MicroRNAs in exhaled breath condensate: A pilot study of biomarker detection for lung cancer.

INTRODUCTION: Quantitation of microRNAs secreted by lung cells can provide valuable information regarding lung health. Exhaled breath condensate (EBC) offers a non-invasive way to sample the secreted microRNAs, and could be used as diagnostic tools for lung cancer. MATERIALS & METHODS: EBC samples from twenty treatment-naïve patients with pathologically confirmed lung cancer and twenty healthy subjects were profiled for miRNAs expression. Selected microRNAs were further validated, using quantitative-PCR, in an independent set of 10 subjects from both groups. RESULTS: A total of 78 miRNAs were found to be significantly upregulated in the EBC of lung cancer patients compared to the control group. Six of these 78 miRNAs were shortlisted for validation. Of these, miR-31-3p, let7i, and miR-449c were significantly upregulated, exhibited good discriminatory power. DISCUSSION: Differential expression of miRNAs secreted by lung cells could be quantitated in EBC samples, and could be used as a potential non-invasive tool for early diagnosis of lung cancer.

Mitochondrial Dysfunction Linking Obesity and Asthma.

The bidirectional epidemiological association between asthma and obesity is well known. Recent evidence suggests that there is an intersection of the pathophysiological molecular pathways leading to either obesity or asthma, at the level of mitochondria. This is not surprising, because mitochondria, beyond their roles as the metabolic powerhouses of the cell, serve as sensors of threats, regulators of stress signaling, and effectors of cytotoxicity. Reduced mitochondrial function and low metabolic activity are well-recognized features of obesity. Three distinct lines of experimental evidences connect mitochondrial dysfunction with asthma. First, asthma is associated with aberrant mitochondrial metabolism. Second, mitochondrial dysfunction may either induce asthma-like features or increase asthma severity. Third, mitochondria-targeted therapies appear effective in preventing or reversing asthma features. Importantly, mitochondrial dysfunction in airway epithelial cells appears to be a powerful trigger for airway remodeling that is independent of cellular inflammation. This is clinically relevant to the obese-asthma phenotype, with exaggerated symptoms despite apparently low levels of inflammation, and poor response to antiinflammatory treatment. In summary, mitochondrial dysfunction is a common thread tying together the twin epidemics of obesity and asthma. Environmental and lifestyle factors leading to primary mitochondrial dysfunction may be increasing the risk for either disease. Further, secondary mitochondrial dysfunction emerging from the pathogenesis of either obesity or asthma may increase the risk of the other. Mitochondrial health-centric strategies may be relevant to prevention and treatment of both obesity and asthma, and should be actively considered.

Hyperinsulinemia adversely affects lung structure and function.

There is limited knowledge regarding the consequences of hyperinsulinemia on the lung. Given the increasing prevalence of obesity, insulin resistance, and epidemiological associations with asthma, this is a critical lacuna, more so with inhaled insulin on the horizon. Here, we demonstrate that insulin can adversely affect respiratory health. Insulin treatment (1 µg/ml) significantly (P < 0.05) increased the proliferation of primary human airway smooth muscle (ASM) cells and induced collagen release. Additionally, ASM cells showed a significant increase in calcium response and mitochondrial respiration upon insulin exposure. Mice administered intranasal insulin showed increased collagen deposition in the lungs as well as a significant increase in airway hyperresponsiveness. PI3K/Akt mediated activation of ß-catenin, a positive regulator of epithelial-mesenchymal transition and fibrosis, was observed in the lungs of insulin-treated mice and lung cells. Our data suggests that hyperinsulinemia may have adverse effects on airway structure and function. Insulin-induced activation of ß-catenin in lung tissue and the contractile effects on ASM cells may be causally related to the development of asthma-like phenotype.