Idiopathic pulmonary fibrosis

Abstract

Idiopathic pulmonary fibrosis (IPF) is a non-neoplastic pulmonary disease that is characterized by the formation of scar tissue within the lungs in the absence of any known provocation. IPF is a rare disease which affects approximately 5 million persons worldwide. The prevalence is estimated to be slightly greater in men (20.2/100,000) than in women (13.2/100,000). The mean age at presentation is 66 years. IPF initially manifests with symptoms of exercise-induced breathless and dry coughing. Auscultation of the lungs reveals early inspiratory crackles, predominantly located in the lower posterior lung zones upon physical exam. Clubbing is found in approximately 50% of IPF patients. Cor pulmonale develops in association with end-stage disease. In that case, classic signs of right heart failure may be present. Etiology remains incompletely understood. Some environmental factors may be associated with IPF (cigarette smoking, exposure to silica and livestock). IPF is recognized on high-resolution computed tomography by peripheral, subpleural lower lobe reticular opacities in association with subpleural honeycomb changes. IPF is associated with a pathological lesion known as usual interstitial pneumonia (UIP). The UIP pattern consists of normal lung alternating with patches of dense fibrosis, taking the form of collagen sheets. The diagnosis of IPF requires correlation of the clinical setting with radiographic images and a lung biopsy. In the absence of lung biopsy, the diagnosis of IPF can be made by defined clinical criteria that were published in guidelines endorsed by several professional societies. Differential diagnosis includes other idiopathic interstitial pneumonia, connective tissue diseases (systemic sclerosis, polymyositis, rheumatoid arthritis), forme fruste of autoimmune disorders, chronic hypersensitivity pneumonitis and other environmental (sometimes occupational) exposures. IPF is typically progressive and leads to significant disability. The median survival is 2 to 5 years from the time of diagnosis. Medical therapy is ineffective in the treatment of IPF. New molecular therapeutic targets have been identified and several clinical trials are investigating the efficacy of novel medication. Meanwhile, pulmonary transplantation remains a viable option for patients with IPF. It is expected that, during the next decade, considerable progress will be made toward the understanding and treatment of this devastating illness.

Figure 1

PA chest radiograph of a 67-year old man with progressive dyspnea revealing bilateral reticular infiltrates with lower lobe predominance. * Reprinted from Fishman's Pulmonary Diseases and Disorders, 4^th edition 2007. Meltzer, EB and Noble, PW: Chapter 70, Idiopathic Pulmonary Fibrosis. With permission from McGraw-Hill Companies.

Figure 2

Computed tomography scan illustrates the "classic" features of IPF. Bilateral, peripheral, subpleural reticular infiltrates are evident. The presence of advanced fibrosis is indicated by honeycomb changes (arrowhead) and traction bronchiectasis (arrow). These features permit experienced clinicians to make a confident radiographic diagnosis of IPF. * Reprinted from Fishman's Pulmonary Diseases and Disorders, 4^th edition 2007. Meltzer, EB and Noble, PW: Chapter 70, Idiopathic Pulmonary Fibrosis. With permission from McGraw-Hill Companies.

Figure 3

Computed tomography scan of an 81-year old man with biopsy-proven IPF. A peripheral distribution of reticular opacities is demonstrated. Honeycombing and traction bronchiectasis are notably absent. In the absence of specific findings, a surgical lung biopsy was needed to make a diagnosis. * Reprinted from Fishman's Pulmonary Diseases and Disorders, 4^th edition 2007. Meltzer, EB and Noble, PW: Chapter 70, Idiopathic Pulmonary Fibrosis. With permission from McGraw-Hill Companies.

Figure 4

a) Low-magnification photomicrograph of UIP showing the characteristic heterogeneous involvement of the parenchyma. Zones of interstitial fibrosis are seen alternating with areas of normal lung. b) Higher-magnification demonstrates enlarged cystic airspaces lined with hyperplastic alveolar epithelium (arrowheads). Beneath the mucosal layer is an advancing region of young fibrosis containing loose extracellular matrix (pale pink staining) and fibroblasts (arrows). * Reprinted from Fishman's Pulmonary Diseases and Disorders, 4^th edition 2007. Meltzer, EB and Noble, PW: Chapter 70, Idiopathic Pulmonary Fibrosis. With permission from McGraw-Hill Companies.

Figure 5

Scanning view of UIP demonstrates the characteristic variegated appearance of UIP. Note the honeycomb change (arrowheads) present in the region of dense fibrosis adjacent to the pleural surface. A fibroblast focus (arrow) is seen at the leading edge of advancing fibrosis. * Reprinted from Fishman's Pulmonary Diseases and Disorders, 4^th edition 2007. Meltzer, EB and Noble, PW: Chapter 70, Idiopathic Pulmonary Fibrosis. With permission from McGraw-Hill Companies.