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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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“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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“Moreover, the two longest ongoing longitudinal studies of asthma, conducted in Australia (3) and New Zealand (4), have shown that deficits in lung function are already present by age 9–10 yr among children with asthma, and that these deficits persist up to mid-adulthood.”
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Bacharier, L. B., Boner, A. L., Carlsen, K. ‐., Eigenmann, P., Frischer, T., Götz, M., Helms, P. J. B., Hunt, J., Liu, A., Papadopoulos, N. G., et al. (2007) · Allergy · doi:10.1111/j.1398-9995.2007.01586.x · Cited by 637
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“Moreover, longitudinal studies that have followed children with asthma to adulthood have shown tracking of abnormal lung function, specifically in those with severe symptoms in childhood (34, 35 ).Althoughclinicallyallsubjectsrecruitedwerethosewith severe, recurrent wheeze, to increase our confidence in identifying a…”
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“These findings confirm and extend to the first years of life the observations made in the Dunedin (26) and in the Melbourne (27) cohorts, which showed strong correlations between asthma symptoms, lung function and bronchial responsiveness assessed during the school years and chronic asthma up to the fifth decade of li…”
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“Asthma may be associated with fixed airflow obstruction (1, 2), which may result from airway remodeling from early life ( 3 ) and/or an increased rate of decline in lung function in patients with asthma (4‐7).”
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“ABIS (Sweden) 6,829 1997-1998 3,576 (537) 40 (37-42) ALSPAC (United Kingdom) 12,485 1991-1992 3,403 (554) 40 (36-42) BILD (Switzerland) 432 1999 3,382 (441) 39 (37-41) CONER (Italy) 389 2004-2005 3,321 (448) 39 (37-41) COPSAC (Denmark) 384 1998-2001 3,513 (524) 40 (37-42) CZECH (Czech Republic) 1,830 2001-2004 3,331 (…”
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Airway Smooth Muscle Hypertrophy and Hyperplasia in Asthma
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Thomas, D., McDonald, V. M., Pavord, I. D., & Gibson, P. G. (2022) · European Respiratory Journal · doi:10.1183/13993003.02583-2021 · Cited by 305
“The majority of these studies included a mix of childhood and adult asthma, which most likely caused an overestimation of the remission rate since the rate of remission in childhood asthma is much higher than that in adult asthma [35 – 37].”
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Devereux, G. S., Turner, S. W., Craig, L. C. A., McNeill, G., Martindale, S., Harbour, P. J., Helms, P. J. B., & Seaton, A. (2006) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.200512-1946oc · Cited by 269
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Hancox, R. J., Milne, B. J., Poulton, R., Taylor, D. R., Greene, J. M., McLachlan, C. R., Cowan, J. O., Flannery, E. M., Herbison, P., & Sears, M. R. (2004) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.200405-623oc · Cited by 247
“This information was updated at subsequent assessments ( 32 ).”
BackgroundDusser, D. J., Montani, D., Chanez, P., Jacques de, B. L. I. C., Delacourt, C., Deschildre, A., Devillier, P., Didier, A. P., Leroyer, C., Marguet, C., et al. (2007) · Allergy · doi:10.1111/j.1398-9995.2007.01394.x · Cited by 253
“The most recent cohort study (4), conducted in New Zealand, found that atopic allergy, persistent bronchial hyperreactivity up to 21 years of age, smoking, and being female were associated with persistence and recurrence of asthma.”
BackgroundPersistence of Asthma Symptoms during Adolescence
Guerra, S., Wright, A. L., Morgan, W. J., Sherrill, D. L., Holberg, C. J., & Martínez, F. D. (2004) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.200309-1224oc · Cited by 248
“For example, in a recent report from Dunedin, New Zealand, where mites and cat dander are the strongest asthma-related allergens, skin test response at age 13 years to house-dust-mite and cat allergens, but not Alternaria, predicted persistent wheezing from childhood up to year 26 (1).”
ResultDiagnosis, management, and prognosis of preschool wheeze
Ducharme, F. M., Tse, S. M., & Chauhan, B. F. (2014) · The Lancet · doi:10.1016/s0140-6736(14)60615-2 · Cited by 245
The Origins of Asthma and Chronic Obstructive Pulmonary Disease in Early Life
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“Similarly to what was found in the Melbourne cohort, the lung function deficits of these two groups of children, relative to those with milder wheezing or without wheezing, remained unchanged between 9 and 26 years (20).”
BackgroundResultAsthma transition from childhood into adulthood
Fuchs, O., Bahmer, T., Rabe, K. F., & von Mutius, E. (2016) · The Lancet Respiratory Medicine · doi:10.1016/s2213-2600(16)30187-4 · Cited by 247
Outcomes of childhood asthma to the age of 50 years
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Asthma phenotypes in childhood: lessons from an epidemiological approach
Stein, R. T., & Martínez, F. D. (2004) · Paediatric Respiratory Reviews · doi:10.1016/j.prrv.2004.01.007 · Cited by 232
“A recent study by Sears et al.(7) evaluated a cohort from Dunedin, New Zealand, followed from 9 to 26 years of age with questionnaires, pulmonary function tests, bronchial challenge testing and allergy testing.”
BackgroundMethodInfluentialPeat, J. K., Mihrshahi, S., Kemp, A. S., Marks, G. B., Tovey, E. R., Webb, K., Mellis, C. M., & Leeder, S. (2004) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2004.06.057 · Cited by 221
Management of severe asthma in children
Bush, A., & Saglani, S. (2010) · The Lancet · doi:10.1016/s0140-6736(10)61054-9 · Cited by 220
Progression of Asthma Measured by Lung Function in the Childhood Asthma Management Program
Covar, R. A., Spahn, J. D., Murphy, J. R., & Szefler, S. J. (2004) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.200308-1174oc · Cited by 217
“In their follow-up study just recently published by Sears and colleagues, males with persistent asthma had a lower FEV1/FVC ratio at age 26 years compared with females ( 20 ).”
BackgroundInfluentialInvestigating the early-life determinants of illness in Africa: the Drakenstein Child Health Study
Zar, H. J., Barnett, W., Myer, L., Stein, D. J., & Nicol, M. P. (2014) · Thorax · doi:10.1136/thoraxjnl-2014-206242 · Cited by 217
Regular Smoking and Asthma Incidence in Adolescents
Gilliland, F. D., Islam, T. S., Berhane, K. T., Gauderman, W. J., McConnell, R., Avol, E. L., & Peters, J. M. (2006) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.200605-722oc · Cited by 212
“Smoking also affects the natural history of asthma, as adolescents with a past history of asthma have increased risk for recurrent asthma symptoms after initiating smoking (22, 23).”
BackgroundAsthma-COPD overlap 2015: now we are six
Gibson, P. G., & McDonald, V. M. (2015) · Thorax · doi:10.1136/thoraxjnl-2014-206740 · Cited by 215
“69 Addressing these issues in childhood asthma may offer opportunities for prevention of asthma – COPD overlap (box 1).”
Allergic rhinitis is associated with poor asthma control in children with asthma
de Groot, E. P., Nijkamp, A., Duiverman, E. J., & Brand, P. L. P. (2012) · Thorax · doi:10.1136/thoraxjnl-2011-201168 · Cited by 210
Guilbert, T. W., Bacharier, L. B., & Fitzpatrick, A. M. (2014) · The Journal of Allergy and Clinical Immunology In Practice · doi:10.1016/j.jaip.2014.06.022 · Cited by 216
A new look at the pathogenesis of asthma
Holgate, S. T., Arshad, H. S., Roberts, G. C., Howarth, P. H., Thurner, P. J., & Davies, D. E. (2009) · Clinical Science · doi:10.1042/cs20090474 · Cited by 215
Research needs in allergy: an EAACI position paper, in collaboration with EFA
Papadopoulos, N. G., Agache, I. O., Bavbek, S., Bilò, M. B., Braido, F., Cardona, V., Čustović, A., de Monchy, J., Demoly, P. M., Eigenmann, P., et al. (2012) · Clinical and Translational Allergy · doi:10.1186/2045-7022-2-21 · Cited by 210
“An additional significant unresolved problem in the management of asthma is the failure to prevent and/or promptly treat asthma exacerbations, which are associated with significant morbidity, risk of death and high treatment cost [54] and whose prevention in children may reduce the risk of subsequent adulthood asthma…”
BackgroundEpithelial–mesenchymal transition in the pathophysiology of airway remodelling in asthma
Hackett, T. (2012) · Current Opinion in Allergy and Clinical Immunology · doi:10.1097/aci.0b013e32834ec6eb · Cited by 199
Age-specific incidence of allergic and non-allergic asthma
Pakkasela, J., Ilmarinen, P., Honkamäki, J., Tuomisto, L. E., Andersén, H., Piirilä, P. L., Hisinger‐Mölkänen, H., Sovijärvi, A. R. A., Bäckman, H., Lundbäck, B., et al. (2020) · BMC Pulmonary Medicine · doi:10.1186/s12890-019-1040-2 · Cited by 215
Functional lung imaging using hyperpolarized gas MRI
Fain, S. B., Korosec, F. R., Holmes, J. H., O’Halloran, R., Sorkness, R. L., & Grist, T. M. (2007) · Journal of Magnetic Resonance Imaging · doi:10.1002/jmri.20876 · Cited by 198
“The variable sensitivity of individual patients to lung diseases (4) and the further development of regional measures of lung function may reveal the underlying mechanisms leading to the development of these diseases.”
BackgroundBallardini, N., Kull, I., Lind, T., Hallner, E., Almqvist, C., Östblom, E., Melén, E., Pershagen, G., Lilja, G., Bergström, A., et al. (2012) · Allergy · doi:10.1111/j.1398-9995.2012.02786.x · Cited by 195
Predicting the atopic march: Results from the Canadian Healthy Infant Longitudinal Development Study
Tran, M. M., Lefebvre, D. L., Dharma, C., Dai, D., Lou, W. Y. W., Subbarao, P., Becker, A. B., Mandhane, P. J., Turvey, S. E., Sears, M. R., et al. (2017) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2017.08.024 · Cited by 198
Prenatal and postnatal bisphenol A exposure and asthma development among inner-city children
Donohue, K. M., Miller, R. L., Perzanowski, M. S., Just, A. C., Hoepner, L., Arunajadai, S. G., Canfield, S. M., Resnick, D. J., Calafat, A. M., Perera, F. P., et al. (2013) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2012.12.1573 · Cited by 198
Bergeron, C., Al-Ramli, W., & Hamid, Q. A. (2009) · Proceedings of the American Thoracic Society · doi:10.1513/pats.200808-089rm · Cited by 196
Sex differences in repetitive stereotyped behaviors in autism: Implications for genetic liability
Szatmari, P., Liu, X., Goldberg, J., Zwaigenbaum, L., Paterson, A. D., Woodbury‐Smith, M., Georgiades, S., Duku, E., & Thompson, A. (2012) · American Journal of Medical Genetics Part B: Neuropsychiatric Genetics · doi:10.1002/ajmg.b.31238 · Cited by 187
“more common in males but more likely to persist in females [Sears et al., 2003].”
BackgroundStructural changes in the airways in asthma: observations and consequences
Bai, T. R., & Knight, D. A. (2005) · Clinical Science · doi:10.1042/cs20040342 · Cited by 182
Trajectories of lung function during childhood
Belgrave, D. C. M., Buchan, I., Bishop, C., Lowe, L., Simpson, A., & Custovic, A. (2014) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.201309-1700oc · Cited by 184
Monitoring and Reducing Exposure of Infants to Pollutants in House Dust
Roberts, J. W., Wallace, L. A., Camann, D., Dickey, P., Gilbert, S. G., Lewis, R. G., & Takaro, T. K. (2009) · Reviews of Environmental Contamination and Toxicology · doi:10.1007/978-1-4419-0032-6_1 · Cited by 186
Age-Related Changes in Eosinophil Function in Human Subjects
Mathur, S. K., Schwantes, E. A., Jarjour, N. N., & Busse, W. W. (2008) · CHEST Journal · doi:10.1378/chest.07-2114 · Cited by 179
Airway smooth muscle thickness in asthma is related to severity but not duration of asthma
James, A. L., Bai, T. R., Mauad, T., Abramson, M. J., Dolhnikoff, M., McKay, K., Maxwell, P. S., Elliot, J., & Green, F. H. Y. (2009) · European Respiratory Journal · doi:10.1183/09031936.00181608 · Cited by 178
Effects of cannabis on lung function: a population-based cohort study
Hancox, R. J., Poulton, R., Ely, M., Welch, D., Taylor, D. R., McLachlan, C. R., Greene, J., Moffitt, T. E., Caspi, A., & Sears, M. R. (2009) · European Respiratory Journal · doi:10.1183/09031936.00065009 · Cited by 177
“Questions were asked about current and prior asthma and asthma symptoms using previously developed questionnaires [22].”
MethodAllergic multimorbidity of asthma, rhinitis and eczema over 20 years in the German birth cohort MAS
Gough, H., Grabenhenrich, L., Reich, A., Eckers, N., Nitsche, O., Schramm, D., Beschorner, J., Hoffmann, U., Schuster, A., Bauer, C., et al. (2015) · Pediatric Allergy and Immunology · doi:10.1111/pai.12410 · Cited by 180
The asthma–COPD overlap syndrome: towards a revised taxonomy of chronic airways diseases?
Bateman, E. D., Reddel, H. K., van Zyl-Smit, R. N., & Agustí, A. G. N. (2015) · The Lancet Respiratory Medicine · doi:10.1016/s2213-2600(15)00254-4 · Cited by 173
“…judgment; for example, Asthma Overlap COPD Source Childhood onset atopic asthma Usually present Compatible with diagnosis Rarely present Sears et al (2003)30 Atopy, allergies, and family history 100% 64% 25% Gibson et al (2009)31 Occupational asthma Compatible with diagnosis…”
Jaddoe, V. W. V., Felix, J. F., Andersen, A. N., Charles, M.-A. A., Chatzi, L., Corpeleijn, E., Donner, N. C., Elhakeem, A., Eriksson, J. G., Foong, R. E., et al. (2020) · European Journal of Epidemiology · doi:10.1007/s10654-020-00662-z · Cited by 171
Childhood factors associated with asthma remission after 30 year follow up
Vonk, J. M. (2004) · Thorax · doi:10.1136/thx.2003.016246 · Cited by 171
Fetal and infant origins of asthma
Duijts, L. (2012) · European Journal of Epidemiology · doi:10.1007/s10654-012-9657-y · Cited by 169
“Long term follow up studies in different populations have shown that impaired respiratory health or lung function in early childhood is associated with asthma and other respiratory diseases in later life [42–48].”
BackgroundMechanisms of airway hyper‐responsiveness in asthma: the past, present and yet to come
Chapman, D. G., & Irvin, C. G. (2015) · Clinical & Experimental Allergy · doi:10.1111/cea.12506 · Cited by 180
Long-term studies of the natural history of asthma in childhood
Bisgaard, H. F., & Bønnelykke, K. (2010) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2010.07.011 · Cited by 179
“The Dunedin Multidisciplinary Health and Development Study assessed history of asthma-like symptoms from age 9 to 26 years at 2- to 5-year intervals in 59% of the original cohort of 1,037 unselected children and reported persistence in 27% of the population followed from age 9 to 26 years.(13) Female sex, smoking, and…”
BackgroundResultInfluentialAssessing Future Need for Acute Care in Adult Asthmatics
Osborne, M. L., Pedula, K. L., O’Hollaren, M. T., Ettinger, K. M., Stibolt, T. B., Buist, A. S., & Vollmer, W. M. (2007) · CHEST Journal · doi:10.1378/chest.05-3084 · Cited by 167
Hancox, R. J., Pavord, I. D., & Sears, M. R. (2018) · European Respiratory Journal · doi:10.1183/13993003.02536-2017 · Cited by 164
“Wheeze included all episodes of reported wheeze in the previous year, excluding only one or two episodes lasting less than one hour.[27] Inhaled corticosteroid use was recorded at each age.”
BackgroundProblematic severe asthma in children, not one problem but many: a GA 2 LEN initiative
Hedlin, G., Bush, A., Carlsen, K. C. L., Wennergren, G., Benedictis, F. M. D., Melén, E., Paton, J. Y., Wilson, N. M., & Carlsen, K. H. (2010) · European Respiratory Journal · doi:10.1183/09031936.00104809 · Cited by 162
Mild to moderate asthma affects lung growth in children and adolescents
Strunk, R. C., Weiss, S. T., Yates, K. P., Tonascia, J., Zeiger, R. S., & Szefler, S. J. (2006) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2006.07.053 · Cited by 158
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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