1) Hospitalization for an acute exacerbation of COPD is associated with significantly higher mortality than hospitalization for an acute myocardial infarction. Mortality at 12 months following COPD exacerbation hospitalization is between 20-40%.
2) Proper treatment of acute exacerbations, including antibiotics, bronchodilators, corticosteroids, and oxygen therapy can help prevent future exacerbations and readmissions. However, quality of care for COPD exacerbations remains suboptimal in many cases.
3) Smoking cessation, influenza vaccination, pneumococcal vaccination, pulmonary rehabilitation, and adherence to maintenance therapies can help prevent COPD exacerbations but uptake and adherence remain low compared to potential benefits. Improving self
Systemic corticosteroids in the treatment of acute exacerbations of copdChoying Chen
- The patient presented with an acute exacerbation of COPD with respiratory acidosis and was treated with BiPAP, bronchodilators, antibiotics, and systemic corticosteroids.
- Despite treatment, he developed hyperglycemia and hypertension which were managed by adjusting antihyperglycemic and antihypertensive medications.
- He showed improvement in respiratory status and was discharged with a tapering course of prednisolone and other medications while continuing home BiPAP use.
Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) are associated with high costs, morbidity, and mortality. They result in enormous healthcare expenditures and lost productivity. AECOPD episodes are also linked to accelerated long-term loss of lung function in continuous smokers. While symptoms may recover within a week, full recovery of health-related quality of life can take months. Noninvasive mechanical ventilation should be tried for patients with respiratory acidosis or increased work of breathing from AECOPD as it reduces intubation rates and improves health outcomes. Preventing and properly managing AECOPD is important for reducing its impacts.
Antibiotics for Acute Exacerbztions of COPD Ashraf ElAdawy
This document discusses the appropriate use of antibiotics in acute exacerbations of chronic obstructive pulmonary disease (COPD). It states that while steroids and bronchodilators are well-established treatments for exacerbations, there is ongoing debate around antibiotic use. Antibiotics are recommended for moderate to severe exacerbations with increased cough and sputum purulence as this indicates likely bacterial infection. Sputum culture alone should not determine antibiotic use, and severity factors like purulence, underlying lung function, age and comorbidities should guide treatment decisions. Antibiotics may reduce mortality and treatment failure when targeted at patients with bacterial exacerbations.
COPD: Management of Acute Exacerbationmustaqadnan1
This document discusses the management of COPD exacerbations. It begins by defining a COPD exacerbation and classifying exacerbations by severity. It then outlines the goals of exacerbation treatment and recommends short-acting bronchodilators as the initial treatment. It advocates for systemic corticosteroids to improve outcomes and antibiotics when indicated. The document also recommends non-invasive ventilation for acute respiratory failure. Finally, it stresses implementing prevention strategies after an exacerbation.
Severe or difficult-to-treat asthma affects approximately 15% of asthma patients and is characterized by persistent symptoms and exacerbations despite high-dose controller medications. These patients experience greater morbidity and increased healthcare use. Characteristics of severe asthma include irreversible airflow obstruction, neutrophilic inflammation, ongoing mediator release, and reduced association with atopy. Management involves accurate diagnosis, treatment of risk factors and comorbidities, appropriate medication including biologics like omeklizumab, and ongoing patient education and support.
The document summarizes a clinical trial of the inhaled corticosteroid/long-acting beta agonist combination Breo Ellipta (fluticasone furoate/vilanterol) for the treatment of moderate to severe COPD. The trial found that Breo Ellipta 100/25mcg significantly improved lung function over 24 weeks compared to placebo, as measured by weighted mean FEV1 and trough FEV1. Treatment was well tolerated with the most common side effects being nasopharyngitis, upper respiratory tract infection, and headache. Based on efficacy and safety results, Breo Ellipta provides an effective once-daily treatment option for patients with moderate to severe COPD
The assessment of management of stable COPD: an update 2014 by Corlateanu for...Alexandru Corlateanu
The document discusses various approaches to assessing and managing stable COPD, including assessments of severity, phenotypes, and multilateral evaluation. It reviews markers used in different assessment approaches, such as FEV1, symptoms, health status, and exacerbation risk. Non-pharmacological treatments like smoking cessation, pulmonary rehabilitation, and vaccinations are outlined. The efficacy and safety of various pharmacological treatments is summarized based on major randomized controlled trials, including long-acting bronchodilators, inhaled corticosteroids, their combinations, and phosphodiesterase inhibitors. Therapeutic strategies for stable COPD are compared between GOLD guidelines and Spanish guidelines.
Systemic corticosteroids in the treatment of acute exacerbations of copdChoying Chen
- The patient presented with an acute exacerbation of COPD with respiratory acidosis and was treated with BiPAP, bronchodilators, antibiotics, and systemic corticosteroids.
- Despite treatment, he developed hyperglycemia and hypertension which were managed by adjusting antihyperglycemic and antihypertensive medications.
- He showed improvement in respiratory status and was discharged with a tapering course of prednisolone and other medications while continuing home BiPAP use.
Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) are associated with high costs, morbidity, and mortality. They result in enormous healthcare expenditures and lost productivity. AECOPD episodes are also linked to accelerated long-term loss of lung function in continuous smokers. While symptoms may recover within a week, full recovery of health-related quality of life can take months. Noninvasive mechanical ventilation should be tried for patients with respiratory acidosis or increased work of breathing from AECOPD as it reduces intubation rates and improves health outcomes. Preventing and properly managing AECOPD is important for reducing its impacts.
Antibiotics for Acute Exacerbztions of COPD Ashraf ElAdawy
This document discusses the appropriate use of antibiotics in acute exacerbations of chronic obstructive pulmonary disease (COPD). It states that while steroids and bronchodilators are well-established treatments for exacerbations, there is ongoing debate around antibiotic use. Antibiotics are recommended for moderate to severe exacerbations with increased cough and sputum purulence as this indicates likely bacterial infection. Sputum culture alone should not determine antibiotic use, and severity factors like purulence, underlying lung function, age and comorbidities should guide treatment decisions. Antibiotics may reduce mortality and treatment failure when targeted at patients with bacterial exacerbations.
COPD: Management of Acute Exacerbationmustaqadnan1
This document discusses the management of COPD exacerbations. It begins by defining a COPD exacerbation and classifying exacerbations by severity. It then outlines the goals of exacerbation treatment and recommends short-acting bronchodilators as the initial treatment. It advocates for systemic corticosteroids to improve outcomes and antibiotics when indicated. The document also recommends non-invasive ventilation for acute respiratory failure. Finally, it stresses implementing prevention strategies after an exacerbation.
Severe or difficult-to-treat asthma affects approximately 15% of asthma patients and is characterized by persistent symptoms and exacerbations despite high-dose controller medications. These patients experience greater morbidity and increased healthcare use. Characteristics of severe asthma include irreversible airflow obstruction, neutrophilic inflammation, ongoing mediator release, and reduced association with atopy. Management involves accurate diagnosis, treatment of risk factors and comorbidities, appropriate medication including biologics like omeklizumab, and ongoing patient education and support.
The document summarizes a clinical trial of the inhaled corticosteroid/long-acting beta agonist combination Breo Ellipta (fluticasone furoate/vilanterol) for the treatment of moderate to severe COPD. The trial found that Breo Ellipta 100/25mcg significantly improved lung function over 24 weeks compared to placebo, as measured by weighted mean FEV1 and trough FEV1. Treatment was well tolerated with the most common side effects being nasopharyngitis, upper respiratory tract infection, and headache. Based on efficacy and safety results, Breo Ellipta provides an effective once-daily treatment option for patients with moderate to severe COPD
The assessment of management of stable COPD: an update 2014 by Corlateanu for...Alexandru Corlateanu
The document discusses various approaches to assessing and managing stable COPD, including assessments of severity, phenotypes, and multilateral evaluation. It reviews markers used in different assessment approaches, such as FEV1, symptoms, health status, and exacerbation risk. Non-pharmacological treatments like smoking cessation, pulmonary rehabilitation, and vaccinations are outlined. The efficacy and safety of various pharmacological treatments is summarized based on major randomized controlled trials, including long-acting bronchodilators, inhaled corticosteroids, their combinations, and phosphodiesterase inhibitors. Therapeutic strategies for stable COPD are compared between GOLD guidelines and Spanish guidelines.
This patient presents with moderate chronic obstructive pulmonary disease (COPD) based on spirometry results. The most appropriate next step in therapy is to add a long-acting beta-2 agonist, as international guidelines recommend the addition of long-acting bronchodilators for patients with moderate COPD to improve quality of life and lung function compared to short-acting bronchodilators alone. Continuing short-acting bronchodilators alone would not provide adequate long-term control.
Asthma-COPD Overlap Translating Guidelines into Clinical Pracice - CasesAshraf ElAdawy
This document discusses the diagnosis of a 50-year-old female patient presenting with increased shortness of breath, cough, and wheezing. Spirometry results show obstructive lung disease with partially reversible airflow obstruction. The document examines features that favor a diagnosis of asthma, COPD, or asthma-COPD overlap syndrome (ACOS). It outlines definitions and diagnostic criteria for ACOS proposed by various medical organizations. ACOS is defined as having characteristics of both asthma and COPD, with persistent airflow limitation and a history of smoking. The document concludes the patient's diagnosis requires consideration of ACOS.
This document discusses the use of venous blood gas (VBG) analysis as an alternative to arterial blood gas (ABG) analysis in emergency situations. It finds that VBG measurements of pCO2, pH, and bicarbonate correlate well with ABG measurements and are sufficient to guide treatment for conditions like diabetic ketoacidosis. It also finds that a VBG pCO2 level below 45 mmHg can reliably rule out clinically significant hypercarbia. The vast majority of patients can be managed using VBG alone. An ABG is only needed if the VBG results are discordant with the clinical presentation, such as in hemodynamically unstable patients.
Updates On Pharmacological Management Of Asthma In AdultsAshraf ElAdawy
The document provides information on pharmacological management of asthma in adults. It defines asthma as a chronic inflammatory airway disease characterized by airway inflammation, obstruction, and hyperresponsiveness. The diagnosis is clinical based on symptoms such as wheezing and tightness. Asthma is caused by airway inflammation and management aims to control inflammation and symptoms. Treatment involves anti-inflammatory controllers such as inhaled corticosteroids and relievers for symptoms. A stepwise treatment approach is used starting with relievers and adding preventers as needed to gain control.
Kristopher R. Maday is an assistant professor and academic coordinator of the surgical physician assistant program at the University of Alabama at Birmingham. The document discusses asthma, including its pathophysiology, risk factors, diagnosis, management, and treatment. It provides detailed information on evaluating and diagnosing the severity of asthma exacerbations. The goals of asthma therapy and examples of common medications used to treat and prevent asthma are also summarized.
Azithromycin for prevention of exacerbations of copdWarawut Ia
This randomized controlled trial tested whether the macrolide antibiotic azithromycin could decrease acute exacerbations of COPD when taken daily for one year. The study found that azithromycin decreased both the frequency of acute exacerbations and the incidence of respiratory pathogen colonization, while also improving quality of life. However, it increased the risk of colonization by macrolide-resistant organisms and slightly decreased hearing in some patients. The long term effects on development of antimicrobial resistance are still unknown.
The document discusses the management of acute severe asthma or status asthmaticus in children. It covers the pathophysiology, clinical assessment, pharmacologic therapies including inhaled beta-2 agonists, corticosteroids, magnesium sulfate, and ventilation. The goals of treatment are to improve oxygenation and bronchodilation while attenuating inflammation through aggressive use of nebulized bronchodilators and systemic corticosteroids. Children not responding require close monitoring, intravenous therapies, and may need intubation and mechanical ventilation to prevent respiratory failure.
This document discusses status asthmaticus in children. It covers the epidemiology, pathophysiology, presentation, assessment and treatment of severe or life-threatening asthma exacerbations in pediatric patients. Key points include rising rates of asthma morbidity and mortality in children, risk factors for fatal asthma, the inflammatory mechanisms that drive asthma symptoms, signs of impending respiratory failure, and first-line as well as advanced treatment approaches including bronchodilators, steroids, mechanical ventilation and other interventions.
Case history of amiodarone induced pulmonary toxicitymohammed sediq
A 75-year-old Sudanese male presented with acute myocardial infarction and was treated including with amiodarone due to frequent PVCs on ECG. He was discharged after improvement but returned two weeks later with shortness of breath, dry cough, and fever. Examination found signs of bilateral lung fibrosis. He was diagnosed with amiodarone-induced interstitial pneumonitis-fibrosis based on radiological findings and improved after stopping amiodarone and receiving steroids and supportive care. Literature review discussed amiodarone-induced pulmonary toxicity as a serious adverse effect, with interstitial pneumonitis-fibrosis being common, and management involving discontinuing amiodarone and considering steroids
This document discusses several key aspects of managing sepsis, including:
1) Definitions of sepsis, severe sepsis, and septic shock. Sepsis is a leading cause of death in ICU patients.
2) Early interventions such as antibiotics, early goal-directed therapy to optimize oxygen delivery, and tight glucose control can improve outcomes but must be carefully implemented to avoid harm.
3) The evidence for corticosteroids and vasopressin in septic shock is mixed, and their use remains controversial. Large randomized trials have had conflicting results.
Management of severe asthma an update 2014avicena1
This document discusses the management of severe asthma. It begins by defining several phenotypes of severe asthma, including refractory asthma and steroid-dependent asthma. It then reviews the diagnostic criteria for severe asthma established by the American Thoracic Society and European Respiratory Society, which requires one or more major criteria and two or more minor criteria. The document further discusses approaches to diagnosing and treating severe asthma, including evaluating for alternative diagnoses, assessing treatment compliance and triggers, addressing comorbidities, and considering immunotherapy options. It emphasizes the importance of phenotyping and endotyping asthma to enable personalized treatment approaches.
Tiotropium is a long-acting muscarinic antagonist (LAMA) that has been shown to improve asthma control when added to inhaled corticosteroids (ICS) and long-acting beta-agonists (LABAs) in adults with severe asthma. The document reviewed the pathophysiology of cholinergic bronchoconstriction in asthma and how tiotropium's M1/M3 receptor selectivity and long duration of action at these receptors provides 24-hour bronchodilation. Phase III clinical trials demonstrated that adding tiotropium to ICS/LABA resulted in improved symptom control, lung function, reduced severe exacerbations, and was well-tolerated with a safety profile comparable to
This document summarizes a meeting to discuss a proof of concept study on asthma-COPD overlap syndrome (ACOS) using electronic medical records. The study aims to test various smoking-related ACOS population definitions across databases to evaluate prevalence and agreement. The meeting reviewed results from a UK pilot study using one database and definitions based on clinical diagnoses over 2 years. Prevalence of ACOS varied from 8-32% depending on the source population. The meeting also discussed expanding the study to other eligible databases and characterizing clinical implications of different definitions.
This document summarizes the case of a 32-year-old man who presented with shortness of breath and was found to have a massive right pleural effusion. Initial investigations did not reveal a clear cause. Over several years he was diagnosed with constrictive pericarditis, mediastinal fibrosis, and recurrent right hilar masses. Further testing found elevated IgG4 levels and biopsy features consistent with IgG4-related sclerosing disease. He responded well to steroid treatment but required long-term maintenance therapy to prevent relapse of this condition, which can involve multiple organs and tissues in the body.
The document discusses the assessment and treatment of acute asthma exacerbations. It outlines markers of severity seen on arterial blood gas measurements, including elevated PaCO2, low oxygen levels, and low pH. For severe or life-threatening exacerbations, initial treatment involves salbutamol 5mg via nebulizer. Ongoing treatment is based on the patient's response and may include additional nebulized bronchodilators, systemic corticosteroids, magnesium, and admission to the hospital for close monitoring.
COPD Translating Guidelines into Clinical Pracice part 2Ashraf ElAdawy
A 68-year-old man with COPD and an FEV1 of 65% was recently discharged from the hospital after his first COPD exacerbation. According to the GOLD guidelines, this patient would be classified in Group C as they have an exacerbation history indicating higher risk. The most appropriate initial treatment for this Group C patient would be to continue his albuterol as needed and add the long-acting bronchodilator tiotropium.
This document discusses the optimal management of severe or refractory asthma. It defines refractory asthma based on medication requirements, symptoms, exacerbations, and airflow limitation. The pathology of refractory asthma involves persistent airway inflammation often with neutrophils and structural changes like increased smooth muscle mass. Treatment involves confirming the diagnosis, treating exacerbating factors, and optimizing standard pharmacotherapy with inhaled corticosteroids and additional controllers. For uncontrolled cases, alternative options like macrolide antibiotics, antifungals, omalizumab, and bronchial thermoplasty may be considered.
This patient presents with moderate chronic obstructive pulmonary disease (COPD) based on spirometry results. The most appropriate next step in therapy is to add a long-acting beta-2 agonist, as international guidelines recommend the addition of long-acting bronchodilators for patients with moderate COPD to improve quality of life and lung function compared to short-acting bronchodilators alone. Continuing short-acting bronchodilators alone would not provide adequate long-term control.
Asthma-COPD Overlap Translating Guidelines into Clinical Pracice - CasesAshraf ElAdawy
This document discusses the diagnosis of a 50-year-old female patient presenting with increased shortness of breath, cough, and wheezing. Spirometry results show obstructive lung disease with partially reversible airflow obstruction. The document examines features that favor a diagnosis of asthma, COPD, or asthma-COPD overlap syndrome (ACOS). It outlines definitions and diagnostic criteria for ACOS proposed by various medical organizations. ACOS is defined as having characteristics of both asthma and COPD, with persistent airflow limitation and a history of smoking. The document concludes the patient's diagnosis requires consideration of ACOS.
This document discusses the use of venous blood gas (VBG) analysis as an alternative to arterial blood gas (ABG) analysis in emergency situations. It finds that VBG measurements of pCO2, pH, and bicarbonate correlate well with ABG measurements and are sufficient to guide treatment for conditions like diabetic ketoacidosis. It also finds that a VBG pCO2 level below 45 mmHg can reliably rule out clinically significant hypercarbia. The vast majority of patients can be managed using VBG alone. An ABG is only needed if the VBG results are discordant with the clinical presentation, such as in hemodynamically unstable patients.
Updates On Pharmacological Management Of Asthma In AdultsAshraf ElAdawy
The document provides information on pharmacological management of asthma in adults. It defines asthma as a chronic inflammatory airway disease characterized by airway inflammation, obstruction, and hyperresponsiveness. The diagnosis is clinical based on symptoms such as wheezing and tightness. Asthma is caused by airway inflammation and management aims to control inflammation and symptoms. Treatment involves anti-inflammatory controllers such as inhaled corticosteroids and relievers for symptoms. A stepwise treatment approach is used starting with relievers and adding preventers as needed to gain control.
Kristopher R. Maday is an assistant professor and academic coordinator of the surgical physician assistant program at the University of Alabama at Birmingham. The document discusses asthma, including its pathophysiology, risk factors, diagnosis, management, and treatment. It provides detailed information on evaluating and diagnosing the severity of asthma exacerbations. The goals of asthma therapy and examples of common medications used to treat and prevent asthma are also summarized.
Azithromycin for prevention of exacerbations of copdWarawut Ia
This randomized controlled trial tested whether the macrolide antibiotic azithromycin could decrease acute exacerbations of COPD when taken daily for one year. The study found that azithromycin decreased both the frequency of acute exacerbations and the incidence of respiratory pathogen colonization, while also improving quality of life. However, it increased the risk of colonization by macrolide-resistant organisms and slightly decreased hearing in some patients. The long term effects on development of antimicrobial resistance are still unknown.
The document discusses the management of acute severe asthma or status asthmaticus in children. It covers the pathophysiology, clinical assessment, pharmacologic therapies including inhaled beta-2 agonists, corticosteroids, magnesium sulfate, and ventilation. The goals of treatment are to improve oxygenation and bronchodilation while attenuating inflammation through aggressive use of nebulized bronchodilators and systemic corticosteroids. Children not responding require close monitoring, intravenous therapies, and may need intubation and mechanical ventilation to prevent respiratory failure.
This document discusses status asthmaticus in children. It covers the epidemiology, pathophysiology, presentation, assessment and treatment of severe or life-threatening asthma exacerbations in pediatric patients. Key points include rising rates of asthma morbidity and mortality in children, risk factors for fatal asthma, the inflammatory mechanisms that drive asthma symptoms, signs of impending respiratory failure, and first-line as well as advanced treatment approaches including bronchodilators, steroids, mechanical ventilation and other interventions.
Case history of amiodarone induced pulmonary toxicitymohammed sediq
A 75-year-old Sudanese male presented with acute myocardial infarction and was treated including with amiodarone due to frequent PVCs on ECG. He was discharged after improvement but returned two weeks later with shortness of breath, dry cough, and fever. Examination found signs of bilateral lung fibrosis. He was diagnosed with amiodarone-induced interstitial pneumonitis-fibrosis based on radiological findings and improved after stopping amiodarone and receiving steroids and supportive care. Literature review discussed amiodarone-induced pulmonary toxicity as a serious adverse effect, with interstitial pneumonitis-fibrosis being common, and management involving discontinuing amiodarone and considering steroids
This document discusses several key aspects of managing sepsis, including:
1) Definitions of sepsis, severe sepsis, and septic shock. Sepsis is a leading cause of death in ICU patients.
2) Early interventions such as antibiotics, early goal-directed therapy to optimize oxygen delivery, and tight glucose control can improve outcomes but must be carefully implemented to avoid harm.
3) The evidence for corticosteroids and vasopressin in septic shock is mixed, and their use remains controversial. Large randomized trials have had conflicting results.
Management of severe asthma an update 2014avicena1
This document discusses the management of severe asthma. It begins by defining several phenotypes of severe asthma, including refractory asthma and steroid-dependent asthma. It then reviews the diagnostic criteria for severe asthma established by the American Thoracic Society and European Respiratory Society, which requires one or more major criteria and two or more minor criteria. The document further discusses approaches to diagnosing and treating severe asthma, including evaluating for alternative diagnoses, assessing treatment compliance and triggers, addressing comorbidities, and considering immunotherapy options. It emphasizes the importance of phenotyping and endotyping asthma to enable personalized treatment approaches.
Tiotropium is a long-acting muscarinic antagonist (LAMA) that has been shown to improve asthma control when added to inhaled corticosteroids (ICS) and long-acting beta-agonists (LABAs) in adults with severe asthma. The document reviewed the pathophysiology of cholinergic bronchoconstriction in asthma and how tiotropium's M1/M3 receptor selectivity and long duration of action at these receptors provides 24-hour bronchodilation. Phase III clinical trials demonstrated that adding tiotropium to ICS/LABA resulted in improved symptom control, lung function, reduced severe exacerbations, and was well-tolerated with a safety profile comparable to
This document summarizes a meeting to discuss a proof of concept study on asthma-COPD overlap syndrome (ACOS) using electronic medical records. The study aims to test various smoking-related ACOS population definitions across databases to evaluate prevalence and agreement. The meeting reviewed results from a UK pilot study using one database and definitions based on clinical diagnoses over 2 years. Prevalence of ACOS varied from 8-32% depending on the source population. The meeting also discussed expanding the study to other eligible databases and characterizing clinical implications of different definitions.
This document summarizes the case of a 32-year-old man who presented with shortness of breath and was found to have a massive right pleural effusion. Initial investigations did not reveal a clear cause. Over several years he was diagnosed with constrictive pericarditis, mediastinal fibrosis, and recurrent right hilar masses. Further testing found elevated IgG4 levels and biopsy features consistent with IgG4-related sclerosing disease. He responded well to steroid treatment but required long-term maintenance therapy to prevent relapse of this condition, which can involve multiple organs and tissues in the body.
The document discusses the assessment and treatment of acute asthma exacerbations. It outlines markers of severity seen on arterial blood gas measurements, including elevated PaCO2, low oxygen levels, and low pH. For severe or life-threatening exacerbations, initial treatment involves salbutamol 5mg via nebulizer. Ongoing treatment is based on the patient's response and may include additional nebulized bronchodilators, systemic corticosteroids, magnesium, and admission to the hospital for close monitoring.
COPD Translating Guidelines into Clinical Pracice part 2Ashraf ElAdawy
A 68-year-old man with COPD and an FEV1 of 65% was recently discharged from the hospital after his first COPD exacerbation. According to the GOLD guidelines, this patient would be classified in Group C as they have an exacerbation history indicating higher risk. The most appropriate initial treatment for this Group C patient would be to continue his albuterol as needed and add the long-acting bronchodilator tiotropium.
This document discusses the optimal management of severe or refractory asthma. It defines refractory asthma based on medication requirements, symptoms, exacerbations, and airflow limitation. The pathology of refractory asthma involves persistent airway inflammation often with neutrophils and structural changes like increased smooth muscle mass. Treatment involves confirming the diagnosis, treating exacerbating factors, and optimizing standard pharmacotherapy with inhaled corticosteroids and additional controllers. For uncontrolled cases, alternative options like macrolide antibiotics, antifungals, omalizumab, and bronchial thermoplasty may be considered.
Beta blockers can reduce mortality in patients with cardiovascular diseases. Chronic obstructive pulmonary disease (COPD) is highly prevalent in this patient group. Cardioselective beta blockers can reduce mortality, hospitalizations, and exacerbations in COPD patients. Continuous treatment with high doses of cardioselective beta blockers does not appear to worsen respiratory function, symptoms, or sensitivity to beta2 agonists. Treatment can begin with low doses and gradual titration if no significant symptoms occur.
This document discusses bacterial infection in chronic obstructive pulmonary disease (COPD). It covers topics such as the mechanisms of infection, outcomes of acute exacerbations of COPD (AECOPD) like mortality and treatment failure rates. It discusses the role of bacteria in acute exacerbations, with a majority of exacerbations being infectious in nature. Common bacterial pathogens include Haemophilus influenzae, Streptococcus pneumoniae, and Moraxella catarrhalis. The document discusses concepts like bacterial load and acquisition of new bacterial strains being linked to exacerbations. It covers studies looking at bacterial colonization in stable versus exacerbated COPD. The impact of long term bacterial colonization on outcomes like lung function decline and exacerbation frequency
When to Use Antibiotics for an Acute Exacerbation of COPDsmanning500
This document summarizes a presentation on the use of antibiotics in acute exacerbations of chronic obstructive pulmonary disease (COPD). It provides an overview of COPD, including epidemiology and pathogenesis of exacerbations. Current research on antibiotic trials is reviewed, showing mixed results. Guidelines recommend antibiotics for patients with 3 cardinal symptoms or severe exacerbations. Future research may help identify biomarkers like C-reactive protein and procalcitonin to better guide antibiotic use.
How to manage a case of acute exacerbation of COPD according to GOLD guidelines. Sincere thanks to Dr. Amardeep Toppo who has prepared most of this presentation.
This patient presents with an acute exacerbation of asthma/COPD. The document reviews guidelines on asthma and COPD, including epidemiology, pathophysiology, diagnosis and treatment approaches. It also presents two case studies, one involving a 19-year old female student with asthma symptoms and another involving a 72-year old female with multiple inhalers for COPD. Treatment strategies and inhaler techniques are discussed.
This document provides guidance on diagnosing and treating patients with asthma, COPD, or asthma-COPD overlap syndrome (ACOS). It outlines a step-wise approach including 1) determining if a patient has chronic airways disease, 2) making a syndromic diagnosis of asthma, COPD, or ACOS, 3) confirming with spirometry, 4) initiating initial treatment, and 5) referring for further testing if needed. Key points include distinguishing features of asthma and COPD, the overlapping characteristics of ACOS, and ensuring appropriate controller therapy is used depending on the diagnosis. The goal is to accurately diagnose this common problem to optimize treatment outcomes.
Non-communicable diseases like heart disease, cancer, respiratory diseases and diabetes are now the leading causes of death worldwide according to the WHO. Chronic respiratory diseases such as COPD are a major contributor to this global burden. COPD is characterized by persistent airflow limitation that is usually progressive and associated with an enhanced inflammatory response in the lungs to noxious particles or gases like cigarette smoke. Spirometry is required to diagnose COPD, with a post-bronchodilator FEV1/FVC ratio of less than 0.7 used to indicate airflow limitation. The severity of COPD is classified based on symptoms and the degree of airflow obstruction measured by spirometry. Treatment involves smoking cessation, bronchodil
Chronic obstructive pulmonary disease (copd) power pointwandatardy
COPD is a chronic lung condition characterized by permanently narrowed airways and difficulty breathing. It encompasses chronic bronchitis and emphysema. COPD develops over many years as a result of lung damage, most commonly from cigarette smoking. It causes inflammation and narrowing of the airways and destruction of lung tissue over time. Symptoms include cough, wheezing, shortness of breath, and frequent respiratory infections. Treatment focuses on reducing symptoms, slowing lung function decline, and improving quality of life through medications, oxygen therapy, and smoking cessation.
Nanotechnology essentially restructures molecules to make materials lighter, stronger, more penetrating or absorbant, among many innovative qualities. In cancer research, it offers a unique opportunity to study and interact with normal and cancer cells in real time, at the molecular and cellular scales, and during the various stages of the cancer process. For cancer researchers, a special interest lies in ligand-targeted therapeutic nanoparticles (TNP), which are expected to selectively deliver drugs and especially cytotoxic agents specifically to tumor cells and enhance intracellular drug accumulation. Targeting can be achieved by various mechanisms. For example, nanoparticles with numerous targeting ligands can provide multi-valent binding to the surface of tumor cells with high receptor density (as opposed to low receptor density on normal cells) or nanoparticle agents can enhance permeability and retention (EPR) effect to exit blood vessels in the tumor, to target surface receptors on tumor cells, and to enter tumor cells by endocytosis before releasing their drug payloads.
In this presentation we shall look at nanotechnology in drug development with a focus on anticancers and the advantages of nanoparticles as therapeutic platform technology. Approved nanotech based drugs and their clinical trials will be discussed. Two specific clinical trial case studies will be focused on along at some length with a mention of some ongoing clinical trials of nanotherapeutics. We shall also take a look at the future direction of nanotechnology based therapeutics.
This study compared outcomes of patients with MDR/XDR Acinetobactor baumannii pneumonia treated with tigecycline or colistin. 70 patients received either tigecycline (n=30) or colistin (n=40). There were no significant differences in clinical outcomes between the two groups except nephrotoxicity, which only occurred in the colistin group. While the study indicates comparable efficacy, limitations include its small size, retrospective design, and exclusions. Further large randomized studies are still needed to properly evaluate tigecycline and optimal treatment combinations for MDR infections.
This document summarizes information on chronic urticaria, including its prevalence, causes, impact on quality of life, and treatment options. It notes that chronic urticaria affects approximately 1% of people with acute urticaria and has a significant negative impact on quality of life. First-line treatment includes non-sedating antihistamines, sometimes at higher off-label doses. If patients do not respond sufficiently to antihistamines alone, second-line options include doxepin, leukotriene antagonists, short-term corticosteroids, dapsone, sulfasalazine, and narrowband UVB phototherapy. The document reviews evidence on the efficacy and safety of these second-
This document discusses the pharmacotherapy of bronchial asthma. It begins by defining asthma as a chronic inflammatory airway disorder characterized by variable airflow obstruction and airway hyperresponsiveness. It then discusses the risk factors, pathophysiology, clinical presentation, diagnosis, and therapeutic objectives of asthma. The mainstay of treatment involves reliever medications like short-acting beta-agonists for acute symptoms and controller medications like inhaled corticosteroids to control inflammation and reduce exacerbations. The document outlines the specific drug classes used for treatment, including beta-agonists, anticholinergics, corticosteroids, leukotriene modifiers, mast cell stabilizers, anti-IgE, and anti-IL5 monoclonal antibodies
This document describes a randomized controlled trial comparing the effectiveness of low-dose theophylline and montelukast for poorly controlled asthma when added to inhaled corticosteroids. The trial involved over 400 participants randomized to receive theophylline, montelukast, or placebo over 24 weeks. The primary outcome was the annualized rate of episodes of poor asthma control, and secondary outcomes included symptom scores, quality of life questionnaires, and lung function tests. The results showed that neither theophylline nor montelukast provided additional benefit over placebo in reducing exacerbations or improving asthma control based on the primary and secondary outcomes.
1) Three studies showed lower mortality for patients with bacteremic pneumococcal pneumonia treated with antibiotic combination therapy compared to monotherapy.
2) Combination therapy including a beta-lactam plus macrolide is recommended for critically ill patients and those with bacteremic pneumococcal pneumonia based on evidence showing lower mortality compared to fluoroquinolone combinations or monotherapy.
3) The optimal duration of combination therapy for bacteremic pneumococcal pneumonia is unclear but guidelines recommend limiting it to 3-5 days once the pathogen is identified.
1) The document summarizes a presentation on chemotherapy options and management issues in HER-2 negative metastatic breast cancer.
2) It discusses whether to use single-agent chemotherapy or combinations, and whether combinations should be given simultaneously or sequentially. The data shows combinations yield higher response rates but similar survival and more toxicity compared to sequential single agents.
3) New chemotherapy agents discussed include eribulin, ixabepilone, and nanoparticle albumin-bound paclitaxel (nab-paclitaxel). Biological agents discussed for HER-2 negative disease include PARP inhibitors and bevacizumab.
Breakout 3.2 Managing Multimorbidity in Practice - Dr Kevin Gruffydd-JonesNHS Improvement
Breakout 3.2 Managing Multimorbidity in Practice - Dr Kevin Gruffydd-Jones
Box Surgery Wilts
Member PCRS(UK)
Respiratory Lead RCGP
Member of NICE COPD
Guidelines Committee and
Asthma/COPD Clinical
Standards Committees
Part of a set of presentations from NHS Improvement event: Better value, better outcomes held on Thursday 21 February 2013,
Guoman Tower Hotel, London
How to deliver quality and value in chronic care:sharing the learning from the respiratory programme
This document discusses principles of antibiotic use in critical care. It notes that up to 50% of antibiotics prescribed are inappropriate and outlines consequences like increased resistance. The key principles for appropriate use are described as using the right antibiotic, at the right time, duration and dose based on the patient's condition and likely pathogens. Factors affecting pharmacokinetics and pharmacodynamics in critical illness are also reviewed to optimize dosing for better outcomes.
Clinical Question 2-Reserveratrol for UCChelsea Hayes
This study evaluated the effects of resveratrol supplementation on inflammatory biomarkers and quality of life in patients with active ulcerative colitis. Researchers conducted a randomized, double-blind, placebo-controlled study of 50 patients with mild to moderate ulcerative colitis, who were divided into a treatment group that received 500 mg of resveratrol daily or a placebo control group. The treatment group demonstrated significant reductions in inflammatory markers like TNF-α and hs-CRP compared to baseline and the placebo group. Quality of life scores also improved significantly in the treatment group. However, the study had limitations like a small sample size from a single hospital. More research with larger, more diverse samples is still needed to substantiate the results.
Điều trị cắt cơn hen phế quản trẻ em - BS Nguyễn Minh Tiến.pdfbuituanan94
The document discusses the treatment of acute asthma exacerbations in children. It defines asthma as a chronic inflammatory airway disease and describes the symptoms and risk factors. Current evidence supports the use of continuous beta agonist (CBA) treatment in the emergency department for patients with severe acute asthma to improve pulmonary function and reduce hospitalization. CBA treatment appears to be safe and well tolerated. The document recommends initial treatment with beta-2 agonists and oxygen, followed by prednisone or budesonide if no response. It also discusses guidelines from GINA, NHLBI and other studies on the use of inhaled corticosteroids for acute asthma exacerbations.
The primary aims of COPD drug research are to develop agents capable of either inhibiting COPD-mediating inflammatory cell recruitment and activation directly, or indirectly - by targeting inflammatory mediators and blocking them from interacting with inflammatory cells.
As neutrophilic inflammation is present in most COPD cases, so first attempts at developing biologics for COPD therapy have focused on targeting the mechanisms of T1 inflammation.
Attempts at safe and effective mAb-mediated CXCR2 inhibition and TNF-a inhibition have also been unsuccessful, with high incidence of adverse effects and no improvements in patient health found in clinical trials.
Thus, further attempts at COPD biologics have turned their attention to primarily treating COPD related eosinophilia.
Beta blockers have a variety of different uses in the management of ischemic heart disease. This presentation by Dr Vivek Baliga, Internal Medicine Physician talks about the role in ST elevation MI.
This document discusses evidence from a clinical trial comparing the NSAIDs etoricoxib and diclofenac for treating pain. The trial involved over 34,000 patients randomized to receive either etoricoxib or diclofenac. Results showed that etoricoxib was as effective as diclofenac at reducing pain, as measured by changes in WOMAC pain scores, but had a more favorable gastrointestinal safety profile with fewer ulcer complications compared to diclofenac. Therefore, the clinical evidence demonstrated that etoricoxib provided comparable pain relief to diclofenac with a reduced risk of gastrointestinal side effects.
The document discusses principles of treating infectious illnesses in critical care, with a focus on antibiotic resistance and choice of antibiotics. It covers several topics: the impact of antibiotic use on resistance; choosing initial antibiotics and tailoring treatment based on culture results; applying pharmacology and pharmacodynamics to optimize bacterial killing; and reviewing guidelines for specific infections. It also provides an overview of antibiotic classes, mechanisms of action, considerations for dosing in renal impairment, and highlights specific agents like penicillins, cephalosporins, and vancomycin.
This document discusses the use of antibiotics in chronic obstructive pulmonary disease (COPD). It provides an overview of COPD, definitions, epidemiology and risk factors. It summarizes current research showing that long-term low-dose macrolide antibiotics can reduce COPD exacerbations. However, long-term antibiotic use may increase antibiotic resistance. The document also summarizes several studies that found 3 months of clarithromycin, moxifloxacin, doxycycline or azithromycin did not significantly reduce airway bacterial loads in stable COPD patients, though antibiotic resistance increased with all treatments.
Pk pd analysis and mic interpretation in microbiological reportsCentral Govt, India
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Recomendações da OMS sobre cuidados maternos e neonatais para uma experiência pós-natal positiva.
Em consonância com os ODS – Objetivos do Desenvolvimento Sustentável e a Estratégia Global para a Saúde das Mulheres, Crianças e Adolescentes, e aplicando uma abordagem baseada nos direitos humanos, os esforços de cuidados pós-natais devem expandir-se para além da cobertura e da simples sobrevivência, de modo a incluir cuidados de qualidade.
Estas diretrizes visam melhorar a qualidade dos cuidados pós-natais essenciais e de rotina prestados às mulheres e aos recém-nascidos, com o objetivo final de melhorar a saúde e o bem-estar materno e neonatal.
Uma “experiência pós-natal positiva” é um resultado importante para todas as mulheres que dão à luz e para os seus recém-nascidos, estabelecendo as bases para a melhoria da saúde e do bem-estar a curto e longo prazo. Uma experiência pós-natal positiva é definida como aquela em que as mulheres, pessoas que gestam, os recém-nascidos, os casais, os pais, os cuidadores e as famílias recebem informação consistente, garantia e apoio de profissionais de saúde motivados; e onde um sistema de saúde flexível e com recursos reconheça as necessidades das mulheres e dos bebês e respeite o seu contexto cultural.
Estas diretrizes consolidadas apresentam algumas recomendações novas e já bem fundamentadas sobre cuidados pós-natais de rotina para mulheres e neonatos que recebem cuidados no pós-parto em unidades de saúde ou na comunidade, independentemente dos recursos disponíveis.
É fornecido um conjunto abrangente de recomendações para cuidados durante o período puerperal, com ênfase nos cuidados essenciais que todas as mulheres e recém-nascidos devem receber, e com a devida atenção à qualidade dos cuidados; isto é, a entrega e a experiência do cuidado recebido. Estas diretrizes atualizam e ampliam as recomendações da OMS de 2014 sobre cuidados pós-natais da mãe e do recém-nascido e complementam as atuais diretrizes da OMS sobre a gestão de complicações pós-natais.
O estabelecimento da amamentação e o manejo das principais intercorrências é contemplada.
Recomendamos muito.
Vamos discutir essas recomendações no nosso curso de pós-graduação em Aleitamento no Instituto Ciclos.
Esta publicação só está disponível em inglês até o momento.
Prof. Marcus Renato de Carvalho
www.agostodourado.com
Basavarajeeyam is a Sreshta Sangraha grantha (Compiled book ), written by Neelkanta kotturu Basavaraja Virachita. It contains 25 Prakaranas, First 24 Chapters related to Rogas& 25th to Rasadravyas.
- Video recording of this lecture in English language: https://youtu.be/kqbnxVAZs-0
- Video recording of this lecture in Arabic language: https://youtu.be/SINlygW1Mpc
- Link to download the book free: https://nephrotube.blogspot.com/p/nephrotube-nephrology-books.html
- Link to NephroTube website: www.NephroTube.com
- Link to NephroTube social media accounts: https://nephrotube.blogspot.com/p/join-nephrotube-on-social-media.html
Realistic and possible abilities in prevention of COPD exacerbation
1. FIFTH CONGRESS OF THE MACEDONIAN RESPIRATORY SOCIETY
Ohrid, 26-29.September,2012
Realistic and possible abilities in prevention
of COPD exacerbation
Dejan Žujović
Municipal Institute for Lung Diseases and Tuberculosis
Belgrade
2. Disclosure
Speaker fees from: GSK, Pfizer, Takeda-Nycomed,
Merck, AstraZeneca, Boehringer Ingelheim, Sanofi
Aventis, MSD.
I have no, real or perceived, conflicts of
interest that relate to this presentation.
3. Effect of acute exacerbations of COPD
(AECOPD) versus myocardial infarction
(MI) on survival
Mortality at 12 months following hospitalization for an exacerbation of
COPD is between 20% and 40%. This is much worse than the mortality
observed following hospital admission with an acute MI, whether or not
patients received acute reperfusion therapy
Halpin D. Mortality in COPD: Inevitable or Preventable? Insights from the Cardiovascular Arena. COPD: Journal of Chronic Obstructive Pulmonary Disease, 2008;5:187–200
5. AECOPD - High readmission rates
2011, St. George’s Hospital
N=577
218 episodes with >1 admission
47% readmissions within 30 days
Nearly half of the patients were
readmitted within 30 days
6. Quality of Care in Hospitalized COPD
Patients
Retrospective cohort study of 360 US
hospitals involving 69,820 patients
hospitalized for AECOPD
66% received all recommended Rx
– O2, bronchodilatators, CS, antibiotics
45% received non-recommended Rx
33% received “ideal” care
Lindenaurer PK, et al. Ann Intern Med. 2006;144:894-903.
7. Antibiotic treatment is associated with
reduced risk of a subsequent AECOPD: an
historical population based cohort study
Roede BM et al. Thorax. 2008;63:968-973.
8. Outcomes With Antibiotic Therapy in
Patients Hospitalized With Exacerbations:
Retrospective Cohort Study
Early Antibiotics No/Late Antibiotics
14
P<0.001
12
10 P<0.001
8
6
4
P<0.001
2
0
In-hospital Mortality Treatment Failure Readmission Within
30 Days for COPD
N= 84 621 patients
Rothberg MB, et al. JAMA.2010; 303(20); 2035-2042
9. Optimizing antibiotic selection in
treating COPD exacerbations
N=572
5 days moxifloxacin PO 400mg od
vs.
7 days amoxicillin PO 500mg tds or clarithromycin PO 500mg bd or cefuroxime-axetil PO 250mg bd
Life-table analysis of time to the first composite event (treatment failure, and/or new exacerbation and/or
any further antibiotic treatment) stratified according to the time of the last exacerbation prior to
randomisation.
AECB > 6 months AECB ≤ 6 months
Moxifloxacin Moxifloxacin
Comparator Comparator
P=0.01
Siddiqi A, Sethi S. Int J Chron Obstruct Pulmon Dis. 2008 March; 3(1): 31–44.
10. Analysis of hospitalizations for COPD
exacerbation: opportunities for improving
care
All patients hospitalized with acute exacerbation of COPD
between January 2005 and December 2006 at 5 New York City
hospitals
1285 unique patients with 1653 hospitalizations
systemic steroids (85%), bronchodilators (94%) and antibiotics
(80%)
On discharge, only 46.0% were prescribed
maintenance bronchodilators and 24% were not
prescribed any inhaled therapy
Yip NH, et al. COPD. 2010 Apr;7(2):85-92.
11. Strategies aimed at preventing
exacerbations
Proven efficacy Questioned efficacy
Smoking cessation Theophyllines
LABAs: salmeterol, formoterol Prophylactic antibiotic in selected
patients
Tiotropium
Immunomodulators
Combination therapy: LABA/ICS
Mucolytic agents
Anti-influenza vaccine
Antioxidants
Antipneumococcal vaccine#
Rehabilitation
Physical exercise
Self-management plans #: efficacy demonstrated in prevention of pneumonia but not in the
prevention of exacerbations
LVRS in selected patients
Miravitlles M. Prevention of exacerbations of COPD with pharmacotherapy. Eur Respir Rev. 2010.19;116:119-126
12. Characteristics of patients with
AECOPD treated in our department
Demonstration of use Written instructions in
Smoking
of inhalation therapy case of exacerbation
12%
31% Current smoker 28%
Ex-smoker 37% No No
Never smoker 63% Yes Yes
57%
72%
Demonstrated Influenza vaccination
breathing exercises last year
28%
42% No No
Yes Yes
58% 72%
126 patients with AECOPD
Zujovic D, Unpublished Data. 2012
13. The Effects of Smoking Cessation on the
Risk of COPD Exacerbations
N= 23 971
Ex-smokers had a significantly reduced risk of COPD exacerbation after
adjusting for age, comorbidity, markers of COPD severity and socio-economic
status (adjusted HR 0.78, 95% CI 0.75–0.87)
Au DH et al. The Effects of Smoking Cessation on the Risk of Chronic Obstructive Pulmonary Disease Exacerbations. J Gen Intern Med. 2009 April; 24(4): 457–463.
14. Prevalence of smoking cessation
pharmacotherapy in hospitalized smokers
with acute myocardial infarction
risk reduction (RR) in reinfarction of 32%
all-cause mortality of 36%
benefit that may exceed standard pharmacotherapy for secondary prevention
N= 1 631
Only 14% (222/1,631) of AMI patients who smoked were
prescribed smoking cessation medication at discharge.
Katz DA et al. Prevalence and correlates of smoking cessation pharmacotherapy in hospitalized smokers with acute myocardial infarction. American Heart Journal. 2011. 162;1:74-80.
15. Potential Quality Gaps in Pharmacological
Treatment for Smoking Cessation Following
Hospitalization for Acute COPD
Exacerbation
Use of medications for tobacco dependence is uncommon in a
high−risk population of smokers following hospitalization for
AECOPD
18% of patients who smoked were prescribed smoking
cessation medication at 30 days post discharge
N= 684
McBurnie et al. Am J Respir Crit Care Med. 179;2009:A2157
16. Tobacco treatment in patients with COPD
25
Complete abstinence rate at 12 months
20
15
10
5
0
None Placebo NRT patch NRT gum NRT NRT Bupropion Varenicline
inhaler lozenge
Wu J, Sin DD. Improved patient outcome with smoking cessation: when is it too late? International Journal of COPD. 2011.6: 259–267
Strassmann R et al. Smoking cessation interventions in COPD: a network meta-analysis of randomized trials. ERJ. 2009.34(3):634-640
17. Influenza vaccine and AECOPD
significant reduction in the total number of exacerbations per vaccinated subject compared with
those who received placebo
Annually for all patients with COPD (SOR: A) GOLD,2011
Poole P, Chacko EE, Wood-Baker R, Cates CJ. Influenza vaccine for patients with chronic obstructive pulmonary disease. Cochrane Database of Systematic Reviews 2006, Issue 1.
18. Influenza and Pneumococcal Vaccine:
An Additive Effect?
1
0,9
The proportion of COPD patients free from
0,8
inf. acute exacerbation
0,7
0,6
0,5
0,4
0,3 Pneumococcal Vaccine + Influenza Vaccine
0,2 Influenza Vaccine
0,1 P=0.037 N=167
0
1 51 101 151 201 251 301 351 401 451 501 551 601 651 701
Time (days)
Furumoto A et al. Additive effect of pneumococcal vaccine and influenza vaccine on acute exacerbation in patients with chronic lung disease. Vaccine 2008; 26:4284-4289.
20. Low coverage rates of PPV23 vaccine
Cumulative doses distributed per 10 000 persons
UK 2123
Germany 1607
Ireland 1488
Spain 1280
Belgium 1220
Greece 922
Sweden 901
Iceland 721
Italy 677 Countries recommending pneumococcal
vaccination for all elderly people and those
Austria 652 considered „at risk‟ of pneumococcal infection
Norway 587 Countries recommending pneumococcal
vaccination only for those considered „at risk‟ of
Switzerland 333 pneumococcal infection
Finland 218
France 583
Portugal 452
Denmark 271
Netherlan… 49
In most European countries coverage rates is 20 - 30%.
Fedson DS et al. Pneumococcal Polysaccharide Vaccination for Adults. Expert Rev Vaccines. 2011;10(8):1143-1167.
21. Pulmonary rehabilitation following
exacerbations of COPD
Pulmonary rehabilitation should be made available to all
appropriate people with COPD including those who have
had a recent hospitalisation for an acute exacerbation.
NICE guideline, 2010
Reduction of hospital admissions
NNT=4
Puhan Maet al. Pulmonary rehabilitation following exacerbations of chronic obstructive pulmonary disease. Cochrane Database of Systematic Reviews 2011, Issue 10.
22. Pulmonary Rehabilitation Should Be
Prescribed in the Same Way Medications
Are Prescribed
“There is no drug that has beneficial effects on as many
clinical variables as pulmonary rehabilitation;
there is no drug with effects that are as long-lasting (up
to 18 months) as those of pulmonary rehabilitation;
and there is no drug with an research and development
investment as low as the costs of the most sophisticated
pulmonary rehabilitation program.”
Alba Ramírez-Sarmiento
Arch Bronconeumol. 2008;44(3):119-21
23. What is reality?
1%
Only 1.2% of the more than 750 000
Canadians suffering from COPD have
access to PR programs
Brooks D et al. Can Respir J. 2007;14(2):87-92.
615 patients with COPD, 139 GPs
5% Pulmonary rehabilitation was prescribed
to 5% of all patients and less than 1/3 of
patients exercised regularly.
Jochmann A et al. Swiss Med Wkly. 2010
Of the 69,820 patients hospitalized for
6% acute exacerbations of COPD, 6% had
chest physiotherapy Lindenauer PK et al. Ann Intern Med. 2006
24. Adherence in COPD: effects on
survival and exacerbations
rate ratio: 0.56; 95% CI: 0.48–0.65; p < 0.001
0.4
admission rates/patient-year
0.35
Nonadherent
0.3
Adherent
0.25
0.2
0.15
0.1
0.05
0
Salmeterol Fluticasone SFC Placebo
44% reduction in admissions rate
N=6112
T=3 year
Good adherence= adherence >80%
Vestbo J, Anderson JA, Calverley PMA et al. Adherence to inhaled therapy, mortality and hospital admission in COPD. Thorax. 2009. 64:939–943
25. Adherence in COPD: effects on
survival and exacerbations
hazard ratio [HR]: 0.40; 95% CI: 0.35–0.46; p < 0.001
35
Nonadherent
30
Adherent
3-year mortality rate
25
20
%
15
10
5
0
Salmeterol Fluticasone SFC Placebo
60% mortality risk reduction
N=6112
T=3 year
Good adherence= adherence >80%
Vestbo J, Anderson JA, Calverley PMA et al. Adherence to inhaled therapy, mortality and hospital admission in COPD. Thorax. 2009. 64:939–943
26. What is reality?
(N>1500) Physicians’ knowledge of inhaler devices and
inhalation techniques remains poor (~14.5%) Spain
Plaza V et al. J Aerosol Med Pulm Drug Deliv. 2012;25(1):16-22
60% nonadherent
85% use their inhaler ineffectively
Restrepo RD et al. Medication adherence issues in patients treated for COPD. Int J Chron Obstruct Pulmon Dis. 2008; 3(3): 371–384.
32. Active prevention of AECOPD?
Patients need personalized education and
encouragement to use treatment properly and
act on symptoms early
33. Comorbidity and risk for exacerbations
Independent effect of depression on COPD
exacerbations and hospitalizations.
* * *
2
Adjusted incidence ratio
1.5
HADS ≤ 7
1 HADS 8-10
HADS ≥ 11
0.5
0
Exacerbation Exacerbation Hospitalisation
(self reported) (event)
HADS: Hospital Anxiety and Depression Scale
Xu W et al. AJRCCM 2008; 178:913-20
34. Proportion of patients with
pathological cognitive deficit when fit
for discharge post-exacerbation
Cognitive Age-matched COPD COPD
p value
Domain Controls -Stable -Exacerbation
Visual Memory 0.003
13% 32% 55%
DR
Verbal Memory <0.001
10% 24% 57%
IR
Trail Making 7% 40% 53% <0.001
Verbal Fluency 7% 10% 41% <0.001
Working
10% 18% 50% 0.001
Memory
Processing
3% 24% 50% <0.001
Speed
Visuo-Spatial 0% 30% 52% <0.001
Dodd JW et al. Submitted
35. Pharmacologic treatments for COPD:
a mixed-treatment comparison meta-
analysis
43 RCT
odds of having an exacerbation
LABA TIO ICS LABA
N= 31 020 +
TROP ICS
IUM
-16% -15%
-24%
-31%
Baker WL, Baker EL, Coleman CI. Pharmacologic treatments for chronic obstructive pulmonary disease: a mixed-treatment comparison meta-analysis. Pharmacotherapy. 2009 Aug;29(8):891-905.
36. Relative Risk of Exacerbations in
COPD Patients Treated With LABA
21% reduction (95% CI, 10%-31%) in COPD
exacerbation rates
Sin DD et al. JAMA. 2003;290(17):2301-2312.
37. Tiotropium versus Salmeterol for the
Prevention of Exacerbations of COPD
N= 7376
FEV1 49% RR 0.89 Tiotropium
12 months
annual rate of exacerbations
P=0.002 Salmeterol
RR 0.93
P=0.048
RR 0.73
P<0.001
all exacerbations moderate exacerbations severe exacerbations
Vogelmeier C et al. Tiotropium versus Salmeterol for the Prevention of Exacerbations of COPD. N Engl J Med 2011;364:1093-1103.
38. LABA/ICS reduces the rate of
exacerbations requiring medical
intervention vs. LABA alone
N=1022
5 +3% FEV1 36%
12 months
0
exacerbations/patient/year
3
Number needed to treat
–5
2.1
Rate of
–10 2
–12%
–15
1
–20
–25 –24% 0
Bud/Form vs. formoterol
*
–30
Bud/Form Budesonide Formoterol
NNT=2.1
*P < 0.05 vs. placebo;
P = 0.015 Bud/Form vs. formoterol
Calverley et al. Eur Respir J 2003;22:912-9.
39. The prevention of COPD exacerbations
by salmeterol/fluticasone propionate or
tiotropium bromide (INSPIRE Trial)
2
1.8
N=1323
annual exacerbation rate
1.6
p = 0.656 FEV1 39%
24 months
1.4
1.2
1,28 1,32
1
0.8
0.6
0.4
0.2
0
Salmeterol/Fluticasone Tiotropium
Wedzicha JA, Calverley PM, Seemungal TA, et al. The prevention of chronic obstructive pulmonary disease exacerbations by salmeterol/fluticasone propionate or tiotropium bromide. (INSPIRE Trial) Am J Respir Crit Care Med
2008; 177:19-26.
40. Optimal Therapy of COPD To Prevent
Exacerbations and Improve Quality of
Life (OPTIMAL) study
p = n.s.
100
N=449
90 FEV1 40%
% patients with exacerbation
12 months
80
70 62.8 64.8 60.0
60
(1 year )
50
40
30
20
10
0
Tiotropium (N=156) Tiotropium + Salmeterol (N=148) Tiotropium +
Salmeterol/Fluticasone (N=145)
Aaron SD, Vandemheen KL, et al. Tiotropium in combination with placebo, salmeterol, or fluticasone-salmeterol for treatment of chronic obstructive pulmonary disease: a randomized trial. Ann Intern Med. 2007;146:545-555.
41. Efficacy and Tolerability of
Budesonide/Formoterol Added to Tiotropium
in Patients with COPD
Rate of severe exacerbations reduced by 62%
0.4
Budesonide/formoterol + tiotropium N= 660
FEV1 38%
Exacerbations/patient
Placebo + tiotropium 12 weeks
0.3 Cox-proportional hazards: rate ratio 0.38 (95% CI 0.25, 0.57, p<0.001)
0.2
0.1
0.0
0 15 30 45 60 75 90
Days since randomisation
Welte T et al. Efficacy and Tolerability of Budesonide/Formoterol Added to Tiotropium in Patients with Chronic Obstructive Pulmonary Disease. Am J Respir Crit Care Med 2009; 180: 741–750
42. The impact of triple therapy on mortality
and exacerbations in COPD
retrospective cohort study
1857 patients LABA/ICS+Tio vs. 996 patients LABA/ICS
Mean follow-up 4.65 years
Short PM et al. CHEST. 2012;141(1):81-86
44. Roflumilast reduced exacerbation rate
when added to ICS
M2-111 and M2-112 pooled post hoc analysis of sub-group with chronic bronchitis
+/- ICS
Rennard SI, Calverley PMA, Goehring UM, et al. Respiratory Research 2011; 12: 18. ICS = Inhaled corticosteroids
45. Effects of roflumilast in highly
symptomatic COPD patients
N=743
395 patients mMRC≥ 2
Tio18 mcg + roflumilast500mcg OD vs. Tio18mcg + placebo OD
24 weeks
0.45 Δ= -23.2% Δ= -45.5%
Rate ratio=0.768 Rate ratio=0.545
0.4 95%Cl 0.515,1.146 95%Cl 0.311,0.955
Annual rate of mod/severe
exacerbation per patient
0.35
p=0.196 p=0.0338
0.3
0.25
Placebo + Tio
0.2
Roflumilast + Tio
0.15
0.1
0.05
0
Total population mMRC ≥ 2 subgroup
Tio= Tiotropium
mMRC= Modified Medical Research Council Dyspnea Scale
Fabbri LM, et al. Effects of roflumilast in highly symptomatic COPD patients [abstract]. In: European Respiratory Society's 22nd Annual Congress; 2012 Sept 1-5; Vienna, Austria: ERS; 2012. Abstract P742.
46.
47. Morbidity and mortality benefits with
statin use in COPD
Dobler CC et al. BMC Pulmonary Medicine 2009, 9:32
48. STATCOPE Study – Phase II
The STATCOPE study is funded by
the National Heart Lung & Blood
Institute and is being conducted to
determine if an FDA approved
statin drug called simvastatin might
reduce swelling in the lungs in
patients with COPD.
If it is found that this statin drug
reduces lung inflammation, there is
a possibility that the statin drug
could also limit the number or the
severity of flare-ups, called
exacerbations, in patients with
COPD.
49. Effect of β blockers in treatment of
COPD
Retrospective
cohort study
N=5977
4.35 years follow-up
Adjusted hazard ratios for hospital admissions due to respiratory disease among patients with
COPD in reference to the control group (who received only inhaled therapy with short acting β
agonists or antimuscarinics).
Short PM et al. BMJ 2011;342:bmj.d2549
50. Effect of β blockers in treatment of
COPD
β blockers may reduce mortality and
COPD exacerbations when added to
established inhaled stepwise therapy for
COPD, independently of overt
cardiovascular disease and cardiac
drugs, and without adverse effects on
pulmonary function.
Short PM et al. BMJ 2011;342:bmj.d2549
52. Realistic and possible abilities in
prevention of COPD exacerbation
Dejan Žujović
Municipal Institute for Lung Diseases and Tuberculosis
Belgrade
Editor's Notes
AbstractContext Guidelines recommend antibiotic therapy for acute exacerbations of chronic obstructive pulmonary disease (COPD), but the evidence is based on small, heterogeneous trials, few of which include hospitalized patients.Objective To compare the outcomes of patients treated with antibiotics in the first 2 hospital days with those treated later or not at all.Design, Setting, and Patients Retrospective cohort of patients aged 40 years or older who were hospitalized from January 1, 2006, through December 31, 2007, for acute exacerbations of COPD at 413 acute care facilities throughout the United States.Main Outcome Measures A composite measure of treatment failure, defined as the initiation of mechanical ventilation after the second hospital day, inpatient mortality, or readmission for acute exacerbations of COPD within 30 days of discharge; length of stay, and hospital costs.Results Of 84 621 patients, 79% received at least 2 consecutive days of antibiotic treatment. Treated patients were less likely than nontreated patients to receive mechanical ventilation after the second hospital day (1.07%; 95% confidence interval [CI], 1.06%-1.08% vs 1.80%; 95% CI, 1.78%-1.82%), had lower rates of inpatient mortality (1.04%; 95% CI, 1.03%-1.05% vs 1.59%; 95% CI, 1.57%-1.61%), and had lower rates of readmission for acute exacerbations of COPD (7.91%; 95% CI, 7.89%-7.94% vs 8.79%; 95% CI, 8.74%-8.83%). Patients treated with antibiotic agents had a higher rate of readmissions for Clostridium difficile (0.19%; 95% CI, 0.187%-0.193%) than those who were not treated (0.09%; 95% CI, 0.086%-0.094%). After multivariable adjustment, including the propensity for antibiotic treatment, the risk of treatment failure was lower in antibiotic-treated patients (odds ratio, 0.87; 95% CI, 0.82-0.92). A grouped treatment approach and hierarchical modeling to account for potential confounding of hospital effects yielded similar results. Analysis stratified by risk of treatment failure found similar magnitudes of benefit across all subgroups.Conclusion Early antibiotic administration was associated with improved outcomes among patients hospitalized for acute exacerbations of COPD regardless of the risk of treatment failure.JAMA:2010; 303(20); 2035-2042
AbstractExacerbations are a frequent event in the evolution of chronic obstructive pulmonary disease (COPD) patients. Individuals with COPD have a mean of 1–3 episodes per year, some of which lead to hospital admission and may even be a cause of death. The importance of COPD exacerbations has become increasingly apparent due to the impact these episodes have on the natural history of disease. It is now known that frequent exacerbations can adversely affect health-related quality of life and short- and long-term pulmonary function. Optimising treatment for stable COPD will help to reduce exacerbations.Long-acting bronchodilators, alone or combined with inhaled corticosteroids, have demonstrated efficacy in reducing the rate of exacerbations in patients with COPD. Other innovative approaches are being investigated, such as the long-term use of macrolides or the use of antibiotics in an effort to suppress bronchial colonisation and consequent exacerbations. Other drugs, such as mucolytics and immunomodulators, have recently provided positive results.Non-pharmacological interventions such as rehabilitation, self-management plans and the maintenance of high levels of physical activity in daily life are also useful strategies to prevent exacerbations in patients with COPD and should be implemented in regular clinical practice.Obstructive lung diseases, particularly chronic obstructive pulmonary disease (COPD) are one of the main causes of morbidity and mortality in developed countries. It is estimated that more than 15 million people in the USA have COPD and more than 12 million have chronic bronchitis [1], with these numbers having increased over recent decades. The age-adjusted mortality rate from COPD doubled from 1970 to 2002 in the USA, whereas mortality rates from stroke and heart disease decreased by 63% and 52%, respectively [2].The prevalence of COPD in Spain is 10.2% in adults between 40–80 yrs of age, although only 27% are diagnosed [3]. This prevalence may even increase in the future. In fact, an international survey showed that up to 11.8% of subjects aged between 20–44 yrs had chronic bronchitis, characterised by chronic respiratory symptoms of cough and sputum production and 3.6% had Global Initiative for Chronic Obstructive Lung Diseases stages I to III COPD with impairment in lung function [4], which is remarkable considering the young age of the participants.The chronic and progressive course of COPD is often aggravated by short periods of increasing symptoms, particularly increasing cough, dyspnoea and sputum production which can become purulent. Exacerbations have been demonstrated to have a negative impact on the quality of life of patients with COPD [5, 6]. Furthermore, acute exacerbations are the most frequent cause of medical visits, hospital admissions and death among patients with chronic lung disease [7]. Therefore, strategies aimed at reducing the frequency of exacerbations are a cornerstone of the treatment of COPD.
AbstractBACKGROUNDSmoking cessation has been demonstrated to reduce the rate of loss of lung function and mortality among patients with mild to moderate chronic obstructive pulmonary disease (COPD). There is a paucity of evidence about the effects of smoking cessation on the risk of COPD exacerbations.OBJECTIVEWe sought to examine whether smoking status and the duration of abstinence from tobacco smoke is associated with a decreased risk of COPD exacerbations.DESIGNWe assessed current smoking status and duration of smoking abstinence by self-report. Our primary outcome was either an inpatient or outpatient COPD exacerbation. We used Cox regression to estimate the risk of COPD exacerbation associated with smoking status and duration of smoking cessation.PARTICIPANTSWe performed a cohort study of 23,971 veterans who were current and past smokers and had been seen in one of seven Department of Veterans Affairs (VA) primary care clinics throughout the US.MEASUREMENTS AND MAIN RESULTSIn comparison to current smokers, ex-smokers had a significantly reduced risk of COPD exacerbation after adjusting for age, comorbidity, markers of COPD severity and socio-economic status (adjusted HR 0.78, 95% CI 0.75–0.87). The magnitude of the reduced risk was dependent on the duration of smoking abstinence (adjusted HR: quit<1 year, 1.04; 95% CI 0.87–1.26; 1–5 years 0.93, 95% CI 0.79–1.08; 5–10 years 0.84, 95% CI 0.70–1.00; ≥10 years 0.65, 95% CI 0.58–0.74; linear trend<0.001).CONCLUSIONSSmoking cessation is associated with a reduced risk of COPD exacerbations, and the described reduction is dependent upon the duration of abstinence.
BackgroundAlthough current performance measures recommend smoking cessation counseling at the time of acute myocardial infarction (AMI), the American College of Cardiology/American Heart Association guidelines recommend pharmacotherapy as well. The aim of this study was to describe the prevalence and correlates of smoking cessation pharmacotherapy in hospitalized patients with AMI.MethodsIn the 24-center TRIUMPH registry, 4,340 AMI patients underwent detailed interviews; and 1,631 reported smoking within 30 days of admission. Prescription of first-line smoking cessation medications at discharge was assessed by medical record review. All patient-related factors associated with smoking cessation treatment, based on literature review, were included in hierarchical modified log Poisson models.ResultsOnly 14% (222/1,631) of AMI patients who smoked were prescribed smoking cessation medication at discharge. After multivariable adjustment for patient characteristics, there was significant variation across sites (range 0%-28%, median rate ratio 1.41, 95% CI 1.23-2.67). Independent factors associated with smoking cessation pharmacotherapy included older age (rate ratio 0.81 per 10-year increment, 95% CI 0.71-0.93), high school graduation (rate ratio 1.37, 95% CI 1.10-1.66), heavy cigarette usage (>20/d) (rate ratio 3.08, 95% CI 2.20-4.12), in-hospital revascularization (rate ratio 1.41, 95% CI 1.0-1.94), and instructions on smoking cessation (rate ratio 2.37, 95% CI 1.40-4.01).ConclusionsSmokers surviving an AMI are infrequently prescribed guideline-recommended smoking cessation treatments, and there is considerable variation across hospitals. Older, less educated, and lighter smokers are less likely to receive aggressive smoking cessation treatment. Novel strategies to augment current practice are needed.
Authors’ conclusionsIt appears, from the limited number of studies performed, that inactivated vaccine reduces exacerbations in COPD patients. The size of effect was similar to that seen in large observational studies, and was due to a reduction in exacerbations occurring three or more weeks after vaccination, and due to influenza. There is a mild increase in transient local adverse effects with vaccination, but no evidence of an increase in early exacerbations.
AbstractTo determine the clinical efficacy of combined vaccination with 23-valent pneumococcal vaccine (PV) and influenza vaccine (IV) against pneumonia and acute exacerbation of chronic lung diseases (CLD), we conducted an open-label, randomized, controlled study among 167 adults with CLD over a 2-year period. Subjects were randomly assigned to a PV + IV group (n = 87) or an IV group (n = 80). The number of patients with CLD experiencing infectious acute exacerbation (P = 0.022), but not pneumonia (P = 0.284), was significantly lower in the PV + IV group compared with the IV group. When these subjects were divided into subgroups, an additive effect of PV with IV in preventing infectious acute exacerbation was significant only in patients with chronic obstructive pulmonary diseases (P = 0.037). In patients with CLD, the Kaplan–Meier survival curves demonstrated a significant difference for infectious acute exacerbation (P = 0.016) between the two groups. An additive effect of PV with IV on infectious acute exacerbation was found during the first year after vaccination (P = 0.019), but not during the second year (P = 0.342), and was associated with serotype-specific immune response in sera of these patients who used PV during the same period.
AbstractBACKGROUND:Pulmonary rehabilitation has become a cornerstone in the management of patients with stable Chronic Obstructive Pulmonary Disease (COPD). Systematic reviews have shown large and important clinical effects of pulmonary rehabilitation in these patients. However, in unstable COPD patients who have recently suffered an exacerbation, the effects of pulmonary rehabilitation are less established.OBJECTIVES:To assess the effects of pulmonary rehabilitation after COPD exacerbations on future hospital admissions (primary outcome) and other patient-important outcomes (mortality, health-related quality of life and exercise capacity).SEARCH STRATEGY:Trials were identified from searches of CENTRAL, MEDLINE, EMBASE, PEDRO and the Cochrane Airways Group Register of Trials. Searches were current as of March 2010.SELECTION CRITERIA:Randomized controlled trials comparing pulmonary rehabilitation of any duration after exacerbation of COPD with conventional care. Pulmonary rehabilitation programmes needed to include at least physical exercise. Control groups received conventional community care without rehabilitation.DATA COLLECTION AND ANALYSIS:We calculated pooled odds ratios and weighted mean differences (MD) using random-effects models. We requested missing data from the authors of the primary studies.MAIN RESULTS:We identified nine trials involving 432 patients. Pulmonary rehabilitation significantly reduced hospital admissions (pooled odds ratio 0.22 [95% CI 0.08 to 0.58], number needed to treat (NNT) 4 [95% CI 3 to 8], over 25 weeks) and mortality (OR 0.28; 95% CI 0.10 to 0.84), NNT 6 [95% CI 5 to 30] over 107 weeks). Effects of pulmonary rehabilitation on health-related quality of life were well above the minimal important difference when measured by the Chronic Respiratory Questionnaire (MD for dyspnea, fatigue, emotional function and mastery domains between 0.81 (fatigue; 95% CI 0.16 to 1.45) and 0.97 (dyspnea; 95% CI 0.35 to 1.58)) and the St. Georges Respiratory Questionnaire total score (MD -9.88; 95% CI -14.40 to -5.37); impacts domain (MD -13.94; 95% CI -20.37 to -7.51) and for activity limitation domain (MD -9.94; 95% CI -15.98 to -3.89)). The symptoms domain of the St. Georges Respiratory Questionnaire showed no significant improvement. Pulmonary rehabilitation significantly improved exercise capacity and the improvement was above the minimally important difference (six-minute walk test (MD 77.70 meters; 95% CI 12.21 to 143.20) and shuttle walk test (MD 64.35; 95% CI 41.28 to 87.43)). No adverse events were reported in three studies.AUTHORS' CONCLUSIONS:Evidence from nine small studies of moderate methodological quality, suggests that pulmonary rehabilitation is a highly effective and safe intervention to reduce hospital admissions and mortality and to improve health-related quality of life in COPD patients who have recently suffered an exacerbation of COPD.
AbstractSTUDY OBJECTIVE:To assess the comparative efficacy of pharmacologic agents for the maintenance treatment of chronic obstructive pulmonary disease (COPD).DESIGN:Traditional and mixed-treatment comparison (MTC) meta-analyses of randomized controlled trials.PATIENTS:A total of 31,020 patients with COPD from 43 trials.MEASUREMENTS AND MAIN RESULTS:A systematic literature search of various databases (through October 2007) was performed to identify randomized controlled trials of long-acting beta(2)-agonists, tiotropium, inhaled corticosteroids, and/or combination therapy with an inhaled corticosteroid and a long-acting beta(2)-agonist in patients with COPD. Forty-three trials were included. Both meta-analyses were used to evaluate the occurrence of one or more episodes of COPD exacerbation, overall mortality, and patient withdrawal rates. With MTC analysis, long-acting beta(2)-agonists, tiotropium, inhaled corticosteroids, and combination inhaled corticosteroid-long-acting beta(2)-agonist therapy each decreased the odds of having an exacerbation by 16%, 31%, 15%, and 24%, respectively, compared with placebo. Moreover, tiotropium use reduced the odds of having at least one exacerbation by 18% compared with long-acting beta(2)-agonists and by 19% compared with inhaled corticosteroids alone. Each of the four drug classes was associated with significant odds reductions in patient withdrawals (26-41%) compared with placebo, and both tiotropium and combination therapy significantly decreased the odds of patient withdrawals compared with long-acting beta(2)-agonists or inhaled corticosteroids alone. Only combination therapy was associated with a mortality benefit, showing a 29% reduction compared with placebo and a 25% reduction compared with long-acting beta(2)-agonists alone. Compared with combination therapy, tiotropium use reduced exacerbations by 9% and increased mortality by only 4%. These findings did not demonstrate significant changes in the sensitivity or subgroup analyses, which were performed to evaluate the effect of heterogeneity among the included studies.CONCLUSIONS:Combination inhaled corticosteroid-long-acting beta(2)-agonist therapy was associated with the greatest positive effect on outcomes in patients with COPD. Of the bronchodilator monotherapies, tiotropium was associated with lower odds of having a COPD exacerbation or withdrawal from a study compared with long-acting beta(2)-agonists.
Speaker notesIn each study, an additive effect of roflumilast on reducing exacerbations was shown.In studies M2-127 and M2-128, and approximately 50% of patients in M2-124/125, this effect was in addition to the benefit already achieved by COPD maintenance therapy with bronchodilators.ReferenceRabe KF. Update on roflumilast, a phosphodiesterase 4 inhibitor for the treatment of chronic obstructive pulmonary disease. Br J Pharm2011;163:53-67.