The role of the small airways in the pathophysiology of asthma and chronic obstructive pulmonary disease

Bonini, Matteo; Usmani, Omar

doi:10.1177/1753465815588064

Cited by 76 publications

(73 citation statements)

References 100 publications

(158 reference statements)

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“…One of the biggest improvements to come from the new pMDI formulations has been based on the scientific discovery showing that the ability to deliver fine particles [20] allows aerosols to penetrate deeper into the lungs to treat the small airways in asthma and also in idiopathic pulmonary fibrosis [21, 22]. With diameters <2 mm, the small airways have been recognised as important sites of chronic inflammation and disease with associated abnormalities [23, 24]. Therefore, for effective treatment of the disease it is important to deliver therapy to both small and large airways [25].…”

Section: What Are the Current Incentives Driving Inhaler Development mentioning

confidence: 99%

Is there room for further innovation in inhaled therapy for airways disease?

Biddiscombe

Usmani

2018

Breathe

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Inhaled medication is the cornerstone in the treatment of patients across a spectrum of respiratory diseases including asthma and chronic obstructive pulmonary disease. The benefits of inhaled therapy have long been recognised but the most important innovations have occurred over the past 60 years, beginning with the invention of the pressurised metered dose inhaler. However, despite over 230 different device and drug combinations currently being available, disease control is far from perfect.Here we look at how innovation in inhaler design may improve treatments for respiratory diseases and how new formulations may lead to treatments for diseases beyond the lungs. We look at the three main areas where innovation in inhaled therapy is most likely to occur: 1) device engineering and design; 2) chemistry and formulations; and 3) digital technology associated with inhalers. Inhaler design has improved significantly but considerable challenges still remain in order to continually innovate and improve targeted drug delivery to the lungs. Healthcare professionals want see innovations that motivate their patients to achieve their goal of improving their health, through better adherence to treatment. Patients want devices that are easy to use and to see that their efforts are rewarded by improvements in their condition.Key pointsThe dictionary definition of innovation is the introduction of new things, ideas or ways of doing something. We show how this definition can be applied to inhaled therapy.We take a look at the past to see what drove innovation in inhaler design and how this has led to the current devices.We look at the current drivers of innovation in engineering, chemistry and digital technology and predict how this may translate to new devices.Can innovation help the healthcare professional manage their patients better?What does the patient expect from innovation in their device?Educational aimsTo understand the importance of inhaled medication in the treatment of lung diseases.To understand how innovation has helped advance some of the devices patients use today from basic and inefficient designs.To understand the obstacles that prevent patients from receiving optimal treatment from their inhalers.To understand how innovation in inhaler design can lead to improved treatment for patients and widen the range of diseases that can be treated via the inhaled route.

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Section: What Are the Current Incentives Driving Inhaler Development mentioning

confidence: 99%

Is there room for further innovation in inhaled therapy for airways disease?

Biddiscombe

Usmani

2018

Breathe

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“…Small airways include all peripheral membranous bronchioles <2 mm in diameter, whereas large airways contain smooth muscle and cartilage and have a luminal diameter >2 mm (bronchi up to terminal bronchioles) [7]. Numerous reviews on the importance of small airways in asthma and other airway diseases have been published in recent years, including the following [8][9][10][11][12].…”

Section: Different Lung Compartments Involved In Asthma(s)mentioning

confidence: 99%

Should lung biopsies be performed in patients with severe asthma?

2015

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Asthma, and severe asthma, in particular, is increasingly recognised as a heterogeneous disease. Identifying these different phenotypes of asthma and assigning patients to phenotype-specific treatments is one of the current conundrums in respiratory medicine. Any diagnostic procedure in severe asthma (or any disease) should have two aims: 1) better understanding or identifying the diagnosis, and 2) providing information on the heterogeneity of asthma phenotypes to guide therapy with the objective of improving outcomes. Lung biopsies can target the large and small airways as well as the lung parenchyma. All compartments are affected in severe asthma; however, knowledge on the distal lung is limited. At this point, it remains uncertain whether lung specimens routinely add diagnostic information that is unable to be obtained otherwise. Indeed, whether a lung biopsy is indicated in the workup of a patient with severe asthma remains an individual decision. It is hoped this review will support rational decision-making and provide a detailed synopsis of the varied histopathological features seen in biopsies of patients with a diagnosis of severe asthma. Due to limited data on this topic this review is primarily based on opinion with recommendations arising primarily from the personal experience of the authors.

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“…The small airways play a role in the pathobiology of asthma and, although they are involved in half of all cases of asthma, they can have a distinct role in specific disease phenotypes [13–17]. …”

Section: Introductionmentioning

confidence: 99%

Manifesto on small airway involvement and management in asthma and chronic obstructive pulmonary disease: an Interasma (Global Asthma Association - GAA) and World Allergy Organization (WAO) document endorsed by Allergic Rhinitis and its Impact on Asthma (ARIA) and Global Allergy and Asthma European Network (GA2LEN)

Braido¹,

Scichilone²,

Lavorini³

et al. 2016

asthma res and pract

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Evidence that enables us to identify, assess, and access the small airways in asthma and chronic obstructive pulmonary disease (COPD) has led INTERASMA (Global Asthma Association) and WAO to take a position on the role of the small airways in these diseases.Starting from an extensive literature review, both organizations developed, discussed, and approved the manifesto, which was subsequently approved and endorsed by the chairs of ARIA and GA2LEN. The manifesto describes the evidence gathered to date and defines and proposes issues on small airway involvement and management in asthma and COPD with the aim of challenging assumptions, fostering commitment, and bringing about change.The small airways (defined as those with an internal diameter <2 mm) are involved in the pathogenesis of asthma and COPD and are the major determinant of airflow obstruction in these diseases. Various tests are available for the assessment of the small airways, and their results must be integrated to confirm a diagnosis of small airway dysfunction.In asthma and COPD, the small airways play a key role in attempts to achieve disease control and better outcomes. Small-particle inhaled formulations (defined as those that, owing to their size [usually <2 μm], ensure more extensive deposition in the lung periphery than large molecules) have proved beneficial in patients with asthma and COPD, especially those in whom small airway involvement is predominant.Functional and biological tools capable of accurately assessing the lung periphery and more intensive use of currently available tools are necessary. In patients with suspected COPD or asthma, small airway involvement must be assessed using currently available tools. In patients with subotpimal disease control and/or functional or biological signs of disease activity, the role of small airway involvement should be assessed and treatment tailored. Therefore, the choice between large- and small-particle inhaled formulations must reflect the physician’s considerations of disease features, phenotype, and response to previous therapy.This article is being co-published in Asthma Research and Practice and the World Allergy Organization Journal.

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The role of the small airways in the pathophysiology of asthma and chronic obstructive pulmonary disease

Cited by 76 publications

References 100 publications

Is there room for further innovation in inhaled therapy for airways disease?

Is there room for further innovation in inhaled therapy for airways disease?

Should lung biopsies be performed in patients with severe asthma?

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