Interstitial Lung Disease

Briefly, during a one to two hour visit, subjects will provide written informed consent and then undergo: 1. brief medical history and vital signs, 2. full pulmonary function tests, 3. proton MRI, 4. spin-density, diffusion weighted, and/or dissolved phase 129-Xe MRI, 5. Low-dose thoracic CT Full pulmonary function tests including spirometry, plethysmography and diffusing capacity of carbon monoxide (DLCO), Multiple Breath Nitrogen Washout (MBNW) to measure Lung Clearance Index (LCI), and Forced Oscillation Technique (FOT) will be performed according to American Thoracic Society (ATS) guidelines. MedGraphics Elite Series, MedGraphics Corporation. St. Paul, Minnesota USA and/or nDD EasyOne Spirometer, nDD Medical Technologies Inc. Andover, Massachusetts USA will be used. All measurements will be performed in the Pulmonary Function Laboratory at Robarts Research Institute. Subjects will be placed in the 3T Magnetic Resonance (MR) scanner with one of three 129-Xe chest coils fitted over their torso and chest. Hearing protection will be provided to each subject to muffle the noise produced by the gradient radiofrequency (RF) coils. A pulse oximeter lead will be attached to all of the subjects to monitor their heart rate and oxygen saturation. MRI will be performed for up to a period of 30 minutes. All subjects will have supplemental oxygen available via nasal cannula at a flow-rate of 2 liters per minute as a precaution in the event of oxygen desaturation. Thoracic low dose CT will be performed with the same inhalation breath-hold volume and maneuver (nitrogen gas only) used for MRI to obtain participant-specific high resolution images of lung anatomy (tissue structure and airway morphology).

This study focuses on the markers that are derived from the interaction of 129Xe with pulmonary capillary red blood cells (RBCs). Specifically, the investigators focus on RBC transfer MRI, cardiogenic oscillations in 129Xe-RBC signal amplitude, and the 129Xe-RBC chemical shift. In addition to healthy volunteers, the population to be studied will consist of patients scheduled to undergo either transfusion or phlebotomy, those with dyspnea, those with a physician diagnosis of interstitial lung disease (ILD), idiopathic pulmonary fibrosis (IPF), non-specific interstitial pneumonias (NSIP), chronic hypersensitivity pneumonitis (cHP), and sarcoid, as well as those with either chronic thromboembolic pulmonary hypertension (CTEPH) and acute pulmonary embolism.

The purpose of this study is to evaluate safety, tolerability, PK and immunogenicity of SV001 compare to placebo in Chinese healthy adult volunteers.

The GENESIS study is a multicenter, prospective, non-interventional, clinical study with a target of 12,000 subjects and an anticipated total duration of 36 months. The aim of study GENESIS is to provide a pilot map of HLA genetic variation in the Greek population in order to be used in medical research and for possible clinical applications (evaluation of possible correlations with selected underlying diseases). During the study, each subject will conduct one visit to the participating cite, in which they will provide: 1. Demographic information \[i.e. date of birth, gender, race, ancestry (including information about the subject's grandparents' birthplace), height, weight\], 2. Other information about smoking/vaping, alcohol consumption, arterial blood pressure, diagnosed diseases (if any), current treatments (if any), and 3. Recent (up to 12 months prior to sample collection) results if/when are available from clinical lab tests such as blood count (Hct, Hb, RBC, WBC, PLT count), including a metabolic panel, liver enzymes and biochemical parameters (Glu, HbA1c, TC, TG, LDL-C, HDL-C, ALT, AST, ALP, γGT, bilirubin, LDH, insulin, C-peptide). Upon completion of the data registry, two buccal swabs will be collected per subject and they will be stored at ALTP premises until their shipment to Galatea.Bio. All buccal swab samples will be subjected to genetic material (DNA) extraction. The DNA samples will be further proceeded for HLA genotyping analysis. A follow up analysis will be performed in selected DNA samples via full low-pass whole genome sequencing (LP-WGS), which aims to further investigate the association between the HLA region and autoimmune diseases. Upon completion of the analysis, an individualized ancestry report will be securely made available to all study subjects which they can access, as and if they elect to.

This study is open to people with idiopathic pulmonary fibrosis (IPF) or progressive pulmonary fibrosis (PPF). They can only take part if they have completed treatment in a previous study with a medicine called nerandomilast or BI 1015550. The goal of this study is to find out how well people with pulmonary fibrosis tolerate long- term treatment with nerandomilast. The study also tests whether nerandomilast improves lung function and prolongs the time until symptoms get worse, participants need to go to the hospital, or die. Every participant takes nerandomilast as tablets for up to 1 year and 10 months. The participants may also continue their regular treatment for pulmonary fibrosis during the study. Participants visit their doctors regularly. During these visits, the doctors collect information on any health problems of the participants. Participants also regularly do lung function tests.

The goal of this observational study is to learn about risk of progressive pulmonary fibrosis (PPF). The main questions it aims to answer are: * Risk factors of PPF * Prevalence of PPF * Mortality of PPF Patients with interstitial lung disease (ILD) of known or unknown etiology other than IPF who has radiological evidence of pulmonary fibrosis will enroll in this study. * All participants will have baseline investigations at the first visit having provided informed consent. * At the first visit, baseline characteristics will be collected including demographics, medical history, smoking history, complications and medication use. 50 mL of blood will be obtained. High resolution computed tomography (HRCT), full lung function tests and a 6 min walk test will be performed. * Further visits at 6 months and 12 months will include further 50 mL blood sampling. HRCT, full lung function tests and a 6 min walk test will be repeated.

The ON-SITE study represents a prospective, observational study focused on the training/tuning and pivotal validation of deep learning algorithms that detect cell/tissue morphology suspicious for cancer in biopsies of peripheral lung nodules/masses and mediastinal/hilar lymph nodes imaged with the NIO Laser Imaging System in the procedure room without requiring traditional sample processing. The study includes four arms based on biopsy location and biopsy modality/tool: 1. Transbronchial forceps biopsy of peripheral lung nodules/masses (peripheral-TBBx) 2. Transbronchial needle aspiration biopsy of peripheral lung nodules/masses (peripheral TBNA) 3. Transbronchial needle aspiration biopsy of mediastinal/hilar lymph nodes (EBUS-TBNA) 4. Transbronchial cryo biopsy of peripheral lung nodules/masses (peripheral-CBx)

PAP is a rare syndrome of surfactant accumulation and resulting hypoxemic respiratory failure that occurs in a number of diseases classified pathogenically into three groups: primary PAP (caused by disruption of GM-CSF signaling - autoimmune PAP, hereditary PAP), secondary PAP (caused by reduction in alveolar macrophage numbers and/or functions), and surfactant dysfunction-related PAP (caused by mutations in genes required for normal surfactant production). In current clinical practice, PAP is diagnosed based on a lung biopsy; an approach that is not able to identify the PAP-causing disease in anyone. Current therapy involves the physical removal of surfactant by a procedure in which the lungs are repeatedly filled with saline and emptied - whole lung lavage, which is invasive, inefficient, and not widely available, especially for children. Importantly, research advances have elucidated the pathogenesis of diseases causing PAP in most patients and have identified new diagnostic and therapeutic approaches. Simple blood-based research tests can now identify the PAP-causing disease in about 95% of patients. Further, several promising potential disease-specific therapies are currently in development. The long-term goals of the Rare Lung Diseases Consortium include improving the diagnosis and therapy of people with PAP. Part A: A major goal of this protocol is to establish a National PAP Registry. Our central hypothesis is that a nationwide campaign to enroll and communicate with a large cohort of PAP patients will have important benefits including 1) accelerating the translation of research diagnostics into clinical practice, 2) increasing knowledge among patient and healthcare communities about PAP, and 3) engagement of PAP patients and doctors in planning and conducting PAP research. The specific objectives of this study are to: 1) determine the ability of the DBSC GMAb Test to correctly identify autoimmune PAP among people with PAP of any type, 2) estimate the prevalence of autoimmune PAP, 3) increase communication and knowledge about PAP-causing diseases, PAP research advances, and future research studies among PAP patients, healthcare providers, the medical community, the PAP Foundation, the Translational Pulmonary Science Center (TPSC) and the general public, 4) evaluate the ability of DBSC-based test to correctly identify genetic factors that increase the risk of developing PAP; and 5) to evaluate the ability of the DBSC GMAb Test to correctly identify autoimmune PAP among people with PAP of any type, or another lung diseases, and healthy controls. The target population is any person diagnosed with PAP. The study design will involve recruitment, screening, and enrollment of Participants via short telephone-based study visits, completion of questionnaires, and collection of capillary blood from the fingertip by Participants in their home using a DBSC, which are then sent by US mail to the TPSC for evaluation. The experimental approach will compare GMAb levels from DBSCs from Participants diagnosed with PAP and determine the fraction of autoimmune PAP patients among individuals with PAP. DBSC-based genetic testing will be compared to current blood-based methods for identification of known genetic risk factors for developing PAP. Lastly, DBSC GMAb values will be compared to GMAb values from healthy and lung disease controls to determine the ability of the DBSC GMAb test to identify patients with autoimmune PAP. Anticipated results will establish a National PAP registry, validate tests for diagnosis of diseases causing PAP in more than 90% of patients, increase awareness and understanding of PAP among patients and healthcare providers, and provide for a patient voice in PAP research. These results will impact the field by: 1) transforming how PAP is diagnosed, 2) increasing access to diagnostic testing - of special importance to those in remote locations, and 3) engaging PAP patient and healthcare communities in planning and implementing PAP research including a prospective natural history study and clinical trials evaluating several potential, disease-specific therapies. Part B: A major goal of Part B of this protocol is to perform a retrospective, longitudinal, chart-based natural history study of aPAP, to develop a disease severity score that reflects how aPAP patients feel and function, including objective measures of lung function and pathology, and to develop and test novel tools to measure the severity of aPAP lung disease. Our central hypothesis is that defining the natural history of aPAP using an outcome measure that incorporates how patients feel, function, and breathe as a function of the severity of their disease and developing tools to measure clinical outcomes will accelerate pharmacotherapeutic development for aPAP. The specific objectives of Part B of this study are to: 1) perform a retrospective, longitudinal, chart-based natural history study of aPAP, 2) host focus groups to obtain patient input regarding health survey content, 3) establish a disease severity score that reflects how aPAP patients feel and function and that includes objective measures of lung function and pathology, and 4) evaluate the ability of a mobile phone-based exercise test to monitor disease severity in aPAP patients. The target population are patients diagnosed with aPAP. The study design will involve review of retrospective, longitudinal review of medical records from aPAP patients and engagement of the patient community to establish a disease severity score that reflects how aPAP patients feel and function and to test a home-based method to remotely evaluate the exercise capacity of aPAP patients. The experimental approach will be to collect and review retrospective, longitudinal medical records of aPAP patients. Additionally, participants will release routine clinic data to the study team and complete questionnaires that measure symptoms, function, and quality of life at the time of routine clinic visits to facilitate development of an aPAP disease severity score (aPAP-DSS). The aPAP-DSS will be a composite of patient-reported and objective function data measuring patient's breathlessness - using a dyspnea index (Dyspnea-I), oxygen delivery - using a lung function index (LungFxn-I), therapeutic oxygen requirement - using a supplemental oxygen index (sO2-I), and health status and function - using a quality of life index (QoL-I). We will compare the multivariate aPAP-DSS with A-aDO2 - the gold standard for measuring lung dysfunction in aPAP, with radiological lung density - a direct measure of amount of pathological surfactant accumulation that causes the clinical manifestations of aPAP, and the St. George's Respiratory Questionnaire - a health outcomes tool. Lastly, aPAP patients will also be able to participate in the pilot testing of a mobile phone-based app to measure the exercise capacity. Specifically, we will evaluate the ability of the 5-minute standardized exercise protocol (STEP) test (5MST) to outperform the 6-minute walk test (6MWT) as a measure of impaired exercise capacity in aPAP patients and the accuracy and acceptability of the app-based remote 6MWT and 5MST compared to standardized clinic-based exercise testing. Anticipated results will be collection and organization of data on the natural history of aPAP and identification of gaps that can be addressed in a future prospective natural history study. We will also evaluate novel tools to measure aPAP disease severity and exercise capacity via a remote, home-based application. These results will impact the field by 1) improving our understanding of the clinical course of aPAP, 2) providing a simple tool to measure disease severity in terms of how aPAP patients feel and function using information readily available in the standard medical record, and 3) develop and test a novel patient-reported outcome assessment tool to measure how aPAP patient's function.

Cystic fibrosis (CF) is a rare autosomal recessive disease involving multiple organs, especially the lungs and digestive organs. It is most commonly seen in Caucasians. Only a few Chinese CF patients have been described in literature, taking into account the large population of China. The main objectives of this study are to accurately evaluate the prevalence of CF, the status of disease, the diagnosis and treatment, the quality of care, and the health related outcomes in China.

Pulmonary lymphangioleiomyomatosis (LAM), a disease characterized by diffuse cystic changes in the lung, is a rare disorder that affects almost exclusively women. The main objectives of this study are to accurately evaluate the prevalence of LAM, the status of disease, the diagnosis and treatment, the quality of care, and the health related outcomes in China. This is a register study lasting 4 years, aims to raise 800 subjects. Primary endpoint is the annual change of forced expiratory volume in the first second (FEV1) and forced vital capacity (FVC) in pulmonary function tests.