Small airway involvement in cystic fibrosis lung disease: routine spirometry as an early and sensitive marker.

BACKGROUND: In young children with cystic fibrosis (CF) the forced expiratory volume in 1 second (FEV1 ) is often normal and a more sensitive measure to detect early obstructive lung disease is needed. AIM: To evaluate the progression of selected spirometry parameters with age in a cohort of CF patients and healthy children aged 6 to 20 years. METHODS: Retrospective comparison of longitudinal spirometry data from CF patients with data from two cohort studies in healthy subjects. Quantile regression was used to calculate the longitudinal 10th percentile (P10 ), 50th percentile (P50 ), and 90th percentile (P90 ) of forced vital capacity (FVC), FEV1 , and the forced expiratory flow at 75% of FVC (FEF75 ). Sample size estimates were calculated using these three parameters as clinical trial endpoints. RESULTS: FVC, FEV1 , and FEF75 were all significantly lower in CF patients than healthy children. Abnormalities in FEF75 occurred at younger ages and remained substantially larger than abnormalities in FEV1 or FVC throughout childhood. Therefore, fewer patients would be required to detect a similar treatment effect if FEF75 is used as a primary endpoint compared with FEV1 or FVC. CONCLUSIONS: Our data support the use of FEF75 as a more sensitive marker of early CF lung disease than FEV1 and FVC, because abnormalities in FEF75 occur at younger age and FEF75 is diminished more than other parameters.

Titrating steroids on exhaled nitric oxide in children with asthma: a randomized controlled trial.

RATIONALE: Corticosteroids are the antiinflammatory treatment of choice in asthma. Treatment guidelines are mainly symptom-driven but symptoms are not closely related to airway inflammation. The fraction of nitric oxide in exhaled air (FENO) is a marker of airway inflammation in asthma. OBJECTIVE: We evaluated whether titrating steroids on FENO improved asthma management in children. METHODS: Eighty-five children with atopic asthma, using inhaled steroids, were allocated to a FENO group (n=39) in which treatment decisions were made on both FENO and symptoms, or to a symptom group (n=46) treated on symptoms only. Children were seen every 3 months over a 1-year period. MEASUREMENTS: Symptoms were scored during 2 weeks before visits and 4 weeks before the final visit. FeNO was measured at all visits, and airway hyperresponsiveness and FEV1 were measured at the start and end of the study. Primary endpoint was cumulative steroid dose. RESULTS: Changes in steroid dose from baseline did not differ between groups. In the FENO group, hyperresponsiveness improved more than in the symptom group (2.5 vs. 1.1 doubling dose, p=0.04). FEV1 in the FENO group improved, and the change in FEV1 was not significantly different between groups. The FENO group had 8 severe exacerbations versus 18 in the symptom group. The change in symptom scores did not differ between groups. FENO increased in the symptom group; the change in FENO from baseline differed between groups (p=0.02). CONCLUSION: In children with asthma, 1 year of steroid titration on FENO did not result in higher steroid doses and did improve airway hyperresponsiveness and inflammation.