Sputum eosinophils from asthmatics express ICAM-1 and HLA-DR.

Sputum from symptomatic asthmatics is a rich source of eosinophils from the respiratory tract. Following liquefaction of sputum with dithioerythritol (DTE), a cell suspension for indirect double immunofluorescence with flow cytometry was obtained. Eosinophils were identified using anti-CD9 fluorescein conjugate, and particular surface markers measured with the relevant mouse MoAb followed by goat anti-mouse immunoglobulin phycoerythrin conjugate. Blood and sputum eosinophil surface markers were determined in parallel from asthmatics not receiving steroid therapy. Sputum eosinophils were found to have considerably elevated levels of CD11b, a reflection of eosinophil activation. Sputum but not blood eosinophils were found to express ICAM-1 (nine out of 11 cases) and HLA-DR (eight out of 11 cases). Furthermore, following culture of normal blood eosinophils with pooled T cell supernatants, ICAM-1 and HLA-DR could be induced in vitro. The induction of eosinophil adhesion molecules such as ICAM-1 and HLA-DR may influence eosinophil localization and function in asthma.     

Safety and application of induced sputum analysis in childhood asthma

BACKGROUND: The value of sputum induction in pediatric asthma lies in its potential to directly and noninvasively assess airway inflammation in children, because bronchoscopy and biopsy carry some risk. The Childhood Asthma Management Program (CAMP) study was designed to evaluate the long-term effects of budesonide and nedocromil compared with placebo in children with mild to moderate asthma across 8 centers. OBJECTIVE: At the Denver CAMP site, we sought to evaluate the safety of sputum induction, to determine differences in airway inflammation between treatment groups by using induced sputum analysis, and to examine correlations between other biomarkers and sputum eosinophils. METHODS: Sputum induction was performed, and exhaled nitric oxide, circulating eosinophil counts, and serum eosinophil cationic protein were obtained at treatment discontinuation and after washout. Spirometry and a methacholine challenge were also performed according to the CAMP protocol. RESULTS: Ninety of 117 children provided an adequate sputum sample for analysis. In 9 subjects (3 nedocromil and 6 placebo), sputum induction resulted in bronchospasm. These subjects had greater disease severity, as measured by a lower median prebronchodilator FEV 1 percentage predicted (85.0% vs 96.0%; P =.024) and FEV 1 /FVC ratio (70.0% vs 79.0%; P =.0008); greater bronchodilator reversibility (16.5% vs 6.8%; P =.004); higher serum IgE (1390.0 vs 495.0 ng/mL; P =.017) and circulating eosinophil count (757.0 vs 282.0/mm 3; P =.04); greater use of prednisone (1.9 vs 0.9 courses per 100 person-years; P =.05); and greater supplemental inhaled steroid doses (85.3 vs 0 mg; P =.016). At treatment discontinuation, budesonide-treated patients had a lower median (1st, 3rd quartile) sputum percentage eosinophil (SPEos) (0.2% [0%, 1.2%] vs 0.8% [0.2%, 4.6%]; P =.03) compared with those treated with placebo; no significant difference was noted between nedocromil- and placebo-treated patients. Higher SPEos at the time of treatment discontinuation was associated with asthma worsening that required rescue prednisone (n = 23) during the washout period compared with patients who remained stable (3.6% [0.4%, 6.4%] vs 0.6% [0.2%, 3.2%] SPEos; P =.023). Finally, greater SPEos was associated with atopy, higher bronchodilator reversibility, lower FEV 1 /FVC ratio, higher exhaled nitric oxide levels, circulating eosinophils, sputum and serum eosinophil cationic protein, more prednisone courses during the treatment period, and greater asthma severity. CONCLUSIONS: Sputum induction is a relatively noninvasive and safe procedure that can provide information on eosinophilic inflammation and treatment response and is also associated with several measures of asthma control. However, this procedure still remains a research tool in asthma because of its requirements for technical expertise.     

Eosinophils and eosinophilic cationic protein in induced sputum and blood: effects of budesonide and terbutaline treatment.

BACKGROUND: There is a need for easily measurable markers of airway inflammation to guide the use of anti-inflammatory treatment in asthma. Eosinophilic cationic protein (ECP) levels in sputum and blood correlate with clinical severity, and serial measurements of ECP have been proposed as a suitable candidate. AIMS AND METHODS: Our aim was to confirm that sputum and serum ECP measurements would provide a more sensitive indicator of responses to asthma treatment than eosinophil counts per se, in a randomized, placebo-controlled, crossover study of terbutaline, budesonide, and their combination in patients with chronic persistent asthma. We compared the changes in eosinophil counts and ECP in induced sputum and blood during each treatment period. RESULTS: Budesonide and combined treatment caused a significant reduction in sputum eosinophils (-2.7% and -2.3%, respectively, P < 0.05). Sputum eosinophils increased with terbutaline (+3.9%, P = 0.049). In contrast, the changes for sputum ECP were not significant. There was a similar treatment effect on blood eosinophils, but not for serum ECP. Correlations between sputum and blood eosinophils were significant with and without budesonide, but were nonsignificant between sputum and blood ECP during the active treatments. Correlations between sputum eosinophils and ECP, and between blood eosinophils and serum ECP were greatest during treatment with placebo or terbutaline alone: budesonide weakened or abolished these relationships. CONCLUSIONS: Compared with eosinophil counts, ECP measurements in either induced sputum or serum failed to reflect treatment-related changes in chronic asthma. We conclude that ECP is not a sensitive or reliable means of evaluating airway inflammation, and can not be recommended for assessing responses to anti-inflammatory therapy.     

Eosinophil markers in seasonal allergic rhinitis

Background The purpose was to study activation markers of the eosinophil granulocytes in seasonal allergic rhinitis, and the impact of topical steroid therapy thereupon.
Methods Sixty-three rhinitis patients with monoallergy to grass were examined before and at peak pollen season. Blood eosinophil count, eosinophil cationic protein (ECP), and eosinophil peroxidase (EPO) in serum and nasal lavage fluid were measured. During the season, patients were randomized to treatment with intranasal fluticasone propionate 0.1 mg o.d. ( n =26), 0.2 mg o.d. ( n =25), or placebo (n = 12). Six healthy persons served as controls.
Results During the season, all parameters, except nasal lavage ECP, increased in the placebo group (P<0.001 – P<0.05). Significant differences were seen between the steroid grotips and the placebo group for all parameters (P<0.001–F<0.05). Higher eosinophil count (P<0.05), serum EPO (F<0.02), and nasal lavage EPO (P<0.05) were found in patients before season than in controls. The following winter, 44 patients returned for repeated measurement. Lower levels of nasal lavage EPO were observed for patients than levels at the beginning of the season (P<0.0001).
Conclusions Intranasal fluticasone propionate reduced inflammation of the nasal mucosa, demonstrated locally by nasal lavage ECP and EPO, and systemically by blood eosinophils, serum ECP, and serum EPO. EPO seemed more sensitive than ECP as indicator of allergic inflammation. EPO demonstrated some perennial eosinophil activity in hay fever patients, increasing locally during spring.     

Diagnostic accuracy of sputum outcomes in chronic stable asthma

BACKGROUND: Asthma with non-remitting airflow obstruction may not always be differentiated from COPD with airway hyperreactivity. Many attempts have been made to find useful markers for the distinction between these two disorders. OBJECTIVE AND METHODS: In order to help the finding of a useful marker for the diagnosis of asthma in the population of patients with airway obstruction we analysed the diagnostic accuracy of sputum eosinophils and sputum ECP in 91 patients with asthma, 15 patients with chronic bronchitis, 32 patients with chronic obstructive pulmonary disease (COPD) and 20 controls subjects, by performing ROC analysis. RESULTS: Sputum eosinophils were above the normal range of our laboratory (0-3.7%) in 48 asthma patients and in six COPD patients, while sputum ECP (normal range < 85 microg/L) was high in 65 asthma patients, in 24 COPD patients and in nine chronic bronchitis patients. The ROC analysis revealed that sputum eosinophils count (AUC = 0.82) was more accurate than both sputum ECP levels (AUC = 0.56) (P < 0.0001) and beta2-reversibility (AUC = 0.53) (P = 0.0001) in differentiating asthmatic from non-asthmatic subjects (COPD, chronic bronchitis patients and normal subjects). The diagnostic accuracy of ECP was similar to that of bronchial reversibility (P = 0.76). When ROC analysis was performed by including only patients with airway obstruction (36 asthmatics with airway obstruction and COPD patients), both eosinophil count (AUC = 0.77) and beta2-reversibility (AUC = 0.66) were more accurate than ECP measurement (AUC = 0.39) in discriminating asthmatics from COPD patients (P < 0.00001 and P = 0.04, respectively). CONCLUSION: Sputum eosinophils seem to be valid markers for detecting asthma in a population of patients with airway obstruction. Moreover, the higher diagnostic accuracy of eosinophils in the sputum compared to sputum ECP and bronchial reversibility reinforces the role of cytological analysis of sputum in the diagnosis of chronic stable bronchial asthma.     

No effect of anti-interleukin-5 therapy (mepolizumab) on the atopy patch test in atopic dermatitis patients

BACKGROUND: The atopy patch test (APT) is an in vivo model to study the induction of eczema by inhalant allergens in atopic dermatitis (AD) patients. Mepolizumab is a monoclonal antibody to interleukin-5, which reduces peripheral blood eosinophils. Previously, we reported that mepolizumab treatment did not result in clinical improvement in AD. The current study investigates the effect of mepolizumab therapy on the APT in the same patients. METHODS: Mepolizumab treatment was given at days 0 and 7 in a double-blind placebo-controlled design. The APT was applied at days -2, 0, 14 and 28. Clinical evaluation of each APT was conducted 48 h after application at days 0, 2, 16 and 30. Skin biopsies were taken at days 0, 2 and 16 for eosinophil counts. RESULTS: The mepolizumab-treated group showed no significant reduction in macroscopic outcome of the APT. Tissue eosinophils were reduced in the mepolizumab-treated group at day 16 compared with placebo; however, this was not significant. CONCLUSION: Mepolizumab therapy cannot prevent the eczematous reaction induced by the APT. Furthermore, the influx of tissue eosinophil numbers in the APT is not significantly inhibited after mepolizumab treatment compared with placebo, despite a significant reduction in peripheral blood eosinophils.     

Clinical evaluation of eosinophils in the sputum.

The sputum differential eosinophil/neutrophil count was done in 384 patients using Leishman staining. The patients were distributed in four groups: bronchial asthma (197 patients); chronic bronchitis with wheezing (45 patients); chronic bronchitis and/or emphysema without wheezing (73 patients); other pulmonary diseases (64 patients). Eosinophils were present in patients from all groups but more frequently (P less than 0.001) in asthma: 142 (72%) of 197 patients. In bronchial asthma and chronic bronchitis with wheezing the percentages of eosinophils were more frequently (P less than 0.001) above 80%: 57% and 58% of the patients respectively. The other two groups had more cases with 19% or less eosinophils. There is no percentage level specific for asthma but levels above 80% of eosinophils are strongly suggestive of asthma or of chronic bronchitis with wheezing.     

Nitric oxide metabolites,eosinophils, and eosinophilic cationic protein in patients with asthma: sputum versus blood

The monitoring of airway inflammation has assessed in bronchial asthma directly by sputum examination, and indirectly by measurements in peripheral blood. To investigate the diagnostic value of these two methods, we compared nitric oxide (NO) metabolites, eosinophils, and eosinophil cationic protein (ECP) in sputum and blood in patients with asthma and control subjects. Sputum and serum were obtained from fifteen patients with asthma, and then were examined before anti-asthma treatment, including steroid preparations. ECP was measured by fluoroimmunoassay. NO metabolites were assayed by using modified Griess reaction. Asthmatic patients, compared with control subjects, had significantly higher level of NO metabolites, higher proportion of eosinophils, and higher levels of ECP in sputum. Asthmatic patients, compared with control subjects, however, had significantly higher number of eosinophils, and were at higher levels of ECP in blood. FEV1, FEV1/FVC was negatively correlated with sputum eosinophils. The area under receiver operating characteristic (ROC) curve showed that eosinophils in sputum are significantly accurate markers than NO metabolites in sputum and blood. These findings suggest that the proportion of eosinophils in sputum have more accurate diagnostic marker of asthmatic airway inflammation than NO metabolites in sputum in differentiating asthmatic patients from control subjects.     

Eosinophilic bronchitis in asthma: a model for establishing dose-response and relative potency of inhaled corticosteroids

BACKGROUND: Newer generations and formulations of inhaled corticosteroids have necessitated the development of a clinically relevant model to compare their clinical potency. OBJECTIVE: We evaluated whether sputum eosinophil counts could demonstrate a dose-response to inhaled corticosteroids, and compared the response with other inflammatory markers. METHODS: Fourteen steroid-naive patients with asthma with an initial sputum eosinophilia of > or = 2.5% entered a 6-week sequential, placebo-controlled, patient-blinded, cumulative dose-response study. After 7 days of placebo, they received incremental doses of fluticasone propionate (FP), 50, 100, 200, and 400 microg/d, each for 7 days. Measurements were made of sputum and blood eosinophils, exhaled nitric oxide, spirometry, airway responsiveness to methacholine (methacholine PC20), and symptom scores before and after each dose. RESULTS: Sputum eosinophils and exhaled nitric oxide were extremely sensitive to the effects of FP, and exhibited significant dose-dependent reductions of 99.4% and 99.8 parts per billion, respectively, where each variable was expressed per 100 microg/d FP. This compared with a 0.5 doubling dose increase of airway responsiveness to methacholine and a 0.3 decrease in symptom scores. Airway responsiveness to methacholine was the only variable that increased throughout the study. CONCLUSION: These results suggest that the model of eosinophilic bronchitis could be used to compare the effect of cumulative doses of an inhaled corticosteroid delivered by different types of delivery systems or preparations using a relatively small number of patients. CLINICAL IMPLICATIONS: Future clinical studies based on this model will allow clinicians to make informed decisions regarding the relative potencies of different inhaled corticosteroids.     

Double-blind study of ipratropium bromide, a new anticholinergic bronchodilator.

The efficacy and acceptability of ipratropium given by metered-dose inhaler were evaluated in two double-blind crossover tests against placebo, one preceding and one following a 2-wk period of continual open-label ipratropium treatment. Ten patients with chronic bronchitis and 10 with bronchial asthma participated. Ipratropium produced increase in FEV 1 of more than 15% within 5 min of inhalation, and this effect was maintained for 4 to 5 hr. Statistically significant mean increases over the FEV 1 baseline values were recorded after ipratropium treatment in both the initial and the final crossover tests. There were no adverse reactions to any of the placebo or ipratropium test doses or to the ipratropium treatment. Serial electrocardiograms, laboratory tests, blood pressure, and pulse rate showed no change from lthe baseline. Sputum volume and dry-weight determinations in the patients with bronchitis before and after the 14-day treatment revealed no changes.     

Eosinophilic gastroenteritis in children-report of one case

Eosinophilic gastroenteritis is rare in pediatric patients. The three main manifestations, defined by Klein et al. in 1970, were (a) predominant mucosal, (b) predominant muscular-layer, and (c) predominant subserosal disease. The predominant subserosal type is the rarest of the three. We report on a 43-month-old boy who, on admission, suffered from recurrent abdominal pain, vomiting and diarrhea for one week, with ascites and pleural effusion noted. The white blood cell (WBC) count of ascites fluid was 8,000/mm3, with a differential count of 99% eosinophils. The peripheral WBC count was 44,000/mm3, with 78% eosinophils. Three days after diagnosis, ascites, pleural effusion and other gastrointestinal symptoms were gradually relieved using steroid therapy, with the peripheral eosinophil count returning to normal. The steroid therapy was discontinued after two months with tapering dose. The boy was in good health with no recurrence of symptoms in a follow-up conducted after one year.     

The changes in the nasal secretions of eosinophils during the immediate nasal response to allergen challenge

In 162 patients with allergic rhinitis due to immediate hypersensitivity, nasal provocation tests (NPT) were supplemented by recording of the eosinophils in the nasal secretions (NS). Nasal secretion specimens were obtained before and repeatedly after allergen challenge and stained by a modified Hansel's method. The 188 positive immediate nasal responses (INR) that correlated with positive skin tests and history and 92 negative INR that correlated with negative skin tests and history were studied. Several different types of eosinophil response to allergen challenge were observed. Eosinophilia was found in the NS in 84% of patients with positive INR but in only 49% of patients with negative INR. The eosinophil count before allergen challenge was low in 79.5% of positive INR and in 76.5% of negative INR, whereas it was high in 20.5% of positive INR and in 23.5% of negative INR. The positive INR were accompanied by significant changes (p less than 0.01) in the eosinophil count between before and after allergen challenge in 74% and the negative INR in only 19% of the cases. These changes appeared within 30 min after allergen challenge. This study shows that only a single count of eosinophils in the NS is not a suitable indicator of nasal allergy. The recording of eosinophils in the NS can be considered as a useful supplementary diagnostic parameter for the possible involvement of immediate hypersensitivity in the nasal mucosa if (1) the eosinophil count is related to a certain allergen and (2) the eosinophils are recorded before and repeatedly up to 60 min after allergen challenge.     

The influence oc glycocorticoid therapy on sputum ECP concentration in symptomatic patients with bronchial asthma

ECP released from the granules of activated eosinophils is regarded to be a marker of airway inflammation in asthma. The study was performed to compare the usefulness of measuring serum and sputum ECP for monitoring the asthma treatment. 29 subjects with mild to moderate asthma (mean age 41 +/- 17) were admitted in exacerbation (FEV1 55.54 +/- 87.49% N). 10 subjects with grass pollen asymptomatic asthma and 10 healthy subjects were also enrolled in the study. Patients with symptomatic asthma were ordered 30 mg prednisone for 2 weeks and they continued during next 2 weeks inhaled budesonide therapy. The concentrations of ECP (mcg/L) were determined by CAP-system (Pharmacia). The total eosinophil count and serum ECP in all subjects treated orally and next by inhaled GKS didn't differ statistically. The highest sputum ECP concentration was determined in exacerbation of asthma 84.5 +/- 78 mcg/L and statistically were reduced after 2-weeks of prednisone treatment 24.4 +/- 12.1 mcg/L (p = 0.05). In following 2 weeks of budesonide treatment sputum ECP concentration was statistically negligible in relation to previous treatment in spite of increasing tendency (50 +/- 61.3 mcg/L (p = 0.2394). In asymptomatic grass pollen asthma sputum ECP concentration was 19.7 +/- 9.4 mcg/L, higher than in controls 12 +/- 5.8 mcg/L (p = 0.04). There were a significant correlations between total eosinophil count and serum (r = 0.6396) and sputum ECP(r = 0.4683) in exacerbation. CONCLUSIONS: 1. In asthma exacerbation elevated sputum ECP concentration was observed. 2. In consequence of prednisone treatment the sputum ECP concentration was reduced. 3. Sputum ECP measurement is more accurate than serum ECP for monitoring the effectiveness of treatment. 4. Sputum ECP concentration is a sensitive parameter which discriminate asymptomatic patients with asthma from healthy subjects.     

Asthma biomarkers in sputum

Several inflammatory cells are thought to contribute to the pathogenesis of asthma. Among these, the eosinophil appears to be a major effector cell. This review focuses primarily on the clinical utility of sputum eosinophil counts in asthma. Several studies have shown sputum eosinophils to be associated with both asthma severity and level of asthma control. In addition, the presence of sputum eosinophilia is strongly predictive of a favorable response to glucocorticoid therapy. Conversely, the absence of sputum eosinophilia is predictive of a poor response to glucocorticoid therapy. Sputum eosinophilia also predicts asthma relapse in subjects who have their inhaled glucocorticoid reduced or withdrawn. Lastly, inhaled glucocorticoid therapy can be titrated to keep the sputum eosinophil count at or below 2%.     

Sequential alterations in the human eosinophil content of arylsulfatase B during therapy of Bancroftian filariasis

Since transient increases in blood eosinophilia of varying levels accompany diethylcarbamazine therapy of filariasis, possible qualitative alterations in such eosinophils were assessed in 21 patients from an area hyperendemic for Bancroftian filariasis. The activities of arylsulfatase B, peroxidase, and β-glucuronidase were assayed in sonicates of eosinophil-enriched peripheral blood granulocytes obtained prior to, on the eighth day of, and 10–14 days after antifilarial chemotherapy. The activities of arylsulfatase B, which were attributable largely to eosinophils, decreased significantly from 36.0 to 26.0 μg p-nitrocatechol generated/hr/10⁶ eosinophils at the height of eosinophilia during therapy and rose significantly to 47.0 μg p-nitrocatechol generated/hr/10⁶ eosinophils after therapy, while the levels of other enzymes were unchanged. The extent of fall in the arylsulfatase B level per eosinophil with therapy was unrelated to either the increase in eosinophil count or the magnitude of the maximal eosinophil count, which suggested that the fall was not simply a function of a lower content of arylsulfatase B in young eosinophils. The significant fluctuations in eosinophil arylsulfatase B activity and the increased variability in eosinophil cellular content of arylsulfatase B during therapy suggested that eosinophil degranulation may accompany the host response to the filarial infection initiated by antifilarial therapy.     

Efficacy and onset of action of fluticasone propionate aqueous nasal spray on nasal symptoms, eosinophil count, and mediator release after nasal allergen challenge in patients with seasonal allergic rhinitis

We studied the effect and onset of action of fluticasone propionate aqueous nasal spray (FPANS) on mediator release and eosinophil accumulation in nasal secretions and on nasal symptoms of patients with seasonal allergic rhinitis after nasal allergen challenge (NAC). At the end of the pollen season, 28 patients were randomized in a double-blind and crossover design to receive 7 days' treatment with FPANS (200 μg, once daily) and matching placebo. NACs were performed before and at 6 h and 1. 2. 3. and 7 days during treatment with FPANS or placebo. Nasal secretions were collected for a quantitative determination of mediators and eosinophil count before and 5 min after each challenge. Nasal symptoms were assessed by scales grading the severity of symptoms at the same time. Results showed that for mediator concentrations there was a significant decrease of leukotriene C4 (P<0.001) at 7 days after the first administration of FPANS as compared to placebo. Two days after FPANS. both eosinophil counts and eosinophil cationic protein (ECP) concentrations were lower than those of placebo (eosinophils; f=0.032; ECP; F=0.038). The onset became even more important at day 7 (eosinophils; P=0.001; ECP; P=0.009) during the FPANS treatment period. For the subjective nasal symptoms, a significant reduction of symptom scores for nasal obstruction occurred also at day 3 (F=0.017) and for sneezing at day 7 (f=0.003). There was not yet any significant improvement of the objective nasal airway resistance after the different NACs during the study period. In conclusion, this study demonstrated that topical fluticasone propionate is effective in the treatment of mucosal inflammation induced by NAC. For optimal control of nasal symptoms induced by repeated maximal allergen challenges, a treatment period of more than 1 week is required.     

Corticosteroid-sensitive lymphocytes are normal in atopic asthma

Corticosteroids, well known to increase susceptibility to infection, are often administered to atopic patients. Atopy may be associated with lymphocyte abnormalities and increased susceptibility to infections caused by intracellular organisms. We sought to determine whether atopic and nonatopic subjects respond in a similar manner to corticosteroids administered both systemically and locally. We compared the response of peripheral blood leukocytes of 15 atopic asthmatics and 10 nonatopic control subjects to prednisone or beclomethasone dipropionate. We determined leukocyte number, total eosinophil count, T-cell number, complement receptor lymphocyte number, and concanavalin A (Con A)- and phytohemagglutinin (PHA)-induced lymphocyte proliferation before and 5 hr after administration of 20 mg of prednisone orally or 336 jig of beclomethasone dipropionate by aerosol inhalation. Baseline values of the groups differed. The atopic asthmatic group had higher total eosinophil count, lower percent lymphocyte count, and slightly lower Con A- and PHA (high concentration) -induced lymphocyte proliferation. T-cell and complement receptor lymphocyte number were equivalent in both groups. Prednisone caused a profound eosinopenia, monocytopenia, T lymphopenia, depression of mitogen-induced lymphocyte proliferation, and increase in leukocyte number and complement receptor lymphocyte percent. Beclomethasone dipropionate was associated with little or no change in these parameters. We conclude that atopic asthma is not associated with a defect in corticosteroid-sensitive leukocyte populations and that beclomethasone dipropionate aerosol, as opposed to prednisone, does not alter peripheral blood mononuclear cell populations.     

Minimum dose requirements of steroid-dependent asthmatic patients for aerosol beclomethasone and oral prednisone

In 34 steroid-dependent asthma patients who improved markedly during 2 mo of treatment when progressively larger doses of beclomethasone aerosol were added to their oral prednisone regimen, we subsequently reduced both steroids to ascertain the minimum dose of each needed to prevent recurrence of significant asthmatic disability. After 80 wk of follow-up, 15 patients had successfully terminated oral prednisone; 19 were better controlled with a combination of aerosol plus oral steroid than with either drug alone; all patients previously unable to convert to alternate-day prednisone did so successfully during the combined therapy. The minimum effective maintenance dosage varied greatly among these patients-the median values being 2.5 mg prednisone and 1,200 μg beclomethasone per day. The latter ranged from 200 to 1, 800 μg. Only 4 patients were satisfactorily controlled without prednisone on 400 μg beclomethasone per' day or less. Seven needed extra intranasal beclomethasone to help control the nasal polyps which worsened after prednisone withdrawal. Suppression of plasma corlisol levels, apparently attributable to the beclomethasone, persisted in most patients, but on the average this was no worse than before commencing this treatment and valuable clinical improvement accrued. There were no other important complications of the regimen. In most of these patients with severe chronic asthma, optimum control of the disease required combined aerosol-oral therapy and maintenance doses of beclomethasone higher than those usually recommended. In some patients, effective control of chronic asthma by beclomethasone treatment may require acceptance of some persisting suppression of adrenal function as a considered risk.     

Eosinophil infiltration in posttransurethral resection prostatitis and cystitis with special reference to sequential changes of eosinophilia

Posttransurethral resection (TUR) status in the prostate and urinary bladder has been infrequently documented. Furthermore, sequential changes in eosinophil count in peripheral blood (PB) after TUR have not been investigated in detail. In the present study, eosinophil counts and changes in eosinophils in PB were examined before to after TUR of the prostate (P) in 20 patients with benign prostatic hyperplasia. Among them, 14 patients exhibited increased numbers of eosinophils, the greatest increase being 17%. After TUR to treat bladder tumor (BT), massive infiltration of eosinophils into the resected areas, peaking 1 month later, was also detected in 8 of 15 cases of post-TUR cystitis. The PB eosinophil counts increased by more than 5% in two of five cases of post-TUR cystitis in which eosinophil counts were obtained before and after surgery. Most infiltrating eosinophils reacted positively to antibodies to eosinophil cationic proteins. These results indicated that, in patients with post-TUR prostatitis, the number of eosinophils in PB increased, and peaked 1 month later, with infiltration by eosinophils observed. Pathologists and urologists should be aware of the potential for increase in eosinophils not only in regions of TUR but also in PB.     

Histologic responses in human skin test reactions to ragweed. IV. Effects of a single intravenous injection of steroids.

A controlled study has been carried out dealing with the early effects of a single intravenous dose of either methylprednisolone or placebo or newly developed and ongoing cellular inflammatory responses in immediate hypersensitivity skin test reactions. There was no significant difference in the tissue eosinophil responses to ragweed injected 2 hr before and 2 hr after placebo; there was a significant rise (101% +/- 39) from the second to fourth hour after antigen injection. By contrast, there was a marked decrease in the tissue eosinophil response to antigen injected 2 hr after steroids as compared to the pattern seen in the presteroid reaction. In addition, the eosinophil numbers not only did not increase from the second to fourth hour when steroids were injected at the second hour but decreased markedly. These findings suggest early suppressive effects on tissue eosinophil responses within 2 hr after steroid were administered intravenously. Also, there may be trafficking of eosinophils both into and out of these inflammatory sites during the first hours after intradermal antigen injection.