Synchronous airway lesions in children: an analysis of characteristics and comorbidities.

OBJECTIVES: To analyze the characteristics and the associated medical co-morbidities in children with synchronous airway lesions (SALs) found during rigid bronchoscopy. METHODS: Retrospective case series and chart review of patients who were found to have more than one airway lesion after undergoing airway evaluation via rigid endoscopy at a tertiary care pediatric hospital between 2001 and 2011. Patient demographics, presence of associated non-airway pathologies, and the number and types of airway lesions were collected. For analysis, airway lesions were classified based on the anatomical subsites involved (supraglottic, glottic, subglottic, tracheal and bronchial). RESULTS: Out of 592 rigid bronchoscopies performed, there were 73 cases with SALs (12.3%). Of these, only 20% of patients were term infants without associated congenital anomalies. Over 70% of patients with SALs have combinations of lesions involving the trachea, subglottis and supraglottis. Neurological anomalies and GERD were both independently associated with a three-time increase in the odds of having synchronous involvement of these three anatomical subsites (OR 3.15, 95% CI 1.06-9.41; OR 3.0, 95% CI 1.05-8.50, respectively). Glottic lesions were present in 28.7% of patients. Prematurity and cardiac anomalies were both associated with tendency of doubling the odds of glottic lesions (OR 2.34, 95% CI 0.84-6.52; OR 2.0, 95% CI 0.76-5.60, respectively). Overall, almost 10% of newly diagnosed lesions in context of SALs required an additional intervention. CONCLUSIONS: The majority of patients with SALs are either born prematurely or have associated congenital anomalies. In SAL patients with associated neurological anomalies or GERD, the lesions are more likely to be localized to the supraglottis, subglottis and trachea whereas prematurity and cardiac anomalies could both be increasing the odds of a glottic lesion. High suspicious index should be kept in mind when rigid bronchoscopy is performed to not miss an associated lesion.

Pharmacological AMP-kinase activators have compartment-specific effects on cell physiology.

5'-AMP-activated kinase (AMPK) regulates numerous biological events and is an essential target for the treatment of type 2 diabetes. The objectives of the present study were first to determine the compartment-specific effects of three established AMPK activators on Thr172 phosphorylation of the α-subunit, an indicator of AMPK activation. Second, we examined how cytoplasmic and nuclear processes are modulated by pharmacological AMPK activators. Specifically, the impact of phenformin, resveratrol, and 5-aminoimidazole-4-carboxamide riboside (AICAR) on Thr172 phosphorylation in the cytoplasm and nucleus was quantified by different methods. To analyze how these activators change cell physiology, we measured the inactivation of acetyl-CoA-carboxylase 1, a predominantly cytoplasmic enzyme that is crucial for lipid metabolism. As a criterion for activities associated with the nucleus, de novo RNA synthesis in nucleoli was quantified. Our studies demonstrate that pharmacological activators of AMPK can alter the balance between nuclear and cytoplasmic AMPK pools. Thus, phenformin and resveratrol caused a strong activation of AMPK in the cytoplasm, whereas the effect was less pronounced in nuclei. By contrast, AICAR elicited a comparable rise in Thr172 phosphorylation in both compartments. Notably, these activators differed drastically in their effects on physiological processes that are located in distinct subcellular compartments. All compounds led to a substantial inactivation of acetyl-CoA-carboxylase 1 in the cytoplasm, with only minor changes to the nuclear enzyme. In the nucleolus, transcription was strongly inhibited by resveratrol, while a moderate inhibition was observed with phenformin and AICAR. Taken together, the compartment-specific phosphorylation of AMPK and downstream events are determined by the activator.