Saber-sheath deformity is limited to the intrathoracic part of the trachea, which is flattened from side to side so that the coronal diameter is two-thirds or less of the sagittal diameter at the same level. ²⁷ The condition occurs almost exclusively in men, usually in those more than 50 years of age; the youngest recorded patient was 37 years of age. ⁷³ Saber-sheath trachea is strongly associated with the presence of chronic obstructive pulmonary disease (COPD), and in one series COPD was present in 93% of patients with the deformity compared with 18% of control subjects. ⁷³ The pathogenesis of the lesion is obscure, but probably it is an acquired deformity related to the abnormal pattern and magnitude of intrathoracic pressure changes in COPD. In a study of 40 patients, 20 of whom had a saber-sheath trachea, there was a significant relationship between the ratio of the coronal:sagittal tracheal diameter on CT and functional residual capacity (r = 0.61, p < 0.001), supporting the view that saber-sheath trachea is a consequence of hyperinflation. ⁷⁴ A reduction in coronal diameter of the trachea, short of the forme complète of saber-sheath deformity, correlates significantly with forced expiratory volume in 1 second (FEV₁)/forced vital capacity (FVC). ⁷⁵

Saber-sheath trachea can be detected on chest radiography (Fig. 12.2) but is better demonstrated on CT. The narrowing usually affects the whole of the intrathoracic trachea, with an abrupt return to normal caliber at the thoracic inlet²⁷ (Fig. 12.3). In Greene’s⁷³ series of 60 patients with saber-sheath trachea and 60 control subjects, the mean coronal diameter of the deformed trachea was reduced to 61% and the sagittal diameter increased to 115%, giving a mean tracheal area of 75% compared with control subjects. Cartilage rings are commonly calcified or ossified (but not thickened) both pathologically and on imaging.27. ^{and 76.}

Patients with both saber-sheath trachea and mediastinal lipomatosis are described, in whom the appearance on the plain radiograph therefore strongly resembles a mediastinal mass. ⁷⁷ The original studies described the trachea as displaying the usual changes in configuration in relation to respiration and considered the trachea to be normally compliant (Fig. 12.4). ⁷³ Others, however, have described an abnormal degree of narrowing on forced expiration⁷⁶ and have noted that the cross-sectional area was reduced mainly by apposition of the lateral walls with slight invagination of the posterior membrane. ⁷⁸

Saber-sheath deformity, although usually of little functional consequence, may occasionally cause difficulties for patients undergoing general anesthesia, specifically in terms of intubation,^{79. and 80.} ventilation, ⁸¹ and the rare association with negative-pressure pulmonary edema. ⁸² Preoperative awareness of the deformity is clearly desirable, but even when a chest radiograph is available, a saber-sheath trachea will often be overlooked. In the few individuals in whom marked airflow obstruction can be ascribed to a saber-sheath deformity, intervention in the form of balloon dilation with or without stenting may rarely be required.^{83.84. and 85.}

Fibrotic tracheal stenoses of obscure, presumed inflammatory, origin have been described, but truly idiopathic cases are extremely rare. ⁸⁶ These may occur at any site but tend to be subglottic and are occasionally multiple.^{45.87. and 88.} In a series of 15 cases of idiopathic laryngotracheal stenoses, patients were, in common with other reports, predominantly female (94%) and middle aged (30–60 years). ²⁶ One-third of the stenoses were tracheal, and these were hourglass or eccentric in configuration with smooth or less commonly irregular lobulated internal margins (Fig. 12.5). Stenoses were 2–4 cm long and 3–5 mm wide. The histologic changes were nonspecific, consisting of scarring of the adventitia and lamina propria.

Some patients with cryptogenic stenoses have positive titers of antineutrophil cytoplasmic antibodies. ⁸⁹ In these patients stenoses have been recurrent and the histologic features either granulomatous or nonspecific. It seems likely that such cases are part of the Wegener granulomatosis spectrum.

Tuberculosis of the trachea is now very rare. It may be associated with cavitary lung disease and grossly infected sputum.^{38. and 45.} Pathologic study shows mucosal thickening and ulceration and subsequent healing by fibrosis with stricture formation. ⁴⁵ Occasionally the trachea is involved by direct spread from adjacent nodes²⁴ and fistula formation subsequent to this is described. ⁹⁰ On CT the extent of irregular and circumferential tracheobronchial narrowing is clearly demonstrated^{23. and 91.} (Fig. 12.6) and in some patients an accompanying mediastinitis (opacification of the mediastinal fat) is evident. CT shows differences between active disease in which the narrowed trachea (and frequently one or other main bronchus) has an irregularly thickened wall; by contrast in the fibrotic or healed phase the trachea is narrowed but has a smooth and sometimes normal thickness wall. ⁹¹ Surgical resection or balloon dilation and stenting may be required to treat the resulting stenosis.^{24. and 92.}

Scleroma is a chronic progressive granulomatous infection that affects primarily the nose but may also involve the nasopharynx, larynx, trachea, and bronchi. It is caused by Gram-negative coccobacilli. Scleroma is uncommon in the West, occurring mainly in Asia, north Africa, Central and South America, and eastern Europe. The disease passes through three phases: catarrhal, granulomatous and proliferative, and scarring. ⁹³ Occasionally there is a soft tissue mass or bone destruction suggesting a nasal carcinoma. Laryngeal involvement is usually manifest as glottic or subglottic narrowing and vocal cord thickening.94. ^{and 95.} About 5% of patients have tracheal involvement, which is nearly always accompanied by laryngeal disease and almost invariably paranasal sinus disease. ⁴⁵ Scleroma can be treated by antibiotics such as ciprofloxacin. ⁴¹

All or, more commonly, part of the trachea is involved (bronchial involvement is rare), typically the proximal rather than the distal segment. ⁴⁰ Stenoses are usually concentric and may be nodular or smooth. ⁹⁶

Tracheopathia osteoplastica was first described more than 100 years ago, ⁹⁷ yet it remains a curiosity of obscure etiology. Although rare, it is more common than airway amyloidosis, a condition that some have considered to be the precursor of tracheopathia osteoplastica. ⁹⁸ Pathologic characteristics include the development of cartilaginous and bony submucosal nodules⁴⁵ in the trachea and proximal airways. The nodules are typically found in the lower two-thirds of the trachea and in the main, lobar, and segmental bronchi. ⁹⁹ The disorder, however, sometimes starts more proximally and affects the first tracheal ring region. ⁶⁵ The osteochondral nodules develop adjacent to the airway cartilages and rarely, ¹⁰⁰ if ever, ¹⁰¹ involve the posterior membranous part of the trachea. The nodules give rise to sessile and polypoidal elevations of the mucosa, which produce airway narrowing, ⁶⁵ and sometimes lobar collapse. ¹⁰² The cause of the condition is obscure. One theory considers the nodules to be a form of ecchondrosis of the airway cartilage because of their distribution in the airways and because they have bony, cartilaginous, and fibrous connections to the cartilage rings themselves. ⁶⁵ A second theory is that the disorder is due to amyloidosis, a condition in which cartilage and bone formation is known to occur. Several workers have in fact found evidence of amyloid in pathologic specimens from patients with tracheopathia.^{98. and 103.} Most patients are male, and the disease usually develops in middle age (sixth decade), although the age range is wide, from 11 to 78 years. ⁴⁵ The common early symptoms are dyspnea, hoarseness, cough that is often productive, hemoptysis, and recurrent pulmonary infections. ⁹⁹ The disease progresses very slowly.

The chest radiograph may be normal⁹⁹ or may demonstrate evidence of collapse or infective consolidation. Airway calcification has diagnostic value but may be invisible on chest radiography. ⁴⁵ Tracheal calcification is manifest as irregular or scalloped opacities lying inside the cartilage rings. ⁶⁵ If the tracheal air column is clearly seen, the irregular nodularity of the tracheal wall and the encroachment of these nodules on the lumen can be appreciated. CT descriptions of the condition are sparse but confirm the expected finding of strikingly nodular thickening of the tracheal wall, with calcification in some of the nodules^{102.104.105.106. and 107.} (Fig. 12.7). The definitive diagnosis is made with bronchoscopy, ⁶⁶ during which the passage of the instrument may generate a grating sensation.

The most striking diffuse increase in tracheal diameter is seen in tracheobronchomegaly (Mounier–Kuhn syndrome). This is a rare abnormality of the trachea and large airways that is associated with recurrent respiratory tract infection and was first described in 1932. ¹²¹ The elastic and muscular elements of both the cartilaginous and membranous parts of the trachea are atrophic.^{115. and 122.} In the past the condition was considered to be acquired and to be caused by recurrent infections weakening the airway walls. However, evidence strongly suggests that this is a primary process. ¹¹⁵ Thus in some patients the condition is familial with an autosomal recessive pattern of transmission. ¹²³ There is a recognized association with anatomic variants of the lungs, ribs, and bronchial tree (including a double tracheal lumen, tracheal trifurcation, and a short left main bronchus).^{115. and 124.} Many patients have a history of disease dating back to childhood; ¹²⁵ presentation as early as 18 months of age has been reported. ¹²⁶

No reliable data on prevalence are available, but in a review of 1800 bronchograms the frequency was about 1%. ¹²² However, it seems likely that the condition is underdiagnosed, since some patients are asymptomatic or have only minor symptoms. ¹¹⁵ It is markedly male predominant (only about 5% of patients are female) and has a possible racial predisposition: in a review of 27 patients 52% were black, ¹¹⁵ indicating a significant excess of black individuals if, as seems likely, most of the populations from which cases were derived were predominantly white. The condition most commonly presents in the third or fourth decade and more than three-quarters of the patients have presented by the age of 40 years. ¹²⁴ Symptoms, however, often date back a decade or even into childhood.^{110.122. and 127.} Ineffective cough, because of widened central airways, and diverticula of the large bronchi predispose the patient to recurrent pulmonary infections. A minority of patients have no or surprisingly mild symptoms.^{115. and 128.} Pulmonary function tests usually show airflow obstruction, and increased total lung capacity and residual volume, but occasionally results are normal.^{115. and 129.} Airway compliance is increased, and dynamic airway collapse on expiration and cough can be demonstrated.^{110.115. and 130.} The prognosis is variable; some patients have recurrent infections leading to progressive lung damage, bronchiectasis, scarring, and eventual respiratory failure, whereas others survive into old age with relatively mild, nonprogressive disease. ¹¹⁵

The diagnosis is based on imaging findings. The immediately subglottic trachea has a normal diameter, but it expands as it passes to the carina (Figs 12.9 and 12.10) and this dilatation usually continues into the major bronchi.^{122. and 124.} The dilatation may vary from segment to segment but overall tends to be relatively even. Atrophic mucosa prolapses between cartilage rings and gives the trachea a characteristically corrugated outline that on a plain radiograph is best appreciated on the lateral view.^{123. and 131.} Corrugations may become exaggerated to form sacculations or diverticula.^{124. and 132.} Tracheal changes are well shown on CT^{78.128.132.133. and 134.} (Fig. 12.11). Large vessels may indent the overcompliant trachea. ¹³²

The bronchiectasis of tracheobronchomegaly particularly affects first- to fourth-order branches^{123. and 133.} (Fig. 12.12). Characteristically there is an abrupt transition from large central airways to normal peripheral ones.^{122. and 132.} Small branches that arise from bronchiectatic segments tend to remain patent; this is atypical of bronchiectasis in general, in which they are usually obliterated. The dramatic but delicate nature of the typical saccular and cystic bronchiectasis is well shown on high-resolution CT (HRCT) (Figs 12.11 and 12.13). Dynamic collapse of the trachea and central airways on expiration and cough can be demonstrated by a variety of imaging techniques, including CT.^{130.132.135. and 136.}

Dilatation of the trachea is generalized in tracheobronchomegaly, whereas in other conditions the trachea is usually locally dilated. For example a tracheocele is defined as a localized ballooning of the membranous posterior tracheal wall of obscure etiology.^{137. and 138.} Tracheoceles tend to arise from the right posterior tracheal wall, and their size varies with transmural tracheal pressure. ¹³¹ They may affect the cervical¹³⁷ or thoracic trachea and in the latter instance may be seen as a paratracheal, thin-walled cyst with or without an air–fluid level. ¹²⁰ Smaller, frequently multiple outpouchings (diverticula) may arise from the trachea and mainstem airways. ¹³⁹ Small diverticula are a feature of tracheobronchomegaly¹⁴⁰ and may reflect cystic dilatation of mucous gland ducts, ¹³¹ perhaps similar to those seen in chronic bronchitis (see Fig. 12.70, p. 756).

Ectopic thyroid is a rare cause of an intratracheal filling defect, ¹⁸⁰ with about 150 cases in the literature. ¹⁸¹ Females outnumber males by about 3 : 1. ¹⁸² The ectopic thyroid may be histologically normal, although it is usually goitrous. Occasionally it is malignant. ¹⁸³ Three-quarters of intratracheal thyroid nodules are associated with extratracheal goiter. Foci of ectopic thyroid may occur anywhere between the subglottis and main carina, ¹⁸¹ but typically they are a few centimeters below the vocal cords, arising as smooth, sessile nodules from the posterolateral wall of the trachea. ¹⁸² Ectopic thymus has also been described as causing a submucosal intratracheal mass. ¹⁸⁴

Squamous papillomas of the trachea are usually multiple and may be a manifestation of laryngeal papillomatosis with tracheobronchial dissemination (see p. 834).^{183. and 185.} Recurrent respiratory papillomatosis seems to have a bimodal age distribution with the mean age of the juvenile form being 2 years old, and adult-onset approximately 40 years of age.^{37. and 186.} Solitary squamous cell papillomas of the trachea are also recognized in adults and may undergo malignant transformation.^{183. and 187.}

By pathologic definition, dilatation of the airways is a prerequisite for the diagnosis of bronchiectasis. Thus the major sign of HRCT bronchiectasis is dilatation of the bronchi (with or without bronchial wall thickening). The characteristics of bronchiectasis on CT, first described over 25 years ago, ²⁸⁴ have withstood the test of time with subsequent minor refinements and additions.^{285.286.287.288.289. and 290.} Absolute measurements for the diameter of all generations of the bronchi are not available for normal individuals, and relating the size of a bronchus to its immediately adjacent (homologous) pulmonary artery has been the most widely used criterion for the detection of abnormal dilatation. ²⁹¹ In normal individuals the overall diameter of a bronchus is approximately the same, at any given level, as that of its accompanying pulmonary artery. The ratio of the diameter of the bronchus (internal lumen) to the pulmonary artery diameter for subjects has been estimated to be 0.62 ± 0.13 (mean ± SD). ²⁹² Recognition of abnormal dilatation of a bronchus by comparison with its accompanying pulmonary artery can be readily made for airways running perpendicular to the CT section. When bronchial dilatation is marked, the cross-sectional appearance of the combined bronchus and artery resembles a pearl or signet ring²⁹³ (Fig. 12.23).

In healthy individuals minor discrepancies in the bronchoarterial diameter ratio may occasionally be encountered.^{291. and 294.} Furthermore, there are many factors that can cause transient or permanent changes in diameter of the relatively compliant pulmonary arteries, so invalidating this sign. For example, a left-to-right cardiac shunt will result in generalized increase in perfusion and thus caliber of the pulmonary arteries; conversely any cause of underventilation of a region of lung will result in hypoxic vasoconstriction. Thus bronchial dilatation in isolation cannot always be regarded as diagnostic of bronchiectasis and this is especially true in children. ²⁰⁸ This caveat has been emphasized by Lynch et al., ²⁹⁴ who showed that 59% of normal individuals had at least one bronchus with a diameter greater than that of the homologous pulmonary artery; in these healthy subjects bronchial wall thickening was not a common association. One of the factors that appears to have contributed to the apparently high frequency of a decreased bronchoarterial ratio in normal individuals, in this particular study, was hypoxic vasoconstriction: the study group investigated were all examined in Colorado, at approximately 1600 m above sea level. ²⁹⁴ Kim et al. ²⁹² subsequently performed a detailed study which compared the bronchoarterial ratio of normal individuals at sea level with that of normal individuals at high altitude (1600 m above sea level). The mean bronchoarterial ratio in individuals at altitude was 0.76 (SD 0.14) compared with 0.62 (SD 0.13) at sea level (p < 0.001).

When airways lie parallel to the plane of section, abnormal dilatation is recognized by a lack of normal tapering, producing a tramline or even flared appearance (Fig. 12.24). These airways are conspicuous in the lung periphery because of associated bronchial wall thickening.

The cylindrical and varicose patterns of bronchiectasis, described by Reid, ²⁰⁹ can be appreciated only for bronchi that lie within the plane of the CT section. Cylindrical bronchiectasis is by far the commonest morphologic pattern of bronchiectasis identified on CT. ²⁹⁵ A bronchoarterial ratio of greater than 1 has been reported in 95% of patients with cylindrical bronchiectasis. ²⁹⁰ Varicose bronchiectasis is characterized by a beaded appearance (Fig. 12.25) and cystic (or saccular) bronchiectasis is seen as thin-walled cystic spaces which may contain fluid levels. In cystic bronchiectasis, recognition that large cystic airspaces represent massively dilated bronchi may sometimes be difficult or impossible (Fig. 12.26). In this type of severe bronchiectasis the accompanying pulmonary artery is often obliterated. When varicose bronchiectatic airways are imaged in cross-section, they may appear as either cystic or cylindrical bronchiectatic airways because the characteristic corrugation of the bronchial walls cannot be identified in this orientation. Sections obtained at end-expiration have been advocated to differentiate cystic bronchiectasis from other cystic lung diseases; ²⁹⁶ bronchiectatic airways usually decrease in size on expiratory scans in contrast with other cystic lesions. However, one study has reported that most cystic lesions in the lungs, whether bronchiectatic or another etiology, decrease in size, ²⁹⁷ rendering this sign of doubtful discriminatory value.

Bronchial wall thickening is a usual, but inconstant, feature of bronchiectasis (Fig. 12.27). Problems with this variable feature have been widely debated and the definition of what constitutes ‘abnormal bronchial wall thickening’ remains unresolved. ²⁸⁹ Minor to mild degrees of bronchial wall thickening are seen in healthy subjects, particularly elderly individuals, ²⁹⁸ asthmatic people, individuals with acute lower respiratory tract infections, ²⁹⁹ and asymptomatic smokers.^{294.300. and 301.} There is no simple and robust criterion for the identification of abnormal bronchial wall thickening. ³⁰² Remy-Jardin et al. ³⁰⁰ defined a bronchus as being thick walled when the bronchial wall was at least double the thickness of a normal bronchus. However, such a judgment is possible only when comparable ‘normal’ bronchi can be identified. An assessment can also be made by relating the bronchial wall thickness to the diameter of accompanying pulmonary artery,^{295. and 303.} but in practice this does not overcome the difficulties of identifying subtle bronchial wall thickening. ³⁰⁴ Diederich et al. ³⁰⁵ defined abnormal bronchial wall thickening as being present if the internal diameter of the bronchus was less than 80% of the external diameter. While this sign was associated with good interobserver agreement it cannot be applied to conditions in which there is marked accompanying bronchial dilatation.

Normal airways within 2 cm of the visceral pleural surface are not usually visible because their walls are below the spatial resolution of HRCT. ³⁰⁶ However, perhaps as a consequence of improving CT technology, it has been pointed out that bronchi may be identified within 1 cm of the mediastinal pleura in normal subjects, but that airways seen within 1 cm of the costal pleura or paravertebral pleura should be regarded as abnormal. ²⁹⁰ Large plugged bronchi are visible as lobulated or branching opacities – such airways are usually seen in the presence of nonfluid-filled but obviously bronchiectatic airways. A less frequent pattern is plugging and thickening of the smaller peripheral centrilobular airways, producing V- and Y-shaped opacities, the so-called ‘tree-in-bud’ appearance^{307.308. and 309.} (Fig. 12.28); similarly, this pattern is almost invariably accompanied by abnormal, if not frankly bronchiectatic, larger airways.

In many patients with bronchiectasis, areas of decreased attenuation of the lung parenchyma can be identified (Fig. 12.29); this mosaic attenuation pattern reflects accompanying obliteration of small airways disease.^{286. and 310.} Sections taken at end-expiration enhance the feature of decreased attenuation, the extent of which correlates with functional indices of airways obstruction.^{310. and 311.} This finding is most prevalent in lobes with severe bronchiectasis but may be seen in some lobes in which there are no CT features of bronchiectasis. Kang et al. ²⁸⁶ identified a mosaic pattern in just over half of bronchiectatic lobes subsequently resected, and there was pathologic evidence of obliterative bronchiolitis in 85% of these resected lobes. Areas of decreased attenuation on CT representing constrictive obliterative bronchiolitis may sometimes be confused with the features of emphysema. ³¹² Nevertheless, the rare association of bronchiectasis and true emphysema does sometimes occur. When a panacinar emphysema pattern (uniform decrease in attenuation of the lung parenchyma – see p. 763) is identified in the lower lobes, as part of α₁-antitrypsin deficiency, it is often accompanied by bronchiectasis.^{313. and 314.} Serial fluctuation in pulmonary function measures of airflow obstruction most closely correlate with alterations in the degree of mucus plugging on serial HRCTs. ³¹⁵

Subtle degrees of volume loss may be seen in lobes in relatively early bronchiectasis and this is most evident in the lower lobes where crowding of the mildly bronchiectatic airways and posterior displacement of the oblique fissure may be an early sign of bronchiectasis (Fig. 12.30). CT will readily show completely collapsed lobes containing bronchiectatic airways although the diagnosis of bronchiectasis in acutely collapsed or consolidated lobes is usually considered uncertain because of the reversibility of bronchial dilatation in these situations.^{204. and 205.} An interesting and not readily explained accompaniment to bronchiectasis is thickening of the interlobular septa; this occurs in up to 60% of patients with idiopathic bronchiectasis and appears to be more prevalent in cases of more severe and extensive bronchiectasis³¹⁶ (Fig. 12.31).

Distortion and dilatation of segmental and subsegmental bronchi are predictable features in patients with retractile interstitial fibrosis, ³¹⁷ of whatever cause, and this has been termed (not particularly usefully) ‘traction bronchiectasis’. Many of the HRCT signs of bronchiectasis coexist, particularly in longstanding disease. The signs of bronchiectasis, discussed above, are summarized in Box 12.13 in the approximate sequence in which they occur.

There are several situations in which the signs of bronchiectasis may be obscured by technical artifacts, or mimicked by other lung pathologies,287. ^{and 288.} and these are summarized in Chapter 4 (Box 4.9, p. 189).

Cystic fibrosis, also known as cystic fibrosis of the pancreas, fibrocystic disease, and mucoviscidosis, is the most common autosomal recessive disorder in the Caucasian population, with a frequency of about 1 in 2500 livebirths.339. ^{and 340.} The disease is uncommon in African Americans and rare in Asians and Native Americans. Worldwide, 60 000 people are affected. ³⁴¹ Cystic fibrosis is caused by a mutation in a gene on chromosome 7 that codes for the cystic fibrosis transmembrane conductance regulator (CTFR).^{342. and 343.} Although over 800 mutations have been identified, ³⁴⁴ the most common mutation that causes cystic fibrosis is known as delta-F508. ³⁴² CFTR functions primarily as a chloride ion channel and the defective protein affects pancreatic function and the consistency of mucosal secretions. Although the defective gene has been identified, gene replacement therapy is still far from clinical realization. ³⁴⁵

The primary manifestations of cystic fibrosis include abnormal sweat electrolytes, sinus and pulmonary disease, exocrine pancreatic insufficiency, and male infertility. ³⁴⁶ However, most organ systems are affected, to a greater or lesser extent, because of the wide tissue distribution of CFTR, but the lungs bear the brunt of the disease. Despite major advances in treatment, pulmonary infection remains the major cause of morbidity and mortality.

Staphylococcus aureus and Haemophilus influenzae are the most common infecting organisms in the first decade of life, but infections caused by Pseudomonas and Burkholderia species dominate thereafter. By adulthood, 80% of patients are colonized with P. aeruginosa and 3.5% with Burkholderia cepacia, Stenotrophomonas maltophilia, and Achromobacter xylosoxidans. Nontuberculous mycobacteria are emerging as important pathogens in patients with cystic fibrosis, particularly Mycobacterium abscessus, M. avium–intracellulare, Mycobacterium fortuitum and Mycobacterium kansasii.^{347. and 348.} There are difficulties in interpreting the importance (colonization versus infection) of the presence of these organisms when they are isolated from the sputum of patients with cystic fibrosis, ³⁴⁹ especially because of the similarity in HRCT appearances of cystic fibrosis with or without nontuberculous infection.

Although the disease is present at birth, radiographic abnormalities may not become apparent for months or years, but thereafter are progressive (Fig. 12.32). The earliest findings are nonspecific and include diffuse bronchial wall thickening, focal atelectasis, and recurrent pneumonia. At this stage, the clinical features of the disease, not the chest radiographic findings, suggest the diagnosis. Progression of disease with worsening radiographic abnormalities is usually inexorable, despite treatment, but the rate of deterioration is highly variable. Patients with early manifestations of the disease tend to deteriorate the most rapidly. ³⁵⁰ In the fully developed form of the disease the radiographic findings are remarkably uniform and include the following:^{351.352.353.354. and 355.}

Parenchymal findings seen on chest radiographs of patients with longstanding cystic fibrosis are usually more severe in the upper than lower lungs (Fig. 12.34). Nevertheless, in younger children this upper lobe predominance may be less noticeable. ³⁵⁷

Chest radiographs over a number of years generally reflect the patient’s deteriorating status, but short-term clinical fluctuations are not necessarily accompanied by any readily detectable radiographic changes. Greene et al. ³⁵⁸ studied 14 specific radiographic findings in a group of adults with and without acute exacerbations of cystic fibrosis. They were unable to find a statistically significant association between any of the findings and the presence or absence of acute symptoms. These authors concluded that the value of the chest radiograph in the setting of an acute cystic fibrosis exacerbation lay more in excluding a major complication such as pneumothorax. In part, this must reflect the inherent difficulties in detecting small focal radiographic abnormalities against a background of diffuse bronchiectasis and lung destruction. Nevertheless, a number of scoring systems use findings on chest radiographs to grade the severity of cystic fibrosis.^{351. and 359.}

Common complications of cystic fibrosis include pneumothorax and hemoptysis. Pneumothorax is caused by rupture of emphysematous blebs or bullae. ³⁶⁰ Hemoptysis usually originates from hypertrophied bronchial arteries and varies in severity from minor blood-streaked sputum to massive hemoptysis (greater than 240 mL/24 h). ³⁶¹ Affected patients tend to have very severe lung disease and a high incidence of infection by multidrug-resistant bacteria. ³⁶¹ Bronchial artery embolization (BAE) is an effective treatment for cystic fibrosis patients with pulmonary bleeding.^{361.362. and 363.} Brinson et al. ³⁶¹ reviewed their experience with BAE in 18 patients treated over a 10-year period. They found that the overall efficacy of BAE for initial control of bleeding was 75% after one, 89% after two, and 93% after three treatments. Unfortunately, they also found that the rate of recurrent bleeding was high (46%); the mean time to recurrence was approximately 12 months. They also found a high incidence (75%) of bleeding from nonbronchial systemic collateral vessels in the patients who had undergone previous BAE, indicating the necessity of evaluating all potential systemic collateral vessels. Lung abscess and empyema are surprisingly uncommon complications of cystic fibrosis.

The CT findings of cystic fibrosis on conventional³⁶⁴ and thin-section CT have been extensively documented.^{235.236.334.365.366.367.368.369. and 370.} As might be expected, CT delineates the morphologic changes of cystic fibrosis with much greater accuracy and detail than chest radiographs. As with chest radiography, CT has only limited usefulness in the investigation of patients with acute exacerbations of cystic fibrosis. The only finding in the study of Shah et al. ³⁶⁸ that had a correlation with acute exacerbation was the presence of air–fluid levels. Another study has confirmed that changes in mucus plugging on HRCT are the most labile abnormality in acute exacerbations. ³⁷¹ Brody et al. ³⁷² have shown that scores of severity of disease on CT over a period correlate with the number of exacerbations in that period, although no CT feature reliably predicted exacerbations.

Numerous investigators have reported moderate to good correlation between functional impairment and CT findings using a variety of CT scoring methods.236.^{357.365.369.373.374.375.376. and 377.} While these methods for quantifying disease severity may be useful from a research standpoint, potentially providing surrogate endpoints in clinical trials, the usefulness of routine monitoring of individuals with cystic fibrosis with CT in everyday clinical practice remains controversial.^{378.379. and 380.}

The CT findings of CF vary with duration and severity of disease.^{236.357.365.369.370.373.374.381. and 382.} Bronchiectasis is the predominant abnormality. Cylindrical bronchiectasis is more common than cystic bronchiectasis, particularly in patients with mild lung disease.^{235. and 334.} Over time the bronchiectasis progresses and HRCT may depict changes in the face of stable or minimal decline in lung function^{382. and 383.} (Fig. 12.37). In advanced cases, both cylindrical and cystic forms of bronchiectasis tend to be more severe in the upper lungs (Fig. 12.38). Bronchial and peribronchial thickening is also a common finding on CT³⁸⁴ that reflects the chronic inflammatory changes in the bronchial wall. Mucus plugs, a very common finding, are seen to advantage with CT (Fig. 12.39). Abscesses may be difficult to distinguish from cystic bronchiectasis, particularly as both may contain air–fluid levels. Other CT findings include: focal areas of collapse or consolidation; tree-in-bud pattern; mosaic attenuation; bullae, hilar, and mediastinal adenopathy; and pleural thickening. Bullae may be difficult to distinguish from cystic bronchiectasis, particularly in fibrotic upper lobes (Fig. 12.40). A mosaic attenuation pattern likely reflects obstruction of small airways (Fig. 12.40). Pleural thickening is often apparent on chest radiographs and is demonstrated to advantage by CT. ²³⁵ The extent of such thickening may have some bearing on difficulties at lung transplantation, although it has been convincingly shown that assessment with pretransplantation CT is, in fact, of little value. ³⁸⁵ In some patients who develop a pneumothorax CT may usefully identify the optimal site for chest drain insertion because the visceral pleura is often tethered to the chest wall as a result of pleural adhesions³⁸⁶ (Fig. 12.41). The CT features of cystic fibrosis are summarized in Box 12.15.

MRI has been used for investigation of patients with cystic fibrosis;387. ^{and 388.} it can demonstrate many of the salient features of cystic fibrosis, but lacks the spatial resolution of CT. Donnelly et al. ³⁴⁴ used hyperpolarized ³He-enhanced MRI to image patients with cystic fibrosis. The technique is quite sensitive for small airway obstruction³⁸⁹ and can provide a means of evaluating progression of disease in patients with cystic fibrosis without use of ionizing radiation, a use which is likely to be limited to research applications.

The ciliary dyskinesia syndrome (CDS) is an example of one of many specific causes of bronchiectasis, and with changing patterns of etiology it is becoming relatively more important. In a selected series of patients referred to a specialist hospital for investigation of chronic cough and sputum production, ciliary dyskinesia was, after postinfection bronchiectasis, the most frequent etiology, ³⁹⁰ but was less prevalent in another series. ²¹⁵ In, ciliary dyskinesia, first identified in 1976, ³⁹¹ a variety of genetically determined defects in ciliary structure and function³⁹² interfere with mucociliary clearance. ³⁹³ Impaired mucus clearance is associated with recurrent upper and lower respiratory tract infections. ³⁹⁴ CDS shares many features with cystic fibrosis but is less disabling and carries a better prognosis.^{282. and 395.} Kartagener syndrome³⁹⁶– situs inversus, paranasal sinusitis, and bronchiectasis – is a subtype of CDS, and about 50% of patients with CDS have Kartagener syndrome^{282.394. and 397.} (see Fig. 12.21). About one-fifth of subjects with dextrocardia have Kartagener syndrome. ³⁹⁸ CDS has autosomal recessive transmission with an equal sex incidence. In Europe and the USA CDS has a prevalence of about 1 : 20 000 individuals. ³⁹⁹ Ciliary function is abnormal throughout the body, and sperm are immotile; thus males are infertile. Fertility in females is generally unaffected, although there are exceptions. ³⁹⁷ Respiratory symptoms may be delayed in onset but can generally be traced back to childhood, and CDS is increasingly recognized as a cause of neonatal respiratory distress.^{400. and 401.} Symptoms are those of bronchitis, rhinitis, and sinusitis, which are universal, and otitis, which is less common. Bronchiectasis develops in childhood and adolescence and is associated with recurrent infections. Prognosis is generally good, and the diagnosis is compatible with a full lifespan. ³⁹⁸ The diagnosis is regarded as established in the following circumstances: (1) complete Kartagener syndrome, (2) men with normal situs but a classic history and immotile sperm, (3) women and children with normal situs but typical history and an affected sibling, and (4) subjects with normal situs but with a classic history and ultrastructural defects of nasal or bronchial cilia on biopsy.^{394. and 402.} Findings on the chest radiograph and CT are of bronchial wall thickening (almost invariably) and bronchiectasis with a predilection for involvement of the middle lobe and lingula⁴⁰³ (Fig. 12.42). In a few patients with CDS there is abnormal calcium deposition within the affected airways, such that this may be visible on imaging; lithoptysis (coughing up of broncholiths) is also a rare association. ⁴⁰⁴

Young syndrome266. ^{and 267.} clinically resembles CDS. However, in Young syndrome ciliary function is normal and infertility is due to obstructive azoospermia. Obstruction occurs at the level of the epididymis, which is palpably enlarged. The pathogenesis of increased sinopulmonary infection in these patients is obscure.

Inflammation of the bronchioles (bronchiolitis) with or without subsequent scarring and obliteration is a very common lesion in the lungs. ⁴²⁴ However, the extent of such lesions is rarely extensive enough to cause clinical symptoms. Texts in the pathology often emphasize the frequent involvement of the bronchioles in diverse diffuse lung diseases.

The specific and classical term obliterative bronchiolitis (synonymous with bronchiolitis obliterans) has historically been the subject of confusion, primarily because of its use in the context of BOOP. The clinicopathologic entity of BOOP, now termed cryptogenic organizing pneumonitis,^{425. and 426.} is now regarded as quite distinct from obliterative bronchiolitis (Fig. 12.44). There are several reports in the older literature describing cases of ‘bronchiolitis obliterans’ whose pathologic descriptions contain all the hallmarks of an organizing pneumonia (characterized by buds of loose granulation tissue occupying the airspaces and respiratory bronchioles, without any obliteration of the small airways).^{427.428. and 429.} It is now generally accepted that there is no direct connection between obliterative bronchiolitis and BOOP, ⁴³⁰ such that in the interests of clarity most authorities suggest that the bronchiolitis obliterans part of BOOP should be discarded. In those patients in whom no causative agent for the organizing pneumonia can be found, the term cryptogenic organizing pneumonia is more appropriate⁴²⁶ (see p. 575).

The various conditions included within the term ‘small airways diseases’ are usually classified into pathologic subtypes or by less precise clinical criteria (usually by presumed cause or association). While pathologists categorize small airways diseases according to their histopathologic subtypes, the difficulty with this classical approach is that there are not always obvious clinical (or HRCT) correlates with these subtypes.^{431.432.433. and 434.}

A simple approach relies on the fundamental difference between the indirect HRCT signs of constrictive obliterative bronchiolitis and the direct visualization of exudative forms of bronchiolitis (typified by diffuse panbronchiolitis). ⁴³⁵ These two patterns of small airways disease account for the majority encountered in clinical practice. Other miscellaneous forms of small airways disease with more or less distinctive pathologic and imaging features, if not clinical presentations, are dealt with separately.

Asthma is an inflammatory condition of the airways characterized by abnormal reactivity of the bronchi to various stimuli and by airflow obstruction that is at least partly reversible. This definition does not specify the degree of variation of airflow, but it is usually taken to be 15–20% of predicted values.

The pathologic changes of asthma have been studied largely,^{594. and 595.} but not exclusively,^{596.597. and 598.} by postmortem examination of lungs of patients who have died as a direct consequence of their asthma. Such findings represent the severe end of a spectrum of change. On gross examination the lungs are overinflated and fail to deflate because of tenacious mucus plugs in medium-sized airways. Bronchial mucosa is damaged or shed, and there are submucosal edema and inflammatory cell infiltrates of eosinophils, sometimes with lymphocytes and plasma cells, causing bronchial wall thickening. Other changes contributing to a general thickening of the bronchial walls include mucus gland hypertrophy, basement membrane thickening, and smooth muscle hyperplasia. ⁵⁹⁹

Pulmonary function tests are often normal in remission. In acute asthma the findings are increased airway resistance, increased total lung capacity (TLC), and increased residual volume and functional residual capacity (FRC) with decreased vital capacity (VC), indicating air trapping. ⁶⁰⁰ Diffusing capacity for carbon monoxide (DLco), particularly when corrected for accessible alveolar volume (Kco), is preserved in nonsmoking asthmatic people, even when the condition is severe. ⁶⁰¹ Not surprisingly cigarette smoking adversely affects the pulmonary function profile of asthmatic individuals. ⁶⁰²

Chronic bronchitis is clinically defined as a chronic or recurrent increase in the volume of mucoid bronchial secretions sufficient to cause expectoration and occurring on most days for 3 months in 2 or more successive years, other causes for expectoration having been excluded.^{203.586. and 662.}

Chronic bronchitis is a common disease, affecting up to 20% of the adult population in some studies. ⁶⁶³ It seems to be much more common in males than females, ⁶⁶³ but when smoking habits are taken into account the difference is only 2 : 1. ⁵⁸⁷ Cigarette smoking is the most important factor associated with the development of chronic bronchitis. In eight combined series in England there was a sixfold rise in prevalence of chronic bronchitis, from 6.3% in nonsmokers to 40% in heavy smokers. ⁵⁸⁷ In epidemiologic studies a linear relationship exists between the amount smoked and the frequency of chronic bronchitis. ⁶⁶⁴ Less important factors include occupation, ⁶⁶⁵ environment, ⁶⁶⁶ age, and gender. ⁶⁶⁷ Given the subjective nature of the diagnosis, ⁶⁶⁸ it is not surprising that there appear to be substantial differences in the prevalence of chronic bronchitis even when there is no obvious difference in risk factors between cities in the same (Baltic) region. ⁶⁶⁹

The major pathologic changes are in the mucous glands, which show hypertrophy and hyperplasia and develop enlarged ducts. The enlargement of mucous glands can be quantified histologically using either the proportional mucous gland area or the Reid index, which is the ratio of gland thickness to bronchial wall thickness measured from epithelial basement membrane to perichondrium. ⁶⁷⁰ However, these indices do not clearly distinguish normal subjects from those with chronic bronchitis, since there is considerable overlap.^{671. and 672.} Other pathologic changes in chronic bronchitis include goblet cell hyperplasia, squamous metaplasia of the epithelium, and a variable and often mild⁶⁷⁰ chronic inflammatory cell infiltrate. ²⁰³ Mucous plugs occur in the smaller airways, which themselves may be stenotic.^{587.673. and 674.}

Chronic bronchitis typically occurs as a persistent productive cough following an acute chest infection. Such symptoms may persist for years with normal respiratory function tests and chest radiographs. Indeed the majority of such patients do not develop chronic airway obstruction, although they are at risk for recurrent episodes of purulent bronchitis. ⁶⁷⁵ In these patients the annual decrease in FEV₁ is within the normal range,^{675. and 676.} but, in heavy smokers, there is detectable airflow obstruction with a greater than predicted annual fall in FEV₁. These patients become dyspneic, with copious sputum, and tend to become hypoxemic. ⁶⁷⁷ In such patients pulmonary arterial hypertension and cor pulmonale may develop. The majority of acute exacerbations in chronic bronchitis can be ascribed to a lower respiratory tract infection; ⁶⁷⁸ up to 30% are viral but other organisms, including atypical bacteria, such as Chlamydia pneumoniae, may occasionally be responsible. ⁶⁷⁹ However, the exact role of bacterial infections in exacerbations of COPD remains controversial. ⁶⁸⁰

Radiographic signs in ‘pure’ chronic bronchitis are poorly documented (Box 12.26). Nearly all the available information is derived from three series of patients, in whom there may have been coexistent emphysema.^{681.682. and 683.} Overinflation of the lungs described in these reports is in conflict with the normal total lung capacity usually found in chronic bronchitis, ⁶⁸⁴ and can probably be ascribed to coexistent emphysema.

The majority of patients with symptoms of chronic bronchitis have a normal chest radiograph. ⁶⁸⁵ Radiographic signs of chronic bronchitis include bronchial wall thickening and ‘increased lung markings’. Bronchial wall thickening might be expected in chronic bronchitis because of the known pathologic changes in the airways. However, histologic studies suggest that the magnitude of these changes is small; in one report the absolute increase in gland thickness was only 0.1 mm. ⁶⁷² Bates and co-workers⁶⁸¹ described parallel line shadows on radiographs representing large airways seen side on (tramline opacities) in 42% of patients with chronic bronchitis. Ring shadows of approximately 6 mm in diameter adjacent to the upper poles of the hila represent the end-on anterior or posterior segmental airways of the upper lobes. This is a normal finding, whereas visible side-on airways (tramline opacities) are generally considered abnormal. Fraser and co-workers⁶⁸⁶ assessed the frequency of detection of end-on airways and their wall thickness in approximately 150 control subjects and 150 patients with chronic bronchitis. They found end-on airways visible in about 80% of both groups and a slight increase in wall thickness in chronic bronchitis, which was of limited value in distinguishing patients with chronic bronchitis from normal subjects (the sign was subject to significant interobserver variation). In functional terms, the ratio of wall thickness to external diameter in end-on airways does not appear to correlate with the degree of airflow obstruction. ⁶⁸⁷ Another radiographic sign described in the series of Bates and co-workers⁶⁸¹ was increased lung markings, detected in 18%. The sign consists of small, ill-defined linear opacities with or without accentuation of small vascular opacities. ⁶⁸⁵ It is a subjective sign that pathologic examination, in one study, was shown to correlate with perivenous edema, inflammatory cell infiltration, and fibrosis. ⁶⁸⁸

Support for the finding of bronchial wall thickening in chronic bronchitis has come from HRCT studies^{300. and 560.} in which proximal and distal bronchial wall thickening was present in 33% of smokers (compared with 18% of control subjects). ³⁰⁰ Contrary to expectation, HRCT has not fully elucidated the nature of the increased markings that constitute the ‘dirty lung’ of cigarette smokers, ⁶⁸⁹ but the spectrum of smoking-related parenchymal and airways is now better understood thanks largely to the investigations of Remy-Jardin.^{300.560. and 690.} Air-trapping ascribable to airways (size unknown) dysfunction in cigarette smokers can be readily detected using expiratory HRCT, and can be demonstrated even in those individuals with normal pulmonary function test results.^{561. and 691.} It has been shown that some parameters of histologic inflammation in cigarette smokers correlate with the degree of air-trapping as judged by attenuation of differences on inspiratory and expiratory HRCT in cigarette smokers. ⁶⁹²

Bronchial wall thickening cannot be regarded as a pathognomonic sign of smoking-related chronic bronchitis because it is nonspecific and is encountered in other inflammatory airway disease including asthma⁶³¹ and infective or suppurative airways diseases, in particular bronchiectasis. ³⁰⁵ A study which evaluated wall thickness of airways in patients with chronic obstructive pulmonary disease showed that those patients with symptomatic chronic bronchitis had markedly thicker bronchial walls than those not fulfilling the clinical criteria for chronic bronchitis. ⁶⁹³ Automated software has shown that cigarette smokers with functional evidence of COPD have thicker airways than smokers without COPD or nonsmokers. ⁶⁹⁴ Quantitative CT studies have shown that bronchial wall thickening, over and above the extent of emphysema evident on CT, contributes to functional airflow limitation in cigarette smokers (Fig. 12.69).^{695. and 696.}

Bronchial dilatation does not appear to be a clear-cut consequence of the bronchial wall inflammation associated with chronic bronchitis and, outside the ambit of age-related change²⁹⁸ and α₁-antitrysin deficiency, ³¹³ frank bronchiectasis does not seem to be a direct result of cigarette smoking. One of the original signs of chronic bronchitis, reported as a frequent finding in the era of bronchography, that is dilated mucous glands, seen as ‘bronchial pits’ on bronchograms, has been revisited by Zompatori et al., ⁶⁹⁷ who have pointed out that these small pits can be identified on CT along the inner surfaces of the large bronchi. These are shown to advantage on reformatted volumetric thin section CT (coronal reconstructions through the major airways) (Fig. 12.70). Whether this sign can be regarded as specific for chronic bronchitis (keeping in mind that Gamsu et al. ⁶⁹⁸ showed that such pits were relatively common in healthy adults on bronchography) is not known.