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In Mycobacterium avium infections, macrophages play a critical role in the host defense response. Apoptosis inhibitor of macrophage (AIM), also known as CD5L, may represent a novel supportive therapy against various diseases, including metabolic syndrome and infectious diseases. The mechanisms of AIM include modulating lipid metabolism in macrophages and other host cells. We investigated the role of AIM in M. avium infections in vitro and in vivo. In a mouse model of M. avium pneumonia, foamy macrophages were induced 6 wk after infection. The bacteria localized in these macrophages. Flow cytometric analysis also confirmed that the percentage of CD11chighMHCclassIIhigh interstitial and alveolar macrophages, a cell surface marker defined as foamy macrophages, increased significantly after infection. AIM in alveolar lavage fluid and serum gradually increased after infection. Administration of recombinant AIM significantly increased the number of bacteria in the lungs of mice, accompanied by the induction of inflammatory cytokine and iNOS expression. In mouse bone marrow–derived macrophages, the mRNA expression of AIM after M. avium infection and the amount of AIM in the supernatant increased prior to the increase in intracellular bacteria. Infected cells treated with anti-AIM Abs had fewer bacteria and a higher percentage of apoptosis-positive cells than infected cells treated with isotype control Abs. Finally, AIM in the sera of patients with M. avium-pulmonary disease was measured and was significantly higher than in healthy volunteers. This suggests that AIM production is enhanced in M. avium–infected macrophages, increasing macrophage resistance to apoptosis and providing a possible site for bacterial growth.

IntroductionBronchial thermoplasty (BT) is a bronchoscopic procedure that involves the delivery of thermal radiofrequency energy to the bronchial wall for treating severe asthma. It has been suggested that too many radiofrequency activations could induce serious adverse events (SAEs) at an early stage. We aimed to examine the number of radiofrequency activations at each session and early lung function changes from baseline to determine whether these are related to SAEs.MethodsWe retrospectively investigated 13 consecutive patients who underwent three sessions each of BT for severe asthma from February 2015 to January 2016. Lung function tests were performed on the day before and after each BT procedure. Since we compared the number of activations and lung function changes from baseline after each session, a total of 39 sessions were reviewed. The relationship between the number of radiofrequency activations and each lung function change from baseline was also examined by linear regression analysis.ResultsA total of 10 SAEs (4 of pneumonia, 3 of atelectasis, 2 of bronchial asthma exacerbation and 1 of hemoptysis) were observed following the 39 BT sessions. When we compared sessions with and without SAEs, there were no differences in the number of activations (mean ± SD, 71.5 ± 28.6 times in sessions with SAEs; 66.5 ± 25.1 times in sessions without SAEs;p = 0.772) and lung function changes (mean changes in FVC/%FVC/FEV1/%FEV1/%PEF from baseline; − 0.49 l/− 14.2%/− 0.36 l/− 11.7%/− 9.6% in sessions with SAEs; − 0.43 l/− 13.3%/− 0.34 l/− 12.1%/− 9.4% in sessions without SAEs;p > 0.05 for all the above). Increase in the number of activations correlated with decreased FEV1(R2 = 0.17,p = 0.0088) and %FEV1(R2 = 0.11,p = 0.0357).ConclusionsIncrease in the number of radiofrequency activations during BT is related to a decrease in FEV1and %FEV1from baseline. The number of radiofrequency activations, however, is not associated with SAEs after BT.

BACKGROUND: We investigated the measurement of end-tidal partial pressure of carbon dioxide (PETCO2) with a capnometer in patients with respiratory failure, and we determined whether this technique could provide an alternative to measurement of PaCO2 using arterial blood gas analysis in the clinical setting. METHODS: We measured PETCO2 in subjects with hypoxemic and hypercarbic respiratory failure using a capnometer. We simultaneously measured PaCO2, venous partial pressure of carbon dioxide (PvCO2), and transcutaneously measured partial pressure PCO2 (PtcCO2). We analyzed agreements among these parameters with Bland-Altman analysis. We obtained 30 samples from subjects with hypoxemic respiratory failure and 30 samples from subjects with hypercarbic respiratory failure. RESULTS: Thirty subjects with hypoxemic respiratory failure and 18 subjects with hypercarbic respiratory failure participated in this study. Significant relationships were found between PETCO2 and PaCO2, between PtcCO2 and PaCO2, and between PvCO2 and PaCO2. Bland-Altman analysis of PETCO2 and PaCO2 in all subjects revealed a bias of 6.48 mm Hg (95% CI 4.93–8.03, P CONCLUSIONS: PETCO2 can be measured simply using a capnometer, and PETCO2 measurements can estimate PaCO2. However, the limits of agreement were wide. Therefore, care providers must pay attention to the characteristics and errors of these devices. These results suggest that measurement of PETCO2 might be useful for screening for hypercarbic respiratory failure in the clinical setting.

Mycobacterium avium complex is a causative organism for refractory diseases. In this study, we examined the effects of N-acetyl-cysteine on M. avium infection in vitro and in vivo. N-acetyl-cysteine treatment suppressed the growth of M. avium in A549 cells in a concentration-dependent manner. This effect was related to the induction of the antibacterial peptide human β-defensin-2. In a mouse model, N-acetyl-cysteine treatment significantly reduced the number of bacteria in the lungs and induced murine β-defensin-3. In interleukin-17-deficient mice, the effects of N-acetyl-cysteine disappeared, indicating that these mechanisms may be mediated by interleukin-17. Moreover, an additional reduction in bacterial load was observed in mice administered N-acetyl-cysteine in combination with clarithromycin. Our findings demonstrate the potent antimycobacterial effects of N-acetyl-cysteine against M. avium by inducing antimicrobial peptide, suggesting that N-acetyl-cysteine may have applications as an alternative to classical treatment regimens.

Development of aspergilloma is common in cases with a fungus ball-like shadow in cavities due to old tuberculosis. Some reports have shown that blood clots tend to appear as a fungus ball-like shadow. A 71-year-old man with a history of pulmonary tuberculosis presented with a fungus ball-like shadow in an old cavity and hemoptysis. There was no evidence of aspergillus infection on various examinations. We confirmed a blood clot and aneurysm of an artery under direct vision by bronchoscopy. A lateral thoracic artery aneurysm was detected by angiography. Transcatheter arterial embolization was performed. After treatment, the artery aneurysm disappeared.

Early-onset pulmonary emphysema is uncommon and its pathogenesis is poorly defined. A 30-year-old man was admitted to our intensive care unit with severe respiratory failure. Besides smoking heavily since the 14 years of age, he had habitually inhaled organic solvents, such as toluene, in his adolescence. High-resolution computed tomography showed evident pulmonary emphysema throughout the lung fields. Based on the findings of right heart catheterization, he was diagnosed with an acute exacerbation of chronic obstructive pulmonary disease complicated with pulmonary hypertension. Heavy smoking from a young age and exposure to toluene were the suspected causes of the patient's severe pulmonary emphysema.

We investigated the measurement of end-tidal partial pressure of carbon dioxide (PWe measured PThirty subjects with hypoxemic respiratory failure and 18 subjects with hypercarbic respiratory failure participated in this study. Significant relationships were found between PP

Background Yellow nail syndrome (YNS) is a rare disease characterized by the triad of thickened, slow-growing yellow nails, lymphedema, and chronic respiratory manifestations. The cause of YNS is not known; however, it is suggested to be due to a congenital lymph abnormality. Since YNS is accompanied by chronic bronchial infection in more than half of patients, we hypothesized that treatment with clarithromycin (CAM) could be effective. We therefore evaluated the effectiveness of CAM against nail discoloration and respiratory manifestation in patients with YNS. Methods We conducted an observational study involving 5 patients with YNS who were treated at our institution between January 2005 and January 2016. CAM was prescribed for every patient. Patient demographic information, comorbidities, medications, chest radiographs, and clinical data such as nail color were extracted to evaluate clinical outcome. Results Mean patient age was 71.6 years, and 2 patients (40%) were male. Four patients had sinusitis, and 2 had rheumatoid arthritis. Regarding respiratory manifestations, 4 patients had sinobronchial syndrome and 2 had pleural effusion. Nail discoloration improved in every patient after CAM treatment. Four patients also experienced improvement in their respiratory manifestations. Conclusions In patients with YNS, the anti-inflammatory activity of macrolides might improve their systemic inflammation. This improvement could help to reduce lymphedema and promote nail growth. Trial registration Ethical approval was provided by the institutional review board of the National Center of Global Health and Medicine (NCGM-G-002143-00), in January 2017. This study is retrospectively registered for UMIN Clinical Trial Registry (UMIN000028514) in August 4th, 2017.

RATIONALE: Anti-aminoacyl transfer RNA synthetases (ARS) antibodies are a group of myositis specific autoantibodies. It also is frequently found in patients with complicating interstitial pneumonia. However, the clinical characteristics in these patients with anti-ARS antibody were not yet fully elucidated. METHODS: We retrospectively investigated clinical symptoms, radiological findings, treatments, and its outcome in 30 patients with anti-ARS antibody-positive interstitial pneumonia (ARS-IP) in our institution. The radiological patterns of interstitial pneumonia were evaluated with thin-sliced HRCT by two specialists. Anti-ARS antibodies were evaluated using RNA immunoprecipitation assey and anti-synthetase ELISA kit (BML, Japan). RESULTS: Mean age was 59.4 years (28-82), 60.0% were female. Nine patients were with anti-Jo-1, 7 with anti-EJ, 4 with anti-PL-12, 3 with anti-PL-7, 2 with anti- OJ, and 5 with unknown or anti-KS. Seven cases were diagnosed as having ARS-IP with dermatomyositis (DM), and 7 with polymyositis. There were no differences in the demographic features, laboratory data, HRCT findings, between ARS-IP with myositis and without. ARS-IP with myositis recurs more often than without myositis (p=0.019). Serum creatinine kinase (CK) levels were elevated in 13 patients. Patient achieved good responses to initial corticosteroid and immunosuppressant. Mean observation time was 64.9 months (4 months- 138 months). CONCLUSIONS: Most of the patients with interstitial pneumonia associated with anti-ARS antibodies showed remarkable responses to the therapy and favorable outcome.

Background N-Acetyl-cysteine (NAC) is widely used in patients with chronic pulmonary diseases. In previous studies, its antimicrobacterial and antimycobacterial effects have been reported. Among its effect in Mycobacteria, it has been mainly studied in Mycobacterium tuberculosis. Here, we examined whether NAC has antibiotic activity against M. avium. Methods The antimycobacterial effect of NAC was assessed in JCM 15430 M. avium strain infected A-549 (human lung epithelial cells) and MH-S (mouse alveolar macrophages). These cells were infected with M. avium at multiplicity of infection of 10 for 1 hours, washed and then cultivated for 5 days. Bacterial uptake was evaluated at 0 days and 5 days of cultivation. For the NAC treatment group, 5% FBS medium with 10 mM NAC was used as culture medium. We also tested its effect in combination with clarithromycin in vivo. BALB/c mice were infected intranasally with M. avium, and were given NAC (400 mg/kg) or clarithromycin (100 mg/kg) or both by gavage daily for 6 days. On day 7 of infection, lungs were harvested and CFU, cytokines and antimicrobial peptides were measured. Results NAC treatment of M. avium-infected A-549 and MH-S resulted in a significant reduction of mycobacterial loads (P = 0.014 and P = 0.014). In vivo, NAC treatment resulted in a significant reduction of mycobacterial loads in the lungs of M. avium-infected mice (P = 0.007). When in combination with clarithromycin, we also had an additional reduction (vs. clarithromycin monotherapy; P = 0.001). Several antimicrobial peptides significantly increased when treated with NAC and clarithromycin combination therapy. Conclusion NAC exhibits potent anti-mycobacterial effects and may limit M. avium infection. In addition with clarithromycin, it showed an additive effect in reduction of mycobacterial loads. Interestingly, in our study, several antimicrobial peptides increased significantly which may be one of the possibility on how NAC is involved in antimycobacterial effects. These results indicate that NAC may be an additional option in treating M. avium-infected patients in future, along with its classical drug regimens containing clarithromycin. Disclosures All authors: No reported disclosures.