Interstitial Lung Disease

Background: Injury or diseases of the heart and lung can sometimes cause scar tissue (fibrosis) to build up in those organs. Current imaging scans can see this scar tissue once it has formed, but researchers want to find a way to detect the fibrosis in its earliest stages, while there might still be time to prevent serious damage. A new tracer (a radioactive substance injected during imaging scans) may be able to help. Objective: To test a new tracer (18F-FAPI-74) during imaging scans in people with heart or lung disease. Eligibility: People aged 18 years and older with lung or heart disease that may cause scarring in those organs. Design: Participants will have 6 clinic visits over 2 years. Participants will be screened: They will have blood tests and tests of their heart and lung function. Those with heart disease will have a magnetic resonance imaging (MRI) scan of the heart. The study tracer will be used with positron emission tomography (PET)/computed tomography (CT) scans. The study tracer will be injected into a vein in the arm. Participants will lie on a padded bed that slides through a donut-shaped machine. Participants will have scans with the study tracer 2 times, 8 to 12 months apart. They will also have standard CT scans and blood tests during these visits. They will also have blood tests at 3 and 6 months between these visits. Participants will have a follow-up visit after 18 to 24 months. The study scans, MRI and standard CT scans, and lung function tests may be repeated....

Study RIN-PF-305 is designed to evaluate the safety and efficacy of inhaled treprostinil in subjects with progressive pulmonary fibrosis (PPF) over a 52-week period.

Background: Injury or diseases of the heart and lung can sometimes cause scar tissue (fibrosis) to build up in those organs. Current imaging scans can see this scar tissue once it has formed, but researchers want to find a way to detect the fibrosis in its earliest stages, while there might still be time to prevent serious damage. A new tracer (a radioactive substance injected during imaging scans) may be able to help. Objective: To test a new tracer (18F-FAPI-74) during imaging scans in people with heart or lung disease. Eligibility: People aged 18 years and older with lung or heart disease that may cause scarring in those organs. Design: Participants will have 6 clinic visits over 2 years. Participants will be screened: They will have blood tests and tests of their heart and lung function. Those with heart disease will have a magnetic resonance imaging (MRI) scan of the heart. The study tracer will be used with positron emission tomography (PET)/computed tomography (CT) scans. The study tracer will be injected into a vein in the arm. Participants will lie on a padded bed that slides through a donut-shaped machine. Participants will have scans with the study tracer 2 times, 8 to 12 months apart. They will also have standard CT scans and blood tests during these visits. They will also have blood tests at 3 and 6 months between these visits. Participants will have a follow-up visit after 18 to 24 months. The study scans, MRI and standard CT scans, and lung function tests may be repeated.

Background: Interstitial lung disease affects the tissues that aid the transfer of oxygen and carbon dioxide between the air and the bloodstream. The disease can cause fibrosis, a thickening and scarring of lung tissue. Fibrosis often continues getting worse, and most people with this disease die in 3 to 5 years. Objective: To test a study drug (hymecromone) in people with interstitial lung disease or lung fibrosis. Eligibility: People aged 18 years and older with interstitial lung disease or lung fibrosis. Design: Participants will have at least 7 clinic visits over 5 months. Participants will have screening and baseline visits. They will have blood tests and tests of their heart function. They will give a sputum sample. Other tests will include: Spirometry: Participants will breathe in and out through a mouthpiece to measure how much air they can hold in their lungs and how hard they can breathe. Diffusion capacity of lungs for carbon monoxide: Participants will breathe in a gas that contains a small amount of carbon monoxide. Then they will breathe through a mouthpiece. This test measures how well oxygen moves from the air into the blood. Resting energy expenditure. Participants will lie still for 30 minutes with a clear dome over their head. This test measures the calories their body burns at rest. 6-minute walk test. Participants will walk at their normal pace for 6 minutes. Their vital signs and blood oxygen levels will be checked. Hymecromone is a tablet taken by mouth. Participants will take 2 tablets every morning and 2 tablets every night for 12 weeks. Tests will be repeated at study visits.

Idiopathic pulmonary fibrosis (IPF) is a type of scarring (fibrotic) lung disease. Reduced exercise capacity is a key symptom experienced by patients. In previous research the investigators identified that an interval-based exercise programme led to significant improvements in exercise capacity (Wallis et al Antioxidants. 2023). An unexpected finding was that in patients with IPF, exercise led to a reduction in blood nitrite concentrations an observation the investigators did not see in non-affected individuals. Research has identified that nitrite concentrations are expected to increase after exercise and the size of this increase is related to an individual's exercise capacity. There is also evidence from healthy individuals and patients with chronic obstructive pulmonary disease (COPD) that nitrate supplementation (a source of nitrite) improves response to exercise training. However, in both these groups an exercise-induced fall in blood nitrite concentrations has not been observed. Hence our finding of an exercise-induced fall in blood nitrite levels in IPF patients suggest that they may be especially sensitive to supplementation with nitrate, commercially available as nitrate-rich beetroot juice (NRBJ). This current study investigates this in a pilot placebo-controlled, double-blind, randomised, cross-over study of NRBJ on exercise capacity in IPF patients. Aims In patients with IPF * Quantify the effect of nitrate supplementation on exercise capacity * Determine the effect of nitrate supplementation on blood markers of nitric oxide production/metabolism. * Determine the effect of nitrate supplementation on forearm blood flow. Sample size: n=8 IPF patients, aged 18-85years and medical research breathlessness scale 1-3 Intervention: 3-days (two-times daily) NRBJ or nitrate-depleted placebo juice (both commercially available) with subsequent constant-load exercise test (Primary outcome). Following at least 1 week wash-out period participants will cross-over and repeat. A cohort (n=8) of age, sex-matched controls without IPF will be enrolled for comparison of forearm blood flow and pre-exercise venous blood samples for biomarkers comparison only. Number of sites: 1

Study LTI-401 is an open-label, multicenter study which will evaluate the safety and tolerability of LIQ861 in subjects who have WHO Group 1 \& 3 PH.

The aim of this multicenter crossover trial is to describe the effect of adding a therapeutic dose of exertional oxygen therapy, in terms of exercise performance, gas exchange, heart rate, symptoms perception and subjective easiness of performance, in a cohort of subjects hospitalized in specialized pulmonary rehabilitation centers with a diagnosis of chronic respiratory failure and/or exertional hypoxemia due to chronic obstructive pulmonary disease or interstitial lung disease. Researchers will compare the walking performance during 6-minute walk test performed with the liters of oxygen administered as prescribed at rest (for patients with chronic respiratory failure) or in room air (for patients with exertional hypoxemia only), to the performance during a 6-minute walk test performed with the double the flow rate prescribed at rest, or with 2 L/min for patients with exertional hypoxemia only. The two tests will be performed in random order, at least 3 hours apart and no later than 24 hours apart from each other. The main outcome will be the difference between the distance walked in the two 6-minute walk test in the two conditions. Furthermore, will be also collected and compared: the oxygen saturation and heart rate every minute, the initial and final dyspnea and fatigue, as assessed by Borg scale, and the easiness of performance through a dedicated questionnaire. The estimated sample size will be 114 patients. This study will provide some basis for a more accurate prescription of exercise-related oxygen therapy, offering insights into the phenotype of patients who may derive the greatest benefit from this intervention. It will also stimulate discussion regarding the optimal timing and dosing of oxygen administration during exertion in patients with respiratory failure.

Study RIN-PF-305 is designed to evaluate the safety and efficacy of inhaled treprostinil in subjects with progressive pulmonary fibrosis (PPF) over a 52-week period.

This is a proof of concept study to determine if Emapalumab appears effective for the treatment of anti-MDA5 antibody positive rapidly progressive interstitial lung disease (MDA5 RP-ILD). Emapalumab is a medication that is currently used for a severe problem with the immune system, called macrophage activation syndrome, and this disease shares some similar features with MDA5 RP-ILD.

Fibrotic forms of interstitial lung disease (ILD) and chronic obstructive pulmonary disease (COPD) are chronic lung disease which often affect how well oxygen can get from the lungs into the blood. Low blood oxygen levels often leads to shortness of breath which can affect patients' activity levels and quality-of-life. Many people with fibrotic ILD and COPD only have low oxygen levels when they are walking or exercising. Oxygen that is only used for walking or exercise is called ambulatory oxygen therapy (AOT). Laboratory studies suggest that AOT improves shortness of breath and exercise ability. However, real-world studies of AOT have not shown similar results. AOT can be given to patients through different types of equipment, most commonly oxygen tanks or portable oxygen concentrators (POCs). While previous studies have suggested that AOT does not significantly improve patients' breathing or activity in the real-world, these studies most often gave all participants the same amount of oxygen with the same device. However, patients with ILD and COPD often have very different oxygen needs during exercise, and POCs and oxygen tanks are very different in how oxygen is administered. This trial will test the feasibility of a study to determine whether real-world activity, symptoms, and quality-of-life are different with the use of different oxygen equipment when oxygen therapy has been adjusted to meet each participants' oxygen needs. A total of 24 participants (12 with fibrotic ILD and 12 with COPD) who only have low oxygen levels with activity will be randomly assigned to 2-week periods using either no oxygen therapy or oxygen delivered by oxygen tanks or POC. This trial will provide preliminary data to support a larger clinical trial to further test how different AOT equipment titrated to meet individual patients' needs may affect real-world outcomes in people with ILD and COPD.

This is a prospective, real world, multicenter, registry of patients with pulmonary hypertension associated with interstitial lung disease (PH-ILD) and interstitial lung disease (ILD).

The primary objective of this study is to evaluate the effect of 24-weeks of once daily treatment with TPIP versus placebo on exercise capacity in adults with PH-ILD.

The primary objective of this study is to evaluate the safety and tolerability of the long-term use of TPIP in participants with PH-ILD from Study INS1009-311 (NCT07179380).

The use of lung ultrasound is instrumental in the evaluation of many chest pathologies and its ability to detect pleuro-pulmonary pathology is widely accepted. However, the use of ultrasound to explore the state of the peripheral lung parenchyma, when the organ is still aerated, is a relatively new application. Horizontal and vertical artifacts are separate and distinct artifacts that can be seen during ultrasound examination of the lungs. While the practical role of lung ultrasound artifacts is accepted to detect and monitor many conditions, further research is needed for the physical interpretation of ultrasound artifacts. These artifacts are diagnostic signs, but we don't fully understand their origin. The artifactual information deriving from the surface acoustic interaction, beyond the pleural line, in the ultrasound images of the normally aerated and non-deflated lung, represents the final result of complex interactions of acoustic waves with a specific three-dimensional structure of the biological tissue. Thus, the umbrella term "vertical artifacts" oversimplifies many physical phenomena associated with a pathological pleural plane. There is growing evidence that vertical artifacts are caused by physiological and pathological changes in the superficial lung parenchyma. Therefore, the need emerges to explore the physical phenomena underlying the artifactual ultrasound information deriving from the surface acoustic interaction of ultrasound with the pleuro-pulmonary structures.

Exercise training as part of a structured pulmonary rehabilitation program is a key factor in improving quality of life and symptoms in people with interstitial lung disease (ILD). Optimal methods of exercise training are yet to be explored in ILD. Drinking beetroot juice, which is rich in nitrate, has been shown to improve exercise performance in a variety of groups, but its effects in ILD have not been tested. The purpose of this study is to determine if drinking nitrate-rich beetroot juice can improve exercise performance compared to drinking nitrate-free beetroot juice in people with ILD.

Dyspnea (i.e. breathlessness) and exercise intolerance are common symptoms for patients with interstitial lung disease (ILD), yet it is not known why. It has been suggested that muscle dysfunction may contribute to dyspnea and exercise intolerance in ILD. Our study aims to: i) examine differences in the structure and function of the leg muscles in ILD patients, ii) determine if leg muscle fatigue contributes to dyspnea and exercise limitation in patients with ILD, and iii) determine the effects of breathing extra oxygen on leg muscle fatigue, as well as ability to exercise in ILD patients.

Connective tissue disease (CTD), an autoimmune and inflammatory disease, usually accompanied by lung interstitial/alveolar inflammation and fibrosis (so called interstitial lung disease, ILD). The prevalence and mortality rate of CTD-ILD increase in recent several years. Although the use of corticosteroids and strong immunosuppressants can improve ILD in some patients with CTD, progressive lung fibrosis which needs lung transplantation and results in respiratory failure, even with mortality is observed. Currently, stem cell therapy is a breakthrough in the treatment of CTD-ILD, and the effective therapy with stem cells for patients with ILD have been reported.

Main objective: To explore the safety and tolerability of human umbilical cord mesenchymal stem cell injection in the treatment of interstitial lung disease (ILD); Secondary objective: To explore the preliminary effectiveness of human umbilical cord mesenchymal stem cell therapy for interstitial lung disease (ILD) and recommend appropriate cell therapy doses for subsequent clinical studies; Exploring the immunogenicity of human umbilical cord mesenchymal stem cell injection in the treatment of interstitial lung disease (ILD).

The goal of this observational study is to identify early biomarkers that can predict the development of progressive pulmonary fibrosis (PPF) in participants with interstitial lung diseases (ILDs). The participant population includes adults diagnosed with idiopathic pulmonary fibrosis (IPF), familial pulmonary fibrosis (FPF), other fibrotic ILDs, and interstitial lung abnormalities (ILA). The main questions it aims to answer are: * What biomarkers and risk factors are linked to fibrosis progression or can predict rapid worsening and sudden flare-ups in IPF and FPF patients? * What biomarkers and risk factors can predict the development of a PPF phenotype in different types of ILD? * What biomarkers and risk factors can help identify ILA patients who may develop significant ILD? * What biomarkers and risk factors can predict how well ILD patients will respond to treatment? Researchers will compare the outcomes between participants diagnosed with IPF/FPF, other fibrotic ILDs, and ILA to see if early detection biomarkers differ among these groups. Participants will: * Undergo blood sampling. * Perform lung function tests. * Have CT scans. * Perform breath analysis * Participate in exposome and microbiome analyses. * Complete questionnaires. * A subgroup of participants will be offered bronchoscopy.

The purpose of this study is to investigate how immunosuppression treatment affects measurements of active collagen deposition using \[68Ga\]CBP8 positron emission tomography (PET) and tissue injury using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in individuals with non-idiopathic pulmonary fibrosis interstitial lung disease (non-IPF ILD).

The purpose of this study is to develop and evaluate the usefulness of hyperpolarized (HP) 129Xe gas MRI for regional assessment of pulmonary function.

Rheumatoid arthritis is an autoimmune disease that can affect various organs, including the lungs, and lead to rheumatoid arthritis-interstitial lung disease (RA-ILD). RA-ILD is responsible for increased mortality in rheumatoid arthristis (RA) patients. The prevalence of RA-ILD varies according to the screening tool used. The current gold standard is chest CT, but this is an expensive, time-consuming and irradiating examination, and recommendations on when and how often it should be performed are not clearly established. Lung ultrasound (LUS) is an emerging tool for the detection of lung parenchymal damage, particularly in systemic scleroderma and idiopathic pulmonary fibrosis (IPF). LUS is a non-irradiating, non-expensive examination that can be performed rapidly. The aim of our study is to evaluate LUS as a screening tool for RA-ILD, in patients with risk factors for developing RA-ILD.

The overall goal of this study is to define the phenotype of Interstitial Lung Disease (ILD), and identify factors that predict radiologic progression in those with subclinical RA-ILD, in patients with rheumatoid arthritis (RA). The investigators hypothesize that there are common core elements (e.g. clinical features, genetic variants, and/or biologic markers) between other forms of ILD (e.g. idiopathic pulmonary fibrosis, IPF) and subclinical RA-ILD that places individuals at risk for the development of lung disease.

This study evaluates the effects of a structured home exercise program in participants with pulmonary hypertension associated with interstitial lung disease. Participants will complete a defined exercise regimen over a 16-week period, and functional capacity and patient reported outcomes will be assessed at baseline and after the intervention. The study aims to determine whether a home-based exercise approach is feasible and associated with improvements in functional performance.

To develop a repository of blood samples from patients with ILD to support future studies into the development of such biomarkers. Patients with pneumonia and healthy patients will also be recruited as a control group.