Publications

African men who have sex with men (MSM) frequently, and often concurrently, have female partners, raising concerns about HIV sexual bridging. We explored potential HIV transmission in Mozambique from and to female partners of MSM focusing on preferred anal sex role and circumcision status. Data collected in a respondent-driven sampling study of MSM in 2011 in Maputo and Beira. Men who had oral or anal sex with other men 12 months prior completed a questionnaire and consented for HIV testing. Statistical analysis explored demographic/risk characteristics and associations among circumcision status, anal sex with men, sexual positions during anal sex with men and vaginal or anal sex with women. We identified 326 MSM in Maputo and 237 in Beira with both male and female partners 3 months before the study. Of these, 20.8% in Maputo and 36.0% in Beira had any receptive anal sex with men 12 months prior, including 895 unprotected sexual acts with males in Maputo and 692 in Beira. Uncircumcised and exclusively insertive males, 27.7% of the sample in Maputo and 33.6% in Beira, had the most unprotected sex with females: 1159 total acts in Maputo and 600 in Beira. Sexual bridging between MSM and women likely varies geographically and is probably bi-directional, occurring within a generalized epidemic where HIV prevalence is higher among reproductive-age women than MSM. Prevention strategies emphasizing correct and consistent condom use for all partners and circumcision for bisexual men should be considered.

Background

Heavy alcohol use can lead to progressive liver damage, especially in individuals with chronic hepatitis C (HCV); however, the impact of nonheavy use is not clear. We studied long-term effects of modest alcohol use on fibrosis progression in a large cohort of women coinfected with human immunodeficiency virus (HIV)/HCV.

Methods

Alcohol intake was ascertained every 6 months and use categorized as abstinent, light (1-3 drinks/week), moderate (4-7 drinks/week), heavy (>7 drinks/week), and very heavy (>14 drinks/week). Fibrosis progression was defined as the change in Fibrosis-4 Index for Liver Fibrosis (FIB-4) units per year using random-intercept, random-slope mixed modeling.

Results

Among 686 HIV/HCV-coinfected women, 46.0% reported no alcohol use; 26.8% reported light use, 7.1% moderate use, and 19.7% heavy use (6.7% had 8-14 drinks/week and 13.0% had >14 drinks/week) at cohort entry. Median FIB-4 at entry was similar between groups. On multivariable analysis, compared to abstainers, light and moderate alcohol use was not associated with fibrosis progression (0.004 [95% confidence interval {CI}, -.11 to .12] and 0.006 [95% CI, -.18 to .19] FIB-4 units/year, respectively). Very heavy drinking (>14 drinks/week) showed significant fibrosis acceleration (0.25 [95% CI, .01-.49] FIB-4 units/year) compared to abstaining, whereas drinking 8-14 drinks per week showed minimal acceleration of fibrosis progression (0.04 [95% CI, -.19 to .28] FIB-4 units/year).

Conclusions

Light/moderate alcohol use was not substantially associated with accelerated fibrosis progression, whereas drinking >14 drinks per week showed increased rates of fibrosis progression. Women with HIV/HCV infection should be counseled against heavy alcohol consumption, but complete abstinence may not be required to prevent accelerated liver fibrosis progression.

BACKGROUND

Previously, we and other investigators have described reversible loss of lung elastic recoil in patients with acute and persistent, moderate-to-severe, chronic, treated asthma who never smoked, and its adverse effect on maximal expiratory airflow. In four consecutive autopsies, we reported the pathophysiologic mechanism(s) has been unsuspected mild, diffuse, middle and upper lobe centrilobular emphysema.

METHODS

We performed prospective studies (5 to 22 years) in 25 patients (12 female) with chronic asthma, age 55 ± 15 years, who never smoked, with persistent moderate-to-severe expiratory obstruction. Studies included measuring blood eosinophils, IgE, total exhaled nitric oxide (NO), central airway NO flux, peripheral airway/alveolar NO concentration, impulse oscillometry, heliox curves, lung elastic recoil, and high-resolution thin-section (1 mm) lung CT imaging at full inspiration with voxel quantification.

RESULTS

In 25 patients with stable asthma with varying type 2 phenotype, after 270 μg of aerosolized albuterol sulfate had been administered with a metered dose inhaler with space chamber, FVC was 3.1 ± 1.0 L (83% ± 13% predicted) (mean ± SD), FEV was 1.8 ± 0.6 L (59% ± 11%), the FEV/FVC ratio was 59% ± 10%, and the ratio of single-breath diffusing capacity of the lung for carbon monoxide to alveolar volume was 4.8 ± 1.1 mL/min/mm Hg/L (120% ± 26%). All 25 patients with asthma had loss of static lung elastic recoil pressure, which contributed equally to decreased intrinsic airway conductance in limiting expiratory airflow. Lung CT scanning detected none or mild emphysema. In all four autopsied asthmatic lungs previously reported and one unreported explanted lung, microscopy revealed unsuspected mild, diffuse centrilobular emphysema in the upper and middle lung fields, and asthma-related remodeling in airways. In eight cases, during asthma remission, there were increases in measured static lung elastic recoil pressure-calculated intrinsic airway conductance, and measured maximal expiratory airflow at effort-independent lung volumes.

CONCLUSIONS

As documented now in five cases, unsuspected microscopic mild centrilobular emphysema is the sentinel cause of loss of lung elastic recoil. This contributes significantly to expiratory airflow obstruction in never-smoking patients with asthma, with normal diffusing capacity and near-normal lung CT scan results.

TRIAL REGISTRY

Protocol No. 20070934 and Study No. 1090472, Western Institutional Review Board, Olympia, WA; ClinicalTrials.gov; No. NCT00576069; URL: www.clinicaltrials.gov.

Asthma is characterized by mucus abnormalities. Airway epithelial hyperplasia and metaplasia result in changes in stored and secreted mucin and the production of a pathologic mucus gel. Mucus transport is impaired, culminating in mucus plugging and airway obstruction-a major cause of morbidity in asthma. The polymeric mucins MUC5AC and MUC5B are integral components of airway mucus. and gene expression is altered in asthma, and recent work sheds light on their contribution to asthma pathogenesis. Herein, we review our current understanding of the role of MUC5AC and MUC5B in mucus dysfunction in asthma.