Background : Methotrexate (MTX) has been used to treat a wide range of malignant and benign diseases including osteosarcoma, advanced stage non-Hodgkin's lymphoma, psoriasis, severe rheumatoid arthritis, sarcoidosis, and Wegener's granulomatosis. MTX-induced lung injury occurs in up to 10% of treated patients. Although both acute and chronic presentations have been described, typical manifestation of MTX-induced lung injury is subacute with symptoms usually developing within several months after starting therapy. Nonspecific interstitial pneumonia (NSIP) is the most common histopathologic manifestation of MTX-induced lung disease, while bronchiolitis obliterans organizing pneumonia (BOOP) and diffuse alveolar damage (DAD) are less common. Granuloma formation is reported in 34.7%. In Korea, Two reports of MTX pneumonitis have been published. The one presented with NSIP and the other with DAD. We recently experienced a case of MTX pneumonitis with presentation of hypersensitivity pneumonitis.
Background : Idiopathic pulmonary fibrosis (IPF) is a fatal progressive fibrous disease of the lung of unknown etiology. Recently it has been classified into several distinct entities on the basis of pathologic and clinical characteristics, ie : usual interstitial pneumonia (UIP), desquamative interstitial pneumonia (DIP), acute interstitial pneumonia (AIP), bronchiolitis obliterans with organizing pneumonia (BOOP), and nonspecific interstitial pneumonia (NSIP). IPF is now applied only for UIP, which has the worst prognosis. The previous reports of 3-5 year median survival appears to be overoptimistic because other types with better prognosis like NSIP or BOOP might have been included. Therefore, this study was performed to determine the clinical course and the prognostic factors of UIP as diagnosed by surgical lung biopsy. Methods : The subjects were 72 UIP patients (age $58.2{\pm}11.6$ years, M : F=45 : 27, median follow up period : 18.1 months (0.7-103.6) diagnosed by surgical lung biopsy at the Asan Medical Center (68 patients) and the Paik Hospital in Seoul (4 patients). Clinical scores (level of dyspnea : 1-20 points), radiologic score (honeycombing : HC score 0-5 points, ground glass : GG score 0-5 points), and physiologic scores (FVC : 1-12 points, $FEV_1$ : 0-3 points, TLC : 0-10 points, $D_{LCO)$ : 0-5 points, $AaDO_2$ : 0-10 points) were summed into a total CRP score. Results : 1) The one year survival rate was 78.3%, while the rate for three year survival was 58.1%, and the median survival period was 42.5months. 2) Short term (1 year) prognosis : The patients who died within one year of diagnosis (14 patients) had the higher initial total CRP score ($28.6{\pm}8.3$ vs. $16.6{\pm}9.7$) than those who lived longer than one year (46 patients). The difference in the total CRP score was attributed to the symptom score ($8.4{\pm}2.1$ vs. $5.7{\pm}3.9$) and the physiologic score ($15.7{\pm}7.1$ vs. $6.7{\pm}5.7$) including FVC, $D_{LCO)$ and $AaDO_2$. 3) Long-term (3year) prognosis : The total CRP score ($12.2{\pm}6.7$ vs. $28.7{\pm}7.9$ : including symptom score, FVC, $D_{LCO)$ and $AaDO_2$) at the time of diagnosis were also different for the long-term survivors and those who lived less than 3 years. 4) Cox regression analysis showed $D_{LCO)$ (${\geq}$60%) (Hazard ratio : 4.56, 95% CI : 2.30-16.04) was the independent prognostic factors of UIP (P<0.05). Conclusion : These results suggest that $D_{LCO)$ at the time of diagnosis seem to be a prognostic markers of biopsy-proven UIP.
Kim, Ae-Ran;Kim, Tae-Young;Lee, Young-Min;Lee, Seung-Heon;Jung, Soo-Jin;Lee, Hyun-Kyung
Tuberculosis and Respiratory Diseases
/
v.69
no.4
/
pp.293-297
/
2010
A 60-year-old man was diagnosed with stage IV squamous cell carcinoma of lung and treated with weekly doses of docetaxel and cisplatin. Tumor mass and mediastinal lymphadenopathy disappeared after 4.5 cycles of chemotherapy. At one week post final chemotherapy, the patients developed sudden shortness of breath. New, multifocal infiltrations developed on both lungs without definitive evidence of infection. Despite administration of broad spectrum antibiotics, the lung lesion did not improve, so bronchoalveolar lavage and computed tomography-guided lung biopsy were performed. The proportion of lymphocytes was increased markedly and histopathology revealed squamous cell carcinoma combined with bronchiolitis obliterans organizing pneumonia. After high dose corticosteroid therapy, dyspnea and the newly developed consolidation had decreased slightly. However, dyspnea and hypoxemia increased again because of aggravated lung cancer since chemotherapy had stopped. Chemotherapy couldn't be restarted due to the poor performance status of the patient. Later, patient died of respiratory failure from poor general condition and progression of lung cancer.
Yoon, Hyeon Young;Oh, Suk Ui;Park, Jong Gyu;Sin, Tae Rim;Park, Sang Myeon
Tuberculosis and Respiratory Diseases
/
v.62
no.6
/
pp.540-544
/
2007
The patient is a 62-year-old man with known diabetes mellitus who presented with a two-weeks-history of dyspnea, cough, and fever. He was diagnosed with a lung abscess in the right upper lobe and was treated with intravenous antibiotics. The patient's clinical and radiological findings improved within seven days after medical treatment. However, newly developed ground-glass opacity and infiltrations were observed in the right lower lung. Fourteen days after admission, the patient's symptoms and imaging finding became aggravated despite trestment with susceptible antibiotics for lung abscess. Trans-bronchial lung biopsy (TBLB) was performed in the lateral basal segment of the right lower lobe of the lung. A histologic photomicrograph showed organizing pneumonia, also called bronchiolitis obliterans with organizing pneumonia(BOOP), that became more definite as the terminal bronchioles and alveoli became occluded with masses of inflammatory cells and fibrotic tissue. The clinical symptoms and radiograph findings resolved quickly with prednisone treatment. We report a case of secondary organizing pneumonia diagnosed after TBLB following lung abscess treatment and provide a review of the literature.
Acute respiratory failure with diffuse pulmonary infiltration was occurred in a patient with malignant lymphoma 1month after the $8^{th}$ CHOP chemotherapy. The ground glass and consolidation appearances on chest C-T in this immunodeficient patient could be presented in many clinical situations such as pneumonia by opportunistic infections (fungal, parasites, viral, and usual bacterial pathogens), anti-tumor drug's pulmonary toxicity and tumor invasion. And the other diseases of acute interstitial pneumonitis, alveolar proteinosis, BOOP, puhnonary edema and alveolar hemorrhage, which could present the same radiological findings, should included in differential diagnosis. This patient was diagnosed as the opportunistic pneumonia by Pneumocystis carinii and probably Cytomegalovirus through bronchoalveolar lavage and transbronchial lung biopsy
Background : Approximately 10-13% of patients with interstitial lung disease(ILD) die of lung cancer, and patients with ILD have been reported to have a 7 fold higher incidence of lung cancer compared to the normal population. Recently, overexpression of the p53 and p21 proteins were observed in the epithelial cells from pathologic specimens of ILD. Overexpression of these proteins may result from chronic or recurrent DNA damage by unknown causes of inflammation. However, these proteins may also contribute to oncogenesis if other genetic alterations such as K-ras are superimposed. Methods : Immunohistochemical stains for p53 and K-ras proteins were performed with pathologic specimens from 38 cases with ILD(M/F : 27/11, mean agea : $54{\pm}10$ years) and from 10 control subjects. Results : The p53 protein was expressed in 21.1% (8/38 ILD cases) and K-ras protein expression was observed in 65.8% (25/38 ILD cases). However, neither p53 nor the K-ras protein staining was observed in the control subjects. Conclusion : A significant proportion of cases with ILD expressed the p53 and K-ras proteins in their bronchial epithelial cells. These proteins may be potentially oncogenic with the addition of further genetic alterations. However, to clarify the significance of these findings, further studies looking for correlations with the incidence of lung cancer and other genetic changes are needed.
Kim, Youn-Seup;Myung, Na-Hye;Park, Jae-Seuk;Jee, Young-Koo;Lee, Kye-Young
Tuberculosis and Respiratory Diseases
/
v.53
no.2
/
pp.136-147
/
2002
Background : Interstitial lung disease has various manifestations that are differentiated by their pathology, progress and treatment. However, all manifestations eventually progresses to pulmonary fibrosis. Recent studies have shown that apoptosis of pulmonary epithelial cells might be related to pulmonary fibrosis. The correlation of the apoptotic index with the clinical manifestations, pathological findings, HRCT findings and the response to treatment were examined. Materials and Methods : Twenty subjects (14 men, 16 women), who had been diagnosed with interstitial lung disease through an open lung biopsy, were enrolled in this study. The subtypes were one AIP, two NIP, eight BOOP, and seven UIP cases. The apoptotic index was scaled from 0-2 depending on the fraction of positive staining cells by TUNEL method. The clinical severity was assessed by a modification of a previously developed CRP scoring system. The pathologic scores were based on 4 components: fibrosis, cellularity, desquamation, and granulation. In the HRCT study, each lobe was scored by the radiologists on a scale for both fibrosis and ground-glass attenuation. The treatment response was assessed by an increase in more than 10% of the CRP score, and comparing the results 3 months before and after treatment. Results : The apoptotic index showed no correlation with the CRP and HRCT scoring system. The apoptotic index correlated with the pathologic elements including fibrosis, cellularity and the desquamation score (p<0.05). Of the 16 patients who received corticosteroid therapy, 9 patients (56.3%) responded to therapy. There was no correlation between the response to corticosteroid and the apoptotic index. In the case of patients with acute and subacute ILD, the apoptotic index showed a correlation with the cellularity, desquamation, and the total histological score (p<0.05). In the case of patients with chronic ILD, the apoptotic index correlated with the fibrosis and cellularity score (p<0.05). Conclusion : Apoptosis of the pulmonary epithelial cells is implicated in the pathogenesis of interstitial lung disease particularly on a pathological basis.
Cho, Joo Yeon;Lee, Hyun Kyung;Lee, Sung Soon;Lee, Hye Kyung;Lee, Young Min;Lee, Hyuk Pyo;Kim, Joo In;Choi, Soo Jeon;Yum, Ho-Kee
Tuberculosis and Respiratory Diseases
/
v.61
no.5
/
pp.479-483
/
2006
Acute fibrinous and organizing pneumonia (AFOP) is a histological pattern consisting of prominent intra-alveolar fibrin and organizing pneumonia, with out hyaline membranes or prominent eosinophilia. The clinical manifestations of AFOP resemble those of acute lung injury such as acute interstitial pneumonia (AIP). However, the classic histological patterns of AFOP differ from diffuse alveolar damage (DAD), bronchiolitis obliterans with organizing pneumonia (BOOP) or acute eosinophilic pneumonia (AEP). The characteristic intra-alveolar fibrin ball and lack of classic hyaline membrane are the predominant histological features of AFOP. Although some reports suggest that its clinical course is less catastrophic than DAD, the clinical entity that distinguishes AFOP from DAD has not been established. We present a case of pathologically demonstrated AFOP in a 79-year-old man. The radiological findings of our case were similar to those of DAD, presented with diffuse bilateral lung infiltrations. However, despite the rapid development of respiratory failure, the patient had a better response and outcome to steroid therapy than what would be expected for DAD.
Background: Transbronchial lung biopsy(TBLB) has known to yield useful information for pulmonary infiltrates of uncertain etiology, However, its safety and usefulness have not been conclusive in the critically ill patients with respiratory failure. Moreover, TBLB has not been recommended for patients with mechanical ventilation. This study was conducted to investigate the diagnostic values and risks of Will performed on critically ill patients at bedside to obtain information on the pulmonary infiltrate of unknown etiology. Methods: Twenty patients(21 admissions with 23 cases) with diffuse pulmonary infiltrates who were treated in a medical intensive care unit of a tertiary referral hospital from January 1994 to May 1998, were enrolled for the study. Their medical records were retrospectively reviewed. TBLB was opted when a noninvasive diagnostic work-up failed to reveal the cause for the pulmonary infiltrate. The procedure was performed at patients' bedside without assistance of fluoroscopy. Bronchial washing or bronchoalveolar lavage was performed on the same pulmonary segment before performing TBLB. Results: Adequate specimens were obtained in 18 cases(78%). TBLB provided a specific diagnosis in two cases. The results of TBLB suggested the underlying etiology in 9 cases; bacterial pneumonitis(4), hypersensitivity pneumonitis(1), polymyositis(1), radiation fibrosis(1), idiopathic pulmonary fibrosis(1), and BOOP(1). Therapeutic decisions were altered in 11 cases(47.8%) based on the TBLB results. Pneumocystis carinii was found in the BAL fluid of another case. Ten patients with a therapeutic change and ten patients without a management change had mortality rates of 40% and 80%, respectively. The APACHE III scores were significantly higher in patients with complications($72.8{\pm}21.8$) compared with those without complications ($48.3{\pm}18.9$)(p<0.05). The complication rates were higher in those with mechanical ventilation(50%) than in those without Mechanical ventilation(33%), but the difference was not statistically significant(p=0.3). Conclusions: TBLB may be a useful diagnostic option for critically ill patients with unknown cause of pulmonary infiltrates. However, it should be cautious be used with care for patients with mechanical ventilation or for severely ill patients.
Background : Open lung biopsy(OLB) has conventionally been regarded as the gold standard for the diagnosis in interstitial lung disease. With recent advances in diagnostic technique such as high resolution computed tomography(HRCT), and transbronchial lung biopsy(TBLB) which provide relatively accurate diagnosis of ILD, it is necessary to reevaluate the role of these methods in the diagnosis of ILD. Methods: We carried out a retrospective analysis of nineteen patients who underwent OLB at Dankook University Hospital for the diagnosis of acute and chronic ILD, between May 1995 and June 1998. By reviewing the medical records, the demographic findings, underlying conditions, HRCT and TBLB findings, OLB diagnosis, therapy after OLB, and complication of OLB were evaluated. Results: Thirteen patients(68.4%) had chronic ILD(symptom duration over 2 weeks prior to OLB), and six patients(31.6%) had acute ILD(symptom duration less than 2 weeks). Specific diagnosis were reached in 92%(12/13) of chronic ILD(5 bronchiolitis obliterans organizing pneumonia(BOOP), 2 constrictive bronchiolitis, 3 usual interstitial pneumonia, 1 hypersensitivity pneumonitis, 1 eosinophilic pneumonia), and in all patients of acute ILD(5 acute interstitial pneumonia, 1 pneumocystis carinii pneumonia). HRCT were performed in all patients and a correct first choice diagnosis rate of HRCT was 42%(5/12) in chronic ILD. In chronic ILD patients, 62%(8/13) received specific therapy(steroid therapy in 7 patients and moving in one patient), after OLB, but in acute ILD, all patients received specific therapy(steroid therapy in 5 patients and steroid and antibiotic therapy in one patient) after OLB. The in-hospital mortality after OLB was 5.3%(1/19). Conclusion: OLB is an excellent diagnostic technique with relatively low complications in patients with ILD. Therefore OLB should be considered in patients with ILD when the specific diagnosis is important for the treatment, especially in patients with acute ILD.
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