Relating small airways to asthma control by using impulse oscillometry in children

doi:10.1016/j.jaci.2011.11.002

Journal of Allergy and Clinical Immunology

Volume 129, Issue 3, March 2012, Pages 671-678

https://doi.org/10.1016/j.jaci.2011.11.002 Get rights and content

Background

Previous reports suggest that the peripheral airways are associated with asthma control. Patient history, although subjective, is used largely to assess asthma control in children because spirometric results are many times normal values. Impulse oscillometry (IOS) is an objective and noninvasive measurement of lung function that has the potential to examine independently both small- and large-airway obstruction.

Objective

We sought to determine the utility of IOS in assessing asthma control in children.

Methods

Asthmatic and healthy children (6-17 years) were enrolled in the study. Spirometric and IOS (resistance of the respiratory system at 5 Hz [R5] and 20 Hz [R20], reactance of the respiratory system at 5 Hz [X5], resonant frequency of reactance [Fres], and area under the reactance curve between 5 Hz and Fres [reactance area {AX}]) values were collected in triplicate before and after a bronchodilator was administered. The physicians were blinded to the IOS measurements and assessed asthma control using American Thoracic Society guidelines.

Results

Small-airway IOS measurements, including the difference of R5 and R20 [R5-20], X5, Fres, and AX, of children with uncontrolled asthma (n = 44) were significantly different from those of children with controlled asthma (n = 57) and healthy children (n = 14), especially before the administration of a bronchodilator. However, there was no difference in large-airway IOS values (R20). No differences were found between children with controlled asthma and healthy children in any of the end points. Receiver operating characteristic analysis showed cut points for baseline R5-20 (1.5 cm H₂O · L⁻¹ · s) and AX (9.5 cm H₂O · L⁻¹) that effectively discriminated controlled versus uncontrolled asthma (area under the curve, 0.86 and 0.84) and correctly classified more than 80% of the population.

Conclusion

Uncontrolled asthma is associated with small-airways dysfunction, and IOS might be a reliable and noninvasive method to assess asthma control in children.

Section snippets

Study participants

Children aged 6 to 17 years who were being actively treated for asthma on the Children’s Hospital of Orange County Breathmobile were enrolled in the study. The Breathmobile is a mobile asthma clinic that travels to schools, community clinics, and child development centers in low-income neighborhoods throughout Orange County, California, and provides comprehensive asthma care to children who have or are at risk for asthma. Children were included in the study if they were 6 to 17 years of age and

Study sample

Fourteen healthy control subjects and 107 asthmatic subjects were consented for the study. One hundred one (94%) of the asthmatic subjects were able to perform acceptable IOS maneuvers; 6 patients were excluded from the study because their IOS measurements had coherence lower than the recommended values. On the basis of a physician’s assessment, 57 (56%) of the 101 asthmatic subjects had controlled asthma and 44 (44%) had uncontrolled asthma. The demographics of the 3 asthma groups are

Discussion

Our study compared IOS indices of small- and large-airway resistance and reactance in children with controlled and uncontrolled asthma and established cut points to identify uncontrolled asthma. Prebronchodilator (or baseline) values for small-airway resistance (R5-R20) and reactance (AX) performed best, resulting in sensitivities, specificities, positive predictive values, and negative predictive values that all exceeded 0.80. To our knowledge, this is the first study to investigate the

References (49)

J.G. Teeter et al.
Relationship between airway obstruction and respiratory symptoms in adult asthmatics
Chest
(1998)
N. Nakajima et al.
Relationship between exhaled nitric oxide and small airway lung function in normal and asthmatic children
Allergol Int
(2011)
R.J. Martin
Therapeutic significance of distal airway inflammation in asthma
J Allergy Clin Immunol
(2002)
M.A. Sackner
Physiologic features of upper airway obstruction
Chest
(1972)
I. Cirillo et al.
Role of FEF25%-75% as a predictor of bronchial hyperreactivity in allergic patients
Ann Allergy Asthma Immunol
(2006)
A.F. Gelb et al.
The volume of isoflow and increase in maximal flow at 50 percent of forced vital capacity during helium-oxygen breathing as tests of small airway dysfunction
Chest
(1977)
A. Marotta et al.
Impulse oscillometry provides an effective measure of lung dysfunction in 4-year-old children at risk for persistent asthma
J Allergy Clin Immunol
(2003)
M.D. Goldman et al.
Clinical applications of forced oscillation to assess peripheral airway function
Respir Physiol Neurobiol
(2005)
P. Gaylor et al.
Forced oscillation using impulse oscillometry (IOS) provides objective responses to inhaled corticosteroids (ICS) in asthmatic patients when FEV1 fails to improve
J Allergy Clin Immunol
(2003)
C.K. Saadeh et al.
Forced oscillation using Impulse Oscillometry (IOS) detects false negative spirometry in symptomatic patients with reactive airways
J Allergy Clin Immunol
(2003)

S. Hozawa et al.

Comparison of budesonide/formoterol Turbuhaler with fluticasone/salmeterol Diskus for treatment effects on small airway impairment and airway inflammation in patients with asthma

Pulm Pharmacol Ther

(2011)

J. Frei et al.

Impulse oscillometry: reference values in children 100 to 150 cm in height and 3 to 10 years of age

Chest

(2005)

E.D. Bateman et al.

Global strategy for asthma management and prevention: GINA executive summary

Eur Respir J

(2008)

W.D. Carroll et al.

Parent misperception of control in childhood/adolescent asthma: The room to breathe survey

Eur Respir J

(2011)

K.J. Davis et al.

Is Johnny wheezing? Parent-child agreement in the Childhood Asthma in America survey

Pediatr Allergy Immunol

(2011)

J.D. Spahn et al.

Is forced expiratory volume in one second the best measure of severity in childhood asthma?

Am J Respir Crit Care Med

(2004)

E.G. Meraz et al.

Analysis of impulse oscillometric measures of lung function and respiratory system model parameters in small airway-impaired and healthy children over a 2-year period

Biomed Eng Online

(2011)

T. Takeda et al.

Relationship between small airway function and health status, dyspnea and disease control in asthma

Respiration

(2010)

J. Cohen et al.

Ciclesonide improves measures of small airway involvement in asthma

Eur Respir J

(2008)

I. Annesi et al.

Relationship of upper airways disorders to FEV1 and bronchial hyperresponsiveness in an epidemiological study

Eur Respir J

(1992)

G.L. Marseglia et al.

Role of forced expiratory flow at 25-75% as an early marker of small airways impairment in subjects with allergic rhinitis

Allergy Asthma Proc

(2007)

M. Studnicka et al.

Determinants of reproducibility of lung function tests in children aged 7 to 10 years

Pediatr Pulmonol

(1998)

G.L. Larsen et al.

Impulse oscillometry versus spirometry in a long-term study of controller therapy for pediatric asthma

J Allergy Clin Immunol

(2009)

T.W. Song et al.

Utility of impulse oscillometry in young children with asthma

Pediatr Allergy Immunol

(2008)

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Preschool impulse oscillometry predicts active asthma and impaired lung function at school age
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Asthmatic symptoms often start during early childhood. Impulse oscillometry (IOS) is feasible in preschool children who may be unable to reliably perform spirometry measurements.
We sought to evaluate the use of IOS in a multicenter, multiethnic high-risk asthma cohort titled the Vitamin D Antenatal Asthma Reduction Trial.
The trial recruited pregnant women whose children were followed from birth to age 8 years. Lung function was assessed with IOS at ages 4, 5, and 6 years and spirometry at ages 5, 6, 7, and 8 years. Asthma status, respiratory symptoms, and medication use were assessed with repeated questionnaires from birth to age 8 years.
In total, 220 children were included in this secondary analysis. Recent respiratory symptoms and short-acting β₂-agonist use were associated with increased respiratory resistance at 5 Hz at age 4 years (β = 2.6; 95% CI, 1.0 to 4.4; P = .002 and β = 3.4; 95% CI, 0.7 to 6.2; P = .015, respectively). Increased respiratory resistance at 5 Hz at age 4 years was also associated with decreased lung function from ages 5 to 8 years (β = −0.3; 95% CI, −0.5 to −0.1; P < .001 for FEV₁ at 8 years) and active asthma at age 8 years (β = 2.0; 95% CI, 0.2 to 3.8; P = .029).
Increased respiratory resistance in preschool IOS is associated with frequent respiratory symptoms as well as school-age asthma and lung function impairment. Our findings suggest that IOS may serve as a potential objective measure for early identification of children who are at high risk of respiratory morbidity.
Adding oscillometry to spirometry in guidelines better identifies uncontrolled asthma, future exacerbations, and potential targeted therapy
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The objective of this review is to provide new advances in our understanding of the clinical importance of establishing peripheral airway impairment (PAI) by impulse oscillometry (IOS) and targeted therapy, which could result in better asthma outcomes. Data sources include PubMed and Google search, limited to English language and human disease, with key words IOS and asthma. Key findings include PAI being consistently associated with uncontrolled asthma across ethnicities, using IOS reference equations factoring Hispanic and White reference algorithms. It is noted that PAI is common even in patients considered well-controlled by asthma guidelines. In a large longitudinal analysis (Assessment of Small Airways Involved in Asthma or ATLANTIS study), a composite of R5-R20, AX, and X5 ordinal scores were independently predictive of asthma control and exacerbation in a multivariate analysis, but forced expiratory volume in 1 second was not significantly predictive of morbidities. However, combining forced expiratory volume in 1 second less than 80% with PAI resulted in greater odds of identifying uncontrolled asthma and exacerbations, than either alone. Applying an external validation method in children with asthma offers the clinician the IOS reference equations best fit for their own specific population. Several clinical phenotypes can also identify PAI with high probability, useful when IOS is not available. Poor asthma outcomes for obese patients with asthma are associated with dysanapsis and PAI, not obesity alone. Extrafine inhaled corticosteroids achieve better asthma control and improve peripheral airway function with fewer exacerbations at lower dosages than nonextrafine inhaled corticosteroid aerosols. In conclusion, these data support the benefit of adding IOS to spirometry in future asthma guidelines and suggest the potential benefit from targeted therapy.
Assessing Asthma Control by Impulse Oscillometry and Fractional Expiratory Nitric Oxide in Children With Normal Spirometry
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Because spirometric parameters fail to address current status of asthma in some patients, additional tests are required for better evaluation of asthma.
We aimed to test the ability of impulse oscillometry (IOS) and fractional expiratory nitric oxide (FeNO) in identifying inadequately controlled asthma (ICA) that was not uncovered by spirometry.
Recruited asthmatic children between ages of 8 and 16 years underwent spirometry, IOS, and FeNO measurements on the same day. Only subjects who had spirometric indices within normal range were included. Asthma Control Questionnaire-6 scores of 0.75 or lower and greater than 0.75 indicated well-controlled asthma (WCA) and ICA. Percent predicted values of IOS parameters and IOS reference values for upper and lower limits of normal (>95th and <5th percentiles, respectively) were calculated on the basis of previously published equations.
There were no significant differences in all spirometric indices between the WCA (n = 59) and the ICA (n = 101) groups. The % predicted values of IOS parameters except resistance at 20 Hz (R20) were significantly different between the 2 groups. Receiver operating characteristic analysis showed that the highest and lowest areas under the curve were 0.81 and 0.67 for the difference between the resistances at 5 Hz and 20 Hz (R5–R20) and R20 in discrimination of ICA versus WCA. The areas under the curve for IOS parameters were improved by combination with FeNO. The better discriminative ability of IOS was also supported by the higher values of the concordance index for the resistance at 5 Hz (R5), R5–R20, the reactance at 5 Hz (X5), and the resonant frequency of reactance than those for spirometric parameters. Compared with those with normal values, subjects with abnormal IOS parameters or high FeNO had significantly higher odds of having ICA.
The IOS parameters and FeNO were shown to be useful in identifying children with ICA when spirometry was normal.
Adding spirometry to oscillometry identifies worsening asthma and greater peripheral airway impairment
2023, Journal of Allergy and Clinical Immunology: In Practice
Four weeks of repetitive acute hypoxic preconditioning did not alleviate allergen-induced airway dysfunction in rats
2023, Respiratory Physiology and Neurobiology
Clinical case series suggest beneficial effects of low-dose intermittent hypoxia in asthma. We tested cardiopulmonary effects of repetitive acute hypoxic preconditioning (RAHP) during allergic inflammation. Brown Norway rats were sensitized to house dust mites (HDM) and exposed to 4-week RAHP or normoxia (SHAM), concurrent with weekly HDM or saline (SAL) challenges. We assessed methacholine responses and lung HIF-1α expression at endpoint, and weekly blood pressure (BP). RAHP relative to SHAM: 1) in HDM-challenged rats, showed no protection against HDM-induced airway dysfunction and did not significantly impact BP (week 4 mean BP difference = 10.51 mmHg, p = 0.09) or HIF-1α expression; 2) in SAL-challenged rats, attenuated airway responses to methacholine, reduced BP (week 4 mean BP average difference = −8.72 mmHg, p = 0.04) and amplified HIF-1α expression (p = 0.0086). Four weeks of RAHP did not mitigate the allergen-induced lower airway dysfunction and may detrimentally affect BP. However, it elicited beneficial cardiopulmonary responses in SAL-challenged rats, concurrent with increased HIF-1α expression.
Pathophysiological relevance of sputum MUC5AC and MUC5B levels in patients with mild asthma
2022, Allergology International
Airway mucus hypersecretion is an important pathophysiological feature of asthma. MUC5AC and MUC5B are the major secreted polymeric mucins in airways, and their compositions affect mucus properties. Despite the increasing appreciation of MUC5AC and MUC5B compositions in asthmatic airways, their pathophysiological relevance remains to be fully understood in humans.
In this cross-sectional study, we prospectively enrolled newly referred steroid-untreated patients with mild asthma and healthy controls. We compared induced sputum MUC5AC and MUC5B levels between patients and controls. Subsequently, we assessed the correlation between MUC5AC and MUC5B levels and clinical indices in patients. Sputum MUC5AC and MUC5B levels were measured using enzyme-linked immunosorbent assays.
Sputum MUC5AC and MUC5B levels were significantly higher in patients (n = 87) than in controls (n = 22) (p = 0.0002 and p = 0.006, respectively). The ratio of sputum MUC5AC to MUC5B tended to be higher in patients than in controls (p = 0.07). Sputum MUC5AC levels significantly and positively correlated with fractional exhaled nitric oxide at expiratory flow of 50 mL/s (Spearman's rho = 0.29, p = 0.006), sputum eosinophil proportion (rho = 0.34, p = 0.0013), and airway sensitivity (rho = 0.39, p = 0.0005). By contrast, sputum MUC5B levels significantly and positively correlated with airway sensitivity (rho = 0.35, p = 0.002) and negatively correlated with airway reactivity (rho = −0.33, p = 0.004).
Sputum MUC5AC is increased by protein levels and involved in airway type 2/eosinophilic inflammation and airway hyperresponsiveness in steroid-untreated patients with mild asthma.

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: Supported by National Institutes of Health grant HL070645.

: Disclosure of potential conflict of interest: The authors declare that they have no relevant conflicts of interest.

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Asthma and lower airway diseaseRelating small airways to asthma control by using impulse oscillometry in children

Background

Objective

Methods

Results

Conclusion

Section snippets

Study participants

Study sample

Discussion

Chest

Allergol Int

J Allergy Clin Immunol

Chest

Ann Allergy Asthma Immunol

Chest

J Allergy Clin Immunol

Respir Physiol Neurobiol

J Allergy Clin Immunol

J Allergy Clin Immunol

Pulm Pharmacol Ther

Chest

Global strategy for asthma management and prevention: GINA executive summary

Eur Respir J

Parent misperception of control in childhood/adolescent asthma: The room to breathe survey

Eur Respir J

Is Johnny wheezing? Parent-child agreement in the Childhood Asthma in America survey

Pediatr Allergy Immunol

Is forced expiratory volume in one second the best measure of severity in childhood asthma?

Am J Respir Crit Care Med

Analysis of impulse oscillometric measures of lung function and respiratory system model parameters in small airway-impaired and healthy children over a 2-year period

Biomed Eng Online

Relationship between small airway function and health status, dyspnea and disease control in asthma

Respiration

Ciclesonide improves measures of small airway involvement in asthma

Eur Respir J

Relationship of upper airways disorders to FEV1 and bronchial hyperresponsiveness in an epidemiological study

Eur Respir J

Role of forced expiratory flow at 25-75% as an early marker of small airways impairment in subjects with allergic rhinitis

Allergy Asthma Proc

Determinants of reproducibility of lung function tests in children aged 7 to 10 years

Pediatr Pulmonol

Impulse oscillometry versus spirometry in a long-term study of controller therapy for pediatric asthma

J Allergy Clin Immunol

Utility of impulse oscillometry in young children with asthma

Pediatr Allergy Immunol

Asthma and lower airway disease
Relating small airways to asthma control by using impulse oscillometry in children