Introduction Lymphangioleiomyomatosis (LAM) is a rare, female-predominant, multi-organ disease driven by mutations in tuberous sclerosis complex (TSC) genes. LAM is characterized by abnormal proliferation of smooth muscle cells within the lung parenchyma and lymphatic system, leading to cystic lung disease and extra-pulmonary manifestations. Diagnosis involves detection of serum markers for vascular endothelial growth factor (VGEF-D) or lung biopsy. mTOR inhibitors are first-line therapy. Pericardial effusions and cardiac tamponade are recognized complications of sirolimus in renal transplant patients, but have not been previously reported in individuals with LAM. We present a 71-year-old woman with LAM who experienced recurrent cardiac tamponade attributed to sirolimus therapy. Case Description A 59-year-old lifelong non-smoking female was evaluated for incidental radiographic thin-walled pulmonary cysts and renal angiomyolipoma. Pulmonary function testing showed a mild obstructive defect with hyperinflation and a mild reduction in DLCO. VEGF-D levels were normal (499 pg/mL). Transbronchial biopsy of the right lower lobe revealed emphysematous changes with focal interstitial fibrosis and a single non-necrotizing granuloma. HMB-45 was negative but Smooth Muscle Actin (SMA) staining was positive within blood vessels and peribronchial tissue. Sirolimus 1 mg daily was initiated. The patient remained stable for 11 years, with only mild side effects and minimal lung function decline. She later reported acute shortness of breath and substernal chest pain. Imaging demonstrated stable pulmonary disease and a new pericardial effusion (PCE). POCUS indicated a moderate PCE with tamponade physiology, confirmed by hemodynamic testing showing equalization of chamber pressures. She underwent pericardiocentesis, draining 850 cc of straw-colored sterile fluid. Sirolimus was discontinued. One month later, recurrent cardiac tamponade required a pericardial window despite agent discontinuation. Discussion With an incidence of 3.3 to 7.7 per million women, LAM is driven by mutations and epigenetic modifications in the TSC1 or TSC2 genes, the latter often associated with more severe clinical phenotypes. Common features are atypical smooth muscle cell proliferation around lymphatic channels and airways and chylous effusions in approximately 20% of cases. Pericardial effusions have not been previously reported. mTOR inhibitors have been shown to stabilize and improve lung function in LAM. Sirolimus is a common therapy in solid-organ transplantation and pericardial effusion is observed in up to 28% of renal and cardiac transplant patients. The mechanism remains unclear, though hypotheses suggest nuclear factor (NF)-KB activation leads to serosal inflammation. This case underscores the importance of recognizing sirolimus's potential cardiac side-effects during treatment of LAM.

RATIONALE: The prevalence and comorbidity of chronic pulmonary sarcoidosis and non-tuberculous mycobacterial (NTM) pulmonary infections are unknown. Recently a Delphi consensus study identified high resolution computed tomography (HRCT) phenotypes of pulmonary sarcoidosis.1 We sought to identify clinical and HRCT phenotypes in patients with sarcoidosis and NTM infection. METHODS: We performed a retrospective chart review of all adult patients in the University of Alabama at Birmingham (UAB) Health System with an ICD-10 diagnosis of Sarcoidosis, Infection due to other Mycobacteria, or positive Nontuberculous Mycobacteria PCR. 25 total patients met criteria of sarcoidosis and documented acid fast bacilli (AFB) test for NTM. Three chest radiologists analyzed the HRCT closest to the AFB positive test date and determined which HRCT findings were due to sarcoid and what category based on the Delphi Agreement was discussed among the following non-fibrotic categories: Multiple peribronchovascular, perifissural, or subpleural micronodules (NFA); multiple larger peribronchovascular nodules (NFB); scattered larger nodules (NFC); consolidation as the predomninant or sole abnormality (NFD); and fibrotic categories: bronchocentric reticulation with or without dense parenchymal opacification, without cavitation (FA); bronchocentric reticulation with or without dense parenchymal opacification, with cavitation (FB); large bronchocentric masses (Progressive Massive Fibrosis (PMF) (FC)). RESULTS: 14/15 (93%) of the MAC patients were on immunosuppression before or during MAC diagnosis. 9/15 (60%) of the MAC patients met FA radiographic criteria. Chest radiologists agreed completely on 69% of the categories with most inter-reader variability among the 3 nonfirbotic categories and better agreement on consolidation as the predominant finding category. Most patients were identified to meet F A (10 patients), FB (9 patients), NFA (7 patients), or NFB (7 patients) radiographic categories. There were 5 patients who met NFC, 0 met NFD, and 3 met FC categories. CONCLUSIONS: We identified a large cohort of patients with NTM infection and sarcoidosis and explored the relationship between this cohort and radiographic phenotypes based on Delphi consensus. Interreader variability among chest radiologists reading HRCT on these patients and common phenotypes were assessed. REFERENCES:1.Desai SR, Sivarasan N, Johannson KA, George PM, Culver DA, Devaraj A, Lynch DA, Milne D, Renzoni E, Nunes H, Sverzellati N, Spagnolo P, Baughman RP, Yadav R, Piciucchi S, Walsh SLF, Kouranos V, Wells AU; Sarcoid Delphi Group. High-resolution CT phenotypes in pulmonary sarcoidosis: a multinational Delphi consensus study. Lancet Respir Med. 2024 May;12(5):409-418. doi: 10.1016/S2213-2600(23)00267-9. Epub 2023 Dec 14. PMID: 38104579.

Objective Lymphangioleiomyomatosis (LAM) is a rare, multisystem disease that primarily affects women of reproductive age. Disease progression has been linked to estrogen exposure, and as such many patients are advised to avoid pregnancy. Data are limited regarding the interaction between LAM and pregnancy, and as such we performed a systematic review to summarize available literature reporting outcomes of pregnancies complicated by maternal LAM. Study Design This was a systematic review including randomized controlled trials, observational studies, systematic reviews, case reports, clinical practice guidelines, and quality improvement studies with full-text manuscripts or abstracts in the English language with primary data on pregnant or postpartum patients with LAM. The primary outcome was maternal outcomes during pregnancy as well as pregnancy outcomes. Secondary outcomes were neonatal outcomes and long-term maternal outcomes. This search occurred in July 2020 and included MEDLINE, Scopus, clinicaltrials.gov, Embase, and Cochrane Central. Risk of bias was ascertained using the Newcastle–Ottawa Scale. Our systematic review was registered with PROSPERO as protocol number CRD 42020191402. Results A total of 175 publications were identified in our initial search; ultimately 31 studies were included. Six (19%) studies were retrospective cohort studies and 25 (81%) studies were case reports. Patients diagnosed during pregnancy had worse pregnancy outcomes compared to those diagnosed with LAM prior to pregnancy. Multiple studies reported a significant risk of pneumothoraces during pregnancy. Other significant risks included preterm delivery, chylothoraces, and pulmonary function deterioration. A proposed strategy for preconception counseling and antenatal management is provided. Conclusion Patients diagnosed with LAM during pregnancy generally experience worse outcomes including recurrent pneumothoraces and preterm delivery as compared to patients with a LAM diagnosis prior to pregnancy. Given that there are limited studies available, and that the majority are low-quality evidence and subject to bias, further investigation of the interaction between LAM and pregnancy is warranted to guide patient care and counseling. Key Points

In patients treated with repository corticotrophin injection (RCI) for pulmonary sarcoidosis, effective management of adverse events may improve adherence. However, management of adverse events may be challenging due to limitations in real-world clinical experience with RCI and available published guidelines. We surveyed 12 physicians with a modified Delphi process using three questionnaires. Questionnaire 1 consisted of open-ended questions. Panellists' answers were developed into a series of statements for Questionnaires 2 and 3. In these, physicians rated their agreement with the statements using a Likert scale. Key consensus recommendations included a starting dose of 40 units twice a week for patients with less severe disease, continued at a maintenance dose for patients who responded, particularly those with chronic refractory sarcoidosis. Panellists reached consensus that concomitant steroids should be quickly tapered in patients receiving RCI, but that concomitant use of immunosuppressive medications should be continued. Panellists developed consensus recommendations for adverse event management, and reached consensus that RCI should be down-titrated or discontinued if other interventions for the adverse effects fail or if the adverse effect is severe. In the absence of clinical evidence, our Delphi consensus opinions may provide practical guidance to physicians on the management of RCI to treat pulmonary sarcoidosis.

TYPE: Abstract Publication TOPIC: Diffuse Lung Disease PURPOSE: IPF is a progressive interstitial lung disease with fibrosis of lung parenchyma and clinical hypoxia. The development of PAH adds morbidity and mortality. The effect antifibrotic agents on the development of PAH is unclear. We examined patients with IPF on antifibrotics and untreated with respect to PAH. METHODS: Two cohorts with IPF were collected; Cohort 1 subjects untreated with antifibrotics and cohort 2, subjects treated with antifibrotics. All subjects met ATS criteria for a diagnosis of IPF. PAH was diagnosed with a mean PAP over 25mmHg by right heart catheterization or an estimated PASP over 45mmHg by echocardiogram. Regression analysis of antifibrotics was performed on the outcome of PAH. RESULTS: Complete data were available for 445 subjects in cohort 1 and 159 subjects in cohort 2(table1). 70 cases (16% p.005) of PAH were diagnosed in cohort 1 while 63(39% p .005) cases of PAH were diagnosed in cohort 2 (OR 3.38, CI 2.25-5.06). Analysis demonstrated higher incidence of PAH among subjects who had been on both antifibrotic agents sequentially (42% p.05) and nintedanib (38% P.05) than pirfenidone (18% p.05). CONCLUSIONS: This study shows antifibrotics do not protect against the development of PAH and suggests subjects on nintedanib or those switched from pirfenidone to nintedenib had higher rates of PAH compared to those tolerating pirfenidone as long term therapy. CLINICAL IMPLICATIONS: Given the importance that development of PAH has in patients with IPF, more work on this is needed to understand risk associated with specific agents. DISCLOSURE: No significant relationships. KEYWORDS: Pulmonary fibrosis, pulmonary hypertension, Antifibrotics

TYPE: Abstract Publication TOPIC: Transplantation PURPOSE: Solid organ transplant patients are chronically immunosuppressed and at risk for opportunistic infections. Rates of common viral infections among this population are less well described. We characterized heart, lung, kidney, and liver transplant patients compared to non-transplant subjects with respect to viral pneumonia rates. METHODS: Bronchoscopy data were reviewed on subjects with samples by BAL and viral panel results compared among populations with solid organ transplants to normal subjects. Tacrolimus levels at the time of bronchoscopy were compared to rates of viral pneumonia. Regression analysis was performed on the outcome of viral pneumonia by organ transplant status and descriptive statistics calculated. RESULTS: Complete data were available for 159 subjects, with 25% having some form of solid organ transplant. Solid organ transplant subjects had higher rates of non-CMV viral pneumonia 33% compared to non-transplant subjects with 23% (OR 1.72 CI 0.78,3.8 p=.009). Rhinovirus and enterovirus accounted for the majority of subjects with transplants. Elevated tacrolimus levels had no relationship to rates of viral pneumonia. Subjects on 3 or more immunosuppressive agents had higher viral pneumonia rates. CONCLUSIONS: Solid organ transplant patients have higher rates of common viral pneumonias correlating with number of immunosuppressive agents. Toxic levels of tacrolimus does not seem to add risk for non-cmv pneumonia in this population. CLINICAL IMPLICATIONS: Given the prevalence of common viral respiratory infections, subjects with solid organ transplants on multiple modalities of immunosuppression should be screened aggressively for early diagnosis and consideration given for lowering immunosuppression levels during acute infections. DISCLOSURE: No significant relationships. KEYWORDS: viral pneumonia, solid organ transplant, immunosuppression

TYPE: Abstract Publication TOPIC: Diffuse Lung Disease PURPOSE: Myositis specific autoantibodies can be seen in association with dermatomyositis and polymyositis manifestations with and without ILD and convey higher rates of inflammation when present. The prevalence of the myositis specific autoantibodies MI-2, Tiff 1 gamma, MDA-5, and NXP2 in other ILD’s and their clinic relevance are unknown. We reviewed cases from a regional ILD center and characterized them with respect to phenotype, smoking status, and autoantibody patterns. METHODS: Cases from 2018-2020 were reviewed and subjects with myositis specific autoantibodies were grouped by ILD diagnosis, demographics, cancer history, body mass index, and smoking status. Descriptive statistics were performed. Cases with dermatomyositis or polymyositis were excluded. RESULTS: Complete data were available for 221 subjects with 5 cases (2%) having myositis specific ILD with diagnosis other than dermatomyositis or polymyositis. The median age was 63.6 years with all five subjects being female. Three subjects (60%) had smoking histories and only one subject had concomitant solid organ cancer history. Two subjects had CTD-ILD as their primary diagnosis, two subjects had IPF, and one was diagnosed with ILD NOS. MI-2 autoantibody was not seen in any subjects. CONCLUSIONS: Among subjects with ILD’s not associated with dermatomyositis or polymyositis, myositis specific auto-antibodies are rare. Female gender was highly associated with these phenotypes and smoking seemed to have high prevalence among them. MI-2 was the only myositis associated antibody not seen. CLINICAL IMPLICATIONS: Myositis-associated autoantibodies in non-dermatomyositis ILD phenotypes are rare and and may impact disease progression. Larger prospective data are needed to understand this phenomenon. DISCLOSURE: No significant relationships. KEYWORDS: Interstitial lung disease, Myositis antibodies, Autoimmunity

INTRODUCTION:Sarcoidosis associated pulmonary hypertension (SAPH) is a leading contributor to sarcoidosis-related mortality. The 6-min walk test (6MWT) is widely used in assessment of cardiorespiratory conditions. A reduced 6-min walk distance (6MWD) has been associated with increased mortality in SAPH. We examined patients from the Registry of Sarcoidosis Associated Pulmonary Hypertension (ReSAPH) who had performed 6MWT at enrollment to identify variables that affect 6MWD, and the prognostic value of 6MWT variables regarding death or lung transplantation. MATERIAL AND METHODS:ReSAPH patients with available 6MWT were included. Variables analyzed using pre-defined cutoffs included 6MWD, initial and end of test Borg dyspnea score, oxygen saturation, and heart rate at beginning, end, and after 1-min recovery, absolute change in oxygen saturation, modified distance-saturation product (mDSP), and the heart rate recovery at 1-min (HRR). FINDINGS:174 patients met inclusion criteria; 48 patients died and 8 underwent lung transplantation. Patients with 6MWD<300 m had a higher chance of dying or undergoing transplantation compared to those with 6MWD>300 m (p = 0.012). No associations with outcome were observed with mDSP cutoff 200 m%, desaturation≥5% and oxygen saturation<88% at end of 6MWT, or multiple HRR cutoffs (13,14,16). 6MWD correlated with initial Borg score, (p = 0.001), DLCO% (p = 0.0001) and sPAP (p = 0.031) on multivariate analysis. These variables were significant for both pre- and post-capillary PH subgroups. 6MWD also correlated with fatigue assessment scale (FAS) (p = 0.015). CONCLUSION:Of the parameters evaluated, 6MWD had the greatest prognostic value in SAPH which correlated with other physiologic and hemodynamic variables. 6MWT captures the multidimensional effects of sarcoidosis.

Pulmonary sarcoidosis presents substantial management challenges, with limited evidence on effective therapies and phenotypes. In the absence of definitive evidence, expert consensus can supply clinically useful guidance in medicine. An international panel of 26 experts participated in a Delphi process to identify consensus on pharmacological management in sarcoidosis with the development of preliminary recommendations. The modified Delphi process used three rounds. The first round focused on qualitative data collection with open-ended questions to ensure comprehensive inclusion of expert concepts. Rounds 2 and 3 applied quantitative assessments using an 11-point Likert scale to identify consensus. Key consensus points included glucocorticoids as initial therapy for most patients, with non-biologics (immunomodulators), usually methotrexate, considered in severe or extrapulmonary disease requiring prolonged treatment, or as a steroid-sparing intervention in cases with high risk of steroid toxicity. Biologic therapies might be considered as additive therapy if non-biologics are insufficiently effective or are not tolerated with initial biologic therapy, usually with a tumour necrosis factor-α inhibitor, typically infliximab. The Delphi methodology provided a platform to gain potentially valuable insight and interim guidance while awaiting evidenced-based contributions.

In patients treated with repository corticotrophin injection (RCI) for pulmonary sarcoidosis, effective management of adverse events may improve adherence. However, management of adverse events may be challenging due to limitations in real-world clinical experience with RCI and available published guidelines. We surveyed 12 physicians with a modified Delphi process using three questionnaires. Questionnaire 1 consisted of open-ended questions. Panellists' answers were developed into a series of statements for Questionnaires 2 and 3. In these, physicians rated their agreement with the statements using a Likert scale. Key consensus recommendations included a starting dose of 40 units twice a week for patients with less severe disease, continued at a maintenance dose for patients who responded, particularly those with chronic refractory sarcoidosis. Panellists reached consensus that concomitant steroids should be quickly tapered in patients receiving RCI, but that concomitant use of immunosuppressive medications should be continued. Panellists developed consensus recommendations for adverse event management, and reached consensus that RCI should be down-titrated or discontinued if other interventions for the adverse effects fail or if the adverse effect is severe. In the absence of clinical evidence, our Delphi consensus opinions may provide practical guidance to physicians on the management of RCI to treat pulmonary sarcoidosis. In this paper, a modified Delphi method was used to develop an expert consensus on the use of repository corticotrophin injection therapy for pulmonary sarcoidosis, including dosing, concomitant medications, contraindications and adverse event management. http://bit.ly/2TyauZp

PURPOSE: This study aimed to compare rates of return of spontaneous circulation (ROSC) among patients with intraosseous (IO) and standard venous in-hospital resuscitation and between obese versus non-obese subjects. METHODS: In hospital cardiac arrests between 2013-2018 were reviewed and methods of resuscitation characterized. Subjects resuscitated in the ED, with extracorporeal circulation support, intra-aortic balloon pumps, or central venous access were excluded. Descriptive characteristics including body mass index were collected. The primary outcome of ROSC was compared with IO resuscitation versus peripheral venous access using bivariate analysis. Subanalysis of ROSC by IO resuscitation among patients with body mass index (BMI) 30kg/m2 or greater compared to non-obese subjects was performed. RESULTS: Data were available for 575 subjects 60 percent of which were male, the median age was 61 years and 41 percent of subjects met criteria for obesity. Median BMI for this cohort was 28.3 kg/m2. ROSC was achieved in 466 subjects. Outcomes for ROSC with IO compared to standard IV access were significantly worse in this cohort (OR, 0.59,95%CI 0.39-.091, p=0.016). Subanalysis of obese subjects showed no benefit with IO resuscitation compared to standard methods (OR, 0.41, 95% CI 0.18-0.94, p=0.032). CONCLUSIONS: Intraosseous medication delivery appears to confer significantly inferior rates of ROSC among subjects with in-hospital cardiac arrest compared to standard intravenous methods. Intraosseous resuscitation among obese subjects also conveyed lower rates of ROSC despite providing more rapid method of delivery. CLINICAL IMPLICATIONS: This study recapitulates data among out-of-hospital resuscitation efforts in suggesting the inferiority of IO vs. IV resuscitation in achieving ROSC during cardiac arrest.