Paul Noble, MD: I’m Paul Noble. I’m the chairman of the department of medicine at Cedars-Sinai Medical Center in Los Angeles, California. I’ve been taking care of patients with fibrotic lung diseases and involved in clinical trials for over 2 decades.

Nintedanib and pirfenidone were FDA approved in 2014 to treat idiopathic pulmonary fibrosis. The focus at that time was on trying to do clinical trials with as homogeneous a population of patients as possible. Pulmonary fibrosis can occur in several settings. In addition to idiopathic pulmonary fibrosis, fibrosis can occur in the setting of autoimmune diseases. The famous ones are rheumatoid arthritis and scleroderma, but there are a number of other autoimmune-related diseases. As a pulmonologist, [I often see] a lot of overlap with some of the diagnostic criteria, particularly the serologies with autoimmune diseases, but these patients can also have fibrosis.

There’s also a very large category of patients who have hypersensitivity pneumonitis. This is an inflammatory and fibrotic reaction to inhaled substances, such as molds or birds. Some of those patients can also have fibrosis. Sometimes it’s hard to distinguish them from idiopathic pulmonary fibrosis. The evolution was looking at whether it’s possible to first think about patients as having fibrotic lung disease with a secondary focus on why they have fibrotic lung disease. The difference with autoimmune-related interstitial lung diseases, fibrotic diseases, and hypersensitivity pneumonitis is that many times—not as often as we’d like—we can get patients better. If we can remove the inciting agent—get rid of the birds or fix the mold damage in the home—and treat patients with judicious immunosuppressive therapy, many times we can get people better and prevent progression of the disease.

With autoimmune-related diseases, we can also have some positive impacts, more than what we typically see with idiopathic pulmonary fibrosis. Prior to the approval of nintedanib and pirfenidone, we treated patients with prednisone and other immunosuppressive agents, and we never saw people get better. In retrospect, when we saw salutary effects, patients often later in the course of their illness manifested the underlying autoimmune disease that wasn’t present at the time of initial diagnosis.

I wasn’t involved in generating these guidelines, but the ATS [American Thoracic Society] was trying to look at this group of patients who have fibrosis but show clear evidence of progression. The main way progression of disease is demonstrated is with pulmonary function testing, [when there’s] a decline in the forced vital capacity. In addition, we typically get follow-up high-resolution CT scans on patients with fibrotic lung disease. Those CT scans sometimes show evidence of worsening fibrosis. Finally, there are symptoms. The main symptom with fibrotic lung disease is exertional breathlessness. This can be a little more difficult to quantitate. When I see my patients, I always start with a simple question: Are you better, worse, or the same? They have that subjective feeling about how their breathing is doing.

The evolution of this progressive pulmonary fibrosis is patients who have had evidence of disease progression without concern for the underlying reason that they might have the fibrosis. Whereas with pulmonary fibrosis–associated interstitial lung disease, it’s like 1 point in time: a patient with rheumatoid arthritis who has a high-resolution chest CT scan that shows fibrotic changes, maybe a fibrotic NSIP [nonspecific interstitial pneumonitis] pattern or the usual interstitial pneumonia pattern. With progressive pulmonary fibrosis, I think about it as a dynamic process: change in symptoms, function, or imaging over time.

Transcript edited for clarity.