Krónikus légúti gyulladásos megbetegedések pathomechanizmusa = Pathomechanism of chronic inflammatory airway diseases

A kutatómunka célja a tartós légúti gyulladásos megbetegedések kórfolyamatainak feltárása volt. Vizsgálataink során a világon elsőként sikerült kimutatnunk, hogy az asztmás betegek terhelésre kialakuló hörgőszűkületét a légutaikban egy hörgőszűkítő hatású anyag, az adenozin koncentrációjának növekedése kíséri, aminek jelentős szerepe lehet a kórállapot kialakulásában. Méréseinkben feltártuk különböző légúti megbetegedések lefolyásában szerepet játszó molekuláris folyamatok biomarkereinek változását, így a kilégzett nitrogén monoxidét valamint a tramboxán A2-ét olyan egymástól jelentősen eltérő kórállapotokban, mint az asztma, cisztás fibrózis, valamint tüdőtranszplantáltakban. Elsősorban a légutak működését közvetlenül jelző mintavételezési technikákat alkalmaztunk, melyeknek egy részében fontos metodikai fejlesztéseket is végeztünk. Így kidolgoztunk egy teljesen új megközelítést a légúti pH jellemzésére használt kilégzett levegő kondenzátumának pH meghatározására. A projekt kidolgozása során kapott eredményeink szervesen hozzájárultak az ilyen vizsgáló módszer alkalmazásával kapcsolatos nemzetközi irányelv kidolgozásához. | The aim of the current project was to increase our understanding on the pathomechanism of chronic inflammatory airway diseases. We were the first to describe that adenosine is present with increased concentration in the airways during exercise-induced bronchospasm in asthmatic patients. This mediator is known for its bronchoconstrictor potency therefore this pathway is likely to be involved in the development of bronchospasm. We outlined severel biomarker changes in airway samples that reflect different molecular mechanisms including changes in exhaled nitric oxide and thromboxane A2 metabolites in different disorders including asthma, cystic fibrosis and also in recipients of lung transplants. We mainly used non-invasive methods to sample the airways and in some cases we described new methodologies for certain measurements. In this way we developed a completely new approach for the determination of exhaled breath condensate measurement that is frequently used to assess the pH changes in the airways. Our results gained during the completion of the project formed substantial part in the construction of international recommendations for the use of exhaled breath condensate

Cost of asthma in children: A nationwide, population-based, cost-of-illness study

BACKGROUND: Childhood asthma is very prevalent and costs can be high, especially in severe disease. This study aimed to estimate the cost of asthma in Portuguese children and the variations by level of asthma control. METHODS: A nationwide, population- and prevalence-based cost-of-illness study with a societal perspective was conducted. We measured direct and indirect costs using a bottom-up approach and a human capital method, respectively, for 208 children (<18 years), from two national repositories. Generalized linear modelling for analysis of asthma costs' determinants and sensitivity analysis to assess uncertainty were performed. RESULTS: The mean annualized asthma cost per child was €929.35 (95% CI, 809.65-1061.11): €698.65 (95% CI, 600.88-798.27) for direct costs and €230.70 (95% CI, 197.36-263.81) for indirect costs. Extrapolations for the Portuguese children amounted to €161 410 007.61 (95% CI, 140 620 769.55-184 293 968.55) for total costs. Direct costs represent 75.2% with the costliest domain (51.1% of total costs) being the healthcare service use: 20.7% for scheduled medical visits and 30.4% for acute asthma care-non-scheduled medical visits (7.9%, €12 766 203.20), emergency department visits (11.7%, €18 932 464.80) and hospitalizations (10.8%, €17 406 946.00). Children with partly controlled and uncontrolled asthma had higher mean costs per year (adjusted coefficients: 1.46 [95% CI, 1.12-1.90] and 2.25 [95% CI, 1.56-3.24], respectively). CONCLUSIONS: Costs of childhood asthma are high (0.9% of the healthcare expenditures in Portugal). Direct costs represented three-fourth of total costs, mainly related to the use of healthcare services for acute asthma care. Policies and interventions to improve asthma control and reduce acute use of healthcare services have the potential to reduce asthma costs.info:eu-repo/semantics/publishedVersio

Efficacy in asthma of once-daily treatment with fluticasone furoate: a randomized, placebo-controlled trial

<p>Abstract</p> <p>Background</p> <p>Fluticasone furoate (FF) is a novel long-acting inhaled corticosteroid (ICS). This double-blind, placebo-controlled randomized study evaluated the efficacy and safety of FF 200 mcg or 400 mcg once daily, either in the morning or in the evening, and FF 200 mcg twice daily (morning and evening), for 8 weeks in patients with persistent asthma.</p> <p>Methods</p> <p>Asthma patients maintained on ICS for ≥ 3 months with baseline morning forced expiratory volume in one second (FEV₁) 50-80% of predicted normal value and FEV₁reversibility of ≥ 12% and ≥ 200 ml were eligible. The primary endpoint was mean change from baseline FEV₁at week 8 in pre-dose (morning or evening [depending on regimen], pre-rescue bronchodilator) FEV₁.</p> <p>Results</p> <p>A total of 545 patients received one of five FF treatment groups and 101 patients received placebo (intent-to-treat population). Each of the five FF treatment groups produced a statistically significant improvement in pre-dose FEV₁compared with placebo (p < 0.05). FF 400 mcg once daily in the evening and FF 200 mcg twice daily produced similar placebo-adjusted improvements in evening pre-dose FEV₁at week 8 (240 ml vs. 235 ml). FF 400 mcg once daily in the morning, although effective, resulted in a smaller improvement in morning pre-dose FEV₁than FF 200 mcg twice daily at week 8 (315 ml vs. 202 ml). The incidence of oral candidiasis was low (0-4%) and UC excretion was comparable with placebo for all FF groups.</p> <p>Conclusions</p> <p>FF at total daily doses of 200 mcg or 400 mcg was significantly more effective than placebo. FF 400 mcg once daily in the evening had similar efficacy to FF 200 mcg twice daily and all FF regimens had a safety tolerability profile generally similar to placebo. This indicates that inhaled FF is an effective and well tolerated once-daily treatment for mild-to-moderate asthma.</p> <p>Trial registration</p> <p><a href="http://www.clinicaltrials.gov/ct2/show/NCT00398645">NCT00398645</a></p

A Randomized Placebo-Controlled Trial of Varenicline for Smoking Cessation Allowing Flexible Quit Dates

Introduction: Current smoking cessation guidelines recommend setting a quit date prior to starting pharmacotherapy. However, providing flexibility in the date of quitting may be more acceptable to some smokers. The objective of this study was to compare varenicline 1 mg twice daily (b.i.d.) with placebo in subjects using a flexible quit date paradigm after starting medication. Methods: In this double-blind, randomized, placebo-controlled international study, smokers of ≥10 cigarettes/day, aged 18-75 years, and who were motivated to quit were randomized (3:1) to receive varenicline 1 mg b.i.d. or placebo for 12 weeks. Subjects were followed up through Week 24. Subjects were instructed to quit between Days 8 and 35 after starting medication. The primary endpoint was carbon monoxide-confirmed continuous abstinence during Weeks 9-12, and a key secondary endpoint was continuous abstinence during Weeks 9-24. Results: Overall, 493 subjects were randomized to varenicline and 166 to placebo. Continuous abstinence was higher for varenicline than for placebo subjects at the end of treatment (Weeks 9-12: 53.1% vs. 19.3%; odds ratio [OR] 5.9; 95% CI, 3.7-9.4; p < .0001) and through 24 weeks follow-up (Weeks 9-24: 34.7% vs. 12.7%; OR 4.4; 95% CI, 2.6-7.5; p < .0001). Serious adverse events occurred in 1.2% varenicline (none were psychiatric) and 0.6% placebo subjects. Fewer varenicline than placebo subjects reported depression-related adverse events (2.3% vs. 6.7%, respectively). Conclusions: Varenicline 1 mg b.i.d. using a flexible quit date paradigm had similar efficacy and safety compared with previous fixed quit date studies. © The Author 2011. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco

Inhaled corticosteroids for asthma: impact of practice level device switching on asthma control

Background As more inhaled corticosteroid (ICS) devices become available, there may be pressure for health-care providers to switch patients with asthma to cheaper inhaler devices. Our objective was to evaluate impact on asthma control of inhaler device switching without an accompanying consultation in general practice. Methods This 2-year retrospective matched cohort study used the UK General Practice Research Database to identify practices where ICS devices were changed without a consultation for ≥5 patients within 3 months. Patients 6–65 years of age from these practices whose ICS device was switched were individually matched with patients using the same ICS device who were not switched. Asthma control over 12 months after the switch was assessed using a composite measure including short-acting β-agonist and oral corticosteroid use, hospitalizations, and subsequent changes to therapy. Results A total of 824 patients from 55 practices had a device switch and could be matched. Over half (53%) of device switches were from dry powder to metered-dose inhalers. Fewer patients in switched than matched cohort experienced successful treatment based on the composite measure (20% vs. 34%) and more experienced unsuccessful treatment (51% vs. 38%). After adjusting for possible baseline confounding factors, the odds ratio for treatment success in the switched cohort compared with controls was 0.29 (95% confidence interval [CI], 0.19 to 0.44; p < 0.001) and for unsuccessful treatment was 1.92 (95% CI, 1.47 to 2.56; p < 0.001). Conclusion Switching ICS devices without a consultation was associated with worsened asthma control and is therefore inadvisable