Kathleen Brennan

African Americans and Men with Severe COPD Have a High Prevalence of Osteoporosis

Osteoporosis is a non-pulmonary manifestation whose true prevalence is uncertain in severe chronic obstructive pulmonary disease (COPD). We describe the prevalence and risk factors for osteoporosis in a large, well characterized COPD cohort. Dual energy x-ray absorptiometry of the lumbar spine and hip, full pulmonary function testing, cardiopulmonary exercise test, 6 minute walk distance and demographics were performed in 179 non-selected COPD patients. Patients were 59 ± 7 years old, smoked 53 ± 32 pack years, FEV1 26% ± 9.8, and 45% were currently taking prednisone. Bone mineral density measurements were abnormal in 97%; 66% had dual energy X-ray absorptiometry defined osteoporosis, while 31% had osteopenia. The prevalence of osteoporosis in males versus females was 70% versus 62% (p = 0.33); both groups had similar fracture rates. The prevalence of osteoporosis in African Americans versus Caucasians was 69% versus 65% (p = 0.78). Caucasians had a significantly lower Wards Triangle T score than African Americans (−2.52 ± −0.96 vs. −2.16 ± −0.91, p = 0.04). Those with bone fractures took higher doses of prednisone than those without fractures. Univariate analysis identified BMI and FVC% as predictors for osteoporosis (p = 0.03 OR 0.934 p = 0.006 OR 0.974). Multivariate analysis revealed only FVC% as a significant predictor (p = 0.006, OR 0.974). Osteoporosis is highly prevalent in severe COPD, and affects males and African Americans to a similar degree as females and Whites. Osteoporosis should be considered in severe COPD regardless of race or gender.

Chronic Effects of Inhaled Albuterol on β-Adrenoceptor System Function in Human Respiratory Cells

The in vivo effects of β-adrenergic receptor (βAR) agonists given chronically by metered-dose inhaler (MDI) on the molecular components of the β-adreno-ceptor system expressed by human respiratory cells are poorly understood. This study examined the effects of inhaled albuterol (180 μg four times daily for 7 days) on βAR function of airway epithelial cells (AECs) and alveolar macrophages (AMs) freshly isolated from 10 normal subjects. Responses were related to β2AR genotype in codons 16 and 27, regions which affect chronic responses to β2-agonists. In AEC, βAR density and adenosine cyclic 3′,5′-phosphate (cAMP) production in response to isoproterenol (ISO) were significantly lower in the albuterol versus placebo treatment arm (p < 0.01 for both). Moreover, in AEC, albuterol treatment increased βAR-kinase (βARK) protein immunoreactivity. In contrast, in AM, albuterol tended to decrease βAR density and cAMP production but changes did not achieve statistical significance (p > 0.20 for both) and had no effect on βARK immunoreactivity. Changes in (JAR density occurred in all subjects but tended to be greater in subjects with the glycine 16 genotype. In cultured cells exposed to equal concentrations of β-agonist in vitro, the magnitude of βAR down-regulation (p < 0.05) and cAMP densensiti-zation (p < 0.05) was greater in AEC than AM. These results indicate that albuterol taken by inhalation in a therapeutically relevant dose for 1 week produces pAR down-regulation, densensitizes the cAMP response of airway epithelial cells to a β2-adrenergic agonist, and increases PARK immunoreactivity. Greater densensitization of AEC than AM in response to chronic albuterol inhalation likely reflects cell type-specific responses.

Dose-Response Characteristics of Nebulized Albuterol in the Treatment of Acutely Ill, Hospitalized Asthmatics

We investigated the bronchodilator dose-response to nebulized albuterol and the dose of albuterol which produces maximal bronchodilation in the acutely ill, hospitalized asthmatic. Consecutively admitted patients from the emergency room in status asthmaticus who fulfilled the inclusion criteria (age <41 years old and <12 pack-years of smoking) were studied. Albuterol was administered by nebulizer (Puritan-Bennett Raindrop) in repeated 2.5-mg treatments up to a total dose of 10 mg and the bronchodilator response was measured by a computerized spirometer. Twenty-two patients were studied. Baseline spirometry showed a (mean +/- SE) forced expiratory volume in 1 sec (FEV1) of 1.26 +/- 0.14 L (42 +/- 4.0% predicted), which increased significantly (p < 0.05) during albuterol titration to a maximum FEV1 of 1.70 +/- 0.19 L (57 +/- 5% of predicted). After cumulative doses of 2.5, 5.0, 7.5, and 10.0 mg of nebulized albuterol, 27%, 45%, 72%, and 77% of patients, respectively, attained maximum bronchodilation. The remaining 23% of patients did not respond to doses up to 10 mg of albuterol. The maximum FEV1 response to albuterol did not correlate with the initial severity of airflow obstruction (r = 0.36, p > 0.05). Pulse rate and arterial oxygen saturation were not significantly affected by nebulized albuterol up to a total dose of 10 mg. No arrhythmias were noted. In summary, most hospitalized asthmatics (72%) required a cumulative dose of 7.5 mg of nebulized albuterol to achieve maximum bronchodilation and a large fraction (50%) required higher albuterol doses than the standard 2.5 mg. The bronchodilatory response to nebulized albuterol varied widely among patients in status asthmaticus and could not be predicted from the initial severity of airflow obstruction. Because side effects were minimal, it would be reasonable to use 7.5 mg of nebulized albuterol as initial therapy. Alternatively, dose-response titration with albuterol would be advantageous.

Critical Care Endocrinology

After studying this chapter, you should be able to: Differentiate diabetic ketoacidosis from hyperglycemic hyperosmolar state and understand the management strategies for each disorder. Identify and treat thyroid disorders in the intensive care unit using clinical findings and laboratory data. Correctly determine the causes and treatments of the most common calcium disorders in the critical care unit. Know the clinical findings, diagnostic evaluations, and treatment of adrenocortical excess and insufficiency. Understand the pathogenesis and treatment of diabetes insipidus, and the syndrome of inappropriate antidiuretic hormone secretion.

Brush Biopsy and Culture of Airway Epithelial Cells: β-Adrenergic Receptor System Function.

Stimulation by catecholamine agonists of the β-adrenergic coupled adenylyl cyclase (βAR-AC) system, expressed on human tracheobronchial epithelial cells (ECs), elicits a variety of cellular responses that favorably affect airway function, the intensity of the inflammatory reaction, and even the integrity of the epithelial lining (1-6). For example, β-agonist-stimulated production of second messenger, cyclic adenosine monophosphate (cAMP), enhances salt and water exchange (2), ciliary beating (3), mucus secretion by goblet cells (1,4), proliferation of airway ECs (5), and protection against free radical induced injury (6).