Apoptosis Inhibitor of Macrophages Contributes to the Chronicity of Mycobacterium avium Infection by Promoting Foamy Macrophage Formation.

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.

Intrinsic clarithromycin heteroresistance in Mycobacterium avium.

BACKGROUND: Mycobacterium avium is associated with pulmonary disease in otherwise healthy adults. Several clarithromycin-refractory cases have been reported, including some cases caused by clarithromycin-susceptible strains. OBJECTIVES: To characterize the reason for the discrepancy between clinical response and antibiotic susceptibility results. METHODS: We conducted population analysis of clarithromycin-tolerant and heteroresistant subpopulations of M. avium cultured in vitro and in homogenates of infected lungs of mice. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) were determined for 28 M. avium and two M. kansasii strains. Mice were intranasally infected with M. avium and treated with or without clarithromycin (100 mg/kg) thrice weekly. They were sacrificed on day 35 and the bacteria in lung homogenates were tested for clarithromycin resistance. Population analysis assays were performed based on colony growth on plates containing two-fold dilutions of clarithromycin. RESULTS: The MBC/MIC ratios were ≥8 in all 28 strains of M. avium tested. In the population analysis assay, several colonies were observed on the plates containing clarithromycin concentrations above the MIC (2-64 mg/L). No growth of M. kansasii colonies was observed on the plates containing clarithromycin concentrations ≥2 mg/L. M. avium in the homogenates of infected lungs showed clearer clarithromycin-resistant subpopulations than in vitro, regardless of clarithromycin exposure. CONCLUSION: M. avium shows intrinsic heterogeneous resistance (heteroresistance) to clarithromycin. This may explain the observed discrepancies between clarithromycin susceptibility testing results and clinical response to clarithromycin treatment. Further studies are needed to confirm a link between heteroresistance and clinical outcomes.

Effectiveness of clarithromycin in patients with yellow nail syndrome.

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.

Is the information on infection prevention measures against COVID-19 reaching the target audience? A cross-sectional survey among eating and drinking services in Tokyo, Japan.

Objectives: The study aims to evaluate information gathering behaviour (IGB) and its effectiveness in eating and drinking services for infection control during COVID-19. Study design: A cross-sectional survey using anonymous self-administered questionnaires was conducted in October 2021. Participants were asked what IGB they use to obtain infection control measures, to what extent they understand the measures (and, if they do not understand them, what inhibits their comprehension), and which IGBs they do not currently use and why. Methods: The sample included 957 eating and drinking services in Ota City, Tokyo. The response rate was 14.5%. Binomial logistic regression was used to analyse the factors associated with the baseline characteristics using Stata v.17.0. Results: The highest proportion of respondents used television (88.0%); another large proportion (38.9%) used guidelines. Regarding difficulty in understanding the retrieved information, 'difficulty in coming up with specific actions' had the highest ratio for every IGB. Regarding reasons for not currently using IGB, 'it takes too much time to extract the necessary information' showed the highest ratios of all IGBs. Individuals over 60 years had a negative relationship with the use of guidelines and the Internet. Participants also advised that they did not use time-consuming guidelines. Conclusion: Current information dissemination methods for information on COVID-19 infection control may not successfully convey information or reach their target populations. This study indicates the need for specific expressions and layouts to effectively share information on COVID-19. Also, special means of communication must be established to cater to individuals aged 60 and above.

N-acetyl-cysteine mediates protection against Mycobacterium avium through induction of human ß-defensin-2 in a mouse lung infection model.

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 ß-defensin-2. In a mouse model, N-acetyl-cysteine treatment significantly reduced the number of bacteria in the lungs and induced murine ß-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.

Comparison of End-Tidal, Arterial, Venous, and Transcutaneous PCO2.

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 (Pv̄CO2 ), 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 Pv̄CO2 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 < .001) with a precision of 6.01 mm Hg. Bland-Altman analysis of PETCO2 and PaCO2 with hypoxemic respiratory failure revealed a bias of 5.14 mm Hg (95% CI 3.35-6.93, P < .001) with a precision of 4.80 mm Hg. Bland-Altman analysis of PETCO2 and PaCO2 in subjects with hypercarbic respiratory failure revealed a bias of 7.83 mm Hg (95% CI 5.27-10.38, P < .001) with a precision of 6.83 mm Hg. 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.

Can the Number of Radiofrequency Activations Predict Serious Adverse Events after Bronchial Thermoplasty? A Retrospective Case-Control Study.

INTRODUCTION: Bronchial 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. METHODS: We 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. RESULTS: A 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). CONCLUSIONS: Increase in the number of radiofrequency activations during BT is related to a decrease in FEV1 and %FEV1 from baseline. The number of radiofrequency activations, however, is not associated with SAEs after BT.

Massive Hemoptysis with a Fungus Ball-like Shadow in an Old Tuberculosis Cavity That Was Shown to Be a Clot by Bronchoscopy.

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, Severe Chronic Obstructive Pulmonary Disease with Pulmonary Hypertension that was Likely Induced by Toluene Exposure.

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.