Constrictive (obliterative) bronchiolitis is a clinicopathologic entity of diverse causes denoting inflammation and fibrosis of bronchioles, usually concentric, resulting in obliterative changes. It is a subset of small airway disease characterized by progressive fibrosis limited to small airways. Both “constrictive” and “obliterative” bronchiolitis are used as clinical as well as pathologic designations. The first series with pathologic documentation appeared in 1977, at which time Geddes et al. reported six patients, five with rheumatoid arthritis, with progressive small airway disease leading to respiratory failure. In four autopsied patients from this series, the term “obliterative bronchiolitis” was used
to describe fibrotic small airways in the absence of features of asthma or chronic bronchitis.¹ Soon thereafter, Turton et al. reported 10 patients with “obliterative bronchiolitis” defined clinically (without pathologic confirmation) as obstructive small airway disease in nonsmokers that did not respond to steroid treatment.² In 1985, Epler et al. reported a pathologic series of bronchiolitis obliterans and contrasted the favorable prognosis of the group with organizing pneumonia to the unfavorable one of obliterative bronchiolitis.³ For this reason, constrictive bronchiolitis is not to be confused with “bronchiolitis obliterans organizing pneumonia” (cryptogenic organizing pneumonia; Chapter 19), which has dramatically different clinical, imaging, and pathologic findings.⁴ Unfortunately, the term “bronchiolitis obliterans” has been used interchangeably with constrictive bronchiolitis, necessitating careful evaluation of the older publications to distinguish concentric bronchiolitis from organizing pneumonia.⁵ Because of the potential confusion with organizing pneumonia, the term “constrictive” may be a preferred term over “obliterative,” although the latter term is entrenched, especially in the transplant literature (Table 37.1).

There are three major clinical settings of constrictive bronchiolitis: first is the disease that occurs in native lungs and is often associated with autoimmune diseases or inhalational exposure (see Table 37.1); the second form occurs in patients with stem cell transplants and is a chronic form of graft versus host disease (see Chapter 54); and the third is the hallmark of chronic allograft dysfunction in lung transplant patients (see Chapter 53).^6,7 The current chapter is devoted to primary constrictive bronchiolitis (the first of the three groups).

The initial insult in constrictive bronchiolitis is inflammation of the epithelium and subepithelial structures with aberrant tissue repair mechanism that leads to progression over time to marked narrowing of the lumen, or even obliteration. The remodeling of the airways is considered generally a consequence of immune responses that chronically lead to fibrosis.⁸ Because 50% or more of patients had evidence of rheumatologic disorders, autoimmunity is likely a role in many patients.¹ Studies of patients with bronchiolar constriction and ataxia-telangiectasia suggest that IgA deficiency and T-cell dysfunction may also lead to chronic inflammation and fibrosis in the bronchioles, perhaps triggered by bacterial or viral infections.⁵ Acquired and inherited hypogammaglobulinemias predispose to bronchiolar inflammation in the form of follicular bronchiolitis or diffuse panbronchiolitis but typically without significant fibrosis. Because a similar, if not identical, syndrome to constrictive bronchiolitis occurs after inhalation of smoke and particulate matter, direct injury to the airway epithelium may trigger an immunologically mediated fibrosing bronchiolitis. Although the pathogenesis of transplant-related obliterative bronchiolitis has been extensively studied (see Chapter 53), the pathogenesis of idiopathic constrictive bronchiolitis or the diseases unrelated to lung transplant or bone marrow transplantation is less understood.⁹

Constrictive bronchiolitis is rare; in one series of 2,500 native open lung biopsies, the diagnosis was rendered in 0.4% (10 cases).³

The most important symptoms of constrictive bronchiolitis are nonproductive cough, dyspnea, and signs of airflow obstruction, including wheezing, with slow progression over months to years.^1,2,10 Recurrent infections are common. Pulmonary function test findings include obstructive pattern with forced expiratory volume in 1 second (FEV1) of <60% predicted, air trapping, and clinical exclusion of other causes of obstruction. Rarely, there are predominantly restrictive parameters.¹¹ Typically (or even by definition), there is no improvement following inhaled bronchodilators or steroids.^12,13 In contrast, cryptogenic organizing pneumonia usually responds to steroid therapy.³

Evidence of rheumatologic or autoimmune disease, especially rheumatoid arthritis, is found in variable proportion of patients with constrictive bronchiolitis, ranging from 50% to 83%^1,2 to 20% to 27%.^11,14 In addition to rheumatoid arthritis, there is an association between inflammatory bowel disease, systemic lupus erythematosus, Sjögren syndrome, systemic sclerosis, dermatomyositis, and IgA nephropathy with constrictive bronchiolitis^4,14 (Table 37.2). Paraneoplastic pemphigus, an autoimmune disease that may complicate lymphomas
and other malignancies, usually affects large airways, but a constrictive bronchiolitis related to autoantibodies directed against plakin proteins occasionally occurs and may cause respiratory failure.¹⁵ Up to one-third of patients with constrictive bronchiolitis have autoantibodies without overt collagen vascular disease.¹¹ A further discussion of airway disease in patients with autoimmune disorders is presented in Chapter 50.

Chronic mycobacterial and mycoplasma infection may also predispose to constrictive bronchiolitis,¹⁴ as well as viral and bacterial infections in immunodeficiency syndromes, especially ataxia-telangiectasia.⁵ In contrast to ataxia-telangiectasia, which is associated with constrictive bronchiolitis, other inherited immunodeficiency syndromes, especially those associated with hypogammaglobulinemia, are more likely to result in follicular bronchiolitis (as seen in some patients with HIV disease) or diffuse panbronchiolitis. Constrictive bronchiolitis has rarely been reported in HIV infection, however.⁴

The rate of inhalational exposure in reported series of constrictive bronchiolitis is variable. There were no cases of inhalation in early series² and the largest clinicopathologic study reported just fewer than onethird with inhalational exposure, including two patients with histologic features of hypersensitivity pneumonitis.¹¹ More recently, it is believed that occult exposure may underlie a relatively larger proportion of obliterative bronchiolitis.¹⁶ A recent report of Middle East war veterans described a series of pathologically documented constrictive bronchiolitis related to inhalation of particulate matter from a combination of sulfur mine fires, incinerated waste, dust storms, and combat smoke.¹⁷ This series differed from previous reports of obliterative bronchiolitis in that the presenting symptom was dyspnea without significant cough, most patients did not have obstructive parameters, and the illustrated histologic findings were relatively subtle with minimal fibrosis, concomitant arterial intimal changes, and interstitial silicoanthracotic deposits.¹⁷ There have also been series of obliterative or constrictive bronchiolitis in fiberglass workers and those working in coffee-processing facilities.^18,19,20