i ov 3 0 2001
`6 Jol.120 CU, i CAL .:i .,IE>:CE cc:NTER
`00 HIG\-IL~ 'O /i. E MADISON ~JI 53792
`
`

`

`Supplement to
`THE JOURNAL OF
`
`Allergy AND Clinical
`Immunology
`A\\¥1
`
`VOLUME 108
`
`NUMBER5
`
`A LLERGIC RHINITIS A ND ITS
`IMPACT ON ASTHMA
`
`ARIA WORKSHOP REPORT
`
`In collaboration with the
`World Health Organization
`
`Chair
`Jean Bousquet, MD, PhD
`
`Co-Chair
`Paul van Cauwenberge, MD, PhD
`
`WHO
`Nikolai Khaltaev, MD
`
`www.whiar.com
`
`WESTON LIBRARY
`NOV 3 0 2001
`J5/120 CLINICAL SCIENCt: CENTER
`600 HIGHLAND AVE MADISON WI 53792
`
`Supported through a grant from
`the American Academy of Allergy, Asthma, and Immunology
`and ARIA
`
`

`

`Supplement to
`THE JOURNAL OF
`
`AllergyAND Clinical
`Immunology
`
`VOLUME 108
`
`NUMBER5
`
`OFFICIAL JOURNAL OF THE AMERICAN ACADEMY OF ALLERGY, AsTHMA AND IMMUNOLOGY
`
`Recommendations ............................................... s 147
`Introduction .............................................................. s 148
`1- Classification ..................................................... S150
`1-1- Infectious rhinitis ........................................... S 150
`1-2- Allergic rhinitis ............................................... S150
`1-3- Occupational rhinitis ..................................... S150
`1-4- Drug-induced rhinitis .................................... S 151
`1-5- Hormonal rhinitis ........................................... S151
`1-6- Other causes ..................................................... S 151
`1-6-1- Nasal symptoms related to physical and
`chemical factors ..................................................... S 151
`1-6-2- Food-induced rhinitis ........................................ S 151
`1-6-3- Eosinophilic rhinitis .......................................... S 151
`1-6-4- Emotions ........................................................... S 151
`1-6-5- Atrophic rhinitis ................................................ S 151
`1-6-6- Gastroesophageal reflux ................................... S 152
`1-7- Unknown aetiology (idiopathic rhinitis)S152
`
`2- Epidemiology and genetics ................... S153
`2-1- Epidemiology of allergic rhinitis ............. S153
`2-1-1- Epidemiological definitions .............................. S 15 3
`2- 1-l • l - General definitions ........................................... S 15 3
`2· 1· 1-2- Definition of rhinitis ......................................... S 153
`2-1-2- Prevalence ............ ...................................... ....... S 15 3
`2-1-2·1- Monocentric studies ..... .................................... S153
`2·1·2·2· ISAAC ........................................................... S154
`2·1·2·3· ECRHS ........................................................... S155
`2·1•2·4- SAPALDIA ... .................................................. S 156
`2•1-2-5- SCARPOL ...................................................... S156
`2•1-3- Risk factors ................................................ ....... S157
`2-1·3· 1· Genetics and familial history ............................. S157
`2• l ·3·2· Early life risk factors ........................................ S 15 7
`
`2-1-3-3- Ethnic groups .................................................. Sl 57
`2-1-3·4· Sib•ship size and order and infections in the
`neonatal period .......................................................... S 15 7
`2·1-3•5• Allergen exposure ............................................ $ 157
`2·1-3·6- Rural•urban differences and modification of
`life style ................................................................... S 158
`2-1-3-7• Outdoor and indoor air pollution ........................ S158
`2·1·3• 7•1· Acute effects of outdoor air pollution ..................... S 15 8
`2· 1·3·7·2- Chronic effects of outdoor air pollution ..... .. ... .... ..... S 15 8
`2.1.3. 7.3. Chronic effects of indoor air pollution ... .... ... .... ..... . S 158
`2-1-3-7-4• Future studies .. ....... ...... ................... ............... S 158
`2-1-3·8• Active smoking ................................................ S 159
`2-1·3·9· Social class and occupation ............................... S159
`2- 1-4- Increase in prevalence of allergic rhinitis
`and putative factors ............................................. S159
`2-1-5- Natural history .................................................. S159
`2-1-6- Conclusion ....................................... ................. S 15 9
`2-2- The genetics of allergic rhinitis ................ S159
`2-2-1- Family segregation studies ............................... S159
`2-2-2· Twin studies ...................................................... S160
`2-2-3- Molecular studies .............................................. S160
`2•2-3-1- Candidate gene approach versus genome wide
`search .................................................. ................. S 160
`2-2-3-2- Candidate genes ............................................... S 161
`2·2·3· 2·1 · Genes associ31cd with the HLA system .. ................. S 161
`2·2·3· 2· 2- Genes non•associated with the HLA system ............. S 161
`2-2•4· Conclusion ........................................................ S 161
`
`3-Allergens and trigger factors .............. S162
`3-1- Allergens ............................................................ S162
`3· 1 • 1 · Nomenclature of allergens ................................ S 162
`3-1-2- Molecular characteristics and function of
`allergens .................................................................... S 162
`3-1-3- Inhalant allergens ..................................... ......... S 163
`3· 1· 3· 1· Mites ........ ................................................... S163
`3-1· 3· 1- l - House dust mites .................... ..... .. ............ .. . $ 163
`3· 1-3-1-2- Other dust mites .......... ...... ... ............. ........ .. . S 163
`
`~T~ Mosby Copyright© 2001 by Mosby, Inc.
`
`Continued on page JOA
`
`Statements and opinions expressed in the articles and communications herein are those of the author(s) and not necessarily those of the Editor, publisher, or
`the American Academy of Allergy, Asthma and Immunology. The Editor, publisher, and the American Academy of Allergy, Asthma and Immunology dis(cid:173)
`claim any responsibility or liability for such material and do not guarantee, warrant, or endorse any product or service advertised in this publication nor do
`they guarantee any claim made by the manufacturer of such product or service.
`
`J ALLERGY CUN IMMUNOL
`
`Novembe r 2001 9A
`
`

`

`CONTENTS
`
`CONTINUED
`
`3-1-3-2- Pollens ............................................................ S163
`3-1-3-3-Animal danders ............................................. ... S 164
`3·1-3-3-1- Cat and dog allergens ..•.... .....•..•... . .•. ..•... ...•...•... S 164
`3·1-3-3·2-Horsc . . ... .... •.•.•...•...•....••... .... . ... ....•...•..••. .••.•.. S 164
`3-1-3-3-3- Cattle •... ..•.•..•... .•.........•.•.•....... ..... ...... ....•...•• S 164
`3-1-3-J.4. Rabbit •.... ................••......••••...........•..•• ••.•..••• S 164
`3-1-3-3-5- Other rodents . ..............•....... ..••..••...•.••.••••••••..• S 164
`3-1-3-4- Fungal allergens ...........................•................... S 165
`3-1-3-5- Insects ............................................................ S 16 5
`3-1-3-6- Other inhalants ............................................•... S 165
`3-1-4- Food allergens ................................................... S 166
`3-1-5- Cross-reactive allergens between food and inhalant
`allergens ............................................................ S 16(;
`3-1-6- Occupational allergens ...................................... S166
`3-1-6-1- Latex .............................................................. S166
`3-1-6-2- Low molecular weight compounds ..................... S167
`3-1-6-3- Other occupational allergens .............................. S 167
`3-2- Pollutants ........................................................... S167
`3-2-1- Characteristics of air pollution ......................... S 167
`3-2-1-1- Evolution of outdoor air pollution ................... ... S 167
`3-2-1-2- Automobile pollution ........................................ S 167
`3-2-1-3- Characteristics of diesel emission ...................... .S 168
`3-2-1-4-Indoor air pollution ............ .............................. S168
`3-2-2- Pollutants of possible relevance in allergic
`rhinitis .............................................................. S 168
`3-2-2-1- Ozone ............................................................. S 168
`3-2-2-2- Sulphur dioxide (S02) ...................................... S 168
`3-2-2-3- Nitric dioxide (N02) ........................................ S 169
`3-2-2-4- Particulate matter (PM) ..................................... S 169
`3-2-2-5- Volatile organic compounds (VOC) and
`formaldehyde .................................................. S 169
`3-2-2-6- Automobile pollution ................................. ....... S 169
`3-2-2-7- Tobacco smoke ................................................ S 169
`3-3- Drugs ................................................................... S170
`3-3-1-Aspirin intolerance ............................................ S 170
`3-3-2- Other drugs ......... _. ............................................. S 170
`
`4- Mechanisms ........................................................ S171
`4-1-The normal nasal mucosa ........................... S171
`4-1-1- Anatomy and physiology of the nose ............... S 1 71
`4-1-2- Nasal rnicrovasculature ..................................... S 172
`4-1-3- Mucous glands •................................................. 5173
`4-1-3-1- Goblet cells and mucous glands ......................... S 173
`4-1-3-2- Sources of nasal fluid in rhinorrhea .................... S173
`4-1-3-3- Control of the secretory process ......................... S 173
`4-1-4- Cells of the nose ............................................... S 173
`4-1-5- Nerves of the nose ............................................ S1 73
`4-2- Cells, mediators, cytokines, chemokines
`and adhesion molecules of nasal
`inflammation ........................................................... S 17 4
`4-2-1- Cells .................................................................. Sl 74
`4-2-1-1Mast cells ......................................................... S174
`4-2-1-2- Basophils ........................................................ S 175
`4-2-1-3- Eosinophils ..................................................... S 175
`4-2-1-4- T-lymphocytes ................................................. S 1.76
`4-2-1-5- B-lymphocytes ................................................. S 177
`4-2-1-6- Macrophages and dendritic cells ..................... ... S177
`
`4-2-1-6-1- Macrophages . .............................. .. . ... ...... ....... 5177
`4-2-1·6-2- Dendritic cells .•.•.•.•......••... .. ..........•...•..••....... .• S 177
`4-2-1-7- Epithelial cells ................................................. S 178
`4-2-1-8- Endothelial cells .............................................. S 178
`4-2-1-9- Fibroblasts ...................................................... 5178
`4-2-2- Pro-inflammatory mediators ·····························s 178
`4-2-2-1- Histamine ........................................................ S 178
`4-2-2-2 Arachidonic acid metabolites .............................. S 179
`4-2-2-2-1- Cyclooxygenase pathways: Biosynthesis and biological
`properties of prostanoids .. . ......... .... ......... ................ ..... . S 180
`4·2-2-2-2· Lipoxygenase pathways: Biosynthesis and biological
`properties of Jeukolricnes .... .... ............. .... .... ................ S 180
`4-2•2-2·3- Leukotriene ru:eptors ........................... ....... ...... S iB 1
`4-2-2-2-4- Aspirin-induced asthma and rhinitis . ..... ............ ..... S 181
`4-2-2-3- Kinins ............................................................. s 181
`4-2-3- Cytokines .......................................................... 5182
`4-2-3-1- Pro-inflammatory cytokines .............................. S 182
`4-2-3-2- Th2-related cytokines ....................................... S 183
`4-2-3-3- Other cytokines and growth factors .................... S 183
`4-2-4- Chemokines ...................................................... S 183
`4-2-5- Adhesion molecules ......................................... . S 184
`4-2-5-1- Endothelial adhesion molecules ......................... S 184
`4-2-5-2- ICAM-1 .......................................................... S 184
`4-2-5-3- Soluble adhesion molecules ............................... S 185
`4-2-6- Survival of inflammatory cells ......................... S 18 5
`4-2-7- Conclusions ....................................................... S185
`4-3- Neurotransmitters ........................................... S185
`4-3-1- Non-adrenergic, non-cholinergic system .......... S185
`4-3-2- Nitric oxide ....................................................... S 18 5
`4-4- The lgE immune response .......................... S186
`4-4-1- Regulation of the lgE immune response .......... S 186
`4-4-1-1-Antigen presenting cells .................................... 5186
`4-4-1-2- Th2 cytokines .................................................. S 186
`4-4-1-3- Co-stimulatory signals ...................................... S 187
`4-4-1-4- Cells involved in Th2-cytokine synthesis ........... S187
`4-4 -2- Local IgE immune response ............................. S 187
`4-4 -3- Systemic IgE immune response ........................ S188
`4-4-4- IgE receptors ..................................................... 5188
`4-4-4-1- The high affinity receptor for IgE (FC£RI) .•...•..... S 18 8
`4-4-4-2- The low affinity receptor for IgE (FC£RII, CD23) .. S 189
`4-5- From nasal challenge to chronic rhinitis .. S189
`4-5-1- N asal challenge: early and late-phase reactions .. S 189
`4-5-1-1- The early-phase reaction ................................... S189
`4·5-1- 1-J- Release of vaso•active mediators .......................... S 189
`4-5·1-1-2- Plasma exudation . •...•...•.. ..•...•........ ................•. S 189
`4-5•·1-1-3-Activation of epithelial cells . ...... _. ... ~ .....•........•. .... S 189
`4-5•1-1-4• Neuropeptides ...... ....... . ............ ........ . .. ......... ... S 189
`4.5. J. J.5- Release of chcmotactic factors .... . .... .... .... ....... ..... S 189
`4-5-1-2- Late-phase reaction .......................................... S191
`4-5·1-2-1- Cell activation and release of pro-inflammatory
`mediators ...•..... , •. ....••............... ..... •.. •...... . ......... . .... . $ 191
`4•5•1-2-2- Cytokines, chemokines and the late-phase reaction ... . . S 192
`4-5•1·2-3- Recruitment of inflammatory cells and adhesion molecules S 192
`4•5•1-2-4• Survival of inflammatory cells ... .•.......•..•...... .. . •... S 192
`4-5-2- The priming effect ............................................ S192
`4-5 -3- Minimal persi stent inflarnmation ...................... S193
`4-5 -4- Persistent inflammation ................................... S 193
`
`10A November 2001
`
`J ALLERGY CUN IMMUNOL
`
`

`

`CONTENTS
`
`CONTINUED
`
`4-5-4-1- Seasonal allergic rhinitis .................................. S193
`4.5.4.J.J- Inflammatory cells ....... ..... ..••...•.... .... .... ......... .. S 193
`4-5•4·1·2· Epithelial cells .................... . ... . .... ..... ........ ...... S193
`4-5-4-1•3· Pro•intlammatory mediators .......•..............•......... S 193
`4.5.4.1-4- Cytokines and chemokines ..... ............... ....... ....... S 193
`4-5-4-J.5. Edema .......•....•................ . . ........•.•............... . Sl 93
`4.5-4. J. 6• Neuropeptides ... . ..... .......•. ......•••.•••..••••.••••••.••. . S 194
`4-5-4-2- Perennial allergic rhinitis ....•..........................•.. S 194
`4-5•4-2-1, Inflammatory cells ....... •. ........... ...... ......•.... ...... S 194
`4-5-4-2-2· Epithelial cells ...••...•...•................. ............ ....•• S 194
`4.5.4.z.3. Pro-inflammatory mediators ································s 194
`4.5.4.2-4. Cytokines . ..•...•..... ........•......... ..•........ . ... . ...•... S 194
`4-5-4•2•5• Adhesion molecules ...............•..•... ..... .... . .......... S 194
`4-6- Aspirin induced rhinitis ............................ S 194
`4-7- Nasal hyperreactivity ................................. S195
`4-8- Non-specific triggers ................................. S195
`
`5- Non-infectious, non-allergic rhinitis ... S196
`5-1- Prevalence and natural history ................ S 196
`5-2- Pathophysiology ............................................ S196
`5-2-1- Drug response and mediators ........................... S196
`5-2-2- Nasal hyperreactivity ........................................ S196
`5-3- Symptoms ........................................................ S196
`5-3-1- Sneezers ............................................................ S196
`5-3-2- Runners ............................................................. $ 196
`5-3-3- Blockers ............................................................ S196
`5-4- Causes and classification ........................... S197
`5-4-1- Physiological symptoms ................................... S 197
`5-4-2- Aetiology of non-allergic, non-infectious rhinitis .S 197
`5-4-3- Inappropriate awareness of normal nasal
`symptoms ......................... ......................................... S 197
`5-4-4- Anatomical abnormalities ................................. S 197
`5°5- Diagnosis ........................................................... S197
`5-6- Differential diagnosis .................................. S 197
`5-7- Conclusions ..................................................... S197
`
`6- Co-morbidity and complications ... S198
`6-1- Asthma .............................................................. S198
`6-1-1- Introduction ....................................................... S 198
`6-1-2- Epidemiology .................................................... S198
`• 6-1-2-1- Association between asthma and rhinitis ............... $ 198
`6-1-2-2- Association between rhinitis and non-specific
`bronchial hyperreactivity .......... ............•........... $198
`6-1-3- The same triggers can cause rhinitis and asthma .. S 199
`6-1-4- Natural history of the diseases .......................... S 199
`6-1 •5- The mucosa of the airways ............................... S 199
`6-1-6- Relationships and differences between rhinitis
`and asthma ................................................................ $200
`6-1-7- Physiological relationships between rhinitis and
`asthma ··································· .. ··································s200
`6-1-8· Clinical relationships between rhinitis and
`asthma ·······································································s201
`6-1-9- Costs .................................................................. S201
`6-1-10- Conclusion ...................................................... $201
`6-2- Conjunctivitis ................................................... S201
`6-2-1- Prevalence of the association ............................ S201
`6-2-2- Mechanisms ................................... ................... S203
`
`J ALLERGY CLIN IMMUNOL
`
`6-2-3- Clinical aspects ................................................. S203
`6-3- Sinusitis and nasal polyposis ..................... S203
`6-3-1- Sinusitis ................... .......................................... S203
`6-3-1-1- Relationship between allergy and sinusitis .......... S203
`6--3-1-2- Relationship between asthma and sinusitis ............ S204
`6-3-2- Nasal polyps ...................................................... S204
`6-3-2-1- Relationship between allergy and polyposis ........ S204
`6-3-2-2- Relationship between aspirin intolerance and
`polyposis ................................................................. S204
`6-3-2-3- Relationship between asthma and polyposis ....... S204
`6-4- Otitis media ..................................................... S205
`6-4-1- Introduction ....................................................... S205
`6-4-2- Definition and classification of otitis media ..... S205
`6-4-3- Epidemiological relation between rhinitis and
`otitis media ....... ·························································s206
`6-4-3·1 Infectious rhinitis and otitis media ...................... S206
`6-4-3-2- Allergy and otitis media with effusion ............... S206
`6-4-4- Potential interactions between rhinitis and otitis
`media ........................................................................ S206
`6-4-4-1- Eustachian tube dysfunction ....................... , .......... S206
`6-4-4-2- lnfection .................................................................. S206
`6-4-4-3-Allergy and allergic inflammation ........•................ .5206
`6-4-4-4- The relationship between food allergy and OME .. S207
`6-4-5- Conclusion ........................................................ S207
`
`7- Diagnosis and assessment of severity s2os
`7-1- History ............................................................. S208
`7-1-1- Symptoms of rhinitis and complications .......... S208
`7-1-2- Other historical background ............................. S208
`7-2- Examination of the nose .............................. S209
`7-2-1- Methods ............................................................ S209
`7-2-2- Findings ............................................................ S209
`7-3- Allergy diagnosis ............................................ S209
`7-3-1- Methods ............................................................ S209
`7-3-1-2- Skin tests ........................................................ S210
`7-3·1-2-1• Methods ... ... .... ..... ............. .... ........ .... ............ S210
`7·3·1-2-2- Factors affecting skin testing ................ ........... .... S211
`7•3·1-2·3· Interpretation of skin tests .. ............. ... . .... . .. ...... .. S211
`7•3-1•2-4• Clinical value of skin tests .......... .... .......... ...... ... S211
`7-3·1-3- IgE .......................................................................... S212
`7.3.1.3.1. Serum total JgE .......................................... .... S212
`7·3· 1-3·2- Serum specific lgE . ................. .. ................... ... S212
`7•3-1·3·3- Screening tests using serum specific lgE ................ S212
`7-3-1-4- Other tests ...................................................... S213
`7-3- 1•4· 1- IgG and lgG4 ...... ... ... . .... .... .... ... .............. ....... $213
`7-3· 1-4-2- Peripheral blood activation markers .... ... .. ....... .. .. .. S213
`7.3.1-4-3. Nasal specific lgE ... ............ ............................. S213
`7-3• 1-4-4- Mediators released during allergic reactions . . .. . ........ S213
`7· 3-1·4· 5· Cytology and histology ............... .......•..••.•......... S213
`7•3- 1•4•6- Measurement of nitric oxide in exhaled air ............ : .. S213
`7-3-1-5- Nasal challenge ............................. ................... S213
`7. 3. J.5. J. Nasal chal.tenge with allergen . ....... .......... ..... .....•.. S213
`7•3·1•5•1-1· Provoking agent ................... ...... ... .... ......... S213
`7-3·1-5•1·2· Deposition in the nose ..................... . ... . .. ...... S214
`7-3·1·5•1·3-Assessment of the rcsponse ....... .. .... .. ......... .. .. S214
`7-3· 1-5. J-4- Measurement of mediators and cells during challenge .S215
`Continued on page 12A
`
`November 2001
`
`11A
`
`

`

`CONTENTS
`
`CONTINUED
`
`7-3-1-5-1-5- Factors affecting nasal challenge ........ .... ......... S215
`7-3-1-5-2- Nasal challenge with non-specific agents ........... ..... S215
`7-3-1-5-3- Challenge with occupational agents ................. ..... S215
`7-3-1-5-4-Aspirin-induced rhinitis and asthma ...... ... ... .... ...... S215
`7-3-2- Interpretation of tests and recommendations .... S216
`7-3-2-1- Correlation between tests ................................. S216
`7-3-2-2- Diagnosis of inhalant allergy ............................ S216
`7-3-2-3- Diagnosis of food allergy ................................. S216
`7-3-2-4- Diagnosis of occupational allergy ...................... S216
`7-4- Other ENT diagnosis ................................... S216
`7-4-1- Bacteriology ............... ·-····- ·····-····· .. ···-····-········S216
`7-4-2- Imaging ............................................................ S216
`7-4-2-1- Plain sinus radiographs .................................... S216
`7-4-2-2- Computerised tomography (CT) ................... ..... S217
`7-4-2-3- Magnetic resonance imaging (MRI) ......... .... ..... S217
`7-4-3- Mucociliary function ....................................... S217
`7-4-4- Nasal airway assessment ................................. S217
`7-4-5- Olfaction .......................................................... S217
`7-5- Diagnosis of Asthma ................................... S217
`7-5-1- History and measurement of symptoms .......... S217
`7-5-2- Physical examination ........................................ S218
`7-5-3- Measurement of lung function .......................... S218
`7-5-3-1- Recording airflow obstruction ........................... S218
`7-5-3-2- Assessing the reversibility of airflow obstruction S218
`7-5-3-3-Assessing the diurnal variation of airflow obstruction .S218
`7-5-3-4- Non-specific challenge testing .......................... S219
`7-5-4- Special considerations in difficult groups ....... S219
`7-6- Assessment of severity of rhinitis ............ S219
`
`8- Management ..................................................... s220
`8-1- Allergen avoidance ....................................... S220
`8-1-1- House dust mites ............................................... S220
`8-1-2- Cats and dogs .................................................... S221
`8-1-3- Cockroaches ...................................................... S221
`8-1-4- Outdoor allergens .............................................. S221
`8-1-5- Indoor moulds ................................................... S221
`8-1-6- Occupational agents .......................................... S221
`8-1-7- Food allergens ................................................... S222
`8-1-8- Conclusion ........................................................ S222
`8-2- Medication ........................................................ S222
`8-2-1- Routes of administration ................................... S222
`8-2-1-1-Advantages of intranasal administration ............. S222
`8-2-1-2- Problems of intranasal administration ................ S222
`8-2-2- Oral HI-antihistamines .................................... S223
`8-2-2-1- Mechanisms of action and rationale ................... S223
`8-2-2-1-1- HI-blocking effect . ....•.. .•... ........... . ................ .. S223
`8-2-2-1-2- Anti-allergic effect.s ....•...•...... .. ... .................... .. S223
`8-2-2-2- Clinical and pharmacological effects .................. S224
`8-2-2-3- Side effects of HI-antihistamines ...................... S224
`8-2-2-3-1- Central nervous system side effects ....................... S224
`8-2-2-3-2- Cardiac side effect.s ... ......... .......... -......... -......... S225
`8-2-2-3-3- Carcinogenic effects ...... ..... .......... _ . ......... ......... S225
`8-2-2-3-4- Other side effects ....... ........ .............................. S225
`8-2-2-4- Molecules used ................................................ S226
`8-2-2-4• l- Acrivastine ... ...... ....... .. ............ . ............. .... ..... S226
`8-2-2-4-2- Asternizole ... ........ ..... ............... .... .... ..... ..... .... S226
`8-2-2-4-3- Azelastine ...... .................•.. ...............•••..•. ..... . S226
`8-2-2-4-4- Cetirizine ... ................................................... S226
`
`8-2-2-4-5- Ebastine .... .... ... . ............... ..... ............ ........... S227
`8-2-2-4-6- Emedastine .... ........ ..... .... ... . .. ... ... . ......... ... . .... S227
`8-2-2-4-7- Epinastine .. .... . ... ............... ........................ ... . S227
`8-2-2-4-8- Fexofenadine ... ... .... . ... ....... .. ................. .. ...... . S227
`8-2-2-4-9- Levocabastine ..... ............... . .............. .... ... . .... . S228
`8-2-2-4-10- Loratadine ········· ··· ····· ··· ····-···········-····· .. ·······S228
`8-2-2-4-11- Mequitazine •••••..•••.••••..•..•.•.•.•••••..••••.•. . .. . ... .. $228
`8-2-2-4-12- Mizolastine •.•..•.•••• .••.. .•. ..•.. .•••••••.••.•.••.......... $228
`8-2-2-4-13- Terfenadine ...... ............. ..... ...... ........ .... ........ S228
`8-2-2-4-14- Ketotifen ... ... ..........•.•.•..•..• .•..•.••.•... .••.•.... ... . S229
`8-2-2-4-15- Oxatornide .... .. . .. ... ..... ............... . ...... ............ S229
`8-2-2-4•16- Other molecules .. .. .... ...... .... ......... ..... .... .... .... S229
`8-2-2-5- The future of HI-antihistamines ........................ S229
`8-2-2-6- Recommendations ........................................... S229
`8-2-3-Topical HI-antihistamines ............................... S229
`8-2-3-1- Rationale ........•..........•.....•.....................•........ S229
`8-2-3-2- Efficacy ......................................................... S229
`8-2-3-2-1- Nasal administration . ........ .... ...... ... .... .......... .... S229
`8-2-3-2-1- Ocular administration ..... .... ... .... .. .................... . S230
`8-2-3-3- Safety ............................................................ S230
`8-2-3-4- Recommendations ........................................... S230
`8-2-4- Topical glucocorticosteroids ............................ S230
`8-2-4-1- Mechanisms of action and rationale ................... S230
`8-2-4-1-1- Molecular effects ..... .... ... .......... . .... .... ........... .. S230
`8-2-4-1-2-Anti-inflarnmatory effect.s on cells ........... ........ . .... S231
`8-2-4- 1-3-Anti-inflammatory effects on cytok.ines . ........ ....... .. S231
`8-2-4-1-4- Other effects of intranasal glucocorticosteroids .. .. ..... S231
`8-2-4-2- Clinical and pharmacological effects ................. S231
`8-2-4-3- Side effects of intranasal g!ucocorticosteroids ..... .5232
`8-2-4-3-1-Local side effects .. ........ ..... .... ... . . ................. ... . S232
`8-2-4-3-2- Effect.son hypothalarnic•pituitary-adrenal axis ..... ... . S232
`8-2-4-3-3- Other systemic side effects .... ................ ... ...... .... $232
`8•2-4-3-4- Other side effcct.s ................... .. ........... ............ S232
`8-2-4-3-5- Pregnancy ..... .. ........... ... ......... ...... ....... .......... S232
`8-2-4-4- Molecules used ............................................... S232
`8-2-4-4-1- Beclomethasone dipropionate ........ ... .. ......... ........ S232
`8-2-4-4-2- Budesonide ... .... .. ........ .. .. ... ......... ........ .......... S233
`8-2-4•4-3- Flunisolide ............................... - .................... - ............. S233
`8-2·4-4-4- Triamcinolone acetonide ....... ·-····· .. ·••·······--•···· .............. S233
`8-2-4-4-5- Fluticasone propionate ............................. _., .................... S23 3
`8-2-4-4-6- Mometasone furoate ....................................................... S234
`8-2-4-4-7- Other molecules ............................................................. S234
`8-2-4-5- The future of nasal glucocorticosteroid treatment .S234
`8-2-4-6- Recommendations .................................................. S234
`8-2-5- Systemic glucocorticosteroids .......................... S234
`8-2-5-1- Rationale .................................... :: ........................... S234
`8-2-5-2- Efficacy and safety ................................................. S23 5
`8-2-5-3- Contraindications .................................................... S23 5
`8-2-5-4- Recommendations .................................................. S235
`8-2-6- Chromones ........................................................ S235
`8-2-6-1- Rationale ................................................................. S235
`8-2-6-2- Efficacy and safety ........................................... S23 5
`8-2-6-2-1- Nasal administration ....................... .' .............................. S23 5
`8-2-6-2-2- Ocular administration ..... _ ..................... -• .. ·· -·•·• .... •.S236
`8-2-6-3- Recommendations ........................ : ......................... S236
`8-2-6-4- NAAGA ......................................... , ........................ S236
`8-2-7- Decongestants ...............................