A review of respiratory devices – up to the present
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RESPIRATORY DISEASE IN PRACTICE 2012; Vol 23 No 2 Developments
Inhaler use can be traced back to ancient times, but the first published images of inhalers did not occur until 1654, and the first properly commercialised inhaler was invented by John Mudge in 1778. This review looks at how this new way of delivering medications spread into common use, as well as how the associated and relevant medical science blossomed.
The 19th century
Mudge provided a simple, but robust, device for inhaling vapour, which could be manufactured by any pewterer. This empowered physicians to experiment and publish or document their findings, largely as case reports. The early 1800s were a time when explorers were describing their observations of native cultures from across the world. The smoking of tobacco had long since been brought back to Europe by Columbus and his shipmate Rodrigo de Jerez, who spent three years in prison for demonic possession when smoke was seen coming out of his mouth after smoking a cigarette in front of a superstitious public. That notwithstanding, smoking had become a popular recreation, though not yet a medicinal approach.
In Madras, Dr James Anderson had described the Indian practice of inhaling smoke from the burning leaves of Datura stramonium (which released anticholinergic alkaloids). His work was conveyed to the UK by General Gent, who returned with samples which he gave to Dr Sims. Sims reported his findings, but Gent died from the overuse of stramonium.
The practice of burning the dried leaves of D stramonium slowly grew in popularity, despite the fact that dosing was far from precise and different physicians had their own methods of formulating the mixture, as it was evident that relief for certain lung conditions could be obtained. Eventually, this practice gained increasing popularity, with combustible powder and cigarette forms available (see Figure 1). Some mixtures included other herbal products such as lobelia and belladonna. Typically, the powders would have been burned on a small plate, with a funnel held above it to direct the smoke to the patient. Usage increased across Europe and the USA until asthma cigarettes were finally banned in the 1970s.
These earliest forms of commercial inhalation depended on either the burning of leaves to liberate alkaloids or hot water (to vapourise the medication), but possibly the first attempt at a pressurised inhaler was described by Humphrey1 in 1817, using an apparatus similar to a modern cafetière, with a plunger pressurising the vapour.
Treatment plans were very experimental, but by 1834, Sir Charles Scudamore2 was describing inhaled treatment for consumption with a three-times-daily routine, a specified duration of inhalation and a defined water temperature in the vapour inhaler.
By this time, glass instruments were widely used in many areas of medicine and, of course, glass inhaler apparatus was also developed for some of the early applications of anaesthesia in the late 1840s.
Also in the late 1840s, Dr TK Chambers was experimenting with the inhalation of powdered substances, notably silver nitrate and copper sulphate. His insightful development probably represents the earliest use of particle engineering applied to inhalation. Working without the benefit of sophisticated modern technology, he used the aerodynamic spores of lycopodium as a carrier for his powders.
He reported his work in the Lancet in 1848 and it was repeated in Boston by William Cornell,3 who described the powders as useful in bronchitis, laryngitis and other conditions. The delivery process was rudimentary, with an attendant dusting the powder into the mouth of a funnel through which the patient inhaled.
The next 20 years saw many different key initiatives in inhalation therapy across the world.
l The first atomisers and nebulisers were developed by Auphan, Sales-Girons and Matthieu in France.
l Bergson tubes were developed in Germany, which enhanced the workings of the early nebulisers later incorporated into the steam-powered inhaler developed by Dr Emil Siegle of Stuttgart in 1864, and Dr Adams of Glasgow in 1868.
l In the USA, in 1862, a Dr Broadbent4 published on inhalation as a cure for consumption and provided a long list of inhalants.
l In London, in 1864, Alfred Newton filed a patent for a powder inhaler device, while others across Europe and USA came up with their own alternative approaches.
Mark Sanders BSc MBA Managing Director, Clement-Clarke, Harlow
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Developments RESPIRATORY DISEASE IN PRACTICE 2012; Vol 23 No 2
l The Lancet in 1865 carried news of the improved Dr Nelson vapour inhaler, which persists even to the current day.
l The American Formulary listed inhalants in 1864, and in the UK the 1867 British Pharmacopoeia did likewise, naming five medications: vapour acidi hydrocyanici, vapo chlori, vapour coniae (hemlock), vapour creasoti and vapour iodi.
l In 1867, in France, Trousseau was advocating the use of stramonium together with belladonna and opium in pipes or cigarettes.
l Also in 1867, the advent of vulcanised rubber created the possibility of hand-held atomisers.
l The first critical reviews of inhaler devices were written by DaCosta5 and Cohen6 in the USA, with DaCosta noting the difficulties in standardising dosage from one inhaler to another.
Introducing controls
With all of these developments and a cultural transformation taking place, it soon became commonplace to see inhaler devices advertised in the newspapers of the late 1800s. The most famous medication promoted in this way was the carbolic smoke ball, a rubber squeeze ball that would puff carbolic acid powder for the patient to inhale. The Carbolic Smoke Ball Company proclaimed in their advertisements from the 1890s that the powder would protect against influenza, and offered a cash sum to anyone using the medication properly who contracted influenza (see Figure 2). Of course, one customer claimed and, after being refused the payment, brought a court case that became an important precedent governing contract law; the company was forced to pay up. (Ironically, some 50 years later the claimant succumbed to influenza.)
In the USA, controls were imposed in 1906 through the first Food and Drug Administration (FDA) laws, bringing an outrageously boastful, ungoverned industry to heel rather rapidly. The age of the commercial entrepreneur was giving way to the age of the pharmaceutical scientist, but not before one of the last great inventors, Sir Hiram Maxim, turned his hand to inhalation. Maxim was most famous for the machine gun, known at the time as ‘the world’s most efficient killing machine’, but he had also invented a flying machine, before the Wright brothers, which flew successfully but did not qualify as free flight. An American, Maxim lived in London and suffered from the smogs of the early 1900s. He applied his fertile mind to the problem, inventing (in contrast to his earlier machine) the Pipe of Peace (see Figure 3), which was commercialised in large numbers from 1915. This contained a combination of two volatile substances – menthol and dirigo (wintergreen) – which were inhaled from a glass retort.
Despite such inventions, the pharmaceutical scientists were now making headway. The 1890s saw the discovery of adrenaline and, separately, the isolation of suprarenal material later shown to be cortisone, the two cornerstones of modern pharmacological approaches to treating asthma. The role of hypodermic adrenaline in asthma was demonstrated in 1903 by Kaplan and Bullowa in New York, and by 1911, Pick had reported successful nebulisation in two patients. It rapidly became standard therapy, administered by hand-held atomisers.
Sir William Osler, who had experienced earlier success with suprarenal substances in Addison’s disease, reported success in asthma with pilocarpine, an anticholinergic medication. By the 1920s, atropine was being atomised for asthma.
Ephedrine was identified in 1924 and was shown to be useful in asthma a couple of years later.
Despite pharmaceutical advances, inhaler delivery devices had not really developed since the 1860s, with hand-held atomisers and nebulisers being used as the predominant forms of inhalation. In some larger institutions, more sophisticated nebulisation was being practised with the use of the Spiess–Dräger pressurised gas-driven nebulisation apparatus. In the 1930s, the first electrical compressor nebulisers appeared, and it would have been common practice for high street chemists to have one available in store for patients to use.
Later developments
In 1948, Abbott Laboratories launched a small hand-held plastic dry powder inhaler (DPI), the Aerohalor, invented by Mack Fields, in Chicago, for the delivery of a bronchodilator (norethisterone [should this be noradrenaline or norepinephrine?]) and separately for penicillin from small cartridges. This was widely available in the USA and the UK.
In the 1950s, suprarenal material was identified as cortisone and its value in lung conditions was demonstrated.
Undoubtedly the most significant inhaler event at that time was the development of the pressurised metred dose inhaler (pMDI) by Riker Laboratories, reportedly at the suggestion of the company president’s daughter, who objected to using hand-held nebulisers. Rapid development and testing led to the launch in March 1956 of Medihaler-iso (isoprenaline) and Medihaler-epi (adrenaline). The pMDI has been a remarkable success, with hundreds of millions produced every year, despite the fact that many patients fail to get