Rationale: Interstitial lung disease (ILD) in patients with systemic sclerosis (SSc) is associated with increased morbidity and mortality. Gastroesophageal reflux (GER) is considered a contributing factor in the pathogenesis of ILD. Objectives: To characterize GER (acid and nonacid) in patients with SSc with and without ILD. Methods: Patients with SSc underwent pulmonary high-resolution computer tomography (HRCT) scan and 24-hour impedance–pH monitoring off–proton pump inhibitor therapy. The presence of pulmonary fibrosis was assessed using validated HRCT-scores. Reflux monitoring parameters included number of acid and nonacid reflux episodes, proximal migration of the refluxate, and distal esophageal acid exposure. Unless otherwise specified, data are presented as median (25th–75th percentile). Measurements and Main Results: Forty consecutive patients with SSc (35 female; mean age, 53 yr; range, 24–71; 15 patients with diffuse and 25 with limited SSc) were investigated; 18 (45%) patients with SSc had pulmonary fibrosis (HRCT score ≥ 7). Patients with SSc with ILD had higher (P < 0.01) esophageal acid exposure (10.3 [7.5–15] vs. 5.2 [1.5–11]), higher (P < 0.01) number of acid (41 [31–58] vs. 19 [10–23]) and nonacid (25 [20–35] vs. 17 [11–19]) reflux episodes, and higher (P < 0.01) number of reflux episodes reaching the proximal esophagus (42.5 [31–54] vs. 15 [8–22]) compared with patients with SSc with normal HRCT scores. Pulmonary fibrosis scores (HRCT score) correlated well with the number of reflux episodes in the distal (r² = 0.637) and proximal (r² = 0.644) esophagus. Conclusions: Patients with SSc with ILD have more severe reflux (i.e., more reflux episodes and more reflux reaching the proximal esophagus). Whether or not the development of ILD in patients with SSc can be prevented by reflux-reducing treatments needs to be investigated.

Nonerosive reflux disease (NERD) is the most common form of gastroesophageal reflux disease. While the role of acid reflux has been established, the relevance of nonacid reflux in generating symptoms in NERD is unknown. To evaluate the diagnostic utility of impedance-pH monitoring in NERD patients. Patients with typical reflux symptoms (heartburn and/or regurgitation) and normal endoscopy (NERD) underwent a combined impedance-pH monitoring off proton pump inhibitor (PPI) therapy. Previously investigated 48 healthy volunteers served as controls. Distal esophageal acid exposure (% time pH < 4), number of acid and nonacid reflux episodes, 2-min window symptom index (SI; positive if ≥ 50%), and symptom association probability (SAP; positive if ≥ 95%) were calculated. Between June 2004 and June 2007, 150 NERD patients (82 women, mean age 48 yr, range 18–78 yr) reported symptoms during the impedance-pH monitoring. NERD patients had more reflux episodes (median [25th–75th percentile]) compared with healthy volunteers (total: 46 [26–65] vs 32 [18–43], P < 0.05; acid: 29 [14–43] vs 17 [8.5–31.0], P < 0.05; and nonacid: 20 [15–27] vs 18 [13.5–26.0], P= NS). Sixty-three (42%) patients had abnormal % time pH < 4. Among 87 patients with normal % time pH < 4., 22 (15%) had a positive SAP for acid, 19 (12%) for nonacid reflux, and 7 (5%) for both. Classifying patients with symptomatic nonacid reflux as having a hypersensitive esophagus reduced the number of patients with functional heartburn from 65 (43%) to 39 (26%). Monitoring for nonacid reflux in NERD patients reduces the proportion of patients classified as having “functional heartburn.” Studies assessing the clinical implications of these findings are warranted.

The aim of the study was to characterise gastro-oesophageal reflux (GOR) in idiopathic pulmonary fibrosis (IPF).40 consecutive IPF patients underwent pulmonary high-resolution computed tomography (HRCT) scan and impedance-pH monitoring while off antisecretory therapy. The presence of pulmonary fibrosis was assessed using validated HRCT scores. Reflux features included distal oesophageal acid exposure, number of acid/weakly acidic reflux episodes and their proximal migration. 40 consecutive patients with interstitial lung disease other than IPF (non-IPF patients) and 50 healthy volunteers were also enrolled.IPF patients had significantly higher (p<0.01) oesophageal acid exposure (median (interquartile range (IQR)) 9.25 (4.7–15.4)%versus3.3 (1.4–7.4)%versus0.7 (0.2–4.2)%, number of acid (median (IQR) 45 (23–55)versus32 (19–44)versus18 (10–31)), weakly acidic (median (IQR) 34 (19–43)versus21 (11–33)versus18 (15–28)) and proximal reflux (median (IQR) 51 (26.5–65.5)versus20 (9.5–34.5)versus9 (5–20)) events compared to non-IPF patients and healthy volunteers, respectively. Pulmonary fibrosis HRCT scores correlated well with reflux episodes in both the distal (r²=0.567) and proximal (r²=0.6323) oesophagus. Patients with IPF had more bile acids and pepsin (p<0.03) in bronchoalveolar lavage fluid (BALF) (62% and 67%, respectively) and saliva (61% and 68%, respectively) than non-IPF patients (25% and 25% in BALF, and 33% and 36%, respectively, in saliva) and controls (0% and 0% in BALF and saliva, respectively).Acid GOR is common in IPF, but weakly acidic GOR may also occur. Patients with IPF had a risk of pulmonary aspiration of gastric contents. Outcome studies with intense antireflux therapy are needed.

Introduction: Functional dyspepsia and non-erosive reflux disease (NERD) are prevalent gastrointestinal conditions with accumulating evidence regarding an overlap between the two. Still, patients with NERD represent a very heterogeneous group and limited data on dyspeptic symptoms in various subgroups of NERD are available. Aim: To evaluate the prevalence of dyspeptic symptoms in patients with NERD subclassified by using 24 h impedance-pH monitoring (MII-pH). Methods: Patients with typical reflux symptoms and normal endoscopy underwent impedance-pH monitoring off proton pump inhibitor treatment. Oesophageal acid exposure time (AET), type of acid and non-acid reflux episodes, and symptom association probability (SAP) were calculated. A validated dyspepsia questionnaire was used to quantify dyspeptic symptoms prior to reflux monitoring. Results: Of 200 patients with NERD (105 female; median age, 48 years), 81 (41%) had an abnormal oesophageal AET (NERD pH-POS), 65 (32%) had normal oesophageal AET and positive SAP for acid and/or non-acid reflux (hypersensitive oesophagus), and 54 (27%) had normal oesophageal AET and negative SAP (functional heartburn). Patients with functional heartburn had more frequent (p<0.01) postprandial fullness, bloating, early satiety and nausea compared to patients with NERD pH-POS and hypersensitive oesophagus. Conclusion: The increased prevalence of dyspeptic symptoms in patients with functional heartburn reinforces the concept that functional gastrointestinal disorders extend beyond the boundaries suggested by the anatomical location of symptoms. This should be regarded as a further argument to test patients with symptoms of gastro-oesophageal reflux disease in order to separate patients with functional heartburn from patients with NERD in whom symptoms are associated with gastro-oesophageal reflux.

Aliment Pharmacol Ther 2011; 34: 476–486 Summary Background Limited data are available regarding the frequency of oesophageal motility and bolus transit abnormalities in subgroups of patients with gastro‐oesophageal reflux disease (GERD). Aim To assess oesophageal motility and bolus transit in endoscopically defined GERD subgroups. Methods Patients (N = 755) with typical reflux symptoms underwent upper endoscopy, conventional or impedance oesophageal manometry and/or impedance‐pH testing. They were divided into: erosive oesophagitis (EO; N = 340), Barrett Oesophagus (BO; N = 106), non‐erosive reflux disease (NERD; endoscopy−, abnormal pH and/or SAP/SI+; N = 239) and functional heartburn (FH; endoscopy−, normal pH and SAP/SI−; N = 70). Manometric patterns and bolus transit were defined according to previously published criteria. Results Increasing GERD severity was associated with decreased lower oesophageal sphincter resting pressure (P < 0.05) and distal oesophageal amplitude (P < 0.01), higher prevalence of hiatal hernia (P < 0.01) and increased prevalence of ineffective oesophageal motility (P < 0.01). Patients with EO and BO had a significantly lower percentage of complete bolus transit compared with NERD and FH (P < 0.01). Overall, abnormal bolus transit (ABT) for liquid swallows was found in 12% of FH, 20% of NERD, 54% of EO and 56% of BO (P < 0.01). Combined impedance‐manometry showed abnormal oesophageal function in 4% of FH, 4% of NERD, 22% of EO and 21% of BO patients with normal oesophageal manometry. Conclusions Oesophageal motility abnormalities increase in parallel with the severity of GERD from NERD to EO and BO. Bolus transit abnormalities in severe reflux disease underscore the importance of impaired oesophageal function in the development of mucosal injury.