Source: Net Fan Changzheng’s personal website Zhao Lancai, Department of Infectious Diseases, Xiyuan Hospital, Chinese Academy of Traditional Chinese Medicine
CHINESE CRITICAL CARE 1999 Vol.11 No.11 1999
CICS: R562.21;R563.1 Document ID: B Article ID: 1003-0603(1999)11-0700-03
Dr. Jie-Fu Du: Attending Physician, Department of Emergency Medicine, PLA General Hospital ([email protected]) Bronchiolitis obliterans with organizing pneumonia (BOOP) is a new name proposed in 1985, which is clinically rare. The diagnosis of BOOP requires open-chest lung biopsy. However, the clinical diagnosis can be made on the basis of symptoms, signs, imaging and laboratory tests. We provide the following case for discussion and further understanding of BOOP.
Case: The patient, male, 51 years old, came to the clinic with dry cough for more than 10 months and fever for half a year. 10 months ago, irritating dry cough appeared without any cause and gradually worsened, and half a year ago, fever appeared, mostly low fever in the afternoon, with temperature up to 39 ℃, without chills, sputum production and dyspnea; the fever lasted for 1 to 2 hours daily and could resolve by itself. The blood, urine and fecal routine were normal, the ESR was 120 mm/1 h, the blood glucose was 8.0 mmol/L, the tuberculosis antibody, pure protein derivative (PPD) test and condensation set test were negative, the liver and kidney function were normal. No tumor cells were found in the smear, and eosinophils and neutrophils were seen in the bronchoalveolar lavage fluid. On admission: body temperature 38.5 ℃, pulse 80 times/min, respiration 20 times/min, blood pressure 16.0/10.0 kPa (1 kPa=7.5 mmHg), no yellow staining, rash and bleeding spots on the skin and mucous membranes, no enlarged superficial lymph nodes, slightly congested pharynx, no enlarged tonsils, clear breath sounds in both lungs, no dry or wet sounds, liver 1 cm below the rib cage, soft and no pressure pain. No pressure pain. Blood count: WBC 10.8×109/L, neutrophils (N) 0.74, lymphocytes (L) 0.16, monocytes (M) 0.10, RBC 4.35×1012/L, hemoglobin (Hb) 106 g/L; urine: WBC 5-6/HP, urine glucose (++); fecal routine normal; blood glucose 7.2 mmol/L, carcinoembryonic antigen (CEA) 3 μg/L, ESR 87 mm/1 h, alkaline phosphatase (ALP) 366.7 U/L, gamma glutamyl transpeptidase (GGT) 244.3 U, normal electrolytes, urea nitrogen (BUN), alanine aminotransferase (GPT), aspartate aminotransferase (GOT) were normal. Blood culture was negative, anti-nuclear antibody, anti-dsDNA antibody, anti-RNP antibody, anti-SSA antibody, anti-SSB antibody were negative, hepatitis B surface antigen was negative, X-ray chest film and chest CT did not show any abnormality, ultrasound showed mild splenomegaly. Fiberoptic bronchoscopy showed submucosal inflammatory changes in the bronchus, and no cancer cells were found in the brushings; PPD test (1 U, 5 U) was negative. After admission, he was given isoniazid 0.3 g once daily, rifampicin 0.6 g once daily, and ethambutol 0.75 g once daily orally, and his fever and cough did not ease after 1 week of treatment. In the third week of admission, the patient was given prednisone 60 mg/d, and the body temperature started to drop. After 3 days, the body temperature dropped to normal, and the cough symptoms gradually decreased. The patient was discharged from the hospital and was advised to take long-term medication and follow up.
Dr. Meng Qingyi: Associate Professor, Department of Emergency Medicine, PLA General Hospital ([email protected])
The clinical manifestations of this patient were consistent with the diagnosis of BOOP, mainly based on the following points: (1) the patient had long-term fever and dry cough symptoms; (2) imaging examination excluded lung tumors and lung inflammatory manifestations; (3) eosinophils and neutrophils were seen in bronchoalveolar lavage fluid; (4) clinical manifestations and laboratory tests excluded connective tissue disease and mycoplasma pneumonia; (5) antibiotic treatment was ineffective; (6) after applying adrenocorticosteroids The patient’s clinical symptoms resolved rapidly. However, the patient did not undergo open-chest lung biopsy for definite diagnosis.
The age of onset of BOOP is mostly between 50 and 60 years old, but can also occur in patients between 21 and 80 years old. The clinical presentation of BOOP varies considerably, with most patients having a subacute onset and flu-like symptoms. Common symptoms include fever, dry cough, dyspnea (significantly worse with activity) with peripheral discomfort, anorexia and weight loss. Less common symptoms include increased bronchial secretions, coughing up blood, chest pain, arthralgia, and night sweats.
There are no extra-thoracic clinical manifestations of BOOP, and the chest x-ray of BOOP cases varies widely, with three types of x-ray signs: 1) multiple bilateral pulmonary patchy Infiltrative shadow: It is the most common and characteristic chest x-ray manifestation. Typically, these are bilaterally distributed infiltrative shadows, which can wander on their own, often with one shadow dissipating or even completely dissipating, while others appear in other areas. The density of the shadows ranges from hairy glassy changes to solid lung lesions, which represent mechanized pneumonia. The size of the shadow varies from 3-5 cm to the entire lobe of the lung, and the margins of the shadow are indistinct, often with an “air bronchography” sign within the shadow. In particular, it should be differentiated from eosinophilic pneumonia. (2) Bilateral diffuse asymmetric infiltrative shadows: These shadows are often reticular, nodular or reticulonodular in shape. CT may show small round or irregular shaped shadows. (3) Isolated focal pneumonia: These isolated pulmonary shadows often occur in the lung fields and often show “air bronchograms” within the shadow, occasionally a cavity may be found.
Dr. Kentaro Watanahe: Professor of Internal Medicine II, FUKUOKA University, Japan ([email protected])
We have diagnosed 3 cases of BOOP in the past 2 years. case 1: a 51-year-old male with hypertension and Hodgkin’s lymphoma who had received 3 courses of MOPP (nitrogen mustard, vincristine, methylbenzylhydrazine, prednisone) chemotherapy regimen. at the time of presentation, the patient showed weight loss and prolonged hypothermia. x-ray chest radiograph showed an infiltrative shadow in the left lower lung. the initial diagnosis was considered pneumonia and antibiotics were given, but hypothermia persisted. Case 2: A 41-year-old male with acute myeloma who recently underwent bone marrow transplantation was admitted to the hospital with supraventricular tachycardia and was treated with antiarrhythmic drugs. The diagnosis of BOOP was made by tracheoscopic biopsy. case 3: 70-year-old female with a previous history of asthma was admitted with cough. x-ray chest radiograph showed infiltration of the left lower lung shadow, which was treated with antibiotics and then reexamined on the x-ray chest radiograph. A fine needle biopsy suspected a lung tumor and an open lung biopsy eventually diagnosed BOOP.
Epler et al. in 1985 performed a retrospective study of 2,500 open-chest lung biopsies diagnosed with cryptogenic fibrogenic alveolitis, idiopathic pulmonary fibrosis, and generalized interstitial pneumonia and identified 57 cases of BOOP. the pathologic histology of these cases was interstitial lung disease characterized by occlusive fine bronchitis with varying degrees of mechanized pneumonia. The clinical application of adrenocorticosteroids responded well. This is clearly different from common interstitial pneumonia and pulmonary fibrosis, thus recognizing BOOP as a new disease and BOOP as a specific type of diffuse interstitial lung disease, often mixed with other interstitial lung diseases.BOOP occupies an important position in interstitial lung diseases.
Based on the age, physical condition, and imaging findings of these three patients, we also considered the possibility that the patients had tumors, and the CT-guided fine-needle biopsy in case 3 did indicate “suspicion of malignancy,” so I believe that BOOP should be differentiated from lung tumors.
Dr. Keith A Knoell: MD, University of Virginia, USA ([email protected])
Dermatomyositis is a connective tissue disorder of unknown origin that presents with a characteristic purple rash, edema around the eyelids, and facial erythema. Both dermatomyositis and interstitial lung disease present with diffuse alveolar injury, small airway lesions, or interstitial pneumonia. The relationship between the two is well described, but only eight cases of dermatomyositis with BOOP have been reported so far, and adrenocorticosteroid treatment for BOOP is effective. However, treatment of BOOP with dermatomyositis with hormones alone is not effective. We admitted a 44-year-old black woman with a progressive facial rash that had been aggravated by facial erythema and centripetal edema for more than 2 months, a past medical history of Rayna’s phenomenon for many years, a recent fever with cough for 3 months, and an open lung biopsy that confirmed BOOP 1 month ago. The patient had mild headache and dysphagia; there was no chest pain, abdominal pain or central nervous system dysfunction. Physical examination: body temperature 39.5 ℃, respiration 20 times/min, significant periorbital erythema, facial edema and purplish rash. There were no abnormal findings on bilateral lung auscultation and no abnormalities on abdominal examination. Laboratory examination: WBC 17.8×109/L, ESR 94 mm/1 h, aldolase 300.06 nmol.s-1.L-1, creatine kinase (CK) 517 IU/L, antinuclear antibody 1:5 120, dsDNA 1:20, anti-Sm antibody negative, rheumatoid factor (RF) negative. The patient was diagnosed with BOOP with dermatomyositis and given prednisone 30 mg twice daily and cyclophosphamide 50 mg orally once daily. After 1 month, the patient’s respiratory symptoms disappeared and the facial rash subsided.
Dr. Shen Hong: Associate Professor, Department of Emergency Medicine, PLA General Hospital ([email protected])
Due to the progress of BOOP clinical research, its definition and classification have changed. The definition of BOOP is now as follows: BOOP is a disease caused by obstruction of granulation tissue in the lumen of small airways, which can sometimes completely block the small airways, and the granulation tissue can extend into the alveolar ducts and alveoli. features of BOOP include: proliferation of connective tissue to form intraluminal polyps; fibrous exudate; accumulation of macrophages in the alveoli; inflammation of the alveolar wall; but the lung tissue structure remains intact.
BOOP can be divided into two main categories.
1. obstructive bronchiectasis: it occurs mainly as an injury to the fine bronchi, rarely involving the alveoli and alveolar ducts, accompanied by varying degrees of fine bronchial obstruction, which can range from mild fine bronchial inflammation to scar formation, central fibrosis of the fine bronchi and submucosal granuloma formation, thus leading to narrowing of the fine bronchi.
2. Proliferative fine bronchitis: It is characterized by organic exudation in the trachea, i.e., proliferative granulomas filling the distal and respiratory fine bronchi, and this change can extend to the alveolar ducts and sometimes to the distal alveoli, forming mechanized pneumonia. The basis for the above damage are: (1) mechanized diffuse alveolar injury; (2) obstruction due to mechanized infection of the distal airways; (3) mechanized aspiration pneumonia; (4) exposure to toxic gases; (5) connective tissue disease; (6) allergic pneumonia; (7) drug reactions; and (8) bone marrow and heart-lung transplantation. Usually the obstructive type of fine bronchiectasis responds poorly to hormone therapy, while the proliferative type often responds well to hormone therapy.
Based on the history, concomitant diseases, clinical manifestations and pathological features, BOOP can also be classified as follows.
① Idiopathic BOOP (Idiopathic BO-OP): In fact, the vast majority of BOOP can be classified as idiopathic BOOP, i.e., no clinically apparent etiology. In the majority of cases of idiopathic BOOP, no cause or associated disease can be found. Idiopathic BOOP accounted for 87% (97) of the 112 cases of BOOP that were counted. The remaining 15 cases had an etiology of connective tissue disease, ulcerative colitis, and drug-induced pulmonary disease, respectively.
(ii) Post-infection BOOP: BOOP can develop after infection, but the number of cases is small, and most injuries occur after viral pneumonia or mycoplasma pneumonia, which respond well to prednisone treatment.
(iii) Drug-related BOOP: Several anti-inflammatory drugs and immunosuppressive agents are associated with BOOP, such as gold agents, methotrexate, and other drugs such as vincristine, etanercept and bleomycin. The clinical presentation is similar to idiopathic BOOP, often with cough, dyspnea, flu-like symptoms, increased blood sedimentation, and X-ray chest radiographs showing patchy shadows in both lungs. This type responds well to hormone therapy.
Focal nodular BOOP: X-ray chest film shows isolated nodular shadow, similar to “pneumonia type”, occasionally with air contrast sign or cavity, often in both upper lung fields. It may be a specific type of idiopathic BOOP and may eventually develop into a typical patchy infiltrative image of both lungs. Clinically this focal nodular BOOP often requires surgical exploration, but hormonal therapy also has significant efficacy.
⑤ Connective tissue disease (or rheumatoid) BOOP: BOOP can be commonly seen in lupus erythematosus, polymyositis or dermatomyositis and rheumatoid arthritis, with the same clinical manifestations and radiographic chest manifestations as idiopathic BOOP. although this type of disease can also be treated with hormones, the efficacy is not as good as idiopathic BOOP, especially in active recurrent connective tissue disease (such as dermatomyositis).
(6) BOOP after bone marrow transplantation: Characteristic BOOP can occur after bone marrow transplantation and may be related to infections, including: cytomegalovirus, mycoplasma or other viral infections. However, it is thought that this BOOP is a manifestation of a chronic rejection reaction. Patients receiving transplantation often present with cough and respiratory failure, and X-ray chest radiographs show patchy shadows in both lungs. Open-chest biopsy is typical for BOOP.
(7) BOOP after lung transplantation: BOOP can be complicated in about 10% of patients after lung transplantation.
(8) Others: BOOP can be complicated by radiation therapy, which has been pathologically confirmed. Hormone therapy is effective. A small number of patients with malignant tumors (such as lymphoma, leukemia, etc.) can also be complicated by BOOP. BOOP is also occasionally seen in chronic thyroiditis, ethanolic cirrhosis, etc.
Dr. Zhao Shifeng: Department of Emergency Medicine, PLA General Hospital ([email protected])
Laboratory tests for BOOP include the following.
①Pulmonary function: often restrictive changes, occasionally normal, expiratory volume in 1 second (FEV1) and exertional spirometry (FVC) remain normal in most non-smoking patients, while there is a mild decrease in smoking patients, a decrease in diffusion function in all cases, usually hypoxemia, and an increase in alveolar arterial oxygen partial pressure difference.
C-reactive protein may be increased, WBC may be mildly to moderately increased, and neutrophils may be increased. Autoantibodies are often negative or mildly positive, so they are not consistent with typical autoimmune disease.
(iii) Bronchoalveolar lavage: The recovery of bronchial lavage fluid via fiberoptic bronchoscopy is low. The cellular classification shows a decrease in macrophages and an increase in lymphocytes, neutrophils, and eosinophils, and the “mixed” increase in lymphocytes, neutrophils, and eosinophils in the BOOP multiform alveolar pattern is quite characteristic. There are often “vacuolar” changes within the macrophages (foamy macrophages).
Dr. Marin I Sclucary: Professor, Penn State University School of Medicine, USA (Marin I [email protected])
The initial clinical diagnosis can be made in certain cases based on symptoms, signs, laboratory tests, bronchoalveolar lavage fluid and imaging, with the following features suggestive of BOOP.
(i) slow onset and with prolonged respiratory symptoms (dry cough, fever, shortness of breath), Velcro sounds and peripheral symptoms, weight loss and peripheral discomfort.
(ii) Laboratory tests include elevated blood WBC, increased ESR and positive C-reactive protein.
③Thoracic CT and X-ray chest radiographs showed multiple patchy infiltrative shadows in both lungs, diffuse reticular interstitial shadows in both lungs or alveolar infiltrative shadows with a large lobar distribution, and characteristic changes were wandering shadows.
④Bronchoalveolar lavage may show increased lymphocytes, eosinophils and neutrophils.
⑤ Pulmonary infections such as tuberculosis, mycoplasma and fungi are not clinically supported and antibiotic therapy is ineffective.
(6) Adrenocorticosteroid therapy was effective.
In patients with clinically diagnosed BOOP, an open lung biopsy with pathological histological confirmation of the characteristic findings of BOOP is required to confirm the diagnosis of the disease. If only transbronchoscopic lung biopsy (TBLB) is used, the characteristic pathological findings are often not obtained because too few lung tissue specimens are available.
The characteristic pathological changes of BOOP are mainly the formation of connective tissue granules in the distal air spaces with moderate interstitial involvement. Mechanized pneumonia plays a decisive role in the formation of typical BOOP, both clinically and imaging-wise. The pathology of mechanized pneumonia is characterized by the formation of granulation tissue in the alveoli, consisting of loose collagen-forming and myogenic fibers. The granulation tissue composition varies with the stage of the disease, from fibrous exudate to collagenous fibers. In the early stages of the disease, neutrophils, eosinophils, lymphocytes and plasma cells are seen in the alveolar lumen. Inflammation is present in the interstitial lung space, but is usually mild and without the manifestations of cellular lung.
Injury to the fine bronchi creates granulomatous tissue emboli in the lumen, constituting the “proliferative” type of BOOP, which is usually more pronounced in the alveoli and bronchial lumen. In conclusion, connective tissue granulomas in the alveolar and fine bronchial lumen are the characteristic changes of BOOP. Since BOOP is clinically nonspecific, the differential diagnosis is quite important. I believe that BOOP should be differentiated mainly from various other diffuse diseases.
(1) Idiopathic interstitial pulmonary fibrosis (IPF): common interstitial pneumonia (UIP) in IPF is very similar to BOOP, and it is important to differentiate the two. In terms of clinical manifestations, BOOP is heavier than UIP, with peripheral discomfort, weight loss, fever, etc. Pestle fingers are rare in BOOP patients, and BOOP X-ray chest films are mostly alveolar abnormalities, with wandering patchy shadows in some cases, no change in lung volume, and no manifestation of cellular lung; whereas UIP patients have more dense fine wet sounds, pestle fingers are common, blood sedimentation is low, and bronchoalveolar lavage fluid The lymphocytes are not high, and the X-ray chest film and CT often show interstitial changes, often with reduced lung volume and cellular lung changes. The response to hormone therapy is completely different: BOOP is effective to hormone therapy, symptoms improve, and abnormal X-ray chest images may dissipate. In contrast, UIP responds poorly to hormone therapy and has no significant efficacy in the chronic phase.
②Chronic eosinophilic pneumonia (CEP): BOOP and CEP are clinically similar in that both respond well to hormone therapy, have similar radiographic chest manifestations, and both have an increase in eosinophils. However, the increase in eosinophils in BOOP rarely exceeds 10%. In addition, the pathology of CEP is characterized by a high eosinophil infiltration in the alveolar lumen and stroma.
(iii) Exogenous allergic alveolitis: The clinical presentation and X-ray chest radiograph are similar to BOOP and the lung shadows are also wandering, and both respond well to hormonal therapy. However, the occupational history, environment, inhalation triggering test and antibody complement serology can be used to differentiate these two diseases.
Dr. Shen Hong: Associate Professor, Department of Emergency Medicine, PLA General Hospital ([email protected])
The following talks about the treatment of BOOP. Hormone is currently an effective drug for the treatment of BOOP, but the ideal dose and duration of treatment have not yet been unified, and the following protocols are now commonly used.
①Initial treatment: start with prednisone 1 mg/kg daily for about 1 to 3 months; in general, most cases have improvement in symptoms and imaging within 7 to 10 days after dosing.
(ii) Hormone reduction period: Prednisone was gradually reduced from the initial dose to 20-40 mg during phase 2 treatment for 3 months.
(③) Hormone maintenance treatment period: maintenance dose of prednisone 5-10 mg/d, which can be changed to prednisone 5 mg every other day at a later stage.
The full course of prednisone is 1 year. If prednisone is stopped too early, there is a possibility of relapse. The prognosis for BOOP is fair, with some cases resolving spontaneously. Since the discovery of BOOP is only more than 10 years old, further research on BOOP is still needed.
(compiled by Dutcheff)