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.

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.

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.

Establishing and characterizing a new primary effusion lymphoma cell line harboring Kaposi's sarcoma-associated herpesvirus.

BACKGROUND: Primary effusion lymphoma is a rare distinct large B-cell neoplasm that is associated with Kaposi's sarcoma-associated herpesvirus (KSHV) infection. Over recent years, 9 KSHV-positive/Epstein-Barr virus (EBV)-negative PEL cell lines have been established. METHODS: Tumor cells were collected from the pleural effusion of a 49-year-old male with AIDS. Cells were grown in RPMI1640 culture medium supplemented with 10 % fetus bovine serum. Single cell cloning was performed successfully by a limiting dilution method in a 96-well plate. The cell line obtained was designated SPEL. RESULTS: SPEL cells showed gourd-shaped morphology with a polarized nucleus, expressing CD38, CD138, and Blimp-1, but not B cell markers such as CD19 and CD20. Polymerase chain reaction analysis revealed that SPEL cells were positive for KSHV but negative for EBV. Tetradecanoylphorbol acetate induced expression of KSHV lytic proteins and the production of KSHV particles in SPEL cells. Subcutaneous inoculation of SPEL cells into severe combined immunodeficiency mice resulted in the formation of solid tumors. Next-generation sequencing revealed the 138 kbp genome sequence of KSHV in SPEL cells. Suberic bishydroxamate, a histone deacetylase inhibitor, induced the expression of KSHV-encoded lytic proteins and cell death in SPEL cells. CONCLUSIONS: A new KSHV-positive and EBV-negative PEL cell line, SPEL was established. This cell line may contribute to furthering our understanding of the pathogenesis of PEL and KSHV infection.

Immunocytochemical utility of claudin-4 versus those of Ber-EP4 and MOC-31 in effusion cytology.

BACKGROUND: Recently, claudin-4 (CL4) immunocytochemistry was reported to be useful for differential diagnosis in effusion cytology. We wondered whether CL4 might be useful for "single-shot" identification of metastatic carcinoma. The purpose of this study was to evaluate the usefulness of CL4 in effusion cytology. METHODS: In total, 266 cases (169 metastatic carcinomas, eight malignant mesotheliomas, and 89 reactive mesothelial cells) were selected. Immunocytochemical examinations of cell-block sections were performed for CL4, Ber-EP4, and MOC-31. We used an arbitrary 4-tiered scale based on both staining intensity and positive-cell percentage among all target cells, and calculated a staining index score (sum of the above two scores). RESULTS: In a ROC-curve analysis, higher area-under-curve values were found for CL4 than for Ber-EP4 or MOC-31 (0.982, 0.942, and 0.926, respectively). CONCLUSIONS: Since CL4 exhibited similar or superior usefulness to Ber-EP4 and MOC-31, it could become the first choice for the above differential diagnosis in effusion cytology. Diagn. Cytopathol. 2016;44:499-504. © 2016 Wiley Periodicals, Inc.

Clinico-pathological analysis referring hemeoxygenase-1 in acute fibrinous and organizing pneumonia patients.

Acute fibrinous and organizing pneumonia (AFOP) is a very rare pathological entity of lung injury characterized by intra-alveolar fibrin balls. Hemeoxygenase (HO) -1 is a cytoprotective enzyme against oxidative stress and inflammation. It is known to be expressed in the alveolar macrophages in the healthy adults and overexpressed in other various lung cells of the lung injury patients. We experienced two cases of subacute form AFOP for these 10 years and reviewed clinico-pathological characteristics. The average age was 62 years old and both were male. The etiology of both cases was idiopathic. The average PaO2/FIO2 ratio was 274.5 ± 84.1. The average levels of C-reactive protein and surfactant protein - A of the serum were elevated to 19.8 ± 6.3 mg/dL and 67.6 ± 15.8 ng/mL, respectively. Serum sialylated carbohydrate antigen levels were normal in both cases. The characteristic radiographic findings were bilateral consolidations and ground glass opacities. Lung biopsy specimens revealed fibrin balls and alveolitis with abundant cellular HO-1 expression. Steroid response was excellent and the pulmonary involvements absolutely disappeared for about 3 months.

Secretory phospholipases A2 are secreted from ciliated cells and increase mucin and eicosanoid secretion from goblet cells.

BACKGROUND: Secretory phospholipases A2 (sPLA2) initiate the biosynthesis of eicosanoids, are increased in the airways of people with severe asthma, and induce mucin hypersecretion. We used IL-13-transformed, highly enriched goblet cells and differentiated (ciliary cell-enriched) human bronchial epithelial cell culture to evaluate the relative contribution of ciliated and goblet cells to airway sPLA2 generation and response. We wished to determine the primary source(s) of sPLA2 and leukotrienes in human airway epithelial cells. METHODS: Human bronchial epithelial cells from subjects without lung disease were differentiated to a ciliated-enriched or goblet-enriched cell phenotype. Synthesis of sPLA2, cysteinyl leukotrienes (cysLTs), and airway mucin messenger RNA and protein was measured by real-time-polymerase chain reaction and an enzyme-linked immunosorbent assay, and the localization of mucin and sPLA2 to specific cells types was confirmed by confocal microscopy. RESULTS: sPLA2 group IIa, V, and X messenger RNA expression was increased in ciliated-enriched cells (P < .001) but not in goblet-enriched cells. sPLA2 were secreted from the apical (air) side of ciliated-enriched cells but not goblet-enriched cells (P < .001). Immunostaining of sPLA2 V was strongly positive in ciliated-enriched cells but not in goblet-enriched cells. sPLA2 released cysLTs from goblet-enriched cells but not from ciliated-enriched cells, and this result was greatest with sPLA2 V (P < .05). sPLA2 V increased goblet-enriched cell mucin secretion, which was inhibited by inhibitors of lipoxygenase or cyclooxygenase (P < .02). CONCLUSIONS: sPLA2 are secreted from ciliated cells and appear to induce mucin and cysLT secretion from goblet cells, strongly suggesting that airway goblet cells are proinflammatory effector cells.

Successful diagnosis of tuberculous lymphadenitis by loop-mediated isothermal amplification of cutaneous samples from an ulcerated surface lesion: a case report.

INTRODUCTION: Tuberculous lymphadenitis is the most frequent form of extrapulmonary tuberculous. Although nucleic acid amplification assays such as polymerase chain reaction have recently become mainstream techniques for diagnosing tuberculous lymphadenitis, they are still not routinely performed in developing countries because of their high costs and complicated procedures. CASE PRESENTATION: We describe a case of tuberculous lymphadenitis in a 79-year-old Japanese man who had been on continuous hemodialysis for end-stage renal disease. We employed loop-mediated isothermal amplification and the procedure for ultrarapid extraction to develop a fast and easy-to-perform procedure for diagnosing tuberculous lymphadenitis. CONCLUSIONS: The commercially available loop-mediated isothermal amplification assay kit and a rapid purification procedure enabled us to identify and amplify a Mycobacterium tuberculosis-specific gene within just 1.5 hours.

Pleuroparenchymal fibroelastosis as a series of airway complications associated with chronic graft-versus-host disease following allogeneic bone marrow transplantation.

We herein report the case of a 31-year-old woman who presented with bilateral upper lobe volume loss and pleural irregularities with hilar retraction. She had undergone allogeneic bone marrow transplantation (BMT) for the treatment of acute lymphoblastic leukemia nine years earlier. A surgical lung biopsy showed pleural thickening and subpleural alveolar collapse and fibrosis, consistent with a diagnosis of pleuroparenchymal fibroelastosis (PPFE). Antecedent sicca syndrome and the absence of other causes of fibroelastosis suggested that these abnormalities were associated with chronic graft-versus-host disease (cGVHD). PPFE as a late, noninfectious complication is rare; however, the present case suggests a new class of BMT-related pulmonary complications associated with cGVHD.

[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.

A case of Nocardia asteroides infection in a patient with HIV/AIDS diagnosed by endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA).

We report a 45-year-old man with HIV/AIDS who developed mediastinal lymphadenopathy caused by Nocardia asteroides infection that was diagnosed by endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA). He was an untreated HIV-infected man who was admitted to our hospital because of Pneumocystis pneumonia and Cytomegalovirus pneumonia. After treatment for pneumonia, cough and fever recurred and chest computed tomography revealed subcarinal lymphadenopathy with rim enhancement. To identify the etiology, we performed EBUS-TBNA and obtained purulent exudates which contained N. asteroides. EBUS-TBNA is a useful and safe technique for the diagnosis of mediastinal infectious lymphadenopathy of unknown origin.

Cardiac asthma: transforming growth factor-ß from the failing heart leads to squamous metaplasia in human airway cells and in the murine lung.

BACKGROUND: Cardiac asthma describes symptoms of airflow obstruction due to heart failure. Chronic heart failure is associated with decreased FEV 1 , and FEV 1 improves after heart transplantation. Fibrotic remodeling of the heart and airways is mediated, in part, through transforming growth factor (TGF)- ß . Blood TGF- b 1 concentration correlates with ventricular remodeling in cardiac disease, and TGF- ß decreases after repair. METHODS: We established a coculture of normal human bronchial epithelial (NHBE) cells differentiated at air-liquid interface with submerged basal cardiomyoblasts. Airway cells were immunostained with cytokeratin, actin, and involucrin. TGF- ß synthesis was assayed using enzyme-linked immunosorbent assay. Phosphorylation of Smad in NHBE cells was determined by Western blotting.Mice given doxorubicin developed cardiac failure, and their airways were histologically examined. RESULTS: Coculture induced involucrin-positive squamous metaplasia of NHBE cells, and this was attenuated by TGF- ß antibody. Total TGF- ß 1 was increased in coculture conditioned medium( P < .001). After 14 days of exposure to recombinant TGF- ß 1 , there was squamous transformation of NHBE cells. One week after removing cardiomyoblasts from culture, squamous metaplasia resolved into normal ciliated epithelia. Smad was phosphorylated in NHBE cells with cardiomyoblasts or with recombinant TGF- ß 1 exposure. The airways of mice with heart failure also demonstrated involucrin-positive squamous transformation. CONCLUSIONS: TGF- ß from cardiomyoblasts or from the failing heart can cause airway squamous metaplasia via Smad signaling, and this is blocked by anti-TGF- b antibody and reversed when cardiac cells are removed from culture. This appears to be an important mechanism for airflow obstruction with heart failure, sometimes described as cardiac asthma.

Pulmonary intravascular lymphoma diagnosed by 18-fluorodeoxyglucose positron emission tomography-guided transbronchial lung biopsy in a man with long-term survival: a case report.

INTRODUCTION: 18-Fluorodeoxyglucose positron emission tomography can detect the pulmonary involvement of intravascular lymphoma that presents no abnormality in a computed tomography scan. CASE PRESENTATION: We report the case of a 61-year-old Japanese man who had pulmonary intravascular lymphoma and no computed tomography abnormality. We were able to make an antemortem diagnosis of pulmonary intravascular lymphoma by transbronchial lung biopsy according to 18-fluorodeoxyglucose positron emission tomography findings. He is free of recurrent disease 24 months after chemotherapy. CONCLUSIONS: To the best of our knowledge, this is the first reported case of a long-term survivor of pulmonary intravascular lymphoma diagnosed by transbronchial lung biopsy under the guide of 18-fluorodeoxyglucose positron emission tomography.

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.

Dapsone inhibits IL-8 secretion from human bronchial epithelial cells stimulated with lipopolysaccharide and resolves airway inflammation in the ferret.

BACKGROUND: IL-8 is an important activator and chemoattractant for neutrophils that is produced by normal human bronchial epithelial (NHBE) cells through mitogen-activated protein kinase (MAPK) and nuclear factor-κB (NF-κB) p65 pathways. Dapsone, a synthetic sulfone, is widely used to treat chronic neutrophil dermatoses. We investigated the effects of dapsone on polarized IL-8 secretion from lipopolysaccharide (LPS)-stimulated NHBE cells and further evaluated its ability to decrease LPS-induced inflammation in the ferret airway. METHODS: NHBE cells were grown at air-liquid interface (ALI) to ciliated differentiation. Baseline and endotoxin (LPS)-stimulated IL-8 secretion was measured by enzyme-linked immunosorbent assay at air and basal sides with and without dapsone. Western blotting was used to determine signaling pathways. In vivo, ferrets were exposed to intratracheal LPS over a period of 5 days. Once inflammation was established, oral or nebulized dapsone was administered for 5 days. Intraepithelial neutrophil accumulation was analyzed histologically, and mucociliary transport was measured on the excised trachea. RESULTS: Dapsone, 1 µg/mL, did not influence unstimulated (basal) IL-8 secretion. Apical LPS stimulation induced both apical and basolateral IL-8, but basolateral LPS increased only basolateral IL-8. Dapsone inhibited polarized IL-8 secretion from ALI-conditioned cells. Dapsone also decreased LPS-induced IL-8 mRNA level. LPS led to phosphorylation of extracellular signal-regulated kinase 1/2, but not p38 MAPK or c-Jun NH(2)-terminal kinase. LPS also induced NF-κB p65 phosphorylation, an effect that was inhibited by dapsone. Both oral and aerosol dapsone decreased LPS-induced intraepithelial neutrophil accumulation, but only treatment with aerosol dapsone restored mucociliary transport to normal. CONCLUSIONS: Dapsone, given either systemically or as an aerosol, may be useful in treating neutrophilic airway inflammation.

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.

[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.