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Page 3 Bronchiolar
Airway Disorders and Bronchiolitis Obliterans
BRONCHIOLITIS OBLITERANS The term bronchiolitis obliterans will be utilized for the clinical disorders characterized by airflow obstruction and with pathological findings showing constrictive bronchiolitis or bronchiolitis obliterans with intraluminal polyps (proliferative bronchiolitis obliterans) (35,36). The correlation between the pathological findings and corresponding clinical findings continues to be defined. There is probably a spectrum of clinical consequences, which may depend on the number of bronchioles involved. For example, in a clinical correlation study of four patients with the pathological finding of constrictive bronchiolitis, there was a spectrum of clinical findings of normal physiological studies to severe airflow obstruction (37), and similar findings were noted in a study of nine patients (38). There appears to be a radiographic correlation between these two histological findings. Constrictive bronchiolitis tends to be associated with lobular areas of decreased attenuation and airway dilatation, and bronchiolitis obliterans with intraluminal polyps (proliferative bronchiolitis obliterans) is characterized by air-space opacification (39). There may also be a correlation between steroid-responsiveness and these two lesions. Patients with the constrictive pattern often do not respond to corticosteroid therapy while those with the intraluminal polyps (proliferative bronchiolitis obliterans) pattern often respond and often with complete resolution. Idiopathic or cryptogenic bronchiolitis obliterans is defined as the disorder that occurs in patients who have no obvious inciting agent or associated systemic disorder, yet who clinically have airflow obstruction and constrictive bronchiolitis histologically. The occurrence of this disorder continues to be very rare, despite the recent interest in bronchiolar diseases. Idiopathic bronchiolitis obliterans with the constrictive bronchiolitis pattern is a distinctly different clinical syndrome compared to idiopathic BOOP, Table 5. Common features may include a preceding flu-like illness and dyspnea, but the chest physical findings differ, early inspiratory crackles are present in bronchiolitis obliterans, late inspiratory crackles in BOOP. Chest radiographs are also different, normal or slight hyperinflation in bronchiolitis obliterans and bilateral patchy infiltrates in BOOP. Pulmonary function shows airflow obstruction with FEV1 and FEV1/FVC reductions in the former and abnormal diffusing capacity in the latter. Response to therapy and prognosis differ markedly. In patients with bronchiolitis obliterans, there is variable response to corticosteroid therapy from none to some improvement, while complete recovery is expected in 65 to 80 percent of patients with BOOP. Thus, the distinction is important for successful management of the patient. Patients with idiopathic bronchiolitis obliterans develop a non-productive cough, then dyspnea with duration of symptoms varying from a few months to several years. On physical examination, wheezes are not heard; however, early inspiratory crackles may be heard. Physiological studies show airflow obstruction with no improvement in FEV1 after bronchodilator inhalation. The diffusing capacity is highly variable, from increased, to normal, to markedly decreased. The chest roentgenogram is often normal or shows mild hyperinflation. High resolution chest CT scans may show low attenuation areas in the secondary pulmonary lobules. Prognosis is poor for patients with the constrictive bronchiolitis pattern, despite corticosteroid therapy. Three months of high-dose prednisone (one mg/kg) is often needed to determine effectiveness, with tapering doses for three more months and lower dosages for at least one year. Patients who survive the initial episode may stabilize for several years (37) or progress to end-stage airflow disease and cor pulmonale. In these patients, it is difficult to determine whether progression is a continual process, or is due to intermittent infections with incremental loss of function over time. Lung transplantation may be effective for patients who are non-responsive to therapy and who develop chronic respiratory failure. A report of a 43 year old woman who had idiopathic obliterative bronchiolitis for 24 years showed a relentless progression of airway obstruction with 19 admissions for respiratory failure (23). The autopsy showing narrowing at all levels of the bronchial airways and complete obliteration of large numbers of smaller airways. The FEV1 decreased from 1.06 liters to 0.40 liters at the terminal stage. The chest CT findings in idiopathic bronchiolitis obliterans may have the appearance of diffuse panbronchiolitis as noted in a report of a 68 year-old man (40). The patient had dyspnea and a nonproductive cough for one year, fine crackles, a vital capacity of 2.56 liters (68% predicted), an FEV1 of 1.69 liters (50% predicted), and an FEV1/FVC of 66 percent. The diffusing capacity was 126% predicted. The chest roentgenogram showed micronodular opacities, which had also been present in a film of six years previously. The chest CT showed small peripherally rounded and branching linear opacities. Proximal bronchioles showed thickened walls and dilatation and were connected to peripheral nodules or small ring-like cystic lesions. The histology of a lung biopsy obtained by video thoracoscopy showed some bronchioles completely replaced by fibrotic scar and others with dilated lumens and mucus stasis. The fibrotic tissue had spread into the peribronchiolar tissue with poorly-defined edges. Toxic Fume Bronchiolitis Obliterans Toxic fume bronchiolitis obliterans results from exposure to nitrogen dioxide, sulfur dioxide, and other agents that cause a spectrum of symptoms from mild nasal and throat irritation to immediate asphyxiation and death. Mild symptoms usually resolve without residual effects. The irreversible stage of bronchiolitis obliterans begins with a latent period of no respiratory symptoms for several hours after exposure followed by diffuse alveolar damage and respiratory failure four to six hours later. If recovery occurs, in one to three weeks, some patients then develop irreversible airflow obstruction due to constrictive bronchiolitis with an extensive obliterative component. This is a late lesion and lung biopsy shows irreversible scarring of the bronchioles. At this stage, the findings are identical to idiopathic bronchiolitis obliterans, early inspiratory crackles, a radiograph that is normal or shows hyperinflation and airflow obstruction. The use of potentially toxic chemicals in manufacturing processes is increasing through out the world resulting in an increased possibility of exposed workers developing bronchiolar disorders. For example, two workers in a lithium battery factory were accidentally exposed to thionyl-cholride, and one of them developed a prolonged clinical course and findings consistent with bronchiolitis obliterans (41). This acidic compound is used in the manufacturing process and produces SO2 and HCL fumes when in contact with water. A 1992 study of 20 patients with silo filler's disease in New York (42) confirmed that the irreversible constrictive bronchiolitis lesion is rare; however, the mortality from the acute process remains high, 20 percent died within the first 24 hours from acute alveolar injury and massive pulmonary edema. Among these 20 patients, exposures occurred during September and October, and corn silage was the exposure source in 90 percent. All were young men with an average age of 32 years. Dyspnea was the most common symptom; two of the 16 survivors had persistent respiratory complaints. One patient presented with delayed onset bronchiolitis. This patient became ill in November with five days of fever and progressive dyspnea and a chest radiograph that showed bilateral small nodular opacities. Six weeks previously, he had entered a silo the day after it was filled with corn silage. After three or four breaths, he was nearly overcome, climbed out of the silo and had moderate shortness of breath for several days. He was treated successfully with corticosteroid therapy and had no residual radiographic or clinical effects. A possible occurrence of bronchiolitis obliterans was described in a 39 year-old truck driver who delivered fly ash and developed acute respiratory failure requiring hospitalization (43). The chest radiograph showed bilateral infiltrates, and this episode rapidly improved with corticosteroid therapy. After two weeks, he returned with significant dyspnea. The vital capacity was normal at 5.44 liters (102% predicted), but the FEV1 was decreased to 2.13 liters (52% predicted) and the FEV1/FVC ratio was severely decreased to 39 percent. It was not known whether the direct effect of the fly ash particles, or whether toxic agents such as nitrogen dioxide or sulfur dioxide adsorbed to the fly ash particle caused the injury. Smoke inhalation bronchiolitis obliterans was described in a 23 year-old man who was in a fire while sleeping in his newly constructed house (44). He was unconscious when rescued. He had black sputum production containing soot. There was cough and mild dyspnea after recovery; however, he returned three years later because of persistent dyspnea. He had finger clubbing, an FEV1 of 0.90 liters, and an FEV1/FVC of 34 percent. Transbronchial biopsy showed chronic inflammatory changes in the bronchioles. The synthetic structural materials utilized to build his house produced gases that contained acrolain, formaldehyde, acetaldehyde, NO2, and SO2 when burned. Post Infectious Bronchiolitis Obliterans Post infectious bronchiolitis obliterans may occur after a viral or mycoplasma infection (25). Cough develops several days after the initial infection. Chest radiographs may show diffuse reticular nodular opacities early but are normal or show hyperinflation in the late phase of the illness. The diagnosis is often suspected clinically. Lung specimens may show bronchiolitis obliterans with intraluminal polyps that heals without a scar with complete clinical resolution, or constrictive bronchiolitis with extensive scarring that obliterates many of the bronchioles corresponding clinically with severe airflow obstruction. Among the latter group of patients the illness may be fatal. Clinically, the illness is the same as idiopathic constrictive bronchiolitis obliterans. Swyer-James syndrome is a variant of postinfectious constrictive bronchiolitis. It usually develops as a sequel of pulmonary infection in infancy or early childhood and leads to alveolar destruction and obliterative bronchiolitis (45). Such an infection may prevent the normal development of the affected lung resulting in decreased lung volume and decreased blood flow which radiographically is characterized by unilateral hyperlucent lung with normal or reduced volume during inspiration and air trapping during expiration (19). The CT scan can be a valuable imaging method for evaluating unilateral hyperlucent lung. In a group of nine patients, the CT scan showed loss of lung volume in all cases, decreased attenuation values, and a markedly diminished vasculature and integrity of the main airways (45). Six of the nine patients had serious chest infection in childhood, three with bacterial pneumonia, two with pulmonary tuberculosis and one with frequent episodes of lower respiratory tract infections. The hyperlucent lung occurred on the left side in seven and on the right side in two. Cylindrical or cystic bronchiectasis occurred in six. CT scans performed at maximal expiration in four patients showed air trapping with a shift of the mediastinum towards the normal lung. A report of a 51 year-old woman showed radiographic findings that on expiration the abnormal lung deflates only partially and the mediastinum shifted to the center or into the more normal lung (46). This patient had chronic cough and progressive dyspnea after a severe pneumonia as an infant and recurrent lower respiratory tract infections as an adult, findings suggesting Swyer-James or Macleod's Syndrome.
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