Dr. Sanjay Agarwal talked on “Idiopathic Pulmonary Fibrosis (IPF)” at www.bio2devicegrou.org event. Dr. Agarwal is CEO of the Comprehensive Sleep Center and is affiliated with several hospitals in the Bay area, CA. He specializes in Pulmonology, Critical Care Medicine, Internal Medicine, and Sleep Medicine.
Dr. Agarwal reviewed different types of pulmonary diseases, including pathogenesis, diagnostic modalities, and treatment considerations, with an emphasis on pulmonary fibrosis. Pulmonary fibrosis (PF) is one of the family of related diseases called Interstitital Lung Diseases (ILD) that can result in lung scarring. As the lung tissue becomes scarred, it interferes with a person’s ability to breathe. There are four main classifications. In some cases, the cause of pulmonary fibrosis can be found and that can point to a treatment modality. But in majority of cases of pulmonary fibrosis have no known cause and that falls under the classification of idiopathic pulmonary fibrosis (IPF).
IPF is chronic, progressive fibrosing interstitial pneumonia occurring primarily in older adults. Not only the cause is unknown, but it takes an unpredictable clinical course and always leads to progressive lung function decline and eventually to death. There are about 40,000 new cases of IPF each year, in the US.
Generally, repeat and epithelian injury leads to initiation of normal repair mechanisms that release pro-fibrotic mediators into alveolar lumen and that leads to wound clot formation. Epithelial tissue usually responds to injury through a sequence of highly regulated and overlapping events for successful tissue repair and barrier integrity. However, when normal response to tissue injury becomes dysregulated then abnormal responses occur that lead to fibrosis and thickening of the walls. The progression thus goes from injury to activation of repair response to imbalance to endothelium epithelium fibrolasts to eventual fibrosis. TGF Beta is linked to pathologic activities in IPF.
In the last 20-30 years, it had been assumed that inflammation was one of the primary causes that led to IPF. However, recent research, including patient biopsy samples, indicates that not to be the case, said Agarwal. Also, anti-inflammatory therapies like steroids, do not work and in fact have proven to be harmful.
In addition to genetic factors, various environmental factors are assumed to predispose an individual to IPF. Risk factors include smoking and various enviornmental pollutants. Certain professions considered to be high-risk for IPF include hair cutting salons, stone cutting, polishing, exposure to livestock, animal dust and so on. Viral infections and also infections from micro bacteria, can lead to fibrosis. Strong GERD or acid reflux disease is also implicated to be a factor.
Generally, patient comes in complaining of unexplained chronic exertional dyspnea, chronic cough, bibasilar inspiratory crackles and finger clubbing. In IPF patients, physicians also follow some important parameters, including total lung capacity (TLC), diffusing capacity of the lungs for carbon monoxide (DLCO), and forced vital capacity (FVC) change. But none of these measures are consistent predictors of the progression of the disease. There is a very high inter and intra subject variability in rate of disease progression, said Agarwal. Generally however, the prognosis in IPF is very poor with less than 4 years in median survival rates. Compared to other ILD, the IPF prognosis is worse, said Agarwal. Several related factors including clinically significant depression, loss of independence, inability to perform routine daily tasks, also drastically impact the quality of life. And IPF dramatically increases healthcare costs due to higher admission rates, longer hospital stays, and utilization of more outpatient services.
Some of the early IPF therapeutic research focused on triple drug therapy versus placebo. Though initially deemed a medical success, the triple drug regimen actually led to worse outcomes, including greater mortality, than a placebo or inactive substances. Warfarin was tried and was found to not work well for IPF.
Not only causal factors remained unclear but there wasn’t a clear guideline on ideal treatment modality. Patient education, and pulmonary rehabilitation with extensive exercise regimen to tone the muscles seemed to be helpful. Long term oxygen therapy was found to be helpful in some cases. For some patients lung transplantation was an option. Mechanical ventilation was the course of action for patients ending up in ICU but was not frequently used and was not an ideal modality because it was challenging to get these patients off the ventilators.
Two newer therapies include the drugs Pirfenidone and Nintedanib. Both are orally administered and have some antiinflammatory and antioxidant properties and reduce decline in FVC, slow down progression of the disease and improve quality of life. There is some evidence that they lead to statistically significant improvement in lifespan.
Dr. Agarwal highly advocated a comprehensive approach to treating this complex disease. Many hospitals follow multi-disciplinary treatment approach. For instance GERD affects up to 90% of patients with IPF and may be clinically silent factor with chronic microaspiration of gastric secretions and may play a significant role in pathogenesis of IPF. GERD medication is associated with less radiologic fibrosis and longer survival time. Additionally, pulmonary hypertension is highly prevalent in patients with IPF and should be treated upfront. IPF is also associated with changes in sleep. In IPF, the REM sleep is decreased and its efficiency is greatly reduced, leading to reduced amount of deep sleep, with a lot of fragmentation. Enhancing quality of sleep can impact the progression of the disease. And in summary, patient education, training, enhancing functional exercise capacity, and several behavior modification approaches can together have a significant impact on this progressive and irreversible disease with high morbidity and mortality.
The session ended with Q&A.