Documente Academic
Documente Profesional
Documente Cultură
Abstract
Allergic rhinitis is a specific allergic reaction of the nasal mucosa and is characterized by rhinorrhea, sneezing, nasal congestion
and pruritus of the eyes, nose and throat. The purpose of this study was to evaluate the safety and efficacy of Bresol tablets
in the management of allergic rhinitis. The present study was an open, prospective, noncomparative clinical trial conducted
in 50 patients suffering from allergic rhinitis. At the initial visit, the patients were subjected to a detailed medical history
followed by a thorough clinical examination. The patients were administered Bresol tablets at a dosage of two tablets, twice
a day orally for a period of four weeks. All the patients were followed-up at weekly intervals for a period of four weeks, and
were evaluated for clinical relief from individual symptoms of allergic rhinitis, which included sneezing, nasal congestion,
itching of the eyes and nose, postnasal drip, rhinorrhea and watery eyes using 10-point visual analog scale. They were also
investigated for hematological parameters. Treatment with Bresol tablets showed significant improvements in all the symptoms
of allergic rhinitis by the second week; further improvement was observed with the treatment by the fourth week. All subjects
completed the study. Significant improvement was also observed in hematological parameters such as absolute eosinophil
count and other supporting parameters such as erythrocyte sedimentation rate (ESR), total leukocyte count and differential
count. No adverse effects were reported or observed during the study and compliance to the use of formulation was good.
The findings reported in this study shows that Bresol tablets of The Himalaya Drug Company help in relieving the symptoms
of allergic rhinitis and also normalize absolute eosinophilic count, ESR, total leukocyte count and differential count. None
of the volunteers experienced any hypersensitivity reactions. Therefore, it can be concluded that the test medication Bresol
tablet is safe and effective in the management of allergic rhinitis.
Key words: Allergic rhinitis, Bresol tablet
Original ARticle
sinusitis, recurrence of nasal polyps, otitis media/otitis
media with effusion, hearing impairment, abnormal
craniofacial development, sleep apnea and related
complications, aggravation of underlying asthma and
increased propensity to develop asthma.8
The three basic approaches for the treatment of
allergies are avoidance, pharmacotherapy and immunotherapy. Treatment should start with avoidance
to allergens. In almost all cases, however, some
pharmacotherapy is needed. The available treatment
options for upper and lower respiratory tract allergic
diseases have major limitations due to low efficacy,
associated adverse events and compliance issues.
Antihistamines, sympathomimetics, xanthine derivatives
are commonly used as the first-line treatment for
symptomatic management, but they do not prevent
recurrent episodes.9 Use of glucocorticosteroids and
anticholinergics is questionable due to long-term adverse
effects. Prophylactic use of mast cell stabilizers has the
disadvantage of frequent administration. Decongestant
drugs are effective in the treatment of nasal obstruction;
however, they do not improve other symptoms of rhinitis
and have high incidence of adverse effects. Studies with
the leukotriene receptor antagonists as a sole therapy in
these allergic diseases have proved disappointing.10,11
Several phytotherapeutic herbs with potent antiallergic, antioxidant, immunomodulatory, antitussive
and mucolytic activities have been found to be effective
in the management of allergic rhinitis. Bresol tablet an Ayurvedic formulation containing the extracts of
Curcuma longa, Ocimum sanctum, Adhatoda vasica,
Trikatu, Triphala, Embelia ribes, Cyperus rotundus,
Cinnamomum zeylanicum, Elettaria cardamomum,
Cinnamomum tamala and Mesua ferrea - is claimed to
be effective in the treatment of allergic rhinitis. The
present study was conducted to evaluate the safety and
efficacy of Bresol tablet in the management of allergic
rhinitis.
Material and Methods
The study was an open, prospective, noncomparative
clinical trial conducted at Public Health Centre,
Chennai, India. Fifty patients (17 males and 33
females) in the age group of 18-50 years (mean age:
40.70 17.06 years) who presented with symptoms
of allergic rhinitis (sneezing, nasal congestion, itching of
the nose, postnasal drip and rhinorrhea) were included
in the study after signing the informed consent form
(Table 1). Patients with obstruction-causing nasal
14
Bresol tablet
(n = 50)
Male : Female
17 : 33
Age in years
(mean SD)
No. of patients
presenting the
symptoms
40.70 17.06
Nasal allergy
Allergic rhinitis
18
14
Bronchitis, influenza,
common cold
14
Original ARticle
All the adverse events, either reported or observed by
the patients, were recorded with information about
severity, date of onset, duration and action taken
regarding the study drug. Relation of adverse events
to study medication was predefined as Unrelated
(a reaction that does not follow a reasonable temporal
sequence from the administration of the drug), Possible
(follows a known response pattern to the suspected
drug, but could have been produced by the patients
clinical state or other modes of therapy administered
to the patient) and Probable (follows a known
response pattern to the suspected drug that could not
be reasonably explained by the known characteristics
of the patients clinical state). Patients were allowed to
voluntarily withdraw from the study, if they experienced
serious discomfort during the study or sustained serious
clinical events requiring specific treatment.
Statistical Analysis
Week 0
Week 1
Week 2
Week 3
Week 4
Sneezing (n = 42)
7.57 2.73
5.67 2.63
a
p < 0.05
2.41 2.83
a
p < 0.001
b
p < 0.01
1.05 2.31
a
p < 0.001
b
p < 0.001
0.74 1.68
a
p < 0.001
b
p < 0.001
7.75 1.91
5.88 2.15
2.05 2.57
a
p < 0.001
b
p < 0.001
1.15 2.12
a
p < 0.001
b
p < 0.001
0.78 1.63
a
p < 0.001
b
p < 0.001
6.09 2.45
4.00 2.89
a
p < 0.05
2.00 2.71
a
p < 0.001
1.74 2.73
a
p < 0.001
b
p < 0.05
1.09 1.91
a
p < 0.001
b
p < 0.01
6.75 2.20
4.55 2.44
2.85 2.76
a
p < 0.001
1.35 1.98
a
p < 0.001
b
p < 0.01
1.20 1.82
a
p < 0.001
b
p < 0.001
6.05 1.82
4.35 2.16
2.50 2.37
a
p < 0.001
1.65 2.23
a
p < 0.001
b
p < 0.01
1.35 1.69
a
p < 0.001
b
p < 0.001
Rhinorrhea (n = 23)
7.22 1.95
5.44 2.23
3.17 2.23
a
p < 0.001
1.26 1.79
a
p < 0.001
b
p < 0.001
0.87 1.42
a
p < 0.001
b
p < 0.001
c
p < 0.05
6.39 2.22
4.92 2.36
3.46 2.82
a
p < 0.05
1.77 1.83
a
p < 0.001
b
p < 0.01
1.15 1.41
a
p < 0.001
b
p < 0.001
Statistical analysis was done by repeated measures of ANOVA using Friedman test followed by Dunnetts multiple comparison post-hoc test.
a
As compared to baseline values; bAs compared to week 1 values; cAs compared to week 2 values.
15
Original ARticle
Table 3. Number of Patients Showing Complete Relief
from Symptoms of Allergic Rhinitis at the End of the Study
Symptoms
Parameters
No. of patients
Initial
Final
Significance
Protection (%)
Significance
11,030 2,836
9,864 2,180
p < 0.001
Sneezing
42
p < 0.0001
80.95
Nasal congestion
40
10
p < 0.0001
75
23
p < 0.0001
69.57
Neutrophils (%)
65.65 9.24
64.53 7.23
NS
20
p < 0.0001
65
Lymphocytes (%)
30.40 10.39
32.62 8.50
p < 0.007
Postnasal drip
20
p < 0.0001
55
Eosinophils (%)
4.62 4.34
3.76 4.29
p < 0.015
Rhinorrhea
23
p < 0.0001
69.57
Monocytes (%)
0.40 1.09
0.35 1.03
NS
Watery eyes
13
p < 0.005
53.85
ESR (mm/h)
19.27 9.77
15.20 5.79
p < 0.0001
Absolute
eosinophil count
423.6 255.8
310 185.9
p < 0.0004
Baseline
(before
treatment)
Total leukocyte
count (cells/mm3)
Discussion
Allergic rhinitis is characterized by a two-phase
allergic reaction - the initial sensitization phase (IgE
formation and triggering of the humoral response) and
the clinical disease phase (manifesting symptoms). The
clinical disease phase can be further subdivided into
two distinct phases, namely early (mediated through
mast cells) and late (cellular infiltration and mediator
release).12 In the early phase, mast cells release mediators
as a result of antigen cross-linking of IgE molecules,
which results in an explosive degranulation of mast
cells, leading to the characteristic symptoms of rhinitis
(rhinorrhea, nasal obstruction and itching, sneezing,
postnasal drip and loss of sense of smell).11
Control of cytokine release from airway epithelial cells
is a primary approach in the management of allergic
rhinitis, and topical corticosteroids with oral antihistamines are the mainstay in the management of allergic
rhinitis. In treatment-resistant patients, the effects of
allergen-specific immunotherapy can be beneficial.13
The present study showed excellent symptomatic
control as evident by significant reduction in the mean
scores for sneezing, nasal congestion, itching of the eyes
and nose, postnasal drip, rhinorrhea and watery eyes
at the end of the study. A significant improvement in
the values of hematological parameters (total leukocyte
count, eosinophil count and AEC count) at the end
of the treatment compared to their baseline values was
observed. There was also a significant reduction in
lymphocyte count and ESR at the end of the study.
Indian Journal of Clinical Practice, Vol. 21, No. 1, June 2010
Original ARticle
Curcumin from C. longa is reported to have
antiallergic property, as tested in an in vitro model of
airway hyperresponsiveness.14 In different animal and
human studies, curcumin-I, -II and -III (components
of C. longa) have been shown to inhibit a number of
molecules involved in inflammation [phospholipase,
lipooxygenase, cyclooxygenase (COX)-1 and -2,
leukotrienes, thromboxane (TX), prostaglandins
(PG), nitric oxide, collagenase, elastase, hyaluronidase,
monocyte chemoattractant protein-1, interferoninducible protein, tumor necrosis factor and interleukin12].15-17
Curcumin is also shown to have immunostimulatory
activity, which increases circulating antibody titer,
plaque forming cells, alpha-esterase positive cells and
phagocytosis.18
The active principles of Zingiber officinale (one of
the constituents of Trikatu) are potent inhibitors of
prostaglandin biosynthesizing enzyme (PG synthetase)
and the structures of these compounds indicate that
the inhibitors would also be active against arachidonate
5lipoxygenase (an enzyme of leukotriene biosynthesis).
Z. officinale inhibits biotransformation of arachidonic
acid comparable to indomethacin.19 Other principles of
Z. officinale, oleoresins ([8]-paradol and [8]-shogaol),
have inhibitory effects on COX-2 enzymes20 and the
mechanism of action is hypothesized by the attenuation
of COX-1/TX synthase enzymatic activity.21
Piper longum (another constituent of Trikatu) is a potent
inhibitor of COX-1 and -2, which are the mediators
of inflammation.22 P. longum is also reported to
retard macrophage recruitment and suppress cytokine
production.23
Emblica officinalis (an important constituent of
Triphala) is reported to possess antiphlogistic,
antispasmolytic and antioxidant activities besides
reducing mucus secretion in the airways.24
Terminalia belerica (another constituent of Triphala)
has potent antifungal activity.25 The herb is also
reported to possess potent antioxidant activity.26
C. rotundus inhibits NO and O2 production in vitro
and the inhibition is due to the suppression of iNOS
protein, as well as iNOS mRNA expression.27
O. sanctum is known to stimulate humoral immunologic response (an increase in antibody titer) and
cellular immunologic response (E-rosette formation
Indian Journal of Clinical Practice, Vol. 21, No. 1, June 2010
17
Original ARticle
5. Bucholtz GA, Lockey RF, Wunderlin RP, Binford LR,
Stablein JJ, Serbousek D, et al. A three-year aerobiologic
pollen survey of the Tampa Bay area, Florida. Ann Allergy
1961;67(5):534-40.
6. Sibbald B, Rink E. Epidemiology of seasonal and
perennial rhinitis: clinical presentation and medical
history. Thorax 1991;46(12):895-901.
7. Sampson HA, Ho DG. Relationship between foodspecific IgE concentrations and the risk of positive food
challenges in children and adolescents. J Allergy Clin
Immunol 1997;100(4):444-51.
8. Settipane RA. Complications of allergic rhinitis. Allergy
Asthma Proc 1999;20(4):209-13.
9. White MV, Slater JE, Kaliner MA. Histamine and
asthma. Am Rev Respir Dis 1987;135(5):1165-76.
10. Hansen I, Klimek L, Msges R, Hormann K. Mediators
of inflammation in the early and the late phase of allergic
rhinitis. Curr Opin Allergy Clin Immunol 2004;4(3):
159-63.
11. Salib RJ, Drake-Lee A, Howarth PH. Allergic rhinitis:
past, present and the future. Clin Otolaryngol Allied Sci
2003;28(4):291-303.
12. Naclerio RM. Pathophysiology of perennial allergic
rhinitis. Allergy 1997;52(36 Suppl):7-13.
13. Castells M, Schwartz LB. Tryptase levels in nasal-lavage
fluid as an indicator of the immediate allergic response.
J Allergy Clin Immunol 1988;82(3 pt 1):348-55.
14. Ram A, Das M, Ghosh B. Curcumin attenuates allergeninduced airway hyperresponsiveness in sensitized guinea
pigs. Biol Pharm Bull 2003;26(7):1021-4.
15. Kim JE, Kim AR, Chung HY, Han SY, Kim BS,
Choi JS. In vitro peroxynitrite scavenging activity of
diarylheptanoids from Curcuma longa. Phytother Res
2003;17(5):481-4.
16. Chainani-Wu N. Safety and anti-inflammatory activity
of curcumin: a component of turmeric (Curcuma longa).
J Altern Complement Med 2003;9(1):161-8.
17. Hong CH, Hur SK, Oh OJ, Kim SS, Nam KA,
Lee SK. Evaluation of natural products on inhibition
of inducible cyclooxygenase (COX-2) and nitric oxide
synthase (iNOS) in cultured mouse macrophage cells.
J Ethnopharmacol 2002;83(1-2):153-9.
18. Antony S, Kuttan R, Kuttan G. Immunomodulatory
activity of curcumin. Immunol Invest 1999;28(5-6):
291-303.
19. Kiuchi F, Iwakami S, Shibuya M, Hanaoka F, Sankawa U.
Inhibition of prostaglandin and leukotriene biosynthesis
by gingerols and diarylhepatanoids. Chem Pharm Bull
1992;40(2):387-91.
20. Tjendraputra E, Tran VH, Liu-Brennan D, Roufogatis
BD, Duke CC. Effect of ginger constituents and synthetic
n
18