Asthma Management

Asthma Management: Recent Insights and Updates

 

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Introduction

Asthma, characterized by reversible airflow obstruction, has afflicted people since ancient times. Described by Galen in the second century as epilepsy of the lungs, an array of famous people have suffered from asthma—from Ludwig von Beethoven to Billy Joel, from the ancient Roman philosopher and politician, Seneca to President Bill Clinton, and from baseball pitcher, Jim “Catfish” Hunter to Olympic medalist, Jackie Joyner-Kersee.[1,2] Today, it is estimated that asthma affects 300 million individuals worldwide. In the US, its prevalence has increased dramatically in the last decade and now affects more than 25 million.[3] Asthma is the most common chronic disease among children under 5 years old, and is the leading cause of morbidity reflected in absence from daycare, emergency room visits, and hospitalization.[4]

While the number of hospitalizations and emergency room visits attributed to asthma have stabilized in recent years, the death toll from asthma remains significant. Efforts to simply and refine the treatment of patients with asthma have continued. Global and national initiatives focusing on the treatment and prevention of asthma have been developed over the last twenty years, with periodic updates that reflect not only the increased appreciation of the complex pathophysiology of the disease, but also improvement in the therapeutic agents that target specific aspects of disease.[4-10] In the US, the National Asthma Education and Prevention Program (NAEPP) clinical practice guidelines were first developed in 1991, and since that time there have been significant improvements and three updates of the guideline.[7,8] Despite these advances, however, as the NAEPP notes, the burden of avoidable hospitalizations remains.  People who have asthma have more than 497,000 hospitalizations annually.[8]

Thus, the need to improve the recognition of asthma and to apply the latest evidence-based guidelines continues to be substantial. Recently, three major international asthma guidelines Global Initiative for Asthma [GINA, 2011], the British Thoracic Society [BTS, 2012], and the Canadian Thoracic Society [CTS, 2012]) have been updated and their recommendations reflect a growing consensus about the importance of definition and assessment of asthma control.[4-10] Each of these guidelines offers a consistent step-wise approach to management for young children, older children and adults. While focusing on diagnosis and treatment, they also address the emerging science such as the use of biomarkers and genetic testing that may soon be appropriate for clinical practice.[4-10]

According to the 2012 CTS guideline, the definition of asthma is unchanged from its 2010 iteration:

Asthma is an inflammatory disorder of the airways characterized by paroxysmal or persistent symptoms such as dyspnea, wheezing, coughing and sputum production associated with airflow limitation and airway hyperresponsiveness to exogenous and/or endogenous stimuli.”[10]

Most guidelines address young children (preschoolers or <5 years) separately from older children and adults for a variety of reasons. For example, while wheezing is nearly ubiquitous in patients with asthma, not all young children who wheeze have asthma. Consequently, other possible causes of wheezing, shortness of breath and the other hallmarks of asthma must be ruled out.[6,7]  An additional challenge in diagnosing asthma in young children is the fact that  routine, accurate assessment of airflow limitation and inflammation is often not possible, particularly in children 3 or younger. A trial of short-acting bronchodilator and inhaled corticosteroid along with a compelling clinical history are helpful in suggesting this diagnosis in very young children.[4,5]

Diagnosis of asthma in older children and adults is somewhat less challenging because pulmonary function studies are more reliable diagnostic tools. Indeed, the principal difference between the assessment of control in young children and assessment of adults is the recommendation to use.  Both the 2007 National Asthma Education and Prevention Program, Expert Panel Report 3 and the 2011 GINA update, recommend office spirometry –peak expiratory flow (PEF) and/or forced expiratory volume in one second (FEV1)–as the preferred tool for diagnosis and treatment in children over five and adults.[6,7,8] A diagnosis of asthma is suggested when PEF values improve > 20% after inhalation of a bronchodilator, or if FEV1 increases by > 12%.

Once the diagnosis of asthma is made, management should focus on controlling symptoms, both during the day and at night, and preventing or avoiding exacerbations of disease so that patients can maintain normal activities, including physical activity. The GINA and NAEPP guidelines address acute or subacute exacerbations of asthma separately. Acute or subacute exacerbations are defined as progressive worsening of shortness of breath, cough, wheezing, and chest tightness, or some combination of these symptoms. (See Managing Asthma Exacerbations)

Initial Management Steps: Achieving Control

In general, asthma management consists of four elements: developing a patient/physician partnership to include a mutually agreed, written treatment plan; identification and reduction of risk factors; control of asthma characterized by proper assessment, treatment and monitoring; and management of exacerbations. Importantly, the GINA guidelines as well as the updated Canadian and British guidelines place significant emphasis on patient education, written management plans and forming a close collaborative relationship between the patient and their healthcare provider.[4-10] Patient compliance/adherence remains a major issue in the success of asthma management. Frequent assessment of patient compliance with recommended treatment regimen as well as ensuring proper technique in using inhaled medications are key elements in the successful management. In addition, a critical component of patient education is training on the appropriate use (and avoidance of misuse) of rescue medications, usually short-acting beta2 agonists (SABA).

An array of allergens and pollutants are known to worsen asthma symptoms, including smoke, animal dander, dust mites, pollen, mold, aerosol chemicals and viral infections. Patients should take steps to minimize exposure to these and other environmental factors that aggravate their symptoms.[6,7]

For all children and adults, asthma management is achieved through the use of controller medications with occasional utilization of reliever medications.  Controller medications are long-term agents taken daily with the intent of reducing inflammation and controlling clinical manifestations of asthma.[6,7] Among these agents are inhaled corticosteroids, leukotriene modifiers, long-acting beta agonists (LABA), cromolyn sodium, and theophylline. While some of these agents may be used as monotherapy, most are used in combination and guidelines urge avoidance of LABA alone as monotherapy.[9] To improve clinical control, the dose of the single agent (inhaled corticosteroid) may be increased, or the agents may be combined to target specific mechanisms. For example, leukotriene modifiers are frequently not affective as monotherapy because they address only the leukotriene pathway associated with inflammation but are helpful as add on therapy. In contrast inhaled corticosteroids are very effective broad anti-inflammatory agents and are often effective as monotherapy.[11]

A variety of agents are used in young children, ranging from inhaled corticosteroids, cromolyn sodium (>2 years old), theophylline in rare cases and long-acting inhaled beta agonists (LABA). In most instances, inhaled corticosteroids are preferred and are considered safe in low doses.  Theophylline use has been steadily decreasing due to the potential acute toxicity (cardiac arrhythmias, seizures, death) and the long-term issues including behavioral and learning problems. Cromolyn sodium has not been shown to be more effective than inhaled corticosteroids and its benefit as add-on therapy to inhaled steroids is unclear. Cromones are not generally recommended. The FDA has newer agents such as leukotriene modifiers (LTM) while they may reduce asthma symptoms brought on by a viral infection do not reduce the daytime symptoms, duration of exacerbations, or the frequency of hospitalization. Nevertheless, the GINA guidelines find no safety concerns regarding LTM.[4-10]

Special attention should be given to the medication delivery vehicle in young children. For example, GINA guidelines recommend in children 4 and younger, the use of pressurized metered dose inhalers (pMDIs) with spacer and face masks, or alternatively the use a nebulizer may be appropriate. In children 4 to 5 years of age, pMDIs with space and mouthpiece are recommended; alternatively, pMDIs) with spacer and face masks are recommended, or alternatively the use a nebulizer may be appropriate.[4,5]

In adults and older children, the number of medications that have been used and studied is significantly greater, but general principles of therapy are similar. The NAEPP guidelines use a simple framework for managing patients with asthma, involving a step-wise approach.[8] (See Figure 1) [Adapted from NAEPP Figure 4-5.  Stepwise approach for managing asthma in youths ≥ 12 years of age and adults.

Asthma Control

The principal change in these updated guidelines is the focus on controlling clinical symptoms rather than categorizing patients based on the severity of symptoms (intermittent, mild, moderate and severely persistent), as was done in earlier guidelines.[11] All of the recently updated guidelines emphasize asthma control as the metric to assess their treatment efficacy in young children, older children and adults.[4-10] The third element in asthma management consists of assessing asthma control, treating to achieve control, and monitoring to maintain control.

Patient disease/symptoms are then designated as controlled on their current regimen, partially controlled, or not controlled. (See Table 1: Level of Asthma Control).  In children, this framework defines control as no day or nighttime symptoms, no limitation of activities and use of little rescue/reliever medications two times a week or less. In adults, these same metrics define control plus the addition of a positive response on pulmonary function studies (PEF or FEV1). In the adult and older children, if the pulmonary function studies (PFT) are normal, the asthma is considered controlled with current therapy. If pulmonary function studies that are less than 80% of predicted or if PFTs are less than the individual’s best score, the patient’s symptoms are determined to be partially controlled or uncontrolled, and additional medication or increased dosage is indicated.

In general, patients should be maintained on a treatment regimen for approximately 3 months unless symptom severity warrants more frequent assessment. Improvement should be noted within a month.  Patients with more severe disease or poorly controlled asthma may require more frequent monitoring in order to achieve better control of symptoms. At the end of three months, careful evaluation of the patient should be done.[6,7]  Included in that assessment is a careful history with the patient of their symptoms and the presence or change in risk factors, adherence to treatment, proper inhaler technique, and pulmonary function testing.  Most recently, some guidelines recommend including analysis of sputum cells, particularly the eosinophils as a measure of inflammation.[10]  Other biomarkers, such as exhaled nitric oxide, while it has been extensively reported, has not yet been proven to be a reliable indicator of inflammation and, therefore, asthma control.[10]

If, after the initial treatment period, symptoms and clinical manifestations have not improved, or if the symptom severity increases, the patient would move to Step 2 with either an increase in dose of inhaled corticosteroid or the addition of an LABA. Ideally, through frequent monitoring of asthma control and modification of the treatment regimen (Steps 2-4), acute asthma attacks can be avoided.[4-8]

Patients who do not show improvement in the step-wise approach recommended by these updated guidelines are characterized as having difficult-to-treat asthma. These patients may require multiple medications which may increase the risk of toxicity, and pose a challenge in terms of achieving the best control possible while minimizing side effects.[6,7]  For patients whose symptoms are partially controlled or uncontrolled, an intensification in  medication management is indicated. Guidelines recommend adding a long-acting beta2 agonist or leukotriene modifier to the patient’s low dose inhaled corticosteroid, or increasing the dose of steroid plus adding long-acting beta2 agonist. In some cases, theophylline may be added to the ICS (inhaled corticosteroid) agent.[6-8] (See Figure 1)

Managing Asthma Exacerbations

The fourth and final element in updated asthma care is the recognition and management of asthma exacerbations. Exacerbations are defined as a progressive increase in shortness of breath, cough, wheezing or chest tightness. It is critically that patients and their physicians recognize the signs and symptoms of exacerbations so that prompt care can be obtained and potentially life-threatening symptom worsening can be avoided. Mild exacerbations can frequently be managed at home by patients, but more moderate or severe exacerbations should be treated in the hospital or clinic where rapid-acting agents, oral medications and oxygen can be administered.[6,7] Recognizing patients at increased risk of exacerbations is also an important step.  Among patients at risk for exacerbations are those with prior hospitalizations for asthma, patients with a history of mechanical ventilation or intubation for severe asthma attacks, patients who are currently using oral corticosteroids, patients who have stopped taking their medications, patients who are dependent on rapid-acting beta2 agonists, and patients with a history of noncompliance with their asthma regimen.[6,7] Careful monitoring and patient education are an essential component of asthma care in these patients.

Future Directions

Even as data over the last decade suggest improvement in the management of patients with asthma, study of this disease continues in the hope of better understanding the disease pathophysiology and improving our ability to manage individual patients.

Research on the role of infection, specific genes that may increase hyperresponsiveness to a variety of environmental allergens or that may influence the natural history of the disease, or the value of biomarkers to diagnose or select therapy continues.  In the meantime, the improvement in asthma management has been substantial over the last two decades. These updated guidelines, focusing on recognizing asthma early, initiating a step-wise approach to therapy, and careful monitoring of asthma control will enable patients to maintain optimal activity, and in most cases avoid frequent hospitalization.[12,13]

Addendum

Recently NEJM published two relevant articles on asthma. The first demonstrated that the addition of the COPD drug, inhaled tiotropium lengthens the time to first exacerbation in poorly controlled asthmatic already on inhaled steroids and LABA. The second revisited the issue of the reduction in adult height in those who used inhaled steroids as a child concluding that the initial decrease persists into adulthood.[14,15]

 

Sarah Farrand
Published on September 18, 2012

 

References

  1. Famous People with Asthma. http://www.disabled-world.com/artman/publish/asthma-famous.shtml. Accessed July 2012.
  2. Famous People with Asthma. http://www.medicalnewstoday.com/info/asthma/asthma-famous-people.php. Accessed July 2012.
  3. Akinbami LJ, Moorman JE, Bailey C, et al. Trends in Asthma Prevalence, Health Care Use, and Mortality in the United States, 2001–2010.NCHS Data Brief ,No. 94, May 2012. http://www.cdc.gov/nchs/data/databriefs/db94.pdf. Accessed: July 2012.
  4. Global Initiative for Asthma. 2009. GINA report: Global Strategy for Diagnosis and Management of Asthma in Children 5 years and younger. URL: http://www.ginasthma.org. Accessed July, 2012.
  5. Global Initiative for Asthma. 2009. Pocket Guide for Diagnosis and Management of Asthma in Children 5 years and younger. URL: http://www.ginasthma.org. Accessed July, 2012.
  6. Global Initiative for Asthma, 2011. GINA report: Global Strategy for Asthma Management and Prevention (For adults and children older than 5years). URL: http://www.ginasthma.org. Accessed July,2012.
  7. Global Initiative for Asthma, 2011. GINA report: Pocket Guide For Asthma Management and Prevention (For adults and children older than 5years). URL: http://www.ginasthma.org. Accessed July,2012.
  8. NAEPP. Expert Panel Report 3 (EPR3). Guidelines for the diagnosis and management of asthma; 2007. National Heart, Lung, and Blood Institute. NIH Publication No. 07-4051. URL:http://www.nhlbi.nih.gov/guidelines/asthma/asthgdln.htm. Accessed July 2012.
  9. British Thoracic Society Scottish Intercollegiate Guidelines Network. British guideline on the management of asthma 2011. Updated January 2012. http://www.brit-thoracic.org.uk/. Accessed: July, 2012.
  10. Lougheed MD, Demiere C, Ducharme FM, et al. Canadian Thoracic Society 2012 guideline update: Diagnosis and management of asthma in preschoolers, children and adults. Can Respir J. 2012;19(2):127-164.
  11. Berger WE. New approaches to managing asthma: a US perspective. Clin Risk Manag. 2008:4(2):363–379.
  12. Apter AJ. Advances in adult asthma diagnosis & treatment in 2009. J Allergy Clin Immunol. 2010 January ; 125(1):79–84.
  13. Szefler SJ. Advances in pediatric asthma in 2010: addressing the major issues. J Allergy Clin Immunol. 2011; 127(1):102–115.
  14. Kelly HW, Sternberg AL, Lescher R, et al; the CAMP Research Group. Effect of inhaled glucocorticoids in childhood on adult height. N Engl J Med. 2012 Sep 6;367(10):904-912.
  15. Kerstjens HA, Engel M, Dahl R, et al. Tiotropium in asthma poorly controlled with standard combination therapy. N Engl J Med. 2012 Sep 2. [Epub ahead of print].