A case of Epstein-Barr virus-negative human immunodeficiency virus-related primary effusion lymphoma.

Primary effusion lymphoma (PEL) is a rare subtype of large B-cell lymphoma associated with human herpesvirus-8. Most cases are co-infected with Epstein-Barr virus (EBV). The prognosis of PEL is extremely poor and no optimal treatment regimen has been established. We report a case of EBV-negative PEL in a 49-year-old human immunodeficiency virus-positive man, presenting with massive bilateral pleural effusion.

[A case of eosinophilic granulomatosis with polyangiitis with extra-vascular granuloma and eosinophilic vasculitis diagnosed by transbronchial lung biopsy].

A 62-year-old man was suffering from bronchial asthma and referred to our institution with dry cough and dyspnea on exertion in November, 2010. He was diagnosed with eosinophilic granulomatosis with polyangiitis (EPGA, formerly Churg-Strauss syndrome) by chest radiographic findings, blood eosinophilia, mononeuritis multiplex and cardiomyopathy. Steroid therapy was started and he was rapidly improved. Steroid therapy had been tapered off by May, 2012. After 2 months, however, progressive dyspnea, neural symptoms, deafness, re-elevation of blood eosinophils and bilateral multifocal infiltrations appeared. He was re-admitted to our institution. Transbronchial lung biopsy (TBLB) specimens revealed extra-vascular granuloma, eosinophilic vasculitis and eosinophilic pneumonia and we diagnosed him with the reccurence of EGPA. He was improved by steroid pulse therapy, then tapered. This case was the antineutrophil cytoplasmic autoantibodies negative EGPA. The case of EGPA with granuloma and vasculitis diagnosed by TBLB was rare.

Usefulness of SMART-COP score in prognosis of aspiration pneumonia.

INTRODUCTION: Aspiration pneumonia is becoming a common syndrome in the elderly in aging societies such as Japan. Although a number of tools have been validated for prediction of mortality in patients with community-acquired pneumonia, none have been established for aspiration pneumonia. The purpose of this study was to access the correlations of the A-DROP, CURB-65 and SMART-COP scores at the emergency visit with the 30-day mortality risk in patients with aspiration pneumonia. METHODS: We Titleretrospectively investigated 210 patients who presented to the emergency department at Mishuku Hospital in Tokyo, Japan. RESULTS: The areas under the curve for the ability of A-DROP, Curb-65 and SMART-COP scores to predict the 30-day mortality risk were 0.6359, 0.6468 and 0.7594, respectively. Among the parameters of SMART-COP, involvement of multiple lobes on chest radiographs is the best predictor of the mortality. CONCLUSIONS: The SMART-COP score can be a better predictor of the 30-day mortality risk.

Mechanisms of action and clinical application of macrolides as immunomodulatory medications.

Macrolides have diverse biological activities and an ability to modulate inflammation and immunity in eukaryotes without affecting homeostatic immunity. These properties have led to their long-term use in treating neutrophil-dominated inflammation in diffuse panbronchiolitis, bronchiectasis, rhinosinusitis, and cystic fibrosis. These immunomodulatory activities appear to be polymodal, but evidence suggests that many of these effects are due to inhibition of extracellular signal-regulated kinase 1/2 (ERK1/2) phosphorylation and nuclear factor kappa B (NF-kappaB) activation. Macrolides accumulate within cells, suggesting that they may associate with receptors or carriers responsible for the regulation of cell cycle and immunity. A concern is that long-term use of macrolides increases the emergence of antimicrobial resistance. Nonantimicrobial macrolides are now in development as potential immunomodulatory therapies.

Acute eosinophilic pneumonia following aromatherapy with essential oil.

Essential oils are liquid extracts of various plants with potential health benefits and are often used in aromatherapy. Contact allergy, including skin irritation, is a well-known side effects of these extracts. A Japanese woman visited our emergency department complaining of dyspnea, cough, and fever. Two weeks earlier, she had started aromatherapy using a humidifier and essential oil. Based on clinical and imaging findings, and the results of bronchoalveolar lavage, we diagnosed acute eosinophilic pneumonia due to inhalation of essential oil. Her symptoms resolved after steroid therapy. This case makes the clinicians aware the possibility of acute eosinophilic pneumonia induced by aromatherapy using essential oil.

Clarithromycin inhibits interleukin-13-induced goblet cell hyperplasia in human airway cells.

IL-13 is a T-helper class 2 cytokine that induces goblet cell hyperplasia and mucus production in airway epithelial cells. Because macrolide antibiotics are known to have immunomodulatory and mucoregulatory properties, the aim of this study was to examine the effect of clarithromycin on IL-13-induced goblet cell hyperplasia and mucin hypersecretion in normal human bronchial epithelial (NHBE) cells. NHBE cells were cultured to differentiation at an air-liquid interface with IL-13 plus clarithromycin or vehicle. Histochemical analysis was performed using H&E staining, periodic acid-Schiff (PAS) staining, and MUC5AC immunostaining. MUC5AC synthesis was assayed using RT-PCR and ELISA. Western blotting was used to evaluate signaling pathways. IL-13 significantly increased the number of PAS-positive, MUC5AC-positive goblet cells, and this was significantly attenuated by clarithromycin at concentrations greater than 8 µg/ml (P < 0.01). Clarithromycin also dose-dependently decreased MUC5AC mRNA expression induced by IL-13 (P < 0.001), and, at 24 µg/ml, clarithromycin significantly attenuated the amount of MUC5AC protein in cell supernatants (P < 0.01). Western blotting showed that clarithromycin affected IL-13 receptor janus kinase signal transducers, activators of transcription6 (STAT6), and epidermal growth factor receptor mitogen-activated protein kinase signaling and that inhibition of these pathways by clarithromycin decreased goblet cell hyperplasia via nuclear factor-κB inactivation. We conclude that clarithromycin inhibits goblet cell hyperplasia and may directly regulate mucus secretion by IL-13 in NHBE cells.

[Bronchoscopic follow-up of secondary racemose hemangioma of the bronchial artery].

A 63-year-old woman with cystic bronchiectasis who had been treated in our institute was admitted for recurrent prolonged hemoptysis. Bronchoscopic examination showed bloody discharges in the left basal bronchus and a bulging polypoid lesion covered with intact bronchial mucosa in the left B8. In comparison with the bronchoscopic examination 6 years ago, the lesion was larger and the mucosal color changed more injected. A bronchial arteriogram revealed a convoluted and dilated left bronchial artery. Because bronchial artery embolization failed, a left lower lobectomy was performed. The diagnosis of secondary racemose hemangioma of the bronchial artery was pathologically established. A racemose hemangioma of the bronchial artery is characterized by an enlarged and convoluted bronchial artery. The bronchoscopic findings of this disorder have been rarely reported. This case may provide valuable information about serial bronchoscopic findings and the progression of secondary racemose hemangioma in the bronchial artery.

[Bronchoscopic autologous blood injection for lung volume reduction].

Bronchoscopic lung volume reduction (BLVR) for emphysematous lung diseases has attracted clinical attention. We evaluated the newly developed procedure of BLVR performed by transbronchial infusion of autologous blood. The subjects were 4 patients with a mean age of 57 years with emphysematous lung diseases, consisting of 1 with emphysematous bulla, 1 with lymphangioleiomyomatosis and 2 with advanced emphysema. Informed consent was obtained from all patients, and the Institutional Review Board of Ethics approved the treatment protocol. Intervention was performed as follows: A catheter was inserted into the target area through a flexible bronchoscope under fluoroscopic guidance, and autologous blood followed by thrombin solution was infused via the catheter. This simple procedure was repeated to several different areas as necessary. This BLVR therapy was well tolerated in all 4 patients. There were no severe complications. Symptomatic improvement was noted in all patients. Spirometry showed a mean increase in FVC from 2.68 to 2.75L and FEV1 from 1.10 to 1.25 L, whereas body plethysmography showed a mean reduction in FRC from 5.09 to 4.75L and TLC from 7.18 to 6.80 L. No consistent change in D(Lco)/VA was observed. Arterial blood gas value and the 6-minute walk distance improved in 3 and 2 patients, respectively. This bronchoscopic approach is minimally invasive, easy and inexpensive. BLVR by injection of autologous blood appears to represent a good therapeutic option, and warrants further investigation.

[Analysis of endobronchial aspergillosis in patients without obvious systemic predisposing factors].

BACKGROUND: Endobronchial aspergillosis is still an insufficiently recognized concept. PATIENTS AND METHODS: Ten patients who did not have obvious predisposing factors and parenchymal fungal infection were analyzed. They were confirmed to have endobronchial Aspergillus by histology and culture, and were classified according to the presence of bronchiectasis, allergic reaction, and asthmatic symptom. RESULTS: Bronchiectasis was detected in all 10 patients, IgE elevation (>370 IU/ml) in 7, Aspergillus specific IgE-RAST in 8, eosinophilia in 7, and asthmatic symptom in 5. Cases were classified into allergic bronchopulmonary aspergillosis (ABPA) (5 cases), ABPA not fulfilling Rosenberg's criteria (2 cases), and endobronchial aspergilloma (3 cases). CONCLUSION: We proposed classifying endobronchial aspergillosis without obvious systemic predisposing factors into "ABPA", "ABPA without asthma", "ABPA-S (seropositive)", and "Endobronchial aspergilloma". A fifth subtype of endobronchial aspergillosis containing "saprophyte" is warranted.

Tracheo-broncho-bronchiolar lesions in Sjögren's syndrome.

A 53-year-old woman reported having a persistent cough and bloody sputum. She did not smoke but had received a diagnosis of Sjögren's syndrome. Chest CT revealed middle lobe syndrome, bronchiectasis and diffuse centrilobular nodular lesions. Bronchoscopy displayed multiple whitish polypoid lesions protruding from the cartilage rings and tracheobronchopathia osteochondroplastica was histologically confirmed by the presence of bony tissue in the tracheo-bronchial wall. Video-assisted thoracoscopic biopsy demonstrated lymphocyte aggregation causing follicular broncho-bronchiolitis. Erythromycin therapy resulted in improvement of the follicular bronchiolitis but not the tracheobronchopathia osteochondroplastica.

[Solitary nodular sarcoidosis demonstrating reversed tuberculin skin reaction].

A 29-year-old woman was admitted because of chest radiograph abnormality. She had no respiratory complaints. Chest CT demonstrated an ill-defined nodule of 20mm with the "sarcoid galaxy sign" in the right upper lobe. Transbronchial biopsy (TBB) specimens from right S2 revealed non-caseating epithelioid cell granuloma. Initial clinical findings suggested mycobacterial infection. However, while waiting for the results of mycobacterial cultures in bronchial washing fluid, the tuberculin skin reaction was found to be negative, and enlargement of nodule, mediastinal lymphadenopathy and elevated soluble IL-2R were observed. Cultures for mycobacterium were negative and repeat TBB specimens revealed granulomatous inflammation. We diagnosed with sarcoidosis based on these findings. Solitary nodular sarcoidosis is rare with only 17 cases having been reported. These cases were diagnosed with difficulty because of non-specific clinical findings and of the 17, 16 cases (94%) were diagnosed by surgical procedures. We observed the clinico-radiological course of solitary nodules and the change in tuberculin reaction. Although a negative tuberculin skin reaction was commonly recognized in sarcoidosis patients, we confirmed that initial positive tuberculin reaction changed to negative according to disease progress. To the best of our knowledge, this is the first case report in adults.

[Case of metastatic germ cell tumor with testicular calcification detected by MD-CT].

Metastasis of testicular germ cell tumor should be included in the differential diagnosis when young male patient have multiple pulmonary metastases. However burned-out tumors cannot be easily detected on inspection and palpation of the testis. A 19 year-old man visited to our hospital complaining of anorexia, weight loss and dyspnea. Chest X-ray films showed multiple lung nodules. Physical examination revealed gynecomastia, and many cervical, axillary, and inguinal lymph nodes with a diameter of 1 cm were palpable. Physical examination of testis revealed no laterality. Multi-detector CT showed multiple lung nodules, a hepatic and a retroperitoneal large mass and a tiny calcification in the right testis. Histological findings of the lung obtained by percutaneous biopsy and the presence of a calcification in the testis led to a diagnosis of testicular choriocarcinoma showing burned-out tumor. However there was no previous report of burned-out tumor detected by CT, MD-CT including that of the testis was valuable at the first diagnostic stage when germ cell tumor was suspected.

[Bird-related chronic hypersensitivity pneuminitis demonstrating the fluctuation of disease activity accompanied with environmental changes].

We report a case of bird-related chronic hypersensitivity pneuminitis exhibiting the fluctuation of serum markers for interstitial lung disease along with the changes in life environment. A 65-year-old man had had an abnormal chest radiograph for 2 years and had complained of a non-productive cough. He had had 30 parakeets 20 years previously and had used feather products for 15 years. In autumn and early winter wild birds had visited persimmons trees in the neighboring garden. Antibodies to bird-related antigens in the broncho-alveolar lavage fluids and sera were positive and the thoracoscopic lung biopsy specimens histologically revealed airway-centered fibrosis. We then determined he was having bird-related chronic hypersensitivity pneumonitis. After avoidance of feather products, all of serum SP-A, SP-D and KL-6 decreased. But three markers elevated and radiographic findings worsened accompanied with the increase of visiting wild birds in next autumn. After pruning persimmon trees and starting corticosteroid with cyclosporine, disease activity gradually improved.

[A case of HTLV-1 associated bronchiolo-alveolar disorder showing progressive air trapping].

A 65-year-old woman whose parents were from Okinawa Prefecture, had productive cough and bilateral diffuse nodular lesions on chest X-ray. She had been shown a human T-cell lymphotropic virus type-1 (HTLV-1) carrier. Video-assisted thoracoscopic lung biopsy showed marked peribronchiolar infiltration of lymphocytes and stenosis of bronchioles. HTLV-1 associated bronchiolo-alveolar disorder (HABA) was diagnosed. The symptoms, hypoxemia and chest X-ray findings improved with oral erythromycin. However, expiratory chest CT showing mosaic perfusion, pulmonary function test demonstrating increased thoracic gas volume, and ventilation scintigraphy resulting in decreased clearance during 8 years, all of those findings indicated progression of air trapping. Abnormalities on chest CT partially improved, but bronchiolar lesions have deteriorated. Expiratory chest CT, body phlethysmography and ventilation scintigraphy were recommended to clarify the course of HABA.

[A case of radiographic stage 0 sarcoidosis with severe cough].

A 63-year-old woman complained of continuous dry cough and high fever for two months. Chest radiography showed no abnormality, but inspiratory fine crackles were audible. Interstitial lung disease was suspected and bronchoalveolar lavage was performed via a bronchoscope. Disseminated minute granular lesions with redness and hypervascularity from the upper trachea to bilateral lober bronchi were detected. Lesions were also present in the membranous portion of the left main bronchus. Histological results for bronchial biopsy and transbronchial lung biopsy showed non-caseous epithelioid cell granuloma. This, together with a high CD4/8 lymphocyte ratio (4.11) in bronchoalveolar lavage fluid and the gallium scintigraphic findings, confirmed the diagnosis of sarcoidosis. To the best of our knowledge there are no other reports of cases with a similar bronchoscopic appearance in which the chest roentgenologic classification was stage 0, despite severe respiratory symptoms. Nodular lesions are seen in some cases of endobronchial sarcoidosis, but in this case, these widespread granular lesions were a unique feature that prompted us to make this report.

IgG4-positive pulmonary disease.

We report herein high-resolution computed tomography findings from a patient with IgG4-related pulmonary disease for the first time. The 61-year-old male patient complained of low-grade fever, dry mouth, and night sweats. He was diagnosed as having autoimmune pancreatitis, Sjögren syndrome, and elevated serum IgG4. High-resolution computed tomography of the lungs showed dense alveolar consolidation and air bronchograms in bilateral perihilar regions. IgG4-positive lymphoplasmacytes were detected in pulmonary lesions by immunostaining of biopsy samples. IgG4-related pulmonary disease can be associated with various radiologic findings.

[Resected pulmonary sarcoidosis after corticosteroid treatment still showing pathological granulomatous inflammation].

It is not well understood what kind of histologic resolution is obtained with corticosteroid medication in sarcoidosis, or how we are able to judge cure in that disease. We examined the cases of sarcoidosis who were under steroid medication and received lobectomy and lymphadenectomy for combined lung cancer. Steroid treatment had been introduced for the relief of visual disturbance, not for the pulmonary lesion. Administration of corticosteroid improves clinical, laboratory, bronchoalveolar lavage and radiological findings, but it is difficult to make histological granulomatous inflammation completely disappear. Improvement of radiological and clinical problems in sarcoidosis is not the same as complete cure in patients with steroid-treated sarcoidosis.

Arterial Carboxyhemoglobin Measurement Is Useful for Evaluating Pulmonary Inflammation in Subjects with Interstitial Lung Disease.

Objective The arterial concentration of carboxyhemoglobin (CO-Hb) in subjects with inflammatory pulmonary disease is higher than that in healthy individuals. We retrospectively analyzed the relationship between the CO-Hb concentration and established markers of disease severity in subjects with interstitial lung disease (ILD). Methods The CO-Hb concentration was measured in subjects with newly diagnosed or untreated ILD and the relationships between the CO-Hb concentration and the serum biomarker levels, lung function, high-resolution CT (HRCT) findings, and the uptake in gallium-67 (67Ga) scintigraphy were evaluated. Results Eighty-one non-smoking subjects were studied (mean age, 67 years). Among these subjects, (A) 17 had stable idiopathic pulmonary fibrosis (IPF), (B) 9 had an acute exacerbation of IPF, (C) 44 had stable non-IPF, and (D) 11 had an exacerbation of non-IPF. The CO-Hb concentrations of these subjects were (A) 1.5±0.5%, (B) 2.1±0.5%, (C) 1.2±0.4%, and (D) 1.7±0.5%. The CO-Hb concentration was positively correlated with the serum levels of surfactant protein (SP)-A (r=0.38), SP-D (r=0.39), and the inflammation index (calculated from HRCT; r=0.57) and was negatively correlated with the partial pressure of oxygen in the arterial blood (r=-0.56) and the predicted diffusion capacity of carbon monoxide (r=-0.61). The CO-Hb concentrations in subjects with a negative heart sign on 67Ga scintigraphy were higher than those in subjects without a negative heart sign (1.4±0.5% vs. 1.1±0.3%, p=0.018). Conclusion The CO-Hb levels of subjects with ILD were increased, particularly during an exacerbation, and were correlated with the parameters that reflect pulmonary inflammation.

Squamous Cell Carcinoma of the Lung Spreading Along the Alveolar Walls With a Bubblelike Appearance on HRCT.

On health examination, a nodular opacity of size of 25 mm was detected in a 54-year-old man. High-resolution computed tomography scans showed irregular-shaped ground glass opacity with bubble-like appearance in the right lung. The low-magnified histological findings after right upper lobectomy demonstrated squamous cell carcinoma that progressed along the alveolar septum and resembled the growing pattern of bronchioloalveolar carcinoma. As the mechanism of the formation of air density on computed tomography, the presence of check valve phenomenon was estimated. Squamous cell carcinoma of the lung that multiplies along alveolar walls shows localized ground glass opacity including air density areas similar to those in bronchioloalveolar carcinoma on high-resolution computed tomography.

[Disseminated Mycobacterium avium infection in an immunocompetent aged patient].

We reported an immunocompetent elderly patient with disseminated Mycobacterium avium infection exhibiting bronchial, pulmonary, nodal, otitic and osteitic lesions. An 82-year-old man was initially hospitalized with cervical and mediastinal lymphadenopathy. M. avium was demonstrated in gastric juice and a lymph node. An endobronchial polypoid lesion was formed by perforation of mediastinal mycobacterial lymphadenitis into the right main bronchus. Combined treatment by CAM, RFP, EB, and SM caused the lesions to diminish and the treatment was continued for 18 months. One year after completion of treatment the patient was re-admitted with complaints of left ear pain, and a subcutaneous abscess on his back. M. avium was again demonstrated from external ear exudate and aspirated subcutaneous pus. Re-treatment with combined chemotherapy induced prompt resolution of the ear and bone lesions. It is unusual that immunocompetent patients suffer disseminated non-tuberculous mycobacterial infection, but chest physicians should pay attention to M. avium infection because of its worldwide dissemination.