Ultra-LAMA, ultra-LABA, ultra-inhaled steroids? The future has landed.

We humans tend to believe that the world has always existed in the form in which we know it. History is fine as an object of study, but we rarely make the effort to really situate ourselves in the past. If we ask most pulmonologists who have started or finished their training this century about the origins of inhaled treatment for obstructive lung disease, we might be surprised to find how little they know. But it is difficult to evaluate current developments without taking account of the past. In fact, inhaled therapies, especially those involving acetylcholine receptor antagonists, have been used for centuries. As early as the 1600s the Hindu system of Ayurvedic medicine prescribed the smoking of alkaloid-rich plants with anticholinergic effects, such as Atropa belladonna and Datura stramonium, for the treatment of asthma.1,2 With the opening-up of the trade routes with India in the nineteenth century, these plants were dried and smoked by British patients to relieve their dyspnea. And in the middle of the twentieth century, classical medicine still prescribed atropine or stramonium-rich cigarettes. However, atropine is a tertiary ammonium that is readily absorbed by the blood; it crosses the blood–brain barrier and has significant adverse effects, and so its clinical utility is limited. More than two thousand years ago, the Chinese used epinephrine extracted from the plant Ephedra equisetina, but this substance has low selectivity for receptors and the duration of its effect is short.3 Inhaled isoprenaline, introduced in the middle of the twentieth century, is a highly potent drug and remains the benchmark against which new -agonists are compared.3 To understand the pharmacology of inhaled treatments for obstructive respiratory diseases, it is necessary to clarify certain concepts concerning the innervation of the airways, given its effect on the decision to apply bronchodilator treatments, and also concerning the inflammatory capacity of the bronchial mucosa, given its effect on the decision to apply anti-inflammatory treatments. Let us look briefly at these two issues. Airway tone is maintained primarily through the control exerted by the vagal parasympathetic fibers which maintain a degree of reversible bronchoconstriction as a result of the tone of the airway