Rate Of Pulmonary Exacerbations Research Articles

Long-acting ??-agonists: anti-inflammatory properties and synergy with corticosteroids in asthma

Contemporary asthma management calls for combination inhaled corticosteroid (ICS) and long-acting beta-agonist (LABA) for patients with moderate to severe persistent asthma. This combination has consistently shown superior clinical efficacy compared with monotherapy with higher doses of ICS. It is unclear whether ICS and LABA act additively because of their complementary mechanisms of action, or whether they act synergistically based on possible favorable interactions between them. The purpose of this review is to summarize research findings on the anti-inflammatory activity of LABA published since October 2002 and to speculate on how these findings will affect future asthma management recommendations. Combination ICS plus LABA consistently demonstrates superiority over ICS monotherapy in clinical outcomes such as pulmonary function, symptoms, and exacerbation rates, and is consistent with definitive data published before the review period. However, investigations into possible effects of LABA on inflammatory mediators are preliminary. Positive effects of LABA on some serum and bronchial inflammatory measures have been observed, but the clinical importance of these findings has not been established. Current asthma treatment recommendations are based on clinical trials demonstrating improved clinical outcomes of combination ICS plus LABA over ICS alone. Whether LABA possesses clinically important benefits beyond bronchodilation remains to be established. Distinguishing anti-inflammatory activity of LABA will help define optimal long-term treatment regimens for asthma that not only improve pulmonary function, symptoms, and exacerbation rates but also protect against airway remodeling.

230 Factors associated with increased rate of CF pulmonary exacerbations in the South and West of England

230 Factors associated with increased rate of CF pulmonary exacerbations in the South and West of England

The Effect of Pregnancy on Survival in Women With Cystic Fibrosis

Patients with cystic fibrosis (CF) are currently living to their fourth decade and are making reproductive decisions. Information concerning the reproductive health of women with CF has been limited to small or single-center studies. We conducted a matched parallel-cohort study to assess the impact of pregnancy on the survival of women with CF. A parallel-cohort study included all women > 12 years of age who were enrolled in the US Cystic Fibrosis Foundation National Patient Registry from 1985 to 1997. Six hundred eighty of the 8,136 women in the cohort became pregnant. These 680 women were matched on an index year to 3,327 control women with CF. At the inception of entry into the cohort, women who reported pregnancy were more likely to have had a higher percentage of predicted FEV(1) (67.5% predicted vs 61.7% predicted, respectively; p < 0.001) and a higher weight (52.9 vs 46.4 kg, respectively; p < 0.001). Using Kaplan-Meier survival curves, the 10-year survival rate in pregnant women (77%; 95% confidence interval [CI], 71 to 82%) was higher than in those women who did not become pregnant (58%; 95% CI, 55 to 62%). A separate analysis, matching pregnant patients on FEV(1) percent predicted, age, Pseudomonas aeruginosa colonization, and pancreatic function, obtained similar results. Using Cox proportional hazard modeling to adjust for baseline age, FEV(1) percent predicted, weight, height, and pulmonary exacerbation rate per year, pregnancy was not associated with an increase risk of death. Pregnancy was not harmful in any subgroup including patients with FEV(1) < 40% of predicted or diabetes mellitus. Women with CF who became pregnant were initially healthier and had better 10-year survival rates than women with CF who did not become pregnant. After adjustment for the initial severity of illness, women who became pregnant did not have a significantly shortened survival.

Bolus inhalation of rhDNase with the AERx system in subjects with cystic fibrosis.

Inhaled recombinant human deoxyribonuclease (rhDNase) delivered by nebulizer improves pulmonary function and reduces the rate of pulmonary exacerbations in cystic fibrosis subjects. Standard jet nebulizers are relatively inefficient and require a delivery time of 10-20 min. We conducted an open-label, proof-of-concept study to evaluate whether bolus inhalation of rhDNase with a more efficient delivery system was safe and effective in cystic fibrosis subjects. The AERx system used for this study aerosolized 1.35 mg of rhDNase in three inhalations at a single sitting. The predicted AERx lung dose was approximately 0.68 mg, a dose consistent with lung doses of rhDNase given by jet nebulizer. In our 16 subjects with cystic fibrosis, a mean relative increase in FEV(1) of 7.8% (p < or = 0.001) was observed after 15 days of bolus delivery of rhDNase with the AERx system. The safety profile of rhDNase given as a bolus was similar to that observed with traditional nebulizer delivery. This study demonstrated that bolus inhalation of rhDNase was feasible, reasonably well-tolerated, and associated with improvement in pulmonary function in this small group of cystic fibrosis subjects.

Long term azithromycin in children with cystic fibrosis: a randomised, placebo-controlled crossover trial

The macrolide antibiotic azithromycin has anti-inflammatory properties potentially beneficial in cystic fibrosis. Since findings of open pilot studies seemed to show clinical benefit, we undertook a formal trial. 41 children with cystic fibrosis, aged 8-18 years, and with a median forced expiratory volume in 1 s (FEV1) of 61% (range 33-80%) participated in a 15-month randomised double-blind, placebo-controlled crossover trial. They received either azithromycin (bodyweight < or =40 kg: 250 mg daily, >40 kg: 500 mg daily) or placebo for 6 months. After 2 months of washout, the treatments were crossed over. The primary outcome was median relative difference in FEV1 between azithromycin and placebo treatment periods. Sputum cultures, sputum interleukin 8 and neutrophil elastase, exercise testing, quality of life, antibiotic use, and pulmonary exacerbation rates were secondary outcome measures. Side-effects were assessed by pure tone audiometry and liver function tests. Analysis was by intention-to-treat. Median relative difference in FEV1 between azithromycin and placebo was 5.4% (95% CI 0.8-10.5). 13 of 41 patients improved by more than 13% and five of 41 deteriorated by more than 13% (p=0.059). Forced vital capacity and mid-expiratory flow did not significantly change overall. 17 of 41 patients had 24 fewer oral antibiotic courses when on azithromycin than when taking placebo, and five had six extra courses (p=0.005). Sputum bacterial densities, inflammatory markers, exercise tolerance, and subjective well-being did not change. There were no noticeable side-effects. A 4-6-month trial of azithromycin is justified in children with cystic fibrosis who do not respond to conventional treatment. The mechanism of action remains unknown.