A recent review from the UK general practice showed that, from 2004 to 2009, the use of triple therapy increased from 25% to 59% in patients with very severe COPD, with 14% and 19% mild and moderate (based on lung function) COPD patients, respectively, using triple therapy.12 However, while its use has increased, relatively few studies have been conducted to test the efficacy of triple therapy, administered by individual inhalers, compared to ICS/LABA, LABA/LAMA, or LAMA in terms of preventing exacerbations. This article reviews the available evidence of the efficacy of triple therapy in COPD. (2.4)2120 (1.9)1010 (1.9)Respiratory tract infection viral3331 (1.8)1110 (1.5)1515 (1.4)1413 (2.4)Cough3224 (1.4)77 (1.0)2623 (2.1)99 (1.7)Atrial fibrillation2625 (1.4)99 (1.3)1313 (1.2)54 (0.7)Influenza2624 (1.4)55 (0.7)1110 (0.9)44 (0.7)Dry mouth1514 (0.8)44 (0.6)1313 (1.2)1010 (1.9)Back discomfort2523 (1.3)87 (1.0)66 (0.6)22 (0.4)Top respiratory system infection119 (0.5)1212 (1.8)1111 (1.0)44 (0.7)Cardiac failure1413 (0.7)55 (0.7)97 (0.7)76 (1.1)Anemia1212 (0.7)77 (1.0)77 (0.7)33 (0.6)Viral top tract infection1614 (0.8)22 (0.3)66 (0.6)76 (1.1)Dental candidiasis2118 (1.0)22 (0.3)33 (0.3)53 (0.6)Pyrexia43 (0.2)00 (0.0)44 (0.4)97 (1.3)Vertebral discomfort22 (0.1)11 (0.1)11 (0.1)86 (1.1) Open up in another windowpane Abbreviations: BDP, beclomethasone dipropionate; FF, formoterol fumarate; GB, glycopyrronium bromide; TEAE, treatment-emerging undesirable event. Abstract The goals of COPD therapy are to avoid and control symptoms, decrease the rate of recurrence and intensity of exacerbations, and improve workout tolerance. The triple mixture therapy of inhaled corticosteroids (ICSs), long-acting beta2 agonists (LABAs), and long-acting muscarinic antagonists (LAMAs) is becoming a choice for maintenance treatment of COPD so that as a step-up therapy from solitary or double mixture treatments. There is certainly proof that triple mixture ICS/LABA/LAMA with different inhalers boosts lung function, symptoms, and wellness position and decreases exacerbations. A fresh triple fixed-dose mix of extrafine beclomethasone dipropionate (100 g/puff)/formoterol fumarate (6 g/puff)/glycopyrronium bromide (12.5 g/puff) continues to be developed like a hydrofluoroalkane pressurized metered dosage inhaler. Two huge pivotal studies demonstrated that extrafine set ICS/LABA/LAMA triple mixture is more advanced than fixed ICS/LABA mixed therapy and in addition more advanced than the LAMA tiotropium with regards to lung function and exacerbation avoidance in COPD individuals vulnerable to exacerbation. This review considers the brand new information supplied by these medical tests of extrafine triple therapy as well as the implications for the medical administration of COPD individuals. solid course=”kwd-title” Keywords: COPD, inhaled triple therapy, beclomethasone dipropionate, formoterol Carebastine fumarate and glycopyrronium bromide Intro COPD is among the leading factors behind mortality and morbidity worldwide.1,2 Pharmacological therapy for COPD decreases symptoms, severity and frequency of exacerbations, and improves workout health insurance and tolerance position.3 Currently, the primary treatment plans for COPD individuals participate in a restricted amount of pharmacological classes C that’s, bronchodilators (short-acting beta2 agonists [SABAs], long-acting beta2 agonists [LABAs], short-acting muscarinic antagonists [SAMAs], and long-acting muscarinic antagonists [LAMAs]), inhaled corticosteroids (ICSs), and inhibitors from the enzyme phosphodiesterase-4. Long-acting bronchodilator monotherapy may boost lung function, improve patient-reported results (Benefits) such as for example symptoms and standard of living, enhance exercise efficiency, and decrease exacerbations.4,5 Administering LABA and LAMA concurrently (dual bronchodilator treatment) significantly boosts lung function and PROs in comparison to treatment with an individual bronchodilator;6 also, there is certainly proof for fewer exacerbations when working with two long-acting bronchodilators in comparison to 1.7 The scientific rationale behind the additive results observed when merging bronchodilators includes the various mechanisms of actions of beta2 agonists and muscarinic antagonists (excitement of beta2-adrenergic receptors and inhibition of acetylcholine-induced bronchoconstriction, respectively), as well as the potential intracellular interactions between these pathways.8,9 Several studies show that long-term treatment having a combination inhaler including ICS/LABA works more effectively compared to the individual components in enhancing lung function and PROs and in reducing exacerbation frequency. ICS/LABA mixtures are suggested for make use of in individuals vulnerable to exacerbations, that the very best predictor may be the previous background of exacerbations. For individuals who stay symptomatic and/or continue steadily to exacerbate despite treatment having a dual ICS/LABA or bronchodilator mixture inhaler, the Global Effort for Obstructive Lung Disease (Yellow metal) management technique recommends intensify to triple therapy (ICS plus LABA plus LAMA). In medical practice, individuals intensify to triple from LAMA monotherapy also.3 Because the the different parts of triple therapy possess different pharmacological systems of action, there’s a solid rationale for the usage of these medicines together to increase clinical benefits, like the prevention of exacerbation.10,11 Triple therapy is recommended to COPD individuals in clinical practice widely, commonly using two distinct inhalers: an ICS/LABA combination and also a LAMA. A recently available review from the united kingdom general practice demonstrated that, from 2004 to 2009, the usage of triple therapy improved from 25% to 59% in individuals with very serious COPD, with 14% and 19% light and moderate (predicated on lung function) COPD sufferers, respectively, using triple therapy.12 However, while its make use of has increased, relatively few research have already been conducted to check the efficiency of triple.Pre-specified essential supplementary objectives evaluated the superiority of set triple versus tiotropium and its own non-inferiority versus extemporary triple therapy with regards to differ from baseline in pre-dose FEV1 at week 52. occasions /th th valign=”best” align=”still left” rowspan=”1″ colspan=”1″ Variety of sufferers (%) /th /thead At least one TEAE2,349962 (54.5)928379 (55.7)1,514622 (57.8)740309 (57.5)COPD800565 (32.0)360240 (35.3)588383 (35.6)258167 (31.1)Nasopharyngitis11496 (5.4)4538 (5.6)8566 (6.1)2220 (3.7)Headaches6955 (3.1)1716 (2.4)4841 (3.8)2018 (3.4)Pneumonia5551 (2.9)1818 (2.6)2019 (1.8)1312 (2.2)?Pneumonia4643 (2.4)1616 (2.4)1817 (1.6)1312 (2.2)?Bronchopneumonia44 (0.2)22 (0.3)11 (0.1)00 (0.0)?Lobar pneumonia44 (0.2)00 (0.0)00 (0.0)00 (0.0)?Interstitial lung disease00 (0.0)00 (0.0)11 (0.1)00 (0.0)?Pneumonia Carebastine aspiration11 (0.1)00 (0.0)00 (0.0)00 (0.0)Dyspnea3835 (2.0)1513 (1.9)5237 (3.4)98 (1.5)Hypertension4340 (2.3)1816 (2.4)2120 (1.9)1010 (1.9)Respiratory system infection viral3331 (1.8)1110 (1.5)1515 (1.4)1413 (2.4)Coughing3224 (1.4)77 (1.0)2623 (2.1)99 (1.7)Atrial fibrillation2625 (1.4)99 (1.3)1313 (1.2)54 (0.7)Influenza2624 (1.4)55 (0.7)1110 (0.9)44 (0.7)Dried out mouth area1514 (0.8)44 (0.6)1313 (1.2)1010 (1.9)Back again discomfort2523 (1.3)87 (1.0)66 (0.6)22 (0.4)Top respiratory system infection119 (0.5)1212 (1.8)1111 (1.0)44 (0.7)Cardiac failure1413 (0.7)55 (0.7)97 (0.7)76 (1.1)Anemia1212 (0.7)77 (1.0)77 (0.7)33 (0.6)Viral higher tract infection1614 (0.8)22 (0.3)66 (0.6)76 (1.1)Dental candidiasis2118 (1.0)22 (0.3)33 (0.3)53 (0.6)Pyrexia43 (0.2)00 (0.0)44 (0.4)97 (1.3)Vertebral discomfort22 (0.1)11 (0.1)11 (0.1)86 (1.1) Open up in another screen Abbreviations: BDP, beclomethasone dipropionate; FF, formoterol fumarate; GB, glycopyrronium bromide; TEAE, treatment-emerging undesirable event. Abstract The goals of COPD therapy are to avoid and control symptoms, decrease the regularity and intensity of exacerbations, and improve workout tolerance. The triple mixture therapy of inhaled corticosteroids (ICSs), long-acting beta2 agonists (LABAs), and long-acting muscarinic antagonists (LAMAs) is becoming a choice for maintenance treatment of COPD so that as a step-up therapy from one or double mixture treatments. There is certainly proof that triple mixture ICS/LABA/LAMA with different inhalers increases lung function, symptoms, and wellness position and decreases exacerbations. A fresh triple fixed-dose mix of extrafine beclomethasone dipropionate (100 g/puff)/formoterol fumarate (6 g/puff)/glycopyrronium bromide (12.5 g/puff) continues to be developed being a hydrofluoroalkane pressurized metered dosage inhaler. Two huge pivotal studies demonstrated that extrafine set ICS/LABA/LAMA triple mixture is more advanced than fixed ICS/LABA mixed therapy and in addition more advanced than the LAMA tiotropium with regards to lung function and exacerbation avoidance in COPD sufferers vulnerable to exacerbation. This review considers the brand new information supplied by these scientific studies of extrafine triple therapy as well as the implications for the scientific administration of COPD sufferers. solid course=”kwd-title” Keywords: COPD, inhaled triple therapy, beclomethasone dipropionate, formoterol fumarate and glycopyrronium bromide Launch COPD is among the leading factors behind morbidity and mortality world-wide.1,2 Pharmacological therapy for COPD decreases symptoms, frequency and severity of exacerbations, and improves workout tolerance and wellness position.3 Currently, the primary treatment plans for COPD sufferers participate in a restricted variety of pharmacological classes C that’s, bronchodilators (short-acting beta2 agonists [SABAs], long-acting beta2 agonists [LABAs], short-acting muscarinic antagonists [SAMAs], and long-acting muscarinic antagonists [LAMAs]), inhaled corticosteroids (ICSs), and inhibitors from the enzyme phosphodiesterase-4. Long-acting bronchodilator monotherapy may boost lung function, improve patient-reported final results (Advantages) such as for example symptoms and standard of living, enhance exercise functionality, and decrease exacerbations.4,5 Administering LABA and LAMA concurrently (dual bronchodilator treatment) significantly increases lung function and PROs in comparison to treatment with an individual bronchodilator;6 also, there is certainly proof for fewer exacerbations when working with two long-acting bronchodilators in comparison to a single.7 The scientific rationale behind the additive results observed when merging bronchodilators includes the various mechanisms of actions of beta2 agonists and muscarinic antagonists (arousal of beta2-adrenergic receptors and inhibition of acetylcholine-induced bronchoconstriction, respectively), as well as the potential intracellular interactions between these pathways.8,9 Several studies show that long-term treatment using a combination inhaler filled with ICS/LABA works more effectively compared to the individual components in enhancing lung function and PROs and in reducing exacerbation frequency. ICS/LABA combos are suggested for make use of in sufferers vulnerable to exacerbations, that the very best predictor may be the preceding background of exacerbations. For sufferers who stay symptomatic and/or continue steadily to exacerbate despite treatment using a dual bronchodilator or ICS/LABA mixture inhaler, the Global Effort for Obstructive Lung Disease (Silver) management technique recommends intensify to triple therapy (ICS plus LABA.The scholarly studies, therefore, enrolled patients who in true to life are candidates for step-up treatment. The tiny airways are of significant importance in COPD, and extrafine aerosols of MMAD 1.1 have already been been shown to be able to focus on both larger proximal and smaller distal airways in the lungs.32 A recently available analysis in the SPIROMICS research showed a link between little airways disease as well as the consistent exacerbator phenotype (thought as individual with one exacerbation each year for the 3-season follow-up). (55.7)1,514622 (57.8)740309 (57.5)COPD800565 (32.0)360240 (35.3)588383 (35.6)258167 (31.1)Nasopharyngitis11496 (5.4)4538 (5.6)8566 (6.1)2220 (3.7)Headaches6955 (3.1)1716 (2.4)4841 (3.8)2018 (3.4)Pneumonia5551 (2.9)1818 (2.6)2019 (1.8)1312 (2.2)?Pneumonia4643 (2.4)1616 (2.4)1817 (1.6)1312 (2.2)?Bronchopneumonia44 (0.2)22 (0.3)11 (0.1)00 (0.0)?Lobar pneumonia44 (0.2)00 (0.0)00 (0.0)00 (0.0)?Interstitial lung disease00 (0.0)00 (0.0)11 (0.1)00 (0.0)?Pneumonia aspiration11 (0.1)00 (0.0)00 (0.0)00 (0.0)Dyspnea3835 (2.0)1513 (1.9)5237 (3.4)98 (1.5)Hypertension4340 (2.3)1816 (2.4)2120 (1.9)1010 (1.9)Respiratory system infection viral3331 (1.8)1110 (1.5)1515 (1.4)1413 (2.4)Coughing3224 (1.4)77 (1.0)2623 (2.1)99 (1.7)Atrial fibrillation2625 (1.4)99 (1.3)1313 (1.2)54 (0.7)Influenza2624 (1.4)55 (0.7)1110 (0.9)44 (0.7)Dried out mouth area1514 (0.8)44 (0.6)1313 (1.2)1010 (1.9)Back again discomfort2523 (1.3)87 (1.0)66 (0.6)22 (0.4)Top respiratory system infection119 (0.5)1212 (1.8)1111 (1.0)44 (0.7)Cardiac failure1413 (0.7)55 (0.7)97 (0.7)76 (1.1)Anemia1212 (0.7)77 (1.0)77 (0.7)33 (0.6)Viral higher tract infection1614 (0.8)22 (0.3)66 (0.6)76 (1.1)Dental candidiasis2118 (1.0)22 (0.3)33 (0.3)53 (0.6)Pyrexia43 (0.2)00 (0.0)44 (0.4)97 (1.3)Vertebral discomfort22 (0.1)11 (0.1)11 (0.1)86 (1.1) Open up in another home window Abbreviations: BDP, beclomethasone dipropionate; FF, formoterol fumarate; GB, glycopyrronium bromide; TEAE, treatment-emerging undesirable event. Abstract The goals of COPD therapy are to avoid and control symptoms, decrease the regularity and intensity of exacerbations, and improve workout tolerance. The triple mixture therapy of inhaled corticosteroids (ICSs), long-acting beta2 agonists (LABAs), and long-acting muscarinic antagonists (LAMAs) is becoming a choice for maintenance treatment of COPD so that as a step-up therapy from one or double mixture treatments. There is certainly proof that triple mixture ICS/LABA/LAMA with different inhalers boosts lung function, symptoms, and wellness status and decreases exacerbations. A fresh triple fixed-dose mix of extrafine beclomethasone dipropionate (100 g/puff)/formoterol fumarate (6 g/puff)/glycopyrronium bromide (12.5 g/puff) continues to be developed being a hydrofluoroalkane pressurized metered dosage inhaler. Two huge pivotal studies demonstrated that extrafine set ICS/LABA/LAMA triple mixture is more advanced than fixed ICS/LABA mixed therapy and in addition more advanced than the LAMA tiotropium with regards to lung function and exacerbation avoidance in COPD sufferers vulnerable to exacerbation. This review considers the brand new information supplied by these scientific studies of extrafine triple therapy as well as the implications for the scientific administration of COPD sufferers. solid course=”kwd-title” Keywords: COPD, inhaled triple therapy, beclomethasone dipropionate, formoterol fumarate and glycopyrronium bromide Launch COPD is among the leading factors behind morbidity and mortality world-wide.1,2 Pharmacological therapy for COPD decreases symptoms, frequency and severity of exacerbations, and improves workout tolerance and wellness position.3 Currently, the primary treatment plans for COPD sufferers participate in a restricted amount of pharmacological classes C that’s, bronchodilators (short-acting beta2 agonists [SABAs], long-acting beta2 agonists [LABAs], short-acting muscarinic antagonists [SAMAs], and long-acting muscarinic antagonists [LAMAs]), inhaled corticosteroids (ICSs), and inhibitors from the enzyme phosphodiesterase-4. Long-acting bronchodilator monotherapy may boost lung function, improve patient-reported final results (Advantages) such as for example symptoms and standard of living, enhance exercise efficiency, and decrease exacerbations.4,5 Administering LABA and LAMA concurrently (dual bronchodilator treatment) significantly boosts lung function and PROs in comparison to treatment with an individual bronchodilator;6 also, there is certainly proof for fewer exacerbations when working with two long-acting bronchodilators in comparison to a single.7 The scientific rationale behind the additive results observed when merging bronchodilators includes the various mechanisms of actions of beta2 agonists and muscarinic antagonists (excitement of beta2-adrenergic receptors and inhibition of acetylcholine-induced bronchoconstriction, respectively), as well as the potential intracellular interactions between these pathways.8,9 Several studies show that long-term treatment using a combination inhaler containing ICS/LABA is more effective than the individual components in improving lung function and PROs and in reducing exacerbation frequency. ICS/LABA combinations are recommended for use in patients at risk of exacerbations, for which the best predictor is the prior history of exacerbations. For patients who remain symptomatic and/or continue to exacerbate despite treatment with a dual bronchodilator or ICS/LABA combination inhaler, the Global Initiative for Obstructive Lung Disease (GOLD) management strategy recommends step up to triple therapy (ICS plus LABA plus LAMA). In clinical practice, patients also step up to triple from LAMA monotherapy.3 Since the components of triple therapy have different pharmacological mechanisms of action, there is a strong rationale for the use of these drugs together to maximize clinical benefits, including the prevention of exacerbation.10,11 Triple therapy is widely prescribed to COPD patients in clinical.BDP/FF/GB fixed-dose combination has an extrafine formulation (ie, the mass median aerodynamic diameter [MMAD] is 1.1 m for all active ingredients) designated to target both large and small airways. (2.4)2120 (1.9)1010 (1.9)Respiratory tract infection viral3331 (1.8)1110 (1.5)1515 (1.4)1413 (2.4)Cough3224 (1.4)77 (1.0)2623 (2.1)99 (1.7)Atrial fibrillation2625 (1.4)99 (1.3)1313 (1.2)54 (0.7)Influenza2624 (1.4)55 (0.7)1110 (0.9)44 (0.7)Dry mouth1514 (0.8)44 (0.6)1313 (1.2)1010 (1.9)Back pain2523 (1.3)87 (1.0)66 (0.6)22 (0.4)Upper respiratory tract infection119 (0.5)1212 (1.8)1111 (1.0)44 (0.7)Cardiac failure1413 (0.7)55 (0.7)97 (0.7)76 (1.1)Anemia1212 (0.7)77 Carebastine (1.0)77 (0.7)33 (0.6)Viral upper tract infection1614 (0.8)22 (0.3)66 (0.6)76 (1.1)Oral candidiasis2118 (1.0)22 (0.3)33 (0.3)53 (0.6)Pyrexia43 (0.2)00 (0.0)44 (0.4)97 (1.3)Spinal pain22 (0.1)11 (0.1)11 (0.1)86 (1.1) Open in a separate window Abbreviations: BDP, beclomethasone dipropionate; FF, formoterol fumarate; GB, glycopyrronium bromide; TEAE, treatment-emerging adverse event. Abstract The goals of COPD therapy are to prevent and control symptoms, reduce the frequency and severity of exacerbations, and improve exercise tolerance. The triple combination therapy of inhaled corticosteroids (ICSs), long-acting beta2 agonists (LABAs), and long-acting muscarinic antagonists (LAMAs) has become an option for maintenance treatment of COPD and as a step-up therapy from single or double combination treatments. There is evidence that triple combination ICS/LABA/LAMA with different inhalers improves lung function, symptoms, and health status and reduces exacerbations. A new triple fixed-dose combination of extrafine beclomethasone dipropionate (100 g/puff)/formoterol fumarate (6 g/puff)/glycopyrronium bromide (12.5 g/puff) has been developed as a hydrofluoroalkane pressurized metered dose inhaler. Two large pivotal studies showed that this extrafine fixed ICS/LABA/LAMA triple combination is superior to fixed ICS/LABA combined therapy and also superior to the LAMA tiotropium in terms of lung function and exacerbation prevention in COPD patients at risk of exacerbation. This review considers the new information provided by these clinical trials of extrafine triple therapy and the implications for the clinical management of COPD patients. strong class=”kwd-title” Keywords: COPD, inhaled triple therapy, beclomethasone dipropionate, formoterol fumarate and glycopyrronium bromide Introduction COPD is one of the leading causes of morbidity and mortality worldwide.1,2 Pharmacological therapy for COPD reduces symptoms, frequency and severity of exacerbations, and improves exercise tolerance and health status.3 Currently, the main treatment options for COPD patients belong to a restricted number of pharmacological classes C that is, bronchodilators (short-acting beta2 agonists [SABAs], long-acting beta2 agonists [LABAs], short-acting muscarinic antagonists [SAMAs], and long-acting muscarinic antagonists [LAMAs]), inhaled corticosteroids (ICSs), and inhibitors of the enzyme phosphodiesterase-4. Long-acting bronchodilator monotherapy is known to increase lung function, improve patient-reported outcomes (PROs) such as symptoms and quality of life, enhance exercise performance, and reduce exacerbations.4,5 Administering LABA and LAMA concurrently (dual bronchodilator treatment) significantly improves lung function and PROs compared to treatment with a single bronchodilator;6 also, there is evidence for fewer exacerbations when using two long-acting bronchodilators compared to 1.7 The scientific rationale behind the additive effects observed when combining bronchodilators includes the different mechanisms of action of beta2 agonists and muscarinic antagonists (activation of beta2-adrenergic receptors and inhibition of acetylcholine-induced bronchoconstriction, respectively), and the potential intracellular interactions between these pathways.8,9 A number of studies have shown that long-term treatment having a combination inhaler comprising ICS/LABA is more effective than the individual components in improving lung function and PROs and in reducing exacerbation frequency. ICS/LABA mixtures are recommended for use in individuals at risk of exacerbations, for which the best predictor is the previous history of exacerbations. For individuals who remain symptomatic and/or continue to exacerbate despite treatment having a dual bronchodilator or ICS/LABA combination inhaler, the Global Initiative for Obstructive Lung Disease (Platinum) management strategy recommends step up to triple therapy (ICS plus LABA plus LAMA). In medical practice, individuals also step up to triple from LAMA monotherapy.3 Since the components of triple therapy have different pharmacological mechanisms of action, there is a strong rationale for the use of these medicines together to maximize clinical benefits, including the prevention of exacerbation.10,11 Triple therapy is widely prescribed to COPD individuals in clinical practice, commonly using two SEMA3E independent inhalers: an ICS/LABA combination plus a LAMA. A recent review from the UK general practice showed that, from 2004 to 2009, the use of triple therapy improved from 25% to 59% in individuals with very severe COPD, with 14% and 19% slight and moderate (based on lung function) COPD individuals, respectively, using triple therapy.12 However, while its use has increased, relatively few studies have been conducted to test the effectiveness of triple therapy, administered by independent inhalers, compared to ICS/LABA, LABA/LAMA, or LAMA in terms of preventing exacerbations. This short article evaluations the available evidence of the effectiveness of triple therapy in COPD. We evaluate studies using extemporary triple therapy Carebastine (ie, therapy delivered through.This is particularly evident when the inhalers are of different designs. (1.8)1110 (1.5)1515 (1.4)1413 (2.4)Cough3224 (1.4)77 (1.0)2623 (2.1)99 (1.7)Atrial fibrillation2625 (1.4)99 (1.3)1313 (1.2)54 (0.7)Influenza2624 (1.4)55 (0.7)1110 (0.9)44 (0.7)Dry mouth1514 (0.8)44 (0.6)1313 (1.2)1010 (1.9)Back pain2523 (1.3)87 (1.0)66 (0.6)22 (0.4)Upper respiratory tract infection119 (0.5)1212 (1.8)1111 (1.0)44 (0.7)Cardiac failure1413 (0.7)55 (0.7)97 (0.7)76 (1.1)Anemia1212 (0.7)77 (1.0)77 (0.7)33 (0.6)Viral top tract infection1614 (0.8)22 (0.3)66 (0.6)76 (1.1)Oral candidiasis2118 (1.0)22 (0.3)33 (0.3)53 (0.6)Pyrexia43 (0.2)00 (0.0)44 (0.4)97 (1.3)Spinal pain22 (0.1)11 (0.1)11 (0.1)86 (1.1) Open in a separate windowpane Abbreviations: BDP, beclomethasone dipropionate; FF, formoterol fumarate; GB, glycopyrronium bromide; TEAE, treatment-emerging adverse event. Abstract The goals of COPD therapy are to prevent and control symptoms, reduce the rate of recurrence and severity of exacerbations, and improve exercise tolerance. The triple combination therapy of inhaled corticosteroids (ICSs), long-acting beta2 agonists (LABAs), and long-acting muscarinic antagonists (LAMAs) has become an option for maintenance treatment of COPD and as a step-up therapy from solitary or double combination treatments. There is evidence that triple combination ICS/LABA/LAMA with different inhalers enhances lung function, symptoms, and health status and reduces exacerbations. A new triple fixed-dose combination of extrafine beclomethasone dipropionate (100 g/puff)/formoterol fumarate (6 g/puff)/glycopyrronium bromide (12.5 g/puff) has been developed like a hydrofluoroalkane pressurized metered dose inhaler. Two large pivotal studies showed that this extrafine fixed ICS/LABA/LAMA triple combination is superior to fixed ICS/LABA combined therapy and also superior to the LAMA tiotropium in terms of lung function and exacerbation prevention in COPD individuals at risk of exacerbation. This review considers the new information provided by these clinical trials of extrafine triple therapy and the implications for the clinical management of COPD patients. strong class=”kwd-title” Keywords: COPD, inhaled triple therapy, beclomethasone dipropionate, formoterol fumarate and glycopyrronium bromide Introduction COPD is one of the leading causes of morbidity and mortality worldwide.1,2 Pharmacological therapy for COPD reduces symptoms, frequency and severity of exacerbations, and improves exercise tolerance and health status.3 Currently, the main treatment options for COPD patients belong to a restricted quantity of pharmacological classes C that is, bronchodilators (short-acting beta2 agonists [SABAs], long-acting beta2 agonists [LABAs], short-acting muscarinic antagonists [SAMAs], and long-acting muscarinic antagonists [LAMAs]), inhaled corticosteroids (ICSs), and inhibitors of the enzyme phosphodiesterase-4. Long-acting bronchodilator monotherapy is known to increase lung function, improve patient-reported outcomes (PROs) such as symptoms and quality of life, enhance exercise overall performance, and reduce exacerbations.4,5 Administering LABA and LAMA concurrently (dual bronchodilator treatment) significantly enhances lung function and PROs compared to treatment with a single bronchodilator;6 also, there is evidence for fewer exacerbations when using two long-acting bronchodilators compared to one.7 The scientific rationale behind the additive effects observed when combining bronchodilators includes the different mechanisms of action of beta2 agonists and muscarinic antagonists (activation of beta2-adrenergic receptors and inhibition of acetylcholine-induced bronchoconstriction, respectively), and the potential intracellular interactions between these pathways.8,9 A number of studies have shown that long-term treatment with a combination inhaler made up of ICS/LABA is more effective than the individual components in improving lung function and PROs and in reducing exacerbation frequency. ICS/LABA combinations are recommended for use in patients at risk of exacerbations, for which the best predictor is the prior history of exacerbations. For patients who remain symptomatic and/or continue to exacerbate despite treatment with a dual bronchodilator or ICS/LABA combination inhaler, the Global Initiative for Obstructive Lung Disease (Platinum) management strategy recommends step up to triple therapy (ICS plus LABA plus LAMA). In clinical practice, patients also step up to triple from LAMA monotherapy.3 Since the components of triple therapy have different pharmacological mechanisms of action, there is a strong rationale for the use of these drugs together to maximize clinical benefits, including the prevention of exacerbation.10,11 Triple therapy is widely prescribed to COPD patients in clinical practice, commonly using two individual inhalers: an ICS/LABA combination plus a LAMA. A recent review from the UK general practice showed that, from 2004 to 2009, the use of triple therapy increased from 25% to 59% in patients with very severe COPD, with 14% and 19% moderate and moderate (based on lung function) COPD patients, respectively, using triple therapy.12 However, while its use has increased, relatively few studies have been conducted to test the efficacy of triple therapy, administered by individual inhalers, compared to ICS/LABA, LABA/LAMA, or LAMA in terms of preventing exacerbations. This short article reviews the available evidence of the efficacy of triple therapy in COPD. We evaluate studies using extemporary triple therapy (ie, therapy delivered through separate.