COPD Exacerbator Phenotype is Inversely Associated with Current Smoking But Not with Haptoglobin Phenotype.

BACKGROUND: Frequent chronic obstructive pulmonary disease (COPD) exacerbators are at a higher risk of adverse health outcomes when compared to infrequent exacerbators. A COPD frequent exacerbator phenotype and its definition has been reported. Haptoglobin (Hp) polymorphism has been associated with differing clinical outcomes in cardiovascular and renal disease. The Hp 2-2 phenotype has been found to have bacteriostatic properties, while the Hp 1-1 phenotype was found to be associated with infections. OBJECTIVES: To determine the correlation in haptoglobin phenotypes and the frequent exacerbator status compared to COPD non-exacerbators. METHODS: Inclusion criteria included previous diagnosis of COPD and presence of at least two documented exacerbations of COPD in the previous 12 months (frequent exacerbator group) or absence of such exacerbations in the previous 24 months (non-exacerbator group). Descriptive data was analyzed using Fisher's exact test and the nonparametric Kruskal-Wallis test. Multivariate logistic regression analysis was performed. RESULTS: The multivariate logistic regression yielded a model in which haptoglobin phenotype did not have a statistically significant association with frequent exacerbator status. Smoking status was found to be negatively related with the frequent exacerbator status (odds ratio [OR] 0.240, 95% confidence interval (95%CI) 0.068-0.843, P = 0.03). Number of pack-years was negatively related to being a frequent exacerbator (OR 0.979, 95%CI 0.962-0.996, P = 0.02). CONCLUSIONS: We found no relationship between haptoglobin polymorphism and frequent exacerbator status. However, frequent exacerbator status had a statistically significant association with COPD Assessment Test scores and pack-years and a negative correlation with current smoking status.

Green roof and photovoltaic panel integration: Effects on plant and arthropod diversity and electricity production.

The combination of green roofs with photovoltaic (PV) panels has been proposed to provide synergistic benefits as the panel is cooled by the presence of the vegetation, and thus produces more electricity, while the solar panel enhances growing conditions for vegetation, and increases abiotic heterogeneity, resulting in higher plant diversity. We tested these hypotheses in a non-irrigated green roof in a Mediterranean climate with replicated plots including green roofs only, green roofs with a PV panel, and a conventional roof surface with a PV panel. We found that presence of a panel resulted in higher heterogeneity in substrate moisture, but there was no effect on plant diversity. Plant species showed enhanced growth in plots with PV, including greater growth of Sedum sediforme and longer flowering time of annual species. On the other hand, arthropod diversity was lower during part of the year, and abundance of some arthropod taxa was lower in green roof plots with PV. The presence of the green roof also did not improve electricity production by the panels. We conclude that in a Mediterranean climate, it would be appropriate to examine the use of irrigation in green roofs with PV panels, including effects on the plant community and on electricity production.

Sedum-dominated green-roofs in a semi-arid region increase CO2 concentrations during the dry season.

Green roofs are expected to absorb and store carbon in plants and soils and thereby reduce the high CO2 concentration levels in big cities. Sedum species, which are succulent perennials, are commonly used in extensive green roofs due to their shallow root system and ability to withstand long water deficiencies. Here we examined CO2 fixation and emission rates for Mediterranean Sedum sediforme on green-roof experimental plots. During late winter to early spring, we monitored CO2 concentrations inside transparent tents placed over 1m2 plots and followed gas exchange at the leaf level using a portable gas-exchange system. We found high rates of CO2 emission at daytime, which is when CO2 concentration in the city is the highest. Both plot- and leaf-scale measurements showed that these CO2 emissions were not fully compensated by the nighttime uptake. We conclude that although carbon sequestration may only be a secondary benefit of green roofs, for improving this ecosystem service, other plant species than Sedum should also be considered for use in green roofs, especially in Mediterranean and other semi-arid climates.

Haptoglobin 2-2 Genotype Is Associated With Cerebral Salt Wasting Syndrome in Aneurysmal Subarachnoid Hemorrhage.

BACKGROUND: Haptoglobin (Hp) genotype has been shown to be a predictor of clinical outcomes in subarachnoid hemorrhage. Cerebral salt wasting (CSW) has been suggested to precede the development of symptomatic vasospasm. OBJECTIVE: To determine if Hp genotype was associated with CSW and subsequent vasospasm after aneurysmal subarachnoid hemorrhage. METHODS: Hp genotypic determination was done for patients admitted with a diagnosis of subarachnoid hemorrhage. Outcome measures included CSW, delayed cerebral infarction, and Glasgow Outcome Score of 4 to 5 at 30 days. Criteria for CSW included hyponatremia <135 mEq/L, and urine output >4 L in 12 hours with urine sodium >40 mEq/L. RESULTS: A total of 133 patients were included in the study. The 3 Hp subgroups did not differ in terms of baseline characteristics. CSW occurred in 1 patient (3.4%) with Hp 1-1, 8 (14.0%) patients with Hp 2-1, and 15 (31.9%) patients with Hp 2-2 (P = .004). In the multivariate regression model, Hp 2-2 was associated with CSW (odds ratio [OR]: 4.94; CI: 1.78-17.43; P = .01), but Hp 2-1 was not (OR: 2.92; CI: 0.56-4.95; P = .15) compared with Hp 1-1. There were no associations between Hp genotypes and functional outcome or delayed cerebral infarction. CSW was associated with delayed cerebral infarction (OR: 7.46; 95% CI: 2.54-21.9; P < .001). CONCLUSION: Hp 2-2 genotype was an independent predictor of CSW after subarachnoid hemorrhage. Because CSW is strongly associated with delayed cerebral infarction, the use of Hp genotype testing requires more investigation, and larger prospective confirmation is warranted. Additionally, a more objective definition of CSW needs to be delineated.

The Risk of Coronary Heart Disease Associated With Glycosylated Hemoglobin of 6.5% or Greater Is Pronounced in the Haptoglobin 2-2 Genotype.

BACKGROUND: Research targeting glycosylated hemoglobin A1c (HbA1c) to <6.5% to prevent coronary heart disease (CHD) events has conflicting results. We previously observed the haptoglobin (Hp) Hp2-2 genotype is associated with a ∼10-fold increased CHD risk among individuals with HbA1c ≥6.5%, and thus might be useful in identifying those at high risk of CHD who would benefit from maintaining HbA1c <6.5%. OBJECTIVES: This study sought to model whether HbA1c ≥ 6.5% in the Hp2-2 genotype is associated with CHD in a prospective case-control study nested within the Health Professionals Follow-Up Study (HPFS). METHODS: HbA1c concentration and Hp genotype were determined for 695 incident cases of CHD from 1994 to 2010 and matched control participants. Logistic regression models calculated relative risk (RR) and 95% CI, for the first and second halves of follow-up, adjusting for confounding variables. A dataset from the Nurses' Health Study served as a replication cohort. RESULTS: The prevalence of the Hp2-2 genotype in HPFS was 39%. Compared with HbA1c <6.5%, the RR of CHD for HbA1c ≥6.5% for the Hp2-2 genotype over full follow-up was 3.07 (95% CI: 1.37 to 6.86) to 3.88 (95% CI: 1.31 to 11.52) during the first half of follow-up and 2.16 (95% CI: 0.61 to 7.61) in the second half. The corresponding RRs for the Hp1-1 + Hp2-1 genotypes were: full follow-up, 2.19 (95% CI: 1.14 to 4.24); first half, 1.60 (95% CI: 0.73 to 3.53); and second half, 4.72 (95% CI: 1.26 to 17.65). CONCLUSIONS: In 2 independent cohorts, the risk of CHD associated with HbA1c ≥6.5% is pronounced in the Hp2-2 genotype, particularly in early cases. The Hp2-2 genotype may identify individuals at greatest CHD risk from hyperglycemia.

Lack of Association Between Haptoglobin Phenotype and Cystic Fibrosis Outcomes.

Haptoglobin (Hp), a heme-Iron chelator, has different isoforms which are associated with variable tendency toward infections: Hp 1-1, Hp 2-1, and Hp 2-2. Cystic fibrosis (CF) outcomes are variable and influenced by genetic and environmental factors. The aim of this study was to determine whether Hp phenotype influenced disease severity in CF. One hundred forty-two CF patients from two centers were analyzed for Haptoglobin phenotype using gel electrophoresis of hemoglobin enriched serum. Clinical and microbiological data including bacterial colonization status, lung function, presence of CF-related diabetes and liver disease, rate of exacerbation, and mortality were compared between Hp phenotype groups. We found a trend toward less mucoid PA among Hp 2-2 (20.4 %) compared with Hp 1-1 and Hp 2-1 individuals (33.3 %), p = 0.317. Hp 2-2 individuals also had less antibiotic courses, and lower inflammatory markers without statistical significance. Haptoglobin phenotype is unlikely to be an important modifier of CF phenotype.

Pharmacogenomic interaction between the Haptoglobin genotype and vitamin E on atherosclerotic plaque progression and stability.

OBJECTIVE: Homozygosity for a 1.7 kb intragenic duplication of the Haptoglobin (Hp) gene (Hp 2-2 genotype), present in 36% of the population, has been associated with a 2-3 fold increased incidence of atherothrombosis in individuals with Diabetes (DM) in 10 longitudinal studies compared to DM individuals not homozygous for this duplication (Hp 1-1/2-1). The increased CVD risk associated with the Hp 2-2 genotype has been shown to be prevented with vitamin E supplementation in man. We sought to determine if there was an interaction between the Hp genotype and vitamin E on atherosclerotic plaque growth and stability in a transgenic model of the Hp polymorphism. METHODS AND RESULTS: Brachiocephalic artery atherosclerotic plaque volume was serially assessed by high resolution ultrasound in 28 Hp 1-1 and 26 Hp 2-2 mice in a C57Bl/6 ApoE(-/-) background. Hp 2-2 mice had more rapid plaque growth and an increased incidence of plaque hemorrhage and rupture. Vitamin E significantly reduced plaque growth in Hp 2-2 but not in Hp 1-1 mice with a significant pharmacogenomic interaction between the Hp genotype and vitamin E on plaque growth. CONCLUSIONS: These results may help explain why vitamin E supplementation in man can prevent CVD in Hp 2-2 DM but not in non Hp 2-2 DM individuals.

Presence of haptoglobin-2 allele is associated with worse functional outcomes after spontaneous intracerebral hemorrhage.

OBJECTIVE: To determine if the haptoglobin (Hp) phenotype, which has been shown to be a predictor of clinical outcomes in cerebrovascular disorders, particularly subarachnoid hemorrhage, was predictive of functional outcomes after spontaneous intracerebral hemorrhage (ICH). METHODS: Patients admitted with a diagnosis of ICH were prospectively included and divided into 3 groups based on their genetically determined Hp phenotype: 1-1, 2-1, and 2-2. Outcome measures included mortality and 30-day modified Rankin Scale scores. Demographics and outcomes were compared for each phenotype using multivariate linear regression analysis. RESULTS: The study included 94 patients. The distribution of Hp phenotype was Hp 1-1, 12 (13%); Hp 2-1, 46 (49%); and Hp 2-2, 36 (38%). The 3 Hp subgroups did not differ in terms of demographic variables, comorbidities, or ICH characteristics. There was a nonsignificant trend toward increased mortality in Hp 2-1 and Hp 2-2 compared with Hp 1-1, with mortality of 8% in Hp 1-1, 17% in Hp 2-1, and 25% in Hp 2-2 (P = 0.408). In the regression model adjusted for confounders, Hp 2-1 (odds ratio = 0.05, 95% confidence interval = 0.01-0.47, P < 0.001) and Hp 2-2 phenotypes (odds ratio = 0.14, 95% confidence interval = 0.02-0.86, P = 0.045) had significantly lower odds of modified Rankin Scale scores 0-2 compared with Hp 1-1. CONCLUSIONS: After ICH, individuals with the Hp-2 allele (2-1 and 2-2) had worse functional outcomes than individuals with the Hp-1 allele (Hp 1-1). There was a nonsignificant association between Hp phenotype and mortality. Larger prospective studies with better surrogates of ICH outcomes are warranted.