Effects of inhaled corticosteroids on sputum cell counts in stable chronic obstructive pulmonary disease: a systematic review and a meta-analysis

Background

Whether inhaled corticosteroids suppress airway inflammation in chronic obstructive pulmonary disease (COPD) remains controversial. We sought to determine the effects of inhaled corticosteroids on sputum indices of inflammation in stable COPD.

Methods

We searched MEDLINE, EMBASE, CINAHL, and the Cochrane Databases for randomized, controlled clinical trials that used induced sputum to evaluate the effect of inhaled corticosteroids in stable COPD. For each chosen study, we calculated the mean differences in the concentrations of sputum cells before and after treatment in both intervention and control groups. These values were then converted into standardized mean differences to accommodate the differences in patient selection, clinical treatment, and biochemical procedures that were employed across original studies. If significant heterogeneity was present (p < 0.10), then a random effects model was used to pool the original data. In the absence of significant heterogeneity, a fixed effects model was used.

Results

We identified six original studies that met the inclusion criteria (N = 162 participants). In studies with higher cumulative dose (≥ 60 mg) or longer duration of therapy (≥ 6 weeks), inhaled corticosteroids were uniformly effective in reducing the total cell, neutrophil, and lymphocyte counts. In contrast, studies with lower cumulative dose (< 60 mg) or shorter duration of therapy (< 6 weeks) did not demonstrate a favorable effect of inhaled corticosteroids on these sputum indices.

Conclusions

Our study suggests that prolonged therapy with inhaled corticosteroids is effective in reducing airway inflammation in stable COPD.     

Field trial of diatomaceous earth in cotton gin trash against the larger black flour beetle, Cynaeus angustus (Coleoptera: Tenebrionidae)

The larger black flour beetle, Cynaeus angustus (LeConte) (Coleoptera: Tenebrionidae), is an agricultural and home nuisance pest in North America. In the Southern High Plains of Texas, the larger black flour beetle is associated with cotton gin trash, by-products of cotton ginning that are field stored in large piles for economic reasons. Larger black flour beetle overwinter in gin trash piles but may disperse by the millions in summer and autumn, entering houses as far as 2 km away where they cause distress to homeowners. Because > 1.2 billion kg of gin trash is produced annually in Texas alone, the potential consequences of the larger black flour beetle are enormous. We conducted a field experiment that evaluated the efficacy of diatomaceous earth (DE) on the abundance of the larger black flour beetle in gin trash. There were no significant differences in numbers of larger black flour beetle among treatments and controls (mean number of adults summed over time: controls = 115.41, layered treatment = 87.60, top and bottom treatment = 96.50, bottom treatment = 115.16). There were sufficient numbers of beetles in treated piles to still pose a potential home nuisance problem, likely because the moisture content of field-stored gin trash is too high for DE to work effectively. Therefore, treating cotton gin trash with diatomaceous earth will probably be unable to prevent home infestations of larger black flour beetle. Location within a gin trash pile and season influenced pest numbers, which has implications for long-term field storage of cotton gin trash.     

G-protein-coupled receptors and asthma endophenotypes: the cysteinyl leukotriene system in perspective

Genetic variation in specific G-protein coupled receptors (GPCRs) is associated with a spectrum of respiratory disease predispositions and drug response phenotypes. Although certain GPCR gene variants can be disease-causing through the expression of inactive, overactive, or constitutively active receptor proteins, many more GPCR gene variants confer risk for potentially deleterious endophenotypes. Endophenotypes are traits, such as bronchiole hyperactivity, atopy, and aspirin intolerant asthma, which have a strong genetic component and are risk factors for a variety of more complex outcomes that may include disease states. GPCR genes implicated in asthma endophenotypes include variants of the cysteinyl leukotriene receptors (CYSLTR1 and CYSLTR2), and prostaglandin D2 receptors (PTGDR and CRTH2), thromboxane A2 receptor (TBXA2R), beta2-adrenergic receptor (ADRB2), chemokine receptor 5 (CCR5), and the G protein-coupled receptor associated with asthma (GPRA). This review of the contribution of variability in these genes places the contribution of the cysteinyl leukotriene system to respiratory endophenotypes in perspective. The genetic variant(s) of receptors that are associated with endophenotypes are discussed in the context of the extent to which they contribute to a disease phenotype or altered drug efficacy.     

Mapping density response in maize: a direct approach for testing genotype and treatment interactions

Maize yield improvement has been strongly linked to improvements in stress tolerance, particularly to increased interplant competition. As a result, modern hybrids are able to produce kernels at high plant population densities. Identification of the genetic factors responsible for density response in maize requires direct testing of interactions between genetic effects and density and evaluation of that response in multiple traits. In this article we take a broad view of the problem and use a general approach based upon mixed models to analyze data from eight segmental inbred lines in a B73 background and their crosses to the unrelated parent Mo17 (hybrids). We directly test for the interaction between treatment effects and genetic effects instead of the commonly used overlaying of results on a common map. Additionally, we demonstrate one way to handle heteroscedasticity of variances common in stress responses. We find that some SILs are consistently different from the recurrent parent regardless of the density, while others differ from the recurrent parent in one density level but not in the other. Thus, we find positive evidence for both main effects and interaction between genetic loci and density in cases where the approach of overlapping results fails to find significant results. Furthermore, our study clearly identifies segments that respond differently to density depending upon the inbreeding level (inbred/hybrid).     

Sex dimorphism in digital formulae of children

This paper presents results of a study designed to: 1) test for a sex difference in the relative lengths of the finger bones, including the second-to-fourth digit ratio (2D:4D), using left-hand radiographs taken in young children, 2) test whether sex differences can be explained by sex differences in fetal growth, and 3) test the serial stability of sex differences in relative digit lengths, including 2D:4D. Results are presented from 1,060 subjects of the California Child Health and Development Studies. One serial replication at about 9 years old is available from 271 subjects. Results indicate that relative digit lengths are sex-dimorphic in children (Manning et al. [1998] Hum. Reprod. 13:3000-3004, [2004] Early Hum. Dev. 80:161-168). Sex differences in digit length ratios are more pronounced within sibships, where shared family factors are controlled, and are not strongly associated with gross measures of fetal growth, like birth length or weight. Thus, sex differences in the fetal growth of the body are not implicated in sex differences in digital formulae, leaving open the possibility of more direct hormonal and/or genetic causation. However, 2D:4D declined between ages 6-8 in a longitudinal sample, and was a less consistent sex-dimorphic marker than 3D:4D across ethnic groups, suggesting that 3D:4D may be a better marker of perinatal sex differentiation. Prior conflicting findings about 2D:4D may be partly explained by variations in age and ethnicity of populations studied.     

Characterization of a QTL affecting spike morphology on the long arm of chromosome 3H in barley (Hordeum vulgare L.) based on near isogenic lines and a NIL-derived population

Traits related to spike morphology (SM), including grain density (GD), spike length (SL) and awn length (AL), are of central importance in cereal improvement. A recent study based on a two-row landrace of barley, TX9425, detected QTL controlling all of the three traits in a similar region on the long arm of chromosome 3H. To further characterize this chromosomal region, 12 pairs of near isogenic lines (NILs) for GD were generated from two populations between TX9425 and two different commercial cultivars. A population consisting of 1,028 lines segregating primarily for the target region was also developed using materials generated during the production of these NILs. Results from the analysis of the NILs and the NIL-derived population showed that these three traits were likely controlled by a single-locus which was mapped to a 2.84?cM interval between two SSR markers, GBM1495 and HVM33. Across the 12 pairs of NILs, the presence of the 3HL locus increased GD by 53.4?%, reduced SL and AL by 38.8?% and 62.7?%, respectively. In the NIL-derived population, the presence of the 3HL locus increased GD by 64.6?%, reduced SL and AL by 33.7?% and 62.6?%, respectively. An interesting question arising from this research is why some loci such as the one reported here affect several SM-related traits while others appear to affect one of these traits only. The NILs and the NIL-derived population generated in this study will help answer such questions by providing the germplasm to enable cloning and comparative analysis of the genes responsible for these SM-related traits.