Smoking cessation and bronchial epithelial remodelling in COPD: a cross-sectional study

<p>Abstract</p> <p>Background</p> <p>Chronic Obstructive Pulmonary Disease (COPD) is associated with bronchial epithelial changes, including squamous cell metaplasia and goblet cell hyperplasia. These features are partially attributed to activation of the epidermal growth factor receptor (EGFR). Whereas smoking cessation reduces respiratory symptoms and lung function decline in COPD, inflammation persists. We determined epithelial proliferation and composition in bronchial biopsies from current and ex-smokers with COPD, and its relation to duration of smoking cessation.</p> <p>Methods</p> <p>114 COPD patients were studied cross-sectionally: 99 males/15 females, age 62 ± 8 years, median 42 pack-years, no corticosteroids, current (n = 72) or ex-smokers (n = 42, median cessation duration 3.5 years), postbronchodilator FEV₁63 ± 9% predicted. Squamous cell metaplasia (%), goblet cell (PAS/Alcian Blue⁺) area (%), proliferating (Ki-67⁺) cell numbers (/mm basement membrane), and EGFR expression (%) were measured in intact epithelium of bronchial biopsies.</p> <p>Results</p> <p>Ex-smokers with COPD had significantly less epithelial squamous cell metaplasia, proliferating cell numbers, and a trend towards reduced goblet cell area than current smokers with COPD (p = 0.025, p = 0.001, p = 0.081, respectively), but no significant difference in EGFR expression. Epithelial features were not different between short-term quitters (<3.5 years) and current smokers. Long-term quitters (≥3.5 years) had less goblet cell area than both current smokers and short-term quitters (medians: 7.9% vs. 14.4%, p = 0.005; 7.9% vs. 13.5%, p = 0.008; respectively), and less proliferating cell numbers than current smokers (2.8% vs. 18.6%, p < 0.001).</p> <p>Conclusion</p> <p>Ex-smokers with COPD had less bronchial epithelial remodelling than current smokers, which was only observed after long-term smoking cessation (>3.5 years).</p> <p>Trial registration</p> <p>NCT00158847</p

Red fluorescent biofilm: the thick, the old, and the cariogenic

Background: Some dental plaque fluoresces red. The factors involved in this fluorescence are yet unknown. Objective: The aim of this study was to assess systematically the effect of age, thickness, and cariogenicity on the extent of red fluorescence produced by in vitro microcosm biofilms. Design: The effects of biofilm age and thickness on red fluorescence were tested in a constant depth film fermentor (CDFF) by growing biofilms of variable thicknesses that received a constant supply of defined mucin medium (DMM) and eight pulses of sucrose/day. The influence of cariogenicity on red fluorescence was tested by growing biofilm on dentin disks receiving DMM, supplemented with three or eight pulses of sucrose/day. The biofilms were analyzed at different time points after inoculation, up to 24 days. Emission spectra were measured using a fluorescence spectrophotometer (λexc405 nm) and the biofilms were photographed with a fluorescence camera. The composition of the biofilms was assessed using 454-pyrosequecing of the 16S rDNA gene. Results: From day 7 onward, the biofilms emitted increasing intensities of red fluorescence as evidenced by the combined red fluorescence peaks. The red fluorescence intensity correlated with biofilm thickness but not in a linear way. Biofilm fluorescence also correlated with the imposed cariogenicity, evidenced by the induced dentin mineral loss. Increasing the biofilm age or increasing the sucrose pulsing frequency led to a shift in the microbial composition. These shifts in composition were accompanied by an increase in red fluorescence. Conclusions: The current study shows that a thicker, older, or more cariogenic biofilm results in a higher intensity of red fluorescence

Low risk of treatment failure after substitution of nevirapine for protease inhibitors among human immunodeficiency virus-infected patients with virus suppression

There is little information about the risk of treatment failure after a switch from human immunodeficiency virus (HIV) protease inhibitors (PIs) to nevirapine (Nvp) for patients with successful virus suppression. This study compared the 1-year risk of treatment failure for patients switching from a first PI-containing antiretroviral regimen to Nvp (Nvp group) with the risk for patients switching to second-line PIs (PI group) in the ATHENA (AIDS Therapy Evaluation, The Netherlands) study cohort (n = 2470) whose HIV-1 RNA loads were less than or equal to500 copies/mL. Treatment failure was defined as measurement of HIV-1 RNA loads >500 twice or >10,000 copies/mL once or discontinuation of treatment for any reason. There were 446 eligible patients, 125 in the Nvp group and 321 in the PI group. The risk of treatment failure in the Nvp group, after data were adjusted for other risk factors, was 5-fold (95% confidence interval, 0.1-0.4) lower than the risk in the PI group, primarily because the discontinuation rate was lower. In patients with virus suppression, a switch to Nvp is more likely than a switch to second-line PIs to result in sustained virus suppression and maintenance of the new regime

Risk factors for urological symptoms in a cohort of users of the HIV protease inhibitor indinavir sulfate - The ATHENA cohort

Background: Nephrolithiasis is a well-known complication of indinavir treatment and may result in urological symptoms ranging from renal colic to renal insufficiency. Objective: To obtain further knowledge regarding the incidence and risk factors of urological symptoms associated with indinavir sulfate use. Methods: This study was performed in the ATHENA (AIDS Therapy Evaluation National AIDS Therapy Evaluation Centre) cohort of patients infected with human immunodeficiency virus (HIV) receiving antiretroviral therapy in the Netherlands. The incidence rate of urological symptoms was assessed in a subcohort of 1219 patients starting HIV protease inhibitor treatment after 1996. Urological symptoms were defined as an initial report of nephrolithiasis, renal colic, flank pain, hematuria, renal insufficiency, or nephropathy. Using multivariate Cox regression analysis, risk factors for urological symptoms during indinavir treatment were subsequently studied among the subset of 644 patients who started indinavir treatment after 1996. Results: The incidence of urological symptoms was 8.3 per 100 treatment-years for indinavir vs 0.8 per 100 treatment-years for other HIV protease inhibitors. Risk factors for urological symptoms during indinavir treatment were low weight (relative risk [RR], 2.1, 95% confidence interval [CI], 1.1-3.9), low lean body mass (RR, 1.7;93% CI, 1.0-2.9), undetectable HIV-1 RNA when starting indinavir treatment (RR, 3.2; 95% CI, 1.5-6.0), prior treatment change because of intolerance (RR, 2.4; 95% CI, 1.2-5.1), indinavir regimens of 1000 mg or more twice daily (RR, 3.1; 95% CI, 1.3-8.2), and warm environmental temperatures (RR, 3.9; 95% CI, 1.7-8.8). Risk estimates were highest among patients with a low lean body mass. Conclusion: increased alertness for urological symptoms is warranted for patients starting indinavir treatment, particularly among those with a low lean body mass, during indinavir regimens of 1000 mg or more twice daily, and in warm weather environment

Risk factors for urological symptoms in a cohort of users of the HIV protease inhibitor indinavir sulfate: The ATHENA cohort

Background: Nephrolithiasis is a well-known complication of indinavir treatment and may result in urological symptoms ranging from renal colic to renal insufficiency. Objective: To obtain further knowledge regarding the incidence and risk factors of urological symptoms associated with indinavir sulfate use. Methods: This study was performed in the ATHENA (AIDS Therapy Evaluation National AIDS Therapy Evaluation Centre) cohort of patients infected with human immunodeficiency virus (HIV) receiving antiretroviral therapy in the Netherlands. The incidence rate of urological symptoms was assessed in a subcohort of 1219 patients starting HIV protease inhibitor treatment after 1996. Urological symptoms were defined as an initial report of nephrolithiasis, renal colic, flank pain, hematuria, renal insufficiency, or nephropathy. Using multivariate Cox regression analysis, risk factors for urological symptoms during indinavir treatment were subsequently studied among the subset of 644 patients who started indinavir treatment after 1996. Results: The incidence of urological symptoms was 8.3 per 100 treatment-years for indinavir vs 0.8 per 100 treatment-years for other HIV protease inhibitors. Risk factors for urological symptoms during indinavir treatment were low weight (relative risk [RR], 2.1; 95% confidence interval [CI], 1.1-3.9), low lean body mass (RR, 1.7;95% CI, 1.0-2.9), undetectable HIV-1 RNA when starting indinavir treatment (RR, 3.2;95% CI, 1.5-6.0), prior treatment change because of intolerance (RR, 2.4;95% CI, 1.2-5.1), indinavir regimens of 1000 mg or more twice daily (RR, 3.1;95% CI, 1.3-8.2), and warm environmental temperatures (RR, 3.9;95% CI, 1.7-8.8). Risk estimates were highest among patients with a low lean body mass. Conclusion: Increased alertness for urological symptoms is warranted for patients starting indinavir treatment, particularly among those with a low lean body mass, during indinavir regimens of 1000 mg or more twice daily, and in warm weather environments

Red and Green Fluorescence from Oral Biofilms

<div><p>Red and green autofluorescence have been observed from dental plaque after excitation by blue light. It has been suggested that this red fluorescence is related to caries and the cariogenic potential of dental plaque. Recently, it was suggested that red fluorescence may be related to gingivitis. Little is known about green fluorescence from biofilms. Therefore, we assessed the dynamics of red and green fluorescence in real-time during biofilm formation. In addition, the fluorescence patterns of biofilm formed from saliva of eight different donors are described under simulated gingivitis and caries conditions. Biofilm formation was analysed for 12 hours under flow conditions in a microfluidic BioFlux flow system with high performance microscopy using a camera to allow live cell imaging. For fluorescence images dedicated excitation and emission filters were used. Both green and red fluorescence were linearly related with the total biomass of the biofilms. All biofilms displayed to some extent green and red fluorescence, with higher red and green fluorescence intensities from biofilms grown in the presence of serum (gingivitis simulation) as compared to the sucrose grown biofilms (cariogenic simulation). Remarkably, cocci with long chain lengths, presumably streptococci, were observed in the biofilms. Green and red fluorescence were not found homogeneously distributed within the biofilms: highly fluorescent spots (both green and red) were visible throughout the biomass. An increase in red fluorescence from the <i>in vitro</i> biofilms appeared to be related to the clinical inflammatory response of the respective saliva donors, which was previously assessed during an <i>in vivo</i> period of performing no-oral hygiene. The BioFlux model proved to be a reliable model to assess biofilm fluorescence. With this model, a prediction can be made whether a patient will be prone to the development of gingivitis or caries.</p></div

Non-metric multidimensional scaling plots based on the three-dimensional Bray-Curtis similarity index by gingival health status.

<p>The plots are constructed per visit. The subjects with healthy gingiva are indicated with ○, the subjects with gingivitis are indicated with ●. <i>Stress</i> for the individual plots is (A) 0.1539, (B) 0.1474, (C) 0.1265, (D) 0.1401, (E) 0.1495 and (F) 0.1531.</p

Count of subjects with healthy gingiva and gingivitis per visit.

<p>Count of subjects with healthy gingiva and gingivitis per visit.</p