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.     

Characterization of polymorphic microsatellites for the periwinkle gastropod, Littorina littorea (Linnaeus, 1758) and their cross-amplification in four congeners

Eight polymorphic microsatellite loci are described for Littorina littorea (Linnaeus, 1758). Data on allelic variation in Irish and Celtic Sea samples are reported. The average number of alleles per locus was 11 (range 4–29), and observed and expected heterozygosities ranged from 6.9 to 84.3% and from 9.4 to 95.2%, respectively. Loci did not deviate from Hardy–Weinberg equilibrium and no linkage disequilibrium between loci pairs was detected. Microsatellites were not highly conserved in the congeners, L. fabalis, L. saxatilis, L. compressa and L. obtusata as evidenced by a low rate of cross-amplification. These microsatellites should prove useful in population genetic studies.     

Thiosulfate Disproportionation by Desulfotomaculum thermobenzoicum

Desulfotomaculum thermobenzoicum, but not Desulfotomaculum nigrificans, Desulfotomaculum ruminis, or Desulfosporosinus orientis, grew by disproportionation of thiosulfate, forming stoichiometric amounts of sulfate and sulfide; sulfite was not disproportionated. The addition of acetate enhanced growth and thiosulfate disproportionation by D. thermobenzoicum compared to those observed with thiosulfate alone.     

Importance of eIF2alpha phosphorylation and stress granule assembly in alphavirus translation regulation

Alphavirus infection results in the shutoff of host protein synthesis in favor of viral translation. Here, we show that during Semliki Forest virus (SFV) infection, the translation inhibition is largely due to the activation of the cellular stress response via phosphorylation of eukaryotic translation initiation factor 2alpha subunit (eIF2alpha). Infection of mouse embryo fibroblasts (MEFs) expressing a nonphosphorylatable mutant of eIF2alpha does not result in efficient shutoff, despite efficient viral protein production. Furthermore, we show that the SFV translation enhancer element counteracts the translation inhibition imposed by eIF2alpha phosphorylation. In wild-type MEFs, viral infection induces the transient formation of stress granules (SGs) containing the cellular TIA-1/R proteins. These SGs are disassembled in the vicinity of viral RNA replication, synchronously with the switch from cellular to viral gene expression. We propose that phosphorylation of eIF2alpha and the consequent SG assembly is important for shutoff to occur and that the localized SG disassembly and the presence of the enhancer aid the SFV mRNAs to elude general translational arrest.     

Microbial Penetration through Nutrient-Saturated Berea Sandstone

Penetration times and penetration rates for a motile Bacillus strain growing in nutrient-saturated Berea sandstone cores were determined. The rate of penetration was essentially independent of permeabilities above 100 mdarcys and rapidly declined for permeabilities below 100 mdarcys. It was found that these penetration rates could be grouped into two statistically distinct classes consisting of rates for permeabilities above 100 mdarcys and rates for those below 100 mdarcys. Instantaneous penetration rates were found to be zero order with respect to core length for cores with permeabilities above 100 mdarcys and first order with respect to core length for cores with permeabilities below 100 mdarcys. The maximum observed penetration rate was 0.47 cm . h, and the slowest was 0.06 cm . h; however, these rates may be underestimates of the true penetration rate, since the observed rates included the time required for growth in the flask as well as the core. The relationship of penetration time to the square of the length of the core suggested that cells penetrated high-permeability cores as a band and low-permeability cores in a diffuse fashion. The motile Enterobacter aerogenes strain penetrated Berea sandstone cores three to eight times faster than did the nonmotile Klebsiella pneumoniae strain when cores of comparable length and permeability were used. A penetration mechanism based entirely on motility predicted penetration times that were in agreement with the observed penetration times for motile strains. The fact that nonmotile strains penetrated the cores suggested that filamentous or unrestricted growth, or both, may also be important.     

Phospholipid Fatty Acid Composition of the Syntrophic Anaerobic Bacterium Syntrophomonas wolfei

The membrane phospholipid fatty acids (PLFAs) from several cocultures and a pure culture of Syntrophomonas wolfei were determined by capillary column gas chromatography. Cocultures of S. wolfei with a Desulfovibrio sp. contained PLFAs from both organisms, whereas PLFAs from a coculture with Methanospirillum hungatei contained very little biomass to analyze. The pure culture of S. wolfei grown on crotonate provided the best material for analysis of the PLFAs. The predominant PLFAs of S. wolfei were the monounsaturated 16:1ω7c and 16:1ω9c and the saturated 16:0 and 14:0. A low concentration of the diunsaturated 18:2ω6 was detected. The PLFA analysis provides additional information for consideration in the determination of the profile of PLFAs obtained from anaerobic environments. In addition, this information may aid in the understanding of the physiology and phylogeny of S. wolfei and other syntrophic bacteria.     

Recovery and phylogenetic analysis of novel archaeal rRNA sequences from a deep-sea deposit feeder.

In 1992, two independent reports based on small-subunit rRNA gene (SSU rDNA) cloning revealed the presence of novel Archaea among marine bacterioplankton. Here, we report the presence of further novel Archaea SSU rDNA sequences recovered from the midgut contents of a deep-sea marine holothurian. Phylogenetic analyses show that these abyssal Archaea are a paraphyletic component of a highly divergent clade that also includes some planktonic sequences. Our data confirm that this clade is a deep-branching lineage in the tree of life.