobacterium chimaera as an Underestimated Cause of NTM Lung Diseases in Patients Hospitalized in Pulmonary Wards.

Mycobacterium chimaera is the newly described species belonging to Mycobacterium avium complex (MAC), with morphology and growth characteristics closely related to Mycobacterium intracellulare. The aim of this retrospective study was to analyze the frequency and clinical significance of M. chimaera identification in the population of patients with previous positive respiratory cultures for M. intracellulare or MAC. 200 strains of M. intracellulare or MAC, isolated from respiratory specimens of patients hospitalized in pulmonary wards, between 2011 and 2020, were retrospectively analyzed with GenoType NTM-DR test. 88 (44%) of strains were re-classified to M. chimaera species. Analysis of clinical data in 30 patients with positive M. chimaera isolates revealed that they were diagnosed with chronic obstructive pulmonary disease (COPD) – 27%, past tuberculosis – 20%, or interstitial lung diseases – 17%, respectively. Non-tuberculous mycobacterial lung disease (NTMLD) caused by M. chimaera has been recognized in 53% of patients, most often in those presenting with post-tuberculous lung lesions. M. chimaera was almost exclusively isolated from respiratory specimens of patients with underlying lung diseases, especially those with COPD and/or past tuberculosis. NTMLD due to M. chimaera was diagnosed predominantly in patients with past tuberculosis.

Comparison of clinical and echocardiographic features of first and second waves of COVID-19 at a large, tertiary medical center serving a predominantly African American patient population

As clinicians have gained experience in treating patients with the novel SARS-CoV-2 (COVID-19) virus, mortality rates for patients with acute COVID-19 infection have decreased. The Centers for Disease Control (CDC) has identified the African American population as having increased risk of COVID-19 associated mortality, however little is known about echocardiographic markers associated with increased mortality in this patient population. We aimed to compare the clinical and echocardiographic features of a predominantly African American patient cohort hospitalized with acute COVID-19 infection during the first (March–June 2020) and second (September–December 2020) waves of the COVID-19 pandemic, and to investigate which parameters are most strongly associated with composite all-cause mortality. We performed consecutive transthoracic echocardiograms (TTEs) on 105 patients admitted with acute COVID-19 infection during the first wave and 129 patients admitted during the second wave. TTE parameters including left ventricular ejection fraction (LVEF), left ventricular global longitudinal strain (LVGLS), right ventricular global longitudinal strain (RVGLS), right ventricular free-wall strain (RVFWS), and right ventricular basal diameter (RVBD) were compared between the two groups. Clinical and demographic characteristics including underlying co-morbidities, biomarkers, in-hospital treatment regimens, and outcomes were collected and analyzed. Univariable and multivariable analyses were performed to determine variables associated with all-cause mortality. There were no significant differences between the two waves in terms of age, gender, BMI, or race. Overall all-cause mortality was 35.2% for the first wave compared to 14.7% for the second wave (p < 0.001). Previous medical conditions were similar between the two waves with the exception of underlying lung disease (41.9% vs. 29.5%, p = 0.047). Echocardiographic parameters were significantly more abnormal in the first wave compared to the second: LVGLS (− 17.1 ± 5.0 vs. − 18.9 ± 4.8, p = 0.02), RVGLS (− 15.7 ± 5.9% vs. − 19.0 ± 5.9%, p < 0.001), RVFWS (− 19.5 ± 6.8% vs. − 23.2 ± 6.9%, p = 0.001), and RVBD (4.5 ± 0.8 vs. 3.9 ± 0.7 cm, p < 0.001). Stepwise multivariable logistic analysis showed mechanical ventilation, RVFWS, and RVGLS to be independently associated with mortality. In a predominantly African American patient population on the south side of Chicago, the clinical and echocardiographic features of patients hospitalized with acute COVID-19 infection demonstrated marked improvement from the first to the second wave of the pandemic, with a significant decrease in all-cause mortality. Possible explanations include implementation of evidence-based therapies, changes in echocardiographic practices, and behavioral changes in our patient population. Mechanical ventilation and right-sided strain-based markers were independently associated with mortality.

COVID-19 and the effects on pulmonary function following infection: A retrospective analysis.

BackgroundThe coronavirus disease 2019 (COVID-19) has been identified in over 110 million people with no studies comparing pre-infection pulmonary function to post-infection. This study's aim was to compare pre-infection and post-infection pulmonary function tests (PFT) in COVID-19 infected patients to better delineate between preexisting abnormalities and effects of the virus.MethodsThis was a retrospective multi-center cohort study. Patients were identified based on having COVID-19 and a pre- and post-infection PFT within one year of infection during the time period of March 1, 2020 to November 10, 2020.FindingsThere was a total of 80 patients, with an even split in gender; the majority were white (n = 70, 87·5%) and never smokers (n = 42, 52·5%). The majority had mild to moderate COVID-19 disease (n = 60, 75·1%) with 25 (31·2%) requiring hospitalization. There was no difference between the pre- and post-PFT data, specifically with the forced vital capacity (FVC) (p = 0·52), forced expiratory volume in 1 s (FEV1)(p = 0·96), FEV1/FVC(p = 0·66), total lung capacity (TLC) (p = 0·21), and diffusion capacity (DLCO)(p = 0·88). There was no difference in the PFT when analyzed by hospitalization and disease severity. After adjusting for potential confounders, interstitial lung disease (ILD) was independently associated with a decreased FEV1 (-2·6 [95% CI, -6·7 to - 1·6] vs. -10·3 [95% CI, -17·7 to -2·9]; p = 0·03) and an increasing age (p = 0·01) and cystic fibrosis (-1·1 [95% CI, -4·5 to- 2·4] vs. -36·5 [95% CI, -52·1 to -21·0]; p < 0·01) were associated with decreasing FVC when comparing pre and post infection PFT. Only increasing age was independently associated with a reduction in TLC (p = 0·01) and DLCO (p = 0·02) before and after infection.InterpretationThis study showed that there is no difference in pulmonary function as measured by PFT before and after COVID-19 infection in non-critically ill classified patients. There could be a relationship with certain underlying lung diseases (interstitial lung disease and cystic fibrosis) and decreased lung function following infection. This information should aid clinicians in their interpretation of pulmonary function tests obtained following COVID-19 infection.FundingNo funding was obtained for this study.

Immunity to varicella, measles, and mumps in patients evaluated for lung transplantation

Vaccine-preventable viral infections are associated with increased risk of morbidity and mortality in post-transplant patients on immunosuppression regimens. Therefore, we studied rates of immunity against vaccine-preventable viruses in lungtransplantation(LTx) candidates and their associations with underlying lung disease and clinical characteristics. We retrospectively studied 1025 consecutive adult patients who underwent first-time evaluation for LTx at a single center between January 2016 and October 2018. Viruses studied included varicella zoster (VZV),measles, and mumps. Young age (17-48years old) was negatively associated with immunity for VZV (OR 4.54, p<.001), measles (OR 15.45, p<.001) and mumps (OR 3.1, p<.001), as compared to those 65+. Many LTx candidates with cystic fibrosis (CF) had undetectable virus-specific antibody titers including: 13.5% for VZV, 19.1% for measles, and 15.7% for mumps with significant odds of undetectable titers for VZV (OR 4.54, p<.001) and measles (OR 2.32, p=.010) as compared to those without CF. Therefore, a substantial number of patients undergoing LTx evaluation had undetectable virus-specific antibody titers. Our results emphasize the importance of screening for immunity to vaccine-preventable infections in this population and the need for revaccination in selected patients to boost their humoral immunity prior to transplantation.

Pneumothorax in patients with respiratory failure in ICU.

Pneumothorax is not an uncommon occurrence in ICU patients. Barotrauma and iatrogenesis remain the most common causes for pneumothorax in critically ill patients. Patients with underlying lung disease are more prone to develop pneumothorax, especially if they require positive pressure ventilation. A timely diagnosis of pneumothorax is critical as it may evolve into tension physiology. Most occurrences of pneumothoraces are readily diagnosed with a chest X-ray. Tension pneumothorax is a medical emergency, and managed with immediate needle decompression followed by tube thoracostomy. A computed tomography (CT) scan of the chest remains the gold standard for diagnosis; however, getting a CT scan of the chest in a critically ill patient can be challenging. The use of thoracic ultrasound has been emerging and is proven to be superior to chest X-ray in making a diagnosis. The possibility of occult pneumothorax in patients with thoracoabdominal blunt trauma should be kept in mind. Patients with pneumothorax in the ICU should be managed with a tube thoracostomy if they are symptomatic or on mechanical ventilation. The current guidelines recommend a small-bore chest tube as the first line management of pneumothorax. In patients with persistent air leak or whose lungs do not re-expand, a thoracic surgery consultation is recommended. In non-surgical candidates, bronchoscopic interventions or autologous blood patch are other options.

Definition and assessment of high risk in patients considered for lobectomy for stage I non–small cell lung cancer: The American Association for Thoracic Surgery expert panel consensus document

ObjectiveLobectomy is a standard treatment for stage I non–small cell lung cancer, but a significant proportion of patients are considered at high risk for complications, including mortality, after lobectomy and might not be candidates. Identifying who is at risk is important and in evolution. The objective of The American Association for Thoracic Surgery Clinical Practice Standards Committee expert panel was to review important considerations and factors in assessing who is at high risk among patients considered for lobectomy. MethodsThe American Association for Thoracic Surgery Clinical Practice Standards Committee assembled an expert panel that developed an expert consensus document after systematic review of the literature. The expert panel generated a priori a list of important risk factors in the determination of high risk for lobectomy. A survey was administered, and the expert panel was asked to grade the relative importance of each risk factor. Recommendations were developed using discussion and a modified Delphi method. ResultsThe expert panel survey identified the most important factors in the determination of high risk, which included the need for supplemental oxygen because of severe underlying lung disease, low diffusion capacity, the presence of frailty, and the overall assessment of daily activity and functional status. The panel determined that factors, such as age (as a sole factor), were less important in risk assessment. ConclusionsDefining who is at high risk for lobectomy for stage I non–small cell lung cancer is challenging, but remains critical. There was impressive strong consensus on identification of important factors and their hierarchical ranking of perceived risk. The panel identified several key factors that can be incorporated in risk assessment. The factors are evolving and as the population ages, factors such as neurocognitive function and frailty become more important. A minimally invasive approach becomes even more critical in this older population to mitigate risk. The determination of risk is a clinical decision and judgement, which should also take into consideration patient perspectives, values, preferences, and quality of life.

Multi-omics profiling predicts allograft function after lung transplantation.

Lung transplantation is the ultimate treatment option for patients with end-stage respiratory diseases but bears the highest mortality rate among all solid organ transplantations due to chronic lung allograft dysfunction (CLAD). The mechanisms leading to CLAD remain elusive due to an insufficient understanding of the complex post-transplant adaptation processes. To better understand these lung adaptation processes after transplantation and to investigate their association with future changes in allograft function. We performed an exploratory cohort study of bronchoalveolar lavage samples from 78 lung recipients and donors. We analysed the alveolar microbiome using 16S rRNA sequencing, the cellular composition using flow cytometry, as well as metabolome and lipidome profiling. We established distinct temporal dynamics for each of the analysed data sets. Comparing matched donor and recipient samples, we revealed that recipient-specific as well as environmental factors, rather than the donor microbiome, shape the long-term lung microbiome. We further discovered that the abundance of certain bacterial strains correlated with underlying lung diseases even after transplantation. A decline in forced expiratory volume during the first second (FEV1) is a major characteristic of lung allograft dysfunction in transplant recipients. By using a machine learning approach, we could accurately predict future changes in FEV1 from our multi-omics data, whereby microbial profiles showed a particularly high predictive power. Bronchoalveolar microbiome, cellular composition, metabolome and lipidome show specific temporal dynamics after lung transplantation. The lung microbiome can predict future changes in lung function with high precision.

Pulmonary TB and chronic pulmonary aspergillosis: clinical differences and similarities.

BACKGROUND: Pulmonary TB (PTB) and chronic pulmonary aspergillosis (CPA) are both progressive and debilitating parenchymal lung diseases with overlapping risk factors, symptomatology and radiological findings that often result in misdiagnosis of either disease.METHODS: We undertook a narrative review approach to describe the clinical and radiological manifestations of CPA and PTB and highlight the salient features that differentiate these two closely related maladies.RESULTS: CPA is a frequent complication of treated PTB. In fact, 15-90% of CPA cases occur in patients with residual lung lesions following treatment for PTB. While CPA predominantly affects older patients with underlying lung diseases, both PTB and CPA present with clinically indistinguishable symptoms. Chest imaging findings of cavitation and fibrosis are common to both diseases. However, lymphadenopathy, miliary pattern and pleural effusion are predictive of active PTB, while aspergilloma, pleural thickening and paracavitary fibrosis are more common in CPA. Aspergillus-specific IgG serology has a central role in differentiating PTB (both active and healed) from CPA with a high sensitivity and specificity.CONCLUSION: Aspergillus-specific IgG serology is key in differentiating PTB and PTB relapse from CPA. It may be worthwhile developing clinical predictive scores that can be used in low-income settings to differentiate active TB, post-TB disease and TB+CPA co-infection.

Pneumothorax in otherwise healthy non-intubated patients suffering from COVID-19 pneumonia: a systematic review.

BackgroundCases of spontaneous pneumothorax have been described in patients suffering from coronavirus disease 2019 (COVID-19) pneumonia. The aim of this study is to systematically review all the cases of spontaneous pneumothorax that occurred in healthy patients with no underlying lung disease and who did not receive invasive mechanical ventilation.MethodsA PubMed research was conducted. The following data were collected: age, sex, side of the pneumothorax, smoking habit, time form onset of symptoms to the diagnosis of pneumothorax, the development of new bullous lesions on computed tomography and the type of treatment. In order to analyze the most homogeneous population possible, intubated patients were deliberately excluded. In total, 44 cases of spontaneous pneumothorax in otherwise healthy patients were taken into account. Since the available data were extracted from small observational studies, no particular bias risk assessment was performed. Descriptive statistics were used to synthesize results.ResultsThere were 37 male (84.1%) and 6 female (13.6%) patients. The majority of patients (66%) were treated only by chest tube thoracostomy, which most of the times resulted in a complete resolution of the pneumothorax. Simple surveillance was applied in 10 cases. Three patients underwent minimally invasive surgery. In 14 cases (31.8%) air-filled lesions were detected on imaging. Eleven patients received corticosteroids during their hospital stay. In the majority of cases (86.3%) the pneumothorax was resolved.DiscussionEven if the level of evidence, derived from case reports and small case series is low, the existence of a true secondary spontaneous pneumothorax due to SARS-CoV-2 should be recognized. Imaging techniques should be repeated throughout the clinical course of the patients in order to detect newly developed pulmonary complications. Surgical treatment is feasible and patients whose general condition permits, should be offered surgery according to the existing guidelines regarding spontaneous pneumothorax. National registries and databases are necessary in order to better understand the pathogenesis and complications of this novel entity.

Management of Pulmonary Hypertension Due to Chronic Lung Disease.

Pulmonary hypertension (PH) is a known complication of chronic parenchymal lung diseases, including chronic obstructive lung disease, interstitial lung diseases, and more rare parenchymal lung diseases. Together, these diseases encompass two of the five clinical classifications of PH: group 3 (chronic lung disease [CLD] and/or hypoxia) and group 5 (unclear and/or multifactorial mechanisms). The principal management strategy in PH associated with CLD is optimization of the underlying lung disease. There has been increasing interest in therapies that treat pulmonary arterial hypertension (group 1, PAH), and although some studies have explored the use of these oral PAH-targeted therapies to treat PH associated with CLD, there is currently no evidence to support their routine use; in fact, some studies suggest harm. Inhaled therapies that target the pulmonary vasculature may avoid certain problems observed with oral PAH therapies. Recent studies suggest a promising role for inhaled PAH therapies in group 3 PH, but this requires further study. The objective of this article is to review the current treatment strategies for group 3 and group 5 PH.