pressure separating atmospheric and intrathoracic pressures that reduces air entry from the pharynx and prevents retrograde­ movement of esophageal contents. This pressure varies signi cantly during normal daily activities (ex. respiration, sleep, and coughing) and adaptive changes in pressure are controlled by afferent signaling from the vagus nerve. A number of refexes increase UES tone and play a key role in preventing the refux of gastric contents into the lung. For example, UES tone increases in response to slow dilation of the esophagus or in response to increase in intrathoracic pressure (i.e., gagging or the Valsalva maneuver).

Esophagus and Peristalsis

The esophagus is a 22–24 cm tube in adults that terminates at the gastroesophageal junction (GEJ). Primary peristalsis is triggered by the swallowing mechanism which results in a sequence of contractile events through four distinct segments. Secondary peristalsis can also occur at any segment of the esophagus and occurs in response to luminal distension. These actions propel the esophageal contents distally towards the stomach. Esophageal motility can be abnormal with decreased contractions (hypocontracting esophagus), increased contractions (nutcracker esophagus), or be affected by systemic disorders such as scleroderma ( brosis of esophageal smooth muscle) [30]. Esophageal function is best assessed by high resolution manometry which is discussed in detail in a later section.

Lower Esophageal Sphincter and Diaphragm

The lower esophageal sphincter (LES) is a specialized section of smooth muscle at the junction of the esophagus and stomach. Similar to the UES tonic contraction of this region creates a resting pressure that is 15–30 mmHg higher than intra-abdominal pressure. The most distal portion of the LES lies distal to the diaphragm and is exposed to intra-­abdominal pressures which has a valve-like effect. The portions of the diaphragm adjacent to the LES are the crura, bromuscular structures that originate from the vertebra wrapping around the esophageal hiatus and inserting into the central tendon (Fig. 23.3). The crural diaphragm plays a key role in maintaining LES pressure during dynamic events such as respiration or increased intra-abdominal pressure. Several studies have demonstrated that even in the absence of lower esophageal sphincter tone the activity of the crural diaphragm can prevent refux of gastric contents. In addition to relaxation during swallowing and peristalsis the LES undergoes transient episodes of relaxation to allow for events such as belching. It is thought that during these episodes of relaxation the majority of GER occurs [31].

A hiatal hernia is the translocation of abdominal contents through the esophageal hiatus into the thoracic cavity (Fig. 23.4). There are three recognized types with Type I being the most common (>90% of cases) and describes the

Fig. 23.3  The undersurface of the diaphragm. The esophageal hiatus is marked by the dashed circle. The origins of the left and right crus are marked by (*) originating from the vertebra wrapping around the esophageal hiatus to insert into the central tendon. These structures are essential to maintaining lower esophageal sphincter pressure

herniation of the gastric cardia upwards due to widening of the aperture of the esophageal hiatus [32]. The presence of a hiatal hernia increases the risk of GER through several mechanisms including: decreased LES pressure and length, impaired diaphragmatic sphincter activity, and delayed esophageal acid clearance [33]. Numerous studies have demonstrated that the presence of a hiatal hernia is associated with more frequent GER, increased severity, and a poorer response to pharmacologic therapy [34, 35].

One theory has proposed a causative link between IPF and abnormal GER as a result of decreased compliance of the pulmonary system and distortion of mediastinal structures as brosis progresses. This distortion effect could impact the pressure and behavior of the esophageal sphincter causing increased refux. Furthermore, the presence of pulmonary brosis could lead to increased transdiaphragmatic pressure gradients. This has not been rigorously tested and several studies have not shown any positive correlation between severity of lung function impairment and the presence of GER [9, 36, 37].

Esophageal pH and Impedance Testing

The direct measurement of acid GER is facilitated by the use of a catheter which can measure the pH of the esophageal contents in the area of the sensor. A transnasal catheter is advanced through the esophagus with the end resting at 5 cm above the lower esophageal sphincter (to allow for shifting with head movement). Some catheters have a second sensor at the proximal esophagus to allow for measurements in this

Fig. 23.4  High resolution computed tomography (HRCT) images with sagittal and coronal sections. Panels a and b demonstrate in the sagittal plane a moderate sized hiatal hernia in the thoracic cavity (red circle

and arrows). Panels c and d demonstrate the same nding in a coronal plane. In addition, there are basal predominant subpleural reticular markings and interlobular septal thickening

area. Less commonly, a wireless pH sensor can be placed via endoscopy in the distal esophageal mucosa. The catheter is left in position and takes repeated measurements over a period of 24 h. This duration is chosen to capture and entire circadian cycle with a variety of activities and postures including eating (upright) and sleeping (recumbent). Most reports are provided with tracings showing the pH at both the proximal and distal probes over the duration of the study (Fig. 23.5).

A refux event is de ned as a decrease in the esophageal pH to less than 4. The acid exposure time (AET) can be calculated by determining the percent of time of the total study with a pH < 4. The DeMeester score is a composite of six parameters from the 24-h test including: total AET, upright AET, supine AET, number of refux episodes (of any length), number of refux episodes >5 mins, and the duration of the longest refux episode. A 24-h pH score (DeMeester Score) is

Fig. 23.5  Sample tracing from a 24-h pH monitor study. Time is displayed along the X-axis in 15-min intervals and both the proximal (pH1) and distal (pH2) probes are displayed. The pH measured at each probe is displayed on the Y-axis. Patient-reported events including meals, and symptoms are reported above the pH tracings. In this example an early period of normal pH is demonstrated with periodic

Table 23.1  Components of the DeMeester score [39]

determined by calculating the number of standard deviation equivalents in each measured value of the six components. The normal values for these measurements are displayed in Table 23.1 and a normal total score is <14.7 [38, 39].

A major disadvantage of pH testing is the inability to measure weakly acidic or non-acidic refux episodes which contain other gastric contents that can be introduced to the lower respiratory system. Impedance testing provides the ability to measure and characterize the movement of liquid in the esophagus. Several pairs of electrodes are placed along the esophageal catheter and the electrical resistance between these pairs is measured (as impedance). Impedance is low with liquid present between the electrodes and high when air is present. This allows for anterograde and retrograde movement of esophageal fuid to be quanti ed and characterized. When added to pH testing this increases the speci city and sensitivity of detecting refux episodes [40].

episodes of decreased pH at both the distal and proximal probes associated with a meal (red arrows). A subsequent period in the recumbent position is associated with a prolonged episode of refux (pH < 4) at the distal probe (red box). This example highlights an episode of prolonged refux after eating a meal and lying recumbent shortly thereafter

High Resolution Esophageal Manometry

The evaluation of esophageal function is a critical part of the investigation of patients with IPF and suspected GER or microaspiration. High resolution manometry is the recommended test for identifying major or minor disorders of peristalsis and outfow obstruction of the distal esophagus. A standardized approach to test performance and interpretation has been published in the Chicago Classi cation [41].

A manometry catheter is introduced into the esophagus and in the supine position the patient ingests 10 separate boluses of 5 mL of saline. An additional set of swallowed boluses can be performed with a viscous gel to better simulate the consistency of food. Sensors distributed along the catheter measure pressure along the esophagus and allows for the assessment of peristalsis and sphincter function (Fig. 23.6).

Peristalsis is critical for the propulsion of a food bolus through the esophagus and coordinated function of the upper and lower esophageal sphincters prevent retrograde movement. Impaired esophageal motility can increase the prevalence and severity of GER [42, 43]. Gao et al. compared patients with IPF and matched controls (both groups had GERD) and performed high resolution esophageal manometry, pH, and impedance testing. When compared to controls IPF patients with GER (con rmed with pH testing) had lower upper esophageal sphincter pressures and increased food bolus transit times [44].

While some disagreement exists over whether any speci c ndings on manometry studies correlate with GERD [45, 46] identifying abnormal esophageal motility can iden-