In an unselected birth cohort, more than one in four children had wheezing that persisted from childhood to adulthood or that relapsed after remission. The factors predicting persistence or relapse were sensitization to house dust mites, airway hyperresponsiveness, female sex, smoking, and early age at onset. These findings, together with persistently low lung function, suggest that outcomes in adult asthma may be determined primarily in early childhood.

With the use of FE(NO) measurements, maintenance doses of inhaled corticosteroids may be significantly reduced without compromising asthma control.

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Exhaled nitric oxide (eNO) levels are increased in untreated or unstable asthma and measurements can be made easily. Our aim was to assess the usefulness of eNO for diagnosing and predicting loss of control (LOC) in asthma following steroid withdrawal. Comparisons were made against sputum eosinophils and airway hyperresponsiveness (AHR) to hypertonic saline (4.5%). Seventy-eight patients with mild/moderate asthma had their inhaled steroid therapy withdrawn until LOC occurred or for a maximum of 6 wk. Sixty (77.9%) developed LOC. There were highly significant correlations between the changes in eNO and symptoms (p < 0.0001), FEV(1) (p < 0.002), sputum eosinophils (p < 0.0002), and saline PD(15) (p < 0.0002), and there were significant differences between LOC and no LOC groups. Both single measurements and changes of eNO (10 ppb, 15 ppb, or an increase of > 60% over baseline) had positive predictive values that ranged from 80 to 90% for predicting and diagnosing LOC. These values were similar to those obtained using sputum eosinophils and saline PD(15) measurements. We conclude that eNO measurements are as useful as induced sputum analysis and AHR in assessing airway inflammation, with the advantage that they are easy to perform.

Rationale Airway inflammation in asthma is heterogeneous with different phenotypes. The inflammatory cell phenotype is modified by corticosteroids and smoking. Steroid therapy is beneficial in eosinophilic asthma (EA), but evidence is conflicting regarding non-eosinophilic asthma (NEA). Objectives To assess the inflammatory cell phenotypes in asthma after eliminating potentially confounding effects; to compare steroid response in EA versus NEA; and to investigate changes in sputum cells with inhaled corticosteroid (ICS). Methods Subjects undertook ICS withdrawal until loss of control or 28 days. Those with airway hyperresponsiveness (AHR) took inhaled fluticasone 1000 mg daily for 28+ days. Cut-off points were $/<2% for sputum eosinophils and $/<61% for neutrophils. Results After steroid withdrawal (n¼94), 67% of subjects were eosinophilic, 31% paucigranulocytic and 2% mixed; there were no neutrophilic subjects. With ICS (n¼88), 39% were eosinophilic, 46% paucigranulocytic, 3% mixed and 5% neutrophilic. Sputum neutrophils increased from 19.3% to 27.7% (p¼0.024). The treatment response was greater in EA for symptoms (p<0.001), quality of life (p¼0.012), AHR (p¼0.036) and exhaled nitric oxide (p¼0.007). Lesser but significant changes occurred in NEA (ie, paucigranulocytic asthma). Exhaled nitric oxide was the best predictor of steroid response in NEA for AHR (area under the curve 0.810), with an optimum cut-off point of 33 ppb. Conclusions After eliminating the effects of ICS and smoking, a neutrophilic phenotype could be identified in patients with moderate stable asthma. ICS use led to phenotype misclassification. Steroid responsiveness was greater in EA, but the absence of eosinophilia did not indicate the absence of a steroid response. In NEA this was best predicted by baseline exhaled nitric oxide.