Eosinophilic Chronic Obstructive Pulmonary Disease.

Recent therapeutic advances in the management of asthma have underscored the importance of eosinophilia and the role of pro-eosinophilic mediators such as IL-5 in asthma. Given that a subset of patients with COPD may display peripheral eosinophilia similar to what is observed in asthma, a number of recent studies have implied that eosinophilic COPD is a distinct entity. This review will seek to contrast the mechanisms of eosinophilia in asthma and COPD, the implications of eosinophilia for disease outcome, and review current data regarding the utility of peripheral blood eosinophilia in the management of COPD patients.

Readmissions of adults within three age groups following hospitalization for pneumonia: Analysis from the Nationwide Readmissions Database.

Background: While 30-day readmissions following hospitalization for pneumonia have been well-studied in the elderly, their burden in young adults remains poorly understood.

Objective: To study patterns of readmissions following hospitalization for pneumonia across age groups and insurance payers.

Methods: In the Nationwide Readmission Database for the years 2013 and 2014 we identified all adults (≥18 years) discharged alive after a hospitalization with the primary diagnosis of pneumonia, and examined rates of readmissions within 30-days of discharge.

Hospitalist Perspective of Interactions with Medicine Subspecialty Consult Services.

Background: Medicine subspecialty consultation is becoming increasingly important in inpatient medicine.

Objective: We conducted a survey study in which we examined hospitalist practices and attitudes regarding medicine subspecialty consultation.

Design And Setting: The survey instrument was developed by the authors based on prior literature and administered online anonymously to hospitalists at 4 academic medical centers in the United States.

Eosinophilic Lung Disease.

Eosinophils are involved in the pathogenesis of a number of lung diseases. Recent advances in eosinophil biology have now produced clinically applicable therapies that seek to counter eosinophilia in blood and lungs. This article reviews the basic biology of eosinophils and their role in mediating T-helper 2 cell responses.

Exome sequencing links mutations in PARN and RTEL1 with familial pulmonary fibrosis and telomere shortening.

Idiopathic pulmonary fibrosis (IPF) is an age-related disease featuring progressive lung scarring. To elucidate the molecular basis of IPF, we performed exome sequencing of familial kindreds with pulmonary fibrosis. Gene burden analysis comparing 78 European cases and 2,816 controls implicated PARN, an exoribonuclease with no previous connection to telomere biology or disease, with five new heterozygous damaging mutations in unrelated cases and none in controls (P = 1.

Pleiomorphic adenoma gene-like 2 expression is associated with the development of lung adenocarcinoma and emphysema.

Previous study of transgenic mice with long-term expression of pleiomorphic adenoma gene-like 2 (PLAGL2), a surfactant protein C (SP-C) transactivator, in type II cells showed the manifestation of centrilobular emphysema in vivo. Since emphysema is an independent risk factor for bronchogenic carcinoma, we hypothesized that the mouse lungs with induced PLAGL2-expression had increased incidences in developing lung adenocarcinoma. To test the hypothesis, mouse lungs were examined for the presence of tumors.

PLAGL2 expression-induced lung epithelium damages at bronchiolar alveolar duct junction in emphysema: bNip3- and SP-C-associated cell death/injury activity.

Emphysema and bronchitis are major components of chronic obstructive pulmonary disease (COPD). Pleomorphic adenoma gene like-2 (PLAGL2), a zinc finger DNA-binding protein, is a transcription factor of the surfactant protein C (SP-C) promoter. Using an inducible transgenic mouse model, PLAGL2 and SP-C were ectopically expressed in lung epithelial cells of terminal bronchiole including the bronchoalveolar duct junction (BADJ), where only few cells express both genes under normal conditions.

Modulation of PLAGL2 transactivation activity by Ubc9 co-activation not SUMOylation.

Pleomorphic adenoma gene like-2 (PLAGL2), a developmentally regulated and stress inducible zinc finger protein can be post-translationally modified by small ubiquitin-like modifier peptide (SUMO-1); and SUMOylation attenuates PLAGL2 activity on the interactive promoter. Since PLAGL2 was a transactivator of the surfactant protein-C (SP-C) promoter, we hypothesized that SUMOylation down-regulated PLAGL2-activated SP-C promoter activity. Unexpectedly, the SUMO-conjugating enzyme Ubc9 enhanced, rather than reduced, PLAGL2 activated promoter activity but did not affect TTF-1 activation of the promoter.

PLAGL2 translocation and SP-C promoter activity--a cellular response of lung cells to hypoxia.

Cobalt is a transition metal which can substitute for iron in the oxygen-sensitive protein and mimic hypoxia. Cobalt was known to be associated with the development of lung disease. In this study, when lung cells were exposed to hypoxia-induced by CoCl(2) at a sub-lethal concentration (100 microM), their thyroid transcription factor-1 (TTF-1) expression was greatly reduced.

Adult-onset pulmonary fibrosis caused by mutations in telomerase.

Idiopathic pulmonary fibrosis (IPF) is an adult-onset, lethal, scarring lung disease of unknown etiology. Some individuals with IPF have a familial disorder that segregates as a dominant trait with incomplete penetrance. Here we used linkage to map the disease gene in two families to chromosome 5.

The TTF-1/TAP26 complex differentially modulates surfactant protein-B (SP-B) and -C (SP-C) promoters in lung cells.

Surfactant protein-B (SP-B) and -C (SP-C) are small hydrophobic surfactant proteins that maintain surface tension in alveoli. Both SP-B and SP-C are regulated by a key factor, thyroid transcription factor-1 (TTF-1), in lung cells. Previously, we identified a 26-kDa, TTF-1-associated protein (TAP26) that was shown to interact with TTF-1 and enhance TTF-1-transactivated SP-B promoter activity.

Pleiomorphic adenoma gene-like-2, a zinc finger protein, transactivates the surfactant protein-C promoter.

Expression of surfactant protein (SP)-C occurs principally in type II pneumocytes located in the distal lung alveolae. SP-C expression is thought to be primarily regulated by thyroid transcription factor (TTF)-1 and its associated proteins interacting with a previously defined promoter region between -197 and -158 in mice. We screened a human lung cDNA library using a modified yeast one-hybrid system and identified pleiomorphic adenoma gene-like (PLAGL)-2, a ubiquitously expressed zinc finger protein, as a transfactor of the SP-C promoter.