PubMed Health⌕ Search
Home/Archive/PubMed

PubMed · 9363113

New developments in bronchodilator therapy.

H S Nelson
View original source ↗Export metadata ↓

Abstract

Generally favorable literature was published regarding the contributions of bronchodilators to asthma therapy. Analysis of asthma mortality data suggested that the risk of death from asthma was primarily associated with the use of fenoterol rather than beta-adrenergic bronchodilators as a class, or reflected the severity of the underlying asthma, which resulted in increasing beta-agonist use. Salmeterol was shown to outperform oral beta-adrenergic agonists and individual dose-titrated theophylline in controlling asthma symptoms while causing fewer adverse effects. When salmeterol was added to low-dose inhaled corticosteroids, the combination outperformed moderate-dose inhaled corticosteroids alone. Regular use of salmeterol, but not albuterol, improved the quality of life for patients with asthma to a clinically significant degree. Finally, theophylline, at relatively low blood levels, was clearly shown to improve asthma control, even in patients receiving moderately high-dose inhaled corticosteroids. More importantly, this symptomatic response was accompanied by decreases in activated lymphocytes, eosinophils, and proinflammatory cytokines in bronchial biopsy results.

Explore related subjects

Administration, InhalationAdministration, OralAdrenal Cortex HormonesAdrenergic beta-AgonistsAlbuterolAsthmaBiopsyBronchiBronchodilator AgentsCause of DeathCytokinesDrug CombinationsEosinophilsFenoterolHumansLymphocytesQuality of LifeRisk FactorsSalmeterol XinafoateTheophyllineJournal ArticleReview

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

H S Nelson. 1996. New developments in bronchodilator therapy.. https://pubmed.ncbi.nlm.nih.gov/9363113/

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related citations

PubMed2002

On the inappropriateness of an EM algorithm based procedure for blinded sample size re-estimation.

When planning a clinical trial the sample size calculation is commonly based on an a priori estimate of the variance of the outcome variable. Misspecification of the variance can have substantial impact on the power of the trial. It is therefore attractive to update the planning assumptions during the ongoing trial using an internal estimate of the variance. For this purpose, an EM algorithm based procedure for blinded variance estimation was proposed for normally distributed data. Various simulation studies suggest a number of appealing properties of this procedure. In contrast, we show that (i) the estimates provided by this procedure depend on the initialization, (ii) the stopping rule used is inadequate to guarantee that the algorithm converges against the maximum likelihood estimator, and (iii) the procedure corresponds to the special case of simple randomization which, however, in clinical trials is rarely applied. Further, we show that maximum likelihood estimation leads to no reasonable results for blinded sample size re-estimation due to bias and high variability. The problem is illustrated by a clinical trial in asthma.

Administration, Inhalation↗
PubMed2002

IgG antibody responses to an inhaled antigen in horses with "heaves" (recurrent airway obstruction).

A controlled experimental system for the evaluation of pulmonary immune responses in horses with "heaves" (recurrent airway obstruction) has been developed. We hypothesized that the humoral immune response to an inhaled antigen in diseased horses would be different from that of healthy horses and that chronic pulmonary inflammation would bias the production of IgG isotypes in diseased horses as compared to healthy horses. Healthy and affected horses were housed in a natural challenge environment (stabled, fed dusty hay) and exposed by inhalation, to a nebulized solution of keyhole limpet hemocyanin (KLH). Sera and bronchoalveolar lavage fluids (BALFs) were collected from horses prior to and following their inhalation exposure to the antigen. Differential cell counts were performed on the cells in the BALF. An enzyme-linked immunosorbent assay (ELISA) was used to determine the concentrations of IgGa, IgGb, IgG(T) and combined IgG specific for KLH in the sera and BALF. The percentages of neutrophils in the BALF of diseased horses were increased 4-6-fold over healthy horses. Combined IgG specific for KLH was significantly greater in BALF and serum from healthy compared to diseased horses. Differences in isotypes were also evident; however, only IgGb specific for KLH in the BALF was significantly increased in healthy versus diseased horses. Possible explanations for this difference include: (1) increased destruction of antigen before it could interact with lymphocytes, (2) down-regulation of IgGb production by inhibitory cytokines in diseased horses, or (3) binding of IgGb to Fc receptors on the large numbers of neutrophils in the lungs of diseased horses. In contrast to the prevailing notion that horses with heaves have exaggerated immune responses, our data suggest that diseased horses exposed to an aerosolized protein mount weaker IgG responses compared to healthy horses.

Administration, Inhalation↗
PubMed2002

Toll-like receptor 4 mediates innate immune responses to Haemophilus influenzae infection in mouse lung.

Toll-like receptors (TLRs) have been implicated in the regulation of host responses to microbial Ags. This study characterizes the role of TLR4 in the innate immune response to intrapulmonary administration of Haemophilus influenzae in the mouse. Two different strains of mice efficiently cleared aerosolized H. influenzae concurrent with a brisk elaboration of IL-1beta, IL-6, TNF-alpha, macrophage-inflammatory protein (MIP)-1alpha, and MIP-2 in bronchoalveolar lavage and a corresponding mobilization of intrapulmonary neutrophils. Congenic strains of mice deficient in TLR4 demonstrated a substantial delay in clearance of H. influenzae with diminished IL-1beta, IL-6, TNF-alpha, MIP-1alpha, and MIP-2 in bronchoalveolar lavage and a notable absence of intrapulmonary neutrophils. In TLR4-expressing animals, but not TLR4-deficient animals, TNF-alpha and MIP-1alpha expression was up-regulated in epithelial cells of the conducting airway in response to H. influenzae which was preceded by an apparent activation of the NF-kappaB pathway in these cells based on the findings of decreased overall IkappaB and an increase in its phosphorylated form. This study demonstrates a critical role of TLR4 in mediating an effective innate immune response to H. influenzae in the lung. This suggests that the airway epithelia might contribute to sensing of H. influenzae infection and signaling the innate immune response.

Administration, Inhalation↗