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Year : 2022  |  Volume : 7  |  Issue : 2  |  Page : 45-46

Infantile wheeze: Phenotypes and trajectories

Ad-din Women’s Medical College, Dhaka, Bangladesh

Date of Submission05-Jun-2022
Date of Acceptance07-Jun-2022
Date of Web Publication22-Nov-2022

Correspondence Address:
Prof. A RM Luthful Kabir
Ad-din Women’s Medical College, Dhaka
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/pnjb.pnjb_15_22

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How to cite this article:
Kabir A R. Infantile wheeze: Phenotypes and trajectories. Paediatr Nephrol J Bangladesh 2022;7:45-6

How to cite this URL:
Kabir A R. Infantile wheeze: Phenotypes and trajectories. Paediatr Nephrol J Bangladesh [serial online] 2022 [cited 2023 Mar 30];7:45-6. Available from: http://www.pnjb-online.org/text.asp?2022/7/2/45/361614

Wheeze is defined as a continuous high-pitched sound with musical quality emitting from the chest during expiration when child’s airways are partially blocked or narrowed due to bronchospasm, intraluminal secretions, inflammation or other structural changes in the airway walls, or to dynamic compression of the airway.[1] Wheezing is very common in infancy affecting one in three children during the first three years of life and the cumulative prevalence of wheeze is almost 50% at the age of 6 years.[2],[3] In most cases, wheezing episodes are mild and easily treated.[4] However, some infants will develop persistent or recurrent wheezing, which is often severe.[5] There is no consensus as to the age limit of wheezing disorder in young children. Some experts defined infantile wheezing as recurrent or persistent episodes of wheezing in infants less than 24 months old or others as wheezing in preschool-aged children.[6],[7]

The understanding of preschool wheezing illness has been enhanced by a number of birth cohort studies in particular by highlighting the existence of different phenotypes.[2],[8]

In one birth cohort study,[2] three phenotypes were found more common: (a) transient early wheeze occurs before the age of 3 years of age and resolves by the age of 6 years without lung function impairment; (b) late-onset wheeze develops after 3 years of age and persists in childhood, it is linked to atopy and in some studies, it is associated to reduced lung function and high bronchial hyperresponsiveness; (c) persistent wheeze starts in early life before 3 years of age and is associated with atopy, high IgE, early allergen sensitization and diminished lung function by school age.[2],[9] Children with persistent wheezing or late-onset wheezing more frequently have asthma in adolescent.[10] OworaAH et al. proposed a simple clinical classification of wheezing as “epidodic viral wheezing” (EVW) or “multiple trigger wheezing” (MTW) based on triggers and symptoms.[11] A wheezing typically exacerbated by viral upper respiratory tract infection with few or no symptoms in the interval between the episodes was described as EVW, the commonest phenotype between 1 and 5 years of age. Children who have symptomsthat resemble asthma with wheezing also between respiratory infections and during activity, crying or laughing show the phenotype traditionally called MTW. Children with MTW are usually atopic and may have a family history for asthma. The usefulness of such classification of wheezing is fraught with several limitations: it does not consider that is based on patient characteristics at the time of examination that change over time and it does not take into account the severity of the episode and cannot identify children responding to specific treatments.[12],[13]

In the Manchester Asthma and Allergy Study (MAAS) a new phenotype named persistent troublesome wheeze, has been characterized. Children in this category had more frequent exacerbations, hospitalizations, and unscheduled visits, reduced lung functions, higher bronchial hyperactive airways, higher IgE levels to inhalant allergen in comparison with other phenotypes.[14] In the MAAS cohort, new phenotypes of children with severe wheeze exacerbations were found when trajectories were examined at 8 years of age and at adolescence.[15] Early-onset frequent exacerbations or no exacerbations had shorter breast feeding, lower lung function and higher fractioned exhaled nitric oxide (FeNO). In the Canadian Asthma Primary Prevention Study, pre-school wheezers were classified as early-transient (10%) who did not develop asthma, low-progressive (69%) who gradually develop asthma over time, and early persistent (21%) with higher risk of asthma occurrence.[11]

Other phenotypes of infantile wheeze are never or infrequent wheeze where children who never wheeze or have presented with wheezing once in their life.[2],[16]Intermediate wheeze presents as wheezing with onset between 18 and 42 months that subsequently that subsequently persists into later childhood and is strongly associated with atopy, allergic sensitization, hyperresponsiveness and lower pulmonary function test (PFT) scores.[17]Nonatopic persistent wheezing phenotype accounts for about 40% of persistent wheeze and usually presents as episodic wheezing triggered by viral illness.[2] RSV causes persistent wheezing in children younger than 2 years while rhinovirus is the most common cause of recurrent or persistent wheeze older than 2 years.[18]IgE associated atopic and / or persistent wheezing phenotype accounts for 60% of persistent wheezing cases; begins in the second year of life and persists into late childhood.[2],[19]

The optimal therapy for preventing recurrent episodes of wheezing in preschool children is not well defined and remains a matter of study and debate. Apart from parent education, environmental manipulation, allergen avoidance, intermittent wheezing should be should be treated with intermittent bronchodilator therapy and a controller therapy should be prescribed for a young child with recurrent wheezing.[1],[20]

  References Top

de Benedictis FM, Bush A Infantile wheeze: Rethinking dogma. Arch Dis Child 2017;102:371-5.  Back to cited text no. 1
Martinez FD, Wright AL, Taussig LM, Holberg CJ, Halonen M, Morgan WJ Asthma and wheezing in the first six years of life. The group health medical associates. N Engl J Med 1995;332:133-8.  Back to cited text no. 2
Bisgaard H, Szefler S Prevalence of asthma-like symptoms in young children. Pediatr Pulmonol 2007;42:723-8.  Back to cited text no. 3
Devulapalli CS, Carlsen KC, Håland G, Munthe-Kaas MC, Pettersen M, Mowinckel P, et al. Severity of obstructive airways disease by age 2 years predicts asthma at 10 years of age. Thorax 2008;63:8-13.  Back to cited text no. 4
Bacharier LB, Phillips BR, Bloomberg GR, Zeiger RS, Paul IM, Krawiec M, et al; Childhood Asthma Research and Education Network, National Heart, Lung, and Blood Institute. Severe intermittent wheezing in preschool children: A distinct phenotype. J Allergy Clin Immunol 2007;119:604-10.  Back to cited text no. 5
Ren CL, Esther CR Jr, Debley JS, Sockrider M, Yilmaz O, Amin N, et al; ATS Ad Hoc Committee on Infants with Recurrent or Persistent Wheezing. Official american thoracic society clinical practice guidelines: Diagnostic evaluation of infants with recurrent or persistent wheezing. Am J Respir Crit Care Med 2016;194:356-73.  Back to cited text no. 6
Brand PL, Baraldi E, Bisgaard H, Boner AL, Castro-Rodriguez JA, Custovic A, et al. Definition, assessment and treatment of wheezing disorders in preschool children: An evidence-based approach. Eur Respir J 2008;32:1096-110.  Back to cited text no. 7
Kurukulaaratchy RJ, Fenn MH, Waterhouse LM, Matthews SM, Holgate ST, Arshad SH Characterization of wheezing phenotypes in the first 10 years of life. Clin Exp Allergy 2003;33:573-8.  Back to cited text no. 8
Savenije OE, Granell R, Caudri D, Koppelman GH, Smit HA, Wijga A, et al. Comparison of childhood wheezing phenotypes in 2 birth cohorts: ALSPAC and PIAMA. J Allergy Clin Immunol 2011;127:1505-12.e14.  Back to cited text no. 9
Taussig LM, Wright AL, Holberg CJ, Halonen M, Morgan WJ, Martinez FD Tucson children’s respiratory study: 1980 to present. J Allergy Clin Immunol 2003;111:661-75; quiz 676.  Back to cited text no. 10
Owora AH, Becker AB, Chan-Yeung M, Chan ES, Chooniedass R, Ramsey C, et al. Wheeze trajectories are modifiable through early-life intervention and predict asthma in adolescence. Pediatr Allergy Immunol 2018;29:612-21.  Back to cited text no. 11
van Wonderen KE, Geskus RB, van Aalderen WM, Mohrs J, Bindels PJ, van der Mark LB, et al. Stability and predictiveness of multiple trigger and episodic viral wheeze in preschoolers. Clin Exp Allergy 2016;46:837-47.  Back to cited text no. 12
Schultz A, Brand PL Episodic viral wheeze and multiple trigger wheeze in preschool children: A useful distinction for clinicians? Paediatr Respir Rev 2011;12:160-4.  Back to cited text no. 13
Belgrave DCM, Simpson A, Semic-Jusufagic A, Murray CS, Buchan I, Pickles A, et al. Joint modeling of parentally reported and physician-confirmed wheeze identifies children with persistent troublesome wheezing. J Allergy Clin Immunol 2013;132:575-583.e12.  Back to cited text no. 14
Deliu M, Fontanella S, Haider S, Sperrin M, Geifman N, Murray C, et al. Longitudinal trajectories of severe wheeze exacerbations from infancy to school age and their association with early-life risk factors and late asthma outcomes. Clin Exp Allergy 2020;50:315-24.  Back to cited text no. 15
Golding J, Pembrey M, Jones R, ALSPAC Study Team. ALSPACethe Avon longitudinal study of parents and children. J Paediatr Perinat Epidemiol 2002;15:76–87.  Back to cited text no. 16
Henderson J, Granell R, Heron J, Sherriff A, Simpson A, Woodcock A, et al. Associations of wheezing phenotypes in the first 6 years of life with atopy, lung function and airway responsiveness in mid-childhood. Thorax 2008;63: 974-80.  Back to cited text no. 17
Stein RT, Sherrill D, Morgan WJ, Holberg CJ, Halonen M, Taussig LM, et al. Respiratory syncytial virus in early life and risk of wheeze and allergy by age 13 years. Lancet 1999; 354:541-5.  Back to cited text no. 18
Granell R, Henderson AJ, Sterne JA Associations of wheezing phenotypes with late asthma outcomes in the avon longitudinal study of parents and children: A population-based birth cohort. J Allergy Clin Immunol 2016;138:1060-1070.e11.  Back to cited text no. 19
Al-Shamrani A, Bagais K, Alenazi A, Alqwaiee M, Al-Harbi AS Wheezing in children: Approaches to diagnosis and management. Int J Pediatr Adolesc Med 2019;6:68-73.  Back to cited text no. 20


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