Drawing Breath: A Brief History of InhalersThe modern, metered-dose inhaler is a wonderful example of applied engineering. Tasked with a seemingly straightforward job – delivering medication directly to the human respiratory system – the inhaler has undergone a number of modifications and design revolutions in the seven decades since it was first introduced.** Here, in an easily inhaled format, is a brief history of this remarkable medical technology.**** The introduction of inhalersAn inhaler is a device that delivers medication in aerosol form. The device has a canister that contains the medication and a metering valve that delivers a consistent amount of drug with each dose. A mouthpiece with an actuator atomizes the medication as it’s delivered to the patient. The inhaler also contains a liquefied gas, used as a propellant. Since each dose delivered is measured before it’s transported,** this type of inhaler is called a** Meter Dose Inhaler (MDI).**** The first MDIs**
The first MDI was developed in 1956, by California-based Riker Laboratories, which was acquired in 1970 by what is now the pharmaceutical company, 3M Northridge. The original inhalers used a propellant technique – developed by a perfume company, incidentally – containing chorofluorocarbons (CFC), which are volatile derivatives of carbon gases. Because of their efficiency of delivery, portability, and low cost, inhalers became very popular.
However, due to growing concern about the effect of CFCs on the environment, and specifically their role in ozone depletion, they were eventually phased out and replaced by hydrofluoroalkanes (HFAs).
Delivery problems with MDI inhalers
It was clear that using inhalers was not as simple as taking a pill. There were individual differences in the coordination of the pressing of the actuator of the inhaler, as ewll as the intake of the delivered medication. In addition, throat anatomies vary from individual to individual. This meant that varying amounts of medication were being delivered to the lungs of patients. But in many cases, much of the medication was getting stuck in the back of the throat where it would not have the desired therapeutic effect.
Spacers to the rescue … briefly
Spacers were later introduced to correct the problem. These were chambers placed in front of the inhaler, so that the large aerosol particles that were more likely to get stuck in the throat would stay in the chamber. This allowed just the smaller, air-suspended particles to be delivered. But the spacers made the inhalers bulkier and less practical to carry around.
At the same time, the pharmaceutical companies were growing increasingly reluctant to pay royalties to 3M every time they developed new inhaler medications.
Dry powderGlaxoSmithKline introduced the first dry powder device in the form of a round disc, which made it easier to put in one’s pocket. The disc contained capsules with a fixed dosage of medication. The press of a lever broke up a capsule, so that the user would inhale the powder particles with no need for propellant. This method also allowed for uniform delivery.** The problem was that the uniformity depended on the strength of the inhalation, so the dry-powder inhaler was not suitable for children, or for individuals with severe respiratory disease.**
Another new innovation was that for the first time, there was a combination of two medications in one capsule: one called Advair, which combined an inhaled steroid (Fluticasone), and a long-acting bronchodilator (Salmeterol); the other was a controller medication, to be taken daily regardless of symptoms and that provided a protective and preventive effect.
The fact that two different medications with complementary benefits were being dispensed was preferable to the traditional approach of using one medication to the maximum permitted dose – before adding another if needed. (The efficacy of this dual-medication approach, by the way, was never proven with clinical studies. Nevertheless, the use of combined medications persists to this day.)
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‘Inhaling’ a pill?
The idea of “inhaling” a pill was introduced by the company Boeringer Ingelheim in the form of Tiotropium (Spiriva). The new mechanism worked to pierce a pill or capsule, so that the individual could then inhale its contents.
The advantage of this technique was that patients did not need to constantly replace inhalers every time they used up their medication. Instead, they could buy capsules every month. Some elderly people, though, had problems opening the capsule-piercing device and, if they suffered from tremors for example, they also had difficulty introducing a pill into the small receptacle. In addition, patients on multiple medications ran the risk of confusion and actually swallowing the pills.
The next generation of devices
Many more devices not discussed here include twist-halers, spin-halers, and press-air inhalers. However, some of these were so complicated that even doctors could not easily demonstrate how to use them. (I speak from experience).
In the end there were two new designs that would survive.** Mist delivery**
Given the problems with Spiriva and its delivery system (but also because of the importance of new LAMA or long-acting medication for COPD patients), there was a need for change. The new device, Respimat, featured a round cylinder that required the patient to simply twist it in order to dispense and inhalable mist. Compared to some others, the device was quite simple to use.
Glaxo’s answer to Respimat was a new “dry powder” device that was smaller, could stand upright, and was clearly visible in a medicine cabinet. It’s called the Ellipta, and Glaxo has a patent on it for all the medications they develop.
Today there is a wide array of inhalers offering combinations of medications that treat many different conditions, including combinations of an inhaled steroid with a long-acting bronchodilator in a single dispensing device. Some devices, meanwhile, only dispense single medications.
_NOTE: All of these medications require doctor supervision, and many have side effects or interactions with other medications. _
LABAs are “long-acting beta-agonists” used to treat COPD.
LAMAs are “long-acting muscarinic antagonists” used in the treatment of COPD.
Glaxo Inhalers:* ** Breo Ellipta** offers a combination of a steroid and LABA for asthma (Fluticasone/Vilanterol).
- Anoro Ellipta is a combination of LABA/LAMA for COPD (Umeclinidium/Villanterol).
- Arnuity Ellipta is an inhaled steroid, Fluticasone.
- Incruise Ellipta contains a single LAMA, Umeclinidium.
Boeringer Ingelheim Inhalers:
- Spiriva is the first LAMA once-a-day medication for COPD in Respirmat mist form.
- Stiolto is a combination of Tiotropium (Spiriva) and an LABA, Oldaterol.
- Striverdi offers the LABA, Oldacaterol, in a Respimat mist form.
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Eli Hendel, M.D. is a board-certified Internist and pulmonary specialist with board certification in Sleep Medicine. He is an Assistant Clinical Professor of Medicine at Keck-University of Southern California School of Medicine, Qualified Medical Examiner for the State of California Department of Industrial Relations, and Director of Intensive Care Services at Glendale Memorial Hospital. His areas of expertise in private practice include asthma, COPD, sleep disorders, obstructive sleep apnea, and occupational lung disease.
Eli Hendel, M.D., is a board-certified internist/pulmonary specialist with board certification in Sleep Medicine. An Assistant Clinical Professor of Medicine at Keck-University of Southern California School of Medicine, and Qualified Medical Examiner for the State of California Department of Industrial Relations, his areas include asthma, COPD, sleep disorders, obstructive sleep apnea, and occupational lung diseases. Favorite hobby? Playing jazz music. Find him on Twitter @Lung_doctor.