Consecutive asthmatic children referred for pulmonary function testing were enrolled. The aim of this study was to assess whether FAno could be a marker of distal obstruction and/or mild symptoms. Thus, we first defined a detailed structured questionnaire (symptom and medications) that was prospectively recorded in our population. Recorded symptoms were part of those included in the Asthma Quality of Life Questionnaire (chest tightness, 6 questions; cough, 12 questions; chest heaviness, 14 questions; woken at night by asthma, 24 questions; lack of a good night’s sleep, 29 questions). Symptomatic children were defined as having at least one symptom within 72 h before testing. Since the evaluation was planed to enroll mildly symptomatic children, in order to assess whether exhaled NO measures could reflect the onset of exacerbation (before the occurrence of significant airflow Limitation as decrease in FEV1), wheezing patients were not included. For the same reason daily peak expiratory flow (V) rate was not recorded in this young population. Consequently, only mild asthma symptoms were evaluated.
Only one investigator (B.M.) obtained all clinical histories. This study reports the results obtained in consecutive children or adolescents who were evaluated by functional respiratory tests in the follow-up of asthma. A group of healthy children without history of atopy (relatives of medical staff) was also evaluated.
The breathing circuit consisted of a mouthpiece with a bacterial filter connected to a one-way valve, through which the children exhaled via an expiratory resistance while targeting a fixed mouth pressure of 16 cm H2O displayed on a water column to prevent contamination from nose and sinuses. Each NO measurement was done as recommended by the American Thoracic Society (ATS).
Children exhaled via separate resistances in turn while maintaining the same expiratory pressure, thus producing multiple flows that were measured by a downstream pneumotachograph (Fleisch #1; Fleisch; Lausanne, Switzerland, connected to Vali-dyne ± 2 cm H2O; Validyne Engineering; Northridge, CA). Each child was asked to perform at least one maneuver in five different ranges: very low flow (< 40 mL/s), low flow (40 to 60 mL/s), intermediate flow (60 to 100 mL/s), high flow (100 to 150 mL/s), and very high flow (> 150 mL/s). The criteria used for FEno interpretation were those in the ATS guidelines,17 the expiratory time being at least 6 s with a plateau of at least 3 s.
FEno was measured using a chemiluminescent NO analyzer (EVA4000; Seres; Aix en Provence, France), as previously described. NO concentration, V, and expired volume were displayed on a computer (Biopac Systems; Santa Barbara, CA).
Modeling the Qno/FIow Rate Relationship
We used two different approaches using multiple-flow analysis.