LINKS: Pulmonary Arterial Hypertension  Idiopathic Pulmonary Fibrosis  Sarcoidosis

Pulmonary Arterial Hypertension – A Rare Disease with a High Mortality Rate

Over 250,000 people have been diagnosed with PAH in the US1 and this disease is almost twice as common in women than men.2 PAH is a rapidly progressive disease with an approximate 50% five-year mortality rate.3 The disease is characterized by vascular remodeling in the pulmonary arterial bed. This pathology leads to decreased vessel elasticity, increased arterial blood and resistance in the lungs, and an increased workload for the heart. Individuals with PAH typically succumb to right ventricular heart failure.

Pulmonary Arteriole

pulmonary arteriole

PAH is currently treated with vasodilators, which offer some benefit but fail to address the underlying vessel remodeling believed to be responsible for the disease’s high morbidity and mortality rates. Reducing peripheral serotonin production is a novel approach for the treatment of PAH and has the potential to halt or reverse pulmonary remodeling. Rodatristat is being developed as an adjunctive treatment for PAH as its mechanism of action is thought to be complementary to the current standard of care.

Pulmonary Vasculature Remodels as PAH Progresses10

Pulmonary Vasculature Remodels as PAH Progresses

More detailed information on pulmonary arterial hypertension can be found on the Pulmonary Hypertension Association website.

Idiopathic Pulmonary Fibrosis (IPF)

Idiopathic pulmonary fibrosis is an interstitial lung disease that is diagnosed in approximately 22,000 people annually in the U.S..4 Its incidence is higher in men than women. Median survival for patients with IPF can be less than 3.5 years from diagnosis.5

IPF is triggered by an unknown insult in which functional lung tissue is replaced with fibrous scar tissue. A normal response to injury involves the upregulation of factors that recruit immune cells and promote the production of epithelial and connective tissue. This response subsides on its own. In patients with IPF, this repair process continues unabated, leading to excessive production of fibrotic and extracellular matrix (ECM) proteins. Over time, this leads to a thickening of alveolar walls, a decline in lung function and in severe cases, respiratory failure.

It is believed that genetic mutations, environmental pollutants, certain medications and autoimmune diseases may play a role in IPF, but the root cause of the disease remains unknown.

IPF is currently treated with antifibrotic agents but their effectiveness is limited, and mortality remains high.

Ipf_NIH
Figure A shows the location of the lungs and airways in the body. The inset image shows a detailed view of the lung’s airways and air sacs in cross-section. 
Figure B shows fibrosis (scarring) in the lungs. The inset image shows a detailed view of the fibrosis and how it damages the airways and air sacs.11

More detailed information on IPF can be found in the Pulmonary Fibrosis Foundation website.

Sarcoidosis

Sarcoidosis is a multi-organ disorder caused by an exaggerated immune response to an unknown antigen leading to formation of granulomas (nodules of inflamed tissue) along lymphatic tracts, most commonly in the lung, heart, skin, eyes and joints. The granulomas that develop become encased in fibroblasts, which infiltrate the involved organs, potentially leading to fibrotic organ damage.6

While most sarcoidosis patients experience an acute form of the disease, approximately 20% of sarcoidosis patients develop a chronic form of the disease and approximately 5% progress to advanced pulmonary disease, which accounts for most of the morbidity and mortality associated with sarcoidosis.7

Pulmonary fibrosis due to sarcoidosis can compress pulmonary arteries, resulting in chronic hypoxia and increased vascular strain, similar to that experienced by patients with PAH.8 Pulmonary fibrosis in sarcoidosis patients is an independent predictor of mortality and is closely linked to the development of sarcoidosis.9 Currently, there are no approved treatments or treatment algorithms specifically for sarcoidosis.

More detailed information on sarcoidosis can be on the Foundation for Sarcoidosis Research website.

1. Datamonitor Pulmonary Hypertension Disease Coverage   2. Prins KW and Thenappan T. Cardiol Clin 2016   3. Thenappan T. BMJ 2018   4. Raghu G. European Respiratory Journal 2016   5. Leslie KO. Arch Pathol Lab Med 2012   6. Criado E. Radiographics 2010   7. Spagnolo P et al. Lancet Resp Med 2018   8. Shlobin OA and Nathan SD. Eur Respir J 2012   9. Kirkil G et al. Chest 2017 10. https://www.phaonlineuniv.org/Journal/Article.cfm?ItemNumber=4253 11. National Heart, Lung and Blood Institute