Bronchiolitis Obliterans Organizing Pneumonia

Abstract

The authors define BOOP and present its epidemiology, pathophysiology, clinical manifestations, differential diagnosis, diagnostic studies, and treatment and describe nursing interventions.Bronchiolitis obliterans organizing pneumonia (BOOP) is a form of interstitial lung disease with unique signs and symptoms, radiological findings, and prognostic indicators.1 BOOP was first described as a separate disease by Epler et al2 in 1985 and since then has been extensively investigated and has been reported to occur throughout the world.3 BOOP is clinicopathological syndrome that is an important cause of acute respiratory illness in adults. Patients experience a subacute onset of mild dyspnea, a nonproductive cough, bilateral crackles, sore throat, fever, and malaise. In this article, we define BOOP and present its epidemiology, pathophysiology, clinical manifestations, differential diagnosis, diagnostic studies, and treatment and describe nursing interventions. A case study illustrates the difficulty in diagnosing and treating BOOP.Defining BOOP requires an awareness of bronchiolitis. Bronchiolitis is a generic term used to describe a variety of inflammatory diseases that affect the bronchioles. Bronchiolitis is a common pathological change but is rarely marked enough to cause clinical signs or symptoms.4,5 Obliterans refers to the ability of the pathological change to obliterate, eradicate, or destroy the airways. The term bronchiolitis obliterans was first used in the literature in 1901 by Lange to describe a group of patients who had submucosal and peribronchiolar fibrosis leading to obliteration of the bronchiolar lumens.4,6 These patients did not have organizing pneumonia. Later, Epler and his colleagues2,3,6 described BOOP as an inflammatory clinicopathological lung disease characterized by polypoid intralumenal and endobronchial connective tissue plugs. These plugs are composed of proliferating myxoid fibroblasts and myofibroblasts that fill the lumens of terminal bronchioles and extend in a continuous fashion into the alveolar ducts and alveoli, characteristics of an organizing pneumonia.The airway plugs formed by the proliferation of connective tissue and fibroblasts may lead to a cast formation that outlines the branching of the inflamed alveolar ducts and distal airways. In BOOP the airway lumens are occluded from within, so the background architecture is generally preserved.4 This inflammation and the occlusive infiltrates in the bronchioles lead to restricted lung volumes and decreased vital capacity. BOOP is sometimes referred to as cryptogenic organizing pneumonia, a term that is considered more general and representative of what happens clinically, pathologically, and structurally within the lung tissue. However, the term BOOP is specific for a lesion that occurs in the distal bronchioles and alveoli simultaneously and is a popular term used throughout the world.In many instances, the cause of BOOP cannot be determined. Epler,3 the leading clinical expert on BOOP, identifies several known causes or associated diseases and classifies them according to types (Table 1). No links exist between the types of BOOP except that all the types lead to a final common clinical pathway that may be devastating if not detected promptly.Idiopathic BOOP is the most common type of BOOP that critical care nurses see in practice. Stover and Mangino17 call this type cryptogenic. Patients have flulike signs and symptoms, fever, a mild cough, and dyspnea. Auscultation of lung sounds commonly reveals crackles. The prognosis of idiopathic BOOP is good, and some patients have resolution of signs and symptoms without having any treatment at all.Rapidly progressive BOOP is a deadly form that can be fatal within 1 to 3 days of the onset of signs and symptoms. Patients may have an acute onset of acute respiratory distress syndrome; therefore, clinically, rapidly progressive BOOP can be indistinguishable from acute interstitial pneumonia.2,3 Acute respiratory failure quickly results and leads to death. Early diagnosis based on histological examination of the primary BOOP lesion and initiation of corticosteroid therapy might improve survival in these patients.6 This form of BOOP occurs in less than 10% of patients with BOOP and occurs equally in men and women and at all ages.Focal nodular BOOP is clinically important because distinguishing it from lung cancer is difficult.18–21 It occurs in approximately one fourth of patients who have idiopathic BOOP.22 Although some focal nodular lesions might progress to the typical bilateral process of idiopathic BOOP, most do not, and resection results in a cure. Multiple bilateral nodular lesions may regress on their own without treatment.20 Approximately 50% of patients with multiple nodular lesions (mean number of masses was 5) have pleuritic chest pain.BOOP can occur after a variety of different types of infectious pneumonias,1 including those caused by bacterial pathogens such as Chlamydia,23Legionella, and Mycoplasma pneumoniae.24 Viral causes include cytomegalovirus, parainfluenza virus,25 and adenovirus.26 BOOP after parasitic infections such as malaria27 and fungal infections, including those caused by Cryptococcus neoformans28 and Pneumocystis carinii,29 has also been reported. The relationship between many types of infection and the onset of BOOP is still unknown.1Drug-related BOOP can occur after the use of several different types of medications, including anti-inflammatory and immunosuppressive agents such as bleomycin sulfate,11 gold, cyclophosphamide, penicillamine, and methotrexate; antibiotics such as sulfasalazine, sulfamethoxypyridazine, cephalosporins, and amphotericin B; anti-seizure medications such as carbamazepine9 and phenytoin6,30; illicit use of cocaine; and a massive dose of l-tryptophan. Minocycline-associated BOOP31 has been reported in a woman who was taking this medication for acne. Other medications thought to lead to BOOP and commonly administered by critical care nurses are amiodarone,32 ticlopidine hydrochloride, and nitrofurantoin.33Rheumatologic or connective tissue BOOP can occur in patients with connective tissue diseases such as lupus erythematosus,34 rheumatoid arthritis,35 Sjögren syndrome,36 and dermatomyositis.37 BOOP can also occur in patients with ankylosing spondylitis38 and polymyalgia rheumatica,39,40 and it can affect patients with immunological diseases such as immunodeficiency syndrome41 and cryoglobulinemia.42BOOP can occur in recipients of lung,43 kidney,44 bone marrow,44,46 and stem cell transplants.47 In lung transplantation, BOOP generally occurs up to 10 months after transplantation and is usually associated with an acute rejection reaction.5,48,49 This type of BOOP has been reported in 10% to 28% of lung transplant recipients and is often reversible, especially if the underlying acute rejection is successfully treated. If a transplant recipient is admitted to a critical care unit within this time frame because of an acute onset of shortness of breath, BOOP should be considered as a causative factor. In these patients, the BOOP reactions should be treated aggressively.BOOP has been described in a patient who underwent an allogeneic marrow transplantation and in another patient who received a syngeneic bone marrow transplant from his twin brother.46 Too few reports have been published to determine whether BOOP in these patients was an incidental finding or an actual complication of bone marrow transplantation. BOOP can also occur as a late complication after transplantation of hematopoietic stem cells.47BOOP is an important clinical complication in patients being treated with radiotherapy for breast cancer and may occur in up to 3% of women receiving radiation therapy for breast carcinoma.50–53 The usual signs and symptoms are fever, non-productive cough, and various degrees of shortness of breath that occur up to 12 months after completion of radiotherapy. Chest radiographs show peripheral patchy or alveolar infiltrates, often outside the radiation field.50 In one study,52 patients had infiltrates outside the irradiated lung to the contralateral nonirradiated lung. The underlying mechanism of radiotherapy BOOP remains unknown. A patient’s condition may improve with the initiation of corticosteroid therapy, but relapses may occur.50,51Environment-related BOOP has been reported in relation to textile printing dye14; the authors of the report suggested that the cause was related to the spraying of a respirable aerosol; however, the reactive chemical agent is a mystery. Another environmental cause is Penicillium janthinellum mold dust, inhaled from a powdery dust of a growth on the top of a discarded orange juice container.54 BOOP due to smoke inhalation has been reported in a patient with erythema nodosum who was in a house fire.55Miscellaneous BOOP continues to be reported in association with myelodysplastic syndrome,56 interstitial cystitis,57 chronic thyroiditis,58 and disorders of the liver such as alcoholic cirrhosis58 and primary biliary cirrhosis.59 It has been reported in patients infected with HIV60 and has occurred during pregnancy.61 Guzman et al62 described a case of BOOP in a patient who had coronary artery bypass graft surgery. In patients with inflammatory bowel disease, BOOP is an important treatable abnormality.63 BOOP also can occur in patients with T-cell leukemia or lymphoma.64,65A trigger of some kind, for example, an infectious agent, a drug, or a connective tissue disorder, stimulates the inflammatory process known as BOOP. Because BOOP is an inflammatory lung disease, the key pathophysiological findings are related to the inflammatory pathway rather than to the fibrosing pathway as in idiopathic pulmonary fibrosis. Inflammation in the walls of the alveoli and bronchioles and an increase in foamy, lipid-laden macrophages in the alveoli are significant and lead to accumulations of fibromyxoid connective tissue.66Histological features include clusters of mononuclear inflammatory cells that form granulation tissue and plug the distal airways and alveolar spaces. These plugs of granulation tissue may form polyps that migrate within the alveolar ducts or may be focally attached to the wall.2,3,5 The polyps may extend in a continuous fashion from the alveoli and alveolar ducts into the terminal and distal bronchioles.2,3,5 The FigureF1 provides a summary the pathophysiology of BOOP.BOOP is most common in the fourth to sixth decade of life6,67 and accounts for 20% to 30% of chronic infiltrative lung diseases. BOOP occurs equally in men and women and in all races. It has no corollary relationship with smoking.6 The incidence in the United States does not differ significantly from that of other countries worldwide.6 MacLaughlin and King68 and Epler3 set mortality due to BOOP at 5%, whereas McKee and Epler69 note 3% to 13% mortality, depending on the underlying cause of the BOOP.Most patients with idiopathic BOOP fully recover after a sufficient course of corticosteroids. However, the success of this treatment depends on the presence of other comorbid conditions and associated problems such as connective tissue disorders or underlying pulmonary diseases.1,4,67,68 Compared with treatment of BOOP alone, treatment of BOOP in patients with other disease processes is more challenging because of the multidisciplinary approach required. Furthermore, once successful treatment has been started, relapses occur in approximately one third to one half of patients. The likelihood of relapse may be linked to several factors, including completion of the recommended corticosteroid treatment regimen and the severity of hypoxemia manifested initially.3,22,69The onset of clinical manifestations of BOOP is usually acute (1 week) to subacute (months) no matter what the causative factor; the mean time is 4 to 10 weeks. Patients commonly have weeks to months of nonspecific respiratory signs and symptoms. The clinical manifestations vary according to the type of BOOP. Typical idiopathic BOOP is characterized by a flulike illness, bilateral crackles, and patchy infiltrates on chest radiographs. The initial signs and symptoms may include fever and night sweats, malaise, non-productive cough and dyspnea, and sore throat. Anorexia and weight loss are common. Physical assessment reveals tachypnea, hypoxia, and respiratory crackles over the involved lung fields in more than 80% of patients.68 Wheezing and hemoptysis are rare.6 The severity of the illness depends on the signs and symptoms.Hematologic abnormalities are most prevalent in BOOP, although other serum abnormalities may also be evident (Table 2). White blood cell counts are most consistently elevated.3,4,70 In a differential count, neutrophils may be increased to as high as 0.72 (proportion of 1.00), lymphocytes to 0.16, and monocytes to 0.12.71 Increases in eosinophils are rare.70 In 2 case studies,72 2 patients with fairly typical sequelae of pulmonary tuberculosis had BOOP, and 1 of the 2 had thrombocytosis, which occurs in approximately 20% of cases of BOOP.In addition to the hematologic findings, other laboratory values may be abnormal in BOOP. Patients may have hypoalbuminemia.68 Erythrocyte sedimentation rates can be increased to greater than 60 mm/h as a result of the overwhelming pulmonary inflammatory response that occurs.3,4,71 Serum levels of C-reactive protein are also elevated.4,70,71Both clinically and radiographically, BOOP mimics a variety of other pulmonary abnormalities. Clinically, fever, malaise, nonproductive cough, mild dyspnea, and weight loss of insidious onset can be due to a myriad of causes. Radiographic findings characteristic of BOOP may help in narrowing the list of possible causes to a more manageable number, but the definitive means for confirming BOOP is histological examination.5,74 BOOP should be considered in patients with a suspected infective pulmonary disorder who do not respond to antibiotic therapy.5,74 Table 3 provides a differential diagnosis for patients with indications suggestive of BOOP.In diagnosing BOOP, findings on chest radiographs are merely a means to an end. Because the findings are also consistent with those of other pulmonary disorders, these studies alone are not sufficient to confirm a diagnosis of BOOP. Three main imaging patterns suggest BOOP.The first pattern is patchy alveolar and diffuse interstitial infiltrates, usually bilaterally. These findings are consistently visualized on chest radiographs.1,6,68,69,71,72 In as many as 25% of patients with BOOP, the infiltrates are described as migratory, a term that implies the movement of the newly formed granulation tissue within small distal airways and alveolar ducts.1,68,71 These migratory lesions may also spontaneously regress or vanish.60 These opacities are often present peripherally, indicating their location just under the pleural lining and thus are termed subpleural. On computed tomography, such opacities are seen as a ground-glass pattern with peripheral orientation.3,71,72,81 Pleural effusions and airway hyper-inflation are uncharacteristic in idiopathic BOOP.1–4,68,74The second radiographic finding suggestive of BOOP is multiple foci of consolidation or solitary nodular-appearing lesions.1,74,81 In some patients with cancer, notably renal carcinoma, these lesions have been confused with pulmonary metastases, but the lesions may spontaneously regress, an unlikely occurrence in metastatic disease.67The third and final characteristic radiographic finding is the appearance of small linear or crescent-shaped densities surrounding the ground-glass area of attenuation. This finding is less frequent than other radiograph patterns; it occurs in approximately 20% of patients with BOOP.1,4,74,81In patients with BOOP, high-resolution computed tomography reveals ground-glass attenuation with a subpleural and peribronchial distribution.1,3,5,66,81 The ground-glass appearance may be the result of alveolar septal inflammation and the organizing pneumonia in alveolar ducts.81 In addition, as many as 65% of patients have peripheral lower lobe consolidation.66,71 The pattern of this peripheral consolidation is similar to that of a triangle with the base along the pleural surface and the tip of the triangle toward the mediastinum.6,68,71 In comparison, patients with fibrotic lung disease have a clinical manifestations and radiological findings may suggest BOOP as a diagnosis, histological findings are to confirm the with lung is the for and the This for more tissue and less of due to Because the distal airway and alveolar lesions are migratory, the location of the of should be chest just the is This the most tissue which in help in the most the to for histological examination is because use of the primary treatment for BOOP, is not for many of the differential as a diagnostic means has been used that of often 20% to of the blood cells in the are most characteristic of BOOP. that findings of more than lymphocytes are suggestive of BOOP. Other cell such as and may also be but in cases of BOOP, the main findings on histological examination are granulation tissue in the distal bronchioles and alveolar composed of interstitial infiltrates with mononuclear cells A finding of organizing pneumonia is not diagnostic for BOOP because this type of pneumonia can occur in association with other pulmonary diseases or examination of a tissue lung is the for an of alone cannot be used to histological findings in BOOP are as 4 common values for pulmonary in patients with with BOOP are a because of the acute of the disease and nursing include corticosteroid therapy, other medications such as for with in the pulmonary and and the patients and their and BOOP is generally a infiltrative lung disease, agents are not of the treatment the treatment for BOOP is an course of most patients improve after the initial to 1 of If a patient does improve within this time a be because other diagnostic may be The recommended of is to 1 for 3 then for 3 and to or other for for a treatment time of approximately 1 for of therapy such as and is a of In addition, the for infections is increased because corticosteroid therapy is of thought exist the mechanism by which in BOOP. The of newly formed connective tissue in distal airways and alveolar are a characteristic that may the anti-inflammatory to these The of in the of diffuse peripheral subpleural peribronchial and inflammatory to fibroblasts are a key in the formation of the and also a vital in the of the polypoid requires These by fibroblasts and in the the and resolution of the polyps or by the fibroblasts and This may for those patients who to recover spontaneously without resolution of clinical and radiographic findings associated with BOOP by treatment with has been the of the are the treatment for BOOP, other medications have also been such as for 2 months and then for an 1 can result in resolution of of the of agents the of cells in the and the of which the inflammatory is also in patients with such as and have been used in BOOP patients who had in signs and symptoms and radiographic findings with usual corticosteroid has been used as an The success of therapy is by the in pulmonary signs and symptoms and the of the results of pulmonary to pulmonary assessment and with with the pulmonary are to and which are key to in patients with BOOP. The critical care chest radiographs to the resolution of the findings after corticosteroid therapy is In addition, the findings on and of blood and for indications of the of and the of patients thus the critical care patients and their diagnostic and the use and of Because patients have such as with lung and high-resolution computed tomography, the in to A of associated with use of may occur because patients with BOOP are often treated for the medication be patients with BOOP, in the and of critical care nursing is to the possible Table is a of care for patients with a was being treated on an for having shortness of breath of and a A chest radiograph patchy pulmonary infiltrates and nodular opacities in was admitted to the of and to the to be of breath, with of and a of inhaled was administered a Other vital signs blood and in findings sedimentation blood cell of C-reactive protein and serum Other than indications of and abnormal results in renal all other laboratory findings of the and for of the findings on the chest high-resolution computed tomography of the chest was The bilateral ground-glass opacities with a area of consolidation with the base along the pleural surface of the lung the with a was on the of the pneumonia was that was being treated with 60 the lung problems and on the of his to an lung from 2 lung and 1 lung of BOOP. examination of the myxoid and lymphocytes and eosinophils in the alveolar spaces. of the distal bronchioles and alveolar with inflammatory was also and of the for a second from a the diagnosis of BOOP was was at a dose of for days and then once a The was and at the time of 3 weeks after was taking 60 was from the treatment with at the 12 the of was and treatment with the was the BOOP was is an inflammation of the distal small airways and surrounding alveolar lung tissue. This inflammation can affect a small of the lung or the lung. care nurses should the of BOOP for a patient with suspected pneumonia and respiratory failure who does not respond to antibiotic vital of the critical care nurses as improve by care for patients with BOOP. Early diagnosis and treatment with is in and by critical care nurses are to pulmonary and a high of in BOOP on BOOP, the to for to his so that may and from his The characteristics of the case study have been to with the of the and and patient The patient’s has been to the known expert and of BOOP, for his and during the of the his this not have been