The Relationship of the Bronchodilator Response Phenotype to Poor Asthma Control in Children with Normal Spirometry

doi:10.1016/j.jpeds.2010.11.029

The Journal of Pediatrics

Volume 158, Issue 6, June 2011, Pages 953-959.e1

https://doi.org/10.1016/j.jpeds.2010.11.029 Get rights and content

Objective

To determine the relationship of poor asthma control to bronchodilator response (BDR) phenotypes in children with normal spirometry.

Study design

Children with asthma were assessed for clinical indexes of poorly controlled asthma. Pre- and post-bronchodilator spirometry were performed, and the percent BDR was determined. Multivariate logistic regression assessed the relationship of the clinical indices to BDR at ≥8%, ≥10%, and ≥12% BDR thresholds.

Results

There were 510 controller naïve children and 169 on controller medication. In the controller naïve population the mean age (±1 SD) was 9.5 (3.4); 57.1% were male, 85.7% Hispanic. Demographics were similar in both populations. In the adjusted profile, significant clinical relationships were found particularly to positive BDR phenotypes ≥10% and ≥12% versus negative responses including younger age, (OR 2.0, 2.5; P < .05), atopy (OR 1.9, 2.6; P < .01), nocturnal symptoms in females (OR 3.4, 3.8; P < .01); β₂ agonist use (OR 1.7, 2.8; P < .01); and exercise limitation (OR 2.2, 2.5; P < .01) only in the controller naïve population.

Conclusions

The BDR phenotype ≥10% is significantly related to poor asthma control, providing a potentially useful objective tool in controller naïve children even when the pre-bronchodilator spirometry result is normal.

Section snippets

Methods

Children participating in a school-based, low-income, asthma mobile van program, the Breathmobile,²⁰ were referred for care during the 5-year period 2004 to 2008 by school nurses, community public health clinics, response to flyers, and an asthma questionnaire.²¹ Criteria for the diagnosis of asthma by the asthma specialist included a history of recurrent coughing, wheezing, shortness of breath with rest or with exercise, symptomatic improvement after β₂ agonist use, and exclusion of other

Results

Demographic and clinical data, the latter consistent with guideline impairment and risk characteristics of poor asthma control, are shown in children with normal pre-bronchodilator spirometry (Table I). Of the total population of 892 children, 679 (76%) had normal pre-bronchodilator spirometry and are represented in Table I. The 679 children are divided into 510 who were controller naïve, and 169 who were receiving controller medication. In the controller naïve group, body mass index measure

Discussion

Our data suggest that the BDR phenotype is associated with several important clinical characteristics of poor asthma control and atopy in those with normal pre-bronchodilator spirometry, but only in the controller naïve subset. Nonetheless, this is a very useful observation because spirometry is the only objective in-office clinical tool the physician has; the history is often unreliable and the physical examination normal when the child is asymptomatic. Unfortunately, pre- bronchodilator

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Cited by (47)

Bronchodilator response does not associate with asthma control or symptom burden among patients with poorly controlled asthma
2023, Respiratory Medicine
The purpose of this study was to determine how four different definitions of bronchodilator response (BDR) relate to asthma control and asthma symptom burden in a large population of participants with poorly controlled asthma.
We examined the baseline change in FEV1 and FVC in response to albuterol among 931 participants with poorly controlled asthma pooled from three clinical trials conducted by the American Lung Association - Airways Clinical Research Centers. We defined BDR based on four definitions and analyzed the association of each with asthma control as measured by the Asthma Control Test or Asthma Control Questionnaire, and asthma symptom burden as measured by the Asthma Symptom Utility Index.
A BDR was seen in 31–42% of all participants, depending on the definition used. There was good agreement among responses (kappa coefficient 0.73 to 0.87), but only 56% of participants met all four definitions for BDR. A BDR was more common in men than women, in Blacks compared to Whites, in non-smokers compared to smokers, and in non-obese compared to obese participants. Among those with poorly controlled asthma, 35% had a BDR compared to 25% of those with well controlled asthma, and among those with a high symptom burden, 34% had a BDR compared to 28% of those with a low symptom burden. After adjusting for age, sex, height, race, obesity and baseline lung function, none of the four definitions was associated with asthma control or symptom burden.
A BDR is not associated with asthma control or symptoms in people with poorly controlled asthma, regardless of the definition of BDR used. These findings question the clinical utility of a BDR in assessing asthma control and symptoms.
The case for impulse oscillometry in the management of asthma in children and adults
2017, Annals of Allergy, Asthma and Immunology
To provide a clinical rationale for including impulse oscillometry (IOS) as a part of standard office-based asthma assessment.
PubMed and Google search, limited to English language and human disease, with the keywords IOS and asthma.
Articles included in this review were based on the expert opinion and previous publications by the authors.
In children, IOS was more useful than spirometry in identifying asthma and uncontrolled asthma and predicting loss of control and exacerbations. IOS predicts young children at risk for loss of lung function with age and the potential for early intervention to prevent further sequelae. In adults, peripheral airway impairment detected by IOS or spirometry (ie, forced expiratory flow between 25% and 75%) commonly occurs across severity, and each measure may be complementary in predicting loss of control even with normal forced expiratory volume in 1 second. Extrafine inhaled corticosteroids with or without long-acting β-agonists proved superior to standard particle aerosols in improving IOS-detected peripheral airway obstruction. Our data also suggest that currently available commercial reference values for lung resistance at 5 Hz and lung reactance at 5 Hz are applicable across diverse populations, but further studies are needed.
The findings of this review suggest that IOS can add value to traditional clinical and spirometric assessment and thus improve management of asthma in children and adults, as well as have the potential to detect early dysfunction of the peripheral airways, which may result in better outcomes.
ASTHMA ASSESSMENT: IMPULSE OSCILLOMETRY (IOS)
2017, Revista Medica Clinica Las Condes
El asma es la enfermedad crónica más frecuente de la infancia y el objetivo central de su manejo es lograr un buen control de la enfermedad. Para evaluar el nivel de control, se han diseñado cuestionarios que clasifican a los pacientes en controlados, parcialmente o pobremente controlados. Si bien estos son de utilidad en la práctica clínica tienden a sobrestimar el nivel de control y no siempre se correlacionan bien con mediciones objetivas que incluyen función pulmonar y respuesta broncodilatadora, y evalúan mejor el riesgo. La Oscilometría de Impulso es superior en relación a la espirometría para detectar respuesta broncodilatadora en pacientes con asma no controlada y permite identificar a pacientes que están en riesgo de perder el control de la enfermedad, por lo que debería difundirse su uso en el monitoreo del asma.
Asthma is the most common chronic childhood disease. The current goal of asthma treatment is to achieve and maintain control. To assess the level of control, have been designed questionnaires which classified patients in controlled, partially or poorly controlled. While these are useful in clinical practice they tend to overestimate the level of control and do not always correlate well with objective measures including lung function and bronchodilator response. The impulse IOS is much better in relation to the spirometry to detect patients with uncontrolled asthma bronchodilator response and allows to identify patients who are at risk of losing control of the disease by what should increase its use in the monitoring of asthma.
Distinguishing characteristics of difficult-to-control asthma in inner-city children and adolescents
2016, Journal of Allergy and Clinical Immunology
Citation Excerpt :
Because bronchodilator responsiveness is strongly related to baseline pulmonary function, it was not surprising that FEV1/FVC ratio and FEV1 (percent predicted) values also differentiated these 2 groups.17-20 A retrospective cross-sectional study of low-income, mainly Hispanic children in Los Angeles found that bronchodilator responsiveness of at least 10% was significantly related to poor asthma control in controller-naive children.21 Children with this degree of bronchodilator responsiveness, even in the face of normal spirometric results, had more nocturnal symptoms, increased β-agonist use, and exercise limitation while also having a greater number of allergen sensitizations.
Treatment levels required to control asthma vary greatly across a population with asthma. The factors that contribute to variability in treatment requirements of inner-city children have not been fully elucidated.
We sought to identify the clinical characteristics that distinguish difficult-to-control asthma from easy-to-control asthma.
Asthmatic children aged 6 to 17 years underwent baseline assessment and bimonthly guideline-based management visits over 1 year. Difficult-to-control and easy-to-control asthma were defined as daily therapy with 500 μg of fluticasone or greater with or without a long-acting β-agonist versus 100 μg or less assigned on at least 4 visits. Forty-four baseline variables were used to compare the 2 groups by using univariate analyses and to identify the most relevant features of difficult-to-control asthma by using a variable selection algorithm. Nonlinear seasonal variation in longitudinal measures (symptoms, pulmonary physiology, and exacerbations) was examined by using generalized additive mixed-effects models.
Among 619 recruited participants, 40.9% had difficult-to-control asthma, 37.5% had easy-to-control asthma, and 21.6% fell into neither group. At baseline, FEV₁ bronchodilator responsiveness was the most important characteristic distinguishing difficult-to-control asthma from easy-to-control asthma. Markers of rhinitis severity and atopy were among the other major discriminating features. Over time, difficult-to-control asthma was characterized by high exacerbation rates, particularly in spring and fall; greater daytime and nighttime symptoms, especially in fall and winter; and compromised pulmonary physiology despite ongoing high-dose controller therapy.
Despite good adherence, difficult-to-control asthma showed little improvement in symptoms, exacerbations, or pulmonary physiology over the year. In addition to pulmonary physiology measures, rhinitis severity and atopy were associated with high-dose asthma controller therapy requirement.
Value of bronchial reversibility to salbutamol, exhaled nitric oxide and responsiveness to methacholine to corroborate the diagnosis of asthma in children
2020, Allergologia et Immunopathologia
Citation Excerpt :
The present evidence suggests that waiting for an abnormal spirometry and positive bronchial reversibility to make the diagnosis of asthma in children appears as an unrealistic diagnostic approach. There is not a single best method for studying asthmatic children with normal spirometry, and none of the common asthma tests used in children for detecting airway inflammation, BHR or changes in lung function after bronchodilators can establish the diagnosis of asthma by itself.4–6,9,12,16,23,27,30–34,37–39 Perhaps when there is concurrent normal spirometry, normal BDR and normal FENO, then MTC or other tests for detecting BHR could be a useful contribution for asthma diagnosis and management in these children,17,23,26,27 particularly if they are on regular ICS.
Functional and inflammatory measures have been recommended to corroborate asthma diagnosis in schoolchildren, but the evidence in this regard is conflicting. We aimed to determine, in real-life clinical situation, the value of spirometry, spirometric bronchial reversibility to salbutamol (BDR), bronchial responsiveness to methacholine (MCT) and fractional exhaled nitric oxide (FENO), to corroborate the diagnosis of asthma in children on regular inhaled corticosteroids (ICS) referred from primary care.
One hundred and seventy-seven schoolchildren with mild-moderate persistent asthma, on treatment with regular ICS, participated in the study. Abnormal tests were defined as FENO ≥ 27 ppb, BDR (FEV1 ≥ 12%) and methacholine PC20 ≤ 4 mg/mL.
The proportions of positive BDR, FENO and MCT, were 16.4%, 33.3%, and 87.0%, respectively. MCT was associated with FENO (p < 0.03) and BDR (p = 0.001); FENO was associated with BDR (p = 0.045), family history of asthma (p = 0.003) and use of asthma medication in the first two years of life (p = 0.004). BDR was significantly related with passive tobacco exposure (p = 0.003).
Spirometry, BDR and BDR had a poor performance for corroborating diagnosis in our asthmatic children on ICS treatment; on the contrary, MCT was positive in most of them, which agrees with previous reports. Although asthma tests are useful to corroborate asthma when positive, clinical diagnosis remains the best current approach for asthma diagnosis, at least while better objective and feasible measurements at the daily practice are available. At present, these tests may have a better role for assessing the management and progression of the condition.
Ubi-Asthma: Toward Ubiquitous Asthma Detection Using the Smartwatch
2023, IEEE Internet of Things Journal

View all citing articles on Scopus

: Supported by California Wellness Foundation, Tobacco Settlement Revenue, Asthma Chronic Lung Disease Grant, and Air Quality Management District Southern California.

: The authors declare no conflicts of interest.

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Original ArticleThe Relationship of the Bronchodilator Response Phenotype to Poor Asthma Control in Children with Normal Spirometry

Objective

Study design

Results

Conclusions

Section snippets

Methods

Results

Discussion

Lancet

J Allergy Clin Immunol

J Allergy Clin Immunol

J Allergy Clin Immunol

Clin Ther

Lancet

Chest

J Pediatr

Chest

J Allergy Clin Immunol

J Allergy Clin Immunol

Clinical predictors and outcomes of consistent bronchodilator response in Childhood Asthma Management Program

J Allergy Clin Immunol

Cluster analysis and clinical asthma phenotypes

Amer J Respir Crit Care Med

Expert Panel Report 3 (EPR3): Guidelines for the diagnosis and management of asthma. Summary Report 2007

J Allergy Clin Immunol

Original Article
The Relationship of the Bronchodilator Response Phenotype to Poor Asthma Control in Children with Normal Spirometry