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Effective Date: 09/01/2013 |
Title: Exhaled Breath Tests for Lung Inflammation
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Revision Date:
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Document: BI414:00
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CPT Code(s): 83987, 95012
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Public Statement
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Effective Date:
a)
This policy
will apply to all services performed on or after the above revision date which
will become the new effective date.
b)
For all
services referred to in this policy that were performed before the revision
date, contact customer service for the rules that would apply.
The
measurement of exhaled nitric oxide is used to indicate inflammation in the
lungs in conditions such as asthma. It is considered investigational as there is
insufficient evidence of its effectiveness.
The
measurement of exhaled condensate pH is also used in assessing lung inflammation
and it is considered investigational due to lack of evidence that it is
effective.
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Medical Statement
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QualChoice considers measurement of exhaled nitric oxide experimental and
investigational for assessment of asthma, lung cancer, other pulmonary
diseases, (e.g., chronic obstructive pulmonary disease, pulmonary
tuberculosis, sino-nasal disease) and all other conditions because of
insufficient evidence of its effectiveness.
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QualChoice considers measurement of exhaled breath condensate (EBC) pH
experimental and investigational for assessment of asthma, lung cancer,
other pulmonary diseases, and all other conditions because of insufficient
evidence of its effectiveness.
Codes Used In This BI:
83987
95012
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Background
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Powell, et al. (2011) concluded that asthma exacerbations during pregnancy can be significantly reduced with a validated FENO-based treatment algorithm. The investigators reported on a double-blind, parallel-group, controlled trial in two antenatal clinics in Australia. The investigators randomly assigned 220 pregnant, non-smoking women with asthma to treatment adjustment at monthly visits by an algorithm using clinical symptoms (control group) or FENO concentrations (active intervention group). The primary outcome was total asthma exacerbations. The investigators reported that the exacerbation rate was lower in the FENO group than in the control group (0•288 versus 0•615 exacerbations per pregnancy; incidence rate ratio 0•496, 95% CI 0•325-0•755; p=0•001). In the FENO group, quality of life was improved (score on short form 12 mental summary was 56•9 [95% CI 50•2-59•3] in FENO group versus 54•2 [46•1-57•6] in control group; p=0•037) and neonatal hospitalizations were reduced (eight [8%] versus 18 [17%]; p=0•046). A limitation of this study is that the control group`s algorithm differed from current guidelines and that significantly more women in the FENO group were receiving corticosteroids than in the control group.
Using a similar treatment algorithm, Pike, et al. (2012) concluded that FENO-guided inhaled corticosteroid titration did not reduce corticosteroid usage or exacerbation frequency in children with moderate to severe asthma. The investigators conducted a randomized controlled clinical trial to evaluate whether monitoring FENO can improve outpatient management of children aged 6 to 17 years with moderate to severe asthma. Ninety children were randomized to FENO-driven therapy or to a standard management group where therapy was driven by conventional markers of asthma control. Inhaled corticosteroids or long-acting bronchodilator therapies were altered according to FENO levels in combination with reported symptoms in the FENO group. Subjects were assessed twice monthly for 12 months. Inhaled corticosteroid dose and exacerbation frequency change were compared between groups in an intention to treat analysis. The investigators reported that no difference was found between the two groups in either change in corticosteroid dose or exacerbation frequency. The investigators stated that results were similar in a planned secondary analysis of atopic asthmatics.
Calhoun, et al. (2012) reported the results of the use of FENO in adults from the Best Adjustment Strategy for Asthma in the Long Term (BASALT) trial, a randomized controlled clinical trial conducted by the Asthma Clinical Research Network at 10 academic medical centers in the United States. The investigators found that, among adults with mild to moderate persistent asthma controlled with low-dose inhaled corticosteroid therapy, the use of either FENO-based or symptom-based adjustment of inhaled corticosteroids was not superior to physician assessment-based adjustment of inhaled corticosteroids in time to treatment failure. The investigators reported on the results of a randomized, parallel, 3-group, placebo-controlled, multiply-blinded trial of 342 adults with mild to moderate asthma controlled by low-dose inhaled corticosteroid therapy who were assigned to physician assessment-based adjustment, FENO-based adjustment, and symptom-based adjustment. For physician assessment-based adjustment and FENO-based adjustment, the dose of inhaled corticosteroids was adjusted every 6 weeks; for symptom-based adjustment, inhaled corticosteroids were taken with each albuterol rescue use. The primary outcome was time to treatment failure. The investigators reported that there were no significant differences in time to treatment failure. The 9-month Kaplan-Meier failure rates were 22% (97.5% CI, 14%-33%; 24 events) for physician assessment-based adjustment, 20% (97.5% CI, 13%-30%; 21 events) for FENO-based adjustment, and 15% (97.5% CI, 9%-25%; 16 events) for symptom-based adjustment. The hazard ratio for physician assessment-based adjustment versus FENO-based adjustment was 1.2 (97.5% CI, 0.6-2.3). The hazard ratio for physician assessment-based adjustment versus symptom-based adjustment was 1.6 (97.5% CI, 0.8-3.3).
An editorial accompanying the BASALT trial (O`Connor & Reibman, 2012) concluded that dose adjustment based on exhaled nitric oxide measurements has not been shown to improve outcomes in routine asthma management. The editorialist commented that the result of the BASALT trial is consistent with prior evidence that routine exhaled nitric oxide monitoring is not warranted for managing most patients with asthma. The editorialist noted that the recent American Thoracic Society practice guideline recommends the use of exhaled nitric oxide measurement “in monitoring airway inflammation in patients with asthma (strong recommendation, low quality of evidence),” but that, in light of the BASALT findings, it is difficult to justify additional health care expenditures for routinely monitoring exhaled nitric oxide in adults with mild to moderate asthma. The editorialist noted that there may be a role for exhaled nitric oxide measurement, however, when the diagnosis of asthma is not clear or for specific patient subgroups, but that further research is needed to identify the clinical scenarios in which exhaled nitric oxide measurement may improve clinical outcomes.
Lester, et al. (2012) reported on the use of a comprehensive asthma management program by an urban community health center. The program included serial FeNO measurements among several program components. Other components of the program were: use of asthma management guidelines; use of a team approach to asthma management; use of a standardized tool for screening for asthma risk factors, symptoms, and level of asthma control; use of a workflow algorithm and chart form incorporated into an electronic health record to collect data and track clinical measures for an asthma registry; use of asthma health educators to assist patients in setting asthma self management goals and educate them in asthma self-management; use of community resources (visiting nurses, a state-funded pest control program, and durable medical equipment vendors for products such as aerochambers and nebulizers); and regular followup, with frequency based upon asthma severity. The authors reported that 95.8 percent of patients enrolled in the program had an asthma severity assessment, 95.4 percent of persistent asthmatics were on anti-inflammatory medications, 68.2 percent of asthma patients have documented asthma self-management goals, and 5.2 percent of asthma patients have a self-reported visit to the emergency room in the six months preceding their most recent visit. Because the program includes multiple components, the contribution of FeNO measurements to these outcomes cannot be determined.
Exhaled breath condensate pH is a novel, noninvasive research approach to monitor lung diseases; however, well-designed controlled studies are needed to establish the clinical utility of EBC pH for the assessment of asthma and other chronic pulmonary diseases.
Baraldi and Carraro (2006) stated that EBC is still only a research tool. Ko et al (2007) stated that there is some evidence that certain markers in EBC differ between patients with asthma and controls, and some markers may correlate with asthma severity and lung function, but there are many methodologic pitfalls with EBC assessment that limit its clinical applicability at present. The authors concluded that more studies are needed before this technique can be recommended for clinical use.
Cepelak and Dodig (2007) stated that in spite of many scientific studies involving lung disease patients, methodology for EBC collection and analysis has not yet been realized for daily utilization. Additional studies of the exact origin of condensate constituents and standardization of the overall analytical process, including collection, storage, analysis and result interpretation, are needed. Irrespective of these limitations, further investigation of this sample type is fully justified by the fact that classical specimens used in the management of pulmonary diseases are either obtained by invasive procedures (e.g., induced sputum, biopsy, broncho-alveolar lavage) or cannot provide appropriate information (e.g., urine, serum). Analysis of EBC in the future might contribute significantly to the understanding of the physiological and pathophysiological processes in lungs, to early detection, diagnosis and follow-up of disease progression, and to evaluation of therapeutic response.
Guidelines from the National Asthma Education Program (NIH, 2007) stated that many biomarkers have been proposed, including concentration of hydrogen ions and various other metabolites in an exhaled breath condensate, but that few studies have validated these markers. The guidelines stated that these biomarkers may have a role in asthma management in the future.
Chan and colleagues (2009) stated that breath analysis, which includes gaseous phase analysis that measures volatile organic compounds using electronic noses, FENO, and EBC, has been proposed as a non-invasive and simple technique to investigate neoplastic processes in the airways. Exhaled breath condensate can be easily collected by breathing into a cooling system that condenses the water vapor in the breath. It has already been suggested to be a useful method to monitor severity of diseases such as asthma and to act as a surrogate measure of compliance to medical therapy. Presently, there still remains a relative paucity of lung cancer research involving EBC. However, since EBC is a simple, non-invasive technique that can be easily performed, even in ill patients, it has the potential to be validated for use in screening for the early diagnosis of lung cancer.
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Reference
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Powell H, Murphy VE, Taylor DR, et al. Management of asthma in pregnancy guided by measurement of fraction of exhaled nitric oxide: A double-blind, randomised controlled trial. Lancet. 2011;378(9795):983-990.
Yoon HI, Sin DD. Biomarkers of therapeutic response in patients with chronic obstructive pulmonary disease: A critical review of the literature. Drugs. 2011;71(14):1821-1837.
Global Initiative for Asthma (GINA). Global strategy for asthma management and prevention 2011 (update). Bethesda, MD: Global Initiative for Asthma (GINA); December 2011.
Lester D, Mohammad A, Leach EE, et al. An investigation of asthma care best practices in a community health center. J Health Care Poor Underserved. 2012;23(3 Suppl):255-264.
Rosenberg SR, Kalhan R. Biomarkers in chronic obstructive pulmonary disease. Transl Res. 2012;159(4):228-237.
Jartti T, Wendelin-Saarenhovi M, Heinonen I, et al. Childhood asthma management guided by repeated FeNO measurements: A meta-analysis. Paediatr Respir Rev. 2012;13(3):178-183.
Pike K, Selby A, Price S, et al. Exhaled nitric oxide monitoring does not reduce exacerbation frequency or inhaled corticosteroid dose in paediatric asthma: A randomised controlled trial. Clin Respir J. 2012 Jul 2. [Epub ahead of print]
Petsky HL, Cates CJ, Lasserson TJ, et al. A systematic review and meta-analysis: Tailoring asthma treatment on eosinophilic markers (exhaled nitric oxide or sputum eosinophils). Thorax. 2012;67(3):199-208.
Calhoun WJ, Ameredes BT, King TS, et al.; Asthma Clinical Research Network of the National Heart, Lung, and Blood Institute. Comparison of physician-, biomarker-, and symptom-based strategies for adjustment of inhaled corticosteroid therapy in adults with asthma: The BASALT randomized controlled trial. JAMA. 2012;308(10):987-997.
O’Connor GT, Reibman J. Inhaled corticosteroid dose adjustment in mild persistent asthma. JAMA. 2012;308(10):1036-1037.
Chladkova J, Krcmova I, Chladek J, et al. Validation of nitrite and nitrate measurements in exhaled breath condensate. Respiration. 2006;73(2):173-179.
Zacharasiewicz A, Erin EM, Bush A. Noninvasive monitoring of airway inflammation and steroid reduction in children with asthma. Curr Opin Allergy Clin Immunol. 2006;6(3):155-160.
Boyce PD, Kim JY, Weissman DN, et al. pH increase observed in exhaled breath condensate from welding fume exposure. J Occup Environ Med. 2006;48(4):353-356.
Baraldi E, Carraro S. Exhaled NO and breath condensate. Paediatr Respir Rev. 2006;7 Suppl 1:S20-S22.
Ko FW, Leung TF, Hui DS. Are exhaled breath condensates useful in monitoring asthma? Curr Allergy Asthma Rep. 2007;7(1):65-71.
Cepelak I, Dodig S. Exhaled breath condensate: A new method for lung disease diagnosis. Clin Chem Lab Med. 2007;45(8):945-952.
Borrill ZL, Roy K, Singh D. Exhaled breath condensate biomarkers in COPD. Eur Respir J. 2008;32(2):472-486.
National Institutes of Health (NIH), National Heart, Lung, and Blood Institute, National Asthma Education Program. Expert panel report 3: Guidelines for the diagnosis and management of asthma. Full Report 2007. Bethesda, MD: NIH; 2007.
Chan HP, Lewis C, Thomas PS. Exhaled breath analysis: Novel approach for early detection of lung cancer. Lung Cancer. 2009;63(2):164-168.
Dalaveris E, Kerenidi T, Katsabeki-Katsafli A, et al. VEGF, TNF-alpha and 8-isoprostane levels in exhaled breath condensate and serum of patients with lung cancer. Lung Cancer. 2009;64(2):219-225.
Fila L, Musil J. Examination of exhaled breath condensate in cystic fibrosis. Cas Lek Cesk. 2010;149(4):173-177.
Popov TA. Human exhaled breath analysis. Ann Allergy Asthma Immunol. 2011;106(6):451-456; quiz 457.
Teng Y, Sun P, Zhang J, et al. Hydrogen peroxide in exhaled breath condensate in patients with asthma: A promising biomarker? Chest. 2011;140(1):108-116.
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Application to Products
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This policy applies to all health plans administered by QualChoice, both those insured by QualChoice and those that are self-funded by the sponsoring employer, unless there is indication in this policy otherwise or a stated exclusion in your medical plan booklet. Consult the individual plan sponsor Summary Plan Description (SPD) for self-insured plans or the specific Evidence of Coverage (EOC) for those plans insured by QualChoice. In the event of a discrepancy between this policy and a self-insured customer’s SPD or the specific QualChoice EOC, the SPD or EOC, as applicable, will prevail. State and federal mandates will be followed as they apply.
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Changes: QualChoice reserves the right to alter, amend, change or supplement benefit interpretations as needed.
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