Hospital/Clinic Name
Physician Name
Address
Date
RE:
Date
Patient Name:
Subscriber Number:
Claim Number:
Date of Service:
Exhaled Nitric Oxide per CPT® 95012 and Payment of Services
Asthma care has reached a turning point: not only do I need the clinical history, physical
examination, and functional assessment; I also need an assessment of the state of airway
inflammation to provide optimal care. Exhaled nitric oxide measurement (CPT ® 95012) enables
me to assess airway inflammation quickly and reliably and without the cost, time and process
associated with sputum induction and cytological staining and examination.
Asthma is defined as a chronic inflammatory process which leads to airflow limitation and
increased responsiveness to asthma triggers. Standard methods for diagnosing and monitoring
asthma traditionally focus on symptoms and airway constriction. Until now, routine assessment
of the underlying level of inflammation has not been possible. Today a substantial amount of
data exists to confirm the clinical value of exhaled nitric oxide. The American Thoracic Society
(ATS) has published guidelines for the standardization of exhaled nitric oxide measurement 1. In
addition, the NHLBI Asthma Guidelines state that there is a positive role for exhaled nitric oxide
measurement as an inflammatory marker2. More than 1500 publications in peer reviewed
journals establish exhaled NO as the most effective marker of airway inflammation.







Exhaled NO improves diagnostic accuracy3-6: The levels in asthmatics are 2-6 times
higher, thereby identifying eosinophilic asthma in symptomatic patients which minimizes
inappropriate or ineffective therapy.
Exhaled NO predicts anti-inflammatory response7-9: Steroid response can be expected in
patients with an ongoing eosinophilic inflammation. Exhaled NO can be used for
immediate and non-invasive identification of steroid responsiveness. Patient with normal
exhaled NO values and no symptomatic response to anti-inflammatory treatment may not
have an underlying eosinophilic inflammation.
Exhaled NO determines the best treatment for chronic cough10: Patients with an elevated
exhaled NO value and chronic cough are likely to respond positively to inhaled
corticosteroids, while those with normal values are unlikely to respond.
Exhaled NO values, low and high, are of clinical significance 11: There is improved
management and practitioner diagnostic confidence when treating patients presenting
with non-specific respiratory symptoms.
Exhaled NO improves the patient’s understanding of their airway disease, and improves
compliance12-17: Exhaled NO values change rapidly depending upon anti-inflammatory
treatment intake or allergen exposure, therefore elevated exhaled NO values in patients
taking maintenance doses of inhaled corticosteroids determines whether or not the
patient is adhering to the therapy prescribed, has a poor inhalation technique, is still
exposed to allergens, or has been prescribed enough anti-inflammatory therapy.
Exhaled NO is cost effective18: Both healthcare costs for unscheduled patient visits due
to loss of asthma control and the cost of inhaled corticosteroids are reduced.
Exhaled NO optimizes dose adjustments19: Steroid dose titration according to the
patient’s needs is possible with the routine monitoring of exhaled NO.

Exhaled NO predicts asthma relapse20: When asymptomatic children in clinical remission
stop taking steroids, an exhaled NO value ≥49 ppb, 2-4 weeks later is an effective
predictor of asthma relapse.
Hence, assessment of exhaled NO enables me to alter care in a more timely and appropriate
manner.
Nitric oxide is a gas produced in the airways. Levels of nitric oxide (NO) can be measured with
an FDA approved device and guidelines for measurement and interpretation are published.1
Recent NHLBI Asthma Guidelines indicate the positive role of inflammatory markers; e.g. exhaled
NO measurement.2 Exhaled NO levels correlate strongly with other measures of eosinophilic
airway inflammation (sputum eosinophil levels, bronchial alveolar lavage fluid eosinophil levels,
major basic protein levels in airway epithelium, and measures of bronchial provocation such as
methacholine or histamine challenge with spirometry). 21-25 Measurement of exhaled NI is noninvasive and easy to perform with immediate results. It is significantly less costly than each of the
other tests mentioned (retail fee $62). It is also a better predictor of response to corticosteroid
therapy than other measures of lung function.26 Because this test can predict whether a patient
with non-specific respiratory symptoms (such as cough) will or will not respond to steroid therapy,
it has the potential of reducing health care costs (such as the cost of unnecessary long-term
controller medications due to inaccurate diagnosis of asthma).
I respectfully request a reconsideration of the reimbursement policy for exhaled NO monitoring in
inflammatory airway disease.
Sincerely,
, MD
Department of
Hospital/Clinical Name
The measurement of Exhaled NO has been increasingly used in the management of asthma.
The medical literature extends from mid-1990 and at this point in time contains very strong,
conclusive evidence for the use of Exhaled NO as an important tool in the clinical management of
asthma.
Bibliography:
1. ATS/ERS recommendations for standardized procedures for the online and offline
measurement of exhaled lower respiratory nitric oxide and nasal nitric oxide, 2005. Am J
Respir Crit Care Med. 2005 Apr 15;171(8):912-30.
2. NHLBI National Heart, Lung and Blood Institute. Expert Panel Report 3: Guidelines for the
diagnosis and management of asthma—full report 2007. August 28, 2007. Available at:
www.nhlbi.nih.gov/guidelines/asthma/asthgdln.pdf.
3. Dressel H, de la Motte D, Reichert J, Ochmann U, Petru R, Angerer P, Holz O, Nowak D,
Jörres RA, Exhaled nitric oxide: Independent effects of atopy, smoking, respiratory tract
infection, gender and height. Resp. Med. 2008 Jul;102(7):962-9.
4. Malmberg LP, Petays T, Haahtela T, et al. Exhaled nitric oxide in healthy non-atopic schoolage children: determinants and height-adjusted reference values. Pediatr Pulmonol 2006;
41: 635-42.
5. Smith AD, Cowan JO, Filsell S, McLachlan C, Monti-Sheehan G, Jackson P, Taylor DR.
Diagnosing asthma – Comparisons between exhaled nitric oxide measurements and
conventional tests. Am J Respir Crit Care Med 2004;169:473-8.
6. Malmberg LP, Pelkonen AS, Haahtela T, Turpeinen M. Exhaled nitric-oxide rather than lung
function distinguishes preschool children with probable asthma. Thorax 2003;58:494-9.
7. Smith AD, Cowan JO, Brassett KP, Filsell S, McLachlan C, Monti- Sheehan G, Herbison GP,
Taylor DR. Exhaled nitric oxide: a predictor of steroid response. Am J Respir Crit Care Med
2005;172:453-9.
8. Zeiger RS, Szefler SJ, Phillips BR, Schatz M, Martinez FD, Chinchilli VM, Lemanske RF Jr,
Strunk RC, Larsen G, Spahn JD, Bacharier LB, Bloomberg GR, Guilbert TW, Heldt G,
Morgan WJ, Moss MH, Sorkness CA, Taussig LM; CARE Network of the NHLBI. Response
profiles to fluticasone and montelukast in mild-to-moderate persistent childhood asthma. J
Allergy Clin Immunol. 2006 Jan;117(1):45-52.
9. Bratton DL, Lanz MJ, Miyazawa N, White CW, Silkoff PE. Exhaled nitric oxide before and
after montelukast sodium therapy in school-age children with chronic asthma: A preliminary
study. Pediatr Pulmonol 1999;28:402-407.
10. Hahn PY, Morgenthaler TI, Lim KG. Use of exhaled nitric oxide in predicting response to
inhaled corticosteroids for chronic cough. Mayo Clin Proc 2007; 82: 1350–5.
11. Hewitt RS, Modrich CM, Medlicott T, Cowan JO, Taylor DR. Supporting the diagnosis of nonspecific respiratory symptoms in primary care: the role of exhaled Nitric Oxide measurement
and spirometry. Prim Care Respir J; 2008 Apr; 17(2):97-103.
12. Silkoff PE, et al. The Aerocrine exhaled nitric oxide monitoring system NIOX is cleared by
the US Food and Drug Administration for monitoring therapy in asthma. J Allergy Clin
Immunol 2004;114:1241-56.
13. Sorkness CA, Lemanske RF, Jr., Mauger DT, et al. Long-term comparison of 3 controller
regimens for mild-moderate persistent childhood asthma: The Pediatric Asthma Controller
Trial. J Allergy Clin Immunol 2007; 119: 64-72.
14. Piacentini GL, Bodini A, Costella S, et al. Allergen avoidance is as sociated with a fall in
exhaled nitric oxide in asthmatic children. J Allergy Clin Immunol 1999;104:1323-4.
15. Delgado-Corcoran C, Kissoon N, Murphy SP, Duckworth LJ. Exhaled nitric oxide reflects
asthma severity and asthma control. Pediatr Crit Care Med 2004 Vol.5, No.1.
16. Stirling RG, Kharitonov SA, Campbell D, et al. Increase in exhaled nitric oxide levels in
patients with difficult asthma and correlation with symptoms and disease severity despite
treatment with oral and inhaled corticosteroids. Asthma and Allergy Group. Thorax
1998;53:1030-4.
17. Payne DN, Wilson NM, James A, Hablas H, Agrafioti C, Bush A. Evidence for different
subgroups of difficult asthma in children. Thorax 2001;56:345-50.
18. Berg J, Lindgren P. Economic evaluation of FENO measurement in diagnosis and 1-year
management of asthma in Germany. Respir Med 2008; 102: 219–31.
19. Smith AD, Cowan JO, Brassett KP, Herbison GP, Taylor DR. Use of Exhaled Nitric Oxide
Measurements to Guide Treatment in Chronic Asthma. N Engl J Med 2005;352:2163-73.
20. Pijnenburg MW, Hofhuis W, Hop WC, De Jongste JC. Exhaled nitric oxide predicts asthma
relapse in children with clinical asthma remision. Thorax 2005;60:215-8.
21. Jatakanon A, et al. Correlation between exhaled nitric oxide, sputum eosinophils, and
methacholine responsiveness in patients with mild asthma. Thorax 1998;53:91-95.
22. Dupont LJ, et al. Exhaled nitric oxide correlates with airway hyperresponsiveness in steroidnaïve patients with mild asthma. Am J Respir Crit Care Med 1998; 157:894-898.
23. Berry MA et al. The use of exhaled nitric oxide concentration to identify eosinophilic airway
inflammation: an observational study in adults with asthma. Clin Exp Allergy 2005;35:1175-9.
24. van den Toorn LM et al. Airway inflammation is present during clinical remission of asthma.
Am J Respir Crit Care Med 2001;164:1127-32.
25. Warke TJ, et al. Exhaled nitric oxide correlates with airway eosinophils in childhood asthma.
Thorax 2002:57:383-7.
26. Smith AD, et al. Exhaled nitric oxide: a predictor of steroid response. Am J Respir Crit Care
Med 2005;172:453-9.
Physician’s Current Procedural Terminology (CPT®) codes, descriptions and two-digit numeric
modifiers are copyright ©2007 American Medical Association. All Rights Reserved.