Reduced baseline lung function in asymptomatic and symptomatic infants with recurrent asthma-like symptoms
Main Article Content
Keywords
infants; lung function; spirometry; recurrent asthma-like symptoms; airway narrowing
Abstract
Background: Recurrent asthma-like symptoms (RALS) in infants, defined as three or more physician-diagnosed episodes of wheezing and cough in the past 12 months, are the most com-mon clinical presentation of asthma during the first two years of life. During exacerbations, patients may experience severe episodes and often require emergency department visits or hospitalisation. However, there is limited information on lung function (LF) during symptomatic periods compared to asymptomatic periods and in healthy controls.
Methods: The baseline LF of 264 infants aged < 15 months with RALS (94 symptomatic and 170 asymptomatic) was measured using rapid thoracic compression from the raised volume technique, and 44 healthy infants were included as the control group. The measurements were converted to z-scores for analysis and comparison.
Results: The mean LF was significantly lower in symptomatic than in asymptomatic infants. Additionally, LF in the asymptomatic group was significantly lower than that in healthy infants. Tobacco smoking during pregnancy, frequent wheezing episodes (≥7), and family history of asthma were significantly associated with a higher proportion of abnormal FEV0.5 (z-score < −1.64) across the entire group of RALS infants.
Conclusion: Infants with RALS exhibit markedly reduced LF during symptomatic episodes. Furthermore, even when asymptomatic, they exhibit substantially lower LF than normal infants. These functional features support the notion that LF deficits are present very early in life in infants with RALS. This may also help explain the high prevalence of frequent and severe episodes observed in infants with RALS in clinical practice.
References
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Exhaled nitric oxide predicts persistence of wheezing, exacerbations, and decline in lung function in wheezy infants and toddlers. Clin Exp Allergy. 2013;43:1351-61. doi: 10.1111/cea.12171.
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Pediatr Pulmonol. 2019;54:1567-77. doi: 10.1002/ppul.24429.
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High risk of adult asthma following severe wheezing in early life. Pediatr Pulmonol. 2015;50:789-97. doi: 10.1002/ppul.23071.
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Allergy. 2010;65:503-9. doi: 10.1111/j.1398-9995.2009.02212.x.
27. Ma H, Li Y, Tang L, Peng X, Jiang L, Wan J, et al. Impact of childhood wheezing on lung function in adulthood: A meta-analysis. PLoS One. 2018;13:e0192390. doi: 10.1371/journal.pone.0192390.
28. Castro-Rodríguez JA, Forno E, Padilla O, Casanello P, Krause BJ, Borzutzky A. The asthma predictive index as a surrogate diagnostic tool in preschoolers: Analysis of a longitudinal birth cohort. Pediatr Pulmonol. 2021;56:3183-88. doi: 10.1002/ppul.25592.
29. de Gouveia Belinelo P, Collison AM, Murphy VE, Robinson PD, Jesson K,Hardaker K et al. Maternal asthma was associated with reduced lung function in male infants in a combined analysis of the BLT and BILD cohorts.Thorax. 2021;76:996-1001. doi: 10.1136/thoraxjnl-2020-215526.
30. Gibbs K, Collaco JM, McGrath-Morrow SA. Impact of Tobacco Smoke and Nicotine Exposure on Lung Development. Chest. 2016;149:552-561. doi: 10.1378/chest.15-1858.
31. Miller RL, Lawrence J. Understanding Root Causes of Asthma. Perinatal Environmental Exposures and Epigenetic Regulation. Ann Am Thorac Soc. 2018;15(Suppl 2):S103-S108. doi: 10.1513/AnnalsATS.201706-514MG.
32. Accordini S, Calciano L, Johannessen A, Benediktsdóttir B, Bertelsen RJ, Bråbäck L, et al. Prenatal and prepubertal exposures to tobacco smoke in men may cause lower lung function in future offspring: a three-generation study using a causal modelling approach. Eur Respir J. 2021;58:2002791. doi: 10.1183/13993003.02791-2020.
33. Gatford KL, Wooldridge AL, Kind KL, Bischof R, Clifton VL.
Pre-birth origins of allergy and asthma. J Reprod Immunol. 2017;123:88-93. doi: 10.1016/j.jri.2017.07.002.
34. Garcia-Marcos L, Mallol J, Solé D, Brand PL; EISL Study Group. International study of wheezing in infants: risk factors in affluent and non-affluent countries during the first year of life. Pediatr Allergy Immunol 2010;21:878-88. doi: 10.1111/j.1399-3038.2010.01035.x
35. 2025 GINA Strategy Report. Global Strategy for Asthma Management and Prevention; Diagnosis of asthma in children five years and younger. Accessed 2025, November 5. Available from: https://ginasthma.org/2025-gina-strategy-report/
2. Mallol J, Solé D, García-Marcos L, Rosario N, Aguirre V, Herberto Chong, et al. Prevalence, Severity, and Treatment of Recurrent Wheezing During the First Year of Life: A Cross-Sectional Study of 12,405 Latin American Infants. Allergy Asthma Immunol Res. 2016;8:22-31. doi: 10.4168/aair.2016.8.1.22.
3. Hallas HW, Chawes BL, Rasmussen MA, Arianto L, Stokholm J, Bønnelykke K, et al. Airway obstruction and bronchial reactivity from age 1 month until 13 years in children with asthma: A prospective birth cohort study. PLoS Med. 2019;16:e1002722. doi: 10.1371/journal.pmed.1002722.
4. Owens L, Laing IA, Zhang G, Le Souëf PN. Infant lung function predicts asthma persistence and remission in young adults. Respirology. 2017;22:289-94. doi: 10.1111/resp.12901.
5. Bisgaard H, Nørgaard S, Sevelsted A, Chawes BL, Stokholm J, Mortensen EL, et al. Asthma-like symptoms in young children increase the risk of COPD. J Allergy Clin Immunol. 2021;147:569-76.e9. doi: 10.1016/j.jaci.2020.05.043.
6. Guerra S, Lombardi E, Stern DA, Sherrill DL, Gilbertson-Dahdal D, Wheatley-Guy CM, et al. Foetal Origins of Asthma: A Longitudinal Study from Birth to Age 36 Years. Am J Respir Crit Care Med. 2020;202:1646-55. doi: 10.1164/rccm.202001-0194OC.
7. Martinez FD. Early-Life Origins of Chronic Obstructive Pulmonary Disease.
N Engl J Med. 2016;375:871-8. doi: 10.1056/NEJMra1603287.
8. O'Brian AL, Lemanske RF Jr, Evans MD, Gangnon RE, Gern JE, Jackson DJ. Recurrent severe exacerbations in early life and reduced lung function at school age. J Allergy Clin Immunol. 2012;129:1162-4. doi: 10.1016/j.jaci.2011.11.046.
9. Elliott M, Heltshe SL, Stamey DC, Cochrane ES, Redding GJ, Debley JS.
Exhaled nitric oxide predicts persistence of wheezing, exacerbations, and decline in lung function in wheezy infants and toddlers. Clin Exp Allergy. 2013;43:1351-61. doi: 10.1111/cea.12171.
10. Borrego LM, Stocks J, Leiria-Pinto P, Peralta I, Romeira AM, Neuparth N, et al. Lung function and clinical risk factors for asthma in infants and young children with recurrent wheeze. Thorax. 2009;64:203-9. doi: 10.1136/thx.2008.099903.
11. Lanza FC, Wandalsen GF, Dos Santos AM, Solé D. Bronchodilator response in wheezing infants assessed by the raised volume rapid thoracic compression technique. Respir Med. 2016;119:29-34. doi: 10.1016/j.rmed.2016.08.013.
12. Llapur CJ, Martínez TM, Coates C, Tiller C, Wiebke JL, Li X et al. Lung structure and function of infants with recurrent wheeze when asymptomatic. Eur Respir J. 2009;33:107-12. doi: 10.1183/09031936.00106607.
13. Henderson AJ, Warner JO. Fetal origins of asthma. Semin Fetal Neonatal Med. 2012;17:82-91. doi: 10.1016/j.siny.2012.01.006.
14. Turner S, Fielding S, Mullane D, Cox DW, Goldblatt J, Landau L et al. A longitudinal study of lung function from 1 month to 18 years of age. Thorax. 2014;69:1015-20. doi: 10.1136/thoraxjnl-2013-204931.
15. Turner S. Antenatal origins of reduced lung function-but not asthma?
Respirology. 2016;21:574-5. doi: 10.1111/resp.12794.
16. Mallol J, Aguirre V, Wandalsen G. Common cold decreases lung function in infants with recurrent wheezing. Allergol Immunopathol (Madr). 2010;38:110-4. doi: 10.1016/j.aller.2009.10.001.
17. American Thoracic Society; European Respiratory Society. ATS/ERS statement: raised volume forced expirations in infants: guidelines for current practice. Am J Respir Crit Care Med. 2005;172:1463-71. doi: 10.1164/rccm.200408-1141ST.
18. Mallol J, Aguirre VL, Wandalsen G. Variability of the raised volume rapid thoracic compression technique in infants with recurrent wheezing. Allergol Immunopathol (Madr). 2005;33:74-9. doi: 10.1157/13072917.
19. Morris MG. Nasal versus oronasal raised volume forced expirations in infants--a real physiologic challenge. Pediatr Pulmonol. 2012;47:780-94. doi: 10.1002/ppul.22509.
20. Jones M, Castile R, Davis S, Kisling J, Filbrun D, Flucke R et al. Forced expiratory flows and volumes in infants. Normative data and lung growth. Am J Respir Crit Care Med. 2000;161:353-9. doi: 10.1164/ajrccm.161.2.9903026.
21. Bisgaard H, Szefler S. Prevalence of asthma-like symptoms in young children. Pediatr Pulmonol 2007; 42:723-28. doi: 10.1002/ppul.20644
22. Levine H, Leventer-Roberts M, Hoshen M, Mei-Zahav M, Balicer R, Blau H. Healthcare utilization in infants and toddlers with asthma-like symptoms.
Pediatr Pulmonol. 2019;54:1567-77. doi: 10.1002/ppul.24429.
23. Heikkilä P, Korppi M, Ruotsalainen M, Backman K. Viral wheezing in early childhood as a risk factor for asthma in young adulthood: A prospective long-term cohort study. Health Sci Rep. 2022;5):e538. doi: 10.1002/hsr2.538.
24. Goksör E, Åmark M, Alm B, Ekerljung L, Lundbäck B, Wennergren G.
High risk of adult asthma following severe wheezing in early life. Pediatr Pulmonol. 2015;50:789-97. doi: 10.1002/ppul.23071.
25. Duijts L, Granell R, Sterne JA, Henderson AJ. Childhood wheezing phenotypes influence asthma, lung function and exhaled nitric oxide fraction in adolescence. Eur Respir J. 2016;47:510-9. doi: 10.1183/13993003.00718-2015.
26. Ruotsalainen M, Piippo-Savolainen E, Hyvärinen MK, Korppi M. Adulthood asthma after wheezing in infancy: a questionnaire study at 27 years of age.
Allergy. 2010;65:503-9. doi: 10.1111/j.1398-9995.2009.02212.x.
27. Ma H, Li Y, Tang L, Peng X, Jiang L, Wan J, et al. Impact of childhood wheezing on lung function in adulthood: A meta-analysis. PLoS One. 2018;13:e0192390. doi: 10.1371/journal.pone.0192390.
28. Castro-Rodríguez JA, Forno E, Padilla O, Casanello P, Krause BJ, Borzutzky A. The asthma predictive index as a surrogate diagnostic tool in preschoolers: Analysis of a longitudinal birth cohort. Pediatr Pulmonol. 2021;56:3183-88. doi: 10.1002/ppul.25592.
29. de Gouveia Belinelo P, Collison AM, Murphy VE, Robinson PD, Jesson K,Hardaker K et al. Maternal asthma was associated with reduced lung function in male infants in a combined analysis of the BLT and BILD cohorts.Thorax. 2021;76:996-1001. doi: 10.1136/thoraxjnl-2020-215526.
30. Gibbs K, Collaco JM, McGrath-Morrow SA. Impact of Tobacco Smoke and Nicotine Exposure on Lung Development. Chest. 2016;149:552-561. doi: 10.1378/chest.15-1858.
31. Miller RL, Lawrence J. Understanding Root Causes of Asthma. Perinatal Environmental Exposures and Epigenetic Regulation. Ann Am Thorac Soc. 2018;15(Suppl 2):S103-S108. doi: 10.1513/AnnalsATS.201706-514MG.
32. Accordini S, Calciano L, Johannessen A, Benediktsdóttir B, Bertelsen RJ, Bråbäck L, et al. Prenatal and prepubertal exposures to tobacco smoke in men may cause lower lung function in future offspring: a three-generation study using a causal modelling approach. Eur Respir J. 2021;58:2002791. doi: 10.1183/13993003.02791-2020.
33. Gatford KL, Wooldridge AL, Kind KL, Bischof R, Clifton VL.
Pre-birth origins of allergy and asthma. J Reprod Immunol. 2017;123:88-93. doi: 10.1016/j.jri.2017.07.002.
34. Garcia-Marcos L, Mallol J, Solé D, Brand PL; EISL Study Group. International study of wheezing in infants: risk factors in affluent and non-affluent countries during the first year of life. Pediatr Allergy Immunol 2010;21:878-88. doi: 10.1111/j.1399-3038.2010.01035.x
35. 2025 GINA Strategy Report. Global Strategy for Asthma Management and Prevention; Diagnosis of asthma in children five years and younger. Accessed 2025, November 5. Available from: https://ginasthma.org/2025-gina-strategy-report/