Publications

RATIONALE

HIV seropositivity has long been considered a contraindication to lung transplantation, primarily because of the potential risks of added immunosuppression. In the past decade, however, experience with kidney and liver transplantation in the setting of HIV infection, with achievement of satisfactory outcomes, has grown considerably. This promising development has created a need to reconsider this contraindication to lung transplantation.

OBJECTIVES

There is presently limited evidence upon which to base medical decision-making regarding lung transplantation in individuals with HIV infection. In our present study, we wished to extend the existing literature by reporting the outcomes of three individuals with HIV infection who underwent lung transplantation at two centers.

METHODS

We compiled data for a case series of three HIV-infected subjects undergoing lung transplantation at two centers.

MEASUREMENTS AND MAIN RESULTS

We reviewed medical records to investigate the effects of lung transplantation on the course of HIV infection, the development of HIV-related opportunistic infections or malignancies, the occurrence of lung transplant and HIV drug interactions, and the extent of acute rejection. Subject 1, who underwent transplantation for HIV-associated pulmonary arterial hypertension, experienced recalcitrant acute rejection requiring a lymphocyte-depleting agent with subsequent rapid development of bronchiolitis obliterans syndrome. Subjects 2 and 3, who underwent transplantation for idiopathic pulmonary fibrosis, experienced mild acute rejection but remain free from chronic rejection at 4 and 2 years after transplant, respectively.

CONCLUSIONS

Lung transplantation may be feasible for carefully selected patients in the setting of controlled HIV infection. On the basis of our experience with three patients, we caution that acute graft rejection may be more common in such patients.

BACKGROUND

Exposure to secondhand tobacco smoke (SHS) can be a risk factor for chronic obstructive pulmonary disease (COPD), but its role among relatively heavy smokers with potential co-exposure to workplace vapors, gas, dust, and fumes (VGDF) has not been studied.

METHODS

To estimate the contribution of SHS exposure to COPD risk, taking into account smoking effects and work-related exposures to VGDF, we quantified SHS based on survey responses for 1400 ever-employed subjects enrolled in the COPDGene study, all current or former smokers with or without COPD. Occupational exposures to VGDF were quantified based on a job exposure matrix. The associations between SHS and COPD were tested in multivariate logistic regression analyses adjusted for age, sex, VGDF exposure, and cumulative smoking.

RESULTS AND DISCUSSION

Exposures to SHS at work and at home during adulthood were associated with increased COPD risk: odds ratio (OR) = 1.12 (95% confidence interval [CI]: 1.02-1.23; p = 0.01) and OR = 1.09 (95%CI: 1.00-1.18; p = 0.04) per 10 years of exposure adjusted for smoking and other covariates, respectively. In addition, subjects with employment histories likely to entail exposure to VGDF were more likely to have COPD: OR = 1.52 (95%CI: 1.16-1.98; p < 0.01) (adjusted for other covariates). While adult home SHS COPD risk was attenuated among the heaviest smokers within the cohort, workplace SHS and job VGDF risks persisted in that stratum.

CONCLUSION

Among smokers all with at least 10 pack-years, adult home and work SHS exposures and occupational VGDF exposure are all associated with COPD.

OBJECTIVE

To provide further validation of the Brief Index of Lupus Damage (BILD), assessing its sensitivity to change in disease status and ability to predict mortality risk.

METHODS

Data were from the University of California, San Francisco Lupus Outcomes Study (n = 958), in which the BILD was administered twice, approximately 5 years apart. We examined disease activity and health care utilization among participants who completed the BILD twice (n = 745). We identified increases in disease activity and utilization that would suggest a disease flare between the 2 BILD administrations and compared their occurrence by BILD score increases (0, 1, 2, 3, >3). Deaths were ascertained when annual interviews were attempted. Kaplan-Meier life-table analysis compared mortality rates for 4 groups of initial BILD scores (0, 1, 2, ≥3), and differences were tested using a log rank test. Using Cox proportional hazards models, we estimated the risk of death associated with higher BILD scores.

RESULTS

BILD score increases were associated with spikes in disease activity (P = 0.05) and physician visits (P = 0.004) over baseline, and with hospitalizations (P < 0.001) during the intervening years. Of those with BILD score increases >3, 84% were hospitalized prior to the second BILD. During followup, there were 60 deaths (6.3%). BILD scores of 2 (hazard ratio [HR] 6.1, 95% confidence interval [95% CI] 1.3-30.0) and ≥3 (HR 10.8, 95% CI 2.5-46.2) were associated with higher risk of death.

CONCLUSION

This analysis provides evidence of the predictive validity of the BILD and its ability to detect change. While not intended to replace clinical evaluation of disease damage, the BILD appears to be a useful tool for research.

We conducted a longitudinal study of tobacco use among adults initiating antiretroviral therapy (ART) in Mbarara, Uganda where 11 % of men and 3 % of women use tobacco according to the 2011 Demographic and Health Survey. In a prospective cohort, self-reported tobacco use was assessed before starting ART and reassessed every 3-4 months. Plasma cotinine, a nicotine metabolite, was measured in a subset of adults pre-ART to verify self-report. Among 496 subjects, 50 (10 %) reported current tobacco use (20 % of men, 6 % of women). Most (53 %) adults with elevated cotinine levels (>15 ng/mL) reported no tobacco use. By 6 months after ART initiation, 33 % of tobacco users had quit (95 % CI 20-46 %). By 5 years, 64 % quit (95 % CI 47-77 %). Self-reported tobacco use among rural Ugandans starting ART was twice as common as among the local background population and use may be underreported. ART initiation could be an opportunity for tobacco cessation interventions.

PURPOSE OF REVIEW

It is now widely accepted that HIV-infected individuals remain at a higher risk for mortality and age-related morbidities than the general population, but several unresolved issues need to be addressed by the research community in the coming years to further improve the health of HIV-infected individuals in the modern treatment era.

RECENT FINDINGS

Although recent studies have helped to better define the contribution of HIV to life expectancy and morbidity in the modern antiretroviral therapy (ART) era, questions remain about the generalizability of these findings to a future HIV-infected population that is expected to be much older. Furthermore, although a consensus has emerged that the persistent inflammatory state contributes to morbidity and mortality in this setting, the relative contributions of this process, health-related behaviours, comorbidities and medication toxicities remain incompletely understood. Lastly, significant uncertainty remains over the root causes of the persistent inflammatory state, the specific immunologic pathways to target with interventions and the most appropriate biomarkers to use for surrogate outcomes in pilot trials of immune-based interventions.

SUMMARY

Each of these issues will be addressed in this review, highlighting recently published and presented studies that inform the discussion, and recommendations will be made for prioritizing the future research agenda.

New genomic sequencing technologies enable the high-speed analysis of multiple genes simultaneously, including all of those in a person's genome. Sequencing is a prominent example of a "big data" technology because of the massive amount of information it produces and its complexity, diversity, and timeliness. Our objective in this article is to provide a policy primer on sequencing and illustrate how it can affect health care system and policy issues. Toward this end, we developed an easily applied classification of sequencing based on inputs, methods, and outputs. We used it to examine the implications of sequencing for three health care system and policy issues: making care more patient-centered, developing coverage and reimbursement policies, and assessing economic value. We conclude that sequencing has great promise but that policy challenges include how to optimize patient engagement as well as privacy, develop coverage policies that distinguish research from clinical uses and account for bioinformatics costs, and determine the economic value of sequencing through complex economic models that take into account multiple findings and downstream costs.

OBJECTIVE

To determine whether relationship quality is associated with caregiver benefit or burden and how depression influences these associations.

BACKGROUND

Caregivers influence outcomes of patients with heart failure (HF). Relationship quality, caregiver benefit and burden are key factors in the caregiving experience.

METHODS

Nineteen caregivers of HF outpatients completed measures of relationship quality, caregiver benefit, burden and depression. Associations were assessed using Pearson's correlations.

RESULTS

Relationship quality was positively associated with caregiver benefit (r = 0.45, P = 0.05) and negatively associated with burden (r = -0.80, P < 0.0001) and depression (r = -0.77, P = 0.0001). Relationship quality and burden remained associated after controlling for depression.

CONCLUSIONS

In this exploratory study, relationship quality was positively associated with caregiver benefit and negatively associated with burden. Future studies are needed to further understand these key caregiving factors, which may lead to opportunities to help caregivers see benefits and reduce burden.