Q&A: Dr. Anna Podolanczuk, MD

Dr. Podolanczuk is the Co-Director of the Weill Cornell Interstitial Lung Disease Program

The following questions were submitted from Three Lakes 12-20 subscribers and followers as a part of our Ask the Expert series, where we provide a forum to industry professionals to widen access and education from those who are actively working towards the treatment and future of pulmonary fibrosis.

The existing drugs are antifibrotics, and slow disease but do not stop progression. In terms of stopping the disease upstream of the fibrotic cascades, which of the current trials do you recommend, NR plus Zinc at Cedars Sinai? Rein Therapeutics? Vicore Pharma? Thymidine out of Boston Children’s hospital? Would you recommend any of those?

There has been tremendous progress in understanding the mechanisms driving lung fibrosis, and I am hopeful that we will have more and better treatments in the near future. Each of the trials mentioned, along with many others in the pipeline, targets distinct pathways involved in the initiation and progression of fibrosis. However, these are all relatively early-stage studies with too many unknowns about relative efficacy and safety to recommend one trial over another. Many factors may make one trial a better fit for an individual patient, including the drug's mechanism of action, mode of delivery, safety profile, and the trial's eligibility criteria and design. I would encourage patients to discuss clinical trial options with their physicians, who can help weigh these considerations in the context of their individual disease. Regardless of the specific trial, participation in clinical research is one of the most impactful things a patient can do, not only for their own care, but for advancing the field toward better treatments.

I have had hypersensitive pneumonitis since 2020. I am doing everything possible to keep my condition stable. I was told that stem cell replacement might be potentially something that could help with lung scarring. Is there any evidence for this? Is stem cell replacement something that could be considered a positive treatment for hypersensitive pneumonitis?

Stem cell therapy as a way to repair damaged lung tissue is a very compelling concept. However, while there are promising data from animal models, stem cell therapies have not yet been shown to improve lung function or outcomes in patients with pulmonary fibrosis, including hypersensitivity pneumonitis. I fully support the Pulmonary Fibrosis Foundation's position on this topic, which is that stem cell therapies remain unproven and experimental, and patients should only pursue them as part of an approved clinical trial. Patients should be careful because there are direct-to-consumer clinics marketing stem cells without rigorous scientific support, with inadequate oversight, at high cost, and with serious safety risks.

Will a TGF beta inhibitor if deployed specific to lungs have a chance of working to target IPF without side affects?

While TGF beta is a central mediator of lung fibrosis, it also has many essential maintenance functions in the lungs (and the rest of the body) so directly inhibiting it risks serious side effects. More selective inhibition is needed and this is an active area of research and clinical trials. Direct delivery of antifibrotic medications to the lungs is a very promising approach. By concentrating the drug in affected areas and minimizing systemic exposure, inhaled treatments have the potential to improve efficacy and reduce side effects. There are several ongoing trials evaluating inhaled formulations of existing antifibrotic medications with exactly this goal.

Many patients are diagnosed with pulmonary fibrosis only after significant lung damage has already occurred. What are the most promising ways to detect the disease earlier?

Currently, the diagnosis of pulmonary fibrosis still requires a chest CT. Recent guidelines have focused on identifying which patients should be screened with CT to detect early disease. Screening is most appropriate for individuals with a family history of pulmonary fibrosis or certain autoimmune diseases, although those with high-risk occupational or environmental exposures may also benefit. There is increasing use of AI-enabled algorithms for CT analysis that can detect and characterize subtle changes in the lung that may be difficult to appreciate with the naked eye.

In an ideal world, we would have a blood test that could identify patients with early pulmonary fibrosis, who could then be triaged to chest CT for confirmation. There is a lot of research trying to develop such a biomarker, but nothing is yet available for clinical use. Beyond CT, several other imaging and diagnostic modalities are in development for early disease detection, including lung ultrasound, hyperpolarized xenon MRI, PET imaging, and endobronchial optical coherence tomography. There is also growing interest in non-imaging approaches, such as analysis of exhaled breath (sometimes called eNose technology or breathomics) and AI-enabled digital auscultation (a digital stethoscope).

For patients or family members who may be at higher risk since their family has a history of pulmonary fibrosis, what steps should be taken to monitor or protect their lung health?

Being aware of the role genetics play in pulmonary fibrosis and knowing your family history is the first step in preserving lung health. Many experts suggest screening with a chest CT for individuals over the age of 50 who have a family history of pulmonary fibrosis, especially if there are multiple affected family members. Genetics and environmental factors interact and jointly contribute to risk, so minimizing harmful inhaled exposures is very important. This includes not smoking or vaping, wearing appropriate respiratory protection in occupations with exposures to inhaled particles, being aware of air quality, and staying up to date on vaccinations to reduce the risk of respiratory infections. Regular exercise and maintaining a healthy body weight is also beneficial for overall lung health.

Environmental exposures are increasingly recognized as important contributors to lung disease. What kinds of exposures should patients be most aware of in their homes or workplaces?

There are many exposures that can contribute to fibrotic lung disease. Smoking, including secondhand smoke exposure, has long been known to cause pulmonary fibrosis. More recently, vaping and e-cigarettes have emerged as important sources of lung injury. Air pollution and wildfire smoke are increasingly recognized as potential risk factors for the development, progression and acute exacerbations of ILD. Mold and moisture from water damage, pet birds, feather bedding, and poorly maintained humidifiers can all trigger hypersensitivity pneumonitis. Many occupations can also carry increased risk of ILD, including those involving silica and asbestos, organic dusts and animal proteins, and chemical fumes and aerosols. A thorough assessment of environmental and occupational exposures should be part of every initial ILD evaluation.

If we think about pulmonary fibrosis the way we think about heart disease and treating risk factors early, what prevention strategies might become possible in the future?

There has been so much progress made in reducing deaths from heart disease because of a focus on treating risk factors like high blood pressure, cholesterol and diabetes. We need to think about pulmonary fibrosis in the same way. If we can identify individuals at risk because of a family history, short telomeres, high risk exposures, blood biomarkers, or early CT changes, those individuals can be monitored closely and considered for early intervention. Modifiable factors like exposures should be eliminated. And if we can develop a drug that is well tolerated and affordable enough for long term use, we should consider treating patients before significant fibrosis develops. We are not there yet, but some clinical trials are now beginning to test this approach.

 

What would a successful clinical trial for preventing pulmonary fibrosis look like, and what challenges need to be overcome to make those trials possible?

I believe that the time is right to do such a trial. The key challenges have been identifying individuals at high enough risk to enroll in a therapeutic trial, defining what “success” looks like within a feasible timeframe, and selecting the right drug. With advances in imaging and a better understanding of risk factors, we can now identify individuals with early imaging abnormalities and quantify progression. We just need the right drug, something like a statin for prevention of heart disease.

What kinds of biomarkers or imaging technologies are most promising for identifying people who are at high risk of developing pulmonary fibrosis before symptoms begin?

There are many blood and imaging biomarkers being actively investigated, but most are not yet available in clinical practice. For individuals with a family history of pulmonary fibrosis, genetic testing may play a role, although results are often inconclusive. Telomere length testing is another potential tool to identify those at highest risk. Individuals with short telomeres have an increased likelihood of developing disease and of disease progression. Certain blood biomarkers like higher monocyte counts and low HDL cholesterol have associated with risk in some studies. Automated analysis of CT scans using AI-enable algorithms is also promising. CT scans contain a wealth of quantitative data about the lung interstitium, vasculature and airways. Detecting early changes in these structures could help predict who may develop clinically significant disease in the future.