Inflammation plays a key role in the pathogenesis of asthma. An increased understanding of this inflammation has lead to an emphasis on therapy with anti-inflammatory agents.

Early experiments with RBx 4638, the tris salt of RBx 4209 demonstrated protective activity in animal models of asthma based on bronchial hyperresponsiveness. This activity has been confirmed using the sodium salt of RBx 4209, namely RBx 7796.

The ability of RBx 4638 to inhibit antigen induced bronchio-constriction in sheep (Ascaris scum antigen) was assessed. It was found to exhibit a dose dependent protective effect on airway reactivity.

Phase I clinical trails were conducted as a double blind randomized, placebo, controlled single dose study in healthy adult male subjects. Five dose levels, 50,100,200,400 and 800mg were evaluated. It was safe and well tolerated with minimal side effects like erythematous lesions, headache, dizziness and ventricular premature complexes.

Phase II clinical trail has been initiated at our hospital in patients of either sex in the age group of 18 to 60 years.They should have mild to moderate asthma as defined by an FEV, reversibility >= 12% baseline FEV, >= 60% of predicted normal. Patients who are unwilling to give informed consent, pregnant or lactating women, those with history compatible with severe asthma, patients with significant renal, respiratory, cardiac, gastro-intestinal, hepatic, endocrine or hematological disorders are excluded from the study.

Case 1

A 50 Yr male patient presented with dysphagia of 3 years duration associated with chest pain with no response to proton Pump Inhibitors & Prokinetics. Cardiac Evaluation was normal.

Case 2

A 20 Year old student with progressive difficulty in swallowing of 3 months duration with a similar clinical picture Upper GI endoscopy revealed a hugely dilated esophagus with stasis of food in the esophagus & gastritis.

Physical examination was unremarkable in both patients.

Barium Swallow confirmed : A dilated esophagus with a smooth bird break narrowing at the location of the tight non relaxing LES ( Lower Esophageal Sphincter ) . They taken up for pneumatic dilatation after 24 hours of nil by antibiotics. The microvasive rigiflex pneumatic balloon dilator ( diameter 3 cm ) was used under endoscopic and fluoroscopic guidance and the balloon placed in the esophagus across the lower esophageal sphincter and inflated to 810 PSI for 1 ½ minutes.

Both Patients experienced immediate relief of dysphagia. They were discharged 1 day postpneumatic dilatation and were asymptomatic on the 2nd month of follow up ( last week) .

Discussion

Achalasia Cardia is the most commonly recognized motor disorder of the esophagus. The term Achalasia means "Failure to relax" and describes a cardinal feature of this disorder, a poorly relaxing LES. The annual incidence of Achalasia remains unknown although a viral cause has been postulated.

Abnormalities in both muscle and nerve components can be detected in this disease although the neural is lesion of primary importance. The most important pathophysiologic defect is a reduction in the number of NANC ( Non Adrenergic Non Cholinergic ) inhibitory ganglion cells.

Patients with Achalasia may present with chest pain and pulmonary symptoms and may be preventions of complications including esophagitis from stasis , aspiration pneumonitis and carcinoma . Palliative treatments include drugs , calcium channel blockers and endoscopic therapy including pneumatic dilation and myotomy.

Endoscopic and fluoroscopic assisted pneumatic dilatation causes forceful dilation to a diameter of approximately 3 cm to tear the circular muscle fibres of the LES and Causes reduction in lower esophageal spincter pressure. The advantages of endoscopic pneumatic dilatation are the brief period of discomfort , short hospital stay and relatively lesser expenditure.

Dr. Asha Subbalakshmi,
M.D., D.M
Department of Gastroenterology
Mediciti Hospitals