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Improving Diagnosis and Management

of Asthma through Feno Measurement

a led
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Ex
Oxid e
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na itr ic
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Fe no
What is NO? ”…the new studies... …are highly suggestive of long-
term benefit of Feno inflammometry in asthma man­
Nitric oxide (NO) is produced in the agement. The bottom line is that Feno inflammometry
epi­thelial cells of the bronchial wall
as an intrinsic part of the inflamma- is an easy test which is helpful to target steroid treat-
tory process. NO production has been ment, to reduce steroids where possible, and to provide
shown to increase when there is
eosinophilic airway inflammation1, 2. significant benefits in terms of less hyperresponsive-
The presence of endogenous NO in ness and less inflammation without leading to overall
exhaled air was first reported in 1991 need for more steroids at the group level. On the basis
by Gustafsson et al.3 and in 1993 Al-
ving et al. found that NO in ex­haled of these findings, Feno offers more for day-to-day
air was elevated in patients with asthma management than any of the conventional
asthma4. Since that time research
has been directed at uncovering the lung function tests.”
role that NO plays in airway inflam-
mation. Editorial, Eur Respir J 2005;26:1–35

There has been a continuous flow


of research and a large body of data
(nearly 1,500 publications in peer
reviewed medical journals) to con-
firm the clinical value of exhaled
NO measurement.

Nitric oxide
CONTENTS

Epithelial cell lining Asthma Management Made Easy 3


in the bronchial wall

FeNO Measures the Inflammation


– Not Just the Symptoms 4
Normal epithelial cells. Minimal release
of NO. How Can Feno Measurement
Help Improve Clinical Decision Making? 5-7

Factors Affecting Exhaled NO Levels 8

References 9

Guide to Interpretation of Feno Values in


Symptomatic Steroid Naïve Patients 10
Activated epithelial cells during inflam-
mation demonstrate increased produc-
tion of NO. Guide to Interpretation of Feno Values in
Anti-Inflammatory Treated Patients 11
Asthma Management
Made Easy
The measurement of fractional exhaled nitric oxide (Feno)
has been validated as a way of measuring the airway
inflammation that underlies asthma.

Feno measurement is:

Accurate
Reproducible
Immediate
As informative as biopsy

Feno measurement offers:

Correct asthma diagnosis


Rapid identification of non-
compliance
The American Thoracic Society,
Insights into steroid effectiveness in conjunction with the European
Respiratory Society, have developed

Prediction of steroid response guidelines on how exhaled NO


measurements should be performed6.
Measurements performed according
Steroid dose-titration that to these guidelines are called
Fractional Exhaled Nitric Oxide
reduces cost and improves (Feno). The guidelines state that
exhaled NO measurements must be
patient outcome performed at a controlled and stan-
dardized exhalation flow rate as the
Feno value is highly flow dependent.
Notification of loss of control The Feno values in this brochure are
valid for the standardized 50mL/s
Prediction of asthma relapse flow rate only.



3
FeNO Measures the Inflammation
– Not Just the Symptoms
Asthma is, by definition, a chronic inflammatory process – which leads to air-
flow limitation and increased responsiveness to asthma triggers. Standard
methods for diagnosing and monitoring asthma traditionally focus on symptoms
and airway contraction. Until now, routine assessment of the underlying level of
inflammation has not been possible.

Feno measurement is:


Accurate Reproducible
I mmediate As informative as biopsy

Feno measurement is accurate Exhaled NO values increase


and reproducible when mea­sured even before the onset of symp-
with standardized, ap­proved toms or loss of control. This
devices. Results are available makes Feno measurement a
immediately, allowing the clini- helpful tool both in predicting
cian to measure the under­lying loss of control10 and assessing
inflammation while the patient is compliance with inhaled
in the clinic. steroids11.

Feno measurement has been Feno also responds more rapidly Change was observed in exhaled NO
shown to be as informative as than spirometry to changes in levels in a group of patients with
biopsy1, 2 and bronchoalveolar inflammation following aller- atopic asthma who were placed in
lavage-techniques7, 8 which are gen exposure, making it a more an Alpine home away from their
the traditional “gold standards” sensitive marker of the disease12, 13. allergens. NO levels fell during the
in determining ongoing airway Spirometry and Feno are inde- 3 months in the Alpine home and
remained stable even when gluco-
inflammation. pendent measures of different
corticoids were withdrawn. Three
aspects of the disease. So, there
weeks after return­ing to their homes,
Feno measurement is comparable is little correlation between Feno the patients’ exhaled NO levels in-
to sputum analysis in determin­ levels and pulmonary function creased. In comparison, spirometry
ing the level of inflammation9. tests in asthma patients. results continued to improve after
the patients returned home12.

30

25
FEV1
n = 20
Exhaled NO (ppb)

20

15
n = 20
10 n = 20 n = 10

5 Inhaled steroid withdrawal

Alpine home Town


0
T0 T1 T2 T3

Piacentini, 1999 12

4
How Can FeNO Measurement
Help Improve Clinical Decision Making?
Feno measurement has been shown to be superior to the
majority of conventional tests recommended in international
guidelines for diagnosing asthma in symptomatic patients.

Feno measurement offers:


Correct asthma diagnosis
It has been demonstrated that Feno measurement offers the 1.00
20ppb
while exhaled air from normal clinician:
adult subjects typically contains
Correct asthma diagnosis in 0.75
between 5 and 25 parts per bil-
over 80% of patients 8-75 years
lion (ppb) nitric oxide (5 to
using a cut off of 20ppb9.

Sensitivity
20 ppb in children), the exhaled 0.50
air of asthmatic subjects shows Correct asthma diagnosis in
between double and four times nearly 80% of children 4-8 years
the normal nitric oxide level. using a cut off of 10ppb14. 0.25
Exhaled NO
FEV1
This means that used in con- Exhaled NO (solid line) offers a
junction with well-established higher degree of diagnostic accuracy 0
0 0.25 0.50 0.75 1.00
techniques such as spirometry, for asthma (sensitivity 88% at a
cut-off of 20ppb) than tests based 1- Specificity
Feno measurement can be used Smith, 20049
by clinicians to help in the differ­ on lung function (dotted line). The
diagnosis of asthma was ascertained
ential diagnosis of eosinophilic
by a positive response to broncho-
bronchial asthma, thereby mini- dilator and/or positive bronchial
mizing inappropriate or ineffec- hyperresponsiveness in accordance
tive therapy. with ATS guidelines9.

Feno measurement offers:


R
 apid identification of non-compliance

Feno measurement provides an inflammatory therapy or not ad- also arise from poor inhalation
easy to use and non-invasive hering to the therapy prescribed. technique, inadequate steroid
tool for monitoring adherence dosage, chronic exposure to
to steroid treatment11, 15. Although anti-inflammatory allergen, or non-eosinophilic
treatment in asthma usually airway inflammation as the
In clinical practice, elevated reduces Feno, some patients cause of the asthma. Only rarely
Feno levels in patients taking continue to have elevated Feno will an asthma patient be truly
maintenance doses of inhaled levels, despite steroid treatment. steroid resistant16, 17.
steroids either means the patient This is most frequently a result
is not prescribed enough anti- of non-compliance, but may

5
How Can FeNO Measurement Help Improve Clinical Decision Making?

Feno has been shown to decrease rapidly in asthmatic patients when steroid
treatment is started. The decrease is a useful indicator of steroid response.

Feno measurement offers:


I nsights into steroid effectiveness

Exhaled NO > 100ppb


Feno responds faster than any Feno levels before and during 250
All patients
other marker to changes in anti-inflammatory therapy is now Exhaled NO 60–100ppb
steroid intake18, 19. There is a simple, quick and patient- 200
a clear dose-dependent relation- friendly way of checking that

Exhaled NO (ppb)
ship between the inhaled steroid steroid therapy is having the 150
dose and the fall in Feno level20. desired effect on airway
inflammation20, 21. 100
A reduction in Feno of at least
20% in unstable patients 50
indicates efficacy of the anti- The response to varied doses of
inflammatory treatment 21. The beclomethasone for patients with 0

implication for clinical practice initial Feno values of >100ppb 0 Baseline Placebo 100 400 800
and between 60 to 100ppb20.
is that monitoring a patient’s Beclomethasone dipropionate (µg)
Silkoff, 200120

Feno measurement offers:


P
 rediction of steroid response

Feno measurement can be used leukotriene receptor antagonist23.


for immediate and non-invasive
identification of steroid respon­ Patients with normal Feno levels
siveness. In patients with non- who do not show any symptom­
specific symptoms, a Feno value atic response to anti-inflamma- 1.00

of >47ppb is highly indic­ative tory treatment may have little


47ppb
of a subsequent corticosteriod or no underlying inflammation.
CARA060 Fig 21
0.75
response22. Feno measurement Other forms of therapy should
correctly identifies the respon- be considered, and discon-
Sensitivity

ders better than spirometry or tinuing of anti-inflammatory 0.50


PEF variabil­ity. treatment may also be appro-
priate.
Exhaled NO as a predictor of 0.25
FENO
response might help to identify In a group of patients with non-
FEV1 broncho-
individual children who achieve specific respiratory symptoms, Feno dilator response
measurement was significantly better 0
a greater improvement in asthma 0 0.25 0.50 0.75 1.00
than FEV1 bronchodilator response
control days with an inhaled 1- Specificity
in correctly identifying those who
corticosteroid compared with a will respond to inhaled fluticasone22. Smith, 200522

6
Feno measurement offers:
S
 teroid dose-titration that reduces cost and improves
patient outcome

Titrating the steroid dose to steroids without compromising FENO group


50
match the severity of airway in- asthma control25. In patients Control group
flammation results in a healthier already on steroids, the dose 40
patient with fewer emergency can be gradually reduced just
room visits and significantly to the point at which the Feno

Patients (%)
30
fewer exacerbations24. level starts to rise. Then the
steroid dose should be raised just 20
Several studies have now con- enough to keep the Feno level
firmed that routine monitoring stable.
10

of the Feno level as a marker for


inflammation makes it possible 0
Compared to conventional treat- 0 100 250 500 750 1000
to titrate the steroid dose ac-
ment guidelines, steroid titration Fluticasone (µg/day)
cording to the patient’s specific Smith, 200522
need25, 26. based on Feno and symptoms There was a significant difference
improved asthma prognosis in the distribution of doses of
Use of exhaled NO measure- (measured as im­proved hyper- inhaled fluticasone at the end of the
ments can significantly reduce responsiveness and less inflam- study. The mean dose was 370μg/
maintenance doses of inhaled mation)26. day in the Feno monitored group and
641μg/day in the control group. At
study end, the control of asthma in
the Feno group was non-significantly
Feno measurement offers: better 25.

N
 otification of loss of control

If a patient’s Feno level increases has a positive predictive value


by over 60% from one visit to of over 80% of an imminent de-
the next, even in the absence of terioration in asthma control 10.
asthma symptoms, this increase
1.00

Feno measurement offers: 49ppb


0.75

P
 rediction of asthma relapse
Sensitivity

0.50

When asymptomatic children


0.25
in clinical remission stopped Exhaled NO

taking steroids, a Feno level of A Feno level higher than 49 ppb


more than 49ppb 2 to 4 weeks 4 weeks after steroid removal 0
later was an effective predictor was highly indicative of asthma 0 0.25 0.50 0.75 1.00
of asthma relapse27. re­lapse 27. 1- Specificity
Pijnenburg, 200527

7
Factors Affecting
Exhaled NO Levels

Possible effect on the Feno level (%)

Airway viral infection28 100%


Allergic rhinitis 29
≈50%
Nitrate-rich diet 30
≈50%

Spirometric maneuvers31 10%


Exercise 32
5–25%
Alcohol consumption 33
20%
Bronchoconstriction 32, 34
25%
Ciliary dyskinesia 35
45%
Hypertension 36
50%
Cystic fibrosis 35
60%
Smoking 37
varies with amount
and duration

Always perform exhaled NO measurements first,


prior to any other respiratory test.

Always check if the patient:


• has an upper or lower airway infection
• is a smoker
• has consumed food or liquid in the past hour

Smoking reduces exhaled NO37. Healthy smokers


normally have Feno levels between 2-10ppb. In-
creased Feno levels in smokers are still significant
for ongoing eosinophilic inflammation. However,
near-normal levels (see page 10 and 11) are
difficult to analyze. Results should be interpreted
with great caution.

Upper or lower respiratory tract infections may


lead to increased Feno levels.

8
REFERENCES

1.  Van den Toorn LM, Overbeek SE, De Jongste JC, Leman K, Hoogsteden 20. S ilkoff PE, McClean PA, Spino M, Erlich L, Slutsky AS, Zamel N.
HC, Prins JB. Airway inflammation is present during clinical remission Dose-response relationship and reproducibility of the fall in exhaled
of atopic asthma. Am J Respir Crit Care Med 2001;164:2107-13. nitric oxide after inhaled beclomethasone dipropionate therapy in
2.  Payne DN, Adcock IM, Wilson NM, Oates T, Scallan M, Bush A. asthma patients. Chest 2001;119:1322-8. 
Relationship between exhaled nitric oxide and mucosal eosinophilic 21. Silkoff PE, et al. The Aerocrine exhaled nitric oxide monitoring system
inflammation in children with difficult asthma, after treatment with oral NIOX is cleared by the US Food and Drug Administration for monitoring
prednisolone. Am J Respir Crit Care Med 2001;164:1376-81. therapy in asthma. J Allergy Clin Immunol 2004;114:1241-56.
3. Gustafsson LE, Leone AM, Persson MG, Wiklund NP, Moncada S. 22. S mith AD, Cowan JO, Brassett KP, Filsell S, McLachlan C, Monti-Shee-
Endogenous nitric oxide is present in the exhaled air of rabbits, guinea han G, Herbison GP, Taylor DR. Exhaled nitric oxide: a predictor of
pigs and humans. Biochem Biophys Res Commun 1991;181:852-7. steroid response. Am J Respir Crit Care Med 2005;172:453-9.
4.  Alving K, Weitzberg E, Lundberg JM. Increased amount of nitric oxide 23. Zeiger RS, Szefler SJ, Phillips BR, Schatz M, Martinez FD, Chinchilli
in exhaled air of asthmatics. Eur Respir J 1993;6:1368-70. VM, Lemanske RF Jr, Strunk RC, Larsen G, Spahn JD, Bacharier
5.  De Jongste JC. Yes to NO: the first studies on exhaled nitric oxide- LB, Bloomberg GR, Guilbert TW, Heldt G, Morgan WJ, Moss MH,
driven asthma treatment (editorial). Eur Respir J 2005;26:1–3. Sorkness CA, Taussig LM; CARE Network of the NHLBI. Response
profiles to fluticasone and montelukast in mild-to-moderate persistent
6.  Silkoff PE, et al. ATS/ERS Recommendations for Standardized childhood asthma. J Allergy Clin Immunol. 2006 Jan;117(1):45-52.
Procedures for the Online and Offline Measurement of Exhaled Lower
Respiratory Nitric Oxide and Nasal Nitric Oxide, 2005. Am J Respir 24.Green RH, Brightling CE, McKenna S, et al. Asthma exacerbations and
Crit Care Med 2005;171:912-30. sputum eosinophil counts: a randomised controlled trial.
Lancet 2002;360:1715-21.
7. Warke T J, Fitch PS, Brown V. Exhaled nitric oxide correlates with
airway eosinophils in childhood asthma. Thorax 2002;57:383-87. 25. S mith AD, Cowan JO, Brassett KP, Herbison GP, Taylor DR. Use of
Exhaled Nitric Oxide Measurements to Guide Treatment in Chronic
8. Lex C, Ferreira F, Zacharasiewicz A, Nicholson AG, Haslam PL, Wilson Asthma. N Engl J Med 2005;352:2163-73.
NM, Hansel TT, Payne DN, Bush A. Airway Eosinophilia in Children
with Severe Asthma: Predictive Values of Noninvasive Tests. 26. Pijnenburg MW, Bakker EM, Hop WC, De Jongste JC. Titrating steroids
Am J Respir Crit Care Med. 2006 Sep 14; on exhaled nitric oxide in asthmatic children: a randomized
controlled trial. Am J Respir Crit Care Med 2005;172:831-6.
9. Smith AD, Cowan JO, Filsell S, McLachlan C, Monti-Sheehan G,
Jackson P, Taylor DR. Diagnosing asthma – Comparisons between  ijnenburg MW, Hofhuis W, Hop WC, De Jongste JC. Exhaled nitric
27. P
exhaled nitric oxide measurements and conventional tests. Am J Respir oxide predicts asthma relapse in children with clinical asthma
Crit Care Med 2004;169:473-8. remission. Thorax 2005;60:215-8.
10. Jones SL, Kittelson J, Cowan JO, et al. The predictive value of exhaled 28. M
 urphy AW, Platts-Mills TA, Lobo M, Hayden F. Respiratory nitric
nitric oxide measurements in assessing changes in asthma control. oxide levels in experimental human influenza. Chest 1998;114:452-6.
Am J Respir Crit Care Med 2001;164:738-43. 29. H
 enriksen AH, Sue-Chu M, Lingaas HT, Langhammer A, Bjermer L.
11. Beck-Ripp J, Griese M, Arenz S, Koring C, Pasqualoni B, Bufler P. Exhaled and nasal NO levels in allergic rhinitis: relation to
Changes of exhaled nitric oxide during steroid treatment of childhood sensitization, pollen season and bronchial hyperresponsiveness.
asthma. Eur Respir J 2002;19:1015-9. Eur Respir J 1999;13:301-6.
12. Piacentini GL, Bodini A, Costella S, et al. Allergen avoidance is  lin AC, Aldenbratt A, Ekman A, et al. Increased nitric oxide in
30. O
associated with a fall in exhaled nitric oxide in asthmatic children. exhaled air after intake of a nitrate-rich meal.
J Allergy Clin Immunol 1999;104:1323-4. Respir Med 2001;95:153-8.
13. Ihre E, Gustafsson LE, Kumlin M, Gyllfors P, Dahlen B. Early rise in 31. S ilkoff PE, Wakita S, Chatkin J, et al. Exhaled nitric oxide after beta2-
exhaled no and mast cell activation in repeated low dose allergen agonist inhalation and spirometry in asthma.
challenge. Eur Respir J. 2006;27:1152-1159. Am J Respir Crit Care Med 1999;159:940-4.
14. Malmberg LP, Pelkonen AS, Haahtela T, Turpeinen M. Exhaled nitric 32. Terada A, et al. Exhaled Nitric Oxide Decreases during Exercise-
oxide rather than lung function distinguishes preschool children with induced Bronchoconstriction in Children with Asthma.
probable asthma. Thorax 2003;58:494-9. Am J Respir Crit Care Med 2001;164:1879-84.
15. Delgado-Corcoran C, Kissoon N, Murphy SP, Duckworth LJ. Exhaled 33. Yates DH, Kharitonov SA, Robbins RA, Thomas PS, Barnes PJ.
nitric oxide reflects asthma severity and asthma control. The effect of alcohol ingestion on exhaled nitric oxide.
Pediatr Crit Care Med 2004 Vol.5, No.1. Eur Respir J 1996;9:1130-3.
16. Stirling RG, Kharitonov SA, Campbell D, et al. Increase in exhaled  iacentini GL, Bodini A, Peroni DG, Miraglia del Giudice M, Jr.,
34. P
nitric oxide levels in patients with difficult asthma and correlation with Costella S, Boner AL. Reduction in exhaled nitric oxide immediately
symptoms and disease severity despite treatment with oral and inhaled after methacholine challenge in asthmatic children.
corticosteroids. Asthma and Allergy Group. Thorax 1998;53:1030-4. Thorax 2002;57:771-3.
17. Payne DN, Wilson NM, James A, Hablas H, Agrafioti C, Bush A.  arang I, Ersu R, Wilson NM, Bush A. Nitric oxide in chronic airway
35. N
Evidence for different subgroups of difficult asthma in children. inflammation in children: diagnostic use and pathophysiological
Thorax 2001;56:345-50. significance. Thorax 2002;57:586-9.
18. Massaro AF, Gaston B, Kita D, Fanta C, Stamler JS, Drazen JM. 36. R
 olla G, Colagrande P, Scappaticci E, et al. Exhaled nitric oxide in
Expired nitric oxide levels during treatment of acute asthma. systemic sclerosis: relationships with lung involvement and pulmonary
Am J Respir Crit Care Med 1995;152:800-3. hypertension. J Rheumatol 2000;27:1693-8.
19. Tsai YG, Lee MY, Yang KD, Chu DM, Yuh YS, Hung CH. A single dose of 37. Verleden GM, Dupont LJ, Verpeut AC, Demedts MG. The effect of
nebulized budesonide decreases exhaled nitric oxide in children with cigarette smoking on exhaled nitric oxide in mild steroid-naive
acute asthma. J Pediatr 2001;139:433-7. asthmatics. Chest 1999;116(1):59-64.

9
Diagnosis
Guide to Interpretation of Feno Values in
Symptomatic Steroid Naïve Patients
Do not use this guide if the patient is a smoker. Data are inconclusive for current smokers.
FeNO values are complementary to spirometry values in the diagnosis and assessment of airway disease.

LOW NORMAL INTERMEDIATE HIGH

Eosinophilic Unlikely Unlikely Present, but mild Significant


inflammation

A D U LT S
Feno (ppb)* <5 5–25 25–50 > 50

Consider: Consider: Interpretation based on Consider:


Smoker Neutrophilic asthma clinical presentation Atopic asthma if the
(besides Anxiety/hyper- history is appropriate
considerations ventilation If FEV1 <80% predicted,
in children) Vocal cord dysfunction diagnosis of asthma is
Rhinosinusitis very likely
Gastro-oesophageal Eosinophilic bronchitis
reflux Churg-Strauss
Cardiac disease syndrome
A positive response
to a trial of inhaled
or oral steroid is likely
In ex-smokers with
COPD this may also
be true

C H ILDR EN (<12 year s )


Feno (ppb)* <5 5–20 20–35 > 35

Consider: Consider: Interpretation based on If combined with any


Primary ciliary Wheezy bronchitis clinical presentation objective evidence of
dyskinesia (check Gastro-oesophageal reversible airway
nasal NO) reflux obstruction, asthma
Cystic fibrosis ENT disorders is very likely and a
Chronic lung positive response to
Neutrophilic asthma a trial of inhaled or
disease of Vocal cord dysfunction
prematurity oral steroids is likely
Anxiety/hyper-
ventilation
Immunodeficiencies

10
Management
Guide to Interpretation of Feno Values in
Anti-Inflammatory Treated Patients
Do not use this guide if the patient is a smoker. Data are inconclusive for current smokers.
FeNO values are complementary to spirometry values in the diagnosis and assessment of airway disease.

LOW NORMAL INTERMEDIATE HIGH

Eosinophilic
Unlikely Unlikely Present, but mild Significant
inflammation

A D U LT S
Or a rise of 60% or
Feno (ppb)* <5 5–25 25–50 > 50 more since previous
measurement

Consider: If symptomatic, review If symptomatic, consider: If symptomatic, consider:


Smoker diagnosis: Infection as reason for Inadequate ICS treatment:
(besides Neutrophilic asthma worsening (1) check compliance
considerations Anxiety/hyperventilation High levels of allergen (2) check for poor
in children) Vocal cord dysfunction exposure inhaler technique
Rhinosinusitis Adding in other therapy (3) inadequate ICS dose
Gastro-oesophageal apart from ICS (e.g. Continuous high level
reflux long acting ß-agonist) allergen exposure
Consider ICS dose Imminent exacerbation
If asymptomatic: increase or relapse depending on
Implies good history of individual
compliance with If asymptomatic:
patient (more likely if
treatment. Reduce dose No change in ICS dose,
ICS dose is zero)
or, in case of low ICS if patient is stable
Steroid resistance (rare)
dose, even withdraw
ICS altogether If asymptomatic:
No change in ICS dose,
if patient is stable

C H ILDR EN (<12 year s )


Or a rise of 60% or
Feno (ppb)* <5 5–20 20–35 > 35 more since previous
measurement

Consider: If symptomatic, review If symptomatic (besides If symptomatic


Primary ciliary diagnosis: considerations in adults), (besides considerations
dyskinesia Wheezy bronchitis consider: in adults), consider:
Cystic fibrosis Gastro-oesophageal Possible inadequate Metered dose inhaler
Chronic lung reflux ICS treatment: and spacer if patient is
disease ENT disorders (1) check compliance currently using a dry
For references and Neutrophilic asthma (2) check for poor inhaler powder device
information of exhaled Vocal cord dysfunction technique and consider
If asymptomatic:
NO in asthma see the
Anxiety/hyperventilation metered dose inhaler
Scientific Backgrounder and spacer if patient is No change in ICS dose,
– Exhaled Nitric Oxide, Immunodeficiencies currently using a dry if patient is stable
A Noninvasive Marker powder device
for Inflammation, If asymptomatic:
issued by Aerocrine. Implies good If asymptomatic:
compliance with No change in ICS dose,
*At 50 mL/s flow rate. treatment. Reduce dose if patient is stable
Partly based on Taylor DR, or, in case of low ICS
Pijnenburg MW, Smith AD, dose, even withdraw
De Jongste JC. Exhaled nitric
oxide measurements: clinical ICS altogether
application and interpretation.
Thorax 2006;61:817-27. 11
a led
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Ex
Oxid e

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– Fr
Fe n o

Want to know more?


Nearly 1,500 clinical papers related to the use of Feno measurement in exhaled breath
have been published in peer reviewed journals;
Visit www.aerocrine.com, Feno in Clinical Practice, to view the abstracts.
For a more detailed review of available literature about exhaled NO in asthma,
please refer to the annually updated Scientific Backgrounder
published by Aerocrine.

Aerocrine sells CE marked and FDA cleared exhaled NO systems that provide
repeatable, trustworthy results as proven in GCP clinical trials.
Using a standardized, approved and accurate device is essential
for the interpretation and application of exhaled NO values.

Based on the company’s intellectual property, Aerocrine develops and commercializes products for the monitoring of nitric oxide (NO)
as a marker of inflammation, to improve the management and care of patients with inflammatory disease in the airways.

Patents:
US Patent 5,447,165, US Patent 5,922,610, US Patent 6,038,913, US Patent 6,063,027, US Patent 6,099,480, US Patent 6,149,606, US Patent 6,183,416,
US Patent 6,511,425, US Patent 6,626,844, US Patent 6,723,056, US Patent 6,761,185, US Patent 7,014,692 and patents pending.

EMD-000095-03 December 2006

– Improving management and care of patients with inflammatory disorders

Aerocrine AB, P.O. Box 1024, SE-171 21 Solna, Sweden.


Phone: +46 8 629 07 80. Fax: +46 8 629 07 81. E-mail: info@aerocrine.com.
www.aerocrine.com

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