Chronic bronchitis medical therapy: Difference between revisions

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__NOTOC__
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{{Chronic bronchitis}}
{{Chronic bronchitis}}
{{CMG}} {{AE}}
{{CMG}} {{AE}}{{MehdiP}}; {{NRM}}
==Overview==
The treatment plan for chronic bronchitis is divided into two main categories:
#Reduce symptoms: by relief of [[dyspnea]] and improve exercise tolerance
#Reduce risks: by treating exacerbations, preventing disease progression, and reducing mortality
 
==General Therapy==
* Patient education sessions about the disease, self-treatment plans for exacerbations, and a monthly follow-up calls from the hospital or nurse practitioner are associated with a lower hospitalization rate and fewer emergency department visits.<ref name="pmid15459997">{{cite journal |vauthors=Joy M |title=Management of chronic obstructive pulmonary disease |journal=N. Engl. J. Med. |volume=351 |issue=14 |pages=1461–3; author reply 1461–3 |year=2004 |pmid=15459997 |doi= |url=}}</ref> <ref name="pmid20075385">{{cite journal |author=Rice KL, Dewan N, Bloomfield HE, Grill J, Schult TM, Nelson DB, Kumari S, Thomas M, Geist LJ, Beaner C, Caldwell M, Niewoehner DE |title=Disease management program for chronic obstructive pulmonary disease: a randomized controlled trial |journal=[[American Journal of Respiratory and Critical Care Medicine]] |volume=182 |issue=7 |pages=890–6 |year=2010 |month=October |pmid=20075385 |doi=10.1164/rccm.200910-1579OC |url=http://ajrccm.atsjournals.org/cgi/pmidlookup?view=long&pmid=20075385 |accessdate=2012-03-20}}</ref><ref name="pmid21513435">{{cite journal |author=Dewan NA, Rice KL, Caldwell M, Hilleman DE |title=Economic evaluation of a disease management program for chronic obstructive pulmonary disease |journal=[[Copd]] |volume=8 |issue=3 |pages=153–9 |year=2011 |month=June |pmid=21513435 |doi=10.3109/15412555.2011.560129 |url=http://informahealthcare.com/doi/abs/10.3109/15412555.2011.560129 |accessdate=2012-03-20}}</ref>
* Treatment of COPD requires a careful and thorough evaluation by a physician.
* The most important aspect of treatment is avoiding [[tobacco]] smoke and removing other air pollutants from the patient’s home or workplace.
* Patients who have [[hypoxemia]] are often given supplemental oxygen.
* Oral and inhaled medications are used for patients with stable chronic obstructive pulmonary disease (COPD) to reduce [[dyspnea]], improve exercise tolerance, and prevent complications. Symptoms such as [[coughing]] or [[wheezing]] can be treated with [[bronchodilators]] like subcutaneous medications, [[beta-adrenergic]]s, [[methylxanthine]]s, and [[anticholinergic]]s. They act via decreasing muscle tone in small and large airways in the [[lung]]s.
* Respiratory infections should be treated with antibiotics, if appropriate.
* Nutritional support forms an integral part of management for COPD patients.
==Pulmonary Rehabilitation==
* Decreases the number of hospitalizations and the exacerbations.<ref name="pmid12137716">{{cite journal |vauthors=Lacasse Y, Brosseau L, Milne S, Martin S, Wong E, Guyatt GH, Goldstein RS |title=Pulmonary rehabilitation for chronic obstructive pulmonary disease |journal=Cochrane Database Syst Rev |volume= |issue=3 |pages=CD003793 |year=2002 |pmid=12137716 |doi=10.1002/14651858.CD003793 |url=}}</ref>
* Helpful to alleviate symptoms and improve lung capacities.<ref name="pmid10665556">{{cite journal |vauthors=Griffiths TL, Burr ML, Campbell IA, Lewis-Jenkins V, Mullins J, Shiels K, Turner-Lawlor PJ, Payne N, Newcombe RG, Ionescu AA, Thomas J, Tunbridge J, Lonescu AA |title=Results at 1 year of outpatient multidisciplinary pulmonary rehabilitation: a randomised controlled trial |journal=Lancet |volume=355 |issue=9201 |pages=362–8 |year=2000 |pmid=10665556 |doi= |url=}}</ref>
==Oxygen Therapy==
* [[COPD]] patients commonly have [[hypoxemia]], indicated by PaO2 (partial pressure of oxygen in arterial blood) of < 55 mm Hg or oxygen saturation of less than 90%.<ref name="pmid6110912">{{cite journal |vauthors= |title=Long term domiciliary oxygen therapy in chronic hypoxic cor pulmonale complicating chronic bronchitis and emphysema. Report of the Medical Research Council Working Party |journal=Lancet |volume=1 |issue=8222 |pages=681–6 |year=1981 |pmid=6110912 |doi= |url=}}</ref><ref name="pmid15459997">{{cite journal |vauthors=Joy M |title=Management of chronic obstructive pulmonary disease |journal=N. Engl. J. Med. |volume=351 |issue=14 |pages=1461–3; author reply 1461–3 |year=2004 |pmid=15459997 |doi= |url=}}</ref>
 
* Oxygen administration reduces mortality rates in patients with advanced COPD due to the favorable effects on pulmonary hemodynamics.<ref name="pmid9552012">{{cite journal |vauthors=Rennard SI |title=COPD: overview of definitions, epidemiology, and factors influencing its development |journal=Chest |volume=113 |issue=4 Suppl |pages=235S–241S |year=1998 |pmid=9552012 |doi= |url=}}</ref>
 
* Trials have shown long-term oxygen therapy (15-19 hours/day) improves survival in advanced COPD patients and thus long term oxygen therapy for hypoxemic patients (PaO2 < 55 mm Hg), patients with [[polycythemia]] and PaO2 < 59mm Hg or [[cor pulmonale]] is recommended. These patients require re-evaluation in 1-3 months whether they require long term oxygen therapy or not.
 
* Home oxygen supplementation is also recommended for patients who are well at rest but develop [[hypoxemia]] during exertion.<ref name="pmid6776858">{{cite journal |vauthors= |title=Continuous or nocturnal oxygen therapy in hypoxemic chronic obstructive lung disease: a clinical trial. Nocturnal Oxygen Therapy Trial Group |journal=Ann. Intern. Med. |volume=93 |issue=3 |pages=391–8 |year=1980 |pmid=6776858 |doi= |url=}}</ref><ref name="pmid12869359">{{cite journal |vauthors=Emtner M, Porszasz J, Burns M, Somfay A, Casaburi R |title=Benefits of supplemental oxygen in exercise training in nonhypoxemic chronic obstructive pulmonary disease patients |journal=Am. J. Respir. Crit. Care Med. |volume=168 |issue=9 |pages=1034–42 |year=2003 |pmid=12869359 |doi=10.1164/rccm.200212-1525OC |url=}}</ref>
 
* [[Oxygen therapy]] generally is safe. [[Oxygen toxicity]] from high inspired concentrations (>60%) is well recognized. Additionally, several concerns have been raised regarding carbon dioxide retention as a result of decreased respiratory drive due to increased oxygen concentration. This complication can be best avoided by maintaining PaO2 at 60-65 mm Hg.
* The major physical hazards of oxygen therapy are fires or explosions. Thus, patients and others must be warned not to smoke.<ref name="pmid15459997">{{cite journal |vauthors=Joy M |title=Management of chronic obstructive pulmonary disease |journal=N. Engl. J. Med. |volume=351 |issue=14 |pages=1461–3; author reply 1461–3 |year=2004 |pmid=15459997 |doi= |url=}}</ref>
 
* A [[nasal cannula]] may be used for oxygen therapy. Advantages of this device are<ref name="pmid15459997">{{cite journal |vauthors=Joy M |title=Management of chronic obstructive pulmonary disease |journal=N. Engl. J. Med. |volume=351 |issue=14 |pages=1461–3; author reply 1461–3 |year=2004 |pmid=15459997 |doi= |url=}}</ref>:
** It is simple and well tolerated
** A liter of oxygen increases [[FiO2]] ([[fraction of inspired oxygen]]) by 3-4%
** Nasal oxygen delivery is also beneficial for most mouth-breathing patients
** Humidification generally is not necessary when the patient receives oxygen by nasal cannula at flows of less than 5 L/min
* Noninvasive positive-pressure ventilation (NIPPV) is an alternative device for oxygen therapy. Its advantages include:
** It allows the delivery of positive-pressure ventilation without the use of an [[endotracheal tube]].
** It has a tight-fitting nasal or facial mask that is attached to a [[continuous positive airway pressure]] (CPAP) or a [[bilevel positive airway pressure]] (BiPAP) machine
** The positive pressure is beneficial in [[Hypercapnia|hypercapneic]] respiratory failure by decreasing the work of breathing
** NIPPV has been shown to decrease the need for [[endotracheal intubation]], duration of hospital stay, morbidity, and mortality.
** Contraindication for use:
*** Patients unable to protect airway
*** Hemodynamically unstable
*** Have significant secretions
*** Uncooperative
*** Acute Physiology and Chronic Health Evaluation (APACHE) score of greater than 29
==Smoking Cessation==
* Smoking cessation is the most important therapeutic intervention for COPD. It has been demonstrated that it is more effective than [[bronchodilators]] in the course of treatment.<ref name="pmid7966841">{{cite journal |vauthors=Anthonisen NR, Connett JE, Kiley JP, Altose MD, Bailey WC, Buist AS, Conway WA, Enright PL, Kanner RE, O'Hara P |title=Effects of smoking intervention and the use of an inhaled anticholinergic bronchodilator on the rate of decline of FEV1. The Lung Health Study |journal=JAMA |volume=272 |issue=19 |pages=1497–505 |year=1994 |pmid=7966841 |doi= |url=}}</ref><ref name="pmid15459997">{{cite journal |vauthors=Joy M |title=Management of chronic obstructive pulmonary disease |journal=N. Engl. J. Med. |volume=351 |issue=14 |pages=1461–3; author reply 1461–3 |year=2004 |pmid=15459997 |doi= |url=}}</ref>
* Smoking cessation education and support should be offered to every patient with COPD, at every visit. Even temporary quit or cutting down the numbers will improve the outcomes compared to continued smokers.<ref name="pmid15710956">{{cite journal |vauthors=Anthonisen NR, Skeans MA, Wise RA, Manfreda J, Kanner RE, Connett JE |title=The effects of a smoking cessation intervention on 14.5-year mortality: a randomized clinical trial |journal=Ann. Intern. Med. |volume=142 |issue=4 |pages=233–9 |year=2005 |pmid=15710956 |doi= |url=}}</ref>
* Behavioral counseling (< 10 min) and pharmacotherapy are each effective alone. However, they have a synergistic effect when used together.
 
* Supervised use of pharmacologic agents is an important adjunct to self-help and group smoking cessation programs.
 
* Nicotine addiction is quite strong and cessation at times is difficult. Withdrawal from nicotine may cause unpleasant adverse effects, such as [[anxiety]], [[irritability]], difficulty concentrating, [[fatigue]], [[drowsiness]], [[depression]], and sleep disruption.
 
* Highly addicted individuals (e.g. require a cigarette within 30 minutes of waking in the morning) would benefit from nicotine replacement therapy.
 
===Nicotine Replacement Therapies===
====Transdermal Nicotine Patches====
* Trade name: NicoDerm, Nicotrol, and Habitrol
* Success rates better compared with placebo
* Well tolerated, adverse effects are limited to local skin reactions<ref name="pmid20124230">{{cite journal |vauthors=Schnoll RA, Patterson F, Wileyto EP, Heitjan DF, Shields AE, Asch DA, Lerman C |title=Effectiveness of extended-duration transdermal nicotine therapy: a randomized trial |journal=Ann. Intern. Med. |volume=152 |issue=3 |pages=144–51 |year=2010 |pmid=20124230 |pmc=3782858 |doi=10.7326/0003-4819-152-3-201002020-00005 |url=}}</ref>
====Bupropion====
* Class: Antidepressant
* Trade name: Zyban
* It enhances central nervous system nonadrenergic function
* Better results compared to placebo
* [[Bupropion]] may be effective in patients who failed to quit smoking with nicotine replacement therapy<ref name="pmid24402784">{{cite journal |vauthors=Hughes JR, Stead LF, Hartmann-Boyce J, Cahill K, Lancaster T |title=Antidepressants for smoking cessation |journal=Cochrane Database Syst Rev |volume= |issue=1 |pages=CD000031 |year=2014 |pmid=24402784 |doi=10.1002/14651858.CD000031.pub4 |url=}}</ref>
 
====Varenicline====
* Trade name: Chantix
* [[Varenicline]] is a partial agonist selective for alpha4, beta2 [[Nicotinic acetylcholine receptor|nicotinic acetylcholine receptors]].
* Acts by binding to nicotinic acetylcholine receptors and produces agonist activity and prevents nicotine binding<ref name="pmid18987369">{{cite journal |vauthors=Hays JT, Ebbert JO |title=Varenicline for tobacco dependence |journal=N. Engl. J. Med. |volume=359 |issue=19 |pages=2018–24 |year=2008 |pmid=18987369 |pmc=2959114 |doi=10.1056/NEJMct0800146 |url=}}</ref>
===Vaccination===
* [[Pneumococcal vaccine]] should be given to all patients older than 65 years or to patients of any age with FEV1 of < 40%
* The [[influenza vaccine]] should be given annually to all COPD patients<ref name="pmid15189916">{{cite journal |vauthors=Wongsurakiat P, Maranetra KN, Wasi C, Kositanont U, Dejsomritrutai W, Charoenratanakul S |title=Acute respiratory illness in patients with COPD and the effectiveness of influenza vaccination: a randomized controlled study |journal=Chest |volume=125 |issue=6 |pages=2011–20 |year=2004 |pmid=15189916 |doi= |url=}}</ref>
 
==Medical treatment==
===Beta Adrenergic Receptor Agonists===
====Short Acting Selective B2 Agonist====
* Used for symptomatic relief during acute mild, exacerbation.
* Mechanism of action: increases intracellular [[cyclic adenosine monophosphate]] via activation of B2-adrenergic receptors on smooth muscle cells of airway and causes smooth muscle relaxation.
* These agents are less effective in COPD compared to [[asthma]].
* Patients may not have increase in peak flows with treatment but should be continued if it offers symptomatic relief.
* The inhaled route is preferred as there is less systemic absorption thus less side-effects.
* Adverse effects include [[tachycardia]], [[tremors]] and [[cardiac arrhythmia]].<ref name="pmid12832670">{{cite journal |vauthors=Ram FS, Sestini P |title=Regular inhaled short acting beta2 agonists for the management of stable chronic obstructive pulmonary disease: Cochrane systematic review and meta-analysis |journal=Thorax |volume=58 |issue=7 |pages=580–4 |year=2003 |pmid=12832670 |pmc=1746735 |doi= |url=}}</ref>
Drugs available in this category are:
=====[[Albuterol]], [[Metaproterenol]], [[Pirbuterol]]=====
* Inhalation aerosol or powder: 2 inhalations every 4 to 6 hours as needed
=====[[Levalbuterol]]=====
* [[Albuterol]] is a racemic mixture containing both R and S [[enantiomer]]. The S enantiomer doesn't bind to Beta 2 receptor and may cause side-effects. On the other hand, [[levalbuterol]] has only active R enantiomer thus causes less side-effects.
* It is used for both treatment and prevention of [[bronchospasm]].
 
====Long Acting Beta-2 Adrenergic Receptor Agonist====
* The long acting beta 2 receptor agonists are used to alleviate chronic persistent symptoms.
* They help to increase exercise tolerance, prevent nocturnal [[dyspnea]], and improve quality of life.
* Long-acting beta-agonists include [[salmeterol]], [[formoterol]], [[arformoterol]], and [[indacaterol]].
* They all require twice-daily dosing, except for indacaterol. Bronchodilating effect lasts more than 12 hours. Indacaterol is administered once daily.<ref name="pmid14600189">{{cite journal |vauthors=Sin DD, McAlister FA, Man SF, Anthonisen NR |title=Contemporary management of chronic obstructive pulmonary disease: scientific review |journal=JAMA |volume=290 |issue=17 |pages=2301–12 |year=2003 |pmid=14600189 |doi=10.1001/jama.290.17.2301 |url=}}</ref><ref name="pmid17314337">{{cite journal |vauthors=Calverley PM, Anderson JA, Celli B, Ferguson GT, Jenkins C, Jones PW, Yates JC, Vestbo J |title=Salmeterol and fluticasone propionate and survival in chronic obstructive pulmonary disease |journal=N. Engl. J. Med. |volume=356 |issue=8 |pages=775–89 |year=2007 |pmid=17314337 |doi=10.1056/NEJMoa063070 |url=}}</ref>
 
=====Salmeterol, Formoterol, Arformoterol=====
* Long term relieve of [[bronchospasm]]s.<ref name="pmid17314337">{{cite journal |vauthors=Calverley PM, Anderson JA, Celli B, Ferguson GT, Jenkins C, Jones PW, Yates JC, Vestbo J |title=Salmeterol and fluticasone propionate and survival in chronic obstructive pulmonary disease |journal=N. Engl. J. Med. |volume=356 |issue=8 |pages=775–89 |year=2007 |pmid=17314337 |doi=10.1056/NEJMoa063070 |url=}}</ref>
 
* Facilitate expectoration, improve symptoms and morning peak flows.
 
* Used in addition to [[anticholinergic]] agents.<ref name="pmid14600189">{{cite journal |vauthors=Sin DD, McAlister FA, Man SF, Anthonisen NR |title=Contemporary management of chronic obstructive pulmonary disease: scientific review |journal=JAMA |volume=290 |issue=17 |pages=2301–12 |year=2003 |pmid=14600189 |doi=10.1001/jama.290.17.2301 |url=}}</ref><ref name="pmid24127118">{{cite journal |vauthors=Kew KM, Mavergames C, Walters JA |title=Long-acting beta2-agonists for chronic obstructive pulmonary disease |journal=Cochrane Database Syst Rev |volume= |issue=10 |pages=CD010177 |year=2013 |pmid=24127118 |doi=10.1002/14651858.CD010177.pub2 |url=}}</ref>
 
=====Arformoterol=====
* Higher potency than racemic [[formoterol]].
====Indacaterol====
* [[Indacaterol]] a long-acting beta2-agonist (LABA) is used for long-term, once-daily maintenance in patients with chronic obstructive pulmonary disease (COPD).<ref name="pmid21349928">{{cite journal |author=Chapman KR, Rennard SI, Dogra A, Owen R, Lassen C, Kramer B |title=Long-term safety and efficacy of indacaterol, a long-acting β₂-agonist, in subjects with COPD: a randomized, placebo-controlled study |journal=[[Chest]] |volume=140 |issue=1 |pages=68–75 |year=2011 |month=July |pmid=21349928 |doi=10.1378/chest.10-1830 |url=http://www.chestjournal.org/cgi/pmidlookup?view=long&pmid=21349928 |accessdate=2012-03-19}}</ref>
* It is not for use as initial therapy in patients with acute deteriorating [[COPD]].
 
===Anticholinergics===
* [[Anticholinergic drug|Anticholinergic drugs]] act as a competitive inhibitor of [[acetylcholine]] and block their action on postganglionic muscarinic receptors, thus inhibiting cholinergically mediated [[bronchospasm]] and resulting in [[bronchodilation]].
 
* They block vagally mediated reflex arcs that cause [[bronchoconstriction]].
 
* Reported adverse effects include dry mouth, metallic taste, and prostatic symptoms. Studies have found an increased incidence of acute urinary retention in patient above 66 years using inhaled anticholinergic medications than in nonusers.<ref name="pmid21606097">{{cite journal |author=Singh S, Furberg CD |title=Inhaled anticholinergics for chronic obstructive pulmonary disease: comment on "Inhaled anticholinergic drug therapy and the risk of acute urinary retention in chronic obstructive pulmonary disease" |journal=[[Archives of Internal Medicine]] |volume=171 |issue=10 |pages=920–2 |year=2011 |month=May |pmid=21606097 |doi=10.1001/archinternmed.2011.171 |url=http://archinte.ama-assn.org/cgi/pmidlookup?view=long&pmid=21606097 |accessdate=2012-03-21}}</ref>
 
=====Ipratropium=====
 
* Has similar efficacy as beta 2 adrenergic receptor agonist.
* Has a synergistic effect on [[bronchodilation]] when combined with beta 2 agonist.
* They have a slower onset and longer duration of action, thus may be less helpful in use on an as-needed basis.
* Dose: 2-4 puffs every 6-8 hours.<ref name="pmid12449166">{{cite journal |vauthors=Wadbo M, Löfdahl CG, Larsson K, Skoogh BE, Tornling G, Arweström E, Bengtsson T, Ström K |title=Effects of formoterol and ipratropium bromide in COPD: a 3-month placebo-controlled study |journal=Eur. Respir. J. |volume=20 |issue=5 |pages=1138–46 |year=2002 |pmid=12449166 |doi= |url=}}</ref>
 
====Tiotropium====
* It is the only long-acting muscarinic (once daily) anticholinergic agent available at this time.
* It has become a first-line therapy in patients with persistent symptoms.
* It is more effective than [[salmeterol]] in preventing exacerbation.<ref name="pmid16537846">{{cite journal |vauthors=van Noord JA, Aumann JL, Janssens E, Verhaert J, Smeets JJ, Mueller A, Cornelissen PJ |title=Effects of tiotropium with and without formoterol on airflow obstruction and resting hyperinflation in patients with COPD |journal=Chest |volume=129 |issue=3 |pages=509–17 |year=2006 |pmid=16537846 |doi=10.1378/chest.129.3.509 |url=}}</ref> <ref name="pmid21428765">{{cite journal |author=Vogelmeier C, Hederer B, Glaab T, Schmidt H, Rutten-van Mölken MP, Beeh KM, Rabe KF, Fabbri LM |title=Tiotropium versus salmeterol for the prevention of exacerbations of COPD |journal=[[The New England Journal of Medicine]] |volume=364 |issue=12 |pages=1093–1103 |year=2011 |month=March |pmid=21428765 |doi=10.1056/NEJMoa1008378 |url=http://dx.doi.org/10.1056/NEJMoa1008378 |accessdate=2012-03-19}}</ref>
 
===Phosphodiesterase Inhibitor===
====Xanthine Derivatives (Theophylline) (Non Specific)====
* Causes inhibition of enzyme [[phosphodiesterase]] (non-specific) that in turn increases [[cyclic adenosine monophosphate]] (cAMP), causing the relaxation of bronchial smooth muscles.
 
* It is mostly used as an adjunctive agent and reserved in non-responsive patients or patients having difficulty using inhaled agents.
 
* It has a narrow therapeutic index and several adverse effects, such as [[anxiety]], [[tremors]], [[insomnia]], [[nausea]], [[cardiac arrhythmia]] ([[multifocal atrial tachycardia]]), and [[seizures]] above the therapeutics range. Previously, the recommended target range was 15-20 mg/dL. However, now it has been reduced to 8-13 mg/dL.
 
* It is metabolized via [[Cytochrome P450|cytochrome P 450]] system. Thus, the plasma concentration of [[theophylline]] is affected by age, cardiac status, and liver abnormalities.<ref name="pmid2498658">{{cite journal |vauthors=Murciano D, Auclair MH, Pariente R, Aubier M |title=A randomized, controlled trial of theophylline in patients with severe chronic obstructive pulmonary disease |journal=N. Engl. J. Med. |volume=320 |issue=23 |pages=1521–5 |year=1989 |pmid=2498658 |doi=10.1056/NEJM198906083202304 |url=}}</ref>
====Phosphodiesterase Type 4 Inhibitors (Specific)====
====Cilomilast, Roflumilast====
* Second generation, selective phosphodiesterase-4 inhibitors.<ref name="pmid15639300">{{cite journal |vauthors=Lipworth BJ |title=Phosphodiesterase-4 inhibitors for asthma and chronic obstructive pulmonary disease |journal=Lancet |volume=365 |issue=9454 |pages=167–75 |year=2005 |pmid=15639300 |doi=10.1016/S0140-6736(05)17708-3 |url=}}</ref>
* Decreases inflammatory mediators like [[macrophages]] and [[CD8]] lymphocytes.
* [[Roflumilast]] helps in reducing exacerbations, improve [[dyspnea]], and increase lung function in patients with severe COPD. However, roflumilast has not gained FDA approval for clinical use, largely because of side effects including significant [[nausea]].
* Cilomilast, another drug in this class, is still in preliminary clinical trials. It is administered orally and is given in 15mg dose twice daily.<ref name="pmid15639300">{{cite journal |vauthors=Lipworth BJ |title=Phosphodiesterase-4 inhibitors for asthma and chronic obstructive pulmonary disease |journal=Lancet |volume=365 |issue=9454 |pages=167–75 |year=2005 |pmid=15639300 |doi=10.1016/S0140-6736(05)17708-3 |url=}}</ref>
===Steroid===
* Systemic (high doses intravenous) and inhaled [[corticosteroids]] act as anti-inflammatory agents and reduce the course of the disease, symptoms, treatment failure, and need for additional therapy.
* Systemic steroids may be used in the treatment of acute exacerbation.<ref name="pmid16034972">{{cite journal |vauthors=Walters JA, Walters EH, Wood-Baker R |title=Oral corticosteroids for stable chronic obstructive pulmonary disease |journal=Cochrane Database Syst Rev |volume= |issue=3 |pages=CD005374 |year=2005 |pmid=16034972 |doi=10.1002/14651858.CD005374 |url=}}</ref>
* The 2011 ICSI guidelines conclude that inhaled steroids are appropriate in patients with recurrent exacerbation of COPD.
* Studies have shown inhaled corticosteroids along with long acting beta agonist to be more beneficial than inhaled steroid alone.<ref name="pmid15707484">{{cite journal |vauthors=Gan WQ, Man SF, Sin DD |title=Effects of inhaled corticosteroids on sputum cell counts in stable chronic obstructive pulmonary disease: a systematic review and a meta-analysis |journal=BMC Pulm Med |volume=5 |issue= |pages=3 |year=2005 |pmid=15707484 |pmc=552309 |doi=10.1186/1471-2466-5-3 |url=}}</ref>
* Studies have shown an increased risk of [[pneumonia]] in patients treated with inhaled corticosteroids. The debate continues on the use of inhaled corticosteroids and the risk for pneumonia in patients with COPD.<ref name="pmid19716963">{{cite journal |author=Sin DD, Tashkin D, Zhang X, Radner F, Sjöbring U, Thorén A, Calverley PM, Rennard SI |title=Budesonide and the risk of pneumonia: a meta-analysis of individual patient data |journal=[[Lancet]] |volume=374 |issue=9691 |pages=712–9 |year=2009 |month=August |pmid=19716963 |doi=10.1016/S0140-6736(09)61250-2 |url=http://linkinghub.elsevier.com/retrieve/pii/S0140-6736(09)61250-2 |accessdate=2012-03-21}}</ref><ref name="pmid17314337">{{cite journal |author=Calverley PM, Anderson JA, Celli B, Ferguson GT, Jenkins C, Jones PW, Yates JC, Vestbo J |title=Salmeterol and fluticasone propionate and survival in chronic obstructive pulmonary disease |journal=[[The New England Journal of Medicine]] |volume=356 |issue=8 |pages=775–89 |year=2007 |month=February |pmid=17314337 |doi=10.1056/NEJMoa063070 |url=http://dx.doi.org/10.1056/NEJMoa063070 |accessdate=2012-03-21}}</ref>
* Use of oral steroids in stable COPD patients is not encouraged due to increased adverse effects ([[hypertension]], [[glucose intolerance]], [[osteoporosis]], [[fractures]], and [[cataracts]]).
 
===Antibiotics===
====Anti Inflammatory====
* [[Macrolides]] like [[azithromycin]] have been occasionally used in treatment of COPD due to their anti-inflammatory properties.<ref name="pmid18723437">{{cite journal |author=Seemungal TA, Wilkinson TM, Hurst JR, Perera WR, Sapsford RJ, Wedzicha JA |title=Long-term erythromycin therapy is associated with decreased chronic obstructive pulmonary disease exacerbations |journal=[[American Journal of Respiratory and Critical Care Medicine]] |volume=178 |issue=11 |pages=1139–47 |year=2008 |month=December |pmid=18723437 |doi=10.1164/rccm.200801-145OC |url=http://ajrccm.atsjournals.org/cgi/pmidlookup?view=long&pmid=18723437 |accessdate=2012-03-21}}</ref><ref name="pmid21864166">{{cite journal |author=Albert RK, Connett J, Bailey WC, Casaburi R, Cooper JA, Criner GJ, Curtis JL, Dransfield MT, Han MK, Lazarus SC, Make B, Marchetti N, Martinez FJ, Madinger NE, McEvoy C, Niewoehner DE, Porsasz J, Price CS, Reilly J, Scanlon PD, Sciurba FC, Scharf SM, Washko GR, Woodruff PG, Anthonisen NR |title=Azithromycin for prevention of exacerbations of COPD |journal=[[The New England Journal of Medicine]] |volume=365 |issue=8 |pages=689–98 |year=2011 |month=August |pmid=21864166 |pmc=3220999 |doi=10.1056/NEJMoa1104623 |url=http://dx.doi.org/10.1056/NEJMoa1104623 |accessdate=2012-03-21}}</ref> However, due to increased incidences of [[hearing loss]] and development of antibiotics resistance with azithromycin use, it has not been used on wide scales.
====Infections====
* Common organisms involved in acute exacerbation of COPD are [[S. pneumoniae]], [[Haemophilus influenzae|H. influenzae]], M. catarrhalis and rarely [[Pseudomonas aeruginosa|P. aeruginosa]]. Antibiotics are commonly used in the treatment of acute exacerbation or suggestive of infection. However, regular long term antibiotics used for prevention of COPD exacerbation is not encouraged.
* [[Doxycycline]] has shown superior results for clinical cure, microbiological outcome, use of open label antibiotics, and symptoms.
===Beta Adrenergic Receptor Blocker===
COPD patients have increased risks of cardiovascular diseases. However, non-selective beta blockers have been found to increase the risks of [[bronchospasm]] and are thus not recommended in these patients. Interestingly, a study has shown that addition of cardioselective beta-blocker along with standard inhaled COPD treatment with beta 2 selective agonist didn't affect the pulmonary function of the patients. Additionally, it reduced COPD exacerbation, hospital admission and all-cause mortality during a follow up of 4.35 years with 5977 COPD patients.<ref name="pmid21558357">{{cite journal |author=Short PM, Lipworth SI, Elder DH, Schembri S, Lipworth BJ |title=Effect of beta blockers in treatment of chronic obstructive pulmonary disease: a retrospective cohort study |journal=[[BMJ (Clinical Research Ed.)]] |volume=342 |issue= |pages=d2549 |year=2011 |pmid=21558357 |pmc=3091487 |doi= |url=http://www.bmj.com/cgi/pmidlookup?view=long&pmid=21558357 |accessdate=2012-03-21}}</ref>
===Mucolytic===
* The efficacy of [[Mucolytic agent|mucolytic agents]] in the treatment of COPD remains controversial.
* The oral agent [[N-acetylcysteine]] has antioxidant and mucolytic properties (decreases sputum viscosity and secretion) and is used to treat patients with COPD.
* When used as an inhalational therapy, N-acetylcysteine should be administered along with a [[bronchodilator]] such as [[albuterol]] in order to counteract potential induction of [[bronchospasm]].
 
===Route of Therapy===
* Inhaled delivery is preferred over the oral route as there is less systemic absorption via inhaled route thus less adverse effects. However, some patients may have difficulty achieving effective delivery of the medication using a metered-dose inhaler. Use of spacer or [[nebulizer]] may be beneficial in them.
 
==GOLD Recommendations for Management of COPD==
{| border="1" cellpadding="5" cellspacing="0" align="center" class="sortable"
|+ '''GOLD recommendations for management of COPD'''
|-
  ! Stage
  ! Degree of airway obstruction
  ! Treatment
|-
  ! Stage I
  | Mild
  |
* [[Influenza vaccine]] (decrease risk)
* Short acting Beta 2 receptor agonist
|-
  ! Stage II
  | Moderate
  |
* Influenza vaccine (decrease risk)
* Short acting Beta 2 receptor agonist
* Long-acting [[bronchodilator]]
* [[Cardiopulmonary rehabilitation]]
|-
  ! Stage III
  | Severe
  |
* Influenza vaccine (decrease risk)
* Short acting Beta 2 receptor agonist
* Long-acting bronchodilator
* Cardiopulmonary rehabilitation
* Inhaled steroids in case of frequent exacerbation
|-
  ! Stage IV
  |
Very severe or moderate with evidence of chronic respiratory failure
  |
* Influenza vaccine (decrease risk)
* Short acting Beta 2 receptor agonist
* Long term oxygen therapy
* Lung transplant can be considered
|}
 
 
 
 
Chronic obstructive pulmonary disease treatment
::* Preferred regimen
:::* '''Beta2-agonist'''
:::: (1) Short acting: [[Fenoterol]] 100-200 mcg metered dose inhaler; 1 mg/ml solution for nebulizer ; 0.05 % syrup oral, duration of action 4-6 hrs {{or}} [[Levalbuterol]] 45-90 mcg metered dose inhaler; 0.21 mg/ml -0.42 mg/ml solution for nebulizer ; duration of action 6-8 hrs {{or}} [[Salbutamol]] 100-200 mcg metered dose inhaler and dry powder inhaler; 5 mg/ml solution for nebulizer ; 5 mg pill ; 0.024 % syrup oral; 0.1 mg, 0.5 mg vials for injection ; duration of action 4-6 hrs {{or}} [[Terbutaline]] 400-500 mcg dry powder inhaler and 2.5 mg,5 mg pill oral, duration of action 4-6 hrs
:::: (2) Long acting : [[Formoterol]] 4.5 mcg-12 mcg metered dose inhaler and dry powder inhaler ; 0.01 mg/ml solution for nebulizer ; duration of action 12 hrs {{or}} [[Arformoterol]] 0.0075 mg/ml solution for nebulizer ; duration of action 12 hrs {{or}} [[Indacaterol]] 75 mcg-300 mcg dry powder inhaler; duration of action  24 hrs {{or}} [[Salmeterol]] 25 mcg-50 mcg metered dose inhaler and dry powder inhaler ; duration of action 12 hrs {{or}} [[Tulobuterol]] 2 mg transdermal ; duration of action 24 hrs
 
:::* '''Anticholinergics'''
:::: (1) Short acting: [[Ipratropium bromide]] 20 mcg-40 mcg metered dose inhaler; duration of action 6-8 hrs {{or}} [[Oxitropium bromide]] 100 mcg metered dose inhaler; duration of action 7-9 hrs
:::: (2) Long acting: [[Aclidinium bromide]] 322 mcg dry powder inhaler; duration of action 12 hrs {{or}} [[Glycopyrronium bromide]]  44 mcg dry powder inhaler; duration of action 24 hrs {{or}} [[Tiotropium]] 18 mcg; 5 mcg soft mist inhaler; duration of action 24 hrs {{or}} [[Umeclidinium]] 62.5 mcg dry powder inhaler; duration of action 24 hrs
 
:::* '''Combination of short acting beta2 agonist and anticholinergics in one inhaler''': [[Fenoterol]]/[[Ipratropium bromide]] 200-80 mcg metered dose inhaler; 0.25-0.5 solution for nebulizer; duration of action 6-8 hrs {{or}} [[Salbutamol]]/[[Ipratropium bromide]] 100-20 mcg soft mist inhaler; 1.5 solution for nebulizer; duration of action 6-8 hrs
 
:::* '''Combination of long acting beta2 agonist and anticholinergics in one inhaler''': [[Formoterol]]/[[Aclidinium bromide]] 12 mcg/340 mcg dry powder inhaler; duration of action 12 hrs {{or}} [[Indacaterol]]/[[Glycopyrronium bromide]] 85 mcg/43 mcg dry powder inhaler; duration of action 24 hrs {{or}} Vilanterol/[[Umeclidinium]] 25 mcg/62.5 mcg dry powder inhaler; duration of action 24 hrs
 
:::* '''Methylxanthines''': [[Aminophylline]] 200-600 mg pill oral; 240 mg injection {{or}} [[Theophylline]] 100-600 mg pill oral; duration of action variable upto 24 hrs
 
:::* '''Inhaled corticosteroids''': [[Beclomethasone]] 50 mcg-400 mcg metered dose inhaler and dry powder inhaler; 0.2 mg/ml-0.4  mg/ml solution for nebulizer {{or}} [[Budesonide]] 100 mcg,200 mcg,400 mcg dry powder inhaler; 0.20 mg/ml, 0.25mg/ml ,0.5 mg/ml solution for nebulizer {{or}} [[Fluticasone]] 50 mcg-500 mcg metered dose inhaler and dry powder inhaler
 
:::* '''Combination of long acting beta2 agonist and corticosteroids in one inhaler''': [[Formoterol]]/[[Beclomethasone]] 6/100 metered dose inhaler, dry powder inhaler  {{or}} [[Formoterol]]/[[Budesonide]] 4.5/160 metered dose inhaler ; 9/320 dry powder inhaler {{or}} [[Formoterol]]/[[Mometasone]] 10/200 metered dose inhaler ; 10/400 metered dose inhaler  {{or}} [[Salmeterol]]/[[Fluticasone]] 50/100,250,500 dry powder inhaler {{or}} Vilanterol/[[Fluticasone furoate]] 25/100 dry powder inhaler
 
:::*''' Systemic corticosteroids''': [[Prednisolone]] 5 mg,60 mg pill oral; [[Methylprednisolone]] 4 mg,8 mg,16 mg pill oral
 
:::* '''Phosphodiesterase-4 inhibitors''': [[Roflumilast]] 500 mcg pill oral; duration of action is 24 hrs.
 
:::: Note: [[Formoterol]] nebulized solution is based on the unit dose containing 20 mcg in a volume of 2.0 ml.
 
::* Alternative regimen
:::* '''Vaccination'''
:::: (1) Influenza vaccination containing killed or live inactivated virus is more effective in elderly patients with chronic obstructive pulmonary disease.
:::: (2) Pneumococcal polysaccharide vaccine is recommended for chronic obstructive pulmonary disease in elderly patients 65 years and older, and also in younger patient with significant comorbid conditions such as cardiac disease.This vaccine also shown to reduce the incidence of community acquired pneumonia in chronic obstructive pulmonary disease patients younger than age 65 years with an FEV1< 40 % predicted.
 
:::* '''Alpha-1 antitrypsin augmentation therapy'''
:::: Young patients with severe hereditary alpha-1 antitrypsin deficiency and established significant emphysema may be the candidates for alpha-1 antitrypsin augmentation therapy.
 
:::* '''Antibiotics'''
:::: The use of antibiotics, other than for treating infectious exacerbations of chronic obstructive pulmonary disease and other bacterial infections is currently not indicated.
 
:::* '''Mucolytics (mucokinetic and mucoregulator) and antioxidant agents (ambroxol, erdosteine, carbocysteine, iodinated glycerol, N-acetylcysteine)'''
:::: (1) Although a few patients with viscous sputum may benefit from mucolytics, the overall benefits seems to be very small; their wide spread use is not recommended.
:::: (2) There is some evidence that in chronic obstructive pulmonary disease patients not receiving inhaled corticosteroids, treated with mucolytics and N-acetylcysteine may reduce exacerbations.
 
:::* '''Immunoregulators (immunomodulators,immunostimulators)''': Studies using an immunoregulator in chronic obstructive pulmonary disease report a decrease in the severity and frequency of exacerbations.
 
:::* '''Antitussives''': has a significant protective role but the regular usage of antitussives is not recommended in stable chronic obstructive pulmonary disease patients.
 
:::* '''Narcotics ([[morphine]])''': Oral and parenteral opioids are effective for treating dyspnea in chronic obstructive pulmonary disease patients with very severe disease.
 
:::* Others: Oxygen therapy, ventilation support.


==Overview==
:* '''Initial pharmacological management of chronic obstructive pulmonary disease'''
Antimicrobial therapy is the mainstay of therapy in acute exacerbation of chronic bronchitisPatients with severe disease and existing comorbidities require hospital admission. When pseudomonas infection is suspected, the preferred regimen for inpatient management includes either [[Cephalosporins]] or [[Piperacillin-Tazobactam]].
::* Group A patients: Have few symptoms and low risk of exacerbations.
:::* Preferred regimen: Short acting anticholinergics {{or}} short acting beta2 agonist
:::* Alternative regimen (1): Long acting anticholinergics {{or}} long acting beta2 agonist {{or}} short acting beta2 agonist {{and}} short acting anticholinergics
:::* Alternative regimen (2): [[Theophylline]]
::* Group B patients: Have more significant symptoms but still low risk of exacerbations
:::* Preferred regimen: Long acting anticholinergics {{or}} long acting beta2 agonist
:::* Alternative regimen (1): Long acting anticholinergics {{and}} long acting beta2 agonist
:::* Alternative regimen (2): short acting beta2 agonist {{and}}/ {{or}} short acting anticholinergics
[[Theophylline]]
::* Group C patients: Have few symptoms but high risk of exacerbations
:::* Alternative regimen (1):
:::* Alternative regimen (2):
::* Group D patients: Have many significant symptoms and high risk of exacerbations.
:::* Alternative regimen (1):
:::* Alternative regimen (2):
 
==External Links==
[http://www.cdc.gov/copd/ COPD CDC]


==Medical Therapy==
===Acute exacerbation of chronic bronchitis===
====Antimicrobial Regimen====
:* '''Acute exacerbation of chronic bronchitis'''<ref name="pmid15555829">{{cite journal| author=Sethi S, Murphy TF| title=Acute exacerbations of chronic bronchitis: new developments concerning microbiology and pathophysiology--impact on approaches to risk stratification and therapy. | journal=Infect Dis Clin North Am | year= 2004 | volume= 18 | issue= 4 | pages= 861-82, ix | pmid=15555829 | doi=10.1016/j.idc.2004.07.006 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15555829  }} </ref>
::* '''1. Outpatient management'''
:::* Patients with only 1 of the 3 cardinal symptoms of COPD (↑ dyspnea, ↑ sputum volume, ↑ sputum purulence) may not benefit from antibiotics
:::* Preferred regimen (1): [[Doxycycline]] 100 mg PO bid for 7-10 days
:::* Preferred regimen (2): [[Amoxicillin]] 875 mg PO bid
:::* Preferred regimen (3): [[Amoxicillin]] 500 mg PO tid
:::* Preferred regimen (4): [[Trimethoprim-sulfamethoxazole]] DS 800/160 mg PO bid for 10-14 days
:::* Alternative regimen (1): [[Amoxicillin-clavulanate]] 875/125 mg PO bid for 10-14 days
:::* Alternative regimen (2): [[Levofloxacin]] 500 mg PO qd for 7-10 days
:::* Alternative regimen (3): [[Azithromycin]] 500 mg PO single dose {{then}} 250 mg PO qd for 4 days
:::* Alternative regimen (4): [[Cefpodoxime]] 200 mg PO bid for 10 days
:::* Alternative regimen (5): [[Amoxicillin-clavulanate]] 500/125 mg PO tid for 10-14 days
:::* Alternative regimen (6): [[Moxifloxacin]] 400 mg PO qd for 5 days
:::* Alternative regimen (7): [[Gemifloxacin]] 320 mg PO qd for 5 days
:::* Alternative regimen (8): [[Clarithromycin]] 250-500 mg PO bid for 7-14 days
:::* Alternative regimen (9): [[Clarithromycin]] ER 1000 mg PO qd for 14 days
:::* Alternative regimen (10): [[Cefprozil]] 250-500 mg PO bid for 10 days
:::* Alternative regimen (11): [[Cefixime]] 400 mg PO qd for 10 days
::* '''2. Inpatient management'''
:::* Indications for hospital admission:
::::* Intense symptoms (e.g.: sudden development of resting dyspnea)
::::* Old age
::::* Severe underlying COPD
::::* Cyanosis
::::* Peripheral edema
::::* Serious comorbidities (e.g.: HF, Afib, renal failure)
::::* Failure of outpatient treatment
::::* Frequent exacerbations
::::* Insufficient home support
:::* 2.1 '''Treatment of acute exacerbation of chronic bronchitis, when pseudomonas infection not suspected'''
::::* Preferred regimen (1): [[Moxifloxacin]] 400 mg IV q24h for 5 days
::::* Preferred regimen (2): [[Levofloxacin]] 500 mg IV q24h for 7-10 days
:::* 2.2 '''Treatment of acute exacerbation of chronic bronchitis, when pseudomonas infection is suspected'''
::::* Preferred regimen (1): [[Ceftazidime]] 30-50 mg/kg IV q8hr (maximum dose 6 g/day)
::::* Preferred regimen (2): [[Piperacillin-Tazobactam]] 3.375 g IV q6h for 7-10 days
::::* Preferred regimen (3): [[Cefepime]] 1-2 g IV q8-12hr for 7-10 days (extend to 21 days if culture positive for Pseudomonas)
::::* Alternative regimen (1): [[Ceftriaxone]] 1-2 g IV/IM q12-24h for 4-14 days
::::* Alternative regimen (2): [[Ceftriaxone]] 1-2 g IV/IM q8h for 4-14 days


==References==
==References==
{{Reflist|2}}
{{Reflist|2}}
{{WH}}
{{WS}}


[[Category:Pulmonology]]
[[Category:Pulmonology]]
[[Category:Emergency medicine]]
[[Category:Emergency medicine]]
 
[[Category:Disease]]
{{WH}}
[[Category:Up-To-Date]]
{{WS}}
[[Category:Infectious disease]]

Latest revision as of 20:56, 29 July 2020

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Seyedmahdi Pahlavani, M.D. [2]; Nate Michalak, B.A.

Overview

The treatment plan for chronic bronchitis is divided into two main categories:

  1. Reduce symptoms: by relief of dyspnea and improve exercise tolerance
  2. Reduce risks: by treating exacerbations, preventing disease progression, and reducing mortality

General Therapy

  • Patient education sessions about the disease, self-treatment plans for exacerbations, and a monthly follow-up calls from the hospital or nurse practitioner are associated with a lower hospitalization rate and fewer emergency department visits.[1] [2][3]
  • Treatment of COPD requires a careful and thorough evaluation by a physician.
  • The most important aspect of treatment is avoiding tobacco smoke and removing other air pollutants from the patient’s home or workplace.
  • Patients who have hypoxemia are often given supplemental oxygen.
  • Oral and inhaled medications are used for patients with stable chronic obstructive pulmonary disease (COPD) to reduce dyspnea, improve exercise tolerance, and prevent complications. Symptoms such as coughing or wheezing can be treated with bronchodilators like subcutaneous medications, beta-adrenergics, methylxanthines, and anticholinergics. They act via decreasing muscle tone in small and large airways in the lungs.
  • Respiratory infections should be treated with antibiotics, if appropriate.
  • Nutritional support forms an integral part of management for COPD patients.

Pulmonary Rehabilitation

  • Decreases the number of hospitalizations and the exacerbations.[4]
  • Helpful to alleviate symptoms and improve lung capacities.[5]

Oxygen Therapy

  • COPD patients commonly have hypoxemia, indicated by PaO2 (partial pressure of oxygen in arterial blood) of < 55 mm Hg or oxygen saturation of less than 90%.[6][1]
  • Oxygen administration reduces mortality rates in patients with advanced COPD due to the favorable effects on pulmonary hemodynamics.[7]
  • Trials have shown long-term oxygen therapy (15-19 hours/day) improves survival in advanced COPD patients and thus long term oxygen therapy for hypoxemic patients (PaO2 < 55 mm Hg), patients with polycythemia and PaO2 < 59mm Hg or cor pulmonale is recommended. These patients require re-evaluation in 1-3 months whether they require long term oxygen therapy or not.
  • Home oxygen supplementation is also recommended for patients who are well at rest but develop hypoxemia during exertion.[8][9]
  • Oxygen therapy generally is safe. Oxygen toxicity from high inspired concentrations (>60%) is well recognized. Additionally, several concerns have been raised regarding carbon dioxide retention as a result of decreased respiratory drive due to increased oxygen concentration. This complication can be best avoided by maintaining PaO2 at 60-65 mm Hg.
  • The major physical hazards of oxygen therapy are fires or explosions. Thus, patients and others must be warned not to smoke.[1]
  • A nasal cannula may be used for oxygen therapy. Advantages of this device are[1]:
    • It is simple and well tolerated
    • A liter of oxygen increases FiO2 (fraction of inspired oxygen) by 3-4%
    • Nasal oxygen delivery is also beneficial for most mouth-breathing patients
    • Humidification generally is not necessary when the patient receives oxygen by nasal cannula at flows of less than 5 L/min
  • Noninvasive positive-pressure ventilation (NIPPV) is an alternative device for oxygen therapy. Its advantages include:
    • It allows the delivery of positive-pressure ventilation without the use of an endotracheal tube.
    • It has a tight-fitting nasal or facial mask that is attached to a continuous positive airway pressure (CPAP) or a bilevel positive airway pressure (BiPAP) machine
    • The positive pressure is beneficial in hypercapneic respiratory failure by decreasing the work of breathing
    • NIPPV has been shown to decrease the need for endotracheal intubation, duration of hospital stay, morbidity, and mortality.
    • Contraindication for use:
      • Patients unable to protect airway
      • Hemodynamically unstable
      • Have significant secretions
      • Uncooperative
      • Acute Physiology and Chronic Health Evaluation (APACHE) score of greater than 29

Smoking Cessation

  • Smoking cessation is the most important therapeutic intervention for COPD. It has been demonstrated that it is more effective than bronchodilators in the course of treatment.[10][1]
  • Smoking cessation education and support should be offered to every patient with COPD, at every visit. Even temporary quit or cutting down the numbers will improve the outcomes compared to continued smokers.[11]
  • Behavioral counseling (< 10 min) and pharmacotherapy are each effective alone. However, they have a synergistic effect when used together.
  • Supervised use of pharmacologic agents is an important adjunct to self-help and group smoking cessation programs.
  • Nicotine addiction is quite strong and cessation at times is difficult. Withdrawal from nicotine may cause unpleasant adverse effects, such as anxiety, irritability, difficulty concentrating, fatigue, drowsiness, depression, and sleep disruption.
  • Highly addicted individuals (e.g. require a cigarette within 30 minutes of waking in the morning) would benefit from nicotine replacement therapy.

Nicotine Replacement Therapies

Transdermal Nicotine Patches

  • Trade name: NicoDerm, Nicotrol, and Habitrol
  • Success rates better compared with placebo
  • Well tolerated, adverse effects are limited to local skin reactions[12]

Bupropion

  • Class: Antidepressant
  • Trade name: Zyban
  • It enhances central nervous system nonadrenergic function
  • Better results compared to placebo
  • Bupropion may be effective in patients who failed to quit smoking with nicotine replacement therapy[13]

Varenicline

Vaccination

Medical treatment

Beta Adrenergic Receptor Agonists

Short Acting Selective B2 Agonist

  • Used for symptomatic relief during acute mild, exacerbation.
  • Mechanism of action: increases intracellular cyclic adenosine monophosphate via activation of B2-adrenergic receptors on smooth muscle cells of airway and causes smooth muscle relaxation.
  • These agents are less effective in COPD compared to asthma.
  • Patients may not have increase in peak flows with treatment but should be continued if it offers symptomatic relief.
  • The inhaled route is preferred as there is less systemic absorption thus less side-effects.
  • Adverse effects include tachycardia, tremors and cardiac arrhythmia.[16]

Drugs available in this category are:

Albuterol, Metaproterenol, Pirbuterol
  • Inhalation aerosol or powder: 2 inhalations every 4 to 6 hours as needed
Levalbuterol
  • Albuterol is a racemic mixture containing both R and S enantiomer. The S enantiomer doesn't bind to Beta 2 receptor and may cause side-effects. On the other hand, levalbuterol has only active R enantiomer thus causes less side-effects.
  • It is used for both treatment and prevention of bronchospasm.

Long Acting Beta-2 Adrenergic Receptor Agonist

  • The long acting beta 2 receptor agonists are used to alleviate chronic persistent symptoms.
  • They help to increase exercise tolerance, prevent nocturnal dyspnea, and improve quality of life.
  • Long-acting beta-agonists include salmeterol, formoterol, arformoterol, and indacaterol.
  • They all require twice-daily dosing, except for indacaterol. Bronchodilating effect lasts more than 12 hours. Indacaterol is administered once daily.[17][18]
Salmeterol, Formoterol, Arformoterol
  • Facilitate expectoration, improve symptoms and morning peak flows.
Arformoterol

Indacaterol

  • Indacaterol a long-acting beta2-agonist (LABA) is used for long-term, once-daily maintenance in patients with chronic obstructive pulmonary disease (COPD).[20]
  • It is not for use as initial therapy in patients with acute deteriorating COPD.

Anticholinergics

  • Reported adverse effects include dry mouth, metallic taste, and prostatic symptoms. Studies have found an increased incidence of acute urinary retention in patient above 66 years using inhaled anticholinergic medications than in nonusers.[21]
Ipratropium
  • Has similar efficacy as beta 2 adrenergic receptor agonist.
  • Has a synergistic effect on bronchodilation when combined with beta 2 agonist.
  • They have a slower onset and longer duration of action, thus may be less helpful in use on an as-needed basis.
  • Dose: 2-4 puffs every 6-8 hours.[22]

Tiotropium

  • It is the only long-acting muscarinic (once daily) anticholinergic agent available at this time.
  • It has become a first-line therapy in patients with persistent symptoms.
  • It is more effective than salmeterol in preventing exacerbation.[23] [24]

Phosphodiesterase Inhibitor

Xanthine Derivatives (Theophylline) (Non Specific)

  • It is mostly used as an adjunctive agent and reserved in non-responsive patients or patients having difficulty using inhaled agents.

Phosphodiesterase Type 4 Inhibitors (Specific)

Cilomilast, Roflumilast

  • Second generation, selective phosphodiesterase-4 inhibitors.[26]
  • Decreases inflammatory mediators like macrophages and CD8 lymphocytes.
  • Roflumilast helps in reducing exacerbations, improve dyspnea, and increase lung function in patients with severe COPD. However, roflumilast has not gained FDA approval for clinical use, largely because of side effects including significant nausea.
  • Cilomilast, another drug in this class, is still in preliminary clinical trials. It is administered orally and is given in 15mg dose twice daily.[26]

Steroid

  • Systemic (high doses intravenous) and inhaled corticosteroids act as anti-inflammatory agents and reduce the course of the disease, symptoms, treatment failure, and need for additional therapy.
  • Systemic steroids may be used in the treatment of acute exacerbation.[27]
  • The 2011 ICSI guidelines conclude that inhaled steroids are appropriate in patients with recurrent exacerbation of COPD.
  • Studies have shown inhaled corticosteroids along with long acting beta agonist to be more beneficial than inhaled steroid alone.[28]
  • Studies have shown an increased risk of pneumonia in patients treated with inhaled corticosteroids. The debate continues on the use of inhaled corticosteroids and the risk for pneumonia in patients with COPD.[29][18]
  • Use of oral steroids in stable COPD patients is not encouraged due to increased adverse effects (hypertension, glucose intolerance, osteoporosis, fractures, and cataracts).

Antibiotics

Anti Inflammatory

  • Macrolides like azithromycin have been occasionally used in treatment of COPD due to their anti-inflammatory properties.[30][31] However, due to increased incidences of hearing loss and development of antibiotics resistance with azithromycin use, it has not been used on wide scales.

Infections

  • Common organisms involved in acute exacerbation of COPD are S. pneumoniae, H. influenzae, M. catarrhalis and rarely P. aeruginosa. Antibiotics are commonly used in the treatment of acute exacerbation or suggestive of infection. However, regular long term antibiotics used for prevention of COPD exacerbation is not encouraged.
  • Doxycycline has shown superior results for clinical cure, microbiological outcome, use of open label antibiotics, and symptoms.

Beta Adrenergic Receptor Blocker

COPD patients have increased risks of cardiovascular diseases. However, non-selective beta blockers have been found to increase the risks of bronchospasm and are thus not recommended in these patients. Interestingly, a study has shown that addition of cardioselective beta-blocker along with standard inhaled COPD treatment with beta 2 selective agonist didn't affect the pulmonary function of the patients. Additionally, it reduced COPD exacerbation, hospital admission and all-cause mortality during a follow up of 4.35 years with 5977 COPD patients.[32]

Mucolytic

  • The efficacy of mucolytic agents in the treatment of COPD remains controversial.
  • The oral agent N-acetylcysteine has antioxidant and mucolytic properties (decreases sputum viscosity and secretion) and is used to treat patients with COPD.
  • When used as an inhalational therapy, N-acetylcysteine should be administered along with a bronchodilator such as albuterol in order to counteract potential induction of bronchospasm.

Route of Therapy

  • Inhaled delivery is preferred over the oral route as there is less systemic absorption via inhaled route thus less adverse effects. However, some patients may have difficulty achieving effective delivery of the medication using a metered-dose inhaler. Use of spacer or nebulizer may be beneficial in them.

GOLD Recommendations for Management of COPD

GOLD recommendations for management of COPD
Stage Degree of airway obstruction Treatment
Stage I Mild
Stage II Moderate
Stage III Severe
  • Influenza vaccine (decrease risk)
  • Short acting Beta 2 receptor agonist
  • Long-acting bronchodilator
  • Cardiopulmonary rehabilitation
  • Inhaled steroids in case of frequent exacerbation
Stage IV

Very severe or moderate with evidence of chronic respiratory failure

  • Influenza vaccine (decrease risk)
  • Short acting Beta 2 receptor agonist
  • Long term oxygen therapy
  • Lung transplant can be considered



Chronic obstructive pulmonary disease treatment

  • Preferred regimen
  • Beta2-agonist
(1) Short acting: Fenoterol 100-200 mcg metered dose inhaler; 1 mg/ml solution for nebulizer ; 0.05 % syrup oral, duration of action 4-6 hrs OR Levalbuterol 45-90 mcg metered dose inhaler; 0.21 mg/ml -0.42 mg/ml solution for nebulizer ; duration of action 6-8 hrs OR Salbutamol 100-200 mcg metered dose inhaler and dry powder inhaler; 5 mg/ml solution for nebulizer ; 5 mg pill ; 0.024 % syrup oral; 0.1 mg, 0.5 mg vials for injection ; duration of action 4-6 hrs OR Terbutaline 400-500 mcg dry powder inhaler and 2.5 mg,5 mg pill oral, duration of action 4-6 hrs
(2) Long acting : Formoterol 4.5 mcg-12 mcg metered dose inhaler and dry powder inhaler ; 0.01 mg/ml solution for nebulizer ; duration of action 12 hrs OR Arformoterol 0.0075 mg/ml solution for nebulizer ; duration of action 12 hrs OR Indacaterol 75 mcg-300 mcg dry powder inhaler; duration of action 24 hrs OR Salmeterol 25 mcg-50 mcg metered dose inhaler and dry powder inhaler ; duration of action 12 hrs OR Tulobuterol 2 mg transdermal ; duration of action 24 hrs
  • Anticholinergics
(1) Short acting: Ipratropium bromide 20 mcg-40 mcg metered dose inhaler; duration of action 6-8 hrs OR Oxitropium bromide 100 mcg metered dose inhaler; duration of action 7-9 hrs
(2) Long acting: Aclidinium bromide 322 mcg dry powder inhaler; duration of action 12 hrs OR Glycopyrronium bromide 44 mcg dry powder inhaler; duration of action 24 hrs OR Tiotropium 18 mcg; 5 mcg soft mist inhaler; duration of action 24 hrs OR Umeclidinium 62.5 mcg dry powder inhaler; duration of action 24 hrs
  • Combination of short acting beta2 agonist and anticholinergics in one inhaler: Fenoterol/Ipratropium bromide 200-80 mcg metered dose inhaler; 0.25-0.5 solution for nebulizer; duration of action 6-8 hrs OR Salbutamol/Ipratropium bromide 100-20 mcg soft mist inhaler; 1.5 solution for nebulizer; duration of action 6-8 hrs
  • Methylxanthines: Aminophylline 200-600 mg pill oral; 240 mg injection OR Theophylline 100-600 mg pill oral; duration of action variable upto 24 hrs
  • Inhaled corticosteroids: Beclomethasone 50 mcg-400 mcg metered dose inhaler and dry powder inhaler; 0.2 mg/ml-0.4 mg/ml solution for nebulizer OR Budesonide 100 mcg,200 mcg,400 mcg dry powder inhaler; 0.20 mg/ml, 0.25mg/ml ,0.5 mg/ml solution for nebulizer OR Fluticasone 50 mcg-500 mcg metered dose inhaler and dry powder inhaler
  • Phosphodiesterase-4 inhibitors: Roflumilast 500 mcg pill oral; duration of action is 24 hrs.
Note: Formoterol nebulized solution is based on the unit dose containing 20 mcg in a volume of 2.0 ml.
  • Alternative regimen
  • Vaccination
(1) Influenza vaccination containing killed or live inactivated virus is more effective in elderly patients with chronic obstructive pulmonary disease.
(2) Pneumococcal polysaccharide vaccine is recommended for chronic obstructive pulmonary disease in elderly patients 65 years and older, and also in younger patient with significant comorbid conditions such as cardiac disease.This vaccine also shown to reduce the incidence of community acquired pneumonia in chronic obstructive pulmonary disease patients younger than age 65 years with an FEV1< 40 % predicted.
  • Alpha-1 antitrypsin augmentation therapy
Young patients with severe hereditary alpha-1 antitrypsin deficiency and established significant emphysema may be the candidates for alpha-1 antitrypsin augmentation therapy.
  • Antibiotics
The use of antibiotics, other than for treating infectious exacerbations of chronic obstructive pulmonary disease and other bacterial infections is currently not indicated.
  • Mucolytics (mucokinetic and mucoregulator) and antioxidant agents (ambroxol, erdosteine, carbocysteine, iodinated glycerol, N-acetylcysteine)
(1) Although a few patients with viscous sputum may benefit from mucolytics, the overall benefits seems to be very small; their wide spread use is not recommended.
(2) There is some evidence that in chronic obstructive pulmonary disease patients not receiving inhaled corticosteroids, treated with mucolytics and N-acetylcysteine may reduce exacerbations.
  • Immunoregulators (immunomodulators,immunostimulators): Studies using an immunoregulator in chronic obstructive pulmonary disease report a decrease in the severity and frequency of exacerbations.
  • Antitussives: has a significant protective role but the regular usage of antitussives is not recommended in stable chronic obstructive pulmonary disease patients.
  • Narcotics (morphine): Oral and parenteral opioids are effective for treating dyspnea in chronic obstructive pulmonary disease patients with very severe disease.
  • Others: Oxygen therapy, ventilation support.
  • Initial pharmacological management of chronic obstructive pulmonary disease
  • Group A patients: Have few symptoms and low risk of exacerbations.
  • Preferred regimen: Short acting anticholinergics OR short acting beta2 agonist
  • Alternative regimen (1): Long acting anticholinergics OR long acting beta2 agonist OR short acting beta2 agonist AND short acting anticholinergics
  • Alternative regimen (2): Theophylline
  • Group B patients: Have more significant symptoms but still low risk of exacerbations
  • Preferred regimen: Long acting anticholinergics OR long acting beta2 agonist
  • Alternative regimen (1): Long acting anticholinergics AND long acting beta2 agonist
  • Alternative regimen (2): short acting beta2 agonist AND/ OR short acting anticholinergics

Theophylline

  • Group C patients: Have few symptoms but high risk of exacerbations
  • Alternative regimen (1):
  • Alternative regimen (2):
  • Group D patients: Have many significant symptoms and high risk of exacerbations.
  • Alternative regimen (1):
  • Alternative regimen (2):

External Links

COPD CDC


References

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