View source for Chronic obstructive pulmonary disease

{{Infobox_Disease |
  Name           = Chronic obstructive pulmonary disease |
  Image          = |
  Caption        = |
  DiseasesDB     = 2672 |
  ICD10          = {{ICD10|J|40||j|40}} - {{ICD10|J|44||j|40}}, {{ICD10|J|47||j|40}} |
  ICD9           = {{ICD9|490}} - {{ICD9|496}} |
  ICDO           = |
  OMIM           = 606963 |
  MedlinePlus    = 000091 |
  eMedicineSubj  = med |
  eMedicineTopic = 373 |
  eMedicine_mult = {{eMedicine2|emerg|99}} |
  MeshName       = COPD |
  MeshNumber     = C08.381.495.389 |
}}

{{SI}}
'''Editor-in-Chief''' Philip Marcus, M.D., M.P.H. [mailto:pmarcus192@aol.com], Division of Pulmonary Medicine
St. Francis Hospital-The Heart Center 
__NOTOC__
'''Associate Editor-In-Chief:''' {{CZ}}

{{Editor Help}}

==Overview==
'''Chronic obstructive pulmonary disease''' ('''COPD'''), also known as '''chronic obstructive airway disease''' ('''COAD'''), is a group of [[disease]]s characterized by the pathological limitation of airflow in the [[airway]] that is not fully reversible. COPD is the umbrella term for chronic [[bronchitis]], [[emphysema]] and a range of other lung disorders. It is most often due to [[tobacco smoking]],<ref name="dev">Devereux G. ''ABC of chronic obstructive pulmonary disease. Definition, epidemiology, and risk factors.'' [[British Medical Journal|BMJ]] 2006;332:1142-1144. PMID 16690673</ref> but can be due to other airborne irritants such as coal dust, [[asbestos]] or solvents, [[congenital]] conditions such as [[alpha-1-antitrypsin deficiency]] and as well as preserved meats containing nitrites [http://www.webmd.com/news/20070417/study-copd-cured-meats-may-be-linked].

== Epidemiology and Demographics==
According to the [[World Health Organization]] (WHO), 80 million people suffer from moderate to severe COPD and 3 million died due to it in 2005. The WHO predicts that by 2030, it will be the 4th largest cause of mortality worldwide.<ref>[http://www.who.int/respiratory/copd/en/ WHO - COPD]</ref>

Since COPD is not diagnosed until it becomes clinically apparent, prevalence and mortality data greatly underestimate the socioeconomic burden of COPD.<ref name=thoracic /> In the UK, COPD accounts for about 7% of all days of sickness related absence from work.<ref name=kc />

Smoking rates in the industrialized world have continued to fall, causing rates of emphysema and pulmonary neoplasms to slowly decline.

==Pathophysiology and Etiology==
===Chronic bronchitis===
Chronic bronchitis is defined in ''clinical'' terms as a cough with sputum production on most days for 3 months of a year, for 2 consecutive years.<ref name=ohcm>Longmore M, Wilkinson I, Rajagopalan S (2005). ''Oxford Handbook of Clinical Medicine'', 6ed. [[Oxford University Press]]. pp 188-189. ISBN 0-19-852558-3.</ref> 

Chronic bronchitis is hallmarked by [[hyperplasia]] (increased number) and [[hypertrophy]] (increased size) of the goblet cells ([[mucous gland]]) of the airway, resulting in an increase in secretion of mucus which contributes to the airway obstruction.  [[Microscope|Microscopically]] there is [[Infiltration (medical)|infiltration]] of the airway walls with [[Inflammation|inflammatory]] cells, particularly [[neutrophils]]. Inflammation is followed by scarring and remodeling that thickens the walls resulting in narrowing of the small airway. Further progression leads to [[metaplasia]] (abnormal change in the tissue) and [[fibrosis]] (further thickening and scarring) of the lower airway. The consequence of these changes is a limitation of airflow.<ref name=kc>Kumar P, Clark M (2005). ''Clinical Medicine'', 6ed. Elsevier Saunders. pp 900-901. ISBN 0702027634.</ref>.

===Emphysema===
{{main|Emphysema}}
[[Emphysema]] is defined ''[[Histology|histologically]]'' as the enlargement of the air spaces [[distal]] to the terminal bronchioles, with destruction of their walls.<ref name=ohcm /> 

The enlarged air sacs ([[alveoli]]) of the lungs reduces the surface area available for the movement of gases during [[Respiratory system|respiration]]. This ultimately leads to dyspnea in severe cases. The exact mechanism for the development of emphysema is not understood, although it is known to be linked with smoking and age.

==Diagnosis==
The diagnosis of COPD is usually suggested by symptoms; it is a clinical diagnosis and no single test is definitive.  A comprehensive history from the patient is very important with regard to smoking and occupation.

===Differential Diganosis of Underlying Causes===
====Cigarette smoking====
A primary factor of COPD is chronic tobacco smoking. In the United States, around 90% of cases of COPD are due to smoking.<ref name="medcauses">[http://www.medicinenet.com/chronic_obstructive_pulmonary_disease_copd/page3.htm7whatcauses MedicineNet.com - COPD causes]</ref> Not all smokers will develop COPD, but continuous smokers have at least a 25% risk.<ref>Lokke A, Lange P, Scharling H, Fabricius P, Vestbo J. Developing COPD: a 25 year follow up study of the general population. ''Thorax''. 2006 Nov;61(11):935-9. PMID 17071833</ref>

====Occupational pollutants====
Some occupational pollutants, such as [[cadmium]] and silica, have shown to be a contributing risk factor for COPD. The people at highest risk for these pollutants include coal workers, construction workers, metal workers and cotton workers, amongst others. However, in most cases these pollutants are combined with cigarette smoking further increasing the chance of developing COPD.<ref name="medcauses" /> These occupations are commonly associated with [[Occupational lung disease|other respiratory diseases]], particularly [[pneumoconiosis]] (black lung disease).

====Air pollution====
Urban [[air pollution]] may be a contributing factor for COPD as it is thought to impair the development of the lung function. In developing countries indoor air pollution, usually due to biomass fuel, has been linked to COPD, especially in women.

====Genetics====
Very rarely, there may be a deficiency in an [[enzyme]] known as [[alpha 1-antitrypsin]] which causes a form of COPD.<ref>[http://www.nlm.nih.gov/medlineplus/ency/article/000091.htm MedlinePlus Medical Encyclopedia]</ref>

===Other risk factors===
Increasing age, male gender, allergy, repeated airway infection and general impaired lung function are also related to the development of COPD.

===Symptoms and History===
The main [[symptoms]] of COPD include [[dyspnea]] (shortness of breath) lasting for months or perhaps years, possibly accompanied by [[wheezing]], and a persistent [[cough]] with [[sputum]] production.<ref>[http://www.nhlbi.nih.gov/health/dci/Diseases/Copd/Copd_SignsAndSymptoms.html U.S. National Heart Lung and Blood Institute - Signs and Symptoms]</ref> It is possible the sputum may contain blood ([[hemoptysis]]), usually due to damage of the blood vessels of the airways. Severe COPD could lead to [[cyanosis]] (bluish decolorization usually in the lips and fingers) caused by a lack of [[oxygen]] in the blood. In extreme cases it could lead to [[cor pulmonale]] due the extra work required by the heart to get blood to flow through the lungs.<ref>[http://www.medicinenet.com/chronic_obstructive_pulmonary_disease_copd/page4.htm MedicineNet.com - COPD signs & symptoms]</ref>

== Laboratory Studies ==
COPD is particularly characterised by a ratio of forced expiratory volume over 1 second ([[FEV1|FEV<sub>1</sub>]]) to forced vital capacity (FVC) being < 0.7 and the [[FEV1|FEV<sub>1</sub>]]  < 70% of the predicted value <ref>[http://www.patient.co.uk/showdoc/40002357/ PatientPlus - Spirometry]</ref> (see [[Spirometry]]). Other signs include a rapid breathing rate ([[tachypnea]]) and a wheezing sound heard through a [[stethoscope]]. Pulmonary emphysema is NOT the same as subcutaneous emphysema, which is a collection of air under the skin that may be detected by the crepitus sounds produced on [[palpation]].<ref>[http://www.emedicine.com/med/topic209.htm eMedicine - Barotrauma]</ref>

Physical examination with a [[plethysmograph]] can reveal the true extent of COPD. 

The severity of COPD can be classified as follows using spirometry (see above):
{| class="wikitable" style="text-align:center;width:75%;"
|-
! Severity !! Post-bronchodilator [[FEV1|FEV<sub>1</sub>]] /FVC !! FEV<sub>1</sub> % predicted
|-
| At risk || >0.7 || ≥80
|-
| Mild COPD || ≤0.7 || ≥80
|-
| Moderate COPD || ≤0.7 || 50-80
|-
| Severe COPD || ≤0.7 || 30-50
|-
| Very Severe COPD || ≤0.7 || <30 '''or''' 30-50 with Chronic Respiratory Failure symptoms
|}

===Chest X Ray===

[http://www.radswiki.net Images shown below are courtesy of RadsWiki]

<div align="center">
<gallery heights="125" widths="125">
Image:COPD-101.jpg
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==Treatment==
Although COPD is not curable, it can be controlled in a variety of ways.  [[Clinical practice guideline]]s by [http://www.goldcopd.org/ Global Initiative for Chronic Obstructive Lung Disease] (GOLD), a collaboration including the American [http://www.nhlbi.nih.gov National Heart, Lung, and Blood Institute] and the [http://www.who.org World Health Organization], are available.<ref name="pmid17507545">{{cite journal |author=Rabe KF, Hurd S, Anzueto A, ''et al'' |title=Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Pulmonary Disease: GOLD Executive Summary |journal=Am. J. Respir. Crit. Care Med. |volume=176 |issue=6 |pages=532-55 |year=2007 |pmid=17507545 |doi=10.1164/rccm.200703-456SO}}</ref>

===Smoking cessation===

{{Main|Smoking cessation}}
[[Smoking cessation]] is one of the most important factors in slowing down the progression of COPD. Even at a late stage of the disease it can reduce the rate of deterioration and prolong the time taken for disability and death.<ref name=kc />

===Occupational change===

Workers may be able to transfer to a significantly less contaminated area of the company depending on circumstances. Often however, workers may need complete occupational change. 

===Pharmacotherapy===
====Bronchodilators====
There are several types of [[Bronchodilator|bronchodilators]] used clinically with varying efficacy: β<sub>2</sub> agonists, M<sub>3</sub> antimuscarinics, leukotriene antagonists, cromones and xanthines.<ref name=thoracic>American Thoracic Society / European Respiratory Society Task Force (2005). ''Standards for the Diagnosis and Management of Patients with COPD''. Version 1.2. New York: American Thoracic Society. http://www.thoracic.org/go/copd</ref> These drugs relax the [[smooth muscles]] of the airway allowing for improved airflow. The change in [[FEV1|FEV<sub>1</sub>]] may not be substantial, but changes in the [[vital capacity]] are significant. Many patients feel less breathless after taking bronchodilators.

=====β<sub>2</sub> agonists=====
There are several highly specific β<sub>2</sub> agonists available. [[Salbutamol]] (Ventolin) is the most widely used short acting β<sub>2</sub> agonist to  provide rapid relief and should be prescribed as a front line therapy for all classes of patients. Other β<sub>2</sub> agonists are [[Bambuterol]], [[Clenbuterol]], Fenoterol, and [[Formoterol]]. Longer acting β<sub>2</sub> agonists such as [[Salmeterol]] act too slowly to be used as relief for [[dypsnea]] so these drugs should be used as a secondary therapy. An increased risk is associated with long acting β<sub>2</sub> agonists due to decreased sensitivity to inflammation so generally the use of a concomitant [[corticosteroid]] is indicated[http://www.fda.gov/medwatch/SAFETY/2003/serevent.htm][http://www.gsk.com/press_archive/press2003/press_01232003.htm][http://www.medscape.com/viewarticle/527629_print].

=====M<sub>3</sub> muscarinic antagonists (anticholinergics)=====
Derived from the deadly agaric ''[[Amanita muscaria]]'', specific [[Muscarinic antagonist|antimuscarinics]] were found to provide effective relief to COPD. Inhaled antimuscarinics have the advantage of avoiding [[endocrine]] and exocrine M<sub>3</sub> receptors. The quaternary M<sub>3</sub> muscarinic antagonist [[Ipratropium]] is widely prescribed with the β<sub>2</sub> agonist [[salbutamol]]. 
[http://www.neurosci.pharm.utoledo.edu/MBC3320/muscarinic.htm]. Ipratropium is offered combined with salbutamol (Combivent) and with fenoterol (Duovent). [[Tiotropium]] provides improved specificity for M<sub>3</sub> muscarinic receptors.

=====Cromones=====
Cromones are [[mast cell stabilizer]]s that are thought to act on a [[chloride channel]] found on [[mast cells]] that help reduce the production of [[histamine]] and other inflammatory factors. Chromones are also thought to act on IgE-regulated calcium channels on mast cells. [[Cromoglicate]] and [[Nedocromil]], which has a longer half-life, are two chromones available.<ref>http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?holding=npg&cmd=Retrieve&db=PubMed&list_uids=4166895&dopt=Abstract</ref>

=====Leukotriene antagonists=====
More recently [[leukotriene]] antagonists block the signalling molecules used by the immune system. [[Montelukast]], [[Pranlukast]], [[Zafirlukast]] are some of the leukotrienes antagonists.<ref>available.http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=13804592&dopt=Citation</ref>

=====Xanthines=====
[[Theophylline]] is the prototype of the [[xanthine]]<ref>http://www.chemistry.org/portal/a/c/s/1/acsdisplay.html?DOC=HomeMolecule\archive\motw_xanthine_arch.html</ref> class of drug. Teas are natural sources of methylxanthines, xanthines and [[caffeine]] while chocolate is a source of [[theobromine]]. [[Caffeine]] is approximately 16% metabolized into theophylline. Nebulized theophylline is used in the EMR for treatment of [[dyspnea]] (Difficulty in breathing). Patients need continual monitoring as theophylline has a narrow therapeutic range. More aggressive EMR interventions include IV H<sub>1</sub> [[antihistamine]]s and IV [[dexamethasone]].

====Corticosteroids====
Inhaled corticosteriods (specifically [[glucocorticoids]]) act in the inflammatory cascade and may improve airway function considerably,<ref name=kc /> however the long term value has not been proven. Corticosteroids are often combined with bronchodilators in a single inhaler. Some of the more common inhaled steroids in use are [[beclomethasone]], [[Mometasone furoate|mometasone]], and [[fluticasone]].

Salmeterol and fluticasone are combined (Advair), however the reduction in death from all causes among patients with COPD in the combination therapy group did not reach the predetermined level of statistical significance.<ref>http://content.nejm.org/cgi/content/short/356/8/775</ref><ref>http://clinicaltrials.gov/show/NCT00268216</ref>

====TNF antagonists====
Tumor necrosis factor antagonists (TNF) are the most recent class of medications designed to deal with refractory cases. [[Tumor necrosis factor-alpha]] is a cachexin or cachectin and is considered a so-called biological drug. They are considerered immunosopressive with attendant risks. These rather expensive drugs include [[infliximab]], [[adalimumab]] and [[etanercept]].<ref>http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/C/CellSignaling.html</ref>

====Supplemental Oxygen====
In general, long-term administration of oxygen is usually reserved for individuals with COPD who have arterial [[hypoxemia]] (PaO2 less than 55 mm Hg), or a PaO2 between 55 and 60 mm Hg with evidence of [[pulmonary hypertension]], [[cor pulmonale]], or secondary erythrocytosis (hematocrit >55%). In these patients, continuous home oxygen therapy (for >15 h/d) sufficient to correct hypoxemia has been shown to improve survival. <ref>http://linkinghub.elsevier.com/retrieve/pii/S014067368191970X.</ref>

====Vaccination====
Patients with COPD should be routinely [[vaccination|vaccinated]] against [[influenza]], [[pneumococcus]] and other diseases to prevent illness and the possibility of death.<ref name="thoracic" />

====Pulmonary rehabilitation====
Pulmonary rehabilitation is a program of disease management, counseling and exercise coordinated to benefit the individual.<ref>[http://www.nhlbi.nih.gov/health/dci/Diseases/Copd/Copd_Treatments.html U.S. National Heart Lung and Blood Institute - Treatment]</ref> Pulmonary rehabilitation has been shown to relieve difficulties breathing and fatigue. It has also been shown to improve the sense of control a patient has over their disease as well as their emotions.<ref>Lacasse Y, Goldstein R, Lasserson T J, Martin, S. ''Pulmonary rehabilitation for chronic obstructive pulmonary disease''. Cochrane Database of Systematic Reviews. (4):CD003793, 2006. PMID 12137716</ref>

===Diet===

A recent French study conducted over 12 years with almost 43,000 men concluded that eating a [[Mediterranean diet]] "halves the risk of serious lung disease like emphysema and bronchitis". [http://news.bbc.co.uk/2/hi/health/6647811.stm]

==Prognosis==
A good prognosis of COPD relies on an early diagnosis and prompt treatment. Most patients will have improvement in lung function once treatment is started, however eventually signs and symptoms will worsen as COPD progresses. The median survival is about 10 years if two-thirds of expected lung function was lost by diagnosis.
===Bronchitis===
Acute bronchitis usually resolves in 7-10 days with no underlying lung disease. Chronic bronchitis however is dependent on early recognition and smoking cessation which improves the outcome significantly.

===Emphysema===
The outcome is better for patients with less damage to the lung who stop smoking immediately. Still, patients with extensive lung damage may live for many years so predicting prognosis is difficult. Death may occur from respiratory failure, [[pneumonia]], or other complications.

===Asbestosis ===
The outcome is clouded by the many complications associated with asbestosis. [[Malignant]] [[mesothelioma]] is refractory to management affording patients with 6-12 months of life expectancy upon clinical presentation.

===Pneumoconiosis===
The outcome is good for patients with minimal damage to the lung. However, patients with extensive lung damage may live for many years so predicting prognosis is difficult. Death may occur from [[respiratory failure]], [[pneumonia]], [[cor pulmonale]] or other complications.

===Pulmonary neoplasms===
The stage of the [[tumor]](s) has a major impact on [[neoplasm]] prognosis. Staging is the process of determining tumor size, growth rate, potential [[metastasis]], lymph node involvement, treatment options and prognosis. Two-year prognosis for limited small cell pulmonary neoplasms is twenty percent and for extensive disease five percent. The average life expectancy for someone with recurrent small cell pulmonary neoplasms is two to three months.[http://www.lungdiseasefocus.com/lung-cancer/cancer-prognosis.php]

The 5-year overall survival rate for pulmonary neoplasms is 14%.<ref>John D. Minna, "Neoplasms of the Lung," in ''Harrison's Principles of Internal Medicine'', 16th ed. (2005), p. 506</ref>


== References ==
{{reflist|2}}

== External links ==
*[http://www.learnaboutcopd.org National Heart, Lung and Blood Institute - COPD] U.S. NHLBI Information for Patients and the Public page.

== Acknowledgements ==
The content on this page was first contributed by: C. Michael Gibson, M.S., M.D.

[[Category:Pulmonology]]
[[Category:Emergency medicine]]

{{Respiratory pathology}}
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[[es:Enfermedad Pulmonar Obstructiva Crónica]]
[[eu:BGBK]]
[[fr:Broncho-pneumopathie chronique obstructive]]
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[[he:מחלת ריאות חסימתית כרונית]]
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