Estrogen contributes to sex differences in M2a macrophages during multi-walled carbon nanotube-induced respiratory inflammation.

Lung diseases characterized by type 2 inflammation are reported to occur with a female bias in prevalence/severity in both humans and mice. This includes previous work examining multi-walled carbon nanotube (MWCNT)-induced eosinophilic inflammation, in which a more exaggerated M2a phenotype was observed in female alveolar macrophages (AMs) compared to males. The mechanisms responsible for this sex difference in AM phenotype are still unclear, but estrogen receptor (ER) signaling is a likely contributor. Accordingly, male AMs downregulated ERα expression after MWCNT exposure while female AMs did not. Thus, ER antagonist Fulvestrant was administered prior to MWCNT instillation. In females, Fulvestrant significantly attenuated MWCNT-induced M2a gene expression and eosinophilia without affecting IL-33. In males, Fulvestrant did not affect eosinophil recruitment but reduced IL-33 and M2a genes compared to controls. Regulation of cholesterol efflux and oxysterol synthesis is a potential mechanism through which estrogen promotes the M2a phenotype. Levels of oxysterols 25-OHC and 7α,25-OHC were higher in the airways of MWCNT-exposed males compared to MWCNT-females, which corresponds with the lower IL-1ß production and greater macrophage recruitment previously observed in males. Sex-based changes in cholesterol efflux transporters Abca1 and Abcg1 were also observed after MWCNT exposure with or without Fulvestrant. In vitro culture with estrogen decreased cellular cholesterol and increased the M2a response in female AMs, but did not affect cholesterol content in male AMs and reduced M2a polarization. These results reveal the modulation of (oxy)sterols as a potential mechanism through which estrogen signaling may regulate AM phenotype resulting in sex differences in downstream respiratory inflammation.

Respiratory syncytial virus surveillance in the United States, 2007-2012: results from a national surveillance system.

BACKGROUND: Annual respiratory syncytial virus (RSV) outbreaks throughout the US exhibit variable patterns in onset, peak month of activity and duration of season. RSVAlert, a US surveillance system, collects and characterizes RSV test data at national, regional, state and local levels. METHODS: RSV test data from 296 to 666 laboratories from 50 states, the District of Columbia and Puerto Rico (as of 2010) were collected during the 2007-2008 to 2011-2012 RSV seasons. Data were collected in early August/September to the following August/September each season. Participating laboratories provided the total number and types of RSV tests performed each week and test results. RSV season onset and offset were defined as the first and last, respectively, of 2 consecutive weeks during which the mean percentage of specimens testing positive for RSV was ≥10%. RESULTS: Nationally, the RSV season onset occurred in October/November of each year with offset occurring in March/April of the following year. The RSV season averaged 20 weeks and typically occurred earliest in the South and latest in the West. The onset, offset and duration varied considerably within the U.S. Department of Health and Human Services regions. RSV activity in Puerto Rico was elevated throughout the 2-year period studied. Median onset in core-based statistical areas ranged from 2 weeks earlier to 5 weeks later than those in their corresponding states. CONCLUSIONS: Substantial variability existed in the timing of RSV activity at all geographic strata analyzed. RSV actively circulated (ie, ≥10%) in many areas outside the traditionally defined RSV epidemic period of November to March.

Laboratory testing trends for respiratory syncytial virus, 2007-2011.

BACKGROUND: Antigen detection tests have been the most common diagnostic assay used to detect and diagnose respiratory syncytial virus (RSV). The utility and increased sensitivity of polymerase chain reaction (PCR) tests have been reported; however, their use in US hospital laboratories is not well characterized. OBJECTIVE: To describe changes in RSV test types used by US hospital-affiliated laboratories, focusing on PCR testing prevalence. STUDY DESIGN: Data were collected from 480 to 666 laboratories each RSV season (2007-2008 through 2010-2011) across 50 states, the District of Columbia, and Puerto Rico. A descriptive analysis was conducted using this convenience sample of RSV tests conducted from November to April each season. Total numbers and types of RSV tests performed were reported weekly and weekly proportions by test type were calculated. Kendall τ rank correlation was used to quantify associations between time and proportions of each test type. RESULTS: PCR tests accounted for 2%, 3%, 16%, and 21% of weekly tests (total range, 381,068-481,654 over 4 seasons) conducted each season from 2007 to 2011, respectively. The proportion of laboratories reporting ≥1 PCR tests was 4%, 5%, 10%, and 16%, respectively. Decreases in antigen testing and viral culture were similarly observed. CONCLUSIONS: Although antigen detection was the predominant test type reported in the sample of US hospital laboratories for RSV testing, PCR use increased to >20% of tests reported. These results demonstrate the increasing contribution of PCR to RSV surveillance. RSV surveillance systems relying solely on antigen detection results will not capture an increasing proportion of RSV test results.