Clinical implications of correlation between peripheral eosinophil count and serum levels of IL-5 and tryptase in acute eosinophilic pneumonia

SummaryBackgroundThe peripheral eosinophil count (PEC) tends to increase during the course of acute eosinophilic pneumonia (AEP), and an initially elevated PEC is associated with milder disease. However, there is a lack of data regarding these phenomena and inflammatory process of AEP.MethodsWe prospectively evaluated serial changes in serum interleukin (IL)-5 levels and the correlation between the initial level of IL-5 and the PEC to investigate whether the initial PEC indicates a resolving state of inflammation. We also evaluated serum tryptase levels to investigate the possibility of involvement of mast cell activity in AEP.ResultsTwenty-one AEP patients were included, and all patients improved within 10 days after corticosteroid treatment. The median initial serum IL-5 level among all patients was 561.0 pg/mL, which decreased to zero at 10 days of follow-up (n = 15, P < 0.001). The median initial serum tryptase level (detectable in 20 of 21 patients) was 3.7 ng/mL and decreased to a median of 1.1 ng/mL at 10 days of follow-up (n = 15, P < 0.001). The initial serum IL-5 and C-reactive protein levels were positively correlated (P = 0.009, r = 0.556), and the initial serum IL-5 level was inversely correlated with the initial PEC (P = 0.004, r = −0.603).ConclusionsOur data suggest that IL-5 is an important cytokine involved in the recruitment of eosinophils from peripheral blood into the lungs, that an initially elevated PEC is associated with a resolving state of inflammation, and that mast cells are potentially involved in the inflammatory process of AEP

First results from the HAYSTAC axion search

The axion is a well-motivated cold dark matter (CDM) candidate first postulated to explain the absence of $CP$ violation in the strong interactions. CDM axions may be detected via their resonant conversion into photons in a "haloscope" detector: a tunable high-$Q$ microwave cavity maintained at cryogenic temperature, immersed a strong magnetic field, and coupled to a low-noise receiver. This dissertation reports on the design, commissioning, and first operation of the Haloscope at Yale Sensitive to Axion CDM (HAYSTAC), a new detector designed to search for CDM axions with masses above $20$ $\mu\mathrm{eV}$. I also describe the analysis procedure developed to derive limits on axion CDM from the first HAYSTAC data run, which excluded axion models with two-photon coupling $g_{a\gamma\gamma} \gtrsim 2\times10^{-14}$ $\mathrm{GeV}^{-1}$, a factor of 2.3 above the benchmark KSVZ model, over the mass range $23.55 < m_a < 24.0$ $\mu\mathrm{eV}$. This result represents two important achievements. First, it demonstrates cosmologically relevant sensitivity an order of magnitude higher in mass than any existing direct limits. Second, by incorporating a dilution refrigerator and Josephson parametric amplifier, HAYSTAC has demonstrated total noise approaching the standard quantum limit for the first time in a haloscope axion search.Comment: Ph.D. thesis. 346 pages, 58 figures. A few typos corrected relative to the version submitted to ProQues

Nodal Stations and Diagnostic Performances of Endobronchial Ultrasound-Guided Transbronchial Needle Aspiration in Patients with Non-Small Cell Lung Cancer

There are no accurate data on the relationship between nodal station and diagnostic performance of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA). We evaluated the impact of nodal station and size on the diagnostic performance of EBUS-TBNA in patients with non-small cell lung cancer (NSCLC). Consecutive patients who underwent EBUS-TBNA of mediastinal or hilar lymph nodes for staging or diagnosis of NSCLC were included in this retrospective study. Between May 2009 and February 2010, EBUS-TBNA was performed in 373 mediastinal and hilar lymph nodes in 151 patients. The overall diagnostic sensitivity, specificity, accuracy and negative predictive value (NPV) of EBUS-TBNA were 91.6%, 98.6%, 93.8%, and 84.3%, respectively. NPV of the left side nodal group was significantly lower than those of the other groups (P = 0.047) and sensitivity of the left side nodal group tended to decrease (P = 0.096) compared with those of the other groups. Diagnostic sensitivity and NPV of 4L lymph node were 83.3% and 66.7%, respectively. However, diagnostic performances of EBUS-TBNA did not differ according to nodal size. Bronchoscopists should consider the impact of nodal stations on diagnostic performances of EBUS-TBNA

Serial Monitoring of Immune Markers Being Represented Regulatory T Cell/T Helper 17 Cell Ratio: Indicating Tolerance for Tapering Immunosuppression after Liver Transplantation

Recipients of liver transplantation (LT) require long-term immunosuppressive drug treatment, but lifelong immunosuppressive treatment has severe side effects. It is known that some LT recipients develop immune tolerance, and although the development of such operational tolerance should allow a decrease in the burden of immunosuppressive drug treatment, the factors that indicate operational tolerance are not clear. This study aimed to monitor immunological markers over time in LT recipients to identify those markers indicating the development of operational tolerance. We performed a prospective pilot study measuring immune markers, including the ratio of regulatory T (Treg) and T helper (Th) 17 cells in peripheral blood in the 14 most immunologically stable patients among 70 clinically stable LT recipients. The doses of immunosuppressive drugs given to these 14 LT recipients were tapered over time and they were monitored for immunological markers related to the development of immune tolerance. As the doses of immunosuppressive drugs were reduced, the Treg/Th17, Th1/Th17, and CD8/Th17 ratio in tolerant recipients was significantly increased compared with that of nontolerant recipients. These results suggest that monitoring of changes in the immune makers, including Treg/Th17 ratio during tapering of immunosuppression may allow prediction of the development of tolerance

Clinical Characteristics and Treatment Outcomes of Pathologically Confirmed Aspergillus Nodules

Aspergillus nodules represent a subtype of chronic pulmonary aspergillosis, but details on their characteristics and outcomes are limited. We evaluated 80 patients with pathologically confirmed Aspergillus nodules between January 2009 and December 2016. The median age of the patients was 59 years, and 46 (58%) were women. Seventy-three (91%) patients were surgically diagnosed with Aspergillus nodules and the remaining seven (9%) patients were diagnosed by percutaneous transthoracic needle biopsy. The median long-axis diameter of nodules was 22 mm, and nodules had an internal cavity in 49 (61%) patients. Spiculation and calcification were observed in 20% and 39% of patients, respectively. Ninety percent (18/20) of nodules showed uptake on positron emission tomography. Serum Aspergillus precipitin IgG antibody was positive in 42% (10/24) of tested patients. Seventy-three (91%) patients underwent surgery without (n = 58) or with (n = 15) adjuvant antifungal therapy, and the remaining seven (9%) patients received antifungal therapy alone (n = 5) or no treatment (n = 2). Three patients experienced postoperative pulmonary complications: pneumothorax, hemoptysis, and acute lung injury (n = 1 each). There was no recurrence during the median follow-up period of 36.8 months. In conclusion, surgery could be a treatment strategy worth considering for most Aspergillus nodules. However, given that our study population was heterogeneous, further well-designed studies are need

Spontaneous Cultural Conversion Rate of <i>Mycobacterium avium</i> Complex Pulmonary Disease Based on BACES Severity

Background: Only a few clinical factors can aid in predicting spontaneous culture conversion (SCC) in patients with Mycobacterium avium complex-pulmonary disease (MAC-PD). In this study, we aimed to evaluate whether the rate of SCC varies according to the severity of the disease in MAC-PD patients. Methods: We retrospectively classified 373 MAC-PD patients who had undergone watchful waiting without antibiotics based on the severity assessment using the ‘body mass index (BMI), age, cavity, erythrocyte sedimentation rate (ESR), and sex (BACES)’ criteria. We evaluated the rate of SCC in MAC-PD patients based on BACES severity and analyzed the relevant factors. Results: Of 373 patients, 153 (41%) achieved SCC without antibiotics during a median follow-up of 48.1 months. There was a trend toward a higher SCC rate in patients with lower BACES severity: 48% (87/183), 37% (58/157), and 24% (8/33) in the mild, moderate, and severe BACES groups, respectively. In addition, a favorable outcome, defined as maintaining SCC or having two consecutive negative sputum cultures until the last follow-up date, was also more common in patients with lower BACES severities of 53% (97/183), 34% (54/157), and 18% (6/33) in the mild, moderate, and severe BACES groups, respectively. In multivariate analysis, moderate BACES (hazard ratio [HR] = 0.63; 95% confidence interval [CI] 0.44–0.91; p = 0.013) and severe BACES (HR 0.37; 95% CI 0.16–0.90; p = 0.028) had a significantly negative impact on favorable outcomes compared to mild BACES. Conclusions: Lower BACES severity may be associated with SCC in MAC-PD patients

Epidemiology of Nontuberculous Mycobacterial Infection, South Korea, 2007–2016

The prevalence and incidence of nontuberculous mycobacterial (NTM) infections increased in South Korea from 2007 to 2016. Annual prevalence of NTM infection increased to 39.6 cases/100,000 population in 2016 and annual incidence to 19.0 cases/100,000 population. Overall prevalence for the study period was higher in the elderly, in females, and in cities

Immunological benefits by ginseng through reciprocal regulation of Th17 and Treg cells during cyclosporine-induced immunosuppression

Background: It is not clear whether ginseng affects cyclosporine A (CsA)-induced desirable immunosuppressive action. In this study, we evaluated the immunological influence of combined treatment of ginseng with CsA. Methods: Using CD4+ T cells from mouse spleens stimulated with the T cell receptor (TCR) or allogeneic antigen-presenting cells (APCs), we examined the differentiation of naïve T cells into T helper 1 (Th1), Th2, Th17, and regulatory T cells (Tregs), and their cytokine production during treatment by Korean Red Ginseng extract (KRGE) and/or CsA. The influence of KRGE on the allogeneic T cell response was evaluated by mixed lymphocyte reaction (MLR). We also evaluated whether signal transducer and activator of transcription 3 (STAT3) and STAT5 are implicated in this regulation. Results: Under TCR stimulation, KRGE treatment did not affect the population of CD4+interferon gamma (IFNγ)+ and CD4+interleukin (IL)-4+ cells and their cytokine production compared with CsA alone. Under the Th17-polarizing condition, KRGE significantly reduced the number of CD4+IL-17+ cells and CD4+/phosphorylated STAT3 (p-STAT3)+ cells, but increased the number of CD4+CD25+forkhead box P3 (Foxp3)+ cells and CD4+/p-STAT5+ cells compared with CsA alone. In allogeneic APCs-stimulated CD4+ T cells, KRGE significantly decreased total allogeneic T cell proliferation. Consistent with the effects of TCR stimulation, KRGE reduced the number of CD4+IL-17+ cells and increased the number of CD4+CD25+Foxp3+ cells under the Th17-polarizing condition. Conclusion: KRGE has immunological benefits through the reciprocal regulation of Th17 and Treg cells during CsA-induced immunosuppression

¹⁸F-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography for Assessing Treatment Response of Pulmonary Multidrug-Resistant Tuberculosis

Background: The purpose of this prospective study was to evaluate the role of 18F-Fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) for assessing treatment response in patients with pulmonary multidrug-resistant tuberculosis (MDR-TB). Methods: The study subjects were four patients diagnosed with pulmonary MDR-TB who underwent MDR-TB treatment and serial 18F-FDG PET/CT at baseline and 6 and 12 months after treatment. The highest lung maximum standardized uptake value (SUVmax), average SUVmean (average of all hypermetabolic parenchymal lesions), total metabolic lung volume (TMLV, sum of metabolic volumes from the hypermetabolic parenchymal lesions), and total lung glycolysis (TLG, sum of lesion glycolysis from the hypermetabolic parenchymal lesions) were determined as representative quantitative PET parameters for each patient. Results: All patients except one had negative sputum culture conversion after one month of treatment and achieved successful treatment outcomes. Baseline TMLV and TLG PET parameters were much higher in the single patient with treatment failure than in the remaining three patients with treatment success. No other PET parameters at baseline or follow-up were associated with the treatment results. Conclusions: Pretreatment volume-based 18F-FDG PET/CT lung parameters were associated with the final therapeutic response in patients with pulmonary MDR-TB. Our preliminary results warrant a larger study