Inhaler technique in asthma and COPD: challenges and unmet knowledge that can contribute to suboptimal use in real life

ABSTRACT

Introduction: Inhalers are the most commonly used devices for lung drug delivery in asthma and COPD. Inhaler use offers several advantages but requires the user’s proper mastery. The issue of inhaler technique is very important as inhaler misuse remains common in real life regardless of the inhaler used and is associated with poor disease control.

Areas covered:This narrative review analyses the key-steps of inhaler mastery and the significance of the errors of use for the main devices. There are uncertainties on many tasks of inhaler use and on those variations from recommended steps that are considered as critical errors.

Expert opinion: Despite technological advancements, an easy-to-use device is not yet available. Whatever the chosen inhaler, health care givers’ proper practical education with the opportunity of feedback learning has a key-role for improving inhaler technique, but is time-consuming, and remains limited to few successful experiences. Newer digital technologies will be applied to the field of inhaler education, but the lack of knowledge on many practical aspects of inhaler technique might be a limit for its extensive implementation. Possibly digital innovation might substantially contribute to reduce inhaler misuse only if clinicians, manufacturers, and subjects will cooperate together on this issue.

KEYWORDS:

• Asthma
• copd
• devices
• dry powder inhalers
• education
• inhalation therapy
• metered dose inhalers
• respimat

Article highlights

• Inhalers are specifically designed devices for lung drug delivery in asthma and COPD. Inhaler use offers several advantages, but requires user’s proper mastery

• Inhaler misuse is common in a range of care settings and patient populations regardless of the used inhaler and is associated with poor disease control.

• Despite technology advancements an easy-to-use inhaler is not yet available. There is a need for inhalers that can successfully be used from subjects with comorbidities and no or little skill

• Health care givers’ education with practical demonstration of inhaler technique and the opportunity for the users to show how they use their inhaler and receive feedback is associated with improvement of inhaler technique, but is time-consuming and not widespread

• Many essential steps of inhaler usage and storage for the marketed drug/device systems remain not fully defined

• Newer technologies should be applied to the field of inhaler education. Clinicians, researchers, manufacturers, and patients should work together for achieving the best outcomes from digital innovation

Abbreviations: Chronic Obstructive Pulmonary Disease, COPD; Press-and Breathe Inhaler, PBI; Breath-Actuated Inhaler, BAI; Metered Dose Inhaler, MDI; Soft Mist Inhaler SMI; Dry Powder Inhaler, DPI; Single Dose Dry Powder Inhaler, SDDPI; MultiDose Dry Powder Inhaler, MDDPI; ChloroFluoroCarbon, CFC; Hydrofluoroalkane, HFA; RV, Residual Volume; FRC Functional Residual Capacity, total emitted dose, TED; FPD fine particle dose, FPF fine particle fraction, MMAD, mass median aerodynamic diameter, Peak inhalation flow Rate, PIFR; Beclomethasone Dipropionate, BDP; litre per minute, lpm; Relative Humidity, RH

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

A reviewer of this manuscript discloses receiving grants and personal fees from Boehringer Ingelheim, Novartis, Pfizer and personal fees from Teva, GSK, AstraZeneca, Chiesi, Sanofi, Trudell, Zambon. Peer reviewers on this manuscript have no other relevant financial or other relationships to disclose.

MDIs

MDIs are reliable, portable and self-contained. MDIs are the first inhalers that have been introduced for asthma and COPD management. They have ubiquitous diffusion and remain the most used orally inhaled devices. Although their external aspect with shape, dimensions, and basic mechanisms of action did no change very much along the years, newer MDIs show a lot of technology advancement. Hydrofluoroalkanes (HFAs) are the currently used propellants and have replaced old chlorofluorocarbon propellants (CFC), less ecologically friendly. Replacing the propellant, some manufacturers have tried to keep unchanged properties of the newer products, while others have reformulated them as a solution and delivering softer, warmer and finer aerosols. Nevertheless, MDIs are constituted by: A) the canister containing the drug formulation and including the metering valve, which determines the quantity of formulation dispensed upon actuation; C) the actuator, where the canister is encased, including the mouthpiece and its nozzle which directs the aerosol plume when the dose is actuated. The canister is usually made of aluminum and has a typical volume of about 10-20 ml. Some canisters are coated to avoid drug sedimentation on the internal surface. The valve ensures that, over the lifespan of device, a consistent amount of liquid formulation (and ideally drug) is released from the canister each time that the user actuates the device. Each actuation releases approximately 20-5000 µg of drug in metered volumes of 25-100 ml. The actuator nozzle has a diameter ranging from 0.25 to 0.5 mm. Within certain limits required for avoiding nozzle blockage, smaller orifices produce longer, warmer and softer aerosols. The propellant is non-aqueous, has to be toxicologically safe, nonflammable, chemically inert, compatible with the formulation and with high-pressure levels (>10 atm), appropriate boiling points and densities during the entire life of the product. Other non-active components, influencing the solubility of the drug into the propellant, may be added. When the pMDI is actuated, pressing down the canister into the case, a dose of liquid formulation is released that, due to a pressure gradient, rapidly vaporizes into an aerosol. At the nozzle exit of the mouthpiece the aerosol droplets measure tens of micrograms and have a velocity of 100-150 mps, but they cool and go down rapidly in size and speed as propellant evaporates. Each MDI has its own characteristics that do not change between inhalers of a same brand and with full vs. almost empty device.

Strings: (COPD OR chronic obstructive pulmonary disease OR Asthma) AND (error OR mishandling OR inhaler handling OR device handling OR incorrect use OR incorrect technique OR improper use OR improper technique OR inadequate technique OR inadequate use OR critical error OR significant error OR device error OR handling error OR inhal* technique OR inhal* error OR drug stor* OR expir* date OR shelf-life OR shelf life) AND (inhaler* OR inhalat* OR device* OR aerosol* OR inhal* device OR drypowder inhaler OR DPI OR pressurized metered dose inhaler OR metered-dose inhaler OR metered dose inhaler OR pMDI OR MDI OR hydrofluoroalkane inhaler OR HFA OR CFC-free inhaler OR CFC free inhaler OR soft mist inhaler OR soft-mist inhaler OR SMI OR smart inhaler OR intelligent device OR smart device OR at least one name of the marketed devices

Basic characteristics of therapeutic aerosols

The labeled dose (nominal dose) is the mass of drug that is available within the aerosol generation per actuation or inhalation. The total emitted dose (TED) or delivered dose is the mass of drug emitted per actuation that is available for inhalation at the mouth, which is lower than the labeled dose. The aerosol particle size distribution is very important for efficient lung drug delivery. The inhaled drugs most likely to reach the airways, and thus exert local clinical effects, are aerosol particles in the fine-particle fraction of 1–5 µm. The most known parameters for describing a therapeutic aerosols are MMAD and GSD. Mass median aerodynamic diameter (MMAD) is the diameter at which 50% of the particles of an aerosol by mass are larger and 50% are smaller. The geometric standard deviation (GSD) measures the dispersion of particle diameter. Aerosols with a GSD <1.2 are considered polydisperse, as most therapeutic aerosols are. The fine-particle dose is the mass of particles <5µm within the emitted dose. Fine-particle fraction is the fine particle dose divided by the emitted dose. This is also referred to as the respirable fraction

Dry Powder Inhalers (DPIs)

DPIs are environmental-friendly, reliable, portable and self-contained. All currently marketed DPIs are breath-actuated. Some DPIs had been produced with an auxiliary energy source to control powder dispersion, but they have been withdrawn to the market, because they were expensive and vulnerable. The drug is usually available in micronized form, blended with larger carrier particles, to make simpler dosing during the manufacturing process and fluidization. Lactose monohydrate, that has an established safety and stability profile, is the most commonly used carrier. The carrier constitutes most powder formulation by weight. Shape, smoothness and dimensions of carrier particles influence DPI performances. Other added components may include buffering, surfactants, stabilizing salts and force-control agents useful to improve aerodynamics of delivered aerosols. Each DPI contains specific technology, design and handling features, only partially shared with other devices. Two major types of DPIs are available based on drug metering system: Multi-dose (MDDPI) and Single-dose (SDDPI) DPI. MDDPIs contain the micronized drug for many doses inside the device, either into a reservoir or in pre-packed foil blisters. SDDPIs do not contain the drug inside the device, but into capsules kept separately in sealed packages.

Additional information

Funding

This paper was not funded.