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## Complete Summary

#### GUIDELINE TITLE

Allergic rhinitis and its impact on asthma.

#### BIBLIOGRAPHIC SOURCE(S)

Allergic rhinitis and its impact on asthma. Geneva (Switzerland): World
Health Organization (WHO); 2008. \[2241 references\]

#### GUIDELINE STATUS

This is the current release of the guideline.

This guideline updates a previous version: Allergic rhinitis and its
impact on asthma. J Allergy Clin Immunol 2001 Nov;108(5):S147-334.

### COMPLETE SUMMARY CONTENT

 SCOPE\
 METHODOLOGY - including Rating Scheme and Cost Analysis\
 RECOMMENDATIONS\
 EVIDENCE SUPPORTING THE RECOMMENDATIONS\
 BENEFITS/HARMS OF IMPLEMENTING THE GUIDELINE RECOMMENDATIONS\
 CONTRAINDICATIONS\
 QUALIFYING STATEMENTS\
 IMPLEMENTATION OF THE GUIDELINE\
 INSTITUTE OF MEDICINE (IOM) NATIONAL HEALTHCARE QUALITY REPORT
CATEGORIES\
 IDENTIFYING INFORMATION AND AVAILABILITY\
 DISCLAIMER

### SCOPE

#### DISEASE/CONDITION(S)

Allergic rhinitis and asthma

#### GUIDELINE CATEGORY

Assessment of Therapeutic Effectiveness\
Diagnosis\
Management\
Prevention\
Treatment

#### CLINICAL SPECIALTY

Allergy and Immunology\
Family Practice\
Infectious Diseases\
Internal Medicine\
Nursing\
Otolaryngology\
Pediatrics\
Preventive Medicine\
Pulmonary Medicine

#### INTENDED USERS

Advanced Practice Nurses\
Health Care Providers\
Health Plans\
Managed Care Organizations\
Nurses\
Physician Assistants\
Physicians

#### GUIDELINE OBJECTIVE(S)

-   To update clinicians\' knowledge of allergic rhinitis

-   To highlight the impact of allergic rhinitis on asthma

-   To provide an evidence-based documented revision on the diagnosis
    methods

-   To provide an evidence-based revision on the treatments available

-   To provide a stepwise approach to the management of the disease

#### TARGET POPULATION

Patients of all ages in all geographic locations who have allergic
rhinitis and asthma

#### INTERVENTIONS AND PRACTICES CONSIDERED

**Diagnosis**

1.  History and general ear, nose, and throat (ENT) examination

2.  Symptom assessment

3.  Skin tests (allergen specific immunoglobulin E \[IgE\])

4.  In vitro tests, including serum allergen-specific IgE

5.  Nasal challenge tests

6.  Diagnosis of inhalant allergy, food allergy, and occupational
    allergy

7.  Other ENT diagnosis and tests, as indicated

8.  Assessment of the severity and control of rhinitis

    -   Control questionnaires and visual analogue tests

    -   Objective measures of severity

**Management**

1.  Environmental control

2.  Drug treatment

    -   Second generation oral or intranasal H~1~-antihistamines

    -   Topical H~1~-antihistamines

    -   Intranasal glucocorticosteroids

    -   Montelukast

    -   Combination therapy with intranasal glucocorticosteroids

    -   Cromones

    -   Intranasal and oral decongestants

    -   Intranasal ipratropium

    -   Systemic glucocorticosteroids

3.  Allergen-specific immunotherapy (subcutaneous, sublingual,
    intranasal)

4.  Surgical treatment

5.  Treatment of allergic rhinitis and co-morbidities

6.  Preventive measures, including breastfeeding, avoidance of
    environmental tobacco smoke, and primary prevention of occupational
    airway disease

#### MAJOR OUTCOMES CONSIDERED

-   Sensitivity and specificity of diagnostic tests

-   Side effects of treatment

-   Response of symptoms (sneezing, rhinorrhea, nasal obstruction, nasal
    itch, eye symptoms) to treatment

-   Quality of life

-   Cost-effectiveness of treatments

### METHODOLOGY

#### METHODS USED TO COLLECT/SELECT EVIDENCE

Hand-searches of Published Literature (Primary Sources)\
Searches of Electronic Databases

#### DESCRIPTION OF METHODS USED TO COLLECT/SELECT THE EVIDENCE

**Identifying and Summarizing the Evidence**

The Grading of Recommendations Assessment, Development and Evaluation
(GRADE) approach to developing guidelines postulates that before grading
the quality of evidence and strength of each recommendation, guideline
developers should first identify a recently well-done systematic review
of the appropriate evidence answering the relevant clinical questions,
or conduct one when there is none available. This should be followed by
a transparent evidence summary, such as creation of GRADE evidence
profiles, on which to base judgments.

For the Allergic Rhinitis and its Impact on Asthma (ARIA) guideline 2008
update, this postulate is partially fulfilled. Members of the ARIA
guideline panel, including the GRADE representatives, performed
extensive literature searches addressing the clinical questions covered
by the guideline. In addition, they identified up-to-date valid
systematic reviews by searching the MEDLINE database, Cochrane Library,
and in selected cases also reference lists of the most recent narrative
views, related systematic reviews, or studies on the topic. They based
their judgments on these systematic reviews and, if applicable, on
additional randomized trials published afterwards. They developed GRADE
evidence profiles (see Figure 1 in the methodology document \[see the
\"Availability of Companion Documents\"\] field) based on the systematic
reviews. These concise evidence profiles allowed panel members to base
their judgments on the same and concisely summarized evidence.

When there was no recent systematic review available, the panel did not
perform its own systematic reviews, but followed a pragmatic approach
and searched MEDLINE, Cochrane Central Register of Controlled Trials
(CENTRAL), and Google Scholar for relevant randomized trials.

For many questions randomized trials were not available, and the panel
relied on available observational studies that were identified for a
prior ARIA guideline edition, its subsequent updates, or additional
non-structured searches for observational studies. Panel members
evaluated the original observational studies to inform judgments about
the quality of the underlying evidence. In such situations, they based
the judgments about the quality of evidence on a crude examination of
the most important studies.

#### NUMBER OF SOURCE DOCUMENTS

Not stated

#### METHODS USED TO ASSESS THE QUALITY AND STRENGTH OF THE EVIDENCE

Weighting According to a Rating Scheme (Scheme Given)

#### RATING SCHEME FOR THE STRENGTH OF THE EVIDENCE

See \"Rating Scheme for the Strength of the Recommendations.\"

#### METHODS USED TO ANALYZE THE EVIDENCE

Review of Published Meta-Analyses\
Systematic Review with Evidence Tables

#### DESCRIPTION OF THE METHODS USED TO ANALYZE THE EVIDENCE

Not stated

#### METHODS USED TO FORMULATE THE RECOMMENDATIONS

Expert Consensus

#### DESCRIPTION OF METHODS USED TO FORMULATE THE RECOMMENDATIONS

**Formulation of Recommendations**

Guidelines make a set of recommendations advising the clinicians,
patients, and other healthcare professionals which of the alternative
management strategies is likely to be most beneficial for patients.
Consequently, wording of the recommendations in the Allergic Rhinitis
and its Impact on Asthma (ARIA) guidelines update clearly states what is
the proposed course of action. In this document, the guideline panel
followed the Grading of Recommendations Assessment, Development and
Evaluation (GRADE) working group\'s advice to use the phrase \"we
recommend\" for strong recommendations and a less definitive \"we
suggest\" for weak recommendations. Wording of strong and weak
recommendations was particularly important since the ARIA guidelines are
intended for patients and clinicians in different regions, cultures,
traditions, and usage of language. When appropriate, recommendations are
supplemented with an explanatory statement of values and preferences
that the members of the guideline panel considered in formulating the
recommendation and determining its strength. Further remarks
occasionally follow, when the panel thought that additional statements
are justified (such as dosing), but are not recommended actions per se.

**Panel Meeting**

Based on the available evidence, the estimates of effect and their
gradients, assumed values and preferences, and resource utilization
issues, members of the ARIA guideline panel made decisions regarding the
strength of each recommendation. To achieve this, guideline panel held a
1-day meeting on June 20^th^, 2007, under the auspices of Agenzia
ltaliana del Farmaco (AIFA) in Rome, Italy, which included 6 members of
ARIA and 2 members of AIFA, to discuss the procedures and to draft
recommendations. After having agreed on the procedures and additional
work that needed to be done, a second meeting was arranged to discuss
the final recommendations based on a second draft of the updated
guidelines. During this subsequent meeting on 15 September 2007 in
Stockholm, Sweden, members of the ARIA guideline panel reviewed these
judgments and made decisions on the quality of evidence, the balance of
benefits and downsides (harms, burden, and occasionally cost) of a
considered management strategy, and on the final strength of each
recommendation. Recommendations are based on a consensus of the panel.
For the formulation and discussion about the final recommendations, all
panel members were asked to consider their own and other conflicts
during the discussion and decision making as well as to abstain from
discussion and voting if necessary. Subsequent interaction and
discussion took place through email, but recommendations were not
changed after the final meeting except for minor wording changes or
correction of factual errors.

#### RATING SCHEME FOR THE STRENGTH OF THE RECOMMENDATIONS

  ----------------------------------------------------------------------------------
  **Notation**   **Strength of     **Clarity of  **Quality of     **Implications**
                 Recommendation    Balance       Supporting       
                 and Quality of    Between       Evidence**       
                 Evidence**        Desirable and                  
                                   Undesirable                    
                                   Effects**                      
  -------------- ----------------- ------------- ---------------- ------------------
  1A             Strong            Desirable     Consistent       Recommendation can
                 recommendation\   effects       evidence from    apply to most
                 \                 clearly       randomized       patients in most
                 High quality      outweigh      controlled       circumstances.\
                 evidence          undesirable   trials (RCTs) or \
                                   effects or    exceptionally    Further research
                                   vice versa    strong evidence  is unlikely to
                                                 from unbiased    change the
                                                 observational    confidence of the
                                                 studies          estimate of effect

  1B             Strong            Desirable     Evidence from    Recommendation can
                 recommendation\   effects       RCTs with        apply to most
                 \                 clearly       important        patients in most
                 Moderate quality  outweigh      limitations      circumstances.\
                 evidence          undesirable   (inconsistent    \
                                   effects or    results,         Further research
                                   vice versa    methodological   (if performed) is
                                                 flaws, indirect  likely to have an
                                                 or imprecise) or important impact
                                                 unusually strong on the confidence
                                                 evidence from    in the estimate of
                                                 unbiased         effect and may
                                                 observational    change the
                                                 studies          estimate.

  1C             Strong            Desirable     Evidence for at  Recommendation may
                 recommendation\   effects       least one        change when higher
                 \                 clearly       critical outcome quality evidence
                 Low quality       outweigh      from RCTs with   becomes
                 evidence          undesirable   serious flaws,   available.\
                                   effects or    observational    \
                                   vice versa    studies or       Further research
                                                 indirect         (if performed) is
                                                 evidence         likely to have an
                                                                  important impact
                                                                  on the confidence
                                                                  in the estimate of
                                                                  effect and is
                                                                  likely to change
                                                                  the estimate.

  1D             Strong            Desirable     Evidence for at  Recommendation may
                 recommendation\   effects       least one of the change when higher
                 \                 clearly       critical         quality evidence
                 Very low quality  outweigh      outcomes from    becomes
                 evidence (very    undesirable   unsystematic     available.\
                 rarely            effects or    clinical         \
                 applicable)       vice versa    observation or   Any estimate of
                                                 very indirect    the effect for at
                                                 evidence         least one critical
                                                                  outcome is very
                                                                  uncertain.

  2A             Weak              Desirable     Consistent       The best action
                 recommendation\   effects       evidence from    may differ
                 \                 closely       well performed   depending on
                 High quality      balance with  RCTs or          circumstances or
                 evidence          undesirable   exceptionally    patients\' or
                                   effects       strong evidence  societal views.\
                                                 from unbiased    \
                                                 observational    Further research
                                                 studies          is very unlikely
                                                                  to change the
                                                                  confidence in the
                                                                  estimate of
                                                                  effect.

  2B             Weak              Desirable     Evidence from    Alternative
                 recommendation\   effects       RCTs with        approach is likely
                 \                 closely       important        to be better for
                 Moderate quality  balance with  limitations      some patients
                 evidence          undesirable   (inconsistent    under some
                                   effects       results,         circumstances.\
                                                 methodological   \
                                                 flaws, indirect  Further research
                                                 or imprecise) or (if performed) is
                                                 unusually strong likely to have an
                                                 evidence from    important impact
                                                 unbiased         on the confidence
                                                 observational    of the estimate of
                                                 studies          effect and may
                                                                  change the
                                                                  estimate.

  2C             Weak              Uncertainty   Evidence for at  Other alternatives
                 recommendation\   in the        least one        may be equally
                 \                 estimates of  critical outcome reasonable.\
                 Low quality       desirable and from RCTs with   \
                 evidence          undesirable   serious flaws,   Further research
                                   effects;      observational    is very likely to
                                   desirable     studies, or      have important
                                   effects may   indirect         impact on the
                                   be closely    evidence         confidence in the
                                   balanced with                  estimate of effect
                                   undesirable                    and is likely to
                                   effects                        change the
                                                                  estimate.

  2D             Weak              Major         Evidence for at  Other alternatives
                 recommendation\   uncertainty   least one        may be equally
                 \                 in the        critical outcome reasonable.\
                 Very low quality  estimates of  from             \
                 evidence          desirable and unsystematic     Any estimate of
                                   undesirable   clinical         the effect for at
                                   effects;      observation or   least one critical
                                   desirable     very indirect    outcome is very
                                   effects may   evidence         uncertain.
                                   be closely                     
                                   balanced with                  
                                   undesirable                    
                                   effects                        
  ----------------------------------------------------------------------------------

#### COST ANALYSIS

The panel could have considered cost or resource expenditure as one of
the outcomes when weighing up desirable (less resource expenditure) and
undesirable (more resource expenditure) consequences of competing
interventions for each recommendation. Resource expenditure, however, is
much more variable over jurisdictions, time, and availability of the
over-the-counter medications. In addition, the resource implications
also vary widely. Thus, while higher costs will reduce the likelihood of
a strong recommendation in favour of a particular intervention, the
context of the recommendation can be critical. In considering resource
allocation issues, guideline panels must thus be very specific about the
setting to which a recommendation applies and the perspective that they
had chosen, i.e., which costs were considered and whether resource
expenditure was considered from the perspective of the patient
(depending on insurance status, these costs differ) or society within a
given health care system (this includes indirect or opportunity cost
saved or incurred by following a recommendation). Furthermore,
recommendations that are heavily influenced by costs are likely to
change over time as resource implications evolve. The Allergic Rhinitis
and its Impact on Asthma (ARIA) guideline panel considered cost
implicitly and not in detail, mostly because ARIA guidelines are
intended for users around the world and drug costs are highly variable
between different regions. However, when resource utilization was likely
to play a role and influenced a recommendation, this was labeled in the
values and preferences section in the original guideline document.

#### METHOD OF GUIDELINE VALIDATION

Peer Review

#### DESCRIPTION OF METHOD OF GUIDELINE VALIDATION

Not stated

### RECOMMENDATIONS

#### MAJOR RECOMMENDATIONS

**Summary of Major Recommendations**

1.  Allergic rhinitis is a major chronic respiratory disease due to its:

    -   Prevalence

    -   Impact on quality of life

    -   Impact on work/school performance and productivity

    -   Economic burden

    -   Links with asthma

2.  In addition, allergic rhinitis is associated with sinusitis and
    other co-morbidities such as conjunctivitis.

3.  Allergic rhinitis should be considered as a risk factor for asthma
    along with other known risk factors.

4.  A new subdivision of allergic rhinitis has been proposed:

    -   Intermittent (IAR)

    -   Persistent (PER)

5.  The severity of allergic rhinitis has been classified as \"mild\'
    and \"moderate/severe\" depending on the severity of symptoms and
    quality-of-life outcomes.

6.  Depending on the subdivision and severity of allergic rhinitis, a
    stepwise therapeutic approach has been proposed.

7.  The treatment of allergic rhinitis combines:

    -   Allergen avoidance (when possible)

    -   Pharmacotherapy

    -   Immunotherapy

    -   Education

8.  Patients with persistent allergic rhinitis should be evaluated for
    asthma by means of a medical history, chest examination and, if
    possible and when necessary, the assessment of airflow obstruction
    before and after bronchodilator.

9.  Patients with asthma should be appropriately evaluated (history and
    physical examination) for rhinitis.

10. Ideally, a combined strategy should be used to treat the upper and
    lower airway diseases in terms of efficacy and safety.

**Specific Recommendations**

**Diagnosis**

*Diagnosis of Allergic Rhinitis*

-   The diagnosis of allergic rhinitis is based upon the coordination
    between a typical history of allergic symptoms and diagnostic tests.

-   Typical symptoms of allergic rhinitis include rhinorrhea, sneezing,
    nasal obstruction, and nasal pruritus.

-   Ocular symptoms are common, in particular in patients allergic to
    outdoor allergens.

-   Diagnostic tests are based on the demonstration of allergen-specific
    immunoglobulin E (IgE) in the skin (skin tests) or the blood
    (specific IgE).

-   The measurement of total IgE is not useful in the diagnosis of
    allergic rhinitis.

-   Many asymptomatic subjects can have positive skin tests and/or
    detectable serum-specific IgE.

-   Many patients have positive tests which are irrelevant.

-   In some countries, the suspicion of allergic rhinitis may be raised
    in the pharmacy.

-   Patients with persistent and/or moderate/severe symptoms of rhinitis
    should be referred to a physician.

-   Most patients with rhinitis are seen in primary care and, in
    developed countries, allergy tests are available to screen for
    allergy.

-   Patients with persistent and/or moderate/severe symptoms of rhinitis
    need a detailed allergy diagnosis.

**Management**

*Environmental Control*

[Tertiary Environmental Control]{.underline}

-   The vast majority of single preventive measures of indoor allergen
    control have failed to achieve any clinically relevant improvement
    of asthma and rhinitis. Tertiary prevention of indoor allergens is
    not a public health measure.

-   In patients allergic to furred pets who have symptoms on contact
    with the allergen, pet avoidance is recommended.

-   In low-income settings with a high load of pollutants (and
    allergens), a multifaceted intervention may be useful.

-   Total avoidance of occupational agents is recommended in sensitized
    subjects.

-   Occupational agent control may be useful when total avoidance is not
    possible.

*Drug Treatment*

[Pharmacotherapy of Allergic Rhinitis and Conjunctivitis]{.underline}

-   Second-generation oral or intranasal H~1~-antihistamines are
    recommended for the treatment of allergic rhinitis and
    conjunctivitis in adults and children.

-   First-generation oral H~1~-antihistamines are not recommended when
    second-generation ones are available due to safety concerns.

-   Topical H~1~-antihistamines are recommended for the treatment of
    allergic rhinitis and conjunctivitis.

-   Intranasal glucocorticosteroids are recommended for the treatment of
    allergic rhinitis in adults and children. They are the most
    effective drugs for the treatment of allergic rhinitis.

-   Intra-muscular glucocorticosteroids and long-term use of oral
    glucocorticosteroids are not recommended due to safety concern.

-   Topical cromones are recommended in the treatment of allergic
    rhinitis and conjunctivitis, but they are only modestly effective.

-   Montelukast is recommended in the treatment of seasonal allergic
    rhinitis in patients over 6 years of age.

-   Intranasal ipratropium is recommended in the treatment of rhinorrhea
    associated with allergic rhinitis.

-   Intranasal decongestants may be used for a short period of time in
    patients with severe nasal obstruction.

-   Oral decongestants (and their associations) may be used in the
    treatment of allergic rhinitis in adults, but side effects are
    common.

-   The treatment of allergic rhinitis should consider the severity and
    duration of the disease, the patient\'s preference, as well as the
    efficacy, availability, and costs of drugs.

-   A stepwise approach depending on the severity and duration of
    rhinitis is proposed.

-   A tailored approach is needed for each individual patient.

-   Not all patients with moderate/severe allergic rhinitis are
    controlled despite optimal pharmacotherapy.

*Allergen-Specific Immunotherapy: Therapeutic Vaccines for Allergic
Disease*

[Specific Immunotherapy]{.underline}

-   Allergen-specific immunotherapy is classically administered by
    subcutaneous route but local routes are now available.

-   Specific immunotherapy needs a precise diagnosis of IgE-mediated
    allergy.

-   Subcutaneous immunotherapy is effective in adults and children for
    pollen and mite allergy, but it is burdened by the risks of side
    effects. These reactions may be exceptionally life-threatening.

-   Sublingual immunotherapy is recommended for the treatment of pollen
    allergy in adults.

-   Sublingual immunotherapy may be used for the treatment of patients
    with mite allergy.

-   Intranasal immunotherapy may be used for the treatment of patients
    with pollen allergy.

-   Allergen-specific immunotherapy may alter the natural course of
    allergic diseases.

-   Subcutaneous immunotherapy appears to be effective several years
    after its cessation.

-   Immunotherapy appears to reduce the development of new
    sensitizations.

-   Administered to patients with rhinitis, subcutaneous immunotherapy
    appears to reduce the development of asthma.

[Classifications of Systemic Reactions Induced by
Immunotherapy]{.underline}

I.  **No symptoms or non-immunotherapy related symptoms**

II. **Mild systemic reactions**

> *Symptoms*: Localized urticaria, rhinitis or mild asthma (Peak flow
> \[PF\] \<20% decrease from baseline)

III. **Moderate systemic reactions**

> *Symptoms*: Slow onset (\>15 min) of generalized urticaria and/or
> moderate asthma (PF \<40% decrease from baseline)

IV. **Severe (non-life-threatening) systemic reactions**

> *Symptoms*: Rapid onset (\<15 min) of generalized urticaria,
> angioedema, or severe asthma (PF \>40% decrease from baseline)

V.  **Anaphylactic shock**

> *Symptoms*: Immediate evoked reaction of itching, flushing, erythema,
> generalized urticaria, stridor (angioedema), immediate asthma,
> hypotension, etc.

[Considerations for Initiating Immunotherapy]{.underline}

1.  Presence of a demonstrated IgE-mediated disease:

    -   Positive skin tests and/or serum-specific IgE

2.  Documentation that specific sensitivity is involved in symptoms:

    -   Exposure to the allergen(s) determined by allergy testing
        related to appearance of symptoms

    -   If required allergen challenge with the relevant allergen(s)

3.  Characterization of other triggers that may be involved in symptoms

4.  Severity and duration of symptoms:

    -   Subjective symptoms

    -   Objective parameters, e.g., work loss, school absenteeism

    -   Pulmonary function (essential in asthmatics): exclude patients
        with severe asthma

    -   Monitoring of the pulmonary function by peak flow

5.  Response of symptoms to pharmacotherapy

6.  Availability of standardized or high-quality vaccines

7.  Contraindications:

    -   Treatment with beta-blockers

    -   Other immunologic disease

    -   Inability of patients to comply

    -   Starting immunotherapy with inhalant allergens during known
        pregnancy

8.  Sociologic factors:

    -   Cost

    -   Occupation of candidate

9.  Objective evidence of efficacy of immunotherapy for the selected
    patient (availability of randomized controlled studies)

[Indications for Subcutaneous Immunotherapy]{.underline}

-   Patients with symptoms induced predominantly by allergen exposure

-   Patients with clinical symptoms due to a single or few allergens

-   Patients with a prolonged season or with symptoms induced by
    succeeding pollen seasons

-   Patients with rhinitis and symptoms from the lower airways during
    peak allergen exposure

-   Patients in whom antihistamines and moderate dose topical
    glucocorticoids insufficiently control symptoms

-   Patients who do not want to be on constant or long-term
    pharmacotherapy

-   Patients in whom pharmacotherapy induces undesirable side effects

[Indications for Sublingual Immunotherapy]{.underline}

High-dose sublingual-swallow specific immunotherapy may be indicated in
the following cases:

-   Carefully selected patients with rhinitis, conjunctivitis, and/or
    asthma caused by pollen and mite allergy

-   Patients insufficiently controlled by conventional pharmacotherapy

-   Patients who have presented with systemic reactions during
    injection-specific immunotherapy

-   Patients showing poor compliance with or refusing injections

*Complementary and Alternative Medicine*

-   Many patients who use complementary and alternative medicine appear
    to be satisfied.

-   Evidence-based recommendations are difficult to propose for most
    complementary and alternative medicine interventions due to
    methodological problems.

-   Butterbur was found to be effective in the treatment of allergic
    rhinitis, but more data are needed.

-   Safety of phytotherapy raises concerns.

**Health Promotion and Prevention**

*Primary and Secondary prevention*

-   Breastfeeding is recommended irrespective of the atopic background
    of the infant.

-   Current dietary manipulations of maternal and infant feeding do not
    have a preventive role for atopic diseases and are not recommended.

-   Environmental tobacco smoke should be avoided in pregnant women and
    children although more data are needed.

-   Conflicting data exist concerning early-life exposure to pets and
    the development atopy. No general recommendation can be made.

-   House dust mite avoidance in infancy has inconsistent effect on the
    development allergy or asthma and cannot be recommended.

-   Primary prevention of occupational airway disease is recommended.

-   Secondary prevention of asthma is still a matter of debate and more
    data are needed.

**Links between Rhinitis and Asthma**

See the original guideline document for epidemiologic links between
rhinitis and asthma, commonalities and differences in their mechanisms,
and the effect of rhinitis and asthma on quality of life (QOL).

*Therapeutic Consequences*

[Treatment of Rhinitis and Asthma Using a Single Approach]{.underline}

-   Oral H~1~-antihistamines are not recommended in the treatment of
    asthma.

-   Intranasal glucocorticosteroids are inconstantly and at best
    moderately effective in asthma.

-   Intranasal glucocorticosteroids may be effective in reducing asthma
    exacerbations and hospitalizations.

-   The role of intra-bronchial glucocorticosteroids in rhinitis is
    unknown.

-   Montelukast is effective in the treatment of allergic rhinitis and
    asthma in patients over 6 years of age.

-   Subcutaneous immunotherapy is recommended in both rhinitis and
    asthma in adults, but it is burdened by side effects, in particular
    asthmatics.

-   Anti-IgE monoclonal antibody is effective and safe in both rhinitis
    and asthma.

See the original guideline document for a discussion of other
co-morbidities and complications and rhinitis in children.

**Definitions**:

  ----------------------------------------------------------------------------------
  **Notation**   **Strength of     **Clarity of  **Quality of     **Implications**
                 Recommendation    Balance       Supporting       
                 and Quality of    Between       Evidence**       
                 Evidence**        Desirable and                  
                                   Undesirable                    
                                   Effects**                      
  -------------- ----------------- ------------- ---------------- ------------------
  1A             Strong            Desirable     Consistent       Recommendation can
                 recommendation\   effects       evidence from    apply to most
                 \                 clearly       randomized       patients in most
                 High quality      outweigh      controlled       circumstances.\
                 evidence          undesirable   trials (RCTs) or \
                                   effects or    exceptionally    Further research
                                   vice versa    strong evidence  is unlikely to
                                                 from unbiased    change the
                                                 observational    confidence of the
                                                 studies          estimate of effect

  1B             Strong            Desirable     Evidence from    Recommendation can
                 recommendation\   effects       RCTs with        apply to most
                 \                 clearly       important        patients in most
                 Moderate quality  outweigh      limitations      circumstances.\
                 evidence          undesirable   (inconsistent    \
                                   effects or    results,         Further research
                                   vice versa    methodological   (if performed) is
                                                 flaws, indirect  likely to have an
                                                 or imprecise) or important impact
                                                 unusually strong on the confidence
                                                 evidence from    in the estimate of
                                                 unbiased         effect and may
                                                 observational    change the
                                                 studies          estimate.

  1C             Strong            Desirable     Evidence for at  Recommendation may
                 recommendation\   effects       least one        change when higher
                 \                 clearly       critical outcome quality evidence
                 Low quality       outweigh      from RCTs with   becomes
                 evidence          undesirable   serious flaws,   available.\
                                   effects or    observational    \
                                   vice versa    studies or       Further research
                                                 indirect         (if performed) is
                                                 evidence         likely to have an
                                                                  important impact
                                                                  on the confidence
                                                                  in the estimate of
                                                                  effect and is
                                                                  likely to change
                                                                  the estimate.

  1D             Strong            Desirable     Evidence for at  Recommendation may
                 recommendation\   effects       least one of the change when higher
                 \                 clearly       critical         quality evidence
                 Very low quality  outweigh      outcomes from    becomes
                 evidence (very    undesirable   unsystematic     available.\
                 rarely            effects or    clinical         \
                 applicable)       vice versa    observation or   Any estimate of
                                                 very indirect    the effect for at
                                                 evidence         least one critical
                                                                  outcome is very
                                                                  uncertain.

  2A             Weak              Desirable     Consistent       The best action
                 recommendation\   effects       evidence from    may differ
                 \                 closely       well performed   depending on
                 High quality      balance with  RCTs or          circumstances or
                 evidence          undesirable   exceptionally    patients\' or
                                   effects       strong evidence  societal views.\
                                                 from unbiased    \
                                                 observational    Further research
                                                 studies          is very unlikely
                                                                  to change the
                                                                  confidence in the
                                                                  estimate of
                                                                  effect.

  2B             Weak              Desirable     Evidence from    Alternative
                 recommendation\   effects       RCTs with        approach is likely
                 \                 closely       important        to be better for
                 Moderate quality  balance with  limitations      some patients
                 evidence          undesirable   (inconsistent    under some
                                   effects       results,         circumstances.\
                                                 methodological   \
                                                 flaws, indirect  Further research
                                                 or imprecise) or (if performed) is
                                                 unusually strong likely to have an
                                                 evidence from    important impact
                                                 unbiased         on the confidence
                                                 observational    of the estimate of
                                                 studies          effect and may
                                                                  change the
                                                                  estimate.

  2C             Weak              Uncertainty   Evidence for at  Other alternatives
                 recommendation\   in the        least one        may be equally
                 \                 estimates of  critical outcome reasonable.\
                 Low quality       desirable and from RCTs with   \
                 evidence          undesirable   serious flaws,   Further research
                                   effects;      observational    is very likely to
                                   desirable     studies, or      have important
                                   effects may   indirect         impact on the
                                   be closely    evidence         confidence in the
                                   balanced with                  estimate of effect
                                   undesirable                    and is likely to
                                   effects                        change the
                                                                  estimate.

  2D             Weak              Major         Evidence for at  Other alternatives
                 recommendation\   uncertainty   least one        may be equally
                 \                 in the        critical outcome reasonable.\
                 Very low quality  estimates of  from             \
                 evidence          desirable and unsystematic     Any estimate of
                                   undesirable   clinical         the effect for at
                                   effects;      observation or   least one critical
                                   desirable     very indirect    outcome is very
                                   effects may   evidence         uncertain.
                                   be closely                     
                                   balanced with                  
                                   undesirable                    
                                   effects                        
  ----------------------------------------------------------------------------------

#### CLINICAL ALGORITHM(S)

Algorithms are provided in the original guideline document for the
following:

-   Diagnosis of allergic rhinitis

-   Rhinitis management

-   Management of allergic rhinitis in the pharmacy

### EVIDENCE SUPPORTING THE RECOMMENDATIONS

#### TYPE OF EVIDENCE SUPPORTING THE RECOMMENDATIONS

The type of evidence supporting the recommendations is not specifically
stated.

### BENEFITS/HARMS OF IMPLEMENTING THE GUIDELINE RECOMMENDATIONS

#### POTENTIAL BENEFITS

-   Improved diagnosis and cost-effective management of allergic
    rhinitis

-   Improved recognition that asthma and rhinitis are common
    co-morbidities

-   Improved respiratory function and quality of life for patient with
    allergic rhinitis and asthma

#### POTENTIAL HARMS

The side effects associated with medications

-   The safety of sublingual immunotherapy has been demonstrated in
    adults and children by several papers, Phase I trials and by
    post-marketing surveillance data Local side effects have been
    described in clinical trials. These include itching and swelling of
    the lips and under the tongue. These effects are more common in
    studies involving high dosage. In general, these effects are well
    tolerated, requiring no medication or dosage modifications, and
    often resolve with continued treatment.

See Table 17 in the original guideline document for information about
side effects associated with medications used in allergic rhinitis.

### CONTRAINDICATIONS

#### CONTRAINDICATIONS

Contraindications to immunotherapy include:

-   Treatment with beta-blockers

-   Other immunologic disease

-   Inability of patients to comply

-   Starting immunotherapy with inhalant allergens during known
    pregnancy

### QUALIFYING STATEMENTS

#### QUALIFYING STATEMENTS

-   The Allergic Rhinitis and its Impact on Asthma (ARIA) document was
    not intended to be a standard-of-care document for individual
    countries. It was provided as a basis for physicians, health care
    professionals and organizations involved in the treatment of
    allergic rhinitis and asthma in various countries to facilitate the
    development of relevant local standard-of-care documents for their
    patients.

-   Limitations of these guidelines include that the guideline
    developers did not consistently and explicitly define all the
    important outcomes that the panel should have considered for each
    recommendation and no formal decision on the relative importance of
    these outcomes. Secondly, there is a small possibility that the
    guideline developers missed studies, because they did not perform
    full systematic reviews (in particular reviews of observational
    studies) for all recommendations. Thirdly, the guideline developers
    did not search EMBASE and some trials are published in journals not
    referenced in MEDLINE. As a result, methodological evaluation of the
    available studies was not always as rigorous as the Grading of
    Recommendations Assessment, Development and Evaluation (GRADE)
    approach warrants. The primary reason for not conducting complete
    systematic reviews for each relevant question was the lack of time.
    However, due to the extensive knowledge of the ARIA panel of the
    published literature, it is thought all important studies have been
    discussed. Fourth, when the systematic reviews were not available,
    the guideline developers performed only few statistical pooling
    exercises of primary study results. Finally, sparse data on how
    patients value the outcomes and what are patient preferences for
    recommended interventions is an additional limitation inherent to
    most clinical practice guidelines.

### IMPLEMENTATION OF THE GUIDELINE

#### DESCRIPTION OF IMPLEMENTATION STRATEGY

An implementation strategy was not provided.

#### IMPLEMENTATION TOOLS

Clinical Algorithm\
Pocket Guide/Reference Cards\
Slide Presentation

For information about
[availability](#identifying-information-and-availability), see the
\"Availability of Companion Documents\" and \"Patient Resources\" fields
below.

### INSTITUTE OF MEDICINE (IOM) NATIONAL HEALTHCARE QUALITY REPORT CATEGORIES

#### IOM CARE NEED

Getting Better\
Living with Illness\
Staying Healthy

#### IOM DOMAIN

Effectiveness\
Patient-centeredness

### IDENTIFYING INFORMATION AND AVAILABILITY

#### BIBLIOGRAPHIC SOURCE(S)

Allergic rhinitis and its impact on asthma. Geneva (Switzerland): World
Health Organization (WHO); 2008. \[2241 references\]

#### ADAPTATION

Not applicable: The guideline was not adapted from another source.

#### DATE RELEASED

2001 Nov (revised 2008)

#### GUIDELINE DEVELOPER(S)

Allergic Rhinitis and its Impact on Asthma Workshop Group - Independent
Expert Panel

#### SOURCE(S) OF FUNDING

Supported through a grant from the American Academy of Allergy, Asthma,
and Immunology and Allergic Rhinitis and its Impact on Asthma (ARIA)

#### GUIDELINE COMMITTEE

Allergic Rhinitis and its Impact on Asthma (ARIA) Workshop Group

#### COMPOSITION OF GROUP THAT AUTHORED THE GUIDELINE

*Workshop Group Members*: Jean Bousquet; Nikolai Khaltaev; Alvaro Cruz;
Judah Denburg; Wytske Fokkens; Alkis Togias; Torsten Zuberbier; Carlos
Baena-Cagnani; G Walter Canonica; Chris van Weel; Nadia Aït-Khaled;
Michael Blaiss; Philippe-J Bousquet; Kai-Hakon Carlsen; Adnan Custovic;
Pascal Demoly; Stephen Durham; Roy Gerth van Wijk; Richard Lockey; Eli O
Meltzer; Joaquim Mullol; Robert Naclerio; Nikolaos Papadopoulos;
Giovanni Passalacqua; Glenis Scadding; F Estelle R Simons; Erkka
Valovirta; Claus Bachert; Sergio Bonini; Louis-Philippe Boulet; Paulo
Camargos; Yuzhi Chen; Ronald Dahl; Omer Kalayci; Michael Kaliner;
You-Young Kim; Marek Kowalski; Le Thi Tuyet Lan; Jing Li; Yousser
Mohammad; Robyn O\'Hehir; Ken Ohta; Susanna Palkonen; Ruby Pawankar;
Todor Popov; Klaus Rabe; José Rosado-Pinto; Elina Toskala; Paul van
Cauwenberge; De Yun Wang; Magnus Wickman; Barbara Yawn; Arzu
Yorgancioglu; Osman Yusuf; Heather Zar

#### FINANCIAL DISCLOSURES/CONFLICTS OF INTEREST

Not stated

#### GUIDELINE STATUS

This is the current release of the guideline.

This guideline updates a previous version: Allergic rhinitis and its
impact on asthma. J Allergy Clin Immunol 2001 Nov;108(5):S147-334.

#### GUIDELINE AVAILABILITY

Electronic copies of ARIA documents and resources available from the
[Allergic Rhinitis and its Impact on Asthma (ARIA) Web
site](http://www.whiar.org/).

#### AVAILABILITY OF COMPANION DOCUMENTS

The following are available:

-   Allergic Rhinitis and its Impact on Asthma (ARIA) At-A-Glance Pocket
    Reference. 2007. 6 p. Electronic copies available from the [ARIA Web
    site](http://www.whiar.org/).

-   ARIA Teaching Slides (Power Point Download). Electronic copies
    available from the [ARIA Web site](http://www.whiar.org/).

-   Brozek JL, Baena-Cagnani CE, Bonini S, Canonica GW, Rasi G, van Wijk
    RG, Zuberbier T, Guyatt G, Bousquet J, Schünemann HJ.Methodology for
    development of the Allergic Rhinitis and its Impact on Asthma
    guideline 2008 update. Allergy. 2008 Jan; 63(1):38-46. Electronic
    copies available to subscribers at the [*[Allergy]{.underline}*
    journal Web site](http://www.blackwell-synergy.com/toc/all/63/1).

#### PATIENT RESOURCES

None available

#### NGC STATUS

This summary was completed by ECRI on March 19, 2003. This NGC summary
was updated by ECRI Institute on April 24, 2008. The updated information
was verified by the guideline developer on June 27, 2008.

#### COPYRIGHT STATEMENT

The name and logo of ARIA are registered trademarks. Permission must be
granted by the ARIA Secretariat for the use of ARIA materials.

### DISCLAIMER

#### NGC DISCLAIMER

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approve, or endorse the guidelines represented on this site.

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contact the guideline developer.

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Date Modified: 11/3/2008