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A Longitudinal, Population-Based, Cohort Study of Childhood Asthma Followed to Adulthood
Open accessAbstract
BACKGROUND: The outcome of childhood asthma in adults has been described in high-risk cohorts, but few population-based studies have reported the risk factors for persistence and relapse. METHODS: We assessed children born from April 1972 through March 1973 in Dunedin, New Zealand, repeatedly from 9 to 26 years of age with questionnaires, pulmonary-function tests, bronchial-challenge testing, and allergy testing. RESULTS: By the age of 26 years, 51.4 percent of 613 study members with complete respiratory data had reported wheezing at more than one assessment. Eighty-nine study members (14.5 percent) had wheezing that persisted from childhood to 26 years of age, whereas 168 (27.4 percent) had remission, but 76 (12.4 percent) subsequently relapsed by the age of 26. Sensitization to house dust mites predicted the persistence of wheezing (odds ratio, 2.41; P=0.001) and relapse (odds ratio, 2.18; P=0.01), as did airway hyperresponsiveness (odds ratio for persistence, 3.00; P<0.001; odds ratio for relapse, 3.03; P<0.001). Female sex predicted the persistence of wheezing (odds ratio, 1.71; P=0.03), as did smoking at the age of 21 years (odds ratio, 1.84; P=0.01). The earlier the age at onset, the greater the risk of relapse (odds ratio, 0.89 per year of increase in the age at onset; P<0.001). Pulmonary function was consistently lower in those with persistent wheezing than in those without persistent wheezing. CONCLUSIONS: In an unselected birth cohort, more than one in four children had wheezing that persisted from childhood to adulthood or that relapsed after remission. The factors predicting persistence or relapse were sensitization to house dust mites, airway hyperresponsiveness, female sex, smoking, and early age at onset. These findings, together with persistently low lung function, suggest that outcomes in adult asthma may be determined primarily in early childhood.
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In the citing paper
“Among many factors, house dust mite (HDM) is the most prevalent cause of allergic sensitization [4, 6], and a risk factor for persistent asthma in human subjects [7, 8].”
In the citing paper
“The majority of studies have shown that persistent wheeze is related to reduced lung function development throughout adolescence (31, 45, 152, 153), while some suggest the effects of persistent wheeze and relapsed wheeze on lung function are established from mid-childhood, without further decline in tracking of FEV1 over time (154, 155).”
From Epidemiology of Asthma in Children and Adults (2019) · cites this paper as [154]
In the citing paper
“While a number of studies have reported that childhood asthma itself has no impact on adult lung function decline (154, 157, 158, 160), a study that collected childhood asthma status retrospectively has reported that it is associated with greater lung function decline, which may be related to recall bias (161).”
From Epidemiology of Asthma in Children and Adults (2019) · cites this paper as [154]
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ResultRural health disparities in asthma care and outcomes
Valet, R. S., Perry, T. T., & Hartert, T. V. (2009) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2008.12.1131 · Cited by 102
Adolescents and asthma: Why bother with our meds?
Naimi, D. R., Freedman, T. G., Ginsburg, K. R., Bogen, D. K., Rand, C. S., & Apter, A. J. (2009) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2009.02.022 · Cited by 102
“This also would be consistent with the observation that asthma can remit over the teenage years.(13,54) In these cases appropriate clinical management should include careful evaluation to determine whether regimen intensity can be stepped down.”
ResultLongitudinal Decline in Lung Volume in a Population of Children with Sickle Cell Disease
MacLean, J. E., Atenafu, E. G., Kirby-Allen, M. A., MacLusky, I., Stephens, D., Grasemann, H., & Subbarao, P. (2008) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.200708-1219oc · Cited by 102
“The rate of decline in lung function is similar to that of children with cystic fibrosis (2‐ 3%/yr) (35, 36), and significantly greater than seen in children with asthma (0‐0.88%/yr) (37, 38 ).”
BackgroundInfluentialRönmark, E., Lindberg, A., Watson, L., & Lundbäck, B. (2007) · Respiratory Medicine · doi:10.1016/j.rmed.2007.06.011 · Cited by 102
In utero and childhood exposure to parental tobacco smoke, and allergies in schoolchildren
Rahérison, C., Pénard-Morand, C., Moreau, D., Caillaud, D. M., Charpin, D., Kopfersmitt, C., Lavaud, F., Taytard, A., & Annesi‐Maesano, I. (2006) · Respiratory Medicine · doi:10.1016/j.rmed.2006.04.010 · Cited by 100
“Genetically predisposed children (defined by presence of parental atopy), when exposed to ETS were at higher risk of developing a sensitization against house dust mites, which was related to persistence of wheezing in longitudinal studies.(12,13) However, for rhinitis, smoking exposure seems not to be a risk factor by…”
BackgroundTime trends in asthma and wheeze in Swedish children 1996–2006: prevalence and risk factors by sex
Bjerg, A., Sandström, T., Lundbäck, B., & Rönmark, E. (2009) · Allergy · doi:10.1111/j.1398-9995.2009.02105.x · Cited by 99
“There are two major implications of the rise in sensitization: First, as persistence (13, 14) and severity of symptoms, lung function and bronchial hyper-responsiveness (34), are all related to allergic sensitization, the clinical picture in wheezers will likely change in our study area.”
BackgroundAirway remodelling in COPD : It's not asthma!
Jones, R. L., Noble, P. B., Elliot, J., & James, A. L. (2016) · Respirology · doi:10.1111/resp.12841 · Cited by 99
Sears, M. R. (2015) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2015.04.048 · Cited by 103
Pathophysiological Features of Asthma Develop in Parallel in House Dust Mite–Exposed Neonatal Mice
Saglani, S., Mathie, S. A., Gregory, L. G., Bell, M. J., Bush, A., & Lloyd, C. M. (2009) · American Journal of Respiratory Cell and Molecular Biology · doi:10.1165/rcmb.2008-0396oc · Cited by 98
“This abnormality increases at 3 years and reaches a maximal reduction by approximately 6 years of age, and subsequently persists through to early adulthood (3, 6).”
BackgroundPathophysiology of severe asthma: We’ve only just started
King, G. G., James, A., Harkness, L. M., & Wark, P. A. B. (2018) · Respirology · doi:10.1111/resp.13251 · Cited by 103
Wright, A. L., Stern, D. A., Kauffmann, F., & Martínez, F. D. (2006) · Pediatric Pulmonology · doi:10.1002/ppul.20373 · Cited by 102
“It is often suggested that the disparity in diagnosed asthma between boys and girls can be attributed to gender differences in the prevalence of atopy.(22) The present analysis supports this speculation by showing an excess of atopy among boys and no difference between atopic boys and atopic girls in diagnosis of asth…”
ResultPhenotypic Differences between Pediatric and Adult Asthma
Bush, A., & Menzies-Gow, A. N. (2009) · Proceedings of the American Thoracic Society · doi:10.1513/pats.200906-046dp · Cited by 100
“Sex, male:female 60:42 Age, yr; mean (SD) (range) 11.58 (2.8) (6‐19) Median height percentile (range) 50 (2‐99) Median age at first symptoms, yr (range) 1.25 (0.2‐10) Smokers at home 37/100 ( 37 ) Previous intubation (for asthma) 14/101 (14) Rhinoconjunctivitis (on treatment) 32/101 (31) Positive SPTs/RASTs to grasses…”
InfluentialInfluence of early life exposures on incidence and remission of asthma throughout life
de Marco, R., Pattaro, C., Locatelli, F., Svanes, C., & for the ECRHS Study Group (2004) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2004.01.780 · Cited by 95
Airway Remodeling in Preschool Children with Severe Recurrent Wheeze
Lezmi, G., Gosset, P., Deschildre, A., Taam, R. A., Mahut, B., Beydon, N., & Jacques de, B. L. I. C. (2015) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.201411-1958oc · Cited by 95
“We found that preschoolers with severe recurrent wheeze with atopy, a group known to be at high risk of subsequently experiencing established asthma (31, 32), had a larger ASM area than preschoolers with severe recurrent wheeze without atopy.”
BackgroundYao, X., Fredriksson, K., Yu, Z., Xu, X., Raghavachari, N., Keeran, K. J., Nugent, G. Z., Kwak, M., Amar, M. J., Remaley, A. T., et al. (2010) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.201002-0308oc · Cited by 95
“pteronyssinus), a common aeroallergen that is an environmental trigger and risk factor for the development of persistent asthma (14, 24).”
BackgroundBronchodilation and bronchoconstriction: Predictors of future lung function in childhood asthma
Tantisira, K. G., Fuhlbrigge, A. L., Tonascia, J. M., Natta, M. V., Zeiger, R. S., Strunk, R. C., Szefler, S. J., & Weiss, S. T. (2006) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2006.01.050 · Cited by 94
Bjerg, A., Hedman, L., Perzanowski, M. S., Platts‐Mills, T. A. E., Lundbäck, B., & Rönmark, E. (2007) · PEDIATRICS · doi:10.1542/peds.2006-3742 · Cited by 93
Association of perfluoroalkyl substances exposure with impaired lung function in children
Qin, X.-D., Qian, Z. (., Dharmage, S. C., Perret, J., Geiger, S. D., Rigdon, S. E., Howard, S., Zeng, X.-W., Hu, L.-W., Yang, B.-Y., et al. (2017) · Environmental Research · doi:10.1016/j.envres.2017.01.025 · Cited by 90
Ortega, H. G., Yancey, S. W., Keene, O. N., Gunsoy, N. B., Albers, F. C., & Howarth, P. H. (2018) · The Journal of Allergy and Clinical Immunology In Practice · doi:10.1016/j.jaip.2017.12.019 · Cited by 93
“Several cohort studies and crosssectional studies have suggested that, over time, some patients with asthma lose lung function at a greater rate than do subjects without asthma, and that increased loss of lung function is not seen in all patients.(2,4,5,8) A study reported by Bai et al(9) evaluated the decline in FEV1…”
BackgroundLung function and bronchodilator response in 4-year-old children with different wheezing phenotypes
Oostveen, E., Dom, S., Desager, K., Hagendorens, M. M., Backer, W. D., & Weyler, J. J. (2009) · European Respiratory Journal · doi:10.1183/09031936.00023409 · Cited by 92
The microbiome and development of allergic disease
Lynch, S. V., & Boushey, H. A. (2016) · Current Opinion in Allergy & Clinical Immunology · doi:10.1097/aci.0000000000000255 · Cited by 92
“While effective therapies for controlling asthma are available, none is curative, and the disease often persists from early childhood through adult life [6].”
Prenatal factors and the development of asthma
Kumar, R. (2008) · Current Opinion in Pediatrics · doi:10.1097/mop.0b013e3283154f26 · Cited by 92
Airway remodeling heterogeneity in asthma and its relationship to disease outcomes
Hsieh, A., Assadinia, N., & Hackett, T. (2023) · Frontiers in Physiology · doi:10.3389/fphys.2023.1113100 · Cited by 90
“Several longitudinal studies that have followed children to adulthood have shown that with increasing severity of the disease, fixed airflow obstruction is a persistent feature of the disease (Strachan et al., 1996; Phelan et al., 2002; Sears et al., 2003).”
BackgroundInfluentialChipps, B. E., Szefler, S. J., Simons, F. E. R., Haselkorn, T., Mink, D. R., Deniz, Y. M., & Lee, J. H. (2007) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2006.12.668 · Cited by 89
Belsky, D. W., Sears, M. R., Hancox, R. J., Harrington, H., Houts, R., Moffitt, T. E., Sugden, K., Williams, B. S., Poulton, R., & Caspi, A. (2013) · The Lancet Respiratory Medicine · doi:10.1016/s2213-2600(13)70101-2 · Cited by 90
Clinical predictors of remission and persistence of adult-onset asthma
Westerhof, G. A., Coumou, H., de Nijs, S. B., Weersink, E. J. M., & Bel, E. H. (2017) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2017.03.034 · Cited by 94
“678 12 FEV1, % reversibility 5 (2-9) 5 (2-9) .”
Long-term outcomes of early-onset wheeze and asthma
Grad, R., & Morgan, W. J. (2012) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2012.05.022 · Cited by 91
“As shown in Table I, at age 26 years, subjects with persistent or relapsed wheezing exhibited about a 10% reduction in FEV1 and a 5% reduction in FEV1/FVC ratio in comparison with those who had never wheezed.(10) Thus the Dunedin study reiterated the finding from the Melbourne and British studies that although much ch…”
ResultTrends in the age of diagnosis of childhood asthma
Radhakrishnan, D., Dell, S., Guttmann, A., Shariff, S. Z., Liu, K., & To, T. M. (2014) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2014.05.012 · Cited by 88
Obesity and asthma, what are the links?
Schaub, B., & von Mutius, E. (2005) · Current Opinion in Allergy and Clinical Immunology · doi:10.1097/01.all.0000162313.64308.b5 · Cited by 87
Norton, S. P., Pusic, M. V., Taha, F., Heathcote, S., & Carleton, B. (2006) · Archives of Disease in Childhood · doi:10.1136/adc.2006.097287 · Cited by 87
Clinical reviews in allergy and immunology
Leung, D. Y. M., Ledford, D. K., Wechsler, M. E., Fulkerson, P. C., Bochner, B. S., Gauvreau, G. M., Gleich, G. J., Henkel, T., Kolbeck, R., Mathur, S. K., et al. (2012) · Cited by 87
Recurrent Wheeze in Early Childhood and Asthma Among Children at Risk for Atopy
Ly, N. P., Gold, D. R., Weiss, S. T., & Celedon, J. C. (2006) · PEDIATRICS · doi:10.1542/peds.2005-2271 · Cited by 85
Metadata
- Authors
- Sears, M. R., Greene, J. M., Willan, A. R., Wiecek, E. M., Taylor, D. R., Flannery, E. M., Cowan, J. O., Herbison, G. P., Silva, P. A., & Poulton, R.
- Affiliations
- St. Joseph’s Healthcare Hamilton (CA)
- McMaster University (CA)
- University of Otago (NZ)
- Venue
- New England Journal of Medicine
- Publisher
- Massachusetts Medical Society
- Published
- 2003-10-09
- Volume
- 349
- Issue
- 15
- Pages
- 1414-1422
- ISSN
- 0028-4793 (ISSN-L)
- 1533-4406
- OpenAlex
- W2104537618
- Cited by
- 1,460
- References
- 28
- Citations by year
- 2026: 21 · 2025: 29 · 2024: 39 · 2023: 42 · 2022: 41 · 2021: 56 · 2020: 51 · 2019: 62 · 2018: 54 · 2017: 38 · 2016: 53 · 2015: 72 · 2014: 86 · 2013: 59 · 2012: 70
- FWCI
- 40.25
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- New England Journal of Medicine (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Asthma and respiratory diseases
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Occupational exposure and asthma
- Health Sciences › Medicine › Immunology and Allergy › Allergic Rhinitis and Sensitization
- Keywords
- childhood asthma, adult asthma, asthma persistence, asthma relapse, wheezing, house dust mite sensitization, airway hyperresponsiveness, sex differences, smoking, age at asthma onset, lung function, Dunedin birth cohort
- MeSH terms
- Adolescent, Adult, Asthma, Child, Child, Preschool, Environmental Exposure, Female, Humans, Longitudinal Studies, Male, New Zealand, Surveys and Questionnaires, Recurrence, Respiratory Function Tests, Respiratory Sounds, Risk Factors, Sex Factors, Smoking, Cohort Studies, Bronchial Hyperreactivity, Age of Onset, Disease Progression, Pyroglyphidae
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