A broad perspective of idiopathic pulmonary fibrosis causes were recently discussed in a wide-ranging featured lecture published on AJMC entitled “Idiopathic Pulmonary Fibrosis: Biomarkers and New Treatment Options” by expert in idiopathic pulmonary fibrosis Steven K. Huang, MD at the 2014 American College of Chest Physicians conference in Austin, Texas.
Idiopathic pulmonary fibrosis (IPF) is a life-threatning disease characterized by lungs becoming thick, stiff, and scarred over time. Thus, lungs cannot transport oxygen efficiently, leading to a decrease in oxygen levels in the blood. IPF severity varies between different patients, but ultimately in the most serious cases leads to death by respiratory failure. Other causes, however, include heart failure, pulmonary embolism, pneumonia, and lung cancer. Its heterogeneity is important when selecting treatment strategies, such as pirfenidone or nintedanib.
The speaker focused on the heterogeneity of the disease, since it is a major determinant of disease severity, and it was observed that heterogeneity occurred even within the same patient. As Dr Huang noted, “It can be quite variable, and you can have people who are stable for a long time and acutely deteriorate…there are others with a stepwise decline.” Trials with nintedanib and pirfenidone in IPF have ilustrated exactly this point: INPULSIS trials (INPULSIS-1 and INPULSIS-2) studied the effect of nintedanib for IPF and ASCEND trial the effect for pirfenidone. While the INPULSIS trials oberserved an improvement in IPF associated syndroms (forced vital capacity and St. George’s Respiratory Questionnaire), there were differences in the time of occurrence of the first acute exacerbation between INPULSIS-1 and INPULSIS-2, which according to Dr. Huang may be due to heterogeneity in patients with IPF. The same issue was observed in the ASCEND trial, however, here a clear benefit was observed with pirfenidone.
“Cearly there was a benefit…change in FVC was clearly better in the pirfenidone arm versus the placebo arm,” according to Dr Huang. Thus, heterogeneity is a key factor for IPF but unlike many other diseases, including asthma, chronic obstructive pulmonary disease, and lung cancer that are classified into distinctive classes (for asthma, for example, there are exercise-induced asthma, allergic asthma, and eosinophilic asthma ) no such classification occurs in IPF patients.”
Inherited heterogeneity can only account for a small fraction of IPF patients, since familial cases happen in 1.5% to 2.2% of all diagnoses of IPF. Therefore, other genetic and even epigenetic factors are probably associated with IPF and their identification will allow better diagnosis and markers of IPF disease.