Tucson children's respiratory study: 1980 to present

doi:10.1067/mai.2003.162

Journal of Allergy and Clinical Immunology

Volume 111, Issue 4, April 2003, Pages 661-675

https://doi.org/10.1067/mai.2003.162 Get rights and content

Abstract

Continuing Medical Education examination

The Tucson Children's Respiratory Study (TCRS), begun in 1980, has followed 1246 subjects from birth together with their family members to delineate the complex interrelationships between a large number of potential risk factors, acute lower respiratory tract illnesses, and chronic lung disorders later in childhood and early adult life, especially asthma. Nine hundred seventy-four (78%) of the original subjects are still being followed. Among its numerous findings, the TCRS has (1) described various wheezing disorders (transient, nonatopic, atopic) and their characteristics; (2) developed an Asthma Predictive Index; (3) delineated the respiratory and atopic outcomes for children who had respiratory syncytial virus–related wheezing illnesses in infancy; and (4) evaluated a large number of risk factors for acute respiratory tract illnesses during the first 3 years of life. Future TCRS studies will focus on (1) factors in infancy and early childhood that relate to persistent asthma and atopy; (2) role of genetic factors in persistent asthma; and (3) determinants of lung function decline in early adult life. (J Allergy Clin Immunol 2003;111:661-75.)

Section snippets

Acute LRIs

Acute LRIs are common early in life, with rates being highest in infancy. Parents of children in the TCRS were requested to take their children to the pediatrician whenever the child developed certain symptoms (deep or “wet” cough, wheeze, stridor, etc). The pediatrician recorded all relevant signs and symptoms, and nasopharyngeal/throat swabs were obtained for viral culture. The prevalence of wheezing with LRIs in the TCRS among children followed for the entire year was 32.0%, 17.3%, and 12.0%

Environmental, socioeconomic, and gender studies

One of the most important findings from the TCRS is that events occurring early in life appear to be important determinants of subsequent asthma. For example, umbilical cord blood IgE shows no relation to later asthma. However, IgE near the end of the first year of life is associated with later persistent wheezing and asthma,¹⁵ which suggests that some event in the first year of life either alters or unmasks a child's propensity to respond in an allergic fashion.

It has been hypothesized that

Genetic studies

The TCRS was initially conceived as a longitudinal study of the risk factors for and potential sequelae of respiratory diseases. At that time, in 1979, genetic epidemiology per se, and of asthma specifically, was essentially in its infancy. The implementation of the TCRS in 1980 occurred at a most opportune time to take advantage of the growth and development of genetic studies. Thus, although not initially designed as a genetic study per se, the study population (families comprising the index

Immunologic and atopic studies

The prospective, longitudinal design of the TCRS, the breadth of phenotypic data, and the more recent addition of genetic information provide opportunity to relate the maturation and regulation of the immune system to acute LRIs in early life and to the development of asthma, allergy, and asthma-related and allergy-related traits and risk factors. The immunology arm of the TCRS was originally designed to test the premise that IgE responses were critical to and likely causative in the

Physiologic studies

The prospective measurement of lung function has enabled the TCRS to characterize the impact of wheezing illness on lung development from infancy through adolescence. These measurements have also been central to the evolution of the hypothesis that asthma is a developmental disease determined by the interaction of the immune and respiratory systems in early life. Before the design of the TCRS, several epidemiologic studies had demonstrated a strong association between childhood respiratory

Chronic cough, croup, otitis media, and colic

Cough variant asthma, first described in 1972,⁵⁷ is considered to be a mild form of asthma frequently unrecognized, resulting in inadequate treatment.⁵⁸ Risk factors for recurrent cough in childhood and its relation to asthma were assessed in the TCRS. Findings suggested that recurrent cough in the absence of wheeze differs in important respects from asthma.⁵⁹ Children having recurrent cough without wheeze were not different from those without symptom for serum IgE levels, skin test response,

Wheezing syndromes and asthma

One of the most important findings of the TCRS has been the description of distinct wheezing phenotypes that occur during childhood (Table VI).¹⁵ Although there was the suspicion both from clinical practice and from clinical studies that not all children who wheezed at different times during the growing years had the same pathophysiology, it was only with further analyses of data from the TCRS that these different phenotypes were more extensively characterized. As a result, 3 main syndromes

Asthma predictive index

The above discussion has stressed the importance of developing methods to distinguish atopic wheezers from other infants and young children who wheeze in early life but are not destined to have the chronic, more persistent form of asthma-like symptoms. It is possible that, in the future, genetic markers will be used to perform this task. No such markers are yet available, however, and there was the need to test for the predictive capacity of a variety of phenotypic markers that could be used in

Future studies

During the last 22 years, the TCRS has shown new information for our understanding of the natural history of wheezing phenotypes and asthma during the first years of life. The availability of such a wealth of information regarding events occurring during this crucial period for the development of asthma and allergies will continue to provide the basis of future studies in the TCRS. Areas of focus for the next 5 to 10 years include the following:

1.
What factors occurring during childhood determine

Acknowledgements

A large number of people have been involved with this study during the past 22 years. We thank these technicians, fellows, graduate students, post-docs, statisticians, typists, et cetera, for all of their assistance. Special mention needs to be made of the study nurses, Bonnie Presbrey, Marilyn Smith Lindell, and Lydia de la Ossa, who have been involved in the study for many years. We also wish to thank Group Health Medical Associates pediatricians, who were most instrumental and helpful in

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^☆: Supported by grant nos. HL14136, HL03154, and HL 56177 from the National Heart, Lung and Blood Institute, NIH.

^☆☆: Reprints not available.

^★: This activity is available for CME credit. See page 41A for important information.

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Reviews and Feature Articles: Current Reviews of Allergy and Clinical ImmunologyTucson children's respiratory study: 1980 to present☆,☆☆,★

Abstract

Section snippets

Acute LRIs

Environmental, socioeconomic, and gender studies

Genetic studies

Immunologic and atopic studies

Physiologic studies

Chronic cough, croup, otitis media, and colic

Wheezing syndromes and asthma

Asthma predictive index

Future studies

Acknowledgements

J Pediatr

J Pediatr

Lancet

J Allergy Clin Immunol

J Allergy Clin Immunol

J Allergy Clin Immunol

J Allergy Clin Immunol

J Allergy Clin Immunol

J Allergy Clin Immunol

Lancet

The Tucson Children's Respiratory Study. I. Design and implementation of a prospective study of acute and chronic respiratory illness in children

Am J Epidemiol

Determinants of expiratory flows in the newborn infant

J Appl Physiol

Diminished lung function as a predisposing factor for wheezing respiratory illness in infants

N Engl J Med

The Tucson Children's Respiratory Study. II. Lower respiratory tract illness in the first year of life

Am J Epidemiol

Acute lower respiratory illnesses during the first three years of life: potential roles for various etiologic agents

Pediatr Infect Dis J

The etiologic and epidemiologic spectrum of bronchiolitis in pediatric practice

J Pediatr

Respiratory syncytial virus-associated lower respiratory illnesses: possible influence of other agents

Pediatr Infect Dis J

Breast feeding and lower respiratory tract illness in the first year of life

Br Med J

Risk factors for respiratory syncytial virus-associated lower respiratory illnesses in the first year of life

Am J Epidemiol

Maternal age as a risk factor for wheezing lower respiratory illnesses in the first year of life

Am J Epidemiol

Evaporative cooling and other home factors and lower respiratory tract illness during the first year of life: Group Health Medical Associates

Am J Epidemiol

Child day care, smoking by caregivers, and lower respiratory tract illness in the first 3 years of life

Pediatrics

Asthma and wheezing in the first six years of life: relation with lung function, total serum IgE levels and skin test reactivity to allergens

N Engl J Med

Association of non-wheezing lower respiratory tract illnesses in early life with persistently diminished serum IgE levels

Thorax

Exposure to siblings and day care during infancy and subsequent development of asthma and frequent wheeze

N Engl J Med

Factors influencing the relation of infant feeding to asthma and recurrent wheeze in childhood

Thorax

Weight and early puberty are risk factors for increased wheezing in females

Am J Respir Crit Care Med

Parental childhood respiratory illness and respiratory illness in their infants

Pediatr Pulmonol

Complexities of the genetics of asthma

Am Rev Respir Crit Care Med

Evidence for Mendelian inheritance of serum IgE levels in Hispanic and non-Hispanic white families

Am J Hum Genet

Segregation analysis of physician diagnosed asthma in Hispanic and non-Hispanic white families: a recessive component?

Am J Respir Crit Care Med

Differences in familial segregation of FEV1 between asthmatic and non-asthmatic families: role of a maternal component

Am J Respir Crit Care Med

Familial aggregation and segregation analysis of eosinophil levels

Am J Respir Crit Care Med

Reviews and Feature Articles: Current Reviews of Allergy and Clinical Immunology
Tucson children's respiratory study: 1980 to present☆,☆☆,★