Leukotriene B4 levels in sputum from asthma patients.

Poor asthma control is associated with increased airway neutrophils. Leukotriene B4 (LTB4) is a potent neutrophil chemoattractant. We examined the levels of LTB4 levels in the sputum of asthma patients and the relationship with disease severity. 47 asthma patients (categorised according to Global Initiative for Asthma treatment stage) and 12 healthy controls provided sputum samples that were processed first with PBS to obtain supernatants and secondly with dithiothreitol (DTT) to obtain supernatants. LTB4 levels were determined by ELISA. LTB4 levels were significantly higher in step 1 (steroid naïve) and step 3 (inhaled corticosteroid (ICS) plus long acting ß-agonist) patients than step 2 patients (ICS alone) (p=0.02 and p=0.01, respectively). There was very good correlation when comparing PBS processed to DTT processed supernatants. High LTB4 levels were found in the sputum of asthmatics at step 3 despite ICS use.

Repeatability of induced sputum measurements in moderate to severe asthma.

BACKGROUND: Novel therapies are being developed for patients with moderate to severe asthma. These patients may have neutrophilic airway inflammation. Induced sputum is commonly used as an endpoint in clinical trials of asthma therapies. We have performed repeated induced sputum sampling in moderate to severe asthma patients to understand the variability of cell counts, including neutrophils, and performed power calculations for studies in this group of patients. METHODS: Nineteen patients with moderate to severe asthma with evidence of airflow obstruction (FEV1 ≤ 80% predicted) and suboptimal control (ACQ ≥ 1) performed repeated induced sputum separated by 1 month. RESULTS: The Ri of neutrophil percentage and absolute eosinophil count demonstrated good (0.61) and moderate (0.56) repeatability respectively, but there was a poor level of agreement for eosinophil percentage and absolute neutrophil counts. The within subject SD for sputum neutrophil percentage was 15.8. In cross over studies, sample sizes of n = 14 and n = 54 are required to detect changes in neutrophil percentages by 20 and 10 % respectively at 90% power. CONCLUSIONS: Sputum neutrophil percentage has good reproducibility in patients with moderate to severe asthma.

A comparison of the clinical and induced sputum characteristics of early- and late-onset asthma.

BACKGROUND: There are few studies describing the phenotype of late-onset asthma (LOA). We sought to investigate the clinical and induced sputum characteristics of patients with LOA. METHODS: Nineteen patients with LOA diagnosed after the age of 40 years and 19 patients with early-onset asthma (EOA) diagnosed before the age of 20 years were recruited. Subjects performed lung function, reversibility, asthma control questionnaire (ACQ), exhaled nitric oxide (NO), and sputum induction. RESULTS: The FEV(1) % predicted was lower in EOA compared to LOA (87.6 % vs. 103 %, respectively, p = 0.02), while ACQ scores were significantly higher in EOA (1.46 vs. 0.89, respectively, p = 0.03). NO was not different between the groups, but the percentage neutrophil counts were lower in the EOA group compared to the LOA group (36.6 vs. 57.3, respectively, p = 0.02). Asthma duration, but not age, was negatively associated with lung function (r = -0.4, p = 0.01). Neutrophil counts in healthy age-matched controls (n = 10) were similar to EOA and lower than LOA. CONCLUSION: Raised sputum neutrophils in LOA are not an indicator of severe disease and could be a characteristic feature of this asthma phenotype. Duration of asthma influences lung function.