Inhale, exhale: Life with interstitial lung disease
Imagine taking a breath and feeling your lungs fill with ease – a simple action we often take for granted, save for the occasional respiratory infection. But what if every single breath became a struggle, feeling like you were trying to draw air in through a tiny straw? This is the reality for the many individuals living with interstitial lung diseases (ILDs). These conditions, which lead to progressive scarring of lung tissue, make it increasingly difficult to breathe. Though they might not make headlines as frequently as diseases such as cancer or neurodegeneration, ILDs are widespread and significantly impact the lives of the nearly 5 million individuals they are estimated to affect worldwide.
A needle in a haystack: The diagnostic difficulty of ILDs
The category of interstitial lung diseases represents a diverse group of more than 200 lung disorders that primarily affect the lung’s interstitium, the tissue and space between air sacs of the lungs and the blood vessels which absorb oxygen for delivery to the rest of the body and deposit carbon dioxide back into the lungs for exhalation. Unlike other lung diseases that may affect the airways or blood vessels, ILDs are characterized by inflammation, scarring (fibrosis), and stiffening of the lung tissue, which can lead to severe breathing difficulties, chronic cough, impaired oxygen transfer, and constant fatigue. Despite their shared features, ILDs vary widely in their causes, clinical presentations, and outcomes. Some ILDs are idiopathic (meaning their cause is unknown), while others are linked to environmental exposures, medications, or underlying autoimmune diseases. Common types of ILDs include idiopathic pulmonary fibrosis (IPF), hypersensitivity pneumonitis, and sarcoidosis, each with distinct pathological and clinical characteristics. Identifying and understanding these differences is a crucial component of accurate diagnosis and effective treatment.
To untangle the knot, or slice clean through
Clinicians differentiate between various interstitial lung diseases through a comprehensive, multidisciplinary approach that integrates clinical, radiologic, and histopathologic data. The initial diagnostic step involves composing a detailed patient history, including occupational and environmental exposures, smoking habits, and drug use, which can help identify common causes like pneumoconiosis, drug-induced ILD, and hypersensitivity pneumonitis. High-resolution computed tomography (HRCT) of the chest is an often-employed diagnostic tool, capable of identifying definitive patterns indicative of idiopathic pulmonary fibrosis such as usual interstitial pneumonia. Serologic tests can identify connective tissue disease-associated ILDs, while bronchoalveolar lavage and lung biopsies, including transbronchial and video-assisted thoracoscopic biopsies, provide histological confirmation. The final diagnosis is typically made through a multidisciplinary discussion involving pulmonologists, radiologists, and pathologists, ensuring that clinical, radiologic, and histopathologic findings are properly interpreted.
Given the complexity of diagnosis of ILDs, the establishment of specialized centers for pulmonary fibrosis has been instrumental in improving patient outcomes and advancing the understanding of these debilitating diseases. The Pulmonary Fibrosis Foundation (PFF) has been at the forefront of this effort with the PFF Care Center Network (CCN), which it established in 2013. The network ensures that patients with pulmonary fibrosis have access to experienced medical professionals and comprehensive support services. The CCN has expanded to include 88 centers across the country, combining expertise in patient care and research. These centers work collaboratively to provide early diagnosis, cutting-edge treatments, and enhanced awareness of pulmonary fibrosis. Across the US, clinicians at institutions from UCSF Health in San Francisco to Tulane University’s Interstitial Lung Disease Center in New Orleans engage in clinical trials dedicated to advancing treatments for patients suffering from ILDs. Additionally, the network plays a vital role in facilitating research and advocating for the pulmonary fibrosis community, aiming to expedite scientific discoveries, develop effective therapies and ensure patient engagement in the process.
Current treatments for interstitial lung diseases include a variety of pharmacologic and non-pharmacologic strategies. Immunosuppressive agents such as corticosteroids, cyclophosphamide, mycophenolate mofetil, and azathioprine are commonly used, particularly in connective tissue disease-associated ILD. Approved in 2014, the antifibrotic agents nintedanib and pirfenidone have shown efficacy in slowing disease progression, especially in idiopathic pulmonary fibrosis and systemic sclerosis-associated ILD. Biologic therapies, including tocilizumab, have also been approved for specific ILD subtypes. But non-pharmacologic treatments, such as supplemental oxygen and cardiopulmonary rehabilitation, are just as integral to a comprehensive care plan. Finally, lung transplantation remains an option for advanced, progressive ILD unresponsive to other treatments. The choice of therapy is often individualized based on disease severity, progression, and patient-specific factors.
Turning back time: Reversal of fibrosis as a critical target
Unfortunately, the currently available treatments typically only slow the inexorable progression of fibrosis in many ILDs and do not cure existing damage. Normally, myofibroblasts—a cell type that forms in response to tissue injury and aids in tissue repair—undergo controlled cell death and are removed. In progressive fibrosing ILDs like IPF, these cells become resistant to clearance, depositing scar tissue and sending pro-inflammatory signals to nearby cells in an uncontrolled manner. While the recently approved standard-of-care drugs nintedanib and pirfenidone have shown efficacy in stabilizing disease in patients with IPF, these treatments do not reverse existing fibrosis. Thankfully, there have been recent advances including the development of phosphodiesterase 4B inhibitors, which have shown promise in stabilizing pulmonary function in early trials (one instance of which is in ongoing trials by Boehringer Ingelheim), but further research is needed to confirm their efficacy and safety. The Thannickal Lab at the Tulane University School of Medicine is investigating potential gene silencing treatments which could reverse the cellular changes leading to collagen deposition in fibrosis. Additionally, a recent spin-out of the University of Washington School of Medicine’s Institute for Protein Design is developing a miniprotein binder to inhibit αvβ6 integrin, a protein that promotes fibrosis, and is currently carrying out Phase II trials. But even with these potential advances on the horizon, it is clear that further research and innovation are crucial to discovering effective treatments that can halt – and ideally reverse – fibrosis progression.
Advances and challenges in ILD
Significant progress in diagnosis and treatment has improved patient outcomes, but much work remains. Parsing the complex, heterogeneous collection of diseases under the ILD umbrella requires extensive knowledge and ongoing, strategic collaborations among multidisciplinary experts. Advances in medical research and artificial intelligence, along with improved diagnostic criteria, may help reduce the burden of initial disease characterization. However, there are still no remedies for existing lung damage. Specialized centers and collaborative research networks are advancing care and fostering innovation, offering hope for new treatments that can significantly improve the quality of life for those affected by ILD and their families.
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The Tulane Medicine team, who is also the Tulane Digest Team, is partnering at BIO 2024 this week. You can send a request through the BIO partnering system, or email us directly to arrange a time to connect.
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Recent Podcast Episode Drops:
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Curated Research and Research-Related News Summaries, Analyses, and Syntheses. Published on behalf of The Tulane University School of Medicine. Content is generated by reviewing scientific papers and preprints, reputable media articles, and scientific news outlets. We aim to communicate the most current and relevant scientific, clinical, and public health information to the Tulane community – which, in keeping with Tulane’s motto, “Not for Oneself but for One’s Own”, is shared with the entire world.
Alexis L. Ducote, PhD: Editor-in-Chief
Special thanks to James Zanewicz, JD, LLM, RTTP and Elaine Hamm, PhD for copy-editing assistance.