Novel phages of healthy skin metaviromes from South Africa

Recent skin metagenomic studies have investigated the harbored viral diversity and its possible influence on healthy skin microbial populations, and tried to establish global patterns of skin-phage evolution. However, the detail associated with the phages that potentially play a role in skin health has not been investigated. While skin metagenome and -metavirome studies have indicated that the skin virome is highly site specific and shows marked interpersonal variation, they have not assessed the presence/absence of individual phages. Here, we took a semi-culture independent approach (metaviromic) to better understand the composition of phage communities on skin from South African study participants. Our data set adds over 130 new phage species of the skin to existing databases. We demonstrated that identical phages were present on different individuals and in different body sites, and we conducted a detailed analysis of the structural organization of these phages. We further found that a bacteriophage related to the Staphylococcus capitis phage Stb20 may be a common skin commensal virus potentially regulating its host and its activities on the ski

Endothelin receptor antagonist and airway dysfunction in pulmonary arterial hypertension

<p>Abstract</p> <p>Background</p> <p>In idiopathic pulmonary arterial hypertension (IPAH), peripheral airway obstruction is frequent. This is partially attributed to the mediator dysbalance, particularly an excess of endothelin-1 (ET-1), to increased pulmonary vascular and airway tonus and to local inflammation. Bosentan (ET-1 receptor antagonist) improves pulmonary hemodynamics, exercise limitation, and disease severity in IPAH. We hypothesized that bosentan might affect airway obstruction.</p> <p>Methods</p> <p>In 32 IPAH-patients (19 female, WHO functional class II (n = 10), III (n = 22); (data presented as mean ± standard deviation) pulmonary vascular resistance (11 ± 5 Wood units), lung function, 6 minute walk test (6-MWT; 364 ± 363.7 (range 179.0-627.0) m), systolic pulmonary artery pressure, sPAP, 79 ± 19 mmHg), and NT-proBNP serum levels (1427 ± 2162.7 (range 59.3-10342.0) ng/L) were measured at baseline, after 3 and 12 months of oral bosentan (125 mg twice per day).</p> <p>Results and Discussion</p> <p>At baseline, maximal expiratory flow at 50 and 25% vital capacity were reduced to 65 ± 25 and 45 ± 24% predicted. Total lung capacity was 95.6 ± 12.5% predicted and residual volume was 109 ± 21.4% predicted. During 3 and 12 months of treatment, 6-MWT increased by 32 ± 19 and 53 ± 69 m, respectively; p < 0.01; whereas sPAP decreased by 7 ± 14 and 10 ± 19 mmHg, respectively; p < 0.05. NT-proBNP serum levels tended to be reduced by 123 ± 327 and by 529 ± 1942 ng/L; p = 0.11). There was no difference in expiratory flows or lung volumes during 3 and 12 months.</p> <p>Conclusion</p> <p>This study gives first evidence in IPAH, that during long-term bosentan, improvement of hemodynamics, functional parameters or serum biomarker occur independently from persisting peripheral airway obstruction.</p

External validation of a COPD prediction model using population-based primary care data: a nested case-control study

Emerging models for predicting risk of chronic obstructive pulmonary disease (COPD) require external validation in order to assess their clinical value. We validated a previous model for predicting new onset COPD in a different database. We randomly drew 38,597 case-control pairs (total N = 77,194) of individuals aged ≥35 years and matched for sex, age, and general practice from the United Kingdom Clinical Practice Research Datalink database. We assessed accuracy of the model to discriminate between COPD cases and non-cases by calculating area under the receiver operator characteristic (ROC(AUC)) for the prediction scores. Analogous to the development model, ever smoking (OR 6.70; 95%CI 6.41–6.99), prior asthma (OR 6.43; 95%CI 5.85–7.07), and higher socioeconomic deprivation (OR 2.90; 95%CI 2.72–3.09 for highest vs. lowest quintile) increased the risk of COPD. The validated prediction scores ranged from 0–5.71 (ROC(AUC) 0.66; 95%CI 0.65–0.66) for males and 0–5.95 (ROC(AUC) 0.71; 95%CI 0.70–0.71) for females. We have confirmed that smoking, prior asthma, and socioeconomic deprivation are key risk factors for new onset COPD. Our model seems externally valid at identifying patients at risk of developing COPD. An impact assessment now needs to be undertaken to assess whether this prediction model can be applied in clinical care settings

Comparison of the effects of salmeterol/fluticasone propionate with fluticasone propionate on airway physiology in adults with mild persistent asthma

<p>Abstract</p> <p>Background</p> <p>This study compared the effect of inhaled fluticasone propionate (FP) with the combination of salmeterol/fluticasone propionate (SFC) on lung function parameters in patients with mild asthma.</p> <p>Methods</p> <p>Adult patients with mild persistent asthma (≥ 80% predicted FEV₁) receiving 200–500 μg of BDP or equivalent were randomised to receive either FP 100 μg or SFC 50/100 μg twice daily from a Diskus^®inhaler for four weeks. The primary outcome was the change from baseline in airway resistance (sRaw) at 12 hrs post dose measured by whole body plethysmography. Impulse oscillometry and spirometry were also performed.</p> <p>Results</p> <p>A comparison of the geometric mean sRaw at 12 hrs post dose in the SFC group to the FP group gave a ratio of 0.76 (0.66 – 0.89, p < 0.001) at week 2 and 0.81 (0.71 – 0.94, p = 0.006) at week 4. Similarly, significant results in favour of SFC for oscillometry measurements of resistance and reactance were observed. FEV₁was also significantly superior at week 2 in the SFC group (mean difference 0.16L, 95% CI; 0.03 – 0.28, p = 0.015), but not at week 4 (mean difference 0.17L, 95% CI -0.01 – 0.34, p = 0.060).</p> <p>Conclusion</p> <p>SFC is superior to FP in reducing airway resistance in mild asthmatics with near normal FEV₁values. This study provides evidence that changes in pulmonary function in patients with mild asthma are detected more sensitively by plethysmography compared to spirometry</p> <p>Trial registration number</p> <p>NCT00370591.</p

Occupation, smoking, and chronic obstructive respiratory disorders: a cross sectional study in an industrial area of Catalonia, Spain

BACKGROUND: Few studies have investigated the independent effects of occupational exposures and smoking on chronic bronchitis and airflow obstruction. We assessed the association between lifetime occupational exposures and airflow obstruction in a cross-sectional survey in an urban-industrial area of Catalonia, Spain. METHODS: We interviewed 576 subjects of both sexes aged 20–70 years (response rate 80%) randomly selected from census rolls, using the ATS questionnaire. Forced spirometry was performed by 497 subjects according to ATS normative. RESULTS: Lifetime occupational exposure to dust, gases or fumes was reported by 52% of the subjects (63% in men, 41% in women). Textile industry was the most frequently reported job in relation to these exposures (39%). Chronic cough, expectoration and wheeze were more prevalent in exposed subjects with odds ratios ranging from 1.7 to 2.0 being highest among never-smokers (2.1 to 4.3). Lung function differences between exposed and unexposed subjects were dependent on duration of exposure, but not on smoking habits. Subjects exposed more than 15 years to dusts, gases or fumes had lower lung function values (FEV(1 )-80 ml, 95% confidence interval (CI) -186 to 26; MMEF -163 ml, CI -397 to 71; FEV(1)/FVC ratio -1.7%, CI -3.3 to -0.2) than non-exposed. CONCLUSION: Chronic bronchitis symptoms and airflow obstruction are associated with occupational exposures in a population with a high employment in the textile industry. Lung function impairment was related to the duration of occupational exposure, being independent of the effect of smoking

Systematic review of the evidence relating FEV1 decline to giving up smoking

<p>Abstract</p> <p>Background</p> <p>The rate of forced expiratory volume in 1 second (FEV₁) decline ("beta") is a marker of chronic obstructive pulmonary disease risk. The reduction in beta after quitting smoking is an upper limit for the reduction achievable from switching to novel nicotine delivery products. We review available evidence to estimate this reduction and quantify the relationship of smoking to beta.</p> <p>Methods</p> <p>Studies were identified, in healthy individuals or patients with respiratory disease, that provided data on beta over at least 2 years of follow-up, separately for those who gave up smoking and other smoking groups. Publications to June 2010 were considered. Independent beta estimates were derived for four main smoking groups: never smokers, ex-smokers (before baseline), quitters (during follow-up) and continuing smokers. Unweighted and inverse variance-weighted regression analyses compared betas in the smoking groups, and in continuing smokers by amount smoked, and estimated whether beta or beta differences between smoking groups varied by age, sex and other factors.</p> <p>Results</p> <p>Forty-seven studies had relevant data, 28 for both sexes and 19 for males. Sixteen studies started before 1970. Mean follow-up was 11 years. On the basis of weighted analysis of 303 betas for the four smoking groups, never smokers had a beta 10.8 mL/yr (95% confidence interval (CI), 8.9 to 12.8) less than continuing smokers. Betas for ex-smokers were 12.4 mL/yr (95% CI, 10.1 to 14.7) less than for continuing smokers, and for quitters, 8.5 mL/yr (95% CI, 5.6 to 11.4) less. These betas were similar to that for never smokers. In continuing smokers, beta increased 0.33 mL/yr per cigarette/day. Beta differences between continuing smokers and those who gave up were greater in patients with respiratory disease or with reduced baseline lung function, but were not clearly related to age or sex.</p> <p>Conclusion</p> <p>The available data have numerous limitations, but clearly show that continuing smokers have a beta that is dose-related and over 10 mL/yr greater than in never smokers, ex-smokers or quitters. The greater decline in those with respiratory disease or reduced lung function is consistent with some smokers having a more rapid rate of FEV₁decline. These results help in designing studies comparing continuing smokers of conventional cigarettes and switchers to novel products.</p

The effects of almitrine on the ventilatory response to hypoxia and hypercapnia in normal subjects.

1. Almitrine at a dose of 0.5 mg h-1 kg-1 given intravenously over 2 h had no effect on resting ventilation in normal males. 2. There was a small, but insignificant, rise in the hypercapnic drive to breathe as compared with placebo. 3. A large rise in the hypoxic drive to breathe was seen in response to almitrine. 4. These findings support the claim that almitrine has its action on ventilation via the peripheral chemoreceptors. 5. No correlation between blood levels of almitrine and the rise in hypoxic response was seen