Corticosteroids have been used as drug treatment for some time. Lewis Sarett of Merck & Co. was the first to synthesize cortisone, using a complicated 36-step process that started with deoxycholic acid, which was extracted from ox bile .  The low efficiency of converting deoxycholic acid into cortisone led to a cost of US $200 per gram. Russell Marker , at Syntex , discovered a much cheaper and more convenient starting material, diosgenin from wild Mexican yams . His conversion of diosgenin into progesterone by a four-step process now known as Marker degradation was an important step in mass production of all steroidal hormones, including cortisone and chemicals used in hormonal contraception .  In 1952, . Peterson and . Murray of Upjohn developed a process that used Rhizopus mold to oxidize progesterone into a compound that was readily converted to cortisone.  The ability to cheaply synthesize large quantities of cortisone from the diosgenin in yams resulted in a rapid drop in price to US $6 per gram, falling to $ per gram by 1980. Percy Julian's research also aided progress in the field.  The exact nature of cortisone's anti-inflammatory action remained a mystery for years after, however, until the leukocyte adhesion cascade and the role of phospholipase A2 in the production of prostaglandins and leukotrienes was fully understood in the early 1980s.
A 28-week, placebo-controlled US study comparing the safety of salmeterol with placebo, each added to usual asthma therapy, showed an increase in asthma-related deaths in patients receiving salmeterol (13/13,176 in patients treated with salmeterol vs. 3/13,179 in patients treated with placebo; RR , 95% CI , ). This finding with salmeterol is considered a class effect of the LABAs, including formoterol, one of the active ingredients in DULERA. No study adequate to determine whether the rate of asthma-related death is increased with DULERA has been conducted.
Necrosis of hips and joints: A serious complication of long-term use of corticosteroids is aseptic necrosis of the hip joints. Aseptic necrosis is a condition in which there is death and degeneration of the hip bone. It is a painful condition that ultimately can lead to the need for surgical replacement of the hip. Aseptic necrosis also has been reported in the knee joints. The estimated incidence of aseptic necrosis among long-term users of corticosteroids is 3%-4%. Patients taking corticosteroids who develop pain in the hips or knees should report the pain to their doctors promptly.