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Biomedical subjects

H S Nelson

Publications and source records attributed to H S Nelson.

At least 37 records · Page 2Linked to original sources
PubMed2000

The use of standardized extracts in allergen immunotherapy.

BACKGROUND: Double-blind, placebo-controlled studies have established that injection allergen immunotherapy is clinically effective. However, it is not known to what extent the doses of allergen extract commonly used in clinical practice match those that have been used in these controlled studies. OBJECTIVE: The aim of this study was to determine by questionnaire the doses of standardized allergen extracts commonly used by board-certified allergists in the United States and to compare these with doses that have proven effective in double-blind, placebo-controlled studies. METHODS: A questionnaire containing a hypothetical case and asking for a recommended allergen prescription for maintenance immunotherapy was mailed to 500 randomly selected board-certified members of the American Academy of Allergy, Asthma and Immunology living in the United States. The recommended doses were compared with those doses of the extracts that had been proven effective by using major allergen content figures for representative standardized US allergen extracts provided by an allergy extract laboratory. RESULTS: Responses were received from 118 (23%) of the addressees. Eighty (16%) contained interpretable data on maintenance dosing for extracts. The median doses of pollen recommended were comparable with those that have been demonstrated to be clinically effective. Median doses of house dust mites were only slightly lower than those that have proven effective. Median doses of animal dander, on the other hand, were well below those used effectively in controlled studies. Although the median doses used were often in the range of proven doses, the range of doses recommended by allergists included some that were one tenth to one five hundredth those of the median doses. CONCLUSION: In the absence of useful guidance from the federal regulatory authorities, American allergists, for the most part, use doses of pollens and house dust mites that are within the proven range. Their dosing of animal dander is generally below proven effective doses. There is, however, a wide range of dosing of all extracts used, and there is use of mixes that have no botanical basis. Therefore there is need for studies defining what are effective and ineffective allergen extract doses.

Allergens↗
PubMed2000

Fluticasone propionate/salmeterol combination provides more effective asthma control than low-dose inhaled corticosteroid plus montelukast.

BACKGROUND: Asthma is a disease of chronic inflammation and bronchoconstriction. Inhaled corticosteroids (ICSs) provide important anti-inflammatory treatment but may not provide optimal control of asthma when taken alone. Two therapeutic alternatives for enhanced asthma control are to substitute the combination of fluticasone propionate (FP) and salmeterol (FP/Salm Combo) through the Diskus inhaler or to add montelukast to existing ICS therapy. OBJECTIVE: We compared the efficacy and safety of FP/Salm Combo through the Diskus inhaler versus montelukast added to FP (FP + montelukast) in patients whose symptoms were suboptimally controlled with ICS therapy. METHODS: We performed a multicenter, double-blind, double-dummy, parallel-group, 12-week study in 447 patients with asthma who were symptomatic at baseline while receiving low-dose FP. Patients were treated for 12 weeks with one of the following: (1) combination of FP 100 microg plus salmeterol 50 microg twice daily through the Diskus inhaler, or (2) FP 100 microg twice daily through the Diskus inhaler plus oral montelukast 10 mg once daily. RESULTS: FP/Salm Combo treatment provided better overall asthma control than FP + montelukast with significantly greater improvements in morning peak expiratory flow (+24.9 L/min vs +13.0 L/min, P <.001), evening peak expiratory flow (+18.9 L/min vs +9.6 L/min, P <.001), and forced expiratory volume in 1 second (+0.34 L vs +0.20 L, P <.001), as well as a change in the percentage of days with no albuterol use (+26.3% vs +19.1%, P =.032) and the shortness of breath symptom score (-0.56 vs -0.40, P =.017). The groups had comparable improvements in chest tightness, wheeze, and overall symptom scores. Asthma exacerbation rates were significantly lower (P =.031) in the FP/Salm Combo group (4 patients, 2%) than in the FP + montelukast group (13 patients, 6%). Adverse event profiles were comparable. CONCLUSION: Symptomatic patients on low-dose ICS therapy had significantly greater improvement in asthma control when switched to the FP/Salm Combo than when montelukast was added to ICS therapy.

Acetates↗
PubMed2000

Long-term safety of a non-chlorofluorocarbon-containing triamcinolone acetonide inhalation aerosol in patients with asthma. Azmacort HFA Study Group.

In response to environmental concerns regarding chlorofluorocarbon (CFC), two new triamcinolone acetonide (TAA) inhalation aerosol (Azmacort Inhalation Aerosol) formulations have been developed using a more environmentally favorable propellant, HFA-134a (1,1,1,2-tetrafluoroethane). This multicenter, open-label study evaluated the safety of switching asthma patients from TAA-CFC to one of two TAA-HFA formulations. After a 2- or 4-week baseline period during which patients received only CFC-containing TAA Inhaler, 552 patients were randomized to receive TAA-HFA 75 or 225 microg for 6 or 12 months. A total of 493 patients completed treatment. Seven patients discontinued because of adverse events and two because of ineffective asthma control. The incidence of adverse events was similar in the two treatment groups, and most events were mild to moderate in severity and were not considered related to study medication. No clinically relevant suppression of the hypophyseal-pituitary-adrenal (HPA) axis was observed. Pulmonary function tests were not adversely affected by use of either study medication, and improvements were noted in forced expiratory volume in 1 sec (FEV1) and forced expiratory flow between 25% and 75% of forced vital capacity (FEF25%-75%) throughout the course of treatment. This study confirms that TAA-HFA provides effective, long-term asthma control and can safely be substituted for the currently marketed CFC-containing TAA product.

Administration, Inhalation↗
PubMed1999

Administration of budesonide once daily by means of turbuhaler to subjects with stable asthma.

BACKGROUND: Optimal management of chronic, mild-to-moderate asthma with inhaled steroids may include use of the lowest possible doses, as recommended in guidelines, and a reduction in the frequency of daily administration for greater convenience. Lower doses and once daily treatment with inhaled steroids must be rigorously evaluated in controlled clinical trials. OBJECTIVES: The objective of this study was to assess the efficacy and safety of once daily treatment with budesonide in subjects with stable asthma. METHODS: Once daily budesonide was assessed in 309 adult subjects, including those who were and were not using an inhaled steroid at baseline. The subjects were stratified by inhaled steroid use and randomly assigned to one of 3 treatments: 200 microgram budesonide, 400 microgram budesonide, or placebo administered by means of Turbuhaler once daily in the morning for 6 weeks. Beyond this point, treatment was continued unchanged for another 12 weeks (maintenance) in those receiving 200 microgram budesonide once daily and placebo. In those who received 400 microgram budesonide once daily, the dose was reduced to 200 microgram once daily at week 6 and held constant for the remaining 12 weeks (400/200 microgram group). Primary efficacy endpoints were mean change from baseline in FEV1 and morning peak expiratory flow. RESULTS: Once daily budesonide was well tolerated and resulted in significant improvements in all efficacy endpoints, even though baselines were well stabilized. Baseline lung function was elevated with little room for improvement; however, mean increases in FEV1 during the maintenance period were 0.10 L and 0.11 L in the 200 microgram and 400/200 microgram groups, respectively, versus a decrease of -0.09 L in the placebo arm (P <.001). Results for peak expiratory flow were similar. Significant improvements in secondary endpoints, including symptoms, beta-agonist use, and quality of life, also developed with budesonide 200 and 400 microgram once daily. CONCLUSION: Inhaled budesonide, in doses as low as 200 microgram, may be an appropriate introductory or maintenance dose in subjects with stable, mild-to-moderate asthma.

Administration, Inhalation↗
PubMed1999

Clinical experience with levalbuterol.

Although racemic albuterol is an effective bronchodilator, regular use has been associated with some loss of bronchodilator potency, decreased protection against bronchoprovocation, increased sensitivity to allergen challenge, and increased sensitivity to some bronchoconstrictor stimuli. In experimental animals racemic albuterol has produced bronchial hyperresponsiveness, which could also be induced by administration of (S)-albuterol. These findings suggest that the pure or homochiral formulation of (R)-albuterol (levalbuterol) might be more effective as a bronchodilator than the racemic form. Single doses of levalbuterol provided more prolonged protection against methacholine challenge than the racemate, whereas (S)-albuterol significantly increased sensitivity to methacholine. In a 4-week study in adults, equivalent amounts of pure levalbuterol provided greater bronchodilation than did similar amounts of levalbuterol given as racemic mixtures. Furthermore, after 4 weeks, the baseline morning FEV(1 ) was lower in those receiving the racemate than in those receiving placebo or levalbuterol. In a single-dose study in children, the same conclusion regarding greater bronchodilation with pure levalbuterol compared with the same amount of levalbuterol in a racemic mixture was confirmed. These studies appear to confirm the greater efficacy of pure levalbuterol over a similar amount in a racemic mixture. This implies a deleterious effect of (S)-albuterol on both the acute bronchodilator response and baseline airway caliber, the exact mechanism of which will require further investigation.

Adrenergic beta-Agonists↗
PubMed1999

The relationships among environmental allergen sensitization, allergen exposure, pulmonary function, and bronchial hyperresponsiveness in the Childhood Asthma Management Program.

BACKGROUND: Sensitivity and exposure to indoor allergens constitutes a risk factor for the development and persistence of asthma in children. OBJECTIVE: Our purpose was to evaluate the relationship between sensitivity and exposure to inhalant allergens and lung function and bronchial responsiveness in a group of children (n = 1041) aged 8.9 +/- 2.1 years with mild to moderate asthma enrolled in the Childhood Asthma Management Program (CAMP). METHODS: With use of the extensive CAMP baseline cross-sectional data on spirometry, bronchial responsiveness, allergen sensitivities, and household allergen levels, the relationship of sensitization and exposure to allergens to lung function and methacholine sensitivity was evaluated. Children who enrolled in CAMP stopped all antiasthma medication except rescue use of albuterol and prednisone for exacerbations during the 5- to 16-week screening period. During the last 2 of these weeks they underwent spirometry and methacholine challenge. Indoor allergen exposures were determined from questionnaires completed by the parent. Household levels of indoor allergens (mite, cat, dog, cockroach, mold) were determined on house dust samples. Allergen sensitivity was determined by percutaneous skin testing with a standard battery of allergens plus locally important pollen and fungal spores. Lung function and bronchial hyperresponsiveness were compared for children sensitive and not sensitive to both indoor and outdoor allergens on skin testing and, if sensitive, for exposed and not exposed to the allergens to which they were positive on skin testing. RESULTS: There was a strong direct correlation between increased sensitivity to inhaled methacholine and skin test sensitivity to tree, weed, Alternaria, cat, dog, and indoor molds. When the relationship was examined by stepwise regression, the skin test sensitivities showing the strongest associations with the concentration of methacholine that caused a 20% fall in FEV(1) were dog (P =.003), Alternaria (P =.01), and cat (P =.05). Children sensitive to any one of the aeroallergens tested were compared for the presence or absence of exposure to that allergen at the time that the methacholine challenge was performed. Those who were sensitive and exposed to weed and cat had greater methacholine sensitivity than those similarly sensitive but not exposed (P =.003 and P =.02, respectively). CONCLUSIONS: Sensitivity to dog or cat dander or Alternaria by skin testing was associated with increased bronchial responsiveness but not decreased lung function in children with mild to moderate asthma. These findings support the important role that sensitization to certain allergens plays in modulating bronchial responsiveness.

Adolescent↗
PubMed1999

Mechanisms of intranasal steroids in the management of upper respiratory allergic diseases.

Intranasal steroids have proved to be the most effective class of drugs in reducing the symptoms of allergic rhinitis. This clinical response reflects the broad anti-inflammatory activity that has been demonstrated for corticosteroids. Single doses of topical corticosteroids administered before nasal allergen challenge block the late-phase reaction, whereas repeated dosing with intranasal steroids blocks both the early and the late response, as well as the priming phenomenon. Nasal inflammation is accomplished through a number of effector cells and mechanisms, which in turn are produced by director cells through the release of cytokines and chemokines. The anti-inflammatory action of corticosteroids is largely effected through blocking the synthesis and release of these cytokines/chemokines.

Administration, Intranasal↗
PubMed1999

Fluticasone propionate powder: oral corticosteroid-sparing effect and improved lung function and quality of life in patients with severe chronic asthma.

BACKGROUND: Many patients with severe asthma are dependent on oral corticosteroids for maintenance control of their disease. Treatments that allow patients to be weaned off oral corticosteroids may help to minimize the risk of side effects associated with their chronic use. OBJECTIVE: This study evaluated whether inhaled fluticasone propionate powder could maintain pulmonary function while reducing the dose of oral prednisone in patients with chronic, severe asthma. METHODS: Oral prednisone-dependent (5 to 40 mg/day) adolescents and adults with asthma (n = 111; mean FEV1 = 61% of predicted value) were randomized to placebo or twice daily fluticasone propionate 500 or 1000 microg administered by means of a multidose powder inhaler for 16 weeks in a double-blind, parallel-group study. Patients underwent controlled prednisone reduction on the basis of predetermined asthma stability criteria. RESULTS: Oral prednisone was eliminated by 75% and 89% of patients in the twice daily 500 and 1000 microg fluticasone propionate groups, respectively, versus 9% of the placebo group (P <.001). FEV1, morning and evening peak expiratory flow, asthma symptoms, albuterol use, and nighttime awakenings improved with fluticasone propionate treatment, achieving statistical significance (P </=.009) primarily in the 1000 microg twice daily group. Hypothalamic-pituitary-adrenal axis suppression observed at baseline improved when patients were weaned off oral prednisone to fluticasone propionate. Adverse events ascribed to drug treatment were primarily topical effects of inhaled corticosteroids or those associated with prednisone withdrawal. Patient quality of life assessed by means of the Asthma Quality of Life Questionnaire was clinically and significantly improved after fluticasone propionate treatment (P </=.003). CONCLUSION: Fluticasone propionate powder (500 or 1000 microg twice daily) effectively improved lung function, adrenal function, and asthma-specific quality of life in patients with severe chronic asthma previously treated with oral prednisone while allowing most patients to be weaned off oral corticosteroid therapy.

Administration, Inhalation↗
PubMed1999

Lack of subsensitivity to albuterol after treatment with salmeterol in patients with asthma.

The development of tolerance to the bronchodilator effects of beta2-agonists used in asthma therapy has been the subject of debate. We conducted two placebo-controlled crossover studies to assess the bronchodilator response to a short-acting beta2-agonist before and after chronic therapy with salmeterol. Patients in one study were corticosteroid-naive; patients in the other study were using inhaled corticosteroids. Changes in FEV1 after cumulative doubling doses of inhaled albuterol were assessed after a 2-wk beta-agonist washout period, before administering study medication on Day 1, and again after 28 d of therapy. Ipratropium bromide was provided as rapid-relief treatment for asthma, and use of any beta2-agonist except the study treatment was prohibited. On both assessment days for salmeterol, and during placebo administration periods, significant increases from predose FEV1 values were observed beginning with the lowest dose of albuterol and continuing throughout the dose-response assessment (p </= 0.001). These increases in FEV1 were maintained for 6 h after the last dose of albuterol (p < 0.05). There were no statistically significant differences in the albuterol dose response following salmeterol or placebo. These studies indicate that irrespective of concurrent corticosteroid treatment, chronic therapy with salmeterol does not result in tolerance to the bronchodilator effects of albuterol.

Adrenergic beta-Agonists↗
PubMed1999

Interleukin-4 receptor in moderate atopic asthma. A phase I/II randomized, placebo-controlled trial.

UNLABELLED: Interleukin-4 mediates important proinflammatory functions in asthma, including induction of the IgE isotype switch, expression of VCAM-1 on endothelium, mucin production, 15-lipoxygenase activity, and Th2 lymphocyte stimulation leading to the secondary synthesis of IL-4, IL-5, and IL-13. Soluble recombinant human IL-4 receptor (IL-4R; Nuvance; altrakincept) inactivates naturally occurring IL-4 without mediating cellular activation. Nebulized IL-4R has a serum half-life of approximately 1 wk. In this double-blind, placebo-controlled trial, 25 patients with moderate asthma requiring inhaled corticosteroids were randomly assigned to receive a single nebulized dose of IL-4R 1,500 microg, IL-4R 500 microg, or placebo after stopping inhaled corticosteroids. No drug-related toxicity was observed. Treatment with IL-4R produced significant improvement in FEV(1) on Day 4 (1,500 microg versus placebo; p < 0.05) and in FEF(25-75) on Days 2 and 4 (1,500 microg versus placebo; p < 0.05). Asthma symptom scores stabilized among patients treated with IL-4R 1, 500 microg, despite abrupt withdrawal of corticosteroids, but not in the IL-4R 500 microg group or the placebo group (p < 0.05). Patients in the IL-4R 1,500 microg group also required significantly less beta(2)-agonist rescue use (p < 0.05). Anti-inflammatory effects were further demonstrated by significantly reduced exhaled nitric oxide (p < 0.05). CONCLUSIONS: A single dose of IL-4R appears safe and effective in moderate asthma. The 1,500 microg dose appears as safe but significantly more effective than the 500 microg dose.

Administration, Inhalation↗
PubMed1998

Alternative agents for anti-inflammatory treatment of asthma.

Recent guidelines for the management of asthma have emphasized the role of inflammation in persistent asthma. Medications with anti-inflammatory properties are recommended as the primary long-term-control medications. Of the available choices of long-term-control medications, inhaled corticosteroids are the preferred medication. A literature review of the available studies supports this recommendation of inhaled corticosteroids as the preferred agents for long-term control. Other long-term-control medications--specifically nedocromil, theophylline, and leukotriene modifiers, but not cromolyn--can supplement the beneficial effect of inhaled corticosteroids on pulmonary function and symptom control. Long-acting beta2-adrenergic agonists can also provide an additive clinical benefit to inhaled corticosteroids on symptom control and pulmonary function, but they do not provide additional anti-inflammatory effect. Extended long-term studies of each of the long-term-control medications with anti-inflammatory actions are needed to assess their specific effect on airway remodeling and on the natural history of asthma.

Anti-Inflammatory Agents↗
PubMed1998

Aerosol beclomethasone dipropionate spray compared with theophylline as primary treatment for chronic mild-to-moderate asthma. The American Academy of Allergy, Asthma and Immunology Beclomethasone Dipropionate-Theophylline Study Group.

BACKGROUND: Inhaled corticosteroids and oral theophylline are effective treatments for moderate asthma. OBJECTIVE: We sought to compare the benefits and adverse reactions of theophylline and aerosol beclomethasone spray. METHODS: A multicenter, double-blind, double-placebo, randomized, controlled trial of 1-year duration was performed. Seven hundred forty-seven patients with asthma received either beclomethasone dipropionate aerosol spray (84 microg four times per day) or sustained-release theophylline twice per day in doses adjusted for optimum control of the disease. The main outcome measures were daily diary of symptoms and peak flow rates (recorded on a mark-sense computer-readable form); supplemental bronchodilator use; doctor's office or hospital visits and absence from work or school; spirometry; methacholine testing; adverse experiences; and cortisol blood measurements. RESULTS: Both treatment strategies reduced symptoms promptly and achieved low absenteeism from work or school and low rates of emergency treatment for asthma. Both maintained nearly normal pulmonary function. Beclomethasone was statistically significantly more effective in reducing symptoms, supplemental bronchodilator and systemic glucocorticoid doses, bronchial hyperresponsiveness, and eosinophilia. However, the magnitude of these differences was small. Theophylline caused more headache, nervousness, insomnia, and gastrointestinal distress, and more patients discontinued treatment because of side effects. Beclomethasone caused more oropharyngeal candidiases and hoarseness and reduced morning plasma cortisol levels before and after cosyntropin. It reduced the rate of growth in children. No new cataracts or glaucoma developed. CONCLUSION: Theophylline effectively controlled symptoms at lower than the customarily recommended blood level. The risk/ benefit profiles of these agents suggest that inhaled corticosteroids may be the preferred agent for most adult patients and for some children.

Adolescent↗
PubMed1998

Improved bronchodilation with levalbuterol compared with racemic albuterol in patients with asthma.

BACKGROUND: Racemic albuterol is an equal mixture of (R)-albuterol (levalbuterol), which is responsible for the bronchodilator effect, and (S)-albuterol, which provides no benefit and may be detrimental. OBJECTIVE: We sought to compare 2 doses of a single enantiomer, levalbuterol (0.63 mg and 1.25 mg), and equivalent amounts of levalbuterol administered as racemic albuterol with placebo in patients with moderate-to-severe asthma. METHODS: This was a randomized, double-blind, parallel-group trial. Three hundred sixty-two patients 12 years of age or older were treated with study drug administered by means of nebulization 3 times daily for 28 days. The primary endpoint was peak change in FEV1 after 4 weeks. RESULTS: The change in peak FEV1 response to the first dose in the combined levalbuterol group was significantly greater compared with the combined racemic albuterol group (0.92 and 0.82 L, respectively; P =.03), with similar but nonsignificant results after 4 weeks (0.84 and 0.74 L, respectively). Improvement in FEV1 was similar for levalbuterol 0.63 mg and racemic albuterol 2.5 mg and greatest for levalbuterol 1.25 mg. Racemic albuterol 1.25 mg demonstrated the weakest bronchodilator effect, particularly after chronic dosing. The greatest increase in FEV1 was seen after levalbuterol 1.25 mg, especially in subjects with severe asthma. All active treatments were well tolerated, and beta-adrenergic side effects after administration of levalbuterol 0.63 mg were reduced relative to levalbuterol 1.25 mg or racemic albuterol 2.5 mg. At week 4, the predose FEV1 value was greatest in patients who received levalbuterol or placebo when compared with those who received racemic albuterol. The difference was more evident and was statistically significant in patients who were not receiving inhaled corticosteroids. CONCLUSION: Levalbuterol appears to provide a better therapeutic index than the standard dose of racemic albuterol. These results support the concept that (S)-albuterol may have detrimental effects on pulmonary function.

Adolescent↗
PubMed1998

Evaluation of devices for skin prick testing.

BACKGROUND: Previous comparisons of devices for percutaneous skin testing have revealed statistically and clinically significant differences, from one device to another, in the size of reactions to histamine and allergen extracts and at negative control sites. OBJECTIVE: The objective of this study was to compare the performance of several skin test devices which are either new, modified, or used with a modified technique. METHODS: Twenty subjects were tested five to eight times with each of the devices both to glycerol-saline and to 10 mg/ml histamine base. The devices tested were the MultiTest II, Duo Tip-Test (prick and scarification), Quintest, DermaPik (prick and scarification), and small pox needle. RESULTS: There were highly significant differences among the devices for the size of the reaction to histamine (mean wheal diameter 4.28 to 8.59 mm, p < 0.0001), the standard errors of the wheals to histamine (0.82 to 1.45 mm, p < 0.05) and in the mean wheal size with glycerol-saline (0.00 to 2.48 mm, p < 0.0001). CONCLUSIONS: Devices for performing skin prick testing vary greatly in several characteristics, including the size of reactions at both positive and negative test sites. Each skin test technician should be tested with the device used in that skin testing laboratory to establish criteria for positive and negative tests.

Adult↗
PubMed1998

Fluticasone propionate results in improved glucocorticoid receptor binding affinity and reduced oral glucocorticoid requirements in severe asthma.

BACKGROUND: Inhaled glucocorticoids (iGC) have become important first line agents in the management of moderate-to-severe asthma. Severe asthma is associated with reduced glucocorticoid receptor (GCR) binding affinity. METHODS: To evaluate the potential impact of inhaled fluticasone propionate on markers of airway inflammation [GCR binding affinity (Kd) and eosinophil cationic protein (ECP)] and oral GC requirements in steroid-dependent asthmatics, we examined the effects of fluticasone propionate (FP) 500 microg or 1000 microg BID and placebo in a double-blind, randomized study of 13 steroid-dependent asthmatics at a single center. Glucocorticoid receptor binding affinity and ECP values were obtained at baseline, 4, 6, 26, and 52 weeks after patients were enrolled into the study. Oral GC dose and FEV1 values were also recorded at each visit. RESULTS: Inhaled FP resulted in large reductions in oral GC requirement by 6 weeks of therapy while no reduction was seen in the placebo group. All patients in the FP 2000 microg/d group who continued double-blind therapy at 52 weeks were able to eliminate oral prednisone use. In contrast, every patient in the placebo group had to be withdrawn from the study due to poor asthma control. Associated with the oral GC dose reduction on high dose FP therapy, were improvements in GCR binding affinity with the GCR Kd falling from 42.5 nM at baseline to 19.5 nM at 6 weeks (P=.08). The GCR KD values remained stable thereafter with values of 23.5 nM at 26 weeks (P=.02) and 19.5 nM at 52 weeks (P=.01). In addition, high dose FP therapy resulted in reductions in serum ECP values. CONCLUSION: This study suggests that high dose FP therapy results in significant oral GC sparing effects associated with improved GCR binding affinity and reductions in serum ECP levels in patients with steroid-dependent asthma.

Administration, Oral↗
PubMed1998

Oral glucocorticosteroid-sparing effect of budesonide administered by Turbuhaler: a double-blind, placebo-controlled study in adults with moderate-to-severe chronic asthma. Pulmicort Turbuhaler Study Group.

OBJECTIVE: To determine the ability of budesonide via an inhaler (Pulmicort Turbuhaler; Astra Draco AB) to replace oral glucocorticosteroids (GCSs) in adult subjects with moderate-to-severe asthma. DESIGN: Double-blind, randomized, and placebo-controlled study, with parallel groups. SETTING: Multicenter study in outpatient setting. PARTICIPANTS: Eighty men and 79 women, aged 20 to 69 years, with moderate-to-severe asthma and a mean FEV1 of 58.3% predicted normal. All subjects were receiving oral GCS treatment and 79% of subjects were also receiving inhaled beclomethasone dipropionate (BDP). The mean daily doses of prednisone at baseline, including converted dose of BDP, for the placebo, budesonide 400 microg, and budesonide 800 microg, respectively, were 19.7 mg, 19.5 mg, and 18.7 mg. MEASUREMENTS AND INTERVENTIONS: After a 2-week baseline period, subjects entered a 20-week treatment period, during which the oral dose of prednisone was reduced by forced down-titration at 2-weekly intervals. RESULTS: Subjects receiving 400 microg or 800 microg bid of budesonide achieved a significantly greater reduction (82.9% and 79.0% respectively) in oral GCS dose compared with placebo-treated subjects (27%; p<0.001). Two thirds of the subjects receiving budesonide were able to achieve sustained oral corticosteroid cessation, compared with 8% in the placebo group. Additionally, both doses of budesonide resulted in significant improvement in results of pulmonary function tests and asthma symptoms scores, and a significant decrease in the use of bronchodilator therapy. The mean plasma cortisol levels before and after adrenocorticotropic hormone stimulation increased most toward the normal range in the budesonide-treated groups compared with placebo-treated subjects. CONCLUSION: Budesonide administered via Turbuhaler has a significant oral GCS-sparing capacity with maintained or improved asthma control in adult subjects with moderate-to-severe asthma.

Administration, Inhalation↗
PubMed1997

Rush immunotherapy results in allergen-specific alterations in lymphocyte function and interferon-gamma production in CD4+ T cells.

BACKGROUND: Allergen immunotherapy results in a number of changes in clinical, inflammatory, and immunologic parameters. However, the basis for the specificity of this form of therapy is unknown, especially in the context of changes in T- and B-lymphocyte function after desensitization to specific allergens. OBJECTIVE: This study was designed to determine the immunologic consequences of rush immunotherapy. METHODS: We studied 10 patients who had positive skin test responses to the house dust mite Dermatophagoides pteronyssinus (Dpt) and cat dander extract. Each received rush immunotherapy to mite, but not cat dander, over a 2- to 4-week period until maintenance was achieved. Patients were evaluated before and when maintenance was achieved for skin test and nasal reactivity to mite and cat dander; antibody levels to the allergen were monitored, as were lymphocyte proliferative responses and cytokine production. RESULTS: Rush immunotherapy to house dust mite resulted in a significant reduction in skin and nasal reactivity to mite allergen, but not to cat allergen, in 10 of 10 patients. This was accompanied by a rise in serum anti-Dpt IgE, whereas anti-cat IgE was not altered (7 of 7 patients). In seven of seven patients there was an increase in anti-Dpt IgG4 levels. T-cell proliferative responses to mite antigen were suppressed, and numbers of CD8+ T cells increased in frequency. There was a marked increase in interferon-gamma production, particularly by CD4+ T cells in 10 of 10 patients. The correlation between the increases in interferon-gamma production and the changes in cutaneous reactivity was highly significant. CONCLUSION: We show that rush immunotherapy is immunologically specific in eliciting changes in T- and B-cell responses to the desensitization antigen. The specificity and potential benefit of immunotherapy may be linked to the increase in interferon-gamma production by allergen-activated CD4+ T lymphocytes.

Adolescent↗