23  Gastroesophageal Refux: Idiopathic Pulmonary Fibrosis and Lung Transplantation	407

Fig. 23.2  Concepts of gastroesophageal refux and microaspiration in the pathogenesis of IPF. Note the transit of gastric juice from the stomach to the pulmonary system via refux and microaspiration (red dots). Recurrent injury caused by the contents of gastric juice leads to aberrant wound healing and eventual pulmonary brosis

Micro aspiration–gastric juice/contents (acid/alkaline; pepsin, bile)

Predisposing

Factors (genetic/aged lung)

Recurrent

Aberrant

Wound Healing

Over time

Pulmonary Fibrosis

sleep apnea (OSA) is another co-morbid disorder that has been identi ed in as many as 88% of patients undergoing prospective evaluation [22]. While the presence of OSA and nocturnal hypoxia alone have been associated with accelerated lung function decline and increased mortality there is a strong body of evidence supporting a link between nocturnal apnea and abnormal gastroesophageal refux [23]. Several hypotheses exists regarding the link between OSA and GER including periodic decreases in intrathoracic pressure caused by inspiratory efforts against an obstructed upper airway or lower esophageal sphincter dysfunction [24].

GER and the Microbiome

The epithelial tract of the lung is populated with a diverse array of microbes with new bacterial rRNA sequencing techniques allowing for better characterization of these populations compared to traditional culture techniques [25]. The lung microbiome has been an area of increased interest as a possible contributor to the pathogenesis of IPF and a potential therapeutic target [26]. Animal studies have suggested that the presence of gut speci c bacteria in the respiratory tract can potentiate infammation and lung injury [27]. Interestingly, the use of proton pump inhibitors has been shown to have a signi cant effect on both gastric and lung microbiota [28]. Whether the changes in the gut microbiome which have been identi ed in patients with abnormal GER and IPF or the microaspiration of gastric contents have a direct effect on the lung microbiome need further study.

Diagnosis

Clinical History/Physical Exam

When assessing patients for possible GER it is important to determine the presence of any of the typical esophageal symptoms including heartburn, regurgitation, or chest pain. There are also extraesophageal symptoms including cough or laryngitis. However, the presence of symptoms is an unreliable indicator of the presence of GER as a signi cant number of patients with IPF can have signi cant refux without typical symptoms. In a prospective evaluation of 65 IPF patients Raghu et al. found that while 87% had signi cant GER based on 24-h pH testing only 47% experienced classic symptoms [9]. Allaix et al. demonstrated in patients with IPF the prevalence of esophageal symptoms such as heartburn are less common while extraesophageal symptoms such as cough are more prevalent [29].

Investigations

Esophageal Physiology

Upper Esophageal Sphincter

After mastication and formation of a food bolus the swallowing mechanism is initiated, and the bolus is rapidly moved by the tongue via the pharynx to the esophagus. The upper esophageal sphincter (UES) is a region of predominantly striated muscle that begins at the distal pharynx. At rest, it is normally closed and tonically contracted generating a resting