Does Bronchodilator Responsiveness in Infants with Bronchiolitis Depend on Age?

Modl, Manfred; Eber, Ernst; Malle-Scheid, Doris; Weinhandl, Elisabeth; Zach, M

doi:10.1016/j.jpeds.2005.06.005

Cited by 12 publications

(9 citation statements)

References 26 publications

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“…Interestingly, the only factor that was related to BDR was a lower height for age z‐score. These results are seemingly in contrast to work in infants with acute bronchiolitis where age did not seem to predict the magnitude of the bronchodilator response 27. However, in our study, we also found that the response with age was non‐linear and the effect was not seen with age but with height z‐score.…”

Section: Discussioncontrasting

confidence: 99%

Bronchodilator responsiveness in wheezy infants and toddlers is not associated with asthma risk factors

Debley

Stanojevic

Filbrun

et al. 2011

Pediatric Pulmonology

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Background There are limited data assessing bronchodilator responsiveness (BDR) in infants and toddlers with recurrent wheezing, and factors associated with a positive response. Objectives In a multicenter study of children ≤ 36 months old we assessed the prevalence of and factors associated with BDR among infants/toddlers with recurrent episodes of wheezing. Methods Forced expiratory flows and volumes using the raised-volume rapid thoracic compression method were measured in 76 infants/toddlers (mean (sd) age 16.8 (7.6) mos.) with recurrent wheezing before and after administration of albuterol. Prior history of hospitalization or emergency department treatment for wheezing, use of inhaled or systemic corticosteroids, physician treatment of eczema, environmental tobacco smoke exposure, and family history of asthma or allergic rhinitis were ascertained. Results Using the published upper limit of normal for post bronchodilator change (FEV0.5 ≥ 13% and/or FEF25–75 ≥ 24%) in healthy infants, 24% (n=18) of children in our study exhibited BDR. The BDR response was not associated with any clinical factor other than body size. Dichotomizing subjects into responders (defined by published limits of normal)or by quartile to identify children with the greatest change from baseline (4th quartile vs. other) did not identify any other factor associated with BDR. Conclusions Approximately one quarter of infants/toddlers with recurrent wheezing exhibited BDR at their clinical baseline. However, BDR in wheezy infants/toddlers was not associated with established clinical asthma risk factors.

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Section: Discussioncontrasting

confidence: 99%

Bronchodilator responsiveness in wheezy infants and toddlers is not associated with asthma risk factors

Debley

Stanojevic

Filbrun

et al. 2011

Pediatric Pulmonology

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“…However, it is not clear that these drugs are clinically effective: meta-analyses have shown little or no overall benefit, regardless of viral bronchiolitis severity (15,20). Their lack of efficacy has not been explained, although it has often been ascribed to difficulties associated with drug delivery to the small airways of young infants, particularly in the presence of bronchoconstriction and inflammatory exudates or airway obstruction (28). ␤-agonists increase total body oxygen consumption, thereby increasing oxygen demands in infants hospitalized for respiratory compromise, and can potentially exacerbate ventilation-perfusion mismatch by inducing vasodilation without bronchodilation (12).…”

mentioning

confidence: 99%

Respiratory syncytial virus induces insensitivity to β-adrenergic agonists in mouse lung epithelium in vivo

Davis¹,

Xu²,

Gao³

et al. 2007

American Journal of Physiology-Lung Cellular and Molecular Phys

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Davis IC, Xu A, Gao Z, Hickman-Davis JM, Factor P, Sullender WM, Matalon S. Respiratory syncytial virus induces insensitivity to ␤-adrenergic agonists in mouse lung epithelium in vivo. Am J Physiol Lung Cell Mol Physiol 293: L281-L289, 2007. First published April 13, 2007; doi:10.1152/ajplung.00458.2006 is the most common cause of bronchiolitis in infants and children worldwide. We wished to determine whether intratracheal administration of ␤-agonists improved alveolar fluid clearance (AFC) across the distal respiratory epithelium of RSV-infected mice. Following intranasal infection with RSV strain A2, AFC was measured in anesthetized, ventilated BALB/c mice by instillation of 5% BSA into the dependent lung. We found that direct activation of protein kinase A by forskolin or 8-bromo-cAMP increased AFC at day 2 after infection with RSV. In contrast, short-and long-acting ␤-agonists had no effect at either day 2 or day 4. Insensitivity to ␤-agonists was not a result of elevated plasma catecholamines or lung epithelial cell ␤-adrenergic receptor degradation. Instead, RSV-infected mice had significantly higher levels of phosphorylated PKC in the membrane fractions of their lung epithelial cells. In addition, insensitivity to ␤-agonists was mediated in a paracrine fashion by KC (the murine homolog of CXCL8) and reversed by inhibition of either PKC or G protein-coupled receptor kinase 2 (GRK2). These results indicate that insufficient response to ␤-agonists in RSV may be caused, at least in part, by impaired ␤-adrenergic receptor signaling, as a consequence of GRK2-mediated uncoupling of ␤-adrenergic receptors from adenylyl cyclase. paramyxovirus; protein kinase C; G protein-coupled receptor kinase 2; CXCL8 RESPIRATORY SYNCYTIAL VIRUS (RSV) is the most common cause of lower respiratory tract disease in infants and children worldwide (44), is a frequent initiator of acute asthma exacerbations in young children, and has a disease impact comparable to that of nonpandemic influenza A in the elderly (8). Approximately 2-3% of all cases of RSV bronchiolitis result in severe hypoxia or a need for parenteral fluid supplementation that necessitates hospitalization (44). ␤-agonists are frequently used to treat RSV bronchiolitis, primarily because of their perceived ability to relax airway smooth muscle and cause bronchodilation, with the ultimate aim of alleviating hypoxemia. However, it is not clear that these drugs are clinically effective: meta-analyses have shown little or no overall benefit, regardless of viral bronchiolitis severity (15,20). Their lack of efficacy has not been explained, although it has often been ascribed to difficulties associated with drug delivery to the small airways of young infants, particularly in the presence of bronchoconstriction and inflammatory exudates or airway obstruction (28). ␤-agonists increase total body oxygen consumption, thereby increasing oxygen demands in infants hospitalized for respiratory compromise, and can potentially exacerbate ventilation-perfusion mismatch by inducing vaso...

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“…However, infant PFTs studies indicate no difference in bronchodilator response in infants in the age range that we studied. 28 We did not enroll infants in the intensive care unit or very sick infants, so our study cohort had relatively mild disease by the time they received the study medication. Normal reference RIP data for infants in the age range that we studied are not available, but some of our study subjects had baseline F within 2 SD of that reported from limited data in normal newborns.…”

Section: Scarlett Et Almentioning

confidence: 99%

“…A paradoxical response to bronchodilator in infants with VB has been noted before. 28 Since wall tension of a cylinder is inversely proportional to the radius, 29 bronchodilation can potentially lower wall tension and increase airway compliance, leading to airway collapse and obstruction. The potential for a paradoxical response to a bronchodilator highlights the importance of conducting a carefully monitored trial of bronchodilator therapy in VB, and our results suggest that RIP can provide an objective measure to detect this potentially deleterious effect of ALB.…”

Section: Scarlett Et Almentioning

confidence: 99%

Tidal Breathing Responses to Albuterol and Normal Saline in Infants with Viral Bronchiolitis

Scarlett

Walker

Rovitelli

et al. 2012

Pediatric Allergy, Immunology, and Pulmonology

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The American Academy of Pediatrics recommends the use of an objective means of evaluating the response to a trial of bronchodilator therapy in viral bronchiolitis (VB), but there is an inherent subjectivity with the use of clinical assessments. The goal of this study was to explore the possibility of using respiratory inductive plethysmography (RIP) to serve as an objective measure of change in respiratory function in infants with VB receiving albuterol (ALB) therapy. This was a randomized, double-blind, placebo-controlled study in previously healthy infants hospitalized for VB. Study subjects randomly received either ALB (0.1 mg/kg) or normal saline (NS) by nebulization. RIP data were collected during clinically determined quiet sleep before and after treatment. We enrolled a total of 20 study subjects; 10 received ALB and 10 received NS. Mean tidal breathing measures did not change significantly in either group post-treatment. However, the phase angle fell by > 40% of baseline in 3 ALBtreated subjects (30%) and 4 NS (40%)-treated subjects. Using RIP, we observed improvements in the respiratory function in a subset of infants treated with ALB and with NS. It is possible that NS itself has beneficial effects. Our results suggest that RIP can serve as an objective measure of respiratory function in studies of infant VB.

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Does Bronchodilator Responsiveness in Infants with Bronchiolitis Depend on Age?

Cited by 12 publications

References 26 publications

Bronchodilator responsiveness in wheezy infants and toddlers is not associated with asthma risk factors

Bronchodilator responsiveness in wheezy infants and toddlers is not associated with asthma risk factors

Respiratory syncytial virus induces insensitivity to β-adrenergic agonists in mouse lung epithelium in vivo

Tidal Breathing Responses to Albuterol and Normal Saline in Infants with Viral Bronchiolitis

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