Elevated NT-pro-brain natriuretic peptide level is independently associated with all-cause mortality in HIV-infected women in the early and recent HAART eras in the Women's Interagency HIV Study cohort.

BACKGROUND: HIV-infected individuals are at increased risk of right and left heart dysfunction. N-terminal-pro-brain natriuretic peptide (NT-proBNP), a marker of cardiac ventricular strain and systolic dysfunction, may be associated with all-cause mortality in HIV-infected women. The aim of this study was to determine if elevated levels of NT-proBNP is associated with increased mortality in HIV-infected women. DESIGN: Prospective cohort study. METHODS AND RESULTS: We measured NT-proBNP in 936 HIV-infected and 387 age-matched HIV-uninfected women early (10/11/94 to 7/17/97) and 1082 HIV-infected and 448 HIV-uninfected women late (4/1/08 to 10/7/08) in the highly active antiretroviral therapy (HAART) periods in the Women's Interagency HIV Study. An NT-proBNP >75th percentile was more likely in HIV-infected persons, but only statistically significant in the late period (27% vs. 21%, unadjusted p = 0.03). In HIV-infected participants, NT-proBNP>75th percentile was independently associated with worse 5-year survival in the early HAART period (HR 1.8, 95% CI 1.3-2.4, p<0.001) and remained a predictor of mortality in the late HAART period (HR 2.8, 95% CI 1.4-5.5, p = 0.002) independent of other established risk covariates (age, race/ethnicity, body mass index, smoking, hepatitis C serostatus, hypertension, renal function, and hemoglobin). NT-proBNP level was not associated with mortality in HIV-uninfected women. CONCLUSION: NT-proBNP is a novel independent marker of mortality in HIV-infected women both when HAART was first introduced and currently. As NT-proBNP is often associated with both pulmonary hypertension and left ventricular dysfunction, these findings suggest that these conditions may contribute significantly to adverse outcomes in this population, requiring further definition of causes and treatments of elevated NT-proBNP in HIV-infected women.

Contributors to diffusion impairment in HIV-infected persons.

Abnormal diffusing capacity is common in HIV-infected individuals, including never smokers. Aetiologies for diffusing capacity impairment in HIV are not understood, particularly in those without a history of cigarette smoking. Our study was a cross-sectional analysis of 158 HIV-infected individuals without acute respiratory symptoms or infection with the aim to determine associations between a diffusing capacity of the lung for carbon monoxide (D(LCO)) % predicted and participant demographics, pulmonary spirometric measures (forced expiratory volume in 1 s (FEV1) and FEV1/forced vital capacity), radiographic emphysema (fraction of lung voxels < -950 Hounsfield units), pulmonary vascular/cardiovascular disease (echocardiographic tricuspid regurgitant jet velocity, N-terminal pro-brain natriuretic peptide) and airway inflammation (induced sputum cell counts), stratified by history of smoking. The mean D(LCO) was 65.9% predicted, and 55 (34.8%) participants had a significantly reduced D(LCO) (<60% predicted). Lower D(LCO) % predicted in ever-smokers was associated with lower post-bronchodilator FEV1 % predicted (p<0.001) and greater radiographic emphysema (p=0.001). In never-smokers, mean±SD D(LCO) was 72.7±13.4% predicted, and D(LCO) correlated with post-bronchodilator FEV1 (p=0.02), sputum neutrophils (p=0.03) and sputum lymphocytes (p=0.009), but not radiographic emphysema. Airway obstruction, emphysema and inflammation influence D(LCO) in HIV. Never-smokers may have a unique phenotype of diffusing capacity impairment. The interaction of multiple factors may account for the pervasive nature of diffusing capacity impairment in HIV infection.

HIV infection is associated with diffusing capacity impairment in women.

Respiratory dysfunction is common with HIV infection, but few studies have directly assessed whether HIV remains an independent risk factor for pulmonary function abnormalities in the antiretroviral therapy era. Additionally, few studies have focused on pulmonary outcomes in HIV+ women. We tested associations between risk factors for respiratory dysfunction and pulmonary outcomes in 63 HIV+ and 36 HIV-uninfected women enrolled in the Women's Interagency HIV Study. Diffusing capacity (DL(CO)) was significantly lower in HIV+ women (65.5% predicted vs. 72.7% predicted, P = 0.01), and self-reported dyspnea in HIV+ participants was associated with both DL(CO) impairment and airflow obstruction. Providers should be aware that DL(CO) impairment is common in HIV infection, and that either DL(CO) impairment or airflow obstruction may cause respiratory symptoms in this population.

Asthma diagnosis and airway bronchodilator response in HIV-infected patients.

BACKGROUND: Despite the high prevalence of respiratory symptoms and obstructive lung disease in HIV-infected subjects, the prevalence of bronchodilator reversibility (BDR) and asthma has not been systematically studied during the era of combination antiretroviral therapy (ART). OBJECTIVE: We sought to determine the prevalence of asthma diagnosis and related pulmonary function abnormalities in an HIV-infected cohort and to identify potential mechanisms. METHODS: We performed a cross-sectional analysis of 223 HIV-infected subjects with data on respiratory symptoms and diagnoses, pulmonary function, sputum cell counts, and asthma-related cytokines and chemokines in serum/sputum. RESULTS: Doctor-diagnosed asthma was present in 46 (20.6%), and BDR (≥200 mL and ≥12% increase in FEV(1) or forced vital capacity) was present in 20 (9.0%) participants. Pulmonary symptoms and function were worse in those with doctor-diagnosed asthma. Doctor-diagnosed asthma was independently associated with female sex (P = .04), body mass index of greater than 29.6 kg/m(2) (vs <29.6 kg/m(2), P = .03), history of bacterial or Pneumocystis pneumonia (P = .01), and not currently taking ART (P = .04) and in univariate analysis with parental history of asthma (n = 180, P = .004). High sputum eosinophil percentages (>2.3% based on the highest decile) were more likely in those with doctor-diagnosed asthma (P = .02) or BDR (P = .02). Doctor-diagnosed asthma tended to be more common with high sputum IL-4 (P = .02) and RANTES (P = .02) levels, whereas BDR was associated with high plasma macrophage inflammatory protein 1α (P = .002) and sputum macrophage inflammatory protein 1ß (P = .001) levels. CONCLUSION: Asthma diagnosis and BDR are prevalent in an HIV-infected outpatient cohort, and associations with family history, obesity, allergic inflammation, prior infection, absence of ART, and increased HIV-stimulated cytokines suggest possible mechanisms of HIV-associated asthma.

HIV and chronic obstructive pulmonary disease: is it worse and why?

Smoking-related diseases, such as chronic obstructive pulmonary disease (COPD), are of particular concern in the HIV-infected population. Smoking rates are high in this population, and long-term exposure to cigarette smoke in the setting of HIV infection may increase the number of complications seen. Before the era of combination antiretroviral therapy, HIV-infected persons were noted to have an accelerated form of COPD, with significant emphysematous disease seen in individuals less than 40 years old. Unlike many of the AIDS-defining opportunistic infections, HIV-associated COPD may be more common in the current era of HIV because it is frequently reported in patients without a history of AIDS-related pulmonary complications and because many aging HIV-infected individuals have had a longer exposure to smoking and HIV. In this review, we document the epidemiology of HIV-associated COPD before and after the institution of combination antiretroviral therapy, review data suggesting that COPD is accelerated in those with HIV, and discuss possible mechanisms of HIV-associated COPD, including an increased susceptibility to chronic, latent infections; an aberrant inflammatory response; altered oxidant-antioxidant balance; increased apoptosis associated with HIV; and the effects of antiretroviral therapy.

Pulmonary function abnormalities in HIV-infected patients during the current antiretroviral therapy era.

RATIONALE: Before the introduction of combination antiretroviral (ARV) therapy, patients infected with HIV had an increased prevalence of respiratory symptoms and lung function abnormalities. The prevalence and exact phenotype of pulmonary abnormalities in the current era are unknown. In addition, these abnormalities may be underdiagnosed. OBJECTIVES: Our objective was to determine the current burden of respiratory symptoms, pulmonary function abnormalities, and associated risk factors in individuals infected with HIV. METHODS: Cross-sectional analysis of 167 participants infected with HIV who underwent pulmonary function testing. MEASUREMENTS AND MAIN RESULTS: Respiratory symptoms were present in 47.3% of participants and associated with intravenous drug use (odds ratio [OR] 3.64; 95% confidence interval [CI], 1.32-10.046; P = 0.01). Only 15% had previous pulmonary testing. Pulmonary function abnormalities were common with 64.1% of participants having diffusion impairment and 21% having irreversible airway obstruction. Diffusion impairment was independently associated with ever smoking (OR 2.46; 95% CI, 1.16-5.21; P = 0.02) and Pneumocystis pneumonia prophylaxis (OR 2.94; 95% CI, 1.10-7.86; P = 0.01), whereas irreversible airway obstruction was independently associated with pack-years smoked (OR 1.03 per pack-year; 95% CI, 1.01-1.05; P < 0.01), intravenous drug use (OR 2.87; 95% CI, 1.15-7.09; P = 0.02), and the use of ARV therapy (OR 6.22; 95% CI, 1.19-32.43; P = 0.03). CONCLUSIONS: Respiratory symptoms and pulmonary function abnormalities remain common in individuals infected with HIV. Smoking and intravenous drug use are still important risk factors for pulmonary abnormalities, but ARV may be a novel risk factor for irreversible airway obstruction. Obstructive lung disease is likely underdiagnosed in this population.

Acute physiologic effects of secondhand smoke exposure in children.

INTRODUCTION: We investigated the hypothesis that exhaled carbon monoxide (eCO), heart rate (HR), and blood pressure (BP) would increase acutely in exposed but not in unexposed children. METHODS: In a nonrandomized controlled design, parent-child dyads were assigned to groups based on exposure: child subjects, 7-18 years of age, exposed to smoking daily in the home (exposed) or with no household exposure (unexposed control). HR, BP, and eCO were measured before and after exposure to a parent smoking 1 cigarette (exposed) or a time-lapse equivalent (control). The primary analysis compared mean acute changes in physiological measures following intervention or control procedure. RESULTS: Forty-one dyads were enrolled. At baseline, no differences in child gender, race, ethnicity, HR, BP, lipids, or fasting glucose were noted between exposure groups. Following experimental or control procedures, the median change in eCO was similar between groups (-0.1 ppm exposed vs. 0.0 ppm unexposed, p = .27). Acute hemodynamic changes were also similar between exposed and unexposed children, respectively: (HR change 4.2 vs. 2.6 beats per minute, p = .62; systolic blood pressure change 0.08 vs. 0.41 mm Hg, p = .91; diastolic blood pressure 0.08 vs. 2.27 mm Hg, p = .37). DISCUSSION: This is the first study to report on acute physiologic changes of secondhand smoke exposure in children in a naturalistic setting. A single acute dose of passive smoke exposure in children did not alter the physiologic variables of HR or BP. Further in-home study using continuous monitoring is needed. Demonstration of acute effects may serve as clinical feedback to motivate parents to quit smoking.