Biomedical subjects

Fernando D Martinez

Publications and source records attributed to Fernando D Martinez.

47 records · Page 3Linked to original sources

PubMed2003

Tucson Children's Respiratory Study: 1980 to present.

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.

Acute Disease↗

PubMed2003

Respiratory syncytial virus bronchiolitis and the pathogenesis of childhood asthma.

There is now convincing evidence that children who develop lower respiratory symptoms during infection with respiratory syncytial virus (RSV) in early life are at increased risk of developing asthma-like symptoms during the school years. What determines this association is not well-understood, but increased likelihood of allergic sensitization plays a minor role, if any, as a determinant of post-RSV wheeze. Current evidence suggests that both genetic and environmental factors determine the type of immune response to the acute RSV infection and that this response, in turn, may affect the development of the control mechanisms involved in the regulation of airway tone. Many different cytokines appear to play a role in this acute immune response, including interferon-gamma; interleukins 8, 10 and 12; and cytokines produced by T helper (Th) 1 and Th2 cells. Because asthma is a heterogeneous condition, future studies will need to determine the potentially different role of RSV infection as a risk factor for these different asthma phenotypes. It is likely, however, that strategies for the prevention of RSV infection may play a role in the prevention of the subsequent development of persistent wheezing and asthma-like symptoms in childhood.

Asthma↗

PubMed2002

Polymorphisms in toll-like receptor 4 are not associated with asthma or atopy-related phenotypes.

Toll-like receptor 4 (TLR4) is the principal receptor for bacterial endotoxin recognition, and functional variants in the gene confer endotoxin-hyporesponsiveness in humans. Furthermore, there is evidence that endotoxin exposure during early life is protective against the development of atopy and asthma, although this relationship remains poorly understood. It is therefore possible that genetic variation in the TLR4 locus contributes to asthma susceptibility. In this study we characterize the genetic diversity in the TLR4 locus and test for association between the common genetic variants and asthma-related phenotypes. In a cohort of 90 ethnically diverse subjects, we resequenced the TLR4 locus and identified a total of 29 single nucleotide polymorphisms. We assessed five common polymorphisms for evidence of association with asthma in two large family-based cohorts: a heterogeneous North American cohort (589 families), and a more homogenous population from northeastern Quebec, Canada (167 families). Using the transmission-disequilibrium test, we found no evidence of association for any of the polymorphisms tested, including two functional variants. Furthermore, we found no evidence for association between the TLR4 variants and four quantitative intermediate asthma- and atopy-related phenotypes. Based on these results, we found no evidence that genetic variation in TLR4 contributes to asthma susceptibility.

Asthma↗

PubMed2002

Influence of attendance at day care on the common cold from birth through 13 years of age.

OBJECTIVE: To describe trends in the occurrence of the common cold during the first 13 years of life among children who attended different childcare settings early in life. DESIGN: The Tucson Children's Respiratory Study involves 1246 children enrolled at birth and followed up prospectively since May 1980 through October 1984. Children with data regarding day care use during the first 3 years of life were included in this investigation (n = 991). Parents reported the occurrence of frequent (> or = 4) colds during the past year by questionnaire when each child was 2, 3, 6, 8, 11, and 13 years of age. Child care at home (no unrelated children), at small day care (1-5 unrelated children), or at large day care (> or = 6 unrelated children) was reported retrospectively by parental questionnaire when the children were approximately 6 years old. RESULTS: After adjusting for potential confounding variables, compared with children at home those in large day care had more frequent colds at year 2 (odds ratio [OR], 1.9, 95% confidence interval [CI], 1.0-3.4; P =.04), less frequent colds at years 6 (OR, 0.3, 95% CI, 0.1-0.9; P =.02) through 11 (OR, 0.4, 95% CI, 0.1-1.2; P =.09), and the same odds of frequent colds at year 13 (OR,1.0, 95% CI, 0.3-3.8; P =.95). In addition, compared with children in large day care for 1 year or less those attending large day care for more than 2 years had more frequent colds at year 2 (OR, 1.7, 95% CI, 1.0-3.0; P =.04), less frequent colds at years 6 (OR, 0.5, 95% CI, 0.2-1.1; P =.08), 8 (OR, 0.2, 95% CI, 0.1-1.0; P =.04), and 11 (OR, 0.3, 95% CI, 0.1-1.0; P =.05); and the same odds of frequent colds at year 13 (OR, 0.9, 95% CI, 0.3-2.9; P =.80). CONCLUSIONS: Attendance at large day care was associated with more common colds during the preschool years. However, it was found to protect against the common cold during the early school years, presumably through acquired immunity. This protection waned by 13 years of age.

Adolescent↗

PubMed2002

What have we learned from the Tucson Children's Respiratory Study?

The Tucson Children's Respiratory Study was the first longitudinal assessment of the natural history of asthma in which children were enrolled at birth. Over 1200 children were originally included and over 800 were still participating at age 13. The study has provided general indications about the most important risk factors for and the prognosis of different phenotypes associated with recurrent airway obstruction during childhood. The most important conclusion from the study is that asthma is a heterogeneous disease, with different predominant expressions at different ages. The form of the disease that is associated with atopy is not very frequent in early life, but becomes preponderant during the school years. However, this form is more persistent and is associated with significant deficits in lung function growth up to age 11. Up to two-thirds of infants who wheeze have a transient form of recurrent airway obstruction associated with low premorbid lung function. Many children who wheeze during the preschool years do so only during viral infections. These children usually have a history of wheezing due to respiratory syncytial virus during early life and low levels of lung function during the school years. Understanding the different asthma phenotypes of childhood will provide new clues for strategies for the primary prevention of the disease.

Asthma↗

PubMed2002

Single nucleotide polymorphisms in innate immunity genes: abundant variation and potential role in complex human disease.

Under selective pressure from infectious microorganisms, multicellular organisms have evolved immunological defense mechanisms, broadly categorized as innate or adaptive. Recent insights into the complex mechanisms of human innate immunity suggest that genetic variability in genes encoding its components may play a role in the development of asthma and related diseases. As part of a systematic assessment of genetic variability in innate immunity genes, we have thus far have examined 16 genes by resequencing 93 unrelated subjects from three ethnic samples (European American, African American and Hispanic American) and a sample of European American asthmatics. Approaches to discovering and understanding variation and the subsequent implementation of disease association studies are described and illustrated. Although highly conserved across a wide range of species, the innate immune genes we have sequenced demonstrate substantial interindividual variability predominantly in the form of single nucleotide polymorphisms (SNPs). Genetic variation in these genes may play a role in determining susceptibility to a range of common, chronic human diseases which have an inflammatory component. Differences in population history have produced distinctive patterns of SNP allele frequencies, linkage disequilibrium and haplotypes when ethnic groups are compared. These and other factors must be taken into account in the design and analysis of disease association studies.

Animals↗

PubMed2002

Rhinitis as an independent risk factor for adult-onset asthma.

BACKGROUND: For many years, the association between asthma and rhinitis has primarily been attributed to a common allergic background. Recently, it has been suggested that asthma and rhinitis are associated in the absence of atopy. The nature of this association is not well known. OBJECTIVE: The purpose of this study, which was performed in a large, longitudinal community population, was to determine the extent to which rhinitis is an independent risk factor for adult-onset asthma. METHODS: We carried out a nested case-control study from the longitudinal cohort of the Tucson Epidemiologic Study of Obstructive Lung Diseases. One hundred seventy-three incident patients with physician-confirmed asthma were compared with 2177 subjects who reported no asthma or shortness of breath with wheezing. Potential risk factors, including the presence of rhinitis, were assessed before the onset of asthma (patients) or before the last completed survey (control subjects). RESULTS: Rhinitis was a significant risk factor for asthma (crude odds ratio, 4.13; 95% confidence interval, 2.88-5.92). After adjustment for years of follow-up, age, sex, atopic status, smoking status, and presence of chronic obstructive pulmonary disease, the magnitude of the association was reduced but still highly significant (adjusted odds ratio, 3.21; 95% confidence interval, 2.19-4.71). After stratification, rhinitis increased the risk of development of asthma by about 3 times both among atopic and nonatopic patients and by more than 5 times among patients in the highest IgE tertile. Patients with rhinitis with persistent and severe nasal symptoms and a personal history of physician-confirmed sinusitis had an additional increased risk of asthma development. CONCLUSION: We conclude that rhinitis is a significant risk factor for adult-onset asthma in both atopic and nonatopic subjects. The nature of the association between rhinitis and asthma is open to interpretation.

Adult↗

PubMed2002

The relation of body mass index to asthma, chronic bronchitis, and emphysema.

BACKGROUND: Recent studies have suggested a relationship between asthma and obesity. Despite these reports, the effect of being underweight or overweight as a risk factor for airway obstructive diseases (AODs) is not clear. OBJECTIVES: To determine whether a relation of body mass index (BMI) to asthma, chronic bronchitis (CB), or emphysema exists (analysis 1), and, if so, whether the association between obesity and asthma is modified by gender (analysis 2). DESIGN: Nested case-control study from the longitudinal cohort of the Tucson Epidemiologic Study of Airways Obstructive Diseases. PATIENTS: Analysis 1: physician-confirmed incident cases of asthma (n = 102), CB (n = 299), or emphysema (n = 72) who denied any prior AODs. Analysis 2: all 169 incident cases of asthma, regardless of any previous AODs, stratified by gender and by other potential effect modifiers. In both analyses, we selected only subjects at least 20 years old who had weight and height measured during the study. MEASUREMENTS: BMI and other risk factors were assessed prior to the onset of the AOD (cases) or prior to the last completed survey (control subjects). RESULTS: A diagnosis of emphysema was significantly associated with a BMI < 18.5 (odds ratio [OR], 2.97; 95% confidence interval [CI], 1.33 to 6.68, when compared to healthy control subjects). A BMI >/= 28 increased the risk of receiving a diagnosis of asthma (OR, 2.10; 95% CI, 1.31 to 3.36) and CB (OR, 1.80; 95% CI, 1.32 to 2.46). About 30% of the patients with asthma and 25% of the patients with CB (vs 16% of the control subjects, p < 0.001) were preobese or obese, regardless whether BMI was assessed before the diagnosis or before the onset of respiratory symptoms. The relation of elevated BMI to asthma was significant only among women. CONCLUSIONS: Patients with emphysema are more likely to be underweight, and patients with CB are more likely to be obese. However, the temporal relationship between abnormal BMI and the onset of COPD is uncertain. Preobese and obese women are at increased risk of acquiring asthma. This relation, particularly if it is causal, has potentially relevant public health implications.

Adult↗

PubMed2002

Development of wheezing disorders and asthma in preschool children.

Recent longitudinal studies have shed light on the pathogenesis and progression of asthma. The patterns of expression of childhood asthma that persist into adult life have been explored. Distinct asthma phenotypes (transient wheezing, nonatopic wheezing, and atopy-associated asthma) have been identified. Defining which children are at risk for persistent asthma could allow for better management and, potentially, for reduced morbidity and mortality.

Adult↗

PubMedDate not supplied

Is there a common cold constitution?

OBJECTIVE: Constitutional factors might play a role in the susceptibility to clinical illness during the common cold. This study seeks to determine if the likelihood of developing frequent common colds persists during childhood. DESIGN: The Tucson Children's Respiratory Study involves 1246 children enrolled at birth and followed prospectively since 1980 and 1984. Parents reported the occurrence of frequent (> or =4) colds during the past year by questionnaire at 2, 3, 6, 8, 11, and 13 years of age. Blood for ex vivo interferon-gamma responses was obtained at 9 months and 11 years of age. RESULTS: After adjustment for potential confounding variables, children with frequent colds at year 2 or 3 were twice as likely to experience frequent colds at year 6 (relative risk [RR], 2.8; 95% confidence interval [CI], 2.1-3.9), year 8 (RR, 2.6; 95% CI, 2.1-3.3), year 11 (RR, 2.4; 95% CI, 1.8-3.1), and year 13 (RR, 2.1; 95% CI, 1.4-3.3) compared with children who had infrequent colds at years 2 and 3. At 9 months of age, children who ultimately experienced persistent frequent colds had lower interferon-gamma titers than children without persistent frequent colds (3.05 +/- 1.61 vs 3.74 +/- 1.39, P =.016); this finding persisted at 11 years of age. CONCLUSION: These data suggest the existence of a common cold constitution, whereby some children are more susceptible to infection and/or the expression of clinical symptoms when infected than are other children.

Adolescent↗

PubMedDate not supplied

Serious adverse events and death associated with treatment using long-acting beta-agonists.

Two very large, randomized, double-blind clinical trials performed in the United Kingdom and in the United States have suggested that addition of salmeteräE to usual asthma therapy is associated with a significant increase in the incidence of serious adverse events and asthma-related deaths compared with addition of albuterol or placebo to usual therapy in the same type of patients. These results prompted the United States Food and Drug Administration (FDA) to issue a stern warning regarding these potential adverse effects and to advise that long-acting beta-agonists (LABAs) should not used as first-line therapy for the treatment of asthma. Two potential explanations have been proposed for these unexpected adverse effects. It has been suggested that more than a direct pharmacological effect of LABAs, these adverse events result from inadequate concomitant use of inhaled corticosteroids in subjects treated with these medicines. However, a detailed analysis of the results of the two large trials did not provide definitive conclusions regarding the potential protective role of inhaled corticosteroids. A second explanation, which the author here considers more plausible, is that a small group of patients with asthma develop idiosyncratic responses to LABAs, and common or rare variants in the genes that encode for proteins associated with the pharmacological response to these medicines are strongly suspected to predispose for these unusual deleterious responses. Until the biological mechanisms involved are better understood, efforts should be made to confine the use of LABAs to those patients who really need them.

Adrenergic beta-Agonists↗