Serum Amyloid P Therapeutically Attenuates Murine Bleomycin-Induced Pulmonary Fibrosis via Its Effects on Macrophages

Macrophages promote tissue remodeling but few mechanisms exist to modulate their activity during tissue fibrosis. Serum amyloid P (SAP), a member of the pentraxin family of proteins, signals through Fcγ receptors which are known to affect macrophage activation. We determined that IPF/UIP patients have increased protein levels of several alternatively activated pro-fibrotic (M2) macrophage-associated proteins in the lung and monocytes from these patients show skewing towards an M2 macrophage phenotype. SAP therapeutically inhibits established bleomycin-induced pulmonary fibrosis, when administered systemically or locally to the lungs. The reduction in aberrant collagen deposition was associated with a reduction in M2 macrophages in the lung and increased IP10/CXCL10. These data highlight the role of macrophages in fibrotic lung disease, and demonstrate a therapeutic action of SAP on macrophages which may extend to many fibrotic indications caused by over-exuberant pro-fibrotic macrophage responses

Patient Registries in Idiopathic Pulmonary Fibrosis.

Over the past decade, several large registries of patients with idiopathic pulmonary fibrosis (IPF) have been established. These registries are collecting a wealth of longitudinal data on thousands of patients with this rare disease. The data collected in these registries will be complementary to data collected in clinical trials because the patient populations studied in registries have a broader spectrum of disease severity and comorbidities and can be followed for a longer period of time. Maintaining the quality and completeness of registry databases presents administrative and resourcing challenges, but it is important to ensuring the robustness of the analyses. Data from patient registries have already helped improve understanding of the clinical characteristics of patients with IPF, the impact that the disease has on their quality of life and survival, and current practices in diagnosis and management. In the future, analyses of biospecimens linked to detailed patient profiles will provide the opportunity to identify biomarkers linked to disease progression, facilitating the development of precision medicine approaches for prognosis and therapy in patients with IPF

Asbestosis and environmental causes of usual interstitial pneumonia

General view across the field, from the northwest; The Mississauga Civic Centre architecture is based on a "futuristic farm" (the clock tower is the windmill, the main building is the farmhouse, the cylindrical council chamber is the silo, and the pentagonal building is the barn). It is a multi-purpose facility for both government and community use. Besides the government offices it contains a wedding chapel and conservatory. The courtyard contains a reflecting pool/ice rink and a garden. Source: Wikipedia; http://en.wikipedia.org/wiki/Main_Page (accessed 11/5/2007

Approach to the Patient/Diagnostic Methods

Chapter of book discussing occupational and environmental diseases and injuries of lung and pleura

Non-steroidal treatment of cardiac sarcoidosis: A systematic review

The treatment of active cardiac sarcoidosis (CS) usually involves immunosuppressive therapy, with the goal of preventing inflammation-induced scar formation. In most cases, steroids remain the first-line treatment for CS. However, given the side effect profile of their long-term use, steroid-sparing therapies are increasingly used. There are no published randomized trials of steroid-sparing agents in CS. We sought to do a systematic review to evaluate the current published data on the use of non-steroidal treatments in the management of CS. We searched the Cochrane Library, Ovid Medline, Ovid Embase, PubMed, and Web of Science Core Collection databases from inception of database to August 2020 to identify the effectiveness of biological or synthetic disease-modifying antirheumatic agents (s- and bDMARDs). Secondary objectives include safety profile as well as the change in the average corticosteroid dose after treatment initiation. Twenty-three studies were ultimately selected for inclusion which included a total of 480 cases of CS treated with a range of both s- and bDMARDs. In all included studies, sDMARDs and bDMARDs were studied in combination with steroids or as second or higher-line treatments after therapeutic failure or intolerance to corticosteroid use. Methotrexate (MTX) and infliximab (IFX) were the most common synthetic and biologic DMARDs studied respectively, reported in about 35% of the studies reviewed. The use of steroid-sparing agents was associated with a reduction in the maintenance steroid dose used. In conclusion, steroids will remain as the cornerstone of anti-inflammatory management in patients with CS until trials on the use and safety profile of other immunosuppressive agents are completed and published

Rationale and design of the SARCoidosis outcomes in all respiratory Viral Infectious Diseases (SARCOVID) study

Introduction: Respiratory infections are ubiquitous. The COVID-19 pandemic has refocused our attention on how morbid and potentially fatal they can be, and how host factors have an impact on the clinical course and outcomes. Due to a range of vulnerabilities, patients with sarcoidosis may be at higher risk of poor outcomes from respiratory infections. The objective of the SARCoidosis Outcomes in all respiratory Viral Infectious Diseases (SARCOVID) study is to determine the short- and long-term impacts of respiratory viral illnesses (COVID-19 and non-COVID-19) in sarcoidosis. Methods and Analysis: Up to twenty clinical sites across the United States are participating in the recruitment of 2,000 patients for this observational, prospective study. To ensure that the study cohort is representative of the general sarcoidosis population, participating sites include those dedicated to reaching underrepresented minorities or patients from non-urban areas. Baseline data on demographic features, comorbidities, sarcoidosis characteristics, and pre-enrollment lung function will be captured at study entry. During this 3-year study, all acute respiratory infectious events (from SARS-CoV2 and any other respiratory pathogen) will be assessed and recorded at quarterly intervals. The level of required medical care and survival outcomes determine infection severity, and the impact of infection on quality of life measures will be recorded. Post-infection lung function and imaging results will measure the long-term impact on the trajectory of sarcoidosis. Patients will be analyzed according to the clinical phenotypes of cardiac and fibrotic pulmonary sarcoidosis. Control groups include non-infected patients with sarcoidosis and patients with non-sarcoidosis interstitial lung disease. Ethics and Dissemination: Each site received local IRB approval prior to enrolling patients, with the consent process determined by local institution standards. Data will be published in a timely manner (goal < 12 months) at the conclusion of the three-year follow-up period and will be made available upon request

Proteomic profiling demonstrates inflammatory and endotheliopathy signatures associated with impaired cardiopulmonary exercise hemodynamic profile in Post Acute Sequelae of SARS‐CoV‐2 infection (PASC) syndrome

Abstract Approximately 50% of patients who recover from the acute SARS‐CoV‐2 experience Post Acute Sequelae of SARS‐CoV‐2 infection (PASC) syndrome. The pathophysiological hallmark of PASC is characterized by impaired system oxygen extraction (EO2) on invasive cardiopulmonary exercise test (iCPET). However, the mechanistic insights into impaired EO2 remain unclear. We studied 21 consecutive iCPET in PASC patients with unexplained exertional intolerance. PASC patients were dichotomized into mildly reduced (EO2peak‐mild) and severely reduced (EO2peak‐severe) EO2 groups according to the median peak EO2 value. Proteomic profiling was performed on mixed venous blood plasma obtained at peak exercise during iCPET. PASC patients as a group exhibited depressed peak exercise aerobic capacity (peak VO2; 85 ± 18 vs. 131 ± 45% predicted; p = 0.0002) with normal systemic oxygen delivery, DO2 (37 ± 9 vs. 42 ± 15 mL/kg/min; p = 0.43) and reduced EO2 (0.4 ± 0.1 vs. 0.8 ± 0.1; p < 0.0001). PASC patients with EO2peak‐mild exhibited greater DO2 compared to those with EO2peak‐severe [42.9 (34.2–41.2) vs. 32.1 (26.8–38.0) mL/kg/min; p = 0.01]. The proteins with increased expression in the EO2peak‐severe group were involved in inflammatory and fibrotic processes. In the EO2peak‐mild group, proteins associated with oxidative phosphorylation and glycogen metabolism were elevated. In PASC patients with impaired EO2, there exist a spectrum of PASC phenotype related to differential aberrant protein expression and cardio‐pulmonary physiologic response. PASC patients with EO2peak‐severe exhibit a maladaptive physiologic and proteomic signature consistent with persistent inflammatory state and endothelial dysfunction, while in the EO2peak‐mild group, there is enhanced expression of proteins involved in oxidative phosphorylation‐mediated ATP synthesis along with an enhanced cardiopulmonary physiological response