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Biomedical subjects

Thomas A E Platts-Mills

Publications and source records attributed to Thomas A E Platts-Mills.

At least 19 recordsLinked to original sources
PubMed2006

Predictors of cord blood IgE levels in children at risk for asthma and atopy.

BACKGROUND: Increased cord blood IgE levels, in conjunction with a family history of atopy, are associated with the development of allergic diseases in children. However, little is known about predictors of cord blood IgE levels. OBJECTIVE: Our objective was to identify predictors of cord blood IgE levels among infants at increased risk of atopy. METHODS: Cord blood IgE levels were measured in 874 infants who were screened for participation in a birth cohort. Questionnaires were administered after birth of the infant, and maternal and cord blood was obtained for measurement of IgE levels. Logistic and tobit regression models were used to study the association between perinatal factors and cord blood IgE levels. RESULTS: In multivariable models infant male sex, increased maternal total IgE level, maternal allergen sensitization, Hispanic ethnicity, and residence in low-income areas were associated with detectable or increased cord blood IgE levels, whereas increasing maternal age was associated with undetectable or lower cord blood IgE levels. Although maternal smoking during pregnancy was positively associated with cord blood IgE levels in univariable models, the effect did not persist after adjusting for potential confounders. CONCLUSION: Maternal allergen sensitization, markers of socioeconomic disadvantage and race/ethnicity, maternal age, and infant sex might influence fetal production of IgE. We found no association of maternal parity, mode of delivery, gestational age, or season of birth with cord blood IgE levels. CLINICAL IMPLICATIONS: The identification of these definable familial and environmental factors that predict cord blood IgE levels might help in the early detection of infants at risk for atopic disorders.

Adolescent↗
PubMed2006

Paediatric asthma and obesity.

None of the explanations proposed for the increase in paediatric asthma have been adequate. It is becoming apparent that the cause of the increase in asthma must be multi-factorial. Increasing attention has been focused on the role of lifestyle in the development of asthma. Lifestyle changes that have occurred in children are those in diet and decreased physical activity, with obesity being the product of these changes. The increase in asthma, obesity and a sedentary lifestyle have occurred together. However, a temporal relationship between asthma, obesity and decreased physical activity has not been determined in the paediatric literature. Limited data suggest that decreased physical activity could be playing a role in the aetiology of asthma independent of obesity. Furthermore, there has been substantial research on the benefits of exercise programmes for paediatric patients with asthma. Longitudinal trials monitoring physical activity, obesity and the development of asthma are needed.

Asthma↗
PubMed2006

Diagnosis and treatment of atopic dermatitis in children and adults: European Academy of Allergology and Clinical Immunology/American Academy of Allergy, Asthma and Immunology/PRACTALL Consensus Report.

There are remarkable differences in the diagnostic and therapeutic management of atopic dermatitis practiced by dermatologists and pediatricians in different countries. Therefore, the European Academy of Allergy and Clinical Immunology and the American Academy of Allergy, Asthma and Immunology nominated expert teams who were given the task of finding a consensus to serve as a guideline for clinical practice in Europe as well as in North America. The consensus report is part of the PRACTALL initiative, which is endorsed by both academies.

Adult↗
PubMed2006

Environmental factors influencing allergy and asthma.

Despite the strong and consistent association between immediate hypersensitivity, allergy, asthma and exposure, there is still controversy about the role inhaled allergen plays and about the timing of events related to sensitization. However, IgE antibodies are essential for the asthmatic response and the symptoms are much more closely associated with IgE antibodies to perennial than to seasonal allergens. Although there have been many changes in our environment, none of these alone explains the consistency or the scale of the rise in asthma over the 40 years between 1960 and 2000.

Animals↗
PubMed2005

Allergens.

Exposure to allergens is a trigger for symptoms in sensitized individuals with asthma. This is especially true for allergens primarily found indoors but can be true for outdoor allergens with sufficiently high exposure. The role of allergens in attacks can be subtle in that they provide the underlying inflammation necessary for other nonspecific agents to have an effect.

Air Pollutants↗
PubMed2005

Cat and dust mite sensitivity and tolerance in relation to wheezing among children raised with high exposure to both allergens.

BACKGROUND: Recent evidence has suggested that high exposure to cat allergens is associated with decreased prevalence of sensitization to cat and, in some studies, decreased asthma. OBJECTIVE: Our objective was to study antibodies to cat and mite allergens and their relationship to wheezing in a country with high exposure to both allergens. METHODS: Sera from 112 wheezing and 112 control children aged 10 to 11 years in a nested case-control study in New Zealand were assayed for specific IgE antibody, as well as IgG antibody and IgG4 antibody, to Der p 1 and Fel d 1. RESULTS: IgE antibody to both mite (99/224) and cat (41/224) were strongly associated with wheezing (odds ratios, 5.2 and 6.5, respectively). Children who had ever lived with a cat were less likely to have IgE antibody to cat (20/141 vs 21/83, P < .04); however, cat ownership had no effect on IgE antibody to mite (67/141 vs 32/83, P = .23). Among sensitized children, cat ownership was associated with a lower prevalence of IgE antibody to cat (28% vs 66%, P < .001), and this analysis remained significant after exclusion of children whose families had chosen not to own a cat. Among sensitized subjects, the mean titer of IgE antibody to cat (1.7 IU/mL) was 10-fold lower than for mite (22.1 IU/mL). A cat in the home had no significant effect on endotoxin or mite allergen in house dust, whereas cat allergen was much higher (40.8 vs 3.3 microg/g). CONCLUSION: The response to these 2 allergens was distinct on the basis of the prevalence of sensitization, the titer of IgE antibody, and the effect of cat ownership. The results suggest that induction of tolerance to cat allergen is an allergen-specific phenomenon that cannot be attributed to endotoxin or family choice. The strength of the IgE antibody response to dust mite in humid climates could contribute to the increased prevalence and severity of asthma.

Allergens↗
PubMed2005

Quantitative measurement of IgE antibodies to purified allergens using streptavidin linked to a high-capacity solid phase.

BACKGROUND: Commercially available assays for IgE antibody provide results in international units per milliliter for many allergen extracts, but this is not easily achieved with purified or novel allergens. OBJECTIVE: To develop assays for IgE antibody suitable for purified or novel allergens by using a commercially available immunosorbent. METHODS: Streptavidin coupled to a high-capacity immunosorbent (CAP) was used to bind biotinylated purified allergens from mite (Der p 1 and Der p 2), cat (Fel d 1), and dog (Can f 1). Assays for IgE antibody to these allergens were performed on sera from children (asthma and control) as well as adults with atopic dermatitis. RESULTS: The results were validated by serial dilution of sera with high and low levels of IgE antibody and were quantitated in international units per milliliter by using a standard curve. Values for IgE antibody to Der p 1, Der p 2, and Fel d 1 correlated with values obtained with the allergen extracts (r2 = 0.80, 0.84, and 0.95, respectively; P < .001 in each case). Furthermore, the values for IgE antibody in sera from children with high exposure to mite and cat allergens demonstrated 10-fold higher levels of IgE antibody to Der p 1 and Der p 2 than to Fel d 1 (P < .001). CONCLUSION: The streptavidin immunosorbent technique provides a new method for quantifying IgE antibody to purified proteins. The results provide evidence about the high quantities of IgE antibody to purified inhalant allergens in patients with atopic dermatitis. In addition, the results demonstrate major differences in IgE antibodies specific for mite and cat allergens among children with high exposure to both allergens.

Adult↗
PubMed2005

Variation in total and specific IgE: effects of ethnicity and socioeconomic status.

BACKGROUND: Asthma is common in minority and disadvantaged populations, whereas atopic disorders other than asthma appear to be less prevalent. It is unclear whether the same holds true for objective markers of sensitization. OBJECTIVE: To determine the association of asthma, atopic disorders, and specific sensitization with race and socioeconomic factors. METHODS: We analyzed total and specific IgE among 882 women (577 white, 169 black, and 136 Hispanic) who delivered a child at a large tertiary hospital in Boston, Mass, and who were screened for participation in a family and birth cohort study. Race/ethnicity and other characteristics were obtained from screening questionnaires. Addresses were geocoded, and 3 census-based geographic area socioeconomic variables were derived from block group information from the 1990 US Census. RESULTS: Black and Hispanic women were more likely to come from areas with low socioeconomic indicators and were more likely to have asthma than white women. However, these women were less likely to have hay fever and eczema than their white counterparts. Compared with white women, black women had higher mean total IgE levels; had greater proportions of sensitization to indoor, outdoor, and fungal allergens; and were more than twice as likely to be sensitized to > or =3 aeroallergens. CONCLUSION: The racial/ethnic disparities in atopic disorders may represent either underdiagnosis or underreporting and suggest that allergy testing may be underused in some populations. Differences in total IgE levels and specific allergen sensitization are likely a result of the complex interplay between exposures associated with socioeconomic disadvantage.

Adult↗
PubMed2005

Specific IgE and IgG antibody-binding patterns to recombinant cockroach allergens.

BACKGROUND: The specificity of serum antibody responses to different cockroach allergens has not been studied. OBJECTIVE: We sought to quantitate serum IgE and IgG antibodies to a panel of purified cockroach allergens among cockroach-sensitized subjects. METHODS: IgE antibodies to recombinant cockroach allergens (rBla g 1, rBla g 2, rBla g 4, rBla g 5, and rPer a 7) were measured in sera containing IgE antibodies to Blattella germanica extract (n = 118) by using a streptavidin CAP assay and a multiplex flow cytometric assay. Specific IgG antibodies were determined by using radioimmunoprecipitation techniques. RESULTS: Specific IgE antibodies measured by means of CAP assay and multiplex assay were strongly correlated ( r = 0.8, P < .001). The sum of IgE antibodies (in international units per milliliter) against all 5 allergens equated to IgE antibodies to cockroach extract. Although the prevalence of IgE antibodies was highest for rBla g 2 (54.4%) and rBla g 5 (37.4%), patterns of IgE antibody binding were unique to each subject. Surprisingly, only 16% of cockroach-sensitized subjects with IgE antibodies to house dust mite exhibited IgE antibody binding to cockroach tropomyosin (rPer a 7). Specific IgE antibodies were associated with increased IgG antibody levels, although detection of IgG in the absence of IgE was not uncommon. CONCLUSION: The techniques described offer a new approach for defining the hierarchy of purified allergens. IgE antibodies directed against 5 allergens constitute the majority of the IgE antibody repertoire for cockroach. Such distinct patterns of IgE-IgG responsiveness to different cockroach allergens highlight the complexity of B-cell responses to environmental allergens.

Adolescent↗
PubMed2005

Physical activity and exercise in asthma: relevance to etiology and treatment.

There is little doubt that the cause of the increased prevalence and severity of asthma is multifactorial. Although the factors of allergen exposure and hygiene are almost certainly necessary for its development, there is a growing body of literature that implicates lifestyle change, specifically decreased physical activity, as a contributor to the increase in asthma prevalence and severity. Several literature reviews of exercise conditioning in patients with asthma have been published. These reviews and recent controlled trials emphasize that although many of the studies of exercise conditioning in asthmatic patients involved different methods and outcome measures, the overwhelming majority of studies demonstrated the capacity for asthmatic subjects to exercise safely and significantly improve their cardiovascular fitness and quality of life. There are several proposed pathophysiologic mechanisms responsible for the effects of decreased activity on the lung function of patients with asthma. A prescription for exercise has been endorsed for all asthmatic subjects by the American College of Sports Medicine and the American Thoracic Society. The allergy community has placed emphasis on medical therapy and allergen avoidance; in addition, exercise [correction] has not been formally incorporated into the National Asthma Education and Prevention Program guidelines. It is our belief that an exercise prescription should be part of the treatment for all cases of asthma. The real question is whether prolonged physical activity and, in particular, outdoor play of children plays a role in prophylaxis against persistent wheezing. If so, the decrease in physical activity might have played a major role in recent increases in asthma prevalence and severity.

Adolescent↗
PubMed2005

Airborne endotoxin in homes with domestic animals: implications for cat-specific tolerance.

BACKGROUND: Although endotoxin is known to increase symptoms in allergic individuals, early exposure might decrease sensitization. Similarly, the presence of an animal in the home has been associated with decreased sensitization to animal allergens. It has been suggested that the effect of animals could be explained by increased endotoxin exposure. OBJECTIVE: We sought to investigate the effects of domestic animals on airborne endotoxin. METHODS: By using a silent particle collector, air was sampled over 24 hours in homes with or without animals. The total volume sampled was approximately 1000 m3, which provides quantities of allergen and endotoxin that can easily be measured with standard assays. RESULTS: The quantity of endotoxin ranged from less than 0.5 to more than 500 pg/m3, whereas cat and dog allergen ranged from less than 0.002 to more than 5 ng/m3. Overall, the quantity of airborne endotoxin was not higher in homes with at least one animal. However, airborne endotoxin levels were significantly lower in homes with a cat compared with homes with a dog (P < .001). In keeping with this, there was a significant correlation between airborne Can f 1 and airborne endotoxin (r = 0.50, P < .01) but not between endotoxin and Fel d 1 (r = 0.17, P = .27). CONCLUSIONS: The results demonstrate that endotoxin is present in the air of almost all homes. Although higher levels were seen in homes with a dog, similar levels might be present in homes with no animals. The results argue that the effects of cat ownership cannot be explained by increased exposure to endotoxin.

Air Pollutants↗
PubMed2005

Spontaneous sigh rates during sedentary activity: watching television vs reading.

BACKGROUND: Spontaneous sighs are thought to play an important role in preventing atelectasis and in regulating airway tone. Recent studies have provided a mechanism by which expansion of the lungs could cause relaxation of smooth muscle. OBJECTIVE: To investigate breathing patterns during 2 forms of sedentary behavior: reading and watching television. METHODS: Breathing patterns were monitored for 1 to 2 hours to document respiratory rates and sigh rates. Each participant was monitored while reading and while watching a movie on videotape. During the first experiment (17 controls), metabolic rates were also measured. In the second experiment (18 controls and 9 patients with mild-to-moderate asthma), only breathing patterns were monitored. RESULTS: There were no significant differences in respiratory or metabolic rates between the 2 activities. In contrast, in the first experiment, 13 of 17 controls had lower sigh rates while watching a videotape than while reading (P < .01). In the second experiment, the sigh rate was significantly lower overall while watching a videotape (mean, 13.7 sighs per hour; range, 1.8-26.0 sighs per hour) than while reading (mean, 19.3 sighs per hour; range, 7.7-30.0 sighs per hour) (P < .001). A similar decrease was observed in patients with asthma (P < .01). CONCLUSIONS: Given that many children and adults watch television for 5 or more hours per day, breathing patterns during this time may be relevant to lung function. Our results demonstrate that prolonged periods of watching a videotape are associated with lower sigh rates than while reading. Further research is needed to determine whether these changes are relevant to increased bronchial reactivity.

Adolescent↗
PubMed2005

Role of viral infections, atopy and antiviral immunity in the etiology of wheezing exacerbations among children and young adults.

BACKGROUND: At least 101 serotypes of rhinoviruses have been identified. Rhinoviruses have often been associated with trivial upper respiratory infections but more recent evidence suggests that they play a significant role in the pathogenesis of asthma exacerbations. METHODS: The impact of rhinoviruses as a cause of respiratory morbidity in infancy and the role of rhinoviruses in causing asthma exacerbations in the children and adult population is discussed. Past and current experimental and epidemiologic evidence was assessed to suggest a causal role rather than just an association. Mechanism of susceptibility to virus infection in asthmatics were discussed, as were data indicating important interactions between allergic sensitization and rhinovirus infections in risk of asthma exacerbations. RESULTS: Asthmatic individuals have increased severity and duration of lower airway symptoms and greater declines in lung function upon infection with rhinovirus, suggesting greater susceptibility to rhinovirus infection because of impaired antiviral immunity. Early virus-induced apoptosis, which aborts virus replication, was impaired in asthmatics. Treating allergic airway inflammation may reduce the frequency and severity of symptoms triggered by rhinoviruses. CONCLUSIONS: The evidence in children and young adults suggests that atopy and allergic inflammation in the airways may be critical determinants of an adverse response to rhinovirus. Increased awareness of the spectrum of age groups that are affected by rhinoviruses is needed to encourage the development of new treatments and strategies that may be helpful in reducing the frequency and severity of symptoms triggered by rhinoviruses.

Adolescent↗
PubMed2005

A prospective study of wheezing in young children: the independent effects of cockroach exposure, breast-feeding and allergic sensitization.

The objective of this study was to evaluate risk factors for persistent wheezing in a group of 2-4-year-old children after an index-wheezing episode in infancy. Eighty infants who had been seen at the Emergency Department for an episode of acute wheezing were followed for 2 yr in this prospective study. Caregivers completed a questionnaire, and children underwent clinical evaluation and skin prick testing 2 yr following the index-wheezing episode. Detection of respiratory viruses and analysis of exposure to major indoor allergens were carried out at enrollment. Immunoglobin E antibodies were measured at the beginning of the study and at the end of follow-up, using the CAP system. Logistic regression analysis was performed to identify factors associated with persistent wheezing. Seventy-three children (44 boys) completed the study. After 2 yr, 38 (52%) reported three or more wheezing episodes in the past 12 months (persistent wheezers). Independent risk factors for persistence of wheezing were allergic sensitization and exposure to cockroach allergen in the kitchen. Breast-feeding for at least 1 month was a protective factor. A strong association between allergic sensitization and persistence of wheezing was found in a group of very young children living in a subtropical area.

Allergens↗
PubMed2004

A role for IL-10-mediated HLA-DR7-restricted T cell-dependent events in development of the modified Th2 response to cat allergen.

Although high dose exposure to inhaled cat allergen (Fel d 1) can cause a form of tolerance (modified Th2 response), the T cell mechanism for this phenomenon has not been studied. T cell responses to Fel d 1 were characterized in both allergic (IgE(pos)) and modified Th2 (IgE(neg)IgG(pos)) responders as well as serum Ab-negative controls (IgE(neg)IgG(neg)). Fel d 1 stimulated high levels of IL-10 in PBMC cultures from all individuals, with evidence of Th2 and Th1 cytokine skewing in allergic and control subjects, respectively. Using overlapping peptides, epitopes at the N terminus of Fel d 1 chain 2 were shown to stimulate strong T cell proliferation and to preferentially induce IL-10 (peptide 2:1 (P2:1)) or IFN-gamma (P2:2) regardless of the allergic status of the donor. Injection of cat extract during conventional immunotherapy stimulated expansion of IL-10- and IFN-gamma-producing chain 2 epitope-specific T cells along with increased Fel d 1-specific serum IgG and IgG4 Ab. Six of 12 modified responders expressed the major HLA-DRB1 allele, *0701, and both P2:1 and P2:2 were predicted ligands for this allele. Cultures from DR7-positive modified responders produced the highest levels of IL-10 to P2:1 in addition to other major and minor epitopes within chains 1 and 2. In the presence of anti-IL-10 mAb, both T cell proliferation and IFN-gamma production were enhanced in a Fel d 1- and epitope-specific manner. We conclude that IL-10-producing T cells specific for chain 2 epitopes are relevant to tolerance induction, and that DR7-restricted recognition of these epitopes favors a modified Th2 response.

Adult↗
PubMed2004

Risk factors for wheezing in a subtropical environment: role of respiratory viruses and allergen sensitization.

BACKGROUND: Risk factors for acute wheezing among children in subtropical areas are largely unknown. OBJECTIVE: To investigate the role of viral infections, allergen sensitization, and exposure to indoor allergens as risk factors for acute wheezing in children 0 to 12 years old. METHODS: One hundred thirty-two children 0 to 12 years of age who sought emergency department care for wheezing and 65 children with no history of wheezing were enrolled in this case-control study. Detection of respiratory syncytial virus antigen, rhinovirus and coronavirus RNA, adenovirus, influenza, and parainfluenza antigens was performed in nasal washes. Total IgE and specific IgE to mites, cockroach, cat, and dog were measured with the CAP system. Major allergens from mites, cockroach, cat, and dog were quantified in dust samples by ELISA. Univariate and multivariate analyses were performed by logistic regression. RESULTS: In children under 2 years of age, infection with respiratory viruses and family history of allergy were independently associated with wheezing (odds ratio, 15.5 and 4.2; P = .0001 and P = .008, respectively). Among children 2 to 12 years old, sensitization to inhalant allergens was the major risk factor for wheezing (odds ratio, 2.7; P = .03). High-level allergen exposure, exposure to tobacco smoke, and lack of breast-feeding showed no association with wheezing. CONCLUSIONS: Some risk factors for wheezing previously identified in temperate climates were present in a subtropical area, including respiratory syncytial virus infection in infants and allergy in children older than 2 years. Rhinovirus was not associated with wheezing and did not appear to be a trigger for asthma exacerbations.

Allergens↗