Introduction In a multicenter study of 831 patients (age ...
2
Introduction Allergic Rhinitis (AR) is the most common type of chronic rhinitis, affecting 10-20% of the population, and evidence suggests that the prevalence of the disorder is increasing. Allergic rhinitis is a common disorder that is strongly linked to asthma and conjunctivitis. It is usually 1 a long-standing condition that often goes undetected in the primary-care setting. Asthma is characterized by a chronic inflammation process with increased numbers of activated eosinophils, mast cells, macrophages and T lymphocytes in the airway mucosa and lumen, which 2 produce mediators of inflammation such as histamine, prostaglandins and leucotrienes. Airway mucus hypersecretion is a feature of asthma, 3 COPD and cystic fibrosis (CF). Allergic rhinitis and asthma are both chronic heterogeneous disorders, with an overlapping epidemiology of prevalence, health care costs and 4 social costs in quality of life. Both are inflammatory disorders with a similar pathophysiology, and both share same treatment approaches. Mucoactive agents have been the medication of choice for the treatment of respiratory diseases in which mucus hypersecretion is a clinical 5 complication. Mucoactive medications include expectorants, mucoregulators, mucolytics and mucokinetics. Acebrophylline is an airway mucus regulator and mucokinetic with anti-inflammatory action. Studies indicate that acebrophylline is therapeutically effective in patients with acute or chronic bronchitis, chronic obstructive or asthma-like bronchitis and 6 recurrence of chronic bronchitis. Fexofenadine hydrochloride is a potent, selective, nonsedating H1-receptor antagonist with proven efficacy in clinical symptom relief and 7 in improving QoL in patients with AR and chronic idiopathic urticaria. Montelukast is a selective Leukotriene receptor antagonist (LTRA) that inhibits the cysteinyl leukotriene receptor 1. Montelukast is used in 8 the treatment of both asthma and Allergic Rhinitis. 9 Montelukast is the only LTRA approved by the USFDA for the treatment of Seasonal Allergic Rhinitis. This article discusses the efficacy of plausible combination of Acebrophylline, Fexofenadine and Montelukast in the treatment of Allergic Rhinitis and Asthma. Allergic Rhinitis and Asthma: The united airways disease and a Bidirectional link between the nose and Bronchi Allergic rhinitis is frequently associated with asthma, which is found in 15% to 38% of patients with AR, and nasal symptoms are present in 6% to 85% patients with asthma. In addition, AR is a risk factor for asthma, and uncontrolled 10 moderate-to-severe AR affects asthma control. Rhinitis and asthma are often associated and the two disorders interact at various levels. Rhinitis typically precedes the development of asthma and can contribute to unsatisfactory asthma control. The presence and type of asthma is influenced by sensitization, and the duration and severity of allergic rhinitis. There is increasing evidence that suggests a major involvement of airway epithelial cells in the pathogenesis of both asthma and allergic rhinitis. Studies have shown that, even in the absence of clinical symptoms of asthma, patients with seasonal AR have an increase in inflammatory cells in their 'in-season' bronchial biopsies. Similarly, patients with asthma but without symptoms of rhinitis have an increased number of eosinophils in their nasal biopsies and secretions. The hypothesis of the pathophysiological network sustaining the 11 concept of the 'one airway disease' is summarized in Figure 1. Acebrophylline: Mechanism of action Acebrophylline is obtained by targeted salification of the ambroxol base [trans- 4(2-amino-3,5 dibromobenzylamino) cyclohexanol] and theophylline 7 acetic acid. Acebrophylline has dual action on pathological secretions: it acts directly as a mucoregulator, and indirectly by stimulating surfactant synthesis. Acebrophylline also has anti-inflammatory-antireactive action essential for clearing bronchial 6 obstruction (Figure 2). Clinical efficacy of Acebrophylline in Asthma and Chronic Bronchitis Acebrophylline is superior to Theophylline in terms of efficacy and tolerability in patients with mild bronchial asthma - Indian Study A randomized, open, parallel Indian study compared the efficacy and tolerability of Theophylline and Acebrophylline in 100 mild persistent asthma patients. Theophylline was prescribed to 50 patients and Acebrophylline to remaining 50 patients for 4 weeks. The study results showed that intensity of cough and sputum quantity reduced significantly in Acebrophylline group than Theophylline group in (p<0.001) and (p<0.001; Figure 3). Highly significant improvement in Peak expiratory flow rate (PEFR) & FEV was noticed in Acebrophylline group. Adverse effects were 1 significantly low in Acebrophylline than Theophylline group. Acebrophylline was found to be superior to Theophylline in terms of efficacy and tolerability in patients with mild bronchial asthma as 12 evidenced by subjective and objective means. In stable bronchial asthma and asthma-like chronic bronchitis A multicentre, randomised, parallel-groups trial, evaluated the efficacy of acebrophylline and ambroxol in 122 patients with stable asthma-like chronic bronchitis. Sixty patients were treated with ambroxol (one 30-mg sachet t.i.d.), and the other 62 received acebrophylline (one 100-mg sachet b.i.d.) for 45 days. The results of the study showed that acebrophylline was more active than ambroxol, in relieving clinical signs and symptoms (amount and appearance of sputum, pathological auscultation and dyspnea) and improving respiratory function (vital 1 capacity (VC), FEV and forced expiratory flow, FEF ). The frequency of bronchospastic attacks between 15 and 30 days of treatment was 25-75 seen in 21% of patients in the acebrophylline group and in 54% patients taking Ambroxol (Figure 4). The action of acebrophylline was significantly superior to that of ambroxol as a result of the stronger stimulation of pulmonary surfactant 13 production and more effective mucoregulation. Safety of Acebrophylline in adults Acebrophylline is well-tolerated in adults, with a low rate of adverse reactions, normally only mild gastrointestinal upset (2.6%) not requiring 14 any treatment discontinuation. Fexofenadine: Efficacy in Allergic Rhinitis Fexofenadine is a selective, non-sedating, second-generation H1 receptor antagonist which has an additional impact on the inflammatory 15 mediators and does not cause electrocardiographic effects. Results of a multicenter, 14-day, placebo-controlled, double-blind trial of fexofenadine HCl at dosages of 60, 120, and 240 mg bid in 570 patients with ragweed seasonal allergic rhinitis showed that Fexofenadine HCl at each dosage provided significant improvement in total symptom score (p ≤0.003) and in all individual nasal symptoms compared with placebo. 60 mg bid appeared to be the optimal therapeutic 16 dosage for these patients. Results of Meta-analysis: Fexofenadine can be recommended for the treatment of Seasonal Allergic Rhinitis Results of 8 studies with 3,532 participants evaluating the efficacy and safety of fexofenadine in the treatment of AR showed that Fexofenadine can be recommended for the treatment of Seasonal Allergic Rhinitis. The primary outcome was the 12- or 24-hour reflective total symptom scores (TSS), the sum of sneezing, rhinorrhea, itchy nose/palate, and itchy/watery/ red eyes, excluding nasal congestion. Fexofenadine-treated participants showed a significant reduction of TSS compared with those treated with placebo (SMD –0.42; p<0.00001: 7 Figure 5). Montelukast: An effective drug in treating Allergic Rhinitis and Asthma Montelukast, a Leukotriene receptor antagonist (LTRA) is an FDA-approved drug for the treatment of chronic asthma and prophylaxis and the prevention of exercise-induced bronchoconstriction. It is also approved for the relief of symptoms of both seasonal and perennial 17 allergic rhinitis. Figure 2. Effects on mucus and anti-inflammatory action of acebrophylline Figure 3. Intensity of cough before and after treatment with theophylline and acebrophylline Figure 4. Improved attacks of bronchospasm in acebrophylline vs. ambroxol Figure 5. Efficacy of fexofenadine in patients with AR compared to placebo (outcomes: reflective TSS) In a multicenter study of 831 patients (age 15-85 years) with seasonal allergen sensitivity, active symptoms of seasonal allergic rhinitis, and active asthma, treatment with oral montelukast 10 mg (n = 415) or placebo (n = 416) daily for 2-week, double-blind, active-treatment period resulted in significant relief from symptoms of seasonal allergic rhinitis, conferring a benefit for asthma, in patients with both allergic rhinitis 18 and asthma. A phase IV study investigated the efficacy and safety of montelukast 10mg in adults with both asthma and allergic rhinitis in a real-life setting. Data from 5855 patients (mean age: 42.8±15.4 years) were collected and analyzed following treatment for 4-6 weeks. Overall QoL was "very good" or "good" in 85.2% of patients (n=4991; Figure 6) and a "strong" or "marked" improvement in each of the four domains of sleep, work, everyday life and physical activity. 19 The study results showed that Montelukast 10mg was a safe and effective treatment for patients with both asthma and allergic rhinitis. Efficacy of combination of Montelukast and Fexofenadine in Allergic Rhinitis and Asthma Ceibiada et al., conducted a study to investigate the effects of treatment with a combination of fexofenadine and either montelukast or a fluticasone in patients with persistent allergic rhinitis and newly diagnosed asthma. Forty patients with persistent allergic rhinitis and newly diagnosed asthma received fexofenadine (120 mg/day) with fluticasone (200 μg/day) for 6 weeks then fexofenadine (120 mg/day) with montelukast (10 mg/day) for another 6 weeks. Symptom scores, anterior rhinoscopy, spirometry and serum concentrations of soluble intercellular adhesion molecule 1 (sICAM-1) were evaluated before and after 6-week treatment periods. The combination of fexofenadine with either montelukast or fluticasone equally reduced the serum sICAM-1 concentration and gave the 20 same clinical effect in patients with persistent allergic rhinitis and newly diagnosed asthma (Table 1). Figure 6. Overall improvement in Asthma, Rhinitis and QoL Figure 1. Physiopathological hypotheses explaining the concept of 'one airway disease'. Solid lines: experimental data confirm the impact of the mechanism mentioned. Dotted lines: some experimental evidence suggests the impact of the mechanism mentioned, but only preliminary or suggestive data are available (sometimes without a full understanding of the mechanism itself). Postnasal drip Nose (sinu) bronchial relfex Physical filter impairment Adhesion molecules Cytokines Epithelial cells Bone marrow Infections Inflammation Bronchial hyperreactivity Pneumocyte Phosphatidylcholine Surfactant A Phospholipase 2 Lipophosphatidylcholine Arachidonic Acid Lipooxygenase Phlogogen (Leukotriens, SRS-A) Acebrophylline Theophylline Acebrophylline 2.5 2 1.5 1 0.5 0 2.1 2.233 1.967 1.867 1.767 1.767 1.567 1.433 0.633 2nd week 3rd week 4th week 1st week Baseline 1.3 Cough intensity Acebrophylline Ambroxol 60 50 40 30 20 10 0 21 54 44 5 B/w 15-30 days of treatment B/w 30-45 days of treatment *p<0.01 acebrophylline vs. ambroxol Bronchospastic attacks ( Patients %) 2.56 282 202 232 6.78 5.4 5.42 1.88 2.34 2.81 292 201 225 718 16.5 11.4 13.2 41.2 –0.41 (–0.51, –0.30) –0.32 (–0.50, –0.14) –0.55 (–0.75, –0.36) –0.38 (–0.55, –0.22) 2.4 2.11 4.81 2.15 9.16 7.45 2.11 4.81 2.16 126 141 138 107 469 981 9.8 8.3 7.9 6.2 58.8 26.6 –0.42 (–0.51, –0.34) (–0.54, –0.11) –0.32 (–0.56, –0.09) –0.45 (–0.69, –0.21) –0.52 (–0.79, –0.26) (–0.59, –0.33) Study or subgroup Fexofenadine Placebo Std. mean difference IV, fixed, 95% CI mean SD total mean SD total weight, % 1.1.1 12-hour reflective TSS Berger 6.26 2.37 260 7.03 2.37 –0.32 Bernstein 6.55 144 7.32 2.37 Bronsky 6.5 137 Schapowal 6.63 113 Wahn 4.86 463 5.86 –0.46 Subtotal (95% CI) 1,117 2 2 Heterogeneity: X = 2.50, d.f. = 4 (p = 0.65); I = 0% Test for overall effect: Z = 9.51 (p < 0.00001) 1.1.2 24-hour reflective TSS Casale 6.07 1.85 Howarth 4.1 2.34 Van Cauwenberge 4.56 Subtotal (95% CI) 716 2 2 Heterogeneity: X = 3.07, d.f. = 2 (p = 0.22); I = 35% Test for overall effect: Z = 7.66 (p < 0.00001) Total (95% CI) 1,833 1,699 100.0 –0.42 (–0.49, –0.35) 2 2 Heterogeneity: X = 5.62, d.f. = 7 (p = 0.58); I = 0% Test for overall effect: Z = 12.21 (p < 0.00001) 2 2 Test for subgroup differences: X = 0.05, d.f. = 1 (p = 0.82); I = 0% –2 –1 Favours treatment Favours control 0 1 2 Std. mean difference IV, fixed, 95% CI * * Overall improvement of asthma V. Good Good Sat. Suff. Not Suff. 0 10 20 30 40 50 60 70 Degree of improvement n (%) V. Good Good Sat. Suff. Not Suff. 0 10 20 30 40 50 60 Degree of improvement n (%) Overall improvement of allergic rhinits Overall improvement in QoL V. Good Good Sat. Suff. Not Suff. 0 10 20 30 40 50 60 Degree of improvement n (%) Sat: satisfactory Suff: sufficient
Transcript of Introduction In a multicenter study of 831 patients (age ...
IntroductionAllergic Rhinitis (AR) is the most common type of chronic rhinitis, affecting 10-20% of the population, and evidence suggests that the prevalence of the disorder is increasing. Allergic rhinitis is a common disorder that is strongly linked to asthma and conjunctivitis. It is usually
1a long-standing condition that often goes undetected in the primary-care setting. Asthma is characterized by a chronic inflammation process with increased numbers of activated eosinophils, mast cells, macrophages and T lymphocytes in the airway mucosa and lumen, which
2produce mediators of inflammation such as histamine, prostaglandins and leucotrienes. Airway mucus hypersecretion is a feature of asthma,
3COPD and cystic fibrosis (CF). Allergic rhinitis and asthma are both chronic heterogeneous disorders, with an overlapping epidemiology of prevalence, health care costs and
4 social costs in quality of life. Both are inflammatory disorders with a similar pathophysiology, and both share same treatment approaches.Mucoactive agents have been the medication of choice for the treatment of respiratory diseases in which mucus hypersecretion is a clinical
5complication. Mucoactive medications include expectorants, mucoregulators, mucolytics and mucokinetics.Acebrophylline is an airway mucus regulator and mucokinetic with anti-inflammatory action. Studies indicate that acebrophylline is therapeutically effective in patients with acute or chronic bronchitis, chronic obstructive or asthma-like bronchitis and
6recurrence of chronic bronchitis.Fexofenadine hydrochloride is a potent, selective, nonsedating H1-receptor antagonist with proven efficacy in clinical symptom relief and
7in improving QoL in patients with AR and chronic idiopathic urticaria.Montelukast is a selective Leukotriene receptor antagonist (LTRA) that inhibits the cysteinyl leukotriene receptor 1. Montelukast is used in
8the treatment of both asthma and Allergic Rhinitis. 9Montelukast is the only LTRA approved by the USFDA for the treatment of Seasonal Allergic Rhinitis.
This article discusses the efficacy of plausible combination of Acebrophylline, Fexofenadine and Montelukast in the treatment of Allergic Rhinitis and Asthma.
Allergic Rhinitis and Asthma: The united airways disease and a Bidirectional link between the nose and BronchiAllergic rhinitis is frequently associated with asthma, which is found in 15% to 38% of patients with AR, and nasal symptoms are present in 6% to 85% patients with asthma. In addition, AR is a risk factor for asthma, and uncontrolled
10moderate-to-severe AR affects asthma control.Rhinitis and asthma are often associated and the two disorders interact at various levels. Rhinitis typically precedes the development of asthma and can contribute to unsatisfactory asthma control. The presence and type of asthma is influenced by sensitization, and the duration and severity of allergic rhinitis. There is increasing evidence that suggests a major involvement of airway epithelial cells in the pathogenesis of both asthma and allergic rhinitis. Studies have shown that, even in the absence of clinical symptoms of asthma, patients with seasonal AR have an increase in inflammatory cells in their 'in-season' bronchial biopsies. Similarly, patients with asthma but without symptoms of rhinitis have an increased number of eosinophils in their nasal biopsies and secretions. The hypothesis of the pathophysiological network sustaining the
11concept of the 'one airway disease' is summarized in Figure 1.
Acebrophylline: Mechanism of actionAcebrophylline is obtained by targeted salification of the ambroxol base [trans-4(2-amino-3,5 dibromobenzylamino) cyclohexanol] and theophylline 7 acetic acid. Acebrophylline has dual action on pathological secretions: it acts directly as a mucoregulator, and indirectly by stimulating surfactant synthesis. Acebrophylline also has anti-inflammatory-antireactive action essential for clearing bronchial
6obstruction (Figure 2).
Clinical efficacy of Acebrophylline in Asthma and Chronic BronchitisAcebrophylline is superior to Theophylline in terms of efficacy and tolerability in patients with mild bronchial asthma - Indian StudyA randomized, open, parallel Indian study compared the efficacy and tolerability of Theophylline and Acebrophylline in 100 mild persistent asthma patients. Theophylline was prescribed to 50 patients and Acebrophylline to remaining 50 patients for 4 weeks.
The study results showed that intensity of cough and sputum quantity reduced significantly in Acebrophylline group than Theophylline group in (p<0.001) and (p<0.001; Figure 3). Highly significant improvement in Peak expiratory flow rate (PEFR) & FEV was noticed in Acebrophylline group. Adverse effects were 1
significantly low in Acebrophylline than Theophylline group. Acebrophylline was found to be superior to Theophylline in terms of efficacy and tolerability in patients with mild bronchial asthma as
12evidenced by subjective and objective means.
In stable bronchial asthma and asthma-like chronic bronchitisA multicentre, randomised, parallel-groups trial, evaluated the efficacy of acebrophylline and ambroxol in 122 patients with stable asthma-like chronic bronchitis. Sixty patients were treated with ambroxol (one 30-mg sachet t.i.d.), and the other 62 received acebrophylline (one 100-mg sachet b.i.d.) for 45 days. The results of the study showed that acebrophylline was more active than ambroxol, in relieving clinical signs and symptoms (amount and appearance of sputum, pathological auscultation and dyspnea) and improving respiratory function (vital
1capacity (VC), FEV and forced expiratory flow, FEF ). The frequency of bronchospastic attacks between 15 and 30 days of treatment was 25-75
seen in 21% of patients in the acebrophylline group and in 54% patients taking Ambroxol (Figure 4).
The action of acebrophylline was significantly superior to that of ambroxol as a result of the stronger stimulation of pulmonary surfactant 13production and more effective mucoregulation.
Safety of Acebrophylline in adults Acebrophylline is well-tolerated in adults, with a low rate of adverse reactions, normally only mild gastrointestinal upset (2.6%) not requiring
14any treatment discontinuation.
Fexofenadine: Efficacy in Allergic RhinitisFexofenadine is a selective, non-sedating, second-generation H1 receptor antagonist which has an additional impact on the inflammatory
15mediators and does not cause electrocardiographic effects.Results of a multicenter, 14-day, placebo-controlled, double-blind trial of fexofenadine HCl at dosages of 60, 120, and 240 mg bid in 570 patients with ragweed seasonal allergic rhinitis showed that Fexofenadine HCl at each dosage provided significant improvement in total symptom score (p ≤0.003) and in all individual nasal symptoms compared with placebo. 60 mg bid appeared to be the optimal therapeutic
16dosage for these patients.
Results of Meta-analysis: Fexofenadine can be recommended for the treatment of Seasonal Allergic Rhinitis Results of 8 studies with 3,532 participants evaluating the efficacy and safety of fexofenadine in the treatment of AR showed that Fexofenadine can be recommended for the treatment of Seasonal Allergic Rhinitis. The primary outcome was the 12- or 24-hour reflective total symptom scores (TSS), the sum of sneezing, rhinorrhea, itchy nose/palate, and itchy/watery/ red eyes, excluding nasal congestion. Fexofenadine-treated participants showed a significant reduction of TSS compared with those treated with placebo (SMD –0.42; p<0.00001:
7Figure 5).
Montelukast: An effective drug in treating Allergic Rhinitis and AsthmaMontelukast, a Leukotriene receptor antagonist (LTRA) is an FDA-approved drug for the treatment of chronic asthma and prophylaxis and the prevention of exercise-induced bronchoconstriction. It is also approved for the relief of symptoms of both seasonal and perennial
17allergic rhinitis.
Figure 2. Effects on mucus and anti-inflammatory action of acebrophylline
Figure 3. Intensity of cough before and after treatment with theophylline and acebrophylline
Figure 4. Improved attacks of bronchospasm in acebrophylline vs. ambroxol
Figure 5. Efficacy of fexofenadine in patients with AR compared to placebo (outcomes: reflective TSS)
In a multicenter study of 831 patients (age 15-85 years) with seasonal allergen sensitivity, active symptoms of seasonal allergic rhinitis, and active asthma, treatment with oral montelukast 10 mg (n = 415) or placebo (n = 416) daily for 2-week, double-blind, active-treatment period resulted in significant relief from symptoms of seasonal allergic rhinitis, conferring a benefit for asthma, in patients with both allergic rhinitis
18and asthma.
A phase IV study investigated the efficacy and safety of montelukast 10mg in adults with both asthma and allergic rhinitis in a real-life setting. Data from 5855 patients (mean age: 42.8±15.4 years) were collected and analyzed following treatment for 4-6 weeks. Overall QoL was "very good" or "good" in 85.2% of patients (n=4991; Figure 6) and a "strong" or "marked" improvement in each of the four domains of sleep, work, everyday life and physical activity.
19The study results showed that Montelukast 10mg was a safe and effective treatment for patients with both asthma and allergic rhinitis.
Efficacy of combination of Montelukast and Fexofenadine in Allergic Rhinitis and Asthma Ceibiada et al., conducted a study to investigate the effects of treatment with a combination of fexofenadine and either montelukast or a fluticasone in patients with persistent allergic rhinitis and newly diagnosed asthma.Forty patients with persistent allergic rhinitis and newly diagnosed asthma received fexofenadine (120 mg/day) with fluticasone (200 μg/day) for 6 weeks then fexofenadine (120 mg/day) with montelukast (10 mg/day) for another 6 weeks. Symptom scores, anterior rhinoscopy, spirometry and serum concentrations of soluble intercellular adhesion molecule 1 (sICAM-1) were evaluated before and after 6-week treatment periods.The combination of fexofenadine with either montelukast or fluticasone equally reduced the serum sICAM-1 concentration and gave the
20same clinical effect in patients with persistent allergic rhinitis and newly diagnosed asthma (Table 1).
Figure 6. Overall improvement in Asthma, Rhinitis and QoL
Figure 1. Physiopathological hypotheses explaining the concept of 'one airway disease'. Solid lines: experimental data confirm the impact of the mechanism mentioned. Dotted lines: some experimental evidence suggests the impact of the mechanism mentioned, but only preliminary or suggestive data are available (sometimes without a full understanding of the mechanism itself).
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Ep
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llsBone marrow
Infections
Inflammation
Bro
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ial h
yper
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tivi
tyPneumocyte
Phosphatidylcholine Surfactant
A Phospholipase2
Lipophosphatidylcholine
Arachidonic Acid
Lipooxygenase
Phlogogen(Leukotriens, SRS-A)
Acebrophylline
Theophylline Acebrophylline
2.5
2
1.5
1
0.5
0
2.12.233
1.9671.867 1.7671.767 1.5671.433
0.633
2nd week 3rd week 4th week1st weekBaseline
1.3
Co
ugh
inte
nsi
ty
AcebrophyllineAmbroxol
60
50
40
30
20
10
0
21
54
44
5
B/w 15-30 days oftreatment
B/w 30-45 days oftreatment
*p<0.01 acebrophylline vs. ambroxol
Bro
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s (
Pat
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ts %
)
2.56
282202232
6.785.45.42
1.882.342.81
292201225718
16.511.413.241.2 –0.41 (–0.51, –0.30)
–0.32 (–0.50, –0.14)–0.55 (–0.75, –0.36)–0.38 (–0.55, –0.22)
2.42.114.812.15
9.167.45 2.11
4.812.16
126141138107469981
9.88.37.96.2
58.826.6
–0.42 (–0.51, –0.34)
(–0.54, –0.11)–0.32 (–0.56, –0.09)–0.45 (–0.69, –0.21)
–0.52 (–0.79, –0.26)(–0.59, –0.33)
Study orsubgroup
Fexofenadine Placebo Std. mean differenceIV, fixed, 95% CI
mean SD total mean SD total weight, %
1.1.1 12-hour reflective TSSBerger 6.26 2.37 260 7.03 2.37 –0.32 Bernstein 6.55 144 7.32 2.37Bronsky 6.5 137Schapowal 6.63 113Wahn 4.86 463 5.86 –0.46 Subtotal (95% CI) 1,117
22
Heterogeneity: X = 2.50, d.f. = 4 (p = 0.65); I = 0%Test for overall effect: Z = 9.51 (p < 0.00001)
1.1.2 24-hour reflective TSSCasale 6.07 1.85Howarth 4.1 2.34Van Cauwenberge 4.56Subtotal (95% CI) 716
22Heterogeneity: X = 3.07, d.f. = 2 (p = 0.22); I = 35%
Test for overall effect: Z = 7.66 (p < 0.00001)
Total (95% CI) 1,833 1,699 100.0 –0.42 (–0.49, –0.35)2
2Heterogeneity: X = 5.62, d.f. = 7 (p = 0.58); I = 0%Test for overall effect: Z = 12.21 (p < 0.00001)
22Test for subgroup differences: X = 0.05, d.f. = 1 (p = 0.82); I = 0%
–2 –1
Favours treatment Favours control
0 1 2
Std. mean differenceIV, fixed, 95% CI
*
*
Overall improvement of asthma
V. Good Good Sat. Suff. Not Suff.
0
10
20
30
40
50
60
70
Degree of improvement
n (
%)
V. Good Good Sat. Suff. Not Suff.0
10
20
30
40
50
60
Degree of improvement
n (
%)
Overall improvement of allergic rhinits Overall improvement in QoL
V. Good Good Sat. Suff. Not Suff.0
10
20
30
40
50
60
Degree of improvement
n (
%)
Sat: satisfactory Suff: sufficient
Fexofenadine + fluticasone Fexofenadine + montelukast
Baseline After treatment Baseline After treatment
Total nasal symptom score
Table 1. Results in patients with persistent allergic rhinitis and newly diagnosed asthma treated for 6 weeks either
with combination of fexofenadine and fluticasone or with combination of fexofenadine and montelukast. Valuesare presented as mean ± SEM
Anterior rhinoscopy score
Asthma symptom score
Spirometry [I/S]
sICAM-1 [ng/ml]
8.15 ± 1.37
6.9 ± 1.3
7.1 ± 0.8
3.6 ± 0.17
243.4 ± 20.7
3.62 ± 0.77
3.2 ±0.9
2.1 ± 1.5
3.76 ± 0.6
221 ± 20.4
8.27 ± 1.38
6.5 ±1.3
6.9 ± 2.3
3.69 ± 0.2
240.9 ± 19.8
3.55 ± 0.78
3.0 ±1.1
1.7± 1.4
3.72 ± 0.21
218.3 ± 17.6
2019
Summary Ÿ Allergic rhinitis is the most common type of chronic rhinitis, affecting 10-20% of the population.Ÿ Allergic asthma is a complex and chronic inflammatory disorder which is associated with airway hyper-responsiveness and
tissue remodelling of the airway structure.Ÿ Allergic rhinitis and asthma have overlapping epidemiology of prevalence, health care costs and social costs in quality of life.
Both are inflammatory disorders with a similar pathophysiology, and both share same treatment approaches.Ÿ Airway mucus hypersecretion is a common feature of asthma, COPD and cystic fibrosis.Ÿ Mucoactive agents have been the medication of choice for the treatment of respiratory diseases in which mucus
hypersecretion is a clinical complication. Ÿ Acebrophylline is an effective airway mucus regulator with anti-inflammatory activity. Ÿ Clinical studies reveal that Acebrophylline is superior to Theophylline in terms of efficacy and tolerability in patients with
mild bronchial asthma and is effective in stable bronchial asthma and asthma-like chronic bronchitis. Acebrophylline is well-tolerated in adults.
1Ÿ Fexofenadine is a selective, non-sedating, second-generation H receptor antagonist and is a recommended drug for the
treatment of SAR.Ÿ Montelukast, a Leukotriene receptor antagonist (LTRA) is an FDA-approved drug for the treatment of chronic asthma,
prophylaxis and the prevention of exercise-induced bronchoconstriction and relief of symptoms of both seasonal and perennial allergic rhinitis.
Ÿ Montelukast is a safe and effective treatment for patients with both asthma and allergic rhinitis.Ÿ Combination of Montelukast and Fexofenadine is effective in treatment of patients with persistent allergic rhinitis and
newly diagnosed asthma. Overall, Acebrophylline, Montelukast and Fexofenadine may present as a valuable combination in treating patients with Asthma, Allergic Rhinitis and Chronic Bronchitis.
References: 1.Small P et al. Allergy Asthma Clin Immunol.2018;14(Suppl 2):51:32-41. 2.Joos S et al. Thorax 2008;63:453–462. 3.Rogers DF. Respir Care. 2007; 52(9):1176-1193. 4.Kim H et al. Can Respir J. 2008;15(2):91-98. 5.Balsamo R et al. Eur Respir Rev. 2010;19(116):127-33. 6.Pozzi E. Monaldi Arch Chest Dis. 2007; 67:2,106-115. 7.Compalati E et al. Int Arch Allergy Immunol. 2011;156(1):1-15. 8.Neighbour H et al. Clin. Pract. 2013;10(3):257-263. 9.Dykewicz MS et al. Ann Allergy Asthma Immunol. 2017;119(6):489-511.e41. 10.Brozek JL et al. J Allergy Clin Immunol.2017; 140(4):951-958. 11.Compalati E et al. Expert Rev Clin Immunol. 2010;6(3):413-423. 12.Saravanakumar C et al. Int J Pharm Bio Sci 2014; 5 (2) : (P) 214- 222. 13.Catena E et al. Giorn It Mal Tor. 1992; 1 (s): 97-102. (Original article). Cited in: Pozzi E. Monaldi Arch Chest Dis. 2007; 67: 2, 106-115. 14.Goldrub N et al. Advan Ther. 1992; 9: 107-115. 15.Mahatme MS et al. Indian J Pharmacol. 2016;48(6):649–653. 16.Bernstein DI et al. Ann Allergy A s t h m a I m m u n o l . 1 9 9 7 ; 7 9 ( 5 ) : 4 4 3 - 4 4 8 . 1 7 . B a d r i T e t a l . A c c e s s e d f r o m w e b s i t e https://www.ncbi.nlm.nih.gov/books/NBK459301/ as on 11.01.2019. 18.Philip G et al. Curr Med Res Opin. 2004;20(10):1549-1558. 19.Virchow JC et al. Respir Med. 2006;100(11):1952-1959. 20.CiebiadaM et al. Arch Med Sci. 2009;4,:1-6.
For significant relief ofsymptoms in Asthma, Allergic
Rhinitis and Chronic Bronchitis
Acebrophylline 200mg (Sustained Release)+Fexofenadine 120mg+Montelukast 10mg Tablets
Acebrophylline 200mg (Sustained Release)+Fexofenadine 120mg+Montelukast 10mg Tablets
Acebrophylline 200mg (Sustained Release)+Fexofenadine 120mg+Montelukast 10mg Tablets
Acebrophylline 50mg + Levocetirizine Di HCl 2.5mg +Montelukast 4mg Suspension
Acebrophylline 100mg Capsules
Acebrophylline 50mg Syrup
Acebrophylline 100mg Tablets
Acebrophylline 200mg SR Tablets
Acebrophylline 100mg + Acetylcysteine 600mg Tablets
