Serum dehydroepiandrosterone sulfate concentration as an indicator of adrenocortical suppression in asthmatic children treated with inhaled steroids

ACTH regulates adrenal androgen production, which may thus be reduced during glucocorticosteroid therapy. Dehydroepiandrosterone sulfate is the most abundant androgen secreted by the adrenals. We wished to evaluate whether serum levels of dehydroepiandrosterone sulfate can be used as an indicator of adrenal suppression during inhaled steroid treatment in children. Sixty school-aged children with newly diagnosed asthma were randomly divided into budesonide (n = 30) and fluticasone propionate (n = 30) groups. Fifteen cromone-treated children served as a control group. The budesonide dose was 800 microg/d during the first 2 months and 400 microg/d thereafter. The respective fluticasone propionate doses were 500 and 200 microg/d. Serum dehydroepiandrosterone sulfate concentrations were measured before and after 2 and 4 months of treatment. In the budesonide group, serum dehydroepiandrosterone sulfate decreased from the baseline by a mean of 21% (95% confidence interval, 13-29%; P < 0.001) after 2 months of high dose treatment and by 16% (95% confidence interval, 8-25%; P < 0.001) after 4 months of treatment. In the fluticasone propionate group, the respective figures were 10% (95% confidence interval, 4-16%; P < 0.01) and 6% (95% confidence interval, 16% decrease-3% increase; P = NS). A low dose ACTH test indicated adrenocortical suppression at 4 months in 14 (23%) steroid-treated children. In these children, dehydroepiandrosterone sulfate decreased by a mean of 21% (95% confidence interval, 14-28%), whereas in those 46 steroid-treated children with normal ACTH test results, dehydroepiandrosterone sulfate decreased by 8% (95% confidence interval, 0-16%; P < 0.05 between these groups). In the control group, dehydroepiandrosterone sulfate levels tended to increase (by a mean of 26%), reflecting the normal physiological change at this age. In conclusion, inhaled steroid treatment suppresses dehydroepiandrosterone sulfate production in a dose-dependent manner. Monitoring of serum dehydroepiandrosterone sulfate concentrations can be used as a practical method to follow adrenocortical function and to detect its suppression during inhaled steroid treatment in children.     

Serum homocysteine concentration as an indicator of survival in patients with acute coronary syndromes

BACKGROUND: Circulating homocysteine levels are predictive of survival in patients with stable coronary artery disease. The prognostic value of serum homocysteine levels, obtained in the acute phase in patients with myocardial infarction or unstable angina, is unknown. OBJECTIVES: To test the hypothesis that circulating homocysteine levels, obtained during the first 24 hours following hospital admission in patients with acute coronary syndromes, are predictive of long-term mortality. METHODS: To test this hypothesis we performed a prospective inception cohort study at a teaching hospital in Gothenburg, Sweden. A total of 579 patients (179 women and 400 men; median age, 67 years) were included (Q-wave myocardial infarction in 163 patients, non-Q-wave myocardial infarction in 210 patients, unstable angina pectoris in 206 patients). Main Outcome Measure: All-cause mortality. RESULTS: During a median follow-up of 628 days, 65 patients died. The serum homocysteine level (mean [SD]) was significantly lower in long-term survivors (n = 514) than in nonsurvivors (n=65) (12.3 [7.0] vs 14.3 [5.9] pmol/L; P=.003). The relative risk (all-cause mortality) for patients with homocysteine levels in the upper quartile was 2.4 (95% confidence interval, 1.5-4.0) compared with that of patients in the 3 lower quartiles. After adjustment for relevant confounders, the relative risk estimate remained significant (relative risk= 1.69; 95% confidence interval, 1.02-2.80). In a stepwise model the homocysteine level provided prognostic information additional to that of patient age, diabetes mellitus, and diuretic usage prior to hospital admission (P=.03). CONCLUSION: The serum homocysteine level on hospital admission is an independent predictor of long-term survival in patients with acute coronary syndromes.     

Serum albumin concentration as an independent prognostic indicator in patients with pulmonary arterial hypertension

Background

Serum albumin is a strong prognostic indicator for many disease processes, yet limited data exist regarding its prognostic relationship in pulmonary arterial hypertension (PAH). Our study aims to assess the relationship of hypoalbuminemia with disease severity and mortality in this population.

Hypothesis

Serum albumin concentrations are a predictor of outcomes in PAH.

Methods

A retrospective review of all patients with World Health Organization group 1 PAH evaluated between March 2001 and August 2008 was performed. Patients were stratified into groups based on serum albumin concentration ≤3.3 g/dL (hypoalbuminemia) vs >3.3 g/dL. Clinical, hemodynamic, and survival comparisons were compared between groups using Student t test and χ² test, followed by univariate analysis and multivariate logistic regression.

Results

A total of 163/273 (59.7%) patients had a documented serum albumin concentration. Hypoalbuminemia was present in 41 (25.2%) patients and serum albumin ≤3.3 g/dL represented the lowest quartile of serum albumin. Patients with hypoalbuminemia had higher rates of renal dysfunction (26.8% vs 9.8%, P =0.0069) and hepatic dysfunction (29.3% vs 6.6%, P <0.001), and lower hemoglobin levels (11.6 vs 13.4 g/dL, P < 0.001). Hemodynamic and functional capacity assessments were comparable between groups. Independent predictors of mortality included low albumin levels (hazard ratio [HR]: 0.485, P = 0.008), high right atrial systolic area (HR: 1.062, P = 0.003), low Fick‐derived cardiac index (HR: 1.465, P = 0.016), and high New York Heart Association functional class (HR: 1.767, P = 0.042). Patients with hypoalbuminemia demonstrated a significantly lower survival rate at latest follow‐up (P = 0.01).

Conclusions

Lower serum albumin concentrations in patients with PAH are associated with higher mortality and can serve as a marker of disease severity in this patient population.     

Adrenal effect of inhaled corticosteroids in adult asthmatic patients]

Inhaled corticosteroids (ICS) are usually well tolerated with smaller systemic effects than intravenous steroids, however, when the dose is high the likelihood of steroid-related systemic side effects like hypothalamic pituitary adrenal (HPA) axis suppression and osteoporosis are reported. We reviewed HPA axis suppression related to different ICS characteristics by affinity to steroid receptor and their pharmacokinetics, and also reviewed by randomized, controlled clinical trials. Within the approved dosages for each ICS in Japan, HPA axis suppression is basically minimal and clinically negligible.     

Underuse of inhaled steroid therapy in elderly patients with asthma

STUDY OBJECTIVES: Despite their proven efficacy, inhaled steroids may be underused in the elderly asthmatic population. The objectives of this study were to determine if inhaled steroids are underused in the elderly asthmatic population, who are at a high risk for rehospitalization and mortality, and to identify certain risk factors that predict lower use of inhaled steroids in this group of patients. DESIGN: Population-based, retrospective, cohort study using linked data from hospital discharge and outpatient drug databases. PARTICIPANTS: All people > or = 65 years old in Ontario, Canada, who survived an acute exacerbation of asthma between April 1992 and March 1997. MEASUREMENTS AND RESULTS: Of the 6,254 patients, 2,495 patients (40%) did not receive inhaled steroid therapy within 90 days of discharge from their initial hospitalization for asthma. Patients > 80 years old were at a greater risk of not receiving inhaled steroid therapy, compared to those 65 to 70 years of age (adjusted odds ratio [OR], 1.23; 95% confidence interval [CI], 1.05 to 1.47). Patients with a Charlson comorbidity index of > or = 3 were also at an increased risk of not receiving inhaled steroid therapy, compared to those having no comorbidities (adjusted OR, 3.45; 95% CI, 1.56 to 7.69). Moreover, receipt of care from a primary-care physician was independently associated with an elevated risk of not receiving inhaled steroid therapy, compared to receipt of care from respirologists/allergists (adjusted OR, 1.35; 95% CI, 1.10 to 1.61). INTERPRETATION: Forty percent of Ontario patients > or = 65 years old who experienced a recent acute exacerbation of asthma did not receive inhaled steroid therapy near discharge from their initial hospitalization for asthma. Nonreceipt of inhaled steroid therapy was particularly prominent in the older patients with multiple comorbidities. Moreover, those who received care from primary-care physicians were also less likely to receive inhaled steroid therapy, compared to those who received care from specialists.     

Serum pro-hepcidin as an indicator of iron status in dialysis patients

Hepcidin has recently been recognized as a hormone essential to the negative regulation of iron. Synthesis of hepcidin is increased by iron overload or inflammation, and decreased by iron deficiency, anemia and erythropoietin. Dialysis patients frequently suffer the effects of both hepcidin increasing and decreasing factors. In this study, we investigated, for the first time, pro-hepcidin in dialysis patients while minimizing or manipulating these factors. We measured the serum pro-hepcidin in 23 hemodialysis patients without inflammation (the HD group) and 10 age-matched healthy volunteers. Those patients in the HD group were assigned to an iron-deficiency group (the ID group) or a non-iron deficiency subgroup (non-ID group). The HD group was followed up for two months. Iron therapy was performed in the ID group during the follow-up period. At the end of this time we evaluated the influence of iron therapy. Pro-hepcidin was similar in the HD groups and the healthy controls (295.1 [241.9, 413.7] vs. 301.7 [280.5, 383.5] ng/mL; not significant) despite the presence of hepcidin-decreasing factors. Pro-hepcidin in the ID group was significantly lower than in the non-ID group (262.6 [233.1, 295.1] vs. 359.2 [282.3, 446.5] ng/mL; P < 0.05). In patients newly acquiring ID during follow-up without iron supplementation, pro-hepcidin fell significantly (from 444.7 [389.4, 470.1] to 299.8 [233.4, 330.4] ng/mL; P < 0.05). Pro-hepcidin also showed an increase after ID was treated with iron administration (from 246.9 [205.5, 329.1] to 344.6 [290.1, 377.9] ng/mL; not significant). Pro-hepcidin could serve as a marker for functional iron deficiency and disordered iron utilization in HD. Underlying mechanisms and improvements in measurement techniques will require additional investigation.     

Serum triiodothyronine level as an indicator of inflammation in patients undergoing dialysis

INTRODUCTION. It has been shown that inflammation affects thyroid function. In patients with end-stage renal disease, low plasma triiodothyronine (T3) may be an unsuspected expression of the inflammatory state of these patients. This study evaluated the correlation between T3 and high-sensitivity C-reactive protein (HSCRP) levels in patients on peritoneal dialysis (PD) and hemodialysis. MATERIALS AND METHODS. This is a cross-sectional study aiming at the correlation between T3 and HSCRP levels among 30 patients on PD, 30 patients on hemodialysis, and 20 healthy individuals. Serum levels of HSCRP, T3, thyroxine (T4), thyroid stimulating hormone, T3 resin uptake, and free T3 index (FT3I) and free T4 index (FT4I) were compared between the three groups. RESULTS. There were no significant differences between hemodialysis and PD patients in respect to T3, T4, FT3I, and FT4I. In PD and hemodialysis patients, T3 and FT3I were lower than in controls (P < .001), but there was no significant difference between PD and hemodialysis patients. T3 resin uptake and thyroid stimulating hormone differed significantly between PD and hemodialysis patients. There was a significant inverse correlation between HSCRP and T3 and FT3I among hemodialysis patients (P = .04); however, there was no such correlations in PD patients. CONCLUSIONS. The relationship between T3 and HSCRP suggests that inflammation might be involved in the low T3 syndrome in hemodialysis patients, but we did not find a significant correlation between T3 and HSCRP levels in patients on peritoneal dialysis.     

Effect of inhaled steroid therapy on distribution of Tc-99m DTPA radioaerosol in asthmatic children.

The aim of this study was to evaluate the effect of inhaled steroid therapy on the distribution of inhaled Tc-99m DTPA in asthmatic children. Twenty-one asthmatic children and 15 healthy controls were entered in this study. The distribution of radioaerosols was scored by using a modified standardized score system over both lungs and expressed as homogeneity score/patient. The baseline homogeneity score was calculated before the inhalation therapy of budesonide (400 micrograms/day) for six months. The homogeneity score was repeated at the end of the second and sixth months of therapy. Asthmatic symptom scores and peak-flow rate variability, which were observed to improve throughout the study, were also recorded. Although homogeneity scores of the controls demonstrated no abnormality, mean baseline homogeneity scores of asthmatics was significantly high, 1.7 +/- 0.4/patient, and decreased to 0.6 +/- 0.2 and 0.3 +/- 0.1/patient at the end of second and sixth months, respectively (p < 0.05). These results revealed significant improvement in the radioaerosol distribution after inhaled steroid therapy. It was concluded that the lack of homogeneity in the distribution of Tc99m-DTPA in the lung, as an indicator for ventilation defects, may be accepted as a useful, noninvasive tool to monitor the efficacy of the therapy with inhaled agents in childhood asthma.     

Serum concentrations of dehydroepiandrosterone sulfate and leptin in obese patients with normal serum cholesterol

Normal (< 200 mg/dL) serum concentrations of cholesterol and a favorable ratio of cholesterol/high-density lipoprotein (HDL)-cholesterol are frequently seen in morbidly obese (body mass index [BMI] > 35 kg/m2) patients. Because it is unknown whether this subgroup is characterized by differences in other potential markers of cardiovascular disease, serum concentrations of dehydroepiandrosterone sulfate (DHEAS) and leptin were determined in 155 obese patients (BMI > 35 kg/m2, aged 20 to 50 years) with normal (n = 72) or with elevated (n = 83) total serum cholesterol. We found that seemingly negative marginal correlations between serum concentrations of DHEAS and cholesterol, as well as between DHEAS and the ratio cholesterol/HDL-cholesterol, were not any more apparent after correction for age, sex, and BMI. A negative correlation between serum leptin concentrations and the ratio cholesterol/HDL-cholesterol persisted after correction for age, sex, and BMI. In morbid obesity, there appears to be an association between serum concentrations of leptin and a more favorable lipid profile, whereas there is no direct interrelation between serum concentrations of cholesterol and DHEAS.     

Serum concentration of dehydroepiandrosterone sulfate and testosterone in women with severe atopic eczema/dermatitis syndrome.

BACKGROUND: Although a growing body of evidence indicates that androgens modulate immune response and certain alterations in sex hormone metabolism and balance are thought to predispose an individual to immune-mediated diseases, few studies have investigated the role of androgens in atopic eczema/dermatitis syndrome (AEDS). OBJECTIVE: We evaluated serum concentration of dehydroepiandrosterone sulfate (DHEA-S) and total testosterone in women with severe AEDS to characterize the hormonal milieu of such patients. METHODS: Serum concentrations of DHEA-S and total testosterone in 13 female patients with severe AEDS were compared with concentrations in weight- and age-matched healthy controls. Measurement was by electrical chemiluminescence immunoassay. RESULTS: There were no significant differences in serum concentrations of DHEA-S or testosterone between the 2 groups. We found no correlation between serum concentrations of DHEA-S and total immunoglobulin E. CONCLUSION:This small study suggests there may be no abnormalities in peripheral blood concentrations of DHEAS-S and total testosterone in women with severe AEDS.     

Serum alpha-fetroprotein concentration in adult patients under corticoid, estroprogestative or androgen therapy.

The serum alpha-fetoprotein concentration was measured by radioimmunoassy in 41 women with or without hormonal contraception, 21 patients with rheumatoid arthritis given corticosteroids or not, and 6 patients under androgen therapy for aplastic anemia. None of these therapies induced any significant variation of the serum alpha-fetoprotein level. More extensive studies are needed to investigate the possible effect of these hormones on the metabolism of this protein at a cellular level.     

Comparable effects of inhaled fluticasone propionate and budesonide on the HPA-axis in adult asthmatic patients

This randomized, double-blind, double-dummy, multicentre cross-over study compared the effects on the hypothalamic-pituitary-adrenal (HPA) axis of fluticasone propionate (750 microg twice daily given via the Diskus) and budesonide (800 microg twice daily given via the Turbuhaler). Two treatment periods of 2 weeks each were preceded by a 2-week run-in period and separated by a 2-week washout period. During run-in and washout, patients received beclomethasone dipropionate (BDP) or budesonide at a constant dose of 1500-1600 microg day(-1). Sixty patients aged 18-75 years with moderate to severe asthma not fully controlled by treatment with 1500-1600 microg day(-1) budesonide or BDP entered run-in and 45 completed the study. HPA axis suppression was assessed by morning serum cortisol (area under the curve from 08.00 to 10.30 hours) and 12-h nocturnal urinary cortisol excretion, measured at the end of run-in (baseline 1), at the end of washout (baseline 2), and at the end of each treatment period. Neither budesonide nor fluticasone produced significant suppression of either parameter compared to baselines. Only a few patients had serum-cortisol and urinary cortisol values below the normal range, before and after treatment. This shows that the patients did not have adrenal suppression before entering the study. The ratio between the AUC serum cortisol measured after fluticasone treatment and after budesonide treatment was 0.99 (95% CI 0.92-1.06), indicating equivalent effects on the HPA axis. This result was achieved after having omitted two patients' results, due to their very sensitive reaction to budesonide, but not to fluticasone. Two exacerbations of acute asthma occurred during budesonide treatment and none during fluticasone treatment. Both treatments were well tolerated. In conclusion, budesonide 1600 microg day(-1) via Turbuhaler and fluticasone propionate 1500 microg day(-1) via Diskus had no clinical effects on the HPA axis in patients with moderate to severe asthma.     

Frequency distribution of breath sounds as an indicator of bronchoconstriction during histamine challenge test in asthmatic children

In order to study changes in respiratory sounds associated with acute bronchoconstriction and -dilatation, breath sounds of 11 children with asthma (age range, 10–14 years) were recorded at the chest and at the trachea during histamine challenge test and after subsequent bronchodilatation. The changes in frequency spectra of breath sounds were compared with simultaneous changes in forced expiratory volume in 1 second (FEV₁). In seven children who responded to histamine with a decrease in FEV, of more than 15%, there was a significant relationship between percentage change in FEV₁ (ΔFEV₁) and percentage change in median frequency (ΔF50) of expiratory breath sounds recorded at the chest (r = 0.865; β = ?0.706, P = 0.0001) and at the trachea (r = 0.888; β = 1.12, P = 0.0001). The association between breath sound intensity and FEV₁ was weaker. Based on ANOVA, the increase of F50 during the challenge test was significantly larger in children who responded to histamine than in those who were non-responsive (P = 0.0016). At the chest, a decrease of 15% in FEV₁ corresponded to an increase of 8% in expiratory F50. The provocative dose of histamine inducing a decrease of 15% in FEV₁ (PD15FEV₁) and the provocative dose causing an increase of 8% in F50 (PD8F50) were significantly related (r = 0.927, P = 0.003). We conclude that spectral analysis of breath sounds can be used to indicate airway obstruction during bronchial challenge tests in children, and may be adapted for tests in pre-school children. The results suggest that the same mechanisms that induce airflow limitation due to inhaled histamine may generate an increase in frequency content of breath sounds in children with asthma. Pediatr Pulmonol. 1994;18:170–177. © 1994 Wiley-Liss, Inc.     

Evaluation of step-down therapy from an inhaled steroid to montelukast in childhood asthma

BackgroundAsthma guidelines allow antileukotriene medications to be used as an alternative to inhaled corticosteroids (ICSs) in second-step intensity therapy. The aim of this study was to determine whether asthma control can be maintained after reducing treatment from low-dose ICS to montelukast.MethodsIn this prospective, real-life 12-week trial, 84 young patients with asthma (7–18 years) controlled by low-dose ICS, had treatment switched to montelukast. Symptoms and PEF were monitored daily; exhaled nitric oxide (eNO) and spirometry every four weeks; sputum eosinophil (sEo) and bronchial hyperreactivity (BHR) assessed at the beginning and at the end of the study. The primary endpoint was number of patients discontinued from the study due to asthma exacerbations.ResultsEleven patients (13.1%) were discontinued due to asthma exacerbations. At the beginning, patients with elevated percentage of sEo had increased risk of exacerbations (relative risk RR, 6.6; 95% CI, 1.2–35.6), as well as those with augmented BHR (RR, 4.24; 95% CI, 1.1–16.2) as compared to patients who completed the study. An intensification of symptoms and increased use of beta-adrenergics were observed during the last visit before exclusion from the study, but not changes in spirometry, PEF, and eNO. No change in clinical parameters, inflammatory markers or BHR was observed in patients remaining in the study.ConclusionsAfter treatment switch from low-dose ICS to montelukast, asthma control was maintained in the majority of patients during the 12-week observation period. Sputum eosinophilia or BHR before the treatment switch was exacerbation risk factor.     

Increased risk of nontuberculous mycobacterial infection in asthmatic patients using long-term inhaled corticosteroid therapy

Background and objective: The risk of pneumonia is increased among COPD patients using inhaled corticosteroids (ICS). However, there is uncertainty regarding the association between long‐term use of ICS and exacerbations of respiratory tract infections among asthmatic patients. Methods: A case‐control nested cohort study was performed to assess the association of asthma with nontuberculous mycobacterium (NTM) infection. Results: Among this cohort of 464 asthmatic patients, 14 experienced complications due to NTM infections, of which eight were caused by Mycobacterium avium‐intracellulare complex, three by M. kansasii, one by M. terrae and the remaining two by unclassifiable scotochromogens. Asthmatic patients with NTM infections were older (67.1 ± 8.6 vs 58.8 ± 12.3 years, P < 0.01) and had more severe airflow limitation (FEV₁%, 60.6 ± 10.3 vs 72.3 ± 18.3, P < 0.03) than those without NTM infections. All except one had received ICS treatment for more than 5 years, and 12 of the 14 patients used inhaled fluticasone propionate daily (four patients at a dose of 400 µg/day and eight patients at a dose >800 µg/day). Conclusions: These findings suggest that the risk of NTM infection may be greater in asthmatic patients who are older, have more severe airflow limitation and receive higher doses of ICS therapy.     

Urine pentamidine as an indicator of lung pentamidine in patients receiving aerosol therapy

To determine if urine pentamidine was reflective of lung pentamidine, we compared levels of the drug in bronchoalveolar lavage fluid and simultaneously obtained urine. Thirty-one patients who were receiving aerosolized pentamidine either as treatment or as prophylaxis underwent BAL and submitted urine samples for pentamidine analysis. Pentamidine was analyzed in both phases of BAL fluid (supernatant and cell pellet) and in urine using high performance liquid chromatography. Urine results were normalized for creatinine. Patients were categorized as prophylaxis failures (active Pneumocystis carinii pneumonia on prophylaxis), electives (free from PCP on prophylaxis), treatment (daily AP in treatment doses for active PCP, or miscellaneous (single dose of AP). Levels in BAL fluid and urine varied widely over several orders of magnitude. However, for all patients, we found a highly significant relationship between BAL supernatant and urine (r = 0.97, p less than 0.0001). No statistical differences were found when comparing levels of pentamidine between failures and electives; however, the number of failures was small. We conclude that urine pentamidine is related to lung pentamidine and can be used as a clinical indicator in patients receiving aerosolized therapy.     

Intestinal calcium absorption and parathyroid hormone secretion in asthmatic patients on prolonged oral or inhaled steroid treatment.

A secondary hyperparathyroidism resulting from decreased intestinal calcium (Ca) absorption has been proposed as a contributory factor to glucocorticoid-induced osteoporosis. Inhaled steroids do not usually suppress adrenal gland function unless daily doses above 1,500 microgram are used. A recent study, however, has shown a reduced total body calcium in patients on regular beclomethasone treatment. In theory, osteopenia in these patients could be due to a direct effect of inhaled steroids on bone or due to an impaired intestinal calcium absorption. In this study, Ca absorption and parathyroid hormone (PTH) secretion were evaluated in three groups: 1) asthmatics on continuous oral and inhaled steroid treatment (11.3 +/- 4.4, range 5-33.5 mg.day-1 prednisone and 660 +/- 265, range 400-1,600 microgram.day-1 beclomethasone, respectively); 2) asthmatics on regular beclomethasone therapy (585 +/- 210, range 400-1,200 microgram.day-1); and 3) healthy subjects. The prevalence of vertebral fractures was evaluated by a spinal X-ray. No differences were found in either Ca absorption or PTH serum levels between asthmatics and healthy subjects (analysis of variance-ANOVA). Vertebral fractures were significantly more frequent in patients from group 1 (14 of 25) than in those from group 2 (2 or 25). We conclude that both prolonged oral steroid treatment and inhaled steroids, at doses lower than 1,600 microgram.day-1 do not cause Ca malabsorption, and that hyperparathyroidism does not contribute to osteoporosis in these patients.