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International Journal of Chronic... 2020The use of inhaled corticosteroids (ICSs) in long-term treatment of COPD has been a debated topic for a long time. According to the evidence produced till now, ICSs are... (Review)
Review
The use of inhaled corticosteroids (ICSs) in long-term treatment of COPD has been a debated topic for a long time. According to the evidence produced till now, ICSs are presently advocated in combination with long-acting bronchodilators for high-risk symptomatic COPD patients with a history of frequent COPD exacerbations. However, the heterogeneity of COPD patients in terms of prevalent underlying disease, with its associated biological and functional characteristics, and different types of exacerbation makes this recommendation highly questionable. This review aims to discuss the usefulness of ICSs in the pharmacological management of COPD and trys to detect those aspects that may likely anticipate a beneficial response following their therapeutic use related to respiratory function, functional decline, prevention of exacerbation, and quality of life. In this respect, the BERN acronym, meaning Bronchiolitis, Eosinophilia, Responsiveness to bronchodilator, and Non-smoker, may be of practical utility to select among COPD patients those that can take more advantage from ICS adoption when positive and vice versa when negative.
Topics: Administration, Inhalation; Adrenal Cortex Hormones; Bronchodilator Agents; Drug Therapy, Combination; Humans; Pulmonary Disease, Chronic Obstructive; Quality of Life
PubMed: 32368028
DOI: 10.2147/COPD.S233462 -
CMAJ : Canadian Medical Association... Mar 1988Outpatient management of chronic obstructive pulmonary disease (COPD) is reviewed in this paper. Smoking cessation is probably important, although its benefit in... (Review)
Review
Outpatient management of chronic obstructive pulmonary disease (COPD) is reviewed in this paper. Smoking cessation is probably important, although its benefit in established COPD is unproven. Bronchodilator therapy may be of more than symptomatic benefit and is indicated in virtually all patients. Specific beta 2-agonists are the most widely used agents and can be given in substantially larger doses than are usually recommended. Ipratropium bromide, an anticholinergic drug, is about as effective as a beta 2-agonist, but in large doses the two drugs do not seem to have additive effects, unlike theophylline and beta 2-agonists. Systemic corticosteroids decrease airway obstruction substantially in a small number of patients with COPD; these agents should be reserved for these patients and used sparingly. Inhaled steroids are of little benefit, as are respiratory stimulants and depressants. Broad-spectrum antibiotic therapy helps to relieve symptomatic exacerbations of COPD, particularly those characterized by increased dyspnea, sputum volume and sputum purulence. Cor pulmonale is best managed by diuretics and oxygen, with digoxin reserved for left ventricular failure and supraventricular arrhythmias. Continuous oxygen therapy at home is indicated for the patients who have chronic arterial hypoxemia.
Topics: Adrenal Cortex Hormones; Aged; Ambulatory Care; Anti-Bacterial Agents; Bronchodilator Agents; Digoxin; Diuretics; Humans; Influenza Vaccines; Lung Diseases, Obstructive; Oxygen Inhalation Therapy; Smoking
PubMed: 3278783
DOI: No ID Found -
PloS One 2016There is much debate surrounding the use of inhaled bronchodilators and corticosteroids for infants with bronchopulmonary dysplasia (BPD). (Review)
Review
BACKGROUND
There is much debate surrounding the use of inhaled bronchodilators and corticosteroids for infants with bronchopulmonary dysplasia (BPD).
OBJECTIVE
The objective of this systematic review was to identify strengths and knowledge gaps in the literature regarding inhaled therapies in BPD and guide future research to improve long-termoutcomes.
METHODS
The databases of Academic Search Complete, CINAHL, PUBMED/MEDLINE, and Scopus were searched for studies that evaluated both acute and long-term clinical outcomes related to the delivery and therapeutic efficacy of inhaled beta-agonists, anticholinergics and corticosteroids in infants with developing and/or established BPD.
RESULTS
Of 181 articles, 22 met inclusion criteria for review. Five evaluated beta-agonist therapies (n = 84, weighted gestational age (GA) of 27.1(26-30) weeks, weighted birth weight (BW) of 974(843-1310) grams, weighted post menstrual age (PMA) of 34.8(28-39) weeks, and weighted age of 53(15-86) days old at the time of evaluation). Fourteen evaluated inhaled corticosteroids (n = 2383, GA 26.2(26-29) weeks, weighted BW of 853(760-1114) grams, weighted PMA of 27.0(26-31) weeks, and weighted age of 6(0-45) days old at time of evaluation). Three evaluated combination therapies (n = 198, weighted GA of 27.8(27-29) weeks, weighted BW of 1057(898-1247) grams, weighted PMA of 30.7(29-45) weeks, and age 20(10-111) days old at time of evaluation).
CONCLUSION
Whether inhaled bronchodilators and inhaled corticosteroids improve long-term outcomes in BPD remains unclear. Literature regarding these therapies mostly addresses evolving BPD. There appears to be heterogeneity in treatment responses, and may be related to varying modes of administration. Further research is needed to evaluate inhaled therapies in infants with severe BPD. Such investigations should focus on appropriate definitions of disease and subject selection, timing of therapies, and new drugs, devices and delivery methods as compared to traditional methods across all modalities of respiratory support, in addition to the assessment of long-term outcomes of initial responders.
Topics: Administration, Inhalation; Adrenal Cortex Hormones; Bronchodilator Agents; Bronchopulmonary Dysplasia; Humans; Infant, Newborn
PubMed: 26840339
DOI: 10.1371/journal.pone.0148188 -
Lakartidningen Jan 2022Approximately 500 000 individuals in Sweden have chronic obstructive pulmonary disease (COPD). Co-morbid, especially cardiovascular, conditions are common in COPD and...
Approximately 500 000 individuals in Sweden have chronic obstructive pulmonary disease (COPD). Co-morbid, especially cardiovascular, conditions are common in COPD and globally COPD is the third most common cause of mortality. Mortality in COPD is driven by dyspnea, exacerbations and comorbidities and is reduced by smoking cessation and lung rehabilitation. Also, pharmacological treatment, in particular inhaled corticosteroids, reduces mortality in COPD. The reduction in mortality that can be achieved by treatment with inhaled corticosteroids in combinations with long-acting bronchodilators is of the same order of magnitude as the effect on mortality by treatment of hyperlipidemia and hypertension.
Topics: Adrenal Cortex Hormones; Bronchodilator Agents; Dyspnea; Humans; Pulmonary Disease, Chronic Obstructive; Smoking Cessation
PubMed: 35020190
DOI: No ID Found -
American Journal of Respiratory and... Jul 2017Decreasing the frequency and severity of exacerbations is one of the main goals of treatment for patients with chronic obstructive pulmonary disease. Several studies... (Review)
Review
Decreasing the frequency and severity of exacerbations is one of the main goals of treatment for patients with chronic obstructive pulmonary disease. Several studies have documented that long-acting bronchodilators can reduce exacerbation rate and/or severity, and others have shown that combinations of long-acting β-adrenergic agonists (LABAs) and long-acting muscarinic antagonists (LAMAs) provide greater reductions in exacerbation frequency than either their monocomponents or LABA/inhaled corticosteroid combinations in patients at low and high risk for these events. In this review, small groups of experts critically evaluated mechanisms potentially responsible for the increased benefit of LABA/LAMA combinations over single long-acting bronchodilators or LABA/inhaled corticosteroids in decreasing exacerbation. These included effects on lung hyperinflation and mechanical stress, inflammation, excessive mucus production with impaired mucociliary clearance, and symptom severity. The data assembled and analyzed by each group were reviewed by all authors and combined into this manuscript. Available clinical results support the possibility that effects of LABA/LAMA combinations on hyperinflation, mucociliary clearance, and symptom severity may all contribute to decreasing exacerbations. Although preclinical studies suggest LABAs and LAMAs have antiinflammatory effects, such effects have not been demonstrated yet in patients with chronic obstructive pulmonary disease.
Topics: Administration, Inhalation; Adrenergic beta-2 Receptor Agonists; Bronchodilator Agents; Drug Therapy, Combination; Humans; Muscarinic Antagonists; Pulmonary Disease, Chronic Obstructive
PubMed: 27922741
DOI: 10.1164/rccm.201609-1794CI -
International Journal of Chronic... 2021Current pharmacological treatments for chronic obstructive pulmonary disease (COPD) are mostly limited to inhaled bronchodilators and corticosteroids. Azithromycin can... (Review)
Review
Current pharmacological treatments for chronic obstructive pulmonary disease (COPD) are mostly limited to inhaled bronchodilators and corticosteroids. Azithromycin can contribute to exacerbation prevention. Roflumilast, a phosphodiesterase (PDE) 4 inhibitor administered orally, also prevents exacerbations in selected patients with chronic bronchitis, recurrent exacerbations, severe airflow limitation and concomitant therapy with long-acting inhaled bronchodilators. This outcome likely results from anti-inflammatory effects since PDE4 is expressed by all inflammatory cell types involved in COPD. The use of this agent is, however, limited by side-effects, particularly nausea and diarrhea. To address remaining unmet needs and enrich therapeutic options for patients with COPD, inhaled dual PDE3/4 inhibitors have been developed, with the aim of enhancing bronchodilation through PDE3 inhibition and modulating inflammation and mucus production though PDE4 inhibition, thus producing a potentially synergistic effect on airway calibre. Experimental preclinical data confirmed these effects in vitro and in animal models. At present, RPL554/ensifentrine is the only agent of this family in clinical development. It decreases sputum markers of both neutrophilic and eosinophilic inflammation in patients with COPD. Clinical Phase II trials confirmed its bronchodilator effect and demonstrated clinically meaningful symptom relief and quality of life improvements in these patients. The safety profile appears satisfactory, with less effects on heart rate and blood pressure than salbutamol and no other side effect. Altogether, these data suggest that ensifentrine could have a role in COPD management, especially in addition to inhaled long-acting bronchodilators with or without corticosteroids since experimental studies suggest potentiation of ensifentrine effects by these agents. However, results from ongoing and future Phase III studies are needed to confirm both beneficial effects and favourable safety profile on a larger scale and assess other outcomes including exacerbations, lung function decline, comorbidities and mortality.
Topics: Animals; Bronchodilator Agents; Humans; Phosphodiesterase 3 Inhibitors; Phosphodiesterase 4 Inhibitors; Phosphoric Diester Hydrolases; Pulmonary Disease, Chronic Obstructive; Quality of Life
PubMed: 34429594
DOI: 10.2147/COPD.S226688 -
The European Respiratory Journal Feb 2015In this article, we focus on the scientific evidence from randomised trials supporting treatment with inhaled corticosteroids (ICS) in chronic obstructive pulmonary... (Review)
Review
In this article, we focus on the scientific evidence from randomised trials supporting treatment with inhaled corticosteroids (ICS) in chronic obstructive pulmonary disease (COPD), including treatment with combinations of long-acting β-agonist (LABA) bronchodilators and ICS. Our emphasis is on the methodological strengths and limitations that guide the conclusions that may be drawn. The evidence of benefit of ICS and, therefore, of the LABA/ICS combinations in COPD is limited by major methodological problems. From the data reviewed herein, we conclude that there is no survival benefit independent of the effect of long-acting bronchodilation and no effect on FEV1 decline, and that the possible benefit on reducing severe exacerbations is unclear. Our interpretation of the data is that there are substantial adverse effects from the use of ICS in patients with COPD, most notably severe pneumonia resulting in excess deaths. Currently, the most reliable predictor of response to ICS in COPD is the presence of eosinophilic inflammation in the sputum. There is an urgent need for better markers of benefit and risk that can be tested in randomised trials for use in routine specialist practice. Given the overall safety and effectiveness of long-acting bronchodilators in subjects without an asthma component to their COPD, we believe use of such agents without an associated ICS should be favoured.
Topics: Administration, Inhalation; Adrenal Cortex Hormones; Adrenergic beta-2 Receptor Agonists; Bronchodilator Agents; Eosinophils; Forced Expiratory Volume; Humans; Inflammation; Phenotype; Pulmonary Disease, Chronic Obstructive; Randomized Controlled Trials as Topic; Research Design; Sputum; Treatment Outcome
PubMed: 25537556
DOI: 10.1183/09031936.00128914 -
International Journal of Chronic... 2019Bronchodilation with muscarinic antagonists, β-agonists, and inhaled corticosteroids remains the foundation of pharmaceutical treatment for patients with stable COPD.... (Review)
Review
Bronchodilation with muscarinic antagonists, β-agonists, and inhaled corticosteroids remains the foundation of pharmaceutical treatment for patients with stable COPD. These drugs are delivered from a variety of devices, including dry powder inhalers, pressurized metered-dose inhalers, soft-mist inhalers, or nebulizers. Nebulized delivery is often preferable in patients who are elderly, are cognitively impaired, are unable to generate sufficient inspiratory force to use their inhaler, have difficulty coordinating hand-breath activity, are too dyspneic to hold their breath for a sufficient time, and/or may be acutely ill. Revefenacin, a once-daily long-acting muscarinic antagonist for nebulization recently approved by the US FDA for the treatment of patients with COPD, was discovered and developed using "duration and lung selectivity-by-design." This strategy selected a molecule with a high lung-selective index to maximize bronchodilation and limit systemic anti-muscarinic side effects. In early-phase clinical studies, revefenacin for nebulization led to a rapid onset of bronchodilation that was sustained for 24 hrs in patients with moderate to severe COPD. Revefenacin also demonstrated minimal systemic exposure and good tolerability in these studies. Statistically and clinically significant improvements in lung function (ie, peak and/or trough FEV) relative to placebo were observed with revefenacin in Phase III clinical trials of up to 3 months in patients with moderate to very severe COPD. Revefenacin was well tolerated in Phase III clinical trials with a low incidence of systemic antimuscarinic adverse events, which is consistent with its lung-selective design. There was no evidence of an increased risk of major cardiovascular events. Patient-reported outcome data from clinical trials indicated statistically significant improvements in several disease-specific measures. Revefenacin 175 μg for nebulization provides an effective once-daily treatment option for patients with moderate to very severe COPD who require or prefer nebulized therapy.
Topics: Benzamides; Bronchodilator Agents; Carbamates; Delayed-Action Preparations; Humans; Muscarinic Antagonists; Nebulizers and Vaporizers; Pulmonary Disease, Chronic Obstructive; Treatment Outcome
PubMed: 31908443
DOI: 10.2147/COPD.S157654 -
Respiratory Medicine May 2016Exacerbation frequency is related to disease progression, quality of life, and prognosis in COPD. Earlier diagnosis, along with interventions aimed at preventing... (Comparative Study)
Comparative Study Review
BACKGROUND
Exacerbation frequency is related to disease progression, quality of life, and prognosis in COPD. Earlier diagnosis, along with interventions aimed at preventing exacerbations and delaying progression, may help reduce the global burden of disease. Long-acting inhaled bronchodilators are effective at maintaining symptom relief and are recommended as first-choice therapy for more symptomatic patients and those at risk of exacerbation.
METHODS
As prevention of exacerbations is a priority goal in COPD management and a number of different long-acting bronchodilators are available, we conducted a systematic review of exacerbation data from randomized controlled trials (published January 2000 to May 2014) comparing the effect of tiotropium versus placebo and/or other maintenance therapies.
RESULTS
Exacerbations were a primary endpoint in 12 publications (five studies: four comparing tiotropium with placebo; one with active comparator) and a secondary endpoint in 17 publications (seven studies: six comparing tiotropium with placebo; one with active comparator). Overall, tiotropium was associated with a longer time to first exacerbation event and fewer exacerbations (including severe exacerbations/hospitalizations) compared with placebo and long-acting β2-agonists. Tiotropium also showed similar efficacy to glycopyrronium and a fixed long-acting muscarinic antagonist/long-acting β2-agonist combination (glycopyrronium/indacaterol), although not all studies were powered to demonstrate differences in exacerbation outcomes. Exacerbation outcomes were comparable with both formulations of tiotropium (HandiHaler(®) 18 μg/Respimat(®) 5 μg).
CONCLUSIONS
The results of this comprehensive systematic review demonstrate tiotropium is beneficial in reducing exacerbation risk versus placebo or other maintenance treatments.
Topics: Administration, Inhalation; Bronchodilator Agents; Cholinergic Antagonists; Glycopyrrolate; Humans; Indans; Muscarinic Antagonists; Pulmonary Disease, Chronic Obstructive; Quinolones; Randomized Controlled Trials as Topic; Tiotropium Bromide
PubMed: 27109805
DOI: 10.1016/j.rmed.2016.02.012 -
International Journal of Chronic... 2017The combination of a long-acting muscarinic antagonist (LAMA) and a long-acting β-agonist (LABA) in a single inhaler is a viable treatment option for patients with... (Review)
Review
OBJECTIVE
The combination of a long-acting muscarinic antagonist (LAMA) and a long-acting β-agonist (LABA) in a single inhaler is a viable treatment option for patients with chronic obstructive pulmonary disease (COPD). Here, we systematically review the current knowledge on double bronchodilation for the treatment of COPD, with a specific focus on its efficacy versus placebo and/or monotherapy bronchodilation.
METHODS
A systematic review of clinical trials investigating LABA/LAMA combination therapies was conducted. Articles were retrieved from PubMed, Embase, and Scopus on June 26, 2016. We specifically selected clinical trials with a randomized controlled or crossover design published in any scientific journal showing the following characteristics: 1) comparison of different LABA/LAMA combinations in a single inhaler for patients with COPD, 2) dose approved in Europe, and 3) focus on efficacy (versus placebo and/or bronchodilator monotherapy) in terms of lung function, respiratory symptoms, or exacerbations.
RESULTS
We analyzed 26 clinical trials conducted on 24,338 patients. All LABA/LAMA combinations were consistently able to improve lung function compared with both placebo and bronchodilator monotherapy. Improvements in symptoms were also consistent versus placebo, showing some lack of correlation for some clinical end points and combinations versus monotherapy bronchodilation. Albeit being an exploratory end point, exacerbations showed an improvement with LABA/LAMA combinations over placebo in some trials; however, scarce information was available in comparison with bronchodilator monotherapy in most studies.
CONCLUSION
Our data show consistent improvements for LABA/LAMA combinations, albeit with some variability (depending on the clinical end point, the specific combination, and the comparison group). Clinicians should be aware that these are average differences. All treatments should be tailored at the individual level to optimize clinical outcomes.
Topics: Administration, Inhalation; Adrenergic beta-2 Receptor Agonists; Bronchodilator Agents; Clinical Trials as Topic; Disease Progression; Drug Combinations; Forced Expiratory Volume; Humans; Lung; Muscarinic Antagonists; Pulmonary Disease, Chronic Obstructive; Treatment Outcome
PubMed: 28694697
DOI: 10.2147/COPD.S132962