Obstructive Sleep Apnea in the Formerly Preterm Infant: An Overlooked Diagnosis

Background: Obstructive sleep apnea syndrome (OSA) is a frequent disorder in children. The clinical characteristics of OSA in very young children under 2 years of age, and more particularly, in those born prematurely, and who have respiratory complications such as bronchopulmonary dysplasia (BPD), are not well defined. We therefore retrospectively reviewed our experience in a group of preterm infants with OSAS. Methods: The records of premature infants with BPD followed in the Pediatric Pulmonary Clinic at the University of Chicago who were diagnosed with OSA from 2004 to 2009 were reviewed and analyzed. Results: Twelve children, eight males, and four females with a mean gestational age of 27 weeks were found to have OSA. Mean age at diagnosis was 19 months. Inability to wean nighttime oxygen, the need to resume oxygen after intercurrent respiratory illness, and snoring were the most common presenting symptoms. The apnea–hypopnea index ranged from 1 to 120/h total sleep time (TST; mean: 29). SpO2 nadir ranged from 50 to 91%. Despite adenotonsillectomy (AT), all children had persistent sleep disordered breathing. Conclusion: In preterm infants, while snoring is a frequent symptom, poor weight gain, and inability to wean nighttime oxygen may indicate the need for further investigation for OSA. In the former preterm infant structural changes in the airway may play an important role along with adenotonsillar hypertrophy. A high level of clinical awareness is required to identify OSA in the formerly preterm infant

Variation in ITGB3 Is Associated with Asthma and Sensitization to Mold Allergen in Four Populations

Rationale: Recent genetic studies have implicated integrins in asthma and atopy susceptibility. We therefore evaluated the integrin-β3 gene (ITGB3), an integrin gene within an asthma linkage peak on chromosome 17, as a candidate for susceptibility to asthma- and atopy-related phenotypes. Methods and Measurements: We genotyped and performed association tests on 19 single nucleotide polymorphisms in ITGB3 in the Hutterites, a founder population, and in three outbred replication populations. Main Results: Variation in ITGB3 was strongly associated with susceptibility to bronchial hyperresponsiveness and protection from allergic sensitization to mold allergens in this population. Three independent case-control populations representing Caucasians and African Americans were used to replicate this finding, also revealing ITGB3 alleles that are associated with asthma susceptibility and protection from mold allergen sensitization. Conclusions: This study provides evidence that ITGB3 plays a role in the pathogenesis of asthma and sensitization to mold allergens

Genomewide Screen and Identification of Gene-Gene Interactions for Asthma-Susceptibility Loci in Three U.S. Populations: Collaborative Study on the Genetics of Asthma

The genomewide screen to search for asthma-susceptibility loci, in the Collaborative Study on the Genetics of Asthma (CSGA), has been conducted in two stages and includes 266 families (199 nuclear and 67 extended pedigrees) from three U.S. populations: African American, European American, and Hispanic. Evidence for linkage with the asthma phenotype was observed for multiple chromosomal regions, through use of several analytical approaches that facilitated the identification of multiple disease loci. Ethnicity-specific analyses, which allowed for different frequencies of asthma-susceptibility genes in each ethnic population, provided the strongest evidence for linkage at 6p21 in the European American population, at 11q21 in the African American population, and at 1p32 in the Hispanic population. Both the conditional analysis and the affected-sib-pair two-locus analysis provided further evidence for linkage, at 5q31, 8p23, 12q22, and 15q13. Several of these regions have been observed in other genomewide screens and linkage or association studies, for asthma and related phenotypes. These results were used to develop a conceptual model to delineate asthma-susceptibility loci and their genetic interactions, which provides a promising basis for initiation of fine-mapping studies and, ultimately, for gene identification

Variation in the Interleukin 4–Receptor α Gene Confers Susceptibility to Asthma and Atopy in Ethnically Diverse Populations

After a genomewide screen in the Hutterites was completed, the IL4RA gene was examined as the 16p-linked susceptibility locus for asthma and atopy. Seven known variants and one novel variant, representing all nonsynonymous substitutions in the mature protein, were examined in the Hutterites; on the basis of studies in the Hutterites, outbred white, black, and Hispanic families were genotyped for selected markers. All population samples showed evidence of association to atopy or to asthma (P values .039–.0044 for atopy and .029–.0000061 for asthma), but the alleles or haplotypes showing the strongest evidence differed between the groups. Overall, these data suggest that the IL4RA gene is an atopy- and asthma-susceptibility locus but that variation outside the coding region of the gene influences susceptibility