Immunotherapy in asthma & allergy.pptx

Asthma Immunotherapy
Subcutaneous and Sublingual Immunotherapy
To Treat Asthma

Introduction
! Asthma is chronic complex inflammatory airways
disease with various inflammatory phenotypes
! 300 million people live with it worldwide
! Has a diverse presentation from mild to severe form
! Cornerstone remains inhaled corticosteroids &
bronchodilators
The prevalence of asthma in the general U.S. population is
approximately 9 percent, and approximately 62 percent of
individuals with asthma have evidence of atopy (i.e., the
genetic predisposition to produce elevated immunoglobulin E
[IgE] in response to environmental allergens).
Lin SY, Erekosima N, Suarez-Cuervo C, et al. AHRQ Comparative Effectiveness Review No. 111. Available at
http://www.effectivehealthcare.ahrq.gov/allergy-asthma-immunotherapy.cfm.
Min YG. Allergy Asthma Immunol Res. 2010 Apr;2(2):65-76. PMID: 20358020.

© Global Initiative for Asthma, www.ginasthma.org
 Asthma is the most common chronic non-communicable
disease, affecting over 260 million people globally in 2019
 Asthma is characterized by variable respiratory symptoms such
as wheeze, shortness of breath, chest tightness and cough, and
variable expiratory airflow limitation. It is usually associated with
airway inflammation
 People with asthma often have periods of worsening symptoms
and worsening airway obstruction, called exacerbations (also
called attacks or flare-ups), that can be fatal
 Most of the morbidity and mortality associated with asthma is
preventable, particularly with use of inhaled corticosteroids
About asthma

Lungs: The organ of respiration
10,000 liters air
pass in and out
every 24 hours1
Surface area: 50–100 m2 of alveolar epithelium1
Continuing Education in Anaesthesia, Critical Care & Pain. 2013 Jan 11;13(3):98-102.
10,000 liters
blood pass
every 24 hours
350 Liters of oxygen delivered every day
Asthma is a
heterogeneous
disease, usually
characterized by
chronic airway
inflammation.

Understanding the two components of asthma
Bronchospasm
Inflammation
.Allergic And Environmental Induced Asthma. [Updated 2019 Jun 3].. Available from: https://www.ncbi.nlm.nih.gov/books/NBK526018/
The pathophysiology of asthma
involves both bronchospasm
and chronic inflammation
hence treatment aimed at
asthma management should
target both these mechanisms
for effective disease control.

© Global Initiative for Asthma, www.ginasthma.org
 NOT just about medications, NOT one-size-fits-all
Personalized asthma management
GINA 2021 Box 3-2

The medical management of patients with allergic rhinitis
and allergic asthma includes:
 Allergen avoidance
 Pharmacotherapy
 Immunotherapy
Daily use of pharmacotherapies for allergic asthma and
rhinitis symptoms raises issues related to adherence,
safety, and cost.
Long-term use of inhaled steroids, long-acting
bronchodilators, and leukotriene antagonists for asthma
control can have adverse effects.
Background: Management of Allergy Symptoms
http://www.effectivehealthcare.ahrq.gov/allergy-asthma-immunotherapy.cfm

 Allergen-specific immunotherapy is typically used for:
 Patients whose allergic rhinoconjunctivitis and asthma symptoms cannot
be controlled by medication and environmental control
 Patients who cannot tolerate their medications
 Patients who do not comply with chronic medication regimens
 The U.S. Food and Drug Administration has approved the use
of allergen extracts for subcutaneous immunotherapy in treating
seasonal and perennial allergic rhinitis and allergic asthma.
 In the United States, a patient with allergies undergoing
immunotherapy receives subcutaneous injections—in
increasing doses until a maintenance dose is found—of an
allergen-containing extract comprised of the relevant allergens
to which he or she is sensitive in an attempt to suppress or
eliminate allergy-related symptoms.
Background:
Subcutaneous Immunotherapy for Allergies

 There is considerable interest in using similar allergen extracts as
sublingual immunotherapy (SLIT) as an alternative to
subcutaneous immunotherapy.
 SLIT involves placing drops or tablets with the allergen extract
under the tongue for local absorption to desensitize the allergic
individual over a period of months to years and to diminish allergic
symptoms.
 In the United States, there currently are no sublingual forms of
immunotherapy approved by the U.S. Food and Drug
Administration.
 However, some physicians are using subcutaneous aqueous
extracts off-label for sublingual desensitization in the treatment of
allergic respiratory conditions.
Background:
Sublingual Immunotherapy for Allergies

Objective
 To evaluate the efficacy, effectiveness, and safety of subcutaneous
(SCIT) and sublingual (SLIT) immunotherapies that are presently
available for use by clinicians and patients in the United States
Key Questions
 For patients with allergic rhinoconjunctivitis and/or asthma:
 Efficacy and effectiveness of SCIT, SLIT, and SCIT versus SLIT
 Safety of SCIT, SLIT, and SCIT versus SLIT
 Safety and effectiveness of SCIT, SLIT, and SCIT versus SLIT in the
pediatric subpopulation
Systematic Review: Objective and Key Questions
http://www.effectivehealthcare.ahrq.gov/allergy-asthma-immunotherapy.cfm

Outcomes of Interest
Primary Outcomes
 Clinical endpoints:
 Symptom control
 Medication use
 Quality of life
 Disease evolution/remission
 New allergen sensitivities
 Overall health care utilization
 Missed days of school/work
Secondary Outcomes
 Functional tests (pulmonary function
test‒forced expiratory volume)
 Provocational test
 Adherence
 Convenience and compliance
 Biomarkers
Adverse Effects
 Local reactions
 Skin, mouth, and throat
(including irritation, itching,
swelling, or pain in the oral
cavity)
 General symptoms (such as
headache, fatigue, arthritis)
 Systemic reactions
 Ocular
 Rhinitis/nasal
 Cutaneous
 Rash
 Gastrointestinal
 Respiratory/asthma
 Cardiovascular
 Anaphylaxis
 Death

 142 studies were included in the review with these populations: adults only
(52%), children only (24%), and adults and children (22%).
 Studies on SLIT mainly included patients with allergic rhinitis and/or mild
asthma.
 All included studies were randomized controlled trials.
 Efficacy and safety of SCIT: n = 74
 Efficacy and safety of SLIT*: n = 60
 Comparisons of SCIT versus SLIT: n = 8
 The types of scales/scoring systems used in the studies were not uniform.
 Followup varied and ranged from one pollen season to 6 years.
 Standard therapy varied across trials.
 Due to heterogeneity in reported outcomes, results often only reflect the
percentage of trials in which a significant effect was seen for the
immunotherapy arm versus controls and not the magnitude of effect.
Overview of Studies Included in the
Systematic Review
*SLIT refers to allergen extracts that are administered sublingually in the form of drops. Studies on sublingual tablets are not
included here.

Allergen SCIT SLIT SCIT vs. SLIT
Dust mite 21 14 6
Grass 11 15 ‒
Weeds 9 7 ‒
Cat 5 2 ‒
Dog 1 ‒ ‒
Mold 6 2 ‒
Tree 6 13 2
Multiple allergens 15 7 ‒
Included Studies by Type of Allergen for SCIT, SLIT,
and SCIT Versus SLIT
SCIT = subcutaneous immunotherapy; SLIT = sublingual immunotherapy

 74 articles were included with a total of 4,350 patients.
 The primary diagnoses were:
 Asthma in 19 studies
 Asthma with rhinitis in 18 studies
 Rhinoconjunctivitis in 14 studies
 Asthma with rhinoconjunctivitis in 14 studies
 Types of allergens evaluated:
 Seasonal allergens such as trees, grasses, weeds, and seasonal molds in 59
percent of studies
 Perennial allergens in 38 percent of studies
 Seasonal and perennial allergens in 3 percent of studies
 The heterogeneity of the data on clinical outcomes precluded pooling
of the data for further analysis. Consequently, the results often only
reflect the percentage of trials in which a significant effect was seen for
the immunotherapy arm versus controls and not the magnitude of
effect.
Included Studies for Subcutaneous Immunotherapy
Versus Placebo or Standard Therapy

Primary
Outcome Results*
No. of RCTs,
No. of Patients (n)
Strength of
Evidence
Asthma
symptom score
17‒84% greater
improvement vs.
controls
16 RCTs,
n = 1,178
High
Use of asthma
medications
Decreased in
42% of studies
vs. controls
12 RCTs,
n = 1,062
High
Combined
asthma symptom
and medication
score
Significant
improvement in
83% of studies
vs. placebo
6 RCTs,
n = 196
Low
Subcutaneous Immunotherapy Versus Placebo or
Standard Therapy: Asthma Outcomes
RCT = randomized controlled trial

Primary Outcome Results
No. of RCTs,
No. of Patients (n)
Strength
of Evidence
Rhinitis/
rhinoconjunctivitis
symptoms
Significant improvement in
73% of studies vs. controls 25 RCTs,
n = 1,734
High
Use of rhinitis/
rhinoconjunctivitis
medications
Significantly decreased in
n = 564
Moderate
Combined rhinitis/
rhinoconjunctivitis
symptom and
medication score
n = 400
Low
SCIT Versus Placebo or Standard Therapy:
Rhinitis/Rhinoconjunctivitis Outcomes (1 of 2)
RCT = randomized controlled trial; SCIT = subcutaneous immunotherapy

No. of RCTs,
No. of Patients (n)
Strength
of Evidence
Conjunctivitis symptoms Significant improvement
in 43% of studies vs.
placebo
14 RCTs,
n = 1,104
High
Combined symptoms
(nasal, ocular, and
bronchial)
Significant improvement
placebo
6 RCTs,
n = 591
High
Disease-specific quality of
life in patients with rhinitis/
rhinoconjunctivitis
by RQLQ in 67% of studies
vs. placebo
6 RCTs,
n = 889
High
Rhinitis/Rhinoconjunctivitis Outcomes (2 of 2)
RCT = randomized controlled trial; RQLQ = Rhinoconjunctivitis Quality of Life Questionnaire; SCIT =
subcutaneous immunotherapy

No. of RCTs,
No. of Patients (n)
Strength
of Evidence
Asthma plus rhinitis/
rhinoconjunctivitis
symptoms
21‒68% greater
improvement vs.
controls
5 RCTs,
n = 175
Moderate
Use of asthma plus
rhinoconjunctivitis
medications
• 14–83% greater
reduction in asthma-
based studies vs.
controls
• Significantly
decreased in 91% of
rhinitis-based
studies vs. controls
5 RCTs,
n = 203
11 RCTs,
n = 768
High
Asthma Plus Rhinitis/Rhinoconjunctivitis Outcomes

 60 articles on sublingual immunotherapy (SLIT) that included 4,870
patients were eligible for inclusion.
 Allergens evaluated included:
 Seasonal allergens (66%)
 Perennial allergens (31%)
 Both seasonal and perennial allergens (3%)
 Comparators included:
 Placebo (71%)
 Another sublingual intervention without a placebo group (15%)
 Conventional treatment without placebo (pharmacotherapy or rescue
medications; 14%)
 Duration of treatment ranged from 3 months to 5 years.
 There was great heterogeneity in:
 Dosages of maintenance or cumulative treatments
 The units to report dosing
 Standard therapy used across trials
 Reported results often only reflect the percentage of trials in which a
significant effect was seen for the immunotherapy arm versus controls
and not the magnitude of effect.
Included Studies for Sublingual Immunotherapy
Versus Placebo or Standard Therapy

Sublingual Immunotherapy Versus Placebo
or Standard Therapy: Asthma Outcomes
No. of RCTs,
No. of Patients (n)
Strength of Evidence
Asthma symptom
score
Significant
improvement across
all studies vs.
controls
13 RCTs,
n = 625
High

SLIT Versus Placebo or Standard Therapy:
Rhinitis/Rhinoconjunctivitis Outcomes
No. of RCTs,
No. of Patients (n)
Strength
of Evidence
Rhinitis/
rhinoconjunctivitis
symptoms
56% of studies vs. controls
36 RCTs,
n = 2,658
Moderate
Conjunctivitis
symptoms
46% of studies vs. placebo
13 RCTs,
n = 1,074
Moderate
Disease-specific
quality of life in patients
with rhinitis/
rhinoconjunctivitis
Significant improvement by
RQLQ in 75% of studies vs.
controls
8 RCTs,
n = 819
Moderate
RCT = randomized controlled trial; RQLQ = Rhinoconjunctivitis Quality of Life Questionnaire

No. of RCTs,
No. of Patients (n)
Strength
of Evidence
rhinoconjunctivitis
symptoms
Significantly
improved in 80% of
5 RCTs,
n = 308
Moderate
Use of asthma plus
rhinoconjunctivitis
medications
Significant
improvement in 47%
of studies vs.
controls
38 RCTs,
n = 2,724
Moderate
rhinoconjunctivitis
symptom and medication
score
Significant
improvement in 68%
of studies vs.
controls
19 RCTs,
n = 1,462
Moderate
SLIT Versus Placebo or Standard Therapy:

No. of RCTs,
No. of Patients (n)
Strength of
Evidence
Improves asthma symptom
score
SCIT may improve asthma
symptoms more effectively
than SLIT
4 RCTs,
n = 171
Low
Improves rhinitis/
rhinoconjunctivitis symptoms
SCIT is superior to SLIT for
improving allergic nasal
and/or eye symptoms
6 RCTs,
n = 412
Moderate
Decreases use of asthma plus
rhinoconjunctivitis
medications
There are no consistent
differences between SCIT and
SLIT
5 RCTs,
n = 219
Low
Improves asthma plus
rhinitis/rhinoconjunctivitis
symptom and medication
score
SCIT is favored in 1 of 2
studies 2 RCTs,
n = 65
Low
Subcutaneous Versus Sublingual Immunotherapy:
All Outcomes
RCT = randomized controlled trial; SCIT = subcutaneous immunotherapy; SLIT = sublingual
immunotherapy

Thirteen studies on subcutaneous immunotherapy included
920 pediatric patients.
The pediatric population ranged in age from 3 to 18 years.
Primary diagnoses included:
 Asthma in 7 studies
 Asthma with rhinitis in 3 studies
 Asthma with rhinoconjunctivitis in 2 studies
 Rhinoconjunctivitis in 1 study
All studies allowed either conventional pharmacotherapy or
rescue allergy medications during the study.
Standard therapy varied across studies.
Due to heterogeneity in reported clinical outcomes, results
often only reflect the percentage of trials in which a
significant effect was seen for the immunotherapy arm versus
controls and not the magnitude of effect.
Included Studies for SCIT Versus Placebo or
Standard Therapy in the Pediatric Population

Primary Outcome
Results
No. of RCTs,
No. of Patients (n)
Strength of
Evidence
Asthma symptom
score
Significant
improvement in
50% of studies vs.
controls
6 RCTs,
n = 550
Moderate
Use of asthma
medications
Significant
reduction in 50%
of studies
4 RCTs,
n = 470
Low
Pediatric Patients—SCIT Versus Placebo or

No. of RCTs,
No. of Patients (n)
Strength of
Evidence
Rhinitis/
rhinoconjunctivitis
symptoms
placebo
3 RCTs,
n = 285
Moderate
Conjunctivitis
symptoms
placebo
3 RCTs,
n = 285
Low
Disease-specific
quality of life in
patients with rhinitis/
rhinoconjunctivitis
in both studies vs.
controls 2 RCTs,
n = 350
Low
Pediatric Patients—SCIT Versus Placebo or Standard
Therapy: Rhinitis/Rhinoconjunctivitis Outcomes
RCT = randomized controlled trial ; SCIT = subcutaneous immunotherapy

No. of RCTs,
No. of Patients (n)
Strength
of Evidence
Use of asthma plus
rhinoconjunctivitis
medications
Decreased in
both studies vs.
controls
2 RCTs,
n = 80
Low
Improves combined
asthma or asthma
plus rhinitis/
rhinoconjunctivitis
symptom and
medication score
Significant
improvement in
both studies vs.
placebo
2 RCTs,
n = 85
Low
Pediatric Patients—SCIT Versus Placebo or Standard Therapy:

 18 studies including 1,583 pediatric patients (≤ 18 years of age)
 Primary diagnoses:
 Asthma (n = 3 studies)
 Rhinitis (n = 2 studies)
 Rhinoconjunctivitis (n = 4 studies)
 Asthma and rhinitis (n = 4 studies)
 Asthma with rhinoconjunctivitis (n = 5 studies)
 Perennial and/or seasonal allergies were included
 Comparator groups included:
 Placebo (n = 15 studies)
 Sublingual immunotherapy (SLIT) comparator group (n = 3 studies)
 Pharmacotherapy/symptomatic therapy (n = 2 studies)
 Due to heterogeneity in reported clinical outcomes, results often only
reflect the percentage of trials in which a significant effect was seen for
the immunotherapy arm versus controls and not the magnitude of effect.
Included Studies for SLIT Versus Placebo or
Standard Therapy in the Pediatric Population

Primary
Outcome Results
No. of RCTs,
No. of Patients (n)
Strength of
Evidence
Asthma
symptom score
Significant
improvement in
all studies vs.
controls
9 RCTs,
n = 471
High
Pediatric Patients—SLIT Versus Placebo or
RCT = randomized controlled trial; SLIT = sublingual immunotherapy

No. of RCTs,
No. of Patients (n)
Strength of
Evidence
Rhinitis/
rhinoconjunctivitis
symptoms
Significant
improvement in
42% of studies vs.
controls
12 RCTs,
n = 1,065
Moderate
Conjunctivitis
symptoms
Significant
improvement in
40% of studies vs.
placebo
5 RCTs,
n = 513
Moderate
Pediatric Patients—SLIT Versus Placebo or Standard
Therapy: Rhinitis/Rhinoconjunctivitis Outcomes

No. of RCTs,
No. of Patients (n)
Strength
of Evidence
rhinoconjunctivitis
symptoms
Significant
improvement with
high- and low-dose
SLIT vs. placebo
1 RCT,
n = 98
Moderate
Use of asthma plus
rhinoconjunctivitis
medications
Significantly reduced in
42% of studies vs.
controls
13 RCTs,
n = 1,078
Moderate
rhinoconjunctivitis
symptom and
medication score
Significant
improvement in 50% of
2 RCTs,
n = 329
Low
Pediatric Patients—SLIT Versus Placebo or Standard
Therapy: Asthma Plus Rhinitis/Rhinoconjunctivitis Outcomes

No. of RCTs,
No. of Patients (n)
Strength of
Evidence
Improves asthma symptom
score
SCIT is favored in 67% of
studies vs. SLIT
3 RCTs,
n = 135
Low
Improves asthma plus
rhinitis/ rhinoconjunctivitis
symptoms
SCIT may be favored over
SLIT for reducing nasal
and/or eye symptoms
3 RCTs,
n = 135
Low
Decreases use of asthma
plus rhinoconjunctivitis
medications
SLIT may decrease
medication use more than
SCIT, but results are
inconsistent
3 RCTs,
n = 135
Low
Pediatric Patients—SCIT Versus SLIT:
All Outcomes
RCT = randomized controlled trial; SCIT = subcutaneous immunotherapy; SLIT = sublingual
immunotherapy

Misdiagnosis and mistreatment can be dangerous
Even deadly
But it doesn’t have to be
And it shouldn’t be
Patient selection

Potential risks
• Misinterpretation of test
results
• Over-diagnosis
• Mismanagement
• Over-prescription of
medications and
treatments
• Costly and unnecessary
allergen avoidance

General approach
• Perform allergy testing
• Identify source of suffering
• Diagnose condition
• Treat more than just symptoms
• Develop plan that eliminates symptoms
• Provide most cost-effective care and outcomes

The approach:
• Evaluation
• Medical history
• Physical exam
• Testing (allergy and breathing)
• Prevention education and management plans
• Environmental pollutant and allergens
• Self-management and trigger avoidance
• Partnerships with other health care providers and
caregivers
• Treatment, including allergy shots
(immunotherapy)

Immunotherapy (Allergy
Shots):
Alters progression of disease
Cures patients of symptoms
Prevents asthma and
development of other allergies

The benefits and adverse effects of subcutaneous (SCIT) or
sublingual (SLIT) immunotherapy for them or their child
Any comorbid conditions that they or their child may have
that would affect their ability to take SCIT or SLIT
Other prescription or over-the-counter medications they are
taking during SCIT or SLIT treatment
What adverse effects to look for and when to call their doctor
How often they should be taking SCIT or SLIT
How long they can expect to take SCIT or SLIT
The costs of SCIT and SLIT
Shared Decisionmaking:
What To Discuss With Your Patients

The result:
Greater satisfaction with care
Improved quality of life
Better outcomes
Lower costs

Local reactions (such as redness, swelling, pruritus, or
induration at the injection site) were usually mild and
occurred in 5 to 58 percent of patients and 0.6 to 54
percent of injections and were more common than
systemic reactions.
The most common systemic reactions were respiratory
reactions, occurring in up to 46 percent of patients and in
up to 3 percent of injections.
General symptoms (such as headache, fatigue, and
arthritis) occurred in up to 44 percent of patients and were
usually mild or unspecified.
Gastrointestinal reactions were reported in only one study.
Thirteen anaphylactic reactions were reported in four trials.
No deaths were reported in the included studies.
Adverse Effects:
Subcutaneous Immunotherapy in Adults

Local reactions (such as irritation, itching, swelling, or pain in
the oral cavity) were common and usually mild and occurred
in 0.2 to 97 percent of patients receiving sublingual
immunotherapy (SLIT).
Systemic reactions occurred more frequently in the SLIT arm
versus controls and included ocular, rhinitis/nasal,
respiratory/asthma, cutaneous, gastrointestinal, and
cardiovascular adverse effects.
No life-threatening reactions, anaphylaxis, or deaths were
reported in the included trials.
SLIT studies mainly include patients with allergic rhinitis
and/or mild asthma. Safety outcomes should not be
extrapolated to more severely affected patients.
Adverse Effects:
Sublingual Immunotherapy in Adults

The recording and reporting of the adverse events was
neither uniform nor comparable across studies.
Local reactions were common and were all of mild or
moderate severity.
There was one report of anaphylaxis with subcutaneous
immunotherapy.
There were no reported deaths in the included studies.
Adverse Effects: Subcutaneous Versus Sublingual
Immunotherapy in Adults

Local reactions were the most common adverse reactions
in the pediatric population receiving subcutaneous
immunotherapy.
There were no reports of anaphylaxis or deaths.
Adverse Effects: Subcutaneous Immunotherapy in
Pediatric Patients

Local reactions (such as irritation, itching, swelling, or pain
in the oral cavity) were common but mild.
No life-threatening reactions, anaphylaxis, or deaths were
reported in these trials.
The strength of evidence for all other adverse effects is
insufficient.
Adverse Effects: Sublingual Immunotherapy in
Pediatric Patients

Local reactions were reported in both patient groups.
No systemic reactions were reported in patients
receiving sublingual immunotherapy.
In the pediatric population taking subcutaneous
immunotherapy, one anaphylaxis event and three
respiratory systemic reactions were reported.
Adverse Effects: Subcutaneous Versus Sublingual
Immunotherapy in Pediatric Patients

There is sufficient evidence to support the overall
effectiveness and safety of both subcutaneous
immunotherapy (SCIT) and sublingual immunotherapy
(SLIT) for treating allergic rhinoconjunctivitis and asthma.
However, there is not enough evidence to determine if
either SCIT or SLIT is superior.
SCIT and SLIT are usually safe, although local reactions
are commonly reported regardless of the mode of delivery.
Overview of Conclusions (1 of 2)

Serious, life-threatening reactions are rare, although they
can occur.
 Studies of sublingual immunotherapy (SLIT) mainly include
patients with allergic rhinitis and/or mild asthma.
 Safety outcomes should not be extrapolated to more severely
affected patients.
Most of the studies in the review used a single allergen for
immunotherapy, and it may be difficult to extrapolate these
results to the use of multiple-allergen regimens, which are
commonly used in clinical practice in the United States.
Due to the wide variety of reported regimens, the target
SLIT maintenance dose and duration of therapy are
unclear.
Overview of Conclusions (2 of 2)

Additional studies are needed on:
 The efficacy and safety of multiple-allergen subcutaneous (SCIT) and
sublingual (SLIT) immunotherapy
 The effectiveness of single-allergen versus multiple-allergen SCIT and
SLIT for desensitization
 The efficacy and safety of SCIT and SLIT in specific subpopulations
(pregnant women, monosensitized vs. polysensitized patients,
patients with severe asthma, and urban vs. rural patients)
 Whether or not SCIT and SLIT can prevent or modify the atopic march
in pediatric patients at high risk for allergic rhinitis and asthma, as
well as the optimal age to initiate therapy
 Determining the target maintenance dose, dosing strategies, and the
necessary durations of treatment for SCIT and SLIT
 Direct comparisons of SCIT to SLIT in pediatric and adult patients
 Optimizing allergen standardization for subcutaneous and sublingual
regimens
Gaps in Knowledge

Immunotherapy in asthma & allergy.pptx

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