Performance of a new hand-held device for exhaled nitric oxide measurement in adults and children

BACKGROUND: Exhaled nitric oxide (NO) measurement has been shown to be a valuable tool in the management of patients with asthma. Up to now, most measurements have been done with stationary, chemiluminescence-based NO analysers, which are not suitable for the primary health care setting. A hand-held NO analyser which simplifies the measurement would be of value both in specialized and primary health care. In this study, the performance of a new electrochemical hand-held device for exhaled NO measurements (NIOX MINO) was compared with a standard stationary chemiluminescence unit (NIOX). METHODS: A total of 71 subjects (6–60 years; 36 males), both healthy controls and atopic patients with and without asthma were included. The mean of three approved exhalations (50 ml/s) in each device, and the first approved measurement in the hand-held device, were compared with regard to NO readings (Bland-Altman plots), measurement feasibility (success rate with 6 attempts) and repeatability (intrasubject SD). RESULTS: Success rate was high (≥ 84%) in both devices for both adults and children. The subjects represented a FE(NO )range of 8–147 parts per billion (ppb). When comparing the mean of three measurements (n = 61), the median of the intrasubject difference in exhaled NO for the two devices was -1.2 ppb; thus generally the hand-held device gave slightly higher readings. The Bland-Altman plot shows that the 95% limits of agreement were -9.8 and 8.0 ppb. The intrasubject median difference between the NIOX and the first approved measurement in the NIOX MINO was -2.0 ppb, and limits of agreement were -13.2 and 10.2 ppb. The median repeatability for NIOX and NIOX MINO were 1.1 and 1.2 ppb, respectively. CONCLUSION: The hand-held device (NIOX MINO) and the stationary system (NIOX) are in clinically acceptable agreement both when the mean of three measurements and the first approved measurement (NIOX MINO) is used. The hand-held device shows good repeatability, and it can be used successfully on adults and most children. The new hand-held device will enable the introduction of exhaled NO measurements into the primary health care

Expression of transforming growth factor-β (TGF-β) in chronic idiopathic cough

In patients with chronic idiopathic cough, there is a chronic inflammatory response together with evidence of airway wall remodelling and an increase in airway epithelial nerves expressing TRPV-1. We hypothesised that these changes could result from an increase in growth factors such as TGFβ and neurotrophins

Assessing airway inflammation in clinical practice – experience with spontaneous sputum analysis

<p>Abstract</p> <p>Background</p> <p>The assessment of airway inflammation for the diagnosis of asthma or COPD is still uncommon in pneumology-specialized general practices. In this respect, the measurement of exhaled nitric oxide (NO), as a fast and simple methodology, is increasingly used. The indirect assessment of airway inflammation, however, does have its limits and therefore there will always be a need for methods enabling a direct evaluation of airway inflammatory cell composition. Sampling of spontaneous sputum is a well-known, simple, economic and non-invasive method to derive a qualitative cytology of airway cells and here we aimed to assess today's value of spontaneous sputum cytology in clinical practice.</p> <p>Methods</p> <p>Three pneumologists provided final diagnoses in 481 patients having sputum cytology and we retrospectively determined posterior versus prior probabilities of inflammatory airway disorders. Moreover, in a prospective part comprising 108 patients, pneumologists rated their confidence in a given diagnosis before and after knowing sputum cytology and rated its impact on the diagnostic process on an analogue scale.</p> <p>Results</p> <p>Among the 481 patients, 45% were diagnosed as having asthma and/or airway hyperresponsiveness. If patients showed sputum eosinophilia, the prevalence of this diagnosis was elevated to 73% (n = 109, p < 0.001). The diagnosis of COPD increased from 40 to 66% in patients with neutrophilia (n = 29, p < 0.01).</p> <p>Thirty-three of the 108 patients were excluded from the prospective part (26 insufficient samples, 7 incomplete questionnaires). In 48/75 cases the confidence into a diagnosis was raised after knowing sputum cytology, and in 15/75 cases the diagnosis was changed as cytology provided new clues.</p> <p>Conclusion</p> <p>Our data suggest that spontaneous sputum cytology is capable of assisting in the diagnosis of inflammatory airway diseases in the outpatient setting. Despite the limitations by the semiquantitative assessment and lower sputum quality, the supportive power and the low economic effort needed can justify the use of this method, particularly if the diagnosis in question is thought to have an allergic background.</p

Are exhaled nitric oxide measurements using the portable NIOX MINO repeatable?

<p>Abstract</p> <p>Background</p> <p>Exhaled nitric oxide is a non-invasive marker of airway inflammation and a portable analyser, the NIOX MINO (Aerocrine AB, Solna, Sweden), is now available. This study aimed to assess the reproducibility of the NIOX MINO measurements across age, sex and lung function for both absolute and categorical exhaled nitric oxide values in two distinct groups of children and teenagers.</p> <p>Methods</p> <p>Paired exhaled nitric oxide readings were obtained from 494 teenagers, aged 16-18 years, enrolled in an unselected birth cohort and 65 young people, aged 6-17 years, with asthma enrolled in an interventional asthma management study.</p> <p>Results</p> <p>The birth cohort participants showed a high degree of variability between first and second exhaled nitric oxide readings (mean intra-participant difference 1.37 ppb, 95% limits of agreement -7.61 to 10.34 ppb), although there was very close agreement when values were categorised as low, normal, intermediate or high (kappa = 0.907, p < 0.001). Similar findings were seen in subgroup analyses by sex, lung function and asthma status. Similar findings were seen in the interventional study participants.</p> <p>Conclusions</p> <p>The reproducibility of exhaled nitric oxide is poor for absolute values but acceptable when values are categorised as low, normal, intermediate or high in children and teenagers. One measurement is therefore sufficient when using categorical exhaled nitric oxide values to direct asthma management but a mean of at least two measurements is required for absolute values.</p

Association of elevated fractional exhaled nitric oxide concentration and blood eosinophil count with severe asthma exacerbations

Blood eosinophil count (BEC) and fractional exhaled nitric oxide (FeNO) concentration are established biomarkers in asthma, associated particularly with the risk of exacerbations. We evaluated the relationship of BEC and FeNO as complementary and independent biomarkers of severe asthma exacerbations.This article is freely available via Open Access. Click on the Publisher URL to access the full-text

Factors affecting exhaled nitric oxide measurements: the effect of sex

<p>Abstract</p> <p>Background</p> <p>Exhaled nitric oxide (F_ENO) measurements are used as a surrogate marker for eosinophilic airway inflammation. However, many constitutional and environmental factors affect F_ENO, making it difficult to devise reference values. Our aim was to evaluate the relative importance of factors affecting F_ENO in a well characterised adult population.</p> <p>Methods</p> <p>Data were obtained from 895 members of the Dunedin Multidisciplinary Health and Development Study at age 32. The effects of sex, height, weight, lung function indices, smoking, atopy, asthma and rhinitis on F_ENO were explored by unadjusted and adjusted linear regression analyses.</p> <p>Results</p> <p>The effect of sex on F_ENO was both statistically and clinically significant, with F_ENO levels approximately 25% less in females. Overall, current smoking reduced F_ENO up to 50%, but this effect occurred predominantly in those who smoked on the day of the F_ENO measurement. Atopy increased F_ENO by 60%. The sex-related differences in F_ENO remained significant (p < 0.001) after controlling for all other significant factors affecting F_ENO.</p> <p>Conclusion</p> <p>Even after adjustment, F_ENO values are significantly different in males and females. The derivation of reference values and the interpretation of F_ENO in the clinical setting should be stratified by sex. Other common factors such as current smoking and atopy also require to be taken into account.</p

Corticosteroid suppression of lipoxin A4 and leukotriene B4from alveolar macrophages in severe asthma

<p>Abstract</p> <p>Background</p> <p>An imbalance in the generation of pro-inflammatory leukotrienes, and counter-regulatory lipoxins is present in severe asthma. We measured leukotriene B₄(LTB₄), and lipoxin A₄(LXA₄) production by alveolar macrophages (AMs) and studied the impact of corticosteroids.</p> <p>Methods</p> <p>AMs obtained by fiberoptic bronchoscopy from 14 non-asthmatics, 12 non-severe and 11 severe asthmatics were stimulated with lipopolysaccharide (LPS,10 μg/ml) with or without dexamethasone (10^-6M). LTB₄and LXA₄were measured by enzyme immunoassay.</p> <p>Results</p> <p>LXA₄biosynthesis was decreased from severe asthma AMs compared to non-severe (p < 0.05) and normal subjects (p < 0.001). LXA₄induced by LPS was highest in normal subjects and lowest in severe asthmatics (p < 0.01). Basal levels of LTB₄were decreased in severe asthmatics compared to normal subjects (p < 0.05), but not to non-severe asthma. LPS-induced LTB₄was increased in severe asthma compared to non-severe asthma (p < 0.05). Dexamethasone inhibited LPS-induced LTB₄and LXA₄, with lesser suppression of LTB₄in severe asthma patients (p < 0.05). There was a significant correlation between LPS-induced LXA₄and FEV₁(% predicted) (r_s= 0.60; p < 0.01).</p> <p>Conclusions</p> <p>Decreased LXA₄and increased LTB₄generation plus impaired corticosteroid sensitivity of LPS-induced LTB₄but not of LXA₄support a role for AMs in establishing a pro-inflammatory balance in severe asthma.</p

IL-17 mRNA in sputum of asthmatic patients: linking T cell driven inflammation and granulocytic influx?

BACKGROUND: The role of Th2 cells (producing interleukin (IL-)4, IL-5 and IL-13) in allergic asthma is well-defined. A distinct proinflammatory T cell lineage has recently been identified, called Th(17 )cells, producing IL-17A, a cytokine that induces CXCL8 (IL-8) and recruits neutrophils. Neutrophilic infiltration in the airways is prominent in severe asthma exacerbations and may contribute to airway gland hypersecretion, bronchial hyper-reactivity and airway wall remodelling in asthma. AIM: to study the production of IL-17 in asthmatic airways at the mRNA level, and to correlate this with IL-8 mRNA, neutrophilic inflammation and asthma severity. METHODS: We obtained airway cells by sputum induction from healthy individuals (n = 15) and from asthmatic patients (n = 39). Neutrophils were counted on cytospins and IL-17A and IL-8 mRNA expression was quantified by real-time RT-PCR (n = 11 controls and 33 asthmatics). RESULTS: Sputum IL-17A and IL-8 mRNA levels are significantly elevated in asthma patients compared to healthy controls. IL-17 mRNA levels are significantly correlated with CD3γ mRNA levels in asthmatic patients and mRNA levels of IL-17A and IL-8 correlated with each other and with sputum neutrophil counts. High sputum IL-8 and IL-17A mRNA levels were also found in moderate-to-severe (persistent) asthmatics on inhaled steroid treatment. CONCLUSION: The data suggest that Th(17 )cell infiltration in asthmatic airways links T cell activity with neutrophilic inflammation in asthma

MMP-9 gene variants increase the risk for non-atopic asthma in children

<p>Abstract</p> <p>Background</p> <p>Atopic and non-atopic wheezing may be caused by different etiologies: while eosinophils are more important in atopic asthmatic wheezers, neutrophils are predominantly found in BAL samples of young children with wheezing. Both neutrophils as well as eosinophils may secrete matrix metalloproteinase 9 (MMP-9). Considering that MMP-9 plays an important role in airway wall thickening and airway inflammation, it may influence the development of obstructive airway phenotypes in children. In the present study we investigated whether genetic variations in <it>MMP-9 </it>influence the development of different forms of childhood asthma.</p> <p>Methods</p> <p>Genotyping of four HapMap derived tagging SNPs in the <it>MMP-9 </it>gene was performed using MALDI-TOF MS in three cross sectional study populations of German children (age 9-11; N = 4,264) phenotyped for asthma and atopic diseases according to ISAAC standard procedures. Effects of single SNPs and haplotypes were studied using SAS 9.1.3 and Haploview.</p> <p>Results</p> <p>SNP rs2664538 significantly increased the risk for non-atopic wheezing (OR 2.12, 95%CI 1.40-3.21, p < 0.001) and non-atopic asthma (OR 1.66, 95%CI 1.12-2.46, p = 0.011). Furthermore, the minor allele of rs3918241 may be associated with decreased expiratory flow measurements in non-atopic children. No significant effects on the development of atopy or total serum IgE levels were observed.</p> <p>Conclusions</p> <p>Our results have shown that homozygocity for <it>MMP-9 </it>variants increase the risk to develop non-atopic forms of asthma and wheezing, which may be explained by a functional role of MMP-9 in airway remodeling. These results suggest that different wheezing disorders in childhood are affected differently by genetic alterations.</p