Chronic Bronchiolitis in Adults

Introduction

Bronchiolitis (or bronchiolitis obliterans) primarily affects the small conducting airways (3 mm or less in diameter), with limited involvement of the interstitium. The small airways, bronchioles, are divided into terminal (membranous) and respiratory bronchioles (Fig. 3.1). Bronchiolitis results from damage to the bronchiolar epithelium, resulting in some degree of in ammation, narrowing, or obliteration of the small airways. The severity and persistence of the injury may determine whether there is resolution and recovery or progression to a less reversible intramural or intraluminal fbrotic state.

There may be extensive damage to the small airways before the patient becomes symptomatic or develops detectable abnormalities on lung function testing. Most cases have

an insidious onset characterized by cough or dyspnea. Initially, patients are assumed to have more common problems, such as asthma or chronic obstructive pulmonary disease (COPD).

The epidemiology of bronchiolitis is poorly understood. Bronchiolitis in infants and children is recognized worldwide and is often associated with outbreaks of infection (especially respiratory syncytial virus and rhinovirus) [1]. Adult bronchiolitis is rare and has not been well-studied. Many cases are associated with accidents that result in inhalation injuries.

This chapter reviews the clinical, radiographic, and histopathological fndings of the bronchiolar syndromes in adults and is orientated toward practical management. More exhaustive reviews can be found elsewhere [2, 3].

Fig. 3.1  The junctional area between the purely conductive airways and the respiratory portion of the lung. The terminal (non-respiratory) bronchiole has a continuous cuboidal epithelium, whereas the alveoli open off the respiratory bronchiole. (Courtesy of Marco Chilosi, MD, Dipartimento di Patologia, Università di Verona)

Terminal bronchiole

Respiratory bronchioles

Alveolar ducts

Alveolar sacs

Classi cation

“Bronchiolitis” is often confusing because the term describes both a clinical syndrome and a constellation of histopathological abnormalities that may occur in a variety of disorders.

Thus, two classifcation schemes appear useful in defning cases of bronchiolitis: (1) a clinical classifcation based on the etiology (Table 3.1) and (2) a histopathological classifcation, which includes two major morphological types (proliferative bronchiolitis and constrictive bronchiolitis) [3].

“Cellular bronchiolitis” is a descriptive histological term that refers to in ammatory infltrates that involve the lumen, the walls of bronchioles, or both. The in ammation may be acute, chronic, or both.

Follicular Bronchiolitis

Follicular bronchiolitis is a distinctive subset of cellular bronchiolitis characterized by the dramatic proliferation of lymphoid follicles with germinal centers along the airways and an infltration of the epithelium by lymphocytes (lymphoid hyperplasia of bronchus-associated lymphoid tissue (BALT)) (Fig. 3.2) [4, 5]. Most cases occur in patients with connective tissue diseases (e.g., rheumatoid arthritis (RA) and Sjögren’s syndrome) [4, 6]. Other associations include immunodefciency syndromes, familial lung disorders, chronic infections, and a heterogeneous group of patients with a hypersensitivity-type reaction [4].

Small airway

Respiratory bronchiolitis is characterized by a cellular reaction in and around respiratory bronchioles. There is mild in ammation of the walls of the respiratory bronchioles, which extends to involve the adjacent alveoli [7]. Slight fbrosis may be present. This lesion is common in smokers and is often associated with a prominent increase in pigmented macrophages in the airway lumina and alveolar spaces.

Airway-Centered Interstitial Fibrosis

Airway-centered interstitial fbrosis (ACIF), also called idiopathic bronchiolocentric interstitial pneumonia and chronic bronchiolitis with fbrosis, is characterized by centrilobular and bronchiolocentric in ammatory infltrates with peribronchiolar fbrosis and an absence of granulomas [8, 9]. The typical patient is a middle-aged woman (40–50 years old) with a chronic nonproductive cough. Many cases are believed to be characteristic of hypersensitivity pneumonitis on clinical grounds, although no specifc antigen has been identifed [10]. Unlike hypersensitivity pneumonitis, the percentage of lymphocytes on bronchoalveolar lavage (BAL) is less than 40% [9]. Many of the reported patients have a history of smoking, raising concerns that cigarette smoking may be a contributor to airway injury. Chronic silent microaspiration and toxic or hypersensitivity reactions may contribute to the development of this pattern of injury in some patients.

Alveolar

walls

Lymphoid follicles

Fig. 3.2  Follicular bronchiolitis. Prominent lymphoid follicles adjacent to and impinging on the distal airways. (Courtesy of Jeffrey L Myers, MD, Department of Pathology University of Michigan)

Difuse Panbronchiolitis

Diffuse panbronchiolitis is an in ammatory process characterized by mononuclear cell in ammation of the respiratory bronchioles and the presence of foamy macrophages in the bronchiolar lumina and adjacent alveoli (Fig. 3.3). These fndings often produce nodular lesions [11]. This distinctive form of small airway disease is relatively common in Japan, China, and Korea; it is rare in other parts of the world [11, 12].