Trajectories of Host-Response Subphenotypes in Patients With COVID-19 Across the Spectrum of Respiratory Support.

BACKGROUND: Hospitalized patients with severe COVID-19 follow heterogeneous clinical trajectories, requiring different levels of respiratory support and experiencing diverse clinical outcomes. Differences in host immune responses to SARS-CoV-2 infection may account for the heterogeneous clinical course, but we have limited data on the dynamic evolution of systemic biomarkers and related subphenotypes. Improved understanding of the dynamic transitions of host subphenotypes in COVID-19 may allow for improved patient selection for targeted therapies. RESEARCH QUESTION: We examined the trajectories of host-response profiles in severe COVID-19 and evaluated their prognostic impact on clinical outcomes. STUDY DESIGN AND METHODS: In this prospective observational study, we enrolled 323 inpatients with COVID-19 receiving different levels of baseline respiratory support: (1) low-flow oxygen (37%), (2) noninvasive ventilation (NIV) or high-flow oxygen (HFO; 29%), (3) invasive mechanical ventilation (27%), and (4) extracorporeal membrane oxygenation (7%). We collected plasma samples on enrollment and at days 5 and 10 to measure host-response biomarkers. We classified patients by inflammatory subphenotypes using two validated predictive models. We examined clinical, biomarker, and subphenotype trajectories and outcomes during hospitalization. RESULTS: IL-6, procalcitonin, and angiopoietin 2 persistently were elevated in patients receiving higher levels of respiratory support, whereas soluble receptor of advanced glycation end products (sRAGE) levels displayed the inverse pattern. Patients receiving NIV or HFO at baseline showed the most dynamic clinical trajectory, with 24% eventually requiring intubation and exhibiting worse 60-day mortality than patients receiving invasive mechanical ventilation at baseline (67% vs 35%; P < .0001). sRAGE levels predicted NIV failure and worse 60-day mortality for patients receiving NIV or HFO, whereas IL-6 levels were predictive in all patients regardless of level of support (P < .01). Patients classified to a hyperinflammatory subphenotype at baseline (< 10%) showed worse 60-day survival (P < .0001) and 50% of them remained classified as hyperinflammatory at 5 days after enrollment. INTERPRETATION: Longitudinal study of the systemic host response in COVID-19 revealed substantial and predictive interindividual variability influenced by baseline levels of respiratory support.

Trajectories of host-response biomarkers and inflammatory subphenotypes in COVID-19 patients across the spectrum of respiratory support.

Purpose: Enhanced understanding of the dynamic changes in the dysregulated inflammatory response in COVID-19 may help improve patient selection and timing for immunomodulatory therapies. Methods: We enrolled 323 COVID-19 inpatients on different levels of baseline respiratory support: i) Low Flow Oxygen (37%), ii) Non-Invasive Ventilation or High Flow Oxygen (NIV_HFO, 29%), iii) Invasive Mechanical Ventilation (IMV, 27%), and iv) Extracorporeal Membrane Oxygenation (ECMO, 7%). We collected plasma samples upon enrollment and days 5 and 10 to measure host-response biomarkers. We classified subjects into inflammatory subphenotypes using two validated predictive models. We examined clinical, biomarker and subphenotype trajectories and outcomes during hospitalization. Results: IL-6, procalcitonin, and Angiopoietin-2 were persistently elevated in patients at higher levels of respiratory support, whereas sRAGE displayed the inverse pattern. Patients on NIV_HFO at baseline had the most dynamic clinical trajectory, with 26% eventually requiring intubation and exhibiting worse 60-day mortality than IMV patients at baseline (67% vs. 35%, p<0.0001). sRAGE levels predicted NIV failure and worse 60-day mortality for NIV_HFO patients, whereas IL-6 levels were predictive in IMV or ECMO patients. Hyper-inflammatory subjects at baseline (<10% by both models) had worse 60-day survival (p<0.0001) and 50% of them remained classified as hyper-inflammatory on follow-up sampling at 5 days post-enrollment. Receipt of combined immunomodulatory therapies (steroids and anti-IL6 agents) was associated with markedly increased IL-6 and lower Angiopoietin-2 levels (p<0.05). Conclusions: Longitudinal study of systemic host responses in COVID-19 revealed substantial and predictive inter-individual variability, influenced by baseline levels of respiratory support and concurrent immunomodulatory therapies.

Pulmonary Function Trajectories in People with HIV: Analysis of the Pittsburgh HIV Lung Cohort.

Rationale: Human immunodeficiency virus (HIV) infection is associated with chronic lung disease and impaired pulmonary function; however, longitudinal pulmonary function phenotypes in HIV are undefined. Objectives: To identify pulmonary function trajectories, their determinants, and outcomes. Methods: We used data from participants with HIV in the Pittsburgh HIV Lung Cohort with three or more pulmonary function tests between 2007 and 2020. We analyzed post-bronchodilator forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), and FEV1/FVC, and diffusing capacity of the lung for carbon monoxide (DlCO) using group-based trajectory modeling to identify subgroups of individuals whose measurements followed a similar pattern over time. We examined the association between participant characteristics and trajectories using multivariable logistic regression. In exploratory adjusted analyses restricted to individuals with available plasma cytokine data, we investigated the association between 18 individual standardized cytokine concentrations and trajectories. We compared mortality, dyspnea prevalence, respiratory health status, and 6-minute-walk distance between phenotypes. Results: A total of 265 participants contributed 1,606 pulmonary function measurements over a median follow-up of 8.1 years. We identified two trajectories each for FEV1 and FVC: "low baseline, slow decline" and "high baseline, rapid decline." There were three trajectory groups for FEV1/FVC: "rapid decline," "moderate decline," and "slow decline." Finally, we identified two trajectories for DlCO: "baseline low" and "baseline high." The low baseline, slow decline FEV1 and FVC, rapid decline, and moderate decline FEV1/FVC, and baseline low DlCO phenotypes were associated with increased dyspnea prevalence, worse respiratory health status, and decreased 6-minute-walk distance. The baseline low DlCO phenotype was also associated with worse mortality. Current smoking and pack-years of smoking were associated with the adverse FEV1, FEV1/FVC, and DlCO phenotypes. Detectable viremia was the only HIV marker associated with the adverse DlCO phenotype. C-reactive protein and endothelin-1 were associated with the adverse FEV1 and FVC phenotypes, and endothelin-1 trended toward an association with the adverse DlCO phenotype. Conclusions: We identified novel, distinct longitudinal pulmonary function phenotypes with significant differences in characteristics and outcomes. These findings highlight the importance of lung dysfunction over time in people with HIV and should be validated in additional cohorts.

Associations of HIV persistence, cigarette smoking, inflammation, and pulmonary dysfunction in people with HIV on antiretroviral therapy.

We aimed to investigate the relationship between measures of HIV persistence with antiretroviral therapy (ART) and cigarette smoking, systemic markers of inflammation, and pulmonary function. Retrospective study of 82 people with HIV (PWH) on ART for a median of 6.9 years (5.6-7.8) and plasma HIV RNA levels <50 copies/mL. HIV DNA and cell-associated HIV RNA (CA-RNA) were measured in peripheral blood mononuclear cells (PBMC) and plasma HIV RNA was measured by single-copy assay (SCA). Plasma levels of 17 inflammatory mediators were measured by Bio-Plex, and standard pulmonary function tests (PFT) were performed in all participants. Median age was 52 years and 41% were women. Most had preserved CD4+ T cell counts (median (IQR) 580 (361-895) cells/mm3). Median plasma HIV RNA was 1.3 (0.7-4.6) copies/mL, and median levels of HIV DNA and CA-RNA in PBMC were 346 (140-541) copies and 19 (3.7-49) copies per 1 million PBMC, respectively. HIV DNA was higher in smokers than in nonsmokers (R = 0.3, P < 0.05), and smoking pack-years positively correlated with HIV DNA and CA-RNA (R = 0.3, P < 0.05 and R = 0.4, P < 0.01, respectively). HIV DNA, CA-RNA, and plasma HIV RNA were not significantly associated with any measure of pulmonary function or inflammation. Cigarette smoking was associated with HIV DNA and CA-RNA levels in blood, but measures of HIV persistence were not associated with pulmonary function or inflammation.

Plasma SARS-CoV-2 RNA Levels as a Biomarker of Lower Respiratory Tract SARS-CoV-2 Infection in Critically Ill Patients With COVID-19.

Plasma SARS-CoV-2 viral RNA (vRNA) levels are predictive of COVID-19 outcomes in hospitalized patients, but whether plasma vRNA reflects lower respiratory tract (LRT) vRNA levels is unclear. We compared plasma and LRT vRNA levels in serially collected samples from mechanically ventilated patients with COVID-19. LRT and plasma vRNA levels were strongly correlated at first sampling (n = 33, r = 0.83, P < 10-9) and then declined in parallel in available serial samples except in nonsurvivors who exhibited delayed vRNA clearance in LRT samples. Plasma vRNA measurement may offer a practical surrogate of LRT vRNA burden in critically ill patients, especially early after ICU admission.

Plasma SARS-CoV-2 RNA levels as a biomarker of lower respiratory tract SARS-CoV-2 infection in critically ill patients with COVID-19.

Plasma SARS-CoV-2 viral RNA (vRNA) levels are predictive of COVID-19 outcomes in hospitalized patients, but whether plasma vRNA reflects lower respiratory tract (LRT) vRNA levels is unclear. We compared plasma and LRT vRNA levels in simultaneously collected longitudinal samples from mechanically-ventilated patients with COVID-19. LRT and plasma vRNA levels were strongly correlated at first sampling (r=0.83, p<10 -8 ) and then declined in parallel except in non-survivors who exhibited delayed vRNA clearance in LRT samples. Plasma vRNA measurement may offer a practical surrogate of LRT vRNA burden in critically ill patients, especially early in severe disease.

Association of Monocyte Migration Marker CD11b With Pulmonary Function in People Living With HIV.

BACKGROUND: Maladaptive immune responses contribute to the pathogenesis of many chronic lung diseases. Here, we tested hypotheses that CD4 and CD8 T-cell and monocyte phenotypes are associated with lung function in people living with HIV and those without HIV. METHODS: Markers of T cell differentiation, activation, exhaustion and senescence, and markers of monocyte recruitment and migration were quantified in 142 HIV-positive and 73 HIV-negative participants of the Pittsburgh HIV Lung Cohort. All participants underwent lung function testing. RESULTS: CD4 or CD8 T-cell phenotypes were not associated with measures of lung function in HIV-positive or HIV-negative participants after adjustment for multiple comparisons. In HIV-positive participants, however, the percentage of classical monocytes that were CD11b+ had positive associations at the Bonferroni-adjusted significance threshold of P = 0.05/63 with prebronchodilator and postbronchodilator forced expiratory volume in 1 second (FEV1)/forced vital capacity (FVC) ratio (ß = 0.36; P = 0.00003 and ß = 0.31; P = 0.0003, respectively). In stratified analyses of n = 87 participants with CD4 ≥ 500 cells/µL, associations of percentage of classical monocytes that were CD11b+ with prebronchodilator and postbronchodilator FEV1/FVC ratio were stronger (ß = 0.48 and ß = 0.41, for pre- and post-, respectively) than in the entire HIV-positive study population. Significant associations of monocyte phenotypes were not observed in HIV-negative participants after adjustment for multiple comparisons. CONCLUSIONS: CD11b+ expression on classical monocytes is positively associated with FEV1/FVC ratio in people living with HIV including in those with CD4 T-cell recovery. Given the normal surveillance activity of monocytes, such association suggests this monocyte subset may play a role in preservation of pulmonary function in PLWH.

Lung function in men with and without HIV.

OBJECTIVES: Initial studies suggest HIV-positive persons may be at increased risk for chronic lung diseases such as chronic obstructive pulmonary disease, but have commonly relied on single-center designs, lacked HIV-negative controls, or assessed lung function with only spirometry. We tested differences in spirometry and single-breath diffusing capacity for carbon monoxide (DLCO) in persons with and without HIV. DESIGN: Cross-sectional, observational study. METHODS: Participants were enrolled from the Multicenter AIDS Cohort Study, a longitudinal cohort study of men who have sex with men (both HIV-positive and HIV-negative) at four sites in the United States. Standardized spirometry and DLCO testing were performed in all eligible, consenting participants at routine study visits. We tested associations between HIV status and spirometry and DLCO results, using linear and logistic regression. RESULTS: Among 1067 men, median age was 57 years, prevalence of current marijuana (30%), and cigarette (24%) use was high, and another 45% were former cigarette smokers. Median forced expiratory volume in 1 s was 97% of predicted normal and DLCO was 85% of predicted normal. HIV-positive persons demonstrated no statistical difference in forced expiratory volume in 1 s compared with HIV-negative persons, but had worse DLCO (adjusted difference -2.6% of predicted; 95% confidence interval: -4.7 to -0.6%) and a higher risk of DLCO impairment (odds ratio for DLCO < 60% of predicted 2.97; 95% confidence interval: 1.36-6.47). Lower DLCO was associated with lower nadir CD4 cell counts. CONCLUSION: HIV-positive men are at increased risk of abnormal gas exchange, indicated by low DLCO, compared with men without HIV.

Association Between Inflammatory Pathways and Phenotypes of Pulmonary Dysfunction Using Cluster Analysis in Persons Living With HIV and HIV-Uninfected Individuals.

BACKGROUND: Persons living with HIV (PLWH) are at risk of developing different phenotypes of chronic lung disease, including chronic obstructive pulmonary disease. Mechanisms underlying these phenotypes are unclear. OBJECTIVE: To identify clusters of peripheral inflammatory mediators associated with pulmonary function to determine inflammatory pathways and phenotypes of chronic obstructive pulmonary disease in PLWH and HIV-uninfected individuals. METHODS: Study participants were PLWH and HIV-uninfected individuals enrolled in the Pittsburgh HIV Lung Cohort. Pulmonary function tests were performed for all participants. Chest computed tomographic scans were performed in a subset of PLWH. Plasma levels of 19 inflammatory mediators were measured by Luminex or ELISA. Clusters were identified based on the expression pattern of inflammatory mediators in PLWH and HIV-uninfected individuals, and the relationships among clinical parameters were evaluated within clusters by using cluster and network analyses. RESULTS: In PLWH, we identified a distinct cluster with higher levels of Th1, Th2, and Th17 inflammatory mediators with increased complexity of these mediators and inferred presence of pathogenic Th17 cell types. Individuals in this cluster had worse airway obstruction and more radiographic emphysema. In HIV-uninfected individuals, a cluster with high-grade systemic inflammation also had worse diffusing capacity for carbon monoxide. CONCLUSIONS: Inflammatory pathways associated with pulmonary dysfunction in PLWH suggest multifaceted immune dysregulation involved in different phenotypes of pulmonary dysfunction with a potential specific contribution of the Th17 pathway to airway obstruction in PLWH. Identification of these associations may help in development of treatments that could alter the course of the disease.

Lung Function, Coronary Artery Disease, and Mortality in HIV.

Rationale: Impaired lung function is a potent independent predictor of coronary artery disease (CAD) in individuals without human immunodeficiency virus (HIV) infection; however, the relationship between lung function and CAD in HIV remains undefined. Objectives: To examine the relationship between lung function, CAD, mortality, and circulating biomarkers in HIV. Methods: Spirometry, diffusing capacity of the lung for carbon monoxide (DlCO), emphysema, coronary artery calcium, mortality, cause of death, and biomarkers were examined in HIV-infected and uninfected individuals enrolled in a cohort study at the University of Pittsburgh. Results were then validated in the Multicenter AIDS Cohort Study (MACS) cohort. Results: We examined data on 234 participants in the Pittsburgh cohort. The mean ± standard deviation age was 49.5 ± 10.2 years old, 82.1% were male, and 67.5% were ever smokers. Among the 177 of 234 individuals with HIV infection, lower DlCO (not forced expiratory volume in 1 second or emphysema) was independently associated with greater coronary artery calcium (odds ratio, 1.43 per 10% lower DlCO; 95% confidence interval, 1.14-1.81). HIV-infected individuals with both reduced DlCO and coronary artery calcium had a much higher mortality than those with either low DlCO or coronary calcium alone or with neither condition. Endothelin-1, a circulating biomarker of endothelial dysfunction, was associated with both lower DlCO and greater coronary artery calcium in those with HIV infection. Results were reproducible in 144 individuals enrolled in the MACS cohort; intercellular adhesion molecule 1 was the biomarker of endothelial dysfunction assessed in the MACS cohort. Conclusions: Impaired DlCO and CAD were associated with each other and with higher mortality in individuals with HIV infection.

HIV infection is an independent risk factor for decreased 6-minute walk test distance.

BACKGROUND: Ambulatory function predicts morbidity and mortality and may be influenced by cardiopulmonary dysfunction. Persons living with HIV (PLWH) suffer from a high prevalence of cardiac and pulmonary comorbidities that may contribute to higher risk of ambulatory dysfunction as measured by 6-minute walk test distance (6-MWD). We investigated the effect of HIV on 6-MWD. METHODS: PLWH and HIV-uninfected individuals were enrolled from 2 clinical centers and completed a 6-MWD, spirometry, diffusing capacity for carbon monoxide (DLCO) and St. George's Respiratory Questionnaire (SGRQ). Results of 6-MWD were compared between PLWH and uninfected individuals after adjusting for confounders. Multivariable linear regression analysis was used to determine predictors of 6-MWD. RESULTS: Mean 6-MWD in PLWH was 431 meters versus 462 in 130 HIV-uninfected individuals (p = 0.0001). Older age, lower forced expiratory volume (FEV1)% or lower forced vital capacity (FVC)%, and smoking were significant predictors of decreased 6-MWD in PLWH, but not HIV-uninfected individuals. Lower DLCO% and higher SGRQ were associated with lower 6-MWD in both groups. In a combined model, HIV status remained an independent predictor of decreased 6-MWD (Mean difference = -19.9 meters, p = 0.005). CONCLUSIONS: HIV infection was associated with decreased ambulatory function. Airflow limitation and impaired diffusion capacity can partially explain this effect. Subjective assessments of respiratory symptoms may identify individuals at risk for impaired physical function who may benefit from early intervention.

Factors Associated With Progression of Lung Function Abnormalities in HIV-Infected Individuals.

BACKGROUND: HIV is an independent risk factor for chronic obstructive pulmonary disease; however, baseline risk factors for lung function decline remain largely unknown in this population. METHODS: HIV-infected participants in the Pittsburgh Lung HIV Cohort with at least 3 pulmonary function measurements between 2007 and 2016 were included. Pulmonary function testing including postbronchodilator (BD) spirometry and diffusion capacity for carbon monoxide (DLco) was performed every 18 months. We used a mixed-effect linear model to evaluate factors associated with pulmonary function testing and DLco decline and logistic regression models to evaluate factors associated with rapid FEV1 decline (defined as >80 mL per year) and any DLco decline. RESULTS: Two hundred eighty-five HIV-infected participants were included. Median baseline CD4 cell count was 521 cells per micro liter, 61.9% had an undetectable HIV viral load at baseline, and 78.5% were receiving ART. Approximately 20% of participants met Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria for a diagnosis of chronic obstructive pulmonary disease at baseline. Older age and baseline GOLD stage 1 compared with stage 0 were associated with faster decline in post-BD FEV1%, whereas female sex was associated with slower decline. Similarly, female sex was associated with slower decline in DLco%. HIV-related factors including CD4 cell count, viral load, and ART use were not significantly associated with pulmonary function decline. CONCLUSIONS: Older age, male sex, and higher baseline GOLD stage were associated with more rapid post-BD FEV1% decline in HIV-infected individuals.

Pulmonary disease in HIV-infected adults in the era of antiretroviral therapy.

: HIV in the antiretroviral therapy era is characterized by multimorbidity and the frequent occurrence of HIV-associated non-AIDS chronic health conditions. Respiratory symptoms and chronic pulmonary diseases, including chronic obstructive pulmonary disease, asthma, and cardiopulmonary dysfunction, are among the conditions that may present in persons living with HIV. Tobacco smoking, which is disproportionately high among persons living HIV, strongly contributes to the risk of pulmonary disease. Additionally, features associated with and at times unique to HIV, including persistent inflammation, immune cell activation, oxidative stress, and dysbiosis, may also contribute. This review summarizes the available literature regarding epidemiology of and risk factors for respiratory symptoms and chronic pulmonary disease in the current era.

Intravenous versus oral paracetamol for acute pain in adults in the emergency department setting: a prospective, double-blind, double-dummy, randomised controlled trial.

OBJECTIVE: To determine if intravenous paracetamol was superior to oral paracetamol as an adjunct to opioids in the management of moderate to severe pain in the ED setting. METHODS: A prospective, randomised, double-blind, double-dummy, controlled trial was conducted at a single academic tertiary care ED. Adult patients with moderate to severe pain were randomly assigned to receive either the intravenous paracetamol or oral paracetamol. The primary outcome was Visual Analogue Scale (VAS) pain reduction at 30 min. A clinically significant change in pain was defined as 13 mm. RESULTS: 87 participants were included in the final analysis, with a median age of 43.5 years and 59.8% were female. Overall mean baseline VAS pain score was 67.9 mm (±16.0). Both formulations achieved a clinically significant mean pain score reduction at 30 min, with no significant difference between the groups with 16.0 mm (SD 19.1 mm) in the intravenous group and 14.6 mm (SD 26.4) in the oral group; difference -1.4 mm (95% CI -11.6 to 8.8, P=0.79). Secondary outcomes, including postintervention intravenous opioid administration, patient satisfaction, side effects and length of stay, did not differ between groups. CONCLUSIONS: Overall, there was a small but clinically significant decrease in pain in each group. No superiority was demonstrated in this trial with intravenous paracetamol compared with oral paracetamol in terms of efficacy of analgesia and no difference in length of stay, patient satisfaction, need for rescue analgesia or side effects.

Assessment of coronary artery calcium by chest CT compared with EKG-gated cardiac CT in the multicenter AIDS cohort study.

RATIONALE: Individuals with HIV are at increased risk for coronary artery disease (CAD). Early detection of subclinical CAD by assessment of coronary artery calcium (CAC) may help risk stratify and prevent CAD events in these individuals. However, the current standard to quantify CAC i.e. Agatston scoring requires EKG-gated cardiac CT imaging. OBJECTIVE: To determine if the assessment of CAC using non-EKG-gated chest CT and the Weston scoring system is a useful surrogate for Agatston scores in HIV-infected and HIV-uninfected individuals. METHODS AND MEASUREMENTS: CAC was assessed by both the Weston and Agatston score in 108 men enrolled in the Multicenter AIDS Cohort Study. RESULTS: Participants were 55.2 (IQR 50.4; 59.9) years old and 62 (57.4%) were seropositive for HIV. Inter-observer agreement (rs = 0.94, κ = 90.0%, p<0.001, n = 21) and intra-observer agreement (rs = 0.95, κ = 95.2%, p<0.001, n = 97) for category of Weston score were excellent. Weston scores were associated with similar CAD risk factors as Agatston scores (age, race, HDL cholesterol level, all p<0.05) in our cohort. There was excellent correlation (rs = 0.92, p<0.001) and agreement (κw = 0.77, p<0.001) between Weston and Agatston scores. CONCLUSIONS: This study is the first to examine calcium scoring using chest CT in HIV-infected individuals and to independently validate the Weston score as a surrogate for the Agatston score. In clinical or research settings where EKG-gated cardiac CT is not feasible for the assessment of coronary calcium, Weston scoring by using chest CT should be considered.

Emphysema is associated with thoracic vertebral bone attenuation on chest CT scan in HIV-infected individuals.

BACKGROUND: Age-related chronic diseases are prevalent in HIV-infected persons in the antiretroviral therapy (ART) era. Bone mineral density (BMD) loss and emphysema have separately been shown to occur at a younger age and with lesser risk exposure in HIV-infected compared to HIV-uninfected individuals. In non-HIV infected smokers, emphysema has been shown to independently predict low BMD. We hypothesized that emphysema would independently associate with thoracic vertebral bone attenuation, a surrogate for bone mineral density, in HIV-infected individuals. METHODS: Clinical, pulmonary function, and radiographic data were analyzed for 164 individuals from the University of Pittsburgh's HIV Lung Research Center cohort. Chest CT scans were used to quantify emphysema and compute Hounsfield Unit (HU) attenuation of the 4th, 7th, and 10th thoracic vertebrae. The association between mean HU attenuation values across the three vertebrae and radiographic emphysema, age, sex, body mass index (BMI), steroid use, viral load, CD4 count, and forced expiratory volume in the first second (FEV1) was assessed by univariate and multivariate analyses. RESULTS: In univariate analysis, mean HU attenuation decreased with increasing age (p<0.001), pack years (p = 0.047), and percent emphysema (p<0.001). In a multivariable model, including pack years, age, sex, ART and steroid use, greater emphysema was independently associated with this surrogate marker of BMD in HIV-infected individuals (p = 0.034). CONCLUSIONS: The association of emphysema with thoracic bone attenuation in HIV-infected individuals is consistent with previous reports in non-HIV infected smokers. These findings suggest that emphysema should be considered a potential marker of osteoporosis risk in HIV-infected individuals.

Development and implementation of a risk identification tool to facilitate critical care transitions for high-risk surgical patients.

QUALITY PROBLEM: Patients recently discharged from the intensive care unit (ICU) are at high risk for clinical deterioration. INITIAL ASSESSMENT: Unreliable and incomplete handoffs of complex patients contributed to preventable ICU readmissions. Respiratory decompensation was responsible for four times as many readmissions as other causes. CHOICE OF SOLUTION: Form a multidisciplinary team to address care coordination surrounding the transfer of patients from the ICU to the surgical ward. IMPLEMENTATION: A quality improvement intervention incorporating verbal handoffs, time-sensitive patient evaluations and visual cues was piloted over a 1-year period in consecutive high-risk surgical patients discharged from the ICU. Process metrics and clinical outcomes were compared to historical controls. EVALUATION: The intervention brought the primary team and respiratory therapists to the bedside for a baseline examination within 60 min of ward arrival. Stakeholders viewed the intervention as such a valuable adjunct to patient care that the intervention has become a standard of care. While not significant, in a comparatively older and sicker intervention population, the rate of readmissions due to respiratory decompensation was 12.5%, while 35.0% in the control group (P = 0.28). LESSONS LEARNED: The implementation of this ICU transition protocol is feasible and internationally applicable, and results in improved care coordination and communication for a high-risk group of patients.

Use of rosuvastatin in HIV-associated chronic obstructive pulmonary disease.

OBJECTIVES: Chronic obstructive pulmonary disease (COPD) is more prevalent in HIV-infected individuals and is associated with persistent inflammation. Therapies unique to HIV are lacking. We performed a pilot study of the 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor rosuvastatin to determine effects on lung function. DESIGN: Randomized, placebo-controlled, triple-blinded trial. METHODS: HIV-infected individuals with abnormal lung function were recruited from an ongoing lung function study. Participants were randomized to 24 weeks of placebo (n = 11) or rosuvastatin (n = 11) using an adaptive randomization based on change in peripheral C-reactive protein levels at 30 days of treatment. Forced expiratory volume in 1 s (FEV1) and diffusing capacity for carbon monoxide (DLco)%-predicted were compared to baseline at 24 weeks in the two groups using a Wilcoxon rank-sum test. The %-predicted change at 24 weeks in pulmonary function variables was compared between groups using simulated randomization tests. RESULTS: The placebo group experienced a significant decline in FEV1%-predicted (P = 0.027), and no change in DLco%-predicted over 24 weeks. In contrast, FEV1%-predicted remained stable in the rosuvastatin group, and DLco%-predicted increased significantly (P = 0.027). There was no significant difference in absolute change in either measure between placebo and rosuvastatin groups. CONCLUSION: In a pilot study, the use of rosuvastatin for 24 weeks appeared to slow worsening of airflow obstruction and to improve DLco in HIV-infected individuals with abnormal lung function, although comparison of absolute changes between the groups did not reach significance. This study is the first to test a therapy for COPD in an HIV-infected population, and large-scale clinical trials are needed.