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The Pathology of Chronic Obstructive Pulmonary Disease: Progress in the 20th and 21st Centuries.

Chronic obstructive pulmonary disease (COPD) is the fourth leading cause of death in the developed world, (1) and thus it constitutes a major focus of medical investigation. The pathologic study of COPD includes gross, microscopic, and molecular modalities. Although the aim of pathologic analyses was once to distinguish COPD from asthma, bronchiectasis, and the interstitial lung diseases, the focus shifted toward providing clinical and physiologic correlations. The focus then progressed again toward understanding the mechanisms involved in the genesis of the alteration of tissue components, and it has culminated in analyses of gene regulation.

The practicing pathologist needs to be able to recognize the gross and histologic changes of COPD. This will allow pathologists to not only provide diagnostic information to correlate with the patient's symptomatology and physiologic findings, but also to provide information to correlate with genetic and molecular biologic analyses. This article is not meant to be an all-inclusive review, but rather to provide a reprise of these developments and indicate areas in which there is a need for further research.

DEFINITION

Chronic obstructive pulmonary disease is one of a group of conditions defined by airflow limitation and thus must be distinguished from asthma, bronchiectasis, and airway obliteration. It is defined in the most recent update of the Global Initiative for Chronic Obstructive Lung Disease (GOLD) (1) as "a common preventable and treatable disease, characterized by persistent airflow limitation that is usually progressive and associated with an enhanced chronic inflammatory response in the airways and the lung to noxious particles or gases. Exacerbations and comorbidities contribute to the overall severity in individual patients." This definition is quite different from those of the American Thoracic Society (1995) and the European Respiratory Society (1995), (2) which respectively defined COPD as "a disease state characterized by the presence of airflow limitation due to chronic bronchitis or emphysema; the airflow obstruction is generally progressive, may be accompanied by airway hyper-reactivity, and may be partially reversible" and "reduced maximum expiratory flow and slow forced emptying of the lungs, which is slowly progressive and mostly irreversible to present medical treatment." The newer GOLD definition highlights the usually preventable nature of the disease, as well as the contribution of the patient's inflammatory response, and variability between individuals. These clinical definitions, however, are not particularly helpful to the pathologist in making a clinical-pathologic correlation.

PATHOLOGY

The histology of pathologic descriptions of the lung disease that is now known as COPD is really the history of the description of emphysema and its differentiation from tuberculosis, which developed during the 20th century (see Snider (3,4) for discussion). This not only includes gross pathologic descriptions but also microscopic descriptions, and early speculations on pathophysiology.

In 1952, Gough (5) used paper-mounted sections to describe what he termed "fundamentally different" types of emphysema, types that we now know as centriacinar (centrilobular) and panacinar (panlobular) emphysema. He also first described how to pathologically differentiate emphysema from status asthmaticus and pneumoconiosis. This was followed by work involving microscopic 3-dimensional reconstruction, demonstrating that centrilobular emphysematous spaces were based on architectural alterations, inflammation, and destruction of the respiratory bronchi oles. (6-8) Then, in 1958, McLean (9) described vascular alterations in emphysema. (9) This work brought us to the modern triad of pathologic alterations in COPD, namely, emphysema, smokers' bronchiolitis, and vascular alterations (summarized in the Table).

The 21st century has not yet seen any major changes to the pathologic description of COPD, but it has seen increasing recognition of the coexistence of COPD with interstitial lung disease, an area that is still being explored (see last subsection, Combination of COPD and Interstitial Lung Disease).

Emphysema

Emphysema is defined as "a condition of the lung characterized by permanent, abnormal enlargement of the respiratory airspaces, accompanied by destruction of their walls without obvious fibrosis." (10) It is important to note here that the fibrosis refers to gross fibrosis, not microscopic fibrosis, and thus differentiates emphysematous destruction of airspaces from the airspace remodeling seen in interstitial lung diseases. The inclusion of "destruction" in the definition serves to differentiate emphysema from the simple airspace enlargements seen in aging, compensatory emphysema and congenital lobar hyperinflation.

There are 4 main types of emphysema: proximal acinar emphysema (including the centriacinar emphysema seen characteristically in cigarette smokers and the focal centriacinar emphysema seen in pneumoconiosis); panacinar emphysema, characteristically found in [alpha]1-antitrypsin (protease) deficiencies; distal acinar (paraseptal) emphysema, characteristically seen in young adults with spontaneous pneumothorax, or in association with centrilobular emphysema; and finally airspace enlargement with fibrosis (also termed scar, irregular, or paracicatricial emphysema).

The synonymous use of "lobular" and "acinar" makes sense when one considers the anatomy of the lung. A lobule is a gross and microscopic term defined as the amount of lung parenchyma that is encompassed by pleura and/or venous septa on its borders. It is usually approximately 2 to 3 cm on a side and so can be seen grossly on a lung slice (Figure 1). Each lobule itself contains 3 to 6 acini. To understand the acinus, one needs to recall the 3-dimensional anatomy of the lung, but beginning at the level of the terminal membranous bronchiole. The terminal membranous bronchiole is the final conducting airway with a complete fibromuscular wall. The terminal membranous bronchiole gives rise to 3 generations of respiratory bronchioles (airways with alveoli forming a component of their walls). An acinus is then defined as the amount of lung tissue that subtends from a single terminal membranous bronchiole. Thus, the acinus cannot be identified on a normal gross specimen but would require a 3-dimensional process to visualize the conelike arrangement of 3 generations of respiratory bronchioles with their branches of alveolar ducts, alveolar saccules, and alveoli.

Centriacinar emphysema affects respiratory bronchioles, with relative sparing of the distal alveoli. Because respiratory bronchioles are generally clustered in the center of the secondary lobule, their destruction (proximal acinar destruction) is seen as a hole in the center of the lobule, and hence the synonym centrilobular emphysema (Figure 2). In panacinar (panlobular) emphysema, the enlarged acini are uniformly distributed from the respiratory bronchioles to the terminal alveoli (Figure 3). In paraseptal emphysema, almost the entire proximal part of the acinus is normal, whereas distal alveolar ducts and sacs are abnormal (Figure 4). Irregular emphysema can be found in any area of the lobule because it is associated with scars from prior inflammatory processes, such as tuberculous complexes.

High-resolution computerized tomography scans can now essentially replace paper-mounted sections to characterize and grade emphysema phenotypes (11,12) (Figures 2B through 4B). Thus, it is not necessary for the pathologist to prepare paper-mounted sections, obviating the need for sledge microtomes and specialized technical processes. Instead, to make the appropriate correlations with clinical or radiologic features, the pathologist can inflate the lungs (or lobes) with an appropriate fixative, slice them thinly using a standardized knife board, and examine the cut surfaces. Such an examination can be aided by immersing the lung tissue in a water bath and then lifting the tissue out and evaluating how the tissue "drops away" or remains stable.

Alteration of the Airways

The pathologic changes of the airways are important for the practicing pathologist to be familiar with, because these changes are central to the clinical symptoms of COPD. Increased airflow resistance in COPD is associated with the alteration, remodeling, and obliteration of the small bronchioles (less than 2 mm internal diameter). The initial pathologic descriptions of these airway alterations in emphysema highlighted the importance of two features: inflammation as a mechanism, and respiratory bronchioles as the primary site of involvement. (8) Smokers' bronchiolitis, or respiratory bronchiolitis, is recognized pathologically as an increase of macrophages, which contain a finely granular golden brown pigment, present within the lumen of the respiratory bronchiole and subtending alveolar spaces (Figure 5). Other inflammatory cell types, such as neutrophils and eosinophils, may be numerically increased, but such increases are generally subtle. Lymphoid follicles or aggregates can also often be identified within the adventitia of the airway. A mild degree of alveolar wall fibrosis is often associated with respiratory bronchiolitis and should not be interpreted as evidence of respiratory bronchiolitis-interstitial lung disease, which remains a diagnosis that should be considered only in conjunction with clinical information. (13)

Detailed morphometric analysis has extensively expanded our knowledge of airway alterations in both membranous and respiratory bronchioles, (14) and it has documented airway narrowing with inflammation and fibrosis, and loss of the peribronchiolar alveolar attachments. These alterations, as least theoretically, correlated with the early physiologic studies that demonstrated that airway resistance in COPD was determined by the peripheral rather than the central airway compartment. (15) With the development of more sophisticated physiologic tests of airway dysfunction, studies also showed that inflammation and fibrosis were the most important pathologic alterations in the bronchioles. (16,17)

Unlike evaluation of emphysema in the parenchyma, computed tomography analysis of the airways is, at present, restricted to airways greater than 2 mm in diameter. More recently, however, the combination use of micro-computed tomography and detailed morphometry has demonstrated narrowing and reduction in numbers of the terminal membranous bronchioles, which actually precedes emphysematous lung destruction. (18) These data again emphasize that the 3 tissue compartments in lung are affected with different severities and at different times during the development of COPD.

Changes in the airway epithelium can also be found, with the most marked changes in the larger conducting airways. The most obvious of these is goblet cell metaplasia of the usual pseudostratified epithelium (larger airways), or ciliated columnar epithelium (smaller airways), although squamous metaplasia can also often be identified in the larger airways.

The practicing pathologist can certainly comment on the extent and severity of the above-described airway remodeling. As a caution, however, although goblet cell metaplasia is a feature of asthma, its presence should not cause the pathologist to suggest that airway hyperresponsiveness may be present in COPD; indeed, there is sufficient overlap between the airway pathology of asthma and that of COPD that a definitive separation based solely on evaluation of the conducting airways is quite difficult.

Alteration of the Vasculature

As noted above, McLean (9) as early as 1958 described intimal thickening with reduplication of the internal elastic fiber network and patchy "destruction" of the media in the arteries adjacent to the bronchioles. He interpreted these changes as secondary to inflammation of the bronchi and hypothesized that they were due to inflammation-induced thrombosis of the vessel. McLean also made the prescient suggestion that these changes would not only narrow and obliterate the small arteries, but would result in decreased distensibility, one of the basic premises behind endothelial dysfunction in COPD (see below).

Pulmonary hypertension (PHT) is now considered an important complication of COPD because it has been shown to be a significant predictor of mortality and is a major cause of morbidity in patients with COPD (19) in which PHT is the strongest prognostic factor, independent of the severity of airflow limitation. The importance of PHT in COPD is apparent when one considers that, as a lower estimate, approximately 8% of people older than 40 years will develop COPD. (20) If PHT develops in approximately 6% of these individuals, (21) and is present in approximately 40% of patients with a forced expiratory volume in 1 second of less than 1 L, then 16.8 million people worldwide will experience significant morbidity and mortality related to PHT.

The increased thickness of the intima in the arterial vasculature in COPD has been shown to be caused by smooth muscle proliferation, with increased deposition of both elastin and collagen (see Wright et al, (22) Peinado et al, (23) and Budhiraja et al (24) for review). In the very small arteries and large arterioles, the longitudinal smooth muscle remodeling results in the formation of a definite muscularis media (Figure 6).

The mechanisms by which such remodeling occurs, and their physiologic consequences, are postulated by the "endothelial dysfunction" paradigm. Endothelial dysfunction is defined as a physiologic alteration of the normal biochemical processes carried out by the endothelium. (24) The characteristic feature of dysfunction is the inability of the arteries to dilate fully in response to exercise, acetylcholine, or increases in flow. This dysfunction in COPD could be explained by several contributing factors, including an increased production of vasoconstrictors, and a chronic insufficiency in the production of vasodilators, thus allowing constriction to be either progressive or maintained. Other factors relate to the action of vasoactive mediators, particularly endothelin and nitric oxide synthetases (eNOS and iNOS), which regulate cell growth and vascular contraction. Long-term smoking appears to be associated with a decreased nitric oxide response, (25) and impaired endothelium-dependent relaxation of the main pulmonary artery is found in patients with COPD. (26,27) In addition, reduced immunohistochemical expression of nitric oxide synthase has been found in the vessels of patients who had pulmonary hypertension due to a variety of etiologies. (28) Thus, the stage is set for proliferation of the vascular muscle cells and fibroblasts, culminating in thick-walled vessels with narrowed lumens, and impaired ability to vasodilate. The endothelial-targeted treatment aspects of this hypothesis have been tested in both humans and in animal models of COPD, with variable results. This is an area of ongoing research that will be needed to provide any therapeutic interventions for this aspect of COPD.

The practicing pathologist should be aware of the above vascular changes, if only to exclude idiopathic pulmonary hypertension.

Combination of COPD and Interstitial Lung Disease

People who smoke cigarettes not only can develop respiratory bronchiolitis-interstitial lung disease, but they also have a higher incidence of developing usual interstitial pneumonia/idiopathic interstitial fibrosis. Mixtures of these diseases with emphysema are not uncommon. (29-31) The practicing pathologist must be aware of this coexistence; we have recently reviewed this topic with a focus on the pathologic differential diagnosis. (30) Computed tomography scans generally show findings typical of COPD, with centrilobular or mixed centrilobular and paraseptal emphysema in the upper lobes, and also findings typical of usual interstitial pneumonia, with increased reticular markings, traction bronchiectasis, and honeycomb remodeling in the lower lobes. Pathologically, there are defined areas of emphysema, both gross and microscopic, and areas of defined usual interstitial pneumonia, with interstitial fibrosis and fibroblast foci in the areas of active fibrosis.30 Correlation with computed tomography findings is essential because biopsy samples are usually directed toward the areas of usual interstitial pneumonia.

PATHOGENESIS

There are several mechanisms that appear to be pertinent to the genesis of emphysema, none of which are entirely mutually exclusive. (32,33) Although the mechanisms are discussed below as distinct theories, there is considerable overlap between them, and it is likely that emphysema and airway remodeling are a consequence of the interplay of the inflammatory and immunologic systems, resulting in genetic alterations and abnormal maintenance and repair of the lung.

Protease/Antiprotease Hypothesis

The most longstanding theory is that emphysema results from an imbalance between inflammatory-induced proteolytic enzymes and the ability of the antiproteolytic activities of the lung to inhibit these proteases. There is a long list of proteases of importance, including serine and metalloproteases, and there is an equally long list of inflammatory cascades that may be involved in the induction of these proteases. Environmental oxidants have effects both in inflammatory protease activation and antiprotease inactivation.

Disruption of Homeostatic Maintenance and Repair System

This hypothesis suggests that there is an intrinsic balance between apoptosis and cell proliferation in the lung, and that vascular endothelial growth factor is central to the stability of this system as a survival signal. The hypothesis suggests that cigarette smoke activation of caspase, ceramide, and oxidative stress acts to induce apoptosis and will ultimately produce emphysema through induction of senescence. This results in cellular dropout and loss of alveolar wall integrity.

This theory also includes speculation as to the role of autoimmunity in induction of both centriacinar and panacinar emphysema. Certainly, there are data that imply that an adaptive immune response is involved in either or both of the genesis and perpetuation of emphysema. Exposure of recognition domains, membrane lipid alteration, and dendritic cell activation can all lead to activation of T cells targeted toward the lung endothelium and/or epithelium.

The lung microbiome appears to be important in the host immune response in COPD. Recently, Sze and colleagues (34) have found not only that analysis of the microbiome can be used to discriminate between control and severe COPD lung tissue, but they also demonstrated that a decline in microbial diversity correlated with emphysematous lung destruction, airway remodeling, and CD4 T-cell lymphocyte accumulation within the lung.

Genetic changes in COPD can occur at several levels. There are germ line alterations, such as are found in Fabry disease, Ehlers-Danlos syndrome, and Marfan syndrome, which result in alteration of the lung matrix proteins. Genetic alterations may also explain some of the familial related susceptibilities for emphysema and airway disease. In a general population of COPD patients, genome-wide study of emphysema has identified loci associated with emphysema-related phenotypes. (35) One of the most interesting associations are variants near SERPINA10 that are not due to PI ZZ antitrypsin. Further, a rather diverse number of single-nucleotide polymorphisms have been found not only in severe but also in mild COPD, suggesting that clinical heterogeneity may be at least partially related to genetic heterogeneity (36); this is an area of ongoing research. Epigenetic modifications, through DNA methylations and histone modifications, may also have an important role in COPD progression or exacerbations. (37)

SUMMARY

In the 20th and now in the 21st century there have been remarkable advances in our knowledge of the pathology and pathophysiology of COPD. Alterations of lung anatomy can be identified not only by the pathologist but also by the radiologist, and have shown that the 3 lung compartments of parenchyma, airways, and vasculature must be considered both separately and together. Genetic and epigenetic studies have placed us on the threshold of the ability to identify populations who are at risk of developing COPD and COPD exacerbations. It continues to be necessary for the practicing pathologist to be able to identify all components of COPD (Table: emphysema, smokers' bronchiolitis, and pulmonary vascular alterations) at the autopsy or surgical pathology bench.

Kyra Berg, MD; Joanne L. Wright, MD, FRCP(C)

Accepted for publication March 22, 2016.

From the Department of Pathology at St Paul's Hospital, University of British Columbia, Vancouver, British Columbia, Canada.

The authors have no relevant financial interest in the products or companies described in this article.

Reprints: Joanne L. Wright, MD, FRCP(C), Department of Pathology, St Paul's Hospital, 1081 Burrard St, Vancouver, BC V6Z 1Y6, Canada (email: jlwright@mail.ubc.ca).

References

(1.) Global strategy for the diagnosis, management, and prevention of COPD. Global Initiative for Chronic Obstructive Lung Disease (GOLD) Web site. http:// www.goldcopd.org/guidelines-global-strategy-for-diagnosis-management.html. Updated December 2015. Accessed December 4, 2015.

(2.) Mannino DM. Chronic obstructive pulmonary disease: definition and epidemiology. Respir Care. 2003;48(12):1185-1191.

(3.) Snider GL. Emphysema: the first two centuries - and beyond (part 1). Am Rev Respir Dis. 1992;146(5):1334-1344.

(4.) Snider GL. Emphysema: the first two centuries - and beyond (part 2). Am Rev Respir Dis. 1992;146(6):1615-1622.

(5.) Gough J. Discussion on the diagnosis of pulmonary emphysema: the pathological diagnosis of emphysema. Proc R Soc Med. 1952;45(9):576-577.

(6.) McLean KH. The histology of generalized pulmonary emphysema: the genesis of the early centrilobular lesion: focal emphysema. Australas Ann Med. 1957;6(2):124-140.

(7.) McLean KH. The pathology of acute bronchiolitis-a study of its evolution, I: the exudative phase. Australas Ann Med. 1956;5(4):254-267.

(8.) McLean KH. The pathology of acute bronchiolitis--a study of its evolution, II: the repair phase. Australas Ann Med. 1957;6(1):29-43.

(9.) McLean KH. The significance of pulmonary vascular changes in emphysema. Australas Ann Med. 1958;7(1):69-84.

(10.) Snider GL, Kleinerman J, Thurlbeck WM, Bengali ZH. The definition of emphysema: report of a National Heart, Lung, and Blood Institute Division of Lung Diseases workshop. Am Rev Respir Dis. 1985;132(1):182-185.

(11.) Thurlbeck WM, Dunnill MS, Hartung W, Heard B, Heppleston A, Ryder RC. A comparison of three methods of measuring emphysema. Hum Pathol. 1970;1(2):215-226.

(12.) Lynch DA, Austin JH, Hogg JC, et al. CT-definable subtypes of chronic obstructive pulmonary disease: a statement of the Fleischner Society. Radiology. 2015;277(1):192-205.

(13.) Churg A, Muller NL, Wright JL. Respiratory bronchiolitis/interstitial lung disease: fibrosis, pulmonary function, and evolving concepts. Arch Pathol Lab Med. 2010;134(1):27-32.

(14.) Thurlbeck WM, Wright JL. Thurlbeck's Chronic Airflow Obstruction. 2nd ed. Hamilton, ON: B.C. Decker;1999.

(15.) Hogg JC, Macklem PT, Thurlbeck WM. Site and nature of airway obstruction in chronic obstructive lung disease. N Engl J Med. 1968;278(25): 1355-1360.

(16.) Cosio MG, Ghezzo H, Hogg JC, et al. The relations between structural changes in small airways and pulmonary-function tests. N Engl J Med. 1977; 298(23):1277-1281.

(17.) Wright JL, Lawson LM, Kennedy S, Wiggs B, Hogg JC. The detection of small airways disease. Am Rev Respir Dis. 1984;129(6):989-994.

(18.) McDonough JE, Yuan R, Suzuki M, et al. Small-airway obstruction and emphysema in chronic obstructive pulmonary disease. N Engl J Med. 2011; 365(17):1567-1575.

(19.) Traver GA, Cline MG, Burrows B. Predictors of mortality in chronic obstructive pulmonary disease. Am Rev Respir Dis. 1979;119(6):895-902.

(20.) Celli BR. Chronic obstructive pulmonary disease: from unjustified nihilism to evidence-based optimism. Proc Am Thorac Soc. 2006;3(1):58-65.

(21.) Weitzenblum E, Hirth C, Ducolone A, Mirhom R, Rasaholinjanahary J, Ehrhart M. Prognostic value of pulmonary artery pressure in chronic obstructive pulmonary disease. Thorax. 1981;36(10):752-758.

(22.) Wright JL, Levy RD, Churg A. Pulmonary hypertension in chronic obstructive pulmonary disease: current theories of pathogenesis and their implications for treatment. Thorax. 2005;60(7):605-609.

(23.) Peinado VI, Pizarro S, Barbera JA. Pulmonary vascular involvement in COPD. Chest. 2008;134(4):808-814.

(24.) Budhiraja R, Tuder RM, Hassoun PM. Endothelial dysfunction in pulmonary hypertension. Circulation. 2004;109(2):159-165.

(25.) Kiowski W, Linder L, Stoschitzky K, et al. Diminished vascular response to inhibition of endothelium-derived nitric oxide and enhanced vasoconstriction to exogenously administered endothelin-1 in clinically healthy smokers. Circulation. 1994;90(1):27-34.

(26.) Dinh-Xuan AT, Higenbottam TW, Clelland CA, et al. Impairment of endothelium-dependent pulmonary-artery relaxation in chronic obstructive lung disease. N Engl; Med. 1991;324(22):1539-1547.

(27.) Dinh-Xuan AT, Pepke-Zaba J, Butt AY, Cremona G, Higenbottam TW. Impairment of pulmonary-artery endothelium-dependent relaxation in chronic obstructive lung disease is not due to dysfunction of endothelial cell membrane receptors nor to L-arginine deficiency. Br J Pharmacol. 1993;109(2):587-591.

(28.) Giaid A, Saleh D. Reduced expression of endothelial nitric oxide synthase in the lungs of patients with pulmonary hypertension. N Engl J Med. 1995;333(4): 214-221.

(29.) Cottin V, Nunes H, Brillet PY, et al. Combined pulmonary fibrosis and emphysema: a distinct underrecognised entity. Eur Respir J. 2005;26(4):586-593.

(30.) Wright JL, Tazelaar H, Churg A. Fibrosis with emphysema. Histopathology. 2011;58(4):517-524.

(31.) Kawabata Y, Hoshi E, Murai K, et al. Smoking-related changes in the background lung of specimens resected for lung cancer: a semiquantitative study with correlation to postoperative course. Histopathology. 2008;53(6):707-714.

(32.) Wright JL, Churg A. Current concepts in mechanisms of emphysema. Toxicol Pathol. 2007;35(1):111-115.

(33.) Bagdonas E, Raudoniute J, Bruzauskaite I, Aldonyte R. Novel aspects of pathogenesis and regeneration mechanisms in COPD. Int J COPD. 2015;10:995-1013.

(34.) Sze MA, Dimitriu PA, Suzuki M, et al. Host response to the lung microbiome in chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2015;192(4):438-445.

(35.) Cho MH, Castaldi PJ, Hersh CP, et al. A genome-wide association study of emphysema and airway quantitative imagin phenotypes. Am J Respir Crit Care Med. 2015;192(5):559-569.

(36.) Lee JH, Cho MH, McDonald ML, et al. Phenotypic and genetic heterogeneity among subjects with mild airflow obstruction in COPDGene. Respir Med. 2014;108(10):1469-1480.

(37.) Footitt J, Mallia P, Durham AL, et al. Oxidative and nitrosative stress and histone deacetylase-2 activity in exacerbations of chronic obstructive pulmonary disease. Chest. 2016;149(1):62-73.

Please Note: Illustration(s) are not available due to copyright restrictions.

Caption: Figure 1. Paper-mounted section illustrating a lung lobule.

Caption: Figure 2. A, Cross photograph of a lung lobule with centrilobular destruction. B, High-resolution computerized tomography image showing the radiologic correlate with "holes" in the center of the lung lobules.

Caption: Figure 3. A, Gross photograph of a lung lobule with panlobular destruction. B, High-resolution computed tomography image showing the radiologic correlate with the entire lobule destroyed.

Caption: Figure 4. A, Paper-mounted section illustrating paraseptal emphysema. B, High-resolution computed tomography correlate showing a large space in the subpleural position.

Caption: Figure 5. First-generation respiratory bronchiole with macrophages within the airway lumen and also within the adjacent alveolar airspaces (hematoxylin-eosin, original magnification x4.5).

Caption: Figure 6. Muscularization of the normally poorly muscularized small arteries/arterioles adjacent to alveolar ducts (immunohistochemistry for smooth muscle actin, original magnification x20).
Histopathologic Features of Chronic Obstructive Pulmonary Disease

Emphysema         Proximal acinar emphysema
                    * Destruction of respiratory bronchioles
                      with relative sparing of distal alveoli
                  Panacinar emphysema
                    * Destruction of respiratory bronchioles
                      through to terminal alveoli

Alteration of     Respiratory (smoker's) bronchiolitis
the airways       Inflammation and fibrosis of terminal
                  and respiratory bronchioles
                  Reduction in terminal bronchioles
                  Goblet cell metaplasia
                  Squamous metaplasia

Alteration of     Intimal thickening with smooth muscle
the vasculature   proliferation and elastin/collagen deposition
                  Smooth muscle hyperplasia of the media
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Title Annotation:Resident Short Reviews
Author:Berg, Kyra; Wright, Joanne L.
Publication:Archives of Pathology & Laboratory Medicine
Date:Dec 1, 2016
Words:4251
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