Breathing Together: What We Learned About PAP and Pulmonary Fibrosis
Two communities, one conversation
On June 24, 2026, PAP Alliance partnered with the Wescoe Foundation for Pulmonary Fibrosis to host Breathing Together: Understanding PAP, Pulmonary Fibrosis & Where They Meet. Many people in our community know pulmonary alveolar proteinosis (PAP) well, and many in the pulmonary fibrosis (PF) community know fibrosis well. Far fewer know how the two conditions can overlap.
Kelsea Arford, founder and director of PAP Alliance, co-hosted with Jen Wescoe, Executive Director of the Wescoe Foundation for Pulmonary Fibrosis. Jen's work is personal: her father lived with idiopathic pulmonary fibrosis. Our speaker was Dr. McCarthy, a respiratory physician in Dublin, Ireland, who cares for patients with rare lung diseases, including both PAP and interstitial lung disease (ILD).
Here are the highlights for anyone who missed it, or who wants a refresher.
This recap is for education only and is not medical advice. Please talk with your care team about your own diagnosis and treatment.
What PAP is
PAP is a rare syndrome in which surfactant, the substance that helps the lungs expand and contract, builds up in the air sacs (alveoli). Normally, immune cells called macrophages clear and recycle that surfactant. In PAP, the macrophages become overloaded and stop working properly, and the air sacs fill with a thick mix of protein and lipid. The result is shortness of breath and reduced oxygen exchange.
Dr. McCarthy walked through three forms:
Primary PAP accounts for about 95% of cases. Most of these are autoimmune: the body makes antibodies against GM-CSF, a signal macrophages need to mature and handle surfactant. A rarer hereditary form involves a missing GM-CSF receptor.
Secondary PAP occurs when something else disrupts macrophage number or function, such as certain blood disorders or inhaled exposures like silica or indium.
Congenital PAP is very rare and usually identified in early childhood.
A study using a U.S. claims dataset of about 15 million patients found roughly 7 cases of PAP per million people. It affects men and women equally, across all ages, ethnicities and regions. Dr. McCarthy believes that figure is a minimum, because PAP is likely underdiagnosed. Its symptoms, including breathlessness, fatigue, lingering cough and chest tightness, overlap with many more common lung conditions.
Asked about risk factors, he explained that age does not appear to be a cause. Diagnoses happen in people's 20s and in their 70s. Dust and fume exposures are more common among people with PAP, and Jen raised military exposures as something veterans should keep in mind. Even with an exposure history, Dr. McCarthy said the first step is still the antibody blood test.
A blood test that points to the cause
One of the most hopeful points of the webinar: autoimmune PAP can be identified with a blood test. Dr. McCarthy noted how unusual that is. For IPF, most other forms of pulmonary fibrosis and sarcoidosis, there is no blood test that reveals the exact cause of the lung disease.
The test measures antibodies against GM-CSF. It is highly sensitive and specific, but the result has to be above a certain threshold, so it is run at specialized labs. In the U.S., samples can be sent to centers in Cincinnati or Denver, and there are centers in Europe as well. The international PAP guidelines, published about a year and a half before the webinar, list which labs to use.
Dr. McCarthy and Kelsea both stressed that a lung biopsy should be a last resort, not a first step. PAP is patchy, so a biopsy can land on healthy tissue right beside affected tissue. In a study of about 100 patients in the PAP Foundation registry, around 80% had undergone a biopsy, and just under a third of the autoimmune PAP patients who had one received results that did not even show PAP. Kelsea shared that she chose the blood test route herself after learning about it through the PAP Foundation.
Where PAP and pulmonary fibrosis meet
New data suggest that PAP can progress to fibrosis over time, and more often than earlier reports suggested. Past estimates put it at 5% to 10% of patients. Dr. McCarthy shared early results from a study of just over 70 people with confirmed autoimmune PAP, treated at expert centers in Ireland, France, Germany and two U.S. sites. At the start, 27% already showed signs of fibrosis on CT, including features like honeycombing and traction bronchiectasis that are usually associated with fibrotic ILD rather than PAP.
Fifty of those patients had follow-up scans over an average of about three years:
Changes seen on follow-up CT scans:
Any fibrosis: 26% at baseline → 40% at follow-up
Traction bronchiectasis: 24% at baseline → 38% at follow-up
Honeycombing: 14% at baseline → 22% at follow-up
The fibrosis also covered more of the lung over time. The change was seen regardless of which treatment patients had received. About 89% of new or worsening fibrosis appeared in the same areas where surfactant had built up, and fibrosis was linked to a higher likelihood of death or needing a transplant.
This matters in both directions. Some people with PAP may need monitoring for fibrosis. And because PAP scans do not always look "classic," some people told they have an unclassified or progressive fibrosing ILD may actually have PAP. Dr. McCarthy said hypersensitivity pneumonitis is the diagnosis he suspects is most often confused with PAP. The research is ongoing, with more centers and patients being added.
Treatments today and on the horizon
For pulmonary fibrosis, Dr. McCarthy described a growing set of options, pointing to positive results from the FIBRONEER trials of nerandomilast and the TETON trials of inhaled treprostinil. No studies have yet tested antifibrotics specifically in PAP-related fibrosis. He has used them in a small number of his own PAP patients whose disease was behaving like progressive fibrosis.
For PAP, whole lung lavage remains a core treatment. How often people need it varies widely. Historical data show a median of about 15 months between lavages, but some people need only one in their lifetime while others need one every few months. Dr. McCarthy recommended that lavage be guided by an experienced center, even if the procedure is done locally.
Inhaled GM-CSF has shown strong results. The Phase III IMPALA-2 trial of inhaled molgramostim met its primary endpoint, improving lung function. At the time of the webinar, Dr. McCarthy said both molgramostim and sargramostim were pursuing approval from the FDA and the European Medicines Agency, and that sargramostim was approved for PAP only in Japan. In the U.S., sargramostim is often prescribed off-label and covered by insurers case by case.
There are important open questions. Patients with fibrosis were excluded from IMPALA-2, and some lab research suggests GM-CSF could encourage fibrosis in certain settings. So it is not yet known whether GM-CSF is right for people whose PAP is mainly fibrotic. Dr. McCarthy also mentioned newer approaches in early development, including therapies that target the antibodies directly and therapies aimed at how macrophages handle lipids.
For people where GM-CSF is hard to access, he noted that drug makers sometimes provide early or compassionate access, and that the guidelines briefly discuss some low-cost, widely used medicines with limited supporting data. Those are decisions to make with a PAP specialist.
Talking with your provider
Jen asked the question many patients and care partners carry: how do you raise PAP or PF with your doctor? Dr. McCarthy's advice was practical. PAP is still rare, but if your diagnosis is not a clear-cut case of IPF, it is reasonable to ask whether PAP was considered.
That applies especially if your diagnosis has been described as:
unclassifiable or indeterminate ILD
progressive pulmonary fibrosis that is not IPF
hypersensitivity pneumonitis that comes and goes
a mix of fibrosis and ground-glass changes on CT
In those cases, you can ask: "Could I have the GM-CSF antibody test?" It is a simple blood draw sent to a specialized lab. If it is negative, PAP is very unlikely. If it is positive, it may open the door to treatments that can help.
You don't have to do this alone
When Kelsea was diagnosed, she felt alone. "Seven in a million's pretty small," she said. Meeting other PAP patients changed that, and it is why she started PAP Alliance: so that no one is left behind.
PAP Alliance offers:
educational resources and guidance on getting properly diagnosed
a list of doctors around the world who treat PAP
patient stories on our blog
a support group every other month, open to patients and caregivers
The Wescoe Foundation for Pulmonary Fibrosis offers support groups for people from diagnosis through supplemental oxygen and lung transplant, including groups for veterans and for women living with ILD. They also host the Pulmonary Fibrosis Podcast and a new podcast on lung transplant.
We are also hoping to connect with PAP patients in India, where one attendee is looking for peer support. If you know someone, please reach out.
Thank you to Dr. McCarthy for sharing his time and expertise, to Jen Wescoe and the Wescoe Foundation for partnering with us, and to everyone who joined and asked such thoughtful questions.
Learn more: papalliance.org · wescoe.org
