Recognition of the peripheral airway impairment phenotype in children with well-controlled asthma.

BACKGROUND: Peripheral airway impairment, although frequently unrecognized, is a risk factor for poor asthma control, loss of control, increased exacerbations, airway hyperresponsiveness, and loss of lung function with age, even in patients with well-controlled asthma. OBJECTIVE: To determine the presence of peripheral airway impairment by impulse oscillometry and forced expiratory flow between 25% and 75% (FEF25%-75%) in children whose asthma is well controlled by National Asthma Education and Prevention Program (NAEPP) guidelines. METHODS: In this retrospective, cross-sectional analysis, outcomes were evaluated across 192 encounters in 139 patients with moderate to severe asthma, ages 4-18 years. Receiver operator characteristic curves were created and oscillometry thresholds determined by maximizing the sum of sensitivity and specificity to identify those whose condition is not well controlled. Impairment was then identified for those whose condition was well controlled when these age-dependent oscillometry thresholds were met for each IOS measure or FEF25%-75% < 65% of predicted. RESULTS: Reactance at 5 Hz (X5) appeared most robust to identify peripheral airway impairment. In 96 well-controlled asthma encounters, impairment was identified by X5 in approximately 20% and 45% for those younger than 12 years and adolescents, respectively, compared with a maximum of 10% with FEF25%-75% in the adolescent cohort (P < .05). CONCLUSION: We conclude that peripheral airway impairment, determined by oscillometry, is common in patients with well-controlled asthma across age cohorts. X5 with optimal cut points ≤ -3.8, ≤ -2.5, and ≤ -1.5 cmH2O/L/s for ages 4-7, 8-11, and >12 years, provides the clinician with a practical tool to identify the presence of the peripheral airway impairment phenotype that is consistently superior to FEF25%-75%. This recognition, if confirmed, may reduce the risk of asthma-associated consequences with earlier and more targeted therapy.

Standardized IOS Reference Values Define Peripheral Airway Impairment-Associated Uncontrolled Asthma Risk Across Ethnicity in Children.

BACKGROUND: Although clinically useful in identifying peripheral airway impairment (PAI), impulse oscillometry (IOS) has not received universal acceptance. This may be due to variable cutoff points, and the perception that available standardized reference values may not be clinically relevant in all populations. OBJECTIVE: To establish the relationship between PAI, based on standardized IOS reference values, and uncontrolled asthma as well as interchangeability between Hispanic and white reference algorithms. METHODS: IOS reference values were established for upper and lower limits of normal (>95th and <5th percentile, respectively) using published algorithms in Hispanic and white children. Values exceeding normal limits (PAI) were compared in those uncontrolled and controlled for significance of differences. Probability estimates and odds ratio of uncontrolled asthma were determined for R5, R5-R20, AX, and X5 using adjusted generalized estimating equation analyses. Intraclass correlation coefficients determined interchangeability of Hispanic and white reference algorithm values. RESULTS: Those with uncontrolled asthma had significantly greater PAI and a higher frequency of PAI than those well controlled (P < .05), whereas odds of uncontrolled asthma increased with increasing PAI (P < .001) for all IOS measures, particularly for X5, where odds ratios ranged from 2.70 to 11.01.There was good to excellent (>70%) agreement between Hispanic and white algorithms, except for R5-R20 (<70%). CONCLUSIONS: PAI, defined by IOS reference values, not central airway markers (R20), is consistently related to the risk of uncontrolled asthma. This is true whether using Hispanic or white reference algorithms. Thus, standardized reference values in children offer the clinician readily available IOS cutoff points that are clinically relevant across ethnicity.