Fig. 3.5  (a) Normal inspiratory high-resolution CT scan image. (b) Expiratory high-resolution CT scan image showing characteristic mosaic pattern with areas of decreased and increased attenuation re ecting air trapping. Note that areas in which lung density remains virtually unchanged are indicative of substantial air trapping

Pulmonary Function Testing

In constrictive bronchiolitis, lung function may be normal or may show obstructive changes with air trapping. In proliferative bronchiolitis, a restrictive pattern is common. Diffusing capacity is usually reduced in both types, particularly as the disease progresses. Resting hypoxemia is frequently present in both patterns of bronchiolitis.

Lung Biopsy

In the majority of cases, an open or thoracoscopic lung biopsy is required to make a defnitive diagnosis [3]. A transbronchial lung biopsy is often inadequate for diagnosis. Tissue confrmation may not be necessary in patients with a

Mineral Dusts

Pathological changes in the small airways (respiratory bronchiolitis) secondary to exposure to inorganic mineral dusts, including asbestos, silica, iron oxide, aluminum oxide, several different sheet silicates, and coal have been reported [24, 25]. The clinical relevance of the lesions found in these subjects awaits a better defnition. Nevertheless, the development of air ow obstruction, rather than the classic restriction, is seen in subjects with inorganic mineral dust exposure.

Organic Dusts

Numerous agents are associated with the development of hypersensitivity pneumonitis. Although interstitial pneumonitis is seen in virtually 100% of patients with hypersensitivity pneumonitis and granulomas are seen in approximately 70%, bronchiolar lesions are seen in essentially all cases. The bronchioles contain granulomata within the walls or lumina or show tufts of granulation tissue as seen in bronchiolitis obliterans.

Volatile Flavoring Agents

Several reports have described the development of severe obstructive lung diseases in workers exposed to avoring chemicals at microwave popcorn plants and avoring production plants [26–30]. Chest radiographs showed hyperin-ation in several cases. HRCT fndings included diffuse cylindrical bronchiectasis and a mosaic pattern suggestive of air trapping [31]. This pattern suggests a predominant constrictive bronchiolitis pattern. Pathology consistent with obliterative bronchiolitis has been found [28].

Electronic cigarettes (e-cigarettes) are devices that produce an aerosol by heating a liquid containing various chemicals, including harmful substances, e.g., nicotine, avorings, vitamin E acetate, volatile organic compounds, heavy metals, ultrafne particles, and carbonyl compounds [32, 33]. E-cigarettes can also be used to deliver tetrahydrocannabinol (THC). The use of e-cigarettes (“vaping” or “dabbing”) has been associated with the development of severe lung diseases, including bronchiolitis obliterans [34, 35].

Infectious Causes of Bronchiolitis

Infection is the most common cause of acute bronchiolitis. Infectious causes of bronchiolitis are more commonly found in children than in adults. Acute bronchiolitis in older children and young adults has been primarily associated with Mycoplasma pneumoniae; however, a number of other viruses (e.g., respiratory syncytial virus (RSV), especially in the elderly) and bacterial agents have been identifed [2, 3]. The clinical presentation of infectious bronchiolitis in adults is not well-defned, and no systematic study has been reported. Most have a history of an upper respiratory tract illness that precedes the onset of dyspnea with exertion, cough, tachypnea, fever, and wheezing. Measles, varicella zoster, and pertussis have been reported to cause bronchiolitis obliterans in adults. A number of adults have developed an acute or subacute diffuse ventilatory obstruction that has occasionally been fatal.

Idiopathic Forms of Bronchiolitis

Several idiopathic clinicopathological syndromes associated with prominent involvement of the bronchioles have recently been reported. Although no specifc etiology has been identifed for these syndromes, the constellation of fndings in reported cases suggests that these are unique syndromes that must be distinguished from more common problems, such as COPD, pneumonia, or pulmonary fbrosis.

Cryptogenic adult bronchiolitis is a rare clinicopathological syndrome that is found in middle-aged women who

have a nonproductive cough, shortness of breath, or other nonspecifc chest complaints, usually of a relatively short duration (6–24 months) [36–39]. Few cases have been reported, and it is not entirely clear whether all of those reported are the same entity. The disorder is largely diagnosed by exclusion and requires a high index of suspicion, along with an awareness of its unique clinical features.

Airway-centered interstitial fbrosis is characterized by chronic cough and progressive dyspnea [8]. Most cases have not been smokers [40]. A history of possible inhalational exposures has been found in the majority of cases [9]. It is speculated that this is not a unique and specifc disease but may be a response to some occupational or environmental agent (especially hypersensitivity pneumonitis) or chronic aspiration [9, 10, 41–45]. Pathologically, airway-centered interstitial fbrosis is characterized by central-bronchiolar or centrilobular patchy distribution, peribronchiolar fbroplasia associated with smooth muscle hyperplasia, and hyperplasia of smooth muscles in vessel walls and extending around toward the lung parenchyma. Pulmonary architectural reconstruction, metaplastic bronchiolar epithelium (honeycomb lung formation under a microscope), and subpleural focal pulmonary fbrosis were also seen.

Connective Tissue Diseases

Bronchiolitis occurs infrequently in connective tissue diseases and is common in patients with rheumatoid arthritis (especially in association with Sjögren’s syndrome), both constrictive bronchiolitis and follicular bronchiolitis. The majority of patients are middle-aged women with seropositive rheumatoid arthritis. The clinical manifestations include an abrupt onset of dyspnea and dry cough, often associated with inspiratory crackles and a mid-inspiratory squeak. A positive rheumatoid factor is present, often at high levels (1:640–1:2560). Most patients have a chronic course. The prognosis is poor, with early deaths reported [46].

Organ Transplantation

“Bronchiolitis obliterans syndrome (BOS),” manifested by progressive air ow obstruction, is a frequent, noninfectious, post-transplantation respiratory complication [47]. The incidence of bronchiolitis obliterans among single lung recipients is approximately 20%; in double or bilateral sequential single lung recipients, the incidence is 12% [48]; however, double lung recipients showed a better chance of survival despite developing BOS compared to single lung recipients [49]. Bronchiolitis obliterans is the main pulmonary complication in long-term survivors of heart–lung transplantation. The prevalence has been estimated to be as high as 65% at