Kathleen M. Akgün

Risk factors for hospitalization and medical intensive care unit (MICU) admission among HIV infected Veterans

Objective:With improved survival of HIV-infected persons on antiretroviral therapy and growing prevalence of non-AIDS diseases, we asked whether the VACS Index, a composite measure of HIV-associated and general organ dysfunction predictive of all-cause mortality, predicts hospitalization and medical intensive care unit (MICU) admission. We also asked whether AIDS and non-AIDS conditions increased risk after accounting for VACS Index score. Methods:We analyzed data from the Veterans Aging Cohort Study (VACS), a prospective study of HIV-infected Veterans receiving care between 2002 and 2008. Data were obtained from the electronic medical record, VA administrative databases, and patient questionnaires and were used to identify comorbidities and calculate baseline VACS Index scores. The primary outcome was first hospitalization within 2 years of VACS enrollment. We used multivariable Cox regression to determine risk factors associated with hospitalization and logistic regression to determine risk factors for MICU admission, given hospitalization. Results:Of 3410 patients, 1141 were hospitalized within 2 years; 203 (17.8%)/1141 patients included an MICU admission. Median VACS Index scores were 25 (no hospitalization), 34 (hospitalization only), and 51 (MICU). In adjusted analyses, a 5-point increment in VACS Index score was associated with 10% higher risk of hospitalization and MICU admission. In addition to VACS Index score, Hispanic ethnicity, current smoking, hazardous alcohol use, chronic obstructive pulmonary disease, hypertension, diabetes, and prior AIDS-defining event predicted hospitalization. Among those hospitalized, VACS Index score, cardiac disease, and prior cancer predicted MICU admission. Conclusions:The VACS Index predicted hospitalization and MICU admission as did current smoking, hazardous alcohol use, and AIDS and certain non-AIDS diagnoses.

Epidemiology and Management of Common Pulmonary Diseases in Older Persons

Pulmonary disease prevalence increases with age and contributes to morbidity and mortality in older patients. Dyspnea in older patients is often ascribed to multiple etiologies such as medical comorbidities and deconditioning. Common pulmonary disorders are frequently overlooked as contributors to dyspnea in older patients. In addition to negative impacts on morbidity and mortality, quality of life is reduced in older patients with uncontrolled, undertreated pulmonary symptoms. The purpose of this review is to discuss the epidemiology of common pulmonary diseases, namely pneumonia, chronic obstructive pulmonary disease, asthma, lung cancer, and idiopathic pulmonary fibrosis in older patients. We will review common clinical presentations for these diseases and highlight differences between younger and older patients. We will also briefly discuss risk factors, treatment, and mortality associated with these diseases. Finally, we will address the relationship between comorbidities, pulmonary symptoms, and quality of life in older patients with pulmonary diseases.

The Changing Epidemiology of HIV-Infected Patients in the Intensive Care Unit

With the introduction of highly active antiretroviral therapy (HAART), HIV has become a chronic disease. As HIV-infected patients are aging, they are at increased risk for comorbid diseases. These non-AIDS related diseases account for a growing proportion of intensive care unit (ICU) admissions in HIV-infected patients in recent studies. HIV-infected patients still present to the ICU with HIV-related conditions such as Pneumocystis jirovecii pneumonia (PCP), but these conditions are becoming less common. Respiratory failure remains the most common indication for ICU admission. Immune reconstitution inflammatory response syndrome and toxicities related to HAART may also result in ICU admission. While ICU survival has improved since the earliest era of the HIV epidemic, hospital mortality for HIV-infected patients admitted to the ICU remains around 30%. Risk factors for ICU mortality include poor functional status, weight loss, more than one year between HIV diagnosis and ICU admission, lower serum albumin, higher severity of illness, need for mechanical ventilation, and respiratory failure-particularly if due to PCP and accompanied by pneumothorax. The impact of HAART on ICU outcomes is unclear. HAART administration in the ICU can be challenging due to limited delivery routes, concern for viral resistance and medication toxicities. There are no data to determine the safety or efficacy of HAART initiation in the ICU. Future studies are needed to address the role of age, associated comorbidities and impact of HAART on outcomes of HIV-infected patients admitted to the ICU

Increased Risk of Radiographic Emphysema in HIV Is Associated With Elevated Soluble CD14 and Nadir CD4

BACKGROUND The association between HIV and emphysema remains incompletely understood. We sought to determine whether HIV is an independent risk factor for emphysema severity and whether markers of HIV severity and systemic biomarkers of inflammation (IL-6), altered coagulation (D-dimer), and immune activation (soluble CD14) are associated with emphysema. METHODS We performed a cross-sectional analysis of 114 participants with HIV infection and 89 participants without HIV infection in the Examinations of HIV-Associated Lung Emphysema (EXHALE) study. Participants underwent chest CT imaging with blinded semiquantitative interpretation of emphysema severity, distribution, and type. We generated multivariable logistic regression models to determine the risk of HIV for radiographic emphysema, defined as > 10% lung involvement. Similar analyses examined associations of plasma biomarkers, HIV RNA, and recent and nadir CD4 cell counts with emphysema among participants with HIV infection. RESULTS Participants with HIV infection had greater radiographic emphysema severity with increased lower lung zone and diffuse involvement. HIV was associated with significantly increased risk for > 10% emphysema in analyses adjusted for cigarette smoking pack-years (OR, 2.24; 95% CI, 1.12-4.48). In multivariable analyses restricted to participants with HIV infection, nadir CD4 < 200 cells/μL (OR, 2.98; 95% CI, 1.14-7.81), and high soluble CD14 level (upper 25th percentile) (OR, 2.55; 95% CI, 1.04-6.22) were associated with increased risk of > 10% emphysema. IL-6 and D-dimer were not associated with emphysema in HIV. CONCLUSIONS HIV is an independent risk factor for radiographic emphysema. Emphysema severity was significantly greater among participants with HIV infection. Among those with HIV, nadir CD4 < 200 cells/μL and elevated soluble CD14 level were associated with emphysema, highlighting potential mechanisms linking HIV with emphysema.

Medical ICU admission diagnoses and outcomes in human immunodeficiency virus-infected and virus-uninfected veterans in the combination antiretroviral era.

Objectives:Human immunodeficiency virus (HIV)–infected (HIV+) patients on combination antiretroviral therapy are living longer but have increased risk for aging-associated disease which may lead to increasing critical care requirements. We compare medical ICU admission characteristics and outcomes among HIV infected and demographically similar uninfected patients (uninfected) and considered whether an index which combines routine clinical biomarkers (the Veterans Aging Cohort Study Index) predicts 30-day medical ICU mortality. Design:Observational data analyses (Veterans Aging Cohort Study). Setting:Eight Veterans Affairs medical centers nationwide. Patients:HIV infected and uninfected with a medical ICU admission between 2002 and 2010. Intervention:None. Measurements and Main Results:Medical ICU admission was determined using bedsection (Veterans Affairs) and revenue center codes (Medicare). For Veterans Affairs admissions, we used clinical data to calculate Veterans Aging Cohort Study Index scores and multivariable logistic regression to determine factors associated with 30-day mortality. Overall, 539 of 3,620 (15%) HIV infected and 375 of 3,639 (10%) uninfected had a medical ICU admission; 72% and 78%, respectively, were Veterans Affairs based. HIV+ patients were younger at admission (p < 0.0001). Although most HIV+ patients were on antiretroviral therapy (71%) with undetectable HIV-1 RNA (54%), compared with uninfected they were more commonly admitted with respiratory diagnoses or infections (21% vs. 12%), were more likely to require mechanical ventilation (17% vs. 9%; p = 0.001), and had a higher mortality rate (18.6% vs. 11.2%, p = 0.003). Cardiovascular diagnoses were less common among HIV infected (18% vs. 29%; p < 0.0001). In logistic regression (c-statistic 0.87), a 5-point increment in Veterans Aging Cohort Study Index was associated with an odds ratio of death of 1.22 (95% confidence interval 1.14–1.30) among HIV infected and of 1.50 (95% confidence interval 1.29–1.76) among uninfected; infection/sepsis and respiratory diagnoses were also associated with mortality. Conclusions:Medical ICU admission was frequent, 30-day mortality higher, and mechanical ventilation more common in HIV infected compared with uninfected. The Veterans Aging Cohort Study Index calculated at medical ICU admission predicted 30-day mortality for HIV infected and uninfected. As more individuals age with HIV, their requirements for medical ICU care may be greater than demographically similar uninfected individuals.

An adapted frailty-related phenotype and the VACS index as predictors of hospitalization and mortality in HIV-infected and uninfected individuals.

Background:Frailty is a geriatric syndrome of decreased physiologic reserve and a risk factor for hospitalization and mortality. We hypothesized that an adapted survey-based frailty-related phenotype (aFRP) predicts hospitalization and mortality among HIV-infected and uninfected individuals in adjusted models but is uncommon among those achieving undetectable HIV-1 RNA. Methods:Defined from self-reported domains of physical shrinking, exhaustion, slowness, and low physical activity in Veterans Aging Cohort Study (VACS) participants, aFRP was considered present with ≥3 domains and prefrailty with 1–2 domains. Cox survival analysis determined hazard ratios (HRs) for 5-year hospitalization and mortality risk adjusting for frailty states, demographics, health behaviors, comorbidities, and a validated risk index incorporating HIV-specific and general organ system biomarkers, the VACS Index. Model discrimination was assessed. Results:Participants with complete data were included [6515/7324 (89%)]. Of these, 3.9% of HIV-infected individuals with HIV-1 RNA >400 copies per milliliter; 2.0% of HIV-infected individuals with HIV-1 RNA ⩽400 copies per milliliter; and 2.8% of uninfected individuals met aFRP criteria (P = 0.01). After adjustment for other covariates, aFRP was associated with hospitalization (HR = 1.78; 95% confidence interval: 1.48 to 2.13) and mortality (HR = 1.75; 95% confidence interval: 1.28 to 2.40). C-statistics for the VACS Index for hospitalization (0.633) and for mortality (0.756) were higher than for aFRP (0.565 and 0.584, respectively). C-statistic for hospitalization improved modestly when VACS Index and aFRP were both included (0.646) and minimally for mortality (0.761). Conclusions:aFRP was independently associated with adverse health outcomes among HIV-infected and uninfected individuals. aFRP modestly improved prediction for hospitalization. However, the aFRP is rare among HIV-infected individuals with undetectable HIV-1 RNA.

Findings in asymptomatic HIV-infected patients undergoing chest computed tomography testing: implications for lung cancer screening.

Background:HIV-infected persons have a two-fold to five-fold increased unadjusted risk of lung cancer. In the National Lung Screening Trial (NLST), computed tomography (CT) screening was associated with a reduction in lung cancer mortality among high-risk smokers. These results may not generalize to HIV-infected persons, particularly if they are more likely to have false-positive chest CT findings. Methods:We utilized data including standardized chest CT scans from 160 HIV infected and 139 uninfected Veterans enrolled between 2009 and 2012 in the multicenter Examinations of HIV Associated Lung Emphysema (EXHALE) Study. Abnormal CT findings were abstracted from clinical interpretations of the scans and classified as positive by NLST criteria vs. other findings. Clinical evaluations and diagnoses that ensued were abstracted from the medical record. Results:There was no significant difference by HIV in the proportion of CT scans classified as positive by NLST criteria (29% of HIV infected and 24% of HIV uninfected, P = 0.3). However, HIV-infected participants with CD4+ cell counts less than 200 cells/&mgr;l had significantly higher odds of positive scans, a finding that persisted in multivariable analysis. Evaluations triggered by abnormal CT scans were also similar in HIV-infected and uninfected participants (all P > 0.05). Conclusion:HIV status was not associated with an increased risk of abnormal findings on CT or increased rates of follow-up testing in clinically stable outpatients with CD4+ cell count more than 200. These data reflect favorably on the balance of benefits and harms associated with lung cancer screening for HIV-infected smokers with less severe immunodeficiency.

Association of chronic cough and pulmonary function with 6-minute walk test performance in HIV Infection

Objective:Chronic lung disease has been associated with greater impairment in self-reported physical function in HIV-infected patients. We sought to study this association using objective measures of physical function and pulmonary function. Design:Baseline data from the Examinations of HIV Associated Lung Emphysema study, a multicenter observational cohort of HIV-infected and uninfected veterans. Methods:We assessed the association between clinical, laboratory, and pulmonary function measures with 6-minute walk test (6-MWT). Multivariable linear regression models were generated to identify factors associated with 6-MWT performance. Results:Three hundred forty participants completed 6-MWT (mean age 55 years), with 68% blacks, 94% men, and 62% current smokers. Overall, 180 (53%) were HIV-infected and 63 (19%) had spirometry-defined chronic obstructive pulmonary disease. In a multivariable model, age, current smoking, and obesity (body mass index > 30) were independently associated with lower 6-MWT performance, but HIV infection was not; there was a significant interaction between HIV and chronic cough, such that distance walked among HIV-infected participants with chronic cough was 51.76 m less (P = 0.04) compared with those without cough or HIV. Among HIV-infected participants, the forced expiratory volume in 1 second (FEV1, percent predicted), to a greater extent than total lung capacity or diffusing capacity, attenuated the association with chronic cough; decreased FEV1 was independently associated with lower 6-MWT performance in those with HIV. Conclusions:Older age, current smoking, and airflow limitation were important determinants of 6-MWT performance in the HIV-infected participants. These findings suggest that potential interventions to improve physical function may include early management of respiratory symptoms and airflow limitation.

Critical Illness in HIV-Infected Patients in the Era of Combination Antiretroviral Therapy

As HIV-infected persons on combination antiretroviral therapy (ART) are living longer and rates of opportunistic infections have declined, serious non-AIDS-related diseases account for an increasing proportion of deaths. Consistent with these changes, non-AIDS-related illnesses account for the majority of ICU admissions in more recent studies, in contrast to earlier eras of the AIDS epidemic. Although mortality after ICU admission has improved significantly since the earliest HIV era, it remains substantial. In this article, we discuss the current state of knowledge regarding the impact of ART on incidence, etiology, and outcomes of critical illness among HIV-infected patients. In addition, we consider issues related to administration of ART in the ICU and identify important areas of future research.

Risk factors associated with acute exacerbation of chronic obstructive pulmonary disease in HIV-infected and uninfected patients

Objective:To determine the association between HIV infection and other risk factors for acute exacerbation of chronic obstructive pulmonary disease (AECOPD). Design:Longitudinal, national Veterans Aging Cohort Study including 43 618 HIV-infected and 86 492 uninfected veterans. Methods:AECOPD was defined as an inpatient or outpatient COPD ICD-9 diagnosis accompanied by steroid and/or antibiotic prescription within 5 days. We calculated incidence rate ratios (IRR) and 95% confidence intervals (CI) for first AECOPD over 2 years and used Poisson regression models to adjust for risk factors. Results:Over 234 099 person-years of follow-up, 1428 HIV-infected and 2104 uninfected patients had at least one AECOPD. HIV-infected patients had an increased rate of AECOPD compared with uninfected (18.8 vs. 13.3 per 1000 person-years, P < 0.001). In adjusted models, AECOPD risk was greater in HIV-infected individuals overall (IRR 1.54; 95% CI 1.44–1.65), particularly in those with more severe immune suppression when stratified by CD4+ cell count (cells/&mgr;l) compared with uninfected (HIV-infected CD4+ < 200: IRR 2.30, 95% CI 2.10–2.53, HIV-infected CD4+ ≥ 200–349: IRR 1.32, 95% CI 1.15–1.51, HIV-infected CD4+ ≥ 350: IRR 0.99, 95% CI 0.88–1.10). HIV infection also modified the association between current smoking and alcohol-related diagnoses with risk for AECOPD such that interaction terms for HIV and current smoking or HIV and alcohol-related diagnoses were each significantly associated with AECOPD. Conclusion:HIV infection, especially with lower CD4+ cell count, is an independent risk factor for AECOPD. Enhanced susceptibility to harm from current smoking or unhealthy alcohol use in HIV-infected patients may also contribute to the greater rate of AECOPD.