Thomas A. Dillard

Hemodynamic Effects of Altitude Exposure and Oxygen Administration in Chronic Obstructive Pulmonary Disease

PURPOSE Cardiovascular events are the leading cause of death during air travel. Because patients with chronic obstructive pulmonary disease (COPD) develop severe hypoxemia at altitude, we sought to determine whether changes in systemic hemodynamics may contribute to health risks during hypobaric hypoxia. PATIENTS AND METHODS We recorded radial artery catheter blood pressure, cardiac frequency, and cardiac ectopy in 18 men (aged 68 +/- 6 years, mean +/- SD) with severe COPD (forced expiratory volume in 1 second 0.97 L +/- 0.32 L) at sea level, after 45 minutes of steady-state hypobaric hypoxia at 2,438 m in a hypobaric chamber, and after oxygen supplementation at 2,438 m. RESULTS Mean arterial pressure (mm Hg), systolic blood pressure (SBP), diastolic blood pressure, and pulsus paradoxus during acute hypobaric exposure did not differ from baseline. During oxygen supplementation, SBP declined (p = 0.028). Decreases in pulsus paradoxus and pulse pressure were noted on oxygen (p < 0.05). We found no changes in cardiac frequency. Cardiac ectopy was uncommon; for one subject, ectopy increased with hypobaric hypoxia and decreased with oxygen administration. CONCLUSION Vasopressor responses to hypoxia do not add to the risk of air travel in patients with severe COPD. Supplemental oxygen may cause beneficial hemodynamic changes in patients with COPD during acute hypobaric exposure.

Assessments of endothelial function and arterial stiffness are reproducible in patients with COPD

Background Elevated cardiovascular disease risk is observed in patients with COPD. Non-invasive assessments of endothelial dysfunction and arterial stiffness have recently emerged to provide mechanistic insight into cardiovascular disease risk in COPD; however, the reproducibility of endothelial function and arterial stiffness has yet to be investigated in this patient population. Objectives This study sought to examine the within-day and between-day reproducibility of endothelial function and arterial stiffness in patients with COPD. Methods Baseline diameter, peak diameter, flow-mediated dilation, augmentation index, augmentation index at 75 beats per minute, and pulse wave velocity were assessed three times in 17 patients with COPD (six males, eleven females, age range 47–75 years old; forced expiratory volume in 1 second =51.5% predicted). Session A and B were separated by 3 hours (within-day), whereas session C was conducted at least 7 days following session B (between-day). Reproducibility was assessed by: 1) paired t-tests, 2) coefficients of variation, 3) coefficients of variation prime, 4) intra-class correlation coefficient, 5) Pearson’s correlations (r), and 6) Bland–Altman plots. Five acceptable assessments were required to confirm reproducibility. Results Six out of six within-day criteria were met for endothelial function and arterial stiffness outcomes. Six out of six between-day criteria were met for baseline and peak diameter, augmentation index and pulse wave velocity, whereas five out of six criteria were met for flow-mediated dilation. Conclusion The present study provides evidence for within-day and between-day reproducibility of endothelial function and arterial stiffness in patients with COPD.

An unusual cause of massive pleural effusion

Pleural effusions in ovarian hyperstimulation syndrome, whether transudative or exudative, can occur in up to 30% of cases. This disorder is always reversible but may have various clinical presentations and degrees of severity. Although assessing for risk factors to predict clinical severity is helpful, it is rare for ovarian hyperstimulation syndrome to present as a massive pleural effusion requiring emergent intervention. In this study, such a case is reported.

Acute Tetrahydrobiopterin Improves Endothelial Function in Patients With COPD

BACKGROUND: Cardiovascular diseases represent a hallmark characteristic in COPD, and endothelial dysfunction has been observed in these patients. Tetrahydrobiopterin (BH4) is an essential cofactor for nitric oxide (NO) synthesis and a regulator of endothelial function. The goal of this study was to test the hypothesis that a single dose of BH4 would improve endothelial function in patients with COPD via an increase in NO bioavailability. METHODS: Seventeen patients with COPD completed a randomized, double‐blind, placebo (PLC)‐controlled, crossover trial with an acute dose of either BH4 (Kuvan; BioMarin Pharmaceutical Inc) or PLC. Flow‐mediated dilation (FMD), a bioassay of endothelial function, was completed prior to and 3 h following each treatment. Phospho‐ and total endothelial NO synthase (NOS3) protein was evaluated after incubating endothelial cells with plasma from the patients prior to and following treatment. Fifteen demographically matched control subjects were tested at baseline for case control comparisons. RESULTS: Treatment with BH4 significantly (P ≤ .004) increased FMD, improving endothelial function in patients compared to control values (P ≥ .327). BH4 increased (P = .013) the ratio of phospho‐NOS3 to total NOS3 protein. No changes in FMD (P ≥ .776) or the protein ratio (P = .536) were observed following PLC. CONCLUSIONS: An acute dose of BH4 was able to improve endothelial function in patients with COPD to values similar to control subjects. The improvement in endothelial function was accompanied by an increase in NOS3 phosphorylation. BH4 may represent a potential novel therapy to improve endothelial function and reduce cardiovascular disease risk in patients with COPD. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT01398943; URL: www.clinicaltrials.gov.

A 67-Year-Old Woman With Cough and Shortness of Breath

67-year-old woman was admitted to the hospital with complaints of cough and shortness of breath. She had immigrated to the United States from Pakistan 4 months earlier and subsequently developed the cough, which had worsened over the past months. Two weeks prior to admission she developed worsening dyspnea on exertion. The patient did not speak English, and her daughter did the translation. Her cough was mostly dry with occasional production of minimal whitish-brown sputum. She had received amoxicillinclavulanate and ciprofl oxacin for her symptoms by her primary care physician without any benefi t. She denied any complaints of persistent fever, night sweats, chest pain, skin rash, joint pains, hemoptysis, or weight loss. Her remaining medical history was signifi cant for hypertension, diabetes mellitus, and asthma. Her medications included amlodipine, metformin, glyburide, and albuterol metered-dose inhaler. She denied any history of tobacco or alcohol abuse; however, she had been exposed to biomass fuels as a child. There was no history of prior pulmonary infection or positive purifi ed protein derivative skin test.