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RHINITIS IS A GLOBAL PROBLEM AND IS DEFINED AS THE PRESENCE OF AT LEAST ONE OF THE FOLLOWING: congestion, rhinorrhea, sneezing, nasal itching, and nasal obstruction. The two major classifications are allergic and nonallergic rhinitis (NAR). Allergic rhinitis occurs when an allergen is the trigger for the nasal symptoms. NAR is when obstruction and rhinorrhea occurs in relation to nonallergic, noninfectious triggers such as change in the weather, exposure to caustic odors or cigarette smoke, barometric pressure differences, etc. There is a lack of concomitant allergic disease, determined by negative skin prick test for relevant allergens and/or negative allergen-specific antibody tests. Both are highly prevalent diseases that have a significant economic burden on society and negative impact on patient quality of life. Treatment of allergic rhinitis includes allergen avoidance, antihistamines (oral and intranasal), intranasal corticosteroids, intranasal cromones, leukotriene receptor antagonists, and immunotherapy. Occasional systemic corticosteroids and decongestants (oral and topical) are also used. NAR has 8 major subtypes which includes nonallergic rhinopathy (previously known as vasomotor rhinitis), nonallergic rhinitis with eosinophilia, atrophic rhinitis, senile rhinitis, gustatory rhinitis, drug-induced rhinitis, hormonal-induced rhinitis, and cerebral spinal fluid leak. The mainstay of treatment for NAR are intranasal corticosteroids. Topical antihistamines have also been found to be efficacious. Topical anticholinergics such as ipratropium bromide (0.03%) nasal spray are effective in treating rhinorrhea symptoms. Adjunct therapy includes decongestants and nasal saline. Investigational therapies in the treatment of NAR discussed include capsaicin, silver nitrate, and acupuncture.
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ALLERGIC RHINITIS
Definition
Rhinitis is dened as the presence of at least one of the follow-
ing: congestion, rhinorrhea, sneezing, nasal itching, and nasal
obstruction.1,2 Other reported symptoms include throat clearing,
headaches, facial pain, ear pain, itchy throat and palate, snoring,
and sleep disturbances.3,4 A system of rating symptom severity
has been developed using a 7-point visual analog scale that in-
cludes elements of nasal symptoms, non-nasal symptoms, and
the eects of medications. (See reference for copies of assess-
ment forms).5 Allergic rhinitis is present when these symptoms
are triggered by an allergen. Perennial allergic rhinitis is most
often attributed to dust mites, mold spores, and animal dander,
whereas seasonal allergic rhinitis is attributed to a large variety
of pollens that varies based on geographical region.2
Epidemiology
Allergic rhinitis is very common condition throughout the
Management of Rhinitis: Allergic and Non-Allergic
Nguyen P Tran,1 John Vickery,1 Michael S Blaiss1,2*
1LeBonheur Children’s Medical Center, Memphis, TN, USA
2Department of Pediatrics and Medicine, University of Tennessee Health Sciences Center, Memphis, TN, USA
world.6 In the United States it affects between 10-30% of the
adult general population and up to 40% of children. is ac-
counts for 30-60 million people in the United States1 and the
prevalence has been increasing in recent decades,2 making it
the fth most common chronic disease in the US.7 Risk factors
include an atopic family history, IgE levels above 100 IU/mL
before the age of 6 years, higher socioeconomic status, and pos-
itive epicutaneous allergen testing.1 However, 44-87% of people
with rhinitis have mixed allergic and non-allergic rhinitis,1 and
therefore all that sneezes is not necessarily purely allergic in eti-
Review
Allergy Asthma Immunol Res. 2011 July;3(3):148-156.
doi: 10.4168/aair.2011.3.3.148
pISSN 2092-7355 • eISSN 2092-7363
Rhinitis is a global problem and is dened as the presence of at least one of the following: congestion, rhinorrhea, sneezing, nasal itching, and nasal
obstruction. The two major classications are allergic and nonallergic rhinitis (NAR). Allergic rhinitis occurs when an allergen is the trigger for the
nasal symptoms. NAR is when obstruction and rhinorrhea occurs in relation to nonallergic, noninfectious triggers such as change in the weather, ex-
posure to caustic odors or cigarette smoke, barometric pressure differences, etc. There is a lack of concomitant allergic disease, determined by neg-
ative skin prick test for relevant allergens and/or negative allergen-specic antibody tests. Both are highly prevalent diseases that have a signicant
economic burden on society and negative impact on patient quality of life. Treatment of allergic rhinitis includes allergen avoidance, antihistamines
(oral and intranasal), intranasal corticosteroids, intranasal cromones, leukotriene receptor antagonists, and immunotherapy. Occasional systemic corti-
costeroids and decongestants (oral and topical) are also used. NAR has 8 major subtypes which includes nonallergic rhinopathy (previously known as
vasomotor rhinitis), nonallergic rhinitis with eosinophilia, atrophic rhinitis, senile rhinitis, gustatory rhinitis, drug-induced rhinitis, hormonal-induced
rhinitis, and cerebral spinal uid leak. The mainstay of treatment for NAR are intranasal corticosteroids. Topical antihistamines have also been found
to be efcacious. Topical anticholinergics such as ipratropium bromide (0.03%) nasal spray are effective in treating rhinorrhea symptoms. Adjunct
therapy includes decongestants and nasal saline. Investigational therapies in the treatment of NAR discussed include capsaicin, silver nitrate, and
acupuncture.
Key Words: Allergic rhinitis; nonallergic rhinitis; intranasal corticosteroids; immunotherapy; intranasal antihistamines; oral antihistamines
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits
unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Correspondence to: Michael S Blaiss, MD, Allergy and Asthma Care, 7205
Wolf River Boulevard, Germantown, TN 38138, USA.
Tel: +1-901-757-6100; Fax: +1-901-757-6110;
E-mail: michael.blaiss@gmail.com
Received: January 12, 2011; Accepted: February 8, 2011
Blaiss Conflicts
Speaker’s Bureau: AstraZeneca, Merck, GSK, Sunovion, Nycomed, ISTA,
Genentech
Consultant: Sanofi, Merck, Sunovion, Proctor & Gamble, Meda, Allergan, ISTA
Management of Rhinitis: Allergic and Non-Allergic
Allergy Asthma Immunol Res. 2011 July;3(3):148-156. doi: 10.4168/aair.2011.3.3.148
AAIR
149
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ology.
While many patients downplay rhinitis symptoms as an in-
convenience rather than a disease, the economic burden is
quite signicant. In the United States, the direct medical costs
(physician services, diagnostics, medications, etc.) nearly dou-
bled from US$6.1 billion in 2000 to US$11.2 billion in 2005.8 In
Europe, it was estimated that by the late 1990s, €1.0-1.5 billion
were spent on direct costs.2 Additionally, the indirect costs (trav-
el for physician visits, decreased work productivity, missed
school and loss of parents’ pay from missed work to care for
their children, etc.) are also considerable. In the US, there are
3.5 million lost workdays and 2 million lost school days due to
allergic rhinitis. It is estimated that productivity decreases by
US$600 per aected employee per year, which is a greater loss
than asthma, diabetes, and coronary heart disease. Overall, al-
lergic rhinitis was the fth costliest chronic disease in the Unit-
ed States with 75% of the costs coming from decreased produc-
tivity.4,8 e indirect costs in Europe were estimated to be more
than the direct costs at €1.5-2.0 billion.2
Pathophysiology
Cellular signals
Allergic rhinitis is an IgE-mediated disease resulting in inam-
mation of the nasal mucosa. Allergic patients have increased
levels of allergen specic IgE in their nasal mucosa compared
to controls. Histamine release from resident mast cells is a ma-
jor mediator in the inammation of allergic rhinitis. Eosinophil-
ic inammation also plays an important role. A 2 response
ensues with the release of IL-4 and IL-5. Recently, thymic stro-
mal lymphopoietin (TSLP), IL-25 (or IL-17E), and IL-33 have
also been implicated. As eosinophils produce IL-5 and granu-
locyte macrophage-colony stimulating factor (GM-CSF), they
perpetuate their own survival. After allergen exposure, rhinitis
can persist for several weeks.2,9 ere is an immediate and a late
phase to allergic rhinitis. Both are characterized by the same
symptoms, but the late phase’s predominate symptom is nasal
congestion. Eosinophils release mediators that can induce tis-
sue damage, and pre-treating with topical glucocorticoids re-
duces eosinophil inltration and cytokine release.1
Neuronal aspects
e interplay between sensory nerve bers and the eerent
sympathetic and parasympathetic neurons helps to regulate
the mucosal barrier of the nasal epithelium. e thinly myelin-
ated Aδ fibers convey the sensations of pain and cold to the
central nervous system. A thick mucosal lining decreases the
ability of these neurons to sense passing airow, which contrib-
utes, to the sensation of nasal obstruction and dyspnea. When
menthol receptors on these nerves are stimulated, the result is
a false sense of nasal patency and less dyspnea. After the initial
rapid stimulation of Aδ bers, a delayed activation of the non-
myelinated slowly conducting C bers ensues. In addition to
multiple allergens, the C bers can be stimulated by nicotine,
cigarette smoke, aldehyde, formaldehyde, isocyanates, sulfur
dioxide, and other toxicants. Capsaicin is the naturally occur-
ring substance in spicy peppers that induces the sensation of
heat, and it activates transient receptor potential and ion chan-
nel proteins (TRPs). A stinging sensation similar to that induced
by capsaicin occurs when the osmotic tonicity rapidly changes
at the cellular surface. is can happen when dry pollen and
dust grains land on mucosal surfaces, causing water to eux
from epithelial cells.
Acetylcholine is released from parasympathetic nerve bers
that innervate glands and vessels of the airway mucosa. Eosin-
ophils interfere with the activation of the presynaptic M2 mus-
carinic receptor, which decreases the negative feedback on ace-
tylcholine release. e result is an increase in bronchoconstric-
tion and glandular secretion. To balance the eects of the para-
sympathetic nervous system, sympathetic neurons induce va-
soconstriction in the epithelium. Stimulation of α-adrenergic
receptors by nasal decongestants (discussed below) reduces
mucosal thickness.
e nociceptive C bers innervate glands and deep subepithe-
lial vessels. eir release of substance P may lead to increased
expression of E-selectin and VCAM on endothelial cells. e re-
sult is increased inltration of leukocytes, which is a critical part
of the late-phase response of allergic rhinitis. Interestingly, when
substance P is administered to allergic individuals, mRNA lev-
els of IL-1, IL-2, IL-3, IL-4, IL-5, IL-6, TNFα, and γ-interferon vs.
only an increase of IL-6 and IL-6 mRNA in non-allergic individ-
uals. Neural plasticity also comes into play in allergic subjects.
is occurs when persistent stimulation from allergens increas-
es the sensitivity of involved neurons to depolarize. Allergic in-
dividuals’ neurons will depolarize in the presence of bradykinin
and endothelin, whereas these substance induce no response in
non-allergic subjects.
Because it is more dicult to localize visceral compared to
peripheral sensations, the activation of nerve bers that inner-
vate deep tissues often results in referred pain. Sinus headaches
are a common example. Noxious stimulation of the inferior tur-
binate induces the sensation of pain in the maxillary teeth, zy-
goma, and eyes. e middle turbinates refer pain to the temple,
zygoma, inner canthus, and forehead.10
Genetics
Monozygotic twins show a concordance of 45-60% in the de-
velopment of allergic rhinitis, and dizygotic twins have a con-
cordance rate of about 25%. ese data point to a genetic link.
However studies into the genetics of allergic rhinitis are lacking,
and current ndings are preliminary. Chromosome 3 has three
regions linked to allergic rhinitis, 3q13, 3q13.31, and 3p24. A
possible involved region on chromosome 4 is 4q24-q27. Cer-
tain single nucleotide polymorphisms (SNPs) have been impli-
cated GATA3 and IL-13.9 Specic HLA haplotypes have been
Tran et al.
Allergy Asthma Immunol Res. 2011 July;3(3):148-156. doi: 10.4168/aair.2011.3.3.148
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150 http://e-aair.org
associated with allergic responses to particular allergens.is
may be due to more than just an association since HLAs pres-
ent antigens to T-cells. ere is also evidence that points to ge-
netic associations of the T-cell receptor (TCR) α-chain and the
high affinity IgE receptor FcεRI with increased allergy. Other
candidate genes for further investigation include those involved
with the production of IgE, IL-4, IL-5, and IL-13.11
Treatment
Avoidance
Since allergic rhinitis is induced by specic allergens, it makes
sense that avoiding those triggers would be an eective treat-
ment. However, this is not always possible as in the case of pol-
lens, and for those with mixed allergic and non-allergic rhinitis,
avoidance will not completely alleviate their symptoms. Some
allergens can and should be avoided as the severity of rhinitis
correlates with the levels of allergens in the environment. Pre-
cautions can be taken against dust mites. Carpet removal, re-
moval of soft toys from the bedroom, using allergen-imperme-
able bedding covers for the mattress and pillow, vacuuming
with a high-eciency particulate air (HEPA) lter, and washing
bedclothes and bed sheets in hot water (60°C) are helpful. Any
single method alone is unlikely to provide benet, and patient
should be encouraged to use multiple interventions. For those
with animal allergies, ideally, removal of the pet from the home
would be best along with careful vacuuming of all carpets, up-
holstered furniture, and mattresses. It may be impossible to
clear cat dander or take up to 20 weeks for cat dander levels to
decrease to cat free homes. Isolating the pet to a single room
and using a HEPA lter is a second best option. Studies have
been inconsistent on the benets of regular bathing of cats.1,2
Spaying or neutering cats and dogs increases levels of their ma-
jor allergens found in homes, Fel d 1 and Can f 1 respectively.
Having fewer pets correlates with lower dander levels. Interest-
ingly, keeping cats outside does not significantly reduce the
presence of Fel d 1, while the less access dogs have to the home
and bedroom correlates with lower amounts of Can f 1 found in
the bedroom.12,13 Environmental moisture control can improve
mold levels. Using pesticides and meticulous control of food
debris can decrease cockroach environmental allergens. How-
ever, it may take over 6 months to remove residual cockroach
allergen.1
Antihistamines
Histamine activates the H1 receptor on a distinct set of neu-
rons to produce the sensation of itching. is leads to sneezing,
nose rubbing, and the allergic salute.10 H1-antihistamines are
inverse agonists, rather than H1-antagonists, that combine with
and stabilize the inactive form of the H1 receptor leading toward
a shift in equilibrium to the inactive state. In addition to the in-
verse agonist eect at the H1 receptor, the newer second-gener-
ation agents have both anti-allergic and anti-inflammatory
properties.
e rst generation H1 antihistamines such as diphenhydr-
amine, chlorpheniramine, brompheniramine and hydroxyzine
are also referred to as the sedating antihistamines. ese agents
are eective at controlling the rhinorrhea, sneezing and pruri-
tus associated with allergic rhinitis. Unfortunately these agents
cross the blood-brain barrier thus producing undesirable side
effects such as central nervous system depression, sedation
leading to impaired performance at home, work and school
and cardiotoxicity. ere are no long-term safety studies on the
rst generation antihistamines. ese agents have poor H1 re-
ceptor selectivity and act on muscarinic receptors causing anti-
cholinergic eects such as dry mouth, urinary retention, consti-
pation and tachycardia. e second-generation antihistamines
developed in the early 1980’s, have improved H1 receptor selec-
tivity, absent or decreased sedation, faster onset and longer du-
ration of action and fewer adverse eects. eir half-lives are
longer (12-24 hours) compared to the first generation (4-12
hours).14 Of the second generation H1-antagonists, fexofenadine
has no sedating eects even at higher than recommended dos-
es. Loratadine and desloratadine are non-sedating at recom-
mended doses but may cause sedation at higher doses. Cetiri-
zine, and its puried enantiomer levocetirizine, have more se-
dation potential that other second generation H1-antagonists.15
All rhinitis symptoms, except for obstruction, can be alleviated
by H1-antihistamines, and there does not seem to be a superi-
ority of any one of the second generation H1-antihistmines over
another.
Topical H1-antihistamines (azelastine, olopatadine) provided
faster onset of action (less than 15 minutes) and similar to great-
er ecacy compared to oral preparations in regard to rhinitis
and conjunctivitis. ere has even been an association with im-
provement of congestion. However, their results are limited to
the local organ eects, and require twice daily use to maintain a
sustained response; whereas second generation oral H1-antag-
onists can be taken on a daily basis. Some patients may com-
plain of a bitter taste, and intranasal H1-antagonists are less ef-
fective than intranasal steroids.1,2 In a direct comparison trial
between azelastine nasal spray versus oral cetirizine, azelastine
was found to have a signicant improvement in nasal symptom
scores for the specic symptoms of sneezing and nasal conges-
tion over cetirizine.16
Steroids
In addition to oral H1-antihistamines, intranasal corticoste-
roids are a mainstay of treatment. ey are the most eective
medications for controlling all rhinitis symptoms. eir onset of
action is from 3-12 hours. eir use on an as needed basis is not
as eective as continual use1 but may not be required continu-
ally in all patients. ey are generally safe, and there is little evi-
dence to support suppression of the hypothalamic-pituitary-
adrenal axis with prolonged use. Side eects are generally mild
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(crusting, dryness, and minor epistaxis). ey can be minimized
by proper nasal spray technique. Septal perforation has only
been described anecdotally.2 For patients whose symptoms are
not optimally controlled with intranasal steroids, adding an in-
tranasal (but not oral) antihistamine may give some additional
benet.3
Systemic corticosteroids should be considered a last resort
treatment option, but they may be necessary for severe or in-
tractable symptoms. If they are used, then oral is preferred over
parenteral because of the lower risk of systemic side eects and
the ability to adjust doing. Steroids should never be injected
into the turbinates. Recommendations on short courses oral
steroids dier from 5-7 days1 to no more than 3 weeks.2
Decongestants
Decongestants are also available in oral and topical formula-
tions. ey are eective in relieving congestion. However, stud-
ies of H1-antihistamine in combination with oral decongestants
failed to show improved benet compared to either alone. Side
eects include insomnia, anorexia, irritability, and rarely ele-
vated blood pressure. Oral decongestants should be avoided in
children less the 1-year of age, adults over 60 years of age, and
any patient with a cardiac condition. The main side effect of
topical decongestants is the development of rhinitis medica-
mentosa, which can appear in some patients after only 3 days
of use or not at all in other patients after six weeks of use. Euro-
pean guidelines recommend a maximum of 10 days use.1,2
Cromones
Intranasal formulations of cromolyn and nedocromil have
been used to treat allergic rhinitis but are less effective than
topical corticosteroids. It is believed that cromones are less ef-
fective than topical antihistamines,2 but adequate comparative
studies have not been performed.1 Although the exact mecha-
nism is unknown, they work mainly by inhibiting mast cell acti-
vation. Studies have shown that nedocromil inhibits the activa-
tion of neutrophils, eosinophils, monocytes, and macrophages
as well. ere may even be an inhibitory eect on neural sig-
nals involved in rhinitis.2 Overall, they are safe with minimal to
no side eects.1,2
Miscellaneous
e anticholinergic ipratropium bromide is available in a na-
sal form and blocks the parasympathetic signaling that leads to
watery rhinorrhea, and it has been shown eective in control-
ling this particular symptom. ere are little to no side eects.
Guidelines state it does not decrease sneezing or nasal obstruc-
tion,1,2 but one study in children showed improvement in rhi-
norrhea, congestion, and sneezing although to a lesser degree
than intranasal steroids.17
Leukotriene receptor antagonists have been shown to be ef-
fective controlling allergic rhinitis, and they are comparably ef-
fective with oral antihistamines.1 After 2 weeks of therapy, mon-
telukast progressively decreased symptoms scores, but still to a
lesser degree than intranasal uticasone.18 For patients whose
symptoms are not controlled with intranasal corticosteroids,
adding montelukast did not oer any further benet.19
e anti-IgE antibody omalizumab may be ecacious, but it
has not been shown to be superior to current allergic rhinitis
treatments. Additionally, its high cost limits it use as a standard
treatment.1
Taken as a whole, intranasal corticosteroids seem to be the
most eective in controlling nasal symptoms. e next most ef-
fective are oral and intranasal antihistamines. However, it is dif-
cult to fully stratify medication classes because of the lack of
sucient uniform data. For instance, studies on antihistamines
have excluded nasal congestion as a component of symptoms
scores because they are not expected to improve this symptom.
ere may be some dierences between seasonal and perenni-
al allergic rhinitis where, for some patients with perennial aller-
gic rhinitis, oral antihistamines may be as eective as nasal ste-
roids. Additionally, there is variable response to treatments
among individuals.3 Table 1 lists the eectiveness of dierent
medications in symptom control of allergic rhinitis.
Immunotherapy
Subcutaneous immunotherapy (SCIT) has been shown to be
eective in treating allergic rhinitis in patients with identiable
IgE mediated symptom triggers. It has some advantages over
the above mention treatments. Eects can be sustained for years,
and it may prevent the development of new allergen sensitivi-
ties or even asthma.1 It is eective for not only control of allergic
Table 1. Effectiveness in symptom control of various medications for allergic rhinitis
Symptom Oral antihistamine Nasal antihistamine Nasal steroids Nasal decongestant Nasal ipratropium bromide Nasal cromone
Rhinorrhea XX XX XXX XX X
Sneezing XX XX XXX X
Nasal itching XX XX XXX X
Nasal congestion X X XXX XXXX X
Ocularsymptoms XX XX
Adapted from van Cauwenberge et al.2.
–, no effect; X: least; XXXX: most effective.
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rhinitis but also of allergic conjunctivitis and allergen induced
asthma.20 However, immunotherapy is underutilized with only
2 to 3 million US individuals on SCIT of the estimated 55 mil-
lion people with allergic diseases.21 In regard to specic inhaled
allergens, evidence supports immunotherapy for pollens, ani-
mal dander, and dust mite. Large local reactions at the injection
site are the most common adverse reaction. e risk of severe
systemic reactions during subcutaneous immunotherapy is
rare but present in less than 1% of those receiving standard im-
munotherapy. Near fatal events occurred at a rate of 5.4 per
million injections. High ambient pollen levels and dosing er-
rors were the two main risk factors for such a reaction. It is ad-
vised that patients receive immunotherapy injections in a set-
ting with sta and equipment that can handle anaphylaxis, and
that patient be observed for 30 minutes after each injection.20
Other disadvantages include injection discomfort, the frequen-
cy of shot visits, and the total cost. However, immunotherapy is
the only treatment that can modify the disease. When the direct
costs of symptomatically managed allergic rhinitis are compared
to the cost of immunotherapy, the values are virtually the same.8
When indirect costs are factored, immunotherapy may be much
more economical.
Subcutaneously is the most common way to deliver immuno-
therapy, but sublingual immunotherapy (SLIT) is also used.
SLIT has been reported to cause oral itching and gastrointesti-
nal side eects, but in most studies, these rates seem to be the
same as those observed in the placebo arm.2 ere is a lack of
standardization in SLIT with timothy grass pollen extracts be-
ing the only commercially available therapy (Grazax by ALK-
Abelló Hørsholm. Denmark), and there are no SLIT therapies
approved for the US by Food and Drug Administration. Advan-
tages of SLIT include an extremely low risk of anaphylaxis and
the ability to begin therapy at the maintenance dose without a
build-up phase.22 SLIT for dust mite allergy has been specical-
ly studied in the Korean population and found to be eective in
reducing symptom scores.23,24 Although anaphylaxis has not
been noticed in studies on SLIT, there are case reports of ana-
phylaxis occurring during treatment, even with the rst dose.21
SLIT is not as well established as SCIT, and further investigation
is required to determine the optimal dose and patient selec-
tion.2
A meta-analysis25 done in January of 2010 reviewed the past
20 years of studies on SLIT. Nineteen studies were included with
a total of 2,971 study subjects. SLIT was found to improve both
symptom scores and medication use for allergic rhinitis. It ap-
pears that a minimal dose of 450 μg of antigen per treatment
was necessary and that using higher doses produced to benet.
Upon subgroup analysis, SLIT was far less eective in children
than adults. is conclusion may have been confounded by the
fact that most of the pediatric studies used doses of less than
276 μg and the only pediatric study that showed statistically sig-
nificant benefit used a dose of 600 μg. Along these lines, the
meta-analysis showed that SLIT tablets were more effective
than drops in reducing symptom scores with the caveat that
this dierence is mostly noticed in pediatric studies where drops
administered a lower dose than tablets. Additionally, some of
the pediatric studies included allergens other than grass. Other
pertinent conclusions were: that SLIT was more eective when
given for 12 months or less compared to over 1 year of use; SLIT
was not more eective for rhinitis control in allergic asthmatics
than in subjects without allergic asthma; and the more impor-
tant that the length of treatment was the timing of beginning
SLIT with initiation at least three months before grass season
being optimal.
NONALLERGIC RHINITIS
Definition
Nonallergic rhinitis (NAR) is generally described as chronic
nasal symptoms, such as obstruction and rhinorrhea that occur
in relation to nonallergic, noninfectious triggers such as change
in the weather, exposure to caustic odors or cigarette smoke,
barometric pressure dierences, etc. ere is a lack of concom-
itant allergic disease, determined by negative skin prick test for
relevant allergens and/or negative allergen-specific antibody
tests.26 The term vasomotor is often used which suggests in-
volvement of neural, glandular, and vascular pathways; howev-
er, this term is misleading because it implies a true understand-
ing of the underlying pathophysiology of the disease when this
has not been denitively established.27
In December of 2008, a roundtable conference which includ-
ed 8 expert physicians on rhinitis convened to establish a con-
sensus on the clinical denition of nonallergic vasomotor rhi-
nitis and to develop appropriate inclusion and exclusion crite-
ria for the enrollment of subjects in future clinical studies. From
this NAR Consensus Panel Proceedings, there were at least 8
subtypes that lled the criteria for NAR (Table 2).1,26,28 Nonaller-
gic rhinopathy (formerly known as vasomotor rhinitis) accounts
for the majority of NAR. It is a diverse group of patients that have
chronic nasal symptoms with a lack of nasal eosinophilia and
Table 2. Chronic rhinitis subtypes not associated with allergies, infection, or
anatomic abnormalities
Nonallergic rhinopathy, previously known as vasomotor rhinitis, or idio-
pathic nonallergic rhinitis
Nonallergic rhinitis with eosinophilia
Atrophic rhinitis
Senile rhinitis
Gustatory rhinitis
Drug-induced rhinitis, including rhinitis medicamentosa
Hormonal-induced rhinitis, including the rhinitis of pregnancy
Cerebral spinal uid leak
Adapted from Scarupa and Kaliner,28 Wallace et al.1, and Kaliner.26
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an etiology that is neither immunologic nor due to infection.
NAR with eosinophilia is characterized by patients who have
year-round nasal symptoms but eosinophils are found on nasal
smear though they lack positive skin tests and/or specic IgE
antibodies in the serum. Atrophic rhinitis, as the name implies,
refers to a chronic condition in which there is progressive atro-
phy of the nasal mucosa with crusting and dryness as the most
prominent features. It is typically not inammatory mediated.1
Senile rhinitis occurs most commonly in the elderly, presents
mostly with watery rhinorrhea that may worsen after certain
foods or environmental irritants. Gustatory rhinitis occurs after
eating, especially hot or spicy foods. Rhinitis medicamentosa is
included in drug-induced rhinitis, though a variety of medica-
tions have been implicated in causing chronic nasal congestion.
Rhinitis medicamentosa most commonly occurs after repeated
use of topical nasal decongestants such as oxymetzaoline or
phenylephrine. Hormone induced rhinitis refers to the conges-
tion and nasal symptoms that occur in response to endogenous
female hormones, such as seen in pregnancy. Cerebrospinal
uid (CSF) leak should be considered in patients with a history
of cranio-facial trauma or past facial surgery that have persis-
tent, clear rhinorrhea.26
Epidemiology
e exact prevalence and impact of NAR is not as established
as it is for allergic rhinitis. It is estimated that it aects more than
19 to 20 million patients in the United States, with vasomotor
rhinitis being the most common subtype seen.26,29 European
studies evaluating the prevalence of NAR found that approxi-
mately 1 in 4 patients with nasal symptom complaints had
“pure” NAR and it is estimated that 50 million Europeans have
NAR, with a total prevalence of more than 200 million world-
wide.26
With many subtypes of disease, the true economic burden of
NAR is most likely grossly underestimated. Schatz et al.29 re-
viewed the records of more than 1 million patients enrolled in
the Kaiser Permanente Southern California Medical care pro-
gram from 2002-2005 and found that 15% had at least 1 encoun-
ter with the diagnosis. Another 14% received rhinitis medica-
tion with no medical encounter.ey also found that patients
from either group had signicantly more health care visits per
year for asthma (2-4 times as many), acute sinusitis (6-8 times
as many) and all other diagnoses (almost twice as many). ey
also found that patients with rhinitis or treated for rhinitis had a
higher prevalence of comorbid diseases such as asthma, acute
and chronic sinusitis, nasal polyposis, conjunctivitis, acute oti-
tis media, chronic serous otitis media, sleep apnea, and fatigue.
When reviewing the patient demographics, those with NAR
were significantly older, mean age of 42.6 vs. 35.8 and more
likely to be female than the patients with the diagnosis of aller-
gic rhinitis.29
Importance of treatment
As Ledford30 points out in his symposium on assessing the
damage of inadequately diagnosed NAR, patients are often em-
pirically treated with oral second generation antihistamines,
which are usually not sufficient in relieving their symptoms.
e patients are then subjected to multiple rounds of treatment
failures that lead to frustration towards seeking medical care
and medication use. ey must incur additional expenditures
for doctor appointments, medication prescriptions, and lost
time from work on top of their reduced quality of life. Besides
this decrease in quality of life, untreated rhinitis does signi-
cantly increase the risk of other comorbid conditions such as
obstructive sleep apnea, fatigue, headache, malaise, poor appe-
tite and weakness. is eect is not limited to impaired work
performance in adults but can also manifest as learning disabil-
ities, behavioral, and psychological eects in children. Children
are also at risk for permanent facial changes from untreated rhi-
nitis such as increased facial length, retrognathic maxilla and
mandible, and dental malocclusions from obstructed breath-
ing.30
Beyond these physical and emotional impacts on patients
there is also an economic burden from the incomplete diagno-
sis and treatment of rhinitis. Recent evidence shows that asth-
ma and rhinitis are often coexisting in atopic and nonatopic pa-
tients and that eective treatment of rhinitis frequently improves
asthma.31
Treatment
Avoidance
Avoidance of environmental triggers such as strong odors
(perfumes, soaps, paint, etc.) and air pollutants (smoke fumes,
tobacco smoke) that are respiratory irritants is recommended
in those who nd these worsen their rhinitis symptoms.1,32
Antihistamines
Oral second generation antihistamines are not as eective in
the treatment of NAR, though first generation oral antihista-
mines may haves some benet due to anticholinergic activity.33
Topical antihistamines on the other hand have been found to
be very eective for the overall treatment of NAR. Of the two
topical antihistamines on the market in the United States (az-
elastine and olopatadine), azelastine is the only one that has
been shown to be ecacious for nonallergic rhinitis.1,32,34 Banov
and Lieberman32 evaluated the ecacy of the azelastine nasal
spray in patients with nonallergic vasomotor rhinitis in a multi-
center, randomized, placebo-controlled trial and found a sig-
nificant improvement in total vasomotor rhinitis symptom
scores (TVRSS) in those patients receiving azelastine (two sprays
twice a day, 1.1 mg) versus placebo. In an open label, 2-week
study with azelastine 2 sprays per nostril twice daily in patients
with allergic rhinitis, mixed rhinitis, and nonallergic vasomotor
rhinitis it was found that azelastine had improvement in control
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154 http://e-aair.org
of all rhinitis symptoms including nasal congestion, postnasal
drip, sneezing, and sleeping diculty.34 e previously men-
tioned metallic aftertaste that some patients describe with az-
elastine is dose-dependent and often dissipates over time.33
Steroids
Intranasal corticosteroids have been found to be eective in
nonallergic rhinitis, especially in vasomotor rhinitis and NA-
RES. Fluticasone propionate and beclomethasone are the only
topical corticosteroids approved by the FDA in the US for the
treatment of NAR. Clinically, there does not appear to be a dif-
ference between the intranasal steroids available at this time.1
Most are dosed twice daily and patients should be informed
that it may take 24 to 72 hours before symptoms start to im-
prove though the onset of action is said to be from 3-12 hours.33
In a randomized, double-blind, placebo-controlled trial with
983 patients with perennial nonallergic rhinitis performed by
Webb et al.35 patients received uticasone propionate 200 mcg,
400 mcg or placebo for 28 days. Primary endpoint was the mean
change in total nasal symptom score (TNSS), which was a sum
of patient ratings of nasal obstruction, postnasal drip, and rhi-
norrhea. Patients that were found to have NARES as well as
those that did not, were shown to have similar statistically sig-
nicant improvement on either dose of uticasone propionate
compared with placebo.33 However, there is a subgroup of NAR
patients that fail to respond to intranasal corticosteroids and
further study is warranted in these nonresponders.36
Decongestants
Currently there are no specic studies looking at the eective-
ness of oral decongestants in the treatment of NAR. us, they
should be considered adjunctive therapy, which is used on an
as needed basis for nasal congestion that is not responsive to
intranasal corticosteroids, topical antihistamines, or a combi-
nation of both.
Anticholinergics
e only topical anticholinergic medication approved in the
United States for topical application is ipratropium bromide.
Ipratropium bromide (0.03%) nasal spray is recommended
when rhinorrhea is the predominant or only symptom, as in
the case of gustatory rhinitis. From the updated rhinitis practice
parameters, its use in combination with an intranasal cortico-
steroid is more effective than either drug alone for the treat-
ment of rhinorrhea. is is not only eective, but safe as well
since there is not an increased incidence of adverse events.1
Nasal saline
Nasal lavage with saline solution has also been found to be a
helpful alone or as an adjuvant therapy in patients with chronic
rhinorrhea and rhinosinusitis.1 It is best performed immediate-
ly prior to intranasal corticosteroids or azelastine and may be
especially helpful in reducing postnasal drip, sneezing, and
congestion.37 A 2007 Cochrane database review found 8 ran-
domized controlled trials in which saline was evaluated in
comparison with either no treatment, placebo, as an adjunct to
other treatments or against treatments. ere was no evidence
that saline alone was benecial in the treatment of chronic rhi-
nosinusitis nor was it more eective than an intranasal cortico-
steroid. However, there was favorable evidence for saline as an
adjunct treatment. e nal conclusion was that saline irriga-
tions are a well tolerated with very minor side eects that can
be included as a treatment adjunct for chronic rhinosinusitis
symptoms.38 In a prospective, randomized controlled trial with
121 adults with chronic nasal and sinus symptoms, Pynnonen
et al.39 looked to determine if isotonic sodium chloride nasal ir-
rigations performed with large volume and low positive pres-
sure was more eective than saline sprays at improving quality
of life and decreasing medication use. e primary outcomes
measured were a change in symptom severity measure by a
mean 20-item Sino-Nasal Outcome Test (SNOT-20) score, med-
ication use, and symptom frequency. e outcomes were looked
at 3 dierent time points (2, 4, and 8 weeks). e high volume,
low positive pressure group had lower SNOT-20 scores at all
time points. They also had a lower frequency of often or al-
ways” nasal symptom reporting compared to the spray group
(40% of subjects versus 61%). A signicant dierence was not
found in sinus medication use in either group.39
e exact mechanism of how saline is helpful in allergic rhini-
tis and rhinosinusitis has not been conrmed but it is postulat-
ed that it may improve mucus clearance; remove antigen, in-
flammatory mediators, or biofilm; enhance ciliary beat; and
protect the nasal mucosa. Side eects from its use are typically
minor and consist of burning, irritation, and nausea. ere is
not an established consensus regarding method of delivery,
volume to use, ratio of isotonic to hypertonic, or frequency.1
Investigational therapies
1. Capsaicin
Capsaicin is the chemical contained within the oil of Capsi-
cum pepper and while it is initially irritating to the applied area,
it eventually desensitizes the sensory neural bers. It has been
used intranasal to try and decrease nasal hyperreactivity re-
sponsible for rhinorrhea, sneezing, and congestion.37 A place-
bo-controlled studies using intranasal capsaicin in patient with
nonallergic, noninfectious perennial rhinitis found a signicant
and long-term reduction in the visual analogue scale (VAS)
scores in the treatment group but no dierence objective mea-
sures of inammation such as concentration of leukotriene C4/
D4/E4, prostaglandin D2, and tryptase.40
2. Silver nitrate
Topically applied silver nitrate was found to be eective in a
trial comparing silver nitrate, flunisolide, and placebo in pa-
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Allergy Asthma Immunol Res. 2011 July;3(3):148-156. doi: 10.4168/aair.2011.3.3.148
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tients with NAR. Improvement was found in patient reported
rhinorrhea, sneezing and nasal congestion.41 Two prospective
studies in patients with vasomotor rhinitis also found signi-
cant improvement in nasal symptoms.42,43
3. Acupuncture
From a systematic review of complementary and alternative
medicine for rhinitis and asthma published in the Journal of Al-
lergy and Clinical Immunology in 2006, the majority of studies
on acupuncture were in allergic rhinitis and were not random-
ized, controlled, or descriptive. There was 1 nonrandomized
study in NAR that showed no dierence in nasal airow and
symptoms between acupuncture and electrostimulation.44
However, in 2009, a random, placebo-controlled study by Fleck-
enstein et al.45 was published that showed a signicant change
in nasal sickness score (NSS, max 27 points) in patients with va-
somotor rhinitis treated with acupuncture versus those who had
sham laser acupuncture treatment. e treatment group had a
NSS that went from 9.3±3.89 to 4.1±3.2 (P<0.001) while the
sham groups NSS went from 5.6±2.74 to 3.7±2.4.45
Surgery
After 6-12 months of failed medical therapy (intranasal corti-
costeroid with azelastine and/or decongestants and/or ipratro-
pium bromide) then surgical options may be considered. It
may also be indicated if the patient has comorbid conditions
such as nasal obstruction from severe nasal septal deviation or
inferior turbinate hypertrophy, adenoidal hypertrophy, or re-
fractory sinusitis.1 Treatment similarities and dierences in al-
lergy and nonallergic rhinitis are outlined in Table 3.
SUMMARY
Rhinitis is a prevalent disease worldwide that causes a signi-
cant impact on patient quality of life, can affect multiple co-
morbid conditions, and is a substantial economic burden on
society. It is important to note that a majority of rhinitis patients
experience signicant non-allergic triggers and thus may non-
allergic or mixed (allergic and non-allergic) rhinitis. An im-
proved consensus criterion for dening rhinitis subtypes is es-
sential. is will allow for better understanding the prevalence
and epidemiology of chronic rhinitis subtypes and for selecting
the appropriate study populations to investigate mechanisms
and specic therapies of these disorders.
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... Studies have shown that intranasal GCSs are superior to antihistamines in effectively reducing nasal inflammation and improving mucosal pathology. Oral and injectable GCSs may cause significant systemic adverse effects; therefore, even though they have been shown to be effective in alleviating AR symptoms, their use is not recommended and routine use should be avoided [38,39]. ...
... Although GCSs can decrease remodeling, they seem to have minimal effects on reversing the structural changes in the nasal mucosa [1]. In addition, treatment with intranasal GCSs has been shown to control the preonset activation of eosinophils and MCs present in AR [38]. ...
Article
Full-text available
Allergic rhinitis (AR) is a common rhinopathy that affects up to 30% of the adult population. It is defined as an inflammation of the nasal mucosa, develops in allergic individuals, and is detected mostly by a positive skin-prick test. AR is characterized by a triad of nasal congestion, rhinorrhea, and sneezing. Mast cells (MCs) are innate immune system effector cells that play a pivotal role in innate immunity and modulating adaptive immunity, rendering them as key cells of allergic inflammation and thus of allergic diseases. MCs are typically located in body surfaces exposed to the external environment such as the nasal mucosa. Due to their location in the nasal mucosa, they are in the first line of defense against inhaled substances such as allergens. IgE-dependent activation of MCs in the nasal mucosa following exposure to allergens in a sensitized individual is a cardinal mechanism in the pathophysiology of AR. This review is a comprehensive summary of MCs’ involvement in the development of AR symptoms and how classical AR medications, as well as emerging AR therapies, modulate MCs and MC-derived mediators involved in the development of AR.
... Despite this, there is substantial overlap between both the medical and surgical management strategies across all subtypes. 6 Several newer techniques, including cryotherapy, have been developed that target the more distal posterior nasal nerves and successfully avoid drawbacks attributed to vidian neurectomy. 7 Although the earliest studies of using cryotherapy in the treatment of chronic rhinitis date back as early as 1975, the currently available cryotherapy device (Stryker ENT, Plymouth, MN, USA) was recently approved for use by the US Food and Drug Administration (FDA) in 2017. ...
Article
Background: ClariFix for posterior nasal nerve ablation has been approved for use since 2017, and this is the first study attempting to synthesize and assess the efficacy of this new device on the management of chronic rhinitis. Objective: The primary objective of this meta-analysis is to assess the efficacy of ClariFix in the symptomatic management of patients with chronic rhinitis. The main outcome measure is the mean difference in the reflective total nasal symptom score (rTNSS). Methods: A systematic search of Pubmed/Medline, Web of Science, and EBSCOhost was conducted from inception to May 2022. Peer-reviewed clinical trials reporting postcryotherapy rTNSS at both 1- and 3-month intervals for patients with chronic rhinitis were included. A random-effects model was utilized for meta-analysis. Study heterogeneity, bias, and overall quality were all assessed. The authors followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline. The primary outcome measures included mean differences in rTNSS from baseline to both 1- and 3-month postoperative time points. Secondary measures included other questionnaires including the Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ). Results: There were 5 studies that met the criteria (247 individuals). The pooled rTNSS mean difference from baseline to 1 and 3 months postoperatively was found to be -3.48 points (95% CI: -3.73 to -3.23, I2 = 0.13). and -3.50 (95% CI: -3.71 to -3.29, I2 = 0.00), respectively. The mean difference from baseline to 3 months postoperatively regarding the RQLQ was found to be -1.53 (95% CI: -1.74 to -1.31, I2 = 0.00). The most common adverse effects included facial or surgical site pain (40.4%), followed by headache (18.2%), oral numbness (11.1%), and sinusitis (4.0%). Conclusions: The findings of this systematic review suggest that cryoablation with Clarifix is an effective treatment modality for chronic rhinitis. However, higher-quality randomized controlled trials will need to be performed to affirm the findings of this study.
... Inflamasi pada lapisan mukosa hidung ini menimbulkan gejala seperti produksi lendir berlebihan, hidung tersumbat, bersin-bersin, serta rasa gatal pada hidung. 1 ...
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Rhinitis merupakan salah satu gejala gangguan saluran pernafasan yang sering terjadi pada orang dewasa muda. Latihan fisik adalah aktivitas fisik yang dilakukan secara terencana, terstruktur, dan berulang-ulang dengan tujuan mengembangkan atau mempertahankan kesehatan. Beberapa studi terdahulu mengindikasikan bahwa olahraga dengan intensitas sedang yang dilakukan secara teratur dapat menurunkan terjadinya gangguan saluran pernafasan. Studi cross-sectional ini bertujuan untuk mengetahui hubungan antara tingkat intensitas latihan fisik terhadap prevalensi rhinitis pada mahasiswa Universitas Tarumanagara. Subyek studi berjumlah 192 responden dengan rentang usia 18-24 tahun yang direkrut secara konsekutif dan data subyek dikumpulkan dengan menggunakan Google form. Studi ini mendapatkan pada kelompok yang tidak melakukan latihan fisik rutin risiko rhinitis sebesar 1,61 kali lebih besar dibandingkan dengan mereka yang melakukan latihan fisik rutin; namun hubungan antara latihan fisik dan prevalensi rhinitis tersebut tidak bermakna secara statistik (PR=1,61; P=0,14). Latihan fisik rutin kemungkinan berkontribusi untuk menurunkan kejadian rhinitis.
... Важными являют ся меры по исключению контакта с пылевыми клещами, перхотью животных. Даже изоляция домашнего животно го в отдельной комнате дома может свести к минимуму симптомы аллергии [24]. Важным также является приме нение кварцевых ламп и увлажнителей воздуха, еже дневная влажная уборка, смена наполнителя подушек на синтетический, переезд на время цветения причинно значимых растений в другую климатическую зону [22]. ...
Article
Allergic rhinitis (AR) is one of the most common diseases in the world, which is based on immunoglobulin E (IgE) – mediated inflammation that develops after contact with various allergens. About 40 % of people suffer from various allergic diseases, every 3 rd inhabitant of the Earth has symptoms of allergic rhinitis and every 10 th has bronchial asthma. The early phase of allergen binding to IgE antibodies occurs within a few minutes after contact, the late phase develops after 4–6 hours. In addition to the airborne pathway of penetration, contact with the allergen is possible through the skin and mucous membranes, gastrointestinal tract, with parenteral administration of drugs. Taking into account the etiotropic factor, there are year-round allergic rhinitis (CAR) and seasonal (SAR). By the nature of the course, intermittent and persistent allergic rhinitis are distinguished. The most basic symptoms of allergic rhinitis include: sneezing, rhinorrhea, nasal congestion, itching, decreased sense of smell. Treatment includes antihistamines, intranasal steroids, leukotriene receptor antagonists and immunotherapy. To date, antihistamines of the second generation are recommended and widely used for the treatment of patients with allergic rhinitis, the main representative of which is levocetirizine (levocetirizine dihydrochloride). The purpose of the work is an analytical review of the results of clinical trials of levocetirizine for allergic rhinitis. The article discusses in detail the prevalence, etiology and pathogenesis, classification of the disease, treatment regimens for patients with allergic rhinitis, and provides two own clinical observations. Based on the data of a number of studies, the advantages of using antihistamines of the second generation in allergic rhinitis have been demonstrated, expanding not only the possibilities of treating patients, but also preventing the transition of the disease into a chronic process.
... hinitis is a chronic inflammation of the nasal mucosa characterized by the excessive mucosal influx of inflammatory cells such as eosinophils, basophils, mast cells, neutrophils, macrophages, B and T cells [1,2]. The two major forms of rhinitis have commonly been defined in the clinic, including Allergic Rhinitis (AR) and Nonallergic Rhinitis (NAR) [3]. Acute inflammation is a salutary response of the host to eliminate and eradicate the invading pathogens or damaging agents. ...
Article
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Background: Rhinitis is a prevalent chronic inflammatory illness of the nasal mucosa. Arachidonic acid-derived lipoxin A4 (LXA4) has long been recognized to exert crucial anti-inflammatory and pro-resolving effects on inflammatory responses through a specific receptor named LXA4 receptor/formyl peptide receptor-2 (ALX/FPR2). This study aimed to determine the serum level of LXA4 and the relative mRNA expression level of FPR2 in peripheral blood cells of patients with rhinitis (allergic and nonallergic) compared to healthy individuals. Materials And Methods: The study groups consisted of 37 patients with Allergic Rhinitis (AR), 16 patients with Nonallergic Rhinitis (NAR), and 20 sex- and age-matched healthy individuals. The measurement of LXA4 serum level was performed by the Enzyme-Linked Immunosorbent Assay (ELISA) technique, and the analysis of FPR2 mRNA expression level was performed by quantitative real-time PCR method. Results: The serum concentrations of LXA4 decreased in AR and NAR patients compared to healthy controls; however, this difference was not statistically significant (P>0.05). Besides, the mRNA expression level of FPR2 in peripheral blood cells of patients with nonallergic rhinitis was significantly lower than that in allergic rhinitis (P<0.05). Conclusion: Our results suggest that reduced gene expression of FPR2 may contribute to developing persistent and chronic nasal mucosa inflammation seen in NAR patients. Therefore, stable analogs of LXA4 and its receptor agonist may help develop new therapeutic approaches for rhinitis.
... Dizygotic twins exhibit a concordance rate of about 25%, while monozygotic twins exhibit a range of 45% to 60%. Specific areas on chromosomes 3 and 4 have also been linked to allergy reactions [6] . Eczema (atopic dermatitis) and asthma are predisposing factors for allergic rhinitis. ...
... AR is a prevalent and persistent childhood illness [18]. Associations between migraine and atopic disorders have been reported in both adults and children [19]. ...
Article
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Headache and allergic rhinitis (AR) are common in children and often co-occur. We investigated the clinical characteristics of pediatric headaches and the association of AR and chronic headaches. We retrospectively reviewed the medical records of patients admitted to our pediatric inpatient and outpatient clinics with complaints of headache between January 2017 and June 2020 for headache-specific history, AR signs and symptoms, allergy skin prick test, inhalant multiple allergen simultaneous test results, laboratory and imaging findings, and medication history. The patients were divided into three subgroups: AR, non-AR, and headache groups, reporting 45.7% patients with headache alone, 13.7% with additional AR, and 31.6% with abnormal imaging findings, suggesting that headache was combined with sinusitis (24.3%) or mastoiditis (7.3%). Furthermore, 6% of the patients had both AR and sinusitis. Body mass index (BMI) differed significantly between the AR and the non-AR and headache groups (p = 0.03). The BMI differed significantly according to headache severity (p ˂ 0.001). The most common allergen was “dust or mites” (41.1%). Acetaminophen (35.9%) was the most commonly used painkiller. The coexistence of AR and headache may indicate that these conditions share a similar pathophysiology. Better management of allergies may facilitate diagnosis, treatment, and prophylaxis of headaches.
... It is prudent for clinicians to anticipate that children prescribed topical nasal medications for rhinitis, asthma management or obstructive apnoea may find it an unacceptable route of drug delivery, which may affect their compliance and play a significant role in treatment efficacy. [5,6] Usually, most approved IN drug products are delivered through nasal drops, sprays or aerosol devices. Advances within the field of nasal sprays (NSs) and aerosols have addressed similar challenges using technological approaches, including active targeting (Exo-CD24, Taflix) and passively (viscosity, pH) protecting the mucosa from pathogen uptake. ...
Article
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Objectives Nanotechnology-based nasal delivery systems have gained interest as a way of overcoming low drug bioavailability, limited brain exposure, fast metabolism and elimination, high doses, and unwanted side effects. The main benefits of intranasal administration include the non-invasive method, easy accessibility, porous epithelial barrier and highly vascularized tissue. However, it is imperative to identify interactions between the materials used and the nasal biological environment to ensure proper release. Methods Specific factors have been considered to comply with the strict nasal drug administration criteria. Given the broad interest in the nasal drug delivery system, this review summarizes ways to develop formulations for intranasal drug delivery and the main biopharmaceutical challenges. Key findings We have examined principal factors in nasal administration, such as physiological aspects of the nose, drug and biopharmaceutical properties, formulation properties, and nasal devices for drug delivery. Conclusions This review highlights new insights into different nanotechnology-based approaches for intranasal use and focuses on recent developments in topical nasal drug delivery systems (DDS), outlining the advantages and limitations of each system. The present article confines itself to research and novel concepts and the different strategies developed to increase bioavailability, safety, and a route to brain delivery.
Article
Objectives Rhinitis, one of the most common inflammatory conditions of the nasal mucosa, is known to affect a large proportion of people worldwide. It is generally classified into allergic and non-allergic types and both are associated with several unpleasant symptoms. Several medications prescribed for different medical conditions can cause unpleasant rhinitis as an adverse effect, which is known as drug-induced non-allergic rhinitis. The aims of this article were to review the literature to identify drugs that could induce rhinitis, prevalence of drug-induced rhinitis, and the associated pathogenic mechanisms if known. Methods Literature search screening for eligible papers published up to December 31st, 2021, in Medline (via PubMed) and Embase was conducted. The search included the following combination of keywords and terms: rhinitis, sneezing, congestion, allergic, non-allergic, rhinorrhea, vasomotor, medication, drug-induced. Results The review findings suggest that 12 subtypes of drugs potentially could induce rhinitis. Based on their mechanisms of action, the pathogenic causes for the induction of rhinitis have been recognized for some drugs, while others remain unknown. Conclusion Awareness of the list of drugs that reportedly induce non-allergic nasal symptoms, along with taking the patient’s medication history, is important in the diagnosis of rhinitis.
Article
Objective: To review the pharmacology, efficacy, and safety of intranasal olopatadine hydrochloride-mometasone furoate (OM) combination in the treatment of seasonal allergic rhinitis (SAR). Data sources: The PubMed database and ClinicalTrials.gov were searched using the following terms: mometasone + olopatadine, GSP301, mometasone furoate, and olopatadine hydrochloride. Study selection and data extraction: Articles published in English between January 1987 and August 2022 related to pharmacology, safety, and clinical trials were assessed. Data synthesis: In 2 phase II clinical trials, twice-daily (BID) and once-daily (QDay) intranasal OM demonstrated significant improvements in reflective total nasal symptom score (rTNSS) (BID P < 0.001 and QDay P < 0.001) and instantaneous total nasal symptom score (iTNSS) (BID P < 0.001 and P < 0.0001; QDay P < 0.001 and P < 0.0001). In 2 phase III clinical trials, BID OM showed significant improvements in rTNSS vs. placebo (P < 0.001), olopatadine monotherapy (P = 0.03 and P = 0.003), and mometasone monotherapy (P = 0.02 and P = 0.059). Relevance to patient care and clinical practice: OM is indicated for treatment of SAR symptoms. Caution with use must be considered for certain high-risk patients, existing tuberculosis; fungal, bacterial, viral, or parasitic infections; or ocular herpes simplex. Due to its quick and sustained onset of action, OM may be an ideal agent for initial treatment of moderate-severe SAR for patients 12 years and older. Conclusion: OM significantly improves SAR symptoms and is a viable treatment option in short-term SAR.
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Many patients have nasal syndromes that are nonallergic and noninfectious and not caused by mechanical or anatomic abnormalities. There are at least 8 recognized nonallergic rhinitis syndromes: drug-induced rhinitis including rhinitis medicamentosa, gustatory rhinitis, hormonally induced rhinitis including the rhinitis of pregnancy, nonallergic rhinitis with eosinophilia syndrome, senile rhinitis, atrophic rhinitis, cerebral spinal fluid leak, and vasomotor rhinitis. Few studies have explored etiologic causes. These syndromes are distinguished by clinical characteristics, recognized triggering conditions, and concomitant observations such as nasal eosinophilia or cerebral spinal fluid leak. Until more specific subjective clinical characteristics and/or objective measures can better define and differentiate underlying causes for these disparate diseases, they will remain a murky group of overlapping syndromes.
Article
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"Nonallergic vasomotor rhinitis" (also referred to as nonallergic rhinitis and/or idiopathic rhinitis) is a term that has been used to describe a common nasal condition of unclear pathophysiology. Clinical options for patients are limited by a lack of straightforward diagnostic criteria and poorly defined and heterogeneous populations in clinical trials. A roundtable conference convened in December 2008 addressed these challenges. The outcomes were (1) a revised clinical definition and (2) appropriate inclusion and exclusion criteria (based on the revised definition) to be used for the enrollment of subjects in future clinical studies.
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The use of nasal irrigation for the treatment of nose and sinus complaints has its foundations in yogic and homeopathic traditions. There has been increasing use of saline irrigation, douches, sprays and rinsing as an adjunct to the medical management of chronic rhinosinusitis. Treatment strategies often include the use of topical saline from once to more than four times a day. Considerable patient effort is often involved. Any additional benefit has been difficult to discern from other treatments.
Article
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The term "rhinitis" denotes nasal inflammation causing a combination of rhinorrhea, sneezing, congestion, nasal itch, and/or postnasal drainage. Allergic rhinitis is the most prevalent and most frequently recognized form of rhinitis. However, nonallergic rhinitis (NAR) is also very common, affecting millions of people. By contrast, NAR is less well understood and less often diagnosed. Nonallergic rhinitis includes a heterogeneous group of conditions, involving various triggers and distinct pathophysiologies. Nonallergic vasomotor rhinitis is the most common form of NAR and will be the primary focus of this review. Understanding and recognizing the presence of NAR in a patient is essential for the correct selection of medications and for successful treatment outcomes.
Conference Paper
In the wide spectrum of medical practice, rhinitis is often incorrectly assumed to be solely allergic in etiology. Consequently, other rhinitis subtypes (nonallergic and mixed) remain under-diagnosed. This is of concern because inaccurate diagnosis may lead to unsatisfactory treatment outcome. Contributing to this under-diagnosis is the fact that primary care practitioners do not often have at their disposal the same diagnostic tools as the allergist. Tools that the allergist is more likely to use include nasal cytology, skin testing and in vitro assays for specific immunoglobulin E. Patients with pure nonallergic rhinitis have negative skin tests or clinically irrelevant positive results. Mixed rhinitis refers to the presence of both allergic and nonallergic rhinitis components within the same individual. Allergic rhinitis more commonly develops before the age of 20, whereas nonallergic rhinitis affects an older population and disproportionately more females. The type of nasal symptoms manifested by the patient usually does not differentiate allergic from nonallergic rhinitis. Vasomotor rhinitis is the most common form of nonallergic rhinitis, followed by nonallergic rhinitis with eosinophilia and others. In terms of estimated prevalence, allergic rhinitis affects approximately 58 million Americans, 19 million have pure nonallergic rhinitis and 26 million have mixed rhinitis. Thus a wide spectrum of relevant epidemiologic information can be used to assist in determining the differential diagnosis of rhinitis. Physicians are reminded to look further and consider whether a rhinitis patient truly has pure allergic rhinitis or whether a diagnosis of mixed rhinitis or nonallergic rhinitis is more appropriate.
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Treatment of ‘Vasomotor rhinitis’ by the local application of Silver Nitrate - Volume 106 Issue 6 - K.B. Bhargava
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These parameters were developed by the Joint Task Force on Practice Parameters, representing the American Academy of Allergy, Asthma and Immunology; the American College of Allergy, Asthma and Immunology; and the Joint Council of Allergy, Asthma and Immunology. The American Academy of Allergy, Asthma and Immunology (AAAAI) and the American College of Allergy, Asthma and Immunology (ACAAI) have jointly accepted responsibility for establishing the “Allergen immunotherapy: a practice parameter second update.” This is a complete and comprehensive document at the current time. The medical environment is a changing environment, and not all recommendations will be appropriate for all patients. Because this document incorporated the efforts of many participants, no single individual, including those who served on the Joint Task Force, is authorized to provide an official AAAAI or ACAAI interpretation of these practice parameters. Any request for information about or an interpretation of these practice parameters by the AAAAI or the ACAAI should be directed to the Executive Offices of the AAAAI, the ACAAI, and the Joint Council of Allergy, Asthma and Immunology. These parameters are not designed for use by pharmaceutical companies in drug promotion.
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Acrivastine, astemizole, ebastine, loratadine, and terfenadine are transformed into active metabolites in the liver by the cytochrome P450 system. Mizolastine is active per se and is largely metabolized through glucuronidation. Cetirizine and fexofenadine differ from other antihistamines in that they are not metabolized in the liver, but they are mainly excreted unchanged in the urine or in the faeces ( 64). The cytochrome P450 system is also responsible for the metabolism of other drugs that compete for the active site of the enzyme. The concomitant administration of azolic antifungal agents, such as ketoconazole, or macrolide antibiotics, such as erythromycin, may thus induce elevated concentrations of unmetabolized parent drugs. Grapefruit juice may have similar effects. These interactions have been particularly shown with terfenadine and astemizole. For drugs such as these, which interfere with the cardiac repolarization cycle, this increase in concentration may cause QT prolongation and increase risk of serious cardiac arrhythmia (including torsade de pointes) ( 65). These possible, but extremely rare, cardiotoxic effects are related to the dose-dependent capacity of the parent compound to block the K+ channel of the ventricular myocyte, which plays a central role in ventricular repolarization. As a result, astemizole and terfenadine have been withdrawn from the market in several countries ( 66). At the present time, although reports on cardiac side-effects in a few patients using second-generation antihistamines have been gathered, there is no clinical evidence of a causal relationship with the exception of terfenadine and astemizole. Consequently, these drugs can be considered safe, if the drug-specific recommendations are followed, if concurrent administration of interactive drugs is avoided, and if patients with known liver impairment or at significant risk of cardiac rhythm disturbance are excluded. In patients at risk, antihistamines which are not metabolized and which do not have quinidine-like actions should be chosen ( 65).
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Allergic rhinitis is one of the most common conditions affecting both children and adults. Along with the burden of the disease and decrease in quality of life associated with allergic rhinitis, there are high costs related to the disorder. Costs due to allergic rhinitis can be divided into two categories: direct costs that are related to monies spent on the course of managing the disease and indirect costs that are due to missing work and decreased productivity due to the illness. There are also the costs associated with the comorbidities of allergic rhinitis, such as sinusitis and asthma, which are classified as "hidden" direct costs. Management of allergic rhinitis involves allergen avoidance, proper pharmacologic therapies, and allergen immunotherapy. These treatments add to the direct cost of the condition and need to be evaluated to determine their cost-effectiveness in the control of the patient's nasal allergies. This article reviews the latest data on cost issues in allergic rhinitis and information of cost-effectiveness of treatments for this condition.