Asthma is a chronic inflammatory disorder involving both large and small airways associated with airway obstruction that is reversible either spontaneously or with treatment. Its incidence has increased over the last two decades. Asthma is diagnosed clinically, and traditionally, the surgical pathologist is not asked to diagnose asthma by examining tissue. However, characteristic histopathologic changes occur as a result of asthma. Therefore, the surgical pathologist will not receive a transbronchial biopsy for the specific purpose of diagnosing asthma but may encounter histopathologic changes due to asthma in a transbronchial biopsy performed for infection or other reasons. The pathologist should recognize the findings of asthma so they are not interpreted as some other type of pathologic process. On endobronchial or transbronchial biopsy, airway inflammation is the primary feature of asthma. Bronchial walls contain a mixed inflammatory infiltrate with a preponderance of eosinophils, hyperplastic bronchial and bronchiolar smooth muscle, basement membrane thickening, and goblet cell metaplasia within bronchial and bronchiolar epithelium. Transbronchial biopsy may show significant inflammation within surrounding alveolar septa.

Chronic bronchitis is clinically defined as persistent cough accompanied by sputum production lasting at least 3 months over at least 2 consecutive years, not attributable to another lung or heart condition. Chronic bronchitis, along with emphysema and obstructive bronchiolitis, are the three morphologic forms of chronic obstructive pulmonary disease (COPD), and they often present as a combination in individual patients. Mucus hypersecretion is a feature of the disease. The pathogenesis of chronic bronchitis involves chronic irritation by inhaled substances and microbiologic infections. The primary cause of chronic bronchitis is cigarette smoking.

As with asthma, chronic bronchitis is a clinical diagnosis, and the pathologist will not be asked to diagnose chronic bronchitis by examining tissue. However, similar to asthma, chronic bronchitis produces characteristic histopathologic changes, and these may be encountered on transbronchial biopsy performed for exacerbation of symptoms or to rule out infection or malignancy. Histologically, chronic bronchitis exhibits enlargement of mucus-secreting glands within the trachea and bronchi, increased inflammatory cells, specifically lymphocytes, and goblet cell metaplasia within bronchial and bronchiolar walls. Increased bronchial smooth muscle may arise in bronchial walls, and squamous
metaplasia and dysplasia may be found in bronchial mucosa. The basement membrane thickness is within the normal range. Submucosal bronchial gland enlargement is an important feature of chronic bronchitis, and the Reid index assists in its evaluation. The Reid index, the calculated ratio of submucosal gland layer thickness to total airway wall thickness, from epithelium base to inner cartilage surface, is generally >0.5. The normal Reid index is 0.3.

Asthma and chronic bronchitis share many histologic features; however, the thickening of the basement membrane with asthma, and the normal range of its thickness with chronic bronchitis, is a key difference between these diseases histologically. Nonetheless, a study by Bourdin et al. found that routine analyses of endobronchial biopsy specimens, performed in the hope of discriminating between the two diseases in complicated cases such as smokers with asthma, do not appreciably assist in differentiating between these diseases.

Tracheobronchial amyloidosis, along with nodular amyloidosis (amyloid tumor) and diffuse alveolar-septal amyloidosis, is one of three patterns of respiratory tract involvement in this rare condition. The tracheobronchial form is generally limited to the submucosa of the trachea and major bronchi but may be found in smaller segmental airways. There may be diffuse thickening and nodularity of the airway mucosa or a more localized nodule or plaque that may obstruct an airway, mimicking a tumor at endoscopy.

Patients, mostly 60 to 70 years of age, are generally symptomatic with dyspnea and cough; hemoptysis is rarely reported. Most of these cases are localized primary amyloidosis, and although around 10% may show serum or urinary monoclonal proteins, associated lymphoproliferative disorders are uncommon.

Bronchial biopsies show an irregular deposition of amorphous, hyaline eosinophilic material in the connective tissues of the submucosa. This may show localized clumping with nodule formation. Deposition may be accentuated around blood vessels and bronchial glands, cuffing the latter in a ring of eosinophilic homogenous deposit. In general the submucosa is relatively paucicellular, but there may be lymphocytes, macrophages, plasma cells, and even multinucleated giant cells admixed with the amyloid. Osseous metaplasia may occur. The Congo Red stain is most useful for identifying the amyloid nature of the eosinophilic deposits, giving the amyloid protein a deep orange or reddish hue when viewed by ordinary light, and more specifically showing (apple-green) birefringence during polarizing microscopy.

Immunohistochemistry may be used as a supplement to diagnosis but is not necessary. Most tracheobronchial amyloid is AL-type protein, although some cases may demonstrate AA or ATTR (transthyretin) types.

Differential diagnosis includes light chain deposition disease, a carcinoid tumor stroma, basement membrane thickening in asthma or as a cross-cutting artifact, and tracheobronchopathia osteochondroplastica.