9-10: Bronchiolitis

Bronchiolitis is a generic term applied to varied inflammatory processes that affect the bronchioles, which are small conducting airways less than 2 mm in diameter. In infants and children, bronchiolitis is common and usually caused by respiratory syncytial virus or adenovirus infection. In adults, bronchiolitis is less common but is encountered in multiple clinical settings. Disorders associated with bronchiolitis include organ transplantation, connective tissue diseases, and hypersensitivity pneumonitis. Inhalational injuries as well as postinfectious and drug-induced causes are identified by association with a known exposure or illness prior to the onset of symptoms. Idiopathic cases are characterized by the insidious onset of dyspnea or cough.

The clinical approach to bronchiolitis divides patients into groups based on etiology, but different clinical syndromes may have identical histopathologic findings. As a result, no single classification scheme has been widely accepted, and there is an overlapping array of terms to describe these disorders from the viewpoints of the clinician, the pathologist, and the radiologist.

Acute bronchiolitis has a neutrophilic and mononuclear infiltration in the absence of fibroblast proliferation or collagen deposition. Constrictive bronchiolitis (also referred to as obliterative bronchiolitis, or bronchiolitis obliterans) is characterized by patchy chronic inflammation, concentric submucosal and peribronchiolar fibrosis, and smooth muscle hypertrophy causing luminal obstruction (obliteration).

In contrast to the minimally cellular pattern of constrictive bronchiolitis, proliferative bronchiolitis occurs when there is an organizing intraluminal exudate, consisting of fibroblasts, lipid laden (“foamy”) macrophages, and other cells that obstruct the bronchiolar lumen. These findings are more common than the constrictive pattern. When the organizing intraluminal exudate extends through the bronchiole into the alveolar space, with prominent intraluminal buds of fibroblasts embedded in immature collagen, the proliferative pattern is referred to as cryptogenic organizing pneumonitis (COP) (see Table 9–17). Follicular bronchiolitis is characterized by chronic peribronchiolar inflammation and hyperplastic lymphoid follicles with reactive germinal centers arising from bronchus-associated lymphoid tissue (BALT). Respiratory bronchiolitis is a disorder of small airways in cigarette smokers characterized by accumulation of pigmented alveolar macrophages within respiratory bronchioles, associated with mild interstitial fibrosis and chronic inflammation. In some patients, however, respiratory bronchiolitis causes diffuse parenchymal infiltrates, a syndrome referred to as respiratory bronchiolitis–associated interstitial lung disease (RB-ILD) and considered with desquamative interstitial pneumonia (DIP) to represent part of the spectrum of the smoking-related interstitial lung diseases.

Diffuse panbronchiolitis is an idiopathic disorder of respiratory bronchioles, characterized by a peribronchiolar mixed inflammatory cell infiltrate and accumulation of lipid laden (“foamy”) macrophages within the interstitium and alveolar spaces.

Acute bronchiolitis can be seen following viral infections.

Constrictive bronchiolitis (also referred to as obliterative bronchiolitis, or bronchiolitis obliterans) is relatively infrequent, although it is the most common finding following inhalation injury. It may also be seen in rheumatoid arthritis; medication reactions; and chronic rejection following heart-lung, lung, or bone marrow transplant. Patients with constrictive bronchiolitis have airflow obstruction and air trapping on spirometry, unremarkable plain chest radiographs but heterogeneous airflow obstruction and air trapping on chest CT scans, and a progressive, deteriorating clinical course.

Proliferative bronchiolitis is associated with diverse pulmonary disorders, including infection, aspiration, ARDS, hypersensitivity pneumonitis, connective tissue diseases, and organ transplantation. Compared with constrictive bronchiolitis, proliferative bronchiolitis is more likely to have an abnormal chest radiograph.

Cryptogenic organizing pneumonitis (COP) affects men and women between the ages of 50 and 70 years, typically with a dry cough, dyspnea, and constitutional symptoms that may be present for weeks to months prior to seeking medical attention. A history of a preceding viral illness is present in half of cases. Pulmonary function testing typically reveals a restrictive ventilatory defect and impaired oxygenation. The chest radiograph frequently shows bilateral patchy, ground-glass or alveolar infiltrates, although other patterns have been described.

Follicular bronchiolitis is most commonly associated with connective tissue disease, especially rheumatoid arthritis and Sjögren syndrome, and with immunodeficiency states.

Respiratory bronchiolitis usually occurs without symptoms or physiologic evidence of lung impairment.

Diffuse panbronchiolitis is most frequently diagnosed in Japan. Men are affected about twice as often as women, two-thirds are nonsmokers, and most patients have a history of chronic pansinusitis. Patients complain of dyspnea, cough, and sputum production, and chest examination shows crackles and rhonchi. Pulmonary function tests reveal obstructive abnormalities, and the chest radiograph shows a distinct pattern of diffuse, small, nodular shadows with hyperinflation.

Constrictive bronchiolitis is relatively unresponsive to corticosteroids and is frequently progressive. Corticosteroids are effective in two-thirds of patients with proliferative bronchiolitis, and improvement can be prompt. Therapy is initiated with prednisone at 1 mg/kg/day orally for 1–3 months. The dose is then tapered slowly to 20–40 mg/day, depending on the response, and weaned over the subsequent 3–6 months as tolerated. Relapses are common if corticosteroids are stopped prematurely or tapered too quickly. Most patients with COP recover following corticosteroid treatment. Diffuse panbronchiolitis is effectively treated with azithromycin.