Plasma aldosterone is related to severity of obstructive sleep apnea in subjects with resistant hypertension

OBJECTIVE: Obstructive sleep apnea (OSA) and primary aldosteronism are common in subjects with resistant hypertension; it is unknown, however, if the two disorders are causally related. This study relates plasma aldosterone and renin levels to OSA severity in subjects with resistant hypertension, and in those with equally severe OSA but without resistant hypertension serving as control subjects. METHODS: Seventy-one consecutive subjects referred to the University of Alabama at Birmingham (UAB) for resistant hypertension (BP uncontrolled on three medications) and 29 control subjects referred to UAB Sleep Disorders Center for suspected OSA were prospectively evaluated by an early morning plasma aldosterone concentration (PAC) and renin level, and by overnight, attended polysomnography. RESULTS: OSA (apnea-hypopnea index [AHI] > or = 5/h) was present in 85% of subjects with resistant hypertension. In these subjects, PAC correlated with AHI (rho = 0.44, p = 0.0002) but not renin concentration. Median PAC was significantly lower in control subjects compared to subjects with resistant hypertension (5.5 ng/dL vs 11.0 ng/dL, p < 0.05) and not related to AHI. In male subjects compared to female subjects with resistant hypertension, OSA was more common (90% vs 77%) and more severe (median AHI, 20.8/h vs 10.8/h; p = 0.01), and median PAC was significantly higher (12.0 ng/dL vs 8.8 ng/dL, p = 0.006). CONCLUSION: OSA is extremely common in subjects with resistant hypertension. A significant correlation between PAC and OSA severity is observed in subjects with resistant hypertension but not in control subjects. While cause and effect cannot be inferred, the data suggest that aldosterone excess may contribute to OSA severity.     

Age-related changes in eosinophil function in human subjects

BACKGROUND: Aging results in changes in immune cell function that have been described for T-cells, macrophage, neutrophils, and dendritic cells but not for eosinophils. We sought to define age-related changes in eosinophil function and their potential implications for asthma. METHODS: We recruited human subjects with asthma in two age groups: a younger group (20 to 40 years), and an older group (55 to 80 years). Lung function, induced sputum, and peripheral blood were obtained from each subject. Eosinophils isolated from the peripheral blood were examined for in vitro functional activities including degranulation, superoxide anion production, adhesion, and chemotaxis. RESULTS: Eosinophil degranulation in response to interleukin-5 stimulation was significantly decreased in the older group (p = 0.025). Eosinophil production of superoxide anions in response to phorbol myristate acetate was lower in the older group but did not achieve statistical significance (p = 0.097). Eosinophil adhesion, eosinophil chemotaxis, lung function, and the percentage of sputum eosinophils were similar in the two groups. CONCLUSION: Airway eosinophilia is comparable in younger and older asthma subjects. However, there are age-related changes in peripheral blood eosinophil "effector" functions. Diseases such as asthma, in which eosinophils are thought to play a pathophysiologic role, may exhibit important clinical differences in the elderly due to age-related changes in inflammatory cell function that affect the manifestations of the disease and/or responsiveness to specific classes of medications.     

Inspiratory muscle unloading by neurally adjusted ventilatory assist during maximal inspiratory efforts in healthy subjects

BACKGROUND: Neurally adjusted ventilatory assist (NAVA) is a mode of mechanical ventilation in which the ventilator is controlled by the electrical activity of the diaphragm (EAdi). During maximal inspirations, the pressure delivered can theoretically reach extreme levels that may cause harm to the lungs. The aims of this study were to evaluate whether NAVA could efficiently unload the respiratory muscles during maximal inspiratory efforts, and if a high level of NAVA would suppress EAdi without increasing lung-distending pressures. METHOD: In awake healthy subjects (n = 9), NAVA was applied at increasing levels in a stepwise fashion during quiet breathing and maximal inspirations. EAdi and airway pressure (Paw), esophageal pressure (Pes), and gastric pressure, flow, and volume were measured. RESULTS: During maximal inspirations with a high NAVA level, peak Paw was 37.1 +/- 11.0 cm H(2)O (mean +/- SD). This reduced Pes deflections from - 14.2 +/- 2.7 to 2.3 +/- 2.3 cm H(2)O (p < 0.001) and EAdi to 43 +/- 7% (p < 0.001), compared to maximal inspirations with no assist. At high NAVA levels, inspiratory capacity showed a modest increase of 11 +/- 11% (p = 0.024). CONCLUSION: In healthy subjects, NAVA can safely and efficiently unload the respiratory muscles during maximal inspiratory maneuvers, without failing to cycle-off ventilatory assist and without causing excessive lung distention. Despite maximal unloading of the diaphragm at high levels of NAVA, EAdi is still present and able to control the ventilator.     

Differences in vitamin D concentration between metabolically healthy and unhealthy obese adults: Associations with inflammatory and cardiometabolic markers in 4391 subjects

AimThis study aimed to compare concentrations of serum 25-hydroxy vitamin D and inflammatory markers in metabolically healthy obesity (MHO) and metabolically unhealthy obesity (MUO), and to determine whether the relationship between vitamin D levels and both cardiometabolic and inflammatory markers differs between MHO and MUO.MethodsThis cross-sectional study comprised 4391 obese subjects aged > 18 years. A panel of cardiometabolic and inflammatory markers, including anthropometric variables, glycaemic indices, lipid profiles, liver enzymes, homocysteine, C-reactive protein (CRP), fibrinogen and serum 25-hydroxy vitamin D levels, was investigated. All cardiometabolic and inflammatory markers in MHO and MUO as well as in vitamin D deficiency were compared.ResultsPrevalence of MHO was 41.9% in our obese subjects using International Diabetes Federation criteria. Considering insulin resistance and inflammation, the prevalence of MHO was 38.4%. Individuals with MHO had significantly higher vitamin D concentrations compared with MUO, and this difference in vitamin D status persisted after accounting for BMI and waist circumference. Subjects with MHO had significantly better metabolic status, lower liver enzymes, lower inflammatory markers and higher serum 25-hydroxy vitamin D than those with MUO. Associations between vitamin D levels and inflammatory and cardiometabolic markers differed according to MHO/MUO status. Among MUO subjects, vitamin D deficiency was associated with higher liver marker and homocysteine levels. Serum vitamin D was negatively associated with fasting plasma glucose and HbA_1c in MHO only.ConclusionSerum 25-hydroxy vitamin D levels were lower in MUO vs MHO, and reduced vitamin D concentrations were more strongly associated with cardiometabolic and inflammatory markers in MUO than in MHO subjects. These findings suggest that a deficiency in vitamin D could be a key component of MUO.     

Granulocyte chemotactic activity in exhaled breath condensate of healthy subjects and patients with COPD

BACKGROUND: Several chemoattractants have been measured in exhaled breath condensate (EBC) from patients with COPD. The aim of this study was to compare the eosinophil and neutrophil chemotactic activity contained in EBC from healthy subjects and patients with COPD. METHODS: EBC collected using a commercially available condenser (EcoScreen; Erich Jaeger Viasys; Hoechberg, Germany) was compared in 45 COPD patients and 65 healthy subjects. EBC chemotactic activity for eosinophils and neutrophils was assessed using microchambers (Boyden; Neuro Probe; Cabin John, MD). Chemotactic index (CI) was used to evaluate cell migration. RESULTS: EBC from patients with COPD (CI, 2.21 +/- 0.16 [mean +/- SEM]) and healthy subjects (CI, 1.67 +/- 0.11) displayed significant neutrophil chemotactic activity (p < 0.0001 for both), which was however higher in patients with COPD (p < 0.001). Healthy smokers had a significantly raised CI for neutrophils by comparison with healthy nonsmokers (p < 0.01) and ex-smokers (p < 0.05). Likewise, current COPD smokers tended to have greater neutrophil CI than COPD who stopped smoking (p = 0.08). COPD ex-smokers had raised chemotactic activity by comparison with healthy ex-smokers (p < 0.05). Anti-interleukin-8 (10(-6) g/mL) antibodies reduced neutrophil chemotactic activity by 35.2% (p < 0.05). EBC also contained significant eosinophil chemotactic activity in healthy subjects (CI, 1.68 +/- 0.09; p < 0.0001) and patients with COPD (CI, 1.23 +/- 0.07; p < 0.01), with a significantly lower CI in patients with COPD as compared to healthy subjects (p < 0.001). Smoking did not influence eosinophil chemotactic activity in healthy subjects or patients with COPD. CONCLUSIONS: Current smoking favors neutrophil chemotactic activity. As compared to healthy subjects, EBC from patients with COPD displays a skewed chemotactic activity toward neutrophils vs eosinophils.     

Radial artery pulse pressure variation correlates with brachial artery peak velocity variation in ventilated subjects when measured by internal medicine residents using hand-carried ultrasound devices

BACKGROUND: Rapid prediction of the effect of volume expansion is crucial in unstable patients receiving mechanical ventilation. Both radial artery pulse pressure variation (DeltaPP) and change of aortic blood flow peak velocity are accurate predictors but may be impractical point-of-care tools. PURPOSES: We sought to determine whether respiratory changes in the brachial artery blood flow velocity (DeltaVpeak-BA) as measured by internal medicine residents using a hand-carried ultrasound (HCU) device could provide an accurate corollary to DeltaPP in patients receiving mechanical ventilation. METHODS: Thirty patients passively receiving volume-control ventilation with preexisting radial artery catheters were enrolled. The brachial artery Doppler signal was recorded and analyzed by blinded internal medicine residents using a HCU device. Simultaneous radial artery pulse wave and central venous pressure recordings (when available) were analyzed by a blinded critical care physician. RESULTS: A Doppler signal was obtained in all 30 subjects. The DeltaVpeak-BA correlated well with DeltaPP (r = 0.84) with excellent agreement (weighted kappa, 0.82) and limited intraobserver variability (2.8 +/- 2.8%) [mean +/- SD]. A DeltaVpeak-BA cutoff of 16% was highly predictive of DeltaPP > or = 13% (sensitivity, 91%; specificity, 95%). A poor correlation existed between the CVP and both DeltaVpeak-BA (r = - 0.21) and DeltaPP (r = - 0.16). CONCLUSIONS: The HCU Doppler assessment of the DeltaVpeak-BA as performed by internal medicine residents is a rapid, noninvasive bedside correlate to DeltaPP, and a DeltaVpeak-BA cutoff of 16% may prove useful as a point-of-care tool for the prediction of volume responsiveness in patients receiving mechanical ventilation.     

Quadriceps weakness is related to exercise capacity in idiopathic pulmonary fibrosis

STUDY OBJECTIVE: In COPD, it has been shown that peripheral muscle dysfunction is a factor determining exercise intolerance. We examined the hypothesis that exercise capacity of patients with idiopathic pulmonary fibrosis (IPF) is, at least in part, determined by peripheral muscle dysfunction. METHODS: Maximum oxygen uptake (V(O2)max) was evaluated in 41 consecutive patients with IPF, along with potential determinants of exercise capacity, both in the lungs and in the peripheral muscles. RESULTS: Patients had reduced V(O2)max (893 +/- 314 mL, 46.0% predicted) and reduced quadriceps force (QF) [65% predicted]. Significant correlates of V(O2)max reduction were vital capacity (VC) [r = 0.79], total lung capacity (r = 0.64), diffusion capacity (r = 0.64), QF (r = 0.62), maximum expiratory pressure (r = 0.48), and Pa(O2) at rest (r = 0.33). In stepwise multiple regression analysis, VC and QF were independent predictors of V(O2)max. Furthermore, in subgroup analysis, QF was a significant contributing factor for V(O2)max in patients who discontinued exercise because of dyspnea and/or leg fatigue. CONCLUSIONS: We conclude that QF is a predictor of exercise capacity in IPF. Measures that improve muscle function might improve exercise tolerance.     

Dietary non-enzymatic antioxidant capacity and the risk of myocardial infarction: A case-control study in Italy

Background and aimsOxidative processes have been related to atherosclerosis, but there is scanty information on the role of dietary antioxidants in the prevention of acute myocardial infarction (AMI).Methods and resultsThe relationship between non-enzymatic antioxidant capacity (NEAC) and the risk of nonfatal AMI was investigated in a case-control study conducted in Milan, Italy, between 1995 and 2003. Cases were 760 patients below 75 years with a first episode of AMI and controls were 682 patients admitted to hospitals for acute conditions, who completed an interviewer-administered food frequency questionnaire, tested for validity and reproducibility. NEAC (excluding coffee) was measured using Italian food composition tables in terms of ferric reducing-antioxidant power (FRAP), Trolox equivalent antioxidant capacity (TEAC) and total radical-trapping antioxidant parameter (TRAP). The odds ratios (OR) of AMI, and the corresponding 95% confidence intervals (CI), were obtained by multiple logistic regression models including terms for main risk factors of AMI and total energy intake. NEAC was inversely related with the risk of AMI. The ORs for the highest quintile compared with the lowest one were 0.41 (95% CI, 0.27–0.63) for FRAP, 0.42 (95% CI, 0.27–0.65) for TEAC and 0.41 (95% CI, 0.27–0.62) for TRAP, with significant trends in risk. The inverse relationship was apparently stronger in women and in subjects aged ≥60 years.ConclusionsOur results support a favorable role of dietary NEAC in the prevention of AMI, and encourage a high consumption of fruit and vegetables and a moderate consumption of wine and whole cereals.     

Induced sputum in the very young: a new key to infection and inflammation

BACKGROUND: Chronic inflammation and infection in patients with cystic fibrosis (CF) and other lung diseases begin early, making noninvasive diagnostic techniques vital. As induced sputum (IS) testing is useful in older patients, we investigated its adaptation to young nonexpectorating children. METHODS: Following the inhalation of a 4.5% saline solution, sputum was collected by nasopharyngeal or oropharyngeal suction for culture and testing for inflammatory markers, with paired preceding oropharyngeal cough swabs (OCSs) in a subgroup. Specimens from 48 IS procedures (46 successful) in 20 CF children (median age, 3 years) were compared with 8 specimens from 8 non-CF pulmonary patients (median age, 4.5 years). RESULTS: The procedure was safe, with arterial oxygen saturation remaining at > or = 96%. Cultures from 14 of 46 CF patients (30%) grew Pseudomonas aeruginosa, whereas cultures from 19 of 46 CF patients (41%) had no growth. Cultures from seven of eight non-CF subjects grew bacteria, but none were P aeruginosa. Comparing 29 paired IS and OCS samples, 11 and 5 samples, respectively, cultured P aeruginosa (not significant), whereas 12 and 21 samples, respectively, had no growth (p = 0.02). A correlation was found between the independent inflammatory markers NE and both interleukin (IL)-8 (r = 0.85; p < 0.001) and the percentage of neutrophils (r = 0.35; p < 0.05), confirming the validity of IS samples in evaluating early airway disease. IL-8 levels also increased with age (r = 0.41; p < 0.05). Inflammation was similar in CF and non-CF subjects. CONCLUSIONS: IS testing in the young is feasible, safe, and clinically useful, and could serve as an outcome measure for new therapies.     

Differences in airway cytokine profile in severe asthma compared to moderate asthma

BACKGROUND: Some studies of severe asthma suggest that persistence or alteration in the pattern of inflammation may be associated with the severity of the disease. Whether there are differences in the expression of the principal cytokines and chemokines relevant to eosinophilic and neutrophilic inflammation in the airway tissues of severe compared to moderate asthmatics has not been determined. The aim of this study was to compare the patterns of expression of representative T-helper (Th) type 1 (interferon [IFN]-gamma) and Th-2 cytokines (interleukin [IL]-4, IL-5) and the neutrophil- and eosinophil-associated chemokines (IL-8 and eotaxin) in the airway tissues of patients with severe and moderate asthma. METHODS: Subjects with severe asthma (n = 24) and a comparison moderate asthma group (n = 26) were assessed using spirometry, induced sputum, exhaled nitric oxide, and bronchial biopsy. The expression of proteins of interest in the epithelium and subepithelium of the airway wall was examined by immunocytochemistry. RESULTS: Subjects with severe asthma were more symptomatic, had a lower FEV(1), and had more sputum neutrophilia (p = 0.007) and eosinophilia (p = 0.001). Exhaled nitric oxide was similar between groups. IL-8 and IFN-gamma expression were increased and IL-4 expression was decreased in severe asthma compared to moderate disease (p < 0.001 for each comparison). Eotaxin and IL-5 expression did not differ between the groups. CONCLUSION: Patients with severe asthma have increases in neutrophils and eosinophils in the sputum, and differ in airway cytokine/chemokine expression from moderate asthmatics. Excess neutrophilia may be explained by increased expression of IL-8, but differences in eosinophilia do not appear to be associated with IL-5 and eotaxin expression.     

Diagnostic and prognostic utility of brain natriuretic Peptide in subjects admitted to the ICU with hypoxic respiratory failure due to noncardiogenic and cardiogenic pulmonary edema

BACKGROUND: Brain natriuretic peptide (BNP) is useful in diagnosing congestive heart failure (CHF) in patients presenting in the emergency department with acute dyspnea. We prospectively tested the utility of BNP for discriminating ARDS vs cardiogenic pulmonary edema (CPE). METHODS: We enrolled ICU patients with acute hypoxemic respiratory failure and bilateral pulmonary infiltrates who were undergoing right-heart catheterization (RHC) to aid in diagnosis. Patients with acute coronary syndrome, end-stage renal disease, recent coronary artery bypass graft surgery, or preexisting left ventricular ejection fraction /= 1,200 pg/mL, BNP had a specificity of 92% for CPE. Higher levels of BNP were associated with a decreased odds for ARDS (odds ratio, 0.4 per log increase; p = 0.007) after adjustment for age, history of CHF, and right atrial pressure. BNP was associated with in-hospital mortality (p = 0.03) irrespective of the final diagnosis and independent of APACHE (acute physiology and chronic health evaluation) II score. CONCLUSION: In ICU patients with hypoxemic respiratory failure, BNP appears useful in excluding CPE and identifying patients with a high probability of ARDS, and was associated with mortality in patients with both ARDS and CPE. Larger studies are necessary to validate these findings.     

Influence of atrial fibrillation on plasma von willebrand factor, soluble E-selectin, and N-terminal pro B-type natriuretic peptide levels in systolic heart failure

BACKGROUND: Endothelial dysfunction is present in patients with heart failure (HF) due to left ventricular systolic dysfunction, as well as in patients with atrial fibrillation (AF) who have normal cardiac function. It is unknown whether AF influences the degree of endothelial dysfunction in patients with systolic HF. METHODS: We measured levels of plasma von Willebrand factor (vWF) and E-selectin (as indexes of endothelial damage/dysfunction and endothelial activation, respectively; both enzyme-linked immunosorbent assay) in patients with AF and HF (AF-HF), who were compared to patients with sinus rhythm and HF (SR-HF), as well as in age-matched, healthy, control subjects. We also assessed the relationship of vWF and E-selectin to plasma N-terminal pro B-type natriuretic peptide (NTpro-BNP), a marker for HF severity and prognosis. RESULTS: One hundred ninety patients (73% men; mean age, 69.0 +/- 10.1 years [+/- SD]) with systolic HF were studied, who were compared to 117 healthy control subjects: 52 subjects (27%) were in AF, while 138 subjects (73%) were in sinus rhythm. AF-HF patients were older than SR-HF patients (p = 0.046), but left ventricular ejection fraction and New York Heart Association class were similar. There were significant differences in NT-proBNP (p < 0.0001) and plasma vWF (p = 0.003) between patients and control subjects. On Tukey post hoc analysis, AF-HF patients had significantly increased NT-proBNP (p < 0.001) and vWF (p = 0.0183) but not E-selectin (p = 0.071) levels when compared to SR-HF patients. On multivariate analysis, the presence of AF was related to plasma vWF levels (p = 0.018). Plasma vWF was also significantly correlated with NT-proBNP levels (Spearman r = 0.139; p = 0.017). CONCLUSIONS: There is evidence of greater endothelial damage/dysfunction in AF-HF patients when compared to SR-HF patients. The clinical significance of this is unclear but may have prognostic value.