Influence of corticosteroid therapy on the serum antibody response to influenza vaccine in elderly patients with chronic pulmonary diseases

Annual influenza vaccination is strongly recommended for patients with chronic pulmonary diseases, such as bronchial asthma, chronic obstructive pulmonary disease (COPD), and interstitial pulmonary diseases. However, many of these patients regularly receive systemic and/or inhaled corticosteroid therapy, and the impact of corticosteroid therapy on influenza vaccine efficacy and safety is unclear. Patients with chronic pulmonary diseases were enrolled in the study and divided into three groups based on their maintenance therapy: (A) without corticosteroid therapy (17 males, three females; mean age, 72.3 ± 7.9), (B) oral corticosteroid therapy (four males, seven females; mean age, 66.1 ± 10.6), and (C) inhaled corticosteroid therapy (eight males, nine females; mean age, 62.4 ± 16.0). All patients received influenza vaccine, and serum hemagglutination inhibition (HI) antibodies against influenza strains A/H1N1, A/H3N2, and B were measured at baseline (before vaccination) and 4-6 weeks after vaccination. Sufficient antibody titers or significant increases were observed after vaccination compared with titers before vaccination in all three groups. No systemic reactions were reported. Long-term oral/inhaled corticosteroid therapy was not associated with vaccination side effects and did not affect the immune response to the influenza vaccine

Two cases of bronchiolitis obliterans organizing pneumonia syndrome after postoperative irradiation for breast cancer

We report two cases of bronchiolitis obliterans organizing pneumonia (BOOP) syndrome that developed after postoperative radiation therapy for breast cancer. In both patients, chest radiographs and computed tomography (CT) showed multiple consolidations outside the irradiation fields after several months of tangential radiation therapy. These patients were diagnosed as having radiation-associated BOOP syndrome, based on their clinical course and the findings on examination. After treatment with a systemic corticosteroid, radiographic consolidations and symptoms improved rapidly. In cases where consolidations appear outside the irradiated field, it is important to consider BOOP syndrome as a pulmonary complication of radiation therapy for breast cancer

Osimertinib as treatment for EGFR exon 20 insertion-positive lung adenocarcinoma

A 20-year-old woman was diagnosed with stage 4 lung adenocarcinoma with an epidermal growth factor receptor (EGFR) exon 20 insertion gene mutation. Although the patient underwent chemotherapy, her lesions progressed. Liquid biopsy for EGFR T790M mutation showed negative results. After administering osimertinib, reduction of the lesions at the primary site was observed, and the patient’s respiratory condition improved. Previous reports showing successful treatment of EGFR exon 20 insertion-positive lung adenocarcinoma with the standard osimertinib dose of 80 mg are limited. The present case demonstrated that osimertinib could be a possible treatment option for EGFR exon 20 insertion-positive lung adenocarcinoma

Enhanced interleukin-10 signaling with 14-member macrolides in lipopolysaccharide-stimulated macrophages

Immunomodulatory effects of 14-member macrolides, namely erythromycin (EM) and clarithromycin (CAM), have been reported in chronic respiratory infectious diseases. It has been suggested that 14-member macrolides have immunomodulatory effects on various lung cells such as alveolar macrophages. Interleukin (IL)-10 is an immunomodulatory cytokine that performs an irreplaceable role in negatively regulating inflammation, primarily via a mechanism that selectively blocks the expression of pro-inflammatory genes. It activates sig-nal transducer and activator of transcription (STAT)-3, and subsequently induces the suppres-sor of cytokine signaling-3 (SOCS-3), resulting in the resolution of inflammatory response in macrophages. However, it has been still unclear whether 14-member macrolides exert immu-nomodulatory effects via IL-10 signaling pathway. We aimed to evaluate whether 14-member macrolides affect the IL-10 signaling pathway. The RAW264.7 macrophage cell line was pre-treated with EM or CAM, and stimulated with lipopolysaccharide (LPS). The levels of IL-10, IL-10 receptor, phosphorylated (p) STAT-3, and SOCS-3 were determined by RT-PCR, ELISA and immunoblotting. We observed increased levels of IL-10, p-STAT-3 and SOCS-3 in the treated cells. In addition, while the levels of tumor necrosis factor-α 6 h after LPS stimulation was equal between vehicle-treated and CAM-treated macrophage cells, those of CAM-treated cells were repressed 36 h following LPS stimulation, compared with those of the control cells. Therefore, the 14-member macrolides may initiate an early resolution of inflammation, in part, via the enhancement of the IL-10/STAT-3/SOCS-3 pathway

Effect of antibiotic therapy on the inflammatory responses during streptococcal pneumonia in emphysematous mice

Background and objective: Bacterial infection is one of the most important causes of acute exacerbation of respiratory failure in patients with chronic obstructive pulmonary disease (COPD). There were few studies evaluating the effects of early intervention by antibiotic on respiratory bacterial infection in COPD subjects. We investigated the effect of early intervention by respiratory quinolone antibiotic on the systemic inflammatory responses induced by streptococcal pneumonia using a mouse model of experimental emphysema. Methods: Experimental pulmonary emphysema was developed by a single intratracheal instillation of porcine pancreatic elastase in ICR mice. Three weeks later, lethal doses of Streptococcus pneumoniae were intratracheally inoculated, followed by oral administration of 50 mg/kg body weight of Grepafloxacin (GPFX) every day from a day after tracheal inoculation. Results: While all emphysematous mice without GPFX treatment died within 8 days, all emphysematous mice with GPFX treatment survived. Seventy two hrs after infection, serum levels of tumor necrosis factor alpha, chemokine (C-X-C motif) ligand 1, and CXCL2 (Macrophage inflammatory protein-2) in emphysematous mice with antibiotic therapy were significantly lower than those without therapy. Conclusions: Thus, the early intervention using a respiratory quinolone antibiotic prevents emphysematous mice with pneumonia from severe systemic inflammation, and rescues these mice from death. These results suggest that early intervention using a respiratory quinolone may improve the outcome of the exacerbated COPD patients

Undifferentiated pleomorphic sarcoma in the anterior mediastinum with a rapidly progressive course

A 77-year-old woman with heart failure was admitted to our hospital. Computed tomography (CT) of the chest revealed an anterior mediastinal tumor. CT-guided biopsy revealed a malignant nonepithelial tumor of unknown origin. She was not treated with chemotherapy or radiotherapy because of her poor clinical condition. She died 33 days after admission. Following autopsy, we confirmed that the mediastinal tumor had infiltrated the large blood vessels. After final histological examination, undifferentiated pleomorphic sarcoma was diagnosed. Primary mediastinal sarcomas are very rare; clinicians should be aware of their possibility because some cases may progress rapidly as evidenced in this case

E-selectin as a prognostic factor of patients hospitalized due to acute inflammatory respiratory diseases

When examining patients with acute inflammatory respiratory diseases, it is difficult to distinguish between infectious pneumonia and interstitial pneumonia and predict patient prognosis at the beginning of treatment. In this study, we assessed whether endothelial selectin (E-selectin) predicts the outcome of patients with acute inflammatory respiratory diseases. We measured E-selectin serum levels in 101 patients who were admitted to our respiratory care unit between January 2013 and December 2013 because of acute inflammatory respiratory diseases that were eventually diagnosed as interstitial pneumonia (n = 38) and lower respiratory tract infection (n = 63). Seven of these patients (n = 101) died. The pneumonia severity score was significantly higher and the oxygen saturation of arterial blood measured by pulse oximeter (SpO2)/fraction of inspiratory oxygen (FiO2) was significantly lower in the deceased patients than in the surviving patients. There were significantly fewer peripheral lymphocytes and significantly higher E-selectin serum levels in the deceased patients than in the surviving patients. In the multiple logistic regression analysis, the E-selectin serum levels and SpO2/FiO2 ratio were independent predictive factors of prognosis. The risk of death during acute respiratory disease was determined using a receiver operating characteristic (ROC) curve analysis. The area under the curve (AUC) was 0.871 as calculated from the ES, and the cutoff value was 6453.04 pg/ml, with a sensitivity of 1.00 and a specificity of 0.72 (p = 0.0027). E-selectin may be a useful biomarker for predicting the prognosis of patients with acute inflammatory respiratory diseases

MafB silencing in macrophages does not influence the initiation and growth of lung cancer induced by urethane

An increased number of tumor-associated macrophages (TAMs) that exhibit the M2 macrophage phenotype is related to poorer prognosis in cancer patients. MafB is a transcription factor regulating the differentiation of macrophages. However, involvement of MafB for the development of TAMs is unknown. This study was designed to investigate the role of MafB in a murine urethane-induced lung cancer model. Urethane was injected intraperitoneally into wild-type and dominant-negative MafB transgenic mice. Twenty-four weeks later, mice were sacrificed and their lungs removed for pathological analysis. The numbers and mean areas of lung cancer were evaluated. In addition, the numbers of Mac-3-positive macrophages were evaluated in each tumor. The numbers and mean areas of lung cancer induced by urethane administration were not significantly different between wild-type and dominant-negative MafB transgenic mice. The numbers of TAMs in lung cancer tissue were not significantly different between the two groups. MafB silencing using dominant-negative MafB did not influence the initiation and growth of lung cancer in mice exposed to urethane. These data suggest that MafB may not be related to the development of TAMs