A Case of Autoimmune Pulmonary Alveolar Proteinosis With Predominantly Peripheral Opacities Diagnosed by Transbronchial Lung Biopsy.

Although pulmonary alveolar proteinosis (PAP) showed various shadows, its shadows are usually distributed predominantly in the central lung area. We report a case of autoimmune PAP with localized subpleural ground-glass shadows in the bilateral upper lobes, which was diagnosed based on transbronchial lung biopsy (TBLB) specimen findings and anti-granulocyte macrophage colony PAP stimulating factor antibody positivity. PAP should be listed as a differential diagnosis for subpleural shadows. If subpleural shadows are observed, TBLB should be performed aggressively, and anti-granulocyte macrophage colony-stimulating factor (anti-GM-CSF) antibodies should be submitted.

A Long-term Survival Case of Pulmonary Tumor Thrombotic Microangiopathy due to Gastric Cancer Confirmed by the Early Diagnosis based on a Transbronchial Lung Biopsy.

Pulmonary tumor thrombotic microangiopathy (PTTM) is an acute, progressive, and fatal disease. PTTM manifests as subacute respiratory failure with pulmonary hypertension, progressive right-sided heart failure, and sudden death. An antemortem diagnosis of PTTM is very difficult to obtain, and many patients die within several weeks. We herein report a case of PTTM diagnosed based on a transbronchial lung biopsy. In this case, we finally diagnosed PTTM due to gastric cancer because of its histological identity. The patient was administered chemotherapy, including angiogenesis inhibitors, against gastric cancer at an early age and survived for a long time.

A Tuberculous Bronchial Artery Aneurysm with Abnormal Findings on Autofluorescence Imaging Bronchoscopy.

Pulmonary tuberculosis is a common disease that may result in hemoptysis. Fetal hemoptysis is known to be related to the rupture of a pulmonary aneurysm formed in the cavity wall. We herein report a case of non-cavity pulmonary tuberculosis that developed with massive hemoptysis following bronchial artery aneurysm. Bronchial artery embolization was performed, and autofluorescence imaging bronchoscopy was conducted one month after the anti-tuberculosis treatment. Bright-green color was observed in the ulcerative lesion with a white coat, corresponding to the bronchial artery aneurysm. This is the first report of the autofluorescence imaging observation of an ulcerative lesion caused by bronchial tuberculosis.

[PARADOXICAL RESPONSE DURING TREATMENT OF PULMONARY TUBERCULOSIS].

BACKGROUND: Paradoxical response (PR) is defined as a clinical or radiological worsening in patients receiving adequate anti-tuberculosis treatment, with the exclusion of documented relapse or of other disease presentations. Although most patients with PR show spontaneous improvement, some cases presenting with diffuse alveolar damage have also been reported. METHODS: Retrospective clinical and laboratory data were collected on 89 patients of pulmonary tuberculosis who were treated at our hospital between April 2013 and January 2019. RESULTS: PR occurred in 21 patients (24%), and the median onset time after anti-tuberculosis treatment was 22 days. The time to onset of PR was shorter in diffuse pulmonary infiltrates group than in local pulmonary infiltrates group or in pleural effusion group. Low serum albumin, elevated lactate dehydrogenase (LDH), high Creactive protein (CRP) and chest radiographic appearance exceeding one-lung area were associated with PR incidence. There was no difference in sputum smear grading and pulmonary cavitation. Six out of the ten patients died, developing PR with diffuse pulmonary infiltrates. CONCLUSION: Low albumin and chest radiographic appearance exceeding one-lung area were risk factors for developing PR. Diffuse pulmonary infiltrates in early phase of anti-tuberculosis treatment was related with Inhospital mortality.

Bronchopleural fistula following M. abscessus infection 11 years after lobectomy for lung cancer.

Bronchopleural fistula (BPF) is a potentially fatal complication of lung cancer resection surgery that occurs during the healing process of the bronchial stump. However, the vulnerability of the healed surgical wound to overlapping acquired airway destruction has not yet been determined in detail. We herein present a case of fatal BPF following Mycobacterium abscessus (M. abscessus) infection, which occurred 11 years after right upper lobectomy for lung cancer. The findings of the present study suggest that patients with M. abscessus pulmonary disease in which airway destruction is progressing towards the bronchial stump of previous lobectomy should be considered for early completion pneumonectomy to prevent fatal BPF.

[A case of pulmonary nontuberculous mycobacteriosis induced by tocilizumab treatment for rheumatoid arthritis].

A 65-year-old woman whose rheumatoid arthritis was treated with tocilizumab (TCZ) was found in chest radiography to have a new consolidation in the right lower lung field. Positive Mycobacterium intracellulare and Mycobacterium avium cultures in sputum and bronchial secretions yielded a diagnosis of pulmonary nontuberculous mycobacteriosis. The most common adverse TCZ effect is infection. This case highlights the fact that those treated with TCZ should be considered at elevated risk for developing nontuberculous mycobacteriosis.

Chylothorax caused by acupuncture.

Chylothorax, the accumulation of fatty fluid within the chest cavity, is associated with multiple etiologies including surgical injuries. A rare complication of acupuncture in a 37-year-old woman who developed left pneumothorax and pleural fluid collection after acupuncture was performed on the neck and upper back is described. Chest tube drainage resulted in complete lung expansion, and analysis of the milky fluid revealed chyle leakage. Conservative treatment with a diet low in lipids and rich in medium-chain triacylglycerols allowed extubation. Acupuncture-induced thoracic duct injury, although extremely rare, should be considered as a cause of chylothorax.

[Two cases of drug-induced intrathoracic lesions caused by mesalazine in patients with ulcerative colitis].

We encountered 2 cases of drug-induced intrathoracic lesions caused by allergic reactions to mesalazine in patients with ulcerative colitis. Case 1: A 26-year-old man had a fever, cough and exertional dyspnea after 1 month of mesalazine treatment. He was hospitalized because of bilateral pulmonary infiltrates on a chest X-ray film. Case 2: A 27-year-old woman complained of fever and left back pain that exacerbated after 2 weeks of mesalazine treatment. She was hospitalized because of bilateral pulmonary effusions on chest CT. Both patients showed a positive reaction to a drug lymphocyte stimulation tests (DLST) for mesalazine. The first case was given a diagnosis of eosinophilic pneumonia by bronchoscopic examination, and responded to steroid therapy after discontinuation of mesalazine. The second case was given a diagnosis of pleuritis and improved on cessation of Mesalazine treatment.

Immunoglobulin D-lambda type multiple myeloma presenting with FDG-PET/CT negative bone marrow involvement.

We here report a rare case of a patient with IgD-lambda-positive multiple myeloma presenting with FDG-PET/CT negative bone marrow involvement. A 72-year-old man was admitted to our hospital for evaluation of a paravertebral tumor of the chest. Thoracotomy was performed and a histopathological evaluation of resected intrathoracic tumor demonstrated a plasmacytic neoplasma. Initially we thought that this case was a solitary plasmacytoma because there were no positive findings on postoperative FDG-PET/CT. However, bone marrow aspiration study demonstrated massive infiltration of myeloma cells (72%). It is necessary to recognize that IgD-lambda type myeloma cells may not be sufficiently metabolically active to form high uptake on FDG-PET/CT.

Autopsy case of rapid progressive atypical carcinoid of the lung discovered with multiple nodular shadows.

We report an autopsy case of rapid progressive atypical carcinoid of the lung discovered as multiple nodular shadows. The patient was an 82-year-old man with non-productive cough. Both chest radiography and computed tomography revealed multiple nodules in both the lung and pleural effusion. Multiple metastases to bone and liver were also noted. Samples from the wall-side pleural lesion were obtained by video-assisted thoracoscopic surgery under local anesthesia, and histological examination led to a diagnosis of atypical carcinoid. Treatment was ineffective and the patient died on day 39 after admission. The primary site was identified as the lung after autopsy. We believe that early detection is crucial in the treatment of atypical carcinoid due to poor prognosis.

Role of alpha1-acid glycoprotein in therapeutic antifibrotic effects of imatinib with macrolides in mice.

RATIONALE: Imatinib is an inhibitor of platelet-derived growth factor receptors. We have reported that treatment with imatinib inhibited bleomycin-induced pulmonary fibrosis in mice. However, late treatment with imatinib had no effect. OBJECTIVES: To clarify why imatinib had no antifibrotic effect when its administration was delayed, we focused on alpha(1)-acid glycoprotein (AGP), because it was reported to bind imatinib and mediate drug resistance. METHODS: The concentration of AGP in serum of mice and patients with idiopathic pulmonary fibrosis was measured by radial immunodiffusion testing. The effects of AGP in vitro were evaluated by assaying the growth of lung fibroblasts. We examined the combined effects of erythromycin (EM) or clarithromycin (CAM) on bleomycin-induced pulmonary fibrosis in mice. MEASUREMENTS AND MAIN RESULTS: Addition of AGP abrogated imatinib-mediated inhibition of the growth of fibroblasts. However, treatment with EM or CAM restored the growth-inhibitory effects of imatinib. The elevated level of AGP was detected in serum and lung homogenates in bleomycin-exposed mice and reached a plateau on Day 14. Imatinib alone did not ameliorate pulmonary fibrosis when treatment was started on Day 15, whereas coadministration of imatinib and EM or CAM significantly reduced the fibrogenesis via inhibition of the growth of fibroblasts in vivo. Serum levels of AGP were higher in patients with idiopathic pulmonary fibrosis than in healthy subjects. CONCLUSIONS: AGP is an important regulatory factor modulating the ability of imatinib to prevent pulmonary fibrosis in mice, and combined therapy with imatinib and EM or CAM might be useful for treatment of pulmonary fibrosis.

[A case of adult onset idiopathic pulmonary hemosiderosis markedly improved by steroid therapy].

A case of adult onset idiopathic pulmonary haemosiderosis (IPH) was reported. A 53-year-old man was admitted to our hospital because of repeated bloody sputum on June 2, 2006. Chest radiograph on admission disclosed diffuse infiltrative shadows in both lung fields, and one month later these shadows became more marked. The chest CT on July 5, 2006 showed patchy areas of ground-glass opacity and consolidation, exhibiting a distinctly peripheral distribution. Bronchoscopic findings revealed oozing bleeding from the orifice of B5 in the right lung and B9 in the left lung. We employed video-assisted thoracoscopic surgery for lung biopsy and he as primary IPH was diagnosed clinicopathologically. His symptoms and radiographic findings were markedly improved after steroid therapy, followed by no signs of recurrence. It may be important to establish a definitive diagnosis early, even in IPH, using VATS, for further effective therapy.

A novel IkappaB kinase-beta inhibitor ameliorates bleomycin-induced pulmonary fibrosis in mice.

RATIONALE: IkappaB kinase-beta is a critical regulator in the activation of nuclear factor-kappaB (NF-kappaB), a transcription factor related to the expression and regulation of proinflammatory cytokines. OBJECTIVE: To evaluate if inhibition of IkappaB kinase-beta ameliorates pneumonitis and pulmonary fibrosis. METHODS: We examined whether a novel IkappaB kinase-beta inhibitor, IMD-0354, attenuates bleomycin-induced pulmonary fibrosis in mice. MEASUREMENTS AND MAIN RESULTS: Administration of IMD-0354 significantly improved the loss of body weight and survival of mice treated with bleomycin, whereas IMD-0354 alone did not cause any morphologic change in the lung. When mice were evaluated 28 d after bleomycin administration, IMD-0354 dose-dependently reduced the collagen content and fibrotic scores as shown by histologic examination. The findings in the bronchoalveolar lavage demonstrated that the proportions of neutrophils and lymphocytes were decreased in mice treated with IMD-0354 on Day 7 and 14, respectively. IMD-0354 treatment was confirmed to inhibit the activation of NF-kappaB, but not activator protein-1, in the lungs treated with bleomycin. The production of inflammatory cytokines tumor necrosis factor-alpha and interleukin-1beta was reduced in the lungs of mice treated with IMD-0354. CONCLUSIONS: These results suggest that IMD-0354 might be useful to ameliorate the inflammation in the lungs induced by fibrotic injury and the subsequent fibrogenesis via inhibiting the expression of profibrotic cytokines related to the activation of NF-kappaB.

Retreatment of lung adenocarcinoma patients with gefitinib who had experienced favorable results from their initial treatment with this selective epidermal growth factor receptor inhibitor: a report of three cases.

Gefitinib is a selective inhibitor of epidermal growth factor receptor (EGFR) tyrosine kinases, and shows favorable antitumor activity against chemorefractory non-small cell lung cancer (NSCLC). The majority of responders (patients who are sensitive to gefitinib), however, relapse within 1.5 years, indicating an acquired resistance to gefitinib. Here we report three chemotherapy refractory NSCLC patients who were retreated with gefitinib. All three cases were nonsmokers and showed an adenocarcinoma histology. While they had experienced successful control from their initial treatment with gefitinib for more than 12 months, gefitinib therapy was terminated because two cases (cases 1 and 3) relapsed during the therapy and case 2 suffered alveolar hemorrhage. After more than 7 months from the time of discontinuation of the initial gefitinib treatment, they were retreated with gefitinib, as further tumor progression was observed. Of the three cases, cases 1 and 2 were well controlled by retreatment with gefitinib monotherapy for more than 7 months, suggesting sensitivity to retreatment. Case 3 also showed a regression in size of several tumors, while some other lesions progressively enlarged and developed a malignant pleural effusion after 4 months. These observations suggest the possibility that retreatment with gefitinib might be useful when 1) initial treatment shows a favorable clinical response, and 2) there has been a period of time following the termination of the initial gefitinib treatment.

Imatinib as a novel antifibrotic agent in bleomycin-induced pulmonary fibrosis in mice.

Imatinib mesylate is a potent and specific tyrosine kinase inhibitor against c-ABL, BCR-ABL, and c-KIT, and has been demonstrated to be highly active in chronic myeloid leukemia and gastrointestinal stromal tumors. We examined the antifibrotic effects of imatinib using a bleomycin-induced lung fibrosis model in mice because imatinib also inhibits tyrosine kinase of platelet-derived growth factor receptors (PDGFRs). Imatinib inhibited the growth of primary murine lung fibroblasts and the autophosphorylation of PDGFR-beta induced by PDGF. Administration of imatinib significantly prevented bleomycin-induced pulmonary fibrosis in mice, partly by reducing the number of mesenchymal cells incorporating bromodeoxyuridine. Analysis of bronchoalveolar lavage cells demonstrated that imatinib did not suppress early inflammation on Days 7 and 14 caused by bleomycin. These results suggest that imatinib has the potential to prevent pulmonary fibrosis by inhibiting the proliferation of mesenchymal cells, and that imatinib might be useful for the treatment of pulmonary fibrosis in humans.

Elevation of macrophage-derived chemokine in eosinophilic pneumonia: a role of alveolar macrophages.

Macrophage-derived chemokine (MDC/CCL22) and thymus-and activation-regulated chemokine (TARC/CCL17) are ligands for CC chemokine receptor 4. Recently, TARC has been reported to play a role in the pathogenesis of idiopathic eosinophilic pneumonia (IEP). The purpose of this study was to evaluate the role of MDC in IEP and other interstitial lung diseases (ILDs). MDC and TARC in the bronchoalveolar lavage fluid (BALF) were measured by enzyme-linked immunosorbent assay in patients with ILDs and healthy volunteers (HV). We also examined the expression of MDC mRNA in alveolar macrophages (AM) by real-time quantitative reverse transcriptase-polymerase chain reaction. Both MDC and TARC were detected only in BALF obtained from IEP patients. The concentration of MDC was higher than that of TARC in all cases. The level of MDC in IEP correlated with that of TARC. AM from IEP patients expressed a significantly higher amount of MDC than that from HV at the levels of protein and mRNA. MDC in BALF from IEP dramatically decreased when patients achieved remission. These findings suggest that MDC, in addition to TARC, might be involved in the pathogenesis of IEP, and AM play a role in the elevation of MDC in IEP.

A case of early-stage lung cancer detected by autofluorescence bronchoscopy.

A 71-year-old man was referred to our hospital for further examination of abnormal sputum cytology. No abnormal nodular shadows were detected in chest X-ray and chest CT. The location of the tumor was clearly identified as a defect of autofluorescence by autofluorescence bronchoscopy at the bifurcation between the left B1+2 and B3 bronchi, whereas it was quite difficult by conventional bronchoscopy. Transbronchial biopsy revealed squamous cell carcinoma. Further examinations yielded the diagnosis of early-stage lung cancer. Photodynamic therapy was performed and complete response was confirmed. This case indicates the efficacy of autofluorescence bronchoscopy for detecting early-stage lung cancer.