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Sputum and nasal lavage lung-specific biomarkers before and after smoking cessation.

Background: Little is known about the effect of smoking cessation on airway inflammation. Secretory Leukocyte Protease Inhibitor (SLPI), Clara Cell protein 16 (CC16), elafin and human defensin beta-2 (HBD-2) protect human airways against inflammation and oxidative stress. In this longitudinal study we aimed to investigate changes in sputum and nasal lavage SLPI, CC16, elafin and HBD-2 levels in healthy smokers after 6 and 12 months of smoking cessation. Methods: Induced sputum and nasal lavage was obtained from healthy current smokers (n = 76) before smoking cessation, after 6 months of smoking cessation (n = 29), after 1 year of smoking cessation (n = 22) and from 10 healthy never smokers. SLPI, CC16, elafin and HBD-2 levels were measured in sputum and nasal lavage supernatants by commercially available ELISA kits. Results: Sputum SLPI and CC-16 levels were increased in healthy smokers before smoking cessation versus never-smokers (p = 0.005 and p = 0.08 respectively). SLPI and CC16 levels did not differ before and 6 months after smoking cessation (p = 0.118 and p = 0.543 respectively), neither before and 1 year after smoking cessation (p = 0.363 and p = 0.470 respectively). Nasal lavage SLPI was decreased 12 months after smoking cessation (p = 0.033). Nasal lavage elafin levels were increased in healthy smokers before smoking cessation versus never-smokers (p = 0.007), but there were no changes 6 months and 1 year after smoking cessation. Conclusions: Only nasal lavage SLPI decrease after 1 year after smoking cessation. We may speculate that there is an ongoing inflammatory process stimulating the production of counter-regulating proteins in the airways of healthy ex-smokers.

Systematic review with meta-analysis of the epidemiological evidence relating smoking to COPD, chronic bronchitis and emphysema

Background: Smoking is a known cause of the outcomes COPD, chronic bronchitis (CB) and emphysema, but no previous systematic review exists. We summarize evidence for various smoking indices. Methods: Based on MEDLINE searches and other sources we obtained papers published to 2006 describing epidemiological studies relating incidence or prevalence of these outcomes to smoking. Studies in children or adolescents, or in populations at high respiratory disease risk or with co-existing diseases were excluded. Study-specific data were extracted on design, exposures and outcomes considered, and confounder adjustment. For each outcome RRs/ORs and 95% CIs were extracted for ever, current and ex smoking and various dose response indices, and meta-analyses and meta-regressions conducted to determine how relationships were modified by various study and RR characteristics. Results: Of 218 studies identified, 133 provide data for COPD, 101 for CB and 28 for emphysema. RR estimates are markedly heterogeneous. Based on random-effects meta-analyses of most-adjusted RR/ORs, estimates are elevated for ever smoking (COPD 2.89, CI 2.63-3.17, n = 129 RRs; CB 2.69, 2.50-2.90, n = 114; emphysema 4.51, 3.38-6.02, n = 28), current smoking (COPD 3.51, 3.08-3.99; CB 3.41, 3.13-3.72; emphysema 4.87, 2.83-8.41) and ex smoking (COPD 2.35, 2.11-2.63; CB 1.63, 1.50-1.78; emphysema 3.52, 2.51-4.94). For COPD, RRs are higher for males, for studies conducted in North America, for cigarette smoking rather than any product smoking, and where the unexposed base is never smoking any product, and are markedly lower when asthma is included in the COPD definition. Variations by sex, continent, smoking product and unexposed group are in the same direction for CB, but less clearly demonstrated. For all outcomes RRs are higher when based on mortality, and for COPD are markedly lower when based on lung function. For all outcomes, risk increases with amount smoked and pack-years. Limited data show risk decreases with increasing starting age for COPD and CB and with increasing quitting duration for COPD. No clear relationship is seen with duration of smoking. Conclusions: The results confirm and quantify the causal relationships with smoking.

Why is spirometry underused in the diagnosis of the breathless patient: a qualitative study

Background: Use of spirometry is essential for the accurate diagnosis of respiratory disease but it is underused in both primary and specialist care. In the current study, we have explored the reasons for this underuse. Methods: Five separate focus groups were undertaken with final year medical undergraduates, junior hospital doctors, general practitioners (GPs) and specialist trainees in respiratory medicine. The participants were not told prior to the session that we were specifically interested in their views about spirometry but discussion was moderated to elicit their approaches to the diagnosis of a breathless patient, their use of investigations and their learning preferences. Results: Undergraduates and junior doctors rarely had a systematic approach towards the breathless patient and tended, unless prompted, to focus on the emergency room situation rather than on patients with longer term causes of breathlessness. Whilst their theoretical knowledge embraced the possibility of a non-respiratory cause for breathlessness, neither undergraduates nor junior doctors spontaneously mentioned the use of spirometry in the diagnosis of respiratory disease. When prompted they cited lack of familiarity with the use and location of equipment, and lack of encouragement to use it as being major barriers to utilization. In contrast, GPs and specialist respiratory trainees were enthusiastic about its use and perceived spirometry as a core element of the diagnostic workup. Conclusions: More explicit training is needed regarding the role of spirometry in the diagnosis and management of those with lung disease and this necessitates both practical experience and training in interpretation of the data. However, formal teaching is likely to be undermined in practice, if the concept is not strongly promoted by the senior staff who act as role models and trainers.

Effectiveness of anti-inflammatory treatment versus antibiotic therapy and placebo for patients with non-complicated acute bronchitis with purulent sputum. BAAP Study protocol

Background: Acute bronchitis is one of the most prevalent respiratory infections in primary care, and in more than 90% of the cases antibiotics are prescribed, mainly when purulent expectoration is present. However, this process is usually viral in origin and the benefits of antibiotic treatment are marginal. On the other hand, in recent years bronchitis has been considered more as an inflammatory than an infectious process. Thus, the aim of this study is to evaluate the clinical effectiveness of a schedule of an oral anti-inflammatory compared with an antibiotic regimen and another group assigned to receive a placebo.Methods and design: A total of 420 patients from 15 to 70 years of age with no associated comorbidity, presenting respiratory tract infection of at least one week of evolution, with cough as the predominant symptom, the presence of purulent expectoration and at least one other symptom of the respiratory tract (dyspnoea, wheezing, chest discomfort or pain), with no alternative explanation such as pneumonia, will be included in a prospective, randomised and controlled, clinical trial with placebo. The patients will be randomised to receive one of three treatments: ibuprofen, amoxycillin and clavulanic acid or placebo for 10 days. The main outcome measure is the number of days with frequent cough defined by the symptom diary with a score of 1 or more.DiscussionThis trial is designed to evaluate the number of days with frequent cough with anti-inflammatory treatment compared with antimicrobial treatment and placebo in previously healthy patients with a clinical picture of acute bronchitis and purulent expectoration. It is hypothesized that anti-inflammatory treatment is more effective than antibiotic treatment to reduce cough, which is the most disturbing symptom for patients with this infection.Trial registration: ISRCTN07852892

Innovative new diagnostic test to detect TB and rifampin resistance

Tuberculosis remains a major public health concern. Existing diagnostic tools are slow and result in delays initiating appropriate treatment. This is particularly a problem in patients with HIV, in whom sputum–smear analysis is frequently negative and those with multi-drug resistant strains.

In this study, the performance of an automated molecular assay for Mycobacterium tuberculosis (MTB) and resistance to rifampin (RIF) (Xpert MTB/RIF) was assessed. This test, through detection of an MTB-specific sequence of the rpoB gene and probing for rifampin-resistance determining region mutations, provides results within 2 h.

Three sputum samples were analysed from 1730 eligible patients with suspected tuberculosis in reference laboratories in Peru, Azerbaijan, South Africa and India. With a single test, 98.2% of patients with smear-positive, culture-positive tuberculosis were identified. Among those with smear-negative, culture-positive disease, the sensitivity of the assay was 72.5% with one test, 85.1% for two tests and 90.2% for three tests. The...

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