The National Asthma Education and Prevention Program's (NAEPP) revised guidelines, the Expert Panel Report 3 (EPR-3), published in 2007, represents a shift in the approach to asthma: the EPR-3 recommends that clinicians think of asthma as a chronic disease with an inflammatory basis. EPR-3 guidelines also represent a shift in the treatment paradigm for asthma in line with the shift in approach: although symptomatic relief is still necessary, the primary goal of asthma treatment is now long-term control, with the aim of minimizing exacerbation frequency and severity and limiting possible permanent airway damage that can result from frequent asthma exacerbations. To help clinicians implement the new EPR-3 guidelines into daily practice, the NAEPP's Guidelines Implementation Panel has identified 6 key action-focused recommendations. This article describes those recommendations and the evidence supporting them.
Rhinitis is one of the most prevalent conditions affecting Americans today. Twenty to 40 million Americans (10%-30% of adults and up to 40% of children) are estimated to have allergic rhinitis. In recent decades, its prevalence in Western societies has increased dramatically, and studies from around the world are reporting similar trends. Although studies have traditionally reported a 3:1 ratio of allergic to nonallergic rhinitis, recent data suggest that as many as 87% of patients with rhinitis may have mixed rhinitis, a combination of both allergic and nonallergic rhinitis. Untreated or inappropriately managed rhinitis can significantly affect a patient's quality of life and ability to perform activities of daily living. It is often associated with concomitant conditions, such as fatigue, headache, sleep disturbance, cognitive impairment, and respiratory conditions, complicated by rhinitis, including asthma and sinusitis. It is a significant cause of morbidity, health care expenditure, reduced work productivity, and absences from school. According to the recently released updated practice parameters, The Diagnosis & Management of Rhinitis, rhinitis is characterized by the presence of one or more of the following nasal symptoms: Congestion, Rhinorrhea (anterior and posterior), Sneezing, Itching. Inflammation is normally associated with rhinitis, but certain subtypes of the disease, such as vasomotor (increasingly known as chronic idiopathic rhinitis) or nonallergic rhinitis and atrophic rhinitis, are not predominantly inflammatory. The diagnosis of rhinitis may appear to be a fairly straightforward undertaking; however, rhinitis is composed of numerous subtypes and etiologies, and differentiating them can be a challenge for primary care practitioners. Further complicating matters is the fact that many patients have both an allergic and a nonallergic component to their rhinitis. Whether or not identification of rhinitis subtype should be an integral component of initial diagnosis remains an area of controversy. While standard treatment for allergic and nonallergic rhinitis is often the same, certain subtypes of the disease do not respond well to the usual first-line treatments for allergic rhinitis. Identification of subtype, therefore, can potentially have important implications for treatment choice. In the following section, we present a discussion between 2 members of the Respiratory & Allergic Disease (RAD) Foundation, Thomas B. Casale, MD, and Michael S. Blaiss, MD. Drs. Casale and Blaiss debate the question, "Should clinicians routinely determine rhinitis subtype on initial diagnosis and evaluation?" Each expert was randomly assigned a position to take: Dr. Casale's views represent the "pro" argument while Dr. Blaiss was asked to speak to the "con" argument. The debate concludes with a synthesis of their arguments and final points, including important takeaway messages for the primary care practitioner.
Recent statistics indicate that overweight and obesity have become an increasingly serious clinical and socioeconomic problem worldwide, and one of the greatest public health challenges of our time. In the United States, 133.6 million (66%) adults are overweight or obese (body mass index [BMI] >/=25 kg/m(2)), with 63.3 million (31.4%) considered to be obese (BMI >/=30 kg/m(2)). The International Obesity Task Force estimates that worldwide at least 1.1 billion adults are overweight, including 312 million who are obese. Overweight and obese patients are at an increased risk for developing numerous cardiometabolic complications, including hypertension, type 2 diabetes mellitus, dyslipidemia, and cardiovascular diseases, as well as conditions such as osteoarthritis, obstructive sleep apnea, hepatobiliary diseases, and certain types of cancers. Owing to the major health risks and complications associated with obesity, which negatively affect quality of life and reduce average life expectancy, in addition to placing an enormous burden on health care resources, the treatment of overweight and obesity is a public health imperative. Treatment must begin with long-term lifestyle changes, including increased physical activity and dietary modifications. For overweight and obese individuals for whom lifestyle changes alone are insufficient, pharmacotherapy may be added. However, patients who choose adjunctive pharmacotherapy should be advised of the risks and benefits of drug therapy, the lack of long-term safety data, and the temporary and modest nature of the weight loss that can be achieved with these agents. Bariatric surgery is an effective treatment option for morbidly obese patients or obese patients with multiple comorbidities who have not been successful in achieving sufficient weight loss with nonsurgical approaches. However, appropriate candidates for bariatric surgery must also be committed to long-term lifestyle changes.
While global prevalence of obesity continues to increase dramatically, treatment options remain less than optimal. The etiology of obesity is multifactorial, ranging from lifestyle choices such as excess food intake and insufficient physical activity, to use of medications that have weight gain as an undesirable side effect. Economic and political determinants of available foodstuffs and even social networks may also contribute to obesity. Successful management of obesity requires the understanding and acceptance of a new paradigm that identifies obesity as a disease--one defined by waist circumference--that requires treatment. Obesity meets all accepted criteria of a medical disease, including a known etiology, recognized signs and symptoms, and a range of structural and functional changes that culminate in pathologic consequences. Excess adipose tissue acts as an endocrine organ to produce excess free fatty acids, as well as tumor necrosis factor-alpha, interleukin-6, leptin, and plasminogen activator inhibitor-1. These bioactive molecules are associated with hyperinsulinemia, hyperglycemia, insulin resistance, development of diabetes, endothelial damage, and the onset and progression of atherosclerotic lesions. Options for treating obesity include lifestyle modifications (dietary changes, increased physical activity, behavior modification) and, for the morbidly obese, surgery. Lifestyle modification is rarely successful over the long term; therefore, addition of pharmacotherapy should be considered for obese individuals who have difficulty achieving and maintaining weight goals with lifestyle modifications alone. Several weight loss drugs are available for long-term use, with others in various stages of clinical development.
The US Food and Drug Administration (FDA) has launched an investigation into the safety of long-acting beta(2)-agonists (LABAs). While the impact of this investigation is yet to be seen, clinicians should be circumspect in the use of these agents and prescribe them according to the recommendations of current asthma guidelines, informing patients and their caretakers about potential risks. As clinical trials attempt to address the question of whether LABAs are safe for use in pediatric and adult populations, current data provide no clear answers. A special hearing of the FDA's Pulmonary-Allergy Drugs Advisory Committee, Drug Safety and Risk Management Advisory Committee, and Pediatric Advisory Committee attempted to seek consensus on the matter as it reviewed the results of controlled clinical trials and conducted a benefit:risk assessment of LABAs to make recommendations on their safety.
Angiotensin receptor blockers (ARBs) are the most recently approved major class of antihypertensive agents. The primary mechanism of action of ARBs is the selective blockade of the AT(1) receptor. There are 7 ARBs presently approved for clinical use in the United States, several with other indications in addition to blood pressure reduction in patients with hypertension. While ARBs appear to be no more potent than angiotensin-converting enzyme inhibitors for lowering blood pressure when used as monotherapy, they are a beneficial alternative and even compelling in certain populations. This class of agents also has the added benefit of placebo-like side effects, potentially enhancing adherence. In this review, studies are presented as positive evidence supporting the use of ARBs in special populations (including persons with diabetic nephropathy), in patients with heart failure (especially with systolic dysfunction), for cardioprotection in high-risk cardiac patients (including postmyocardial infarction and stroke), and for delaying new-onset diabetes. Clinical information on the effects of ARBs related to race and ethnicity are also discussed, although the data in most large trials are not substantial. Despite the fact that African American patients have the highest prevalence of hypertension (with increased mortality and morbidity), studies have been less robust regarding ARBs and protection against cardiovascular disease in this population. Although at least 1 major study has confirmed the benefit of ARBs in Asian patients with diabetic nephropathy, overall, treating patients based on race and ethnicity remains fraught with difficulty.
A meta-analysis recently published in the Journal of the American Medical Association found an increased risk of nonfatal myocardial infarction, stroke, and cardiovascular death associated with inhaled anticholinergic use in patients with chronic obstructive pulmonary disease (COPD); however, inherent limitations in the meta-analysis and contradictory results from other studies cast uncertainty onto its conclusions. For example, the Understanding Potential Long-term Impacts on Function with Tiotropium trial, a large, prospective, 4-year outcome study in nearly 6000 patients with COPD, did not demonstrate an increase in cardiovascular events with anticholinergic therapy. Until more data are available, clinicians should always carefully weigh safety and efficacy data and help patients make informed decisions about their COPD care.
Obesity, particularly abdominal adiposity, is increasingly recognized as a cause of elevated cardiometabolic risk--the risk of developing type 2 diabetes mellitus (DM) and cardiovascular disease (CVD). The predominate mechanisms appear to involve the promotion of insulin resistance, driven largely by excess free fatty acids secreted by an expanded adipose tissue mass, and the development of an inflammatory milieu due to increased secretion of inflammatory cytokines and adipokines from adipose tissue. Key proinflammatory cytokines secreted by adipocytes include tumor necrosis factor-alpha, interleukin-6, leptin, resistin, and plasminogen activator inhibitor-1. All have been variously associated with hyperinsulemia, hyperglycemia, insulin resistance, diabetes, and endothelial dysfunction, as well as plaque development, progression, and rupture. Adiponectin, another important adipocyte, has protective cardiometabolic actions; however, adiponectin levels decline with increasing obesity. Understanding the role of obesity in the pathogenesis of cardiometabolic risk is crucial for the development of treatment strategies that will provide maximum benefit for patients with, or at risk for, type 2 DM and CVD.
Studies have shown that obesity increases cardiometabolic risk across the span of life. Obesity results in increased production of proinflammatory adipokines and decreased production of the anti-inflammatory adipokine, adiponectin, which eventually leads to atherosclerosis and type 2 diabetes mellitus. Lifestyle changes are the cornerstone for treatment of overweight and obese patients; however, pharmacotherapy and surgery are 2 additional treatment options that may be considered when lifestyle changes alone are unsuccessful. Adipose tissue, particularly central adipose tissue, is an endocrine organ, the actions of which tie together all components of cardiometabolic risk. Weight loss reduces levels of most proinflammatory adipokines, attenuates inflammation, improves endothelial function, and enhances insulin sensitivity. In view of these effects, obesity represents an obvious target for pharmacologic intervention. However, the benefits associated with the pharmacologic management of weight loss must be weighed against the potential for drug-related adverse events.
The strong association between allergy and asthma is well documented; however, few practitioners-even asthma specialists-accurately estimate the percentage of patients with asthma who have clinically relevant allergies. Because allergen exposure can prompt airway inflammation, trigger asthma exacerbations, and possibly lead to negative health outcomes for patients with asthma, identifying allergies and immunoglobulin E (IgE)-mediated disease in patients with persistent asthma is crucial. Updated Expert Panel 3 asthma guidelines from the National Asthma Education and Prevention Program reinforce the need for clinicians to identify allergic sensitivities in patients with persistent asthma and determine their clinical relevance. Allergy testing can be useful in educating the patient with IgE-mediated asthma about the need for allergic trigger avoidance and can help determine optimal therapy for patients with concomitant asthma and allergy. Implementing this guideline recommendation, however, requires active clinical engagement. Data from a recent observational study indicate that there may be a substantial gap between guideline recommendations and actual clinical practice. These data also suggest that when clinicians participate in education about the role of IgE in asthma and begin testing their patients for allergy, the recognition of allergies among patients with asthma dramatically increases.
The manufacture, sale, and distribution of chlorofluorocarbon-propelled albuterol metered-dose inhalers ceased as of December 31, 2008. Clinicians should actively transition patients to currently available hydrofluoroalkane-propelled devices, providing concise education and instruction for using the newer devices.
Jenny B. is an active 12-year-old white female who recently stopped participating in junior high school track because of respiratory symptoms she experiences while running. On presentation to her pediatrician's office for a consultation, it immediately became apparent that she was anxious to rejoin her team to compete. This article will navigate through a patient case and explore multiple clinical approaches to exercise-induced broncho-spasm from diagnosis to treatment. As clinicians, our goal is to partner with all patients who experience asthma or respiratory symptoms, enabling them to have a life without limitations. Let us review Jenny B.'s case and examine what might be the best approach to get her back on track.
Renin-angiotensin-aldosterone system (RAAS) overactivity is associated with increased cardiovascular risk, a finding that may be explained by the key role of the RAAS in stimulating vascular and cardiac remodeling. Inhibition of RAAS activity with the use of angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptor blockers (ARBs) has been shown to reduce cardiovascular mortality in patients with heart failure. ACE inhibitors have also been shown to reduce the incidence of stroke, myocardial infarction (MI), and heart failure in high-risk patients without heart failure. These findings led to the evaluation of the ARB telmisartan versus the ACE inhibitor ramipril in the ONgoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial (ONTARGET), a cardioprotection trial conducted in high-risk patients without left ventricular dysfunction or heart failure. The results of this trial showed that the ACE inhibitor ramipril and the ARB telmisartan are equally effective in reducing the incidence of cardiovascular death, MI, stroke, and hospitalization for heart failure in patients without heart failure or left ventricular dysfunction but at high risk for cardiovascular disease (CVD). These results confirm that RAAS inhibition, using ACE inhibitors or ARBs, is an effective approach to reducing cardiovascular mortality and morbidity in patients without heart failure who are at high risk for CVD.
High blood pressure (HBP) is one of the most prevalent conditions seen today by clinicians, affecting an estimated 73 million--or 1 in 3--adult Americans, only one third of whom have achieved control of their hypertension (HBP). Central to the management of this pervasive medical condition are the issues of accurate diagnosis and maintaining control through appropriate treatment. Accurate diagnosis depends primarily on reliable measurement. Over the years, it has become increasingly recognized that blood pressure (BP) measurement occurring in clinical settings produces far less accurate and reliable readings than do other methods, notably 24-hour ambulatory BP monitoring and home BP measurement. Beyond technique, there are additional challenges to obtaining accurate readings, including emotional factors that produce either falsely elevated or lowered results, having the potential to mislead the clinician. The need to overcome obstacles to proper diagnosis and determine effective treatments has reached heightened urgency, especially for patients with compelling comorbidities such as diabetes, renal disease, congestive heart failure, and other cardiovascular diseases. The continuing evolution of the management of HBP is reflected in updated guidelines from the American Heart Association and evidence-based information stemming from recent studies and randomized clinical trials. The appropriate selection of antihypertensive agents, at the proper doses, is a complex issue requiring greater understanding of our pharmacologic options. The contributions of some of the more recent and salient studies and trials are mentioned here, although there is no attempt in this brief review to match drug classes with compelling indications. The trials discussed involve such pharmacologic treatments as diuretic therapy, alpha-blockers, conventional beta-blockers, calcium channel blockers, angiotensin-converting enzyme inhibitors, and angiotensin receptor blockers. Trial outcomes shed light on the relative benefits and drawbacks of these agents, often within the context of various patient characteristics such as age, comorbidities, and risk status. Successful management of HBP is a multi-faceted and ongoing endeavor, in which developing knowledge constantly tempered by new questions moves us toward the goal of improving the lives of our patients.
The continuing evolution of asthma treatment and prevention are reflected in updated guidelines from the National Asthma Education and Prevention Program and Global Initiative for Asthma as well as other recent publications. The 2007 Expert Panel Report 3 guidelines designate severity and control, mediated by considerations of current impairment and future risk, as the primary concepts in assessing and monitoring asthma. Severity should ideally be determined at the time of diagnosis, after which control becomes the central focus of asthma management. In the area of treatment, inhaled corticosteroids (ICSs) remain first-line therapy for long-term asthma management in children and adults. For patients whose severity of asthma requires more than low-dose ICSs, or whose asthma cannot be well controlled on monotherapy with low-dose ICSs, evidence supports the efficacy of combination therapy consisting of an ICS plus an inhaled long-acting beta(2)-agonist (LABA) or an increase to medium-dose ICSs. For children >5 years of age and adults not controlled on low-dose ICSs, the combination of a low-dose ICS plus an inhaled LABA is equivalent in terms of outcomes to the use of medium-dose ICS. For children <5 years of age not controlled on low-dose ICSs, increasing the dose of ICSs is preferred to the addition of a LABA to low-dose ICS therapy as no studies using combination therapy have been conducted for patients in this age group. With regard to asthma prevention, approaches to primary prevention (to avoid allergen sensitization) and secondary prevention (to avoid disease progression) are still very much in the developmental stage, while tertiary prevention (to avoid asthmatic stimuli) has been more successful particularly in pediatric patients. Written action plans as part of self-management processes appear to improve physician-patient communication and disease status tracking. Other considerations in successful asthma management include patient education and monitoring of adherence to treatment regimens.
Data from clinical trials underscore the fact that loss of beta-cell function and insulin hyposecretion are progressive in type 2 diabetes. To achieve adequate glycemic control, most patients will eventually require insulin. Addition of insulin to sulfonylurea therapy, when maximal sulfonylurea does not adequately maintain fasting plasma glucose levels at <108 mg/dL, has been found to be more effective than initiating insulin therapy after oral agents have failed to maintain glycemic control. Nonetheless, both patients and providers are reluctant to begin insulin therapy. Research has shown that providers often delay modification of the diabetes treatment regimen because they believe their patients would be concerned about starting insulin therapy. In addition, they are concerned about patient nonadherence to nonpharmacologic and pharmacologic therapy. There are multiple reasons for patient nonadherence to insulin therapy; however, patients must be made to understand, early in the course of the disease, the progressive nature of type 2 diabetes and that exogenous insulin is an additional therapeutic option to help them achieve and maintain adequate glycemic control.
