Nasal Congestion Relief in

Rhino-Sinusitis

Dr. Damayanti Soetjipto, Sp THT

 Rhinosinusitis: Clinical
Definition
• Rhinosinusitis is defined as inflammation of the
nose and the paranasal sinuses resulting in:
≥2 MAJOR SYMPTOMS AND either
• Blockage/congestion ENDOSCOPIC SIGNS of
• Loss of smell • Polyps or
• Discharge anterior/postnasal drip • Mucopurulent discharge from
middle meatus or
• Facial pain/pressure
• Edema/mucosal obstruction
primarily in middle meatus
OR
CT CHANGES
• Mucosal changes within ostiomeatal
complex and/or sinuses
EAACI. Rhinol Suppl. 2005;18:1.
Fokkens et al. Allergy. 2005;60:583.
 Rhinosinusitis: Clinical Definition
Duration
Severity • Acute/intermittent
• Mild = VAS 0-4 – <12 weeks
– Complete resolution
• Moderate/severe = VAS 5-10
of symptoms

• Persistent/chronic
10 cm – >12 weeks
– No complete resolution
No Worst of symptoms
possible

VAS = visual analogue scale.

EAACI. Rhinol Suppl. 2005;18:1.
Fokkens et al. Allergy. 2005;60:583.
 Rhinosinusitis:
Intensity of Symptoms and Signs
• Acute rhinosinusitis • Adults
• Chronic rhinosinusitis • Children
• Recurrent acute rhinosinusitis
• Acute exacerbations of
chronic rhinosinusitis

Acute rhinosinusitis
Intensity of symptoms

Chronic rhinosinusitis
and signs

Recurrent acute rhinosinusitis

Acute exacerbation
of chronic rhinosinusitis

12
Weeks
 Incidence and Diagnosis of
Rhinosinusitis
Incidence
(Millions) Diagnosed (%)
US 37 65

Japan 11 48
Germany 12 75
France 7 70
Italy 5 55
Spain 4 56
Source: Decision Resources Report.
UK 8 71
 Acute Rhinosinusitis Continuum
Spectrum of acute rhinosinusitis based on clinical
criteria

Increasing symptom severity

Mild Moderate to severe acute Fulminant

rhinosinusitis rhinosinusitis bacterial
• Allergic rhinosinusitis
• Viral
• Bacterial colonization/infection
 Common Cold/Acute
Rhinosinusitis
Viral rhinosinusitis/common cold
Acute rhinosinusitis/increase after 5 days
Acute rhinosinusitis/persist after 10 days
Symptoms

No need for antibiotic

therapy Consider treatment with antibiotics
and/or steroids

0 5 10 15
Days

Fokkens et al. EP3OS Guidelines. Rhinol Suppl. 2005;18:1.

 Bacterial Infection in Acute
Rhinosinusitis
• Antibiotics for acute rhinosinusitis are a common
prescription in primary care
• Acute bacterial rhinosinusitis is usually a secondary
infection resulting from sinus obstruction following acute
viral URI
– Streptococcus pneumoniae Most common pathogens
– Haemophilus influenzae

• Acute bacterial and viral rhinosinusitis are difficult to

differentiate on clinical grounds

URI = upper respiratory infection.

Hickner et al. Ann Intern Med. 2001;134:498.
 Acute Rhinosinusitis = Bacterial
Infection?
• Estimated 1 billion viral URIs occur each year in US
• Only 0.2%-2% of viral URIs are estimated to be
complicated by bacterial rhinosinusitis
– ~40% of acute bacterial infections resolve spontaneously

• However, 85%-98% of patients with acute

rhinosinusitis are needlessly prescribed an antibiotic by
their primary care physicians

URI = upper respiratory infection.

Fokkens et al. EP3OS Guidelines. Rhinol Suppl. 2005;18:1.
Meltzer et al. J Allergy Clin Immunol. 2004;114(suppl):155.
Objectives of Medical Treatment of
Acute Rhinosinusitis
Multifaceted
treatment regimen

• Eliminate infection
• Reduce inflammation
• Improve symptoms
 Acute Rhinosinusitis Treatment
• Acute rhinosinusitis is usually a self-limiting disease
• Treatment can be symptomatic in mild disease
• Antibiotics should be reserved only for persistent moderate
to severe disease
• Early treatment of inflammation allows sinus drainage and
helps to prevent bacterial infection
• Antibiotic prescriptions should be based on local resistance
patterns
• Local corticosteroids are an effective therapy

EAACI. Rhinol Suppl. 2005;18:1.

Fokkens et al. Allergy. 2005;60:583.
 Treatment Options for Acute
Rhinosinusitis
Agent Primary Action
Antibiotics Eliminate (bacterial) infection
Saline lavage Remove secretions, promote nasal mucosal
healing
Oral and topical Reduce congestion and improve drainage
decongestants
Mucolytics Thin mucus secretions, reduce mucus stasis,
and promote clearing
Antihistamines Decrease production of mucus and diminish
rhinorrhea
Intranasal corticosteroids Reduce inflammation and improve associated
EAACI. Rhinol Suppl. 2005;18:1.
symptoms
Fokkens et al. Allergy. 2005;60:583.
 European Guidelines for Acute/Intermittent
Rhinosinusitis: Signs and Symptoms Requiring
Immediate Intervention

• Unilateral symptoms • Double vision

• Bleeding • Reduced vision
• Crusting • Severe unilateral frontal
• Cacosmia headache
• Orbital symptoms • Frontal swelling
• Eye/lid swelling • Signs of meningitis or
• Eye redness focal neurological signs
• Displaced globe • Systemic symptoms
Fokkens et al. EP3OS Guidelines. Rhinol Suppl. 2005;18:1.
Fokkens et al. Allergy. 2005;60:583.
 European Guidelines for Management
of Acute/Intermittent Rhinosinusitis
• Recommendations for GPs
– Mild symptoms: symptomatic relief, analgesics
– Moderate/severe symptoms: additional topical steroids
• Recommendations for ENT specialists
– Mild symptoms: symptomatic relief, analgesics
– Moderate/severe symptoms
• Antibiotic therapy according to national recommendations
• Topical steroids
• +/- decongestion of the middle meatus
• +/- microbiology culture/resistance pattern
– Persistent moderate disease: second course of antibiotics
– Persistent severe disease: hospitalization, microbiology culture,
change antibiotic and route of administration, CT scan
EAACI. Rhinol Suppl. 2005;18:1.
Fokkens et al. Allergy. 2005;60:583.
 Level of Evidence and Grade of
Recommendation for Treatment of
Acute/Intermittent Rhinosinusitis
Level of
Therapy Evidence Recommendation Relevance
Antibiotic Ia A Yes: after 5
days or in
severe cases

Topical steroid Ib A Yes

Topical steroid + Ib A Yes

antibiotic
Ia: Evidence from meta-analysis of randomized, A: Consistent level 1 studies.
controlled trials. B: Consistent level 2 or 3 studies or extrapolations
Ib: Evidence from at least 1 randomized, controlled trial. from level 1 studies.

EAACI. Rhinol Suppl. 2005;18:1.

Fokkens et al. Allergy. 2005;60:583.
Clinical Efficacy of
NASONEX®

(mometasone furoate) in
Rhinosinusitis
 Why Mometasone
Monotherapy Treatment?
• Value of antibiotics in
question
– American Academy of Family
Physicians
– Canadian Medical Association
– Agency for Health Care Policy
and Research
• Rx recommendation
– Symptomatic therapy and
watchful waiting prior to
antibiotics
• German guidelines do not
recommend antibiotic use
• Facilitates symptom resolution
– Inhibits local inflammation
– Relieves ostial obstruction
– Restores mucociliary function
– Stimulates host defense and
repair mechanisms
– Promotes bacterial clearance
• Does not increase bacterial
infections, including in allergic
rhinitis
• Stems progression to bacterial
infection in experimental models
 NASONEX® vs Antibiotic Monotherapy in
Acute Rhinosinusitis: Study Design
15-day 14-day
treatment phase* follow-up phase

Visit 1 Visit 2 Phone- Visit 3 Visit 4 Visit 5

call
Days -3 Day 1 Day 3/4 Day 8 Day 15 Day 29
to 1 Baseline
NASONEX® 200 μg od (n=243)

NASONEX® 200 μg bid (n=235)

Amoxicillin 0.5 g tid (n=251)

Placebo (n=252)

*Patients randomized to amoxicillin received active treatment for 10 days, according to standard practice.
Meltzer et al. J Allergy Clin Immunol. In press. 2005.
 NASONEX Monotherapy in Acute
Rhinosinusitis: Effect on Major
Symptom Score
Mean AM/PM Major Symptom

5
Score (Days 2-15)

*
4 †
*

3
NASONEX NASONEX Amoxicillin Placebo
200 µg od 200 µg bid 0.5 g tid

*P≤0.018 vs placebo; †P=0.002 vs amoxicillin.

n=234–252 per treatment group; baseline mean major symptom score ranged from 8.17–8.53.
Meltzer et al. J Allergy Clin Immunol. In press. 2005.
 NASONEX Monotherapy in Acute
Rhinosinusitis: Effect on Total Symptom
Score
Mean AM/PM Total Symptom

5
Score (Days 2-15)

*
*†
4

3
NASONEX NASONEX Amoxicillin Placebo
200 µg od 200 µg bid 0.5 g tid

*P≤0.025 vs placebo; †P=0.011 vs amoxicillin.

n=234–252 per treatment group; baseline mean total symptom score ranged from 9.13–9.53.
Meltzer et al. J Allergy Clin Immunol. In press. 2005.
 NASONEX Monotherapy in Acute
Rhinosinusitis: Effect on Individual
Nasal Symptom Scores
Mean Individual Nasal Symptom Scores (2-15 days)
1.6
NASONEX 200 µg od
Mean AM/PM symptom
score (days 2-15)

NASONEX 200 µg bid

Amoxicillin 0.5 g tid
1.2 Placebo
* *
*† * *
†
0.8
*

* † *†
0.4
Congestion Facial pain Headache Rhinorrhea

*P≤0.048 vs placebo; †P≤0.018 vs amoxicillin.

n=234-252 per treatment group.
Meltzer et al. J Allergy Clin Immunol. In press. 2005.
 Therapeutic Response in Acute
Rhinosinusitis: NASONEX® bid Superior
to Amoxicillin or Placebo
1.6 Therapeutic Response at 15 Days
(0 = complete relief to 4 = no relief)
LS means score (points)

1.5

1.4 P=0.932 P=0.431

1.3

1.2
P=0.001*
1.1

1
NASONEX® NASONEX® Amoxicillin Placebo
200 µg od 200 µg bid 0.5 g tid (N=213)
(N=216) (N=212) (N=226)
All P values vs placebo
*P=0.013 vs amoxicillin.
Meltzer et al. J Allergy Clin Immunol. In press. 2005.
 NASONEX® in Acute Rhinosinusitis:
Treatment Failures/Recurrences
No. of Patients (%)
Failures Recurrences

NASONEX® 200 µg od 25 (10.3%) 10 (4.3%)

NASONEX® 200 µg 11 (4.7%)* 16 (7.0%)

bid

Amoxicillin 0.5 g tid 18 (7.2%) 20 (8.2%)

Placebo
*P=0.017 vs placebo.
27 (10.7%) 17 (7.0%)
Meltzer et al. J Allergy Clin Immunol. In press. 2005.
 NASONEX® in Acute Rhinosinusitis:
Summary of Adverse Events
No. of Patients (%)
NASONEX® NASONEX® Amoxicillin
200 µg od 200 µg bid 0.5 g tid Placebo
Any adverse event 86 (35.4%) 85 (36.2%) 84 (33.5%) 96 (38.1%)
Headache 16 (6.6%) 10 (4.3%) 15 (6.0%) 21 (8.3%)
Epistaxis* 9 (3.7%) 14 (6.0%) 13 (5.2%) 13 (5.2%)
Any GI event 27 (11.1%) 31 (13.2%) 28 (11.2%) 33 (13.1%)
Abdominal pain 5 (2.1%) 7 (3.0%) 3 (1.2%) 3 (1.2%)
Diarrhea 7 (2.9%) 6 (2.6%) 7 (2.8%) 10 (4.0%)
Nausea 9 (3.7%) 8 (3.4%) 9 (3.6%) 7 (2.8%)

*Epistaxis was defined as a wide range of bleeding episodes, from frank bleeding to bloody nasal
discharge to flecks of blood in the mucus.
Meltzer et al. J Allergy Clin Immunol. In press. 2005.
NASONEX® Monotherapy in Acute
Rhinosinusitis: Conclusions
• NASONEX® 200 µg bid monotherapy was statistically
superior to placebo and to amoxicillin for total and major
symptom relief in acute rhinosinusitis
• The major symptom score for amoxicillin was not
significantly different from placebo
• NASONEX® 200 µg bid relieves the problems considered
most important by patients, especially runny nose, need to
blow nose, and nasal discharge
 Adjunctive NASONEX® in Acute
Rhinosinusitis: Study Design
Baseline exam (Day -1) ACP 875 mg bid +
 History
NASONEX 400 μg bid
 Symptoms

 Physician evaluation Follow-up exam

ACP 875 mg bid + (day 21)
 CT scan
NASONEX 200 μg bid  Symptoms

 Physician
ACP 875 mg bid + evaluation
placebo  CT Scan

Symptom diary
for 21 days bid

ACP = amoxicillin clavulanate potassium (Augmentin®).

Nayak et al. Ann Allergy Asthma Immunol. 2002;89:271.
 Changes in Symptoms Over 21 Days With
Adjunctive NASONEX® in Acute
Rhinosinusitis
Placebo (n=290) NASONEX® 400 μg bid (n=291) NASONEX® 200 μg bid (n=280)
Facial Pain Rhinorrhea
Congestion Headache Postnasal drip
-40 -30
Total symptom score (%)

symptom score (%)

Improvement in

Improvement in
-45 -40

*
-50 -50
†
* *
-55 -60
* †
†
-60 -70
*P<0.05 vs placebo.
†P<0.02 vs placebo.

Nayak et al. Ann Allergy Asthma Immunol. 2002;89:271

Data on file, Schering Corporation, Kenilworth, NJ.
 Adjunctive NASONEX® Produced More
Rapid Relief of Total Symptoms in Acute
Rhinosinusitis
10
Improvement in total

8 † * *
† *
symptom score

†
†
†
‡
6
†

4
Placebo (baseline = 11.61)
NASONEX 200 μg bid (baseline = 11.57)
2
NASONEX 400 μg bid (baseline = 11.61)

0
1 3 5 7 9 11 13 15
Days of Treatment
*P<0.05 NASONEX 400 μg bid vs placebo; †P<0.05 both doses vs. placebo;
‡P<0.05 NASONEX 200 μg bid vs placebo.

Nayak et al. Ann Allergy Asthma Immunol. 2002;89:271.

 Adjunctive NASONEX® in Acute
Rhinosinusitis: Summary of Treatment-
Related Adverse Events*
Percent
NASONEX NASONEX
200 μg bid 400 μg bid
Adverse Event (n=318) (n=324) Placebo (n=325)
Epistaxis† 5 6 6

Nasal burning 1 1 2

Nasal irritation <1 2 0

Headache 2 1 2

*Occurring in ≥ 2% of patients.
†pistaxis was defined as a wide range of bleeding episodes, from frank bleeding to bloody nasischarge

to flecks of blood in the mucus.

Nayak et al. Ann Allergy Asthma Immunol. 2002;89:271.
 Adjunctive NASONEX® in Acute
Recurrent Rhinosinusitis: Study Design
Baseline exam (Day 1) ACP 875 mg bid +
 History NASONEX 400 μg bid
 Symptoms

 Physician evaluation Follow-up exam

 CT scan (day 21)
 Symptoms

 Physician
ACP 875 mg bid +
Placebo evaluation
 CT scan

Symptom diary
for 21 days bid

ACP = amoxicillin clavulanate potassium (Augmentin®).

Meltzer et al. J Allergy Clin Immunol. 2000;106:630.
 Adjunctive NASONEX® in Acute
Recurrent Rhinosinusitis: Changes in
Symptoms at 21 Days
Placebo
Improvement in symptom score

Improvement in symptom score

7 1.4 NASONEX 400 μg bid
* *
6 1.2 * †
5 1.0
4 0.8
3 0.6
2 0.4
1 0.2

0 0
Total symptom
score

*P≤0.01 vs placebo.
†P<0.05 vs placebo.

Meltzer et al. J Allergy Clin Immunol 2000;106:630.

 Adjunctive NASONEX® Produced
More Rapid Relief of Total
Symptoms in Acute Recurrent
† †
8
Rhinosinusitis * †

*
Improvement in total

*
symptom score

Placebo (baseline = 11.28)

2
NASONEX 400 μg bid (baseline = 11.36)

0
0 2 4 6 8 10 12 14 16
Days of treatment
*P<0.05 vs placebo.
†P<0.01 vs placebo.

Meltzer et al. J Allergy Clin Immunol. 2000;106:630.

 Adjunctive NASONEX® in Acute
Recurrent Rhinosinusitis: Summary of
Treatment-Emergent Adverse Events*
Percent
NASONEX
400 μg bid Placebo
Adverse Event (n=200) (n=207)
Headache 2 3
Epistaxis† 3 1
Nasal burning 2 1
Nasal irritation 2 2
Pharyngitis 2 3
*Occurring in ≥2% of patients.
†Epistaxis was defined as a wide range of bleeding episodes, from frank bleeding to bloody nasal

discharge to flecks of blood in the mucus.

Meltzer et al. J Allergy Clin Immunol. 2000;106:630.
 Conclusions:
Is There a Role for Intranasal
Corticosteroids in Acute Rhinosinusitis?
• Most cases of acute rhinosinusitis are viral rather than
bacterial
• First-line treatment should be symptomatic, with
antibiotics reserved for patients with a clinical diagnosis of
bacterial rhinosinusitis
• Intranasal corticosteroids
– Provide anti-inflammatory benefits
– Provide effective relief of symptoms
– Play an important role in management of acute rhinosinusitis either
prior to, or as adjunctive treatment to, antibiotics
Chronic Rhinosinusitis
 Symptoms of Chronic
Rhinosinusitis
• Major symptoms • Minor symptoms
– Facial pain/pressure – Headache
– Facial congestion/fullness – Fever
– Nasal obstruction/ – Halitosis
blockage – Fatigue
– Nasal discharge/ – Dental pain
purulence/postnasal drip
– Cough
– Hyperosmia/anosmia
– Ear pain/pressure/fullness
– Fever
 Differential Diagnosis of
Chronic Rhinosinusitis
• Infectious rhinitis (eg; viral upper respiratory tract infections)
• Allergic rhinitis: seasonal, perennial, occupational
• Nonallergic rhinitis: ‘vasomotor rhinitis’, nonallergic rhinitis eosinophilia
syndrome, aspirin sensitivity
• Rhinitis medicamentosa
• Rhinitis secondary to pregnancy, hypothyroidism
• Anatomical abnormalities: severe septal deviation, foreign body
• Nasal polyps
• Inverted papilloma, benign and malignant tumours
• Cerebrospinal fluid leak, meningoencephaloceles
• Mucoceles
• Morbus wegener
• Cocaine abuse
• Atrophic rhinitis
• Specific or tropic infections
• Fungal sinus disease
• Ophthalmologic or neurologic diseases
 Symptoms Suggestive of
Chronic Rhinosinusitis
Initial evaluation
• Medical history: major, minor symptoms
• General examination
• Anterior rhinoscopy, nasal endoscopy
• Evaluation of underlying disease and
comorbidities
• CT scan (after treatment,
not in acute episode)
Special indications
(differential diagnosis
and underlying disease)
• Allergy tests
• Microbiology (eventually sinus puncture)
• Challenge test for aspirin sensitivity
• Nasal cytology (eosinophils, neutrophils)
• MRI
• Ciliary function studies
• Biopsy
• Blood examinations (Morbus wegener,
immunodeficiencies)
• Sweat chloride test
• Electron microscopy
• Genetic analyses
• Consultations of other specialties
(ophthalmologist, neurologist, etc)
 Chronic Rhinosinusitis:
Bacteriology
• Streptococcus pneumoniae
• Haemophilus influenzae
• Moraxella catarrhalis
• Staphylococcus aureus
• Coagulase-negative
Staphylococcus
• Pseudomonas aeruginosa
• Anaerobes
• Mixed infections

Pathogenic?
All fungus?
 Chronic Rhinosinusitis:
Cytokine/Mediator Profile
• IL-1α/β
• IL-6
• IL-8
• TNF-α
• IL-3
• GM-CSF
• ICAM-1
• Myeloperoxidase
• ECP
• No VCAM-1
• No IL-5 Neutrophilic inflammation with minor eosinophilia

Bachert et al. Allergy. 1998;53:2.

Demoly et al. Rev Mal Respir. 2000,17:925.
Nonoyama et al. Auris Nasus Larynx. 2000,27:51.
Rhyoo J Allergy Clin Immunol. 1999,103:395.
 Management of Chronic
Rhinosinusitis
Diagnosis

Medical treatment

Topical Systemic

CT scan

Surgery
 Chronic Rhinosinusitis:
Medical Treatment
• Steroids
– Topical
– Systemic
• Antibiotics: short/long courses
• Douching
• Mucolytics, immunomodulators,
immunostimulants, bacterial lysates
• Antifungals
 European Guidelines for Management of
Chronic Rhinosinusitis
• Recommendations for GPs
– Topical steroids
– Nasal douches
– Antihistamines and allergen avoidance in allergic patients
• Recommendations for ENT specialists
– Mild symptoms
• Topical steroids
• Nasal douches
• Long-term antibiotics if previous treatment fails after 3 months
– Moderate/severe symptoms
• Long-term antibiotics additional to topical steroids
• Nasal douches
• For treatment failure after 3 months, CT scan and consider surgery

Fokkens et al. Allergy. 2005;60:583.

 European Guidelines: Level of Evidence
and Grade of Recommendation for
Treatment of Chronic Rhinosinusitis

Level of
Therapy Evidence Recommendation Relevance
Long-term
III C Yes
oral antibiotic

Topical steroid Ib A Yes

Yes, for
Nasal saline III (no data
C symptomatic
douche on single use)
relief
Ib: Evidence from at least 1 randomized, controlled trial. A: Consistent level 1 studies
III: Evidence from nonexperimental, descriptive studies, C: Level IV studies or extrapolations
such as comparative studies, correlation studies, and from level 2 or 3 studies
case-control studies.

Fokkens et al. Allergy. 2005;60:583.

 Conclusions

• NASONEX® 200 µg bid monotherapy was statistically superior to

placebo and to amoxicillin for total and major symptom relief in acute
rhinosinusitis
• Adjunctive NASONEX® Produced More Rapid Relief of Total
Symptoms in Acute and Acute Recurrent Rhinosinusitis
• Intranasal corticosteroids
– Provide anti-inflammatory benefits
– Provide effective relief of symptoms
– Play an important role in management of acute rhinosinusitis either
prior to, or as adjunctive treatment to, antibiotics
• European Guidelines for Management of Chronic Rhinosinusitis
recommends Intranasal Corticosteroids for mild symptoms and
adjunctive to antibiotics for moderate/severe symptoms