Airway resistance variability and response to bronchodilator in children with asthma

Variability of airway function is a feature of asthma, spanning timescales from months to seconds. Short-term variation in airway resistance (Rrs) is elevated in asthma and is thought to be due to increased variation in the contractile activation of airway smooth muscle. If true, then variation in Rrs should decrease in response to bronchodilators, but this has not been investigated. Using the forced oscillation technique, Rrs and the variation in Rrs from 4–34 Hz were measured in 39 children with well-controlled mild-to-moderate asthma and 31 healthy controls (7–13 yrs) before and after an inhaled bronchodilator (200 µg salbutamol) or placebo. In agreement with other findings, baseline Rrs at all frequencies and the sd of Rrs (Rrs sd) below 14 Hz were found to be elevated in asthma while neither forced expiratory volume in one second nor the mean forced expiratory flow between 25 and 75% of forced vital capacity were different compared with controls. The present authors found that Rrs sd changed the most of any measurement in asthma, and this was the only measurement that changed significantly more in children with asthma following bronchodilator administration. The present results show that like airway narrowing, short-term airway variability of resistance may be a characteristic feature of asthma that may be useful for monitoring response to therapy.

[1]  Tilo Winkler,et al.  Self-organized patchiness in asthma as a prelude to catastrophic shifts , 2005, Nature.

[2]  D. Moneret-vautrin,et al.  Specificity and sensitivity of respiratory impedance in assessing reversibility of airway obstruction in children. , 1995, Chest.

[3]  P. Macklem,et al.  Effects of lung volume on maximal methacholine-induced bronchoconstriction in normal humans. , 1987, Journal of applied physiology.

[4]  C. Irvin Lung volume: a principle determinant of airway smooth muscle function , 2003, European Respiratory Journal.

[5]  R. Pauwels,et al.  GLOBAL STRATEGY FOR ASTHMA MANAGEMENT AND PREVENTION , 1996 .

[6]  J. Pekkanen,et al.  Short-term variations in oscillatory and spirometric lung function indices among school children. , 1997, The European respiratory journal.

[7]  A. Coates,et al.  Spirometry in the asthmatic child: Is FEF25–75 a more sensitive test than FEV1/FVC? , 1993, Pediatric pulmonology.

[8]  S. Venkataraman,et al.  Flow and Volume Dependence of Respiratory Mechanics in Anesthetized Children , 1999, Pediatric Research.

[9]  Jose G. Venegas,et al.  The distribution of ventilation during bronchoconstriction is patchy and bimodal: A PET imaging study , 2005, Respiratory Physiology & Neurobiology.

[10]  A. Coates,et al.  Measurement of respiratory system resistance by forced oscillation in normal children: A comparison with spirometric values , 1991, Pediatric pulmonology.

[11]  J. Hankinson,et al.  Standardisation of spirometry , 2005, European Respiratory Journal.

[12]  G. Town,et al.  Asthma control during long term treatment with regular inhaled salbutamol and salmeterol , 1998, Thorax.

[13]  K. Lutchen,et al.  Pseudorandom signals to estimate apparent transfer and coherence functions of nonlinear systems: applications to respiratory mechanics , 1992, IEEE Transactions on Biomedical Engineering.

[14]  D. Postma,et al.  Asthma: from childhood to adulthood , 1996, Allergy.

[15]  K. P. Van de Woestijne,et al.  Changes of respiratory input impedance during breathing in humans. , 1992, Journal of applied physiology.

[16]  A. Morice,et al.  Evaluation of impulse oscillation system: comparison with forced oscillation technique and body plethysmography , 2001, European Respiratory Journal.

[17]  A. Kusy,et al.  An equivalent network for resistance and temperature coefficient of resistance versus temperature and composition of thick resistive films , 1987 .

[18]  P. Macklem,et al.  Homeokinesis and short-term variability of human airway caliber. , 2001, Journal of applied physiology.

[19]  K. P. Van de Woestijne,et al.  Total respiratory impedance measured by means of the forced oscillation technique in subjects with and without respiratory complaints. , 1996, The European respiratory journal.

[20]  Merryn Tawhai,et al.  Identifying airways responsible for heterogeneous ventilation and mechanical dysfunction in asthma: an image functional modeling approach. , 2005, Journal of applied physiology.

[21]  A. Forchel,et al.  Experimental and theoretical study of strain-induced AlGaAs/GaAs quantum dots using a self-organized GaSb island as a stressor , 1999 .

[22]  H Lorino,et al.  Comparison of the forced oscillation technique and the interrupter technique for assessing airway obstruction and its reversibility in children. , 2001, American journal of respiratory and critical care medicine.

[23]  J. Malo,et al.  Comparison of circadian variations using FEV1 and peak expiratory flow rates among normal and asthmatic subjects. , 1994, Thorax.

[24]  E. Bleecker,et al.  Peripheral lung resistance in normal and asthmatic subjects. , 1990, The American review of respiratory disease.

[25]  E. R. Mcfadden,et al.  A reduction in maximum mid-expiratory flow rate. A spirographic manifestation of small airway disease. , 1972, The American journal of medicine.

[26]  M. Goldman,et al.  Within‐ and between‐day variability of respiratory impedance, using impulse oscillometry in adolescent asthmatics , 2002, Pediatric pulmonology.

[27]  Arnab Majumdar,et al.  Risk of severe asthma episodes predicted from fluctuation analysis of airway function , 2005, Nature.

[28]  R. van Altena,et al.  Variability of forced oscillation (Siemens Siregnost FD 5) measurements of total respiratory resistance in patients and healthy subjects. , 1993, Annals of allergy.

[29]  K. Lutchen,et al.  Airway remodeling in asthma amplifies heterogeneities in smooth muscle shortening causing hyperresponsiveness. , 1999, Journal of applied physiology.

[30]  H Lorino,et al.  Forced oscillation technique vs spirometry to assess bronchodilatation in patients with asthma and COPD. , 1995, Chest.

[31]  A. Ferguson Persisting airway obstruction in asymptomatic children with asthma with normal peak expiratory flow rates. , 1988, The Journal of allergy and clinical immunology.

[32]  H. Trübel,et al.  Variability analysis of oscillatory airway resistance in children , 2005, European Journal of Applied Physiology.

[33]  J H Bates,et al.  Regional lung impedance from forced oscillations through alveolar capsules. , 1993, Respiration physiology.

[34]  F. Marchal,et al.  Input respiratory impedance measured by head generator in preschool children , 2000, Pediatric pulmonology.

[35]  K. P. Van de Woestijne,et al.  Total respiratory resistance and reactance as a measurement of response to bronchial challenge with histamine. , 1989, The American review of respiratory disease.

[36]  H. Bisgaard,et al.  Budesonide/formoterol maintenance plus reliever therapy: a new strategy in pediatric asthma. , 2006, Chest.

[37]  H. Bisgaard,et al.  Discriminative capacity of bronchodilator response measured with three different lung function techniques in asthmatic and healthy children aged 2 to 5 years. , 2001, American journal of respiratory and critical care medicine.

[38]  M. Demedts,et al.  Evaluation of impulse oscillation system: comparison with forced oscillation technique and body plethysmography. , 2001, The European respiratory journal.

[39]  M. Lebowitz,et al.  The maximal expiratory flow-volume curve. Normal standards, variability, and effects of age. , 1976, The American review of respiratory disease.

[40]  K P Van de Woestijne,et al.  Measurement of total respiratory impedance in calves by the forced oscillation technique. , 1988, Journal of applied physiology.

[41]  F. Ducharme,et al.  Pediatric reference values for respiratory resistance measured by forced oscillation. , 1998, Chest.

[42]  J Clément,et al.  Forced oscillation technique. Reference values for resistance and reactance over a frequency spectrum of 2-26 Hz in healthy children aged 2.3-12.5 years. , 1985, Bulletin europeen de physiopathologie respiratoire.

[43]  K. V. D. Woestijne The forced oscillation technique in intubated, mechanically-ventilated patients , 1993 .

[44]  B Suki,et al.  Serial distribution of airway mechanical properties in dogs: effects of histamine. , 1994, Journal of applied physiology.

[45]  L. Boulet,et al.  Canadian Asthma Consensus Report, 1999. Canadian Asthma Consensus Group. , 1999, CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne.

[46]  K. Desager,et al.  Measurement of total respiratory impedance in infants by the forced oscillation technique. , 1991, Journal of applied physiology.

[47]  F. Cibella,et al.  Variability of peak expiratory flow rate as a prognostic index in asymptomatic asthma. , 1984, Respiration; international review of thoracic diseases.

[48]  E. Oostveen,et al.  The forced oscillation technique in clinical practice: methodology, recommendations and future developments , 2003, European Respiratory Journal.

[49]  R. Peslin,et al.  Methacholine-induced volume dependence of respiratory resistance in preschool children. , 1999, The European respiratory journal.