Impact of heterozygote CFTR Mutations in COPD patients with Chronic Bronchitis

Background

Cigarette smoking causes Chronic Obstructive Pulmonary Disease (COPD), the 3rd leading cause of death in the U.S. CFTR ion transport dysfunction has been implicated in COPD pathogenesis, and is associated with chronic bronchitis. However, susceptibility to smoke induced lung injury is variable and the underlying genetic contributors remain unclear. We hypothesized that presence of CFTR mutation heterozygosity may alter susceptibility to cigarette smoke induced CFTR dysfunction. Consequently, COPD patients with chronic bronchitis may have a higher rate of CFTR mutations compared to the general population.

Methods

Primary human bronchial epithelial cells derived from F508del CFTR heterozygotes and mice with (CFTR+/-) and without (CFTR+/+) CFTR heterozygosity were exposed to whole cigarette smoke (WCS); CFTR-dependent ion transport was assessed by Ussing chamber electrophysiology and nasal potential difference measurements, respectively. Caucasians with COPD and chronic bronchitis, age 40 to 80 with FEV₁/FVC < 0.70 and FEV₁ < 60% predicted, were selected for genetic analysis from participants in the NIH COPD Clinical Research Network’s Azithromycin for Prevention of Exacerbations of COPD in comparison to 32,900 Caucasian women who underwent prenatal genetic testing. Genetic analysis involved an allele-specific genotyping of 89 CFTR mutations.

Results

Exposure to WCS caused a pronounced reduction in CFTR activity in both CFTR (+/+) cells and F508del CFTR (+/-) cells; however, neither the degree of decrement (44.7% wild-type vs. 53.5% F508del heterozygous, P = NS) nor the residual CFTR activity were altered by CFTR heterozygosity. Similarly, WCS caused a marked reduction in CFTR activity measured by NPD in both wild type and CFTR heterozygous mice, but the severity of decrement (91.1% wild type vs. 47.7% CF heterozygous, P = NS) and the residual activity were not significantly affected by CFTR genetic status. Five of 127 (3.9%) COPD patients with chronic bronchitis were heterozygous for CFTR mutations which was not significantly different from controls (4.5%) (P = NS).

Conclusions

The magnitude of WCS induced reductions in CFTR activity was not affected by the presence of CFTR mutation heterozygosity. CFTR mutations do not increase the risk of COPD with chronic bronchitis. CFTR dysfunction due to smoking is primarily an acquired phenomenon and is not affected by the presence of congenital CFTR mutations.     

Towards an ecological understanding of biological nitrogen fixation

Biogeochemistry - N limitation to primary production and other ecosystem processes is widespread. To understand the causes and distribution of N limitation, we must understand the controls of...     

Nitrogen and yield potential of irrigated rice

Yield potential of modern rice varieties and implications for N management were evaluated in a series of field studies that provided data for validation of an eco-physiological simulation model for rice. We tested the hypothesis that N was the major factor limiting yield potential of irrigated rice. The simulation model ORYZA1 was used to evaluate the observed yield differences between varieties grown with different N management and in different environments. The model explained differences in yield of the treatments resonably well on the basis of differences in radiation, temperature, leaf N content and variety coefficients for phenological development. It was demonstrated by the model and experimental data that yield levels of 6 t ha^-1 in the wet season and 10 t ha^-1 in the dry season can be obtained in the tropics with the current short duration varieties only when the N supply from soil and fertilizer is adequately maintained at key growth stages. Yield probabilities for rice crops were simulated for different environments using long term weather data at two Philippine sites.     

Plant nutrient management for enhanced productivity in intensive grain production systems of the United States and Asia

Plant and Soil - Are present nutrient management recommendations for the world's major cereal cropping systems adequate to sustain the productivity gains required to meet food demand while also...     

Acidification of Soil in a Dry Land Winter Wheat-sorghum/corn-fallow Rotation in the Semiarid U.S. Great Plains

Soil pH is decreasing in many soils in the semiarid Great Plains of the United States under dry land no-till (NT) cropping systems. This study was conducted to determine the rate of acidification and the causes of the acidification of a soil cropped to a winter wheat (Triticum aestivum L.)-grain sorghum [Sorghum bicolor (L.) Moench]/corn (Zea mays L.)-fallow rotation (W-S/C-F) under NT. The study was conducted from 1989 to 2003 on soil with a long-term history of either continuous NT management [NT(LT)] (1962–2003) or conventional tillage (CT) (1962–1988) then converted to NT [NT(C)] (1989–2003). Nitrogen was applied as ammonium nitrate (AN) at a rate of 23 kg N ha⁻¹ in 1989 and as urea ammonium nitrate (UAN) at an average annual rate of 50 kg N ha⁻¹ from 1990 to 2003 for both NT treatments. Soil samples were collected at depth increments of 0–5, 5–10, 10–15, and 15–30 cm in the spring of 1989 and 2003. Acidification rates for the NT(LT) and NT(C) treatments were 1.13 and 1.48 kmol H⁺ ha⁻¹ yr⁻¹ in the 0–30 cm depth, respectively. The amount of CaCO₃ needed to neutralize the acidification is 57 and 74 kg ha⁻¹ yr⁻¹ for the NT(LT) and NT(C) treatments, respectively. A proton budget estimated by the Helyar and Porter [1989, Soil Acidity and Plant Growth, Academic Press] method indicated that NO₃⁻ leaching from the 30 cm depth was a primary cause of long-term acidification in this soil. Nitrate leaching accounted for 59 and 66% of the H⁺ from the acid causing factors for NT(LT) and NT(C) treatments, respectively. The addition of crop residues to the soil neutralized 62 and 47% of the acidity produced from the leaching of NO₃⁻, and 37 and 31% of the acid resulting from NO₃⁻ leaching and the other acid-causing constituents for the NT(LT) and NT(C) treatments, respectively. These results document that surface soils in dry land W-S/C-F rotations under NT are acidifying under current management practices. Improved management to increase nitrogen uptake efficiency from applied fertilizer would help reduce the rate of acidification. The addition of lime materials to prevent negative impacts on grain yields may be necessary in the future under current management practices. A contribution of the university of Nebraska Agricultural Research Division, Lincoln, NE 68583. Journal series No. 15120     

Improvements in Life Cycle Energy Efficiency and Greenhouse Gas Emissions of Corn-Ethanol

Corn-ethanol production is expanding rapidly with the adoption of improved technologies to increase energy efficiency and profitability in crop production, ethanol conversion, and coproduct use. Life cycle assessment can evaluate the impact of these changes on environmental performance metrics. To this end, we analyzed the life cycles of corn-ethanol systems accounting for the majority of U.S. capacity to estimate greenhouse gas (GHG) emissions and energy efficiencies on the basis of updated values for crop management and yields, biorefinery operation, and coproduct utilization. Direct-effect GHG emissions were estimated to be equivalent to a 48% to 59% reduction compared to gasoline, a twofold to threefold greater reduction than reported in previous studies. Ethanol-to-petroleum output/input ratios ranged from 10:1 to 13:1 but could be increased to 19:1 if farmers adopted high-yield progressive crop and soil management practices. An advanced closed-loop biorefinery with anaerobic digestion reduced GHG emissions by 67% and increased the net energy ratio to 2.2, from 1.5 to 1.8 for the most common systems. Such improved technologies have the potential to move corn-ethanol closer to the hypothetical performance of cellulosic biofuels. Likewise, the larger GHG reductions estimated in this study allow a greater buffer for inclusion of indirect-effect land-use change emissions while still meeting regulatory GHG reduction targets. These results suggest that corn-ethanol systems have substantially greater potential to mitigate GHG emissions and reduce dependence on imported petroleum for transportation fuels than reported previously.