Summary
Respiratory syncytial virus (RSV) infection often exacerbates bronchial asthma, but there is no licensed RSV vaccine or specific treatments. Here we show that RSV-induced alveolar macrophages, which produce high levels of matrix metalloproteinase-12 (MMP-12), exacerbate allergic airway inflammation with increased neutrophil infiltration. When mice subjected to allergic airway inflammation via exposure to the house dust mite antigen (HDM) were infected with RSV (HDM/RSV), MMP-12 expression, viral load, neutrophil infiltration, and airway hyperresponsiveness (AHR) were increased compared to those in the HDM and RSV groups. These exacerbations in the HDM/RSV group were attenuated in MMP-12-deficient mice and mice treated with MMP408, a selective MMP-12 inhibitor, but not in mice treated with dexamethasone. Finally, M2-like macrophages produced MMP-12, and its production was promoted by increase of IFN-β-induced IL-4 receptor expression with RSV infection. Thus, targeting MMP-12 represents a potentially novel therapeutic strategy for the exacerbation of asthma.
Background and objectives The number of patients with pulmonary Mycobacterium avium complex (MAC) disease is increasing worldwide, especially among middle-aged women and never-smokers. However, little is known about the factors causing exacerbations of pulmonary MAC disease in untreated patients. The aim of the present study was to identify the predictors of radiological aggravations of pulmonary MAC disease. Methods From April 2011 to December 2018, 238 MAC patients at our institute were newly diagnosed with pulmonary MAC disease according to the 2007 American Thoracic Society/Infectious Disease Society guideline. Their medical records were examined retrospectively for their clinical findings. The radiological findings at the time of the diagnosis and 1 year later were evaluated. To identify the predictors of radiological aggravation, multivariable analysis was performed with the data of 167 treatment-naïve patients. Results Female, never-smoker, and nodular/bronchiectatic (NB) type were predominant in patients with pulmonary MAC disease. Univariate analysis of data from treatment-naïve subjects showed that no lung diseases other than MAC, extensive radiological findings, and a positive acid-fast bacilli (AFB) smear were significantly associated with radiological aggravations. On multivariate analysis, the radiological factor (larger affected area) and absence of other lung disease were significantly associated with radiological aggravations. In particular, the presence of abnormal shadows in more than 3 lobes was significantly associated with radiological aggravations. Conclusions In this study, the presence of extensive radiological findings and the absence of lung diseases other than MAC were predictors of radiological aggravations of treatment-naïve
Whether or not tiotropium has anti-inflammatory and anti-remodeling effects in humans with asthma is an important issue. Predictors that would identify patients who would derive the maximal potential benefit from treatment with tiotropium in addition to their current therapy are also needed. Although the cardiovascular toxicity of tiotropium is less remarkable in asthma than in chronic obstructive pulmonary disease, longer and larger studies are still needed to confirm the safety of tiotropium for treating asthma.
Association between serum anti-glycopeptidolipid-core IgA antibody titers and clinical characteristics of Mycobacterium avium complex pulmonary disease,
A 38-year-old male presented to our hospital with the chief complaint of chronic cough. Eight years previously he was diagnosed with cilioretinal malignant melanoma and underwent left ophthalmectomy. On chest CT, pleural effusion and diffuse thickening of left pleura were suspected (Picture 1). The differential diagnosis included mesothlioma and metastatic melanoma. In thoracoscopic findings multiple melanotic elevated lesions were observed (Picture 2) but there was no pleural thickening (Picture 3). Thoracoscopic pleural biopsy was performed and he was diagnosed with malignant melanoma. Intrathoracic metastasis of melanoma reportedly includes pulmonary nodules (61.5%), mediastinal adenopathy (7%), pleural effusion (2%), lytic bony lesin (0.8%), extra-pleural mass (0.8%), and combined lesions (28%) (1). The present case was found to have pleural effusion and an extra-pleural mass. There was no evidence of other metastasis. Thoracoscopy was useful in confirming the diagnosis of pleural metastatic melanoma.
Mycobacterium avium complex pulmonary disease (MAC-PD) can be serologically diagnosed according to the presence of anti-glycopeptidolipid (GPL)-core IgA antibodies. However, few studies have examined the association between serum anti-GPL-core IgA antibody titers and the clinical characteristics of patients with MAC-PD. From April 2014 to June 2019, we determined the level of anti-GPL-core IgA antibodies in 489 MAC-PD patients at our institute. Of them, 89 patients fulfilled the criteria of the American Thoracic Society and the Infectious Diseases Society of America statement on the diagnosis, treatment, and prevention of nontuberculous mycobacterial diseases. These patients were divided into antibody-positive (n = 59) or -negative (n = 30) groups according to their serum anti-GPL-core IgA antibody results. Additionally, the positive antibody group was further divided into a strong positive group (n = 27) and a weak positive group (n = 32), and their clinical characteristics were retrospectively compared. Disease progression requiring treatment during the 12 months following diagnosis and extensive radiological findings were significantly abundant in the strong positive group compared with the weak positive group. Our findings revealed that serum anti-GPL-core IgA antibody titers are useful not only for diagnosing MAC-PD but also for predicting the risk of exacerbation.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.