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Bronchiectasis: an update on current pharmacotherapy and future perspectives.

Bronchiectasis is a common condition and is likely to be underestimated, as bronchiectasis is now a recognised problem complicating other chronic lung diseases such as severe asthma, severe chronic obstructive pulmonary disease and advanced pulmonary fibrosis.

In more advanced bronchiectasis, there is a vicious cycle of excess neutrophilic airways inflammation and chronic infection of the airways. This leads to the clinical syndrome, including a chronic productive cough and recurrent chest infections. Areas covered: This review provides an overview of the current pharmacotherapy options available and the potential future perspectives for treatment in adult patients with idiopathic or post-infection bronchiectasis.

A PUBMED search for all Phase III and above trials on current therapies focusing on optimising airway dilatation and treatments to break the vicious cycle of infection and inflammation were sought. These therapies include antibiotics, anti-inflammatory and mucoactive therapies alongside chest physiotherapy. Landmark Phase II studies were also included.

Expert opinion: Current practice has predominantly been based on treatment advised from national guidelines that are mainly grade D expert opinion. Randomised controlled trials are greatly needed to improve practice of evidence-based medicine.

Neural regulation of inflammation in the airways and lungs.

Many pulmonary diseases are characterized by inflammatory pathologies which in turn are responsible for obstruction, mucus hypersecretion, dyspnea, cough and other clinical symptoms of lung disease. Understanding processes that regulate inflammation will therefore provide insights into mechanisms that contribute to pulmonary dysfunction.

The airways and lungs are densely innervated by autonomic and sensory nerves which might regulate aspects of pulmonary inflammation. In this review we provide a critical appraisal of the available literature on the topic of neuro-immune interactions in the airways and ask the question 'how strong is the evidence that pulmonary nerves regulate inflammation?'

Evaluation of Matrix Metalloproteinase-2 in Lung Cancer.

There is an obvious need to diagnose lung cancer using novel non-invasive and sensitive biomarkers. In this regard, the aim of the present study was to evaluate and compare sputum MMP-2 in relation to serum MMP-2 of lung cancer patients and other non-malignant lung diseases in order to establish a new diagnostic and prognostic biomarker with a valid non-invasive technique.

DESIGN AND METHODS: Group (1) included (32) newly diagnosed lung cancer patients and group (2) included (20) patients with benign pulmonary diseases. In addition, (38) healthy subjects served as control group. MMP-2 activity levels were evaluated in serum and sputum samples of the studied groups using ELISA and zymography techniques.

RESULTS: There was a highly significant increase in serum and sputum MMP-2 levels in malignant group in comparison with benign and control groups. In addition, there was a significant difference in the levels of serum and sputum MMP-2 as regards the different histopathological types of lung cancer and advanced stages of lung cancer. Gelatin zymography was used to confirm the enzymatic activity of MMP-2. A higher MMP-2 activity was detected in lung cancer group in comparison with benign and control groups.

CONCLUSION: Serum and to a larger extent sputum MMP-2 appear to be potential non-invasive markers for detecting lung cancer. This article is protected by copyright. All rights reserved.

Azithromycin Analog CSY0073 Attenuates Lung Inflammation induced by Lipopolysaccharide Challenge.

Azithromycin is a macrolide antibiotic with anti-inflammatory and immunomodulating effects. Long-term azithromycin therapy in patients with chronic lung diseases such as cystic fibrosis has been associated with increased antimicrobial resistance, emergence of hypermutable strains, ototoxicity, and cardiac toxicity. The aim of this study is to assess the antiinflammatory effects of the non-antibiotic azithromycin derivative CSY0073.

EXPERIMENTAL APPROACH: We compared CSY0073 and azithromycin in experiments on bacterial cultures, Pseudomonas aeruginosa biofilm, lung cells, and mice challenged intranasally with P. aeruginosa lipopolysaccharide (LPS).

KEY RESULTS: In contrast to azithromycin, CSY0073 did not inhibit the growth of P. aeruginosa, Staphylococcus aureus, or Haemophilus influenzae and had no effect on established P. aeruginosa biofilm. Bronchoalveolar lavage fluids and lung homogenates collected after the LPS challenge in mice showed that CSY0073 and azithromycin (intraperitoneal administration, 200 mg/kg) induced decreases in neutrophil counts at 24h and TNFα, CXCL-1 and CXCL-2 levels in the BAL fluid after 3 hours and in IL-6, CXCL-2 and IL-1β levels in the lung after 3 hours compared to the vehicle. Only azithromycin reduces IL-1β level in the lung 24h post LPS challenge. CSY0073 and azithromycin similarly diminished the production of proinflammatory cytokines by macrophages, but not lung epithelial cells, exposed to P. aeruginosa LPS.

CONCLUSIONS AND IMPLICATIONS: CSY0073 has no antibacterial effects but shares the anti-inflammatory profile of azithromycin. CSY0073 may hold promise for the long-term treatment of patients with chronic lung diseases.

Assessing Progress in Reducing the Burden of Cancer Mortality, 1985-2005.

Measuring the effect of cancer interventions must take into account rising cancer incidence now that people live longer because of declines in mortality from cardiovascular disease (CVD). Cancer mortality rates in the population do not accomplish this objective. We sought a measure that would reveal the effects of changing mortality rates from other diseases.

METHODS: We obtained annual breast, colorectal, lung, and prostate cancer mortality rates from the Surveillance, Epidemiology, and End Results registries; we obtained noncancer mortality rates from national death certificates, 1975 to 2005. We used life-table methods to calculate the burden of cancer mortality as the average person-years of life lost (PYLL) as a result of cancer (cancer-specific PYLL) and quantify individual-and perhaps offsetting-contributions of the two factors that affect cancer-specific PYLL: mortality rates as a result of cancer and other-cause mortality.

RESULTS: Falling cancer mortality rates reduced the burden of mortality from leading cancers, but increasing cancer incidence as a result of decreasing other-cause mortality rates partially offset this progress. Between 1985 and 1989 and between 2000 and 2004, the burden of lung cancer in males declined by 0.1 year of life lost. This decline reflects the sum of two effects: decreasing lung cancer mortality rates that reduced the average burden of lung cancer mortality by 0.33 years of life lost and declining other-cause mortality rates that raised it by 0.23 years. Other common cancers showed similar patterns.

CONCLUSION: By using a measure that accounts for increased cancer incidence as a result of improvements in CVD mortality, we find that prior assessments have underestimated the impact of cancer interventions.

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