Document Detail

Clinical application of exhaled nitric oxide measurement in pediatric lung diseases.
Jump to Full Text
MedLine Citation:
PMID:  23273317     Owner:  NLM     Status:  Publisher    
ABSTRACT: Fractional exhaled nitric oxide (FeNO) is a non invasive method for assessing the inflammatory status of children with airway disease. Different ways to measure FeNO levels are currently available. The possibility of measuring FeNO levels in an office setting even in young children, and the commercial availability of portable devices, support the routine use of FeNO determination in the daily pediatric practice. Although many confounding factors may affect its measurement, FeNO is now widely used in the management of children with asthma, and seems to provide significantly higher diagnostic accuracy than lung function or bronchial challenge tests. The role of FeNO in airway infection (e.g. viral bronchiolitis and common acquired pneumonia), in bronchiectasis, or in cases with diffuse lung disease is less clear. This review focuses on the most recent advances and the current clinical applications of FeNO measurement in pediatric lung disease.
Angelo Manna; Carlo Caffarelli; Margherita Varini; Carlotta Povesi Dascola; Silvia Montella; Marco Maglione; Francesco Sperlì; Francesca Santamaria
Related Documents :
22168387 - Detection of human bocavirus from children and adults with acute respiratory tract illn...
19497627 - Non-invasive assessment of benign vocal folds lesions in children by means of ultrasono...
16952597 - Defective in vitro contractility of ureteropelvic junction in children with functional ...
21620157 - Maternal mental illness and the safety and stability of maltreated children.
12070947 - The post-mortem pathology of hiv-1-infected african children.
23088247 - Perimetry in children: survey of current practices in the united kingdom and ireland.
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-12-31
Journal Detail:
Title:  Italian journal of pediatrics     Volume:  38     ISSN:  1824-7288     ISO Abbreviation:  Ital J Pediatr     Publication Date:  2012 Dec 
Date Detail:
Created Date:  2012-12-31     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101510759     Medline TA:  Ital J Pediatr     Country:  -    
Other Details:
Languages:  ENG     Pagination:  74     Citation Subset:  -    
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

Full Text
Journal Information
Journal ID (nlm-ta): Ital J Pediatr
Journal ID (iso-abbrev): Ital J Pediatr
ISSN: 1824-7288
Publisher: BioMed Central
Article Information
Download PDF
Copyright ©2012 Manna et al.; licensee BioMed Central Ltd.
Received Day: 11 Month: 10 Year: 2012
Accepted Day: 19 Month: 12 Year: 2012
collection publication date: Year: 2012
Electronic publication date: Day: 31 Month: 12 Year: 2012
Volume: 38First Page: 74 Last Page: 74
PubMed Id: 23273317
ID: 3545741
Publisher Id: 1824-7288-38-74
DOI: 10.1186/1824-7288-38-74

Clinical application of exhaled nitric oxide measurement in pediatric lung diseases
Angelo Manna1 Email:
Carlo Caffarelli2 Email:
Margherita Varini2 Email:
Carlotta Povesi Dascola2 Email:
Silvia Montella1 Email:
Marco Maglione1 Email:
Francesco Sperlì1 Email:
Francesca Santamaria1 Email:
1Department of Pediatrics, Federico II University, Via Sergio Pansini, 5 80131, Naples, Italy
2Department of Pediatrics, University Hospital of Parma, Parma, Italy


Nitric oxide (NO) is a biological mediator synthesized by NO synthase (NOS), an enzyme that catalyzes the oxidation of L-arginine to NO and L-citrulline. Constitutive NOS isoenzymes include neuronal NOS (NOS1) and endothelial NOS (NOS3), both of which are activated by calcium ions to produce small amounts of NO [1]. Inducible NOS (NOS2), that is induced by inflammatory and infectious stimuli, produces large amounts of NO independent of calcium ion influx [2]. NO was first described as a vascular smooth muscle relaxant and was subsequently found to be present in the expired breath of animals and humans [1]. In the lungs, NO determines smooth muscle relaxation, affects ciliary beat frequency, mucus secretion and plasma exudation, and is involved in neurotransmission, blood flow regulation, inflammation and cell-mediated immunity processes [3]. In the upper respiratory tract NO levels are higher than in the lower airways, with the maximal concentration in the paranasal sinuses, probably because of local increased NOS activity and of poor ventilation [4].

During the last years the availability of NO analyzers and the publication of official guidelines made the measurement of fractional exhaled NO (FeNO) a useful tool in the diagnosis of various pediatric airway disorders [5-10]. This review summarizes the most recent advances and the current clinical applications of FeNO measurement in the pediatric clinical practice.

How should FeNO be measured?

Several methods are used to measure FeNO in children, and the choice depends on the subject’s age and cooperation. Online measurement allows FeNO testing with a real-time display of NO breath profiles, which is available in stationary devices only. Offline testing, instead, refers to collection of exhaled air into suitable receptacles for delayed analysis [5]. The single breath online measurement is the gold standard in school-age children [5,11]. The subject is asked to inhale to near total lung capacity and to exhale at a constant flow of 50 mL/s until a NO plateau of at least 2 seconds can be identified. The offline method with constant flow rate is the offline method of choice in school-age children [5]. The child blows air through a mouthpiece into a receptacle. Nasal contamination is prevented by closing the velum by exhaling against at least 5 cm H2O oral pressure. NO concentrations in balloons can be stable for several hours, and the measurement can take place also at a distant site. Flow rate standardization improves the reproducibility of the offline technique, with results similar to the online constant flow rate methods [11]. In subjects younger than 5 years, single-breath online measurement is not well standardized since children cannot adequately cooperate. In the age group from 2 to 5 years, FeNO levels are measured online during spontaneous breathing, with the exhalation flow adjusted to 50 mL/s by changing the exhalation resistance [12]. The child breathes quietly, slowly and regularly through a mouthpiece connected to a two-way valve. NO-free air is continuously flushed through the inlet of the valve. However, NO levels measured during spontaneous breathing may not equate with single-breath online measurements. In children younger than 2 years, the tidal breathing method has been used both online and offline, but it is not standardized [11].

Finally, the agreement between different devices gave inconsistent results, with some studies showing significant differences between analyzers [13], while others showed a high degree of agreement between different devices [14-16]. In particular, a recent study demonstrated an acceptable degree of agreement only between devices from the same manufacturer, both stationary and portable [17].

FeNO reference values in exhaled air

Several recent publications have reported reference values for FeNO in children and adolescents [18-28] (Table 1). There are important differences among these studies regarding to the size of the examined population as well as the range of statistical variables that have been included or excluded, limiting their value. Several factors may affect FeNO levels: measurement techniques, exhalation flow rate, nasal NO contamination, NO analyzer used, race, age, sex, atopy, anthropometric measures, smoking, and diet. While some of these (height, age, smoke, atopy) are universally accepted as crucial in increasing FeNO values [20,29], there is uncertainty regarding the others [30-32].

FeNO and bronchial asthma
FeNO in the diagnosis of bronchial asthma

Chronic airway inflammation is an important feature in the development and progression of bronchial asthma [10,33-36]. FeNO levels are increased in asthmatic patients [37-39] as a result of induction of NOS2 by proinflammatory cytokines [3,40-43]. There is some degree of correlation between elevated FeNO levels and increased eosinophils in blood, bronchoalveolar lavage fluid [28], bronchial biopsies [44], sputum [45], this indicating that FeNO reflects eosinophilic inflammation [28,33,46,47]. However, asthma is probably not a single disease since at least 3 adult phenotypes of airway inflammation have been identified on the basis of predominant eosinophilic, neutrophilic, or pauci-granulocitic cellular pattern [48]. It is therefore not surprising that the difference in FeNO levels between symptomatic and asymptomatic children is relatively small, and a large overlap in the distribution of FeNO levels from subjects with and without asthma has been reported [49-58] (Table 2). Another limitation is that even though FeNO is increased in children with allergic asthma [59-62], the obtained levels cannot discriminate among schoolchildren with non-allergic asthma, or those with allergy without asthma, or the healthy population [63]. Moreover, levels of FeNO appear increased in asthmatics with pollen allergy during the season also in the absence of symptoms of lung function impairment [64]. Children with atopic eczema exhibit high levels of FeNO even though they do not have asthma [65], but the mechanism is unclear.

Obesity is another confounding factor in the assessment of FeNO levels. A consistent body of data now indicates that asthma is closely related to obesity, and obese patients with asthma usually have more severe symptoms than non-obese asthmatics [66]. Indeed, obese asthma may be a unique phenotype that is characterized by more severe symptoms for a given degree of lung function impairment, destabilization or lack of asthma control, worse quality of life, lack of eosinophilic inflammation and a different response to controller medication [67]. At any age, obesity can adversely impact on lung function, and obesity duration is a determinant of lower pulmonary function [68]. FeNO levels have been extensively investigated in pediatric excess adiposity [9,69]. Some pediatric studies showed that FeNO is negatively associated with body mass index, waist-to-hip ratio, and percent body fat [70], while others found no relationship between FeNO levels and adiposity measures [69,71]. Furthermore, FeNO levels do not differ between obese and normal weight subjects with asthma [9]. A possible explanation for this results might be a selection bias, in particular overdiagnosis of asthma attributable to non specific obesity-related respiratory symptoms among obese children. Indeed, recent meta-analyses have pointed out that some obese patients with “asthma” may have respiratory symptoms caused by obesity without objective physiological criteria for asthma, or an exaggerated symptom perception [72].

As far as the discrimination between children with asthma and healthy subjects, FeNO measurement provides significantly higher diagnostic accuracy than lung function tests [58,73], and has diagnostic value comparable to that of conventional bronchial challenge tests [57]. Several studies showed an inverse correlation between FeNO levels and bronchial hyperreactivity tests in children [58,70-76], and only one group did not confirm this finding [77]. Nevertheless, elevated FeNO levels increase the probability of exercise-induced bronchoconstriction in asthmatic school-age children [78]. These conflicting results may be explained with the different methods used to measure FeNO as well as with the heterogeneity of the study populations, in particular regarding the presence of atopy and the use of steroids.

Cut-points rather than reference values have been proposed to interpret FeNO levels [33,34,72,79]. In children, FENO values less than 20 ppb indicate that eosinophilic inflammation is less likely, or that in patients presenting with non specific respiratory symptoms alternative diagnoses to asthma should be considered [79]. High FeNO concentration (>35 ppb in children) strongly suggests significant airway eosinophilia [79]. At high expiratory flows, ranging from 200 to 280 mL/s, the negative and positive predictive values for FeNO >25 ppb as predictor of asthma rise to 80% and 100%, respectively [80]. Nonetheless, intermediate FeNO levels (20-35 ppb in children) indicate that cautious interpretation in the etiology of the airway disorder is required.

An additional, novel, potential and attractive application of FeNO in asthma is the “prediction” of asthma onset. In the absence of symptoms, increased FeNO levels may reflect subclinical airway inflammation that may be predictive of “early asthma”, especially in allergic subjects [81,82]. This could be explained by an enhanced Th2 cytokine-driven airway response in allergic individuals that may precede the clinical presentation. Furthermore, in asymptomatic adolescents, increased FeNO may predict the development of rhinitis symptoms within a follow-up period of 4 years [83], suggesting that FeNO may be a sensitive biomarker of the “allergic march”. These findings have potential clinical and therapeutic implications, also because studies in animal models seem to show a possibility to block induction of Th2 responses, thus preventing the development of future asthma [84].

FeNO in the follow-up of bronchial asthma

The goal of asthma long-term treatment is to reduce inflammation for controlling symptoms. Treatment options are usually guided by symptoms and lung function. However, these factors do not reflect chronic airway inflammation. This is also shown by contrasting results of studies on the relationship between FeNO levels and both symptoms (including recent symptoms, symptom frequency, symptom scores), symptom control, or rescue ß2-agonist use [77,85-94] and pulmonary function test results [25,85-87,89,91,93-100].

Inhaled corticosteroids (ICS) are the first choice for asthma maintenance treatment. Interestingly, inhaled or systemic corticosteroid administration results in dose dependent reductions of FeNO levels [27,100]. Moreover, in corticosteroid-naïve patients with suspected asthma, the baseline FeNO value may predict an ICS response in terms of improved lung function and reduced airway reactivity [73]. Therefore, FeNO seems a suitable biomarker for modifying ICS dose in order to obtain better asthma control [101]. However, in children, daily monitoring of FeNO at home [102], as well as measurement of FeNO levels every 3 months for 1 year [103], or 5 times in 6 weeks [104] do not provide any advantage in improving the symptom score. In adolescents and adults, Szefler et al showed that the addition of FeNO measurement as an indicator of asthma control resulted in higher doses of ICS and long-acting β2 agonists than did standard guideline-based treatment, and did not determine improvements in asthma symptoms or lung function [105]. A recent meta-analysis concluded that the number of asthma exacerbations is not significantly reduced in adults and children when ICS was tailored based on FeNO [106].

These findings may be explained by the fact that day-to-day variations of FeNO are common and do not correlate with changes in symptom score [107]. Furthermore, some atopic asthmatic patients showed a lack of FeNO responsiveness to ICS [108,109], or may have increased FeNO levels despite high dose ICS [110].

Another issue is whether the change in FeNO values may be a better predictor than absolute levels. FeNO levels quickly decrease in response to ICS and therefore they may be useful to ascertain that ICS is regularly taken. Finally, baseline FeNO seems a worse predictor of asthma improvement than the change in FeNO after 80 days of ICS [111].

According to the Clinical Practice Guideline of the American Thoracic Society (ATS) [79] it has been suggested to consider as significant the increase in FeNO greater than 20% for values over 50 ppb, or more than 10 ppb for values lower than 50 ppb from one visit to the next. The second one recommends to use a reduction of at least 20% in FeNO for values over 50 ppb (or more than 10 ppb for values lower than 50 ppb) as the cut point to indicate as significant the response to antiinflammatory therapy.

The results of two recent studies indicate new possible clinical applications of FeNO measurement in pediatric asthma. Pifferi et al assessed the value of spirometry and FeNO measurements, alone or in combination, in models developed by a machine learning approach for the objective classification of asthma control [112]. The combined use of spirometry parameters and FeNO levels modeled by a soft computing learning approach applied to spirometry could discriminate the level of asthma control. Van der Valk et al found that FeNO measured daily by a hand-held device started to increase approximately 10 days before moderate exacerbations occurred, this suggesting that regular FeNO measurements in the home setting could help to detect and even to prevent the loss of asthma control [113]. Apart from ICS, other established controller therapies, such as leukotriene modifiers or anti-IgE therapy with omalizumab, have been demonstrated to reduce FeNO in children, alone or combined with ICS [114-117].

On the basis of the studies that have provided evidence regarding the applications of NO measurements in clinical practice, ATS recently indicated the rationale for FeNO measurement in asthma, even in the pediatric population [79], highlighting the following situations:

– Diagnosis of eosinophilic airway inflammation

– Support of asthma diagnosis when objective evidence is needed

– Baseline evaluation and follow-up monitoring of airway inflammation

– Assessment of potential response or failure to respond to inhaled corticosteroids

– Evaluation of adherence to antiinflammatory medications

– Guide for dose changes in antiinflammatory medications

FeNO in viral bronchiolitis

Respiratory Syncytial Virus (RSV) manifests restricted tropism for the respiratory epithelium stimulating an inflammatory response [118]. RSV increases NOS2 messenger RNA, and upregulates NOS2 and its nitrite products in lines and cultures of respiratory epithelial cells [119-121]. Despite in vitro and animal data demonstrated NO involvement in bronchiolitis [120,122], only few studies evaluated FeNO levels in children with RSV bronchiolitis. Surprisingly, FeNO appeared significantly lower in infants with bronchiolitis than in healthy controls or in preschool children with recurrent wheezing [123]. However, the same study demonstrated that 3 months after the diagnosis of RSV bronchiolitis, FeNO appeared significantly higher in affected children than in normal subjects, suggesting that low FeNO reflects the active suppression of NO production occurring during the active infection, while the increased levels might be interpreted as a “rebound” phenomenon. Future studies will hopefully provide more insights on the relationship between viral infections and subsequent chronic bronchial asthma.

FeNO in community acquired pneumonia

The scientific literature on FeNO modifications during community acquired pneumonia (CAP) in children is scarce. Since NO is part of the innate inflammatory response, its levels are expected to rise in acute lung infection. Healthy children with an abnormally high FeNO had significantly increased frequency of previous bronchitis or pneumonia in the past year [124]. However, Carraro and colleagues measured FeNO three times over a 1 month period in the exhaled breath condensate obtained from children with chest x-ray evidence of CAP, and found no significant differences in FeNO levels either from children with CAP compared to healthy controls, or from baseline levels during the follow-up [125]. Different hypotheses might explain this paradox. First, NO output from expiratory flows of 50 mL/s mainly derives from airway NO diffusion, and therefore at higher flow rates, that sample from the deeper parts of the lung, higher NO levels might be found. Second, NO might also react rapidly with reactive oxygen species, forming NO-metabolites. Unfortunately, the above mentioned data do not allow to reach definitive conclusions, and highlight the need for further studies on the role of FeNO in children with CAP.

FeNO in bronchiectasis

Bronchiectasis is caused by, or associated with, many disorders including congenital/genetic conditions, e.g. cystic fibrosis (CF), primary immunodeficiency, primary ciliary dyskinesia (PCD), Mounier-Kuhn syndrome, chronic obstructive pulmonary disease, bronchiolitis obliterans, sarcoidosis, autoimmune disorders, and acquired post-infectious diseases [126-131]. High-resolution computed tomography (HRCT) is the gold standard for the diagnosis [128,132], even though radiation, magnetic resonance imaging has been proposed as an alternative radiation-free technique, especially in children [133,134].

Levels of inflammation in stable bronchiectasis seem to correlate with a reduction of patient’s quality of life [135]. Therefore, monitoring inflammation is of outstanding relevance in the management of affected patients, especially for preventing the disease progression. Since current markers of inflammation in the blood and in the sputum are indirect, variable and invasive, FeNO measurement may represent a useful way to assess airway inflammation in patients with bronchiectasis. Some studies found that FeNO levels from adults with non-CF, non-PCD bronchiectasis are significantly higher compared to controls [136-138], but others did not confirm this [80,139,140]. In children with bronchiectasis due to CF or PCD, FeNO levels are abnormally low compared to non CF- non PCD-patients or to controls, but there are no significant differences between PCD and CF [80,141-143].

NO measurement at different expiratory flow rates allows to assess the contribution of NO from different parts of the lung. A two-compartment model of pulmonary NO exchange dynamics has been proposed to demonstrate relative contributions of bronchial (J) and peripheral (Calv) airway NO to the final FeNO concentration [144]. In adults with non CF- non PCD- bronchiectasis an increase in CalvNO with normal JNO levels has been recently demonstrated [136]. In children with CF-related bronchiectasis results appear conflicting, with one study showing lower JNO in CF than controls and no difference in CalvNO between groups [145], whereas other authors demonstrated that children with CF had a significantly higher CalvNO, but no significant difference in JNO compared to healthy children [146]. On the other hand, in children with PCD, very low levels of nasal NO are still a partially unexplained feature, whereas FeNO levels show considerable overlap with healthy subjects [80]. Paraskakis and colleagues found that in children with PCD JNO was significantly reduced, but CalvNO was normal compared with healthy controls [147]. On the basis of these findings, authors speculate that the normal CalvNO values militate against a generalized disorder of NO metabolism in PCD children, and hypothesize that NOS3 (endothelial) has normal function in PCD, while the uncoupling of the contractile process of the cilia from NOS2 (inducible) may result in failure of NO production.

Notwithstanding the conflicting results between affected children and adults, FeNO measurement could represent a useful non invasive tool to monitor bronchial inflammation over time.

FeNO in diffuse lung disease

The term diffuse lung disease (DLD) encompasses a heterogeneous group of chronic respiratory disorders characterized by abnormal gas exchange and diffuse radiographic and histopathologic abnormalities [148]. DLD is rare in children, and diagnosis requires detailed history, complete physical examination, lung imaging, pulmonary function testing, bronchoalveolar lavage (BAL), and in most cases an open lung biopsy to confirm the suspicion [148,149].

Several studies evaluated FeNO levels in adults with DLD. In systemic sclerosis, FeNO concentrations are lower in subjects with interstitial lung involvement than in those without, whereas patients without pulmonary disease have higher FeNO than healthy subjects [150]. Moreover, FeNO levels seem to be increased in subjects with asbestosis [151], but not in pulmonary sarcoidosis [152]. To the best of our knowledge, no studies ever evaluated FeNO levels in children with DLD. This would likely be crucial in the management of these critical conditions, hopefully being useful in the evaluation of the progression of the disease, or of the response to treatment.

FeNO in bronchiolitis obliterans

Bronchiolitis obliterans (BO) is almost secondary to lung transplantation in adults [153], while the most common form in children is post-infectious BO [154]. FeNO levels are increased in adult BO that occurs after lung transplantation [155,156], and correlate with NOS2 expression in the bronchial epithelium and with the percentage of BAL neutrophils [157-161]. No pediatric studies evaluating the role of FeNO in children with BO after lung transplantation have been published. The availability of a non-invasive biomarker that can identify patients in whom more invasive diagnostic procedures such as BAL or lung biopsies are justified (or can be avoided) would be very helpful to improve the management of children with BO.


NO seems to significantly influence a variety of physiological and pathophysiological processes in the upper and lower airways. FeNO measurement is easy to perform, and seems reproducible also in the preschool age. The availability of hand-held devices will hopefully increase its use in the pediatric practice. Combined with symptoms registration and lung function measurements, FeNO provides additional information that can be applied to support the diagnosis of asthma and to optimize the management of affected children. Moreover, recent studies suggest that FeNO is helpful in predicting both onset and exacerbations of asthma. Since most studies have been performed in adult populations, more research is needed to confirm the usefulness of NO measurement in the diagnosis and management of pediatric chronic airway disorders different from asthma.


NO: Nitric oxide; NOS: NO synthase; FeNO: Fractional exhaled nitric oxide; ICS: Inhaled corticosteroids; RSV: Respiratory syncytial virus; CAP: Community acquired pneumonia; CF: Cystic fibrosis, PCD, Primary ciliary dyskinesia; HRCT: High-resolution computed tomography; DLD: Diffuse lung disease; BAL: Bronchoalveolar lavage; BO: Bronchiolitis obliterans.

Competing interests

All authors declare that they have no significant competing financial, professional or personal interests that might have influenced the performance or presentation of the work described in this manuscript.

Authors’ contributions

AM has been involved in drafting the manuscript; CC has been involved in revising the manuscript critically for important intellectual content; MV has made substantial contributions to acquisition, analysis and interpretation of data; CP has made substantial contributions to acquisition, analysis and interpretation of data; SM has been involved in drafting the manuscript; MM has been involved in drafting the manuscript; FSp has made substantial contributions to acquisition, analysis and interpretation of data; FS has been involved in drafting the manuscript, revising it critically for important intellectual content and has given final approval of the version to be published. All authors read and approved the final manuscript.

Moncada S,Higgs A,The L-arginine-nitric oxide pathwayN Engl J MedYear: 19933292002201210.1056/NEJM1993123032927067504210
Maniscalco M,Sofia M,Pelaia G,Nitric oxide in upper airways inflammatory diseasesInflamm ResYear: 200756586910.1007/s00011-006-6111-117431742
Kharitonov SA,Barnes PJ,Exhaled markers of pulmonary diseaseAm J Respir Crit Care MedYear: 20011631693172211401895
Lundberg JO,Farkas-Szallasi T,Weitzberg E,Rinder J,Lidholm J,Anggåard A,Hökfelt T,Lundberg JM,Alving K,High nitric oxide production in human paranasal sinusesNat MedYear: 1995137037310.1038/nm0495-3707585069
American Thoracic Society; European Respiratory SocietyATS/ERS recommendations for standardized procedures for the online and offline measurement of exhaled lower respiratory nitric oxide and nasal nitric oxide, 2005Am J Respir Crit Care MedYear: 200517191293015817806
Baraldi E,Carraro S,Exhaled NO and breath condensatePaediatr Respir RevYear: 20067Suppl 12022
Montella S,Alving K,Maniscalco M,Sofia M,De Stefano S,Raia V,Santamaria F,Measurement of nasal nitric oxide by hand-held and stationary devicesEur J Clin InvestYear: 2011411063107010.1111/j.1365-2362.2011.02501.x21413977
Santamaria F,De Stefano S,Montella S,Barbarano F,Iacotucci P,Ciccarelli R,Sofia M,Maniscalco M,Nasal nitric oxide assessment in primary ciliary dyskinesia using aspiration, exhalation, and hummingMed Sci MonitYear: 2008148085
Santamaria F,Montella S,De Stefano S,Sperlì F,Barbarano F,Spadaro R,Franzese A,Asthma, atopy, and airway inflammation in obese childrenJ Allergy Clin ImmunolYear: 200712096596710.1016/j.jaci.2007.06.00217637474
Corradi M,Zinelli C,Caffarelli C,Exhaled breath biomarkers in asthmatic childrenInflamm Allergy Drug TargetsYear: 2007615015910.2174/18715280778169643717897051
Baraldi E,de Jongste JC,European Respiratory Society/American Thoracic Society (ERS/ATS) Task ForceMeasurement of exhaled nitric oxide in children, 2001Eur Respir JYear: 20022022323710.1183/09031936.02.0029310212166573
Buchvald F,Bisgaard H,FeNO measured at fixed exhalation flow rate during controlled tidal breathing in children from the age of 2 yrAm J Respir Crit Care MedYear: 200116369970411254527
Borrill Z,Clough D,Truman N,Morris J,Langley S,Singh D,A comparison of exhaled nitric oxide measurements performed using three different analysersRespir MedYear: 20061001392139610.1016/j.rmed.2005.11.01816431095
Alving K,Janson C,Nordvall L,Performance of a new hand-held device for exhaled nitric oxide measurement in adults and childrenRespir ResYear: 200676710.1186/1465-9921-7-6716626491
Boot JD,de Ridder L,de Kam ML,Calderon C,Mascelli MA,Diamant Z,Comparison of exhaled nitric oxide measurements between NIOX MINO electrochemical and Ecomedics chemiluminescence analyzerRespir MedYear: 20081021667167110.1016/j.rmed.2008.06.02118694637
Menzies D,Nair A,Lipworth BJ,Portable exhaled nitric oxide measurement: Comparison with the "gold standard" techniqueChestYear: 200713141041410.1378/chest.06-133517296641
Korn S,Telke I,Kornmann O,Buhl R,Measurement of exhaled nitric oxide: comparison of different analysersRespirologyYear: 2010151203120810.1111/j.1440-1843.2010.01847.x20920124
Baraldi E,Azzolin NM,Cracco A,Zacchello F,Reference values of exhaled nitric oxide for healthy children 6-15 years oldPediatr PulmonolYear: 199927545810023792
Buchvald F,Baraldi E,Carraro S,Gaston B,De Jongste J,Pijnenburg MW,Silkoff PE,Bisgaard H,Measurements of exhaled nitric oxide in healthy subjects age 4 to 17 yearsJ Allergy Clin ImmunolYear: 20051151130113610.1016/j.jaci.2005.03.02015940124
Kovesi T,Kulka R,Dales R,Exhaled nitric oxide concentration is affected by age, height, and race in healthy 9- to 12-year-old childrenChestYear: 200813316917510.1378/chest.07-117717925422
Wong GW,Liu EK,Leung TF,Yung E,Ko FW,Hui DS,Fok TF,Lai CK,High levels and gender difference of exhaled nitric oxide in Chinese schoolchildrenClin Exp AllergyYear: 20053588989310.1111/j.1365-2222.2005.02263.x16008675
Malmberg LP,Petäys T,Haahtela T,Laatikainen T,Jousilahti P,Vartiainen E,Mäkelä MJ,Exhaled nitric oxide in healthy nonatopic school-age children: determinants and height-adjusted reference valuesPediatr PulmonolYear: 20064163564210.1002/ppul.2041716703576
Yao TC,Lee WI,Ou LS,Chen LC,Yeh KW,Huang JL,PATCH Study GroupReference values of exhaled nitric oxide in healthy Asian children aged 5 to 18 yearsEur Respir JYear: 20123937838410.1183/09031936.0001391121622584
Dötsch J,Demirakça S,Terbrack HG,Hüls G,Rascher W,Kühl PG,Airway nitric oxide in asthmatic children and patients with cystic fibrosisEur Respir JYear: 199692537254010.1183/09031936.96.091225378980966
Silvestri M,Spallarossa D,Frangova Yourukova V,Battistini E,Fregonese B,Rossi GA,Orally exhaled nitric oxide levels are related to the degree of blood eosinophilia in atopic children with mild-intermittent asthmaEur Respir JYear: 19991332132610.1034/j.1399-3003.1999.13b17.x10065675
Franklin PJ,Taplin R,Stick SM,A community study of exhaled nitric oxide in healthy childrenAm J Respir Crit Care MedYear: 199915969739872820
Latzin P,Beck J,Griese M,Exhaled nitric oxide in healthy children: variability and a lack of correlation with atopyPediatr Allergy ImmunolYear: 200213374610.1034/j.1399-3038.2002.00066.x12000497
Jouaville LF,Annesi-Maesano I,Nguyen LT,Bocage AS,Bedu M,Caillaud D,Interrelationships among asthma, atopy, rhinitis and exhaled nitric oxide in a population-based sample of childrenClin Exp AllergyYear: 2003331506151110.1046/j.1365-2222.2003.01800.x14616861
Grob NM,Dweik RA,Exhaled nitric oxide in asthma. From diagnosis, to monitoring, to screening: are we there yet?ChestYear: 200813383783910.1378/chest.07-274318398112
Olin AC,Bake B,Torén K,Fraction of exhaled nitric oxide at 50 mL/s: reference values for adult lifelong never-smokersChestYear: 20071311852185610.1378/chest.06-292817565022
Travers J,Marsh S,Aldington S,Williams M,Shirtcliffe P,Pritchard A,Weatherall M,Beasley R,Reference ranges for exhaled nitric oxide derived from a random community survey of adultsAm J Respir Crit Care MedYear: 200717623824210.1164/rccm.200609-1346OC17478616
Taylor DR,Mandhane P,Greene JM,Hancox RJ,Filsell S,McLachlan CR,Williamson AJ,Cowan JO,Smith AD,Sears MR,Factors affecting exhaled nitric oxide measurements: the effect of sexRespir ResYear: 200788210.1186/1465-9921-8-8218005450
Global Strategy for Asthma Management and Prevention. Global Initiative for Asthma (GINA)
British Thoracic Society Scottish Intercollegiate Guidelines NetworkBritish Guideline on the Management of AsthmaThoraxYear: 200863Suppl 4112118156562
Chedevergne F,Le Bourgeois M,de Blic J,Scheinmann P,The role of inflammation in childhood asthmaArch Dis ChildYear: 200082Suppl 269
Caffarelli C,Calcinai E,Rinaldi L,Povesi Dascola C,Terracciano L,Corradi M,Hydrogen peroxide in exhaled breath condensate in asthmatic children during acute exacerbation and after treatmentRespirationYear: 20128429129810.1159/00034196923018317
Alving K,Weitzberg E,Lundberg JM,Increased amount of nitric oxide in exhaled air of asthmaticsEur Respir JYear: 19936136813707507065
Kharitonov SA,Yates D,Robbins RA,Logan-Sinclair R,Shinebourne EA,Barnes PJ,Increased nitric oxide in exhaled air of asthmatic patientsLancetYear: 199434313313510.1016/S0140-6736(94)90931-87904001
Hamid Q,Springall DR,Riveros-Moreno V,Chanez P,Howarth P,Redington A,Bousquet J,Godard P,Holgate S,Polak JM,Induction of nitric oxide synthase in asthmaLancetYear: 19933421510151310.1016/S0140-6736(05)80083-27504773
Baraldi E,Azzolin NM,Zanconato S,Dario C,Zacchello F,Corticosteroids decrease exhaled nitric oxide in children with acute asthmaJ PediatrYear: 199713138138510.1016/S0022-3476(97)80062-59329413
Byrnes CA,Dinarevic S,Shinebourne EA,Barnes PJ,Bush A,Exhaled nitric oxide measurements in normal and asthmatic childrenPediatr PulmonolYear: 19972431231810.1002/(SICI)1099-0496(199711)24:5<312::AID-PPUL2>3.0.CO;2-K9407563
Lundberg JO,Nordvall SL,Weitzberg E,Kollberg H,Alving K,Exhaled nitric oxide in paediatric asthma and cystic fibrosisArch Dis ChildYear: 19967532332610.1136/adc.75.4.3238984919
Warke TJ,Fitch PS,Brown V,Taylor R,Lyons JD,Ennis M,Shields MD,Exhaled nitric oxide correlates with airway eosinophils in childhood asthmaThoraxYear: 20025738338710.1136/thorax.57.5.38311978911
Payne DN,Adcock IM,Wilson NM,Oates T,Scallan M,Bush A,Relationship between exhaled nitric oxide and mucosal eosinophilic inflammation in children with difficult asthma, after treatment with oral prednisoloneAm J Respir Crit Care MedYear: 20011641376138111704581
Lim S,Jatakanon A,Meah S,Oates T,Chung KF,Barnes PJ,Relationship between exhaled nitric oxide and mucosal eosinophilic inflammation in mild to moderately severe asthmaThoraxYear: 20005518418810.1136/thorax.55.3.18410679535
Silvestri M,Sabatini F,Sale R,Defilippi AC,Fregonese L,Battistini E,Biraghi MG,Rossi GA,Correlations between exhaled nitric oxide levels, blood eosinophilia, and airway obstruction reversibility in childhood asthma are detectable only in atopic individualsPediatr PulmonolYear: 20033535836310.1002/ppul.1026412687592
Lex C,Ferreira F,Zacharasiewicz A,Nicholson AG,Haslam PL,Wilson NM,Hansel TT,Payne DN,Bush A,Airway eosinophilia in children with severe asthma: predictive values of noninvasive testsAm J Respir Crit Care MedYear: 20061741286129110.1164/rccm.200603-352OC16973985
Wenzel SE,Asthma: defining of the persistent adult phenotypesLancetYear: 200636880481310.1016/S0140-6736(06)69290-816935691
Brussee JE,Smit HA,Kerkhof M,Koopman LP,Wijga AH,Postma DS,Gerritsen J,Grobbee DE,Brunekreef B,de Jongste JC,Exhaled nitric oxide in 4-year-old children: relationship with asthma and atopyEur Respir JYear: 20052545546110.1183/09031936.05.0007960415738288
Dupont LJ,Demedts MG,Verleden GM,Prospective evaluation of the validity of exhaled nitric oxide for the diagnosis of asthmaChestYear: 200312375175610.1378/chest.123.3.75112628874
Sivan Y,Gadish T,Fireman E,Soferman R,The use of exhaled nitric oxide in the diagnosis of asthma in school childrenJ PediatrYear: 200915521121610.1016/j.jpeds.2009.02.03419394049
Sachs-Olsen C,Lødrup Carlsen KC,Mowinckel P,Håland G,Devulapalli CS,Munthe-Kaas MC,Carlsen KH,Diagnostic value of exhaled nitric oxide in childhood asthma and allergyPediatr Allergy ImmunolYear: 2010211 Pt 2213221
Pérez Tarazona S,Martínez Camacho RM,Alfonso Diego J,Escolano Serrano S,Talens Gandía J,Diagnostic value of exhaled nitric oxide measurement in mild asthmaAn Pediatr (Barc)Year: 20117532032810.1016/j.anpedi.2011.05.00821703952
Yao TC,Ou LS,Lee WI,Yeh KW,Chen LC,Huang JL,PATCH study groupExhaled nitric oxide discriminates children with and without allergic sensitization in a population-based studyClin Exp AllergyYear: 20114155656410.1111/j.1365-2222.2010.03687.x21338427
Cordeiro D,Rudolphus A,Snoey E,Braunstahl GJ,Utility of nitric oxide for the diagnosis of asthma in an allergy clinic populationAllergy Asthma ProcYear: 20113211912610.2500/aap.2011.32.341921439165
Woo SI,Lee JH,Kim H,Kang JW,Sun YH,Hahn YS,Utility of fractional exhaled nitric oxide (F(E)NO) measurements in diagnosing asthmaRespir MedYear: 20121061103110910.1016/j.rmed.2012.03.02222534041
Berkman N,Avital A,Breuer R,Bardach E,Springer C,Godfrey S,Exhaled nitric oxide in the diagnosis of asthma: comparison with bronchial provocation testsThoraxYear: 20056038338810.1136/thx.2004.03110415860713
Malmberg LP,Pelkonen AS,Haahtela T,Turpeinen M,Exhaled nitric oxide rather than lung function distinguishes preschool children with probable asthmaThoraxYear: 20035849449910.1136/thorax.58.6.49412775859
Frank TL,Adisesh A,Pickering AC,Morrison JF,Wright T,Francis H,Fletcher A,Frank PI,Hannaford P,Relationship between exhaled nitric oxide and childhood asthmaAm J Respir Crit Care MedYear: 1998158103210369769256
Lúdvíksdóttir D,Janson C,Högman M,Hedenström H,Björnsson E,Boman G,Exhaled nitric oxide and its relationship to airway responsiveness and atopy in asthma. BHR-Study GroupRespir MedYear: 19999355255610.1016/S0954-6111(99)90154-310542988
Gratziou C,Lignos M,Dassiou M,Roussos C,Influence of atopy on exhaled nitric oxide in patients with stable asthma and rhinitisEur Respir JYear: 19991489790110.1034/j.1399-3003.1999.14d28.x10573239
Silvestri M,Sabatini F,Spallarossa D,Fregonese L,Battistini E,Biraghi MG,Rossi GA,Exhaled nitric oxide levels in non-allergic and allergic mono- or polysensitised children with asthmaThoraxYear: 20015685786210.1136/thorax.56.11.85711641510
Linn WS,Rappaport EB,Berhane KT,Bastain TM,Avol EL,Gilliland FD,Exhaled nitric oxide in a population-based study of southern California schoolchildrenRespir ResYear: 2009102810.1186/1465-9921-10-2819379527
Vahlkvist S,Sinding M,Skamstrup K,Bisgaard H,Daily home measurements of exhaled nitric oxide in asthmatic children during natural birch pollen exposureJ Allergy Clin ImmunolYear: 20061171272127610.1016/j.jaci.2006.03.01816750986
Zinelli C,Caffarelli C,Strid J,Jaffe A,Atherton DJ,Measurement of nitric oxide and 8-isoprostane in exhaled breath of children with atopic eczemaClin Exp DermatolYear: 20093460761210.1111/j.1365-2230.2008.03142.x19508477
Tantisira KG,Weiss ST,Complex interactions in complex traits: obesity and asthmaThoraxYear: 200156Suppl 26473
Santamaria F,Montella S,Pietrobelli A,Obesity and pulmonary disease: unanswered questionsObes RevYear: 20121382283310.1111/j.1467-789X.2012.01008.x22646804
Santamaria F,Montella S,Greco L,Valerio G,Franzese A,Maniscalco M,Fiorentino G,Peroni D,Pietrobelli A,De Stefano S,Sperlì F,Boner AL,Obesity duration is associated to pulmonary function impairment in obese subjectsObesity (Silver Spring)Year: 2011191623162810.1038/oby.2011.121311508
Santamaria F,Montella S,De Stefano S,Sperlì F,Barbarano F,Valerio G,Relationship between exhaled nitric oxide and body mass index in children and adolescentsJ Allergy Clin ImmunolYear: 20051161163116410.1016/j.jaci.2005.07.01816275394
Berg CM,Thelle DS,Rosengren A,Lissner L,Torén K,Olin AC,Decreased fraction of exhaled nitric oxide in obese subjects with asthma symptoms: data from the population study INTERGENE/ADONIXChestYear: 20111391109111610.1378/chest.10-129921183611
Leung TF,Li CY,Lam CW,Au CS,Yung E,Chan IH,Wong GW,Fok TF,The relation between obesity and asthmatic airway inflammationPediatr Allergy ImmunolYear: 20041534435010.1111/j.1399-3038.2004.00164.x15305944
Peroni DG,Pietrobelli A,Boner AL,Asthma and obesity in childhood: on the road aheadInt J Obes (Lond)Year: 20103459960510.1038/ijo.2009.27320065975
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 testsAm J Respir Crit Care MedYear: 200416947347814644933
Ciprandi G,Tosca MA,Capasso M,Exhaled nitric oxide in children with allergic rhinitis and/or asthma: a relationship with bronchial hyperreactivityJ AsthmaYear: 2010471142114710.3109/02770903.2010.52702620950134
Steerenberg PA,Janssen NA,de Meer G,Fischer PH,Nierkens S,van Loveren H,Opperhuizen A,Brunekreef B,van Amsterdam JG,Relationship between exhaled NO, respiratory symptoms, lung function, bronchial hyperresponsiveness, and blood eosinophilia in school childrenThoraxYear: 20035824224510.1136/thorax.58.3.24212612304
Jatakanon A,Lim S,Kharitonov SA,Chung KF,Barnes PJ,Correlation between exhaled nitric oxide, sputum eosinophils, and methacholine responsiveness in patients with mild asthmaThoraxYear: 199853919510.1136/thx.53.2.919624291
Strunk RC,Szefler SJ,Phillips BR,Zeiger RS,Chinchilli VM,Larsen G,Hodgdon K,Morgan W,Sorkness CA,Lemanske RF Jr,Childhood Asthma Research and Education Network of the National Heart, Lung, and Blood InstituteRelationship of exhaled nitric oxide to clinical and inflammatory markers of persistent asthma in childrenJ Allergy Clin ImmunolYear: 200311288389210.1016/j.jaci.2003.08.01414610474
Grzelewski T,Grzelewska A,Majak P,Stelmach W,Kowalska A,Stelmach R,Janas A,Stelmach I,Fractional exhaled nitric oxide (FeNO) may predict exercise-induced bronchoconstriction (EIB) in schoolchildren with atopic asthmaNitric OxideYear: 201227828710.1016/j.niox.2012.05.00222584259
Dweik RA,Boggs PB,Erzurum SC,Irvin CG,Leigh MW,Lundberg JO,Olin AC,Plummer AL,Taylor DR,American Thoracic Society Committee on Interpretation of Exhaled Nitric Oxide Levels (FENO) for Clinical ApplicationsAn official ATS clinical practice guideline: interpretation of exhaled nitric oxide levels (FENO) for clinical applicationsAm J Respir Crit Care MedYear: 201118460261510.1164/rccm.9120-11ST21885636
Narang I,Ersu R,Wilson NM,Bush A,Nitric oxide in chronic airway inflammation in children: diagnostic use and pathophysiological significanceThoraxYear: 20025758658910.1136/thorax.57.7.58612096200
Warke TJ,Mairs V,Fitch PS,McGovern V,Ennis M,Shields MD,Exhaled nitric oxide in relation to the clinical features of childhood asthmaJ AsthmaYear: 20044175175710.1081/JAS-20002783815584635
Bastain TM,Islam T,Berhane KT,McConnell RS,Rappaport EB,Salam MT,Linn WS,Avol EL,Zhang Y,Gilliland FD,Exhaled nitric oxide, susceptibility and new-onset asthma in the Children's Health StudyEur Respir JYear: 20113752353110.1183/09031936.0002121020634264
Malinovschi A,Alving K,Kalm-Stephens P,Janson C,Nordvall L,Increased exhaled nitric oxide predicts new-onset rhinitis and persistent rhinitis in adolescents without allergic symptomsClin Exp AllergyYear: 20124243344010.1111/j.1365-2222.2011.03947.x22356144
Siegle JS,Hansbro N,Dong C,Angkasekwinai P,Foster PS,Kumar RK,Blocking induction of T helper type 2 responses prevents development of disease in a model of childhood asthmaClin Exp ImmunolYear: 2011165192810.1111/j.1365-2249.2011.04392.x21501148
Franklin PJ,Turner SW,Le Souëf PN,Stick SM,Exhaled nitric oxide and asthma: complex interactions between atopy, airway responsiveness, and symptoms in a community population of childrenThoraxYear: 2003581048105210.1136/thorax.58.12.104814645971
Stirling RG,Kharitonov SA,Campbell D,Robinson DS,Durham SR,Chung KF,Barnes PJ,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 GroupThoraxYear: 1998531030103410.1136/thx.53.12.103010195074
Artlich A,Busch T,Lewandowski K,Jonas S,Gortner L,Falke KJ,Childhood asthma: exhaled nitric oxide in relation to clinical symptomsEur Respir JYear: 1999131396140110.1183/09031936.99.1361402910445618
Roberts G,Hurley C,Bush A,Lack G,Longitudinal study of grass pollen exposure, symptoms, and exhaled nitric oxide in childhood seasonal allergic asthmaThoraxYear: 20045975275610.1136/thx.2003.00872215333850
Nordvall SL,Janson C,Kalm-Stephens P,Foucard T,Torén K,Alving K,Exhaled nitric oxide in a population-based study of asthma and allergy in schoolchildrenAllergyYear: 20056046947510.1111/j.1398-9995.2005.00735.x15727578
Stern G,de Jongste J,van der Valk R,Baraldi E,Carraro S,Thamrin C,Frey U,Fluctuation phenotyping based on daily fraction of exhaled nitric oxide values in asthmatic childrenJ Allergy Clin ImmunolYear: 201112829330010.1016/j.jaci.2011.03.01021489612
Debley JS,Stamey DC,Cochrane ES,Gama KL,Redding GJ,Exhaled nitric oxide, lung function, and exacerbations in wheezy infants and toddlersJ Allergy Clin ImmunolYear: 20101251228123410.1016/j.jaci.2010.03.02320462633
Green RJ,Klein M,Becker P,Halkas A,Lewis H,Kitchin O,Moodley T,Masekela R,Disagreement between common measures of asthma control in childrenChestYear: 2012 in press.
Waibel V,Ulmer H,Horak E,Assessing asthma control: symptom scores, GINA levels of asthma control, lung function, and exhaled nitric oxidePediatr PulmonolYear: 20124711311810.1002/ppul.2152922241569
Rosias PP,Dompeling E,Dentener MA,Pennings HJ,Hendriks HJ,Van Iersel MP,Jöbsis Q,Childhood asthma: exhaled markers of airway inflammation, asthma control score, and lung function testsPediatr PulmonolYear: 20043810711410.1002/ppul.2005615211692
Colon-Semidey AJ,Marshik P,Crowley M,Katz R,Kelly HW,Correlation between reversibility of airway obstruction and exhaled nitric oxide levels in children with stable bronchial asthmaPediatr PulmonolYear: 20003038539210.1002/1099-0496(200011)30:5<385::AID-PPUL4>3.0.CO;2-#11064429
Hunt J,Gaston B,Airway nitrogen oxide measurements in asthma and other pediatric respiratory diseasesJ PediatrYear: 2000137142010.1067/mpd.2000.10752610891815
Piacentini GL,Bodini A,Costella S,Suzuki Y,Zerman L,Peterson CG,Boner AL,Exhaled nitric oxide, serum ECP and airway responsiveness in mild asthmatic childrenEur Respir JYear: 20001583984310.1034/j.1399-3003.2000.15e05.x10853846
del Giudice MM,Brunese FP,Piacentini GL,Pedullà M,Capristo C,Decimo F,Capristo AF,Fractional exhaled nitric oxide (FENO), lung function and airway hyperresponsiveness in naïve atopic asthmatic childrenJ AsthmaYear: 20044175976510.1081/JAS-20002786215584636
Zietkowski Z,Bodzenta-Lukaszyk A,Tomasiak MM,Szymanski W,Skiepko R,Effect of ciclesonide and fluticasone on exhaled nitric oxide in patients with mild allergic asthmaRespir MedYear: 20061001651165610.1016/j.rmed.2005.12.00416443353
van Rensen EL,Straathof KC,Veselic-Charvat MA,Zwinderman AH,Bel EH,Sterk PJ,Effect of inhaled steroids on airway hyperresponsiveness, sputum eosinophils, and exhaled nitric oxide levels in patients with asthmaThoraxYear: 19995440340810.1136/thx.54.5.40310212103
Taylor DR,Pijnenburg MW,Smith AD,De Jongste JC,Exhaled nitric oxide measurements: clinical application and interpretationThoraxYear: 20066181782710.1136/thx.2005.05609316936238
de Jongste JC,Carraro S,Hop WC,Baraldi E,CHARISM Study GroupDaily telemonitoring of exhaled nitric oxide and symptoms in the treatment of childhood asthmaAm J Respir Crit Care MedYear: 2009179939718931330
Pijnenburg MW,Bakker EM,Hop WC,De Jongste JC,Titrating steroids on exhaled nitric oxide in children with asthma: a randomized controlled trialAm J Respir Crit Care MedYear: 200517283183610.1164/rccm.200503-458OC15976380
Fritsch M,Uxa S,Horak F Jr,Putschoegl B,Dehlink E,Szepfalusi Z,Frischer T,Exhaled nitric oxide in the management of childhood asthma: a prospective 6-months studyPediatr PulmonolYear: 20064185586210.1002/ppul.2045516850457
Szefler SJ,Mitchell H,Sorkness CA,Gergen PJ,O'Connor GT,Morgan WJ,Kattan M,Pongracic JA,Teach SJ,Bloomberg GR,Eggleston PA,Gruchalla RS,Kercsmar CM,Liu AH,Wildfire JJ,Curry MD,Busse WW,Management of asthma based on exhaled nitric oxide in addition to guideline-based treatment for inner-city adolescents and young adults: a randomised controlled trialLancetYear: 20083721065107210.1016/S0140-6736(08)61448-818805335
Petsky HL,Cates CJ,Lasserson TJ,Li AM,Turner C,Kynaston JA,Chang AB,A systematic review and meta-analysis: tailoring asthma treatment on eosinophilic markers (exhaled nitric oxide or sputum eosinophils)ThoraxYear: 20126719920810.1136/thx.2010.13557420937641
Pijnenburg MW,Floor SE,Hop WC,De Jongste JC,Daily ambulatory exhaled nitric oxide measurements in asthmaPediatr Allergy ImmunolYear: 20061718919310.1111/j.1399-3038.2006.00394.x16672005
Pijnenburg MW,Bakker EM,Lever S,Hop WC,De Jongste JC,High fractional concentration of nitric oxide in exhaled air despite steroid treatment in asthmatic childrenClin Exp AllergyYear: 20053592092510.1111/j.1365-2222.2005.02279.x16008679
Gelb AF,Taylor CF,Shinar CM,Gutierrez CA,Zamel N,Effect of fluticasone 250 microg/salmeterol 50 microg and montelukast on exhaled nitric oxide in asthmatic patientsCan Respir JYear: 20081519319818551200
Buchvald F,Eiberg H,Bisgaard H,Heterogeneity of FeNO response to inhaled steroid in asthmatic childrenClin Exp AllergyYear: 2003331735174010.1111/j.1365-2222.2003.01822.x14656363
Michils A,Baldassarre S,Van Muylem A,Exhaled nitric oxide and asthma control: a longitudinal study in unselected patientsEur Respir JYear: 20083153954610.1183/09031936.0002040718057062
Pifferi M,Bush A,Pioggia G,Di Cicco M,Chinellato I,Bodini A,Macchia P,Boner AL,Monitoring asthma control in children with allergies by soft computing of lung function and exhaled nitric oxideChestYear: 201113931932710.1378/chest.10-099220930008
van der Valk RJ,Baraldi E,Stern G,Frey U,de Jongste JC,Daily exhaled nitric oxide measurements and asthma exacerbations in childrenAllergyYear: 20126726527110.1111/j.1398-9995.2011.02734.x21999328
Bisgaard H,Loland L,Oj JA,NO in exhaled air of asthmatic children is reduced by the leukotriene receptor antagonist montelukastAm J Respir Crit Care MedYear: 19991601227123110508811
Ghiro L,Zanconato S,Rampon O,Piovan V,Pasquale MF,Baraldi E,Effect of montelukast added to inhaled corticosteroids on fractional exhaled nitric oxide in asthmatic childrenEur Respir JYear: 20022063063410.1183/09031936.02.0151200212358339
Straub DA,Minocchieri S,Moeller A,Hamacher J,Wildhaber JH,The effect of montelukast on exhaled nitric oxide and lung function in asthmatic children 2 to 5 years oldChestYear: 200512750951410.1378/chest.127.2.50915705989
Silkoff PE,Romero FA,Gupta N,Townley RG,Milgrom H,Exhaled nitric oxide in children with asthma receiving Xolair (omalizumab), a monoclonal anti-immunoglobulin E antibodyPediatricsYear: 200411330831210.1542/peds.113.4.e308
Hoffman SJ,Laham FR,Polack FP,Mechanisms of illness during respiratory syncytial virus infection: the lungs, the virus and the immune responseMicrob InfectYear: 2004676777210.1016/j.micinf.2004.03.010
Stark JM,Khan AM,Chiappetta CL,Xue H,Alcorn JL,Colasurdo GN,Immune and functional role of nitric oxide in a mouse model of respiratory syncytial virus infectionJ Infect DisYear: 200519138739510.1086/42724115633098
Song W,Liu G,Bosworth CA,Walker JR,Megaw GA,Lazrak A,Abraham E,Sullender WM,Matalon S,Respiratory syncytial virus inhibits lung epithelial Na+ channels by up-regulating inducible nitric-oxide synthaseJ Biol ChemYear: 20092847294730619131335
Tsutsumi H,Takeuchi R,Ohsaki M,Seki K,Chiba S,Respiratory syncytial virus infection of human respiratory epithelial cells enhances inducible nitric oxide synthase gene expressionJ Leukoc BiolYear: 1999669910410410996
Kao YJ,Piedra PA,Larsen GL,Colasurdo GN,Induction and regulation of nitric oxide synthase in airway epithelial cells by respiratory syncytial virusAm J Respir Crit Care MedYear: 200116353253911179135
Gadish T,Soferman R,Merimovitch T,Fireman E,Sivan Y,Exhaled nitric oxide in acute respiratory syncytial virus bronchiolitisArch Pediatr Adolesc MedYear: 201016472773110.1001/archpediatrics.2010.12820679163
Kovesi T,Dales R,Exhaled nitric oxide and respiratory symptoms in a community sample of school aged childrenPediatr PulmonolYear: 2008431198120510.1002/ppul.2092719003883
Carraro S,Andreola B,Alinovi R,Corradi M,Freo L,Da Dalt L,Baraldi E,Exhaled leukotriene B4 in children with community acquired pneumoniaPediatr PulmonolYear: 20084398298610.1002/ppul.2088918781641
Pasteur MC,Bilton D,Hill AT,British Thoracic Society Bronchiectasis non-CF Guideline GroupBritish Thoracic Society guideline for non-CF bronchiectasisThoraxYear: 201065115810.1136/thx.2009.11877820029032
Santamaria F,Montella S,Tiddens HA,Guidi G,Casotti V,Maglione M,de Jong PA,Structural and functional lung disease in primary ciliary dyskinesiaChestYear: 200813435135710.1378/chest.07-281218403663
Santamaria F,Montella S,Pifferi M,Ragazzo V,De Stefano S,De Paulis N,Maglione M,Boner AL,A descriptive study of non-cystic fibrosis bronchiectasis in a pediatric population from central and southern ItalyRespirationYear: 20097716016510.1159/00013751018523381
Patel IS,Vlahos I,Wilkinson TM,Lloyd-Owen SJ,Donaldson GC,Wilks M,Reznek RH,Wedzicha JA,Bronchiectasis, exacerbation indices, and inflammation in chronic obstructive pulmonary diseaseAm J Respir Crit Care MedYear: 200417040040710.1164/rccm.200305-648OC15130905
Chang AB,Masel JP,Masters B,Post-infectious bronchiolitis obliterans: clinical, radiological and pulmonary function sequelaePediatr RadiolYear: 199828232910.1007/s0024700502869426269
Chang AB,Bilton D,Exacerbations in cystic fibrosis: 4–Non-cystic fibrosis bronchiectasisThoraxYear: 20086326927610.1136/thx.2006.06091318308962
Santamaria F,Montella S,Camera L,Palumbo C,Greco L,Boner AL,Lung structure abnormalities, but normal lung function in pediatric bronchiectasisChestYear: 200613048048610.1378/chest.130.2.48016899848
Montella S,Santamaria F,Salvatore M,Pignata C,Maglione M,Iacotucci P,Mollica C,Assessment of chest high-field magnetic resonance imaging in children and young adults with non-cystic fibrosis chronic lung disease: comparison to high-resolution computed tomography and correlation with pulmonary functionInvest RadiolYear: 20094453253810.1097/RLI.0b013e3181b4c1ba19652613
Montella S,Maglione M,Bruzzese D,Mollica C,Pignata C,Aloj G,Manna A,Esposito A,Mirra V,Santamaria F,Magnetic resonance imaging is an accurate and reliable method to evaluate non-cystic fibrosis paediatric lung diseaseRespirologyYear: 201217879110.1111/j.1440-1843.2011.02067.x21943039
Wilson CB,Jones PW,O'Leary CJ,Hansell DM,Cole PJ,Wilson R,Effect of sputum bacteriology on the quality of life of patients with bronchiectasisEur Respir JYear: 1997101754176010.1183/09031936.97.100817549272915
Shoemark A,Devaraj A,Meister M,Ozerovitch L,Hansell DM,Wilson R,Elevated peripheral airway nitric oxide in bronchiectasis reflects disease severityRespir MedYear: 201110588589110.1016/j.rmed.2011.01.01521398103
Kharitonov SA,Wells AU,O'Connor BJ,Cole PJ,Hansell DM,Logan-Sinclair RB,Barnes PJ,Elevated levels of exhaled nitric oxide in bronchiectasisAm J Respir Crit Care MedYear: 1995151188918937767536
Horváth I,Loukides S,Wodehouse T,Csiszér E,Cole PJ,Kharitonov SA,Barnes PJ,Comparison of exhaled and nasal nitric oxide and exhaled carbon monoxide levels in bronchiectatic patients with and without primary ciliary dyskinesiaThoraxYear: 200358687210.1136/thorax.58.1.6812511725
Ho LP,Innes JA,Greening AP,Exhaled nitric oxide is not elevated in the inflammatory airways diseases of cystic fibrosis and bronchiectasisEur Respir JYear: 1998121290129410.1183/09031936.98.120612909877479
Tsang KW,Leung R,Fung PC,Chan SL,Tipoe GL,Ooi GC,Lam WK,Exhaled and sputum nitric oxide in bronchiectasis: correlation with clinical parametersChestYear: 2002121889410.1378/chest.121.1.8811796436
Zihlif N,Paraskakis E,Lex C,Van de Pohl LA,Bush A,Correlation between cough frequency and airway inflammation in children with primary ciliary dyskinesiaPediatr PulmonolYear: 20053955155710.1002/ppul.2020215806596
Robroeks CM,Rosias PP,van Vliet D,Jöbsis Q,Yntema JB,Brackel HJ,Damoiseaux JG,den Hartog GM,Wodzig WK,Dompeling E,Biomarkers in exhaled breath condensate indicate presence and severity of cystic fibrosis in childrenPediatr Allergy ImmunolYear: 20081965265918312532
Grasemann H,Michler E,Wallot M,Ratjen F,Decreased concentration of exhaled nitric oxide (NO) in patients with cystic fibrosisPediatr PulmonolYear: 19972417317710.1002/(SICI)1099-0496(199709)24:3<173::AID-PPUL2>3.0.CO;2-O9330413
Tsoukias NM,George SC,A two-compartment model of pulmonary nitric oxide exchange dynamicsJ Appl PhysiolYear: 1998856536669688744
Keen C,Gustafsson P,Lindblad A,Wennergren G,Olin AC,Low levels of exhaled nitric oxide are associated with impaired lung function in cystic fibrosisPediatr PulmonolYear: 20104524124820146368
Suri R,Paraskakis E,Bush A,Alveolar, but not bronchial nitric oxide production is elevated in cystic fibrosisPediatr PulmonolYear: 2007421215122110.1002/ppul.2073017969001
Paraskakis E,Zihlif N,Bush A,Nitric oxide production in PCD: possible evidence for differential nitric oxide synthase functionPediatr PulmonolYear: 20074287688010.1002/ppul.2067017722051
Vece TJ,Fan LL,Diagnosis and management of diffuse lung disease in childrenPaediatr Respir RevYear: 20111223824210.1016/j.prrv.2011.04.00122018037
Doan ML,Guillerman RP,Dishop MK,Nogee LM,Langston C,Mallory GB,Sockrider MM,Fan LL,Clinical, radiological and pathological features of ABCA3 mutations in childrenThoraxYear: 20086336637310.1136/thx.2007.08376618024538
Malerba M,Radaeli A,Ragnoli B,Airo' P,Corradi M,Ponticiello A,Zambruni A,Grassi V,Exhaled nitric oxide levels in systemic sclerosis with and without pulmonary involvementChestYear: 200713257558010.1378/chest.06-292917550935
Sandrini A,Johnson AR,Thomas PS,Yates DH,Fractional exhaled nitric oxide concentration is increased in asbestosis and pleural plaquesRespirologyYear: 20061132532910.1111/j.1440-1843.2006.00852.x16635093
Wilsher ML,Fergusson W,Milne D,Wells AU,Exhaled nitric oxide in sarcoidosisThoraxYear: 20056096797010.1136/thx.2004.03385216244094
Estenne M,Hertz MI,Bronchiolitis obliterans after human lung transplantationAm J Respir Crit Care MedYear: 200216644044410.1164/rccm.200201-003PP12186817
Zhang L,Irion K,Kozakewich H,Reid L,Camargo JJ,da Silva Porto N,Silva FA Ae,Clinical course of postinfectious bronchiolitis obliteransPediatr PulmonolYear: 20002934135010.1002/(SICI)1099-0496(200005)29:5<341::AID-PPUL2>3.0.CO;2-410790245
Fisher AJ,Gabbay E,Small T,Doig S,Dark JH,Corris PA,Cross sectional study of exhaled nitric oxide levels following lung transplantationThoraxYear: 19985345445810.1136/thx.53.6.4549713443
Verleden GM,Dupont L,Lamont J,Buyse B,Delcroix M,Van Raemdonck D,Lerut T,Vanhaecke J,Demedts MG,Is there a role for measuring exhaled nitric oxide in lung transplant recipients with chronic rejection?J Heart Lung TransplantYear: 1998172312329513863
Neurohr C,Huppmann P,Leuschner S,von Wulffen W,Meis T,Leuchte H,Ihle F,Zimmermann G,Baezner C,Hatz R,Winter H,Frey L,Ueberfuhr P,Bittmann I,Behr J,Munich Lung Transplant GroupUsefulness of exhaled nitric oxide to guide risk stratification for bronchiolitis obliterans syndrome after lung transplantationAm J TransplantYear: 20111112913710.1111/j.1600-6143.2010.03327.x21087415
Van Muylem A,Knoop C,Estenne M,Early detection of chronic pulmonary allograft dysfunction by exhaled biomarkersAm J Respir Crit Care MedYear: 200717573173610.1164/rccm.200609-1301OC17234904
Brugière O,Thabut G,Mal H,Marceau A,Dauriat G,Marrash-Chahla R,Castier Y,Lesèche G,Colombat M,Fournier M,Exhaled NO may predict the decline in lung function in bronchiolitis obliterans syndromeEur Respir JYear: 20052581381910.1183/09031936.05.0005700415863637
Verleden GM,Dupont LJ,Van Raemdonck DE,Vanhaecke J,Leuven Lung Transplant GroupAccuracy of exhaled nitric oxide measurements for the diagnosis of bronchiolitis obliterans syndrome after lung transplantationTransplantationYear: 20047873073315371677
Gabbay E,Walters EH,Orsida B,Whitford H,Ward C,Kotsimbos TC,Snell GI,Williams TJ,Post-lung transplant bronchiolitis obliterans syndrome (BOS) is characterized by increased exhaled nitric oxide levels and epithelial inducible nitric oxide synthaseAm J Respir Crit Care MedYear: 20001622182218711112135

[TableWrap ID: T1] Table 1 

FeNO reference values in healthy children and adolescents

Author [reference] N Subjects Normal values* Analyzer
Dötsch 1996 [24]
Caucasian, 4-18 years
3.1 ppb
CLD 700; Eco Physics, Dürnten, Switzerland
Baraldi 1999[18]
Caucasian, 6–15 years
8.7 ppb
CLD 700, Al-Med, Ecophysics, Durnten, Switzerland
Silvestri 1999[25]
Caucasian, 11-12 years
4.0 ppb
LR 2000, Logan System, Rochester, Kent, UK
Franklin 1999[26]
Caucasian, 7-13 years
7.4 ppb
NOA 280, Seivers Instruments Inc., Boulder, CO
Latzin 2002[27]
Caucasian, 4-18 years
9.2 ppb
LR 2000, Logan Research, Rochester, UK
Jouaville 2003[28]
Caucasian, 9-10 years
13.3 ppb
Sievers Instruments, Boulder, CO, USA, kit bag collection
Buchvald 2005[19]
Caucasian, Hispanic, Asian, Black, 4–17 years
9.7 ppb
NIOX, Aerocrine AB, Stockholm, Sweden
Wong 2005[21]
Chinese, 11-18 years
19.9 ppb
NIOX, Aerocrine AB, Stockholm, Sweden
Caucasian, 11-18 years
12.7 ppb
Malmberg 2006[22]
Caucasian, 7.2-15.7 years
Mean values not reported; range 7-14 ppb
NIOX, Aerocrine AB, Stockholm, Sweden
Kovesi 2008[20]
White, Black, Asian, 9.1-12.9 years
12.7 ppb
CLD 88sp, Eco Medics AG; Durnten, Switzerland
Yao 2012[23] 693 Asiatic, 5-18 years 13.7 ppb CLD 88sp, Eco Medics AG; Durnten, Switzerland

*Expressed as mean values.

[TableWrap ID: T2] Table 2 

Diagnostic accuracy of FeNO measurement in patients with asthma

Author [reference] Subjects Patients with asthma (%) FeNO cut-point Sensitivity (%) Specificity (%)
Malmberg 2003[58]
Children, 3-7 years
83 (25)
> 9.7 ppb
Dupont 2003[50]
160 (66)
> 16 ppb
Berkman 2005[57]
40 (47)
> 7 ppb
Sivan 2009[51]
Children, 12-18 years
106 (70)
> 19 ppb
Sachs-Olsen 2010[52]
Children, 10-12 years
60 (45)
> 20.4 ppb
Pérez Tarazona 2011[53]
Children, 6-14 years
57 (40)
> 19 ppb
Yao 2011[54]
Children, 5-18 years
70 (4.5)
> 28 ppb
Cordeiro 2011[55]
Adults, Children
42 (30)
> 27 ppb
Woo 2012[56] Children, 8-16 years 167 (68) > 22 ppb 57 87

Article Categories:
  • Review

Keywords: Exhaled nitric oxide, Children, Airway diseases, Asthma, Bronchiolitis, Community acquired pneumonia, Bronchiectasis, Diffuse lung disease.

Previous Document:  A 2:1 Dicationic Complex of Tetraethyl Methylenebisphosphonate with Uranyl Ion in Acetonitrile and I...
Next Document:  Reannotation of translational start sites in the genome of Mycobacterium tuberculosis.