|Year : 2005 | Volume
| Issue : 3 | Page : 86-91
Quality of life assessment in asthmatic patients receiving fluticasone compared with equipotent doses of beclomethasone or budesonide
Sabin Thomas1, Gurumurthy Parthasarathi1, Shilpa Palaksha1, BS Jayaraj2, H Basavana Gowda3, PA Mahesh2
1 Department of Pharmacy, JSS Medical College Hospital, Ramanuja Road, Mysore- 570 004., India
2 Department of Pulmonology, JSS Medical College Hospital, Ramanuja Road, Mysore- 570 004., India
3 Department of Medicine, JSS Medical College Hospital, Ramanuja Road, Mysore- 570 004., India
Department of Clinical Pharmacy, JSS Medical College Hospital, Ramanuja Road, Mysore- 570 004.
Source of Support: None, Conflict of Interest: None
| Abstract|| |
Aims: To assess the quality of life in patients with asthma receiving either fluticasone or other inhaled steroids like beclomethasone or budesonide. To assess the effect of equipotent dosage of inhaled steroids at 3 months duration.
Methods: Patients were randomised to receive either fluticasone or beclomethasone/budesonide. After spirometry, St. George's Respiratory Questionnaire (SGRQ) was administered at baseline and at 15 th , 30 th , 45 th , 60 th and 90 th day, to assess improvement in lung function and HRQoL.
Results: Out of 96 patients who were enrolled, eighty patients completed three months duration of the study, while sixteen patients dropped out. Forty patients received fluticasone and forty received either beclomethasone or budesonide. No significant difference (p>0.05) was found in the baseline values of St. George's Respiratory Questionnaire (SGRQ) scores and Forced Expiratory Volume at first second (FEV 1 ) between the two groups. However, significant difference (p<0.05) was noted between the above two groups, in Quality of Life (QoL) but not in pulmonary functions, on 15th day favoring fluticasone. No significant difference (p>0.05) was noted either in QoL or in pulmonary function tests on subsequent follow-ups.
Conclusion: Early response in terms of improved QoL was observed in fluticasone treated group in patients with moderate to severe asthma.
Keywords: Inhaled corticosteroids (ICS), Quality of life (QoL), Asthma
|How to cite this article:|
Thomas S, Parthasarathi G, Palaksha S, Jayaraj B S, Gowda H B, Mahesh P A. Quality of life assessment in asthmatic patients receiving fluticasone compared with equipotent doses of beclomethasone or budesonide. Lung India 2005;22:86-91
|How to cite this URL:|
Thomas S, Parthasarathi G, Palaksha S, Jayaraj B S, Gowda H B, Mahesh P A. Quality of life assessment in asthmatic patients receiving fluticasone compared with equipotent doses of beclomethasone or budesonide. Lung India [serial online] 2005 [cited 2020 Aug 9];22:86-91. Available from: http://www.lungindia.com/text.asp?2005/22/3/86/44450
| Introduction|| |
Asthma is one among the common chronic diseases, which has significant effects on patients' health and QoL. The prevalence of asthma has been increasing since the early 1980s for all age, sex, and racial groups. Despite better understanding of the disease process and improved treatment modalities, the increasing incidence and prevalence of asthma in many parts of the world continue to make it a global health concern  .
The basic pathology behind asthma is the inflammatory process. Hence the main goal of treatment is to reduce the underlying inflammation. Anti-inflammatory agents like inhaled corticosteroids are considered to be the mainstay of treatment in asthma because of their proven efficacy compared to any other class of antiasthmatic agents  . The goals in using corticosteroids in asthma treatment can be viewed in two ways. First to gain control over the underlying disease process and secondly to maintain this control for as long as possible with least amount of side effects. These initial actions usually require high doses of ICS or more frequently systemic corticosteroids. Remittive therapy requires an oral steroid burst whose duration varies considerably among patients with the goal to improve lung functions, minimize symptoms and reduce the use of rescue medications. ICS therapy also should be started at doses sufficient to control the remissions for a longer duration emphasizing that the abrupt discontinuation may cause acute exacerbations  .
Relatively little is known about the impact of asthma on health related quality of life, even with the existing epidemiological and economic literature on asthma. Health related quality of life is increasingly being used in the evaluation of medical interventions on chronic diseases. The clinical measures provide valuable information only about the affected organ system but not the functional impairment (physical, emotional and social) which is also important to the patients in their everyday lives ,. Thus it is important that treatment goals should not only be directed towards improving physiologic end points but also patients' physical and mental health (i.e. quality of life) with overall goal of reducing the debilitating impact of asthma on patients' lives.
The older inhaled steroids beclomethasone and budesonide have shown equipotency and efficacy  both in terms of improving objective measurements in lung function and subjective indices like quality of life. Fluticasone, a more recently introduced inhaled steroid is being used extensively. There are very few studies comparing the older steroids beclomethasone and budesonide with fluticasone, and its equipotent effects on quality of life. This study was conducted to assess and compare quality of life in patients with asthma receiving fluticasone or other inhaled steroids (beclomethasone or budesonide), and to assess the effect of equipotent dosage of inhaled steroids at three month duration so as to assist in making an informed decision when choosing one of the inhaled steroids.
| Methodology|| |
The study was conducted at J.S.S. Medical College Hospital, Mysore. It was a prospective open labeled randomized study of 3 month duration. The patients enrolled into the study were asthmatics taken from the Departments of Pulmonology and Medicine. The pre and post bronchodilator spirometry values showing 12% or 200ml improvement in FEV 1 was used to confirm diagnosis as per GINA guidelines  . Stable asthmatic patients were classified under GINA grade II, III, and IV  , and who were able to perform study related tests after signing the consent form, were included in the study. Those who were already using inhaled or oral steroids, having acute exacerbation of asthma or with any other co - morbidities (tuberculosis, COPD, cardiac complications) and those less than 80% adherent to medication were excluded from the study. Medication adherence checking was done by the accepted methods like patient interview, medication checking, prescription refill and health out≠come measures. Patients satisfying inclusion criteria after giving informed consent were randomized by simple randomization method. Institutional review board ethics approval for the study protocol was obtained from JSS Medical College, Mysore.
Quality of life questionnaire
Enrolled patients received either fluticasone or other inhaled steroids (beclomethasone or budesonide). Validated Kannada (the local language) version of St.George's Respiratory Questionnaire (SGRQ) was administered. SGRQ is a disease specific questionnaire used to measure health related quality of life in respiratory diseases like asthma and COPD. It contains 50 items and 76 scale levels, categorized in 3 domains like symptoms, impacts and activity. The total score of all these domains gives the overall quality of life estimate of each patient. The threshold for a clinically significant difference between groups of patients and for changes within groups of patients is four units  . Decrease in the total score reflects improved QoL.
Spirometry was performed before and after bronchodilation to assess the baseline status and to confirm the diagnosis of asthma. Patients were educated on the use of inhaled medicines. Clinical evaluation, SGRQ and spirometry was done during follow up visits at 15, 30, 45, 60 and 90 days. Equipotent dosages of the three inhaled corticosteroids were used according to their disease severity based on GINA guidelines  [Table 1]. Salmeterol 100mcg/ day in two divided doses was used for all patients (GINA II, III & IV). Salbutamol 200mcg was used as a rescue medication.
Statistical Analysis: Statistical analysis was performed using EPI Info-2000 version-1.1.2 November 2, 2001. To assess the similarities between the groups at baseline, chi-square test was used. ANOVA was used to test significance within the groups at different time intervals. For testing significance between groups, students't' test was used. Pearson correlation was used to check linear relationship between QoL and lung function.
| Results|| |
A total of ninety-six patients were enrolled to the study and eighty patients completed the study. The patients recruited into the study were steroid naive and had been prescribed only oral bronchodilators with some of them having used short courses of oral steroids during exacerbations. The baseline demographic data, spirometry and SGRQ scores of the two groups were similar at baseline [Table 2].
Pulmonary function test FEV 1 was measured for all the patients. After randomization, FEV 1 was compared between the two groups which showed no significant difference. SGRQ was administered to all the patients who were enrolled. There was no significant difference in the baseline quality of life scores between the two groups. SGRQ was administered on the follow up days of 15 th , 30 th , 60 th and 90 th day to measure the improvement in QoL after initiation of the therapy. The change in SGRQ total score reflecting the improvement in QoL in the two groups is represented in [Figure 1]. FEV 1 was measured before starting the therapy and also on the follow up days. The improvement seen on each follow up is represented in [Figure 2], which shows that there was improvement in lung functions on the initiation of the therapy.
The SGRQ scores decreased on each follow up in both the groups, which signifies the improvement in quality of life. The pattern of improvement in individual domains of symptoms, impacts and activity are represented in [Figure 3],[Figure 4],[Figure 5] respectively.
The sub group analysis of the 15 th results of the different treatment groups was done. It was found that the superior improvement observed with fluticasone in terms of HRQoL on the 15 th day follow-upwas more with GINA grade III & Grade IV patients than in grade II patients[Figure 6].
| Discussion|| |
Inhaled Steroids have been the mainstay of therapy in patients with asthma, hence new formulations and dosage forms are being continuously developed. Clinical studies have shown that treatment with inhaled steroids not only improves the symptoms of asthma but also the quality of life. The present study was designed as an open label, randomized trial to compare the quality of life between patients using flucticasone and budesonide/beclomethasone.
The study results, representing responses to a diseases specific quality of life instrument SGRQ, demonstrate that asthma treatment with inhaled fluticasone has no additional benefit in health-related quality of life over that of budesonide/ beclomethasone at equipotent doses. At baseline, the demographics, SGRQ scores and FEV 1 values showed no significant difference between the two treatment groups. The initial greater SGRQ scores indicated the decreased quality of life in all the patients. The improvement in QoL was evaluated with in the group as well as between the groups. There was significant decrease in SGRQ scores (P<0.05) during the follow ups in both the treatment groups showing improvement in quality of life. Although the improvement was seen in both the treatment groups at 15 days of treatment, it was observed that the improvement seen with fluticasone group was significantly (P<0.05) greater than that of beclomethasone/budesonide treatment group. This may be due to the reason that moderate to severe persistent asthma patients (GINA III & GINA IV) have responded better to fluticasone when compared to beclomethasone/ budesonide in the early course of treatment. The response shown by the patients with GINA grade II was similar in both the treatment groups. As the treatment continued further, in the subsequent follow up, there was no difference observed between the two groups in QoL scores until 90 days of follow up.
There is some evidence that fluticasone may be superior to other inhaled corticosteroids in patients with severe asthma. A recent meta-analysis of clinical trials with fluticasone propionate and beclomethasone dipropionate or budesonide suggest that fluticasone propionate may provide equal or greater asthma control at lower doses in patients with moderate-to severe asthma 8 . An open multicentre randomised parallel group study in Australia evaluated the safety and efficacy of switching to fluticasone propionate (1000-2000 mcg/day) compared with continuing beclomethasone/budesonide≥ 1750mcg/day for six months. This study used QoL as an outcome measure and questionnaires like Asthma Quality of Life Questionnaire and Short Form-36 were used. Only patients with severe disease requiring high doses of inhaled corticosteroids were selected for the study. Patients with severe asthma who received fluticasone (at approximately half the dose of beclomethasone/ budesonide) experienced statistically significant, as well as clinically meaningful, improvements in their HRQoL  .
In the present study the patients included varied from mild persistent to severe persistent asthma (GINA II to GINA IV) which was more representative of the spectrum of asthma severity seen in routine clinical practice. The improvement seen in QoL were clinically and statistically favourable to fluticasone only at the 15th day of follow up as compared to beclomethasone/budesonide, whereas no difference was noted in the lung functions. On continuation of treatment for three months, there was no difference in improvement of quality of life between the treatment groups. This may suggest that there is no advantage of fluticasone compared to beclomethasone/budesonide on prolonged therapy. This is further supported by the studies reviewed by Neil Barnes  where the author has concluded that the difference between fluticasone and beclomethasone/budesonide in terms of safety and efficacy may be of importance only in patients with asthma that is more difficult to control and require higher doses of inhaled steroids.
Pulmonary function test (FEV 1 ) also improved with both the drugs during the treatment. There was significant improvement in lung function (p<0.05) after 30 days of treatment which further did not change in both the groups. The same magnitude of improvement in lung functions were observed in both the groups supporting the evidence that at equipotent doses beclomethasone/budesonide was comparable to fluticasone. There was no correlation (r = 0.2) between the changes in QoL scores and change in FEV 1 values. This may be due to the reason that even with small change in FEV 1 values, patients felt much better, because of which their quality of life improved to a greater extent. At the end of the treatment there was no significant difference in SGRQ scores and lung functions between the different treatment groups. Similar results were noted in the study conducted by Belgian multicenter study group where patients receiving beclomethasone and half the dose of fluticasone, demonstrated similar asthma control, improvement in lung functions, symptom - free days and nights, days free from rescue medications and rate of asthma exacerbations in a population of moderate to severe asthmatics  .
There are few studies on the improvement inquality of life in asthma patients using inhaled corticosteroids and all of them demonstrated significant improvement in quality of life. A few of them have used generic quality of life measures like SF-36 and a few have used disease specific quality of life questionnaire like AQLQ. To our knowledge, this may be the first study in asthma patients using Saint George's Respiratory Questionnaire to compare between different inhaled steroids.
It is clear from the study that there is little to choose between different inhaled steroids. The lung functions showed the same degree of improvement at every follow up until three months. There was a clinically and statistically significant superior improvement in quality of life among patients receiving fluticasone in the 15 th day follow up. But by the second follow up on the 30 th day and subsequently thereafter, there was no difference between the two groups. The improvement on the 15 th day was seen in the impact and activity scores, but not in the symptom scores and this was seen in patients with higher severity of disease. Given that inhaled corticosteroids are used for long-term therapy in asthma management, the clinical significance of this early response is unlikely to be important.
In conclusion, early response to fluticasone was noticed in the QoL scores, in moderate to severe asthma patients. On subsequent follow-ups there was no difference in QoL scores between the two groups. SGRQ scores continued to improve, showing significant improvement between 60 and 90 days of treatment in both the groups. No linear relation between improvement in pulmonary function tests and improvement in quality of life was found. When equipotent doses of inhaled corticosteroids are used to treat asthma, there is no advantage of fluticasone over the other inhaled corticosteroids in the long term.
| Acknowledgements|| |
The authors sincerely thank JSS Mahavidhyapeeta, Medical Superintendent, JSS Medical College Hospital; Principal, JSS College of Pharmacy for their support. We also express our gratitude to Dr. Prabhakar, Senior epidemiologist for his expert opinion. Our thanks to University Grants Commission, Govt. of India, New Delhi, for funding and CIPLA Ltd for providing free drug samples for the study.
| References|| |
|1.||Robert F Lemanske, William W Busse. Allergic disorders≠Asthma. J Allergy Clin Immunol 2003; 111:S502-19. |
|2.||Thomas B.Casale, Harold S. Nelson, James Kemp, Bhash Parasuraman, et al. Budesonide turbuhaler delivered once daily improves health-related quality of life and maintains improvements with a stepped-down dose in adults with mild to moderate asthma. Ann Allergy Asthma Immunol 2003; 90:323-30. |
|3.||Lynn J Okamoto, Michael Noonan, Bennett P De Boisblanc, Donald J Kellerman. Fluticasone propionate improves quality of life in patients with asthma requiring oral corticosteroids. Ann Allergy Asthma Immunol 1996; 76: 455-61. |
|4.||EF Juniper. Assessing health-related quality of life in asthma. Can Respir J 1997; 4: 145-51. |
|5.||B.Davies. A comparison of beclomethasone propionate and budesonide in the treatment of asthma.Br J Clin Pract March/April 1993; 47:87-93. |
|6.||Clark TJH, Cagnanai CB, Bousquet J, et al. Global Initiative for asthma. Global strategy for asthma management and prevention. NIH Publication No.02-3659, 2002, 1-176. |
|7.||Paul W Jones, Frances H. Quirk, Chloe M. Baveystock and Peter Littlejohns. A self-complete measure of health status for chronic airflow limitation-The St. Georges Respiratory Questionnaire. Am Rev Respir Dis 1992; 145:1321-27. |
|8.||Barnes NC, Hallet C, Harris TA. Clinical experience with fluticasone propionate in asthma: a meta-analysis of efficacy and systemic activity compared with budesonide and beclomethasone dipropionate at half the microgram dose or less. Respir Med 1998; 92:95-104. |
|9.||Carolyn Rutherford, Rose Mills, Peter G. Gibson, Martin J.Price. Improvement in health-related quality of life with fluticasone propionate compared with budesonide or beclomethasone dipropionate in adults with severe asthma. Respirology 2003; 8:371-75. |
|10.||Neil Barnes "Relative safety and efficacy of Inhaled steroids". J Allergy Clin Immunol 1998; 101:S460-4. |
|11.||RA Pauwels, JC Yernault, MG Demedts and P Geusens. Safety and efficacy of fluticasone and beclomethasone in moderate to severe asthma. Am J Respir Crit Care Med. 1998; 157: 827-32. |
[Figure 1], [Figure 2], [Figure 3], [Figure 5]
[Table 1], [Table 2]