Advances in combination therapy for asthma and COPD

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The number of people with asthma continues to grow with over million people affected worldwide and , annual deaths attributed to the disease. It affects people of all ages and has a varying degree of severity. In this article, we look at the ideal characteristics for asthma inhalers and highlight some of the most important reasons for the failure of current asthma treatments. No funding was received in the publication of this article.

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Compliance with Ethics: This study involves a review of the literature and did not involve any studies with human or animal subjects performed by any of the authors. Authorship: All named authors meet the International Committee of Medical Journal Editors ICMJE criteria for authorship of this manuscript, take responsibility for the integrity of the work as a whole, and have given final approval to the version to be published.

This article is published under the Creative Commons Attribution Noncommercial License, which permits any non-commercial use, distribution, adaptation and reproduction provided the original author s and source are given appropriate credit. Inhalation therapy has long been recognised as the optimal mode of treatment for the majority of patients with asthma and has played a pivotal role in their management for decades.

Much smaller doses are necessary compared with oral and intravenous treatments reducing the risk of side effects.


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However, despite huge investment in new asthma drugs and inhalers over the past 30 years, disease control is still unsatisfactory. Asthma is a highly complex and challenging chronic inflammatory disease of which, despite significant breakthroughs in recent years, our understanding is still far from complete.

Indeed, due to its heterogeneous nature, the word asthma may in the future be considered just an umbrella term to define several different phenotypes. The main inhaler designs will be discussed as well as the most desirable characteristics of the aerosol discharged from the inhaler.

We also discuss the reasons why inhaled therapy is not as effective as it could be. Desirable inhaler characteristics for treating asthma Traditionally, there are three main categories of inhaler devices used to treat asthma. It is an entirely new type of portable device that operates in a different way from both the pMDI and DPI, but currently only one such device is available.

Asthma inhalers should be intuitive and easy to use by patients as it is often their inability to use the device that hinders adequate asthma control. Patient preference should be taken into account as it may have an effect on adherence to treatment. The ideal inhaler should be capable of delivering a predictable and consistent lung dose giving the desired clinical effect, while minimising side effects.

Delivering a sufficient dose of drug to the lungs is not easy, as the lungs have evolved to repel inhaled foreign substances in order to keep the airways clear for its primary purpose of gas exchange. The patient must first overcome the unnatural sensation of drawing a solid or liquid aerosol into their lungs. Once inhaled, the dose of drug must bypass the upper airways without significant impaction losses and then be carried by the inhaled airstream to the bronchial region and beyond, while avoiding any disease-related obstructions.

A number of factors come into play when targeting the site of action in the airways. Some of these are human factors and some are associated with the physical properties of the aerosol itself. Human factors related to inhaler use can significantly influence the probability of correct medication use. However, this is often neglected and it is assumed that the patient needs only basic training.

In reality, regular checking of inhalation technique is crucial, as correct inhalation is one of the cornerstones of successful asthma management.

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This point is underlined by a recent study based on data from a multicentre crosssectional study of adults with asthma iHARP. The study highlighted the importance of good training as part of primary and secondary care management to reduce the incidence of critical errors by patients. The diseased state of the lung is a major factor which can prevent the drug dose penetrating to the site of action.

As most asthma therapy is topically acting, the inhaler is of little use if it can only deliver a dose to the healthy part of the lungs while the diseased part goes untreated. Particle size is the most important physical property of the aerosol cloud and is an important determinate of how far into the airways a dose can be delivered. Particles of this size are considered to have the greatest potential for penetrating and depositing in the adult lungs.

Figure 1 illustrates the influence of aerosol particle size on drug deposition in the lungs. Small particles of size 1. Figure 2 shows the effect of inhalation flow rate on lung deposition.

Small particles were less affected by inhalation flow than large particles. To fully treat asthma adequate drug must be deposited in both the central and peripheral airways as it is known that both are involved in the disease. This has now changed due to the widespread availability of measures of the function of small airways such as impulse oscillometry and the multiple-breath nitrogen washout test, as well as innovation in imaging techniques.

However, it has been shown that distal airways are the major determinant of airflow obstruction in asthma.

Recent advances in chronotherapy for the management of asthma

Probably the single most important development in inhaler technology was the introduction of the pMDI in by Riker Laboratories, Inc. However, despite showing its age, the pMDI is still the most widely prescribed inhalation device for treating asthma. It relies on a metering valve to accurately and reproducibly deliver a known volume of propellant and micronised drug at each valve actuation.

However, internally it has undergone significant device engineering and formulation changes resulting in a new generation of pMDIs. Trimmable chip resistors and altering resistive values 6. Application and recommended usage of thin film chip resistors 7. Application and recommended usage of small high power thin film ship resistors 8. Various methods of current sensing and advantage of current sensing resistors 9.

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Herbal treatment in asthma and COPD – current evidence

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