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Role of MicroRNAs in Lung Disease.

MicroRNAs (miRNAs) are small non-coding RNA molecules that negatively regulate gene expression. They actively participate in the modulation of important cell physiological processes and are involved in the pathogenesis of lung diseases such as lung cancer, pulmonary fibrosis, asthma and chronic obstructive pulmonary disease.

A better understanding of the role that miRNAs play in these diseases could lead to the development of new diagnostic and therapeutic tools. In this review, we discuss the role of some miRNAs in different lung diseases as well as the possible future of these discoveries in clinical applications.

Scaling up interventions to achieve global tuberculosis control: progress and new developments.

Tuberculosis is still one of the most important causes of death worldwide. The 2010 Lancet tuberculosis series provided a comprehensive overview of global control efforts and challenges. In this update we review recent progress.

With improved control efforts, the world and most regions are on track to achieve the Millennium Development Goal of decreasing tuberculosis incidence by 2015, and the Stop TB Partnership target of halving 1990 mortality rates by 2015; the exception is Africa. Despite these advances, full scale-up of tuberculosis and HIV collaborative activities remains challenging and emerging drug-resistant tuberculosis is a major threat.

Recognition of the effect that non-communicable diseases--such as smoking-related lung disease, diet-related diabetes mellitus, and alcohol and drug misuse--have on individual vulnerability, as well as the contribution of poor living conditions to community vulnerability, shows the need for multidisciplinary approaches. Several new diagnostic tests are being introduced in endemic countries and for the first time in 40 years a coordinated portfolio of promising new tuberculosis drugs exists. However, none of these advances offer easy solutions.

Achievement of international tuberculosis control targets and maintenance of these gains needs optimum national health policies and services, with ongoing investment into new approaches and strategies. Despite growing funding in recent years, a serious shortfall persists. International and national financial uncertainty places gains at serious risk.

Perseverance and renewed commitment are needed to achieve global control of tuberculosis, and ultimately, its elimination.

Developing an algorithm to identify people with Chronic Obstructive Pulmonary Disease (COPD) using administrative data.

An important prerequisite for the Chronic Care Model is to be able to identify, in a valid, simple and inexpensive way, the population with a chronic condition that needs proactive and planned care. We investigated if a set of administrative data could be used to identify patients with Chronic Obstructive Pulmonary Disease in a Danish population.

METHODS: Seven general practices were asked to identify patients with known Chronic Obstructive Pulmonary Disease in their practices. For the 266 patients (population A), we used administrative data on hospital admissions for lung-related diagnoses, redeemed prescriptions for lung-diseases drugs and lung- function tests combined to develop an algorithm that identified the highest proportion of patients with Chronic Obstructive Pulmonary Disease with the fewest criteria involved. We tested nine different algorithms combining two to four criteria. The simplest algorithm with highest positive predictive value identified 532 patients (population B); with possible diagnosis of Chronic Obstructive Pulmonary Disease in five general practices. The doctors were asked to confirm the diagnosis. The same algorithm identified 2,895 patients whom were asked to confirm their diagnosis (population C).

RESULTS: In population A the chosen algorithm had a positive predictive value of 72.2 % and three criteria: a) discharged patients with a chronic lung-disease diagnosis at least once during the preceding 5 years; or b) redeemed prescription of lung-medication at least twice during the preceding 12 months; or c) at least two spirometries performed at different dates during the preceding 12 months. In population B the positive predictive value was 65.0 % [60.8;69.1 %] and the sensitivity 44.8 % [41.3;48.4 %)] when the "uncertain" were added to where doctors agreed with the diagnosis. For the 1,984 respondents in population C, the positive predictive value was 72.9 % [70.8;74.8 %] and the sensitivity 29.7 % [28.4;31.0 %].

CONCLUSIONS: An algorithm based on administrative data has been developed and validated with sufficient positive predictive value to be used as a tool for identifying patients with Chronic Obstructive Pulmonary Disease. Some of the identified patients had other chronic lung-diseases (asthma). The algorithm should mostly be regarded as a tool for identifying chronic lung-disease and further development of the algorithm is needed. Trial registration www.clinicaltrials.gov (NCT01228708).

Small cell lung cancer doubling time and its effect on clinical presentation: a concise review.

Small cell lung cancer (SCLC) is one of many types rapidly growing malignant diseases, such as Burkitt's lymphoma and testicular germ cell cancers. At present, there is no reliable way to screen for SCLC, and imaging modalities tend to be delayed in detecting this type of cancer.

The clinical presentation of acutely and rapidly growing SCLC can mimic those of pulmonary inflammatory or infectious disorders, and in some instances, this delays appropriate management and negatively affects patient outcome.

Molecular Link Mechanisms between Inflammation and Cancer.

Inflammation is part of the body's response to internal and external environmental stimuli that normally eliminate the aggressor agent and restore the tissue physiology. However, when it becomes chronic, it can cause several pathologies such as cardiovascular, diabetes, rheumatoid arthritis, Alzheimer's, lung, autoimmune diseases and cancer.

Currently, epidemiological data indicate that over 25% of all cancers are related to chronic infections and other types of unresolved inflammation. Further evidence of this relationship is the fact that prolonged use of non-steroidal anti-inflammatory drugs (NSAIDs) has been associated with reduced risk for developing many types of cancers. Some randomized trials have shown that NSAIDs have protective action against colon adenomas, breast, prostate, and lung cancers. The inflammation present on tumor microenvironment is characterized by leukocyte infiltration, ranging in size, distribution and composition, as: tumor-associated macrophages (TAM), mast cells, dendritic cells, natural killer (NK) cells, neutrophils, eosinophils and lymphocytes. These cells produce a variety of cytotoxic mediators such as reactive oxygen and nitrogen species (ROS and RNS respectively), serine and cysteine proteases, membrane perforating agents, matrix metalloproteinase (MMP), tumor necrosis factor α (TNFα), interleukins (IL-1, IL-6, IL-8), interferons (IFNs) and enzymes, as cyclooxygenase-2 (COX-2), lipooxygenase-5 (LOX-5) and phospholipase A2 (PLA2), which activate or are activated by transcription factors nuclear factor κB (NF-κB) and signal transducers and activators of transcription-3 (STAT3).

Initially this paper will briefly review the main mediators present on tumor microenvironment, addressing the cytokines, chemokines, transcription factors, eicosanoid, and kinins and later, will present an overview of the role of inflammation in the different steps of carcinogenesis.

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