Soup Kettle Topics: Epidemiology — Platts-Mills

Title: Searching for the Cause of the Increase in Asthma
Author: Crater, S. E.; Platts-Mills, T. A.; (Date: Dec, 1998)
Journal: Curr Opin Pediatr; V. 10; Issue: 6; Pages: 594-9

Abstract: The prevalence of asthma has increased dramatically over the last 30 years, and the clearest evidence for the increase has come from population-based studies of school-aged children and young adults. The strongest established risk factors for asthma are family history and sensitization to one or more indoor allergens. Some studies suggest that the increase in asthma has been part of an overall increase in atopic disease. The American data, however, suggest that hay fever was already common in 1960. Thus the primary increase has been in wheezing among allergic children. It seems unlikely that increases in mite, cockroach, and domestic animal allergens have been sufficient to explain the scale or the consistency of the increase in asthma prevalence. The challenge is to identify a change that could have increased inflammation of the lungs or lowered the threshold for wheezing.
Notes: Journal Article
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Author Address: Health Sciences Center, University of Virginia, Charlottesville 22908, USA.


Title: Dog and Cat Allergens and Asthma among School Children in Los Alamos, New Mexico, USA: Altitude 7,200 Feet
Author: Platts-Mills, T. A.; Sporik, R.; Ingram, J. M.; Honsinger, R.; (Date: May-Jun, 1995)
Journal: Int Arch Allergy Immunol; V. 107; Issue: 1-3; Pages: 301-3

Abstract: A survey of the Middle School in Los Alamos, N.M., USA, identified 57 children with symptoms of asthma and 54 controls. Among these children, sensitization to cat and dog allergens was very strongly associated with bronchial reactivity and symptoms. In contrast, sensitization to mites, cockroach, or grass pollen allergens was not significantly associated with symptoms or bronchial reactivity. In keeping with these results, dust from houses in Los Alamos only contained high levels of cat or dog allergens.
Notes: Journal Article
Author Address: Department of Medicine, University of Virginia, Charlottesville 22908, USA.


Title: Is There a Dose-Response Relationship between Exposure to Indoor Allergens and Symptoms of Asthma?
Author: Platts-Mills, T. A.; Sporik, R. B.; Wheatley, L. M.; Heymann, P. W.; (Date: Oct, 1995)
Journal: J Allergy Clin Immunol; V. 96; Issue: 4; Pages: 435-40

Notes: Editorial
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Title: Changing Concepts of Allergic Disease: The Attempt to Keep up with Real Changes in Lifestyles
Author: Platts-Mills, T. A.; Woodfolk, J. A.; Chapman, M. D.; Heymann, P. W.; (Date: Dec, 1996)
Journal: J Allergy Clin Immunol; V. 98; Issue: 6 Pt 3; Pages: S297-306

Abstract: In the past 100 years, changes have occurred in the outdoor environment and in houses that have contributed to the increased prevalence of hay fever and asthma. Much evidence indicates that exposure to indoor allergens is an important cause of asthma. Changes in housing that have contributed to the increased prevalence and severity of asthma include increased temperature, decreased ventilation, and permanent carpeting. In addition to these changes, geographic differences in allergens, deficiencies in cleanliness, poor health care, passive smoke, and lack of exercise also contribute to the increase in severity of asthma that has occurred. The management of asthma includes controlling exposure to indoor allergens and seeking additional treatable causes of asthma (e.g., fungal allergens). Changes will continue to occur, and physicians who treat allergic diseases should become involved in the design of houses to limit exposure. Many questions regarding allergen measurement and control remain.
Notes: Journal Article
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Author Address: University of Virginia Asthma and Allergy Disease Center, Charlottesville 22908, USA.


Title: Rise in Asthma Cases
Author: Platts-Mills, T. A.; Woodfolk, J. A.; (Date: Nov 7, 1997)
Journal: Science; V. 278; Issue: 5340; Pages: 1001

Notes: Comment
Letter
URL: http://www.sciencemag.org/cgi/content/full/278/5340/997c


Title: Indoor Versus Outdoor Allergens in Allergic Respiratory Disease
Author: Platts-Mills, T. A.; Wheatley, L. M.; Aalberse, R. C.; (Date: Dec, 1998)
Journal: Curr Opin Immunol; V. 10; Issue: 6; Pages: 634-9

Abstract: Immediate hypersensitivity to indoor or outdoor allergens is strongly associated with asthma or hay fever, respectively. Recent progress has defined the sequences, tertiary structures and enzymatic functions of many of the proteins involved; furthermore, the immune responses to these proteins have been examined; however, the mechanisms responsible for the dichotomous response remain elusive. The resolution of such mechanisms may explain the large increase in the prevalence of eosinophil-rich inflammation of the lower respiratory tract.
Notes: Journal Article
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URL: http://www.biomednet.com/article/ima608
Author Address: Asthma and Allergic Disease Center Department of Medicine University of Virginia Charlottesville Virginia VA 22908 USA.


Title: The Relevance of Allergen Exposure to the Development of Asthma in Childhood
Author: Platts-Mills, T. A.; Rakes, G.; Heymann, P. W.; (Date: Feb, 2000)
Journal: J Allergy Clin Immunol; V. 105; Issue: 2 Pt 2; Pages: S503-8

Abstract: Sensitization to 1 or more of the common indoor allergens has been consistently associated with asthma among children and young adults (odds ratios for asthma, 3-18). For dust mite and cockroach allergens, there is a dose response relationship between domestic exposure and sensitization. Given that allergen provocation can induce many of the features of asthma, the findings strongly suggest that there is a causal relationship between allergen exposure in the home and asthma. However, it remains unclear at what time the critical exposure occurs (ie, in infancy or later) and what role allergen exposure has played in the increasing prevalence and severity of asthma. Objective evidence of an immune response to allergens is generally not present until after 2 years of age. Viral infections play several different roles in asthma in childhood. In infancy, respiratory syncytial virus infection can induce bronchiolitis and set up recurrent wheezing over the next few years. However, the risk factors for this are maternal smoking and small lungs at birth, rather than allergy. By contrast, the role of rhinovirus in precipitating attacks in children and young adults is strongly associated with allergy. Thus the likely scenario is that allergen exposure over the first few years of life induces sensitization (ie, T(H2) cells and IgE antibodies). Continuing exposure can maintain inflammation in the nose and lungs. However, many other factors contribute to wheezing such that there is no simple relationship between allergen exposure and asthma. Nonetheless, it is clear that the changes that have increased asthma have acted on allergic children.
Notes: Journal Article
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URL: http://www1.mosby.com/scripts/om.dll/serve?action=searchDB&searchDBfor=art&artType=abs&id=a99979&target=
Author Address: Asthma and Allergic Diseases Center, University of Virginia 22908, USA.


Title: Determinants of Clinical Allergic Disease. The Relevance of Indoor Allergens to the Increase in Asthma
Author: Platts-Mills, T. A.; Blumenthal, K.; Perzanowski, M.; Woodfolk, J. A.; (Date: Sep, 2000)
Journal: Am J Respir Crit Care Med; V. 162; Issue: 3 Pt 2; Pages: S128-33

Notes: Journal Article
Review
Review, Tutorial
Author Address: Division of Asthma, Allergy, and Immunology, Health Sciences Center, University of Virginia, Charlottesville, Virginia, USA. tap2z@unix.mail.virginia.edu


Title: Specific and Nonspecific Obstructive Lung Disease in Childhood: Causes of Changes in the Prevalence of Asthma
Author: Platts-Mills, T. A.; Carter, M. C.; Heymann, P. W.; (Date: Aug, 2000)
Journal: Environ Health Perspect; V. 108 Suppl 4; Pages: 725-31

Abstract: Reversible airway obstruction in childhood includes two major groups of patients: those with recurrent wheezing following bronchiolitis in early childhood, and those with allergic asthma, which represents an increasingly large proportion of cases through the school years. Over the last 40 years of the 20th century, allergic asthma has increased in many countries and in relation to several different allergens. Although this increase has differed in magnitude in different countries and also in the social groups most affected, it has had several features in common. The increase generally started between 1960 and 1970, has been progressive since then, and has continued into the 1990s without a defined peak. Among children 5-18 years of age, the increase has predominantly been among allergic individuals. Theories about the causes of the increase in asthma have focused on two scenarios: a) that changes in houses combined with increased time spent indoors have increased exposure to relevant allergens, or b) that changes in diet, antibiotic use, immunizations, and the pattern of infections in childhood have led to a change in immune responsiveness such that a larger section of the population makes T(H)2, rather than T(H)1 responses including IgE antibodies to inhalant allergens. There are, however, problems with each of these theories and, in particular, none of the proposed changes can explain the progressive nature of the increase over 40 years. The fact that the change in asthma has much in common with epidemic increase in diseases such as Type II diabetes or obesity suggests that similar factors could be involved. Several lines of evidence are reviewed that suggest that the decline in physical activity of children, particularly those living in poverty in the United States, could have contributed to the rise in asthma. The hypothesis would be that the progressive loss of a lung-specific protective effect against wheezing has allowed allergic children to develop symptomatic asthma. What is clear is that current theories do not provide either an adequate explanation of the increase or a practical approach to reversing the current trend.
Notes: Journal Article
Review
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URL: http://ehpnet1.niehs.nih.gov/members/2000/suppl-4/725-731platts-mills/platts-mills-full.html
http://ehpnet1.niehs.nih.gov/docs/2000/suppl-4/725-731platts-mills/abstract.html
Author Address: Asthma and Allergic Diseases Center, University of Virginia, Charlottesville, Virginia 22908, USA. tap2z@virginia.edu


Title: Sensitisation, Asthma, and a Modified Th2 Response in Children Exposed to Cat Allergen: A Population-Based Cross-Sectional Study
Author: Platts-Mills, T.; Vaughan, J.; Squillace, S.; Woodfolk, J.; Sporik, R.; (Date: Mar 10, 2001)
Journal: Lancet; V. 357; Issue: 9258; Pages: 752-6

Abstract: BACKGROUND: Although asthma is strongly associated with immediate hypersensitivity to indoor allergens, several studies have suggested that a cat in the house can decrease the risk of asthma. We investigated the immune response to cat and mite allergens, and asthma among children with a wide range of allergen exposure. METHODS: We did a population-based cross-sectional study of children (aged 12-14 years), some of whom had symptoms of asthma and bronchial hyper-reactivity. Antibodies to mite (Der f 1) and cat (Fel d 1) allergens measured by isotype (IgG and IgG4) specific radioimmunoprecipitation assays were compared with sensitisation and allergen concentrations in house dust. FINDINGS: 226 children were recruited, 47 of whom had symptoms of asthma and bronchial hyper-reactivity. Increasing exposure to mite was associated with increased prevalence of sensitisation and IgG antibody to Der f 1. By contrast, the highest exposure to cat was associated with decreased sensitisation, but a higher prevalence of IgG antibody to Fel d 1. Thus, among children with high exposure, the odds of sensitisation to mite rather than cat was 4.0 (99% CI 1.49-10.00). Furthermore, 31 of 76 children with 23 microg Fel d 1 at home, who were not sensitised to cat allergen had >125 units of IgG antibody to Fel d 1. Antibodies to Fel d 1 of the IgG4 isotype were strongly correlated with IgG antibody in both allergic and non-allergic children (r=0.84 and r=0.66, respectively). Sensitisation to mite or cat allergens was the strongest independent risk factor for asthma (p<0.001). INTERPRETATION: Exposure to cat allergen can produce an IgG and IgG4 antibody response without sensitisation or risk of asthma. This modified T-helper-2 cell response should be regarded as a form of tolerance and may be the correct objective of immunotherapy. The results may also explain the observation that animals in the house can decrease the risk of asthma.
Notes: Journal Article
Author Address: University of Virginia Asthma and Allergic Diseases Center, University of Virginia Department of Medicine, Charlottesville, USA. tap2z@virginia.edu


Title: Serum Igg and Igg4 Antibodies to Fel D 1 among Children Exposed to 20 Microg Fel D 1 at Home: Relevance of a Nonallergic Modified Th2 Response
Author: Platts-Mills, T. A.; Vaughan, J. W.; Blumenthal, K.; Pollart Squillace, S.; Sporik, R. B.; (Date: Jan-Mar, 2001)
Journal: Int Arch Allergy Immunol; V. 124; Issue: 1-3; Pages: 126-9

Abstract: Exposure to foreign antigens is an essential element of all immune responses, including allergic sensitization. For some allergens (e.g. mite and cockroach), the prevalence of sensitization is directly correlated with exposure. However, for allergens derived from domestic animals, several studies have suggested that children with a cat in the home have a decreased risk of sensitization and asthma. We have now shown that many children exposed to greater than 20 microg of Fel d 1/g of dust at home made an IgG and IgG4 antibody response to Fel d 1 without IgE antibody. This modified Th2 response is not associated with symptoms and should be regarded as a form of immunological tolerance. The fact that the dose-response relationship between cat exposure and sensitization is bell shaped, while that for mite exposure and sensitization is linear, is highly relevant to understanding the role of allergens in the increase in allergic disease. Copyright 2001 S. Karger AG, Basel
Notes: Journal Article
URL: http://www.online.karger.com/library/karger/renderer/dataset.exe?jcode=IAA&action=render&rendertype=fulltext&uid=IAA.iaa24126
http://www.karger.com/journals/iaa/iaa_jh.htm
Author Address: Asthma and Allergic Diseases Center, University Health Systems, Charlottesville, VA 22908-1355, USA. nkm8t@virginia.edu


Title: Incidence and Remission of Asthma in Schoolchildren: Report from the Obstructive Lung Disease in Northern Sweden Studies
Author: Ronmark, E.; Jonsson, E.; Platts-Mills, T.; Lundback, B.; (Date: Mar, 2001)
Journal: Pediatrics; V. 107; Issue: 3; Pages: E37

Abstract: OBJECTIVE: An increasing prevalence of asthma has been reported worldwide as well as in Sweden. In 1996, the prevalence of asthma and type 1 allergy was investigated in a cohort of 3525 children 7 and 8 years old in 3 areas of northern Sweden. The aim of the present study was to estimate the incidence of asthma and to identify risk factors for incident cases over 1 year. METHODS: The study started with a parental questionnaire, the International Study of Asthma and Allergies in Childhood questionnaire with additional questions, a skin prick test, and a validation study. The cohort was followed up after 1 year with the same questions. The response rate to the questionnaire was 97% in 1996, and 3339 children (97%) participated both in 1996 and 1997. RESULTS: The incidence of physician-diagnosed asthma was 0.9/100/year; of wheezing, 3.8/100/year; and of new frequent or daily users of asthma medicines, 1.1/100/year. There was no difference by sex. The risk factor pattern based on incident cases of asthma was different from that based on prevalent cases. Significant risk factors for incident asthma were a positive skin test (odds ratio [OR]: 9.3; 95% confidence interval [CI]: 3.8-22.7); low birth weight (OR: 7.4; 95% CI: 2.2-24.5); and family history of asthma (OR: 2.6; 95% CI: 1.1-6.3). Having or having had pets at home was associated with a decreased risk for asthma and wheezing based on prevalent cases, although it was associated with an increased risk for incidence of wheezing (OR: 2.9; 95% CI: 1.3-6.2). Remission of asthma, which was reported by 10% of the children with current asthma during 1 year, was associated with a negative skin test. CONCLUSION: The incidence of asthma at the age of 8 years was high, but remission was also common. Important risk factors for the development of asthma at this age were type 1 allergy, low birth weight, and family history of asthma. Furthermore, the results suggest that in a region where sensitivity to domestic animals is a strong risk factor for asthma, the presence of pets in the home may have different effects in early childhood compared with later in childhood.
Notes: Journal Article
Author Address: OLIN Study Group, Department of Medicine, Sunderby Central Hospital of Norrbotten, Lulea, Sweden. eva.ronmark@nll.se

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