Idiopathic pulmonary fibrosis (IPF) is the most common idiopathic interstitial pneumonia comprising about 20% of specific interstitial lung diseases in the United States (1). IPF is a chronic, progressive fibrotic interstitial lung disease that is characterized by the progressive accumulation of scar tissue within the lung, loss of alveolar architecture and eventually loss of lung function due to respiratory insufficiency. As the name implies, the cause of the disease is unknown. It is often diagnosed following a careful examination of the patients exposure history, characteristic imaging obtained by HRCT scans (bilateral reticulation and honeycombing that is peripheral and predominant in the lower lobes) or histology (pathologic diagnosis of usual interstitial pneumonia) seen on biopsy specimens when a patient presents with unexplained shortness of breath, chronic cough and/or Velcro-like crackles on physical examination (2). The disease is also more common in adults over 50 years of age and affects men more than women. Sadly, IPF carries a poor prognosis and for patients that are over the age of 65, the median survival is only 3.8 years (1). This mortality rate is far worse than most cancers.
The disease occurs worldwide and the prevalence is 10-60 cases per 100,000, but some studies report even higher incidence (3). Patients with IPF are often misdiagnosed which is problematic because recent studies have shown that immunosuppressive therapies are potentially harmful in these patients (4) and currently available therapies are likely to be more effective if initiated early (5,6).
The pathobiology of IPF is still poorly understood but current hypotheses suggest the disease is initiated by repetitive, subclinical injury of the alveolar epithelium. This repetitive stress to the epithelium may lead to a premature “aging” of the tissue, release of profibrotic factors and dysregulated repair. Chronic innate immune inflammation is also a feature of the disease along with the accumulation of apoptosis-resistant myofibroblasts that promote contraction of the tissue and deposition of extracellular matrix (reviewed in (1). There is a growing interest in how innate immunity and alterations to the lung microbiota might contribute to disease pathogenesis (7-9). Patients can experience variability in disease course with some patients experiencing a steady rate of respiratory decline, while others may experience episodes known as “acute exacerbations” (10) which often result in precipitous decline. Patients with IPF are also at risk for poor outcomes from pneumonias due to respiratory infections with viruses or bacteria.
Treatments for the disease remain sub-optimal. Supplemental oxygen is strongly recommended for patients with IPF and pulmonary rehabilitation can also be beneficial. Two new drugs were approved by the FDA in 2014 (nintedanib and pirfenidone) and both were shown in placebo-controlled trials to slow the rate of decline in forced vital capacity by approximately 50% (11,12) over the course of a year. However, the drugs are not a cure and the costs for each are estimated at over $100,000 annually (1). Lung transplantation is the only known cure for IPF, but this procedure carries significant morbidity and mortality as well and not all patients are candidates for the procedure. Thus, a better understanding of the pathogenesis and heterogeneity of the disease is needed to inform new therapies and there is also an urgent need to identify relevant biomarkers of disease activity to better assess efficacy in clinical trials of new investigational therapies.
Important Facts About Pulmonary Fibrosis |
|
