Solitary pulmonary caseating granulomas: A 5-year retrospective single-center analysis.

Solitary pulmonary caseating granulomas (SPCGs) are a characteristic type of tuberculomas associated with infection with non-tuberculous mycobacteria (NTM) and other microbes; however, their significance remains unclear. The aim of the present study was to describe the clinical characteristics of patients with SPCGs in terms of diagnosis, presence of lung cancer and treatment status. A retrospective analysis of 17 immunocompetent patients with histopathologically confirmed caseating granulomas after undergoing video-assisted thoracoscopic surgery (VATS) was conducted at our center between 2011 and 2015. The patients comprised 10 men and 7 women with a mean age of 59.1±14.4 years. Of the 17 patients, 14 (82.4%) were asymptomatic and the lesions were discovered incidentally. In 2 patients the SPCGs were accompanied by a small satellite nodule (SPCG mean diameter, 16.2±5.1 mm). Mycobacteria, including Mycobacterium tuberculosis (11.8%), Mycobacterium avium (11.8%) Mycobacterium kansasii (23.5%) and other Mycobacterium spp. (5.9%), were isolated from 9 of the patients (52.9%). Concurrent lung cancer was present in 3 patients (17.6%). When microbial agents could not be isolated, the interferon-γ release assay was useful for diagnosis. Positron emission tomography was not found to be useful for differentiating SPCGs from lung cancer, or for differentiating tuberculomas from NTM pulmonary nodules (NTMPNs). NTMPNs in cases of SPCGs were diagnosed more frequently in men. The findings indicate that a course of observation may be sufficient for patients in whom an SPCG from NTM (NTMPN) is identified by VATS. However, the presence of concurrent lung cancer in certain cases indicates that malignancy should not necessarily be excluded, particularly in NTMPNs, and highlights the necessity of aggressive diagnosis by VATS.

Successful desensitization therapy involving fluoroquinolone for the treatment of a solitary tuberculoma: A case report and literature review.

The patient was a 31-year-old female with no previous health problems; however, during a health checkup in 2013, a nodule (2.5 cm in diameter) was identified in the S10 area of the left lung. No clinical symptoms were apparent. Positron emission tomography/computed tomography revealed an accumulation in the same region. The patient was suspected of having lung cancer, and video-assisted thoracoscopic surgery was performed. A histopathological examination of the resected specimen revealed epithelioid granulomas accompanied by caseous necrosis in the lesion. The culture was positive for Mycobacterium tuberculosis, which led to the final diagnosis of tuberculoma. Initially, the patient underwent anti-M.tuberculosis treatment [isoniazid (INH) + rifampicin (RFP) + ethambutol (EB) + pyrazinamide (PZA)]. However, two weeks later, the development of epatic dysfunction necessitated suspension of the medication. Treatment was resumed following improvement of the hepatic function. However, this relapsed two weeks later, resulting in discontinuation of the treatment. The patient was negative for each of the four drugs in the drug-induced lymphocyte stimulation test (DLST), and drug-induced hepatotoxicity (DIH) attributable to the anti-tuberculous drugs that were administered. Therefore, desensitization therapy was initiated. EB + PZA were changed to levofloxacin (LVFX) at an initial dose of 250 mg/day (dose level increased to the maintenance dose). Subsequently, desensitization therapy with RFP and INH was applied in accordance with the Japanese Society for Tuberculosis protocol. After each drug dose level reached the maintenance dose level, the therapy was completed following administration of the drugs for the recommended duration of 6 months. There were no signs of relapse 6 months following completion of the therapy. Therefore, the patient responded well to the substitute therapy with LVFX and desensitization therapy, and the present case report provided information regarding the treatment of tuberculoma.

Remission of ALK-negative primary pulmonary inflammatory myofibroblastic tumor on treatment with clarithromycin: A case report and review of the literature.

Inflammatory myofibroblastic tumors (IMTs) belong to an intermediate group of soft-tissue tumors, they are relatively rare but exhibit a wide range of pathologies, from benign to malignant. At present, no standard treatment has been established, however, it is known to be important to determine the grade of malignancy of the tumor, prior to treatment. The present study reports a 73-year-old female patient with no clinical manifestations, who, when examined radiographically at a health check exhibited bilateral thoracic infiltrative shadows and nodular shadows by chest CT. A metastatic tumor or an organizing pneumonia were suspected. Blood examination showed no abnormal findings, and a pathological diagnosis of IMT was given from the histological findings of the tissue extracted by video-assisted thoracic surgery. Histological analysis established the lack of expression of anaplastic lymphoma kinase (ALK1) and immunoglobulin subtype G4 (IgG4). Alteration of the radiological shadows was observed over several weeks, and after concluding that chronic inflammation was worsening the patient's condition, clarithromycin was administered as a long-term macrolide therapy. The IMT decreased in size, and eight months later it had almost resolved. The patient was last reported to be maintaining a stable condition with no relapse. Some IMT cases have malignant pathology, and should be carefully followed-up. However, in the present case, where the IMT is both ALK1-negative and IgG4-negative, its biological immune responsiveness appears to differ from positive cases, and an inflammatory response was predominant. Clarithromycin, has immunomodulatory and anti-inflammatory effects and appeared to be effective in treating the IMT of the patient in the present study.

Diffuse alveolar hemorrhage after use of a fluoropolymer-based waterproofing spray.

A 30-year-old man developed chills, cough and dyspnea a few minutes after using a fluoropolymer-based waterproofing spray in a small closed room. He visited our hospital 1 h later. Examination revealed that the patient had incessant cough, tachypnea, fever and decreased peripheral arterial oxygen saturation. Blood tests revealed leukocytosis with elevated serum C-reactive protein levels. Chest radiographs and computed tomography (CT) scan showed bilateral ground glass opacities, mainly in the upper lobes. Bronchoalveolar lavage (BAL) fluid obtained from the right middle lobe showed a bloody appearance. Microscopic examination of a BAL cytospin specimen revealed the presence of numerous red blood cells associated with extreme neutrophilia. Microbiological studies of the BAL fluid were negative. The patient was observed without corticosteroid therapy, and his symptoms and abnormal shadows on the chest radiographs and CT improved. On day 7 after admission, the patient was discharged from the hospital. Accidental inhalation of waterproofing spray may cause diffuse alveolar hemorrhage, a rare manifestation of acute lung injury. Supportive treatment may be effective and sufficient.

Repeated exposure to 5-bromo-2'-deoxyuridine causes decreased proliferation and low-grade inflammation in the lungs of mice.

Incorporation of 5-bromo-2'-deoxyuridine (BrdU) into proliferating cells has been used to label dividing cells in many tissues. Although BrdU has been shown to be genotoxic, teratogenic and mutagenic, such adverse effects have largely been ignored by researchers. We determined whether long-term BrdU exposure causes any histopathological changes in the lungs of mice. Eight-week-old male C57/BL6J mice were administered BrdU by intraperitoneal injection on 3 consecutive days of each week for 14 weeks. While no obvious structural changes such as tissue damage, fibrosis, emphysema, airway remodeling, vascular thickening or tumorigenesis were noted, a moderate degree of macrophage infiltration was observed in the airways and lung parenchyma in the lungs of the mice exposed repeatedly to BrdU (BrdU-exposed mice). The proliferative activities of the airway and alveolar epithelial and mesenchymal cells were reduced in the BrdU-exposed mice, although the numbers of these cells in the lungs were maintained. Double immunofluorescence study of the lungs of the BrdU-exposed mice showed overexpression of IL-6 in the airway epithelial and alveolar wall cells, some of which were also double-positive for BrdU. These results indicate that long-term exposure to BrdU inhibits cell proliferation and induces low-grade inflammation in the lungs of mice. Our findings underscore the need for caution in the interpretation of studies that involve long-term exposure to BrdU.

Clinical factors associated with negative urinary antigen tests implemented for the diagnosis of community-acquired pneumococcal pneumonia in adult patients.

OBJECTIVE: This study investigated clinical factors associated with negative urinary antigen tests (UAT) implemented for the diagnosis of pneumococcal community-acquired pneumonia (CAP) in adult patients. SUBJECTS AND METHODS: We reviewed the medical records of 755 adult patients who completed the UAT in our hospital between 2009 and 2012. Of these, we evaluated 63 patients with bacteriologically confirmed definite pneumococcal CAP (33 were UAT-positive, and 30 were UAT-negative). RESULTS: There was no significant difference between the UAT-positive and the UAT-negative patients regarding age, dehydration, respiratory failure, orientation, blood pressure (ADROP) score (the CAP severity score proposed by the Japanese Respiratory Society), gender, white blood cell counts, liver/kidney function tests, or urinalysis. However, serum C-reactive protein (CRP) concentrations were 31% lower in the UAT-negative patients than in the UAT-positive patients (p = 0.02). Furthermore, the prothrombin time-international normalized ratio was 50% higher in the UAT-negative patients than in the UAT-positive patients, although the difference did not reach statistical significance (p = 0.06). The prevalence of comorbidities was similar in both UAT-positive and UAT-negative patients. However, warfarin had been prescribed in 8 (27%) of the UAT-negative patients compared to only 1 (3%) of the UAT-positive patients (odds ratio = 11.6; p = 0.01). CONCLUSIONS: These results suggested that low serum CRP concentrations and the use of warfarin increased the possibility with which false-negative UAT results occurred in these patients with pneumococcal CAP.

Tracheobronchial foreign body aspiration demonstrating serial bronchopulmonary changes on computed tomography.

INTRODUCTION: Tracheobronchial foreign body may often be treated as asthma, chronic bronchitis or etc. especially in patients with no memories of aspiration episodes. CASE PRESENTATION: A 74-year-old woman, suffering from persistent cough, was temporarily misdiagnosed with allergic bronchopulmonary aspergillosis and treated for six months. During this period, computed tomography (CT) findings changed from thickened bronchial walls and a "tree-in-bud" pattern to clubbing bronchiectasis and atelectasis, and no significant bacteria was detected. Finally, a vegetable core was subsequently extracted via flexible bronchofiberscopy. Although the patient's symptoms improved dramatically, the bronchopulmonary lesion remained practically. CONCLUSIONS: We assume that chronologic CT findings of the bronchopulmonary damage by aspiration of a vegetable core, without significant detection of bacteria during the course, will be quite valuable for clinicians.

Lung metastasis of transitional cell cancer of the urothelium, with fungus ball-like shadows closely resembling aspergilloma: A case report and review of the literature.

The present study reports the case of a 67-year-old female patient who was initially diagnosed with pulmonary aspergilloma. This diagnosis was based on a chest computed tomography (CT) scan showing a cavitary lesion of 3.5 cm in diameter, with fungus ball-like shadows inside, and an air crescent sign in the right upper lung. At 63 years old, the patient was treated for transitional cell cancer of the urothelium (non-invasive, pT1N0M0) by total cystectomy, ileal conduit diversion and urostomy. For 4 years post-operatively, the patient was healthy and had no clinical symptoms, and the air crescent sign was not identified by chest CT until the patient had reached 67 years of age. However, a final diagnosis of lung metastasis of transitional cell cancer of the urothelium was histopathologically identified subsequent to video-assisted thoracic surgery. Although it is rare that transitional cell cancer moves to the lung and makes a cavitary lesion, a differential diagnosis of cancer is necessary, even when examining infected patients with air crescent signs that are characteristic of aspergilloma. The physician must be mindful of metastatic pulmonary tumors that closely resemble aspergillomas, not only in infectious diseases, but also in oncological practice. Primary surgical removal should be considered.

The role of Mycoplasma pneumoniae infection in the initial onset and exacerbations of asthma.

Asthma is a disease in which airway hyperresponsiveness, increased airway contraction, and airway secretion occur as a result of allergic airway inflammation. Mycoplasma infections are well known to exacerbate asthma pathology as well as to cause the onset of asthma itself. Mechanisms of airway epithelial injury, activation of innate immunity, or increased Th2-dominant immune responses caused by community-acquired distress syndrome toxin (CARDSTx) or diacylated lipoprotein have been reported in exacerbations or the onset of asthma because of Mycoplasma infections. In addition, involvement of cysteinyl leukotriene and transforming growth factor beta has been reported in the increased airway hyperresponsiveness and exacerbation of airway remodeling by Mycoplasma. Recent evidence suggests that treatment with macrolides improves asthma control through an inhibitory action on airway inflammation as well as by eradicating Mycoplasma.

Palliation of malignant tracheal stenosis with a second implantation of an expandable metallic stent under endotracheal intubation.

A 74-year-old man was admitted with respiratory failure and treated for tracheobronchial stenosis due to metastasis of renal cell carcinoma. It improved after implantation of an expandable metallic stent (EMS). One year later, the metastatic tumor at the near distal side of the EMS increased; eventually serious respiratory failure occurred again. However, the delivery catheter of EMS could not be inserted by the usual procedure because there was a strong tracheobronchial curve. Finally it passed along the inside of the endotracheal intubation tube. The respiratory failure was improved by the second implantation of EMS with the method of stent in stent. EMS is often effective in a case with a strong curve and twist of the trachea/bronchi. It was also considered one way of letting the delivery catheter pass inside the endotracheal intubation tube if the patient's respiratory condition was maintained.

Bronchial asthma developing after 15 years of immunosuppressive treatment following renal transplantation.

A 42-year-old woman who underwent renal transplantation from her mother at the age of 26 due to IgA nephropathy had since been treated with immunosuppressive agents, including prednisolone (PSL), azathioprine (AZA) and cyclosporine (CsA). The patient had remained clinically stable for 15 years. However, in the middle of May 2010, she developed bronchial asthma for the first time after performing house-cleaning activities and was treated with corticosteroids and antiasthmatic agents. The use of immunosuppressive agents as a treatment for severe bronchial asthma might have been related to the manifestation of bronchial asthma in this case.

[Flow and inspiratory pressure characteristics of In-Check(tm) and training whistles].

BACKGROUND: The optimal inhalation effort using dry powder inhalers (DPI's) varies with the specific inhaler. Accordingly, the device used for instruction in the proper use of the specific DPI should have physical characteristics similar to the actual DPI. However, the precision with which these devices mimic the actual DPI's has not been established. METHODS: We measured mouthpiece pressure (PI) and flow through the In-Check with an added flow resistance (for DiskusTM, DiskhalerTM, PulmicortTM, HandihalerTM, and ClickhalerTM) and the training whistles (for Diskus, Pulmicort, SymbicortTM, TwisthalerTM) at different inhalation pressures. RESULTS: Both the In-Check with an added flow resistance for individual DPI and the training whistles for each DPI had parabolic PI-flow relationships similar to the actual DPI. When a curve was drawn from direct readings of the In-Check scale, it fell consistently below that based on the pneumotachometer values. PI-flow curves of the actual DPI fell below both of the above curves. Among the same type of DPI, PI-flow relationships resembled each other, but one of 13 in the Diskus group demonstrated curves above and one of 6 in Pulmicort demonstrated curves below the others. The flows at which sounds were generated from the whistle were between 25-50 L/min. CONCLUSIONS: Both In-Check and training whistles had suitable PI-flow relationships. Flow readings taken directly from In-Check tended to be lower than the measured value. A few training whistles might generate sounds with efforts below the optimal one.

[The relationship between inspiratory pressure and flow through dry powder inhaler available in Japan].

OBJECTIVE: Recently many of the inhaled drugs are provided as dry powder formula and prescribed for such diseases as COPD and asthma exacerbation. Inspiratory flow rate through the dry powder device (DPI) has a significant influence on therapeutic response in these disease conditions. We planned to measure flow vs. pressure relationships of almost all of the DPIs available in Japan. METHODS: Driving pressure (PI) and flow through the DPI were measured and the linear regression lines between PI and flow(2) were drawn. RESULTS: The slope and intercept of the regression lines were as follows: Turbuhaler for Pulmicort 79.26 (l/s)(2)/cmH2O, 626 (l/s)(2), Turbuhaler for Symbicort 88.99, 688, Twisthaler 56.37, 478, Diskus 125.98, 872, Diskhaler, 166.98, 780, Handihaler, 54.88, 498, Clickhaler, 78.37, 452. We drew P(I) vs flow curves of each DPIs for instruction of DPI devices to the patients. CONCLUSION: Inspiratory pressure is an excellent parameter to indicate optimal flow through DPI. Early escalation of medication may be important in the patients using Turbuhaler or Twisthaler that has higher resistance in inspiratory channel.

The efficacy of an oxygen mask with reservoir bag in patients with respiratory failure.

BACKGROUND: Oxygen masks with reservoir bags (OMR) are widely used for oxygen therapy in patients with severe respiratory failure. The purpose of the present study was to determine whether OMRs are effectively used in clinical practice. METHODS AND RESULTS: In the first phase of the study on the patients with severe respiratory failure, no apparent respiratory motions of the reservoir bag were noted, and the oxygen saturation level as determined by pulseoximetry (SpO2) did not decrease even after shrinkage of the reservoir bag. In the second phase, when a healthy female volunteer wore an OMR, pressure swings in the reservoir bag were less than 0.1 cmH2O, even when she was breathing with her maximal respiratory efforts (tidal volume, 1.14 L and respiratory frequency, 19.2 bpm). These pressure swings provoke a less than 50 mL oxygen supply from the reservoir bag. The decreased efficacy of OMR in oxygen therapy may be primarily due to the large space between the OMR and the nose but this space is inevitable in sitting or orthopneic subjects. CONCLUSIONS: Fixing an OMR very tightly to the face is mandatory for its effective use. It should also be kept in mind that there are limitations to the efficacy of OMR, even when they are used with such careful management.

Increase of atypical lymphocytes expressing CD4+/CD45RO+ in an infectious mononucleosis-like syndrome associated with hepatitis A virus infection.

Subpopulations of regular and atypical lymphocytes in the peripheral blood of a 24-year-old man with an infectious mononucleosis (IM)-like syndrome associated with hepatitis A virus (HAV) infection were analyzed. The ratio of CD4+ to CD8+ cells was in the normal range (1.19 and 1.23 in the regular and atypical lymphocytes, respectively), with no increase in CD8+ cells. The percentage of CD8+/CD11b- cells was not increased in the atypical lymphocytes. However, CD45RO+ was expressed on 86.3% of CD4+ atypical lymphocytes. The present data suggest that atypical lymphocytes expressing CD4+/CD45RO+ may play the role of helper T cells in the immune system in the development of IM-like syndrome associated with HAV infection.

Chlamydia pneumoniae growth inhibition in cells by the steroid receptor antagonist RU486 (mifepristone).

Since steroids are powerful anti-inflammatory agents and increase susceptibility to a variety of infections, including Chlamydia (Chlamydophila) pneumoniae respiratory tract infections, the effect of the steroid receptor antagonist RU486 (mifepristone) on C. pneumoniae growth in epithelial HEp-2 cells was examined. Treatment of HEp-2 cells with RU486 significantly inhibited the growth of C. pneumoniae in a dose-dependent manner. Electron microscopic studies also revealed that the treatment of infected cells with RU486 resulted in a marked destruction of infecting organisms. The addition of the host cell protein synthesis inhibitor cycloheximide to the infected cells did not alter the inhibition of C. pneumoniae growth by RU486. Pretreatment of C. pneumoniae organisms with RU486 before addition to culture also did not result in any modulation of bacterial growth in the cells. However, the binding of RU486 to C. pneumoniae organisms in cells at 24 h after infection was demonstrated by immune electron microscopy with anti-RU486 antibody. Incubation of cells with anti-RU486 antibody completely diminished the inhibition of C. pneumoniae growth by RU486. These results indicate that RU486 may directly bind to the bacteria within cells and cause the destruction of C. pneumoniae. This novel mode of regulation of C. pneumoniae growth in cells by RU486 might provide a new approach to understanding complicated aspects of C. pneumoniae infection.

Chlamydia pneumoniae growth inhibition in human monocytic THP-1 cells and human epithelial HEp-2 cells by a novel phenoxazine derivative.

In this study the effects of 2-amino-phenoxazine-3-one (phenoxazine derivate, Phx-3) on Chlamydia (Chlamydophila) pneumoniae growth in human monocytic THP-1 cells as well as human epithelial HEp-2 cells were examined. Cells were infected with bacteria at an m.o.i. of 10 by centrifugation. After washing to remove any remaining bacteria, the cells were incubated with or without Phx-3 in the presence or absence of tryptophan for 72 h. The bacteria in cells were assessed by staining of chlamydial inclusions with FITC-labelled anti-chlamydial antibody, electron microscopic analysis, real-time RT-PCR specific for C. pneumoniae 16S rRNA and propagation on HEp-2 cells. Treatment with Phx-3 significantly inhibited growth of C. pneumoniae in THP-1 and HEp-2 cells. A decrease in the number of bacterial 16S rRNA transcripts was also confirmed in both cell lines by real-time RT-PCR. Electron microscopic studies revealed that treatment with Phx-3 induces bacterial destruction in most of the inclusion bodies in these cells. Addition of tryptophan to the culture slightly blocked the growth inhibition of C. pneumoniae by Phx-3. The reagents did not show any cytotoxicity to the cells at the concentrations used. The results suggest that Phx-3 inhibits C. pneumoniae replication in human monocytic cells as well as epithelial cells, partially depending on the tryptophan-metabolic pathway of host cells. Thus, Phx-3 might be a useful compound for controlling C. pneumoniae growth in cells and may be an alternative conventional therapy.

Prevalence of viable Chlamydia pneumoniae in peripheral blood mononuclear cells of healthy blood donors.

BACKGROUND: Demonstration of viable Chlamydia (Chlamydophila) pneumoniae in peripheral blood mononuclear cells (PBMNCs) is essential to understand the involvement of C. pneumoniae in atherosclerosis. Nevertheless, the prevalence of viable C. pneumoniae in the blood of healthy donors has not yet been studied. STUDY DESIGN AND METHODS: The presence of C. pneumoniae transcript in PBMNCs from blood of healthy human donors was assessed by real-time reverse transcription-polymerase chain reaction (RT-PCR) with primers for C. pneumoniae 16S rRNA, which is more sensitive than genomic-DNA-based analysis, and by the use of staining with fluorescein isothiocyanate-conjugated chlamydia monoclonal antibody (MoAb). RESULTS: Thirteen of 70 donors (18.5%) showed the presence of bacterial transcript in cultured PBMNCs. The prevalence of bacterial detection and bacterial numbers was significantly increased in PBMNC cultures incubated with cycloheximide. Immunostaining of PBMNCs with antichlamydial MoAb also revealed the presence of bacterial antigen in the PBMNCs judged as positive. Nevertheless, cultivation of C. pneumoniae from all PCR-positive donors was unsuccessful. There was no significant correlation between the presence of chlamydia and either sex or current smoking habits. A possible age variation, however, in the presence of chlamydia in blood of healthy donors was suggested by the results obtained. CONCLUSION: The bacterial transcripts in PBMNCs obtained from healthy donors were detected by the RT-PCR method. Viable C. pneumoniae may be present in healthy human PBMNCs.