Sputum mast cell subtypes relate to eosinophilia and corticosteroid response in asthma.

Mast cells are a resident inflammatory cell of the airways, involved in both the innate and adaptive immune response. The relationship between mast cells and inflammatory phenotypes and treatment response of asthma is not clear.Clinical characteristics of subjects with stable asthma (n=55), inflammatory cell counts and gene expression microarrays in induced sputum were analysed.

Biomarker-based asthma phenotypes of corticosteroid response.

Background: Asthma is a heterogeneous disease with different phenotypes. Inhaled corticosteroid (ICS) therapy is a mainstay of treatment for asthma, but the clinical response to ICSs is variable.

Objective: We hypothesized that a panel of inflammatory biomarkers (ie, fraction of exhaled nitric oxide [Feno], sputum eosinophil count, and urinary bromotyrosine [BrTyr] level) might predict steroid responsiveness.

Sputum gene expression signature of 6 biomarkers discriminates asthma inflammatory phenotypes.

Background: Airway inflammation is associated with asthma exacerbation risk, treatment response, and disease mechanisms.

Objective: This study aimed to identify and validate a sputum gene expression signature that discriminates asthma inflammatory phenotypes.

Methods: An asthma phenotype biomarker discovery study generated gene expression profiles from induced sputum of 47 asthmatic patients.

Asthma phenotypes: consistency of classification using induced sputum.

Background And Objective: Asthma can be classified as eosinophilic or non-eosinophilic based on the cell profile of induced sputum. This classification can help determine whether corticosteroid treatment is indicated. We assessed the stability of these phenotypes over time and with different treatment regimens.

Predicted versus absolute values in the application of exhaled nitric oxide measurements.

Background: Constitutional factors such as age, sex and height, and acquired factors such as atopy and smoking, influence exhaled nitric oxide (F(E)NO) levels. The utility of predicted values based on reference equations which account for these factors has not been evaluated.

Aim: To compare the performance characteristics of absolute versus % predicted values for F(E)NO as predictors of diagnosed asthma and steroid response.

Simvastatin in the treatment of asthma: lack of steroid-sparing effect.

Background: Statins have anti-inflammatory actions which in theory are potentially beneficial in asthma. Small trials have failed to show a significant benefit, but a systematic study to evaluate the steroid-sparing effect of statin treatment has not been carried out.

Methods: A randomised, placebo-controlled, crossover trial was conducted of simvastatin 40 mg at night with simultaneous stepwise reduction of fluticasone propionate dose until loss of control occurred, followed by an increase until regain of control ('minimum' dose required) in 51 patients with asthma and sputum eosinophils (steroid-free) ≥ 2%.

Long term performance characteristics of an electrochemical nitric oxide analyser.

Background: The NIOX MINO(®) is a nitric oxide (FE(NO)) analyser based on electrochemical technology. It includes a replaceable sensor. Quality control procedures are recommended, but regular calibration is not possible.

Exercise-induced wheeze: Fraction of exhaled nitric oxide-directed management.

Background And Objective: Exercise-induced wheeze (EIW) is common. Several treatment options exist. Patients with low fraction of exhaled nitric oxide (F(E)NO) are unlikely to be steroid-responsive and might benefit from non-steroidal therapies.

Effects of steroid therapy on inflammatory cell subtypes in asthma.

RATIONALE Airway inflammation in asthma is heterogeneous with different phenotypes. The inflammatory cell phenotype is modified by corticosteroids and smoking. Steroid therapy is beneficial in eosinophilic asthma (EA), but evidence is conflicting regarding non-eosinophilic asthma (NEA).

Outcomes using exhaled nitric oxide measurements as an adjunct to primary care asthma management.

Background: Exhaled nitric oxide (FENO) measurements may help to highlight when inhaled corticosteroid (ICS) therapy should or should not be adjusted in asthma. This is often difficult to judge. Our aim was to evaluate a decision-support algorithm incorporating FENO measurements in a nurse-led asthma clinic.

Bromotyrosines in sputum proteins and treatment effects of terbutaline and budesonide in asthma.

Background: Inhaled corticosteroids are widely used in the treatment of persistent asthma, usually combined with inhaled beta2-agonists. Previous research suggests that short-acting beta2-agonists (SABAs) may downregulate the anti-inflammatory effects of inhaled corticosteroids, thereby increasing asthma morbidity.

Objective: To determine whether 3-bromotyrosine and 3,5-dibromotyrosine levels, specific markers of eosinophil activation, reflect treatment effects on airway inflammation of inhaled corticosteroids and SABAs and support previous conclusions.

Exhaled nitric oxide levels in asthma: Personal best versus reference values.

Background: Factors affecting the fraction of nitric oxide in exhaled air (FE(NO)) are multiple. Interpreting values when assessing airways disease may be problematic. Clinically optimum levels have not been defined.

Predicting corticosteroid response in chronic obstructive pulmonary disease using exhaled nitric oxide.

Rationale: Predicting corticosteroid response in COPD is important but difficult. Response is more likely to occur in association with eosinophilic airway inflammation, for which the fraction of exhaled nitric oxide (Fe(NO)) is a good surrogate marker.

Objectives: We aimed to establish whether Fe(NO) levels would predict the clinical response to oral corticosteroid in COPD.

The association between obesity and asthma: interactions between systemic and airway inflammation.

Rationale: Both obesity and asthma are common conditions, and both are characterized by the presence of inflammation. Animal studies suggest that the development of airway hyperresponsiveness with antigen challenge is exaggerated with obesity. However, clear evidence for either an additive or a synergistic pathologic interaction between obesity and asthma is lacking in humans.

Supporting the diagnosis of non-specific respiratory symptoms in primary care: the role of exhaled nitric oxide measurement and spirometry.

Aims: To assess whether exhaled nitric oxide (FENO) measurements improve management and clinician confidence in patients presenting with non-specific respiratory symptoms.

Methods: This observational study was based in a large primary care practice (15,500 patients, 14 GPs). Patients had non-specific respiratory symptoms for at least six weeks.

Serial exhaled nitric oxide measurements in the assessment of laboratory animal allergy.

Background: Laboratory animal allergy (LAA) may cause eosinophilic airway inflammation, for which exhaled nitric oxide (FE(NO)) measurements are sensitive and specific. Our objective was to assess whether serial FE(NO) measurements might detect exposure-related inflammation in laboratory animal workers. METHODS.

Dynamic hyperinflation with bronchoconstriction: differences between obese and nonobese women with asthma.

Rationale: Symptoms and respiratory function tests may be difficult to assess and interpret in obese patients with asthma, particularly if the asthma is severe. It is unclear whether the dynamic changes that occur during bronchoconstriction differ between obese versus nonobese patients with asthma.

Objectives: To explore whether the changes in airway caliber and lung volumes that occur with acute bronchoconstriction are different in obese and nonobese patients with asthma and whether any differences contribute to the quality and intensity of symptoms.

Association between exhaled nitric oxide and systemic inflammatory markers.

Background: Asthma is an inflammatory condition of the airways, and there is some evidence to suggest that it is associated with a systemic inflammatory response, as measured by C-reactive protein (CRP) and fibrinogen. Exhaled nitric oxide is a noninvasive measure of asthmatic airway inflammation.

Objective: To determine if there is an association between exhaled nitric oxide and these systemic inflammatory markers.

Factors affecting exhaled nitric oxide measurements: the effect of sex.

Background: Exhaled nitric oxide (F(E)NO) measurements are used as a surrogate marker for eosinophilic airway inflammation. However, many constitutional and environmental factors affect F(E)NO, making it difficult to devise reference values. Our aim was to evaluate the relative importance of factors affecting F(E)NO in a well characterised adult population.

Association between exhaled nitric oxide and systemic inflammatory markers.

Background: Asthma is an inflammatory condition of the airways, and there is some evidence to suggest that it is associated with a systemic inflammatory response, as measured by C-reactive protein (CRP) and fibrinogen. Exhaled nitric oxide is a noninvasive measure of asthmatic airway inflammation.

Objective: To determine if there is an association between exhaled nitric oxide and these systemic inflammatory markers.

Associations between respiratory symptoms, lung function and gastro-oesophageal reflux symptoms in a population-based birth cohort.

Background: Several studies have reported an association between asthma and gastro-oesophageal reflux, but it is unclear which condition develops first. The role of obesity in mediating this association is also unclear. We explored the associations between respiratory symptoms, lung function, and gastro-oesophageal reflux symptoms in a birth cohort of approximately 1000 individuals.

Bronchodilator response in relation to beta2-adrenoceptor haplotype in patients with asthma.

Rationale: Genetic variation of the beta2-adrenoceptor (ADRB2) influences receptor function in vitro. There are reports that, in vivo, bronchodilator response is related to ADRB2 genotype, and that clinical outcomes during chronic therapy with beta2-agonist drugs are also influenced by genotype. Whether these features are related to single nucleotide polymorphisms or to combinations (haplotypes) is unclear.

Use of exhaled nitric oxide measurements to guide treatment in chronic asthma.

Background: International guidelines for the treatment of asthma recommend adjusting the dose of inhaled corticosteroids on the basis of symptoms, bronchodilator requirements, and the results of pulmonary-function tests. Measurements of the fraction of exhaled nitric oxide (FE(NO)) constitute a noninvasive marker that may be a useful alternative for the adjustment of inhaled-corticosteroid treatment.

Methods: In a single-blind, placebo-controlled trial, we randomly assigned 97 patients with asthma who had been regularly receiving treatment with inhaled corticosteroids to have their corticosteroid dose adjusted, in a stepwise fashion, on the basis of either FE(NO) measurements or an algorithm based on conventional guidelines.

Exhaled nitric oxide: a predictor of steroid response.

Rationale: The initial management of patients who present with persistent respiratory symptoms includes recognizing those with the potential to benefit from inhaled steroid therapy. To date, this has required undertaking a "trial of steroid" to identify responders. There is increasing evidence that steroid response is more likely in patients with eosinophilic airway inflammation, and this can be assessed indirectly using exhaled nitric oxide (FENO) measurements.

Sex differences in factors associated with childhood- and adolescent-onset wheeze.

Rationale: Factors predicting the development of wheeze may differ between sexes and between childhood and adolescence.

Methods: A New Zealand birth cohort of 1,037 children was followed to age 26. For this analysis, those reporting recurrent wheezing at two or more assessments were classified as "wheezers.