Tezepelumab reduces exacerbations across all seasons in patients with severe, uncontrolled asthma (NAVIGATOR).

BACKGROUND: Asthma exacerbation frequencies vary throughout the year owing to seasonal triggers. Tezepelumab is a human monoclonal antibody that targets thymic stromal lymphopoietin. In the phase 3 NAVIGATOR study (NCT03347279), tezepelumab significantly reduced the annualized asthma exacerbation rate (AAER) vs placebo in patients with severe, uncontrolled asthma. OBJECTIVE: To evaluate the effect of tezepelumab on asthma exacerbations across all seasons in NAVIGATOR patients (post hoc). METHODS: NAVIGATOR was a multicenter, randomized, double-blind, placebo-controlled study. Patients (12-80 years old) were randomized 1:1 to tezepelumab 210 mg or placebo subcutaneously every 4 weeks for 52 weeks. AAER over 52 weeks was assessed by season. Data from patients in the Southern Hemisphere were transformed to align with Northern Hemisphere seasons. RESULTS: Tezepelumab reduced the AAER vs placebo by 63% (95% confidence interval [CI], 52-72) in winter, 46% (95% CI, 26-61) in spring, 62% (95% CI, 48-73) in summer, and 54% (95% CI, 41-64) in fall. In matched climates, during the spring allergy season (March 1 to June 15) and ragweed allergy season (September), tezepelumab reduced the AAER vs placebo in patients with seasonal allergy by 59% (95% CI, 29-77) and 70% (95% CI, 33-87), respectively. In patients with perennial allergy and in those with seasonal allergy, tezepelumab reduced the AAER vs placebo across all seasons. CONCLUSION: Tezepelumab reduced exacerbations across all seasons vs placebo in patients with severe, uncontrolled asthma, including patients with seasonal and perennial allergies. These data further support the efficacy of tezepelumab in a broad population of patients with severe, uncontrolled asthma. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03347279 (https://clinicaltrials.gov/ct2/show/NCT03347279).

Wheeze is an unreliable endpoint for bronchial methacholine challenges in preschool children.

BACKGROUND: Onset of wheeze is the endpoint often used in the determination of a positive bronchial challenge test (BCT) in young children who cannot perform spirometry. We sought to assess several clinical endpoints at the time of a positive BCT in young children with recurrent wheeze compared to findings in school-aged children with asthma. METHODS: Positive BCT was defined in: (1) preschool children (n = 22) as either persistent cough, wheeze, fall in oxygen saturation (SpO2 ) of ≥5%, or ≥50% increase in respiratory rate (RR) from baseline; and (2) school-aged children (n = 22) as the concentration of methacholine (MCh) required to elicit a 20% decline in FEV1 (PC20 ). RESULTS: All preschool children (mean age 3.4 years) had a positive BCT (median provocative MCh concentration 1.25 mg/ml [IQR, 0.62, 1.25]). Twenty (91%) school-aged children (mean age 11.3 years) had a positive BCT (median PC20 1.25 mg/ml [IQR, 0.55, 2.5]). At the time of the positive BCT, the mean fall in SpO2 (6.9% vs. 3.8%; p = .001) and the mean % increase in RR (61% vs. 22%; p < .001) were greater among preschool-aged than among school-aged children. A minority of children developed wheeze at time of positive BCT (23% preschool- vs. 15% school-aged children; p = .5). CONCLUSIONS: The use of wheeze as an endpoint for BCT in preschool children is unreliable, as it rarely occurs. The use of clinical endpoints, such as ≥25% increase in RR or fall in SpO2 of ≥3%, captured all of our positive BCT in preschool children, while minimizing undue respiratory distress.

Lung mechanical properties distinguish children with asthma with normal and diminished lung function.

BACKGROUND: Children with asthma, even those with severe persistent disease, can have forced expiratory volume in 1 second (FEV1 ) values ≥100% of predicted, while others have diminished FEV1 . OBJECTIVE: We sought to characterize the lung mechanical properties underlying these two asthma phenotypes and the mechanisms explaining the paradox of severe asthmatic children, whom when clinically stable can have an FEV1 >100% of predicted, but during an acute bronchospastic episode can experience a life-threatening asthma event. METHODS: Lung mechanics were evaluated in three groups of children: asthmatics with FEV1 ≥100% (HFEV1 ; n = 13), asthmatics with FEV1 ≤80% (LFEV1 ; n = 14) and non-asthmatic controls (n = 10). A linear mixed model was used to examine the relationship between volume and static transpulmonary pressures obtained at total lung capacity (TLC); actual TLC %of predicted and flow; and static transpulmonary pressure and flow. RESULTS: HFEV1 asthmatics had larger airways (FEV1 z-scores 1.12 vs -2.37; P < .05), greater lung volumes (mean % of predicted TLC 134.8% vs 109.6%; P < .05) and lower airway resistance (mean %of predicted Raw 101.9% vs 199.9%; P < .05) compared to the LFEV1 group. Moreover, HFEV1 asthmatics had significantly reduced elastic recoil pressure (pressure-volume curve shifted upward and to the left) and higher lung compliance (0.21 vs 00.9 L/cm H2 O; P < .05) compared to the LFEV1 group. The pressure-flow curves revealed the LFEV1 group to have significantly increased resistance to flow in the upstream segment of the airways at all lung volumes studied compared to HFEV1 . CONCLUSION AND CLINICAL RELEVANCE: HFEV1 asthmatic children display distinct lung mechanical proprieties compared to their LFEV1 asthmatic peers. With loss of elastic recoil pressure, the HFEV1 group could generate normal FEV1 due to proportionally enlarged airways and reduced airway resistance, while airflow limitation in the LFEV1 is due to increased airway resistance. Loss of elastic recoil and interdependence during acute bronchoconstriction episodes may predispose the HFEV1 group to catastrophic reductions in airflow.

Fractional exhaled nitric oxide response to oral corticosteroids in children with mild-to-moderate asthma: Influence of race.

BACKGROUND: Fractional exhaled nitric oxide (FeNO) is a noninvasive biomarker of type 2 asthma that can predict response to inhaled corticosteroid therapy. Little is known regarding the magnitude of FeNO reduction after an oral corticosteroid (OCS) course, and less is known whether there are differential responses based on race in children with mild-to-moderate asthma. OBJECTIVE: To assess the effect of a short course of OCS on FeNO in children with asthma and to determine whether the effect is influenced by race. METHODS: Children presenting with an acute asthma exacerbation, who had a FeNO measurement within the past 6 months when clinically stable, were enrolled. Spirometry and FeNO were obtained at the time of exacerbation and after a short course of prednisone. RESULTS: A total of 92 children were identified (aged 11 ± 3.3 years; white, n = 46 [50%], Hispanics, n = 30 [33%], African Americans [AAs], n = 16 [7%]). At baseline, AAs were more atopic and had higher mean FeNO values than both white (48.9 vs 25.6 ppb; P < .05) and Hispanic children (22.5 ppb; P < .05), despite being prescribed similar inhaled corticosteroid doses. During the exacerbation, AAs had the highest FeNO values, whereas there was no difference in lung function between AAs and non-AAs. After prednisone therapy, there was a 56.6% reduction in FeNO, and although AAs maintained the highest FeNO levels, the relative reduction was similar between AAs and non-AAs (53.9% vs 57.8%, respectively). CONCLUSION: FeNO levels reduced by more than 50% after an OCS course. African American children had a greater degree of type 2-driven airway inflammation at baseline, during an exacerbation and after a short course of OCS, compared with non-AAs, although the relative reduction in FeNO was similar between the groups.

The chitinase-like protein YKL-40 is not a useful biomarker for severe persistent asthma in children.

BACKGROUND: The chitinase-like protein YKL-40 is thought to play a role in inflammation and tissue remodeling. In adults with severe asthma, YKL-40 is expressed in the airway and YKL-40 levels are elevated in the serum. OBJECTIVE: To compare YKL-40 levels in children with severe persistent asthma with those in adults with severe persistent asthma and to determine whether YKL-40 levels correlate with increasing asthma severity in childhood asthma. METHODS: In this prospective, cross-sectional study, 23 adults and 19 children with severe persistent asthma, 23 children with moderate persistent asthma, and 19 children with mild persistent asthma were enrolled. The following data were collected on each patient: spirometry, exhaled nitric oxide, percutaneous skin testing results to aeroallergens, peripheral eosinophils, serum IgE levels, and serum YKL-40 levels. RESULTS: Compared with adults, children with severe persistent asthma had significantly lower YKL-40 levels, higher values for forced vital capacity and forced expiration volume in 1 second, higher serum IgE levels, and higher exhaled nitric oxide levels. YKL-40 levels did not correlate with increasing asthma severity in the pediatric cohort. CONCLUSION: Severe persistent asthma in childhood is not associated with elevated YKL-40 levels, unlike in adults with severe persistent asthma. YKL-40 is not a useful biomarker for asthma severity in childhood asthma.

The changing face of severe childhood asthma: a comparison of two cohorts of children evaluated at National Jewish Health over the past 20 years.

Novel asthma pharmacotherapy has changed the management of severe childhood asthma. This study determined whether the introduction and use of second-generation inhaled glucocorticoids (GCs), long-acting beta-agonists (LABAs), and combination inhaled GC/LABA (iGC/LABA) products and leukotriene receptor antagonists (LTRAs) have impacted children with severe asthma. A retrospective review of children (aged 6-18 years) referred to National Jewish Health for severe asthma between 2003 and 2007 (current cohort) was performed (n = 65); the results were compared with a published cohort from 1993 to 1997 (historic cohort; n = 164). When comparing the current cohort to the historic cohort, the percentage requiring chronic oral GC therapy (28% versus 51%; p = 0.001), average dose (3.7 ± 2.4 mg/dose versus 16.7 ± 1.4 mg/dose; p < 0.0001), and duration of oral GC use (17.8 ± 8.6 months versus 33.7 ± 3.5 months; p = 0.09) were less. Ninety-seven percent of the current cohort was on a second-generation iGC either alone or in combination with an LABA, 76% were on an LTRA, and 66% were on combination iGC/LABA product, while none of the historic cohort received these medications. In addition, the current cohort had a higher forced expiratory volume in 1 second (84 ± 2.5% versus 76 ± 2% of predicted; p = 0.008), required less albuterol (33 ± 9 inhalations/week versus 71 ± 7 inhalations/week; p = 0.0007), had fewer intubations in the past (13% versus 21%; p = 0.13) and had fewer GC-induced adverse effects compared with the historic cohort. The current cohort required less chronic oral GCs, had better asthma control, and had fewer GC-induced adverse effects compared with the historic cohort studied 10 years ago. This is most likely because of the use of more effective medications for childhood asthma.

Step-up therapy for children with uncontrolled asthma receiving inhaled corticosteroids.

BACKGROUND: For children who have uncontrolled asthma despite the use of low-dose inhaled corticosteroids (ICS), evidence to guide step-up therapy is lacking. METHODS: We randomly assigned 182 children (6 to 17 years of age), who had uncontrolled asthma while receiving 100 microg of fluticasone twice daily, to receive each of three blinded step-up therapies in random order for 16 weeks: 250 microg of fluticasone twice daily (ICS step-up), 100 microg of fluticasone plus 50 microg of a long-acting beta-agonist twice daily (LABA step-up), or 100 microg of fluticasone twice daily plus 5 or 10 mg of a leukotriene-receptor antagonist daily (LTRA step-up). We used a triple-crossover design and a composite of three outcomes (exacerbations, asthma-control days, and the forced expiratory volume in 1 second) to determine whether the frequency of a differential response to the step-up regimens was more than 25%. RESULTS: A differential response occurred in 161 of 165 patients who were evaluated (P<0.001). The response to LABA step-up therapy was most likely to be the best response, as compared with responses to LTRA step-up (relative probability, 1.6; 95% confidence interval [CI], 1.1 to 2.3; P=0.004) and ICS step-up (relative probability, 1.7; 95% CI, 1.2 to 2.4; P=0.002). Higher scores on the Asthma Control Test before randomization (indicating better control at baseline) predicted a better response to LABA step-up (P=0.009). White race predicted a better response to LABA step-up, whereas black patients were least likely to have a best response to LTRA step-up (P=0.005). CONCLUSIONS: Nearly all the children had a differential response to each step-up therapy. LABA step-up was significantly more likely to provide the best response than either ICS or LTRA step-up. However, many children had a best response to ICS or LTRA step-up therapy, highlighting the need to regularly monitor and appropriately adjust each child's asthma therapy. (ClinicalTrials.gov number, NCT00395304.)

Inflammometry in pediatric asthma: a review of fractional exhaled nitric oxide in clinical practice.

The burden of pediatric asthma remains high with one-third of patients being under- or overtreated because of the unique challenges in the assessment and management of childhood asthma. Until recently, there has been no point of care tool for assessing the underlying airway inflammation (i.e., inflammometry) in asthma. Recently, fractional exhaled nitric oxide (FeNO) has emerged as an important biomarker for the assessment and management of asthma. Recent evidence indicates that FeNO identifies T-helper cell type 2 (Th2)­mediated airway inflammation with a high positive and negative predictive value for identifying corticosteroid responsive airway inflammation. This article examines the evidence for FeNO as a predictor of Th2-mediated inhaled corticosteroid (ICS) responsive airway inflammation and reviews recent studies evaluating the role of FeNO, whether helpful or not, in the assessment and management of pediatric asthma. FeNO is a reliable adjunct to traditional tests in the assessment of suspected asthma. Importantly, it is useful for identifying and for excluding ICS-responsive airway inflammation. Although individual study results have varied, collectively, asthma managed using FeNO is associated with lower exacerbation rates compared with clinical algorithms alone. Finally, FeNO may be useful in identifying patients at risk for future impairment or loss of asthma control during reduction/cessation of ICS treatment. FeNO testing has an important role in the assessment of pediatric patients with suspected asthma and in the management of pediatric patients with established asthma. Additional studies will continue to define the exact role of FeNO testing in pediatric asthma.

Effect of Biologic Therapies on Airway Hyperresponsiveness and Allergic Response: A Systematic Literature Review.

Background: Airway hyperresponsiveness (AHR) is a key feature of asthma. Biologic therapies used to treat asthma target specific components of the inflammatory pathway, and their effects on AHR can provide valuable information about the underlying disease pathophysiology. This review summarizes the available evidence regarding the effects of biologics on allergen-specific and non-allergen-specific airway responses in patients with asthma. Methods: We conducted a systematic review in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines, including risk-of-bias assessment. PubMed and Ovid were searched for studies published between January 1997 and December 2021. Eligible studies were randomized, placebo-controlled trials that assessed the effects of biologics on AHR, early allergic response (EAR) and/or late allergic response (LAR) in patients with asthma. Results: Thirty studies were identified for inclusion. Bronchoprovocation testing was allergen-specific in 18 studies and non-allergen-specific in 12 studies. Omalizumab reduced AHR to methacholine, acetylcholine or adenosine monophosphate (3/9 studies), and reduced EAR (4/5 studies) and LAR (2/3 studies). Mepolizumab had no effect on AHR (3/3 studies), EAR or LAR (1/1 study). Tezepelumab reduced AHR to methacholine or mannitol (3/3 studies), and reduced EAR and LAR (1/1 study). Pitrakinra reduced LAR, with no effect on AHR (1/1 study). Etanercept reduced AHR to methacholine (1/2 studies). No effects were observed for lebrikizumab, tocilizumab, efalizumab, IMA-638 and anti-OX40 ligand on AHR, EAR or LAR; benralizumab on LAR; tralokinumab on AHR; and Ro-24-7472 on AHR or LAR (all 1/1 study each). No dupilumab or reslizumab studies were identified. Conclusion: Omalizumab and tezepelumab reduced EAR and LAR to allergens. Tezepelumab consistently reduced AHR to methacholine or mannitol. These findings provide insights into AHR mechanisms and the precise effects of asthma biologics. Furthermore, findings suggest that tezepelumab broadly targets allergen-specific and non-allergic forms of AHR, and the underlying cells and mediators involved in asthma.

Predictors of remitting, periodic, and persistent childhood asthma.

BACKGROUND: The course of mild to moderate persistent asthma in children is not clearly established. OBJECTIVE: To determine the rate and predictors for remitting, periodic, and persistent asthma in adolescence. METHODS: The Childhood Asthma Management Program (CAMP) was a 4.3-year randomized, double-masked, multicenter trial in children with mild to moderate persistent asthma that compared continuous therapy with either budesonide or nedocromil, each to placebo, followed by a 4-year observational follow-up period. Asthma activity during the observation period included remitting (no asthma activity in the last year), persistent (asthma activity in every quarter), and periodic asthma (neither remitting nor persistent). RESULTS: Asthma was identified as remitting in 6%, periodic in 39%, and persistent in 55% of the 909 participants, with no effect noted from earlier anti-inflammatory treatment during the CAMP trial. Within all 3 asthma activity categories, improvements in airway hyperresponsiveness, eosinophilia, and asthma morbidity were observed over time. Features at entry into CAMP associated with remitting versus persistent asthma were lack of allergen sensitization and exposure to indoor allergens (odds ratio [OR], 3.23; P < .001), milder asthma (OR, 2.01; P = .03), older age (OR, 1.23; P = .01), less airway hyperresponsiveness (higher log methacholine FEV(1) PC(20) (OR, 1.39; P = .03), higher prebronchodilator FEV(1) percent predicted (OR, 1.05; P = .02), and lower forced vital capacity percent predicted (OR, 0.96; P = .04). CONCLUSION: Remission of asthma in adolescence is infrequent and not affected by 4 years of anti-inflammatory controller therapy. Factors such as sensitization and exposure, low lung function, and airway greater hyperresponsiveness decrease the likelihood of remitting asthma.

Clinical assessment of asthma progression in children and adults.

Asthma is a heterogeneous disorder with a variable course, characterized by episodes of cough, wheezing and shortness of breath, reversible airflow limitation, and bronchial hyperresponsiveness. It begins early in life in many subjects with intermittent symptoms occurring with viral respiratory tract infections. Over time, and in genetically susceptible children (those with an atopic predisposition), the disease becomes more persistent with symptoms occurring in the absence of respiratory tract infections. Children with persistent wheezing are eventually diagnosed with asthma, with those at greatest risk having developed allergic sensitization early in life. Among children with asthma, some will have lifelong asthma with active symptoms and progressive loss of lung function over time, whereas other children will undergo asthma remission in adolescence. Once in remission, the disease may remain quiescent, or it may relapse in midadult life. This review focuses on studies that have enhanced our understanding of the progression of asthma from infancy to adulthood. Studies evaluating progressive loss of lung function, the best-studied measure of asthma progression, are also reviewed, followed by a brief discussion of whether asthma progression can be modified by inhaled glucocorticoid therapy.

Proportion of Severe Asthma Patients Eligible for Mepolizumab Therapy by Age and Age of Onset of Asthma.

BACKGROUND: Mepolizumab is an anti-IL-5 antibody approved for the treatment of severe eosinophilic asthma. However, the prevalence of patients with severe asthma eligible for mepolizumab remains unknown, especially among children. OBJECTIVE: To determine, in a population of patients with severe asthma from a tertiary referral center, the proportion of patients with an eosinophilic phenotype who would be eligible for mepolizumab, when stratified for the age of onset of asthma, and the prevalence of phenotypic features that favor mepolizumab therapy. METHODS: An extensive database of 245 adults and children referred for severe asthma was used. The prevalence of severe asthma was estimated by using the European Respiratory Society/American Thoracic Society criteria. Patients with an eosinophilic uncontrolled phenotype qualified for mepolizumab. RESULTS: In our cohort, 216 (88%) had severe asthma. Based on blood eosinophils of either greater than or equal to 150 cells/µL or greater than or equal to 300 cells/µL, 61%/41% had an eosinophilic phenotype, while 49%/34% were eligible for mepolizumab therapy. A greater percentage of adults (60%/47% of adults with asthma onset in adulthood [AoA] and 48%/26% adults with childhood-onset asthma [<18 years, CoA]) were eligible compared with children (33%/24%), for eosinophil counts of ≥150 and ≥300 cells/µL, respectively; P < .05. Compared with adults, children had a similar number of exacerbations while having better lung function (P < .05). Among adults, those with AoA were older, were more likely to have nasal polyps (28% vs 5%; P < .05), and had higher blood eosinophil counts (272 vs 150 cells/µL; P < .05) compared with those with CoA, with no difference in lung function noted between the 2 groups. Subjects showing greater than or equal to 500 eosinophils/µL, a strong indicator for mepolizumab therapy, had more nasal polyps, higher inhaled steroid dose, lower lung function, and AoA predominance than did those with less than 500 eosinophils/µL (P < .05). CONCLUSIONS: A smaller percentage of children with severe asthma were eligible for mepolizumab compared with their adult peers. Severe AoA has distinct phenotypic features that favor treatment with mepolizumab, including greater eosinophilia and nasal polyposis, in contrast to CoA, which appears to have fewer features of type 2 mucosal inflammation.

Asthma biomarkers in sputum.

Several inflammatory cells are thought to contribute to the pathogenesis of asthma. Among these, the eosinophil appears to be a major effector cell. This review focuses primarily on the clinical utility of sputum eosinophil counts in asthma. Several studies have shown sputum eosinophils to be associated with both asthma severity and level of asthma control. In addition, the presence of sputum eosinophilia is strongly predictive of a favorable response to glucocorticoid therapy. Conversely, the absence of sputum eosinophilia is predictive of a poor response to glucocorticoid therapy. Sputum eosinophilia also predicts asthma relapse in subjects who have their inhaled glucocorticoid reduced or withdrawn. Lastly, inhaled glucocorticoid therapy can be titrated to keep the sputum eosinophil count at or below 2%.

Racial differences in T-lymphocyte response to glucocorticoids.

BACKGROUND: Asthma morbidity and mortality is increased in blacks. OBJECTIVE: The primary objective of this cross-sectional study was to determine if blacks, asthmatic or nonasthmatic, displayed diminished T-lymphocyte response to glucocorticoids in vitro compared to their white counterparts. If differences were noted, this would suggest a racial predisposition to decreased glucocorticoid responsiveness among blacks. METHODS: Asthmatic (n = 395, 27% blacks) and control (n = 202, 52% blacks) subjects recruited from National Jewish Medical and Research Center and from the surrounding community participated in the study. In vitro glucocorticoid responsiveness was determined by assessing the log-transformed concentration of dexamethasone required to suppress phytohemagglutinin-induced T-lymphocyte proliferation by 50% (log(10) IC(50)). Asthma medication history, atopic status, and spirometric lung function measures corrected for race were collected. RESULTS: Black and white asthmatic subjects had similar FEV(1) percentage of predicted values and inhaled and oral glucocorticoid requirements. Black asthmatic subjects displayed significantly diminished glucocorticoid responsiveness compared to white asthmatic subjects, as follows: median (first, third quartile) log(10) IC(50) values of 1.00 nmol (0.48, 1.83) vs 0.78 nmol (0.29, 1.45) [p = 0.028]. Similar results were found between black and white control subjects, as follows: median, 1.26 nmol (0.70, 2.14) vs 0.95 nmol (0.55, 1.48) [p = 0.01]. Age, race, and basal T-lymphocyte activity were significantly positively correlated to the log(10) IC(50) values. CONCLUSION: Our observation that black asthmatic subjects and non-asthmatic control subjects require greater concentrations of glucocorticoid in vitro to suppress T-lymphocyte activation suggests that blacks have a racial predisposition to diminished glucocorticoid responsiveness, which may contribute to their heightened asthma morbidity.

Do NHLBI lung function criteria apply to children? A cross-sectional evaluation of childhood asthma at National Jewish Medical and Research Center, 1999-2002.

Although National Heart Lung Institute (NHLBI) guidelines categorize asthma severity based on spirometry, few studies have evaluated the utility of these spirometric values in grading asthma severity in children. Asthma is thought to be progressive, but little is known about the loss of lung function in childhood. This study sought to determine the spirometric indices in children from 4-18 years of age. Retrospective cross-sectional analysis was performed on all spirometries done in children at the National Jewish Medical and Research Center from 1999-2002. In total, 2,728 children performed 24,388 measures. The mean +/- SD values for forced vital capacity (FVC), forced expired volume in 1 sec (FEV(1)), FEV(1)/FVC ratio, and forced expiratory flow (FEF)(25-75) were 92.7 +/- 16.2, 92.2 +/- 18.0, 85.3 +/- 9.3, and 78.0 +/- 36.5 percent predicted, respectively. Seventy-seven percent of FEV(1) values were >/= 80%, 18.6% were between 60-80%, and 3.1% were <60% of predicted. FEV(1) was highest in 5-year-old children; it declined thereafter, reaching a nadir at 11 years, followed by a partial recovery from 12-18 years. Expressed in liters, FEV(1) values were lower than expected at every age, with the greatest difference at 18 years. FEV(1)/FVC ratios declined through childhood, suggesting impaired airway but not lung growth in children with asthma. In conclusion, the majority of asthmatic children attending a tertiary care facility had FEV(1) values within normal range. With increasing age, the increase in FEV(1) lags behind that of nonasthmatics, so that by 18 years, maximum FEV(1) is impaired. The NHLBI FEV(1) cutoff values do not appear to accurately stratify pediatric asthma, and no useful FEV(1) cutoff could be generated.

Quantitative computed tomography detects peripheral airway disease in asthmatic children.

The aim of this study was to compare air-trapping as quantified by high-resolution computed tomography (HRCT) of the chest with measures of lung function and airway inflammation in children with mild to moderate asthma. Plethysmography indices, respiratory resistance, and reactance before and after bronchodilator with impulse oscillation (IOS), exhaled nitric oxide (eNO), total eosinophil count (TEC), and serum eosinophil cationic protein (ECP) levels were measured in 21 subjects. A single-cut HRCT image at end-expiration was obtained. Air-trapping was quantified and expressed in terms of the pixel index (PI) by determining the percentage of pixels in lung fields below -856 and -910 Hounsfeld units (HU). Pairwise linear correlations between PI and other parameters were evaluated. Subjects had only mild airflow limitation based on prebronchodilator forced expiratory volume in 1 sec (FEV(1)), but were hyperinflated and had air-trapping based on elevated total lung capacity (TLC) and residual volume (RV)/TLC ratio, respectively. The PI at -856 HU was positively correlated with % predicted TLC, total gas volume (TGV), and ECP level, and was inversely correlated with FEV(1)/forced vital capacity (FVC) and % predicted forced expiratory flow between 25-75% FVC (FEF(25-75)). The PI at -910 HU correlated similarly with these variables, and also correlated positively with IOS bronchodilator reversibility. This data suggest that quantitative HRCT may be a useful tool in the evaluation of peripheral airflow obstruction in children with asthma.