After the initial insult, inflammation affecting terminal bronchioles, respiratory bronchioles, and alveolar ducts can result in the obliteration of the airway lumen (Fig. 386-1). Epithelial damage resulting in abnormal repair is characteristic of BO. Complete or partial obstruction of the airway lumen can result in air trapping or atelectasis. Bronchiolitis obliterans organizing pneumonia (BOOP) is a fibrosing lung disease that includes the histologic features of BO with extension of the inflammatory process from distal alveolar ducts into alveoli and proliferation of fibroblasts. BOS appears histologically similar to BO. The etiology of BOS is unclear, however, and may be unrelated to the mechanisms responsible for BO in nontransplant patients.

Figure 386-1 Complete obliteration of airway lumen with fibromyxoid tissue in lung transplant recipient with bronchiolitis obliterans.

(From Kurland G, Michelson P: Bronchiolitis obliterans in children, Pediatr Pulmonol 39:193–208, 2005.)

Clinical Manifestations and Diagnosis

Cough, fever, cyanosis, dyspnea, chest pain, and respiratory distress followed by initial improvement may be the initial signs of BO. In this phase, BO is easily confused with pneumonia, bronchitis, or bronchiolitis. Progression of the disease can ensue, with increasing dyspnea, chronic cough, sputum production, and wheezing. Physical examination findings are usually nonspecific and can include wheezing, hypoxemia, and crackles. Chest radiographs may be relatively normal compared with the extent of physical findings but can demonstrate hyperlucency and patchy infiltrates. Occasionally, a Swyer-James syndrome (unilateral hyperlucent lung; Chapter 384) develops. Pulmonary function tests demonstrate variable findings but typically show signs of airway obstruction. Ventilation-perfusion scans reveal a typical moth-eaten appearance of multiple matched defects in ventilation and perfusion. Chest CT often demonstrates patchy areas of hyperlucency and bronchiectasis. Physical and radiologic signs can wax and wane over weeks or months. Open lung biopsy or transbronchial biopsy remains the best means of establishing the diagnosis of BO or BOOP.

Treatment

No definitive therapy exists for BO. Administration of corticosteroids may be beneficial. Immunomodulatory agents such as sirolimus, tacrolimus, aerosolized cyclosporine, and macrolide antibiotics have been used in post–lung transplant recipients with BO with variable success. Infliximab, a monoclonal antibody that binds tumor necrosis factor-α (TNF-α), has been successful in 1 patient with BO after a bone marrow transplant. Azithromycin may be effective in patients with BOS. For BOOP, use of oral corticosteroids for up to 1 yr has been advocated as first-line therapy for symptomatic and progressive disease. Patients with asymptomatic or nonprogressive BOOP can be observed.

Prognosis

Some patients with BO experience rapid deterioration in their condition and die within weeks of the initial symptoms; most nontransplant patients survive with chronic disability. BOS has a higher mortality rate. Unlike in BO, total recovery is seen in 60-80% of patients with BOOP, although this depends on the underlying systemic disease. BOOP can relapse, especially if treatment is <1 yr and is amenable to repeat courses of oral corticosteroids. Unlike the more common idiopathic BOOP, progressive BOOP characterized by acute respiratory distress syndrome (ARDS) is rare but is aggressive in its clinical course, leading to death.

Bibliography

Epler GR. Bronchiolitis obliterans organizing pneumonia. Arch Intern Med. 2001;161:158-164.

Fullmer JJ, Fan LL, Dishop MK, et al. Successful treatment of bronchiolitis obliterans in a bone marrow transplant patient with tumor necrosis factor-α blockade. Pediatrics. 2005;116:767-770.

Hardy KA, Schidlow DV, Zaeri N. Obliterative bronchiolitis in children. Chest. 1988;93:460-466.

Kurland G, Michelson P. Bronchiolitis obliterans in children. Pediatr Pulmonol. 2005;39:193-208.

Moonnumakal SP, Fan LL. Bronchiolitis obliterans in children. Curr Opin Pediatr. 2008;20:272-278.

Zhang L, Irion K, Kozakewich H, et al. Clinical course of postinfectious bronchiolitis obliterans. Pediatr Pulmonol. 2000;29:341-350.

386.2 Follicular Bronchitis

Steven R. Boas

Follicular bronchitis (FB) is a lymphoproliferative lung disorder characterized by the presence of lymphoid follicles coursing alongside the airways (bronchi or bronchioles) and infiltration of the walls of bronchi and bronchioles. Although the cause is unknown, an infectious etiology (viral) has been proposed. It can occur in adults and children; in children, onset of symptoms generally occurs by 6 wk of age and peaks between 6 and 18 mo. Cough, moderate respiratory distress, fever, and fine crackles are common clinical findings. Fine crackles generally persist over time, and recurrence of symptoms is common. Chest radiographs may be relatively benign initially (air trapping, peribronchial thickening) but evolve into the typical interstitial pattern. Chest CT can show a fine reticular pattern. Definitive diagnosis is made by open lung biopsy. Some patients with FB respond to therapy with corticosteroids. Prognosis is variable, with some patients having significant progression of pulmonary disease and others developing only mild obstructive airway disease. In children it is generally associated with immunodeficiency; the differential diagnosis includes the pulmonary complications of HIV infection.

Bibliography

Bramson RT, Cleveland R, Blickman JG, et al. Radiographic assessment of follicular bronchitis in children. AJR Am J Roentgenol. 1996;166:1447-1450.

Kinane BT, Mansell AL, Zwerdling RG, et al. Follicular bronchitis in the pediatric population. Chest. 1993;104:1183-1186.

Yousem SA, Colby TV, Carrington CB. Follicular bronchitis/bronchiolitis. Hum Pathol. 1985;16:700-706.

386.3 Pulmonary Alveolar Microlithiasis

Steven R. Boas

Approximately 400 cases of pulmonary alveolar microlithiasis (PAM), an unusual disorder, have been reported. Although the underlying cause of PAM is unknown, the disease is characterized by the formation of lamellar concretions of calcium phosphate or “microliths” within the alveoli, creating a classic pattern on the radiograph (see Fig. 386-2 on the Nelson Textbook of Pediatrics website at www.expertconsult.com).

Figure 386-2 Radiograph of the chest of a 7 yr old boy with pulmonary alveolar microlithiasis.

(From Clark RB III, Johnson FC: Idiopathic pulmonary alveolar microlithiasis: a case report and brief review of the literature, Pediatrics 28:650, 1961.)

Epidemiology and Etiology

Although the mean age at time of diagnosis is in the mid 30s, the onset of the disease can occur in childhood. A strong familial association is seen in 50% of the reported cases, with a probable autosomal recessive pattern of inheritance. In some families, progression of disease is rapid. An equal male and female incidence is noted. A relatively large proportion of patients with PAM have Turkish ancestry. The nonfamilial or sporadic form appears to be associated with other medical conditions including mitral stenosis, nephrolithiasis, pulmonary fibrosis, milk alkali syndrome, or environmental factors (sand).

Clinical Manifestations

When symptomatic, patients with PAM usually complain of dyspnea on exertion and nonproductive cough. Physical examination of the lungs can reveal fine inspiratory crackles and diminished breath sounds. Clubbing occurs, although this is usually a more advanced sign. Discordance between the clinical and radiographic manifestations is common. Children are often asymptomatic on initial presentation. Complications of pneumothorax, pleural adhesions and calcifications, pleural fibrosis, apical bullae, and extrapulmonary sites of microliths have been reported (kidneys, prostate, sympathetic chain, and testes).

Diagnosis

Chest radiography typically reveals bilateral infiltrates with a fine sandlike micronodular appearance or “sandstorm” appearance with greater density in the lower and middle lung fields (see Fig. 386-2). CT of the chest shows diffuse micronodular calcified densities, with thickening of the microliths along the septa and around distal bronchioles, especially in the inferior and posterior regions. Diffuse uptake of technetium-99 methylene diphosphonate (^99mTc) by nuclear scan has been reported. Open lung and transbronchial lung biopsy reveal 0.1-0.3 mm laminated calcific concretions within the alveoli. Although the alveoli are often normal initially, progression to pulmonary fibrosis with advancing disease usually ensues. Sputum expectoration might reveal small microliths, although this finding is not diagnostic for PAM and is not typically seen in children. Pulmonary function testing reveals restrictive lung disease with impaired diffusing capacity as the disease progresses, whereas exercise testing demonstrates arterial oxygen desaturation. The differential diagnosis includes sarcoidosis, miliary tuberculosis, hemosiderosis, healed disseminated histoplasmosis, pulmonary calcinosis, and metastatic pulmonary calcifications.