Advances in Combination Therapy for Asthma and COPD

Jan Lotvall, Jan Lotvall

• Editore: Wiley
• Anno: 2011
• ISBN:
  9781119978466
• Edizione: 1
• Argomento: Medicine
• Categoria: Pulmonary & Thoracic Medicine

Aimed at specialists in respiratory medicine, this new book comprehensively reviews the variety of agents currently available for treatment of asthma, COPD, and other airway diseases and covers practical guidelines as well as challenges and complications in their use. Advances in Combination Therapy for Asthma and COPD is the first book to address the complexity of multi-agent therapy and deal with management issues in an integrated fashion. A review of currently available agents and their applications, as well as new therapies soon to become available are outlined. Advantages of combined therapies and additional considerations that arise from multi-agent programs are highlighted.

1

Similarities and differences in the pathophysiology of asthma and COPD

J. Christian Virchow

Department of Pneumology, University Medical Clinic, Rostock, Germany

1.1 Introduction

In the early 1960s, when pulmonary function testing was limited to spirometry, a hypothesis was put forward that pulmonary diseases with similar clinical symptoms and spirometry findings such as asthma, chronic bronchitis and emphysema might be different expressions of one disease entity, in which both endogenous (host) and exogenous (environmental) factors would play a role in the pathogenesis.1 More refined diagnostic tools such as bodyplethysmography or helium-based pulmonary function analysis, which can measure pulmonary hyperinflation, were not available at that time. Pathophysiological as well as immunological characteristics of asthma such as IgE, mast cells and their mediators, leukotrienes, T-cell subsets, cytokines and chemokines had not been discovered. Still, the proposal that asthma, chronic obstructive pulmonary disease (COPD) and chronic bronchitis or emphysema might have a common pathogenic background has been repeated,2 and even now there is some debate about whether asthma and COPD should be regarded as:

• two different diseases in one lung;
• two diseases with one common pathogenesis; or
• one disease with different clinical phenotypes.

These hypotheses reflect some of the clinical uncertainties that can arise when end-stage COPD and bronchial asthma have to be distinguished based on spirometry and clinical findings alone. This can be especially challenging in patients who smoke on top of an atopic background.

Epidemiological, genetic and pathophysiological data collected in the past 50 years, however, allow a relatively clear separation of COPD and asthma into rather distinct entities. These findings, which will be summarized below, make a common pathogenic origin for bronchial asthma and COPD most unlikely.

Among the epidemiological features that can separate asthma from COPD are differences in the age of onset,3,4 different risk factors5–10 and comorbidities,11–16 differences in the genetic background17–20 and differences in prognosis. While asthma is generally associated with a normal life expectancy, this is significantly reduced in COPD. Furthermore, marked differences in inflammatory cells and mediators21,22 present in the airways and lungs result in different patterns of inflammation and their intrabronchial and intrapulmonary distribution. As a consequence of these there are distinctly different features in the respective impairment of pulmonary function, different responses to airway irritants in bronchoprovocation tests,23,24 as well as marked differences in response to treatment and a different prognosis. These will be discussed in more detail below:

The clinical hallmark of asthma is episodic symptoms related to airflow limitation, often in response to external specific (allergen) or non-specific (airway irritants) factors. The characteristic feature of COPD in industrialized countries (which is also its main risk factor) is the long-term exposure to inhaled tobacco smoke or biomass combustion (the latter being more relevant to developing countries).

Asthma and COPD can sometimes be difficult to separate due to similarities in reported symptoms, airflow limitation and response to treatment. While individual patients may occasionally evade a clear separation into either asthma or COPD these patients are more likely an exception than the rule. These are often patients with asthma who have a longstanding smoking history or patients with a smoking history who develop intrinsic asthma. However, they do not support the hypothesis of a common pathogenetic origin or common pathogenetic pathways. The fact that end-stage asthma and COPD can display a number of pathophysiological similarities rather reflects the fact that the lung and its airways have a limited spectrum of responses to endogenous or exogenously induced inflammation irrespective of the origin of the insult. It would be unscientific to understand this limited spectrum of reactions, however, as evidence for a common pathogenesis. In an analogy, while end-stage fibrosing lung disease can appear with similar symptoms and even histopathology, irrespective of the underlying interstitial lung disease and the causative agents, a common pathogenesis is not suspected.

Accordingly, the so-called Dutch hypothesis from 1961 has been refuted in the past decades due to increasing knowledge about the underlying inflammatory processes in asthma and more recently in COPD.

From a clinical perspective, early stages of asthma as well as COPD can be differentiated based on patients’ history and clinical, laboratory and pulmonary function findings (Table 1.1).

Table 1.1 Typical clinical features of COPD.

Feature	Asthma	COPD
Age of onset	Childhood/adolescence	>40 years
Smoking history prior to onset	Rare	Common
Nocturnal symptoms	Common	Rare
Dyspnoea	Variable	On exertion
Allergy	Common	Rare
Course	Variable	Progressive
Airflow obstruction	Variable	Fixed
FEV1 reversibility	Good, >20%	Limited, <20%
Airway hyperresponsiveness	Characteristic feature	Occasionally
Response to corticosteroids	+++	(+)
Sputum production	+	+ to +++
FEV1, forced expiratory volume in 1 second.

It should be noted that none of the clinical features on its own clearly distinguishes asthma from COPD. Recent studies indicate that the forced expiratory volume in 1 second (FEV1)-reversibility to large doses of brochodilators in COPD can change over time,25 possibly to a degree indistinguishable from bronchial asthma. Nevertheless, in severe COPD pulmonary function abnormalities are usually not responsive to β2-agonists and/or corticosteroids and the absolute magnitude of response still differs.

Therefore, with increasing

• smoking history
• irreversibility of the airflow obstruction
• age
• dyspnoea on exertion
• Paco2
• comorbidities such as coronary heart disease, arteriosclerosis, depression, osteoporosis, etc.

there is a rise in the likelihood that the patient has COPD.

1.2 Pulmonary function abnormalities in asthma and COPD

Pulmonary function abnormalities in asthma and COPD can be very similar. Both are characterized by airflow obstruction but careful analysis can reveal noticeable differences in pulmonary function testing that help to differentiate asthma from COPD (Table 1.2).

Table 1.2 Pulmonary function abnormalities in asthma and COPD.

Abnormality	Asthma	COPD
Site of airflow obstruction	Central airways	Peripheral airways
Reversibility	From +++ to +	From + to ++
Hyperinflation	From + to ++ (dynamic)	From +++ to ++ (largely fixed)
Airflow obstruction increases in response to hyperinflation	+	+++
Airway resistanc...

Indice dei contenuti

• Cover
• Title Page
• Copyright
• Contributors
• Preface
• Chapter 1: Similarities and differences in the pathophysiology of asthma and COPD
• Chapter 2: Glucocorticoids: pharmacology and mechanisms
• Chapter 3: Inhaled corticosteroids: clinical effects in asthma and COPD
• Chapter 4: LABAs: pharmacology, mechanisms and interaction with anti-inflammatory treatments
• Chapter 5: Long- and ultra-long-acting β2-agonists
• Chapter 6: The safety of long-acting beta-agonists and the development of combination therapies for asthma and COPD
• Chapter 7: Inhaled combination therapy with glucocorticoids and long-acting β2-agonists in asthma and COPD, current and future perspectives
• Chapter 8: Novel anti-inflammatory treatments for asthma and COPD
• Chapter 9: Novel biologicals alone and in combination in asthma and allergy
• Chapter 10: Anti-infective treatments in asthma and COPD
• Chapter 11: Long-acting muscarinic antagonists in asthma and COPD
• Chapter 12: Phosphodiesterase inhibitors in obstructive lung disease
• Chapter 13: Biological therapies in development for COPD
• Chapter 14: ‘Triple therapy’ in the management of COPD: inhaled steroid, long-acting anticholinergic and long-acting β2-agonist
• Index