Specific IgE Response and Omalizumab Responsiveness in Severe Allergic Asthma.

Objective: Omalizumab has demonstrated clinical efficacy in patients with severe allergic asthma sensitized to perennial allergens and/or severe pollinosis through inhibition of IgE-dependent allergic response. When considering the "one airway, one disease" concept, sensitization to pollen could predict responsiveness to omalizumab. This study aimed to assess whether the pretreatment specific IgE response could be a predictor of responsiveness to omalizumab in severe allergic asthma sensitized to perennial allergens. Methods: In this retrospective study, 41 adult patients with severe allergic asthma sensitized to perennial allergens (27 females; mean age 59 years) who had completed 52-week omalizumab treatment were enrolled. The Global Evaluation of Treatment Effectiveness was performed, and demographic characteristics and the positive ratios of specific IgE responses classified into five subgroups (pollen, dust mite, house dust, mold, and animal dander) were compared between responders and non-responders. Multivariate logistic regression analyses were performed to identify predictors of responsiveness to omalizumab. Results: Thirty-one patients (76%) were identified as responders. The number of sensitized aeroallergen subgroups and sensitization to pollens were significantly higher in responders than in non-responders (both p<0.05). Multivariate logistic regression analysis showed that sensitization to pollen (OR = 8.41, p = 0.02) was independently associated with the effectiveness of omalizumab. Conclusion: Pretreatment serum pollen-specific IgE could be a predictor of responsiveness to omalizumab.

Serum levels of the chemokine CCL2 are elevated in malignant pleural mesothelioma patients.

BACKGROUND: Malignant pleural mesothelioma (MPM) is a debilitating disease of the pleural cavity. It is primarily associated with previous inhalation of asbestos fibers. These fibers initiate an oxidant coupled inflammatory response. Repeated exposure to asbestos fibers results in a prolonged inflammatory response and cycles of tissue damage and repair. The inflammation-associated cycles of tissue damage and repair are intimately involved in the development of asbestos-associated cancers. Macrophages are a key component of asbestos-associated inflammation and play essential roles in the etiology of a variety of cancers. Macrophages are also a source of C-C motif chemokine ligand 2 (CCL2), and a variety of tumor-types express CCL2. High levels of CCL2 are present in the pleural effusions of mesothelioma patients, however, CCL2 has not been examined in the serum of mesothelioma patients. METHODS: The present study was carried out with 50 MPM patients and 356 subjects who were possibly exposed to asbestos but did not have disease symptoms and 41 healthy volunteers without a history of exposure to asbestos. The levels of CCL2 in the serum of the study participants was determined using ELISA. RESULTS: Levels of CCL2 were significantly elevated in the serum of patients with advanced MPM. CONCLUSIONS: Our findings are consistent with the premise that the CCL2/CCR2 axis and myeloid-derived cells play an important role in MPM and disease progression. Therapies are being developed that target CCL2/CCR2 and tumor resident myeloid cells, and clinical trials are being pursued that use these therapies as part of the treatment regimen. The results of trials with patients with a similar serum CCL2 pattern as MPM patients will have important implications for the treatment of MPM.

Optimal cut-off value and clinical usefulness of the Adherence Starts with Knowledge-12 in patients with asthma taking inhaled corticosteroids.

BACKGROUND: Non-adherence to inhalation regimens is common in asthmatic patients. The Adherence Starts with Knowledge-12 (ASK-12) survey was developed to detect and address patient-specific barriers to medication adherence. Our objective is to investigate the clinical usefulness of the ASK-12 for assessing and addressing adherence to inhalation therapy in asthma. METHODS: The ASK-12 was administered to 138 asthmatic patients. Using pharmacy-refill data, we examined the cut-off value of the ASK-12 to identify patients who were non-adherent to inhalation regimens and identify factors associated with non-adherence. To verify the usefulness of the ASK-12, inhalation regimens were prospectively switched to less-expensive and simpler (once-daily) dosing regimens in eight non-adherent asthmatic patients who reported specific-barriers in "inconvenience of twice-daily inhaler use" and "cost". RESULTS: Valid responses were received from 114 (82.6%) patients. A significant correlation was found between pharmacy-refill rates and the ASK-12 total score (r=-0.55, P<0.0001). The optimal cut-off value of the ASK-12 total score to discriminate non-adherent patients (defined by pharmacy-refill rate <80%) was 23, with 71.4% specificity and 93.3% sensitivity. Using this value, 52 (45.6%) patients were classified as non-adherent. Univariate followed by multivariate analysis identified younger age as a predictor of non-adherence to inhalation regimens (odds ratio, 2.67; 95% CI, -0.95 to -0.06; P=0.027). Switching inhaled medicines in eight patients resulted in significant improvements in both ASK-12 scores and asthma control. CONCLUSIONS: The ASK-12 is a brief, practical, and clinically useful measure for assessing and addressing adherence to inhalation regimens in asthma.

[A case of Legionnaires' disease with abnormal neurological findings showing the corpus callosum abnormality on brain MRI].

A 47-year-old man was admitted to our hospital because of dysarthric speech and high fever. His brain magnetic resonance imaging (MRI) showed high intensity in the splenium of the corpus callosum (SCC) on diffusion-weighted and FLAIR imaging. His chest CT showed ground-glass attenuation in bilateral lung upper lobes, and consolidation in the right lower lobe. Because of his neurological findings and radiographic imaging, we started antibiotic therapy using quinolone, which is effective for Legionellosis. Later, Legionella species were identified by sputum culture. Pneumonia was relieved after antibiotic therapy and in parallel with clinical improvement, and the MRI findings also resolved. We report a patient who showed abnormal neurological findings and abnormality on brain MRI, both of which were reversible, in the setting of acute Legionnaires' disease.

Microscopic polyangiitis associated with diffuse panbronchiolitis.

There are several case reports of systemic vasculitis associated with chronic suppurative lung diseases. We describe a 46-year-old female, previously diagnosed as having diffuse panbronchiolitis (DPB), presenting with hemosputum and dyspnea. Her serum titer of MPO-ANCA was positive together with a high titer of BPI-ANCA. Chest X-ray and chest CT scan showed pulmonary hemorrhage, and the renal biopsy specimen revealed necrotizing, crescentic glomerulonephritis. She was diagnosed as having ANCA-associated vasculitis, and more specifically, microscopic polyangiitis accompanied by DPB. She was treated with methylprednisolone pulse therapy, followed by intravenous cyclophosphamide. This case suggested a possible association with chronic bacterial infection, which may play a role in the pathogenesis of ANCA-associated vasculitis.