John Thompson-Figueroa

Inhaled salmeterol and/or fluticasone alters structure/function in a murine model of allergic airways disease

BackgroundThe relationship between airway structural changes (remodeling) and airways hyperresponsiveness (AHR) is unclear. Asthma guidelines suggest treating persistent asthma with inhaled corticosteroids and long acting β-agonists (LABA). We examined the link between physiological function and structural changes following treatment fluticasone and salmeterol separately or in combination in a mouse model of allergic asthma.MethodsBALB/c mice were sensitized to intraperitoneal ovalbumin (OVA) followed by six daily inhalation exposures. Treatments included 9 daily nebulized administrations of fluticasone alone (6 mg/ml), salmeterol (3 mg/ml), or the combination fluticasone and salmeterol. Lung impedance was measured following methacholine inhalation challenge. Airway inflammation, epithelial injury, mucus containing cells, and collagen content were assessed 48 hours after OVA challenge. Lungs were imaged using micro-CT.Results and DiscussionTreatment of allergic airways disease with fluticasone alone or in combination with salmeterol reduced AHR to approximately naüve levels while salmeterol alone increased elastance by 39% compared to control. Fluticasone alone and fluticasone in combination with salmeterol both reduced inflammation to near naive levels. Mucin containing cells were also reduced with fluticasone and fluticasone in combination with salmeterol.ConclusionsFluticasone alone and in combination with salmeterol reduces airway inflammation and remodeling, but salmeterol alone worsens AHR: and these functional changes are consistent with the concomitant changes in mucus metaplasia.

A Breath Biofeedback Computer Game for Children With Cystic Fibrosis

The authors sought to develop and test a breath-controlled video game using a digital spirometer that, by providing visual breath biofeedback, could promote awareness of breathing techniques in children with cystic fibrosis (CF). To assess improvement in game performance during hospitalizations for CF exacerbations, the authors conducted a trial on 10 inpatients. Subjects had at least five 15-minute exposures to a breath biofeedback game that challenged them to track a moving target using their breath. Subjects reacted positively to the breath tracking challenge. Repeated-measures analysis of variance of a tracking fidelity statistic showed improvement in eye—breath coordination over 5 sessions ( P = .026). It was concluded that an electronic breath game is safe and can improve breath awareness among children with CF. This technology could also contribute to awareness of respiratory symptoms and foster social ties among CF patients.

Thoracic gas volume measurements in paralyzed mice

We have previously measured thoracic gas volume (VTG) in spontaneously breathing mice using a whole body plethysmograph and have now extended our technique to allow for VTG measurements during paralysis. BALB/c mice were anesthetized and placed in a body-box and ventilated via a tracheostomy cannula through the box wall. Box pressure (Pb) and tracheal pressure (Pao) were measured during spontaneous breathing, and again after paralysis while mechanically compressing the chest. VTG was much larger after paralysis (0.49 ± 0.06 ml, positive end-expiratory pressure = 2 cmH2O) when compared with spontaneous breathing (0.31 ± 0.01 ml). External chest compression produced looping in the plots of Pb versus Pao that was attributable to gradual changes in Pb upon release of the mechanical chest compression and had the character of thermal transients. Under the assumption that the rate of heating of the air in the chamber was proportional to the pressure applied to the animals chest, and that any increase in air temperature was dissipated by heat absorption by the chamber walls, we developed an algorithm that corrected for the thermal events. This yielded similar results for VTG (0.30 ± 0.02 ml) as obtained during spontaneous efforts. Our method may prove particularly useful when paralysis is required for the precise measurement of lung mechanics.

Ex Vivo Measurement of Mouse Pulmonary Artery Biomechanics

Primary pulmonary hypertension (PPH) is a rapidly progressing and often fatal disease that induces substantial pulmonary vascular remodeling [1]. Although a genetic factor has been identified in familial and sporadic cases of pulmonary hypertension [2], the etiology of the disease for most victims remains unknown.Copyright