Fuelling the mechanisms of asthma: Increased fatty acid oxidation in inflammatory immune cells may represent a novel therapeutic target.

BACKGROUND: Increasing evidence has shown the close link between energy metabolism and the differentiation, function, and longevity of immune cells. Chronic inflammatory conditions such as parasitic infections and cancer trigger a metabolic reprogramming from the preferential use of glucose to the up-regulation of fatty acid oxidation (FAO) in myeloid cells, including macrophages and granulocytic and monocytic myeloid-derived suppressor cells. Asthma is a chronic inflammatory condition where macrophages, eosinophils, and polymorphonuclear cells play an important role in its pathophysiology. OBJECTIVE: We tested whether FAO might play a role in the development of asthma-like traits and whether the inhibition of this metabolic pathway could represent a novel therapeutic approach. METHODS: OVA- and house dust mite (HDM)-induced murine asthma models were used in this study. RESULTS: Key FAO enzymes were significantly increased in the bronchial epithelium and inflammatory immune cells infiltrating the respiratory epithelium of mice exposed to OVA or HDM. Pharmacologic inhibition of FAO significantly decreased allergen-induced airway hyperresponsiveness, decreased the number of inflammatory cells, and reduced the production of cytokines and chemokines associated with asthma. CONCLUSIONS AND CLINICAL RELEVANCE: These novel observations suggest that allergic airway inflammation increases FAO in inflammatory cells to support the production of cytokines, chemokines, and other factors important in the development of asthma. Inhibition of FAO by re-purposing existing drugs approved for the treatment of heart disease may provide a novel therapeutic approach for the treatment of asthma.

Effects of intrathecal fentanyl as an adjunct to hyperbaric bupivacaine in spinal anesthesia for elective caesarean section.

Hyperbaric bupivacaine is the most common drug used in spinal anesthesia for caesarean section. The aim of this study was to compare the effects of adding fentanyl to intrathecal bupivacaine on the onset and duration of spinal anesthesia and its effect on mother and neonate. Seventy healthy parturients with singleton pregnancy scheduled for elective cesarean section were randomly allocated to receive subarachnoid block with 0.5% bupivacaine heavy 2.4 ml (Group A) or fentanyl 20 microgram (0.4 ml) added to 0.5% bupivacaine heavy 2 ml (Group B). Blood pressure, heart rate, respiratory rate, oxygen saturation, along with characteristics of spinal block were assessed throughout the surgery and in the postoperative ward until the patient requested for analgesia. It was found that duration of sensory block was prolonged in fentanyl group (p < 0.05). Duration of complete analgesia (97 ± 8.23 minutes vs 153 ± 7 minutes; p value = 0.00) and effective analgesia (134 ± 5.6 minutes vs 164 ± 9; p value = 0.00) were also found to be prolonged in Group B. There was not much difference in the occurrence of side effects in both the groups. Addition of fentanyl to intrathecal bupivacaine for cesarean section increases the duration of postoperative analgesia without increasing maternal or neonatal side effects.