Top PDF Exhaled nitric oxide and clinical phenotypes of childhood asthma

Exhaled nitric oxide and clinical phenotypes of childhood asthma

Exhaled nitric oxide and clinical phenotypes of childhood asthma

This single centre cohort conducted in a secondary care out-hospital clinic enrolls asthmatic children since 1997. Since 2008, exhaled NO and clinical events were recorded. Levels of asthma control were systematically assessed using only two levels of GINA guidelines dur- ing past three months:[11] controlled versus partially/ uncontrolled asthma (omitting lung function since PFT were obtained without treatment). Severe exacerbations, according to ATS/ERS definition, [12] and the number of days (1) with symptoms (GINA guidelines) [11] and (2) with systemic steroid were specifically recorded. This cohort has been declared to our regulatory agency for computer data collection (Commission Nationale Informatique et Libertés, n°1408710), and approval from the Ethics Committee of French learned Society of Pulmonology - SPLF was obtained (CEPRO 2009/019). All children and parents were informed of the prospective recording of clinical and physiological data.
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Inflammatory phenotypes underlying uncontrolled childhood asthma despite inhaled corticosteroid treatment: rationale and design of the PACMAN2 study

Inflammatory phenotypes underlying uncontrolled childhood asthma despite inhaled corticosteroid treatment: rationale and design of the PACMAN2 study

Methods/design: The purpose of the PACMAN2 study is to identify inflammatory phenotypes that can discriminate uncontrolled childhood asthma from controlled childhood asthma by measures in peripheral blood and exhaled air. PACMAN2 is a nested, case – control follow-up study to the ongoing pharmacy-based “ Pharmacogenetics of Asthma medication in Children: Medication with Anti-inflammatory effects ” (PACMAN) study. The original PACMAN cohort consists of children aged 4 – 12 years with reported use of asthma medication. The PACMAN2 study will be conducted within the larger PACMAN cohort, and will focus on detailed phenotyping of a subset of the PACMAN children. The selected participants will be invited to a follow-up visit in a clinical setting at least six months after their baseline visit based on their adherence to usage of inhaled corticosteroids, their asthma symptoms in the past year, and their age ( ≥ 8 years). During the follow-up visit, current and long-term asthma symptoms, medication use, environmental factors, medication adherence and levels of exhaled nitric oxide will be reassessed. The following measures will also be examined: pulmonary function, exhaled volatile organic compounds, as well as inflammatory markers in peripheral blood and blood plasma. Comparative analysis and cluster-analyses will be used to identify markers that differentiate children with uncontrolled asthma despite their use of inhaled corticosteroids (ICS) (cases) from children whose asthma is controlled by the use of ICS (controls).
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Exhaled nitric oxide is related to atopy, but not asthma in adolescents with bronchiolitis in infancy

Exhaled nitric oxide is related to atopy, but not asthma in adolescents with bronchiolitis in infancy

Background: The fraction of exhaled nitric oxide (FeNO) has been suggested as a non-invasive marker of eosinophilic inflammation in asthma, but lately rather as a biomarker of atopy than of asthma itself. Asthma after bronchiolitis is common up to early adolescence, but the inflammation and pathophysiology may differ from other phenotypes of childhood asthma. We aimed to assess if FeNO was different in children with former hospitalization for bronchiolitis and a control group, and to explore whether the role of FeNO as a marker of asthma, atopy or bronchial hyperresponsiveness (BHR) differed between these two groups of children.
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Comparison of treatment guidance based on bronchial  responsiveness to mannitol, spirometry or exhaled nitric oxide in stable asthmatic children

Comparison of treatment guidance based on bronchial responsiveness to mannitol, spirometry or exhaled nitric oxide in stable asthmatic children

Mannitol dry powder (MDP) challenge is an indirect bronchial provocation test, which is well studied in adults and is used more and more in the assessment of childhood asthma. A recent study has proven that the MDP challenge is safe and feasible in asthmatic children [34]. However, only few studies have investigated the use of mannitol as diagnostic tool to evaluate BHR. Anderson and Lipworth evaluated relationships between mannitol BHR and methacholine challenge as well as measures of airway inflammation (FeNO and salivary eosinophilic cationic protein) in adult persistent asthmat- ics receiving inhaled corticosteroids [35]. The authors observed a good correlation between mannitol, meth- acholine and FeNO and concluded that mannitol chal- lenge adequately reflects bronchial inflammation. Inter- estingly, a recent study suggested that FeNO is sensitive and specific for accurately predicting BHR, measured by the response to inhaled mannitol, in steroid-naïve ado- lescents and young adults, revealing an optimal cut-off at 25 ppb [36]. The authors concluded that inhaled mannitol challenge does not add additional diagnostic information when FeNO values are low. Moreover, mannitol has been shown to be less sensitive than methacholine to predict BHR in youth athletes with exercise-induced bronchoconstriction, pointing to a possible influence of asthma phenotype in the value of diagnostic methods for BHR [37].
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Metabolic origins of childhood asthma

Metabolic origins of childhood asthma

asthma, poor asthma control, frequent exacerbations, and asthma-related hospitalizations [17,25,26,32-34]. The age of the weight gain may play a role, as pronounced weight gain early in life was identified as a risk factor for develop- ing asthma in the first 6 years of age [35]. Two types of asthma in obese subjects can be distinguished by age of onset and clinical presentation. Early-onset asthma in obese presents before the age of 12 years, has no gender preference, and is characterized by severely decreased pul- monary function, significant airway hyperresponsiveness, and poor asthma control. These patients are atopic; serum immunoglobulin E (IgE) is increased, airway inflammation is eosinophilic, and fraction of exhaled nitric oxide (FeNO) is high [28]. In contrast, obese late-onset asthmatics be- come symptomatic after the age of 12 and are predomin- antly females without atopic characteristics. Compared to early-onset asthmatics, they have little airway obstruction with less airway hyperresponsiveness and better asthma control. This phenotype has a TH2 low profile with pre- dominant neutrophilic airway infiltration [36], which may at least in part explain the poor response to standard asthma therapy in this patient group.
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Importance of fractional exhaled nitric oxide in the differentiation of asthma–COPD overlap syndrome, asthma, and COPD

Importance of fractional exhaled nitric oxide in the differentiation of asthma–COPD overlap syndrome, asthma, and COPD

Background: Fractional exhaled nitric oxide (FeNO) is an easy, sensitive, reproducible, and noninvasive marker of eosinophilic airway inflammation. Accordingly, FeNO is extensively used to diagnose and manage asthma. Patients with COPD who share some of the features of asthma have a condition called asthma–COPD overlap syndrome (ACOS). The feasibility of using FeNO to differentiate ACOS patients from asthma and COPD patients remains unclear. Methods: From February 2013 to May 2016, patients suspected with asthma and COPD through physician’s opinion were subjected to FeNO measurement, pulmonary function test (PFT), and bronchial hyperresponsiveness or bronchodilator test. Patients were divided into asthma alone group, COPD alone group, and ACOS group according to a clinical history, PFT values, and bronchial hyperresponsiveness or bronchodilator test. Receiver operating characteristic (ROC) curves were obtained to elucidate the clinical functions of FeNO in diagnosing ACOS. The optimal operating point was also determined.
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Both fractional exhaled nitric oxide and sputum eosinophil were associated with uncontrolled asthma

Both fractional exhaled nitric oxide and sputum eosinophil were associated with uncontrolled asthma

Background: Sputum eosinophil and fractional exhaled nitric oxide (FeNO), noninvasive biomarkers of local eosinophilic airway inflammation, can be used to assess asthma outcome. Nevertheless, the clinical application of the association between FeNO and sputum eosinophil is controversial. The aim of the study was to investigate the predictive relationship between FeNO and sputum eosinophil in uncontrolled asthmatic patients and the correlation between sputum eosinophil and FeNO in bronchial reversibility and bronchial hyperresponsiveness (BHR). Methods: A total of 69 uncontrolled asthmatic patients were included in the study. All patients underwent a clinical assessment on the same day as follows: FeNO, spirometry with BHR or bronchodilator reversibility test and induced sputum in turn. Eosinophilic airway inflammation was defined as sputum eosinophil percentage (≥2.5%)/FeNO level (≥32 parts per billion [ppb]). Results: FeNO level and sputum neutrophilic percentage were higher in the sputum eosinophilia group compared to those without (49 versus 27, p=0.011; 71.12 versus 87.67, p=0.012, respec­ tively). Sputum eosinophil percentage was higher with raised FeNO level compared to those without (10.3% versus 2.75%, p=0.03). A significant correlation was observed between sputum eosinophil percentage and FeNO level (r=0.4016; p=0.0006). There were no significant relation­ ships between sputum eosinophilic percentage and provocative dose (PD 20 )/∆FEV 1 (improvement
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Original Article Analysis of the diagnostic value of fractional exhaled nitric oxide and IgE in children with asthma

Original Article Analysis of the diagnostic value of fractional exhaled nitric oxide and IgE in children with asthma

coughing, recurrent coughing, sleep disorders, nasal flaring, and pulmonary rales; Patients with atypical symptoms, accompanied by posi- tive bronchial provocation tests or exercise tests positive; No presence of allergic diseas- es; No history of glucocorticoid therapy; No his- tory of drug allergies; No history of respiratory diseases; Complete clinical data. Exclusion cri- teria: Cases with wheezing, shortness of breath, or coughing caused by other diseases; Children treated with anti-IgE antibody drugs; Presence of abnormal bleeding or coagulation disorders; Cardiovascular and cerebrovascular diseases; Liver and kidney diseases; Digestive diseases; Transfers; Relatives of the children did not cooperate with the treatment; Presence of mental disorders. Healthy children aged 1-10 years with complete data were included. Children with a history of allergic rhinitis, bron- chial asthma, family allergies, and acute respi- ratory infections before treatment were also excluded. The current study was approved by the Medical Ethics Committee of the Affiliated Renji Hospital, Shanghai Jiaotong University School of Medicine. All patients and family members provided informed consent.
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<p>Clinical Utility Of The Exhaled Nitric Oxide (NO) Measurement With Portable Devices In The Management Of Allergic Airway Inflammation And Asthma</p>

<p>Clinical Utility Of The Exhaled Nitric Oxide (NO) Measurement With Portable Devices In The Management Of Allergic Airway Inflammation And Asthma</p>

NOS or iNOS/NOS-2, and endothelial NOS or eNOS/ NOS-3). Endogenous NO production is dependent on the concentration of extracellular L-arginine, which is the sub- strate for both arginase, yielding L-ornithine and urea, and NOS, yielding NO and L-citrulline. NO production in airway epithelial cells is closely coupled to cellular L-arginine uptake. Therefore, in the airways, NO production depends not only on NOS isoform bioactivities but also on the bioa- vailability of the substrate by competing for their common substrate. After production, NO is dissolved in the cyto- plasm, then diffused through the cell membrane to the extra- cellular environment. In the respiratory system (airways and lungs), NO acts as a signaling molecule of the intercellular information process for modulating vascular and bronchial tone, promoting bronchial and vascular dilatation, facilitating ciliary beating of epithelial cells, and playing the crucial role of neurotransmitter of the non-adrenergic and non-choliner- gic systems. 18 – 20 NO can be detected in exhaled breath from the nose (nasal concentration of NO or nNO), through the bronchial tree (fractional concentration of exhaled NO or FE NO ) and to lung parenchyma (alveolar concentration of
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Diagnosing asthma in general practice with portable exhaled nitric oxide measurement – results of a prospective diagnostic study

Diagnosing asthma in general practice with portable exhaled nitric oxide measurement – results of a prospective diagnostic study

stantial over-diagnosis of COPD [41]. However, most patients identified as COPD were heavy smokers (21 of 25 with at least ten pack years), and patients with asthma had positive bronchodilation response or positive bronchial provocation result. That makes a false diagnostics improb- able from a clinical point of view. Another point of discus- sion is the correct classification of the eight patients with only incomplete bronchodilator response. The best way for differentiation would have been a long term follow-up with trials of inhaled steroids, which was not possible within the study design. Beside that, bronchial provoca- tion in all patients might have been helpful for further dif- ferentiation. However, this was not allowed by the Ethics Committee due to the risk of severe bronchial spasm. Based on medical history and spirometry investigation, five patients were very similar to COPD (all were heavy smokers) and the remaining three were most probably asthma patients with fixed airway obstruction. The sensi- tivity analyses showed that the cut-off point of FENO remained the same when actually non-smoking patients initially labelled as COPD or overlap were classified as asthma patients with fixed airway obstruction. This might attenuate the potential limitation, in particular as this dif- ficult diagnostic group was small.
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Fractional exhaled nitric oxide for the management of asthma in adults: Systematic review

Fractional exhaled nitric oxide for the management of asthma in adults: Systematic review

There are at least two previous systematic reviews on the effectiveness of F eNO monitoring to guide management [9, 11]. P ETSKY et al. [9] compared adjustments of asthma therapy based on F eNO with conventional methods (typically clinical symptoms and spirometry). The review suggested some benefits associated with F eNO for several outcomes, in particular the number of subjects with >1 exacerbation, exacerbation rates, FEV 1 % predicted at final visit and geometric change in F eNO from baseline; however, none of these results were statistically conclusive. F eNO appeared to have some beneficial effect on symptom score (mean difference: −0.14, 95% CI −0.42–0.14) and lowered ICS dose (mean difference: − 450.03 μ g, 95% CI − 676.73 –− 223.34 μ g). Furthermore, there was substantial clinical heterogeneity among the study cohorts, with no two studies using exactly the same step-up/step-down protocols. There TABLE 6 Relationship between inhaled corticosteroid (ICS) use, step-up/step-down protocol and exacerbations
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Exhaled nitric oxide and inhaled corticosteroid dose reduction in asthma: a cohort study

Exhaled nitric oxide and inhaled corticosteroid dose reduction in asthma: a cohort study

In addition to the failure to predict ICS reduction using FeNO we found that none of the baseline clinical indices (including induced sputum, methacholine responsiveness and spirometry) had predictive value for future stability following ICS step down. This has important implications for ICS dose reduction and suggests better methods of identification of those at risk of a loss of control following ICS dose reduction are needed.

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The STOPPA Twin Study Explains the Exhaled Nitric Oxide and Asthma Link by Genetics and Sensitization

The STOPPA Twin Study Explains the Exhaled Nitric Oxide and Asthma Link by Genetics and Sensitization

The strengths of this study were the twin-design with within-pair analyses, which by design adjust for deter- minants of FENO that are shared within twin pairs, both unknown and unmeasurable, and known determinants like sex, age, and genetics. Furthermore, the children were examined objectively: FENO was measured according to ATS/ERS guidelines (American Thoracic & European Respiratory, 2005), and analyzed as both categorical and linear measures; information on current asthma was based on definitions from the ISAAC study (Asher et al., 1995); and reliable measures of zygosity were based on a validated algorithm or confirmed by DNA testing (Lichtenstein et al., 2002). A potential limitation of this study was the cross-sectional design and sample size. The study was not large enough to perform reliable within-pair analyses of asthma and sensitization phenotypes stratified by zygosity using the dichotomized FENO measure. However, compar- isons could be done using FENO as a continuous outcome measure. Another limitation was the generalizability of results from twin studies to the singleton population. While twins differ from singletons in that they on average are born smaller, we have recently shown that after taking gestational age into account, twins are not at higher risk of asthma (Ullemar et al., 2015).
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Elevated fractional exhaled nitric oxide and blood eosinophil counts are associated with a 17q21 asthma risk allele in adult subjects

Elevated fractional exhaled nitric oxide and blood eosinophil counts are associated with a 17q21 asthma risk allele in adult subjects

phil count was used as an inclusion criterion to enrich the study with potential responders. Based on our report, the SNP rs7216839 represents a genotypic biomarker in asthma. We speculate that the SNP rs7216839, possibly in conjunction with other SNPs, may serve as a genotypic biomarker and predictor of response to asthma therapies such as those cur- rently available and in development for asthma. Traditional biomarkers are subject to variability due to medication use and comorbidities. Therefore, identification of combinations of genotypic biomarkers may provide a more accurate stratifi- cation of asthma phenotypes for achieving personalized care of asthma. Further studies of large cohorts will be essential to confirm and validate these results.
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Comparison of Fractional Exhaled Nitric Oxide in Elderly Patients with Asthma-chronic Obstructive Pulmonary Disease Overlap and Other Airway Inflammatory Diseases

Comparison of Fractional Exhaled Nitric Oxide in Elderly Patients with Asthma-chronic Obstructive Pulmonary Disease Overlap and Other Airway Inflammatory Diseases

In a study by Schneider A et al 10 the exhaled NO level was found to be higher (44.3 ppb) in asthmatic patients with eosinophilic inflammation, and lower (18.5 ppb) with neutrophilic inflammation. We found the median level of FeNO in the Asthma group (36.3 ppb) was slightly under the previously value with eosinophilic inflammation, which might be due to the genetic, regional difference, and small sample size in our study. On the other hand, non-eosinophilic inflammation was likely to contribute to this low FeNO level, 21 suggesting that FeNO measurements should be used to identify the inflammatory phenotypes of asthma in the elderly, and to help tailor asthma therapy appropriately. 22,23 Moreover, the median level of FeNO in the elderly with COPD or chronic cough was below the previously published threshold levels of adult healthy subjects (26 ppb). 24 Based on this it can be concluded that the ability of FeNO to estimate the inflammatory properties of COPD or chronic cough is limited, and other factors including smoking status, oxidative products and atopic symptoms should be always considered or analyzed.
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Clinical application of exhaled nitric oxide measurement in pediatric lung diseases

Clinical application of exhaled nitric oxide measurement in pediatric lung diseases

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]. More- over, in corticosteroid-naïve patients with suspected asthma, the baseline FeNO value may predict an ICS re- sponse 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 measure- ment 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 de- termine 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].
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Clinical utility of fractional exhaled nitric oxide and blood eosinophils counts in the diagnosis of asthma-COPD overlap

Clinical utility of fractional exhaled nitric oxide and blood eosinophils counts in the diagnosis of asthma-COPD overlap

of the ACO took into consideration the following general categories: age at onset, pattern of symptoms, lung func- tion, patient or family history, time course, and chest X-ray. Participants in this study fulfilled three or more features of COPD. Among patients with COPD, we further identified ACO patients as those with three or more features of asthma as follows: onset before age 20 years, family history of asthma or allergic rhinitis or eczema, normal findings on chest X-rays without severe hyperinflation, common time course in asthmatic patients, variable respiratory symptoms, and vari- able expiratory airflow limitation. The common time course included spontaneous improvement and immediate response to bronchodilator or to ICS over weeks. Variable respiratory symptoms included wheezing and shortness of breath that varied over minutes, hours, or days and worsened during the night or early morning. Variable expiratory airflow limitation was defined as improvement in forced expiratory volume in 1 second 200 mL and 12% from baseline immediately
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The Breathing for Life Trial: a randomised controlled trial of fractional exhaled nitric oxide (FENO) based management of asthma during pregnancy and its impact on perinatal outcomes and infant and childhood respiratory health

The Breathing for Life Trial: a randomised controlled trial of fractional exhaled nitric oxide (FENO) based management of asthma during pregnancy and its impact on perinatal outcomes and infant and childhood respiratory health

Background: Asthma exacerbations are common during pregnancy and associated with an increased risk of adverse perinatal outcomes. Adjusting asthma treatment based on airway inflammation rather than symptoms reduces the exacerbation rate by 50 %. The Breathing for Life Trial (BLT) will test whether this approach also improves perinatal outcomes. Methods/design: BLT is a multicentre, parallel group, randomised controlled trial of asthma management guided by fractional exhaled nitric oxide (FENO, a marker of eosinophilic airway inflammation) compared to usual care, with prospective infant follow-up. Women with physician-diagnosed asthma, asthma symptoms and/or medication use in the previous 12 months, who are 12 – 22 weeks gestation, will be eligible for inclusion. Women randomised to the control group will have one clinical assessment of their asthma, including self-management education. Any treatment changes will be made by their general practitioner. Women randomised to the intervention group will have clinical assessments every 3 – 6 weeks during pregnancy, and asthma treatments will be adjusted every second visit based on an algorithm which uses FENO to adjust inhaled corticosteroid (ICS) dose (increase in dose when FENO >29 parts per billion (ppb), decrease in dose when FENO <19 ppb, and no change when FENO is between 19 and 29 ppb). A long acting beta agonist (LABA) will be added when symptoms remain uncontrolled. Both the control and intervention groups will report on exacerbations at a postpartum phone interview. The primary outcome is adverse perinatal outcome (a composite measure including preterm birth, intrauterine growth restriction, neonatal hospitalisation at birth or perinatal mortality), assessed from hospital records. Secondary outcomes will be each component of the primary outcome, maternal exacerbations requiring medical intervention during pregnancy (both smokers and non-smokers), and hospitalisation and emergency department presentation for wheeze, bronchiolitis or croup in the first 12 months of infancy. Outcome assessment and statistical analysis of the primary outcome will be blinded. To detect a reduction in adverse perinatal outcomes from 35 % to 26 %, 600 pregnant women with asthma per group are required.
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Analysis of nitrogen oxides (NOx) in the exhaled breath condensate (EBC) of subjects with asthma as a complement to exhaled nitric oxide (FeNO) measurements: a cross sectional study

Analysis of nitrogen oxides (NOx) in the exhaled breath condensate (EBC) of subjects with asthma as a complement to exhaled nitric oxide (FeNO) measurements: a cross sectional study

through exhaled breath condensates (EBC) appears pro- mising in this regard. This noninvasive method is both simple and reproducible, making it possible to explore the more specific factors of both inflammation and oxi- dative stress, through the study of NOx in EBC [13-15]. Despite the wide interest in this method, many metho- dological pitfalls remain, including the choice of systems for collection, storage and analysis [3,11]. The high intra assay variability of biomarker measurements is an important factor that explains its limited use in daily clinical practice [10,16]. The necessity for standardisa- tion has been the subject of numerous publications over the past five years [11].
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Study of nasal exhaled nitric oxide levels in diagnosis of allergic rhinitis in subjects with and without asthma

Study of nasal exhaled nitric oxide levels in diagnosis of allergic rhinitis in subjects with and without asthma

From January 2015 to May 2016, 628 subjects were included in the present study, including 217 control subjects, 168 subjects with AR (AR non-asthma), and 243 subjects with AR-asthma. The anthropometric and clinical and functional characteristics of the study subjects are presented in Table 1. There were no significant differences between the three groups in mean age, male to female ratio, or BMI. The AR symptoms were significantly different between subjects with AR vs those with AR-asthma, with predominance of nasal congestion in the AR-asthma cohort (92% vs 75%, P < 0.05; Table 1). There was no significant difference in the percentage of positive skin tests between subjects with AR and those with AR-asthma (Table 1). The FEV 1 was significantly lower in subjects with AR-asthma than in control subjects and subjects with AR non- asthma (77% ± 23% vs 97% ± 11% and 93% ± 12%, P < 0.001 and P < 0.01, respectively; Table 1). Nasal PIF and PEF were significantly lower in subjects with AR and AR-asthma than in control subjects (86 ± 22 and 89 ± 37 L/min vs 134 ± 33 L/min, P < 0.01 and P < 0.01; and 134 ± 50 and 113 ± 33 L/min vs 175 ± 48 L/min, P < 0.05 and P < 0.01, respectively; Table 1). The levels of nasal FENO were significantly higher in subjects with AR and AR-asthma than in control subjects (1614 ± 629 and 1686 ± 614 ppb vs 582 ± 161 ppb; P < 0.001 and P < 0.001, respectively).
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