Asthma Overview

In the United States, asthma affects over 22 million people and accounts for over 4000 deaths every year. Asthma is a clinical diagnosis based on a symptom complex of episodic shortness of breath typically associated with wheezing, chest tightness, and cough and with objective physiological evidence of variable and reversible airflow obstruction with bronchial hyper-responsiveness.

Airway inflammation plays a key role in the pathogenesis of asthma and ongoing research indicates that the underlying biology of asthma is complex and heterogeneous. Airway remodeling is presumed to be a result of under-treatment of airway inflammation.

However, several features of airway remodeling may not be a direct result of airway inflammation and may be driven by genetics and factors as yet unappreciated.

Inhaled corticosteroids remain the mainstay controller maintenance therapy for most asthmatics while other anti-inflammatory medications, such as leukotriene receptor antagonists, 5 lipoxygenase inhibitors or anti-IgE agents, may be helpful for certain individuals.

An assessment of the severity of a patient’s asthma is important as a basis for deciding on initial therapeutic interventions. However, for deciding if therapy needs to be stepped up or stepped down, it is important to establish a patient’s personal best and arrange subsequent follow-up to ensure the patient is optimally controlled.

Researchers are now focused on improving our understanding of the biological heterogeneity of asthma and increasing our capability to biologically phenotype patients by assessment of airway inflammation and/or pharmacogenomics. These novel clinical assessment tools will allow for better individualized therapy for asthma patients.

Asthma is one of the most common chronic medical conditions in the developed world and is increasing in its prevalence in less developed countries as well. In the United States, over 22.2 million people are diagnosed with asthma. Over 12.2 million people suffer asthma exacerbations (requiring increased asthma therapy and/or additional interventions) each year.

The total annual costs of asthma in the United States in 2002 were estimated to be $16.1 billion of which $11.5 billion were direct costs related to medical expenses and $4.5 billion were indirect costs related to lost work productivity and school days as well as mortality.

There were 24.5 million lost workdays and 12.8 million missed school days in 2003 due to asthma. There were almost half a million hospitalizations related to asthma in 2002, which approximates to about 16 hospitalizations per 10,000 population in the United States compared with 19.8 for diabetes and 37.4 for coronary atherosclerosis.

There were over 4200 asthma deaths in 2002, indicating that over 11 people per day die of asthma in the United States. Many of the asthma deaths occur in otherwise healthy young productive individuals. Many of these deaths were almost certainly preventable if patients were treated more aggressively for their asthma.

Data from the Salmeterol Multicenter Asthma Research Trial (SMART) showed that a number of those whose death was related to asthma had low use of inhaled corticosteroids despite having severe asthma.

What is Asthma?

The clinical presentation of asthma includes typical symptoms of episodic dyspnea variably associated with other symptoms, such as chest tightness, wheezing, and coughing. Typical triggers for asthma symptoms include allergens, exertion, cold air, irritant exposures, and strong odors.

The hallmark features of asthma include reversible airflow obstruction (O12% improvement in forced expiratory volume in 1 second [FEV1] with a minimum of 200-mL improvement postbronchodilator), bronchial hyperresponsiveness, and airway inflammation, which most often involves an elevation in sputum eosinophils and or elevations in exhaled nitric oxide.

While these elements represent the clinical features that lead to the diagnosis of asthma, these clinical features are not unique or the sole domain of asthma and these clinical characteristics are seen in a wide assortment of respiratory disorders.

The symptom complex, the physiological features, and even certain histological features found in asthma are also found in other obstructive airway diseases and even in interstitial lung diseases that have an obstructive component, such as sarcoidosis and hypersensitivity pneumonitis.

Furthermore, bronchoscopic and sputum studies that have examined the inflammatory features of patients who have the clinical diagnosis of asthma reveal that there is indeed significant heterogeneity in the magnitude and types of inflammatory cells and mediators involved in various patients that fit the clinical phenotype we refer to as asthma.

This biological diversity is part of the explanation for the variable response to pharmacological and non-pharmacological interventions observed in the asthma population. Hence, it is best to think of asthma as a clinical diagnosis that has typical symptom and physiological features but also has several biological mechanisms that contribute to the final clinical phenotype.

There are several distinct clinical phenotypes of asthma and it is likely that these are the result of environmental factors and different biological pathways being less or more active for different clinical presentations.

We recognize early-versus lateonset asthma and we know that most early-onset asthmatics have environmental allergies whereas late-onset asthmatics are less atopic yet tend to have higher eosinophil counts in sputum and/or bronchoalveolar lavage.

Some asthmatics appear to have primarily nocturnal asthma, exercise-induced asthma, or cough variant asthma in isolation. These patients may have distinct biological characteristics that differentiate them from the more common group of asthmatics that have any or all of these features as a reflection of poorly controlled disease in general.

Meanwhile, some people develop occupational asthma related to high molecular weight allergens (eg, flour, latex, animal proteins) with classic IgE-mediated allergic reactions versus low molecular weight antigens, most often such chemicals as isocyanates or acid anhydrides where the precise mechanism is not as clear.

In addition, some individuals develop reactive airways dysfunction syndrome because of single or multiple high-dose exposures to irritants. Finally, some patients have so-called ‘‘inner-city asthma’’ or ‘‘urban asthma,’’ which is based on reports of higher prevalence rates and more severe disease found in urban populations.

This asthma most likely reflects a complex interaction of socio-economic, environmental, and, potentially, biological factors. Asthma among urban populations has gained recognition and is an area of focused research.