Lung Function Variability in Children and Adolescents With and Without Asthma (LUV Study): Protocol for a Prospective, Nonrandomized, Clinical Trial

Eirini-Sofia Frima, Ilias Theodorakopoulos, Dimos Gidaris, Nikolaos Karantaglis, Grigorios Chatziparasidis, Panagiotis Plotas, Michael Anthracopoulos, Sotirios Fouzas, Eirini-Sofia Frima, Ilias Theodorakopoulos, Dimos Gidaris, Nikolaos Karantaglis, Grigorios Chatziparasidis, Panagiotis Plotas, Michael Anthracopoulos, Sotirios Fouzas

Abstract

Background: Variability analysis of peak expiratory flow (PEF) and forced expiratory volume at 1 second (FEV1) has been used in research to predict exacerbations in adults with asthma. However, there is a paucity of data regarding PEF and FEV1 variability in healthy children and adolescents and those with asthma.

Objective: The objective of this study is the assessment of PEF and FEV1 variability in (1) healthy children and adolescents, to define the normal daily fluctuation of PEF and FEV1 and the parameters that may influence it, and (2) children and adolescents with asthma, to explore the differences from healthy subjects and reveal any specific variability changes prior to exacerbation.

Methods: The study will include 100 healthy children and adolescents aged 6-18 years (assessment of normal PEF and FEV1 variability) and 100 children and adolescents of the same age with diagnosed asthma (assessment of PEF and FEV1 variability in subjects with asthma). PEF and FEV1 measurements will be performed using an ultraportable spirometer (Spirobank Smart; MIR Medical International Research) capable of smartphone connection. Measurements will be performed twice a day between 7 AM and 9 AM and between 7 PM and 9 PM and will be dispatched via email to a central database for a period of 3 months. PEF and FEV1 variability will be assessed by detrended fluctuation and sample entropy analysis, aiming to define the normal pattern (healthy controls) and to detect and quantify any deviations among individuals with asthma. The anticipated duration of the study is 24 months.

Results: The study is funded by the "C. Caratheodory" Programme of the University of Patras, Greece (PN 47014/24.9.2018). It was approved by the Ethics Committee (decision 218/19-03-2019) and the Scientific Board (decision 329/02-04-2019) of the University Hospital of Patras, Greece. Patient recruitment started in January 2020, and as of June 2020, 100 healthy children have been enrolled (74 of them have completed the measurements). The anticipated duration of the study is 24 months. The first part of the study (assessment of lung function variability in healthy children and adolescents) will be completed in August 2020, and the results will be available for publication by October 2020.

Conclusions: Healthy children and adolescents may present normal short- and long-term fluctuations in lung function; the pattern of this variability may be influenced by age, sex, and environmental conditions. Significant lung function variability may also be present in children and adolescents with asthma, but the patterns may differ from those observed in healthy children and adolescents. Such data would improve our understanding regarding the chronobiology of asthma and permit the development of integrated tools for assessing the level of control and risk of future exacerbations.

Trial registration: ClinicalTrials.gov NCT04163146; https://ichgcp.net/clinical-trials-registry/NCT04163146.

International registered report identifier (irrid): DERR1-10.2196/20350.

Keywords: adolescents; asthma; children; fluctuation analysis; lung function variability.

Conflict of interest statement

Conflicts of Interest: None declared.

©Eirini-Sofia Frima, Ilias Theodorakopoulos, Dimos Gidaris, Nikolaos Karantaglis, Grigorios Chatziparasidis, Panagiotis Plotas, Michael Anthracopoulos, Sotirios Fouzas. Originally published in JMIR Research Protocols (http://www.researchprotocols.org), 07.08.2020.

Figures

Figure 1
Figure 1
Study flow chart.
Figure 2
Figure 2
Standard protocol items: recommendations for interventional trials (SPIRIT) checklist.
Figure 3
Figure 3
Example of the monitoring table presenting the number of acceptable tests per day/time point for each participant. Green cells: full adherence; orange cells:

References

    1. Chronic respiratory diseases: asthma. World Health Organization, Geneva. 2019. [2020-06-18]. .
    1. Global Strategy for asthma management and prevention, 2019. Global Initiative for Asthma (GINA) [2020-06-18]. .
    1. Papi A, Brightling C, Pedersen SE, Reddel HK. Asthma. Lancet. 2018 Feb 24;391(10122):783–800. doi: 10.1016/S0140-6736(17)33311-1.
    1. Spengler CM, Shea SA. Endogenous circadian rhythm of pulmonary function in healthy humans. Am J Respir Crit Care Med. 2000 Sep;162(3 Pt 1):1038–46. doi: 10.1164/ajrccm.162.3.9911107.
    1. Martin RJ, Banks-Schlegel S. Chronobiology of asthma. Am J Respir Crit Care Med. 1998 Sep;158(3):1002–7. doi: 10.1164/ajrccm.158.3.9712132.
    1. Frey U, Brodbeck T, Majumdar A, Taylor DR, Town GI, Silverman M, Suki B. Risk of severe asthma episodes predicted from fluctuation analysis of airway function. Nature. 2005 Dec 01;438(7068):667–70. doi: 10.1038/nature04176.
    1. Thamrin C, Stern G, Strippoli MF, Kuehni CE, Suki B, Taylor DR, Frey U. Fluctuation analysis of lung function as a predictor of long-term response to beta2-agonists. Eur Respir J. 2009 Mar;33(3):486–93. doi: 10.1183/09031936.00106208.
    1. Thamrin C, Taylor DR, Jones SL, Suki B, Frey U. Variability of lung function predicts loss of asthma control following withdrawal of inhaled corticosteroid treatment. Thorax. 2010 May;65(5):403–8. doi: 10.1136/thx.2009.129668.
    1. Thamrin C, Nydegger R, Stern G, Chanez P, Wenzel SE, Watt RA, FitzPatrick S, Taylor DR, Frey U. Associations between fluctuations in lung function and asthma control in two populations with differing asthma severity. Thorax. 2011 Dec;66(12):1036–42. doi: 10.1136/thx.2010.156489.
    1. Delgado-Eckert E, Fuchs O, Kumar N, Pekkanen J, Dalphin J, Riedler J, Lauener R, Kabesch M, Kupczyk M, Dahlen S, Mutius EV, Frey U, PASTUREBIOAIR Study groups Functional phenotypes determined by fluctuation-based clustering of lung function measurements in healthy and asthmatic cohort participants. Thorax. 2018 Feb;73(2):107–115. doi: 10.1136/thoraxjnl-2016-209919.
    1. Ginsberg D. An unidentified monster in the bed--assessing nocturnal asthma in children. Mcgill J Med. 2009 Jan;12(1):31–8.
    1. Kamps AW, Roorda RJ, Brand PL. Peak flow diaries in childhood asthma are unreliable. Thorax. 2001 Mar;56(3):180–2.
    1. Aliverti A. Wearable technology: role in respiratory health and disease. Breathe (Sheff) 2017 Jun;13(2):e27–e36. doi: 10.1183/20734735.008417.
    1. Kaminsky DA, Wang LL, Bates JHT, Thamrin C, Shade DM, Dixon AE, Wise RA, Peters S, Irvin CG. Fluctuation Analysis of Peak Expiratory Flow and Its Association with Treatment Failure in Asthma. Am J Respir Crit Care Med. 2017 Apr 15;195(8):993–999. doi: 10.1164/rccm.201601-0076OC.
    1. Faul F, Erdfelder E, Lang A, Buchner A. G*Power 3: a flexible statistical power analysis program for the social, behavioral, and biomedical sciences. Behav Res Methods. 2007 May;39(2):175–91.
    1. Quanjer PH, Stanojevic S, Cole TJ, Baur X, Hall GL, Culver BH, Enright PL, Hankinson JL, Ip MSM, Zheng J, Stocks J, ERS Global Lung Function Initiative Multi-ethnic reference values for spirometry for the 3-95-yr age range: the global lung function 2012 equations. Eur Respir J. 2012 Dec;40(6):1324–43. doi: 10.1183/09031936.00080312.
    1. Lung Function Variability in Children and Adolescents Study. [2020-06-18].
    1. Graham BL, Steenbruggen I, Miller MR, Barjaktarevic IZ, Cooper BG, Hall GL, Hallstrand TS, Kaminsky DA, McCarthy K, McCormack MC, Oropez CE, Rosenfeld M, Stanojevic S, Swanney MP, Thompson BR. Standardization of Spirometry 2019 Update. An Official American Thoracic Society and European Respiratory Society Technical Statement. Am J Respir Crit Care Med. 2019 Oct 15;200(8):e70–e88. doi: 10.1164/rccm.201908-1590ST.
    1. Peng C- K, Mietus J, Hausdorff JM, Havlin S, Stanley HE, Goldberger AL. Long-range anticorrelations and non-Gaussian behavior of the heartbeat. Phys Rev Lett. 1993 Mar 01;70(9):1343–6. doi: 10.1103/PhysRevLett.70.1343.
    1. Gonem S, Umar I, Burke D, Desai D, Corkill S, Owers-Bradley J, Brightling CE, Siddiqui S. Airway impedance entropy and exacerbations in severe asthma. Eur Respir J. 2012 Nov;40(5):1156–63. doi: 10.1183/09031936.00228611.
    1. Boezen HM, Schouten JP, Postma DS, Rijcken B. Relation between respiratory symptoms, pulmonary function and peak flow variability in adults. Thorax. 1995 Feb;50(2):121–6. doi: 10.1136/thx.50.2.121.
    1. Thamrin C, Zindel J, Nydegger R, Reddel HK, Chanez P, Wenzel SE, FitzPatrick S, Watt RA, Suki B, Frey U. Predicting future risk of asthma exacerbations using individual conditional probabilities. J Allergy Clin Immunol. 2011 Jun;127(6):1494–502.e3. doi: 10.1016/j.jaci.2011.01.018.
    1. Veiga J, Lopes AJ, Jansen JM, Melo PL. Airflow pattern complexity and airway obstruction in asthma. J Appl Physiol (1985) 2011 Aug;111(2):412–9. doi: 10.1152/japplphysiol.00267.2011.
    1. Dames KK, Lopes AJ, de Melo PL. Airflow pattern complexity during resting breathing in patients with COPD: effect of airway obstruction. Respir Physiol Neurobiol. 2014 Feb 01;192:39–47. doi: 10.1016/j.resp.2013.12.004.
    1. Macklem PT. Emergent phenomena and the secrets of life. J Appl Physiol (1985) 2008 Jun;104(6):1844–6. doi: 10.1152/japplphysiol.00942.2007.
    1. Kaminsky DA, Irvin CG. What long-term changes in lung function can tell us about asthma control. Curr Allergy Asthma Rep. 2015 Mar;15(3):505. doi: 10.1007/s11882-014-0505-x.

Source: PubMed

Sponsors and Collaborators

Medical Conditions

Drug Interventions

3
Subscribe