Inflammatory Bowel Disease

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Chapter 79 Inflammatory Bowel Disease

Thoracic involvement by Crohn disease (CD) and ulcerative colitis (UC) is part of the spectrum of extraintestinal manifestations of inflammatory bowel disease (IBD). The distinctive pathologic changes associated with IBD can involve the upper respiratory tract, the large and small airways, the interstitium of the lung, the pleura, and the heart and pericardium. It is often difficult to prove with certainty that a particular lung disease is causally related to an IBD. The presentation is not always temporally related to the bowel disease, and the pathologic findings can overlap with those seen in other inflammatory lung diseases. However, the correlation of pulmonary function with IBD severity and the striking response to corticosteroid therapy by many of the lesions suggests a common mechanism.

Anatomically, the gastrointestinal and respiratory systems have some common features. The cephalad end of the respiratory tract (larynx and trachea) is intimately associated with the foregut until their separation by the mesodermal tracheoesophageal folds. Both epithelia are of endodermal origin, and both mucosal surfaces contain mucosa-associated lymphoid tissue (MALT), columnar epithelium with surface differentiations (villi and cilia), goblet cells, and submucosal glands. The pathogenesis of extraintestinal manifestations is poorly understood. The emerging theme of the proposed mechanisms for bowel damage in IBD is an intricate interplay among innate and acquired immunologic factors, intraluminal microbial flora, and the mucosal barrier separating both. Several studies found a limited repertoire of T cell specificity in IBD patients, suggesting that a cellular immune response is elicited by only a small number of antigens. Autoantibodies, including atypical antinuclear antibodies (ANAs), found in some patients suggest an aberrant B cell functionality. The diapedesis (migration) of inflammatory cells into areas of inflammation suggests abnormalities in the homing of leukocytes. Lastly, increased levels of cytokines (e.g., interferon, tumor necrosis factor) suggest a dysregulation of inflammatory mediators in patients with IBD. Evidence has been found supporting all these mechanisms in sites other than the respiratory tract.

In addition, genetic linkage studies of affected kindred have identified several genes associated with IBD. The first susceptibility gene discovered (IBD1, also known as NOD2) encodes a protein that activates transcription in macrophages on encountering bacterial lipopolysaccharides. Another, more recent, example is the discovery of nonfunctional variants of the interleukin-23 (IL-23) receptor or some of its downstream effectors. IL-23 helps generate Th17 helper cells that play a central role in immune response regulation. Genetic factors are associated not only with the development of IBD but also with its extraintestinal manifestations. A study of more than 250 parent-child and sibling pairs showed concordance of extraintestinal involvement in 70% and over 80% of the pairs, respectively. Other studies more specifically sought associations with certain genes. IBD1 and IL-23 are associated with sacroiliitis and ankylosing spondylitis, respectively. CD patients carrying major histocompatibility complex (MHC) genes HLA-A2, HLA-DR1, HLA-DQw5, HLA-DRB1*0103 (DR103), or HLA-B*27 are more likely to develop extraintestinal manifestations. UC patients with HLA-B*58 have been found to have more joint, skin, and eye manifestations. HLA-B8 is more common in UC patients with primary sclerosing cholangitis than those without. No specific genetic link has been established between IBD and respiratory tract involvement. However, some genetic alterations may also be involved in other lung diseases; abnormalities of NOD2, for example, have been found in early-onset and advanced pulmonary sarcoidosis.

Thoracic conditions seen in IBD can conceptually be grouped into four categories: (1) nonspecific conditions (e.g., infection), (2) anatomic complications (e.g., fistulas); (3) therapy-related complications (e.g., drug toxicity); and (4) distinctive pathologic changes that statistically show a more-than-incidental association with IBD. This chapter focuses on the fourth category.


The true incidence of thoracic complications in IBD patients is unknown. There have been no screening tests performed on large populations of IBD patients. The proportion of IBD patients with subjective respiratory symptoms such as cough, sputum production, wheezing, or shortness of breath has been reported to be as high as 50%. One or more pulmonary function tests (PFTs) are abnormal in approximately 40% of IBD patients, with forced expiratory volume in 1 second (FEV1), inspiratory vital capacity (IVC), or diffusion capacity (DLCO) showing a 10% to 30% reduction. Between 25% and 50% of asymptomatic IBD patients show abnormalities on high-resolution computed tomography (HRCT) scans. Often, the findings are subtle and include ground-glass opacities, mosaicism suggestive of air trapping, peripheral opacities, and cysts. At the other end of the spectrum are case reports and small series of patients with distinctive manifestations of thoracic involvement. These reports, accounting for 155 patients, were recently reviewed (see Suggested Readings). Although nothing is offered to calculate incidence or prevalence, significant symptomatic thoracic involvement by IBD probably is not a common event. However, it is common enough that physicians need to be cognizant of IBD to recognize it and prevent the potentially debilitating consequences of some of its forms.

The temporal relation of the thoracic manifestation to the bowel disease varies. Approximately 80% of patients have an established history of IBD, whereas in about 10% each, the thoracic symptoms precede the bowel disease or develop concomitantly. About one half of patients with airway disease have had a colectomy, and occasionally the onset of airway disease follows the colectomy by days or weeks, suggesting a shift of the inflammatory reaction from the gut to the bronchial tree.

In ulcerative colitis and Crohn disease, the most common anatomic structures involved are the large airways (39%), followed by infiltrative lung disease (23%) and involvement of the serosa (13%). Small airways inflammation (10%), upper airways inflammation (9%), and involvement of the pulmonary vasculature (6%) are slightly less common. In general, respiratory tract involvement is more common in UC than CD patients. In both diseases, however, all compartments of the respiratory tract can be affected, although with slight differences in incidence.

Severity of thoracic involvement in many cases parallels disease activity in the bowel. Patients with active IBD have a greater chance of exhibiting airway obstruction. Inflammation of the bowel also correlates inversely with diffusion capacity. Serosal disease is more common among those with active IBD, while parenchymal disease is often seen in patients with quiescent bowel disease.

Women appear to be more frequently affected (~2 : 1). When considering only airway disease, this ratio increases up to 4 : 1. However, pleural involvement is about equally distributed between women and men.

Two thirds of patients with thoracic complications also have other extraintestinal manifestations at the same time, such as involvement of the skin, eyes, joints, or the biliary tract. Smoking does not appear to be a risk factor for developing airway inflammation in IBD, because most patients with this manifestation are nonsmokers.

Interestingly, two recent analyses found that CD patients appear to have a slightly increased risk of lung cancer, whereas the risk appears to be decreased in UC patients (standardized incidence ratios of 1.82 vs. 0.39 and 0.72, respectively).

Clinical and Pathologic Features

The diagnostic workup should include chest radiograph and CT scan. PFTs should be obtained, if possible, because they can provide a baseline in the course of treatment. Endoscopy complements imaging studies in the detection of upper airway obstruction or stenosis and in obtaining material for microbiology and histologic studies. A complete blood count with differential as well as a metabolic panel should be performed. Erythrocyte sedimentation rate and C-reactive protein may be helpful in following disease activity during treatment. Between 50% and 70% of patients with ulcerative colitis and 10% to 30% of patients with Crohn disease (predominantly those with colonic involvement) show atypical antineutrophil cytoplasmic antibodies (ANCAs), characterized by a fine granular and perinuclear (“snowdrift”) pattern. Serologic testing for ANCAs may be helpful in patients with suspected underlying IBD. ANAs can help identify drug-induced lupus syndrome in patients with serositis. Since thromboembolic disease is a known cause of morbidity and mortality in IBD patients, the physician should maintain a low threshold to consider and exclude pulmonary embolism in this population.

This section discusses the different compartments of the respiratory tract involved by IBD, including unique considerations of the particular location, clinical presentation, and its pathologic features (Table 79-1).

Airway Disease

Inflammatory bowel disease can affect the entire tracheobronchial tree, including larynx, trachea, and large and small airways, in the form of airway inflammation. Most common is inflammation of the large airways, seen in about 40% of IBD patients. Approximately 10% of patients show involvement of the upper respiratory tract or small airways. Extent and location of involvement are unpredictable; some patients have involvement restricted to a small area, some have patchy disease involving different anatomic levels of the conducting airways, and others show involvement of the entire tracheobronchial tree. The vast majority of patients with airway disease have UC, and only 10% CD. About two thirds of patients are female, with a median age at presentation of 42 years. In about 5% of patients the airway disease predates the diagnosis of IBD, and these patients tend to be much younger (median age, 13 years).

Clinically, laryngeal inflammation affecting the glottis and epiglottis produces narrowing and stenosis. Corresponding symptoms include dry, deep-toned cough with stridor. Severe cases may result in asphyxia, which is why laryngeal inflammation in IBD is one of the three conditions that require emergency treatment. Large airways inflammation in the form of tracheobronchitis manifests with chronic, otherwise unexplained cough that can be dry or productive of copious amounts of mucopurulent sputum. It is this purulent material that led to the historical designation for this condition, “chronic bronchial suppuration.” It is also the condition that established the link between IBD and lung disease in 1976. Long-standing chronic inflammation and suppuration lead to bronchiectasis, often with basilar distribution. Small airways disease manifests as airflow obstruction with or without sputum production. Although unlikely to be the dominant feature, microscopic involvement is often found distally from affected large airways.

Radiographically, airway walls appear thickened with a “tram line” pattern. Larger airways show mucus plugging, smaller airways a tree-in-bud appearance. These changes tend to occur in a basilar-predominant distribution, occasionally with associated volume loss. Small airways disease can be associated with a tree-in-bud pattern, diffuse reticular shadows, or mosaic pattern due to air trapping (Figure 79-1

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