An epistatic interaction between pre-natal smoke exposure and socioeconomic status has a significant impact on bronchodilator drug response in African American youth with asthma.

BACKGROUND: Asthma is one of the leading chronic illnesses among children in the United States. Asthma prevalence is higher among African Americans (11.2%) compared to European Americans (7.7%). Bronchodilator medications are part of the first-line therapy, and the rescue medication, for acute asthma symptoms. Bronchodilator drug response (BDR) varies substantially among different racial/ethnic groups. Asthma prevalence in African Americans is only 3.5% higher than that of European Americans, however, asthma mortality among African Americans is four times that of European Americans; variation in BDR may play an important role in explaining this health disparity. To improve our understanding of disparate health outcomes in complex phenotypes such as BDR, it is important to consider interactions between environmental and biological variables. RESULTS: We evaluated the impact of pairwise and three-variable interactions between environmental, social, and biological variables on BDR in 233 African American youth with asthma using Visualization of Statistical Epistasis Networks (ViSEN). ViSEN is a non-parametric entropy-based approach able to quantify interaction effects using an information-theory metric known as Information Gain (IG). We performed analyses in the full dataset and in sex-stratified subsets. Our analyses identified several interaction models significantly, and suggestively, associated with BDR. The strongest interaction significantly associated with BDR was a pairwise interaction between pre-natal smoke exposure and socioeconomic status (full dataset IG: 2.78%, p = 0.001; female IG: 7.27%, p = 0.004)). Sex-stratified analyses yielded divergent results for females and males, indicating the presence of sex-specific effects. CONCLUSIONS: Our study identified novel interaction effects significantly, and suggestively, associated with BDR in African American children with asthma. Notably, we found that all of the interactions identified by ViSEN were "pure" interaction effects, in that they were not the result of strong main effects on BDR, highlighting the complexity of the network of biological and environmental factors impacting this phenotype. Several associations uncovered by ViSEN would not have been detected using regression-based methods, thus emphasizing the importance of employing statistical methods optimized to detect both additive and non-additive interaction effects when studying complex phenotypes such as BDR. The information gained in this study increases our understanding and appreciation of the complex nature of the interactions between environmental and health-related factors that influence BDR and will be invaluable to biomedical researchers designing future studies.

Novel genetic risk factors for asthma in African American children: Precision Medicine and the SAGE II Study.

Asthma, an inflammatory disorder of the airways, is the most common chronic disease of children worldwide. There are significant racial/ethnic disparities in asthma prevalence, morbidity, and mortality among US children. This trend is mirrored in obesity, which may share genetic and environmental risk factors with asthma. The majority of asthma biomedical research has been performed in populations of European decent. We sought to identify genetic risk factors for asthma in African American children. We also assessed the generalizability of genetic variants associated with asthma in European and Asian populations to African American children. Our study population consisted of 1227 (812 asthma cases, 415 controls) African American children with genome-wide single nucleotide polymorphism (SNP) data. Logistic regression was used to identify associations between SNP genotype and asthma status. We identified a novel variant in the PTCHD3 gene that is significantly associated with asthma (rs660498, p = 2.2 × 10(-7)) independent of obesity status. Approximately 5 % of previously reported asthma genetic associations identified in European populations replicated in African Americans. Our identification of novel variants associated with asthma in African American children, coupled with our inability to replicate the majority of findings reported in European Americans, underscores the necessity for including diverse populations in biomedical studies of asthma.

Anatomy of the ulnar nerve at the elbow: potential relationship of acute ulnar neuropathy to gender differences.

Men develop perioperative ulnar neuropathies more frequently than women. To determine the role of anatomical gender differences in the development of these neuropathies, we performed several studies of the anatomy of the ulnar nerve, cubital tunnel, and elbow region. These studies included detailed dissection of male and female embalmed and unembalmed cadavers, ultrasound measurements of the tissue layers at the elbow, and measurement of various dimensions of the coronoid process of the ulna in multiple skeletal sets. No gross anatomical differences were found between genders regarding the course of the ulnar nerve through the upper limb. However, there was a strikingly larger (2-19 times greater) fat content on the medial aspect of the elbow in women compared to men, and the tubercle of the coronoid process was approximately 1.5 times larger in men (P < or = .002, rank sum test). Our finding suggest that the tubercle of the coronoid process is a likely area for external compression-induced ischemia of the ulnar nerve because the nerve and its arterial supply (the posterior ulnar recurrent artery) are covered at the tubercle only by skin, subcutaneous fat, and a very thin aponeurosis of the flexor carpi ulnaris. Importantly, this tubercle is larger and the nerve and blood vessels passing by it are less protected by subcutaneous fat in men than in women. These two anatomical differences between men and women may contribute to the increased frequency of perioperative ulnar neuropathy induced by external pressure at the medial aspect of the elbow in men.

Diabetes mellitus and difficult laryngoscopy in renal and pancreatic transplant patients.

UNLABELLED: Limited mobility of the cervical spine or temperomandibular joint may contribute to increased difficulty of laryngoscopy in patients who have severe diabetes mellitus. The frequency of difficult laryngoscopy in diabetics undergoing renal and/or pancreatic transplants has been reported to be as high as 32%. We retrospectively reviewed the anesthetic records of all adult patients who underwent renal and/or pancreatic transplant and endotracheal intubation from January 1, 1985 to October 31, 1995. Characteristics specifically reviewed included the presence of diabetes mellitus, type of organ donor, age, gender, body mass index, previous difficult laryngoscopy, known characteristics potentially related to difficult laryngoscopy, and degree of difficulty with laryngoscopy. Laryngoscopy was graded as easy, minimally to moderately difficult, and moderately to extremely difficult to perform. Factors associated with any degree of difficult intubation were univariately assessed by using Fisher's exact test. Of 725 patients, 15 (2.1%) were identified as having difficult laryngoscopies, although all underwent successful endotracheal intubations. Factors associated with difficult laryngoscopy were diabetes mellitus (P = 0.002) and characteristics known to be related to difficult laryngoscopy (P = 0.02). These findings confirm an increase in the frequency of difficult laryngoscopy in diabetic patients undergoing renal and/or pancreatic transplant, although no laryngoscopies were rated as moderately to extremely difficult. We conclude that the frequency of difficult laryngoscopy in these diabetic patients is much lower than previous reports have suggested. IMPLICATIONS: Previous studies have suggested that airway management of many diabetic patients may be difficult. Our medical record review of patients with severe diabetes undergoing organ transplants showed that extraordinary techniques were not required to successfully manage their airways.