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Prostaglandin E2 (PGE2) is thought to be an important inhibitory modulator of inflammatory processes in the airway. Previous studies have shown that it is produced by bovine cultured airway smooth muscle (ASM) cells in large quantities, but its regulation by second messengers has not been studied in this tissue. To determine whether PGE2 production by ASM might be an important action of beta-adrenoceptor agonists in asthma, the regulation of PGE2 production by adenosine 3',5'-cyclic monophosphate (cAMP) was assessed using dibutyryl cAMP (DBcAMP), forskolin, and albuterol. DBcAMP increased PGE2 production over a 24-h time course. Forskolin and albuterol both increased PGE2 production over control cells to similar levels after 24 h. Incubation of albuterol-treated cells with propranolol significantly (70%) reduced the stimulatory effect of albuterol on PGE2 production. Incubation of forskolin-treated cells with Rp-cAMP, a cAMP antagonist, inhibited the PGE2 response evoked by forskolin by 80%. Ro-20-1724, a selective inhibitor of type IV phosphodiesterase, stimulated PGE2 production (P = 0.02). Cycloheximide, a protein-synthesis inhibitor, did not inhibit the response to DBcAMP. The effects of DBcAMP were additive with the effects of bradykinin, a proinflammatory mediator known to increase PGE2 production (P < 0.05). These studies suggest that cAMP may play an important regulatory role in stimulating PGE2 production by ASM. This may be a novel beneficial action of beta-adrenoceptor agonists in asthma.

Traditional asthma maintenance therapy in adults and adolescents comprises inhaled corticosteroids (ICS), with a long-acting β 2 -agonist (LABA) added if ICS monotherapy provides insufficient control [1,2]. For patients with symptoms occurring on two or fewer occasions per week (so-called "intermittent" asthma [2]), who may represent around one-third of the asthma population [3], many guidelines still recommend short-acting β 2 -agonist (SABA) rescue medication alone [2,4]. However, SABA-only treatment is still associated with severe exacerbations [5], the incidence of which is almost halved with low-dose maintenance ICS in intermittent asthma [6], but adherence is poor [7,8]. Since 2019, the Global Initiative for Asthma (GINA) strategy document has advised against SABA monotherapy, even in those with symptoms occurring on fewer than two occasions per month [9,10]. Instead, ICS therapy is now recommended whenever rescue medication is taken, either as combined ICS-formoterol, or a separate ICS inhaler [9]. However, evidence supporting this in patients with symptoms occurring on two or fewer occasions per week is limited.NovelSTART was a 52-week, randomised, open-label, parallel-group study in adults with mild asthma [11]. Eligible patients were using SABA as sole asthma therapy, and had either at least one severe exacerbation in the previous 12 months, or used SABA on at least two occasions in the previous 4 weeks. Patients were randomised to: salbutamol 100 µg two inhalations as-needed; maintenance budesonide 200 µg twice daily plus as-needed salbutamol; or combination budesonide-formoterol 200/6 µg, one inhalation as needed. Overall, as-needed budesonide-formoterol reduced severe exacerbation risk compared with both as-needed salbutamol and maintenance budesonide plus as-needed salbutamol [11], with the effect modulated by the T2 inflammatory profile [12].

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