Managing chronic rhinosinusitis in severe asthma.

PURPOSE OF REVIEW: Over half of all patients with severe asthma have chronic rhinosinusitis (CRS). Although distinct and specialized in function and form, the upper and lower airways share similar and inter-related pathophysiologic mechanisms. The severity of CRS particularly in patients with nasal polyps can correlate with that of asthma and vice versa. The purpose of this review is to elucidate the relationship between these conditions and summarize key elements in the management of these patients. RECENT FINDINGS: Several advances have been made in the evaluation and treatment of patients with CRS and asthma. Further understanding of inflammatory endotypes common to both CRS and severe asthma hopefully will provide appropriate and effective treatments and improve patient outcomes. SUMMARY: CRS significantly impairs quality of life, and therapies are targeted toward improving patient symptoms, and hopefully in the future, treating the underlying immune dysfunction. Management of CRS and severe asthma requires a multidisciplinary approach. Further real-world studies are necessary to determine the best treatment algorithm for these patients.

Hypertonic saline alters hydraulic conductivity and up-regulates mucosal/submucosal aquaporin 4 in resuscitation-induced intestinal edema.

OBJECTIVE: To characterize membrane conductivity by applying mathematical modeling techniques and immunohistochemistry and to localize and predict areas of the bowel where aquaporins may be associated with edema resolution/prevention associated with hypertonic saline. Intestinal edema induced by resuscitation and mesenteric venous hypertension impairs intestinal transit/contractility. Hypertonic saline decreases intestinal edema and improves transit. Aquaporins are water transport membrane proteins that may be up-regulated with edema and/or hypertonic saline. DESIGN: Laboratory study. SETTING: University research laboratory. SUBJECTS: Male Sprague Dawley rats, weighing 270 to 330 g. INTERVENTIONS: Rats were randomized to control (with and without hypertonic saline) and mesenteric venous hypertension with either 80 mL/kg normal saline (RESUS + VH + VEH) or 80 mL/kg normal saline with hypertonic saline (RESUS + VH + HTS). After 6 hrs, intestinal wet/dry ratios, urine output, peritoneal fluid, and intraluminal fluid were measured. Hydraulic conductivity was calculated from our previously known and published pressure-flow data. The cDNA microarray, Western blot, polymerase chain reaction, and immunohistochemistry studies were conducted for candidate aquaporins and distribution in intestinal edema resolution. MEASUREMENTS AND MAIN RESULTS: Hypertonic saline decreased edema and increased urine, intraluminal, and peritoneal fluid volume. RESUS + VH favors fluid flux into the interstitium. Hypertonic saline causes increased hydraulic conductivity at the seromuscular and mucosal surfaces at the same time limiting flow into the interstitium. This is associated with increased aquaporin 4 expression in the intestinal mucosa and submucosa. CONCLUSIONS: Hypertonic saline mitigates intestinal edema development and promotes fluid redistribution secondary to increased membrane conductivity at the mucosal and seromuscular surfaces. This is associated with up-regulation of aquaporin 4 gene expression and protein. Aquaporin 4 may be a useful therapeutic target for strategies to enhance edema resolution.