PAI-1 gain-of-function genotype, factors increasing PAI-1 levels, and airway obstruction: The GALA II Cohort.

BACKGROUND: PAI-1 gain-of-function variants promote airway fibrosis and are associated with asthma and with worse lung function in subjects with asthma. OBJECTIVE: We sought to determine whether the association of a gain-of-function polymorphism in plasminogen activator inhibitor-1 (PAI-1) with airway obstruction is modified by asthma status, and whether any genotype effect persists after accounting for common exposures that increase PAI-1 level. METHODS: We studied 2070 Latino children (8-21y) with genotypic and pulmonary function data from the GALA II cohort. We estimated the relationship of the PAI-1 risk allele with FEV1/FVC by multivariate linear regression, stratified by asthma status. We examined the association of the polymorphism with asthma and airway obstruction within asthmatics via multivariate logistic regression. We replicated associations in the SAPPHIRE cohort of African Americans (n=1056). Secondary analysis included the effect of the at-risk polymorphism on postbronchodilator lung function. RESULTS: There was an interaction between asthma status and the PAI-1 polymorphism on FEV1 /FVC (P=.03). The gain-of-function variants, genotypes (AA/AG), were associated with lower FEV1 /FVC in subjects with asthma (ß=-1.25, CI: -2.14,-0.35, P=.006), but not in controls. Subjects with asthma and the AA/AG genotypes had a 5% decrease in FEV1 /FVC (P<.001). In asthmatics, the risk genotype (AA/AG) was associated with a 39% increase in risk of clinically relevant airway obstruction (OR=1.39, CI: 1.01, 1.92, P=.04). These associations persisted after exclusion of factors that increase PAI-1 including tobacco exposure and obesity. CONCLUSIONS AND CLINICAL RELEVANCE: The decrease in the FEV1 /FVC ratio associated with the risk genotype was modified by asthma status. The genotype increased the odds of airway obstruction by 75% within asthmatics only. As exposures known to increase PAI-1 levels did not mitigate this association, PAI-1 may contribute to airway obstruction in the context of chronic asthmatic airway inflammation.

Maternal age and asthma in Latino populations.

BACKGROUND: Younger maternal age at birth is associated with increased risk of asthma in offspring in European descent populations, but has not been studied in Latino populations. OBJECTIVES: We sought to examine the relationship between maternal age at birth and prevalence of asthma in a nationwide study of Latino children. METHODS: We included 3473 Latino children aged 8-21 years (1696 subjects with physician-diagnosed asthma and 1777 healthy controls) from five US centres and Puerto Rico recruited from July 2008 through November 2011. We used multiple logistic regression models to examine the effect of maternal age at birth on asthma in offspring overall and in analyses stratified by ethnic subgroup (Mexican American, Puerto Rican and other Latino). Secondary analyses evaluated the effects of siblings, acculturation and income on this relationship. RESULTS: Maternal age < 20 years was significantly associated with decreased odds of asthma in offspring, independent of other risk factors (OR = 0.73, 95% CI: 0.57-0.93). In subgroup analyses, the protective effect of younger maternal age was observed only in Mexican Americans (OR = 0.53, 95% CI: 0.36, 0.79). In Puerto Ricans, older maternal age was associated with decreased odds of asthma (OR = 0.65, 95% CI: 0.44-0.97). In further stratified models, the protective effect of younger maternal age in Mexican Americans was seen only in children without older siblings (OR = 0.44, 95% CI: 0.23-0.81). CONCLUSION AND CLINICAL RELEVANCE: In contrast to European descent populations, younger maternal age was associated with decreased odds of asthma in offspring in Mexican American women. Asthma is common in urban minority populations but the factors underlying the varying prevalence among different Latino ethnicities in the United States is not well understood. Maternal age represents one factor that may help to explain this variability.

The role of LTA4H and ALOX5AP genes in the risk for asthma in Latinos.

BACKGROUND: Leukotrienes play an important role in allergic and inflammatory diseases, but reports on the involvement of arachidonate 5-lipoxygenase-activating protein (ALOX5AP) and leukotriene A(4) hydrolase (LTA4H) in asthma have been inconclusive. OBJECTIVE: To determine whether polymorphisms in ALOX5AP and LTA4H genes are risk factors for asthma in two different Latino groups: Mexicans and Puerto Ricans. METHODS: The LTA4H gene was sequenced in individuals from both groups to identify novel polymorphisms. Single-nucleotide polymorphisms (SNPs) in the ALOX5AP and LTA4H genes were analysed for associations with asthma and asthma-related phenotypes in 687 parent-child trios of Mexican and Puerto Rican origin. RESULTS: In LTA4H, five previously unknown polymorphisms were identified. Two SNPs within LTA4H (rs17525488 and rs2540493) were protective for asthma in Latinos (P=0.007 and 0.05, respectively). Among the Mexican patients, LTA4H polymorphisms were associated with baseline lung function and IgE levels. For ALOX5AP, the minor allele at SNP rs10507391 was associated with protection from asthma (odds ratio=0.78, P=0.02) and baseline lung function (P=0.018) in Puerto Ricans. A gene-gene interaction was identified between LTA4H (rs17525488) and ALOX5AP (rs10507391), (P=0.003, in the combined sample). CONCLUSION: Our results support the role of LTA4H and ALOX5AP variants as risk factors for asthma in Latino populations.

Anaerobic power and achievement of VO2 plateau in pre-pubertal boys.

A low anaerobic power has been proposed as a factor that may be limiting the achievement of a plateau in VO2 of children who perform maximal aerobic power tests. This study examined the frequency of plateau achievement in pre-pubertal children and compared VO2max, peak (PP) and mean (MP) anaerobic power in subjects who either achieved a plateau (PLAT) or did not (NO PLAT). Eighteen healthy pre-pubertal (Tanner Stage, pubic hair = 1) males (age = 9.1 1.6 yrs, ht = 134.4 +/- 9.7cm, wt = 33.3 +/- 9.2kg, VO2max = 40.0 +/- 6.7 ml x kg(-1) min(-1)) were tested. All subjects completed a 30 sec Wingate Anaerobic Test and a McMaster aerobic protocol to volitional fatigue on a cycle ergometer. Only 33% of the subjects met the PLAT criterion. No differences were found for PP or MP between those who achieved a plateau and those who did not (PLAT: PP= 6.3 +/- 0.8W/kg and MP = 5.2 +/- 0.7W/kg; NO PLAT: PP= 6.3 +/- 1.2 W/kg and MP = 5.2 +/- 1.3 W/kg). We conclude that anaerobic power is not a factor limiting the achievement of a plateau in VO2 of pre-pubertal boys who perform maximal aerobic power tests.

Neonatal stridor: a life-threatening condition.

Stridor, when present since birth, should alert the physician of the possibility of a major cause of airway obstruction. In some cases, it can be life-threatening if timely and adequate intervention is not performed. In this report we discuss an infant who presented with stridor since birth. It's clinical picture, diagnostic approach and management are reviewed. The use of fiberoptic bronchoscopy as the most important diagnostic tool in the evaluation of stridor is emphasized and prompt referral for proper evaluation is recommended.

Profile of pediatric admissions with diagnosis of asthma at the San Pablo Hospital.

Bronchial Asthma morbidity and mortality appear to be increasing. In our continuing endeavor to investigate the asthma problem in Puerto Rico, we describe the profile or group of pediatric patients admitted with asthma during a three month period of time to a community hospital. This is intended to be an initial step in developing a more detailed study to evaluate risk factors for hospitalization and need for acute care management of children with asthma in Puerto Rico. We evaluated a group of patients admitted with the diagnosis of asthma (ICD-9 code 493). One hundred and nineteen admissions between August 22 and November 21, 1990 (ninety days) were reviewed retrospectively. Data extracted from the records included demographic, laboratory and physiological variables. Results were similar for both sexes. Asthma admissions represented 29 percent of the total admissions with a hospital stay of 4.07 +/- 1.09 days and age of 4.62 +/- 4.29 years (mean +/- SD). No pulmonary function tests were performed as criteria for admission. In conclusion, this study suggests that the need for hospitalization in children with asthma in a community hospital is based on clinical evaluation. The use of pulmonary function tests, peak expiratory flow measurement or both may not be suitable for the majority of children admitted with asthma due to age. Other criteria for younger children with asthma need to be developed.

Flexible bronchoscopy in children at the University of Puerto Rico Pediatric Hospital. Review of 324 consecutive patients.

Described are the findings resulting from 324 bronchoscopies performed with the flexible bronchoscope during the past 8 years at the University of Puerto Rico Pediatric Hospital. Neonates, infants, children and adolescents were included. The most frequent indications for the procedure were stridor, recurrent or persistent pneumonia, atelectasis, recurrent croup and persistent wheezing. An abnormality was detected in 88 per cent of the patients and the finding often resulted in significant modifications of treatment or allowed for reassurance. Complications were minor and there was no mortality. We conclude that the procedure, as we describe it, is save, effective and useful.