Chronic obstructive pulmonary disease exacerbation resident survival guide: Difference between revisions

Latest revision as of 00:59, 17 December 2013

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1];Associate Editor(s)-in-Chief: Abdurahman Khalil, M.D. [2]

Definition

COPD exacerbation commonly caused by infections, should be recognized when any of the following symptoms is noticed in a chronic COPD patient:worsening cough, increasing dyspnea, increasing in sputum production more than the baseline for chronic COPD patients.^[1]

Causes

Life Threatening Causes

Include conditions which may result death or permanent disability within 24 hours if left untreated, and some of them may mimic and/or aggravate exacerbations:

Common Causes

Respiratory tract infections 50%(bacterial or viral).
Exposure to pollutants.
Unknown (⅓ of cases ).

Differential Diagnosis

Management

COPD Exacerbation
↑cough, ↑dyspnea, ↑sputum,
↑wheezing, fever or chest tightness

Admission

Assessment :
1-O2 sat+ ABG
2-CXR
3-EKG
4-CBC

Management:
1-Inhaled bronchodilators
2-Systemic corticosteroids
3-Empirical antibiotics
4-O2 (target Sat >90%)

Corticosteroids(Solumedrol)
Methylprednisolone 125 mg×1 dose
followed with 60-80 mg Q8-12based on severity
IV Solumedrol to PO Prednisone taper 4--60 mg Q 8-12
2-5 days taper depending on severity
Antibiotics
Group A*
Doxycycline Cap Vibramycin PO 100 mg Q12H
(if unable to tolerate choose Cefpodoxime Tab Vantin PO 200 mg Q12H)
Group B*
Ceftriaxone Inj Rocephin 1GM D5W50 ml Q24H 200 ml/Hr
(If Beta-Lactam allergy choose Levofloxacin Tab Levaquin PO 500 mg daily )
Group C*
Ciprofloxacin Tab CiproPO 250 Daily
or Ciprofloxacin Inj Cipro 400 mg premixed at 400 mg /200 ml Q12H 200 ml/Hr.

Respiratory acidosis? OR
PH≤35? OR
PaCo2≥45? OR
Severe signs of dyspnea? OR
Accessory muscles use,
paradoxical motion of abdomen,
retraction of intercostal space

No

Yes

Continue the same management

ICU Admission
NIV

Unable to tolerate NIV?
Severe hemodynamic instability?
Resp/cardiac arrest ?

Invasive mechanical ventilation

*Group A:mild exacerbation, no risk factors, 2>symptoms present Group B:Mod Exacerbation w/risk factors for poor outcomes:comorbid disease, severe COPD, Frequent exacerbation>3, Antimicrobial use within the last 3 months Group C:Severe exacerbation w/risk factors for P.aeruginosa infection.

Do's

Monitor fluid balance,nutrition and patient condition closely.
Consider subcutaneous heparin or low molecular weight heparin.
Treat associated conditions if exist(e.g., heart failure,arrhythmias).

References

↑ Rabe KF, Hurd S, Anzueto A, Barnes PJ, Buist SA, Calverley P; et al. (2007). "Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: GOLD executive summary". Am J Respir Crit Care Med. 176 (6): 532–55. doi:10.1164/rccm.200703-456SO. PMID 17507545.

[pmid17507545-1] Rabe KF, Hurd S, Anzueto A, Barnes PJ, Buist SA, Calverley P; et al. (2007). "Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: GOLD executive summary". Am J Respir Crit Care Med. 176 (6): 532–55. doi:10.1164/rccm.200703-456SO. PMID 17507545.

[1]

@@ Line 1: / Line 1: @@
 __NOTOC__
-{{CMG}}; {{AE}} {{AK}}
+{{CMG}};{{AE}}{{AK}}
+==Definition==
-==Definition==
+COPD exacerbation commonly caused by infections, should be recognized when any of the following symptoms is noticed in a chronic COPD patient:worsening cough, increasing dyspnea, increasing in sputum production more than the baseline for chronic COPD patients.<ref name="pmid17507545">{{cite journal| author=Rabe KF, Hurd S, Anzueto A, Barnes PJ, Buist SA, Calverley P 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 | year= 2007 | volume= 176 |issue= 6 | pages= 532-55 | pmid=17507545 | doi=10.1164/rccm.200703-456SO | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17507545  }} </ref>
-* Exacerbation of COPD is an acute event characterized by a worsening of the patient’s respiratory symptoms that is beyond normal day-to-day variations and leads to a change in medication.<ref name="Burge-2003">{{Cite journal  | last1 = Burge | first1 = S. | last2 = Wedzicha | first2 = JA. | title = COPD exacerbations: definitions and classifications. | journal = Eur Respir J Suppl | volume = 41 | issue =  | pages = 46s-53s | month = Jun | year = 2003 | doi =  | PMID = 12795331 }}</ref><ref name="Celli-2007">{{Cite journal  | last1 = Celli | first1 = BR. | last2 = Barnes | first2 = PJ. | title = Exacerbations of chronic obstructive pulmonary disease. | journal = Eur Respir J | volume = 29 | issue = 6 | pages = 1224-38 | month = Jun | year = 2007 | doi = 10.1183/09031936.00109906 | PMID = 17540785 }}</ref><ref name="Rodriguez-Roisin-2000">{{Cite journal  | last1 = Rodriguez-Roisin | first1 = R. | title = Toward a consensus definition for COPD exacerbations. | journal = Chest | volume = 117 | issue = 5 Suppl 2 | pages = 398S-401S | month = May | year = 2000 | doi =  | PMID = 10843984 }}</ref>
-* The diagnosis of an exacerbation relies exclusively on the clinical presentation of the patient complaining of an acute change of symptoms ('''baseline dyspnea, cough, and/or sputum production''') that is beyond normal day-to-day variation.<ref name="Vestbo-2013">{{Cite journal  | last1 = Vestbo | first1 = J. | last2 = Hurd | first2 = SS. | last3 = Agustí | first3 = AG. | last4 = Jones | first4 = PW. | last5 = Vogelmeier | first5 = C. | last6 = Anzueto | first6 = A. | last7 = Barnes | first7 = PJ. | last8 = Fabbri | first8 = LM. | last9 = Martinez | first9 = FJ. | 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 = 187 | issue = 4 | pages = 347-65 | month = Feb | year = 2013 | doi = 10.1164/rccm.201204-0596PP | PMID = 22878278 }}</ref>
 ==Causes==
-===Life-Threatening Causes===
+===Life Threatening Causes===
-<SMALL>''Life-threatening causes include conditions which may result in death or permanent disability within 24 hours if left untreated.''</SMALL>
+Include conditions which may result death or permanent disability within 24 hours if left untreated, and some of them may mimic and/or aggravate exacerbations:
-* [[Arrhythmia]]
+*[[Pneumonia]]
-* [[Congestive heart failure]]
+*[[PE]]
-* [[Pleural effusion]]
+*[[Pneumothorax]]
-* [[Pneumonia]]
+*[[Pleural effusion]]
-* [[Pneumothorax]]
+*[[CHF]]
-* [[Pulmonary embolism]]
+*[[Cardiac arrhythmias]]
 ===Common Causes===
-* [[Respiratory tract infections]] (~½)
+*Respiratory tract infections 50%(bacterial or viral).
-* Unknown (~⅓)
+*Exposure to pollutants.
-* Air pollutants
+*Unknown (⅓ of cases ).
-==Treatment Setting and Severity==
+==Differential Diagnosis==
-{{Family tree/start}}
+* [[Asthma]]
-{{Family tree |border=2|boxstyle=background: WhiteSmoke;|A1|A1=<div style="float: left; text-align: left; height: 5.5em; width: 9.7em; padding: 1em;">'''COPD Exacerbation''' <BR> ❑ Cough ↑ <BR> ❑ Dyspnea ↑ <BR> ❑ Sputum ↑ </div>}}
+* [[CHF]]
-{{Family tree |!|}}
+* [[PE]]
-{{Family tree |border=2|boxstyle=background:WhiteSmoke;|)|B1|B1=<div style="float: left; text-align: left; height: 4.8em; width: 41em; padding: 1em">
+* [[ACS]]
-'''1. Oxygen Supplement''' <BR> ❑ Pulse oximetry (maintain Sa<sub>O<sub>2</sub></sub> ≥88—92%)<ref name="Austin-2010">{{Cite journal  | last1 = Austin | first1 = MA. | last2 = Wills | first2 = KE. | last3 = Blizzard | first3 = L. | last4 = Walters | first4 = EH. | last5 = Wood-Baker | first5 = R. | title = Effect of high flow oxygen on mortality in chronic obstructive pulmonary disease patients in prehospital setting: randomised controlled trial. | journal = BMJ | volume = 341 | issue =  | pages = c5462 | month =  | year = 2010 | doi =  | PMID = 20959284 }}</ref> <BR> ❑ Arterial blood gas (if acute or acute-on-chronic respiratory failure is suspected)</div>}}
+* [[Pneumothorax]]
-{{Family tree |!|}}
+* [[Pneumonia]]
-{{Family tree |border=2|boxstyle=background:WhiteSmoke;|)|C1|C1=<div style="float: left; text-align: left; height: 7em; width: 39em; padding: 1em">
+* [[Atelectasis|Lobar atelectasis]]
-'''2. Indications for ICU Admission'''<BR> ❑ Hemodynamic instability <BR> ❑ Changes in mental status (confusion, lethargy, coma) <BR> ❑ Severe dyspnea that responds inadequately to initial emergency therapy <BR> ❑ Worsening hypoxemia (Pa<sub>O<sub>2</sub></sub> <40 mm Hg) and/or respiratory acidosis (pH <7.25)</div>}}
-{{Family tree |!| | |!|}}
-{{Family tree |border=2|boxstyle=background:WhiteSmoke;|!| |D1|D1=<div style="float: left; text-align: left; height: 23em; width: 40em; padding: 1em">'''2a. Indications for Noninvasive Mechanical Ventilation''' <BR> ❑ Respiratory acidosis (arterial pH < 7.35 or Pa<sub>CO<sub>2</sub></sub> >45 mm Hg) <BR> ❑ Severe dyspnea with sings of respiratory muscle fatigue <BR> ❑ Increased work of breathing
-----
-'''2b. Indications for Invasive Mechanical Ventilation''' <BR> ❑ Diminished consciousness, psychomotor agitation inadequately controlled by sedation <BR> ❑ Severe hemodynamic instability without response to fluids and vasoactive drugs <BR> ❑ Respiratory pauses with loss of consciousness or gasping for air <BR> ❑ Life-threatening hypoxemia in patients unable to tolerate NIV <BR> ❑ Persistent inability to remove respiratory secretions <BR> ❑ Heart rate <50/min with loss of alertness <BR> ❑ Severe ventricular arrhythmias <BR> ❑ Respiratory or cardiac arrest <BR> ❑ Failure of initial trial of NIV <BR> ❑ Massive aspiration</div>}}
-{{Family tree |!|}}
-{{Family tree |border=2|boxstyle=background:WhiteSmoke;|`|E1|E1=<div style="float: left; text-align: left; height: 23em; width: 41em; padding: 1em">
-'''3. Indications for Hospitalization''' <BR> ❑ Marked increase in intensity of symptoms (eg, sudden development of resting dyspnea) <BR> ❑ Presence of serious comorbidities (eg, heart failure or newly occurring arrhythmias) <BR> ❑ Failure of an exacerbation to respond to initial medical management <BR> ❑ Onset of new physical signs (eg, cyanosis, peripheral edema) <BR> ❑ Severe underlying COPD (GOLD 3—4 categories) <BR> ❑ Frequent exacerbations (≥2 events per year) <BR> ❑ Insufficient home support <BR> ❑ Older age (>65 years)
-----
-'''4. Assessment of Severity of Exacerbation''' <BR> ❑ Sputum purulence <BR> ❑ ECG (identify coexisting cardiac problems) <BR> ❑ Chest radiograph (exclude alternative diagnoses) <BR> ❑ Whole-blood count (identify polycythemia, anemia, or leukocytosis) <BR> ❑ Electrolytes and glucose (identify electrolyte disturbances or hyperglycemia)</div>}}
-{{Family tree | | | |!|}}
-{{Family tree |border=2|boxstyle=background:WhiteSmoke;| | | |F1|F1=<div style="float: left; text-align: left; height: 30em; width: 30em; padding: 1em">
-'''Severe Exacerbation'''  <BR> ❑ Consider inpatient management <BR> ❑ Assess symptoms, ABG, and CXR <BR> ❑ Monitor fluid balance and nutrition <BR> ❑ Identify and treat associated conditions <BR> ❑ Consider subcutaneous heparin or LMWH <BR> ❑ Controlled oxygen therapy (use NIV if indicated) <BR> ❑ Antibiotics (if ↑ sputum purulence or ⊕ bacterial infection) <BR> ❑ Corticosteroids <BR> ❑ Bronchodilators <BR> ▸ Increase doses/frequency of short-acting bronchodilators <BR> ▸ Combine short-acting β2-agonists and anticholinergics <BR> ▸ Use spacers or air-driven nebulizers
-----
-'''Moderate Exacerbation''' <BR> ❑ Consider outpatient management <BR> ❑ Require a short course of antibiotics or oral corticosteroids
-----
-'''Mild Exacerbation''' <BR> ❑ Consider outpatient management <BR> ❑ Require change of inhaled treatment by the patient</div>}}
-{{Family tree/end}}
 ==Management==
-<!--
 {{Family tree/start}}
 {{Family tree | | | | A01 | | | |A01= '''COPD Exacerbation'''<br>↑[[cough]], ↑[[dyspnea]], ↑[[sputum]], <br> ↑[[wheezing]], [[fever]] or chest tightness}}
@@ Line 60: / Line 36: @@
 {{Family tree | | | | C01 |~| C02 | |C01='''Assessment''' :<br>1-O2 sat+ ABG <br>2-[[CXR]] <br>3-[[EKG]] <br>4-[[CBC]]
 <br>
-'''Management:''' <br>1-Inhaled bronchodilators <br>2-Systemic corticosteroids <br>3-Empirical antibiotics <br>4-O2 (target Sat >90%)|C02='''Corticosteroids(Solumedrol)'''<br>Methylprednisolone 125 mg×1 dose <br> followed with 60-80 mg Q8-12based on severity <br> IV Solumedrol to PO Prednisone taper 4--60 mg Q 8-12<br> 2-5 days taper depending on severity<br> '''Antibiotics'''<br>'''Group A'''*<br>Doxycycline Cap '''Vibramycin''' PO 100 mg Q12H<br>(if unable to tolerate choose Cefpodoxime Tab '''Vantin''' PO 200 mg Q12H)<br>'''Group B'''*<br>Ceftriaxone Inj '''Rocephin''' 1GM D5W50 ml Q24H 200 ml/Hr<br>(If Beta-Lactam allergy choose Levofloxacin Tab '''Levaquin''' PO 500 mg daily )<br> '''Group C'''*<br>Ciprofloxacin Tab '''Cipro'''PO 250 Daily<br>or Ciprofloxacin Inj Cipro 400 mg premixed at 400 mg /200 ml Q12H 200 ml/Hr.
+'''Management:''' <br>1-Inhaled bronchodilators <br>2-Systemic corticosteroids <br>3-Empirical antibiotics <br>4-O2 (target Sat >90%)| C02='''Corticosteroids(Solumedrol)'''<br>Methylprednisolone 125 mg×1 dose <br> followed with 60-80 mg Q8-12based on severity <br> IV Solumedrol to PO Prednisone taper 4--60 mg Q 8-12<br> 2-5 days taper depending on severity<br> '''Antibiotics'''<br>'''Group A'''*<br>Doxycycline Cap '''Vibramycin''' PO 100 mg Q12H<br>(if unable to tolerate choose Cefpodoxime Tab '''Vantin''' PO 200 mg Q12H)<br>'''Group B'''*<br>Ceftriaxone Inj '''Rocephin''' 1GM D5W50 ml Q24H 200 ml/Hr<br>(If Beta-Lactam allergy choose Levofloxacin Tab '''Levaquin''' PO 500 mg daily )<br> '''Group C'''*<br>Ciprofloxacin Tab '''Cipro'''PO 250 Daily <br>or Ciprofloxacin Inj Cipro 400 mg premixed at 400 mg /200 ml Q12H 200 ml/Hr.
 }}
 {{Family tree | | | | |!| | | | |}}
-{{Family tree | | | | D01 | | | |D01=Respiratory acidosis? OR <br> PH≤35? OR<br> PaCo2≥45? OR<br> Severe signs of dyspnea? OR <br>Accessory muscles use,<br>paradoxical motion of abdomen,<br> retraction of intercostal space}}
+{{Family tree | | | | D01 | | | |D01=Respiratory acidosis? OR <br> PH≤35? OR<br> PaCo2≥45? OR<br> Severe signs of dyspnea? OR <br>Accessory muscles use, <br>paradoxical motion of abdomen,<br> retraction of intercostal space}}
 {{Family tree | | |,|-|^|-|.| | }}
 {{Family tree | E01 | | | E02 |E01=No | E02= Yes}}
 {{Family tree | |!| | | | |!| |}}
-{{Family tree | F01 | | | F02|F01=Continue the same management |F02='''ICU Admission''' }}
+{{Family tree | F01 | | | F02|F01=Continue the same management |F02='''ICU Admission''' <br>'''NIV''' }}
-{{family tree | | | | | | |!| | | | | | |}}
+{{Family tree | | | | | | |!| |}}
-{{family tree | | | | | | Z01 | | | | | |Z01=Non-invasive ventilation}}
-{{Family tree | | | | | | |!| | |}}
 {{Family tree | | | | | | G01 |G01= Unable to tolerate NIV?<br> Severe hemodynamic instability?<br>Resp/cardiac arrest ?  }}
 {{Family tree | | | | | | |!| | |}}
 {{Family tree | | | | | | H01 | |H01=Invasive mechanical ventilation}}
 {{Family tree/end}}
--->
-==Checklist at Time of Discharge From Hospital==
-{{Family tree/start}}
-{{Family tree |border=2|boxstyle=background: WhiteSmoke;|A1|A1=<div style="float: left; text-align: left; height: 13em; width: 39em; padding: 1em;">'''Action Items at Discharge''' <BR> ❑ Reinforce smoking cessation measures <BR> ❑ Assure effective home maintenance of pharmacotherapy regimen <BR> ❑ Reassess inhaler technique <BR> ❑ Educate about maintenance regimen <BR> ❑ Give instruction regarding completion of steroid therapy and antibiotics <BR> ❑ Assess need for long-term oxygen therapy <BR> ❑ Assure follow-up visit in 4—6 weeks <BR> ❑ Provide a management plan for comorbidities and their follow-up</div>}}
-{{Family tree/end}}
-==Checklist at Follow-Up Visit 4—6 Weeks After Discharge==
+'''*Group A''':mild exacerbation, no risk factors, 2>symptoms present
-{{Family tree/start}}
+'''Group B''':Mod Exacerbation w/risk factors for poor outcomes:comorbid disease, severe COPD, Frequent exacerbation>3, Antimicrobial use within the last 3 months
-{{Family tree |border=2|boxstyle=background: WhiteSmoke;|A1|A1=<div style="float: left; text-align: left; height: 18em; width: 41em; padding: 1em;">'''Action Items at Follow-Up Visit''' <BR> ❑ Smoking cessation measures <BR> ❑ Ability to cope in usual environment <BR> ❑ Reassess inhaler technique <BR> ❑ Measurement of FEV<sub>1</sub> <BR> ❑ Inhaler technique <BR> ❑ Understanding of recommended treatment regimen <BR> ❑ Need for long-term oxygen therapy and/or home nebulizer <BR> ❑ Capacity to do physical activity and activities of daily living <BR> ❑ Chronic Obstructive Pulmonary Disease Assessment Test (CAT) <BR> ❑ Modified British Medical Research Council questionnaire on breathlessness (mMRC) <BR> ❑ Status of comorbidities</div>}}
+'''Group C''':Severe exacerbation w/risk factors for P.aeruginosa infection.
-{{Family tree/end}}
 ==Do's==
-===Assessment===
+*Monitor fluid balance,nutrition and patient condition closely.
-* The presence of purulent [[sputum]] during an exacerbation can be sufficient indication for starting empirical antibiotic treatment.<ref name="Stockley-2000">{{Cite journal  | last1 = Stockley | first1 = RA. | last2 = O'Brien | first2 = C. | last3 = Pye | first3 = A. | last4 = Hill | first4 = SL. | title = Relationship of sputum color to nature and outpatient management of acute exacerbations of COPD. | journal = Chest | volume = 117 | issue = 6 | pages = 1638-45 | month = Jun | year = 2000 | doi =  | PMID = 10858396 }}</ref>
+*Consider subcutaneous heparin or low molecular weight heparin.
+*Treat associated conditions if exist(e.g., heart failure,arrhythmias).
-===Treatment===
-======Treatment Setting======
-* When a patient comes to the [[ED]], the first actions are to provide controlled [[oxygen therapy]] and to determine whether the exacerbation is life-threatening. If so, the patient should be admitted to the [[ICU]] immediately.<ref name="Vestbo-2013">{{Cite journal  | last1 = Vestbo | first1 = J. | last2 = Hurd|first2 = SS. | last3 = Agustí |first3 = AG. | last4 = Jones | first4 = PW. | last5 = Vogelmeier | first5 = C. | last6 = Anzueto | first6 = A. | last7 = Barnes | first7 = PJ. | last8 = Fabbri | first8 = LM. | last9 = Martinez | first9 = FJ. | 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 = 187 | issue = 4 | pages = 347-65 | month = Feb | year = 2013 | doi = 10.1164/rccm.201204-0596PP | PMID = 22878278}}</ref>
-======Short-Acting Bronchodilators======
-* Short-acting inhaled [[Beta2-adrenergic receptor agonist|β2-agonists]] with or without short-acting [[anticholinergic]]s are usually the preferred [[bronchodilator]]s for treatment of an exacerbation.<ref name="Celli-2004">{{Cite journal  | last1 = Celli | first1 = BR. | last2 = MacNee | first2 = W. | title = Standards for the diagnosis and treatment of patients with COPD: a summary of the ATS/ERS position paper. | journal = Eur Respir J | volume = 23 | issue = 6 | pages = 932-46 | month = Jun | year = 2004 | doi =  | PMID = 15219010 }}</ref>
-* A systematic review found no significant differences in [[FEV1|FEV<sub>1</sub>]] between [[Metered-dose inhaler|MDI]] and [[Nebulizer|nebulizers]],<ref name="Turner-">{{Cite journal  | last1 = Turner | first1 = MO. | last2 = Patel | first2 = A. | last3 = Ginsburg | first3 = S. | last4 = FitzGerald | first4 = JM. | title = Bronchodilator delivery in acute airflow obstruction. A meta-analysis. | journal = Arch Intern Med | volume = 157 | issue = 15 | pages = 1736-44 | month =  | year =  | doi =  | PMID = 9250235 }}</ref> although the latter can be more convenient for sicker or frail patients.
-* Intravenous [[methylxanthine]]s ([[theophylline]] or [[aminophylline]]) are only to be used in selected cases when there is insufficient response to [[SABA|short-acting bronchodilators]].<ref name="Barberá-1992">{{Cite journal  | last1 = Barberá | first1 = JA. | last2 = Reyes | first2 = A. | last3 = Roca | first3 = J. | last4 = Montserrat | first4 = JM. | last5 = Wagner | first5 = PD. | last6 = Rodríguez-Roisin | first6 = R. | title = Effect of intravenously administered aminophylline on ventilation/perfusion inequality during recovery from exacerbations of chronic obstructive pulmonary disease. | journal = Am Rev Respir Dis | volume = 145 | issue = 6 | pages = 1328-33 | month = Jun | year = 1992 | doi = 10.1164/ajrccm/145.6.1328 | PMID = 1595998 }}</ref><ref name="Emerman-1990">{{Cite journal  | last1 = Emerman | first1 = CL. | last2 = Connors | first2 = AF. | last3 = Lukens | first3 = TW. | last4 = May | first4 = ME. | last5 = Effron | first5 = D. | title = Theophylline concentrations in patients with acute exacerbation of COPD. | journal = Am J Emerg Med | volume = 8 | issue = 4 | pages = 289-92 | month = Jul | year = 1990 | doi =  | PMID = 2363749 }}</ref><ref name="Lloberes-1988">{{Cite journal  | last1 = Lloberes | first1 = P. | last2 = Ramis | first2 = L. | last3 = Montserrat | first3 = JM. | last4 = Serra | first4 = J. | last5 = Campistol | first5 = J. | last6 = Picado | first6 = C. | last7 = Agusti-Vidal | first7 = A. | title = Effect of three different bronchodilators during an exacerbation of chronic obstructive pulmonary disease. | journal = Eur Respir J | volume = 1 | issue = 6 | pages = 536-9 | month = Jun | year = 1988 | doi =  | PMID = 2971565 }}</ref><ref name="Mahon-1999">{{Cite journal  | last1 = Mahon | first1 = JL. | last2 = Laupacis | first2 = A. | last3 = Hodder | first3 = RV. | last4 = McKim | first4 = DA. | last5 = Paterson | first5 = NA. | last6 = Wood | first6 = TE. | last7 = Donner | first7 = A. | title = Theophylline for irreversible chronic airflow limitation: a randomized study comparing n of 1 trials to standard practice. | journal = Chest | volume = 115 | issue = 1 | pages = 38-48 | month = Jan | year = 1999 | doi =  | PMID = 9925061 }}</ref><ref name="Murciano-1984">{{Cite journal  | last1 = Murciano | first1 = D. | last2 = Aubier | first2 = M. | last3 = Lecocguic | first3 = Y. | last4 = Pariente | first4 = R. | title = Effects of theophylline on diaphragmatic strength and fatigue in patients with chronic obstructive pulmonary disease. | journal = N Engl J Med | volume = 311 | issue = 6 | pages = 349-53 | month = Aug | year = 1984 | doi = 10.1056/NEJM198408093110601 | PMID = 6738652 }}</ref>
-======Corticosteroids======
-* Systemic [[corticosteroids]] in COPD exacerbations shorten recovery time, improve [[FEV1|FEV<sub>1</sub>]] and [[PaO2|Pa<sub>O<sub>2</sub></sub>]],<ref name="Davies-1999">{{Cite journal  | last1 = Davies | first1 = L. | last2 = Angus | first2 = RM. | last3 = Calverley | first3 = PM. | title = Oral corticosteroids in patients admitted to hospital with exacerbations of chronic obstructive pulmonary disease: a prospective randomised controlled trial. | journal = Lancet | volume = 354 | issue = 9177 | pages = 456-60 | month = Aug | year = 1999 | doi =  | PMID = 10465169 }}</ref><ref name="Maltais-2002">{{Cite journal  | last1 = Maltais | first1 = F. | last2 = Ostinelli | first2 = J. | last3 = Bourbeau | first3 = J. | last4 = Tonnel | first4 = AB. | last5 = Jacquemet | first5 = N. | last6 = Haddon | first6 = J. | last7 = Rouleau | first7 = M. | last8 = Boukhana | first8 = M. | last9 = Martinot | first9 = JB. | title = Comparison of nebulized budesonide and oral prednisolone with placebo in the treatment of acute exacerbations of chronic obstructive pulmonary disease: a randomized controlled trial. | journal = Am J Respir Crit Care Med | volume = 165 | issue = 5 | pages = 698-703 | month = Mar | year = 2002 | doi = 10.1164/ajrccm.165.5.2109093 | PMID = 11874817 }}</ref><ref name="Niewoehner-1999">{{Cite journal  | last1 = Niewoehner | first1 = DE. | last2 = Erbland | first2 = ML. | last3 = Deupree | first3 = RH. | last4 = Collins | first4 = D. |last5 = Gross | first5 = NJ. | last6 = Light | first6 = RW. | last7 = Anderson | first7 = P. | last8 = Morgan | first8 = NA. | title = Effect of systemic glucocorticoids on exacerbations of chronic obstructive pulmonary disease. Department of Veterans Affairs Cooperative Study Group. | journal = N Engl J Med | volume = 340 | issue = 25 | pages = 1941-7| month = Jun | year = 1999 | doi = 10.1056/NEJM199906243402502 | PMID = 10379017 }}</ref><ref name="Thompson-1996">{{Cite journal  | last1 = Thompson | first1 = WH. | last2 = Nielson | first2 = CP. | last3 = Carvalho | first3 = P. | last4 = Charan | first4 = NB. | last5 = Crowley | first5 = JJ. | title = Controlled trial of oral prednisone in outpatients with acute COPD exacerbation. | journal = Am J Respir Crit Care Med | volume = 154 | issue = 2 Pt 1 | pages = 407-12 | month = Aug | year = 1996 | doi = 10.1164/ajrccm.154.2.8756814 | PMID = 8756814 }}</ref> and reduce the risk of early relapse, treatment failure, and length of hospital stay.<ref name="Davies-1999">{{Cite journal  | last1 = Davies | first1 = L. | last2 = Angus | first2 = RM. | last3 = Calverley | first3 = PM. | title = Oral corticosteroids in patients admitted to hospital with exacerbations of chronic obstructive pulmonary disease: a prospective randomised controlled trial. | journal = Lancet | volume = 354 | issue = 9177 | pages = 456-60 | month = Aug | year = 1999 | doi =  | PMID = 10465169 }}</ref><ref name="Niewoehner-1999">{{Cite journal  | last1 = Niewoehner | first1 = DE. | last2 = Erbland | first2 = ML. | last3 = Deupree | first3 = RH. | last4 = Collins | first4 = D. | last5 = Gross | first5 = NJ. | last6 = Light | first6 = RW. | last7 = Anderson | first7 = P. | last8 = Morgan| first8 = NA. | title = Effect of systemic glucocorticoids on exacerbations of chronic obstructive pulmonary disease. Department of Veterans Affairs Cooperative Study Group. |journal = N Engl J Med | volume = 340 | issue = 25 | pages = 1941-7 | month = Jun | year = 1999 | doi = 10.1056/NEJM199906243402502 | PMID = 10379017 }}</ref><ref name="Aaron-2003">{{Cite journal  | last1 = Aaron | first1 = SD. | last2 = Vandemheen | first2 = KL. | last3 = Hebert | first3 = P. | last4 = Dales | first4 = R. | last5 = Stiell | first5 = IG. |last6 = Ahuja | first6 = J. | last7 = Dickinson | first7 = G. | last8 = Brison | first8 = R. | last9 = Rowe | first9 = BH. | title = Outpatient oral prednisone after emergency treatment of chronic obstructive pulmonary disease. | journal = N Engl J Med | volume = 348 | issue = 26 | pages = 2618-25 | month = Jun | year = 2003 | doi = 10.1056/NEJMoa023161 |PMID = 12826636 }}</ref>
-* Consensus on optimal [[corticosteroids]] dose and duration for COPD exacerbations has not been reached.<ref name="Walters-2009">{{Cite journal  | last1 = Walters | first1 = JA. | last2 = Gibson | first2 = PG. | last3 = Wood-Baker | first3 = R. | last4 = Hannay | first4 = M. | last5 = Walters | first5 = EH. | title = Systemic corticosteroids for acute exacerbations of chronic obstructive pulmonary disease. | journal = Cochrane Database Syst Rev | volume =  | issue = 1 | pages = CD001288 | month =  | year = 2009 | doi = 10.1002/14651858.CD001288.pub3 | PMID = 19160195 }}</ref>
-======Antibiotics======
-* [[Haemophilus influenzae]], [[Streptococcus pneumoniae]], and [[Moraxella catarrhalis]] are the most common bacterial pathogens involved in an exacerbation.<ref name="Sethi-2008">{{Cite journal  | last1 = Sethi | first1 = S. | last2 = Murphy | first2 = TF. | title = Infection in the pathogenesis and course of chronic obstructive pulmonary disease. | journal = N Engl J Med | volume = 359 | issue = 22 | pages = 2355-65 | month = Nov | year = 2008 | doi = 10.1056/NEJMra0800353 | PMID = 19038881 }}</ref> However, the choice of the antibiotic should be based on the local bacterial resistance pattern.
-* Empirical coverage of [[Pseudomonas aeruginosa]] in GOLD 3 and GOLD 4 patients is important.<ref name="Vestbo-2013">{{Cite journal  | last1 = Vestbo | first1 = J. | last2 = Hurd |first2 = SS. | last3 = Agustí |first3 = AG. | last4 = Jones | first4 = PW. | last5 = Vogelmeier | first5 = C. | last6 = Anzueto | first6 = A. | last7 = Barnes | first7 = PJ. | last8 = Fabbri | first8 = LM. | last9 = Martinez | first9 = FJ. | 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 = 187 | issue = 4 | pages = 347-65 | month = Feb | year = 2013 | doi = 10.1164/rccm.201204-0596PP | PMID = 22878278}}</ref>
-* [[Procalcitonin]] may be of value in the decision to use antibiotics.<ref name="Christ-Crain-2004">{{Cite journal  | last1 = Christ-Crain | first1 = M. | last2 = Jaccard-Stolz | first2 = D. | last3 = Bingisser | first3 = R. | last4 = Gencay | first4 = MM. | last5 = Huber | first5 = PR. | last6 = Tamm | first6 = M. | last7 = Müller | first7 = B. | title = Effect of procalcitonin-guided treatment on antibiotic use and outcome in lower respiratory tract infections: cluster-randomised, single-blinded intervention trial. | journal = Lancet | volume = 363 | issue = 9409 | pages = 600-7 | month = Feb | year = 2004 | doi = 10.1016/S0140-6736(04)15591-8 | PMID = 14987884 }}</ref>
-======Adjunct Therapies======
-* An appropriate fluid balance with special attention to the administration of [[diuretic]]s, [[anticoagulant]]s, treatment of [[comorbidities]], and nutritional aspects should be considered.<ref name="Vestbo-2013">{{Cite journal  | last1 = Vestbo | first1 = J. | last2 = Hurd | first2 = SS. | last3 = Agustí| first3 = AG. | last4 = Jones | first4 = PW. | last5 = Vogelmeier | first5 = C. | last6 = Anzueto | first6 = A. | last7 = Barnes | first7 = PJ. | last8 = Fabbri | first8 = LM. |last9 = Martinez | first9 = FJ. | 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 = 187 | issue = 4 | pages = 347-65 | month = Feb | year = 2013 | doi = 10.1164/rccm.201204-0596PP | PMID = 22878278 }}</ref>
-* Healthcare providers should strongly enforce stringent measures against active [[cigarette]] smoking.<ref name="Vestbo-2013">{{Cite journal  | last1 = Vestbo | first1 = J. | last2 = Hurd | first2 = SS. | last3 = Agustí| first3 = AG. | last4 = Jones | first4 = PW. | last5 = Vogelmeier | first5 = C. | last6 = Anzueto | first6 = A. | last7 = Barnes | first7 = PJ. | last8 = Fabbri | first8 = LM. |last9 = Martinez | first9 = FJ. | 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 = 187 | issue = 4 | pages = 347-65 | month = Feb | year = 2013 | doi = 10.1164/rccm.201204-0596PP | PMID = 22878278 }}</ref>
-======Respiratory Support======
-* Once oxygen is started, [[arterial blood gases]] should be checked 30 to 60 minutes later to ensure satisfactory [[oxygenation]] without [[carbon dioxide]] retention or [[acidosis]].<ref name="Vestbo-2013">{{Cite journal  | last1 = Vestbo | first1 = J. | last2 = Hurd | first2 = SS. | last3 = Agustí| first3 = AG. | last4 = Jones | first4 = PW. | last5 = Vogelmeier | first5 = C. | last6 = Anzueto | first6 = A. | last7 = Barnes | first7 = PJ. | last8 = Fabbri | first8 = LM. |last9 = Martinez | first9 = FJ. | 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 = 187 | issue = 4 | pages = 347-65 | month = Feb | year = 2013 | doi = 10.1164/rccm.201204-0596PP |PMID = 22878278 }}</ref>
-* [[Venturi mask]]s offer more accurate and controlled delivery of [[oxygen]] than do [[Nasal cannula|nasal prongs]] but are less likely to be tolerated by the patient.<ref name="Celli-2004">{{Cite journal  | last1 = Celli | first1 = BR. | last2 = MacNee | first2 = W. | title = Standards for the diagnosis and treatment of patients with COPD: a summary of the ATS/ERS position paper. | journal = Eur Respir J | volume = 23 | issue = 6 | pages = 932-46 | month = Jun | year = 2004 | doi =  | PMID = 15219010 }}</ref>
-* Noninvasive [[mechanical ventilation]] improves [[respiratory acidosis]] and decreases [[respiratory rate]], severity of breathlessness, complications such as [[ventilator-associated pneumonia]], length of hospital stay, [[mortality]], and [[intubation]] rates.<ref name="Brochard-1995">{{Cite journal  | last1 = Brochard | first1 = L. | last2 = Mancebo | first2 = J. | last3 = Wysocki | first3 = M. | last4 = Lofaso | first4 = F. | last5 = Conti | first5 = G. | last6 = Rauss | first6 = A. | last7 = Simonneau | first7 = G. | last8 = Benito | first8 = S. | last9 = Gasparetto | first9 = A. | title = Noninvasive ventilation for acute exacerbations of chronic obstructive pulmonary disease. | journal = N Engl J Med | volume = 333 | issue = 13 | pages = 817-22 | month = Sep | year = 1995 | doi = 10.1056/NEJM199509283331301 | PMID = 7651472 }}</ref><ref name="Bott-1993">{{Cite journal  | last1 = Bott | first1 = J. | last2 = Carroll | first2 = MP. | last3 = Conway | first3 = JH. | last4 = Keilty | first4 = SE. | last5 = Ward | first5 = EM. | last6 = Brown | first6 = AM. | last7 = Paul | first7 = EA. | last8 = Elliott | first8 = MW. | last9 = Godfrey | first9 = RC. | title = Randomised controlled trial of nasal ventilation in acute ventilatory failure due to chronic obstructive airways disease. | journal = Lancet | volume = 341 | issue = 8860 | pages = 1555-7 | month = Jun | year = 1993 | doi =  | PMID = 8099639 }}</ref><ref name="Kramer-1995">{{Cite journal  | last1 = Kramer | first1 = N. | last2 = Meyer | first2 = TJ. | last3 = Meharg | first3 = J. | last4 = Cece | first4 = RD. | last5 = Hill | first5 = NS. | title = Randomized, prospective trial of noninvasive positive pressure ventilation in acute respiratory failure. | journal = Am J Respir Crit Care Med | volume = 151 | issue = 6 | pages = 1799-806 | month = Jun | year = 1995 | doi = 10.1164/ajrccm.151.6.7767523 | PMID = 7767523 }}</ref><ref name="Plant-2000">{{Cite journal  | last1 = Plant | first1 = PK. | last2 = Owen | first2 = JL. | last3 = Elliott | first3 = MW. | title = Early use of non-invasive ventilation for acute exacerbations of chronic obstructive pulmonary disease on general respiratory wards: a multicentre randomised controlled trial. | journal = Lancet | volume = 355 | issue = 9219 | pages = 1931-5 | month = Jun | year = 2000 | doi =  | PMID = 10859037 }}</ref>
-===Hospital Discharge and Follow-up===
-* In the hospital prior to discharge, patients should start [[LABA|long-acting bronchodilators]], either [[anticholinergics]] and/or [[Beta2-adrenergic receptor agonist|β2-agonists]] with or without inhaled [[corticosteroids]].<ref name="Vestbo-2013">{{Cite journal  | last1 = Vestbo | first1 = J. | last2 = Hurd|first2 = SS. | last3 = Agustí |first3 = AG. | last4 = Jones | first4 = PW. | last5 = Vogelmeier | first5 = C. | last6 = Anzueto | first6 = A. | last7 = Barnes | first7 = PJ. | last8 = Fabbri | first8 = LM. | last9 = Martinez | first9 = FJ. | 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 = 187 | issue = 4 | pages = 347-65 | month = Feb | year = 2013 | doi = 10.1164/rccm.201204-0596PP | PMID = 22878278}}</ref>
-* For patients who are [[hypoxia|hypoxemic]] during an exacerbation, [[arterial blood gases]] and/or [[pulse oximetry]] should be evaluated prior to hospital discharge and in the following 3 months. If the patient remains hypoxemic, long-term supplemental [[oxygen therapy]] may be required.<ref name="Vestbo-2013">{{Cite journal  | last1 = Vestbo | first1 = J. | last2 = Hurd|first2 = SS. | last3 = Agustí |first3 = AG. | last4 = Jones | first4 = PW. | last5 = Vogelmeier | first5 = C. | last6 = Anzueto | first6 = A. | last7 = Barnes | first7 = PJ. | last8 = Fabbri | first8 = LM. | last9 = Martinez | first9 = FJ. | 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 = 187 | issue = 4 | pages = 347-65 | month = Feb | year = 2013 | doi = 10.1164/rccm.201204-0596PP | PMID = 22878278}}</ref>
-===Prevention of COPD Exacerbations===
-* [[Smoking cessation]], [[influenza vaccine|influenza]] and [[pneumococcal vaccine]]s, knowledge of current therapy including inhaler technique, and treatment with [[LABA|long-acting inhaled bronchodilators]], with or without inhaled [[corticosteroids]], and [[Phosphodiesterase inhibitors#PDE4-selective inhibitors|phosphodiesterase-4 inhibitors]] are all therapies that reduce the number of exacerbations and hospitalizations.<ref name="Calverley-2007">{{Cite journal  | last1 = Calverley | first1 = PM. | last2 = Anderson | first2 = JA. | last3 = Celli | first3 = B. | last4 = Ferguson | first4 = GT. | last5 = Jenkins | first5 = C. | last6 = Jones | first6 = PW. | last7 = Yates | first7 = JC. | last8 = Vestbo | first8 = 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 | month = Feb | year = 2007 | doi = 10.1056/NEJMoa063070 | PMID = 17314337 }}</ref><ref name="Tashkin-2008">{{Cite journal  | last1 = Tashkin | first1 = DP. | last2 = Celli | first2 = B. | last3 = Senn | first3 = S. | last4 = Burkhart | first4 = D. | last5 = Kesten | first5 = S. | last6 = Menjoge | first6 = S. | last7 = Decramer | first7 = M. | last8 = Schiavi | first8 = E. | last9 = Figueroa Casas | first9 = JC. | title = A 4-year trial of tiotropium in chronic obstructive pulmonary disease. | journal = N Engl J Med | volume = 359 | issue = 15 | pages = 1543-54 | month = Oct | year = 2008 | doi = 10.1056/NEJMoa0805800 | PMID = 18836213 }}</ref><ref name="Calverley-2009">{{Cite journal  | last1 = Calverley | first1 = PM. | last2 = Rabe | first2 = KF. | last3 = Goehring | first3 = UM. | last4 = Kristiansen | first4 = S. | last5 = Fabbri | first5 = LM. | last6 = Martinez | first6 = FJ. | last7 = Abdool-Gaffar | first7 = MS. | last8 = Abdullah | first8 = IA. | last9 = Abdullah | first9 = I. | title = Roflumilast in symptomatic chronic obstructive pulmonary disease: two randomised clinical trials. | journal = Lancet | volume = 374 | issue = 9691 | pages = 685-94 | month = Aug | year = 2009 | doi = 10.1016/S0140-6736(09)61255-1 | PMID = 19716960 }}</ref><ref name="Fabbri-2009">{{Cite journal  | last1 = Fabbri | first1 = LM. | last2 = Calverley | first2 = PM. | last3 = Izquierdo-Alonso | first3 = JL. | last4 = Bundschuh | first4 = DS. | last5 = Brose | first5 = M. | last6 = Martinez | first6 = FJ. | last7 = Rabe | first7 = KF. | last8 = Abdulla | first8 = R. | last9 = Abdullah | first9 = I. | title = Roflumilast in moderate-to-severe chronic obstructive pulmonary disease treated with longacting bronchodilators: two randomised clinical trials. | journal = Lancet | volume = 374 | issue = 9691 | pages = 695-703 | month = Aug | year = 2009 | doi = 10.1016/S0140-6736(09)61252-6 | PMID = 19716961 }}</ref><ref name="Decramer-2009">{{Cite journal  | last1 = Decramer | first1 = M. | last2 = Celli | first2 = B. | last3 = Kesten | first3 = S. | last4 = Lystig | first4 = T. | last5 = Mehra | first5 = S. | last6 = Tashkin | first6 = DP. | last7 = Schiavi | first7 = E. | last8 = Casas | first8 = JC. | last9 = Rhodius | first9 = E. | title = Effect of tiotropium on outcomes in patients with moderate chronic obstructive pulmonary disease (UPLIFT): a prespecified subgroup analysis of a randomised controlled trial. | journal = Lancet | volume = 374 | issue = 9696 | pages = 1171-8 | month = Oct | year = 2009 | doi = 10.1016/S0140-6736(09)61298-8 | PMID = 19716598 }}</ref><ref name="Jenkins-2009">{{Cite journal  | last1 = Jenkins | first1 = CR. | last2 = Jones | first2 = PW. | last3 = Calverley | first3 = PM. | last4 = Celli | first4 = B. | last5 = Anderson | first5 = JA. | last6 = Ferguson | first6 = GT. | last7 = Yates | first7 = JC. | last8 = Willits | first8 = LR. | last9 = Vestbo | first9 = J. | title = Efficacy of salmeterol/fluticasone propionate by GOLD stage of chronic obstructive pulmonary disease: analysis from the randomised, placebo-controlled TORCH study. | journal = Respir Res | volume = 10 | issue =  | pages = 59 | month =  | year = 2009 | doi = 10.1186/1465-9921-10-59 | PMID = 19566934 }}</ref>
-* Early outpatient [[pulmonary rehabilitation]] after hospitalization for an exacerbation is safe and results in clinically significant improvements in exercise capacity and health status at 3 months.<ref name="Man-2004">{{Cite journal  | last1 = Man | first1 = WD. | last2 = Polkey | first2 = MI. | last3 = Donaldson | first3 = N. | last4 = Gray | first4 = BJ. | last5 = Moxham | first5 = J. | title = Community pulmonary rehabilitation after hospitalisation for acute exacerbations of chronic obstructive pulmonary disease: randomised controlled study. | journal = BMJ | volume = 329 | issue = 7476 | pages = 1209 | month = Nov | year = 2004 | doi = 10.1136/bmj.38258.662720.3A | PMID = 15504763 }}</ref>
-==Don'ts==
-===Assessment===
-* Spirometry is '''not''' recommended during an exacerbation because it can be difficult to perform and measurements are not accurate enough.<ref name="Vestbo-2013">{{Cite journal  | last1 = Vestbo | first1 = J. | last2 = Hurd|first2 = SS. | last3 = Agustí |first3 = AG. | last4 = Jones | first4 = PW. | last5 = Vogelmeier | first5 = C. | last6 = Anzueto | first6 = A. | last7 = Barnes | first7 = PJ. | last8 = Fabbri | first8 = LM. | last9 = Martinez | first9 = FJ. | 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 = 187 | issue = 4 | pages = 347-65 | month = Feb | year = 2013 | doi = 10.1164/rccm.201204-0596PP | PMID = 22878278}}</ref>
-===Treatment===
-======Adjunct Therapies======
-* The use of [[Mucolytic agent|mucolytics]] is '''not''' well-supported by evidence.<ref name="McCrory-2001">{{Cite journal  | last1 = McCrory | first1 = DC. | last2 = Brown | first2 = C. | last3 = Gelfand | first3 = SE. | last4 = Bach | first4 = PB. | title = Management of acute exacerbations of COPD: a summary and appraisal of published evidence. | journal = Chest | volume = 119 | issue = 4 | pages = 1190-209 | month = Apr | year = 2001 | doi =  | PMID = 11296189 }}</ref>
 ==References==
-{{Reflist|2}}
+{{reflist|2}}
-[[Category:Resident survival guide]]