The most commonly reported side effects were: oral thrush , nausea , headache , and pain in the pharynx or larynx . More rarely reported side effects (occurring in <1% of patients during the clinical trial) include: tachycardia , palpitations , dry mouth , allergic reaction ( bronchospasm , dermatitis , hives ), pharyngitis , muscle spasms , tremor , dizziness , insomnia , nervousness , and hypertension . Patients experiencing an allergic reaction or increase in difficulty breathing while using this medication should immediately discontinue its use and contact their physician. 
Lewis Sarett of Merck & Co. was the first to synthesize cortisone, using a 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.
LABA+ICS群と比較し、LAMA+LABA群の統合された主要評価項目の結果は以下の通りである：増悪、OR (95％CI ～、P = 、I 2 = 17％、低い質のエビデンス)；重篤な副作用、(95％CI ～、P = 、I 2 = 0％、中等度の質のエビデンス)；St. George's Respiratory Questionnaire (SGRQ)ベースラインからの変化、MD -(95％CI ～、P = 、I 2 = 71％、低い質のエビデンス)；トラフ一秒量ベースラインからの変化、MD (95％CI ～、P <、I 2 = 50%、中程度の質のエビデンス)。同様に二次評価項目の結果は以下の通りである：肺炎、OR (95％CI ～、P = 、I 2 = 0％、低い質のエビデンス)；全死亡、OR (95％CI ～、P = 、I 2 = 0％、低い質のエビデンス)、臨床的有意な最小変化量(4点)以上のSGRQベースラインからの改善、OR (95％CI ～、P = 、I 2 = 0％、中等度の質のエビデンス)。