Airway inflammation in asthma is not measured routinely in clinical practice. Fractional exhaled nitric oxide (FENO), a marker of airway inflammation, is increasingly used as an outcome measure in asthma intervention studies and yet the reproducibility of FENO measurements is unknown.The reproducibility, day-to-day, diurnal variation and perception of standardised FENO measurements were examined in 59 subjects (40 children aged 7-13 yrs and 19 adults aged 18-60 yrs), both healthy (n=30) and with mild (n=29) asthma. FENO was measured on five consecutive days (four measurements on the same day) for adults and twice on the same day for children.The coefficient of reproducibility expressed as the mean pooled standard deviation (n=59, 675 estimations) was 2.11 parts per billion (ppb) and intraclass correlation coefficient was 0.99 in both children and adults. FENO was significantly higher in asthma subjects (32.3 ppb) than in healthy subjects (16.3 ppb). There was no diurnal or day-to-day variation, or a learning effect, as the result of FENO measurements were identical at results of the beginning and at the end of the study.It was concluded that fractional exhaled nitric oxide measurements are simple, reproducible, free from diurnal and day-to-day variation, and acceptable by both healthy and asthmatic adults and children, as a part of their routine visit to a physician. Asthma is an inflammatory disease, yet airway inflammation is not measured directly and routinely in clinical practice [1]. This makes management of asthma difficult, because it is based on indirect measurements of airway inflammation, such as symptoms and lung function. Symptoms may not accurately reflect the extent of underlying inflammation due to differences in perception, and lung function tests may have little room for improvement in mild asthma. None of these parameters is able to distinguish the effect of different doses of inhaled corticosteroids and both may be affected by bronchodilators. The latter is particularly important because of a recent trend towards use of lower doses of inhaled corticosteroids in combination with long-acting b 2 -agonists.Current invasive (bronchoscopy), or semi-invasive (sputum induction) direct methods to measure airway inflammation are difficult to use repeatedly in clinical practice. The use of sputum induction is limited by its pro-inflammatory effect [2], and a considerable bronchospasm has been reported during sputum induction in moderate (14%) and severe (25%) asthma, as a result of the procedure [3].There has been an explosion of research into exhaled nitric oxide (NO) since levels were found to be increased in asthma [1,4]. Standardised [5,6] measurements of fractional exhaled NO (FENO) provide a completely noninvasive means of monitoring airway inflammation and anti-inflammatory treatment in asthma [1], including a dose-dependent onset and duration of action of inhaled corticosteroids [7]. It may be useful in patients using fixed combination inhalers (corticosteroids and longacting b 2 -agon...

Clustering based on clinicophysiologic parameters yielded 4 stable and reproducible clusters that associate with different pathobiological pathways.

U-BIOPRED cohort n=91 epithelial brushings or biopsies IL-17 High Clinical phenotype Nasal polyps Smoking Antibiotic use Epithelial Gene Expression Profile Clinical phenotype FeNO Exacerbations Gene expression shared with psoriasis IDO1 IL1B DEFB4B S100A8, S100A9 PI3 CXCL3, CXCL8 CXCL10, CCL20 Gene signature SERPINB2 POSTN CLCA1 IL-13 High T cell infiltration Neutrophilia Eosinophilia IL-17-high asthma with features of a psoriasis immunophenotype From a the Respiratory,

Background-Exhaled levels of nitric oxide (NO) are raised in asthma but the relationship between exhaled NO levels and a direct measure of airway inflammation has not been investigated in asthmatic patients treated with inhaled steroids. Methods-The relationship between exhaled NO levels, clinical measures of asthma control, and direct markers of airway inflammation were studied in patients with asthma treated with and without inhaled corticosteroids. Thirty two asthmatic patients (16 not using inhaled steroids and 16 using inhaled beclomethasone dipropionate, 400-1000 µg/day) were monitored with respect to measures of asthma control including lung function, symptom scores, medication usage, and variability of peak expiratory flow (PEF) for one month. Measurements of exhaled NO and fibreoptic bronchoscopy were performed at the end of the monitoring period. Bronchial mucosal biopsy specimens were stained with an anti-MBP antibody for quantification of eosinophils. Results-There was no significant diVerence in lung function, symptom scores, or medication usage between the two groups, but there was a significant diVerence in PEF variability (8.7 (1.2)% in steroid naive patients versus 13.6 (1.9)% in steroid treated patients, p<0.05) and exhaled NO levels (9.9 (3.5) ppb in steroid naive patients versus 13.6 (2.0) ppb in steroid treated patients, p<0.05). There was no correlation between exhaled NO and mucosal eosinophils, or between NO and conventional measures of asthma control. There was a significant correlation between mucosal eosinophils and lung function (r = -0.43, p<0.05). Conclusions-Exhaled NO levels do not reflect airway mucosal eosinophilia and these markers reflect diVerent aspects of airway inflammation. The clinical usefulness of exhaled NO needs to be determined in prospective longitudinal studies.

This study aims to evaluate the acute effects of an oscillating positive expiratory pressure device (flutter) on airways resistance in patients with chronic obstructive pulmonary disease (COPD).Randomized crossover study: 15 COPD outpatients from Asthma Lab–Royal Brompton Hospital underwent spirometry, impulse oscillometry (IOS) for respiratory resistance (R) and reactance (X), and fraction exhaled nitric oxide (FeNO) measures.Thirty minutes of flutter exercises: a “flutter-sham” procedure was used as a control, and airway responses after a short-acting bronchodilator were also assessed.Respiratory system resistance (R): in COPD patients an increase in X5insp (−0.21 to −0.33 kPa/L/s) and Fres (24.95 to 26.16 Hz) occurred immediately after flutter exercises without bronchodilator. Following 20 min of rest, a decrease in the R5, ΔR5, R20, X5, and Ax was observed, with R5, R20, and X5 values lower than baseline, with a moderate effect size; there were no changes in FeNO levels or spirometry.The use of flutter can decrease the respiratory system resistance and reactance and expiratory flow limitation in stable COPD patients with small amounts of secretions.