HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:
Guest Access | Sign In via User Name/Password

This Article Abstract Full Text (PDF) Free Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Add to My Personal Article Archive Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (61) Citing Articles via Google Scholar Google Scholar Articles by Foresi, A. Articles by Catena, E. Search for Related Content PubMed PubMed Citation Articles by Foresi, A. Articles by Catena, E.

Low-Dose Budesonide With the Addition of an Increased Dose During Exacerbations Is Effective in Long-term Asthma Control^*

Antonio Foresi, MD; Maria Cristina Morelli, MD; Ernesto Catena, MD and on behalf of the Italian Study Group

^* From the Servizio di Fisiopatologia Respiratoria, Modulo di Allergologia ed Immunopatologia Polmonare, Sesto San Giovanni, Italy; Astra Farmaceutici, S.p.A., Milano, Italy; Cattedra di Malattie dell’Apparato Respiratorio, Ospedale Monaldi, Università di Napoli, Napoli, Italy. A complete list of participants is located in the ^Appendix. This study was supported by a grant from Astra Farmaceutici, S.p.A., Italy.

Correspondence to: Antonio Foresi, MD, Servizio di Fisiopatologia Respiratoria, Modulo di Allergologia ed Immunopatologia Polmonare, Viale Matteotti 83, 20099 Sesto San Giovanni, Italy; e-mail: foresi{at}betacom.it

	Abstract

TOP Abstract Introduction Materials and Methods Results Discussion Appendix 1 References

 
Objectives: This study was designed to compare the effects of a 6-month treatment with budesonide 100 µg bid (low dose) and 400 µg bid (standard reference dose) in controlling symptoms and lung function in a group of asthmatics with moderate asthma (baseline FEV₁ 50% and 90% of predicted values) previously treated with inhaled beclomethasone dipropionate (500 to 1,000 µg/d). Moreover, we investigated whether or not asthma exacerbations could be treated by a short-term increase in the daily dose of budesonide.

Methods: After a 2-week run-in period and 1-month treatment with a high dose of budesonide (800 µg bid), 213 patients with moderate asthma were assigned to randomized treatments. Daily treatment included budesonide (bid) plus an additional treatment in case of exacerbation (qid for 7 days). Treatments were as follows: budesonide 400 µg plus placebo (group 1); budesonide 100 µg plus budesonide 200 µg (group 2); and budesonide 100 µg plus placebo (group 3). Symptoms and a peak expiratory flow (PEF) diary were recorded and lung function was measured each month. An exacerbation was defined as a decrease in PEF > 30% below baseline values on 2 consecutive days.

Results: We found that that 1-month treatment with a high budesonide dose remarkably reduced all asthma symptoms. Moreover, symptoms were under control in all treatment groups throughout the study period. Similarly, lung function improved and remained stable, and no relevant differences between groups were observed. In each treatment group, the majority of patients had no exacerbations. In patients treated with the standard budesonide dose (group 1), the number of exacerbations and days with exacerbations were significantly lower than in group 3 (intention-to-treat analysis). Additionally, patients treated with low budesonide dose plus budesonide (group 2) experienced a significantly lower number of exacerbations and days with exacerbations compared to group 3 (per-protocol analysis).

Conclusions: This study demonstrates that when patients with moderate asthma had reached a stable clinical condition with a high dose of budesonide, a low dose of budesonide (200 µg/d) is as effective as the standard dose (800 µg/d) in the control of symptoms and lung function over a period of several months. Furthermore, results showed that the addition of inhaled budesonide (800 µg/d) at onset of an asthmatic exacerbation has a beneficial clinical effect.

Key Words: asthma • budesonide • exacerbation • inhaled steroids

	Introduction

TOP Abstract Introduction Materials and Methods Results Discussion Appendix 1 References

 

Chronic and acute airways inflammation in asthma are the cause of recurrent bronchial symptoms, variable airflow obstruction, and increase in bronchial responsiveness.^{1 2} Moderate chronic asthma is characterized by almost daily symptoms and recurrent exacerbations, and patients require daily anti-inflammatory treatment to achieve and maintain control of their asthma.³ Also, asthma management in moderate asthmatics is achieved by prolonged therapy with inhaled corticosteroids, which produce minimal or no adverse effects.³

Inhaled corticosteroids are at present the most effective controllers for asthma,³ and budesonide has been shown to be effective and well tolerated in asthma of different severity.^{4 5 6} For moderate asthma, international guidelines recommend at least 800 µg/d inhaled corticosteroid such as budesonide.³ However, in a recent study, van der Molen et al⁷ demonstrated that 200 µg inhaled budesonide is as effective as the recommended daily dose (800 µg) in controlling bronchial symptoms in steroid-naive patients with mild to moderate asthma. This finding suggests that the daily effective dose of inhaled steroids for long-term treatment should be better defined to minimize potential side effects.^{6 8 9}

Besides symptoms, asthma treatment should also prevent exacerbations.³ Clinical control of asthmatic exacerbations until now has been achieved by short course treatments of oral corticosteroids¹⁰ or by adding long-acting ß₂-agonists to inhaled steroids.¹¹ To date, the possibility of preventing and controlling exacerbations by inhaled corticosteroids has received very little attention.^{12 13 14}

The present study, therefore, was designed to do the following: (1) compare the effect of prolonged treatment with a low dose of inhaled budesonide (100 µg bid) in controlling symptoms and maintaining optimal pulmonary function in patients with moderate stable asthma to the effect obtained with a standard dose (400 µg bid); and (2) ascertain whether exacerbations could be treated by early intervention with a short-term increase in the daily dose of inhaled budesonide.

	Materials and Methods

TOP Abstract Introduction Materials and Methods Results Discussion Appendix 1 References

 
Population
We recruited 220 adult patients with perennial asthma from 14 outpatient clinics. All patients had documented histories of asthma as defined by the American Thoracic Society.¹⁵ Patients following an established treatment with inhaled beclomethasone dipropionate (500 to 1,000 µg/d) for at least 4 weeks were selected if they fulfilled the following inclusion criteria: (1) age between 18 and 65 years; (2) baseline FEV₁ 50% and 90% of predicted values;¹⁶ (3) daily peak expiratory flow (PEF) variability 20% on at least 4 different days during a 2-week prestudy observation period; (5) daily requirement of inhaled ß₂-agonists; and (6) presence of wheeze, cough, chest tightness, shortness of breath at rest that interfered with normal daily activity during a 2-week prestudy observation period. Patients were excluded if they required oral or systemic corticosteroids to control asthma during a 1-month period before the study and if they were treated with a high dose of beclomethasone dipropionate (> 1,000 µg/d). Patients with a history of seasonal asthma were not eligible for the study. The presence of atopy was not a prerequisite for enrollment. Patients treated with oral theophyllines, ipratropium bromide, and long-acting bronchodilators were not excluded. In addition, current and ex-smokers were not included since this is a real clinical condition. All patients were trained to use the peak flowmeter.

Ethics committee approvals were obtained in all clinics, and all patients provided informed consent.

Study Design
We conducted a randomized, double-blind, multicenter, parallel-group study. Following the 2-week prestudy observation period, all eligible patients entered a 4-week prestudy treatment period during which they were asked to inhale budesonide 800 µg bid.

The patients were then randomized to receive one of the following treatments for a period of 6 months: budesonide 400 µg bid plus placebo qid in case of an exacerbation (group 1); budesonide 100 µg bid plus a course of budesonide 200 µg qid in case of an exacerbation (group 2); and budesonide 100 µg bid plus placebo qid in case of an exacerbation (group 3).

During the study, treatment with inhaled ß₂-agonists was allowed on an as-needed basis, and treatment with long-acting ß₂-agonists or theophyllines was kept constant. Following randomization, all patients returned to the clinic once a month. At each visit, clinical conditions were assessed and spirometry was performed.

Throughout the study period, the patients kept a daily record of respiratory symptoms (wheeze, cough, chest tightness, and shortness of breath), number of asthmatic exacerbations, morning and evening PEF values, and daily use of additional treatments.

The best values of morning PEF measured during the last 2 weeks of the prestudy treatment period were measured, and the mean was taken as baseline. Exacerbation of asthma was defined by a fall in PEF < 70% from baseline value, calculated during the last 2-week prestudy treatment period on at least 2 consecutive days. In case of an exacerbation, patients were instructed to start with the inhaled additional randomized treatment for 7 days (either placebo or budesonide 200 µg qid). If PEF remained < 70% of baseline value for 2 additional consecutive days, the patients were advised to follow a short course treatment of oral steroids (prednisolone 30 mg for 3 to 10 days, as judged by the investigators) to restore clinical condition and lung function (PEF > 70% of baseline). In case of failure, this procedure was repeated for a maximum of two times during the study. On the third failure, the patient was withdrawn. Moreover, the patient was also withdrawn from the study if PEF value fell < 50% from baseline on 2 consecutive days or on 2 days during 1 week.

As we previously stated, the patients made monthly scheduled hospital visits to check symptoms diary, compliance with treatment, and to measure lung function parameters.

Statistical Analysis
Study outcomes included number of days during which patients experienced cough, wheeze, and shortness of breath. The percentage of days with each symptom was analyzed using analysis of covariance. The percentage of days with each particular symptom during the 2-week prestudy treatment period was taken as covariate. Days where no data were recorded were not used in the denominator of the percentage calculation. Similarly, morning PEF values were analyzed by analysis of covariance, using the appropriate value recorded during the 2-week prestudy treatment period as covariate. FVC, FEV₁, and PEF values at visit 9 were analyzed by the Last Observation Carried Forward method to minimize the potential bias caused by patient withdrawals, using values measured at the end of prestudy treatment period as covariate.

The total number of exacerbations and the number of days with exacerbation during the 6-month treatment period were analyzed using nonparametric statistics due to the skewed distribution of this data. The number of days during which patients had a PEF value < 70% of baseline or during which they were taking oral corticosteroids was expressed as percentage of all treatment days. The difference between each pairwise comparison of treatments was analyzed using the Wilcoxon rank sum test. Moreover, the number of patients with at least one exacerbation during the treatment period was summarized by treatment groups and analyzed using the ² test. Differences in the number of days during which patients received oral corticosteroids were analyzed by the ² test. All analyses were performed on an intention-to-treat and per-protocol basis. All statistical significance tests were two-tailed and performed at the 5% level.

	Results

TOP Abstract Introduction Materials and Methods Results Discussion Appendix 1 References

 
Population
A group of 220 asthmatic patients were enrolled. Seven patients were withdrawn during the run-in phase and four patients just after randomization. Thus, the intention-to-treat analysis was based on 209 patients. Their characteristics are shown in Table 1 . Only 16 patients were current smokers. A group of 22 patients discontinued their treatment: 10 patients were lost at follow-up, 4 patients for adverse events and 8 patients for other reasons. Therefore, out of 213 randomized patients, a group of 191 patients completed the study. Protocol violations were detected in 38 patients. Thus the per-protocol analysis was performed on 175 patients: 56 patients were included in group 1, 55 patients in group 2, and 64 in group 3. The three groups were well matched for demographic details, pulmonary function, duration of asthma, and concomitant medications.

Symptoms
Most patients were still symptomatic at the end of the run-in period. After 1-month treatment with a high dose of budesonide (800 µg bid), the highest proportion of patients reported no symptoms. Percentages of patients reporting wheeze, cough, and shortness of breath are shown in Table 2 .

View larger version (20K): [in this window] [in a new window] [Download PPT slide]   Figure 1. Mean morning PEF in each group recorded during the last 2-weeks of treatment with budesonide, 800 µg bid, and at 2-week intervals during the randomized treatment period.

View larger version (28K): [in this window] [in a new window] [Download PPT slide]   Figure 2. Mean values for FVC, FEV1, and PEF recorded at clinic visits before and after a 1-month treatment with budesonide, 800 µg bid (shaded area), and during randomized treatments. *p < 0.05 compared to group 1.

In addition, the number of days during which patients in group 3 (116 days) received oral corticosteroids was significantly higher than in group 1 (37 days, p < 0.001) and group 2 (47 days, p < 0.001). Throughout the treatment period, only one patient in group 3 received more than two courses of oral steroids.

Adverse Events
During the run-in phase, adverse events with suspected relationship with the treatment were reported in five patients: three patients developed stomatitis, one patient developed pharingitis, and one patient reported a "bitter taste." During the randomized treatment period, the following adverse reactions were recorded: one case of dysphonia and one case of sore throat in group 1, one case of stomatitis and one case of pharingitis in group 2, and two cases of pharingitis in group 3.

	Discussion

TOP Abstract Introduction Materials and Methods Results Discussion Appendix 1 References

 
The results of the present study demonstrate that asthmatic patients with respiratory symptoms are kept under control and lung function is stabilized after a short-term treatment with a high dose of inhaled budesonide followed by a long-term treatment with either a standard dose (400 µg bid) of budesonide or a low dose (100 µg bid) of budesonide. This clinical effect is evident for up to a period of 6 months. Moreover, this study suggests that clinical exacerbations of asthma are effectively treated by early intervention with a high dose of inhaled budesonide.

The introduction of international guidelines for asthma therapy has indeed led to a much earlier use of inhaled steroids in asthma, and inhaled steroids have become the first-line treatment in the clinical management of both adult and childhood asthma.³ According to these guidelines, the recommended dose of inhaled corticosteroids for patients with moderate asthma is at least 800 µg/d. Thus, it is not surprising that patients treated with this daily dose showed a satisfactory control of both symptoms and lung function. On the other hand, our study clearly demonstrates that a low dose of inhaled budesonide (200 µg/d) also produces a clinically relevant outcome for asthma management, as suggested at least by symptoms and PEF variability. Previously, inhaled budesonide (200 to 400 µg/d) was reported to produce adequate control of symptoms in stable asthmatics over a 12-month period¹⁷ and in mild asthmatics over a 6-week period.¹⁸ Moreover, low-dose (300 µg/d) inhaled beclomethasone dipropionate exercises a sparing effect on oral steroids similar to that observed during treatment with a high dose (1,500 µg/d).¹⁹ These findings, together with the results of the present study, strongly suggest that treatment with low-dose inhaled steroids could conceivably be applied as a minimum maintenance therapy in adults with moderate asthma after a stable or "optimal" clinical condition has been achieved. Although the clinical value of long-term prophylactic treatment with inhaled steroids is now firmly established, the minimum effective dose for each patient still needs to be more accurately determined. This practice, in turn, will most likely reduce the occurrence of potential side effects and ensure better compliance.

An important finding of this study is that asthmatic exacerbations can effectively be treated by a short course of inhaled steroids (7 days of inhaled budesonide 800 µg/d) in patients receiving a low-dose regimen (200 µg/d). It is tempting to speculate that an early intervention with inhaled budesonide may have a prolonged preventive effect on further exacerbations. This could explain the difference between the number of single exacerbations between group 2 and group 3. However, it is also possible that the criteria for the presence of an exacerbation does not adequately reflect a deteriorating clinical condition in all patients. We defined the onset of exacerbation of asthma as the 2 consecutive days when either morning or evening PEF fell < 70% of values measured during a 2-week pretreatment period, immediately before randomized treatments started. Although the clinical relevance of exacerbations is well recognized, a clear and widely accepted definition of exacerbation is still lacking. To date, exacerbation of asthma has been defined on the basis of a combination of predetermined criteria, which include increase of respiratory symptoms, increase in the use of rescue medications, changes in lung function, and worsening in daily PEF measurements.^{20 21 22} Generally speaking, a 30% decrease in PEF characterizes a mild exacerbation of adult asthma.^{20 23} Furthermore, a self-management plan for adult asthma based on this criterion has, in the past, led to an improvement in patients’ long-term clinical conditions.^{20 23}

In this regard, although self-management plans for asthma often include an increase in daily doses of inhaled steroids to control mild clinical exacerbations,^{3 20 23} more severe exacerbations are commonly and effectively treated with oral steroids.¹⁰ Recently, however, it has been found that a 2-week treatment with a high dose of fluticasone propionate (2000 µg/d) is as effective as oral prednisolone in treating mild to moderate exacerbations of asthma in adults.¹² Our study extends this observation and demonstrates that the number and duration of asthmatic exacerbations in patients treated with low budesonide dose plus a fixed short-term high-dose treatment do not differ from those of patients treated with a reference dose of budesonide (400 µg bid) only.

In conclusion, this study shows that in treating asthmatic exacerbations in adult patients, after a stable clinical condition has been achieved, low-dose budesonide (200 µg/d) associated with a short-term course of high-dose inhaled budesonide is as effective as a standard budesonide dose (800 µg/d). These results suggest that an attempt to find the minimum effective dose is always worth trying, and that the inhaled route with steroids could be an effective alternative to oral steroids in asthma exacerbations.

	Appendix 1

TOP Abstract Introduction Materials and Methods Results Discussion Appendix 1 References

 
The Italian Study Group includes the following: Prof. Francesco Bariffi, Cattedra Malattie App. Respiratorio, II Facoltà di Medicina Ospedale Monaldi, Università di Napoli; Prof. Alberto Bisetti, 1^a Clinica Tisiologica Università La Sapienza Ospedale Forlanini, Roma; Dr. Fernando De Benedetto, Divisione di Pneumologia, Presidio Ospedaliero S. Camillo de Lellis, Chieti; Dr. Enrico Farina, Divisione di Pneumologia, Ospedale Civile, L’Aquila; Prof. Francesco Ginesu, Clinica Malattie dell’Apparato Respiratorio dell’Università, Ospedale Conti, Sassari; Prof. Giuseppe Girbino, Cattedra Istituto di Malattie Respiratorio, Policlinico Universitario di Messina; Prof. Enzo Gramiccioni, Clinica Pneumologica, Ospedale Policlinico di Bari; Prof. Carlo Grassi, Cattedra Istituto di Tisiologia e Apparato Respiratorio, Università di Pavia; Prof. Vittorio Grassi, Cattedra di Medicina Interna, Università degli Studi di Brescia, Spedali Civili di Brescia; Prof. Giuseppe Gunella, Cattedra di Fisiopatologia Respiratoria, Policlinico S. Orsola, Bologna; Prof. Luigi Marazzini, Servizio di Fisiopatologia Respiratoria, Ospedale di Sesto S. Giovanni; Prof. Giorgio Scano, 3°Clinica Medica Ospedale Careggi, Firenze; and Prof. Giorgio Velluti, Divisione di Tisiologia Policlinico di Modena.

	Footnotes

 
Abbreviations: PEF = peak expiratory flow

Received for publication February 10, 1999. Accepted for publication September 16, 1999.

	References

TOP Abstract Introduction Materials and Methods Results Discussion Appendix 1 References

 

1. Djukanovic, R, Roche, WR, Wilson, JW, et al (1990) Mucosal inflammation in asthma. Am Rev Respir Dis 142,434-457[ISI][Medline]
2. Chetta, A, Foresi, A, Del Donno, M, et al (1996) Bronchial responsiveness to distilled water and methacholine and its relationship to inflammation and remodeling of the airways in asthma. Am J Respir Crit Care Med 153,910-917[Abstract]
3. National Asthma Education and Prevention Program. Expert Panel Report 2: guidelines for the diagnosis and management of asthma. National Institutes of Health, February 1997; Publication No. 97–405
4. Adelroth, E, Rosenthal, L, Glennow, C (1985) High dose inhaled budesonide in the treatment of severe steroid-dependent asthmatics. Allergy 40,58-64[Medline]
5. Juniper, EF, Kline, PA, Vanzieleghem, MA, et al (1990) Effect of long-term treatment with an inhaled corticosteroid (budesonide) on airway hyperresponsiveness and clinical asthma in nonsteroid-dependent asthmatics. Am Rev Respir Dis 142,832-836[ISI][Medline]
6. Shapiro, G, Bronsky, EA, LaForce, CF, et al (1998) Dose-related efficacy of budesonide administered via a dry powder inhaler in the treatment of children with moderate persistent asthma. J Pediatr 132,976-982[CrossRef][ISI][Medline]
7. van der Molen, T, Meyboon-de-Jong, B, Mulder, HH, et al (1996) Inhaled steroid in steroid naive asthmatic patients: is starting with a high dose useful? Eur Respir J 9(suppl 23),79S
8. Ali, NJ, Capewell, S, Ward, MJ (1991) Bone turnover during high dose inhaled corticosteroid treatment. Thorax 46,160-164[Abstract]
9. Corrigan, CJ, Hartnell, A, Kay, AB (1988) T lymphocyte activation in acute severe asthma. Lancet 1,1129-1132[CrossRef][ISI][Medline]
10. Rowe, BH, Keller, JL, Oxman, AD (1992) Effectiveness of steroid therapy in acute exacerbations of asthma: a meta-analysis. Am J Emerg Med 10,301-310[CrossRef][ISI][Medline]
11. Pauwels, RA, Lofdahl, C-G, Postma, DS, et al (1997) Effect of inhaled formoterol and budesonide on exacerbations of asthma. Lancet 337,1405-1411
12. Levy, ML, Stevenson, C, Maslen, T (1996) Comparison of short courses of oral prednisolone and fluticasone propionate in the treatment of adults with acute exacerbations of asthma in primary care. Thorax 51,1087-1092[Abstract]
13. Praparn, Y, Maranetra, N, Charoenratanakul, S, et al (1996) Inhaled as effective as oral steroids after an acute asthma attack. Am J Respir Crit Care Med 153,A341
14. Rodrigo, G, Rodrigo, C (1998) Inhaled flunisolide for acute severe asthma. Am J Respir Crit Care Med 157,698-703[Abstract/Free Full Text]
15. Standards for the diagnosis and care of patients with chronic obstructive pulmonary disease. American Thoracic Society. Am J Respir Crit Care Med 1995; 152:S77–S121
16. Standardized lung function testing: official statement of the European Respiratory Society. Eur Respir J 1993; 16(Suppl):1–100
17. Juniper, EF, Kline, PA, Vanzieleghem, MA, et al (1990) Long-term effects of budesonide on airway responsiveness and clinical asthma severity in inhaled steroid-dependent asthmatics. Eur Respir J 3,1122-1127[Abstract]
18. Lorentzson, S, Boe, J, Eriksson, G, et al (1990) Use of inhaled corticosteroids in patients with mild asthma. Thorax 45,733-735[Abstract]
19. Hummel, S, Lehtonen, L (1992) Comparison of oral-steroid sparing by high-dose and low-dose inhaled steroid in maintenance treatment of severe asthma. Lancet 340,1483-1487[CrossRef][ISI][Medline]
20. Charlton, I, Charlton, G, Broomfield, J, et al (1990) Evaluation of peak flow and symptoms only self management plans for control of asthma in general practice. BMJ 301,1355-1359
21. Taylor, DR, Sears, MR, Herbison, GP, et al (1993) Regular inhaled beta agonist in asthma: effects on exacerbations and lung function. Thorax 48,134-138[Abstract]
22. Chervinsky, P, van As, A, Bronsky, EA, et al (1994) Fluticasone propionate aerosol for the treatment of adults with mild to moderate asthma. The Fluticasone Propionate Asthma Study Group. J Allergy Clin Immunol 94,676-683[CrossRef][ISI][Medline]
23. Ignacio-Garcia, JM, Gonzalez-Santos, P (1995) Asthma self-management education program by home monitoring of peak expiratory flow. Am J Respir Crit Care Med 151,353-359[Abstract]

This article has been cited by other articles:

				J M FitzGerald and P G Gibson Asthma exacerbations {middle dot} 4: Prevention. Thorax, November 1, 2006; 61(11): 992 - 999. [Abstract] [Full Text] [PDF]

				T. Haahtela, K. Tamminen, L. P. Malmberg, O. Zetterstrom, J. Karjalainen, H. Yla-Outinen, T. Svahn, T. Ekstrom, and O. Selroos Formoterol as needed with or without budesonide in patients with intermittent asthma and raised NO levels in exhaled air: a SOMA study Eur. Respir. J., October 1, 2006; 28(4): 748 - 755. [Abstract] [Full Text] [PDF]

				S. Schuh, P. T. Dick, D. Stephens, M. Hartley, S. Khaikin, L. Rodrigues, and A. L. Coates High-Dose Inhaled Fluticasone Does Not Replace Oral Prednisolone in Children With Mild to Moderate Acute Asthma Pediatrics, August 1, 2006; 118(2): 644 - 650. [Abstract] [Full Text] [PDF]

				H. K. Reddel and D. J. Barnes Pharmacological strategies for self-management of asthma exacerbations. Eur. Respir. J., July 1, 2006; 28(1): 182 - 199. [Abstract] [Full Text] [PDF]

				K. F. Rabe, E. Pizzichini, B. Stallberg, S. Romero, A. M. Balanzat, T. Atienza, P. A. Lier, and C. Jorup Budesonide/Formoterol in a Single Inhaler for Maintenance and Relief in Mild-to-Moderate Asthma: A Randomized, Double-Blind Trial. Chest, February 1, 2006; 129(2): 246 - 256. [Abstract] [Full Text] [PDF]

				L. M. Fabbri Does Mild Persistent Asthma Require Regular Treatment? N. Engl. J. Med., April 14, 2005; 352(15): 1589 - 1591. [Full Text] [PDF]

				D. D. Sin, J. Man, H. Sharpe, W. Q. Gan, and S. F. P. Man Pharmacological Management to Reduce Exacerbations in Adults With Asthma: A Systematic Review and Meta-analysis JAMA, July 21, 2004; 292(3): 367 - 376. [Abstract] [Full Text] [PDF]

				J M FitzGerald, A Becker, M R Sears, S Mink, K Chung, and J Lee Doubling the dose of budesonide versus maintenance treatment in asthma exacerbations Thorax, July 1, 2004; 59(7): 550 - 556. [Abstract] [Full Text] [PDF]

				M. Masoli, S. Holt, M. Weatherall, and R. Beasley Dose-response relationship of inhaled budesonide in adult asthma: a meta-analysis Eur. Respir. J., April 1, 2004; 23(4): 552 - 558. [Abstract] [Full Text] [PDF]

				R. A. Pauwels Similarities and Differences in Asthma and Chronic Obstructive Pulmonary Disease Exacerbations Proceedings of the ATS, April 1, 2004; 1(2): 73 - 76. [Abstract] [Full Text] [PDF]

				P. M. O'Byrne Pharmacologic Interventions to Reduce the Risk of Asthma Exacerbations Proceedings of the ATS, April 1, 2004; 1(2): 105 - 108. [Abstract] [Full Text] [PDF]

				M R Partridge Written asthma action plans Thorax, February 1, 2004; 59(2): 87 - 88. [Full Text] [PDF]

				U. G. Lalloo, J. Malolepszy, D. Kozma, K. Krofta, J. Ankerst, B. Johansen, and N. C. Thomson Budesonide and Formoterol in a Single Inhaler Improves Asthma Control Compared With Increasing the Dose of Corticosteroid in Adults With Mild-to-Moderate Asthma Chest, May 1, 2003; 123(5): 1480 - 1487. [Abstract] [Full Text] [PDF]

				J-M. Ignacio-Garcia, M. Pinto-Tenorio, M.J. Chocron-Giraldez, F. Cabello-Rueda, A.I. Lopez-Cozar Gil, J-M. Ignacio-Garcia, and E. de Ramon-Garrido Benefits at 3 yrs of an asthma education programme coupled with regular reinforcement Eur. Respir. J., November 1, 2002; 20(5): 1095 - 1101. [Abstract] [Full Text] [PDF]

				L M Osman, C Calder, D J Godden, J A R Friend, L McKenzie, J S Legge, and J G Douglas A randomised trial of self-management planning for adult patients admitted to hospital with acute asthma Thorax, October 1, 2002; 57(10): 869 - 874. [Abstract] [Full Text] [PDF]

				H. J. van der Woude, R. Aalbers, and A. Foresi Short-term Budesonide Dosage Chest, January 1, 2001; 119(1): 309 - 310. [Full Text] [PDF]

This Article Abstract Full Text (PDF) Free Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Add to My Personal Article Archive Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (61) Citing Articles via Google Scholar Google Scholar Articles by Foresi, A. Articles by Catena, E. Search for Related Content PubMed PubMed Citation Articles by Foresi, A. Articles by Catena, E.