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Biomedical subjects

F D Martinez

Publications and source records attributed to F D Martinez.

At least 19 recordsLinked to original sources
PubMed2001

Differences in proliferation of the hematopoietic cell line TF-1 and cytokine production by peripheral blood leukocytes induced by 2 naturally occurring forms of human IL-3.

BACKGROUND: A naturally occurring polymorphism in the coding region of the human IL3 gene leads to a change in amino acid residue 8 from proline to serine. OBJECTIVE: We sought to determine whether the 2 different forms of IL-3 varied in function. These different forms are available as recombinant proteins (recombinant human IL-3/proline 8 [rhIL-3/P8] and recombinant human IL-3/serine 8 [rhIL-3/S8]). METHODS: The erythroleukemic cell line TF-1 was incubated with varying concentrations of rhIL-3/P8 or rhIL-3/S8 to determine the capacity of each type of IL-3 to induce proliferation. Human leukocytes were primed with rhIL-3/P8 or rhIL-3/S8 for up to 24 hours and then stimulated with anti-IgE and assessed for leukotrienes (LTs), IL-4, and TNF-alpha. RESULTS: Proliferation of TF-1 cells was induced by both forms of IL-3 at 48 and 72 hours but to a greater degree by rhIL-3/P8. In contrast, the mean fold increase over control values of LT and IL-4 production was higher after priming the cells with rhIL-3/S8 versus rhIL-3/P8. Additionally, TNF-alpha production was greater (and reached significance only) for rhIL-3/S8. This activity was independent of IgE and thus directly stimulated by IL-3. Studies with basophil-enriched and basophil-depleted cell preparations revealed that LT production was evident only from the former and TNF-alpha only from the latter. CONCLUSION: We conclude that the 2 naturally occurring forms of human IL-3 have similar spectra of activities on cells with IL-3 receptors, but the 2 forms have reversed relative efficacies for promoting proliferation (rhIL-3/P8 > rhIL-3/S8) compared with priming or inducing mediator secretion (rhIL-3/S8 > rhIL-3/P8).

Cell Line↗
PubMed2001

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

BACKGROUND: The relationship between infant feeding and childhood asthma is controversial. This study tested the hypothesis that the relation between breast feeding and childhood asthma is altered by the presence of maternal asthma. METHODS: Healthy non-selected newborn infants (n = 1246) were enrolled at birth. Asthma was defined as a physician diagnosis of asthma plus asthma symptoms reported on > or = 2 questionnaires at 6, 9, 11 or 13 years. Recurrent wheeze (> or = 4 episodes in the past year) was reported by questionnaire at seven ages in the first 13 years of life. Duration of exclusive breast feeding was based on prospective physician reports or parental questionnaires completed at 18 months. Atopy was assessed by skin test responses at the age of 6 years. RESULTS: The relationship between breast feeding, asthma, and wheeze differed with the presence or absence of maternal asthma and atopy in the child. After adjusting for confounders, children with asthmatic mothers were significantly more likely to have asthma if they had been exclusively breast fed (OR 8.7, 95% CI 3.4 to 22.2). This relationship was only evident for atopic children and persisted after adjusting for confounders. In contrast, the relation between recurrent wheeze and breast feeding was age dependent. In the first 2 years of life exclusive breast feeding was associated with significantly lower rates of recurrent wheeze (OR 0.45, 95% CI 0.2 to 0.9), regardless of the presence or absence of maternal asthma or atopy in the child. Beginning at the age of 6 years, exclusive breast feeding was unrelated to prevalence of recurrent wheeze, except for children with asthmatic mothers in whom it was associated with a higher odds ratio for wheeze (OR 5.7, 95% CI 2.3 to 14.1), especially if the child was atopic. CONCLUSION: The relationship between breast feeding and asthma or recurrent wheeze varies with the age of the child and the presence or absence of maternal asthma and atopy in the child. While associated with protection against recurrent wheeze early in life, breast feeding is associated with an increased risk of asthma and recurrent wheeze beginning at the age of 6 years, but only for atopic children with asthmatic mothers.

Adolescent↗
PubMed2001

Relation of two different subtypes of croup before age three to wheezing, atopy, and pulmonary function during childhood: a prospective study.

OBJECTIVE: Some retrospective evidence suggests that children with a history of croup may be at increased risk of subsequently developing asthma, atopy, and diminished pulmonary function. The objective of this study was to determine the long-term outcome of croup (as diagnosed by a physician) in early life. METHODS: Lower respiratory illnesses (LRIs) in the first 3 years of life were assessed in 884 children who were enrolled in a large longitudinal study of airway diseases at birth. Pulmonary function tests, markers of atopy, and wheezing episodes were studied at different ages between birth and 13 years. RESULTS: Ten percent of children had croup with wheeze (Croup/Wheeze), 5% had croup without wheeze (Croup/No Wheeze), 36% had another LRI (Other LRI), and 48% had no LRI. Respiratory syncytial virus was more frequently isolated in children with Croup/Wheeze and Other LRI than in those with Croup/No Wheeze. There was no association between croup in early life and markers of atopy measured during the school years. Only children with Croup/Wheeze and with Other LRI had a significant risk of subsequent persistent wheeze later in life. Significantly lower levels of indices of intrapulmonary airway function were observed at ages <1 (before any LRI), 6, and 11 years in children with Croup/Wheeze and Other LRI compared with children with No LRI. Conversely, inspiratory resistance before any LRI episode was significantly higher in infants who later developed Croup/No Wheeze than in the other 3 groups. CONCLUSIONS: We distinguish 2 manifestations of croup with and without wheezing. Children who present with croup may or may not be at increased risk of subsequent recurrent lower airway obstruction, depending on the initial lower airway involvement, and preillness and postillness abnormalities in lung function associated with this condition.

Asthma↗
PubMed2000

Siblings, day-care attendance, and the risk of asthma and wheezing during childhood.

BACKGROUND: Young children with older siblings and those who attend day care are at increased risk for infections, which in turn may protect against the development of allergic diseases, including asthma. However, the results of studies examining the relation between exposure to other children and the subsequent development of asthma have been conflicting. METHODS: In a study involving 1035 children followed since birth as part of the Tucson Children's Respiratory Study, we determined the incidence of asthma (defined as at least one episode of asthma diagnosed by a physician when the child was 6 to 13 years old) and the prevalence of frequent wheezing (more than three wheezing episodes during the preceding year) in relation to the number of siblings at home and in relation to attendance at day care during infancy. RESULTS: The presence of one or more older siblings at home protected against the development of asthma (adjusted relative risk for each additional older sibling, 0.8; 95 percent confidence interval, 0.7 to 1.0; P=0.04), as did attendance at day care during the first six months of life (adjusted relative risk, 0.4; 95 percent confidence interval, 0.2 to 1.0; P=0.04). Children with more exposure to other children at home or at day care were more likely to have frequent wheezing at the age of 2 years than children with little or no exposure (adjusted relative risk, 1.4; 95 percent confidence interval, 1.1 to 1.8; P=0.01) but were less likely to have frequent wheezing from the age of 6 (adjusted relative risk, 0.8; 95 percent confidence interval, 0.6 to 1.0; P=0.03) through the age of 13 (adjusted relative risk, 0.3; 95 percent confidence interval, 0.2 to 0.5; P<0.001). CONCLUSIONS: Exposure of young children to older children at home or to other children at day care protects against the development of asthma and frequent wheezing later in childhood.

Adolescent↗
PubMed2000

A cluster of seven tightly linked polymorphisms in the IL-13 gene is associated with total serum IgE levels in three populations of white children.

BACKGROUND: Increased levels of total serum IgE are a strong risk factor for the development of asthma. IgE is also involved in host defenses against parasites and fungi. Linkage of total serum IgE with markers located close to the 3 Mb cluster of cytokine genes in chromosome 5q31 has been reported. IL-4 or IL-13 are regarded as essential for IgE synthesis. OBJECTIVE: We tested whether polymorphisms in the IL-13 gene might explain the linkage between chromosome 5q31 and total serum IgE levels. METHODS: We used denaturing HPLC to detect polymorphisms in overlapping PCR fragments of the IL-13 gene including promoter and 3' untranslated regions. After sequencing was performed to identify the locations of the polymorphisms, PCR and primer-induced restriction site assays were used to genotype subjects in 3 unselected populations. RESULTS: We report here 7 polymorphisms (6 novel) in IL-13. Four of these polymorphisms are tightly linked to a variant in the terminal portion of the coding region of the gene that results in a predicted amino acid change in residue 130 (Arg130Gln). The Gln form is strongly associated (P =.000002) with increased serum IgE levels in 3 different populations comprising a total of 1399 children. Two additional polymorphisms in the promoter region of IL-13 are more loosely linked to Arg130Gln and are also less significantly associated with total serum IgE levels. CONCLUSION: These data suggest that the Arg130Gln polymorphism in IL-13, or others in close linkage with it, is associated with the development of the elevated serum IgE phenotype.

Asthma↗
PubMed2000

A clinical index to define risk of asthma in young children with recurrent wheezing.

Because most cases of asthma begin during the first years of life, identification of young children at high risk of developing the disease is an important public health priority. We used data from the Tucson Children's Respiratory Study to develop two indices for the prediction of asthma. A stringent index included frequent wheezing during the first 3 yr of life and either one major risk factor (parental history of asthma or eczema) or two of three minor risk factors (eosinophilia, wheezing without colds, and allergic rhinitis). A loose index required any wheezing during the first 3 yr of life plus the same combination of risk factors described previously. Children with a positive loose index were 2.6 to 5.5 times more likely to have active asthma between ages 6 and 13 than children with a negative loose index. Risk of having subsequent asthma increased to 4.3 to 9.8 times when a stringent index was used. We found that 59% of children with a positive loose index and 76% of those with a positive stringent index had active asthma in at least one survey during the school years. Over 95% of children with a negative stringent index never had active asthma between ages 6 and 13. We conclude that the subsequent development of asthma can be predicted with reasonable accuracy using simple, clinically based parameters.

Adolescent↗
PubMed1999

Respiratory syncytial virus in early life and risk of wheeze and allergy by age 13 years.

BACKGROUND: The relation between lower respiratory tract illnesses in early life caused by the respiratory syncytial virus (RSV) and the subsequent development of wheezing and atopy in childhood is not well understood. We studied this relation in children who had lower respiratory tract illnesses that occurred before 3 years of age. METHODS: Children were enrolled at birth and cases of lower respiratory tract illness were ascertained by a physician. Viral tests were done for specimens collected at the time of the illness. Children were classified into five groups according to type and cause of lower respiratory tract illness. Children were then followed prospectively up to age 13, and we measured frequency of wheezing, pulmonary function, and atopic status (allergy skin-prick tests, serum IgE concentrations). FINDINGS: RSV lower respiratory tract illnesses were associated with an increased risk of infrequent wheeze (odds ratio 3.2 [95% CI 2.0-5.0], p < 0.001), and an increased risk of frequent wheeze (4.3 [2.2-8.7], p < or = 0.001) by age 6. Risk decreased markedly with age and was not significant by age 13. There was no association between RSV lower respiratory tract illnesses and subsequent atopic status. RSV lower respiratory tract illnesses were associated with significantly lower measurements of forced expiratory volume (2.11 [2.05-2.15], p < or = 0.001) when compared with those of children with no lower respiratory tract illnesses, but there was no difference in forced expiratory volume after inhalation of salbutamol. INTERPRETATION: RSV lower respiratory tract illnesses in early childhood are an independent risk factor for the subsequent development of wheezing up to age 11 years but not at age 13. This association is not caused by an increased risk of allergic sensitisation.

Adolescent↗
PubMed1999

Influence of parental smoking on respiratory symptoms during the first decade of life: the Tucson Children's Respiratory Study.

Compelling evidence suggests a causal relation between exposure to parental cigarette smoking and respiratory symptoms during childhood. Still, the roles of prenatal versus postnatal parental smoking need clarification. In this study, the authors assessed the effects of passive smoking on respiratory symptoms in a cohort of over 1,000 children born during 1980-1984. The children were enrolled in the Tucson Children's Respiratory Study in Tucson, Arizona, and were followed from birth to age 11 years. The population was generally middle class and consisted of two main ethnic groups, non-Hispanic Whites (75%) and Hispanics (20%), reflecting Tucson's population. Information on parental smoking and on wheeze and cough in their children was elicited from parents by using questionnaires at five different surveys. Data were analyzed both cross-sectionally and by using the generalized estimation equation approach, a longitudinal mixed-effects model. The best-fitting model indicated that maternal prenatal but not postnatal smoking was associated with current wheeze (odds ratio = 2.3, 95% confidence interval 1.4-3.8) independently of a family history of asthma, socioeconomic factors, and birth weight. This effect was time dependent and significant only below age 3 years; although independent of gender, the association was stronger for girls (odds ratio = 3.6, 95% confidence interval 1.6-8.0). Cough was not associated with parental smoking during the first decade of life. This transitory effect of maternal prenatal smoking on wheezing could be due to changes that affect the early stages of lung development.

Adult↗
PubMed1999

Present and future treatment of asthma in infants and young children.

Asthma is a chronic inflammatory disease of the airways characterized by the local production of inflammatory mediators and an increase in recruitment of inflammatory cells (predominantly eosinophils and mast cells). It has been proposed that the chronic nature of this inflammatory response may be responsible for long-term pulmonary changes including bronchial hyperresponsiveness, airway remodeling, and irreversible airflow obstruction. Much of the information available on the pathogenesis of asthma is based on studies performed in young adults. Because of numerous complications, studies in infants and young children are often difficult to conduct; therefore information on this age group is lacking. Although studies are limited, data suggest that an asthma-like inflammation is present at a very early age, with increases in inflammatory cells and thickening of the lung basement membrane detected in infants and young children. In addition, lung function of children with persistent wheezing was significantly lower by 6 years of age compared with children who had no wheezing episodes during the same period; differences between groups were not apparent at 6 months of age. These data suggest that airway inflammation in young children with asthma is associated with nonreversible impairment of lung function. Recent National Asthma Education and Prevention Guidelines stress the importance of anti-inflammatory agents, particularly inhaled corticosteroids, in the treatment of young children with persistent asthma. Given data supporting the presence of an inflammatory response early in the disease course, early intervention with anti-inflammatory agents may be indicated at the onset of symptoms to prevent long-term, irreversible, impairment of lung function. Although several studies have shown that inhaled corticosteroids may be effective in the treatment of recurrent wheezing in infancy, tools need to be developed to distinguish infants with early-onset asthma from those with transient wheezing.

Administration, Inhalation↗
PubMed1999

Total serum IgE and its association with asthma symptoms and allergic sensitization among children.

BACKGROUND: Asthma and wheezing during childhood are associated with elevated total serum IgE and with allergic sensitization to local aeroallergens. However, little is known about the longitudinal relationship between total serum IgE and the development of wheezing and allergic sensitization during childhood. OBJECTIVE: The purpose of our investigation was to determine the relationship between total serum IgE and the development of wheezing and allergic sensitization in childhood. METHODS: Our study subjects were participants in the Tucson Children's Respiratory Study who underwent an IgE measurement in at least 1 of 3 surveys (at years 1, 6, and 11) and complete allergy skin tests during the latter 2 surveys. The children's phenotypes were categorized on the basis of skin test response (never, early, and late) and wheezing status (never, early, late, and persistent). Repeated-measures analyses were used, allowing subjects to be included who had unequal numbers of IgE observations (a total of 263 boys and 277 girls). RESULTS: We found that total serum IgE levels track with age: subjects with high serum IgE levels less than 1 year old continued to have high IgE levels at ages 6 and 11 years. Both persistent wheezing and early sensitization were associated with high serum IgE levels at all ages. Boys who had late or persistent wheezing or who were sensitized early or late had high serum IgE levels as early as age 9 months, whereas only girls with persistent wheezing and early sensitization had elevated IgE levels at that age. Children who wheezed only in the first years of life and not after (ie, those with early wheezing) had serum IgE levels that were not different from those of nonwheezing children. CONCLUSION: On the basis of these findings we conclude that although total serum IgE tracks with age, children who are predisposed to persistent wheezing and early sensitization to local aeroallergens already have high levels of IgE at age 9 months. This suggests that the predisposition to respond to environmental stimuli through high levels of IgE precede early allergic sensitization, indicating that there may be a common defect in the development of the immune system involving IgE production and early allergic sensitization.

Asthma↗
PubMed1999

Breast-feeding, maternal IgE, and total serum IgE in childhood.

BACKGROUND: There is controversy regarding the relationship of the effect of breast-feeding on markers of allergy such as total serum IgE in childhood. OBJECTIVE: This study, using longitudinal data, tested the hypothesis that the relation of breast-feeding to IgE in childhood differs depending on maternal total IgE level. METHODS: Total serum IgE was assessed with the paper radioimmunosorbent test at 4 ages in nonselected children enrolled at birth into the prospective Tucson Children's Respiratory Study. Children were classified as never breast-fed, breast-fed less than 4 months, or breast-fed 4 months or longer, on the basis of physician report or questionnaires completed by parents by the time the child was 18 months old. A longitudinal random effects model was used to test for group differences and temporal trends in IgE for children classified with reference to maternal IgE (high tertile vs all others) and breast-feeding history. A total of 664 children with 1457 observations were included. RESULTS: Among children whose mothers were in the 2 lower tertiles of IgE, breast-feeding was associated with lower total serum IgE at age 6 years (24.2 vs 44.3 IU/mL for never breast-fed children; P <.02); similar trends existed at age 11 years. In contrast, for children whose mothers were in the highest tertile of IgE, breast-feeding of 4 months or longer was associated with higher IgE levels in the child compared with those never breast-fed or breast-fed less than 4 months (97.0 vs 38.9 IU/mL; P <. 005). These cross-sectional analyses were confirmed with the longitudinal random effects model, which also showed no effect of confounders. Paternal IgE showed no similar relation with child IgE. CONCLUSION: Breast-feeding appears to have paradoxic relations with IgE in childhood, depending on maternal IgE level. These findings may help explain the contradictory results found in other investigations of the relation of breast-feeding to allergic symptoms and markers.

Breast Feeding↗
PubMed1999

Maturation of immune responses at the beginning of asthma.

The prevalence of childhood asthma appears to be increasing worldwide. A critical element in the development of childhood asthma is maturation of the child's immune system. Most asthmatic children have a history of recurrent lower respiratory tract illnesses associated with airway obstruction during the first year of life. Most infants and young children who will go on to have persistent wheezing and asthma show high IgE production and eosinophilic immune responses at the time of their first viral lower respiratory tract illness. Understanding the genetic and environmental factors that regulate the maturation of the immune response during early life will greatly enhance the development of strategies for the primary and secondary prevention of asthma.

Age Factors↗
PubMed1999

Role of respiratory infection in onset of asthma and chronic obstructive pulmonary disease.

There is renewed interest in the possible role of events occurring during early life in determining predisposition to asthma and allergies. Among these events, respiratory illnesses associated with viral infections have been the matter of considerable research interest. There is now evidence suggesting that an immune response to viral infection in early life that is skewed toward an IgE- or an eosinophil-mediated slant is predictive of persistent wheezing symptoms up to the age of 6 years. Genetic and environmental factors (specifically bacterial infection burden) may be important determinants of the maturation of immune responses from a default 'Th-2-like' at birth to mature, non-Th-2-like responses. Homing of Th-2-like responses to the lung may be determined in part by inheritance of bronchial hyperresponsiveness, and in part by the progressive nature of chronic, uncontrolled airway inflammation. The main risk factor for the development of wheezing episodes in children who are not predisposed to allergic asthma is diminished airway function, which can also be detected shortly after birth. These children may stop wheezing later during childhood, but their levels of lung function track with age. It is tempting to speculate that chronic obstructive pulmonary disease may occur more frequently in these children.

Animals↗
PubMed1999

Recognizing early asthma.

Asthma symptoms often develop during the first years of life. Longitudinal studies show that at least 40% of children with wheezing lower respiratory illnesses (LRIs) during the first 3 years of life still have wheezing episodes at 6 years of age. Thus, it is important to identify children at risk of developing asthma, and to distinguish these from those in whom early wheezing is likely to be transient. This is complicated, however, by the variable nature of asthma and the lack of specific and sensitive markers. Genetic markers and epidemiologic risk factors for asthma have been identified, but cannot be used to predict the development of asthma in an individual patient. Similarly, infants who subsequently develop asthma in childhood have higher serum immunoglobulin E (IgE) and peripheral eosinophil counts than those who do not develop asthma, but, again, these factors are not sufficiently sensitive and specific to allow identification of children at risk of developing asthma. An algorithm is presented that outlines possible criteria to determine the risk of developing asthma in infants.

Algorithms↗