Immunohistochemically detected expression of motility-related protein-1 (MRP-1/CD9) in lung adenocarcinoma and its relation to prognosis

STUDY OBJECTIVE: To determine the effect of adding the nebulized anticholinergic drug ipratropium bromide to standard therapy compared with standard therapy alone for acute severe asthma (peak expiratory flow rate [PEFR] < 50% of predicted) in children presenting to the emergency department. METHODS: Ninety children aged 6 to 18 years were randomly assigned to two groups in a prospective, double-blind, placebo-controlled study performed in the ED of an urban children's hospital. All children received nebulized albuterol solution (.15 mg/kg) every 30 minutes, and all received oral steroids with the second dose of albuterol. Children in group 1 received ipratropium bromide (500 micrograms/dose) with the first and third dose of albuterol those in group 2 received saline placebo instead of ipratropium. Pulmonary functions (PEFR and 1-second forced expiratory volume [FEV1]) and physiologic measurements were assessed every 30 minutes up to 120 minutes. By chance, the baseline values for percent of predicted PEFR and FEV1 differed between the two groups. Therefore a multivariate model accounting for both time and baseline effects was used to compare the response between groups. RESULTS: On average, and adjusting for baseline measures, children in the ipratropium group had a significantly greater improvement in percent of predicted PEFR than did children in the placebo group at 60 minutes (P = .02), 90 minutes (P = .002), and 120 minutes (P < .0001). The improvement in percent predicted FEV1 was significantly greater for children in the ipratropium group only at 120 minutes (P = .013). Nine children (20%) from the ipratropium group and 14 (31.1%) from the control group were admitted (P = .33, chi 2). There were no significant adverse effects attributable to the ipratropium, and there was no relation between ipratropium use and changes in pulse, respiratory rate, blood pressure, or oxygen saturation. CONCLUSION: We detected significant improvement in pulmonary function studies over 120 minutes in children with severe asthma who were given nebulized ipratropium combined with albuterol and oral steroids, compared with children who received the standard therapy. Further study is needed to determine whether early use of ipratropium decreases the need for hospitalization.     

Montelukast, a potent leukotriene receptor antagonist, causes dose-related improvements in chronic asthma. Montelukast Asthma Study Group

The leukotrienes are known to be important mediators of bronchial asthma. The ability of montelukast, a potent and selective CysLT1 leukotriene receptor antagonist, to cause a dose-related improvement in chronic asthma was investigated in a placebo-controlled, multicentre, parallel-group study. After a two week placebo run-in period, chronic asthmatic patients with a forced expiratory volume in one second (FEV1) 40-80% predicted with > or = 15% increase (absolute value) after beta2-agonist were randomly assigned to one of four treatment groups (placebo or montelukast 2, 10, or 50 mg once daily in the evening) for a three week, double-blind treatment period. For patient-reported end-points (daytime symptom score, use of as needed inhaled beta2 agonist, asthma-specific quality of life) and frequency of asthma exacerbations, montelukast 10 and 50 mg caused similar responses, superior to 2 mg and significantly (p<0.05; linear trend test) different from placebo. All three doses caused improvements in FEV1 and morning and evening peak expiratory flow rate (PEFR) that were significantly (p<0.05) different from placebo. Differences (least square mean) between the pooled 10 and 50 mg montelukast treatment groups and placebo were: 7.1% change from baseline in FEV1, 19.23 L x min(-1) in morning PEFR, -0.29 in daytime asthma symptom score (absolute value), and -0.82 in beta2-agonist use (puff x day(-1)). The incidence of adverse experiences was neither dose-related nor different between montelukast and placebo treatments. We conclude that montelukast causes a dose-related improvement in patient-reported asthma end-points over the range 2-50 mg. Montelukast causes benefit to chronic asthmatic patients by improving asthma control end-points.     

Omeprazole improves peak expiratory flow rate and quality of life in asthmatics with gastroesophageal reflux

OBJECTIVE: The aim of this study was to determine if omeprazole improves pulmonary function and quality of life in asthmatics with gastroesophageal reflux. METHODS: This was a double blind, randomized, placebo-controlled cross-over trial. After a 4-wk lead-in period, nine patients with documented asthma and gastroesophageal reflux, were prescribed either omeprazole 20 mg, daily or placebo for 8 wk and then crossed over to the alternate treatment. Outcome measurements included: forced expiratory volume at 1 s (FEV1), peak expiratory flow rate (PEFR), and responses on the Asthma Quality of Life Questionnaire, a validated disease specific measure of functional status. RESULTS: After omeprazole treatment, compared with placebo, patients had higher mean morning and evening PEFR, mean absolute difference (95% CI): morning: 37.8 L/min. (10.9-64.6), evening: 31.2 (3.2-59.2). Omeprazole treatment led to higher mean overall scores on the Asthma Quality of Life Questionnaire, and on the subdomains of activity limitation, symptoms, and emotions (p = 0.039, 0.049, 0.024, 0.040). A trend toward higher FEV1 (mean: 15.6% difference) with omeprazole failed to reach statistical significance (p > 0.2). CONCLUSIONS: After taking omeprazole for 8 wk, asthmatics with GER have better PEFR and quality of life than after placebo.     

Airway response of children with primary ciliary dyskinesia to exercise and beta2-agonist challenge

In primary ciliary dyskinesia (PCD), chest physiotherapy for airway clearance is essential. Exercise and inhaled beta2-agonists can produce bronchodilation thereby augmenting physiotherapy. However, both can also cause bronchoconstriction, and the effects of these stimuli in PCD are not known. In a preliminary study, the mean coefficients of variation for forced expiratory volume in one second (FEV1), forced vital capacity (FVC) and peak expiratory flow rate (PEFR) in children with PCD were determined. They were 5.4%, 4.4% and 8.4%, respectively. Twelve children with PCD and 12 normal children performed pulmonary functions under resting conditions; during and after a validated treadmill exercise test; and before and 15 min after 200 microg of inhaled salbutamol. At baseline, FEV1, FVC, forced mid-expiratory flow (FEF25-75%) and PEFR were significantly reduced in the PCD group compared with the control group. Exercise produced a significant increase in PEFR in the PCD group. There was no significant difference between the groups in response to salbutamol. Within the PCD group, exercise produced a significantly greater increase in PEFR than beta2-agonist therapy. In conclusion, in children with primary ciliary dyskinesia there is evidence of obstructive pulmonary disease. In these children, exercise is a more potent stimulus for bronchodilation than by inhaled beta2-agonists. Enhancement of airway clearance may best be achieved by encouraging patients to exercise before physiotherapy rather than by inhaling beta2-agonists, but the effects of each should be assessed for each individual before instigating treatment.     

Treatment of nocturnal asthma with nedocromil sodium

BACKGROUND: The association of nocturnal asthma symptoms with a diurnal increase in inflammatory activity suggests a role for anti-inflammatory therapy in nocturnal asthma. METHODS: Fifty patients with asthma with nocturnal symptoms entered a randomised, double blind, placebo controlled, crossover study. After a two week baseline period patients received nedocromil sodium (4 mg) or placebo four times daily. After eight weeks of treatment patients crossed to the alternative treatment for a further eight weeks. Symptom severity was recorded on a scale of 0-4 and inhaled bronchodilator use and peak flow (PEFR) were also recorded daily by the patients. Asthma severity, pulmonary function (FEV1, PEFR, FVC), and adverse events were recorded at clinic visits (baseline and after four and eight weeks of treatment). Global effectiveness was rated by clinician and patient, and treatment preference was recorded. RESULTS: Efficacy was assessed from data from 28 patients. Night-time asthma (mean (SE) difference between nedocromil sodium and placebo: -0.52 (0.13)), total nocturnal symptom severity defined as night-time asthma plus morning tightness (-0.72 (0.20)), and night-time bronchodilator use (-0.62 (0.23)) were reduced with nedocromil sodium compared with placebo treatment during the primary efficacy period (weeks 5-8) and during weeks 1-4 (-0.36 (0.12), -0.63 (0.20), and -0.55 (0.28), respectively). Morning and evening PEFR values improved slightly--but not significantly--compared with placebo. Patient and clinician opinions favoured nedocromil sodium treatment. Daytime asthma, daytime cough, and clinic assessment of asthma severity (secondary efficacy variables) were improved with nedocromil sodium treatment; day-time bronchodilator use and clinic pulmonary function were not. CONCLUSIONS: Nedocromil sodium was more effective than placebo in reducing nocturnal symptoms of asthma and bronchodilator use in this group of patients.     

Asthma health status measurement in clinical practice: validity of a new short and simple instrument

Health status (Quality of Life) questionnaires for use in asthma are generally too long or complex for routine use. A new short and simple measure of health status in asthma has been developed for this purpose. There are two versions, one containing 30 items (AQ30) and the other 20 items (AQ20). This study examined their cross-sectional and longitudinal properties and compared them with those of two established measures--the St. George's Respiratory Questionnaire (SGRQ) and the Asthma Quality of Life Questionnaire (AQLQ). Ninety asthmatic patients (mean age 46 years) participated. Mean post-bronchodilator forced expiratory volume in one second (FEV1) was 73 +/- 25 (SD)% predicted at baseline. Questionnaire data were collected twice, 12 weeks apart. Diary records of peak expiratory flow rate (PEFR) and daily asthma were kept for 14 days. The new questionnaires each took 3 min or less to complete. At baseline they correlated well with the SGRQ and AQLQ and showed the same pattern of correlations with clinical measures of asthma. Change scores for the new questionnaires correlated with those for the established measures. There was no advantage of the AQ30 over the AQ20. The AQ20 provides a simple method for obtaining valid health status estimates of asthmatics in routine clinical practice and has properties similar to more complex research instruments.     

Acute treatment-related diarrhea during postoperative adjuvant therapy for high-risk rectal carcinoma

STUDY OBJECTIVES: To examine the main therapeutic response patterns to high doses of salbutamol and to determine the factors that contribute to outcome in acute severe asthma. SETTING: The emergency department (ED) of a large, urban hospital with primary and referral care responsibilities. PATIENTS AND DESIGN: One hundred sixteen consecutive patients with acute exacerbations of asthma were enrolled in the trial, using a prospective sequential design. INTERVENTIONS: All patients were treated with salbutamol delivered with a metered-dose inhaler into a spacer device in four puffs (400 microg) at 10-min intervals. The protocol involved 3 h of this treatment (1,200 microg each 30 min). MEASURES AND RESULTS: A dose-response increase in pulmonary function was found, but only 70% improved sufficiently to be discharged. Of these, almost 70% required < or =2.4 mg of the drug within 1 h to reach the discharge threshold, whereas the remainder 30% need > or =3.6 mg. In 30% of subjects, salbutamol was ineffective. These patients were characterized by a more severe disease as judged by previous beta2-agonist use, larger duration of attack before ED visit, and a more severe obstruction at presentation. However, the most important predictors of outcome were peak expiratory flow rate (PEFR) as percent of predicted, PEFR as liters per minute, and PEFR variation over baseline value, all at 30 min. CONCLUSIONS: This study described two different therapeutic response patterns to salbutamol. Almost 70% of patients were sensitive to salbutamol (good response pattern), and in this group, 2.4 to 3.6 mg represents optimal treatment. In the remainder 30% of patients (poor response pattern), salbutamol in high doses had little effect. However, the outcome was not determined by the intensity of the initial symptoms or by the value of the presenting PEFR, but rather by the early (30 min) short-term response to treatment.     

Randomised, dose-ranging, placebo-controlled study of chimeric antibody to CD4 (keliximab) in chronic severe asthma

BACKGROUND: There is substantial circumstantial evidence that CD4 lymphocytes have a role in the pathogenesis of chronic asthma. We investigated the efficacy and safety in severe corticosteroid-dependent asthma of a single intravenous infusion of keliximab (IDEC CE9.1), a chimeric monoclonal antibody to CD4. METHODS: 22 patients were recruited from two asthma clinics. In an ascending-dose design, the first eight patients were assigned 0.5 mg/kg keliximab (six) or placebo (two); the next seven were assigned 1.5 mg/kg (five) or placebo (two); and the last seven were assigned 3.0 mg/kg (five) or placebo (two). Masked data on safety for each dose group were assessed before progression to the next dose. Patients kept a daily symptom diary and measured morning and evening peak expiratory flow (PEF) at home. PEF and forced expiratory volume in 1 s (FEV1) were measured at follow-up clinic visits. FINDINGS: Patients given 0.5 mg/kg or 1.5 mg/kg keliximab and placebo recipients did not differ in change from baseline of PEF, FEV1, or symptom score. Those given 3.0 mg/kg keliximab differed significantly from placebo recipients in change in morning PEF (median area under curve [AUC] 445 vs -82.5, p=0.005) and evening PEF (median AUC 548 vs -85, p=0.014). Symptom score showed the same pattern (though differences did not achieve significance), but there was no difference in clinic FEV1. There were no serious adverse effects related to treatment. Two patients had mild exacerbations of eczema and one developed a transient maculopapular rash. All doses of keliximab were associated with a reduction from baseline in CD4 count. INTERPRETATION: Our findings raise the possibility that T-cell-directed treatment may be an alternative approach to the treatment of severe asthma.     

Effect of addition of inhaled salmeterol to the treatment of moderate-to-severe asthmatics uncontrolled on high-dose inhaled steroids. European Respiratory Study Group

The aim of this study was to assess the efficacy and safety of inhaled salmeterol 100 micrograms b.d. (SM) versus inhaled salbutamol 400 micrograms q.d.s. (SB), both via the Diskhaler, when added to concurrent treatment, in asthmatic patients who were not controlled on high doses of inhaled steroids (> or = 1,500 micrograms beclomethasone dipropionate (BDP) or equivalent daily). This was a multicentre, parallel group, double-blind study in which 190 patients with a forced expiratory volume in one second (FEV1) or peak expiratory flow rate (PEFR) of 30-75% predicted and 15% reversibility to inhaled bronchodilator were randomized to treatment for 6 weeks. In the SM group, morning PEFR increased from 281 to 315 L-min-1 during treatment and in the SB group from 311 to 315 L.min-1 (p < 0.001). The SM group showed significantly better reduction in diurnal variation, from 39 to 22 L.min-1 during treatment, than the SB group (34 to 37 L.min-1) (p < 0.001). There was a significantly greater improvement in FEV1 in the SM group (from 1.63 to 1.85 L) than in the SB group (from 1.79 to 1.84 L). The SM group had significantly more symptom-free nights than the SB group (p < 0.001), and also more "rescue-free" nights (p = 0.04). The adverse event profile was similar in both groups. This study indicates that in asthmatic patients, not controlled on high-dose inhaled steroids, inhaled salmeterol 100 micrograms b.d. significantly improves lung function and reduces asthma symptoms.     

Observations on the effects of aerosolized albuterol in acute asthma

To determine the dose of albuterol required to terminate acute episodes of asthma, 92 acutely ill subjects received three doses of 2.5 mg each by nebulization every 20 min. Peak expiratory flow rates (PEFR) and signs and symptoms were serially monitored. A dose-response increase in pulmonary function was found, but only 66% of the subjects improved sufficiently to be sent home. Of these, 56% required < or = 5.0 mg of drug to reach the discharge threshold, whereas the remainder needed 7.5 mg. In 34% of participants, albuterol was ineffectual. These individuals were characterized by more severe obstruction at presentation, and after three doses of medication their PEFR still did not exceed 40% of the expected value. Further treatment in the emergency department (ED) or hospital was not immediately helpful, and these patients ultimately required 3.8 +/- 0.4 d of inpatient care to become asymptomatic. There were no discernible differences between responders and nonresponders in the type or quantity of medications used. However, the nonresponders had more severe disease as measured by recurrent hospitalizations and ED visits. This study demonstrates that, in emergency situations, albuterol does not relieve acute airway obstruction in all asthmatic individuals with equal efficacy. Two-thirds of patients are sensitive, and in these patients 5 to 7.5 mg of albuterol provides optimal treatment. In the remainder, albuterol, even in high doses, has little effect for days.     

Prevalence and characteristics of exercise-induced asthma in children

We have evaluated the prevalence and the characteristics of exercise-induced asthma (EIA) in a group of 71 patients with a prior history of mild, moderate or severe asthma (42 males and 29 females), aged 6-16 years-old. Measurements of the forced expiratory volume in 1 second (FEV1) were obtained before and at regular intervals up to 8 hours following exercise. As a control, the same patients were evaluated at similar time intervals on another day when they had not been submitted to an exercise challenge. Using pre-exercise FEV1 values as the reference, 32 patients (45.1%) had a positive exercise challenge, defined as a fall in FEV1 value equal to or greater than 15% from baseline following exercise. Among the patients with a positive exercise challenge, the majority (23/32, 71.8%) had an immediate response alone, with no significant changes in FEV1 within the 8-hour follow-up. However, a subgroup of patients (9/32, 28.1%) had both an immediate and a late-phase response to exercise. During the control day, no significant fall in FEV1 were observed. In keeping with previous investigations, no correlation was found between a history of EIA and a positive exercise challenge in the present study. Positive exercise challenges were found more frequently among patients with moderate and severe asthma than patients with mild asthma.     

Prospective associations between coping and health among youth with asthma.

The present study evaluated whether primary and secondary coping would predict longitudinal asthma-related clinical outcomes, such as peak expiratory flow rate (PEFR) and self-reported school absenteeism, rescue inhaler use, and asthma-related physician contacts, in youth with asthma. The 62 youth (68% males) had an average age of 12.6 ± 2.73 years and were primarily of European origin. Coping and asthma outcomes were obtained by youth self-report at baseline and over a 12-month follow-up period. Greater secondary coping at baseline was related to greater increases in PEFR and a greater likelihood of physician contact over the following year. Greater primary coping at baseline was related to greater likelihood of rescue inhaler use, school absenteeism, and physician contact over the following year. In contrast, asthma measures at baseline did not predict changes in coping over the following year. These patterns suggest that youth who engage in secondary coping accept and adapt to their asthma in ways that improve pulmonary function over time. Youth who engage in primary coping may be more likely to communicate asthma problems to others, and such communication perhaps leads to increases in behaviors meant to address these problems. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Clinical efficacy of low-dose inhaled budesonide once or twice daily in children with mild asthma not previously treated with steroids

The aim of the present study was to examine the efficacy of low-dose inhaled budesonide (BUD) administered via Turbuhaler once or twice daily on symptoms, lung function and bronchial hyperreactivity in children with mild asthma. One hundred and sixty-three children (mean age 9.9 yrs, 56 females/107 males) with mild asthma (forced expiratory volume in one second (FEV1) 103% of predicted, morning peak expiratory flow (PEF) 87% pred, reversibility in FEV1 3%, fall in FEV1 after exercise 10.4% from pre-exercise value) and not previously treated with inhaled steroids, were included in a double-blind, randomized, parallel-group study. After a two-week run-in period, the children received inhaled BUD 100 microg or 200 microg once daily in the morning, 100 microg twice daily or placebo for 12 weeks. Exercise and methacholine challenges were performed before and at the end of treatment. After 12 weeks of therapy, the fall in FEV1 after an exercise test was significantly less in all three BUD groups (43-5.1%) than in the placebo group (8.6%). Bronchial hyperreactivity to methacholine with the provocative dose causing a 20% fall in FEV1 decreased significantly in the BUD 100 microg twice-daily group compared with placebo (ratio at the end of treatment 156%). Changes in baseline lung function (FEV1 and PEF) were less marked than changes in bronchial responsiveness. In conclusion, low doses of inhaled budesonide, given once or twice daily, provided protection against exercise-induced bronchoconstriction in children with mild asthma and near normal lung function.     

The RSNA-AUR-ARRS introduction to research program for 2nd year radiology residents: effect on career choice and early academic performance. Radiological Society of North America. Association of University Radiologists. American Roentgen Ray Society

STUDY OBJECTIVE: To determine whether quantitative measurement of end-tidal carbon dioxide (ETCO2) can differentiate between cardiac and obstructive causes of respiratory distress. DESIGN: Prospective observational study. SETTING: Emergency department (ED) of a tertiary care hospital. PATIENTS: Adult patients who presented to the ED with moderate-to-severe dyspnea. Patients were excluded if they were unable to cooperate with the performance of peak expiratory flow rate (PEFR) or ETCO2 tests, were younger than 18 years of age, or had received prehospital intervention for their respiratory distress. INTERVENTIONS: Physicians obtained an ETCO2 level and PEFR prior to ED pharmacologic intervention. A hand-held capnometer with digital read-out was used to obtain the ETCO2 level. The patient's age, sex, initial vital signs, breath sounds and medication history, the presence or absence of diaphoresis and/or orthopnea, the duration of symptoms, the chest radiograph interpretation, and final diagnosis were also recorded. MEASUREMENTS and RESULTS: Forty-two patients were eligible for inclusion in the analysis. The mean ETCO2 level was 31.1+/-9.4 mm Hg; the mean PEFR was 161.3+/-53.1 L/min. The ETCO2 levels for pulmonary edema/congestive heart failure (CHF) patients differed significantly from those of asthma/COPD patients (27.1+/-7.8 mm Hg vs 33.4+/-9.6 mm Hg; p=0.0375). However, no single ETCO2 level was found to be a reliable predictor of diagnosis. CONCLUSION: ETCO2 levels for pulmonary edema/CHF patients differ significantly from those of asthma/COPD patients. However, no single ETCO2 level reliably differentiates between the two disease processes.     

Lung function in Indian twin children: comparison of genetic versus environmental influence

The relative contributions of genetic and environmental components in the variability of lung function measurements were studied in 54 twin pairs. Thirty pairs of monozygote (MZ) twins and 24 pairs of dizygotic (DZ) twins were examined. All measurements were made with 9-litre closed-circuit-type expirographs using standard spirometric techniques, except for peak expiratory flow rate (PFER) which was recorded with a Wright peak flow meter. Within-pair variances for inspiratory capacity (IC), vital capacity (VC), forced vital capacity (FVC), forced expiratory volume in 1 second (FEV1), forced mid-expiratory flow (FEV25-75%), forced end-expiratory flow (FEF75-85%), maximum expiratory flow (FEF200-1200ml), forced maximum voluntary ventilation MVVF) and PEFR were significantly smaller (p < 0.01) in MZ twins than in DZ twins. Tidal volume (VT), inspiratory reserve volume (IRV), expiratory reserve volume (ERV), forced expiratory volume in 1 second as a percentage of forced vital capacity (FEV1%), and forced expiratory time (FET) were not significantly different. Within-pair correlations were all higher in MZ than DZ twins. All measurements except for VT and PEFR showed high levels of heritability (23-99%). All measurements were positively and significantly correlated with physical characteristics such as weight, standing height, surface area, arm-span, chest circumference and age, except FEV1% and FET. Residual values adjusted for physical characteristics showed similar results to unadjusted values in most cases. These data indicate that major lung function measurements are possibly influenced more by genetic than environmental factors. Genetically influenced measurements show higher levels of heritability estimates and suggest that genetic determination of lung function is possibly independent of the influence of physical characteristics.     

Relationship between pulmonary test variables and asthma and wheezing: a validation of self-report of asthma

We investigated the relationship between the pulmonary test variable measurements and self-reported asthma and wheezing from a cross-sectional study conducted in Saskatchewan. Based on the responses to the questionnaire, the subjects were classified into asthmatic, wheezing, and asymptomatic groups. For both male and female subjects the mean values of forced expiratory volume in 1 s (FEV1), forced expiratory flow during the middle half of the forced vital capacity (FEF25-75), and FEV1/FVC ratio were lowest in asthmatics, followed by wheezing and asymptomatic groups, respectively. This trend was also observed in forced vital capacity (FVC) for men but not for women. After adjusting for current smoking status, the trend in the means across the three groups was statistically significant in men for FEV1 (p = 0.03), FEF25-75 (p = 0.002), and FEV1/FVC ratio (p = 0.002) and in women for FEF25-75 (p < 0.001) and FEV1/FVC ratio (p < 0.001). The differences in the adjusted means of FVC, FEV1, FEF25-75, and FEV1/FVC ratio between asymptomatic subjects and the other two groups were significant in both male and female subjects. Significant differences were also observed between asthmatics and wheezing groups in the adjusted means of FEF25-75 and FEV1/FVC ratio in male and female subjects. We conclude that the self-report of asthma has a high level of validity against the criterion of concurrently measured pulmonary test variables.     

Total blood eosinophils, serum eosinophil cationic protein and eosinophil protein X in childhood asthma: relation to disease status and therapy

Blood eosinophils, and serum levels of the eosinophil proteins, eosinophil cationic protein (ECP) and eosinophil protein X (EPX) were measured in childhood asthma. Seventeen patients mean age 11.9 years who were symptomatic with asthma, were enrolled in a study examining the eosinophil counts and eosinophil proteins at the onset of study and after treatment in relation to changes in their baseline forced expiratory volume at 1 second (FEV1) and % predicted FEV1. The patients with symptomatic asthma were compared with 17 patients mean age 12.0 years with asymptomatic asthma maintained on daily inhaled steroid and 13 patients, mean age 12.0 years, without asthma but with urticaria who served as non-asthma controls. Patients with symptomatic asthma did not have significantly higher initial eosinophil counts compared with those with asymptomatic asthma (0.43 x 10(9)/l vs 0.26 x 10(9)/l, P = 0.09) but had higher serum ECP levels (28.9 micrograms/l vs 18.5 micrograms/l). Both asthma patient groups had significantly higher serum ECP levels (P < 0.01) than the controls (9.8 micrograms/l). After therapy consisting of increased dose of inhaled steroids and/or oral steroids, patients in the symptomatic asthma group demonstrated a significant rise in FEV1 (1.67 l/sec at Visit 1 vs 2.08 l/sec at Visit 2, P < 0.001). A similar rise was seen for % predicted FEV1.(ABSTRACT TRUNCATED AT 250 WORDS)     

Successful myoblast transplantation in primates depends on appropriate cell delivery and induction of regeneration in the host muscle

In a double-blind, cross-over study, we examined the effect of inhaled budesonide (800 microgram twice daily via Turbohaler) on lung function and various markers of airway inflammation including airway responsiveness to methacholine (PC20), exhaled nitric oxide (NO), eosinophils in induced sputum, bronchoalveolar lavage (BAL), and airway biopsies from 14 patients with mild asthma needing beta2- agonist therapy only. After inhaled steroids, there was a significant increase in FEV1 and PC20, and reduction in exhaled NO. Eosinophils in induced sputum and airway biopsy sections were also significantly decreased, although BAL eosinophil counts remained unchanged. At baseline, significant correlations were observed between exhaled NO and PC20 methacholine (r = 0.64, p < 0.05), exhaled NO and peak expiratory flow rate (PEFR) variability (r = 0. 65, p < 0.05), sputum eosinophils and FEV1 (r = -0.63, p = 0.05), and sputum eosinophils and log PC20 methacholine (r = -0.67, p < 0. 05). After treatment with inhaled steroids, there was a significant correlation between eosinophils in biopsy sections, and BAL, with log PC20 methacholine. It is likely that these parameters represent different aspects of the inflammatory process, which are all inhibited by inhaled steroids.     

Formoterol inhaled as dry powder or via pressurized metered-dose inhaler in a cumulative dose-response study

Formoterol administered by a dry-powder (DP) capsule inhaler was compared with a pressurized metered-dose inhaler (pMDI) with regard to bronchodilating and systemic effects. The study used a double-blind, crossover, double-dummy technique. Twelve patients with moderate reversible asthma in a stable phase were examined on two separate study days, and the inhalers were given in randomized order. After baseline measurements, increasing doses of formoterol were given at intervals of 75 min. FEV1 and heart rate and tremor measurements were repeated after each dose, and the doses were 12 + 12 + 24 + 48 micrograms, giving a total dose of 96 micrograms. The peak expiratory flow rate (PEFR) was recorded in the morning before the first dose, after the last dose, and then repeatedly at home until 19 h after the last dose. There was an equal increase in ventilatory capacity at each dose level, independent of inhaler device. Repeated PEFR measurements after the last dose did not reveal any differences in duration of effect. There was a slight but statistically significant increase in heart rate and tremor after the highest doses of the DP formulation compared to the pMDI. These systemic effects can probably be explained by the reduced oral deposition of the aerosol caused by using a spacer. This study indicates that the DP and pMDI formulations of formoterol are equipotent in bronchodilation.     

High-dose inhaled budesonide may substitute for oral therapy after an acute asthma attack

Patients attending the emergency room with acute asthma, participating in a study comparing salbutamol (albuterol in the United States) via a dry powder inhaler (Turbuhaler) with pressurized metered-dose inhaler (pMDI), were included in this 1-week follow-up study with the aim of assessing whether inhaled budesonide via Turbuhaler may be an alternative to prednisolone tablets after an acute asthma attack. Eighty-one patients with a mean age of 38 years and forced expiratory volume in 1 sec (FEV1) of 64% predicted normal value after treatment with salbutamol were randomized in this double-blind, double-dummy, parallel-group study. The doses given were budesonide 1600 microg b.i.d. or prednisolone in daily doses from 40 mg (day 1) decreased to 5 mg (day 7). FEV1 was recorded before and after the 7-day treatments and peak expiratory flow (PEF) morning and evening, clinical symptoms (visual analogue scale 0-100), and doses of rescue medication (terbutaline Turbuhaler 0.25 mg/dose) were recorded daily. The mean increase in FEV1 from baseline to day 7 was 17.3% in the budesonide Turbuhaler group and 17.6% in the prednisolone group. Mean values of morning PEF increased from day 1 to day 7 by 67 L/min in the budesonide Turbuhaler group and by 57 L/min in the prednisolone group (not significant). There were no statistically significant differences between the groups in clinical symptoms and in the number of doses of rescue medication. Because of disease deterioration, five patients in the Turbuhaler group and three in the prednisolone group needed additional symptomatic as well as corticosteroid treatment. Inhaled budesonide in high doses may be a substitute for oral therapy as follow-up treatment after an acute asthma attack.