Considerations for managing chronic obstructive pulmonary disease in the elderly

Chronic obstructive pulmonary disease (COPD) is common in older people, with an estimated prevalence of 10% in the US population aged ≥75 years. Inhaled medications are the cornerstone of treatment for COPD and are typically administered by one of three types of devices, ie, pressurized metered dose inhalers, dry powder inhalers, and nebulizers. However, age-related pulmonary changes may negatively influence the delivery of inhaled medications to the small airways. In addition, physical and cognitive impairment, which are common in elderly patients with COPD, pose special challenges to the use of handheld inhalers in the elderly. Health care providers must take time to train patients to use handheld inhalers and must also check that patients are using them correctly on a regular basis. Nebulizers should be considered for patients unable to use handheld inhalers properly. What follows is a review of issues associated with COPD and its treatment in the elderly patient

PHD2/3-dependent hydroxylation tunes cardiac response to β-adrenergic stress via phospholamban

Ischemic heart disease is the leading cause of heart failure. Both clinical trials and experimental animal studies demonstrate that chronic hypoxia can induce contractile dysfunction even before substantial ventricular damage, implicating a direct role of oxygen in the regulation of cardiac contractile function. Prolyl hydroxylase domain (PHD) proteins are well recognized as oxygen sensors and mediate a wide variety of cellular events by hydroxylating a growing list of protein substrates. Both PHD2 and PHD3 are highly expressed in the heart, yet their functional roles in modulating contractile function remain incompletely understood. Here, we report that combined deletion of Phd2 and Phd3 dramatically decreased expression of phospholamban (PLN), resulted in sustained activation of calcium/calmodulin-activated kinase II (CaMKII), and sensitized mice to chronic β-adrenergic stress–induced myocardial injury. We have provided evidence that thyroid hormone receptor-α (TR-α), a transcriptional regulator of PLN, interacts with PHD2 and PHD3 and is hydroxylated at 2 proline residues. Inhibition of PHDs increased the interaction between TR-α and nuclear receptor corepressor 2 (NCOR2) and suppressed Pln transcription. Together, these observations provide mechanistic insight into how oxygen directly modulates cardiac contractility and suggest that cardiac function could be modulated therapeutically by tuning PHD enzymatic activity

High-Sensitivity Troponin T and Cardiovascular Events in Systolic Blood Pressure CategoriesNovelty and Significance: Atherosclerosis Risk in Communities Study

Based on observational studies there is a linear increase in cardiovascular risk with higher systolic blood pressure, yet clinical trials have not shown benefit across all systolic blood pressure categories. We assessed if troponin-T measured using high-sensitivity assay was associated with cardiovascular disease within systolic blood pressure categories in 11191 Atherosclerosis Risk in Communities study participants. Rested sitting systolic blood pressure by 10-mmHg increments and troponin categories were identified. Incident heart failure hospitalization, coronary heart disease and stroke were ascertained over a median of 12 years after excluding individuals with corresponding disease. Approximately 53% of each type of cardiovascular event occurred in individuals with systolic blood pressure<140 mmHg and troponin-T≥3ng/L. Higher troponin-T was associated with increasing cardiovascular events across most systolic blood pressure categories. The association was strongest for heart failure and least strong for stroke. There was no similar association of systolic blood pressure with cardiovascular events across troponin-T categories. Individuals with troponin-T≥3ng/L and systolic blood pressure<140mmHg had higher cardiovascular risk compared to those with troponin-T<3ng/L and systolic blood pressure 140-159 mmHg