Phase 3 Trial of Inhaled Molgramostim in Autoimmune Pulmonary Alveolar Proteinosis.

Background: Autoimmune pulmonary alveolar proteinosis (aPAP) is a rare disease characterized by progressive surfactant accumulation and hypoxemia caused by autoantibodies against granulocyte-macrophage colony-stimulating factor (GM-CSF), which alveolar macrophages require to clear surfactant. Molgramostim is a formulation of inhaled recombinant human GM-CSF, but its efficacy and safety in patients with aPAP have not been studied sufficiently.

Methods: In this phase 3, double-blind, placebo-controlled trial, we randomly assigned patients with aPAP to receive molgramostim at a dose of 300 μg or placebo once daily for 48 weeks.

A review of Proteases and Antiproteases for Immune Regulation and Potential Therapeutic Application in Pulmonary Fibrosis.

Interstitial lung diseases (ILDs), or diffuse parenchymal lung diseases, are general terms for a group of over 200 conditions that result from the destruction of cells neighbouring the alveoli, leading to extensive inflammation and fibrosis of the lungs. Although different types of ILD have distinct pathophysiology, clinical display and advancement, many forms drive irreversible pulmonary fibrosis (PF), leading to progressive functional impairment, respiratory failure, and mortality. Key components of innate immunity include proteases and their cognate inhibitors, which are involved in respiratory homeostasis.

Systemic autoimmune rheumatic diseases-associated interstitial lung disease: a pulmonologist's perspective.

Connective tissue disease (CTD)-associated interstitial lung disease (ILD) is a complex condition arising in various autoimmune disorders, such as systemic sclerosis, Sjögren disease, systemic lupus erythematosus and idiopathic inflammatory myopathies. The broader term of systemic autoimmune rheumatic diseases (SARDs) and SARD-ILD are increasingly adopted in various guidelines to allow inclusion of other rheumatic diseases such as rheumatoid arthritis. SARD-ILD significantly impacts morbidity and mortality, with disease manifestations ranging from mild to severe and life-threatening.

Current concepts in the pathogenesis and clinical management of lymphangioleiomyomatosis.

Purpose Of Review: Lymphangioleiomyomatosis (LAM) is a systemic, low-grade, metastasizing neoplasm that predominantly affects women. This review demonstrates recent progression in this rare disease, from improved understanding of pathogenesis, to novel treatments. We provide an overview of recent advances that are shaping the future of LAM diagnostic and treatment approaches.

Summary for clinicians: ERS guidelines on pulmonary alveolar proteinosis.

Pulmonary alveolar proteinosis (PAP) is a rare lung disease caused by accumulation of surfactant in the alveoli, leading to debilitating respiratory symptoms and impaired gas exchange. The recent European Respiratory Society guidelines provide evidence-based recommendations for its diagnosis and management. Autoimmune PAP (aPAP) is the most common form, driven by granulocyte-macrophage colony-stimulating factor (GM-CSF) autoantibodies.

Predicting Outcomes using DIGital TechnologY in patients with Interstitial Lung Disease (PRODIGY-ILD): Protocol for a Prospective Cohort Study.

Introduction: Interstitial lung disease (ILD) patients may develop a progressive phenotype usually characterised by progressive pulmonary fibrosis. While this condition is life-limiting, wide variations in its clinical course have made it difficult to predict the rate of disease progression, onset of acute exacerbations and mortality. New approaches are needed to predict the clinical course of ILD, to enable treatment planning, evaluation and clinical trial design.

Deciphering the Role of Fluorodeoxyglucose-Positron Emission Tomography/CT Imaging in the Management of Sarcoidosis.

Background: 2-Deoxy-2-[F]fluoro-d-glucose (FDG)-PET/CT imaging has utility in identifying sites of active sarcoidosis. However, the role of FDG-PET/CT imaging in predicting treatment response and guiding therapy outside of cardiac disease is yet to be completely understood.

Research Question: Do physicians agree on the utility of FDG-PET/CT imaging in sarcoid cases, and do they agree on the appropriate treatment response, based on the associated reports?

Study Design And Methods: Physician respondents were presented with a series of anonymized sarcoidosis case vignettes.

The healthcare burden of pulmonary alveolar proteinosis (PAP).

Introduction: Pulmonary alveolar proteinosis (PAP) is a rare lung syndrome characterized by the accumulation of surfactant in the alveoli. Using a longitudinal claims database, we compared measures of clinical and economic burden between a sample of diagnosed PAP patients and non-PAP matched controls.

Methods: PAP patients were identified leveraging IPM.

Does Adenosine Triphosphate via Purinergic Receptor Signalling Fuel Pulmonary Fibrosis?

Background: Interstitial lung diseases (ILD) are poorly understood disorders characterised by diffuse damage to the lung parenchyma, with inflammation and fibrosis. Some manifest a progressive fibrotic phenotype with high fatality and limited treatment options, such as idiopathic pulmonary fibrosis.

Summary: The degree to which inflammation plays a role in fibrosis progression is unknown.

Childhood interstitial lung disease survivors in adulthood: a European collaborative study.

Background: Interstitial lung disease is rarer in children than adults, but, with increasing diagnostic awareness, more cases are being discovered. The prognosis of childhood interstitial lung disease is often poor, but increasing numbers are now surviving into adulthood.

Aim: To characterise childhood interstitial lung disease survivors and identify their impact on adult interstitial lung disease centres.

Airway macrophage glycolysis controls lung homeostasis and responses to aeroallergen.

The lungs represent a dynamic microenvironment where airway macrophages (AMs) are the major lung-resident macrophages. AMs dictate the balance between tissue homeostasis and immune activation and thus have contradictory functions by maintaining tolerance and tissue homeostasis, as well as initiating strong inflammatory responses. Emerging evidence has highlighted the connection between macrophage function and cellular metabolism.

Diffuse Cystic Lung Disease: A Clinical Guide to Recognition and Management.

Topic Importance: Diffuse cystic lung diseases (DCLDs) represent a group of pathophysiologically heterogeneous entities that share a common radiologic phenotype of multiple thin-walled pulmonary cysts. DCLDs differ from the typical fibroinflammatory interstitial lung diseases in their epidemiology, clinical presentation, molecular pathogenesis, and therapeutic approaches, making them worthy of a distinct classification. The importance of timely and accurate identification of DCLDs is heightened by the impact on patient management including recent discoveries of targeted therapeutic approaches for some disorders.

Meta-analysis of [F]FDG-PET/CT in pulmonary sarcoidosis.

Background: 18F-Fluorodeoxyglucose (FDG) PET/CT is emerging as a tool in the diagnosis and evaluation of pulmonary sarcoidosis, however, there is limited consensus regarding its diagnostic performance and prognostic value.

Method: A meta-analysis was conducted with PubMed, Science Direct, MEDLINE, Scopus, and CENTRAL databases searched up to and including September 2023. 1355 studies were screened, with seventeen (n = 708 patients) suitable based on their assessment of the diagnostic performance or prognostic value of FDG-PET/CT.

Unsupervised Exercise in Interstitial Lung Disease: A Delphi Study to Develop a Consensus Preparticipation Screening Tool for Lymphangioleiomyomatosis.

Background: Little research is available to provide practical guidance to health care providers for exercise preparticipation screening and referral of patients with interstitial lung diseases (ILDs), including lymphangioleiomyomatosis (LAM), to participate in remote, unsupervised exercise programs.

Research Question: What exercise preparticipation screening steps are essential to determine whether a patient with LAM is medically appropriate to participate in a remote, unsupervised exercise program?

Study Design And Methods: Sixteen experts in LAM and ILD participated in a two-round modified Delphi study, ranking their level of agreement for 10 statements related to unsupervised exercise training in LAM, with an a priori definition of consensus. Additionally, 60 patients with LAM completed a survey of the perceived risks and benefits of remote exercise training in LAM.

Neutrophil-Derived Peptidyl Arginine Deiminase Activity Contributes to Pulmonary Emphysema by Enhancing Elastin Degradation.

In chronic obstructive pulmonary disease (COPD), inflammation gives rise to protease-mediated degradation of the key extracellular matrix protein, elastin, which causes irreversible loss of pulmonary function. Intervention against proteolysis has met with limited success in COPD, due in part to our incomplete understanding of the mechanisms that underlie disease pathogenesis. Peptidyl arginine deiminase (PAD) enzymes are a known modifier of proteolytic susceptibility, but their involvement in COPD in the lungs of affected individuals is underexplored.

Pulmonary Manifestations of Sjögren's Disease.

Sjögren's disease (SjD) is a chronic, progressive autoimmune condition of exocrine and extraglandular tissues. It can present with isolated disease characterized by lymphocytic infiltration of salivary or lacrimal glands, but in approximately one-third of the patients, lymphocytic infiltration extends beyond exocrine glands to involve extraglandular organs such as the lungs. Pulmonary complications have been reported to occur between 9 and 27% of patients with SjD across studies.