Could your patient's symptoms be masking aPAP?
Autoimmune pulmonary alveolar proteinosis (aPAP) is a rare lung disease that presents with nonspecific pulmonary symptoms, allowing it to hide behind a diagnosis of more common pulmonary illnesses.1,2
Savara Inc. has launched the aPAP ClearPath™ Testing Program with the goal of improving the understanding of the signs and symptoms of rare respiratory diseases, including pulmonary alveolar proteinosis (PAP), and educating physicians about the clinical benefits of early testing as a diagnostic tool to confirm or rule out autoimmune PAP (aPAP).
Is this lung disease hiding behind common symptoms?
Pulmonary alveolar proteinosis (PAP) is a syndrome defined by progressive accumulation of surfactant components in pulmonary alveoli, which can result in hypoxemia and respiratory failure and an increased risk of secondary infections and/or pulmonary fibrosis.3
Rare but likely underdiagnosed
In the United States, the prevalence of PAP diagnoses is about 7 in 1 million people. However, because of limited awareness and difficulty in reaching an accurate diagnosis, the true prevalence of PAP is not known.1,4,5
Although symptoms can appear in childhood, most patients are diagnosed in their 30s to 50s. PAP affects both males and females, with no geographic or racial predominance.3,6,7
Classification of PAP8
There are multiple types of PAP:
- Primary PAP: Caused by disruption of granulocyte-macrophage colony-stimulating factor (GM-CSF) signaling. This can be categorized as either:
- Autoimmune PAP
- Hereditary PAP
- Secondary PAP: Occurs due to underlying disease or condition that reduces the numbers of alveolar macrophages
- Congenital PAP: Occurs due to genetic mutations
aPAP is the most common form of PAP, accounting for about 90% of PAP cases—but it can be difficult to identify.3
Pathophysiology of aPAP
Alveolar macrophages are responsible for clearing surfactant from the alveolar wall. GM-CSF is required for alveolar macrophage function and surfactant homeostasis.2,10
In aPAP:
- Autoantibodies interfere with the ability of GM-CSF to bind to alveolar macrophages
- The macrophages are prevented from clearing surfactant in the alveoli2,10
- Surfactant accumulates, impacting gas exchange between the alveoli of the lungs and the blood2,10
When the gas exchange is affected because of aPAP, it can lead to these common symptoms1,2,11,12:
Dyspnea
Chronic cough
Fatigue
Unintentional weight loss
Chest pain
On a computerized tomography (CT) scan, aPAP appears as ground-glass opacification with a crazy-paving pattern—a nonspecific sign with a wide etiology, including infection, pulmonary edema, chronic interstitial disease, and acute alveolar injuries.11,12
When a patient presents with common symptoms accompanied by an abnormal CT scan, and you suspect pneumonia or other pulmonary diseases, but the patient is not responding to therapy, it's time to test for aPAP.1,2,11,12
Reprinted from Trapnell BC et al. Pulmonary alveolar proteinosis. Nat Rev Dis Primer. 2019;5:16. doi:10.1038/s41572-019-0066-3 with permission from Springer Nature, Copyright © 2019. Available at https://www.nature.com/articles/s41572-019-0066-3
How does undiagnosed aPAP increase clinical burden?
The current diagnostic journey is lengthy. This increases the clinical burden on patients who have to see multiple healthcare professionals and are faced with uncertainty without a definitive diagnosis.12
~18 months of uncertainty3,10,13
It takes an average of 18 months for someone to be diagnosed accurately with aPAP. Patients with aPAP present with symptoms typical of more common pulmonary illnesses—further complicating the diagnosis and often leading to a misdiagnosis.12,14
Misdiagnoses may continue until the failure of multiple courses of therapy prompts diagnostic reconsideration and referral, thereby delaying accurate diagnosis from months to years.12, 14
Meanwhile, patients deal with12, 14:
- Confusion of a misdiagnosis
- Continued symptoms impacting quality of life
People living with undiagnosed aPAP report that dyspnea and persistent cough disrupt their activities of daily living.12, 14
Chronic cough can12:
- Make it difficult to maintain personal relationships
- Hinder performance at work
- Impact mental health and social well-being
When patients are misdiagnosed, they are at risk of inappropriate treatment and poorer outcomes.2
Invasive, nondefinitive tests
The invasive nature of some diagnostic tests disrupts your patient’s daily activities, thereby negatively impacting their quality of life. Some procedures, such as bronchoscopy with bronchoalveolar lavage and lung biopsy, may require hospitalization.1,12,15
Although these procedures may be helpful in diagnosing PAP, they do not identify the cause of PAP (eg, aPAP).3,10
Confirm or rule out aPAP earlier
Testing for GM-CSF autoantibodies may help you and your patients obtain a definitive diagnosis sooner.1,2
Could a simple blood test unmask aPAP?
When you see:
Common chronic pulmonary
symptoms1,12
An abnormal
CT scan1,12
Other pulmonary infection diagnoses that are refractory to treatment1,12
Then it is time to test for GM-CSF autoantibodies.
Once you suspect aPAP may be causing your patient’s symptoms, request a GM-CSF autoantibody blood test.2,10
European Respiratory Society Guidelines for the Diagnosis and Management of Pulmonary Alveolar Proteinosis. Cormac McCarthy, Francesco Bonella, Marissa O’Callaghan, Clairelyne Dupin, Tiago Alfaro, Markus Fally, Raphael Borie, Ilaria Campo, Vincent Cottin, Aurelie Fabre, Matthias Griese, Alice Hadchouel, Stephane Jouneau, Maria Kokosi, Effrosyni Manali, Helmut Prosch, Bruce C. Trapnell, Marcel Veltkamp, Tisha Wang, Ingrid Toews, Alexander G. Mathioudakis, Elisabeth Bendstrup.
Eur Respir J. 2024;14;64(5):2400725. doi:10.1183/13993003.00725-2024.
How to test
When diagnosing aPAP, consider a simple and accurate GM-CSF autoantibody blood test instead of an invasive diagnostic bronchoalveolar lavage or a lung biopsy.1,2,10
Testing for GM-CSF autoantibodies early will not only help you and your patient avoid invasive diagnostic tests, but can also shorten your patient’s diagnostic journey—which may lead to reduced morbidity and lower healthcare costs.1,2,10
What is the aPAP ClearPath™ Testing Program?
Savara sponsors this no charge, third-party testing program to reduce barriers to GM-CSF autoantibody testing and to provide healthcare professionals and patients with additional knowledge about how testing may be used as a diagnostic resource.
As part of the program, for patients who meet the objective eligibility criteria, healthcare professionals can order a simple, accurate, and noninvasive blood test that can help inform their diagnostic and management decisions for the patient. This blood test is provided at no charge to the patient, the patient’s treating healthcare professional, or the patient’s insurance provider.
This test is designed to provide results as quantitative anti–GM-CSF concentrations. It comes in a compact package with clear, step-by-step instructions.
You can order the test in 1 of 2 forms:
Serum-based test:
blood tube, then spun to isolate serum.
Dried blood spot test:
dropped directly onto a collection card.
Confirm or rule out aPAP at no charge to you, your patient, or your patient's insurance provider with the help of a simple, accurate, and noninvasive GM-CSF autoantibody blood test.1,2
Order a test kitHealthcare professionals and patients who use this program have no obligation to recommend, purchase, order, prescribe, promote, administer, use, or support any Savara product.
The aPAP ClearPath™ Testing Program is not intended to and should not interfere in any way with a healthcare professional’s or patient’s independent judgment and choice in the management options for aPAP. Healthcare professionals and patients should always consider the full range of management options and select those most appropriate for the individual patient.
References: 1. McCarthy C, Avetisyan R, Carey BC, Chalk C, Trapnell BC. Prevalence and healthcare burden of pulmonary alveolar proteinosis. Orphanet J Rare Dis. 2018;13(1):129-133. doi:10.1186/s13023018-0846-y. 2. McCarthy C, Kokosi M, Bonella F. Shaping the future of an ultra-rare disease: unmet needs in the diagnosis and treatment of pulmonary alveolar proteinosis. Curr Opin Pulm Med. 2019;25(5):450-458.doi:10.1097/MCP.0000000000000601. 3. McCarthy C, Carey BC, Trapnell BC. Autoimmune pulmonary alveolar proteinosis. Am J Respir Crit Care Med. 2022;205(9):1016-1035. doi:10.1164/rccm.202112-2742SO. 4. Data on file. REF-00022. Savara Inc. 2021. 5. McCarthy C, Carey B, Trapnell BC. Blood testing for differential diagnosis of pulmonary alveolar proteinosis syndrome. Chest. 2019;155(2):450-452. doi:10.1016/j.chest.2018.11.002. 6. Campo I, Mariani F, Rodi G, et al. Assessment and management of pulmonary alveolar proteinosis in a reference center. Orphanet J Rare Dis. 2013;8:40-46. doi:10.1186/1750-1172-8-40. 7. Data on file. REF-00020. Savara Inc. 2023. 8. McCarthy C, Bonella F, O'Callaghan M, et al. European Respiratory Society guidelines for the diagnosis and management of pulmonary alveolar proteinosis. Eur Respir J. 2024;14;64(5):2400725. doi:10.1183/13993003.00725-2024. 9. Data on file. REF-00021. Savara Inc. 2023. 10. Ataya A, Knight V, Carey BC, Lee E, Tarling EJ, Wang T. The role of GM-CSF autoantibodies in infection and autoimmune pulmonary alveolar proteinosis: a concise review. Front Immunol. 2021;12:752856. doi:10.3389/fimmu.2021.752856. 11. Miyashita K, Hozumi H, Inoue Y, Suzuki T, Suda T. Nationwide survey of adult patients with pulmonary alveolar proteinosis using the National Database of designated intractable diseases of Japan. Respir Investig. 2023;61(3):364-370. doi:10.1016/j.resinv.2023.02.011. 12. Data on file. REF-00012. Savara Inc. 2023. 13. Trapnell BC, Nakata K, Bonella F, et al. Pulmonary alveolar proteinosis. Nat Rev Dis Primers. 2019;5(1):16. doi:10.1038/s41572-019-0066-3. 14. Carey B, Chalk C, Stock J, et al. A dried blood spot test for diagnosis of autoimmune pulmonary alveolar proteinosis. J Immunol Methods. 2022;511:113366. doi:10.1016/j.jim.2022.113366. 15. Inoue Y, Trapnell BC, Tazawa R, et al. Characteristics of a large cohort of patients with autoimmune pulmonary alveolar proteinosis in Japan. Am J Respir Crit Care Med. 2008;177(7):752-762. doi:10.1164/rccm.2007081271OC.