Interstitial Lung Disease and Pulmonary Fibrosis: A Practical Approach for General Medicine Physicians with Focus on the Medical History

Abstract

Interstitial lung disease (ILD) and pulmonary fibrosis comprise a wide array of inflammatory and fibrotic lung diseases which are often confusing to general medicine and pulmonary physicians alike. In addition to the myriad of clinical and radiologic nomenclature used in ILD, histopathologic descriptors may be particularly confusing, and are often extrapolated to radiologic imaging patterns which may further add to the confusion. We propose that rather than focusing on precise histologic findings, focus should be on identifying an accurate etiology of ILD through a comprehensive and detailed medical history. Histopathologic patterns from lung biopsy should not be dismissed, but are often nonspecific, and overall treatment strategy and prognosis are likely to be determined more by the specific etiology of ILD rather than any particular histologic pattern. In this review, we outline a practical approach to common ILDs, highlight important aspects in obtaining an exposure history, clarify terminology and nomenclature, and discuss six common subgroups of ILD likely to be encountered by general medicine physicians in the inpatient or outpatient setting: Smoking-related, hypersensitivity pneumonitis, connective tissue disease-related, occupation-related, medication-induced, and idiopathic pulmonary fibrosis. Accurate diagnosis of these forms of ILD does require supplementing the medical history with results of the physical examination, autoimmune serologic testing, and chest radiographic imaging, but the importance of a comprehensive environmental, avocational, occupational, and medication-use history cannot be overstated and is likely the single most important factor responsible for achieving the best possible outcomes for patients.

Keywords: autoimmune; hypersensitivity; idiopathic pulmonary fibrosis; occupation; smoking.

Figure 1

Schematic overview of interstitial lung disease (ILD) and pulmonary fibrosis, which includes the six ILDs discussed in this review. Other less common ILDs would occupy remaining space within the ILD and fibrosis ovals and would likewise manifest varying degrees of inflammation and/or fibrosis depending on the particular disorder.

Figure 2

Common histopathologic patterns observed in various forms of ILD. Each pair of horizontal panels represent low (left panel) and high (right panel) magnification images taken from the same tissue section, and the high magnification images are taken from areas identified by an asterisk (*) on low magnification. Panels (A,B) demonstrate usual interstitial pneumonia (UIP). Low magnification demonstrates dense fibrotic change and destruction of normal lung architecture on the right side of panel (A), and relatively normal lung on the left side of panel (A). There are widespread areas of honeycomb change observed in the fibrotic areas, as seen on low and high magnification. Panels (C,D) demonstrate non-specific interstitial pneumonia (NSIP). Low magnification demonstrates uniform thickening of the alveolar walls (i.e., the lung interstitium) diffusely throughout the lung, and high magnification demonstrates a combination of cellular inflammation (lymphocytes and macrophages) as well as collagen deposition in these thickened walls. Panels (E,F) demonstrate organizing pneumonia (OP). Low magnification demonstrates preservation of overall lung architecture, but large focal areas of lung abnormality (asterisk in panel (E)) are observed; high magnification demonstrates these focal abnormalities to be areas of organization (arrows in panel (F)). Panels (G,H) demonstrate granulomatous inflammation. Low magnification demonstrates widespread small focal areas of inflammation centered around small airways, and high magnification demonstrates many of these focal areas of inflammation to contain poorly formed granulomas and multinucleated giant cells (arrow in panel H). Horizontal black bars in the lower left of each of the panels (A–H) represent 2 mm (panels A,C,E,G), 300 µm (panel B), and 200 µm (panels D,F,H).

Figure 3

Common radiologic patterns observed on chest CT imaging in various forms of ILD. Panel (A) demonstrates widespread GGO (asterisk) and accompanying traction bronchiectasis (arrows); overall clinical diagnosis was smoking-related ILD. Panel (B) demonstrates findings of fibrosis in the right upper lobe with traction bronchiectasis and volume loss (arrow), and widespread areas of bilateral mosaic attenuation, defined as interspersed areas of hyperattenuated lung (gray) and hypoattenuated lung (black); overall clinical diagnosis was hypersensitivity pneumonitis. Panel (C) demonstrates peripheral areas of consolidation (arrows); overall clinical diagnosis was ILD secondary to systemic lupus erythematosus (SLE). Panel (D) demonstrates widespread areas of GGO (asterisk), mild sparing of the extreme periphery of the lung (black arrow), and mild traction bronchiectasis (white arrow); overall clinical diagnosis was ILD secondary to anti-synthetase syndrome. Panel E demonstrates small nodules, reticular opacities, and prominent interlobular septa in the right upper lobe (asterisk) and to a lesser extent in the left lower lobe, along with calcified mediastinal adenopathy (arrow); overall clinical diagnosis was ILD secondary to chronic beryllium exposure. Panel F demonstrates multiple ill-defined nodules (arrows) along with surrounding GGO; overall clinical diagnosis was ILD secondary to amiodarone.

Figure 4

Typical radiologic findings observed on chest CT imaging in idiopathic pulmonary fibrosis (IPF), with axial (A,B) coronal (C), and sagittal (D) images. The nature of the opacities (curvilinear reticular opacities and honeycomb change) and their distribution (markedly peripheral and lower lobe-predominant) are very consistent with IPF. Note the absence of subpleural sparing, GGO, consolidation, mosaic attenuation, and nodules which are often observed in other forms of ILD as shown in Figure 3.