The impact of expired and empty quick-relief asthma inhalers: The Asthma and Allergy Foundation of America's Asthma Inhaler Design Survey.

BACKGROUND: Despite the available treatments, asthma remains a serious illness, with a considerable socioeconomic burden associated with a high number of unscheduled visits to the emergency department (ED). Poor adherence and inadequate inhaler technique are contributing factors to poor asthma management and control. OBJECTIVE: The Asthma Inhaler Design Survey assessed the behaviors, attitudes, needs, and preferences of patients with asthma and their caregivers with regard to quick-relief inhaler usage and device design. METHODS: The Asthma and Allergy Foundation of America invited 19,157 adult patients and parents of children with asthma to take part in an online survey that focused on previous asthma diagnosis, symptom severity, and quick-relief and controller medication use. Opinions were also collected. RESULTS: Data from 590 respondents (366 adults; 224 children) were included in the final analysis. Relief inhalers were needed and found to be past the expiration date by 284 of 561 (50.6%) and relief inhalers were found to be empty by 270 of 560 (48.2%). Of the empty inhaler group, 28 of 270 (10.4%) had to visit the ED for treatment, 18 of 270 (6.7%) missed work or school for an unscheduled physician office visit, and 54 of 270 (20%) went without treatment. Although 78.5% indicated that they had at least two quick-relief inhalers nearby, these were not always easily accessible. Few respondents (194/578 [33.6%]) indicated that they and/or their child were very confident that they were using their inhaler properly, even though the majority had received some instruction. When asked what they would do to improve satisfaction with their quick-relief inhalers, 173 of 558 (31%) responded that they would add a dose counter. CONCLUSION: Unnecessary health care utilization and avoidable loss of time at work or school were associated with the lack of full availability of properly functioning quick-relief inhalers when needed. Adding a dose counter was the most frequently cited response for improving satisfaction with quick-relief inhalers. Confidence about proper inhaler use was low, despite previous instruction.

An official American Thoracic Society clinical practice guideline: exercise-induced bronchoconstriction.

BACKGROUND: Exercise-induced bronchoconstriction (EIB) describes acute airway narrowing that occurs as a result of exercise. EIB occurs in a substantial proportion of patients with asthma, but may also occur in individuals without known asthma. METHODS: To provide clinicians with practical guidance, a multidisciplinary panel of stakeholders was convened to review the pathogenesis of EIB and to develop evidence-based guidelines for the diagnosis and treatment of EIB. The evidence was appraised and recommendations were formulated using the Grading of Recommendations, Assessment, Development, and Evaluation approach. RESULTS: Recommendations for the treatment of EIB were developed. The quality of evidence supporting the recommendations was variable, ranging from low to high. A strong recommendation was made for using a short-acting ß(2)-agonist before exercise in all patients with EIB. For patients who continue to have symptoms of EIB despite the administration of a short-acting ß(2)-agonist before exercise, strong recommendations were made for a daily inhaled corticosteroid, a daily leukotriene receptor antagonist, or a mast cell stabilizing agent before exercise. CONCLUSIONS: The recommendations in this Guideline reflect the currently available evidence. New clinical research data will necessitate a revision and update in the future.

New intranasal formulations for the treatment of allergic rhinitis.

Intranasal corticosteroids (INSs) have been effectively used for >40 years for the treatment of seasonal allergic rhinitis (SAR) and perennial AR (PAR). Following the Montreal Protocol, the initial aerosol formulations using chlorofluorocarbon (CFC) propellants were phased out. For the past 20 years, aqueous solutions have been the only available option for INS treatment. In 2012, the U.S. Food and Drug Administration approved two new nonaqueous aerosol AR treatments that use a hydrofluoroalkane (HFA) propellant. In 2012, the first intranasal aqueous combination product was also approved. This article reviews the clinical profiles of HFA beclomethasone dipropionate (BDP) and HFA ciclesonide (CIC) and the aqueous combination intranasal antihistamine (INA)/INS formulation of azelastine hydrochloride/fluticasone propionate (AZE/FP). The medical literature was searched for clinical trials investigating the use of BDP, CIC, and AZE/FP in SAR and PAR. Clinical trials involving aqueous solutions and CFC propellant or HFA propellant delivery were included. Data from prescribing information and published efficacy and safety data were presented as part of the clinical profile for the reviewed agents. AZE/FP has shown efficacy and safety comparable or greater with the current AR treatment options. Although efficacy comparisons of new HFA formulations have not been investigated in head-to-head clinical trials with aqueous formulations, HFA formulations have shown similar efficacy rates. Furthermore, HFA formulations may have some additional benefits, including a preferable sensory profile for some patients. These new formulations will provide additional options for clinicians and patients to better individualize therapy for control of AR.

Recommendations for the pharmacologic management of allergic rhinitis.

Allergic rhinitis (AR) affects at least 60 million people in the United States each year, resulting in a major impact on patient quality of life, productivity, and direct and indirect costs. As new therapies, data, and literature emerge in the management of AR, there is a need to communicate and disseminate important information to health care professionals to advance the practice of medicine and lessen the disease burden from AR. Treatment recommendations for AR have not been updated since the 2012 Food and Drug Administration approval of nonaqueous intranasal aerosol agents using hydrofluoroalkane propellants and the first aqueous intranasal combination product. Here, we present an updated algorithm for the pharmacologic treatment of AR that includes these new treatment options. Treatment recommendations are categorized by disease severity (mild versus moderate/severe) and duration of symptoms (episodic versus nonepisodic, with episodic defined as <3 days/wk or for <3 weeks). Preferred treatments are suggested, as well as alternative options for consideration by clinicians in the context of individual patient needs. This recommendation article also outlines the importance of treatment monitoring, which can be conducted using the recently developed Rhinitis Control Assessment Test. Successful therapeutic outcomes depend on multiple factors, including use of the most effective pharmacologic agents as well as patient adherence to therapy. Therefore, it is imperative that rhinitis patients not only receive the most effective therapeutic options, but that they also understand and are able to adhere to the comprehensive treatment regimen. Successful treatment, with all of these considerations in mind, results in better disease outcomes, improved quality of life for patients, and greater economic productivity in the home and workplace.

Efficacy and safety of beclomethasone dipropionate nasal aerosol in pediatric patients with seasonal allergic rhinitis.

BACKGROUND: Aerosolized intranasal corticosteroid formulations are desirable for many patients with allergic rhinitis (AR), especially children, who wish to avoid the "wet feeling" and "drip down the throat" associated with aqueous formulations. Beclomethasone dipropionate (BDP) hydrofluoroalkane nasal aerosol has been shown to be safe and effective in adolescents and adults with AR. OBJECTIVE: To evaluate the efficacy and safety of BDP nasal aerosol in pediatric patients with moderate to severe seasonal AR. METHODS: In this double-blinded, placebo-controlled study, children (6-11 years of age) with seasonal AR were randomized to once-daily treatment with BDP nasal aerosol 80 µg (n = 239) or 160 µg (n = 242) or placebo (n = 234). The primary end point was change from baseline in average morning and evening reflective total nasal symptom score over the 2-week treatment period. RESULTS: Treatment with BDP nasal aerosol showed significantly greater improvements in average morning and evening reflective total nasal symptom score vs placebo (80 µg, -0.71; 160 µg, -0.76; P < .001 for the 2 comparisons). Similarly, significantly greater improvements in average morning and evening instantaneous total nasal symptom score were seen with BDP nasal aerosol vs placebo (80 µg, -0.63; 160 µg, -0.73; P < .001 for the 2 comparisons). The incidence of adverse events from BDP nasal aerosol was comparable to that from placebo. CONCLUSION: BDP nasal aerosol (80 or 160 µg/d) provided significant and clinically meaningful nasal symptom relief and an established overall safety profile similar to that of placebo, suggesting that it is an effective and well-tolerated treatment option for pediatric patients with moderate to severe seasonal AR. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT012073190.

Exercise-induced bronchospasm.

Exercise-induced bronchospasm (EIB) is a relatively common condition that affects both recreational and elite athletes. The latest data suggest that it is an inflammatory process, especially in elite athletes. Proper diagnosis is important to differentiate EIB from other respiratory conditions. Effective treatment usually controls this condition.

Daily use of guaifenesin (Mucinex) in a patient with chronic bronchitis and pathologic mucus hypersecretion: A case report.

We report an improvement in symptoms and quality of life with long-term use of guaifenesin for the treatment of mucus-related symptoms in a patient with chronic bronchitis, who presented with mucus hypersecretion, cough and dyspnea.

Improved lung function and quality of life following guaifenesin treatment in a patient with chronic obstructive pulmonary disease (COPD): A case report.

We report improved lung function and quality of life following daily use of guaifenesin/dextromethorphan (Mucinex DM®, Reckitt Benckiser) for the treatment of mucus-related symptoms in a patient with COPD, who presented with increasing dyspnea, progressive cough and chest congestion.

Asthma associated with exercise.

Exercise is a potent stimulus to asthma. The diagnosis is not always straightforward, and health care providers should have a high index of suspicion. Treatment usually controls exercise-induced asthma but usually requires therapy tailored for each individual patient.

Review of exercise-induced asthma.

PURPOSE: The purpose of this manuscript is to review the recent literature on exercise-induced asthma (EIA) and summarize the pathogenesis, diagnosis, and treatment of this condition. METHOD: A review of the English language medical literature was performed to obtain articles on EIA. RESULTS: The pathophysiology of EIA is not fully understood, but there are two theories: 1) the hyperosmolar theory and 2) the airway rewarming theory. In addition, there have been data to show that airway inflammation is present in some elite athletes, especially in cold weather sports. The diagnosis of EIA is usually straightforward in most patients, but a number of patients may have atypical symptoms and may be more difficult to diagnose. They may well need exercise testing or eucapnic voluntary ventilation testing. Most people respond to treatment with an inhaled beta agonist and or cromolyn before exercise, but some patients will also need other medications, including daily medications such as inhaled steroids. When treatment does not control the problem, then further diagnostic evaluation should be done to rule out conditions other than EIA, such as vocal cord dysfunction or cardiac or pulmonary problems. CONCLUSIONS: EIA is a condition that may occur in schoolchildren in gym class and also in Olympic athletes. The diagnosis and treatment is usually fairly straightforward, but at times it may be challenging. However, all patients should be followed to make sure that the correct diagnosis is made and to make sure that treatment is effective.

Unmet needs in the treatment of allergic asthma: potential role of novel biologic therapies.

OBJECTIVE: To provide a review of the current status of the treatment of asthma and introduce new and developing forms of therapy by means of a review of published literature on asthma and publications on new and emerging therapies. Increased public awareness of asthma, improved patient and provider education, implementation of national treatment guidelines, and availability of safe and effective therapies have combined to provide an effective response to the increase in asthma prevalence. However, the number of persons with poorly controlled asthma and asthma-related complications remains unacceptably high. This is particularly true for the relatively small cohort of patients with moderateto- severe asthma that is poorly controlled with inhaled corticosteroids and other standard-of-care medications. Consequently, these patients often experience frequent exacerbations, leading to a disproportionate consumption of asthma health care resources and a poor quality of life. The National Committee on Quality Assurance suggests that the negative impact of asthma can be minimized if health care providers implement aggressive asthma management programs that include patient education and appropriate medications. Newer therapies such as injectable anti-IgE may provide a benefit for many patients. SUMMARY: Currently available asthma medications have been proven to be generally safe and effective for most asthma patients. However, the subset of patients with difficult-to-treat asthma who experience frequent exacerbations requiring emergency department visits or hospitalizations may benefit from novel therapies designed to target specific mechanisms underlying airway inflammation. CONCLUSIONS: New therapies may help in the treatment of patients whose asthma is not controlled. These include anti-immunoglobulin E (IgE) antibodies, cytokine modulators, and DNA vaccinations. Future research will determine if these targeted biologic therapies are a cost-effective means to improve the clinical and economic outcomes of asthma management.

Improving screening and diagnosis of exercise-induced bronchoconstriction: a call to action.

This article summarizes the findings of an expert panel of nationally recognized allergists and pulmonologists who met to discuss how to improve detection and diagnosis of exercise-induced bronchoconstriction (EIB), a transient airway narrowing that occurs during and most often after exercise in people with and without underlying asthma. EIB is both commonly underdiagnosed and overdiagnosed. EIB underdiagnosis may result in habitual avoidance of sports and physical activity, chronic deconditioning, weight gain, poor asthma control, low self-esteem, and reduced quality of life. Routine use of a reliable and valid self-administered EIB screening questionnaire by professionals best positioned to screen large numbers of people could substantially improve the detection of EIB. The authors conducted a systematic review of the literature that evaluated the accuracy of EIB screening questionnaires that might be adopted for widespread EIB screening in the general population. Results of this review indicated that no existing EIB screening questionnaire had adequate sensitivity and specificity for this purpose. The authors present a call to action to develop a new EIB screening questionnaire, and discuss the rigorous qualitative and quantitative research necessary to develop and validate such an instrument, including key methodological pitfalls that must be avoided.

Allergic rhinitis substantially impacts patient quality of life: findings from the Nasal Allergy Survey Assessing Limitations.

People with allergic rhinitis rate their overall health significantly lower than individuals without nasal allergies. Compared with the general population, more people with AR complain of difficulty getting to sleep, waking up during the night, lack of a good night's sleep, or a combination of these, as a result of their nasal symptoms. More than half of individuals with AR describe their symptoms as impacting daily life a lot or to a moderate degree. More adults with AR report that their health limits them from doing well at work compared with adults without nasal allergies, and their estimated productivity drops by an average of 20% on days when their nasal symptoms are at their worst.

Treatment of patients with osteoarthritis with rofecoxib compared with nabumetone.

BACKGROUND: Rofecoxib and nabumetone were developed to provide gastrointestinal benefits over traditional nonsteroidal antiinflammatory drugs (NSAIDs). However, there is limited comparative information relating to these 2 drugs. OBJECTIVE: The objective of this study was to compare rofecoxib and nabumetone, at their lower, recommended doses, in patients with osteoarthritis (OA). METHODS: Nine hundred seventy-eight patients with knee OA and a positive history of NSAID response were randomized to 12.5 mg rofecoxib per day (N=390), nabumetone 500 mg twice a day (N=392), or placebo (N=196) for 6 weeks. The primary efficacy end point was percent of patients with a "good" or "excellent" Patient Global Assessment of Response to Therapy (PGART) at week 6; PGART was also evaluated over days 1 to 6. Additional end points included investigator assessment of response, pain walking over 6 days and 6 weeks, joint tenderness, discontinuation as a result of lack of efficacy, and quality of life. Adverse experiences (AEs) were collected. RESULTS: Significantly more rofecoxib (50.4%) than nabumetone (43.3%, P=0.043) or placebo (29.5%, P<0.001) patients had a good or excellent PGART at week 6. Median time to a good or excellent PGART was significantly shorter with rofecoxib (52 hours) than nabumetone (100 hours, P=0.001) or placebo (>124 hours, P<0.001). Results for rofecoxib and nabumetone were similar in all additional end points except pain in walking over 6 days and 6 weeks, in both of which the rofecoxib treatment group demonstrated better results. There were significantly (P<0.050) more overall and serious AEs and discontinuations resulting from AEs with rofecoxib than nabumetone. Five rofecoxib and one nabumetone patients had confirmed thrombotic cardiovascular events (P=0.123). Information on thrombotic cardiovascular events from this study was included in a published, prespecified pooled analysis and is included here for completeness. CONCLUSIONS: At their recommended starting doses for OA, both agents were more effective than placebo. Rofecoxib at a dosage of 12.5 mg demonstrated significantly better efficacy in PGART than 1000 mg nabumetone in these patients known to be NSAID responders. Significantly more AEs occurred with rofecoxib than nabumetone. Considering these data and other recent safety information regarding cyclooxygenase-2 selective and nonselective NSAIDS, physicians must make risk/benefit assessments for each individual patient when considering the use of these agents, as recommended by the U.S. Food and Drug Administration.

Concerns about intranasal corticosteroids for over-the-counter use: position statement of the Joint Task Force for the American Academy of Allergy, Asthma and Immunology and the American College of Allergy, Asthma and Immunology.

The Joint Task Force for the American Academy of Allergy, Asthma and Immunology and the American College of Allergy, Asthma and Immunology was charged with formulating a position paper regarding the potential release of intranasal corticosteroids for over-the-counter use. We took the position that safety issues regarding this proposal would be our sole concern. We reviewed the literature to evaluate the frequency and severity of potential adverse events related to the administration of intranasal corticosteroids. We limited this review to 5 areas: (1) effects on growth, (2) ocular effects, (3) effects on bone, (4) effects on the hypothalamic-pituitary-adrenal axis, and (5) local adverse effects. After review of the available data, we concluded that intranasal corticosteroids should remain prescription-only drugs. Patients receiving an intranasal corticosteroid should be instructed in its use and that use should be monitored by a physician or an appropriately trained medical provider (eg, nurse practitioner or physician assistant) under the direct supervision of a physician. This conclusion was reached based on the evidence that corticosteroids administered by any route, including the intranasal route, have the potential to cause adverse effects in all the areas noted herein. Our conclusion was strengthened by the fact that these adverse effects can be insidious and therefore not evident for many years; there is the potential for overuse; patients could also have access to other forms of topically administered corticosteroids, thus increasing their total dose; and individuals vary in their susceptibility to corticosteroid-induced adverse effects. We were also influenced to take this position knowing that generally reassuring data regarding the use of respiratory tract-administered corticosteroids are based on mean data and that all such studies have shown outliers in whom adverse effects were evident. Thus, as stated, we recommend that intranasal corticosteroids remain prescription-only drugs.

Rethinking our approach to allergic rhinitis management.

OBJECTIVE: This article reviews the recommendations by the World Health Organization's new guidelines, "Allergic Rhinitis and Its Impact on Asthma" (ARIA), and the paradigm for treating allergic rhinitis based on disease classification. After reading this article, readers should understand the ARIA guidelines and the salient issues involving the challenges inherent in the management of allergic rhinitis. DATA SOURCES: Relevant and appropriately controlled clinical studies and results of patient surveys were used. Only literature in the English language was reviewed. STUDY SELECTION: Material was taken from academic/scholarly journals, published abstracts, and presentations at a major congress. RESULTS: The ARIA guidelines' new classification categorizes patients' allergic rhinitis as either intermittent or persistent with gradations from mild to moderate-severe. These guidelines propose a stepwise approach to management guided by symptom severity and evaluation of treatment response, with the underlying concept for treatment being to select therapies that address individual patients' symptoms. Although few data were available at the time of their inception, the guidelines recognize that antileukotriene medications may play an important role in the treatment of allergic rhinitis. Results of recent clinical trials support the use of antileukotriene medications in allergic rhinitis, alone or concomitantly with an antihistamine. CONCLUSIONS: Targeting specific and multiple mechanisms of allergic rhinitis and individualizing all available and effective treatments to each patient, with specific medications for specific symptoms, will be of particular benefit to patients with allergic rhinitis.

Pharmacologic approaches to daytime and nighttime symptoms of allergic rhinitis.

Allergic rhinitis is associated with sleep disturbances, daytime somnolence, and fatigue. The exact relationship between rhinitis and sleep disturbance is unknown; however, both the symptoms and underlying pathology of allergic rhinitis can interfere with sleep quality. Nasal congestion, which has been shown to cause sleep-disordered breathing, is thought to be primarily responsible for rhinitis-related sleep disorders. The severity of nasal congestion follows a circadian rhythm, being worst at night and in the early morning. Chronotherapy is the study of the effects of administration time on the safety and efficacy of drug therapy based on circadian influences on the pharmacokinetics and pharmacodynamics of medications. Chronotherapy studies in allergic rhinitis suggest there are benefits to nighttime dosing of antiallergy medications. For example, the antihistamine mequitazine has shown improved efficacy when administered in the evening compared with morning dosing. More study is needed to determine whether this is a class effect. Leukotriene receptor antagonists are indicated for evening administration; these drugs significantly improve nighttime rhinitis symptoms. Intranasal corticosteroids administered in the morning have demonstrated efficacy in improving nighttime symptoms; however, it is unknown whether evening administration would improve their effects on nocturnal rhinitis symptoms. Because of the significant detrimental effects of nocturnal rhinitis symptoms on quality of life, allergic rhinitis therapies should be evaluated for efficacy in ameliorating nighttime symptoms.

Minimal persistent inflammation, an emerging concept in the nature and treatment of allergic rhinitis: the possible role of leukotrienes.

OBJECTIVE: To review the emerging concept of minimal persistent inflammation in allergic rhinitis and its implications for therapy. DATA SOURCES: Relevant clinical studies in the English language were reviewed. STUDY SELECTION: Material was taken from academic/scholarly journals. RESULTS: Accumulating evidence suggests that allergic rhinitis is a chronic inflammatory disease instead of a disease of acute symptoms. An approach to the therapy for allergic rhinitis should consider that even when symptoms are absent, a minimal level of persistent inflammation may persist. To prevent unexpected exacerbations, the treatment strategy may need to include managing subclinical persistent inflammation. Therapeutic options addressing the major inflammatory elements in allergic rhinitis, including eosinophils, the cysteinyl leukotrienes, and histamine, must be evaluated as management strategies that can achieve effective control. Traditional medications include intranasal corticosteroids, antihistamines, and immunotherapy. Recently, a leukotriene receptor antagonist has been approved for major rhinitis symptoms (congestion, rhinorrhea, sneezing, and pruritus), suggesting a new option for the treatment of allergic rhinitis. CONCLUSIONS: Because of the possible presence of a minimal persistent inflammation during rhinitis patients' asymptomatic periods, it is important to consider a prophylactic approach to treating allergic rhinitis to prevent or reduce exacerbations during an acute increase in allergen. In light of the advances in the understanding of the pathogenesis of allergic rhinitis, agents must be considered based on their safety, efficacy, and ability to deal with underlying inflammation as well as symptom relief.