OMT for the Prevention and Management of Chronic Constipation and Distal Intestinal Obstructive Syndrome in Cystic Fibrosis: A Pilot Study.

CONTEXT: Cystic fibrosis (CF) is an autosomal recessive genetic disorder primarily affecting the lungs and digestive system. Patients with CF often have multiorgan dysfunction, including chronic lung infections, pancreatic insufficiency, chronic constipation, and distal intestinal obstructive syndrome (DIOS). OBJECTIVE: To understand the impact of osteopathic manipulative treatment (OMT) on the prevention and management of gastrointestinal symptoms in patients with CF. METHODS: This study used OMT for physical manipulation of the viscera, spine, and other somatic components to improve bowel symptoms and prevent DIOS. These effects were achieved by releasing myofascial restrictions found in the abdomen and somatic structures with the intent to optimize the autonomic and lymphatic systems and improve range of motion. RESULTS: Four of 5 participants had a decrease in pain, and 3 participants had a reduced need for laxatives during treatment. Four participants had an overall increase in satisfaction with their bowel movements while being treated with OMT. CONCLUSION: These findings support the use of OMT as a method for the management of chronic constipation and DIOS in the CF population. However, because of the small population size, more research with larger populations is needed.

In vivo readout of CFTR function: ratiometric measurement of CFTR-dependent secretion by individual, identifiable human sweat glands.

To assess CFTR function in vivo, we developed a bioassay that monitors and compares CFTR-dependent and CFTR-independent sweat secretion in parallel for multiple (~50) individual, identified glands in each subject. Sweating was stimulated by intradermally injected agonists and quantified by optically measuring spherical sweat bubbles in an oil-layer that contained dispersed, water soluble dye particles that partitioned into the sweat bubbles, making them highly visible. CFTR-independent secretion (M-sweat) was stimulated with methacholine, which binds to muscarinic receptors and elevates cytosolic calcium. CFTR-dependent secretion (C-sweat) was stimulated with a ß-adrenergic cocktail that elevates cytosolic cAMP while blocking muscarinic receptors. A C-sweat/M-sweat ratio was determined on a gland-by-gland basis to compensate for differences unrelated to CFTR function, such as gland size. The average ratio provides an approximately linear readout of CFTR function: the heterozygote ratio is ~0.5 the control ratio and for CF subjects the ratio is zero. During assay development, we measured C/M ratios in 6 healthy controls, 4 CF heterozygotes, 18 CF subjects and 4 subjects with 'CFTR-related' conditions. The assay discriminated all groups clearly. It also revealed consistent differences in the C/M ratio among subjects within groups. We hypothesize that these differences reflect, at least in part, levels of CFTR expression, which are known to vary widely. When C-sweat rates become very low the C/M ratio also tended to decrease; we hypothesize that this nonlinearity reflects ductal fluid absorption. We also discovered that M-sweating potentiates the subsequent C-sweat response. We then used potentiation as a surrogate for drugs that can increase CFTR-dependent secretion. This bioassay provides an additional method for assessing CFTR function in vivo, and is well suited for within-subject tests of systemic, CFTR-directed therapeutics.