APOM and high-density lipoprotein cholesterol are associated with lung function and per cent emphysema.

Chronic obstructive pulmonary disease (COPD) is linked to cardiovascular disease; however, there are few studies on the associations of cardiovascular genes with COPD. We assessed the association of lung function with 2100 genes selected for cardiovascular diseases among 20 077 European-Americans and 6900 African-Americans. We performed replication of significant loci in the other racial group and an independent consortium of Europeans, tested the associations of significant loci with per cent emphysema and examined gene expression in an independent sample. We then tested the association of a related lipid biomarker with forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) ratio and per cent emphysema. We identified one new polymorphism for FEV1/FVC (rs805301) in European-Americans (p=1.3×10(-6)) and a second (rs707974) in the combined European-American and African-American analysis (p=1.38×10(-7)). Both single-nucleotide polymorphisms (SNPs) flank the gene for apolipoprotein M (APOM), a component of high-density lipoprotein (HDL) cholesterol. Both were replicated in an independent cohort. SNPs in a second gene related to apolipoprotein M and HDL, PCSK9, were associated with FEV1/FVC ratio among African-Americans. rs707974 was associated with per cent emphysema among European-Americans and African-Americans and APOM expression was related to FEV1/FVC ratio and per cent emphysema. Higher HDL levels were associated with lower FEV1/FVC ratio and greater per cent emphysema. These findings suggest a novel role for the apolipoprotein M/HDL pathway in the pathogenesis of COPD and emphysema.

Replication and fine mapping of asthma-associated loci in individuals of African ancestry.

Asthma originates from genetic and environmental factors with about half the risk of disease attributable to heritable causes. Genome-wide association studies, mostly in populations of European ancestry, have identified numerous asthma-associated single nucleotide polymorphisms (SNPs). Studies in populations with diverse ancestries allow both for identification of robust associations that replicate across ethnic groups and for improved resolution of associated loci due to different patterns of linkage disequilibrium between ethnic groups. Here we report on an analysis of 745 African-American subjects with asthma and 3,238 African-American control subjects from the Candidate Gene Association Resource (CARe) Consortium, including analysis of SNPs imputed using 1,000 Genomes reference panels and adjustment for local ancestry. We show strong evidence that variation near RAD50/IL13, implicated in studies of European ancestry individuals, replicates in individuals largely of African ancestry. Fine mapping in African ancestry populations also refined the variants of interest for this association. We also provide strong or nominal evidence of replication at loci near ORMDL3/GSDMB, IL1RL1/IL18R1, and 10p14, all previously associated with asthma in European or Japanese populations, but not at the PYHIN1 locus previously reported in studies of African-American samples. These results improve the understanding of asthma genetics and further demonstrate the utility of genetic studies in populations other than those of largely European ancestry.

Pulmonary function and left ventricular mass in African Americans: the Atherosclerosis Risk in Communities (ARIC) study.

PURPOSE: Impaired pulmonary function has been associated with increased cardiovascular disease incidence and mortality. The objective of this study was to investigate associations between pulmonary function and left ventricular (LV) mass. METHODS: Participants were African American women (n = 1,069) and men (n = 555) aged 49-73 years, from the Atherosclerosis Risk in Communities study. Mean pulmonary function values at the first (1987-1989) and second (1990-1992) examinations were used. Echocardiograms were performed at the third and early in the fourth examinations (1993-1996). Analysis of covariance and linear regression were used to assess associations. RESULTS: Mean levels of LV mass decreased with increasing quintiles of forced expiratory volume in one second (FEV(1) ) among female never smokers (P = 0.039). Forced vital capacity (FVC) showed stronger associations than FEV(1) with LV mass. Among men, LV mass was positively associated with FEV(1) among current and never smokers, and with FVC among never smokers. Additional analyses among never smokers revealed significant inverse associations between LV mass and FVC among women with waist-to-hip ratios of >0.85 and those with no history of diabetes. In contrast, significant positive associations between LV mass and FVC were seen among male never smokers with body mass index (BMI) of ≤24.9 kg/m(2) , waist-to-hip ratios of ≤0.95, no history of hypertension or diabetes, and ≤60 years old. BMI and waist-to-hip ratio significantly modified associations among men. CONCLUSIONS: Among never smokers, LV mass and pulmonary function were inversely associated among women and positively associated among men. Further studies are warranted.

Pericardial fat is associated with impaired lung function and a restrictive lung pattern in adults: the Jackson Heart Study.

BACKGROUND: Impaired lung function has been linked to obesity and systemic inflammation. Pericardial fat has been shown to be associated with anomalies in cardiac structure, function, and atherosclerosis. We hypothesized that pericardial fat may have a similar role in the impairment of lung function. METHODS: Cross-sectional associations of pericardial fat volumes, quantified by multidetector CT scan, with FEV(1) and FVC assessed by spirometry, were investigated in 1,293 participants (54.5 ± 10.8 years; 66.4% women) in the Jackson Heart Study. We also examined whether these associations were independent of visceral adipose tissue (VAT). RESULTS: Pericardial fat was associated with impaired lung function after multivariable adjustment, but these associations generally did not remain after adjustment for VAT. An exception was the FEV(1)/FVC ratio. Higher pericardial fat volumes were associated with higher odds of a restrictive lung pattern and lower odds of airway obstruction. Participants in the highest quartile had the highest odds of a restrictive lung pattern (OR, 1.85; 95% CI, 1.22-2.79, compared with quartile 1), even after adjustment for VAT. The odds of obstruction decreased across increasing quartiles of pericardial fat. These relationships were generally graded, suggesting dose-response trends. CONCLUSIONS: Pericardial fat is generally associated with lower lung function and independently associated with a restrictive lung pattern in middle-aged and elderly adults. Further research is needed to fully understand the mechanisms through which pericardial fat contributes to pulmonary anomalies.

Diabetes, impaired glucose tolerance, and metabolic biomarkers in individuals with normal glucose tolerance are inversely associated with lung function: the Jackson Heart Study.

The objectives of this study were to test the hypothesis that diabetes and impaired glucose tolerance (IGT), diabetes control and diabetes duration, and metabolic biomarkers in adults with normal glucose tolerance (NGT) are inversely associated with spirometry-measured lung function. We conducted a cross-sectional observational cohort study that included nonsmoking African American adults (n = 2,945; mean age = 52.5 ± 12.6 years; 69.2% female), who were free of cardiovascular disease, from the Jackson Heart Study. The interventions were diabetes, metabolic biomarkers and lung function. We measured the associations of glycemia with forced expiratory volume (FEV) in 1 s, FEV in 6 s, and vital capacity. Multivariable adjusted mean lung function values were lower among adults with diabetes and IGT (in women only, but not after adjustment for waist circumference) than adults with NGT. Among adults with diabetes, no associations were observed between lung function and diabetes control or duration. In women with NGT, lower lung function was consistently associated with higher glucose levels and less consistently with higher insulin levels and insulin resistance. Lower lung function was consistently associated with higher insulin levels and insulin resistance and less consistently associated with insulin and hemoglobin A1c in men with NGT. Overall, our findings generally support the hypothesis that diabetes, IGT, and increased levels of metabolic biomarkers in individuals with NGT are inversely associated with lung function in African Americans, independent of adiposity.

Leptin is inversely associated with lung function in African Americans, independent of adiposity: the Jackson Heart Study.

Leptin, a 16-kDa protein, has proinflammatory properties and has been linked to respiratory physiological responses in majority white populations. Little is known, however, about the relationship of leptin with lung function in nonwhites. Cross-sectional associations of circulating serum leptin concentrations with forced expiratory volume in 1 s (FEV(1)), FEV in 6 s (FEV(6)), and vital capacity (FVC), assessed by spirometry, were examined in 4,679 African-American men and women participants (54.3 ± 12.4 years; 62.7% women) in the Jackson Heart Study (JHS). The independent association of leptin was examined in relation to FEV(1), FEV(6), and FVC% predicted after adjustment for age, education, smoking status, pack-years of cigarette smoking, respiratory medication use, and menopausal status in women; additional adjustment included total body weight, waist circumference, and BMI. Serum leptin was inversely related to FEV(1), FEV(6), and FVC% predicted values in men. A dose-response relationship was observed with men in the highest leptin quartile having a significantly lower lung function compared to men in the lower leptin quartile. BMI significantly modified this relationship in women: leptin was most consistently associated with lung function in obese women, less consistent in overweight women, and absent in normal-weight women. Serum leptin concentration was strongly, inversely, and independently associated with lung function in African Americans, especially African-American men and obese women.

Asthma and asthma severity among African American adults in the Jackson Heart Study.

The aims of this study were to investigate the baseline prevalence of and risk factors associated with asthma, classify asthma severity, and describe medication use in a population-based sample of African American men and women 21 to 84 years of age from the Jackson Heart Study (JHS). Participants provided responses to respiratory and medical history questions and a medication inventory and underwent spirometry and other clinical examinations. These data were used to examine the extent to which novel and traditional risk factors were associated with asthma. Of the 4,098 participants included in this analysis, 9.4% reported lifetime asthma (5.7% current, 3.7% former), and current asthma was higher in women (6.8%) than in men (3.8%). An additional 9.8% reported an attack of wheeze with shortness of breath or non-doctor confirmed asthma (i.e., "probable" asthma). The mean forced expiratory volume in 1 second (FEV(1))% predicted was lower in those reporting current asthma (women: 83.7 +/- 18.0; men: 75.2 +/- 16.8) compared to those not reporting asthma (women: 95.6 +/- 16.7; men: 91.7 +/- 16.0). Current and probable asthma was associated with lower serum cortisol levels and hypertension medication use, along with traditional risk factors (i.e., lower socio-economic status, higher global stress scores, obesity, and fair to poor perceived general health). Severe asthma was low among participants reporting current (9.8%), former (3.3%), and probable (4.9%) asthma. Asthma medication use was reported by nearly 60% of the participants reporting current asthma. Asthma in African American adults is associated with decreased serum cortisol, hypertension medication use, and considerable lung function impairment compared to those who did not report asthma. The prevalence of asthma in the JHS is lower than state and national estimates, although the estimates are not directly comparable. Furthermore, asthma is drastically underdiagnosed in this population.

Effect of smoking on spirometry of African American and White subjects.

BACKGROUND: Smoking is the single most important risk factor for COPD, yet there is still disagreement about the differences in the effect of smoking between white and African-American people. We hypothesized that the results of spirometry between smokers of the two races are equivalent if reference equations and lower limits of normal appropriate for each race are used. METHODS: We retrospectively analyzed all spirometry results in smokers over a 1-year period from the G.V. (Sonny) Montgomery VA Medical Center and excluded those that did not meet American Thoracic Society standards, or those from patients with additional medical problems. The remaining patients were classified by race and then matched for age and smoking history; 108 patients in each group were included, which met the power analysis goal of 98. The two groups were similar in age (57.5 years vs 57.0 years), smoking history (46.1 pack-years vs 46.0 pack-years), and body mass index (27.0 kg/m(2) vs 28.3 kg/m(2)) for African Americans and whites, respectively. Data were analyzed using the unpaired t test, and p values were adjusted for multiple comparisons using the Bonferroni factor. RESULTS: There were statistically significant differences between African American and white smokers in FVC (3.67 +/- 0.07 L vs 4.26 +/- 0.08 L, p = 0.001) and FEV(1) (2.33 +/- 0.07 L vs 2.72 +/- 0.08 L, p = 0.002), as expected from the normal populations; however, there were no differences in FVC as percentage of predicted (89.1 +/- 1.3% vs 86.7 +/- 1.5%, p = 0.71) and FEV(1) as percentage of predicted (71.9 +/- 2.1% vs 72.2 +/- 1.8%, p = 1.00) when the reference equations appropriate for race were used (third National Health and Nutrition Examination Survey). There were also no differences between the number of subject with abnormal FEV(1)/FVC results (56 African Americans vs 58 whites, p = 1.00) when the appropriate lower limits of normal were used. CONCLUSIONS: There are no differences in spirometry findings between African Americans and whites when abnormality is defined appropriately using reference equations and lower limits of normal for each race. By using either percentage cutoffs for abnormality, or by adjusting for African-American equations only appropriate for whites, we were able to mimic with our data conflicting results in the literature.

Pleural tuberculosis in the United States: incidence and drug resistance.

BACKGROUND: Pleural tuberculosis (TB) should be considered in any patient with a lymphocytic pleural effusion. The diagnostic approach is under debate. Knowledge of pleural TB epidemiology would be beneficial. To help clarify pleural TB epidemiology, we analyzed US national TB surveillance data for 1993 to 2003. METHODS: We compared pleural TB to pulmonary TB (where each was reported as the major site of TB disease, and no additional sites of disease were reported). Applicable statistical tests were performed; p < 0.05 was considered to be significant. RESULTS: From 1993 through 2003, 7,549 cases of pleural TB and 156,779 cases of pulmonary TB were reported (in 2003: pleural TB, 536 cases; pulmonary TB, 10,551 cases). The annual proportion of pleural TB was relatively stable (median rate, 3.6%; range, 3.3 to 4.0%) compared to that for pulmonary TB, which steadily decreased (average annual decrease, 0.9%; p < 0.01). Pleural TB occurred significantly more often than pulmonary TB among persons >/= 65 years old (30.4% vs 23.3%, respectively; p < 0.01), and it occurred significantly less often among children < 15 years old (1.8% vs 6.1%, respectively; p < 0.01) and persons 45 to 64 years old (22.9% vs 27.9%, respectively; p < 0.01). Pleural TB patients (63.4%) were born slightly more often in the United States than were pulmonary TB patients (60.9%; p < 0.01). Drug-resistance patterns of pleural TB broadly reflected those of pulmonary TB. However, isolates from pleural TB patients were less often resistant to at least isoniazid (6.0% vs 7.8%, respectively; p < 0.01) and to at least one first-line TB drug (9.9% vs 11.9%, respectively; p < 0.01) compared with pulmonary TB patients. CONCLUSIONS: Knowledge of pleural TB demographic, clinical, and drug-resistance patterns may assist clinicians in making diagnostic and therapeutic decisions.

A prospective randomized comparison of train-of-four monitoring and clinical assessment during continuous ICU cisatracurium paralysis.

STUDY PURPOSE: Train-of-four (TOF) monitoring is often recommended during the continuous use of neuromuscular blockade (NMB) [paralysis] in the ICU. Prior study results are conflicting regarding the benefits of TOF monitoring. DESIGN: Thirty patients in the medical ICU were randomized to TOF monitoring (n = 16) or to clinical assessment (n = 14) during continuous cisatracurium infusion. TOF monitoring was done at least every 4 h, with the goal being maintenance of one to two twitches. Statistical analysis was performed by two-tailed, unpaired t test (with Bonferroni correction for multiple comparisons), chi(2), and Fisher exact test, with p < 0.05 considered significant. Given a power of 80%, and the variance seen in the two groups, we estimate that the sample size used is sufficient to detect a change of > or = 60 min between groups for recovery time. RESULTS: The mean recovery time after cessation of paralytics was no different between TOF and clinical assessment (45 +/- 7 min vs 38 +/- 10 min, respectively [mean +/- SEM]). No differences were noted for mean APACHE (acute physiology and chronic health evaluation) II entry scores, glomerular filtration rates, or use of corticosteroids. No significant differences were noted between TOF monitoring and clinical assessment in mean total paralysis time (4,118 +/- 1,012 min vs 3,188 +/- 705 min, respectively), mean total cisatracurium dose (920 +/- 325 mg vs 715 +/- 167 mg), or dosage (2.3 +/- 0.2 microg/kg/min vs 2.9 +/- 0.2 microg/kg/min). CONCLUSIONS: TOF monitoring does not lead to improved recovery time or lower cisatracurium dosing compared with monitoring by clinical assessment. We conclude that TOF monitoring is unnecessary, and careful titration of the neuromuscular blocking agent by clinical assessment alone is sufficient in patients undergoing continuous cisatracurium NMB.

Comparison of function of commercially available pleural drainage units and catheters.

PURPOSE: Flow rates and pressures generated by commercially available pleural drainage units (PDUs) and flow rates through available pleural drainage catheters (PDCs) are not known. This information may be important clinically depending on the volume of air leak associated with a bronchopleural fistula. DESIGN: Eight PDUs were assessed for flow rates at various suction levels and for the percent accuracy of suction pressures generated at various settings. Eleven commonly used PDCs were assessed for flow rates at various suction control levels. All devices were donated by their manufacturer. Flow rates and pressures were measured by a RT 200 Calibration Analyzer (Timeter Instrument Corporation; St. Louis, MO) at body temperature, ambient pressure, saturated with water vapor. Five devices of each type were tested. Analysis of variance was performed with p < 0.05 being significant. RESULTS: Multiple significant differences between PDUs were noted at a pressure of - 20 cm H(2)O. The Argyle Sentinel Seal (Sherwood Medical; Tillamore, Ireland) had significantly lower flow rates (mean +/- SD, 10.8 +/- 0.6 L/min) compared with all other models. The Argyle Aqua-Seal (Sherwood Medical) had the highest PDU flow rate of devices tested (42.1 +/- 1.0 L/min). The accuracy of PDUs at manufacturer-suggested settings varied from a mean percentage error of 0.0 to 15.5% from expected pressures; significant differences were noted in accuracy among multiple interdevice pressure comparisons. Similarly, multiple significant flow rate differences between PDCs were noted at - 20 cm H(2)O. Lowest flow rates were noted with thoracentesis catheters (used as PDCs) containing side ports. Arrow drainage catheters (14F, pigtail and straight) [Arrow International; Reading, PA] both had significantly greater flow rates (both, 16.8 +/- 0.1 L/min), compared with the 14F (12.8 +/- 0.3) and 16F (14.8 +/- 0.6) Cook devices (Cook; Bloomington, IN). CONCLUSIONS: These differences in flow rates for PDUs and PDCs may be clinically important, particularly in patients with large pneumothorax-related air leaks. Observed differences in PDU-generated pressures are likely not clinically important.