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Transcriptomic studies of the airway field of injury associated with smoking-related lung disease.

Transcriptomic studies of the airway field of injury associated with smoking-related lung disease.

Proc Am Thorac Soc. 2011 May;8(2):173-9

Authors: Gower AC, Steiling K, Brothers JF, Lenburg ME, Spira A

The "field of injury" hypothesis proposes that exposure to an inhaled insult such as cigarette smoke elicits a common molecular response throughout the respiratory tract. This response can therefore be quantified in any airway tissue, including readily accessible epithelial cells in the bronchus, nose, and mouth. High-throughput technologies, such as whole-genome gene expression microarrays, can be employed to catalog the physiological consequences of such exposures in the airway epithelium. Pulmonary diseases such as chronic obstructive pulmonary disease, lung cancer, and asthma are also thought to be associated with a field of injury, and in patients with these diseases, airway epithelial cells can be a useful surrogate for diseased tissue that is often difficult to obtain. Global measurement of mRNA and microRNA expression in these cells can provide useful information about the molecular pathogenesis of such diseases and may be useful for diagnosis and for predicting prognosis and response to therapy. In this review, our aim is to summarize the history and state of the art of such "transcriptomic" studies in the human airway epithelium, especially in smoking and smoking-related lung diseases, and to highlight future directions for this field.

PMID: 21543797 [PubMed - in process]

Proteostasis: a new therapeutic paradigm for pulmonary disease.

Proteostasis: a new therapeutic paradigm for pulmonary disease.

Proc Am Thorac Soc. 2011 May;8(2):189-95

Authors: Bouchecareilh M, Balch WE

Among lung pathologies, α1AT, chronic obstructive pulmonary disease (COPD), emphysema, and asthma are diseases triggered by local environmental stress in the airway that we refer to herein collectively as airway stress diseases (ASDs). A deficiency of α-1-antitrypsin (α1AT) is an inherited genetic disorder that is a consequence of the misfolding of α1AT during protein synthesis in liver hepatocytes, reducing secretion to the plasma and delivery to the lung. Deficiency of α1AT in the lung triggers a similar pathological phenotype to other ASDs. Moreover, the loss of α1AT in the lung is a well-known environmental risk factor for COPD/emphysema. To date there are no effective therapeutic approaches to address ASDs, which reflects a general lack of understanding of their cellular basis. Herein, we propose that ASDs are disorders of proteostasis. That is, they are initiated and propagated by a common theme-a challenge to protein folding capacity maintained by the proteostasis network (PN) (see Balch et al., Science 2008;319:916-919). The PN is a network of chaperones and degradative components that generates and manages protein folding pathways responsible for normal human physiology. In ASD, we suggest that the PN system fails to respond to the increased burden of unfolded proteins due to genetic and environmental stresses, thus triggering pulmonary pathophysiology. We introduce the enabling concept of proteostasis regulators (PRs), small molecules that regulate signaling pathways that control the composition and activity of PN components, as a new and general approach for therapeutic management of ASDs.

PMID: 21543800 [PubMed - in process]

Impact of micronutrients on respiratory infections

Several studies have documented the impact of vitamin D and other micronutrients on host responses to upper and lower respiratory tract infections, such as influenza and tuberculosis. These studies include observational as well as micronutrient intervention studies. Other studies have been conducted to understand the mechanisms by which micronutrients alter immune responses. However, critical information gaps and challenges remain. An immediate need exists for randomized controlled trials of vitamin D supplementation in high‐risk populations, such as infants, children, and patients with immunocompromised health. Other important areas of research include vitamin D genetics, the impact of other micronutrient deficiencies on innate and adaptive immunity, the 25(OH)D threshold for insufficie...

Vitamin D: Stronger lungs as well as stronger bones?

Pulmonary infections and the influence of the sun have been important elements of human experience for millennia. As human populations moved to more extreme latitudes, skin pigmentations that had been advantageous in equatorial regions proved much less so. One major reason for the change in fitness could possibly relate to Vitamin D metabolism. Vitamin D, several related secosteroid hormones involved in the regulation of perhaps 1000 genes, has been of increasing interest for a wide variety of medical conditions.

A meta-analysis of interventional studies has suggested the possibility that Vitamin D may decrease all-cause mortality, although most data on the benefits of supplementation remain suggestive rather than conclusive., The ubiquity of diseases associated with low Vitamin D levels suggest the possibility that low Vitamin D may be a marker of low sunlight exposure, physical inactivity and excess adiposity rather than a reliable therapeutic target. Nevertheless, Vitamin D is mechanistically involved in immunity, including respiratory infections. A large, retrospective nutritional survey suggested an inverse association between Vitamin D levels and the probability of recent respiratory tract infection, even after controlling for season (though not for latitude or other surrogates for sun exposure). Similar results, confounded by smoking and physical inactivity, were observed in Finnish military recruits ...

Effect of early pulmonary rehabilitation on health care utilization and health status in patients hospitalized with acute exacerbations of COPD

Conclusions: An early rehabilitation programme following AECOPD led to improvement in quality of life up to 6 months, but did not reduce health‐care utilization at 1 year. (Source: Respirology)

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