Known Risk Factors For Disease Research Articles

Evaluation and Management of the Individual with Recurrent High Altitude Pulmonary Edema.

Luks AM, Grissom CK. Evaluation and Management of the Individual with Recurrent HAPE. High Alt Med Biol. 00:000-000, 2024. Individuals with a history of acute altitude illness often seek recommendations from medical providers on how to prevent such problems on future ascents to high elevation. Although many of these cases can be managed with pharmacologic prophylaxis and counseling about the appropriate rate of ascent alone, there are some situations in which further diagnostic evaluation may also be warranted. One such situation is the individual with recurrent episodes of high altitude pulmonary edema (HAPE), as one of several predisposing factors may be present that warrants additional interventions beyond pharmacologic prophylaxis and slow ascent and may even preclude future travel to high altitude. This review considers this situation in greater detail. Structured around the case of an otherwise healthy 27-year-old individual with recurrent episodes of HAPE who would like to climb Denali (6,190 m), the review examines the known risk factors for disease and then provides guidance regarding when and how to evaluate such individuals and appropriate steps to prevent HAPE on further ascents to high elevation. Except in rare circumstances, a history of recurrent HAPE does not preclude further ascent to high elevation, as a multipronged approach including pharmacologic prophylaxis, careful planning about the rate of ascent, and the degree of physical effort and other strategies, such as preacclimatization, staged ascent, and use of hypoxic tents, can be employed to reduce the risk of recurrence with future travel.

Obesity May Enhance the Adverse Effects of NO2 Exposure in Urban Schools on Asthma Symptoms in Children

To evaluate relationships between inner-city classroom NO2 exposure and asthma symptoms and morbidity by BMI category.Children aged 4 to 13 (n = 271) years from 37 inner-city schools who had physician-diagnosed asthma for at least 1 year and were using daily preventive asthma medication, had wheezing within the last year, and/or had at least 1 unscheduled health care visit for asthma within the past year.This was a single-center prospective study conducted within the School Inner-City Asthma Study. Before the start of the academic year, baseline demographics, environmental factors, and asthma symptoms and medication use were obtained by questionnaire. Baseline evaluations included skin testing to common seasonal and perennial aeroallergens or by assessment serum-specific IgE to the same allergens, spirometry, and fractional exhaled nitric oxide (FeNO) measurement. BMI percentile was calculated and categorized by using CDC classifications. Classroom NO2 was measured twice during the school year, ∼6 months apart. The primary outcome was the number of days with asthma symptoms within the previous 14 days. The secondary outcomes assessed in the previous 2 weeks were the number of exacerbations (hospitalizations or unscheduled health care visits for asthma), the number of days caretakers had to change plans because of the child’s asthma symptoms, FeNO level, and pulmonary function (forced expiratory volume in 1 second [FEV1] and forced vital capacity [FVC]).Participants were predominantly African American and Hispanic (35% each) and impoverished (49% had an annual household income <$25 000). A total of 50% had normal BMI (fifth percentile to <85th percentile), 15% were overweight (85th percentile to <95% percentile), and 35% were obese (≥95th percentile). Most (69%) were atopic, with specific immunoglobulin E to at least 1 aeroallergen. Obese students with asthma had statistically (but likely not clinically relevant) lower pulmonary function (FEV1 and FVC but not FEV1/FVC ratio), more positive skin test results, and lower FeNO than students with normal weight. The BMI category did not affect asthma symptom days, asthma symptoms, medication use, health care use for asthma, or missed school days. Caretakers of children with normal weight changed their plans more often than those of students who were overweight or obese. For children with normal weight or those who were overweight, NO2 levels were not associated with any of the measured outcomes. However, among children who were obese, for every 10-fold increase in NO2 level there were increased odds of asthma symptom days (1.9-fold), acute asthma-related health care use (2.4-fold), a missed school day because of asthma (3.1-fold), and care takers’ plans being changed because of the child’s asthma (4.2-fold). As compared with children with normal weight, in students who were obese, every 10 parts per billion increase in classroom NO2 level increased the likelihood of an asthma symptom day (odds ratio: 1.86; 95% confidence interval: 1.15 to 3.02) and of care takers changing their plans (odds ratio: 4.24; 95% confidence interval: 2.33 to 7.70). NO2 levels did not affect other outcomes, lung function, or FeNO across BMI categories.Obesity in inner-city students with asthma appears to increase susceptibility to the adverse effects of classroom NO2.NO2 is formed by combustion of liquid or solid fossil fuels. Indoor sources include gas stoves, heaters, and poorly ventilated furnaces and fireplaces. Furthermore, outdoor levels are elevated in heavily trafficked urban areas. The Environmental Protection Agency’s standard for safe outdoor level of NO2 is ∼50 parts per billion over a 1-year averaging time and 100 parts per billion over a 1 hour averaging time. Although the authors of this study do not specifically report classroom NO2 levels, it is clear from the 2 figures in the article that levels did not exceed 30 parts per billion, hence they were nowhere near the level up to which the Environmental Protection Agency considers safe. This is a warning that “safe” might not be safe enough. I think we all recognize the multiple and varied effects that both pollution and obesity have on health. With this study, the authors suggest synergy between 2 health risk factors and indicate that, as physicians, we must address all known risk factors for disease as we provide the best preventive and prospective care we can.

Overview of nontuberculous mycobacterial disease in children.

Nontuberculous mycobacteria (NTM) are ubiquitous organisms in our surrounding environment. Four distinct clinical syndromes associated with NTM infection have been described: skin and soft tissue disease, lymphadenitis, disseminated disease and pulmonary disease. In children, lymphadenitis is the most common NTM clinical entity, particularly affecting those aged 1-5 years who have no known risk factors for disease. Optimal management of NTM lymphadenitis is not entirely clear, although surgical intervention is likely a definitive therapy. Disseminated NTM disease is uncommon and only seen in the setting of immunocompromise. In previously well children, this presentation should always lead to consideration of an underlying immune defect, such as Mendelian susceptibility to mycobacterial disease. Identification of the underlying cause enables more targeted therapy and better prognostic understanding. Pulmonary NTM disease is fundamentally different to the other clinical syndromes, presenting in different hosts, who have different comorbidities, and follow a different clinical course.

Whole genome sequencing for antimicrobial resistance mechanisms, virulence factors and clonality in invasive Streptococcus agalactiae blood culture isolates recovered in Australia

Invasive Streptococcus agalactiae (Group B streptococci, GBS) infections result in a large burden of disease globally. Changes in clinical and molecular epidemiology, as well as antibiotic resistance patterns, are being described globally amongst GBS isolates. Very little is known about the characteristics of invasive GBS disease in the Australian setting. Therefore, this study aimed to define the clinical and genomic characteristics of invasive GBS isolates from the Sunshine Coast region in Australia. Thirty-two isolates were identified over a 3-year period. Known risk factors for disease were present in 71.9% and the leading site of disease was the skin and soft tissue (40.6%). Sequence types (ST) 1, 17 and 23 made up 50% with ST17 making up 56.2% of the total. Serotype Ia was the most prevalent (9/32, 28.1%). Clindamycin and erythromycin resistance was seen in 12.5% and 25%, respectively. Active surveillance and local knowledge of GBS epidemiology and antibiotic resistance has both patient and public health importance. Vaccine candidates are currently in their clinical phase of development.

Influence of Acute Mental Arithmetic Stress on Taste and Pungency.

Mental stress is a known risk factor for disease. This study investigated changes in sensations of taste and pungency before and after mental stress. Thirty healthy male university students rested for 20 min, performed mental arithmetic tasks for 10 min, and then underwent measurement of changes in their taste and ability to discern pungency. Taste was measured with the "Taste Disk®," and pungency was measured by a filter-paper disc method using capsaicin solution. Subjects were not told the order of the reagent solutions used. To quantify pain sensation, a weak current applied to the central inner forearm skin by a Pain Vision® quantitative pain sensation analyzer was gradually increased. The degree of stress was measured by portable electrocardiography (ECG). During mental stress, the cognitive threshold of salty taste, sweet taste, and bitterness was significantly decreased, whereas the sensations of pungency and forearm skin pain were increased and showed significant correlation. Based on sympathetic nerve activity analyzed with the ECG, the subjects were divided into the mental stress group and non-mental stress group. The mental stress group experienced an increase in the pungency threshold and sensation of forearm skin pain with significantly high correlations obtained, whereas no correlation was found between these factors in the non-mental stress group. Acute mental stress increased the sensitivity to taste but decreased the sensitivity to the sensation of pungency on the tongue and pain on the skin. Sympathetic activity activated by stress may affect taste and the sensation of pungency.

A Type I Interferon Transcriptional Signature Precedes Autoimmunity in Children Genetically at Risk for Type 1 Diabetes

Diagnosis of the autoimmune disease type 1 diabetes (T1D) is preceded by the appearance of circulating autoantibodies to pancreatic islets. However, almost nothing is known about events leading to this islet autoimmunity. Previous epidemiological and genetic data have associated viral infections and antiviral type I interferon (IFN) immune response genes with T1D. Here, we first used DNA microarray analysis to identify IFN-β–inducible genes in vitro and then used this set of genes to define an IFN-inducible transcriptional signature in peripheral blood mononuclear cells from a group of active systemic lupus erythematosus patients (n = 25). Using this predefined set of 225 IFN signature genes, we investigated the expression of the signature in cohorts of healthy controls (n = 87), patients with T1D (n = 64), and a large longitudinal birth cohort of children genetically predisposed to T1D (n = 109; 454 microarrayed samples). Expression of the IFN signature was increased in genetically predisposed children before the development of autoantibodies (P = 0.0012) but not in patients with established T1D. Upregulation of IFN-inducible genes was transient, temporally associated with a recent history of upper respiratory tract infections (P = 0.0064), and marked by increased expression of SIGLEC-1 (CD169), a lectin-like receptor expressed on CD14+ monocytes. DNA variation in IFN-inducible genes altered T1D risk (P = 0.007), as exemplified by IFIH1, one of the genes in our IFN signature for which increased expression is a known risk factor for disease. These findings identify transient increased expression of type I IFN genes in preclinical diabetes as a risk factor for autoimmunity in children with a genetic predisposition to T1D.

Systemic inflammation in 222.841 healthy employed smokers and nonsmokers: white blood cell count and relationship to spirometry

BackgroundSmoking has been linked to low-grade systemic inflammation, a known risk factor for disease. This state is reflected in elevated white blood cell (WBC) count.ObjectiveWe analyzed the relationship between WBC count and smoking in healthy men and women across several age ranges who underwent preventive medical check-ups in the workplace. We also analysed the relationship between smoking and lung function.MethodsCross-sectional descriptive study in 163 459 men and 59 382 women aged between 16 and 70 years. Data analysed were smoking status, WBC count, and spirometry readings.ResultsTotal WBC showed higher counts in both male and female smokers, around 1000 to 1300 cell/ml (t test, P < 0.001). Forced expiratory volume in 1 second (FEV1%) was higher in nonsmokers for both sexes between 25 to 54 years (t test, P < 0.001). Analysis of covariance showed a multiple variable effect of age, sex, smoking status, body mass index on WBC count. The relationship between WBC blood count and smoking status was confirmed after the sample was stratified for these variables. Smokers with airway obstruction measured by FEV1% were found to have higher WBC counts, in comparison to smokers with a normal FEV1% among similar age and BMI groups.ConclusionsSmoking increases WBC count and affects lung function. The effects are evident across a wide age range, underlining the importance of initiating preventive measures as soon as an individual begins to smoke.

Multi-locus variable number tandem repeat analysis for investigation of the genetic association of Clostridium difficile isolates from food, food animals and humans

Clostridium difficile is the primary known cause of antibiotic-associated diarrhea. Diarrheal disease in food animals due to C. difficile infection has been well documented. Recently, reports of C. difficile infections in patients with no known risk factors for disease have raised concern of community acquisition through food animals and food. In this study, multi-locus variable number tandem repeat analysis (MLVA) was performed on a collection of 97 C. difficile isolates of human, animal and food origin belonging to either the North American pulsed-field type (NAP) 1 or NAP7/NAP8. MLVA discriminated between NAP1 and NAP7/NAP8 populations. Three clusters of food, food animal and human NAP1 isolates were highly related by MLVA. These data suggest the possibility of either laboratory contamination or widespread distribution of clonal C. difficile populations. Community-associated NAP1 isolates were unrelated to NAP1 food and food animal isolates. Two MLVA loci were absent and 1 was invariant in all NAP7/NAP8 isolates. Therefore, MLVA discrimination was not sufficient to make assessments regarding the genetic associations among food, food animal and human isolates belonging to the NAP7/NAP8 pulsovar. Rigorous epidemiologic and laboratory investigations that employ highly discriminatory genotyping methods are necessary to compare C. difficile isolates from food and food animals to those from humans.

Body fat, abdominal fat and body fat distribution related to VO2PEAKin young children

Aerobic fitness, defined as maximum oxygen uptake (VO(2PEAK)), and body fat measurements represent two known risk factors for disease. The purpose of this study was to investigate the relationship between VO(2PEAK) and body fat measurements in young children at a population-based level. Cross-sectional study of 225 children (128 boys and 97 girls) aged 8-11 years, recruited from a population-based cohort. Total lean body mass (LBM), total fat mass (TBF), and abdominal fat mass (AFM) were measured by dual-energy x-ray absorptiometry. Body fat was also calculated as a percentage of body mass (BF%) and body fat distribution as AFM/TBF. VO(2PEAK) was assessed by indirect calorimetry during maximal exercise test. Significant relationships existed between body fat measurements and VO(2PEAK) in both boys and girls, with Pearson correlation coefficients for absolute values of VO(2PEAK) (0.22-0.36, P< 0.05), and for VO(2PEAK) scaled by body mass (-0.38 - -0.70, P<0.05). No relationships were detected for VO(2PEAK) scaled to LBM (-0.17-0.04, all not significant). Boys and girls in the lowest quartile according to body fat measurements had higher absolute values of VO(2PEAK) and lower values of VO(2PEAK) scaled by body mass, compared with those in the highest quartile. No differences were found for VO(2PEAK) scaled to LBM. Our findings document the coexistence of two known risk factors for disease at a young age and confirms that VO(2PEAK) was scaled to LBM may be a better, body fat independent way of expressing fitness.

Aerobic fitness in prepubertal children according to level of body fat

The purpose of this study was to investigate the relationship between maximum oxygen uptake (VO(2PEAK) ) and body fat in young children on a population-based level. Participants were 586 children (311 boys and 275 girls) aged 6.8±0.4 years, recruited from a population-based cohort. VO(2PEAK) was measured by indirect calorimetry during a maximal exercise test. Percent body fat (BF%) was estimated from skinfold measurements. Significant relationships existed between BF% and absolute values of VO(2PEAK) (mL/min), VO(2PEAK) scaled by body weight (mL/min/kg) and VO(2PEAK) by allometric scaling (mL/min/kg(0.71) ), whereas no relationships were detected for VO(2PEAK) scaled to fat-free mass (FFM) (mL/min/FFM). Person correlation coefficients for boys were 0.26, -0.38, -0.19 and -0.01 NS and for girls 0.33, -0.42, -0.21 and -0.03 NS, respectively. Significant differences in VO(2PEAK) existed between different quartiles of BF%, with the exception when VO(2PEAK) was scaled to FFM. Our findings document the coexistence of two known risk factors for disease at a young age on a population-base and confirms that VO(2PEAK) was scaled to FFM represents a body fat independent way of expressing fitness.

Hepatocellular carcinoma metastases to the epidural space.

Hepatocellular carcinoma (HCC) is relatively uncommon in the United States, although hepatitis C, one of the known risk factors for disease, is currently showing burgeoning growth in the country. Hence, it is possible that the incidence of HCC also will increase. Clinicians and pathologists in the United States are relatively unfamiliar with the patterns of metastatic spread for HCC. We report 2 US-native patients with cirrhosis and HCC who developed epidural space metastasis, a pattern of disease spread seen infrequently, even in endemic areas. Diagnostic testing was delayed in both patients because of the lowered suspicion for metastasis and the fact that neither patient had recognized metastatic spread to more common sites, such as lung or lymph nodes. New-onset neck or back pain-especially with symptoms of paresthesia, radiculopathy, or cord compression-in the setting of HCC warrants prompt investigation for metastases to the spine and epidural space.

Hepatocellular Carcinoma Metastases to the Epidural Space

Hepatocellular carcinoma (HCC) is relatively uncommon in the United States, although hepatitis C, one of the known risk factors for disease, is currently showing burgeoning growth in the country. Hence, it is possible that the incidence of HCC also will increase. Clinicians and pathologists in the United States are relatively unfamiliar with the patterns of metastatic spread for HCC. We report 2 US-native patients with cirrhosis and HCC who developed epidural space metastasis, a pattern of disease spread seen infrequently, even in endemic areas. Diagnostic testing was delayed in both patients because of the lowered suspicion for metastasis and the fact that neither patient had recognized metastatic spread to more common sites, such as lung or lymph nodes. New-onset neck or back pain-especially with symptoms of paresthesia, radiculopathy, or cord compression-in the setting of HCC warrants prompt investigation for metastases to the spine and epidural space.

Salivary slgA and Cortisol: Markers for Functional Dependence in Older Adults

Elderly persons with health problems and physical limitations have reduced independence. Since poor functional ability is a known risk factor for disease among older populations, including oral disease, this study was undertaken to assess whether salivary defense factors and the stress hormone cortisol are significant markers for functional dependence. Oral examinations; salivary and microbial analyses; and interviews using the Activities of Daily Living (ADD index, the Mini Nutritional Assessment (MNA) and the Perceived Life Stress Questionnaire (PLSQ) were conducted for 123 dentate subjects. Of the subjects, 80 lived independently in the community or in apartments at the Baycrest Centre for Geriatric Care in Toronto, Canada, and 43 resided in the Baycrest nursing home or the Baycrest Hospital. Whole saliva samples were assayed for total secretory immunoglobulin A (sIgA), sIgA1, sIgA2, total protein and cortisol using ELISA. Dependent residents in the nursing home/hospital scored significantly lower in the nutritional assessment, had higher mean PLSQ scores, increased total protein and cortisol concentrations, and reduced salivary flow rates in comparison to ambulatory residents in the community/apartments. In multivariable logistic regression, factors associated with functional dependence were: being male, perceiving income as inadequate, having low salivary flow rate and drinking less than 5 cups of water per day. These results indicate that salivary flow and cortisol may be useful markers of functional dependence; however, the ability of these markers to predict functional decline cannot be confirmed until longitudinal studies are conducted.