A simple rule to identify patients with chronic obstructive pulmonary disease who may need treatment reevaluation.

BACKGROUND: A simple rule based on short-acting inhaled ß2-agonist (SABA) use could identify patients with chronic obstructive pulmonary disease (COPD) at increased risk of exacerbations and signal the need for maintenance therapy change, similar to asthma "Rules of Two(®)". METHODS: Associations between SABA use, COPD exacerbations, and health care costs over 1 year were examined retrospectively using de-identified patient data from the Optum Research Database (ORD; N = 56,581) and the Impact National Benchmark Database (IMPACT™; N = 9423). Nebulized and metered-dose inhaler (MDI) SABA doses were normalized to 2.5 mg and 90 mcg albuterol equivalents, respectively. RESULTS: The GOLD initiative establishes ≥2 exacerbations/year as indicative of increased risk in COPD. We identified a correlation (p < 0.0001) between 1.5 SABA doses/day and this frequency of exacerbations. In ORD, patients using ≥1.5 versus <1.5 SABA doses/day experienced significantly more exacerbations: 1.92 (95% confidence interval [CI], 1.89-1.96) versus 1.36 (95% CI, 1.34-1.38) per patient year (PPY). Above-threshold use was associated with higher average annual COPD-related costs (2010 $US): $21,868 (standard deviation [SD], $53,910) versus $11,686 (SD, $32,707) for nebulized SABA only, $9216 (SD, $30,710) versus $7334 (SD, $24,853) for MDI SABA only, and $15,806 (SD, $35,260) versus $11,233 (SD, $27,006) for both nebulized and MDI SABA. IMPACT™ validated these findings. CONCLUSION: Patients with COPD using ≥1.5 SABA doses/day were at increased risk of exacerbations. Our results suggest a "Rule of 3-2": SABA use ≥3 times in 2 days should be considered a clinical marker for needing treatment reevaluation.

Tiotropium in asthma: a systematic review.

INTRODUCTION: The objective of this paper is to systematically review the existing evidence of the effectiveness and safety profile of a long-acting inhaled muscarinic antagonist as add-on therapy in patients with asthma that is uncontrolled despite inhaled corticosteroid (ICS) use. METHODS: With the assistance of two experienced research librarians, we searched Ovid MEDLINE/PubMed (1946 to September 12, 2013), the Cochrane Library review, and the TRIP database. The key search terms were "tiotropium and asthma." The search was limited to human data published in English. Included in the systematic review were all randomized controlled trials that evaluated the efficacy of tiotropium in patients with asthma. The clinical trials had to be at least 4 weeks in duration and to provide adequate information on clinically appropriate end points in asthma care (eg, change in lung function, exacerbation rates, and/or ICS dosing). Data on patient characteristics, study design, outcome measures, concomitant asthma medication, and adverse events were extracted from the full text of each included individual study. Marked heterogeneity of study design precluded statistical pooling of results for a meta-analysis. Consequently, only descriptive summaries of outcomes are provided. RESULTS: Our database search retrieved 149 citations. We found five randomized controlled trials in humans that met our criteria for inclusion in the systematic review. We also found two open-label uncontrolled trials that were considered in the discussion. Each of the five included studies met the Consolidated Standards of Reporting Trials criteria for a well-designed randomized trial. DISCUSSION: The five clinical studies included in this systematic review focused on evaluating the efficacy of tiotropium as add-on therapy to ICS or ICS in combination with a long-acting inhaled ß2-agonist (LABA) in patients with uncontrolled moderate to severe persistent asthma. Tiotropium maintained lung function when ICSs were tapered and when an LABA was discontinued. Tiotropium improved lung function when added to ICS alone or ICS-LABA combination therapy. In the only trial to have compared the addition of tiotropium with doubling the dose of ICS, tiotropium provided significantly superior results. In trials in which the addition of tiotropium was compared with salmeterol, the beneficial effects of these two bronchodilators were similar. No safety concerns were found with use of tiotropium as add-on therapy. CONCLUSION: Tiotropium may have a beneficial role in moderate to severe persistent asthma despite use of an ICS or ICS and LABA. Use of tiotropium as add-on therapy poses no safety concerns.

Comparative effectiveness of intravenous and inhaled magnesium in acute asthma.

Evaluation of: Goodacre S, Cohen J, Bradburn M et al. Intravenous or nebulised magnesium sulphate versus standard therapy for severe acute asthma (3Mg trial): a double-blind, randomized controlled trial. Lancet Respir. Med. 1, 293-300 (2013). Acute exacerbations of asthma are common. The current recommended treatment approach to managing an acute asthma exacerbation is to administer a short-acting inhaled ß2-agonist (SABA). SABAs are rapidly effective but may not provide the bronchodilation needed to restore adequate lung function. Consequently, in severe acute asthma exacerbations, despite a standard approach to treatment including SABAs, hospitalization is common. Magnesium is a bronchodilator that may provide additional benefit to SABAs in managing acute asthma exacerbations. In this article, the comparative effectiveness of inhaled and intravenous magnesium in addition to standard therapy is evaluated in the management of severe acute asthma exacerbations. Although neither inhaled nor intravenous magnesium achieved the protocol-specified benefits, intravenous magnesium was associated with fewer hospitalizations and a trend for greater improvement in the symptom of breathlessness than inhaled magnesium.

Exercise-induced bronchospasm, asthma control, and obesity.

Exercise-induced bronchospasm (EIB) commonly affects patients with asthma. However, the relationship between EIB and asthma control remains unclear. Exercise limitation due to asthma might lead to reduced physical activity, but little information is available regarding obesity and EIB in asthma. A recent survey evaluated the frequency of EIB and exercise-related respiratory symptoms in a large number of patients with asthma. The survey results were reanalyzed to address any relationship between EIB and asthma control and obesity. A nationwide random sample of children aged 4-12 years (n = 250), adolescents aged 13-17 years (n = 266), and adults aged ≥18 years (n = 1001) with asthma were interviewed by telephone. Questions in the survey addressed asthma symptoms in general, medication use, and height and weight. Asthma control was categorized using established methods in the Expert Panel Report 3. Body mass index (BMI) was calculated using standard nomograms and obesity was defined as a BMI ≥ 30 kg/m(2). Most children (77.6%), adolescents (71.1%), and adults (83.1%) had either "not well" or "very poorly" controlled asthma. Children with "not well" controlled asthma reported a history of EIB significantly more often than those with "well" controlled" asthma. Asthma patients of all ages who had "not well" and "very poorly" controlled asthma described multiple (four or more) exercise-related respiratory symptoms significantly more often than those with "well-controlled" asthma. Obesity was significantly more common in adolescents with "not well" and "very poorly" controlled asthma and adults with "very poorly" controlled asthma. Children, adolescents, and adults with asthma infrequently have well-controlled disease. A history of EIB and exercise-related respiratory symptoms occur more commonly in patients with not well and very poorly controlled asthma. Obesity was found more often in adolescents and adults, but not children, with asthma, which was not well and very poorly controlled.

The misuse of asthma drugs.

There are three major problems with asthma care in the USA and misuse of asthma drug therapy contributes to each. Asthma patients suffer from symptoms regularly partly because healthcare providers do not understand the Expert Panel Report III (EPR3) recommendations on assessing asthma symptoms to determine drug treatment and, consequently, undertreat the disease. Asthma patients experience exacerbations often in part because the EPR3 provides limited guidance on using exacerbation risk to guide asthma treatment, again leading to undertreatment. The EPR3 recommends inhaled corticosteroids as the preferred therapy for mild persistent asthma but American healthcare providers disregard this recommendation based on different perceptions about the risks and benefits of inhaled corticosteroids and choose drug treatments with higher healthcare costs.

Inhaler devices for patients with COPD.

Chronic obstructive pulmonary disease (COPD) continues to be associated with increased morbidity and mortality risk in spite of updated guidelines and a better understanding of this condition. Progressive airflow limitation and resultant hyperinflation-the respiratory hallmarks of this complex and often under-diagnosed disease-can be treated with pharmacotherapies emitted via nebulizers, pressurized metered-dose inhalers, dry powder inhalers, or a Soft Mist inhaler. Pharmaceutical company proprietary issues, technological innovations, and societal pressure have expanded the list of available inhalers, with a limited range of medications available for any one device. Each device has different operating and maintenance instructions, and successful use of a given drug/device combination requires that patients understand, maintain, and use each of their devices properly in order to ensure consistent and optimal pulmonary drug delivery. Clinicians are faced with a range of physical and psychosocial issues unique to each patient with COPD that must be overcome in order to match a suitable inhaler to the individual. Improved drug delivery afforded by next-generation inhalers, coupled with an awareness of device-specific and patient-specific variables affecting inhaler use, may improve clinical outcomes in the treatment of COPD.

Practical aspects of inhaler use in the management of chronic obstructive pulmonary disease in the primary care setting.

Sustained bronchodilation using inhaled medications in moderate to severe chronic obstructive pulmonary disease (COPD) grades 2 and 3 (Global Initiative for Chronic Obstructive Lung Disease guidelines) has been shown to have clinical benefits on long-term symptom control and quality of life, with possible additional benefits on disease progression and longevity. Aggressive diagnosis and treatment of symptomatic COPD is an integral and pivotal part of COPD management, which usually begins with primary care physicians. The current standard of care involves the use of one or more inhaled bronchodilators, and depending on COPD severity and phenotype, inhaled corticosteroids. There is a wide range of inhaler devices available for delivery of inhaled medications, but suboptimal inhaler use is a common problem that can limit the clinical effectiveness of inhaled therapies in the real-world setting. Patients' comorbidities, other physical or mental limitations, and the level of inhaler technique instruction may limit proper inhaler use. This paper presents information that can overcome barriers to proper inhaler use, including issues in device selection, steps in correct technique for various inhaler devices, and suggestions for assessing and monitoring inhaler techniques. Ensuring proper inhaler technique can maximize drug effectiveness and aid clinical management at all grades of COPD.

Pragmatic research and outcomes in asthma and COPD.

Asthma and chronic obstructive pulmonary disease (COPD) are common diseases which cause patients and society considerable difficulties. These are costly diseases which cause substantial morbidity and death. Health care policy makers have made improving outcomes in asthma and COPD a priority. Application of guideline recommended approaches to asthma and COPD care in the real-life setting has been emphasized but outcomes have not improved. Failure to improve outcomes may not be because of inconsistent applications of guideline recommendations, but rather because there are difficulties implementing the Expert Panel Report III (EPR 3) method for categorizing asthma severity and the Global Initiative for Obstructive Lung Disease (GOLD) method for diagnosing COPD. As these serve as the foundation for treatment recommendations for these diseases, alternative approaches should be considered for categorizing asthma severity and identifying COPD patients. Claims-based algorithms provide an intriguing option for identifying persistent asthma patients and symptomatic COPD patients in administrative databases. These methods could be used as the basis for pragmatic research, both retrospective and prospective, on assessing outcomes of guideline recommended treatment approaches in asthma and COPD. Important questions urgently need to be answered about how guideline recommended approaches regarding use of long-acting inhaled ß-agonist/inhaled corticosteroid (LABA/ICS) in asthma and long-acting inhaled anti-muscarinic agent (LAMA) and LABA/ICS in COPD affect outcomes in real-life situations.

The CHOICE survey: high rates of persistent and uncontrolled asthma in the United States.

BACKGROUND: Surveys have consistently shown that many patients with asthma do not have their disease well controlled. OBJECTIVES: The CHOICE (Comprehensive Survey of Healthcare Professionals and Asthma Patients Offering Insight on Current Treatment Gaps and Emerging Device Options) survey was designed to evaluate the current status of inhalation devices used in asthma treatment, but questions also were included about asthma severity and control. METHODS: A total of 1,000 patients with asthma were interviewed about their use of inhalation devices and asthma-related burden, medication use, and hospital/emergency care. Based on the responses to these questions, asthma severity and control were categorized using methods established in the Expert Panel Report III (EPR 3). RESULTS: Almost half (490) of the patients with asthma participating in the CHOICE survey were not using controller medications. Most of those not using controllers (79%) had persistent asthma; 47% had either mild or moderate persistent asthma. Of those on controllers (510), only 14.3% were well controlled. Acute care utilization was greater for patients with persistent asthma than those with intermittent asthma and for patients with not well and poorly controlled asthma than those with well-controlled asthma. CONCLUSION: The CHOICE survey is particularly pertinent clinically, because it demonstrates for the first time, using EPR 3 methods, the current extent of poor asthma control in the United States. This situation falls far short of national asthma management targets.

Effect of asthma exacerbations on health care costs among asthmatic patients with moderate and severe persistent asthma.

BACKGROUND: Health care costs increase in patients with more severe asthma, but the effect of asthma exacerbations on costs among patients with more severe asthma has not been quantified. OBJECTIVE: This study compared direct health care costs between patients with moderate/severe persistent asthma with and without exacerbations. METHODS: Patients who had an asthma diagnosis (International Classification of Diseases-ninth revision-Clinical Modification code 493.x), were 12 to 64 years old, and were receiving controller therapy were identified from a large administrative claims database. Patients were categorized as having moderate/severe persistent asthma and were further evaluated for exacerbations during a 12-month exacerbation identification period. Patients with 1 or more exacerbations (asthma-related inpatient or emergency department visit or corticosteroid prescription) were matched to patients without exacerbations on demographic characteristics and asthma severity. Total and asthma-related health care costs during the 1-year study period after the exacerbation index date were calculated. RESULTS: Patients with exacerbations had significantly higher total health care costs ($9223 vs $5011, P < .0001) and asthma-related costs ($1740 vs $847, P < .0001). The cost differences remained significant after controlling for patient differences by using multivariate models. Patients with exacerbations (n = 3830) had higher rates of sinusitis, allergy-related diagnoses or medications, pneumonia, and mental disorders and higher average Charlson Comorbidity Index scores at baseline. Patients with exacerbations filled their prescriptions for controllers more often and had higher asthma-related drug costs. CONCLUSIONS: Patients with moderate/severe persistent asthma who had exacerbations had higher total and asthma-related health care costs than those without exacerbations. Moreover, controller medication use was higher in patients with exacerbations.

Exercise-induced bronchospasm: a case study in a nonasthmatic patient.

PURPOSE: To provide an overview of the clinical presentation, diagnosis, and management of exercise-induced bronchospasm (EIB) without underlying asthma. DATA SOURCES: Case presentation and review of the EIB Landmark Survey. CONCLUSIONS: EIB is a common and well-described occurrence in patients with asthma, as well as in patients with no overt respiratory condition. Treatment with a short-acting beta-agonist before starting exercise is effective, yet this treatment approach is underutilized in the majority of patients with asthma. IMPLICATIONS FOR PRACTICE: This case highlights the implications of undermanaged EIB and the disconnect between healthcare provider recommendations and the beliefs and behaviors in patients with EIB. Inhaled short-acting beta-agonists can attenuate EIB in 80%-95% of patients and are effective during 2-3 h of exercise. Patients with a compromised level of physical activity because of EIB who do not respond to conventional treatment strategies should be referred to a respiratory specialist for diagnostic evaluation and confirmation of underlying asthma. Nurse practitioners should remain vigilant to identify untreated EIB and ensure that affected patients understand the condition and appropriate treatment options.

Exercise-induced bronchospasm: implications for patients with or without asthma in primary care practice.

Exercise-induced bronchospasm (EIB) can represent a substantial barrier to physical activity. We present the cases of two patients with EIB, one with asthma, and one without asthma, who were evaluated at our primary care practice. The first case was a 44-year-old man with a history of seasonal allergic rhinitis but no asthma, who reported difficulty breathing when playing tennis. The second case was a 45-year-old woman who presented with persistent, generally well-controlled asthma, who was now experiencing bouts of coughing and wheezing during exercise. In both cases, an exercise challenge was used to diagnose EIB, and patients were prescribed a short-acting beta agonist to be used immediately before initiating exercise. EIB is a frequently encountered problem among patients presenting to primary care specialists. Affected patients should be made aware of the importance of proactive treatment with a short-acting beta agonist before initiating any exercise.

Emerging therapeutic options for asthma.

Asthma is characterized by eosinophilic airway inflammation and elevated serum immunoglobulin E (IgE) levels. Due to these pathologic features, the foundation of asthma treatment has historically been anti-inflammatory therapy with inhaled corticosteroids (ICSs). Numerous factors in addition to IgE and eosinophils, however, likely play important roles in mediating the airway inflammatory response characteristic of asthma. ICSs are effective therapy for some patients with persistent asthma, but clinical trials have shown that even increasing doses of ICSs under carefully controlled situations does not always result in acceptable asthma control. Consequently, other classes of medications, in addition to ICSs, are recommended in those patients with more severe asthma. The class of medication most commonly used in more severe asthma, along with ICSs, is long-acting inhaled beta2-agonists, but leukotriene modifying agents and anti-IgE monoclonal antibodies may also be used. Agents such as tiotropium, a long-acting inhaled anti-muscarinic agent, and those aimed at inhibiting cytokines, such as mepoluzimab, daclizumab, and etanercept, hold promise in the treatment of asthma. Other agents under investigation include phosphodiesterase type 4 inhibitors and oligonucleotides. Bronchial thermoplasty, a nonpharmacologic option, may also be beneficial in patients with poorly controlled asthma. As our understanding of the complex pathophysiology of asthma increases, it will enable the development of novel therapeutic approaches for patients who are not responding well to traditional treatments. Although more studies are necessary to ensure the efficacy and safety of both pharmacologic and nonpharmacologic approaches, there is future promise for therapeutic advances in severe, persistent asthma.

Exercise-induced bronchospasm in children with asthma in the United States: results from the Exercise-Induced Bronchospasm Landmark Survey.

Despite the availability of effective therapies, uncontrolled asthma remains a common problem. Previous large surveys suggest that exercise-related respiratory symptoms may be a significant element of uncontrolled asthma. The Exercise-Induced Bronchospasm (EIB) Landmark Survey is the first comprehensive, national survey evaluating EIB awareness and impact among the general public, asthma patients, and health care providers. This study was designed to evaluate the prevalence and impact of exercise-related respiratory symptoms in children (aged 4-17 years) with asthma. A national survey was conducted with parents of 516 children diagnosed with asthma or taking medications for asthma in the prior year. The majority of parents reported that their child experienced one or more exercise-related respiratory symptom and almost one-half (47.4%) experienced four or more symptoms. Most commonly reported symptoms were coughing, shortness of breath, and wheezing. Respondents reported that asthma limited their child's ability to participate either "a lot" or "some" in sports (30%), other outdoor activities (26.3%), and normal physical exertion (20.9%). Only 23.1% of children with exercise-related respiratory symptoms were reported to take short-acting beta-agonists such as albuterol "always" or "most of the time" before exercising. Exercise-related respiratory symptoms among pediatric asthma patients are common and substantially limit the ability of children to participate normally and perform optimally in physical activities. Such symptoms may reflect uncontrolled underlying asthma that should be evaluated and treated with appropriate controller medications. Despite the availability of preventative therapy, many children do not use short-acting bronchodilators before exercise as recommended in national guidelines.

Impact of exercise-related respiratory symptoms in adults with asthma: Exercise-Induced Bronchospasm Landmark National Survey.

An estimated 5-20% of the general population and up to 90% of people with asthma experience exercise-induced bronchospasm (EIB). The EIB Landmark Survey is the first comprehensive study on exercise-related respiratory symptoms in the United States. Two surveys were conducted: the first surveyed adults (≥18 years) in the general public and the second surveyed adults with asthma or taking medications for asthma in the prior year. Parameters assessed included exercise-related respiratory symptoms, activity levels, and short-acting beta-antagonist (SABA) use. In the general public survey (n = 1085), 8% were currently diagnosed with asthma. However, 29% reported experiencing one or more of six respiratory-related symptoms during or immediately after exercising. In the EIB in adult asthma survey (n = 1001), although >80% of adults experienced one or more of six exercise-related respiratory symptoms, only 30.6% reported a diagnosis of EIB. Almost one-half (45.6%) of adults with asthma reported that they avoid physical activities because of symptoms. Despite symptoms, only 22.2% of respondents took SABAs before exercise "always" or "most of the time"; 36.3% took rescue medications after or during exercise. Exercise-related respiratory symptoms limit physical activities and negatively impact daily lives. However, adults in the United States lack awareness of EIB. Although many subjects stated that their asthma symptoms limit their physical activity, few adhered to treatment guidelines by using SABAs appropriately before exercising. Findings from this survey support the need for better communication about the proper evaluation and management of EIB in the community and in asthma patients.