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Quality of Life Improvement with Sublingual Immunotherapy: A Prospective Study of Efficacy

  • Allergy Associates of LaCrosse

Abstract and Figures

Due to its excellent safety profile, ease of administration, and economic considerations, sublingual immunotherapy (SLIT) is becoming a preferred form of allergen specific immunotherapy. The efficacy of SLIT is still debated. The purpose of this act of practice trial is to evaluate quality of life outcomes in patients treated with SLIT. Fifty one patients with allergic rhinoconjunctivitis demonstrated by skin testing completed the Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) at initiation, at four months and at 10-12 months of SLIT. Significant improvement (P < 0.05) on six of seven domain categories of the RQLQ questionnaire was noted. Total RQLQ scores also showed significant improvement. This study supports SLIT as a modality effective in controlling allergic symptoms.
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Hindawi Publishing Corporation
Journal of Allergy
Volume 2012, Article ID 253879, 6pages
Research Article
Quality of Life Improvement with Sublingual Immunotherapy:
A Prospective Study of Efficacy
Mary S. Morris,1, 2 Amanda Lowery,2, 3 Demetrios S. Theodoropoulos,1, 4
R. Daniel Duquette,3and David L. Morris1
1Allergy Associates of La Crosse and Mayo Clinic Health System Franciscan Healthcare-La Crosse-Onalaska, WI 54650, USA
2Allergychoices Inc., Onalaska, WI 54650, USA
3College of Science and Health, University of Wisconsin-La Crosse, La Crosse, WI 54601, USA
4Allergy and Asthma Center, Hagerstown, MD 21740, USA
Correspondence should be addressed to Mary S. Morris,
Received 29 September 2011; Revised 23 November 2011; Accepted 24 November 2011
Academic Editor: Nazan Cobanoglu
Copyright © 2012 Mary S. Morris et al. This is an open access article distributed under the Creative Commons Attribution License,
which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Due to its excellent safety profile, ease of administration, and economic considerations, sublingual immunotherapy (SLIT) is
becoming a preferred form of allergen specific immunotherapy. The ecacy of SLIT is still debated. The purpose of this act of
practice trial is to evaluate quality of life outcomes in patients treated with SLIT. Fifty one patients with allergic rhinoconjunctivitis
demonstrated by skin testing completed the Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) at initiation, at four
months and at 10–12 months of SLIT. Significant improvement (P<0.05) on six of seven domain categories of the RQLQ
questionnaire was noted. Total RQLQ scores also showed significant improvement. This study supports SLIT as a modality eective
in controlling allergic symptoms.
1. Introduction
Allergen-specific immunotherapy in the treatment of IgE-
mediated allergy has been used for longer than a century; yet,
its major form, subcutaneous immunotherapy (SCIT) has
not become a widely accepted routine treatment for allergy.
Patients will often suer from severe symptoms and allergic
comorbidities before consulting with an allergist or consid-
ering immunotherapy. Children especially are unlikely to
adhere to SCIT. Subcutaneous injections for immunotherapy
are believed to be tedious and unlikely to lead to sustained
improvement. Standardization, safety, and ecacy concerns,
along with the inconvenience of injections and frequent
oce visits, keep the vast majority of allergic patients from
receiving SCIT. Recruitment to immunotherapy is poor:
less than 5% of all allergic patients receive immunotherapy.
Compliance is even poorer: among adult patients who agree
to undergo SCIT, adherence is disappointing with more than
two thirds dropping out within a year of initiation. One tenth
of SCIT candidates fail to show up for their first injection
[1]. In some countries, the scope of SCIT has been curtailed
substantially by administrative decisions [2]. At the same
time, a wealth of evidence in literature and clinical practice
supports the safety, ecacy, feasibility, compliance, and eco-
nomic profile of sublingual immunotherapy (SLIT) [37]. In
the United States, however, SLIT remains uncommon and
is only oered by few practices with special interest in this
method. With this study, we sought to evaluate the subjective
symptom responses of patients treated with multiantigen
SLIT. The information provided with the present study may
lead to better appreciation of the potential of SLIT and may
foster the design of large-scale, multicenter studies for its full
2. Methods
2.1. Subject Selection and Testing. Subjects were recruited
from patients of Allergy Associates of La Crosse, a single spe-
cialty practice that has been oering SLIT for 41 years. The
study was approved by the Mayo Clinic Health System Fran-
ciscan Healthcare-La Crosse, Institutional Review Board. All
2Journal of Allergy
23 23
Food allergy
Atopic dermatitis
Contact dermatitis
Otitis media
Allergy-related comorbidities among
study population
Chronic fatigue sy...
Multiple chemical s...
Figure 1: Of the 51 study participants, most had one or more comorbid allergic conditions with the average number of 1.9 chronic conditions
per participant.
subjects were diagnosed with allergic rhinoconjunctivitis on
the basis of their history and positive skin test results. Skin
test positivity was assessed by obtaining a response greater
than the negative control and greater than two thirds of the
histamine control using intradermal dilution testing (IDT)
[8]. Antigens selected for testing were determined by a self-
administered patient history questionnaire and initial con-
sultation with their physician. Patients with dermographism
or systemic mastocytosis were not included. Figure 1 also
shows that the patient population was aected by one or
more comorbid allergic condition upon arrival for their first
appointment. Skin test panels included 15–30 antigens rep-
resenting dust mite, weed, tree, grass, and fungal allergens
typical of the northern Midwest (see Ta b le 1 ). The number
of allergen extracts varied by patient, as the number of
oending allergens ranged from six to 24 with the mean
of 15.15. Round one patient enrollment occurred from July
through December and round three visits occurred from
January through November, thus crossing multiple peak
pollen seasons and limiting the influence of allergen season
2.2. Sublingual Immunotherapy Administration. Sublingual
immunotherapy based on skin test reactivity was initiated
according to the La Crosse Method Practice Protocol [9].
A capital aspect of SLIT, at least as practiced in the United
States, is the adjustment of the treating dose to skin reactiv-
ity. For this purpose, allergen extracts are serially diluted
by decrements of ×5. The purpose of such dilution is to
adjust dose to skin reactivity under the premise that adverse
reactions (including local reactions) define a level of toler-
ance. For many patients, skin test reactivity does not nec-
essarily reflect the degree of sensitization. A negative skin
test, however, and minimal/absent late-phase responses do
establish a de facto threshold of tolerance.
Dosing for each patient was tied to skin test results for
each individual antigen and adjusted over the course of
treatment (see Figure 2). With ongoing treatment, the need
to regularly adjust the degree of testing (and dosing) to the
long-term eects of immunotherapy is dictated by the fact
that, over time, skin test reactivity tends to decline with
immunotherapy. Thus, initiation of SLIT at a strength
Tab le 1: Sensitivities detected by skin testing. Grass mix includes
Kentucky Blue/June, Meadow Fescue, Orchard, Perennial Rye,
Redtop, Sweet Vernal, and Timothy. Tree mix includes American
Beech, American/Eastern Sycamore, American Elm, Black Walnut,
Black Willow, Eastern Cottonwood, Red Oak, Red/River Birch,
Shagbark Hickory, Sugar/Hard Maple, and White Ash. Weed mix
includes Cocklebur, Lamb’s Quarter, Common Mugwort, Pigweed
(rough/red), and Dock/Sorrel Mix (red/sheep and yellow dock).
Allergy Associates common environmental allergens and the per-
centage of participants testing positive to the following.
Dust mites 51 (100%)
Ragweed 51 (100%)
Grass mix 48 (94%)
Birch 42 (82%)
Tree mix 50 (98%)
Oak 37 (73%)
Weed mix 42 (82%)
Alternaria 50 (98%)
Cladosporium 49 (96%)
corresponding to the highest dilution that produced a near-
negative skin test establishes a safe threshold of tolerance;
thereafter, upward titration of immunotherapy doses against
declining skin reactivity is used for safe build-up and
unnecessary local or systemic reactions.
A skin test of greater than 7 mm using dilution number 7
correlates with the highest level of reactivity. Thus, the lowest
dose administered of the oending allergen is dilution num-
ber 7. As skin test reactivity improves, doses are escalated
to the next allergen dilution until the patient has reached
dilution number 1 for his/her dierent allergens. The starting
dose of each individual antigen is titrated based on skin test
(or in vitro specific IgE testing) level of reactivity, (see Tables
2and 3). Sublingual immunotherapy with multiantigen
treatment addresses multiple allergies that are specific to each
individual patient. Each bottle consisted of a 90-day supply
that was individually prepared for the patient using Greer
Laboratory and ALK-Abello extracts and compounded in the
Allergy Associates of La Crosse clinical laboratory.
Journal of Allergy 3
Mean dosing levels for common
inhalant allergens
Dosing visit 1
Dosing visit 2
Dosing visit 3
Grass mix
Tree mix
Weed mix
Figure 2:DosinglevelswiththeLaCrosseMethodareescalated
over the course of treatment based on skin test reactivity. Dosing
levels are carefully adjusted in an eort to balance therapeutic
benefit without creating unnecessary patient side eects.
Over a 1000-fold range of antigen dilutions have been
reported to produce clinical improvement with SLIT sug-
gesting that a straight dose-eect does not exist [10]. Other
variables such as dosing frequency, extract quality, and
length of treatment also need to be considered. Numerous
studies have observed and suggested a limited capacity of
the sublingual mucosa and have shown clinical improvement
with lower, but more frequent doses [1113]. Patients were
advised to take their sublingual immunotherapy drops three
times daily. Given that SLIT is retained in the sublingua for
up to 48 hours, administering two to three doses per day
is reasonably expected to secure unbroken allergen-exposure
and overlap generously with antigen uptake by the dendritic
cells and migration to lymphoid organs.
2.3. Questionnaire Administration. Symptom severity was
evaluated by the Rhinoconjunctivitis Quality of Life Ques-
tionnaire (RQLQ). This disease-specific validated question-
naire was developed by Professor Elizabeth Juniper and
has been used extensively throughout the world in a large
number of clinical trials [14]. New clinic patients were asked
to complete the RQLQ at their first visit before the onset of
sublingual immunotherapy treatment and two subsequent
follow-up visits at three- to six-month intervals. The full-
version RQLQ encompasses 28 questions in seven domains
(activity limitations, sleep problems, non-nose/eye symp-
toms, practical problems, nose symptoms, eye symptoms,
and emotional function). Patients were asked to recall their
experiences during the previous seven day period and to give
their responses on a 0- to 6-point scale (none of the time
to all of the time). A total RQLQ score is also calculated by
adding the scores of the individual domains together.
This study was a prospective analysis that compiled and
compared collected RQLQ data from patients undergoing
sublingual immunotherapy. Collected data for each patient
were compared to that particular patient’s baseline data and
Total RQLQ
Total RQLQ
Round 1
Round 2
Round 3
Figure 3: Participants’ aggregate RQLQ scores were compared
from their initial appointment and follow-up visits one and
two. Statistical significance was achieved within four months of
beginning sublingual immunotherapy and continued through their
second return visit (Round 3). P<0.05. Standard error for Round
1=7.74, Round 2 =6.35, and Round 3 =7.61.
two subsequent patient visits for changes in each RQLQ
parameter as well as total RQLQ score. Timing of follow-
up for visit two ranged from 1.23 months to 10.94 months,
with a mean follow-up time of 4.1 months. Follow-up for
visit three ranged from 2.82 months to 17.94 months with a
mean follow-up time of 7.06 months. The average duration
of treatment during the study was 11.19 months.
2.4. Statistical Analysis. Descriptive and bivariate statistics
were performed using the Standard SPSS data package.
Statistical significance was designated as P<0.05.
3. Results
3.1. Patient Characteristics. Paired RQLQ data were available
for 51 patients who were skin tested and started on SLIT.
Participants were comprised of 13 males and 38 females, with
ages ranging from 22 to 63, and a mean age at initiation of
SLIT of 45.8 years.
3.2. Quality of Life Results. Paired RQLQ results revealed
statistically significant (P<0.05) improvement in six of
seven domains evaluated by the RQLQ after four months of
treatment. Improvements were seen in the activities, non-
nose/eye symptoms, practical problems, nasal symptoms, eye
symptoms, and emotional categories. Results are presented
in Tab l e 4 . Statistically significant improvements were noted
in 23 of the 28 overall questions. Furthermore, the total
RQLQ for the whole cohort declined significantly (P<
0.5) from 126.02 to 74.96 within the first four months of
treatment (see Figure 3).
Although just shy of achieving statistical significance,
participants that adhered to three times daily dosing of
sublingual immunotherapy showed better improvement in
RQLQ scores than participants who were suboptimally
compliant. Advised compliance to treatment declined from
round two to three, which may have aected round two
to round three overall RQLQ scores (see Figure 4). Further
studies with larger study populations are needed to validate
4Journal of Allergy
Tab le 2: Serial dilutions are then used to expand La Crosse Method doses from one to seven.
Antigen La Crosse method concentrate Concentration number 1 dilution
Pollens 1 mL 1 : 20 w/v 1 : 100 w/v
Mold 1 : 20 w/v 1 : 100 w/v
Mite mix 1 mL conc + 2mL diluents for 10,000 AU/mL 2000 AU/mL
Cat 1mL + 4 mL diluents for 2000 BAU/mL 400 BAU/mL
Epithelias (except cat) 1 : 20 w/v 1 : 100 w/v
Grass mix 100,000 BAU/mL 20,000 BAU/mL
Bermuda grass 10,000 BAU/mL 4000 AU/mL
Short ragweed 100,000 AU/mL 20,000 AU/mL
Tab le 3: How 1 : 5 serial dilutions are made: from La Crosse Method
number 1 dilution.
1 mL of dilution number 1 + 4 mL of diluent =dilution number 2
1 mL of dilution number 2 + 4 mL of diluent =dilution number 3
1 mL of dilution number 3 + 4 mL of diluent =dilution number 4
1 mL of dilution number 4 + 4 mL of diluent =dilution number 5
1 mL of dilution number 5 + 4 mL of diluent =dilution number 6
1 mL of dilution number 6 + 4 mL of diluent =dilution number 7
treatment compliance and multiple versus single daily dos-
4. Discussion
A number of studies have demonstrated statistically sig-
nificant eects on allergic rhinoconjunctivitis and asthma
symptoms in SLIT [1520]. These studies, however, were all
heterogeneous and of small magnitude. More importantly
since no two studies used the same protocol, the value of their
meta-analysis is questionable. They all used single-allergen
monotherapy to evaluate ecacy, an approach which does
not reflect the sensitization status of patients with allergic
rhinoconjunctivitis, and may in fact have led to undertreat-
ment and subsequent under-appreciation of the ecacy of
SLIT. The number of SLIT (or even SCIT) ecacy studies
employing multiple allergens in the treatment regimen is
so surprisingly small that their low number and insucient
data on ecacy have been addressed unfavorably [21]. These
studies were characterized by their sporadic nature. They
were not followed by subsequent studies that would have
established a continuity of approach which might have made
up, to some extent, for methodological defects. Significantly,
the ultimate end-point, which is improvement of symptoms,
was not assessed by a validated instrument, developed by an
independent party, such as the RQLQ [9]. To our knowledge,
a modified, shortened version of the RQLQ, the mini-RQLQ,
has been used in one study employing SLIT for multiple
allergens but this study relied on retrospective selection of
subjects and only enrolled fifteen patients, thus raising
significant questions as to both its power and freedom of
bias [22]. Our study is the first prospective study of SLIT
ecacy, employing multiple allergen extracts for treatment,
a protocol for SLIT which has been applied for 41 years,
Sublingual immunotherapy
treatment compliance
Round 3
Round 2
Suboptimal compliance
Figure 4: Patients were advised by their providers to take sublingual
immunotherapy drops three times daily. Patient records showed
a greater adherence to three times daily dosing from their initial
appointment to second visit than from their second appointment
to third.
a validated questionnaire, and a number of subjects large
enough to satisfy power requirements.
In the present study, SLIT, as formulated by the La Crosse
Method Protocol, is eective in reducing symptoms and
improving quality of life after four months of treatment (see
Tab l e 4 ). This improvement was most prominent in activity,
non-nose/eye symptoms, nasal symptoms, and emotional
domains. Improvement in the sleep domain of the RQLQ
was also observed, but did not reach statistical significance.
This improvement was sustained and demonstrated again
at 10–12 months of treatment. Given the high compliance
rates with the La Crosse Method SLIT, it is expected that the
improvement achieved is likely to be sustained and possibly
expanded with ongoing treatment beyond the first year.
Sneezing and irritability, two parameters, which in a previous
SLIT ecacy study employing the mini-RQLQ were found
unaected, are demonstrated to decline in the course of the
first four months of SLIT [22].
The mechanism underlying SLIT has been reviewed [7].
Although not fully delineated, it appears that a systemic
alteration of the Th1/Th2 balance is eected in SLIT by
the promotion of tolerogenic T-cell clones. Interaction of
dendritic cells with na¨
ıve T-cells is necessary for this change
to occur. Production of TGF-β, IL-10, and possibly other
regulatory cytokines appears to be critical. Ongoing changes
may in some cases be reflected in skin reactivity as well as
Journal of Allergy 5
Tab le 4: Mean RQLQ Scores Presublingual Immunotherapy and at Subsequent Visits.
Category sum Round 1 Round 2 Round 3
Mean (SE) Mean (SE) Mean (SE)
Activity sum 8.14 (.57) 4.92(.44) 4.63(.52)
Sleep sum 5.84 (.68) 3.61 (.45) 3.92 (.63)
Non-nose/eye sum 17 (1.37) 10.59(1.04) 10.71(1.22)
Practice problem sum 8.43 (.65) 4.63(.50) 5.06(.54)
Nasal symptom sum 11.69 (.74) 7.25(.60) 7.63(.64)
Eye symptom sum 8.92 (.82) 5.49(.67) 6.16(.67)
Emotional sum 10.55 (.87) 4.27(.59) 4.82(.67)
Denotes RQLQ domains found to have a statistically significant decrease in symptom scores throughout the duration of sublingual immunotherapy
treatment. P<0.05.
in specific IgG and IgE production changes. The protocol
used in the present study may be well suited to eect these
changes. It can be summarized in three cardinal points:
(i) initial and thereafter regular titration of treating SLIT
doses against skin reactivity and symptom response with
skin reactivity meant as a biphasic response whose late
phase reactions are also taken into account; (ii) frequent
administration of SLIT doses to secure continuous, maximal,
and uninterrupted saturation of the sublingual dendritic
cells’ potential for phagocytosis and migration, that is, three
doses per 24 hours; and (iii) maintenance of allergens in high
glycerin solutions in order to prevent decay and suppress
proteolytic activity [9].
In summary, this study represented a preliminary
attempt to investigate the eectiveness of multiantigen SLIT
in a complex patient base. Experience with this protocol over
the years has been rewarding and has shown clinical benefit
with a wide variety of allergic conditions including advanced
respiratory disease in adults with mold allergy [23], asthma
prevention in pediatric patients [24], and contact allergies
including nickel [25] and poison ivy [26] while maintaining
a remarkable paucity of adverse reactions of any significance.
The present study underscores the ecacy of SLIT; however,
we recognize that the absence of a placebo group limits the
interpretation of results. Given the large number of patients
currently treated and high rates of compliance, multicenter,
controlled studies are needed of greater magnitude and
expanded scope to include morbidities and associations such
as recurrent/chronic sinusitis, atopic dermatitis, gastroe-
sophageal reflux, and migraines. Sustained suppression of
symptoms after eventual completion of SLIT will also need
to be studied.
5. Conclusion
Statistically significant reduction of symptoms and improve-
ment of quality of life are demonstrated during the initial
four month period of SLIT. After the first four months,
reduction of symptom scores is sustained and continuous.
These data support the ecacy of SLIT and need to be
followed by controlled trials to evaluate the ecacy of this
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... This improvement was sustained and demonstrated again at 10-12 months of treatment. Taking into account the high compliance rates and the La Crosse Method, it is expected that the improvement achieved is likely to be sustained and possibly expanded beyond the first year of ongoing treatment (107). ...
Since it was introduced by Noon in 1911, allergen-specific immunotherapy or desensitization has been widely prescribed in the management of allergic diseases. Aimed at the etiology, it represents the only effective treatment for allergy. The basic mechanisms of immunotherapy are becoming better understood and allow us to improve this technique in the future. The sublingual immunotherapy as an alternative to subcutaneous route has been widely studied. Several clinical trials confirmed that sublingual immunotherapy is efficient in reducing allergic respiratory symptoms. The sublingual immunotherapy reduces the risk of developing serious side effects due to desensitization. We performed a literature review in order to remind the mechanisms of action and to demonstrate efficacy and tolerability of the sublingual immunotherapy in the treatment of allergic rhinoconjunctivitis and asthma and its impact on the quality of life.
... Despite being widely used in several countries [16][17][18][19], SLIT is not officially approved by the American Food and Drug Administration, and the few clinics in America that have experience with SLIT employ the allergens approved for injection immunotherapy in an off-label manner [20,21], therefore most researchers studying the benefits of SLIT are based in Europe [22][23][24]. Despite the difference in administration approach, allergen-specific SLIT and SIT may be indirectly compared [25]. ...
Full-text available
Background: The treatment of polysensitized allergic patients continues to represent a challenge and is a matter for debate amongst allergists who preferentially use allergen-specific immunotherapy. Objective: To study the effect of group-specific sublingual/swallow immunotherapy on quality of life of polysensitized human subjects with allergic rhinitis diagnosed using a comprehensive panel of cutaneous tests. Methods: 60 polysensitized subjects diagnosed with allergic rhinitis who submitted to group-specific sublingual/ swallow immunotherapy treatment corresponding to their cutaneous sensitizations, and who completed 6 months of treatment without the use of any complementary medication were evaluated with a validated quality of life questionnaire. Results: There were significant improvements in all quality of life categories evaluated, which included: sleep, systemic symptoms, practical problems, nasal symptoms, eye symptoms, activities and emotions. Conclusions: The administration of a group-specific multi-allergen sublingual/swallow immunotherapy as indicated by a comprehensive panel of sensitizing agents in cutaneous tests performed by a specialized team, significantly improved the quality of life of human polysensitized subjects with allergic rhinitis without the use of any additional medication.
... In our experience, multiantigen sublingual immunotherapy treatment that is dosed using the patient's allergen test results is both effective and maintains an excellent safety profile. Threshold dosing can be administered using a number of environmental allergens [5,6]. We have observed a combination of clinical symptom improvements, reduced skin test reactivity, and decreases in specific IgE levels in our forty-year history in treating 125,000 patients from the United States. ...
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Numerous sublingual immunotherapy studies have shown efficacy using a wide variety of dosing regimens. Despite a few grade III and one anaphylactic reaction due to a patient over-dose, there have been no fatal reactions resulting from sublingual immunotherapy treatment. Although safer than SCIT, SLIT is still immunotherapy. Special consideration should be given to what will ensure the highest level of safety for the patient given his or her history, exam and allergy test results. Dosing levels for sublingual immunotherapy should be based on what is therapeutically effective for each individual patient and adjusted accordingly throughout the treatment course.
Objectives/HypothesisTo explore quality of life (QoL) improvement after treatment of patients with chronic olfactory disorders; and to correlate QoL with olfactory rehabilitation and evaluate olfactory improvement values over which QoL outcomes are significantly recovered. Study DesignProspective clinical study. Methods Eighty-nine patients following endoscopic sinus surgery for chronic rhinosinusitis (CRS) and immunotherapy for allergic rhinitis (AR) were studied. Olfactory function was evaluated using Sniffin' Sticks test pre-and 12 months after treatment. All patients completed six validated QoL questionnaires either specific for olfaction (Questionnaire of Olfactory Deficits-QOD) and for assessing mental health (Zung Anxiety Scale, State-Trait Anxiety Inventory, Zung Depression Scale, Beck Depression Inventory), or generic one (Short Form-36). ResultsSignificant improvement (all P<0.001) of olfactory function by 27.4% in total cohort (AR: 10.4%, P=0.004; CRS: 39.9%, P<0.001), expressed by the combined Threshold-Discrimination-Identification (TDI) score-and of all QoL questionnaires scores (all P<0.01) as well, was observed after treatment. There was a positive correlation between olfactory recovery and improvement of patients' QoL. ROC analysis revealed that an increase in the TDI score by 3.50 points in AR and 4.75 points in CRS was necessary for a clinically significant improvement in all QoL questionnaires results. Conclusions QoL and mental health of patients suffering from chronic sinonasal diseases are totally recovered after treatment, presenting a direct positive relationship with smell improvement. An increase of olfactory function by 3.50 points for AR and 4.75 points for CRS might be considered the cutoff point for patients' QoL significant recovery.
The purpose of this review is to highlight important articles on tipper airway disease and immunotherapy that appeared in the Journal of Allergy and Clinical Immunology and elsewhere during 2005. In recent studies of tissue from patients with chronic hypertrophic eositiophilic sinusitis, increased leukotriene C-4 synthase and 5-lipoxygenase activity and increased levels of cysteinyl leukotriene production were demonstrated that correlated with disease severity but not with whether the patient was aspirin sensitive. However, the cysteinyl leukotriene 1 receptor was increased in leukocytes; in the sinus tissue only in those patients with aspirin sensitivity. Major basic protein, released by eosinophils into the mucus in the paranasal sinus lumen, was found to reach concentrations capable of damaging the sinus epithelium, predisposing to bacterial infections. Testing the hypothesis that chronic hypertrophic eosinophilic sinusitis represents a reaction to common fungi, a double-blind trial of intranasal instillation of amphotericin B was conducted. There were marginal but significant differences in favor of amphotericin B treatment for sinus mucosal thickening on the basis of computed tomography and the evidence of eosinophilic inflammation in the sinus mucus. The effectiveness of topical nasal corticosteroids for treatment of nasal polyps was confirmed in 2 large studies. Improvement in sleep quality and daytime drowsiness in patients with allergic rhinitis treated with nasal corticosteroids was reported to correlate with reduction in nasal obstruction. The statistical analysis behind studies that reported a decrease in asthma exacerbations with nasal corticosteroids or oral antihistamines has been questioned. It appears that the results of at least one of these studies are indeed too good to be true. Although caution is still indicated in administering immunotherapy to patients receiving beta-adrenergic blocking agents, the prohibition might not be absolute. A study in patients with Hymenoptera sensitivity given venom immunotherapy revealed no increase in serious adverse reactions to venom injections and no greater incidence of reactions to insect stings in those taking beta-blocking agents. Sublingual immunotherapy for 8 to 12 weeks in patients with hazelnut sensitivity significantly increased their tolerance to hazelnut in double-blind, placebo-controlled challenges while inducing increased IgG(4) and IL-10 levels, indicating induction of regulatory T cells. There were a number of articles in the Journal of Allergy and Clinical Immunology in 2005 that addressed the entity of chronic hypertrophic eosinophilic sinusitis. In addition, an update of the "Practice parameters on sinusitis" was published. The major focus in allergen immunotherapy continues to be sublingual administration.
Thirty-nine patients with nickel allergy as diagnosed by results of clinical history and intradermal testing with nickel sulfate were treated by sublingual hyposensitization. Intradermal testing was accurate and titration showed the degree of sensitivity. The immunologic principle of oral tolerance was used in treatment. Eighty-five percent of the thirty-nine patients showed subjective improvement in their dermatitis and all showed objective evidence of decreased intradermal sensitivity. None of the patients' conditions worsened. The use of oral treatment with nickel sulfate deserves broader clinical trial.
Sublingual immunotherapy (SLIT) has been shown to be effective in the treatment of seasonal allergic rhinoconjunctivitis. Despite comparable clinical efficacy to traditional subcutaneous immunotherapy, the mechanisms of SLIT have yet to be fully established. This article considers the role of the local oral mucosa and regional lymphoid tissues in the processing of allergen during SLIT and the subsequent effects on T-cell and B-cell immune compartments and at mucosal sites. The likely time course of events and the evidence for long-lasting tolerance following SLIT are discussed.
Thesis (M.P.H.)--University of Wisconsin -- La Crosse, 2005. Includes bibliographical references (leaves 19-21)
Immunotherapy is the titrated exposure of allergens to induce immunologic tolerance and offers long-term immune modification. Traditional subcutaneous immunotherapy (SCIT) has resulted in several deaths and raised safety concerns. Sublingual immunotherapy (SLIT) is an alternative administration route for allergen-specific immunotherapy. Compared to SCIT, SLIT has a shorter escalation phase, equal or greater efficacy for rhinitis, and an improved safety profile. The purpose of this study was to evaluate quality of life measures in a preliminary patient sample initiating SLIT at our institution. Patients with appropriate allergen reactivity were given the option to pursue immunotherapy by traditional SCIT or by SLIT techniques. Patients choosing SLIT completed the mini-Rhinoconjunctivitis Quality of Life Questionnaire (m-RQLQ), a 14-item Likert-type questionnaire, at baseline and during maintenance therapy. Patients typically reached maintenance dosing in less than 5 weeks. Paired m-RQLQ data were available for 15 patients after antigen titration. Initial m-RQLQ results indicate statistically significant (P < .05) improvement on 12 of 14 domains, including impact on regular and recreational activities, sleep, nose rubbing and nose blowing, stuffy nose and runny nose, itchy eyes, sore eyes, watery eyes, thirst, and tiredness. In addition, total m-RQLQ score showed statistically significant improvement (P = .001). No serious adverse events occurred with the initiation of SLIT. These results indicate that SLIT is effective in controlling allergic symptoms and is safe in an introductory patient sample. Double-blind placebo-controlled trials are needed to confirm our preliminary results.
Allergen-specific sublingual immunotherapy is now recognized to be an efficacious and well-tolerated treatment for allergic rhinitis. Emerging treatment strategies are also aimed at the primary treatment of allergic asthma, particularly allergy to house dust mites. Knowledge of the exact mechanisms of action of sublingual immunotherapy is at a basic level, although there appear to be similarities to the immunological changes seen in subcutaneous immunotherapy. An improved understanding should allow the development of more effective treatment programs and widen the potential use of this form of immunotherapy. This review discusses the possible mechanism of action of sublingual immunotherapy, including data from animal and clinical studies, while comparing this with the current understanding of subcutaneous immunotherapy.
To date, no predictive tests for the clinical response to allergen-specific immunotherapy (ASI) are available. Therefore an in vivo or in vitro test would be of great value. We sought to evaluate pretreatment parameters used in diagnosing allergic rhinitis and determining serum specific IgE (s-IgE) levels, serum total IgE (t-IgE) levels, and blood eosinophil counts and to identify whether can be used to predict clinical improvement in monosensitized patients with allergic rhinitis with or without asthma treated with immunotherapy. We analyzed 279 patients who had undergone 4 years of ASI administered either by means of the subcutaneous immunotherapy (76 patients) or sublingual immunotherapy (203 patients) routes. Serum t-IgE and s-IgE levels, blood eosinophil counts, and serum s-IgE/t-IgE ratios were calculated and tested for correlation with clinical response to ASI. Receiver operating characteristic curves were determined. Predicted probabilities and predictive areas under the curve were calculated. The clinical response to ASI was effective in 145 (52.0%) of 279 total patients, 42 (55.2%) of 76 patients treated with subcutaneous immunotherapy, and 103 (50.7%) of 203 patients treated with sublingual immunotherapy. A significant correlation was found between the serum s-IgE/t-IgE ratio and the clinical response to ASI, with high ratios (>16.2) associated with an effective response. The sensitivity and specificity of the area under the curve of the ratio were higher than those of serum s-IgE and t-IgE alone. The calculation of the serum s-IgE/t-IgE ratio for predicting the clinical response to ASI offers an advantage over measuring t-IgE and s-IgE levels in monosensitized patients for the following allergens: grass, Parietaria judaica, Olea europea, and house dust mite.
The interest in sublingual immunotherapy (SLIT) is still growing worldwide and especially for the pediatric age group, this modality is appealing. Lately, some negative systematic review articles have been published on SLIT in children. However, high quality articles published from 2007 onward had not been included. Explanations are sought for the negative outcomes in these reviews and shortcomings are discussed. New pediatric studies - not included in the previous reviews -designed taking into account the golden rules for SLIT (high daily dose, starting at least 4 months before pollen season) do show statistically significant improvement in symptom and medication scores for rhinitis and asthma in pollen allergy. New house dust mite studies still show inconsistent data. Evidence of effect is confirmed for SLIT in children with allergic rhinitis or asthma caused by pollen exposure. For house dust mite asthma, evidence is still nonconcordant. New techniques to improve SLIT efficacy are under investigation.