scholarly journals The Airways’ Mechanical Stress in Lung Disease: Implications for COPD Pathophysiology and Treatment Evaluation

2019 ◽  
Vol 2019 ◽  
pp. 1-8 ◽  
Author(s):  
Pierachille Santus ◽  
Matteo Pecchiari ◽  
Francesco Tursi ◽  
Vincenzo Valenti ◽  
Marina Saad ◽  
...  

The airway epithelium stretches and relaxes during the normal respiratory cycle, and hyperventilation exaggerates this effect, resulting in changes in lung physiology. In fact, stretching of the airways influences lung function and the secretion of airway mediators, which in turn may cause a potentially injurious inflammatory response. This aim of the present narrative review was to illustrate the current evidence on the importance of mechanical stress in the pathophysiology of lung diseases with a particular focus on chronic obstructive pulmonary disease (COPD) and to discuss how this may influence pharmacological treatment strategies. Overall, treatment selection should be tailored to counterpart the effects of mechanical stress, which influences inflammation both in asthma and COPD. The most suitable treatment approach between a long-acting β2-agonists/long-acting antimuscarinic-agonist (LABA/LAMA) alone or with the addition of inhaled corticosteroids should be determined based on the underlying mechanism of inflammation. Noteworthy, the anti-inflammatory effects of the glycopyrronium/indacaterol combination on hyperinflation and mucociliary clearance may decrease the rate of COPD exacerbations, and it may synergistically improve bronchodilation with a double action on both the cyclic adenosine monophosphate (cAMP) and the acetylcholine pathways.

2021 ◽  
Vol 30 (1) ◽  
pp. 61-69
Author(s):  
O.N. Titova ◽  
S.V. Moiseev

Long-acting β 2 adrenoceptor agonists (LABA) and/or longacting muscarinic antagonists (LAMA) should be used as monotherapy or in combination for the initial treatment in patients with chronic obstructive pulmonary disease (COPD). Triple inhaled therapy with LABA, LAMA, and inhaled corticosteroid (ICS) has been recommended for COPD patients who still have clinically significant symptoms following the use of a dual inhaler with LABA plus LAMA, particularly for those who present with frequent exacerbations, blood eosinophilia and/or concomitant bronchial asthma. Experimental studies on human isolated airways suggested that LABA, LAMA, and ICS synergistically relax the medium and small bronchi probably as a result of enhanced elevation of the cyclic adenosine monophosphate (cAMP) that mediates relaxation of airway smooth muscle cells. Synergy of LABA and LAMA was also shown in a few clinical studies, whereas in the randomized controlled trials triple therapy with two long-acting bronchodilatators and ICS was more effective than various dual combinations (LABA/LAMA or ICS/LABA) in patients with severe COPD. These findings justify triple therapy in patients with severe COPD who have frequent exacerbations and do not respond to dual therapy. Recently, a single inhalers containing ICS, LABA, and LAMA have been developed as a more practical alternative, which may improve therapy compliance.


2021 ◽  
Vol 31 (1) ◽  
pp. 75-87
Author(s):  
I. V. Leshchenko ◽  
A. S. Meshcheryakova

Chronic obstructive pulmonary disease (COPD) is the leading cause of death in the structure of respiratory diseases. The problem of rational pharmacotherapy of COPD have attracted attention of the medical scientific society for many years. The understanding of the pathogenesis of the disease has deepened and approaches to the therapy have changed. Some COPD patients need regular fixed-combination therapy: long-acting bronchodilators (LABD) and inhaled corticosteroids (ICS) in order to prevent exacerbations and reduce the severity of symptoms of the disease. Blood eosinophils count is one of criteria for choosing regular therapy. The appearance of fixed triple combinations of ICS/LABD increased the effectiveness of COPD therapy, and a new delivery device for fixed combination of budesonide/formoterol makes it possible to use ICS successfully in the most severe patients.


2021 ◽  
Author(s):  
Jorge Machado Alba

Introduction: Chronic obstructive pulmonary disease (COPD) affects approximately 174 million people worldwide.The objective was to determine the trends of the use of medications for COPD in a group of Colombian patients. Methods: This was a retrospective study on prescription patterns of bronchodilators and other medications used in COPD from a population database with follow-up at 12 and 24 months. Patients older than 18 years of age of any sex who had COPD between 2017 and 2019 were included. Sociodemographic variables, medications, treatment schedules for COPD, comorbidities, comedications, and the specialty of the prescriber were considered. Results: A total of 9,476 people with a diagnosis of COPD were evaluated. They had a mean age of 75.9 ± 10.7 years, 50.1% were men, and 86.8% were prescribed by a general practitioner. At the beginning of the follow-up, on average, they received 1.6 medications/patient, mainly short-acting antimuscarinics (3784; 39.9%), followed by short-acting β-agonists (2997, 31.6%) and inhaled corticosteroids (ICS) (2239, 23.6%), but 5083 (53.6%) patients received a long-acting bronchodilator. At the beginning of the follow-up, 645 (6.8%) patients were put on triple therapy with antimuscarinics, β-agonists, and ICS, and at 12 months, this rose to 1388 (20.6%). A total of 57.9% had comorbidities, most often hypertension (44.4%). Conclusions: This group of patients with COPD treated in Colombia frequently received short-acting bronchodilators and ICS, but a growing proportion are undergoing controlled therapy with long-acting bronchodilators, a situation that can improve the indicators of morbidity, exacerbations, and hospitalization.


2015 ◽  
Vol 1 (1) ◽  
pp. 00011-2015 ◽  
Author(s):  
Jørgen Vestbo ◽  
Peter Lange

Exacerbations have significant impact on the morbidity and mortality of patients with chronic obstructive pulmonary disease. Most guidelines emphasise prevention of exacerbations by treatment with long-acting bronchodilators and/or anti-inflammatory drugs. Whereas most of this treatment is evidence-based, it is clear that patients differ regarding the nature of exacerbations and are likely to benefit differently from different types of treatment. In this short review, we wish to highlight this, suggest a first step in differentiating pharmacological exacerbation prevention and call for more studies in this area. Finally, we wish to highlight that there are perhaps easier ways of achieving similar success in exacerbation prevention using nonpharmacological tools.


2020 ◽  
Vol 14 ◽  
pp. 175346662093719
Author(s):  
Ching-Yi Chen ◽  
Wang-Chun Chen ◽  
Chi-Hsien Huang ◽  
Yi-Ping Hsiang ◽  
Chau-Chyun Sheu ◽  
...  

Background: Long-acting muscarinic antagonist (LAMA) monotherapy is recommended for chronic obstructive pulmonary disease (COPD) patients with high risk of exacerbations. It is unclear whether long-acting β2-agonist (LABA)/LAMA fixed-dose combinations (FDCs) are more effective than LAMAs alone in preventing exacerbations. The aim of this study was to systematically review the literature to investigate whether LABA/LAMA FDCs are more effective than LAMA monotherapy in preventing exacerbations. Methods: We searched several databases and manufacturers’ websites to identify relevant randomized clinical trials comparing LABA/LAMA FDC treatment with LAMAs alone ⩾24 weeks. Outcomes of interest were time to first exacerbation and rates of moderate to severe, severe and all exacerbations. Results: We included 10 trials in 9 articles from 2013 to 2018 with a total of 19,369 patients for analysis in this study. Compared with LAMA monotherapy, LABA/LAMA FDCs demonstrated similar efficacy in terms of time to first exacerbation [hazard ratio, 0.96; 95% confidence interval (CI) 0.79–1.18; p = 0.71], moderate to severe exacerbations [risk ratio (RR), 0.96; 95% CI 0.90–1.03; p = 0.28], severe exacerbations (RR, 0.92; 95% CI 0.81–1.03; p = 0.15), and a marginal superiority in terms of all exacerbations (RR, 0.92; 95% CI 0.86–1.00; p = 0.04). The incidence of all exacerbation events was lower in the LABA/LAMA FDC group for the COPD patients with a history of previous exacerbations and those with a longer treatment period (52–64 weeks). Conclusion: This study provides evidence that LABA/LAMA FDCs are marginally superior in the prevention of all exacerbations compared with LAMA monotherapy in patients with COPD. The reviews of this paper are available via the supplemental material section.


2019 ◽  
Vol 20 (1) ◽  
Author(s):  
James F. Donohue ◽  
Edward Kerwin ◽  
Sanjay Sethi ◽  
Brett Haumann ◽  
Srikanth Pendyala ◽  
...  

Abstract Background Revefenacin is a long-acting muscarinic antagonist that was recently approved for the nebulized treatment of chronic obstructive pulmonary disease (COPD). Although shorter duration studies have documented the efficacy of revefenacin in COPD, longer-term efficacy has not been described. In a recent 52-week safety trial, revefenacin was well tolerated and had a favorable benefit-risk profile. Here we report exploratory efficacy and health outcomes in patients receiving revefenacin 175 μg or 88 μg daily during the 52-week trial. Methods In this randomized, parallel-group, 52-week trial (NCT02518139), 1055 participants with moderate to very severe COPD received revefenacin 175 μg or 88 μg in a double-blind manner, or open-label active control tiotropium. Results Over the 52-week treatment period, both doses of revefenacin, as well as tiotropium, elicited significant (all p < 0.0003) improvements from baseline in trough forced expiratory volume in 1 s (FEV1). The trough FEV1 profile (least squares mean change from baseline) for revefenacin 175 μg ranged from 52.3–124.3 mL and the trough FEV1 profile for tiotropium ranged from 79.7–112.8 mL. In subgroup comparisons, the effect of revefenacin on trough FEV1 was comparable in patients taking concomitant long-acting β-agonists, with or without inhaled corticosteroids, with patients who were not taking these medications. There were statistically significant (p < 0.05) improvements in all measured health status outcomes (evaluated using St. George’s Respiratory Questionnaire, COPD Assessment Test, Clinical COPD Questionnaire and Baseline and Transition Dyspnea Index) from 3 months onward, in all treatment arms. Conclusions Significant sustained improvements from baseline in trough FEV1 and respiratory health outcomes were demonstrated for 175-μg revefenacin over 52 weeks, further supporting its use as a once-daily bronchodilator for the nebulized treatment of patients with COPD. Trial registration NCT02518139; Registered 5 August 2015.


2018 ◽  
Vol 27 (147) ◽  
pp. 170103 ◽  
Author(s):  
Christian Viniol ◽  
Claus F. Vogelmeier

Chronic obstructive pulmonary disease (COPD) is the third leading cause of death worldwide. While COPD is a mainly chronic disease, a substantial number of patients suffer from exacerbations. Severe exacerbations are related to a significantly worse survival outcome. This review summarises the current knowledge on the different aspects of COPD exacerbations. The impact of risk factors and triggers such as smoking, severe airflow limitation, bronchiectasis, bacterial and viral infections and comorbidities is discussed. More severe exacerbations should be treated with β-agonists and anticholinergics as well as systemic corticosteroids. Antibiotic therapy should only be given to patients with presumed bacterial infection. Noninvasive ventilation is indicated in patients with respiratory failure. Smoking cessation is key to prevent further COPD exacerbations. Other aspects include choice of pharmacotherapy, including bronchodilators, inhaled corticosteroids, phosphodiesterase-4 inhibitors, long-term antibiotics and mucolytics. Better education and self-management as well as increased physical activity are important. Influenza and pneumococcal vaccination is recommended. Treatment of hypoxaemia and hypercapnia reduce the rate of COPD exacerbations, while most interventional bronchoscopic therapies increase exacerbation risk within the first months after the procedure.


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