Local and systemic immunological parameters associated with remission of asthma symptoms in children.

The immunological and clinical parameters that are associated with asthma remission are poorly understood. The cytokine and local mediator changes associated with the resolution of asthma symptoms were examined in three groups of subjects 12-18 years of age (n = 15 in each group): (a) continuing asthma group (CA) who had persistent symptoms since early childhood, (b) an age, sex and atopic status-matched group who had persistent symptoms in early childhood but in whom these had resolved (RA), and (c) a non-atopic, non-asthmatic control group. Clinical parameters, sputum cell counts, peripheral blood mononuclear cell (PBMC) cytokine production and activation marker expression were determined.

Impact of intranasal budesonide on immune inflammatory responses and epithelial remodeling in chronic upper airway inflammation.

Background: Histologic and immunohistologic features of nasal polyps (NP) are similar to those observed in asthma, thus suggesting a similar immunopathology.

Objective: The primary objective of this study was to further understand the anti-inflammatory and immunoregulatory effects of locally delivered corticosteroids. To this end, the effect of intranasal budesonide on the expression of specific cytokines, lymphocyte subsets, and epithelial remodeling in this model of airway tissue inflammation were studied.

Eosinophil activation in the tissue: synthetic steroid, budesonide, effectively inhibits the survival of eosinophils isolated from peripheral blood but not nasal polyp tissues.

We investigated the effect of a potent synthetic steroid, budesonide (BUD), on the survival of nasal polyp (NP) derived eosinophils (EOS). BUD, at the highest dose used, 10(-6) M, decreased this survival but only by approximately one third. We speculated that the relatively small inhibitory effect of budesonide on the survival of NP-EOS could be the result of these EOS being exposed to substantial amounts of GM-CSF, IL-5 or IL-3.

Efficacy and tolerability of fluticasone propionate nasal drops 400 microgram once daily compared with placebo for the treatment of bilateral polyposis in adults.

Background: Chronic eosinophilic rhinosinusitis underlies a range of respiratory disorders including nasal polyposis. Surgical and medical methods are used to control polyps, with topical steroids commonly being used for their anti-inflammatory properties. Fluticasone propionate nasal drops (FPND) is a formulation developed specifically for an effective and well tolerated corticosteroid treatment of nasal polyposis.

TNF-alpha dysregulation in asthma: relationship to ongoing corticosteroidtherapy.

Background: Tumour necrosis factor-alpha (TNF-alpha) is a major proinflammatory cytokine that is thought to be important in the pathogenesis of asthma. However, alterations in systemic regulation of this cytokine in asthma have not been examined in the context of corticosteroid therapy.

Objectives: To examine the ability of peripheral blood mononuclear cells (PBMC) from three different groups of patients with asthma requiring varying amounts of inhaled corticosteroids (ICS) for clinical control, and to examine cells from age- and sex-matched nonasthmatic patients to produce TNF-alpha.

Prednisone-dependent asthma: inflammatory indices in induced sputum.

The kinetics of changes in inflammatory indices in induced sputum from eight prednisone dependent asthmatics whose minimum clinical maintenance and exacerbation doses were known were investigated. The study began on the last day of a course of 30 mg prednisone daily for one week. Thereafter, the daily prednisone was reduced in a structured way to below the maintenance dose.

Nonasthmatic chronic cough: No effect of treatment with an inhaled corticosteroid in patients without sputum eosinophilia.

Background: Inhaled corticosteroids are effective in suppressing a chronic cough without asthma associated with sputum eosinophilia.

Objective: To investigate the inflammatory characteristics in the induced sputum of patients with a chronic cough without asthma or known cause and the effects of budesonide treatment on chronic cough in those patients.

Patients And Methods: Forty-four adults (mean [minimu, maximum] age of 45 years [20,75], 28 women, 17 atopic subjects and 32 nonsmokers], with a daily bothersome cough for at least one year and who had no evidence of asthma or other known cause for the cough, were consecutively enrolled.

Diagnosing occupational asthma: use of induced sputum.

The diagnosis of occupational asthma (OA) needs to be made with as much objective evidence as possible. If there is airway inflammation, measurement of this should be an asset. The objective of this study was to investigate whether there is an increase in induced sputum and blood eosinophils and eosinophil cationic protein (ECP) in OA after work exposure.

Comparison of budesonide Turbuhaler with budesonide aqua in the treatment of seasonal allergic rhinitis. Rhinocort Study Group.

Objective: To compare the effect of budesonide Turbuhaler 400 microg/day with budesonide aqua 256 microg/day in the treatment of seasonal allergic rhinitis (SAR). Secondarily to ascertain patients' preferences for the two nasal devices and to assess quality of life.

Design: Randomized, multicentre, double-blind, double- dummy, parallel groups study.

Sputum eosinophilia predicts benefit from prednisone in smokers with chronic obstructive bronchitis.

A reliable predictor of benefit from corticosteroid treatment in patients with chronic airflow limitation is needed. In a single-blind, sequential crossover trial of placebo and prednisone (30 mg/day) treatment, with each given for 2 wk, we investigated whether an increased proportion of sputum eosinophils (>= 3%) predicts a beneficial effect of prednisone in smokers with severe obstructive bronchitis. Patients were seen before and after each treatment.

Asthma and natural colds. Inflammatory indices in induced sputum: a feasibility study.

We examined the feasibility of using induced sputum to evaluate the airway inflammatory response to natural acute respiratory virus infections. We recruited eight asthmatics and nine healthy subjects on Day 4 of a cold. Viral infection was confirmed in six of the asthmatics (influenza A or B) and six of the healthy subjects (influenza A, rhinovirus, adenovirus, respiratory syncytial virus, and coronavirus).

Induced sputum, bronchoalveolar lavage and blood from mild asthmatics: inflammatory cells, lymphocyte subsets and soluble markers compared.

Airway inflammation in asthma can be measured directly by invasive bronchoalveolar lavage (BAL), directly and relatively noninvasively by induced sputum and indirectly from peripheral blood. We compared cellular and fluid phase indices of inflammation in induced sputum, BAL and blood from 11 adults with mild stable asthma. On one day, induced sputum selected from saliva was collected and on the next, blood and BAL.

Clinical and nasal irrigation fluid findings in perennial allergic rhinitis.

Ten patients with perennial allergic rhinitis and 10 healthy subjects were studied to determine most discriminative nasal irrigation fluid marker(s) and to compare samples that were collected at baseline and over a 1-hour period, every 15 minutes. The latter were pooled and designated 1-hour sample. In the nasal irrigation we investigated the following inflammatory cells and soluble mediators: eosinophils, neutrophils, granulocyte-macrophage colony-stimulating factor, interleukin-4, interleukin-6, interleukin-8, ECP, EPX, MPO, leukotriene C4, leukotriene B4, prostaglandin E2, tryptase and fibrinogen.

Markers of inflammation in induced sputum in acute bronchitis caused by Chlamydia pneumoniae.

Little is known of the inflammatory characteristics of acute infections of the respiratory tract caused by virus and unusual bacteria such as Chlamydia pneumoniae. A case is reported in whom inflammatory indices in sputum were used to investigate, for the first time, the airway inflammation during an episode of acute bronchitis caused by C pneumoniae. The patient presented with a dry cough of five days duration.

Stem cell factor in nasal polyposis and allergic rhinitis: increased expression by structural cells is suppressed by in vivo topical corticosteroids.

Background: Mast cells are increased in nasal polyp (Np) and allergic rhinitis (AR) tissue and are suppressed by topical corticosteroid treatment. Stem cell factor (SCF), a mast cell growth and survival factor, may explain these phenomena.

Objective: We investigated structural cell gene expression and production of SCF in nasal tissues in patients who had received and who had not received in vivo intranasal corticosteroid therapy.

Induced sputum cell and fluid-phase indices of inflammation: comparison of treatment with dithiothreitol vs phosphate-buffered saline.

Treatment of sputum with dithiothreitol (DTT) gives reliable measurements of cellular and fluid-phase markers of airway inflammation. We investigated the extent to which DTT treatment influences these measurements as compared with phosphate-buffered saline (PBS). Hypertonic saline-induced sputum, collected from 20 asthmatic subjects, was examined within 2 h.

Sputum in severe exacerbations of asthma: kinetics of inflammatory indices after prednisone treatment.

We have investigated the time-course of symptoms, forced expiratory volume in one second (FEV1), and the airway inflammatory changes in sputum selected from saliva and blood of 10 patients with severe exacerbation of asthma betwen presentation and after 1, 2, 3, 7, and 21 days of treatment. The sputum was induced by a modified standard protocol, and we examined its safety. The severe exacerbation of asthma was defined by the presence of nocturnal symptoms disturbing sleep and/or the need for inhaled short acting beta2-agonist > or = 8 puffs/d and an FEV1 after bronchodilator < 60% of predicted.

Occupational sensitization to lactase.

Occupational sensitization to lactase is reported in workers formulating and packaging this consumer product, which is used for the relief of gastrointestinal symptoms caused by intolerance to lactose. Allergic rhinitis, conjunctivitis, and some cases of asthma were noted. There was suggestive evidence that atopic individuals may be at greater risk of sensitization.

Measuring airway inflammation in asthma: eosinophils and eosinophilic cationic protein in induced sputum compared with peripheral blood.

Background: Airway eosinophilic inflammation is a characteristic feature of asthma. This can be assessed directly by measurement of eosinophils and eosinophilic cationic protein (ECP) in sputum or indirectly by measurement of the same markers in blood. We investigated the performance of these markers of airway eosinophilic inflammation in a population of patients with asthma compared with control subjects and the extent to which the markers differed.

Spontaneous and induced sputum to measure indices of airway inflammation in asthma.

Inhalation of hypertonic saline to induce sputum may alter cells and fluid-phase markers in sputum. We have compared indices of inflammation in sputum produced spontaneously with sputum induced by an aerosol of hypertonic saline. Twenty-three asthmatics produced spontaneous followed by induced sputum on the same day.

Isolated late asthmatic reaction after exposure to a high-molecular-weight occupational agent, subtilisin.

High-molecular-weight agents generally induce immediate asthmatic reactions. We report the case of a subject who experienced a reaction that started after the first hour following exposure to subtilisin, a high-molecular-weight occupational agent. Any occurrence of immediate reaction was ruled out by measuring both FEV1 and lung volumes every 10 min in the first hour.

Outcome of specific bronchial responsiveness to occupational agents after removal from exposure.

A decrease in specific bronchial responsiveness (SBR) could occur after removal from exposure to an agent causing occupational asthma as a result of loss of immunologic and/or nonspecific bronchial reactivity (NSBR). We studied 15 subjects with occupational asthma (eight to a high- and seven to a low-molecular-weight agent, isocyanate in all instances), proved by specific inhalation challenges (SIC) done 2 yr or more before. Subjects were reexposed in the same way as in the initial SIC: for subjects who did not react, the exposure was increased until either an asthmatic reaction occurred or a maximum of 2 h was reached.

Indices of airway inflammation in induced sputum: reproducibility and validity of cell and fluid-phase measurements.

Methods to examine sputum for indices of airway inflammation are evolving. We have examined the repeatability and the validity of an improved method to measure sputum cells and fluid-phase eosinophil cationic protein (ECP), major basic protein (MBP), eosinophil-derived neurotoxin (EDN), albumin, fibrinogen, tryptase, and interleukin-5 (IL-5). Sputum was induced with hypertonic saline twice within 6 d in 10 healthy subjects, 19 stable asthmatics, and 10 smokers with nonobstructive bronchitis.