Ethnicity in Pulmonary Arterial Hypertension: Possibilities for Novel Phenotypes in the Age of Personalized Medicine.

In the past decade and a half, the introduction of new therapeutic agents has revolutionized the management of pulmonary arterial hypertension (PAH). These new treatment options have improved the quality of life and survival in PAH. With an armamentarium of options available, the identification of unique phenotypes can help practitioners choose tailored treatment regimens. Experts in other cardiovascular diseases, such as congestive heart failure and hypertension, have recommended race-specific treatments in their fields based on data highlighting variations in response to therapies. With this perspective, we review evidence supporting the hypothesis that ethnicity or race plays an important role in the management of PAH. Preliminary research suggests that races/ethnicities have differences in the presentation and outcome of PAH and could respond to PAH-specific medications with varying efficacy. Genetic, physiological, and anatomic differences exist between races, particularly regarding the structure and function of the right ventricle. Unfortunately, clinical trials have not adequately included minorities, and registry data often omit inclusion of this demographic information. Further studies are needed to characterize the role that ethnicity plays in the prevalence, presentation, outcomes, and optimal treatment of PAH.

Predictive Biomarkers for Asthma Therapy.

PURPOSE OF REVIEW: Asthma is a heterogeneous disease characterized by multiple phenotypes. Treatment of patients with severe disease can be challenging. Predictive biomarkers are measurable characteristics that reflect the underlying pathophysiology of asthma and can identify patients that are likely to respond to a given therapy. This review discusses current knowledge regarding predictive biomarkers in asthma. RECENT FINDINGS: Recent trials evaluating biologic therapies targeting IgE, IL-5, IL-13, and IL-4 have utilized predictive biomarkers to identify patients who might benefit from treatment. Other work has suggested that using composite biomarkers may offer enhanced predictive capabilities in tailoring asthma therapy. Multiple biomarkers including sputum eosinophil count, blood eosinophil count, fractional concentration of nitric oxide in exhaled breath (FeNO), and serum periostin have been used to identify which patients will respond to targeted asthma medications. Further work is needed to integrate predictive biomarkers into clinical practice.

Admission for COPD Exacerbation Is Associated with the Clinical Diagnosis of Pulmonary Hypertension: Results from a Retrospective Longitudinal Study of a Veteran Population.

Patients with chronic obstructive pulmonary disease and pulmonary hypertension (PH-COPD) have an increased risk of hospitalizations and death compared to COPD alone. Identifying PH in COPD is challenging because performing right heart catheterization, the gold standard for PH diagnosis, is invasive and not routinely performed. Clinical characterization of COPD patients at risk who are progressing toward PH will aid therapeutic development at earlier stages of progressively fatal PH-COPD. We studied the records of 5,45,086 patients in a large Veterans Affairs healthcare network (2000-2012) with a primary discharge diagnosis of COPD based on encounters' ICD-9 codes and further stratified into those who received an additional ICD-9 code for a PH diagnosis. Patients with PH-COPD were assigned to one of the four subgroups: those with (a) no history of exacerbation or hospital admissions, (b) history of exacerbations but no hospital admissions, (c) hospital admissions unrelated to COPD and (d) history of COPD exacerbation-related hospital admissions. We also examined the COPD and COPD-PH cohorts for associated comorbidities such as cardiac disease and the presence of obstructive sleep apnea (OSA). A regression analysis revealed that patients with COPD exacerbation-related hospital admissions had 7 × higher risk of having a concomitant clinical diagnosis of PH compared to non-hospitalized patients. COPD-PH patients had higher rates of cardiac comorbidities (89% vs. 66%) and OSA (34% vs. 16%) compared to COPD alone. We conclude that COPD patients hospitalized for COPD exacerbations are at a higher risk for developing PH, and hospitalized COPD patients with cardiac comorbidities and/or OSA should be screened as at-risk population for developing PH.

Longitudinal change in pulmonary arterial capacitance as an indicator of prognosis and response to therapy and in pulmonary arterial hypertension.

Pulmonary arterial hypertension (PAH) is a chronic progressive disease that leads to right heart failure and death. Pulmonary arterial capacitance (PAC), defined as stroke volume divided by the pulmonary pulse pressure, has been identified as a prognostic factor in PAH. The impact of changes in PAC over time, however, is unclear. We evaluated changes in PAC over time to determine if such changes predicted transplant-free survival. A single-center retrospective study of consecutive group 1 PAH patients who had two or more right heart catheterizations (RHC) between January 2007 and June 2016 was undertaken. Hemodynamic data, clinical data, and outcomes were collected. Univariate and multivariate Cox proportional-hazards modelling to identify the contribution of risk factors for a composite outcome of death or lung transplantation was done. Mixed-effects logistic regression was performed to investigate the association between the change in PAC value over time and the composite outcome. A P value < 0.05 was considered significant. In total, 109 consecutive patients with a total of 300 RHC data were identified. PAC correlated inversely with functional status ( P < 0.001) and inversely with pulmonary vascular resistance ( P < 0.001). PAC values increased with the addition of new PAH-specific medications. Mixed effects logistic regression modeling using longitudinal data showed that a decrease in PAC over the study period was associated with increased mortality and transplantation (adjusted P = 0.039) over the study period. Change in PAC was a better predictor of outcome over the study period than baseline PAC or changes in other hemodynamic or clinical parameters. Decreases in PAC were predictive of increased mortality or transplantation in patients with group 1 PAH. There was a trend towards increased PAC in response to the addition of a PAH-specific medication. Our data support the use of PAC as a therapeutic target in PAH.

Fungal Sensitization Is Associated with Increased Risk of Life-Threatening Asthma.

BACKGROUND: Fungal sensitization in patients with asthma has been associated with severe asthma and worse asthma outcomes. OBJECTIVE: The purpose of this study was to determine the relationship between fungal and nonfungal sensitization, asthma severity, and clinical outcomes. METHODS: A retrospective review of patients with asthma evaluated in an urban pulmonary subspecialty clinic in the United States was performed. Patients with fungal and nonfungal allergen sensitization were identified based on serum-specific immunoglobulin E (sIgE) testing. Demographic, clinical, laboratory, and spirometric data were obtained. The relationship between fungal sensitization and asthma outcomes was examined. RESULTS: Of 390 patients with asthma identified, 307 had sIgE testing, of whom 53 (17.3%) had fungal sensitization, 117 (38.1%) had nonfungal sensitization, and 137 (44.6%) had no sensitization. Patients with fungal sensitization were more likely to be sensitized to ≥5 allergens than patients with nonfungal sensitization (66% for fungal vs 29% for nonfungal, P < .001). Serum IgE concentrations were highest in patients with fungal sensitization compared with patients with no sensitization or nonfungal sensitization (median, 825, 42, and 203 IU/mL, respectively, P < .001). Fungal sensitized patients were more likely to require intensive care unit (ICU) admission and mechanical ventilation than those with no sensitization or nonfungal sensitization (13.2%, 3.7%, and 3.4%, respectively, for ICU admission, P = .02; 11.3%, 1.5%, and 0.9%, respectively, for ventilation, P < .001). CONCLUSIONS: Fungal sensitization is common in patients with asthma in an urban setting and is associated with greater sensitization to nonfungal allergens and increased risk of life-threatening asthma.

Prevalence of bipolar disorder and schizophrenia in Houston Outreach Medicine, Education, and Social Services (HOMES) Clinic patients: implications for student-managed clinics for underserved populations.

PURPOSE: Psychiatric conditions require aggressive management that is challenging to provide in free clinics. The purpose of this study was to determine the prevalence of certain mental illnesses and comorbid conditions among the patients of a student-managed free clinic for the homeless. METHOD: The authors conducted a retrospective analysis of the records of patients who visited the student-run Houston Outreach Medicine, Education, and Social Services (HOMES) Clinic from May 2007 through May 2008. They assessed the prevalence of bipolar disorder and schizophrenia among patients. They compared demographics, health insurance status, comorbid medical conditions, and social habit data of patients with these mental illnesses with those of other clinic patients. RESULTS: Of 286 patients (74.5% male, mean age 45.8 years), 25 (8.7%) had a diagnosis of schizophrenia and 45 (15.7%) had bipolar disorder. Compared with other clinic patients, patients with bipolar disorder or schizophrenia were less likely to be male (P < .0001) and were more likely to have publicly funded insurance (P = .024). They were also more likely to have certain comorbid conditions, including asthma (P = .0004), seizures (P = .0007), kidney disease (P = .01), and heart disease (P = .02). CONCLUSIONS: The high prevalence of these mental illnesses combined with the increased burden of medical comorbidity among HOMES Clinic patients has implications for student-managed free clinics, which often operate on limited budgets. Strategies for providing care for these patients in this setting include integrated care, street medicine, and case management.