Inhaler dose reliability: Running on fumes? Establishing the reliability of inhaler weight to determine doses remaining for pressurised metered dose inhalers

Professor Will Carroll and Dr Chloe Fairbrother

The Problems with Puffers and Inhaler Dose Reliability

Most people with asthma, or chronic obstructive pulmonary disease use inhalers to help treat their condition and help with flare ups. Both conditions are characterized by a narrowing of the airways that we call obstruction. This can occur because the airways are inflamed or because the muscles around the airways are contracted.

There are two main types of inhaler. Anti-inflammatory inhalers, that we call preventers and bronchodilator inhalers or relievers that help to relax the muscles that surround the breathing tubes. In order to deliver medicines to the lungs, we can use one of a number of technologies. In the UK most inhaled therapies are given via a pressurised metered dose inhaler, or puffer.

Pressurised metered dose inhalers (pMDIs) are relatively old technology. Pressurized Metered Dose Inhalers (pMDIs) were invented in the 1950s by George Maison, an American engineer and pharmacist. Maison, working at the pharmaceutical company Riker Laboratories (later part of 3M), developed the pMDI as a way to deliver medication more effectively to the lungs.

Whilst the pMDI revolutionized the treatment of respiratory conditions like asthma and chronic obstructive pulmonary disease (COPD), providing a convenient, portable, and precise method of inhaling medication, the formulations of medicines used had some unforeseen consequences.

Chlorofluorocarbons (CFCs) were once the primary propellants used in Pressurized Metered Dose Inhalers (pMDIs) to help deliver medication to the lungs. CFCs are compounds made up of carbon, chlorine, and fluorine, and they were widely used in various applications due to their stability and non-flammability. In pMDIs, CFCs served as propellants to pressurize the medication canister, allowing for the release of a metered dose of medication in the form of an aerosol mist. The CFCs helped the medication stay in a liquid state under pressure, turning into a vapour when dispensed through the inhaler. This mechanism enabled precise and efficient delivery of medication to the lungs.

However, by the late 20th century, scientists discovered that CFCs were contributing to the depletion of the ozone layer, which protects the Earth from harmful ultraviolet radiation. As a result, international agreements, such as the Montreal Protocol (1987), were put in place to phase out the use of CFCs and other ozone-depleting substances.

In response to this, pharmaceutical companies started transitioning to alternative propellants, such as hydrofluoroalkanes (HFAs), which do not damage the ozone layer. HFAs are now the standard propellants used in pMDIs, providing a more environmentally friendly option while maintaining the effectiveness of the inhaler. However, these are still potent greenhouse gases in their own right. The HFAs used in pMDIs have a global warming potential (GWP) of over 1000 times more than that of carbon dioxide. Prescribing of inhalers is an obvious target for positive change—the carbon dioxide (CO2) equivalent of prescribed inhalers in the UK in 2019 alone was estimated to exceed 1·3 megatonnes.

Whilst dry powder inhalers may provide a solution for older children and younger adults, we know that many children and older adults cannot generate the inspiratory flow and pressure required to effectively use this type of inhaler device reliably. As peak inspiratory flow rate falls in response to an asthma flare up, this may be a particularly important problem for some individuals who can use a dry powder device when well but not when they are poorly. Cost is a further issue. Dry powder devices are typically more expensive than the pMDI equivalent. Therefore, we are likely to continue to use pMDIs for the foreseeable future in the UK.

A second important problem that can and does arise is the significant issue of how to tell when a pMDI is empty. pMDIs are designed to have a significant overfill of propellant. Therefore, pMDIs will still make a noise well beyond the point when all the drug content is exhausted. This is confusing for patients, under-appreciated by health care professionals and leads to an increased risk to patients.

Understanding inhaler dose reliability could therefore help determine whether patients are receiving medication or simply inhaling the remaining propellant.

Data from recycling projects show that over one third (36%) are disposed of with more than half of their doses unused (3). More worryingly, a similar proportion (30%) are used beyond the point where medication is delivered (4). These patients are literally ‘running on fumes’. The noise they hear is propellant being discharged when the suspended drug has been exhausted. This problem is prevalent in pMDIs with and without dose counters, as a significant proportion of patients appear to disregard or ignore inbuilt dose counters (4,5). This leads to non-intentional non-adherence. The patient believes that they are taking medicine, but in fact they are inhaling propellant alone.

The Running on Fumes Project

We are planning a study to help identify how prevalent this second issue is within our communities. We recognised that pMDIs returned, by post, for recycling may not be wholly representative of patient behaviour in the real world. Therefore we have planned a study to clearly identify the scale of the problem. This has two distinct phases. Phase 1 will require us to weigh inhalers using accurate scales from completely full to completely empty. We will do this for six inhalers for each of the 10 most commonly prescribed pMDIs in the UK.

In the second phase of the study, we will be encouraging patients to return pMDIs to their local pharmacy. We will take the returned inhalers and weigh them to determine whether they are being returned at the right time or not. We have enlisted the help of 12 local pharmacies and look forward to starting the second phase in early 2025.

Recycling Inhalers

Phase 2 of the running on fumes project relies on the ability of the public to return their empty inhalers to local pharmacies. Currently, this is the recommended way for inhalers to be recycled. However, government data estimates that less than 1% of all inhalers supplied by the NHS are being disposed of in this way (6). We therefore suspect that most inhalers end-up in household waste. This is problematic because compared to landfill disposal, incinerating inhalers with clinical waste, as opposed to household waste, would save between 4-18 kg CO2 (eq) per inhaler (7). The benefit of encouraging the public to return their empty inhalers for the running on fumes project is therefore two-fold.

We have recently begun working with GenerationR to design resources that encourage the public to recycle their inhalers in local pharmacies. GenerationR is a national network of Young People’s Advisory Group’s (YPAGs) and is funded by the National Institute for Health Research (NIHR). Our initial aim is to produce a poster that can be displayed in each of the pharmacies we have recruited for the second phase of this project. We look forward to taking this campaign further and encouraging the correct disposal of empty inhalers nationwide.