Health Dictionary
Reliable, easy-to-read patient information on common medical conditions — written in plain language, free of jargon, and grounded in current evidence. Browse the most frequent diagnoses, understand what they mean for everyday life, and learn which steps and questions help you have a focused conversation with your doctor.
COPD exacerbation resident survival guide
Introduction
Overview
Overview
COPD exacerbation is an acute event characterized by a worsening of the patient’s respiratory symptoms (baseline dyspnea, cough, and/or sputum production) that is beyond normal day-to-day variations and leads to a change in medication.[1][2][3][4]
Causes
Causes
Life-Threatening Causes
Life-threatening causes include conditions which may result in death or permanent disability within 24 hours if left untreated.
Common Causes
- Respiratory tract infections (~½)
- Unknown (~⅓)
- Air pollutants
Management
Management
Consider alternative dagnosis:
❑ Pulmonary embolism ❑ Heart failure ❑ Asthma exacerbation ❑ Bronchiectasis ❑ Broncholitis obliterans | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Supplement Oxygen: (Urgent) ❑ Maintain SaO2 ≥ 88-92% )[5] | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Need for ICU admission? ❑ Hemodynamic instability AND/OR ❑ Changes in mental status (confusion, lethargy, coma) AND/OR ❑ Severe dyspnea that responds inadequately to initial emergency therapy AND/OR ❑ Worsening hypoxemia (PaO2 <40 mm Hg) and/or respiratory acidosis (pH <7.25) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| No | Yes | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Indications for Hospitalization: ❑ Marked increase in intensity of symptoms (eg, sudden development of resting dyspnea) ❑ Presence of serious comorbidities (eg, heart failure or newly occurring arrhythmias) ❑ Failure of an exacerbation to respond to initial medical management ❑ Onset of new physical signs (eg, cyanosis, peripheral edema) ❑ Severe underlying COPD (GOLD 3—4 categories) ❑ Frequent exacerbations (≥2 events per year) ❑ Insufficient home support ❑ Older age (>65 years) | Assessment of Exacerbation: ❑ Cardinal symptoms (↑ dyspnea, ↑ sputum volume, and ↑ sputum purulence) ❑ ECG (identify coexisting cardiac problems) ❑ Chest radiograph (exclude alternative diagnoses) ❑ Whole-blood count (identify polycythemia, anemia, or leukocytosis) ❑ Electrolytes and glucose (identify electrolyte disturbances or hyperglycemia) | ❑ Admit patient to ICU ❑ Classify as Life-threatening COPD exacerbation ❑ Assess patients need for mechanical ventilation | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Indications for Noninvasive Mechanical Ventilation ❑ Respiratory acidosis (arterial pH < 7.35 or PaCO2 >45 mm Hg) ❑ Severe dyspnea with signs of respiratory muscle fatigue ❑ Increased work of breathing | Indications for Invasive Mechanical Ventilation ❑ Diminished consciousness, psychomotor agitation inadequately controlled by sedation ❑ Severe hemodynamic instability without response to fluids and vasoactive drugs ❑ Respiratory pauses with loss of consciousness or gasping for air ❑ Life-threatening hypoxemia in patients unable to tolerate NIV ❑ Persistent inability to remove respiratory secretions ❑ Heart rate <50/min with loss of alertness ❑ Severe ventricular arrhythmias ❑ Respiratory or cardiac arrest ❑ Failure of initial trial of NIV ❑ Massive aspiration | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Mild Exacerbation (⊕ 1 cardinal symptom) ❑ Consider outpatient management ❑ Require change of inhaled treatment by the patient | Moderate Exacerbation (⊕ 2 cardinal symptoms) ❑ Consider outpatient management ❑ Require a short course of antibiotics and/or oral corticosteroids | Severe Exacerbation (⊕ 3 cardinal symptoms) ❑ Consider inpatient management ❑ Assess symptoms, ABG, and CXR ❑ Monitor fluid balance and nutrition ❑ Identify and treat associated conditions ❑ Consider subcutaneous heparin or LMWH ❑ Controlled oxygen therapy (consider NIV if indicated) ❑ Antibiotics (if ↑ sputum purulence or ⊕ bacterial infection) ❑ Corticosteroids ❑ Bronchodilators ▸ Increase doses/frequency of short-acting bronchodilators ▸ Combine short-acting β2-agonists and anticholinergics ▸ Use spacers or air-driven nebulizers | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Pharmacologic Treatment
Pharmacologic Treatment
β2-adrenergic agonists ▸ Albuterol MDI 4—8 puffs IH q1—2h OR Nebulizer 2.5—5 mg IH q1—2h Anticholinergics Methylxanthines Treatment Notes[6][7][8][9][10][11][12][13] ❑ Short-acting β2-agonists with or without short-acting anticholinergics are generally preferred ❑ Consider methylxanthine as an adjunct if inadequate response to bronchodilators | |||||
Corticosteroids ▸ Prednisolone 30—40 mg PO q24h for 10—14 days (for mild/moderate exacerbation) ▸ Methylprednisolone 125 mg IV q6h for 3 days (for severe exacerbation) Treatment Notes[4][14][15][16] ❑ Budesonide 400 mcg IH bid may be an alternative to oral corticosteroids ❑ Corticosteroids should be tapered over 2 weeks | |||||
Indications for Antibiotics ❑ Mechanical ventilation required ❑ Severe exacerbation (⊕ 3 cardinal symptoms) ❑ Moderate exacerbation with ↑ sputum purulence Complicated COPD (⊕ Risk Factors) Uncomplicated COPD (⌀ Risk Factors) Treatment Notes[17][18] ❑ Antibiotic choice should reflect local resistance pattern ❑ Use alternative class if antibiotic exposure within 3 months ❑ Re-evaluate and consider sputum culture if failed to respond in 72 hours ❑ The recommended length of antibiotic therapy is usually 5—10 days | |||||
Checklist at Time of Discharge From Hospital
Checklist at Time of Discharge From Hospital
Action Items at Discharge ❑ Reinforce smoking cessation measures ❑ Assure effective home maintenance of pharmacotherapy regimen ❑ Reassess inhaler technique ❑ Educate about maintenance regimen ❑ Give instruction regarding completion of steroid therapy and antibiotics ❑ Assess need for long-term oxygen therapy ❑ Assure follow-up visit in 4—6 weeks ❑ Provide a management plan for comorbidities and their follow-up | |||||
Checklist at Follow-Up Visit 4—6 Weeks After Discharge
Checklist at Follow-Up Visit 4—6 Weeks After Discharge
Action Items at Follow-Up Visit ❑ Smoking cessation measures ❑ Ability to cope in usual environment ❑ Reassess inhaler technique ❑ Measurement of FEV1 ❑ Inhaler technique ❑ Understanding of recommended treatment regimen ❑ Need for long-term oxygen therapy and/or home nebulizer ❑ Capacity to do physical activity and activities of daily living ❑ Chronic Obstructive Pulmonary Disease Assessment Test (CAT) ❑ Modified British Medical Research Council questionnaire on breathlessness (mMRC) ❑ Status of comorbidities | |||||
Do’s
Do’s
Assessment
- The presence of purulent sputum during an exacerbation can be sufficient indication for starting empirical antibiotic treatment.[19]
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.[4]
Short-Acting Bronchodilators
- Short-acting inhaled β2-agonists with or without short-acting anticholinergics are usually the preferred bronchodilators for treatment of an exacerbation.[7]
- A systematic review found no significant differences in FEV1 between MDI and nebulizers,[20] although the latter can be more convenient for sicker or frail patients.
- Intravenous methylxanthines (theophylline or aminophylline) are only to be used in selected cases when there is insufficient response to short-acting bronchodilators.[8][9][10][11][12][21]
Corticosteroids
- Systemic corticosteroids in COPD exacerbations shorten recovery time, improve FEV1 and PaO2,[22][14][23][24] and reduce the risk of early relapse, treatment failure, and length of hospital stay.[22][23][25]
- Consensus on optimal corticosteroids dose and duration for COPD exacerbations has not been reached.[26]
Antibiotics
- Haemophilus influenzae, Streptococcus pneumoniae, and Moraxella catarrhalis are the most common bacterial pathogens involved in an exacerbation.[17] 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.[4]
- Procalcitonin may be of value in the decision to use antibiotics.[27]
Adjunct Therapies
- An appropriate fluid balance with special attention to the administration of diuretics, anticoagulants, treatment of comorbidities, and nutritional aspects should be considered.[4]
- Healthcare providers should strongly enforce stringent measures against active cigarette smoking.[4]
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.[4]
- Venturi masks offer more accurate and controlled delivery of oxygen than do nasal prongs but are less likely to be tolerated by the patient.[7]
- 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.[28][29][30][31]
Hospital Discharge and Follow-up
- In the hospital prior to discharge, patients should start long-acting bronchodilators, either anticholinergics and/or β2-agonists with or without inhaled corticosteroids.[4]
- For patients who are 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.[4]
Prevention of COPD Exacerbations
- Smoking cessation, influenza and pneumococcal vaccines, knowledge of current therapy including inhaler technique, and treatment with long-acting inhaled bronchodilators, with or without inhaled corticosteroids, and phosphodiesterase-4 inhibitors are all therapies that reduce the number of exacerbations and hospitalizations.[32][33][34][35][36][37]
- 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.[38]
Don’ts
Don’ts
Assessment
- Spirometry is not recommended during an exacerbation because it can be difficult to perform and measurements are not accurate enough.[4]
Treatment
Adjunct Therapies
- The use of mucolytics is not well-supported by evidence.[39]
Respiratory Support
- NIPPV is not considered in the following conditions:
Contraindications for NIPPV[40] ❑ Inability to cooperate/protect the airway ❑ Inability to clear respiratory secretions ❑ Facial surgery, trauma, or deformity ❑ Upper airway obstruction ❑ High risk for aspiration ❑ Cardiac or respiratory arrest ❑ Nonrespiratory organ failure ▸ Severe encephalopathy (e.g., GCS <10) ▸ Severe upper gastrointestinal bleeding ▸ Hemodynamic instability or unstable cardiac arrhythmia | |||||
References
References
- ↑ Burge, S.; Wedzicha, JA. (2003). “COPD exacerbations: definitions and classifications”. Eur Respir J Suppl. 41: 46s–53s. PMID 12795331. Unknown parameter
|month=ignored (help) - ↑ Celli, BR.; Barnes, PJ. (2007). “Exacerbations of chronic obstructive pulmonary disease”. Eur Respir J. 29 (6): 1224–38. doi:10.1183/09031936.00109906. PMID 17540785. Unknown parameter
|month=ignored (help) - ↑ Rodriguez-Roisin, R. (2000). “Toward a consensus definition for COPD exacerbations”. Chest. 117 (5 Suppl 2): 398S–401S. PMID 10843984. Unknown parameter
|month=ignored (help) - ↑ 4.00 4.01 4.02 4.03 4.04 4.05 4.06 4.07 4.08 4.09 Vestbo, J.; Hurd, SS.; Agustí, AG.; Jones, PW.; Vogelmeier, C.; Anzueto, A.; Barnes, PJ.; Fabbri, LM.; Martinez, FJ. (2013). “Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: GOLD executive summary”. Am J Respir Crit Care Med. 187 (4): 347–65. doi:10.1164/rccm.201204-0596PP. PMID 22878278. Unknown parameter
|month=ignored (help) - ↑ Austin, MA.; Wills, KE.; Blizzard, L.; Walters, EH.; Wood-Baker, R. (2010). “Effect of high flow oxygen on mortality in chronic obstructive pulmonary disease patients in prehospital setting: randomised controlled trial”. BMJ. 341: c5462. PMID 20959284.
- ↑ Stoller, JK. (2002). “Clinical practice. Acute exacerbations of chronic obstructive pulmonary disease”. N Engl J Med. 346 (13): 988–94. doi:10.1056/NEJMcp012477. PMID 11919309. Unknown parameter
|month=ignored (help) - ↑ 7.0 7.1 7.2 Celli, BR.; MacNee, W. (2004). “Standards for the diagnosis and treatment of patients with COPD: a summary of the ATS/ERS position paper”. Eur Respir J. 23 (6): 932–46. PMID 15219010. Unknown parameter
|month=ignored (help) - ↑ 8.0 8.1 Barberá, JA.; Reyes, A.; Roca, J.; Montserrat, JM.; Wagner, PD.; Rodríguez-Roisin, R. (1992). “Effect of intravenously administered aminophylline on ventilation/perfusion inequality during recovery from exacerbations of chronic obstructive pulmonary disease”. Am Rev Respir Dis. 145 (6): 1328–33. doi:10.1164/ajrccm/145.6.1328. PMID 1595998. Unknown parameter
|month=ignored (help) - ↑ 9.0 9.1 Emerman, CL.; Connors, AF.; Lukens, TW.; May, ME.; Effron, D. (1990). “Theophylline concentrations in patients with acute exacerbation of COPD”. Am J Emerg Med. 8 (4): 289–92. PMID 2363749. Unknown parameter
|month=ignored (help) - ↑ 10.0 10.1 Lloberes, P.; Ramis, L.; Montserrat, JM.; Serra, J.; Campistol, J.; Picado, C.; Agusti-Vidal, A. (1988). “Effect of three different bronchodilators during an exacerbation of chronic obstructive pulmonary disease”. Eur Respir J. 1 (6): 536–9. PMID 2971565. Unknown parameter
|month=ignored (help) - ↑ 11.0 11.1 Mahon, JL.; Laupacis, A.; Hodder, RV.; McKim, DA.; Paterson, NA.; Wood, TE.; Donner, A. (1999). “Theophylline for irreversible chronic airflow limitation: a randomized study comparing n of 1 trials to standard practice”. Chest. 115 (1): 38–48. PMID 9925061. Unknown parameter
|month=ignored (help) - ↑ 12.0 12.1 Murciano, D.; Aubier, M.; Lecocguic, Y.; Pariente, R. (1984). “Effects of theophylline on diaphragmatic strength and fatigue in patients with chronic obstructive pulmonary disease”. N Engl J Med. 311 (6): 349–53. doi:10.1056/NEJM198408093110601. PMID 6738652. Unknown parameter
|month=ignored (help) - ↑ “http://www.nice.org.uk/nicemedia/live/13029/49397/49397.pdf” (PDF). Retrieved 18 December 2013. External link in
|title=(help) - ↑ 14.0 14.1 Maltais, F.; Ostinelli, J.; Bourbeau, J.; Tonnel, AB.; Jacquemet, N.; Haddon, J.; Rouleau, M.; Boukhana, M.; Martinot, JB. (2002). “Comparison of nebulized budesonide and oral prednisolone with placebo in the treatment of acute exacerbations of chronic obstructive pulmonary disease: a randomized controlled trial”. Am J Respir Crit Care Med. 165 (5): 698–703. doi:10.1164/ajrccm.165.5.2109093. PMID 11874817. Unknown parameter
|month=ignored (help) - ↑ Gunen, H.; Hacievliyagil, SS.; Yetkin, O.; Gulbas, G.; Mutlu, LC.; In, E. (2007). “The role of nebulised budesonide in the treatment of exacerbations of COPD”. Eur Respir J. 29 (4): 660–7. doi:10.1183/09031936.00073506. PMID 17251232. Unknown parameter
|month=ignored (help) - ↑ Ställberg, B.; Selroos, O.; Vogelmeier, C.; Andersson, E.; Ekström, T.; Larsson, K. (2009). “Budesonide/formoterol as effective as prednisolone plus formoterol in acute exacerbations of COPD. A double-blind, randomised, non-inferiority, parallel-group, multicentre study”. Respir Res. 10: 11. doi:10.1186/1465-9921-10-11. PMID 19228428.
- ↑ 17.0 17.1 Sethi, S.; Murphy, TF. (2008). “Infection in the pathogenesis and course of chronic obstructive pulmonary disease”. N Engl J Med. 359 (22): 2355–65. doi:10.1056/NEJMra0800353. PMID 19038881. Unknown parameter
|month=ignored (help) - ↑ The Sanford Guide to Antimicrobial Therapy. ISBN 1-9308-0874-7.
- ↑ Stockley, RA.; O’Brien, C.; Pye, A.; Hill, SL. (2000). “Relationship of sputum color to nature and outpatient management of acute exacerbations of COPD”. Chest. 117 (6): 1638–45. PMID 10858396. Unknown parameter
|month=ignored (help) - ↑ Turner, MO.; Patel, A.; Ginsburg, S.; FitzGerald, JM. “Bronchodilator delivery in acute airflow obstruction. A meta-analysis”. Arch Intern Med. 157 (15): 1736–44. PMID 9250235.
- ↑ “http://www.nice.org.uk/nicemedia/live/13029/49397/49397.pdf” (PDF). External link in
|title=(help) - ↑ 22.0 22.1 Davies, L.; Angus, RM.; Calverley, PM. (1999). “Oral corticosteroids in patients admitted to hospital with exacerbations of chronic obstructive pulmonary disease: a prospective randomised controlled trial”. Lancet. 354 (9177): 456–60. PMID 10465169. Unknown parameter
|month=ignored (help) - ↑ 23.0 23.1 Niewoehner, DE.; Erbland, ML.; Deupree, RH.; Collins, D.; Gross, NJ.; Light, RW.; Anderson, P.; Morgan, NA. (1999). “Effect of systemic glucocorticoids on exacerbations of chronic obstructive pulmonary disease. Department of Veterans Affairs Cooperative Study Group”. N Engl J Med. 340 (25): 1941–7. doi:10.1056/NEJM199906243402502. PMID 10379017. Unknown parameter
|month=ignored (help) - ↑ Thompson, WH.; Nielson, CP.; Carvalho, P.; Charan, NB.; Crowley, JJ. (1996). “Controlled trial of oral prednisone in outpatients with acute COPD exacerbation”. Am J Respir Crit Care Med. 154 (2 Pt 1): 407–12. doi:10.1164/ajrccm.154.2.8756814. PMID 8756814. Unknown parameter
|month=ignored (help) - ↑ Aaron, SD.; Vandemheen, KL.; Hebert, P.; Dales, R.; Stiell, IG.; Ahuja, J.; Dickinson, G.; Brison, R.; Rowe, BH. (2003). “Outpatient oral prednisone after emergency treatment of chronic obstructive pulmonary disease”. N Engl J Med. 348 (26): 2618–25. doi:10.1056/NEJMoa023161. PMID 12826636. Unknown parameter
|month=ignored (help) - ↑ Walters, JA.; Gibson, PG.; Wood-Baker, R.; Hannay, M.; Walters, EH. (2009). “Systemic corticosteroids for acute exacerbations of chronic obstructive pulmonary disease”. Cochrane Database Syst Rev (1): CD001288. doi:10.1002/14651858.CD001288.pub3. PMID 19160195.
- ↑ Christ-Crain, M.; Jaccard-Stolz, D.; Bingisser, R.; Gencay, MM.; Huber, PR.; Tamm, M.; Müller, B. (2004). “Effect of procalcitonin-guided treatment on antibiotic use and outcome in lower respiratory tract infections: cluster-randomised, single-blinded intervention trial”. Lancet. 363 (9409): 600–7. doi:10.1016/S0140-6736(04)15591-8. PMID 14987884. Unknown parameter
|month=ignored (help) - ↑ Brochard, L.; Mancebo, J.; Wysocki, M.; Lofaso, F.; Conti, G.; Rauss, A.; Simonneau, G.; Benito, S.; Gasparetto, A. (1995). “Noninvasive ventilation for acute exacerbations of chronic obstructive pulmonary disease”. N Engl J Med. 333 (13): 817–22. doi:10.1056/NEJM199509283331301. PMID 7651472. Unknown parameter
|month=ignored (help) - ↑ Bott, J.; Carroll, MP.; Conway, JH.; Keilty, SE.; Ward, EM.; Brown, AM.; Paul, EA.; Elliott, MW.; Godfrey, RC. (1993). “Randomised controlled trial of nasal ventilation in acute ventilatory failure due to chronic obstructive airways disease”. Lancet. 341 (8860): 1555–7. PMID 8099639. Unknown parameter
|month=ignored (help) - ↑ Kramer, N.; Meyer, TJ.; Meharg, J.; Cece, RD.; Hill, NS. (1995). “Randomized, prospective trial of noninvasive positive pressure ventilation in acute respiratory failure”. Am J Respir Crit Care Med. 151 (6): 1799–806. doi:10.1164/ajrccm.151.6.7767523. PMID 7767523. Unknown parameter
|month=ignored (help) - ↑ Plant, PK.; Owen, JL.; Elliott, MW. (2000). “Early use of non-invasive ventilation for acute exacerbations of chronic obstructive pulmonary disease on general respiratory wards: a multicentre randomised controlled trial”. Lancet. 355 (9219): 1931–5. PMID 10859037. Unknown parameter
|month=ignored (help) - ↑ Calverley, PM.; Anderson, JA.; Celli, B.; Ferguson, GT.; Jenkins, C.; Jones, PW.; Yates, JC.; Vestbo, J. (2007). “Salmeterol and fluticasone propionate and survival in chronic obstructive pulmonary disease”. N Engl J Med. 356 (8): 775–89. doi:10.1056/NEJMoa063070. PMID 17314337. Unknown parameter
|month=ignored (help) - ↑ Tashkin, DP.; Celli, B.; Senn, S.; Burkhart, D.; Kesten, S.; Menjoge, S.; Decramer, M.; Schiavi, E.; Figueroa Casas, JC. (2008). “A 4-year trial of tiotropium in chronic obstructive pulmonary disease”. N Engl J Med. 359 (15): 1543–54. doi:10.1056/NEJMoa0805800. PMID 18836213. Unknown parameter
|month=ignored (help) - ↑ Calverley, PM.; Rabe, KF.; Goehring, UM.; Kristiansen, S.; Fabbri, LM.; Martinez, FJ.; Abdool-Gaffar, MS.; Abdullah, IA.; Abdullah, I. (2009). “Roflumilast in symptomatic chronic obstructive pulmonary disease: two randomised clinical trials”. Lancet. 374 (9691): 685–94. doi:10.1016/S0140-6736(09)61255-1. PMID 19716960. Unknown parameter
|month=ignored (help) - ↑ Fabbri, LM.; Calverley, PM.; Izquierdo-Alonso, JL.; Bundschuh, DS.; Brose, M.; Martinez, FJ.; Rabe, KF.; Abdulla, R.; Abdullah, I. (2009). “Roflumilast in moderate-to-severe chronic obstructive pulmonary disease treated with longacting bronchodilators: two randomised clinical trials”. Lancet. 374 (9691): 695–703. doi:10.1016/S0140-6736(09)61252-6. PMID 19716961. Unknown parameter
|month=ignored (help) - ↑ Decramer, M.; Celli, B.; Kesten, S.; Lystig, T.; Mehra, S.; Tashkin, DP.; Schiavi, E.; Casas, JC.; Rhodius, E. (2009). “Effect of tiotropium on outcomes in patients with moderate chronic obstructive pulmonary disease (UPLIFT): a prespecified subgroup analysis of a randomised controlled trial”. Lancet. 374 (9696): 1171–8. doi:10.1016/S0140-6736(09)61298-8. PMID 19716598. Unknown parameter
|month=ignored (help) - ↑ Jenkins, CR.; Jones, PW.; Calverley, PM.; Celli, B.; Anderson, JA.; Ferguson, GT.; Yates, JC.; Willits, LR.; Vestbo, J. (2009). “Efficacy of salmeterol/fluticasone propionate by GOLD stage of chronic obstructive pulmonary disease: analysis from the randomised, placebo-controlled TORCH study”. Respir Res. 10: 59. doi:10.1186/1465-9921-10-59. PMID 19566934.
- ↑ Man, WD.; Polkey, MI.; Donaldson, N.; Gray, BJ.; Moxham, J. (2004). “Community pulmonary rehabilitation after hospitalisation for acute exacerbations of chronic obstructive pulmonary disease: randomised controlled study”. BMJ. 329 (7476): 1209. doi:10.1136/bmj.38258.662720.3A. PMID 15504763. Unknown parameter
|month=ignored (help) - ↑ McCrory, DC.; Brown, C.; Gelfand, SE.; Bach, PB. (2001). “Management of acute exacerbations of COPD: a summary and appraisal of published evidence”. Chest. 119 (4): 1190–209. PMID 11296189. Unknown parameter
|month=ignored (help) - ↑ “International Consensus Conferences in Intensive Care Medicine: noninvasive positive pressure ventilation in acute Respiratory failure”. Am J Respir Crit Care Med. 163 (1): 283–91. 2001. doi:10.1164/ajrccm.163.1.ats1000. PMID 11208659. Unknown parameter
|month=ignored (help)
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Abdurahman Khalil, M.D. [2]