Overview of Diffuse Parenchymal Lung Diseases

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Overview of Diffuse Parenchymal Lung Diseases

A large group of disorders affects the alveolar wall in a fashion that ultimately may lead to diffuse scarring or fibrosis. These disorders traditionally have been referred to as interstitial lung diseases, although the term is somewhat of a misnomer (see Chapter 8). The interstitium formally refers only to the region of the alveolar wall exclusive of and separating the alveolar epithelial and capillary endothelial cells. However, interstitial lung diseases affect all components of the alveolar wall: epithelial cells, endothelial cells, and cellular and noncellular components of the interstitium. In addition, the disease process often extends into the alveolar spaces and therefore is not limited to the alveolar wall. Many authors now prefer the expression diffuse parenchymal lung disease, which is the term generally used in this book. For practical purposes, however, the reader should recognize that the expressions diffuse parenchymal lung disease and interstitial lung disease typically refer to the same group of disorders causing inflammation and fibrosis of alveolar structures.

There are more than 150 diffuse parenchymal lung diseases. Table 9-1 lists the most common of these disorders, grouped by broad categories according to whether the underlying etiology of the disease is currently known or unknown. A third category of “mimicking disorders” is included in recognition of the fact that a number of additional well-defined clinical problems can produce diffuse parenchymal abnormalities on chest radiograph. Even though these mimicking disorders often are not included in traditional lists of diffuse parenchymal lung diseases, the clinician must remember to consider them in the appropriate clinical settings.

Familiarity with all these diseases is difficult even for the pulmonary specialist, so the novice in pulmonary medicine cannot be expected to amass knowledge regarding each individual entity. Rather, the reader is urged to first develop an understanding of the pathologic, pathogenetic, pathophysiologic, and clinical features common to these disorders. This chapter is an overview of general aspects of diffuse parenchymal lung disease and refers to individual diseases only when necessary. Chapter 10 discusses disorders associated with an identifiable etiologic agent; approximately 35% of patients with diffuse parenchymal lung disease are in this category. Chapter 11 discusses diseases for which a specific etiologic agent has not been identified; the majority of patients with diffuse parenchymal lung disease belong in this second category. These chapters cover only a small number of the described types of diffuse parenchymal disease. The goal throughout is to consider those disorders the reader most likely will encounter. Included in the discussion of diseases of unknown etiology in Chapter 11 are several disorders that affect the lung parenchyma but do not characteristically have diffuse findings on chest radiograph. Examples of diseases in which the findings are more typically focal (or multifocal with more than one area of involvement) include Wegener granulomatosis and cryptogenic organizing pneumonia.

The diseases covered in these three chapters are primarily chronic (or sometimes subacute) diseases affecting the alveolar structures. Another group of diseases is associated with acute injury to various components of the alveolus. These latter disorders, which are of clinical importance as causes of acute respiratory failure, are discussed in Chapter 28.

Pathology

Typically, the diffuse parenchymal lung diseases, regardless of cause, have two major pathologic components: an inflammatory process in the alveolar wall and alveolar spaces (sometimes called an alveolitis) and a scarring or fibrotic process (Fig. 9-1). Both features frequently occur simultaneously, although the relative proportions of inflammation and fibrosis vary with the particular cause and duration of disease. The general presumption has been that active inflammation is the primary process and that fibrosis follows as a secondary feature. Idiopathic pulmonary fibrosis (IPF) is a major exception to this generalization. As discussed in Chapter 11, the primary process in IPF appears to be epithelial cell injury and fibrosis (representing an abnormal repair of injury) rather than alveolar inflammation (see Pathogenesis).

Diffuse parenchymal (interstitial) lung diseases are characterized pathologically by variable amounts of alveolitis and fibrosis.

When active alveolitis is present, a variety of inflammatory cells (e.g., macrophages, lymphocytes, neutrophils, eosinophils, and plasma cells) infiltrate the alveolar wall. Individual types of diffuse parenchymal lung disease may be associated with a prominence of a particular one of these cell types, such as eosinophils in chronic eosinophilic pneumonia. In addition to the presence of inflammatory cells, other characteristic pathologic features that help define a specific disorder may be associated with the alveolitis. These individual patterns are useful in, and in many cases critical to, the diagnosis of a specific pathologic entity.

One of the most important pathologic features associated with several diffuse parenchymal lung diseases is the granuloma. A granuloma is a localized collection of cells called epithelioid histiocytes, which are tissue cells of the phagocytic or macrophage series (Fig. 9-2). These cells are generally accompanied by T lymphocytes within the granuloma, often forming a rim around it. When cellular necrosis is present in the center of a granuloma, the entity is termed a caseating granuloma, but diffuse parenchymal lung diseases are associated almost exclusively with noncaseating granulomas (i.e., granulomas in which the central area is not necrotic). In contrast, caseating granulomas are characteristically seen in infectious diseases, especially tuberculosis (see Chapter 24, Pathology). The granuloma typically also has multinucleated giant cells that result from fusion of several phagocytic cells into a single large cell with abundant cytoplasm and many nuclei (see Fig. 9-2). Examples of diffuse parenchymal lung disease in which granulomas are part of the pathologic process include sarcoidosis and hypersensitivity pneumonitis. Granulomas are often considered to reflect some underlying immune process, specifically an immune reaction to an exogenous agent. In the case of hypersensitivity pneumonitis, many agents have been identified. However, in the case of sarcoidosis, no specific exogenous agent has been identified. Granulomas in the lung have many other causes (e.g., tuberculosis, certain fungal infections, and foreign bodies), but they are not covered here because the granulomas are generally not associated with diffuse parenchymal lung disease.

Diffuse parenchymal lung diseases with granulomas include sarcoidosis and hypersensitivity pneumonitis.

Pathology of Idiopathic Interstitial Pneumonias

The idiopathic interstitial pneumonias represent a subgroup of diffuse parenchymal lung disease. Pathologists and clinicians have spent considerable time and effort trying to refine the description and categorization of this subgroup. These disorders display variable amounts of nonspecific inflammation and fibrosis, and they lack granulomas or other specific pathologic features characteristic of other previously well-defined diseases. Classification of the idiopathic interstitial pneumonias and determination of whether the various pathologic appearances represent different diseases or different stages or parts of the spectrum of a single disease have been subject to uncertainty and confusion. Although the field is still evolving, this chapter attempts to present a simplified framework based on current pathologic and clinical concepts about these disorders.

Some pathologic categories subsumed under the idiopathic interstitial pneumonias include:

This chapter discusses seven pathologic entities subsumed under the broad term idiopathic interstitial pneumonias: (1) usual interstitial pneumonia, (2) desquamative interstitial pneumonia, (3) respiratory bronchiolitis interstitial lung disease, (4) nonspecific interstitial pneumonia, (5) acute interstitial pneumonia, (6) cryptogenic organizing pneumonia, and (7) lymphocytic interstitial pneumonia. This section briefly describes the pathologic characteristics defining these seven entities. Chapter 11 focuses on a broader consideration of the more important clinical counterparts of some of them. An important clinical branch point is distinguishing between UIP and the other conditions, because UIP typically carries a worse prognosis.

Usual interstitial pneumonia (UIP) is characterized by patchy areas of parenchymal fibrosis and interstitial inflammation interspersed between areas of relatively preserved lung tissue (Fig. 9-3). Fibrosis is the most prominent component of the pathology, with focal collections of proliferating fibroblasts called fibroblastic foci. The fibrosis often is associated with honeycombing, which represents cystic air spaces that result from retraction of surrounding fibrotic lung tissue. The inflammatory process in the alveolar walls is nonspecific and typically composed of a variety of cell types, including lymphocytes, macrophages, and plasma cells. Hyperplasia of type II pneumocytes (alveolar epithelial cells) presumably reflects an attempt to replenish damaged type I cells. Importantly, the pathology of UIP is characterized by the simultaneous presence of all stages of fibrosis: from early fibrosis with actively proliferating fibroblasts to end-stage acellular collagen scarring. It is thought the fibrotic process in UIP is ongoing and not related to a single event. By far the most important of the clinical disorders associated with the histopathologic pattern of UIP is idiopathic pulmonary fibrosis (IPF), and the terms are often used synonymously. However, the pathologic appearance of UIP can also result from exposure to certain inhaled dusts (especially asbestos), from a number of drug-induced lung diseases, and as a form of parenchymal lung disease associated with some systemic rheumatic (connective tissue) diseases. Remember that the term UIP refers to the histologic pattern seen under the microscope, whereas IPF refers to the clinical disease associated with idiopathic UIP.

Desquamative interstitial pneumonia (DIP) is a more homogeneous-appearing process than UIP and is characterized by large numbers of intraalveolar mononuclear cells. Although originally thought to represent desquamated alveolar epithelial cells (hence the name), these cells are now known to be intraalveolar macrophages. A less prominent component of the histology is inflammation within alveolar walls, and there is little associated fibrosis. In contrast to UIP, the process is temporally uniform, and architectural distortion is minimal. Based on a strong association of this histologic pattern with a history of smoking, as well as an apparent overlap with smoking-induced inflammation of respiratory bronchioles with pigmented macrophages, smoking is believed to be an important underlying etiology for this pathologic pattern.

Respiratory bronchiolitis interstitial lung disease (RBILD) and DIP are related. In general, RBILD is also associated with pigmented macrophages, which are present within the lumen of respiratory bronchioles. However, in contrast to DIP, interstitial inflammation is not present. RBILD is nearly always associated with smoking. The most important clinical intervention is assisting patients to successfully quit smoking. At times, the distinction between RBILD and DIP is difficult and somewhat arbitrary.

Nonspecific interstitial pneumonia (NSIP) is characterized by a prominent histopathologic component of mononuclear cell infiltration within the alveolar walls. Despite the designation “nonspecific,” NSIP is now considered to be a distinct pathologic entity that presents either in an idiopathic form or in association with a number of connective tissue diseases. In contrast to UIP, the pathologic process in NSIP appears relatively uniform, fibrosis is variable but generally less apparent, and the prognosis is better. In the past, this pattern was often not separated from UIP. As a result, its inclusion in many clinical studies of idiopathic pulmonary fibrosis (IPF) served to confound our understanding of the natural history and treatment of IPF.

Acute interstitial pneumonia (AIP) is believed to represent the organizing or fibrotic stage of diffuse alveolar damage, which is the histologic pattern seen in acute respiratory distress syndrome (ARDS) (see Chapter 28). In most cases of ARDS, an inciting cause is apparent, whereas in AIP, no initiating trigger for ARDS can be identified. The histology shows fibroblast proliferation and type II pneumocyte hyperplasia in the setting of what appears to be organizing diffuse alveolar damage.

Cryptogenic organizing pneumonia (COP) is characterized by organizing fibrosis (also referred to as “granulation tissue”) in small airways, associated with a mild degree of chronic interstitial inflammation. Intraluminal airway involvement is a key feature and distinguishes COP from the other idiopathic interstitial pneumonias. This histologic pattern is also called bronchiolitis obliterans with organizing pneumonia (BOOP). The histologic findings in BOOP are either idiopathic or associated with specific known causes (e.g., infections, toxic inhalants, connective tissue diseases). Although the terms have sometimes been used interchangeably, the term COP generally refers to the idiopathic form of BOOP.

Lymphocytic interstitial pneumonia (LIP) is characterized by infiltration in the alveolar walls and interstitium by lymphocytes and plasma cells. LIP is part of a spectrum of pulmonary lymphoproliferative disorders that range from benign scattered areas of lymphocyte infiltration to malignant lymphomas. This histologic pattern is most commonly associated with Sjögren syndrome or human immunodeficiency virus (HIV) infection (especially in children). Some cases are idiopathic, which explains why LIP is included in the classification of idiopathic interstitial pneumonias.

The most recent international consensus conferences have classified COP and LIP as idiopathic interstitial pneumonias. In older literature and depending on the authority, the classification of these two conditions is variable.

End-Stage Diffuse Parenchymal Lung Disease

When diffuse parenchymal lung disease has been present for a fairly long time and is associated with significant fibrosis, any distinctive features of prior interstitial inflammation or alveolitis are often lost. For example, any of the granulomatous lung diseases may no longer demonstrate the characteristic granulomas after sufficient time has elapsed and a substantial degree of fibrosis has developed. Therefore, at a certain point all the diffuse parenchymal lung diseases, if sufficiently severe and chronic, follow a final common pathway toward end-stage diffuse parenchymal lung disease. Along with severe fibrosis, the lung at end stage exhibits a great deal of distortion that can be seen both grossly and microscopically, with areas of contraction and other areas showing formation of cystic spaces. In many cases, the result is “honeycomb lung,” in which the dense scarring and intervening cystic regions make areas of the lung resemble a honeycomb (Fig. 9-4).

Pathogenesis

A great deal of research during the last 2 decades attempted to clarify the pathogenetic sequence of events in various types of diffuse parenchymal lung disease. However, in most cases what initiates these diseases remains unknown, and our understanding of the cellular and biochemical events producing inflammation and fibrosis remains mostly at the descriptive level. This section outlines the general scheme of events thought to be operative in the production of parenchymal inflammation and fibrosis. Chapters 10 and 11 discuss specific diseases and provide additional information believed to be relevant to the pathogenesis of each disease. The general scheme outlined here has features similar to that of other forms of lung injury described elsewhere in this book (e.g., emphysema in Chapter 6 and ARDS in Chapter 28). A fundamental but unanswered question is what determines whether an injurious agent eventually leads to emphysema, acute lung injury (with acute respiratory distress syndrome), or chronic parenchymal inflammation and fibrosis.

Figure 9-5 summarizes the general sequence of events presumed to be common to many of the diffuse parenchymal lung diseases. The events can be divided into three stages: initiation, propagation, and final pathologic consequences. Each of these stages is considered in turn.

Pathogenetic features of diffuse parenchymal lung disease are:

The initiating stimulus for the diffuse parenchymal lung diseases is generally believed to be either a toxin or an antigen. The most obvious presumed toxins include some of the inhaled inorganic dusts (e.g., asbestos) responsible for producing the pneumoconioses. Inhaled antigens have been best identified as the cause of chronic hypersensitivity pneumonitis. In sarcoidosis and perhaps in idiopathic pulmonary fibrosis, exposure to one or more antigens may initiate the disease, but no specific antigens have been identified.

After exposure to an initiating stimulus occurs, a complex series of interrelated events is responsible for propagation of the disease. At the microscopic level, the consequence of these propagating events is inflammation, a hallmark of many but not all of the diffuse parenchymal lung diseases. Toxins may be directly injurious to pulmonary parenchymal (alveolar epithelial) cells, whereas either toxins or antigens may result in activation and recruitment of inflammatory and immune cells. Inflammatory cells can release a variety of mediators (e.g., proteolytic enzymes, toxic oxygen radicals) that can secondarily further injure pulmonary parenchymal cells. In addition, a wide variety of cytokine mediators produced by epithelial, inflammatory, and immune cells have been identified. These cytokines have complex secondary effects on other inflammatory and immune cells, often acting either to amplify or diminish the inflammatory response.

Some cytokines (e.g., transforming growth factor [TGF]-β and platelet-derived growth factor) are capable of recruiting and stimulating replication of fibroblasts, which are critical for the eventual production of new connective tissue. Action of proteases from inflammatory cells may also be responsible for degradation of connective tissue components. The combination of new synthesis and degradation of connective tissue defines the derangement of the connective tissue matrix that is seen histologically as fibrosis, the final pathologic consequence of diffuse parenchymal lung disease. In idiopathic pulmonary fibrosis, the most recent (and now prevailing) concept is that alveolar epithelial injury results in epithelial cell expression of cytokine mediators that promote fibrogenesis, and that inflammation, although present in variable degrees, is not the critical trigger for the development of fibrosis.

Pathophysiology

With minor exceptions and variations, the pathophysiologic features of the chronic diffuse parenchymal lung diseases are similar and therefore are discussed here as a single group. As a result of the inflammation and fibrosis affecting the alveolar walls, the following abnormalities are generally seen (Fig. 9-6): (1) decreased compliance (increased stiffness) of the lung, (2) generalized decrease in lung volumes, (3) loss of alveolar-capillary surface area resulting in impaired measured diffusion, (4) abnormalities in small airway function without generalized airflow obstruction, (5) disturbances in gas exchange, usually consisting of hypoxemia without CO2 retention, and (6) in some cases pulmonary hypertension. Each of these features is briefly considered in turn.

Decreased Compliance

Lung distensibility is significantly altered by processes involving inflammation and fibrosis of the alveolar walls. The lungs become much stiffer, have greatly increased elastic recoil, and therefore require greater distending (transpulmonary) pressures to achieve any given lung volume. The pressure-volume or compliance curve is shifted to the right (see Fig. 8-3), and at any given lung volume, a much higher elastic recoil pressure is found than in normal lungs. Because wider swings in transpulmonary pressure are required to achieve a normal tidal volume during inspiration, the patient’s work of breathing is increased. As a result, patients with diffuse parenchymal lung disease tend to breathe with smaller tidal volumes but increased respiratory frequency. This method allows the patient to expend less energy per breath but maintain adequate alveolar ventilation.

Compliance curves in diffuse parenchymal lung disease are shifted downward and to the right, reflecting increased stiffness of the lung.

Decrease in Lung Volumes

Early in the course of diffuse parenchymal lung disease, lung volumes may be normal. However, in most cases some reduction in lung volumes is seen shortly thereafter, including a reduction in total lung capacity (TLC), vital capacity (VC), functional residual capacity (FRC), and to a lesser extent, residual volume (RV). The decreases in TLC, FRC, and RV are direct consequences of the change in lung compliance. At TLC, the force generated by the inspiratory muscles is balanced by the inward elastic recoil of the lung. Because the recoil pressure is increased, this balance is achieved at a lower lung volume or lower TLC. At FRC, the outward recoil of the chest wall is balanced by the inward elastic recoil of the lung. The balance is achieved at a lower lung volume or lower FRC because of the greater elastic recoil of the lung. As discussed in Chapter 1, RV is primarily determined by the strength of the expiratory muscles, but a small component is determined by the inward elastic recoil of the lungs. Because the elastic recoil is greater in diffuse parenchymal lung disease, the RV is slightly smaller. Generally, TLC is reduced more than RV, so it follows that VC (representing the difference between TLC and RV) is also decreased.

Lung volumes are characteristically decreased in diffuse parenchymal lung disease.

Abnormalities in Small Airways Function

Large airways generally function normally in these patients, and the forced expiratory volume in 1 second to forced vital capacity ratio (FEV1/FVC) is usually normal or even increased. However, frequently the pathologic process occurring in the alveolar walls also affects small airways within the lung. Light microscopy commonly demonstrates inflammation and fibrosis in the peribronchiolar regions, with narrowing of the lumen of the small airways or bronchioles. Tests of small airways function often show the physiologic effects of this narrowing. The clinical importance of small airways dysfunction in the absence of larger airways abnormalities is uncertain, but it is likely that ventilation-perfusion (image) mismatching and hypoxemia are consequences. Evidence of more significant airflow obstruction may be seen in a few disorders causing diffuse parenchymal lung disease. This relatively infrequent problem sometimes results from severe fibrosis and airway distortion.

Small airways function is often disturbed in diffuse parenchymal lung disease. Large airways function is generally preserved.

Disturbances in Gas Exchange

The gas exchange consequences of diffuse parenchymal lung disease most frequently consist of hypoxemia without CO2 retention or, in fact, with hypocapnia. Although a diffusion block once was proposed as the cause of the hypoxemia, evidence supports image mismatch as the major contributor. The pathologic process in the alveolar walls is uneven, and normal matching of ventilation and perfusion is disrupted. In patients with small airways disease, dysfunction at this level probably also contributes to image mismatch and hypoxemia. Characteristically, patients with diffuse parenchymal lung disease become even more hypoxemic with exercise. Again, the primary mechanism of oxygen desaturation associated with exertion is worsening image mismatch, but diffusion limitation also appears to be a contributing factor. The combination of impaired diffusion and decreased transit time of the red blood cell during exercise may prevent complete equilibration of PO2 in pulmonary capillary blood with alveolar PO2. Despite the often profound hypoxemia in patients with severe pulmonary fibrosis, PCO2 is generally normal or low because patients are able to increase minute ventilation sufficiently to compensate for a decrease in tidal volume and for any additional dead space. Elevation of PCO2 does not generally occur until the very late stages of the disease.

Arterial blood gases in diffuse parenchymal lung disease generally show hypoxemia (due to image mismatch) and normal or decreased PCO2. PO2 falls even further with exercise.

Pulmonary Hypertension

Eventually, pulmonary hypertension and cor pulmonale often develop in patients with severe diffuse parenchymal lung disease. Rarely, the cause of pulmonary hypertension is a primary process affecting pulmonary vessels in addition to the alveolar walls. More frequently, the process in the alveolar walls is the cause of pulmonary hypertension. The two main contributing factors are (1) hypoxemia and (2) obliteration of small pulmonary vessels by the fibrotic process within the alveolar walls. During exercise, pulmonary hypertension becomes even more marked; this is due partly to worsening hypoxemia and partly to limited ability of the pulmonary capillary bed to distend and recruit new vessels to handle the exercise-induced increase in cardiac output.

Pulmonary hypertension is common in severe diffuse parenchymal lung disease, resulting from hypoxemia and obliteration of small pulmonary vessels.

Diagnostic Approach

The chest radiograph is the most important means for making the initial macroscopic assessment of diffuse parenchymal lung disease. The characteristic radiographic picture of diffuse parenchymal involvement that primarily involves alveolar walls is described as either reticular (increased linear markings) or reticulonodular (increased linear and small nodular markings; see Fig. 3-6). The pattern has also previously been called an “interstitial pattern” because it was believed to reflect a process limited to the alveolar walls. However, histopathology often indicates that some of these processes extend into alveolar spaces as well. Absence of radiographic abnormalities does not exclude the presence of diffuse parenchymal disease; entirely normal chest radiographic findings have been reported in up to 10% of patients. The pattern on chest radiograph is not particularly useful for gauging the relative amounts of inflammation versus fibrosis, each of which may result in a similar pattern. Reticular or reticulonodular changes are frequently diffuse throughout both lung fields, although individual causes of diffuse parenchymal lung disease may be more likely to result in either an upper or a lower lung field predominance of the abnormal markings. In addition to the reticular or reticulonodular pattern, certain diseases may reveal other associated findings on chest radiograph, such as hilar adenopathy or pleural disease. These additional features noted with some diseases are discussed in Chapters 10 and 11.

A reticular or reticulonodular pattern on chest radiograph is characteristic of many diffuse parenchymal lung diseases, but up to 10% of patients have normal radiographic findings.

With long-standing and severe disease, the lungs may become grossly distorted. In addition, regions of cyst formation between scarred and retracted areas of lung may occur (see Fig. 9-4). A corresponding pattern of honeycombing on chest radiograph may be apparent. Cor pulmonale may be suspected on chest radiograph by the presence of right ventricular enlargement, best seen on the lateral view.

High-resolution computed tomography (HRCT) of the chest is an important step in the evaluation of diffuse parenchymal lung disease (see Fig. 3-9). Because of the quality of images of the pulmonary parenchyma, early changes that are not evident on routine chest radiography can often be seen by HRCT. In addition, the specific pattern of abnormality on an HRCT scan may be suggestive of a particular underlying diagnosis such as IPF and may help distinguish inflammation from fibrosis.

Despite the importance of the macroscopic evaluation, making a diagnostic distinction between the different types of diffuse parenchymal lung disease usually requires investigation at the microscopic or histologic level. A variety of biopsy procedures have been used to obtain tissue specimens from the lung, which are subjected to several routine staining techniques. The most frequently used biopsy procedures for this purpose are thoracoscopic lung biopsy and transbronchial biopsy (via flexible bronchoscopy). Thoracoscopic biopsy often is the more appropriate of the two procedures for obtaining a sufficiently large specimen of tissue for examination. However, when sarcoidosis (or certain other forms of diffuse parenchymal disease) is suspected, transbronchial biopsy is a particularly suitable initial procedure.

Another procedure for sampling the cell population of the alveolitis is bronchoalveolar lavage. A flexible bronchoscope is placed as distally as possible into an airway, and an irrigation or lavage of fluid through the bronchoscope allows collection of cells from the alveolar spaces. These cells are thought to be representative of the cell populations responsible for the alveolitis. Although this technique has been useful as a relatively noninvasive means of obtaining cells for research studies on diffuse parenchymal lung disease, its clinical usefulness for making a diagnosis or for sequential evaluation of disease activity is limited.

Findings on functional assessment of the patient with diffuse parenchymal lung disease were reviewed under Pathophysiology. Briefly, patients have a restrictive pattern on pulmonary function testing, with decreased lung volumes and preserved airflow. Diffusing capacity usually is reduced, which is indicative of loss of surface area for gas exchange. Hypoxemia is usually (although not necessarily) present, and PO2 falls even further with exercise. Hypercapnia is rarely a feature of the disease. When it occurs, hypercapnia usually reflects preterminal disease or an additional unrelated process.

Treatment

Treatment considerations vary among the diseases. In general, patients with interstitial disease either do not respond well to any form of treatment or respond to immunosuppressive agents (e.g., corticosteroids, cyclophosphamide) to a variable extent. The rationale for immunosuppressive therapy is to reduce the alveolitis component of the disease; the fibrosis is generally considered irreversible. Other interesting therapeutic approaches involve targeting specific growth factors, cytokines, or oxidants involved in the inflammatory and fibrotic process within the lungs. However, these approaches are investigational at present. Specific aspects of treatment are covered in the discussion of individual diseases in Chapters 10 and 11.

Corticosteroids and other immunosuppressive agents are used for decreasing the inflammatory component of a number of the diffuse parenchymal lung diseases.

References

American Thoracic Society and European Respiratory Society. American Thoracic Society/European Respiratory Society international multidisciplinary consensus classification of the idiopathic interstitial pneumonias. Am J Respir Crit Care Med. 2002;165:277–304.

Harari, S, Caminati, A. Update on diffuse parenchymal lung disease. Eur Respir Rev. 2010;19:97–108.

Lama, VN, Martinez, FJ. Resting and exercise physiology in interstitial lung diseases. Clin Chest Med. 2004;25:435–453.

Leslie, KO. Pathology of interstitial lung disease. Clin Chest Med. 2004;25:657–703.

Markart, P, Wygrecka, M, Guenther, A. Update in diffuse parenchymal lung disease. Am J Respir Crit Care Med. 2010;183:1316–1321.

Pipavath, S, Godwin, JD. Imaging of interstitial lung disease. Clin Chest Med. 2004;25:455–465.

Raghu, G, Nicholson, AG, Lynch, D. The classification, natural history and radiological/histological appearance of idiopathic pulmonary fibrosis and the other idiopathic interstitial pneumonias. Eur Respir Rev. 2008;17:108–115.

Rosenbloom, J, Castro, SV, Jimenez, SA. Narrative review: fibrotic diseases: cellular and molecular mechanisms and novel therapies. Ann Intern Med. 2010;152:159–166.

Silva, CI, Müller, NL. Idiopathic interstitial pneumonias. J Thorac Imaging. 2009;24:260–273.

Verschakelen, JA. The role of high-resolution computed tomography in the work-up of interstitial lung disease. Curr Opin Pulm Med. 2010;16:503–510.

Visscher, DW, Myers, JL. Histologic spectrum of idiopathic interstitial pneumonias. Proc Am Thorac Soc. 2006;3:322–329.

Wells, AU. The clinical utility of bronchoalveolar lavage in diffuse parenchymal lung disease. Eur Respir Rev. 2010;19:237–241.

Wittram, C. The idiopathic interstitial pneumonias. Curr Probl Diagn Radiol. 2004;33:189–199.

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