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Diagnosis and Outpatient Management of Chronic Obstructive Pulmonary Disease: A Review.
Riley, CM, Sciurba, FC
JAMA. 2019;(8):786-797
Abstract
IMPORTANCE There are 30 million adults (12%) in the United States who have chronic obstructive pulmonary disease (COPD). Chronic obstructive pulmonary disease accounts for 3.2% of all physician office visits annually and is the fourth leading cause of death (126 000 deaths per year). Most patients are diagnosed by their primary care clinicians who must address the highly variable clinical features and responses to therapy. The diagnosis and treatment of COPD is rapidly changing, so understanding recent advances is important for the delivery of optimal patient care. OBSERVATIONS Chronic obstructive pulmonary disease is characterized by incompletely reversible expiratory airflow limitation. Spirometry is the reference standard for diagnosing and assessing the severity of COPD. All patients should be counseled about and receive preventive measures such as smoking cessation and vaccination. Treatment should be guided by the severity of lung impairment, symptoms such as dyspnea, the amount of cough and sputum production, and how often a patient experiences an exacerbation. When dyspnea limits activity or quality of life, COPD should be treated with once- or twice-daily maintenance long-acting anticholinergic and β-agonist bronchodilators. Patients with acute exacerbations may benefit from the addition of inhaled corticosteroids, particularly those with elevated peripheral eosinophil levels. Pulmonary rehabilitation, which includes strength and endurance training and educational, nutritional, and psychosocial support, improves symptoms and exercise tolerance but is underutilized. Supplemental oxygen for patients with resting hypoxemia (defined as Spo2 <89%) improves survival. CONCLUSIONS AND RELEVANCE Chronic obstructive pulmonary disease is a complicated disease requiring intensive treatment. Appropriate use of long-acting maintenance bronchodilators, inhaled corticosteroids, and pulmonary rehabilitation decreases symptoms, optimizes functional performance, and reduces exacerbation frequency. Supplemental oxygen in patients with resting hypoxemia prolongs life, and other advanced treatments are available based on specific patient characteristics.
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Guideline on management of the acute asthma attack in children by Italian Society of Pediatrics.
Indinnimeo, L, Chiappini, E, Miraglia Del Giudice, M, ,
Italian journal of pediatrics. 2018;(1):46
Abstract
BACKGROUND Acute asthma attack is a frequent condition in children. It is one of the most common reasons for emergency department (ED) visit and hospitalization. Appropriate care is fundamental, considering both the high prevalence of asthma in children, and its life-threatening risks. Italian Society of Pediatrics recently issued a guideline on the management of acute asthma attack in children over age 2, in ambulatory and emergency department settings. METHODS The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology was adopted. A literature search was performed using the Cochrane Library and Medline/PubMed databases, retrieving studies in English or Italian and including children over age 2 year. RESULTS Inhaled ß2 agonists are the first line drugs for acute asthma attack in children. Ipratropium bromide should be added in moderate/severe attacks. Early use of systemic steroids is associated with reduced risk of ED visits and hospitalization. High doses of inhaled steroids should not replace systemic steroids. Aminophylline use should be avoided in mild/moderate attacks. Weak evidence supports its use in life-threatening attacks. Epinephrine should not be used in the treatment of acute asthma for its lower cost / benefit ratio, compared to β2 agonists. Intravenous magnesium solphate could be used in children with severe attacks and/or forced expiratory volume1 (FEV1) lower than 60% predicted, unresponsive to initial inhaled therapy. Heliox could be administered in life-threatening attacks. Leukotriene receptor antagonists are not recommended. CONCLUSIONS This Guideline is expected to be a useful resource in managing acute asthma attacks in children over age 2.
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Inhaled magnesium sulfate in the treatment of acute asthma in children.
Normansell, R, Knightly, R, Milan, SJ, Knopp-Sihota, JA, Rowe, BH, Powell, C
Paediatric respiratory reviews. 2018;:31-33
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4.
Inhaled short-acting bronchodilators for managing emergency childhood asthma: an overview of reviews.
Pollock, M, Sinha, IP, Hartling, L, Rowe, BH, Schreiber, S, Fernandes, RM
Allergy. 2017;(2):183-200
Abstract
International guidelines provide conflicting recommendations on how to use bronchodilators to manage childhood acute wheezing conditions in the emergency department (ED), and there is variation within and among countries in how these conditions are managed. This may be reflective of uncertainty about the evidence. This overview of systematic reviews (SRs) aimed to synthesize, appraise, and present all SR evidence on the efficacy and safety of inhaled short-acting bronchodilators to treat asthma and wheeze exacerbations in children 0-18 years presenting to the ED. Searching, review selection, data extraction and analysis, and quality assessments were conducted using methods recommended by The Cochrane Collaboration. Thirteen SRs containing 56 relevant trials and 5526 patients were included. Results demonstrate the efficacy of short-acting beta-agonist (SABA) delivered by metered-dose inhaler as first-line therapy for younger and older children (hospital admission decreased by 44% in younger children, and ED length of stay decreased by 33 min in older children). Short-acting anticholinergic (SAAC) should be added to SABA for older children in severe cases (hospital admission decreased by 27% and 74% when compared to SABA and SAAC alone, respectively). Continuous nebulization, addition of magnesium sulfate to SABA, and levosalbutamol compared to salbutamol cannot be recommended in routine practice.
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5.
Therapeutic effects of different drugs on obstructive sleep apnea/hypopnea syndrome in children.
Zhang, J, Chen, J, Yin, Y, Zhang, L, Zhang, H
World journal of pediatrics : WJP. 2017;(6):537-543
Abstract
BACKGROUND This study aimed to compare the therapeutic effects of different drugs on obstructive sleep apnea/hypopnea syndrome (OSAHS) in children by using a network meta-analysis approach. METHODS PubMed, Embase and Cochrane Library were searched from the inception of each database to November 2015. Randomized controlled trials (RCTs) concerning the comparisons in the therapeutic effects of eight placebo-controlled drugs on OSAHS in children were included in this study. Network meta-analysis combined direct evidence and indirect evidence to evaluate the weighted mean difference (WMD) and surface under the cumulative ranking curves (SUCRA) of therapeutic effects of eight drugs on OSAHS in children. RESULTS A total of seven RCTs were finally incorporated into our network meta-analysis. Pairwise meta-analysis results revealed that therapeutic effect of placebo was significantly poorer than that of intranasal mometasone furoate, montelukast, budesonide and fluticasone concerning apnea hypopnea index (AHI) value [WMD=1.40, 95% confidence interval (CI)=1.17-1.63; WMD=2.80, 95% CI=1.01-4.59; WMD=3.50, 95% CI=3.34-3.66; WMD=7.20, 95% CI=5.26-9.14, respectively], and fluticasone is better than placebo concerning sleep efficiency (WMD=3.50, 95% CI=2.42-4.58); regarding visual analogue scale, the therapeutic effect of placebo was poorer compared with sucralfate and clindamycin (WMD=1.94, 95% CI=1.13-2.75; WMD=1.06, 95% CI=0.22-1.90), and sucralfate is better than clindamycin (WMD=-0.88, 95% CI=-1.65 to -0.11). However, network meta-analysis results showed no obvious difference in the therapeutic effects of different drugs on OSAHS regarding AHI and sleep efficiency. Furthermore, the best SUCRA value was very high for fluticasone concerning AHI (86.6%) and budesonide concerning sleep efficiency (94.0%) for OSAHS treatment. CONCLUSIONS Fluticasone and budesonide have relatively good effects in the treatment of OSAHS in children, thus providing an important guiding significance for the treatment of OSAHS in children.
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6.
Bronchoprotection and bronchorelaxation in asthma: New targets, and new ways to target the old ones.
Pera, T, Penn, RB
Pharmacology & therapeutics. 2016;:82-96
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Abstract
Despite over 50years of inhaled beta-agonists and corticosteroids as the default management or rescue drugs for asthma, recent research suggests that new therapeutic options are likely to emerge. This belief stems from both an improved understanding of what causes and regulates airway smooth muscle (ASM) contraction, and the identification of new targets whose inhibition or activation can relax ASM. In this review we discuss the recent findings that provide new insight into ASM contractile regulation, a revolution in pharmacology that identifies new ways to "tune" G protein-coupled receptors to improve therapeutic efficacy, and the discovery of several novel targets/approaches capable of effecting bronchoprotection or bronchodilation.
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The potential of methylxanthine-based therapies in pediatric respiratory tract diseases.
Oñatibia-Astibia, A, Martínez-Pinilla, E, Franco, R
Respiratory medicine. 2016;:1-9
Abstract
Caffeine, theophylline and theobromine are the most known methylxanthines as they are present in coffee, tea and/or chocolate. In the last decades, a huge experimental effort has been devoted to get insight into the variety of actions that these compounds exert in humans. From such knowledge it is known that methylxanthines have a great potential in prevention, therapy and/or management of a variety of diseases. The benefits of methylxanthine-based therapies in the apnea of prematurity and their translational potential in pediatric affections of the respiratory tract are here presented.
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[Current position of new fixed-dose combination of tiotropium and olodaterol - its role in the treatment of chronic obstructive pulmonary disease in the Czech Republic].
Koblížek, V, Svoboda, M
Vnitrni lekarstvi. 2016;(12):1011-1020
Abstract
COPD is a serious pulmonary disease with rising global socioeconomic impact. From the perspective of the Czech Republic COPD was responsible for 21 000 acute hospitalizations and 3 500 deaths, mortality reaches 33/100 000 in 2015. Early stages of disease may be associated with a significant reduction of exercise capacity and the reduction of activities of daily living. Moreover early stages of bronchial obstruction are associated with the fastest lung function decline. Finally, early elimination of the risk of inhalation exposure is able to influence the course of the disease and to reduce its mortality. Most current treatment strategies and national recommendations attributed central role to bronchodilator drugs. Long-acting bronchodilators (LAMA and LABA) creates an essential component of the treatment of symptomatic individuals in the Czech COPD guidelines as well. Actual version of this document constitutes as standard therapy: long-lasting inhaled bronchodilators, targeted efforts to eliminate inhalation risk, vaccination, regular exercise, repeated inhalation technique training, identification, and treatment of relevant comorbidities. All other drugs (inhaled-corticosteroids, mucoactive medication, roflumilast, antibiotics), and non-pharmacological (lung volume reductions, nutrition support, long-term oxygen, home non-invasive ventilation, lung transplantation, palliative care) procedures are intended for a specific subgroups of patients only. The newest type of bronchodilator therapy is represented by a fixed dual bronchodilation. Currently we can use four original drug combinations: titropium + olodaterol, glycopyrronium + indacaterol, umeklidinium + vilanterol and aclidinium + formoterol in the Czech Republic. This area is an enterprising research. For example comprehensive scientific program covering eight studies on 15 000 COPD patients (TOviTO) assess the therapeutic benefits of tiotropium + olodaterolu in terms of lung function, quality of life, exercise tolerance, daily physical activity and the incidence of acute exacerbations. Meanwhile the published results of analyzed studies TONADO, OTEMTO, VIVACITO, and the first results of the study DYNAGITO have showed that fixed dual bronchodilation should be a mandatory treatment to all the symptomatic COPD patients. Unfortunately "face to face" comparison of different drug combinations is still missing. However, the treatment with tiotropium + olodaterol combination has been demonstrated to significantly (35 %) reduce the occurrence of clinically significant deterioration, which may lead to the stabilization of this multicomponent disease.Key words: COPD - hospitalizations - inhaled bronchodilators - mortality - treatment.
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9.
Pharmacological management of chronic obstructive pulmonary disease.
Shaddock, E, Richards, G
South African medical journal = Suid-Afrikaanse tydskrif vir geneeskunde. 2015;(9):790
Abstract
There have been significant changes in the approach to the management of chronic obstructive pulmonary disease (COPD) over the pastdecade. The World Health Organization suggests four componentsto a COPD management plan: (i) assess and monitor disease; (ii) reducerisk factors; (iii) manage stable COPD; and (iv) manage exacerbations. Encouraging patients to limit their risk exposure is essential, whetherit be smoking cessation or removing exposure to biomass.The main objective of treatment is to relieve daily symptoms, improve quality of life and importantly decrease the risk of futureexacerbations. Current guidelines are based on grade A and B evidence. Pneumococcal and annual influenza vaccinations are encouraged.A holistic approach that augments pharmacological treatment includes good nutrition and pulmonary rehabilitation.Bronchodilators are the cornerstone of management. Depending on the patient’s placement in the GOLD ABCD classification, treatmentis individualised. Short-acting bronchodilators are used as rescue medication, while long-acting bronchodilators or/and long-actingmuscarinic agents are the treatment of choice for patients in groups B, C and D. Inhaled corticosteroids are only recommended for groups Cand D. Most patients respond well to combinations of the abovementioned medications. For patients who still have frequent exacerbations,alternative choices include long-term macrolides and phosphodiesterase 4 inhibitors.
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10.
Research and development of bronchodilators for asthma and COPD with a focus on G protein/KCa channel linkage and β2-adrenergic intrinsic efficacy.
Kume, H, Fukunaga, K, Oguma, T
Pharmacology & therapeutics. 2015;:75-89
Abstract
Bronchodilators are used to improve symptoms and lung function in asthma and COPD. Airway smooth muscle tone is regulated by both muscarinic and β2-adrenergic receptor activity. Large-conductance Ca(2+)-activated K(+) (KCa) channels are activated by β2-adrenergic receptor agonists, via Gs, and suppressed by muscarinic receptor antagonists via Gi. This functional antagonism converges on the G protein/KCa channel linkages. Membrane potential regulated by KCa channels contributes to airway smooth muscle tension via Ca(2+) influx passing through voltage-dependent Ca(2+) (VDC) channels. The Gs/KCa/VDC channel linkage is a key process in not only physiological effects, but also in dysfunction of β2-adrenergic receptors and airway remodeling. Moreover, this pathway is involved in the synergistic effects between β2-adrenergic receptor agonists and muscarinic receptor antagonists. Intrinsic efficacy is also an important characteristic for both maintenance and loss of β2-adrenergic action. Allosteric modulators of G protein-coupled receptors contribute not only to this synergistic effect between β2-adrenergic and muscarinic M2 receptors, but also to intrinsic efficacy. The effects of weak partial agonists are suppressed by lowering receptor number, disordering receptor function, and enhancing functional antagonism; in contrast, those of full or strong partial agonists are not suppressed. Excessive exposure to full agonists causes β2-adrenergic desensitization; in contrast, exposure to partial agonists does not cause desensitization. Intrinsic efficacy may provide the rationale for the clinical use of β2-adrenergic receptor agonists in asthma and COPD. In conclusion, the G protein/KCa linkage and intrinsic efficacy (allosteric effects) may be therapeutic targets for research and development of novel agents against both airway obstruction and airway remodeling.