Flonase
Combination therapy in asthma--fixed or variable dosing in different patients?

Lotvall J.

Department of Respiratory Medicine & Allergology, Goteborg University, Goteborg, Sweden. jan.lotvall mednet.gu.se

The introduction of combination products, for the coadministration of an inhaled corticosteroid (ICS) with a long-acting beta2-agonist in a single inhaler, has greatly simplified asthma therapy. The two combination inhalers currently available, Symbicort (budesonide/formoterol in a single inhaler) and Seretide (salmeterol/fluticasone), comply with Step 3 of international guidelines that recommend the addition of a long-acting beta2-agonist to ICS in patients who are inadequately controlled on ICS alone. Importantly, combination inhalers ensure that patients cannot neglect their ICS maintenance therapy in favour of the long-acting beta2-agonist--which may improve adherence and overall asthma control. In vitro experiments suggest that ICS and long-acting beta2-agonists may interact beneficially when they are administered via one inhaler. The efficacy and tolerability of budesonide/formoterol and salmeterol/fluticasone have been demonstrated. There are currently two approaches for treating asthma using combination therapy--fixed and adjustable dosing. Fixed dosing with budesonide/formoterol or salmeterol/fluticasone provides effective asthma control in line with guideline goals. However, given the inherent variability of asthma, there is increasing evidence that adjusting the dose of ICS according to fluctuations in symptoms is beneficial. Findings from a series of studies comparing fixed and adjustable symptom-guided dosing regimens demonstrate that adjustable dosing may improve asthma control at an overall lower steroid dose. Ultimately, if adjustable dosing proves to be an effective treatment option, it may be possible to use budesonide/formoterol for both maintenance therapy and symptom relief, thereby overcoming the need for a separate reliever inhaler. This is because formoterol has a more rapid onset and greater dose-related effects than salmeterol in salmeterol/fluticasone. Given that all patients are different, with different disease severities and treatment preferences, both fixed and adjustable dosing strategies are likely to be important in the long-term management of asthma. It is possible that different treatment options will be used for different patients, depending on their disease severity, personality and ability to adhere to therapy.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15537472&dopt=Abstract fluticasone Flonase



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[Efficacy and acceptability of the fixed fluticasone + salmeterol combination in the treatment of acute asthma attacks. Results of a one-year comparative study]

[Article in French]

Tonnel AB, Desfougeres JL.

Service de Pneumologie et Immuno-Allergologie, Hopital Calmette, CHRU, boulevard du Pr-Jules-Leclercq, 59037 Lille Cedex. ab-tonnel chru-lille.fr

BACKGROUND: The objective of an asthma treatment is to control asthma, particularly to prevent exacerbations. OBJECTIVE: To study the efficacy, acceptability and safety of the fluticasone/salmeterol (FP/S) combination in preventing asthma exacerbations in comparison with the continuation of previous treatment (TA). METHODS: This was a multicentre, randomised, parallel-group study to compare the fixed combination FP/S to TA (treatment with a free combination of an inhaled corticosteroid and a long-acting beta2-agonist) over one year in patients whose asthma was well controlled with their current treatment. RESULTS: Five hundred and twenty patients were randomized and their data analyzed on an intent-to-treat basis. Seventy-four percent of the patients in the FP/S group and 71% in the TA group had no exacerbation. The 3.12% difference in favor of the FP/S group (90% CI: -3.32% to 9.56%) demonstrated that FP/S was at least as effective TA in preventing asthma exacerbations. Treatment acceptability, evaluated by the patient on visual analog scales (inclusion as part of the daily habits, constraint, simplicity) was better with FP/S (p<0.001) than with TA. Clinical safety was good and comparable in the two groups. CONCLUSION: The fixed fluticasone/salmeterol combination provided a protection as good as that obtained with free combinations over a one-year treatment period, with a significant improvement in treatment acceptability and a good clinical safety.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15545949&dopt=Abstract fluticasone Flonase



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[Eosinophilic airway disorders: important causes of prolonged cough in Japan]

[Article in Japanese]

Kamachi A, Nakadate M, Hasegawa Y, Hanada T, Ishiguro A.

Department of Respiratory Medicine, Tenshi Hospital.

We studied 223 outpatients who presented between October 2001 and June 2003 with persistent cough of more than 3 weeks' duration. Eosinophilic airway disorders (EAD), including atopic cough and cough variant asthma, were clinically diagnosed in 119 patients, on the basis of the following factors: history of atopic disease, duration of cough, history of previous prolonged cough, or presence of forced expiration wheeze. Since eosinophils are frequently found in the sputum of patients with EAD, a positive test strongly suggests the presence of EAD. In this study, the test was positive in 86% of the patients with EAD. The patients with clinically diagnosed EAD, including those with no eosinophils in the sputum, were treated with inhaled fluticasone 400 or 800 microg/day. Fluticasone was effective in 97% of the patients with EAD and was more effective than bronchodilators or antiallergic drugs. When we compared the results of fluticasone 400 microg/day with those of 800 microg/day doses, the cough disappeared within 1 week in 28% of the patients who received 400 microg/day, whereas in 76% with 800 microg/day. Among the patients with diagnosed EAD, bronchial asthma developed in 6 patients during the observation period. Most of these patients had forced expiration wheeze and lower FEV 1 at the initial visit. This study showed that EAD could be diagnosed in the early stage on the basis of thorough history-taking, the presence of forced expiration wheeze and detection of eosinophils in the sputum. It is important to diagnose and treat EAD as early as possible since inhaled steroid is highly effective.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15566001&dopt=Abstract fluticasone Flonase



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Differential effects of fluticasone and montelukast on allergen-induced asthma.

Palmqvist M, Bruce C, Sjostrand M, Arvidsson P, Lotvall J.

Section of Allergy, The Lung Pharmacology Group, Department of Respiratory Medicine and Allergology, Goteborg University, Gothenburg, Sweden.

Early asthmatic responses (EAR) and late asthmatic responses (LAR) to allergen are induced by the local release of a series of bronchoconstrictor mediators, including leukotrienes and histamine. Both anti-leukotrienes and other anti-asthma drugs, such as inhaled glucocorticoids, have been shown to reduce both EAR and LAR. The aim of the present study was to directly compare the effects of regular treatment with an oral anti-leukotriene, montelukast (Mont; 10 mg once daily, for 8 days), and an inhaled glucocorticoid [fluticasone propionate (FP) 250 microg twice daily for 8 days] on the EAR and LAR to an inhaled allergen challenge. Patients with a documented EAR and LAR at a screening visit were randomized to these treatments, or placebo, in a double-blind, double-dummy, crossover fashion. Allergen challenge at a dose causing both an EAR and LAR was given on the eighth day of treatment. The maximum fall in FEV1 during the EAR was 17.8% during placebo treatment, 8.3% during Mont and 16.3% during FP (P <0.05 for Mont vs placebo). The maximum fall during the EAR was 13.8% during placebo treatment, 11.8% during Mont and 2% during FP treatment (P <0.05 for FP vs placebo and FP vs Mont). PC20 methacholine was significantly higher 24 h after allergen challenge during FP-treatment compared with Mont (P <0.05). Both montelukast and fluticasone reduced the relative amount of sputum eosinophils after allergen compared with placebo treatment. This study shows that anti-leukotrienes are effective to attenuate the EAR, whereas inhaled glucocorticoids are more effective than anti-leukotrienes in attenuating the EARs and improves bronchial hyperresponsiveness to a greater extent. In conclusion, inhaled glucocorticoids have overall greater efficacy than oral anti-leukotrienes to attenuate allergen-induced airway responses in mild asthmatic patients.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15575933&dopt=Abstract fluticasone Flonase



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Exhaled nitric oxide in bronchiectasis: the effects of inhaled corticosteroid therapy.

Tsang KW, Tan KC, Ho PL, Ooi GC, Khong PL, Leung R, Mak JC, Tipoe GL, Ko C, Lam WK.

University Department of Medicine, University of Hong Kong, Queen Mary Hospital, Hong Kong SAR, China. kwttsang hku.hk

SETTING: While exhaled nitric oxide (eNO) levels are reduced by inhaled corticosteroid therapy in asthma, such treatment effect is unclear in bronchiectasis. DESIGN: Stable non-smoking bronchiectasis patients were randomised to receive either fluticasone (1 mg/daily) or identical placebo via the Accuhaler device. RESULTS: Sixty non-smoking patients (38 women; mean age 56.4 +/- 12.7 years) were recruited. Of these, half received inhaled fluticasone and half placebo therapy. eNO was measured using a chemiluminescence analyser at 0, 4, 12, 24, 36 and 52 weeks. There was no significant difference in eNO levels between fluticasone and placebo patients over the study period. There was no correlation between baseline eNO with age, FEV1, FVC, 24 h sputum volume or number of bronchiectatic segments. Patients with Pseudomonas aeruginosa (PA) infection, but not their counterparts, displayed a correlation between 0- and 52-week eNO levels. PA infection was associated with significantly lower eNO levels among the patients. CONCLUSIONS: Inhaled fluticasone therapy, despite being an effective anti-inflammatory agent, has no significant effect on eNO production, either at individual time points or over the entire 52-week profile, in bronchiectasis. It appears that eNO might not reflect the extent of airway inflammation in bronchiectasis.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15581196&dopt=Abstract fluticasone Flonase