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Biomedical subjects

Benjamin M Gaston

Publications and source records attributed to Benjamin M Gaston.

4 recordsLinked to original sources

Features of severe asthma in school-age children: Atopy and increased exhaled nitric oxide.

BACKGROUND: Children with severe asthma have persistent symptoms despite treatment with inhaled corticosteroids (ICSs). The differentiating features of severe asthma in children are poorly defined. OBJECTIVE: To identify features of severe versus mild-to-moderate asthma in school-age children using noninvasive assessments of lung function, atopy, and airway inflammation. METHODS: A total of 75 children (median age, 10 years) with asthma underwent baseline characterization including spirometry and lung volume testing, methacholine bronchoprovocation, allergy evaluation, and offline measurement of exhaled nitric oxide (F(ENO)). Twenty-eight were followed longitudinally over 6 months. Participants were assigned to the severe asthma subgroup if they required high-dose ICS plus 2 or more minor criteria. RESULTS: Children with severe versus mild-to-moderate asthma had more symptoms, greater airway obstruction, more gas trapping, and increased bronchial responsiveness to methacholine. Subjects with severe asthma also had higher concentrations of F(ENO) and significantly greater sensitization to aeroallergens. With long-term study, both the reduction in FEV(1) and increase in F(ENO) persisted in the severe versus mild-to-moderate group. Furthermore, despite adjustments in ICS doses, the frequency of exacerbations was significantly higher in subjects with severe (83%) versus mild-to-moderate asthma (43%). CONCLUSION: Severe asthma in childhood is characterized by poor symptom control despite high-dose ICS treatment and can be differentiated from mild-to-moderate asthma by measurement of lung function and F(ENO). CLINICAL IMPLICATIONS: Clinicians should suspect severe asthma in children with poor response to ICS, airway obstruction, and high F(ENO).

Adolescent↗

Exhaled-breath condensate pH can be safely and continuously monitored in mechanically ventilated patients.

BACKGROUND: Airway inflammation in acute and chronic respiratory diseases is characterized in part by abnormal pH in airway-lining fluid. The pH of exhaled-breath condensate (EBC) is low (acidic) in various pulmonary inflammatory diseases, including asthma, chronic obstructive pulmonary disease, cystic fibrosis, pneumonia, and acute respiratory distress syndrome. Because the time course of pH changes in the airway is not yet clear, we aimed to develop a method for frequent and intensive EBC pH data collection in mechanically ventilated patients. METHODS: We examined the collection, gas-standardizing (CO2 removal), and continuous monitoring of pH of EBC from the expiratory port of a Servo-i ventilator with mechanically ventilated patients. We developed a condensing device that attaches to the exhaust port and is chilled by an electric cooling system. We built a 2-chamber gas-standardization and pH-measuring device that attaches to the condensing system and records pH every 6 s. After safety testing, we enrolled mechanically ventilated patients (with diverse reasons for requiring ventilatory support) for up to 96 h of continuous EBC pH condensimetry. RESULTS: The pressure, volume, and flow of the ventilator attached to a test lung were unchanged by application of the condensimeter, at various flows (2-120 L/min) and ventilator settings. We monitored 19 pediatric patients for 6-96 h. The pH of the accumulated EBC in the storage container correlated with the geometric mean of all the pH data points from the condensimeter during the recording period (r2 = -0.95, p < 0.001), which internally validated that the condensimetry system provides accurate, well gas-standardized readings for up to 96 h. The EBC pH values were similar to published reports of single samples. The EBC pH became more acidic during clinical deterioration and normalized with recovery. CONCLUSION: Continuous monitoring of EBC pH from the ventilator exhaust port is safely achievable and reliably provides data that may become useful in monitoring critically ill patients.

Adolescent↗

S-nitrosylation signaling in cell biology.

S-Nitrosylated proteins form when a cysteine thiol reacts with nitric oxide (NO) in the presence of an electron acceptor to form an S-NO bond. Under physiological conditions, this posttranslational modification affects the function a wide array of cell proteins, ranging from ion channels to nuclear regulatory proteins. Recent evidence suggests that 1) S-nitrosylated proteins can be synthesized by exposure of specific redox-active motifs to NO, through transnitrosation/transfer reactions, or through metalloprotein-catalyzed reactions; 2) S-nitrosothiols can be sequestered in membranes, lipophilic protein folds, or in vesicles to preserve their activity; and 3) S-nitrosothiols can be degraded by a number of enzymes systems. These recent insights regarding the bioactivities, molecular signaling pathways, and metabolism of endogenous S-nitrosothiols have suggested several new therapies for disease ranging from cystic fibrosis to pulmonary hypertension.

DNA-Binding Proteins↗