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.

Critical care in the ED: potentially fatal asthma and acute lung injury syndrome.

Emergency department clinicians are frequently called upon to assess, diagnose, and stabilize patients who present with acute respiratory failure. This review describes a rapid initial approach to acute respiratory failure in adults, illustrated by two common examples: (1) an airway disease - acute potentially fatal asthma, and (2) a pulmonary parenchymal disease - acute lung injury/acute respiratory distress syndrome. As such patients are usually admitted to hospital, discussion will be focused on those initial management aspects most relevant to the emergency department clinician.

Lack of paradoxical bronchoconstriction after administration of tiotropium via Respimat® Soft Mist™ Inhaler in COPD.

Bronchoconstriction has been reported in asthma and chronic obstructive pulmonary disease (COPD) patients after administration of some aqueous inhalation solutions. We investigated the incidence of this event during long-term clinical trials of tiotropium delivered via Respimat(®) Soft Mist™ Inhaler (SMI). We retrospectively analyzed pooled data from two identical Phase III clinical trials, in which 1990 patients with COPD received 48 weeks' treatment with once-daily tiotropium (5 or 10 µg) or placebo inhaled via Respimat(®) SMI. We recorded the incidence of bronchospasm and of a range of respiratory events that could suggest bronchoconstriction during the first 30 minutes after inhalation of study treatment on each of the eight test days. No patients reported bronchospasm. Six patients (0.3%) reported a combination of at least two events suggestive of bronchoconstriction, and 21 (1.1%) reported either rescue medication use or a respiratory adverse event. Asymptomatic falls in forced expiratory volume in one second (FEV(1)) of ≥15% were recorded on all test days, with no change in incidence over time, and affected 8.2% of those in the tiotropium groups and 14.5% of those on placebo. In COPD patients receiving long-term treatment with tiotropium 5 or 10 µg via Respimat(®) SMI, no bronchospasm was recorded, and the number of events possibly indicative of paradoxical bronchoconstriction was very low.

Efficacy and safety of tiotropium Respimat SMI in COPD in two 1-year randomized studies.

Two 1-year studies evaluated the long-term efficacy and safety of tiotropium 5 or 10 microg versus placebo, inhaled via the Respimat Soft Mist Inhaler (SMI). The two studies were combined and had 4 co-primary endpoints (trough FEV(1) response, Mahler Transition Dyspnea Index [TDI] and St George's Respiratory Questionnaire scores all at week 48, and COPD exacerbations per patient-year). A total of 1990 patients with COPD participated (mean FEV(1): 1.09 L). The mean trough FEV(1) response of tiotropium 5 or 10 microg relative to placebo was 127 or 150 mL, respectively (both P < 0.0001). The COPD exacerbation rate was significantly lower with tiotropium 5 microg (RR = 0.78; P = 0.002) and tiotropium 10 microg (RR = 0.73; P = 0.0008); the health-related quality of life and Mahler TDI co-primary endpoints were significantly improved with both doses (both P < 0.0001). Adverse events were generally balanced except anticholinergic class effects, which were more frequent with active treatment. Fatal events occurred in 2.4% (5 microg), 2.7% (10 microg), and 1.6% (placebo) of patients; these differences were not significant. Tiotropium Respimat SMI 5 microg demonstrated sustained improvements in patients with COPD relative to placebo and similar to the 10 microg dose but with a lower frequency of anticholinergic adverse events.

The MRC dyspnoea scale by telephone interview to monitor health status in elderly COPD patients.

Dyspnoea is the most common symptom associated with poor quality of life in patients affected by Chronic Obstructive Pulmonary Disease (COPD). While COPD severity is commonly staged by lung function, the Medical Research Council (MRC) dyspnoea scale has been proposed as a more clinically meaningful method of quantifying disease severity in COPD. We wished to assess whether this scale might also be useful during telephone surveys as a simple surrogate marker of perceived health status in elderly patients with COPD. We conducted a comprehensive health status assessment by telephone survey of 200 elderly patients who had a physician diagnosis of COPD. The telephone survey contained 71 items and explored such domains as educational level, financial status, living arrangements and social contacts, co-morbid illness, and the severity and the impact of COPD on health status. Patients were categorized according to the reported MRC score: mild dyspnoea (MRC scale of 1), moderate dyspnoea (MRC scale of 2 and 3), or severe dyspnoea (MRC of 4 and 5). Deterioration in most of the recorded indicators of health status correlated with an increasingly severe MRC score. This was most evident for instrumental activities of daily living (IADL), perceived health and emotional status, pain-related limitations, limitations in social life, hospital admissions in preceding year and prevalence of most co-morbidities. The MRC dyspnoea scale is a reliable index of disease severity and health status in elderly COPD patients which should prove useful for remote monitoring of COPD and for rating health status for epidemiological purposes.

Asthma patients prefer Respimat Soft Mist Inhaler to Turbuhaler.

Device satisfaction and preference are important patient-reported outcomes to consider when choosing inhaled therapy. A subset of adults (n = 153) with moderate or severe asthma participating in a randomized parallel-group, double-dummy trial that compared the efficacy and safety of 12 weeks' treatment with budesonide delivered via Respimat Soft Mist Inhaler (SMI) (200 or 400 microg bd) or Turbuhaler dry powder inhaler (400 microg bd), completed a questionnaire on patient device preference and satisfaction (PASAPQ) as part of a psychometric validation. As the study used a double-dummy design to maintain blinding, patients used and assessed both devices, rating their satisfaction with, preference for, and willingness to continue using each device. The mean age of patients was 41 years, 69% were female and the mean duration of disease was 16 years. Total PASAPQ satisfaction scores were 85.5 and 76.9 for Respimat SMI and Turbuhaler respectively (p < 0.0001); 112 patients (74%) preferred Respimat SMI and 26 (17%) preferred Turbuhaler. Fourteen subjects (9%) indicated no preference for either inhaler. Willingness to continue using Respimat SMI was higher than that for Turbuhaler (mean scores: 80/100 and 62/100, respectively). Respimat SMI was preferred to Turbuhaler by adult asthma patients who used both devices in a clinical trial setting.

Living with chronic obstructive pulmonary disease: a survey of patients' knowledge and attitudes.

INTRODUCTION: Chronic obstructive pulmonary disease (COPD) is a common respiratory condition and the fourth leading cause of death in Canada. However, little is known about the impact of COPD on the lives and attitudes of individuals living with this condition. The purpose of this study was to determine whether Canadians with COPD are properly educated and supported, and to recommend solutions to any care gaps identified. METHODS: A total of 389 Canadians were surveyed who were 40 years of age and older, physician diagnosed with COPD, and current or former smokers. The telephone survey contained 68 items and took 35 min to complete. COPD severity was classified according to symptom severity using the Medical Research Council (MRC) score. RESULTS: Respondents tended to overestimate their disease severity and reported substantial symptom burden and psychosocial impact of living with COPD. Most individuals claimed to be well informed about COPD; however, their knowledge was poor in several domains including the causes of COPD, the consequences of inadequate therapy and the management of exacerbations. Family physicians were the main health care providers. A minority of respondents had seen a lung health educator. Only 34% had ever received a written action plan and only 33% had been told how to prevent an exacerbation. CONCLUSIONS: The symptom burden and psychosocial impact of living with COPD is substantial. There are significant gaps in patients' knowledge about the management of COPD and little contact with lung health educators. Increased use of COPD-specific, self-management education programs may help rectify these care gaps.

Canadian Thoracic Society recommendations for management of chronic obstructive pulmonary disease - 2007 update.

Chronic obstructive pulmonary disease (COPD) is a major respiratory illness in Canada that is both preventable and treatable. Our understanding of the pathophysiology of this complex condition continues to grow and our ability to offer effective treatment to those who suffer from it has improved considerably. The purpose of the present educational initiative of the Canadian Thoracic Society (CTS) is to provide up to date information on new developments in the field so that patients with this condition will receive optimal care that is firmly based on scientific evidence. Since the previous CTS management recommendations were published in 2003, a wealth of new scientific information has become available. The implications of this new knowledge with respect to optimal clinical care have been carefully considered by the CTS Panel and the conclusions are presented in the current document. Highlights of this update include new epidemiological information on mortality and prevalence of COPD, which charts its emergence as a major health problem for women; a new section on common comorbidities in COPD; an increased emphasis on the meaningful benefits of combined pharmacological and nonpharmacological therapies; and a new discussion on the prevention of acute exacerbations. A revised stratification system for severity of airway obstruction is proposed, together with other suggestions on how best to clinically evaluate individual patients with this complex disease. The results of the largest randomized clinical trial ever undertaken in COPD have recently been published, enabling the Panel to make evidence-based recommendations on the role of modern pharmacotherapy. The Panel hopes that these new practice guidelines, which reflect a rigorous analysis of the recent literature, will assist caregivers in the diagnosis and management of this common condition.

The paradox of adult asthma control: "who's in control anyway?".

Surveys of Canadian patients with asthma and their physicians consistently report satisfaction with asthma management; however, when objective indicators are used, these same surveys also observe very poor levels of asthma control. The reasons for this apparent discrepancy, with an emphasis on the factors influencing adherence to therapy, are explored in the present review. Clues to the identification of patients at risk of dying from asthma and an approach to difficult asthma are discussed.

Burden of illness in venous thromboembolism in critical care: a multicenter observational study.

PURPOSE: The frequency of clinically diagnosed venous thromboembolism (VTE) including deep venous thrombosis (DVT) and pulmonary embolism (PE) in medical-surgical critically ill patients is unclear. The objectives of this study were to estimate the prevalence and incidence of radiologically confirmed DVT and PE in medical-surgical intensive care unit (ICU) patients and to determine the impact of prophylaxis on the frequency of these events. MATERIALS AND METHODS: In a retrospective observational cohort study in 12 adult ICUs, we identified prevalent cases (diagnosed in the 24 hours preceding ICU admission up to 48 hours post-ICU admission) and incident cases (diagnosed 48 hours or more after ICU admission and up to 8 weeks after ICU discharge) of upper or lower limb DVT or PE. Deep venous thrombosis was diagnosed by compression ultrasound or venogram. Each DVT was classified as clinically suspected or not clinically suspected in that the latter was diagnosed by scheduled screening ultrasonography. Pulmonary embolism was diagnosed by ventilation-perfusion lung scan, computed tomography pulmonary angiography, echocardiography, electrocardiography, or autopsy. RESULTS: Among 12,338 patients, 252 (2.0%) patients had radiologically confirmed DVT or PE and another 47 (0.4%) had possible DVT or PE. Prevalent DVTs were diagnosed in 0.4% (95% confidence interval [CI], 0.3%-0.5%) of patients and prevalent PEs were diagnosed in 0.4% (95% CI, 0.3%-0.6%). Incident DVTs were diagnosed in 1.0% (95% CI, 0.8%-1.2%) of patients, and incident PEs were diagnosed in 0.5% (95% CI, 0.4%-0.6%). Of patients with incident VTE, 65.8% of cases occurred despite receipt of thromboprophylaxis for at least 80% of their days in ICU. The median (interquartile range) ICU length of stay was similar for patients with DVT (7 [3-17]) and PE (5 [2-8]). For all patients with VTE, ICU mortality was 16.7% (95% CI, 12.0%-21.3%) and hospital mortality was 28.5% (95% CI, 22.8%-34.1%). CONCLUSIONS: Venous thromboembolism appears to be an apparently infrequent, but likely underdiagnosed problem, occurring among patients receiving prophylaxis. Findings suggest the need for increased suspicion among clinicians, renewed efforts at thromboprophylaxis, and evaluation of superior prevention strategies.

Low incidence of paradoxical bronchoconstriction in asthma and COPD patients during chronic use of Respimat soft mist inhaler.

Respimat Soft Mist Inhaler (SMI) is a new-generation inhaler that offers improved lung deposition compared with chlorofluorocarbon metered dose inhalers (CFC-MDIs). Bronchodilators administered via Respimat SMI are preserved and stabilised with low concentrations of benzalkonium chloride and ethylene diamine tetra-acetic acid, both of which have been reported to cause dose-related paradoxical bronchoconstriction. The aim of this analysis was to compare the incidence of paradoxical bronchoconstriction after chronic use of bronchodilators via Respimat SMI and CFC-MDI. Data from three clinical trials, in which patients with asthma or chronic obstructive pulmonary disease (COPD) received ipratropium bromide alone or in combination with fenoterol hydrobromide, or placebo via Respimat SMI or CFC-MDI for 12 weeks, were included in the analysis. In order to evaluate the risk of paradoxical bronchoconstriction, we identified four respiratory events that might have occurred within 30 min of inhalation on four test days; these were: 'bronchospasm', 'other respiratory adverse events', 'rescue medication use' and 'asymptomatic drop in FEV(1) 15% from baseline'. In total, 631 asthma and 1538 COPD patients participated in the three studies. No occurrences of bronchospasm were reported with Respimat SMI on any test day. Overall, the incidence of respiratory events possibly indicative of paradoxical bronchoconstriction was low and similar for both devices. There was no increase in the incidence of events during 12 weeks' treatment. Delivery of bronchodilators by Respimat SMI is safe with regard to paradoxical bronchoconstriction during chronic use in patients with asthma or COPD.

State of the Art Compendium: Canadian Thoracic Society recommendations for the management of chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) is a common cause of disability and death in Canada. Moreover, morbidity and mortality from COPD continue to rise, and the economic burden is enormous. The main goal of the Canadian Thoracic Society's evidence-based guidelines is to optimize early diagnosis, prevention and management of COPD in Canada. The main message of the guidelines is that COPD is a preventable and treatable disease. Targeted spirometry is strongly recommended to expedite early diagnosis in smokers and former smokers who develop respiratory symptoms, and who are at risk for COPD. Smoking cessation remains the single most effective intervention to reduce the risk of COPD and to slow its progression. Education, especially self-management plans, are key interventions in COPD. Therapy should be escalated on an individual basis in accordance with the increasing severity of symptoms and disability. Long-acting anticholinergics and beta-2-agonist inhalers should be prescribed for patients who remain symptomatic despite short-acting bronchodilator therapy. Inhaled steroids should not be used as first line therapy in COPD, but have a role in preventing exacerbations in patients with more advanced disease who suffer recurrent exacerbations. Acute exacerbations of COPD cause significant morbidity and mortality and should be treated promptly with bronchodilators and a short course of oral steroids; antibiotics should be prescribed for purulent exacerbations. Patients with advanced COPD and respiratory failure require a comprehensive management plan that incorporates structured end-of-life care. Management strategies, consisting of combined modern pharmacotherapy and nonpharmacotherapeutic interventions (eg, pulmonary rehabilitation and exercise training) can effectively improve symptoms, activity levels and quality of life, even in patients with severe COPD.

A review of ipratropium bromide/fenoterol hydrobromide (Berodual) delivered via Respimat Soft Mist Inhaler in patients with asthma and chronic obstructive pulmonary disease.

Asthma and chronic obstructive pulmonary disease (COPD) can be effectively treated by the use of bronchodilator therapies delivered by inhalation. Berodual is a fixed combination of the anticholinergic agent ipratropium bromide (IB) and the beta2-adrenergic agonist fenoterol hydrobromide (FEN). IB/FEN has been available for the treatment of asthma and COPD in a pressurised metered dose inhaler (MDI) [pMDI] formulation for many years. The pMDI is the most widely used device for the delivery of inhaled medications, such as IB/FEN. However, most conventional pMDIs contain chlorofluorocarbon (CFC) propellants, which are currently being withdrawn because of their detrimental effects on the environment. This has resulted in alternative methods of drug delivery being developed. Respimat Soft Mist Inhaler (SMI) is a new generation, propellant-free inhaler that generates a fine, slow-moving cloud (the Soft Mist) which can be easily inhaled. Scintigraphic studies have shown that this improves deposition of drugs in the lung and results in less oropharyngeal deposition than the CFC-MDI. A clinical development programme has been conducted to compare the efficacy and safety of IB/FEN delivered via Respimat SMI with that of IB/FEN via CFC-MDI in the treatment of patients with asthma or COPD. Five clinical studies (two phase II and three phase III) investigated dosages of IB/FEN 5/12.5 microg to 320/800 microg via Respimat SMI in single and multiple dose administration regimens. Four of the trials were conducted in patients with asthma (three in adults and one in children), while one phase III trial was conducted in patients with COPD. In phase III, 2058 patients participated, with a total of 1112 patients treated with IB/FEN via Respimat SMI. In the phase III studies, each dose from Respimat SMI was given in one actuation compared with two actuations with the CFC-MDI. In the paediatric asthma phase III study, all CFC-MDI doses were delivered via a spacer device. The results of the trials demonstrated that IB/FEN via Respimat SMI allows a reduction in the nominal dose of IB/FEN, while offering similar therapeutic efficacy and safety to a CFC-MDI. In children, Respimat SMI obviates the need for a spacer.