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Biomedical subjects

Harold S Nelson

Publications and source records attributed to Harold S Nelson.

At least 37 records · Page 2Linked to original sources
PubMed2004

Comparison of patient preference and ease of teaching inhaler technique for Pulmicort Turbuhaler versus pressurized metered-dose inhalers.

A multicenter, randomized, open-label, crossover study with two 4-week evaluation periods compared patient preference and ease of teaching correct inhaler technique for Pulmicort Turbuhaler versus pressurized metered-dose inhalers (pMDIs). Patients 18 to 65 years of age with stable, mild to moderate asthma, who required or were eligible for inhaled corticosteroid therapy, were randomized to treatment sequences consisting of 4-week evaluation periods with Pulmicort Turbuhaler (budesonide inhalation powder) two puffs (400 microg) bid and one of three inhaled corticosteroids via pMDI: Aerobid-M (flunisolide) four puffs (1 mg) bid, Flovent (fluticasone propionate) two puffs (440 microg) bid, or Vanceril Double Strength (beclomethasone dipropionate) five puffs (420 microg) bid. Patients indicated device preference at study end and completed the Patient Device Experience Assessment (PDEA) questionnaire after each evaluation period. Ease of teaching, time required to master use of the device, percentage of patients demonstrating mastery on the first attempt, and the number of attempts required to demonstrate mastery were assessed. Despite previous use of pMDIs by most patients, Pulmicort Turbuhaler was significantly preferred (p < 0.001) and required significantly less time to master than pMDIs (p < 0.001). Median times to device mastery were 3.67 min for Pulmicort Turbuhaler versus 5.33 min for pMDIs. Patients rated Pulmicort Turbuhaler significantly better than pMDIs on PDEA ease of use (p = 0.0005) and overall satisfaction (p < 0.0001) single-item scales and all four multi-item scales (pharyngeal symptoms, oral sensation, operational use, and inhaler attributes; p < 0.05). Overall, patients preferred Pulmicort Turbuhaler over pMDIs and required less time to be taught how to correctly use Turbuhaler trade mark.

Administration, Inhalation↗
PubMed2003

Prospects for antihistamines in the treatment of asthma.

Antihistamines have been evaluated as potential therapies for asthma for more than 50 years. With first-generation compounds, side effects prevented effective dosing. By reviewing published studies of the effectiveness of terfenadine, cetirizine, and loratadine in clinical asthma, evidence for the relevant effect of the second-generation antihistamines on bronchial asthma can be found. Terfenadine, at doses of 120 or 180 mg twice a day, reduced symptoms and improved pulmonary function in mild and moderate allergic asthma but was ineffective in severe perennial asthma. Fexofenadine at doses used for allergic rhinitis had little effect on seasonal allergic asthma. Research is ongoing to determine the effects of higher doses of fexofenadine. In 5 studies, cetirizine at doses of 10 to 20 mg, once or twice daily, consistently improved asthma symptoms compared with placebo or terfenadine 60 mg twice a day in 2 cases, whereas in 2 studies, loratadine at doses of 10 to 20 mg daily has not produced significant improvement in asthma. However, loratadine 5 mg combined with 60 mg of pseudo-ephedrine twice a day significantly improved both asthma symptoms and peak expiratory flow. Similarly, the combination of loratadine 20 mg and the leukotriene-receptor antagonist montelukast improved asthma symptoms, peak expiratory flow, and beta-agonist use over montelukast alone. Therefore, there might be a role for second- and third-generation antihistamines in treating mild and moderate asthma, which might require administering doses greater than those commonly used to treat allergic rhinitis. If higher doses are sedative, the addition of decongestants or leukotriene-receptor antagonists might enhance the effects of lower doses of the antihistamines.

Anti-Allergic Agents↗
PubMed2003

Budesonide Turbuhaler delivered once daily improves health-related quality of life and maintains improvements with a stepped-down dose in adults with mild to moderate asthma.

BACKGROUND: Budesonide inhalation powder administered via Turbuhaler (budesonide Turbuhaler, AstraZeneca LP, Wilmington, DE) is proven efficacious and safe in the treatment of mild to severe asthma. OBJECTIVE: To evaluate the effect of once-daily budesonide Turbuhaler on health-related quality of life (HRQL) in adults with mild to moderate asthma. METHODS: In this double-blind, parallel-group study, 309 asthmatic patients between 18 and 70 years of age were randomized to receive once-daily treatment with budesonide 200 or 400 microg or placebo for 6 weeks. Patients initially receiving 400 microg budesonide had their dose reduced to 200 microg (400/200-microg group), and patients receiving 200 microg (200/200-microg group) or placebo continued to receive their assigned doses for a 12-week maintenance phase. HRQL was evaluated using the Asthma Quality of Life Questionnaire at randomization, week 6, and week 18. RESULTS: Compared with placebo, patients initially receiving 400 and 200 microg budesonide Turbuhaler demonstrated significantly greater HRQL scores at week 6 (P < or = 0.001 and P < or = 0.010, respectively) that were maintained at week 18 (P < or = 0.001). Clinically important (> or = 0.5 unit) improvement in Asthma Quality of Life Questionnaire overall at week 18 was demonstrated by 55% and 43% of patients in the 400/200-microg and 200/200-microg budesonide Turbuhaler groups, respectively. CONCLUSIONS: In patients with mild to moderate asthma, once-daily budesonide Turbuhaler 200 and 400 microg demonstrates statistically significant and clinically important improvements in HRQL that can be maintained with a low dose of 200 microg.

Administration, Inhalation↗
PubMed2003

Unresponsive wheezing to asthma therapy in a 32-year-old female.

Repeat failure of any patient to respond to asthma therapy, particularly corticosteroids, should alert physicians to carry out further pulmonary evaluation. This will prevent unnecessary side effects of asthma therapy and provide prompt treatment for other diseases that may require urgent attention.

Adult↗
PubMed2003

Clinically important differences in health-related quality of life for patients with asthma: an expert consensus panel report.

BACKGROUND: Standards for change in health-related quality of life (HRQoL) measures used among asthmatic patients have been established by considering only patient preferences to determine important differences and may not reflect an informed clinical evaluation of change. OBJECTIVE: To establish clinically important difference (CID) standards through the consensus of an expert physician panel for the Juniper Asthma Quality of Life Questionnaire (AQLQ) and Medical Outcomes Study Short-Form 36-Item Health Survey (SF-36, version 2) when used to measure HRQoL among asthmatic patients. METHODS: We organized an 8-person panel of physicians familiar with measuring HRQoL among asthmatic patients with the AQLQ and the SF-36. This expert panel participated in 2 rounds of a modified Delphi process before attending an in-person consensus meeting to establish the CID standards for small, moderate, and large changes in the AQLQ and the SF-36. After the consensus meeting, the panel used an iterative improvement process to cooperatively complete their final report. RESULTS: The expert panel's thresholds for detecting CIDs in the domains of the AQLQ were much higher than previously established levels using patient-perceived changes. CIDs for asthma were also ascertained on the scales of the SF-36, version 2, which were markedly greater than previously cited cross-sectional differences between patient groups. CONCLUSIONS: The CID standards established by this expert panel elucidate a potential distinction between patient and physician perspectives of important HRQoL changes. The many stakeholders of HRQoL difference standards should consider this distinction when adopting standards to evaluate patient change.

Asthma↗
PubMed2003

Efficacy and safety of fluticasone propionate 44 microg/salmeterol 21 microg administered in a hydrofluoroalkane metered-dose inhaler as an initial asthma maintenance treatment.

BACKGROUND: We wanted to evaluate whether treatment with an inhaled corticosteroid and an inhaled long-acting beta2-agonist is more effective than an inhaled corticosteroid alone for patients using as-needed albuterol who are initiating maintenance treatment. OBJECTIVE: To compare the efficacy and safety of twice-daily fluticasone propionate (FP) 88 microg and salmeterol 42 microg combined in a chlorofluorocarbon (CFC)-free (hydrofluoroalkane 134a) metered-dose inhaler (MDI) with the individual agents alone, each delivered through an MDI containing CFC propellants, in patient with persistent asthma previously uncontrolled with as-needed short-acting beta2-agonists alone. METHODS: Patients with asthma (n = 283) were randomized to twice-daily treatment for 12 weeks with FP 88 microg combined with salmeterol 42 microg (FSC) in a CFC-free MDI or the individual components alone from CFC-containing MDIs. RESULTS: At endpoint, mean change from baseline in morning predose forced expiratory volume in 1 second was significantly (P < or = 0.016) greater with FSC (0.69 L) compared with FP (0.51 L) or salmeterol (0.47 L). Fewer patients treated with FSC withdrew due to worsening asthma (1%) compared with FP (3%) or salmeterol (8%; P = 0.024). FSC significantly increased (P < or = 0.002) morning and evening peak expiratory flow rate at endpoint (66.5 and 51.5 L/min, respectively) compared with FP (43.0 and 29.9 L/min, respectively) and salmeterol (29.2 and 21.6 L/min, respectively). In addition, asthma symptom scores were reduced, and percentages of days with no asthma symptoms increased in all treatment groups. CONCLUSIONS: Treatment with FSC in a CFC-free MDI is more effective than FP or salmeterol alone in asthma patients who are symptomatic taking short-acting beta2-agonists alone.

Administration, Inhalation↗
PubMed2003

Advances in upper airway diseases and allergen immunotherapy.

Epidemiologic studies continue to find an increased prevalence of rhinitis, asthma, and atopy in more westernized countries. Both allergic and nonallergic rhinitis are risk factors for development of asthma, particularly in adulthood. In patients who have both asthma and rhinitis, treatment of the latter decreases the likelihood of emergency department visits or hospitalization for asthma. The protective effect of intranasal cortico-steroids is much greater than that of antihistamines. This mirrors the effect on rhinitis symptoms, in which nasal corticosteroids are much more effective than antihistamines, leukotriene receptor antagonists, or the combination of both. In patients with severe asthma, sinus mucosal thickening on computed tomography (CT) correlates with the severity of lower airway disease indicated by sputum eosinophilia, exhaled nitrous oxide (NO), functional residual capacity, and diffusing capacity. Preseasonal specific immunotherapy (SIT) is less effective, but additive to treatment with omalizumab. It is also somewhat less effective in reducing nasal symptoms than nasal corticosteroids; however, it is superior to them for reducing lower airway inflammation. SIT in children with only allergic rhinitis reduces both the incidence of asthma and bronchial hyperresponsiveness to methacholine. High-dose sublingual immunotherapy appears to be safe and effective, but less effective than injection immunotherapy. It is not clear that there are cost savings with sublingual immunotherapy, as home administration savings may be offset by the much larger amount of allergen extracts required. New approaches to allergen immunotherapy, designed to increase efficacy and safety, include conjugation of allergens to immunostimulatory sequences and encapsulation in liposomes. Cross-reactivity between inhalants and foods demonstrated by skin prick tests is more predictive of clinically important sensitivity than is that demonstrated by RAST testing. The latter, because of cross-reacting profilins, is often clinically irrelevant.

Administration, Sublingual↗
PubMed2003

Enhanced synergy between fluticasone propionate and salmeterol inhaled from a single inhaler versus separate inhalers.

BACKGROUND: The coadministration of long-acting inhaled beta(2)-agonists and inhaled corticosteroids is the most effective treatment for persistent asthma. OBJECTIVE: This meta-analysis aimed to determine the efficacy of fluticasone propionate and salmeterol inhaled from a single inhaler (combination therapy) or from separate inhalers (concurrent therapy). METHODS: Four similarly designed double-blind studies individually confirmed equivalence between combination and concurrent therapy on the basis of the primary efficacy measure (morning peak expiratory flow [PEF]). Each study showed a consistent trend in favor of combination therapy. Individual patient data from these studies were combined to provide overall estimates of treatment effect for morning PEF and other efficacy measures. RESULTS: Fixed-effects meta-analysis showed a significant advantage for combination therapy compared with concurrent therapy in morning PEF (mean difference between groups in change from baseline over 12 weeks of 5.4 L/min; P =.006; 95% CI = 1.5-9.2). Logistic regression analysis showed that the odds of achieving a greater than 15 or greater than 30 L/min improvement with combination therapy were increased by approximately 40% compared with those after concurrent therapy (15 L/min: odds ratio = 1.42, P =.008, 95% CI = 1.1-1.8; 30 L/min: odds ratio = 1.40, P =.006, 95% CI = 1.1-1.8), representing an additional 7% to 9% and 5% to 14% more patients, respectively, on combination therapy responding compared with those on concurrent therapy. CONCLUSION: The meta-analysis indicates that the fluticasone propionate plus salmeterol combination offers the potential for increased clinical efficacy over concurrent use of the same doses of the same 2 drugs. After administration from a single inhaler, fluticasone propionate and salmeterol might codeposit in the airways. It is hypothesized that this codeposition offers an increased opportunity for synergistic interaction to occur.

Administration, Inhalation↗
PubMed2003

A double-blind, placebo-controlled immunotherapy dose-response study with standardized cat extract.

BACKGROUND: Allergen immunotherapy with doses of cat extract containing approximately 15 microg of the major allergen, Fel d 1, have been proved clinically effective in several double-blind, placebo-controlled studies. However, the maintenance doses used in allergy practice in the United States are often considerably less than this proven dose. OBJECTIVE: The purpose of this investigation was to determine whether maintenance immunotherapy with cat dander extract containing 0.6 microg or 3.0 microg of Fel d 1 was more effective than placebo and similar in efficacy to treatment with extracts containing 15.0 microg Fel d 1, immunologic parameters being used as the outcome. METHODS: Twenty-eight cat-allergic patients were randomly entered, 7 in each group, into a double-blind, placebo-controlled comparison of the immunologic response to treatment with placebo or cat dander extract containing 0.6 microg, 3.0 microg, or 15.0 microg of Fel d 1. Maintenance doses were achieved in 8 visits over a period of 4 weeks through use of a cluster regimen; each subject then received 1 weekly maintenance injection before posttreatment measurements were made. The response to immunotherapy was assessed before immunotherapy and after the first weekly maintenance injection. Studies included responses to titrated skin prick tests to cat extract and an unrelated allergen and serum allergen-specific IgE and IgG4. Titrated nasal challenges were performed with cat extract; measurement of mRNA and secreted cytokines (IL-4, IL-5, and IFN-gamma) was done at 6 hours. Serum cytokines (IL-4, IL-5, IFN-gamma) were measured, and flow cytometric analysis of intracellular cytokines (IL-4, IL-5, IFN-gamma) was performed. Cat allergen-stimulated lymphocyte proliferation was performed with measurement of cytokines in the supernatant (IL-4, IL-5, IFN-gamma). RESULTS: All 28 subjects completed the study. Significant and dose-dependent differences were encountered in the titrated skin prick tests (P =.008), the cat-specific IgG(4) (P =.01), and the reduction in CD4+/IL-4+ PBMCs on flow cytometry (P =.03). There were no significant differences between placebo and cat dander extract containing Fel d 1 0.6 microg. Both extracts containing 3.0 microg and 15.0 microg produced significant decreases in skin prick test sensitivity (P =.02 and P =.002, respectively). The extracts containing 3.0 microg and 15.0 microg produced significant increases in cat-specific IgG4 (P =.01 and P =.006, respectively). Only the 15.0-microg-per-dose extract produced a significant reduction in the percent of CD4+/IL-4+ PBMCs (P =.003). CONCLUSION: In this double-blind, placebo-controlled study, a maintenance dose of cat dander extract containing 15.0 microg Fel d 1 produced the most consistent immunologic response. A dose of 3.0 microg reduced skin prick test sensitivity and increased cat-specific IgG4 but did not reduce the circulating CD4+/IL-4+ PBMCs, a change that is likely related to the clinically significant response to allergen immunotherapy. These findings suggest that a maintenance dose of 15.0 microg of Fel d 1 is most apt to be clinically effective for allergen immunotherapy.

Animals↗
PubMed2003

How ill the wind? Issues in aeroallergen sampling.

The effective size of bioaerosols is the principal determinant of their behavior during takeoff, transport, and deposition. Collection methods involving impaction, impingement, and filtration allow recovery of increasingly small aerosol units and do so "per unit volume of processed air" with more or less well-defined efficiency. These principles offer direction in choosing sampling devices for specific applications; similarly, a particle's appearance, growth potential, and assayability define the scope of relevant analyses. Where a variety of aerosol types occur, multiple collection and/or analytic approaches might be required. The development of a sampling grid in North America makes possible studies of distribution, transport, and climatic effects in ways never previously possible; however, some directive planning and oversight are essential to realize these goals. Methods sensitive to paucimicronic and submicronic particles should be included increasingly in new and ongoing survey protocols. Similarly, available means now facilitate study of aerosols at specific sites, both indoors and outdoors, with estimates of personal exposure during defined events. Resulting data describing airborne prevalence gain special value in light of competent inspection of implicated venues and consideration of alternative sources, such as incursion of bioaerosols into enclosed spaces.

Aerosols↗
PubMed2003

Potential adverse effects of the inhaled corticosteroids.

The purpose of this review is to provide the clinician with an update on the potential adverse effects caused by the inhaled corticosteroids (ICSs). The systemic effects of ICSs are a result of that portion swallowed and absorbed through the gastrointestinal tract and not eliminated by first-pass metabolism and that portion delivered to the lung and absorbed. If administered in high enough doses, any of the ICSs will produce clinically significant systemic activity. This review will explore the risks for clinically significant adverse effects from sustained use of ICSs, as recommended by the current guidelines. The standard method for assessing systemic activity in short-term studies is measurement of hypothalamic-pituitary-adrenal axis function. The ICSs provided in the medium dose range can produce measurable effects on the hypothalamic-pituitary-adrenal axis. However, clinically significant suppression is unlikely to occur except at high doses. The effect on growth in children over 1 to 4 years occurs at low to medium doses, might be dependent on the specific ICS, and is small (1-2 cm). The data are insufficient to determine whether there is an effect on attainment of predicted adult height. The ICSs affect bone mineral density and risk of fractures in a dose-dependent fashion that appears significant at high doses.

Administration, Inhalation↗
PubMed2002

Measurement of changes in mRNA for IL-5 in noninvasive scrapings of nasal epithelium taken from patients undergoing nasal allergen challenge.

Nasal allergen challenge of patients with allergic rhinitis results in increased numbers of inflammatory cells and increased production of pro-inflammatory cytokines including interleukin 5 (IL-5). We report a sensitive, noninvasive method to measure changes in the amount of mRNA for IL-5 in nasal epithelium and have used this method to detect alterations of IL-5 mRNA from patients undergoing a nasal allergen challenge. Ten grass or ragweed allergic adults were challenged out of season with appropriate pollen extracts at sufficient dose to give a rhinitis total symptom score of 5 on a scale of 12. After allergen exposure, symptoms were recorded hourly. At 0, 3, and 6 h after allergen exposure, secreted proteins were collected on filter paper strips and two superficial scrapings of nasal epithelium were obtained. The scrapings of epithelium were immediately immersed in 100 microl of RNAlater (Ambion, Austin, TX) and stored at 4 degrees C for up to 1 month without loss of RNA quality. Total RNA was isolated and RT-PCR was performed. cDNA for IL-5 was then measured by real-time fluorescence quantitative PCR with Pre-Developed TaqMan Assay Reagents (PE Biosystems, Foster City, CA). Sufficient RNA was isolated from eight subjects to measure IL-5 mRNA. Data were normalized for content of ribosomal RNA. The relative amount of cDNA for IL-5 was calculated by comparison with internal standards prepared from phytohemagluttinin-stimulated peripheral blood mononuclear cells. Messenger RNA for IL-5 was increased 8.7+/-2.7-fold at 3 h (p<0.01) and 39.5+/-20.9-fold at 6 h (p<0.01). Increased IL-5 mRNA levels at 6 h closely correlate with total symptom scores at 6 h (r=0.88; p=0.007). IL-5 protein was measured by ELISA in eluates from the filter papers. At 6 h, there was increased IL-5 protein (7.7+/-2.8 ng/ml) compared with time zero (1.8+/-0.5 ng/ml) (p=0.02). The levels of IL-5 protein did not correlate significantly with the symptoms score or with changes in the levels of IL-5 protein with IL-5 mRNA. These data show that changes in IL-5 mRNA in patients with allergic rhinitis undergoing an allergen challenge correlate with total symptom scores better than changes in IL-5 protein eluted from filter paper. Furthermore, these changes can be measured quantitatively in very small amounts of tissue.

Adult↗
PubMed2002

Evaluation of cytokines in nasal secretions after nasal antigen challenge: lack of influence of antihistamines.

BACKGROUND: Previous studies of inflammation in allergic rhinitis using nasal irrication have been unsatisfactory because of 1) poor reproducibility; 2) the tendency of irrigation to overdilute mediators; and 3) the failure of this technique to evaluate interstitial concentrations of relevant mediators. For this study we used filter paper as a matrix to collect nasal secretions in patients undergoing nasal antigen challenge. OBJECTIVE: To evaluate inflammatory mediators of allergen-induced rhinitis during a clinical trial of fexofenadine. METHODS: Subjects evaluated at a referral medical center were placed on traditional dosing of fexofenadine at 60 mg, twice daily, or placebo in a double-blind, crossover fashion for 1 week before the nasal challenge. Nasal challenge was performed with nasal insufflation of either 1,000 AU timothy or 0.1 mL ragweed (1:100 wt/vol) extract outside the pollen season. Nasal secretions were collected at baseline and then at 2, 4, and 6 hours after nasal challenge. Secretions were evaluated for expression of the cellular adhesion molecule-1, tumor necrosis factor (TNF)-alpha, interleukin (IL)-4, IL-10, macrophage inflammatory protein (MIP)-1alpha, and granulocyte-macrophage colony-stimulating factor (GM-CSF) using commercially available enzyme-linked immunoadsorbent assay kits. Patients' symptom scores were evaluated during the nasal challenge. RESULTS: Significantly (P < 0.05) increased peak levels of TNF-alpha, IL-4, IL-10, and MIP-1alpha were detected after antigen challenge as compared with baseline levels. There was a nonsignificant trend toward an increase in GM-CSF after antigen challenge (P = 0.07). There was no difference in the peak levels of TNF-alpha, IL-4, IL-10, MIP-1alpha, or GM-CSF measured when patients were on fexofenadine versus placebo. Finally, there were no significant differences in patients' symptom scores during antigen challenge when subjects were on fexofenadine versus placebo. CONCLUSIONS: Collection of nasal secretions using a filter paper matrix provides a reproducible model for accurately detecting and evaluating changes in cytokine levels after nasal challenge. Cytokine levels tend to peak 3 to 4 hours after antigen challenge. Standard doses of fexofenadine do not seem to have a mitigating effect on the production of these cytokines. Symptoms of allergic rhinitis using this type of antigen challenge did not differ from treatment with fexofenadine versus placebo.

Adolescent↗
PubMed2002

Single isomer versus racemate: is there a difference? Clinical comparisons in allergy and gastroenterology.

Many commonly prescribed drugs exist as a mixture of two distinct chiral isomer forms (enantiomers), each with its own unique chemistry, receptor affinity, and pharmacokinetic profile. Much is unknown concerning the clinical utility of these single enantiomers. This review of the stereoisomers of two commonly used drugs--albuterol for asthma and omeprazole for gastroesophageal reflux disease (GERD) and peptic ulcers--examines the improved efficacy, pharmacokinetics, decreased adverse effects, and fewer drug-drug interactions associated with single enantiomers.

Journal Article↗