Matthew P. Sweet

Does Chronic Microaspiration Cause Idiopathic Pulmonary Fibrosis

Idiopathic pulmonary fibrosis is a diffuse fibrotic lung disease of unknown etiology with no effective treatment. Emerging data support a role for chronic microaspiration (ie, subclinical aspiration of small droplets) in the pathogenesis and natural history of idiopathic pulmonary fibrosis. However, the precise relationship between chronic microaspiration and idiopathic pulmonary fibrosis remains unknown. Gastroesophageal reflux, a presumed risk factor for microaspiration, has been strongly associated with idiopathic pulmonary fibrosis with an estimated prevalence of up to 90%. This review aims to describe the relationship between chronic microaspiration and idiopathic pulmonary fibrosis by laying out the clinical and biologic rationale for this relationship and exploring the scientific evidence available. The gaps in our current understanding of the diagnosis of chronic microaspiration and idiopathic pulmonary fibrosis and the ongoing uncertainties in management and treatment will be highlighted. Defining the role of chronic microaspiration in idiopathic pulmonary fibrosis is essential as it has potential clinical, pathobiological, and treatment implications for this deadly disease.

The aldosteronoma resolution score: predicting complete resolution of hypertension after adrenalectomy for aldosteronoma.

Objective:To develop a prediction model using information readily available, at clinical presentation, which could determine whether patients with aldosterone-producing adenomas would have complete resolution of hypertension after adrenalectomy. Background:Primary aldosteronism is the most common curable cause of secondary hypertension. However, a large number of patients continue to require antihypertensive medications to control their blood pressure. Differentiating patients that will have complete resolution of hypertension without the need for antihypertensive medications from patients that will require continued use of antihypertensive medications is difficult before adrenalectomy. Methods:The predictive logistic regression model was derived using data on 100 patients who underwent adrenalectomy for primary aldosteronism at one tertiary medical center and was externally validated using an independent series of 67 patients from another center. Results:Clinical features were similar for patients in the derivation and validation groups. Four readily available predictors (2 or fewer antihypertensive medications, body mass index ≤25 kg/m2, duration of hypertension ≤6 years, and female sex) yielded the best predictive model for complete resolution of hypertension after adrenalectomy. Based on the resulting 4-item aldosteronoma resolution score (ARS), 3 likelihood levels for complete resolution were identified: low (0–1), medium (2–3), and high (4–5) with a predictive accuracy of 27%, 46%, and 75%, respectively. Conclusion:The ARS accurately identifies individuals at low (ARS ≤1) or high (ARS ≥4) likelihood of complete resolution of hypertension without further need of lifelong antihypertensive medications after adrenalectomy for aldosteronoma. This scoring system can help clinicians objectively inform patients of likely clinical outcomes before surgical intervention.

Gastro-oesophageal reflux and aspiration in patients with advanced lung disease

Numerous small observational studies have shown that gastro-oesophageal reflux is prevalent among patients with advanced lung disease. The fundamental concern is that reflux is a risk factor for recurrent microaspiration, which may cause lung injury. For example, in lung transplant patients, a molecular marker of aspiration was a risk factor for the bronchiolitis obliterans syndrome in one study. To date, however, there are no large prospective studies measuring the impact of aspiration on clinical outcomes. The major obstacle limiting the study of reflux and aspiration in patients with advanced lung disease is the absence of a reliable diagnostic tool. Proximal oesophageal acid detection by pH monitoring is the only widely available measure of aspiration risk. Impedance monitoring may be a superior measure of aspiration risk as it measures both acid and non-acid reflux episodes. Molecular markers of aspiration, such as pepsin or bile salts in the bronchoalveolar lavage or exhaled breath condensate, may be the optimal diagnostic tests, but they are not currently available outside the research setting. Larger observational studies are needed to determine the following: (1) the clinical significance of aspiration in patients with advanced lung disease and in patients who have had lung transplantation and (2) the diagnostic test that best predicts adverse outcomes.

A Standardized Multi-Branched Thoracoabdominal Stent-Graft for Endovascular Aneurysm Repair

Purpose: To assess the feasibility of endovascular thoracoabdominal aortic aneurysm (TAAA) repair using a standard off-the-shelf multi-branched stent-graft. Methods: The aortic anatomy of 66 patients (45 men; mean age 74 years, range 57–87) referred for endovascular repair of TAAA was measured using 3-dimensional reconstructed images from computed tomographic angiograms. In particular, the orientation and longitudinal position of the orifice of each celiac artery, right renal artery, and left renal artery were measured relative to the location of the superior mesenteric artery (SMA) orifice. Based on prior experience, branch insertion with a standard endograft was considered feasible under the following conditions: (1) no more than 4 indispensable (target) arteries to the abdominal viscera, (2) the celiac artery and SMA were 6 to 10 mm in diameter, (3) the renal arteries were 4 to 8 mm in diameter, (4) all target arteries were accessible from a transbrachial approach, (5) the distance between each cuff and the corresponding arterial orifice was ≤50 mm, and (6) the line between the cuff and the orifice deviated by ≤45° from the long axis of the aorta. Results: Seven (11%) of 66 patients violated conditions 1 through 4: 2 had target arteries that were either too wide or too narrow, 2 had >4 indispensable visceral or renal branches, and 3 patients had inaccessible upward directed renal artery branches. Three of the remaining 59 patients had renal arteries outside the boundaries defined by conditions 5 and 6 when the hypothetical stent-graft was positioned with its SMA cuff 25 mm proximal to the corresponding SMA orifice. However, if the stent-graft were deployed in a more caudal location, only 1 of these 3 renal arteries would have been out of range. Therefore, 58 (88%) of 66 patients met all the eligibility criteria for repair using the off-the-shelf stent-graft. Conclusion: A standardized, off-the-shelf, multi-branched stent-graft is applicable in 88% of cases of TAAA that would otherwise have been treated using customized stent-grafts. The use of a pre-made stent-graft has the potential to eliminate long manufacturing delays and expand the scope of endovascular repair of TAAA.

The Prevalence of Distal and Proximal Gastroesophageal Reflux in Patients Awaiting Lung Transplantation

Objective:To determine the prevalence and proximal extent of gastroesophageal reflux (GERD) in patients awaiting lung transplantation. Background:GERD has been postulated to contribute to accelerated graft failure in patients who have had lung transplantations. However, the prevalence of reflux symptoms, esophageal motility abnormalities, and proximal esophageal reflux among patients with end-stage lung disease awaiting lung transplantation are unknown. Methods:A total of 109 patients with end-stage lung disease awaiting lung transplantation underwent symptomatic assessment, esophageal manometry, and esophageal pH monitoring (using a probe with 2 sensors located 5 and 20 cm above the lower esophageal sphincter). Results:Reflux symptoms were not predictive of the presence of reflux (sensitivity, 67%; specificity, 26%). Esophageal manometry showed a high prevalence of a hypotensive lower esophageal sphincter (55%) and impaired esophageal peristalsis (47%) among patients with reflux. Distal reflux was present in 68% of patients and proximal reflux was present in 37% of patients. Conclusions:These data show that in patients with end-stage lung disease: 1) symptoms were insensitive and nonspecific for diagnosing reflux; 2) esophageal motility was frequently abnormal; 3) 68% of patients had GERD; 4) in 50% of the patients with GERD, acid refluxed into the proximal esophagus. We conclude that patients with end-stage lung disease should be screened with pH monitoring for GERD.

Gastroesophageal Reflux Disease and Obesity. Pathophysiology and Implications for Treatment

Although the etiology of gastroesophageal reflux disease (GERD) is multifactorial, the pathophysiology of the disease in morbidly obese patients remains incompletely understood. The aims of this study were to compare in morbidly obese (body mass index (BMI) ≥35) and nonmorbidly patients (BMI <35) with GERD: (a) lower esophageal sphincter (LES) profile; (b) esophageal body function; and (c) esophageal acid exposure. We reviewed esophageal manometry and ambulatory 24-hour pH monitoring studies of 599 consecutive patients with GERD (DeMeester score >14.7). Patients were divided into two groups according to the BMI: (1) 520 patients (86.8%) with BMI <35 and (2) 79 patients (13.2%) with BMI ≥35. While the DeMeester score was not different between the two groups, morbidly obese patients had higher LES pressure and higher amplitude of peristalsis in the distal esophagus (DEA). Among these patients, LES and DEA pressures were often hypertensive. A linear regression model showed that BMI, LES pressure, LES abdominal length, and DEA were independently associated with the DeMeester score. These data showed that: (a) BMI was independently associated to the severity of GERD; and (b) in most morbidly obese patients with GERD, reflux occurred despite normal or hypertensive esophageal motility. These findings show that the pathophysiology of GERD in morbidly obese patients might differ from that of nonobese patients, suggesting the need for a different therapeutic approach.

Antireflux surgery for patients with end-stage lung disease before and after lung transplantation

BackgroundGastroesophageal reflux disease (GERD) is prevalent among patients with end-stage lung disease (ESLD). This disease can lead to microaspiration and may be a risk factor for lung damage before and after transplantation. A fundoplication is the best way to stop reflux, but little is known about the safety of elective antireflux surgery for patients with ESLD. This study aimed to report the safety of laparoscopic fundoplication for patients with ESLD and GERD before or after lung transplantation.MethodsBetween January 1997 and January 2007, 305 patients were listed for lung transplantation, and 189 patients underwent the procedure. In 2003, routine esophageal studies were added to the pretransplantation evaluation. After the authors’ initial experience, gastric emptying studies were added as well.ResultsA total of 35 patients with GERD or delayed gastric emptying were referred for surgical intervention. A laparoscopic fundoplication was performed for 32 patients (27 total and 5 partial). For three patients, a pyloroplasty also was performed. Two patients had a pyloroplasty without fundoplication. Of the 35 operations, 15 were performed before and 20 after transplantation. Gastric emptying of solids or liquids was delayed in 12 (92%) of 13 posttransplantation studies and 3 (60%) of 5 pretransplantation studies. All operations were completed laparoscopically, and 33 patients recovered uneventfully (94%). The median hospital length of stay was 2 days (range, 1–34 days) for the patients admitted to undergo elective operations. Hospitalization was not prolonged for the three patients who had fundoplications immediately after transplantation.ConclusionsThe results of this study show that laparoscopic antireflux surgery can be performed safely by an experienced multidisciplinary team for selected patients with ESLD before or after lung transplantation, and that gastric emptying is frequently abnormal and should be objectively measured in ESLD patients.

Lung transplantation in patients with connective tissue disorders and esophageal dysmotility.

Lung and esophageal dysfunction are common in patients with connective tissue disease (CTD). Recent reports have suggested a link between pathologic gastroesophageal reflux and bronchiolitis obliterans syndrome (BOS) after lung transplant. Because patients with CTD have a high incidence of esophageal dysmotility and reflux, this group may be at increased risk of allograft dysfunction after lung transplantation. Little is known about antireflux surgery in these patients. Our aims were to describe: (i) the esophageal motility and reflux profile of patients with CTD referred for lung transplantation; and (ii) the safety and outcomes of laparoscopic fundoplication in this group. A retrospective review of 26 patients with CTD referred for lung transplantation between July 2003 and June 2007 at a single center. Esophageal studies included manometry and ambulatory 24-h pH monitoring. Twenty-three patients had esophageal manometry and ambulatory 24-h pH monitoring. Nineteen patients (83%) had pathologic distal reflux and 7 (30%) also had pathologic proximal reflux. Eighteen patients (78%) had impaired or absent peristalsis. Eleven of 26 patients underwent lung transplantation. Ten patients are alive at a median follow-up of 26 months (range 3-45) and one has bronchiolitis obliterans syndrome-1. Six patients had a laparoscopic fundoplication, 1 before transplantation and 5 after. All fundoplication patients are alive at median follow-up of 25 months (range 19-45). In conclusion, esophageal dysmotility and reflux are common in CTD patients referred for lung transplant. For this group, laparoscopic fundoplication is safe in experienced hands.

Variation in the shape and length of the branches of a thoracoabdominal aortic stent graft: Implications for the role of standard off-the-shelf components

PURPOSE To describe variations in the shape, orientation, and length of the branches of multi-branched thoracoabdominal stent grafts. METHOD The branches were constructed in situ by attaching a covered stent (Fluency Plus Tracheobronchial Stent Graft; Bard Peripheral Vascular, Tempe, Ariz) to each of four caudally-oriented cuffs on custom-made stent grafts. Pre- and postoperative computed tomography (CT) scans of 38 consecutively treated patients were analyzed using a three-dimensional work station to give the orientation of celiac, superior mesenteric, and right renal and left renal orifices relative to the centerline of the aorta (planned cuff orientation [PCO]) and relative to the centerline of the stent graft (actual vessel orientation [AVO]). The orientation of each cuff (actual cuff orientation [ACO]) was also measured relative to the centerline of the stent graft. These values were used to assess the degree of stent graft malorientation (ACO-PCO), or cuff-to-artery misalignment (ACO-AVO), and combined with measurements of branch length to calculate the resulting lateral displacement (arc distance [AD]) between each cuff and its corresponding arterial orifice and the angle (longitudinal branch angulation [LBA]) between the long axis of the branch and the long axis of the aorta, all in the plane of the aortic surface. RESULTS All 136 branches were inserted as intended. None has since migrated, disconnected, or kinked. In most cases, stent graft orientation was accurate, with a mean ACO-PCO of 18.4 + 12.1 degrees. Cuff-to-artery misalignment was correspondingly low, with a mean ACO-AVO of 19.8 + 14.0 degrees. More than 30 degrees of misalignment was present in 23.2% of branches, yet only 9% (n = 12) had an LBA of >30 degrees. CONCLUSION Moderate degrees of cuff-to-artery misalignment had no effect on the feasibility of multi-branched stent graft insertion.