Faculty Bibliography

INTRODUCTION: Impulse oscillometry (IOS) has been used to demonstrate distal airway dysfunction in symptomatic WTC exposed patients despite normal spirometry. However, it remains to be determined whether the respiratory symptoms can be attributed to the observed functional abnormalities. The present study was designed to assess the simultaneous relationship between the onset of respiratory symptoms and IOS abnormalities in patients undergoing bronchoprovocation for diagnostic evaluation. METHODS: Methacholine challenge testing (MCT) was performed in 113 symptomatic WTC dust exposed patients with normal spirometry that were enrolled WTC Environmental Health Center treatment program. In addition to spirometry, the MCT protocol included performance of IOS and assessment of respiratory symptoms (cough, dyspnea, chest tightness). IOS parameters included resistance at 5 and 20Hz (R⁵ and R₂₀) and frequency dependence of resistance assessed as the difference between these parameters (R_5-20). The PC20 for FEV₁, was used to categorize bronchial hyperreactivity (BHR) as negative (>16mg/ml), borderline (4-16mg/ml) or positive (<4mg/ml). RESULTS: The cohort was 58% female with mean age 49+/-12yr and BMI 29+/-5 kg/m². Baseline spirometry was within normal limits (FEV₁ 98+/-13% predicted, FEV₁/FVC 80+/-4%). Approximately 58% demonstrated abnormal baseline R₅ or R_5-20 indicating respiratory dysfunction despite normal spirometry. MCT revealed BHR, as assessed by spirometry, in 49/113 patients (43%). An additional 27 patients became symptomatic at methacholine doses <4mg/ml despite minimal change in FEV₁ (<5% decrement). All of these patients demonstrated increased R₅, R₂₀ and R_5-20 that coincided with onset of symptoms; median (IQR) increases were 23% (16-41), 13% (7-20), and 92% (39-138), respectively. Following bronchodilator administration, respiratory symptoms resolved and IOS parameters returned towards baseline. CONCLUSIONS: During bronchoprovocation, development of symptoms may coincide with development of distal airway dysfunction as assessed by IOS, even in absence of change in FEV₁. Findings reversed with bronchodilator administration reinforcing the link between symptoms and distal airway dysfunction

Rationale: Exposure to World Trade Center (WTC) dust and fumes is associated with onset of asthma-like respiratory symptoms in exposed community members including local workers, residents and clean-up workers. Although abnormal spirometry measurements are often not detected in these patients, impulse oscillometry (IOS) suggests abnormalities localized to the smaller airways. Peripheral C-reactive protein (CRP) is a marker of systemic inflammation. Since an association between CRP and asthma has been reported, we hypothesized that levels of CRP would be associated with lung function abnormalities as assessed by spirometry and IOS measurements in community members exposed to WTC dust/fumes and gasses. Methods: The WTC Environmental Health Center (EHC) is a treatment program for community members, with presumed WTC-related symptoms. Patients undergo a standardized evaluation including questionnaires and routine blood work, spirometry and IOS measurements. Between 10/1/2009 and 9/29/2011, a measurement of CRP was included for patients undergoing standardized visits. Measurements of lung function were compared utilizing the Wilcoxon test between subjects with normal vs. elevated CRP and further analyzed using linear regression models with log(CRP) as a continuous predictor. Regression analyses were adjusted for potential confounding factors including Body mass index (BMI), exposure category, and smoking history. Results: 208 WTC-exposed individuals met inclusion criteria. Valid spirometry and IOS data were available in 204 and 189 patients, respectively. Mean age was 49 years, 53% were female. Exposure categories (local workers, clean-up workers, residents) were associated with normal/elevated CRP levels (P=0.01). Smokers had a larger portion of elevated CRP (P=0.048). BMI was higher among the high CRP group (Wilcoxon test, P<0.001). FEV₁ and FVC were lower for the high CRP group (P=0.016, P=0.033). However, CRP level was not associated with the ratio FEV₁/FVC (P=0.58). The IOS measurements (R₅, R_5-20, AX ) were higher (P=0.01, P=0.003, P=.001, respectively) among the high CRP group. Multiple regression analysis confirmed that log(CRP) values were inversely correlated with % of predicted FEV 1 (P=0.009) and positively correlated with log(R₅) (P=0.02) and log(AX) (P=0.0045) after adjustment for log(BMI). Conclusions: Peripheral CRP was negatively correlated with levels of FEV₁ and positively correlated with IOS measurements in community members with WTC dust/gas/fume exposure. These data suggest a relationship between systemic inflammation, as reflected by CRP, and both large and small airway abnormalities in a WTC- exposed population

INTRODUCTION: We have previously shown improvement in spirometry parameters in symptomatic WTC dust exposed community members enrolled in the WTC Environmental Health Center treatment program. Additionally, impulse oscillometry (IOS) has demonstrated evidence for distal lung injury not apparent on spirometry. We hypothesize that longitudinal change of spirometry will differ based on presence or absence of distal airway injury and its response to bronchodilator at baseline. METHODS: 810 patients were identified with more than one spirometry and IOS assessment. IOS parameters included resistance at 5 and 20Hz (R₅ and R₂₀) and frequency dependence of resistance assessed as the difference between these parameters (R_5-20). Linear mixed effects modeling evaluated longitudinal changes in IOS parameters, FVC and FEV₁ for the entire population. Separate models were fit for subgroups categorized based on normal vs. abnormal baseline spirometry and normal vs. abnormal baseline IOS (R₅>3.96 cmH2O/L/s). Analyses were adjusted for confounding factors (age, gender, BMI, race/ethnicity, smoking, exposure category and dust cloud exposure). RESULTS: Mean age was 50yr. Patients were mostly female (52%) and had diverse race/ethnicity. At baseline, mean FVC was 91+/-17% predicted and FEV₁ was 88+/-18% predicted. A normal spirometry pattern was noted in the majority (67%; n=542). Despite normal spirometry, IOS revealed abnormalities in 67% (n=364). Longitudinal analysis of IOS parameters (R₅, R₂₀, R_5-20) over time revealed no significant trends for the entire population and for subgroups categorized by baseline spirometry pattern. In contrast, the longitudinal change in spirometry variables differed based on presence of IOS abnormality. In patients with normal spirometry, FEV₁ increased more rapidly in patients with abnormal baseline IOS compared to those with normal IOS (0.76 vs. 0.52 % predicted/yr; Table 1). For patients with abnormal baseline spirometry, FVC increased more rapidly in the abnormal vs. normal IOS patients (1.73 vs. 1.02 % predicted/yr). Patients with IOS response to bronchodilator (highest quartile for improvement of R₅ post bronchodilator) demonstrated a more rapid longitudinal increase in FEV₁ compared with patients without bronchodilator response (lowest quartile)(0.88 vs. 0.53 % predicted/yr,; Table 2). CONCLUSIONS: Spirometry parameters demonstrated improvement over time, while improvement in IOS parameters was not evident, suggesting potential irreversible injury in the distal lung. However, assessment of baseline distal airway function and its acute response to bronchodilator predicted longitudinal response of spirometry in patients enrolled in a treatment program. (Table Presented)

OBJECTIVE: : The course of lung function in community members exposed to World Trade Center (WTC) dust and fumes remains undefined. We studied longitudinal spirometry among patients in the WTC Environmental Health Center (WTCEHC) treatment program. METHODS: : Observational study of 946 WTCEHC patients with repeated spirometry measures analyzed on the population as a whole and stratified by smoking status, initial spirometry pattern, and WTC-related exposure category. RESULTS: : Improvement in forced vital capacity (54.4 mL/yr; 95% confidence interval, 45.0 to 63.8) and forced expiratory volume in 1 second (36.8 mL/yr; 95% confidence interval, 29.3 to 44.3) was noted for the population as a whole. Heavy smokers did not improve. Spirometry changes differed depending on initial spirometry pattern and exposure category. CONCLUSION: : These data demonstrate spirometry improvement in select populations suggesting reversibility in airway injury and reinforcing the importance of continued treatment.

BACKGROUND: The Step Study found that men who had sex with men (MSM) who received an adenovirus type 5 (Ad5) vector-based vaccine and were uncircumcised or had prior Ad5 immunity, had a higher HIV incidence than MSM who received placebo. We investigated whether differences in HIV exposure, measured by reported sexual risk behaviors, may explain the increased risk. METHODS: Among 1764 MSM in the trial, 726 were uncircumcised, 994 had prior Ad5 immunity, and 563 were both uncircumcised and had prior Ad5 immunity. Analyses compared sexual risk behaviors and perceived treatment assignment among vaccine and placebo recipients, determined risk factors for HIV acquisition, and examined the role of insertive anal intercourse in HIV risk among uncircumcised men. RESULTS: Few sexual risk behaviors were significantly higher in vaccine versus placebo recipients at baseline or during follow-up. Among uncircumcised men, vaccine recipients at baseline were more likely to report unprotected insertive anal intercourse with HIV-negative partners (24.9% vs. 18.1%; P = 0.03). Among uncircumcised men who had prior Ad5 immunity, vaccine recipients were more likely to report unprotected insertive anal intercourse with partners of unknown HIV status (46.0% vs. 37.8%; P = 0.05). Vaccine recipients remained at higher risk of HIV infection compared with placebo recipients (hazard ratio = 2.8; 95% confidence interval, 1.2-6.8) controlling for potential confounders. CONCLUSIONS: These analyses do not support a behavioral explanation for the increased HIV infection rates observed among uncircumcised men in the Step Study. Identifying biologic mechanisms to explain the increased risk is a priority .

We used an Internet-based questionnaire to investigate whether viewing pornography depicting unprotected anal intercourse (UAI) was associated with engaging in UAI in a sample of 821 non-monogamous men who have sex with men (MSM). In the 3 months prior to interview, 77.2% viewed pornography depicting UAI, 42.6% engaged in insertive UAI, and 38.9% engaged in receptive UAI. Polytomous logistic regression of the 751 subjects who provided data on pornography viewing showed significantly elevated odds ratios for having engaged in receptive UAI, insertive UAI, and both receptive and insertive UAI associated with increasing percentage of pornography viewed that depicted UAI. We also found independently significant associations of engaging in UAI with age, use of inhalant nitrites, and HIV status. Although the data cannot establish causality, our findings indicate that viewing pornography depicting UAI and engaging in UAI are correlated. Further research is needed to determine if this observation may have utility for HIV prevention

Myeloid and plasmacytoid dendritic cells (DCs) are important mediators of both innate and adaptive immunity against pathogens such as HIV. During the course of HIV infection, blood DC numbers fall substantially. In the present study, we sought to determine how early in HIV infection the reduction occurs and whether the remaining DC subsets maintain functional capacity. We find that both myeloid DC and plasmacytoid DC levels decline very early during acute HIV in-fection. Despite the initial reduction in numbers, those DCs that remain in circulation retain their function and are able to stimulate allogeneic T-cell responses, and up-regulate maturation markers plus produce cytokines/chemokines in response to stimulation with TLR7/8 agonists. Notably, DCs from HIV-infected subjects produced significantly higher levels of cytokines/chemokines in response to stimulation with TLR7/8 agonists than DCs from uninfected controls. Further examination of gene expression profiles indicated in vivo activation, either directly or indirectly, of DCs during HIV infection. Taken together, our data demonstrate that despite the reduction in circulating DC numbers, those that remain in the blood display hyperfunctionality and implicates a possible role for DCs in promoting chronic immune activation

INTRODUCTION: Since 2004, the authors have been operating First Call NYU, an outreach program to identify acute and recent HIV infections, also called primary HIV infections, among targeted at-risk communities in the New York City (NYC) metropolitan area. MATERIALS AND METHODOLOGY: First Call NYU employed mass media advertising campaigns, outreach to healthcare providers in NYC, and Internet-based efforts including search engine optimization (SEO) and Internet-based advertising to achieve these goals. RESULTS: Between October 2004 and October 2008, 571 individuals were screened through this program, leading to 446 unique, in-person screening visits. 47 primary HIV infections, including 14 acute and 33 recent HIV infections, were identified. DISCUSSION: Internet and traditional recruitment methods can be used to increase self-referrals for screening following possible exposure to HIV. CONCLUSION: Community education of at-risk groups, with the goal of increased self-diagnosis of possible acute HIV infection, may be a useful addition to traditional efforts to identify such individuals