Formoterol used as needed in patients with intermittent or mild persistent asthma

OBJECTIVE: To study the effectiveness and safety of as-needed treatment of formoterol compared with the short-acting alternative terbutaline. METHODS: Two double-blind, 12-month, parallel-group, non-inferiority trials comparing as-needed use of formoterol (Oxis) 4.5 microg and terbutaline (Bricanyl) 0.5 mg via dry-powder inhaler (Turbuhaler), one in 675 patients with intermittent and one in 455 patients with mild persistent asthma, overall 6-87 years of age. Peak expiratory flow (PEF), symptoms, rescue medication use, exacerbations, airway responsiveness (metacholine challenge; subgroup of 127 patients), systemic effects (high single-dose test; subgroup of 87 patients), and safety (adverse events) were assessed. RESULTS: Formoterol 4.5 microg was as effective as terbutaline 0.5 mg with regard to morning PEF (non-inferiority; lower 95% confidence interval limit above -10 L/min). Metacholine sensitivity, exacerbation rates or use of rescue medication did not differ between treatments. Formoterol 54 microg was shown to give less systemic effects than terbutaline 6 mg. Both treatments were safe and well tolerated. CONCLUSIONS: Formoterol 4.5 microg used as needed was at least as effective and safe as terbutaline 0.5 mg used as needed in intermittent and mild persistent asthma, and was associated with less systemic effects when administered as high single doses.     

Plasma Nitrate and Nitrite Kinetics after Single Intake of Beetroot Juice in Adult Patients on Chronic Hemodialysis and in Healthy Volunteers: A Randomized,Single-Blind,Placebo-Controlled,Crossover Study

Nitric oxide (NO) contributes to maintaining normal cardiovascular and renal function. This bioactive signalling molecule is generally formed enzymatically by NO synthase in the vascular endothelium. NO bioactivity can also be attributed to dietary intake of inorganic nitrate, which is abundant in our diet, especially in green leafy vegetables and beets. Ingested nitrate is reduced to nitrite by oral commensal bacteria and further to NO systemically. Previous studies have shown that dialysis, by means of removing nitrate and nitrite from the body, can reduce NO bioactivity. Hence, dietary intervention approaches aimed to boost the nitrate–nitrite–NO pathway may be of benefit in dialysis patients. The purpose of this study was to examine the kinetics of plasma nitrate and nitrite after a single intake of nitrate-rich concentrated beetroot juice (BJ) in adult hemodialysis (HD) patients and in age-matched healthy volunteers (HV). Eight HD patients and seven HV participated in this single center, randomized, single-blind, placebo-controlled, crossover study. Each participant received a sequential single administration of active BJ (70 mL, 400 mg nitrate) and placebo BJ (70 mL, 0 mg nitrate) in a random order separated by a washout period of seven days. For the kinetic analysis, blood samples were collected at different time-points before and up to 44 h after BJ intake. Compared with placebo, active BJ significantly increased plasma nitrate and nitrite levels both in HD patients and HV. The area under the curve and the maximal concentration of plasma nitrate, but not of nitrite, were significantly higher in HD patients as compared with HV. In both groups, active BJ ingestion did not affect blood pressure or plasma potassium levels. Both BJs were well tolerated in all participants with no adverse events reported. Our data provide useful information in planning dietary nitrate supplementation efficacy studies in patients with reduced NO bioactivity.     

Controlled Ethyl tert-Butyl Ether (ETBE) Exposure of Male Volunteers: II. Acute Effects

The aim of this study was to evaluate acute effects of ethyltert-butyl ether (ETBE) in man after short-term exposure. ETBEmay in the future replace methyl tert-butyl ether, a widelyused oxygenate in unleaded gasoline. Eight healthy male volunteerswere exposed to ETBE vapor for 2 h at four levels (0, 5, 25,and 50 ppm) during light physical exercise. The subjects ratedirritative symptoms, discomfort, and central nervous systemeffects in a questionnaire. Ocular (eye redness, tear film break-uptime, conjunctival epithelial damage, and blinking frequency),nasal (acoustic rhinometry and analysis of inflammatory markersand cells in nasal lavage fluid), and pulmonary (peak expiratoryflow, forced expiratory volume in 1 s, forced vital capacity,vital capacity, and transfer factor) measurements were performed.Significantly increased ratings of solvent smell (p = 0.001,repeated-measures ANOVA) were seen during exposures and correlatedto exposure levels. Furthermore, significantly elevated ratingsof discomfort in throat and airways were seen during and after50 ppm compared to the control exposure (p = 0.02). Increasednasal swelling (p = 0.001) and blinking frequency (p = 0.01)were noted at all exposure levels, but their magnitudes werenot related to exposure levels. A slightly impaired pulmonaryfunction was seen at 25 and 50 ppm, since forced vital capacity(p = 0.02) and vital capacity (p = 0.04) differed significantlyfrom the clean air exposure. Although the impairments seemedto fall within normal inter- and intraindividual variation andhave no clinical relevance as such, it cannot be excluded thatother individuals may react more severely than eight healthymale volunteers in this study.     

Controlled Ethyl tert-Butyl Ether (ETBE) Exposure of Male Volunteers: I. Toxicokinetics

Ethyl tert-butyl ether (ETBE) might replace methyl tert-butylether (MTBE), a widely used additive in unleaded gasoline. Theaim of this study was to evaluate uptake and disposition ofETBE, and eight healthy male volunteers were exposed to ETBEvapor (0, 5, 25, and 50 ppm) during 2 h of light physical exercise.ETBE and the proposed metabolites tert-butyl alcohol (TBA) andacetone were analyzed in exhaled air, blood, and urine. Comparedto a previous MTBE study (A. Nihlén et al., 1998b, Toxicol.Appl. Pharmacol. 148, 274–280) lower respiratory uptakeof ETBE (32–34%) was seen as well as a slightly higherrespiratory exhalation (45–50% of absorbed ETBE). Thekinetic profile of ETBE could be described by four phases inblood (average half-times of 2 min, 18 min, 1.7 h, and 28 h)and two phases in urine (8 min and 8.6 h). Postexposure half-timesof TBA in blood and urine were on average 12 and 8 h, respectively.The 48-h pulmonary excretion of TBA accounted for 1.4–3.8%of the absorbed ETBE, on an equimolar basis. Urinary excretionof ETBE and TBA was low, below 1% of the ETBE uptake, indicatingfurther metabolism of TBA or other routes of metabolism andelimination. The kinetics of ETBE and TBA were linear up to50 ppm. Based upon blood profile, levels in blood and urine,and kinetic profile we suggest that TBA is a more appropriatebiomarker for ETBE than the parent ether itself. The acetonelevel in blood was higher after ETBE exposures compared to controlexposure, and acetone is probably partly formed from ETBE.     

Once-daily dosing with budesonide/formoterol compared with twice-daily budesonide/formoterol and once-daily budesonide in adults with mild to moderate asthma

Adherence to maintenance therapy is often poor in patients with asthma. Simplifying dosing regimens has the potential to improve both adherence and asthma-related morbidity. In this 12-week, randomized, double-blind, double-dummy, parallel-group study, 617 patients with mild to moderate persistent asthma (mean forced expiratory volume in 1s [FEV1] 78.5% predicted) who were not optimally controlled on inhaled corticosteroids (200-500 microg/day) were randomized to once-daily budesonide/formoterol (80/4.5 microg, 2 inhalations in the evening), twice-daily budesonide/formoterol (80/4.5 microg, 1 inhalation), or a corresponding dose of budesonide once-daily (200 microg, 1 inhalation in the evening). All patients received budesonide (100 microg twice daily) during a 2-week run-in. Changes in mean morning peak expiratory flow (PEF) were similar for od budesonide/formoterol (23.4 l/min) and twice-daily budesonide/formoterol (24.1 l/min), and both were greater than with budesonide (5.5 l/min; both P<0.001). Evening PEF, symptom-free days, reliever-free days, and asthma control days were improved with budesonide/formoterol therapy vs. budesonide (P<0.05 vs. budesonide for all variables). All treatments were well tolerated. Budesonide/formoterol administered once daily in the evening is a convenient treatment regimen that is as effective in improving asthma control as twice-daily dosing in patients with mild to moderate persistent asthma.     

Study on risk factors and phenotypes of acute exacerbations of chronic obstructive pulmonary disease in Guangzhou,China—design and baseline characteristics

Background

To describe a study design that focuses on risk factors and patterns of chronic obstructive pulmonary disease (COPD) exacerbations.

Methods

A 2-year, single centre, observational study was conducted in Guangzhou in China. The study enrolled 318 subjects with COPD aged 40-79 years, stratified into different but equally sized groups according to global initiative for chronic obstructive lung disease (GOLD) stage (including Stage 0) and 86 lung healthy controls. An assessment each year was scheduled including questionnaires, lung function testing, Chest X-ray and blood collection. A sub-group, called sub-group X, consisting of 203 subjects with COPD and 51 lung healthy controls, was selected to answer a symptom questionnaire daily (EXACT-PRO) via a BlackBerry Personal Digital Assistant (PDA) device. Upon an alert that indicated a change in daily symptom pattern, the patients were contacted by the clinic to decide whether they had experienced an exacerbation and should have an extra visit within 24-48 hours. At an extra visit, nasal and throat swabs, induced sputum and blood were collected. Air pollution, temperature and humidity were also monitored daily. A subset of sub-group X, called sub-group M that consisted of 52 COPD patients and 15 healthy controls was dedicated to measure muscle strength and a dexa scan.

Results

More than 78% of the enrolled patients completed the study successfully. There appeared a difference between the patient groups and the controls in gender, age, body mass index (BMI), forced expiratory volume in 1 second (FEV₁), FEV₁/FVC and smoking at baseline. In sub-group X 90 out of 203 (44.4%) selected COPD patients developed one or more exacerbations in the 2-year observation period. They were more severe COPD patients according to GOLD stage at study start. On average most exacerbations occurred in the month March and the least number of exacerbations occurred in October.

Conclusions

This study with the obtained patient dataset will allow a better insight in many aspects of exacerbations in COPD (e.g., the identification, the risk factors, phenotypes and the biomarkers).     

NanoLaser/Microfluidic BioChip for Realtime Tumor Pathology

Through recent interdisciplinary scientific research, modern medicine has significantly advanced the diagnosis and treatment of disease. However, little progress has been made in reducing the death rate due to cancer, which remains the leading cause of death in much of the world. Pathologists routinely rely on microscopic examination of cell morphology using methods that originated over a hundred years ago. These staining methods are labor-intensive, time-consuming, and frequently in error. New micro-analytical methods1 (JBM, 1998; Harrison et al., 1993; Ramsey et al., 1995; Mauro Ferrari, Lynn Jelinski, 1994; Anderson et al., 1996; Carlson et al., 1996) for high speed (real time) automated screening of tissues and cells are critical to advancing pathology and hold the potential for improving diagnosis and treatment of cancer patients.By teaming experts in semiconductor physics, microfabrication, surface chemistry, film synthesis, and fluid mechanics with microbiologists and medical doctors, we are investigating nanostructured biochips to assess the condition of tumor cells by quantifying total protein content. This technique has the potential to quickly identify a cell population that has begun rapid protein synthesis and mitosis, characteristic of tumor cell proliferation. By incorporating microfluidic flow of cells inside the laser microcavity for the first time, we have enabled high throughput screening of cells in their native state, without need of chemical staining, in a sensitive nanodevice.     

Alcohol-induced upper airway symptoms: prevalence and co-morbidity

Little is known about effects of alcohol intake on the upper, nasal airways. The present aim was to examine the prevalence of alcohol-induced nasal symptoms (ANS) and to explore associations between ANS and other respiratory diseases. A postal questionnaire focused on respiratory diseases and symptoms was sent to 11,933 randomly selected adult individuals. Subjects with ANS, n = 316 (3.4%) received a second questionnaire focusing on this condition. Nine thousand three hundred and sixteen (78%) subjects answered the first and 228 (72%) the second questionnaire. Two-thirds of the subjects with ANS were women. Red wine and white wine were the most frequent triggers of ANS, reported by 83% and 31% of the subjects, respectively. Nasal blockage was the most prominent symptom, but also sneezing, nasal discharge, as well as lower airway symptoms occurred after intake of alcoholic drinks. Self-reported physician's diagnoses of asthma, chronic bronchitis/emphysema, chronic obstructive pulmonary disease (COPD), as well as allergic rhinitis were more common in subjects with ANS compared with the general population (P < 0.001 for all comparisons). In conclusion, ANS are common and are about twice as frequent in women than in men. ANS seem to be associated with important respiratory diseases such as asthma, chronic bronchitis, COPD, and allergic rhinitis.