Clinical patterns in asthma based on proximal and distal airway nitric oxide categories.

Background: The exhaled nitric oxide (eNO) signal is a marker of inflammation, and can be partitioned into proximal [J'awNO (nl/s), maximum airway flux] and distal contributions [CANO (ppb), distal airway/alveolar NO concentration]. We hypothesized that J'awNO and CANO are selectively elevated in asthmatics, permitting identification of four inflammatory categories with distinct clinical features.

Methods: In 200 consecutive children with asthma, and 21 non-asthmatic, non-atopic controls, we measured baseline spirometry, bronchodilator response, asthma control and morbidity, atopic status, use of inhaled corticosteroids, and eNO at multiple flows (50, 100, and 200 ml/s) in a cross-sectional study design.

Quantifying proximal and distal sources of NO in asthma using a multicompartment model.

Nitric oxide (NO) is detectable in exhaled breath and is thought to be a marker of lung inflammation. The multicompartment model of NO exchange in the lungs, which was previously introduced by our laboratory, considers parallel and serial heterogeneity in the proximal and distal regions and can simulate dynamic features of the NO exhalation profile, such as a sloping phase III region. Here, we present a detailed sensitivity analysis of the multicompartment model and then apply the model to a population of children with mild asthma.

Impact of analysis interval on the multiple exhalation flow technique to partition exhaled nitric oxide.

Exhaled nitric oxide (eNO) is elevated in asthmatics and is a purported marker of airway inflammation. By measuring eNO at multiple flows and applying models of eNO exchange dynamics, the signal can be partitioned into its proximal airway [J' aw NO (nl/sec)] and distal airway/alveolar contributions [CA(NO)(ppb)]. Several studies have demonstrated the potential significance of such an approach in children with asthma.

An elevated bronchodilator response predicts large airway inflammation in mild asthma.

Exhaled nitric oxide (eNO) is elevated in asthmatics and is a purported marker of airway inflammation. The bronchodilator response (BDR) has also been shown to correlate with markers of airway inflammation, including eNO at 50 ml/sec (FE(NO,50)) which is comprised of NO from both the proximal and distal airways. Using eNO at multiple flows and a two-compartment model of NO exchange, the eNO signal can be partitioned into its proximal [J'aw(NO) (nl/sec)] and distal contributions [CA(NO) (ppb)].

Partitioned exhaled nitric oxide to non-invasively assess asthma.

Asthma is a chronic inflammatory disease of the lungs, characterized by airway hyperresponsiveness. Chronic repetitive bouts of acute inflammation lead to airway wall remodeling and possibly the sequelae of fixed airflow obstruction. Nitric oxide (NO) is a reactive molecule synthesized by NO synthases (NOS).

Prevalence of increased esophageal muscle thickness in patients with esophageal symptoms.

Background: Patients with achalasia, diffuse esophageal spasm (DES), and nutcracker esophagus have a thicker muscularis propria than normal subjects. The goal of our study was to determine the prevalence of increased muscle thickness in a group of unselected patients referred to the esophageal function laboratory for evaluation of the symptoms.

Methods: We studied 40 normal subjects and 94 consecutive patients.

Common cavity pressure during gastroesophageal reflux: reassessment using simultaneous pressure, impedance, and ultrasound imaging.

An increase in intraesophageal pressure during transient lower esophageal sphincter (LES) relaxation [referred to as common cavity (CC) pressure] is thought to be a marker of gastroesophageal reflux (GER). Multiluminal impedance (MII) measurement is a sensitive marker of reflux entry into the esophagus during GER. We recorded GER using esophageal pressure, pH, impedance, and intraluminal ultrasound (US) images to understand the genesis of the esophageal CC pressure.

Asynchrony between the circular and the longitudinal muscle contraction in patients with nutcracker esophagus.

Background & Aims: The increases in intraluminal pressure and muscle cross-sectional area (CSA) during esophageal contraction are markers of circular and longitudinal muscle contractions. The goal of our study was to determine temporal synchrony between circular and longitudinal muscle contraction in healthy subjects and patients with nutcracker esophagus.

Methods: Pressure and high-frequency intraluminal ultrasound (HFIUS) images were recorded simultaneously in healthy subjects and patients with nutcracker esophagus at 2 and 10 cm above the lower esophageal sphincter during wet swallow.

Sensory and motor function of the esophagus: lessons from ultrasound imaging.

Catheter-based high-frequency intraluminal ultrasound imaging is a powerful tool to study esophageal sensory and motor function and dysfunction in vivo in humans. It can be combined with manometry, pH, and impedance measurement techniques to determine the relationships between different physiologic parameters. High-frequency intraluminal ultrasound imaging has provided a number of important insights regarding the longitudinal muscle function of the esophagus.

Crural diaphragm inhibition during esophageal distension correlates with contraction of the esophageal longitudinal muscle in cats.

Esophageal distension causes simultaneous relaxation of the lower esophageal sphincter (LES) and crural diaphragm. The mechanism of crural diaphragm relaxation during esophageal distension is not well understood. We studied the motion of crural and costal diaphragm along with the motion of the distal esophagus during esophageal distension-induced relaxation of the LES and crural diaphragm.

Ultrasound system to measure esophageal varix pressure: an in vitro validation study.

We report our experience with an ultrasound system to measure esophageal varix pressure in an in vitro model. The ultrasound system consists of a 12.5 MHz frequency intraluminal ultrasound probe, a water infusion catheter, and a manometry catheter, all contained within a nondistensible latex bag.

Symptom hypersensitivity to acid infusion is associated with hypersensitivity of esophageal contractility.

Several investigators have observed that repeated acid infusions induce stronger symptoms (symptom hypersensitivity). The goal of our study was to determine whether symptom hypersensitivity is associated with esophageal contractile hypersensitivity. Subjects with chronic heartburn symptoms underwent simultaneous pressure and ultrasound imaging of esophagus.

Hypertrophy of the muscularis propria of the lower esophageal sphincter and the body of the esophagus in patients with primary motility disorders of the esophagus.

Objectives: Patients with diffuse esophageal spasm (DES) and nutcracker esophagus/high amplitude esophageal contraction (HAEC) have a thicker esophageal muscularis propria than do healthy subjects. The goals of this study were to determine the esophageal muscle cross-sectional area (MCSA), a measure of muscle mass, in patients with achalasia of the esophagus; and to compare it with that in patients with DES, patients with HAEC, and normal subjects.

Methods: Using a high-frequency ultrasound probe catheter, concurrent manometry and ultrasound images of the esophagus were recorded in four subject groups: normal volunteers, patients with HAEC, patients with DES, and patients with achalasia of the esophagus.

Measuring esophageal distension by high-frequency intraluminal ultrasound probe.

Distension of the esophagus can cause heartburn and chest pain; however, none of the available techniques to study the esophagus measure esophageal distension. We evaluated the technique of high-frequency intraluminal ultrasound probe (HFIUS) to measure the esophageal cross-sectional area (CSA) during gastroesophageal reflux (GER). The following methods were used: 1) the CSA of agarose gel tubes of known dimensions were measured using ultrasound probes; 2) seven normal subjects were studied to evaluate the esophageal CSA during different bolus volumes (1, 5, 10, 15, and 20 ml) of water swallows (WS); and 3) simultaneous pressures, pH, and ultrasound images of the esophagus were recorded in healthy subjects.

A novel ultrasound technique to study the biomechanics of the human esophagus in vivo.

The objectives of this study were to validate a novel ultrasound technique and to use it to study the circumferential stress-strain properties of the human esophagus in vivo. A manometric catheter equipped with a high-compliance bag and a high-frequency intraluminal ultrasonography probe was used to record esophageal pressure and images. Validation studies were performed in vitro followed by in vivo studies in healthy human subjects.