acute respiratory failure, bronchitis, chronic obstructive pulmonary disease, COPD, dyspnea, emphysema, hypercapnia, hypoxemia, mechanical ventilation



  1. Siela, Debra PhD, RN, CCNS, ACNS-BC, CCRN-K, CNE, RRT


Abstract: Acute exacerbations of chronic obstructive pulmonary disease (COPD) that lead to acute respiratory failure usually require hospitalization. Understanding the pathophysiology of COPD and what leads to acute respiratory failure in these patients is important. Nurses must be able to determine appropriate evidence-based care management of these patients to work effectively with the healthcare team.


Article Content

Mr. B, 72, is brought into the ED by paramedics. He reports that he has had difficulty breathing over the past several days, and the paramedics placed him on oxygen at 2 L/minute by nasal cannula. He states he has a productive cough and has been expectorating yellow mucus.

Figure. No caption a... - Click to enlarge in new windowFigure. No caption available.

Mr. B's initial vital signs are: temperature, 101.3[degrees] F (38.5[degrees] C); heart rate, 122 beats/minute; BP, 160/96 mm Hg; respiratory rate, 40 breaths/minute; and SpO2, 84% on oxygen at 2 L/minute by nasal cannula. He is alert and oriented but anxious; his skin is warm and dry; buccal cyanosis is present. Mr. B has bilateral breath sounds with wheezing and crackles in the lung bases, his S1 and S2 heart sounds are normal, no abnormal heart sounds or murmurs are present, and the cardiac monitor shows sinus tachycardia.


Mr. B's medical history is significant for long-standing chronic obstructive pulmonary disease (COPD). He had an upper respiratory infection about 2 weeks earlier. Mr. B continues to smoke two packs of cigarettes per day and uses oxygen at home. He states that he takes captopril for hypertension.


Mr. B's diagnostic testing (including arterial blood gas [ABG]) analysis reveals the following: pH, 7.30; PaO2, 52 mm Hg; PaCO2, 54 mm Hg; HCO3, 30 mEq/L; and a white blood cell count of 20,000/mm3. His eosinophil count is elevated. A sputum culture was obtained and the Gram stain was positive. The ED physician's diagnosis is acute respiratory failure from an acute exacerbation of COPD complicated by pneumonia.


COPD incidence and risk factors

The global incidence of COPD in 2010 was 384 million, affecting 11.7% of the population.1 Approximately 3 million deaths from COPD occur annually worldwide.2 The Burden of Obstructive Lung Diseases program, run in 29 countries, found a COPD prevalence of 10.1%, with 11.8% in men and 8.5% in adults over age 40.3,4


COPD is a common, preventable, and treatable disease characterized by persistent respiratory symptoms and airflow limitation from airway and/or alveolar abnormalities usually caused by significant exposure to noxious particles or gases.5 The abnormalities result in chronic airflow limitations through changes in small airways (less than 2 mm in diameter; bronchiolitis) and parenchymal destruction (emphysema). These changes evolve at different rates over time. Chronic inflammation causes structural changes, narrowing of the small airways, and decreased lung elastic recoil. These structural changes inhibit the ability of the airways to remain open during expiration. The loss of small airways can contribute to airflow limitation and mucociliary dysfunction.5


The terms emphysema and chronic bronchitis do not describe all of the structural abnormalities in COPD related to airflow limitation. Chronic respiratory signs and symptoms occur prior to the development of airflow limitation and may also occur in acute respiratory events.5 Chronic respiratory impairment signs and symptoms sometimes manifest in individuals with normal airflow as determined by spirometry, and many smokers without airflow limitation have structural evidence of lung disease.5


Genetic factors, gender, and occupational and environmental exposures to pollutants are risk factors for COPD. Smoking is the leading environmental risk factor for COPD, but less than 40% of smokers develop the disease.6 Cigarette smoking is a factor in the decline of volume of air exhaled within the first second of forced expiratory volume (FEV1) related to a dose-response (pack-years).7 However, the variability of FEV1 decline is only partially explained by pack-years of smoking.7,8 Occupational exposure is a risk factor for 19.2% of patients with COPD and 31.1% of never-smokers.9 Primary occupational dust exposure comes from mining and textile manufacturing.7


Lung growth and development processes that reduce maximal lung function may identify individuals at risk for COPD.10,11 Low birthweight is positively associated with FEV1 in adulthood; childhood lung infections may also play a role.7,12


Genetic risk factors include an alpha-1 antitrypsin deficiency, which occurs in 1% to 2% of all patients with COPD.7 Other genetic factors play a role in the development of COPD; genome studies have identified COPD loci that probably contain susceptibility determinants, but have yet to identify specific genes.7



Inflammation is a key component in the pathophysiology of COPD.5,7 This inflammation is a modification of the normal respiratory tract inflammatory response. Lung inflammation occurs because of oxidative stress, protease-antiprotease imbalance, inflammatory cells, inflammatory mediators, and/or peribronchiolar and interstitial fibrosis.5,7 The small airway changes and parenchymal destruction often result in airflow limitation and gas trapping with hyperinflation, gas exchange abnormalities (which include outcomes of hypoxemia and hypercapnia), mucus hypersecretion, and in later stages, pulmonary hypertension from hypoxic vasoconstriction of pulmonary arteries.7


Oxidants from cigarette smoking activate macrophages in the small airways, causing the release of proteinases (also known as proteases) and chemokines that attract other inflammatory cells.7 This increase in proteinases begins the destruction of lung tissue. Cell death can occur from this increased oxidant stress. Self-repair of damaged alveoli in the adult lung seems to be limited.7


Changes in small airways cause the most airflow limitation. Goblet mucus-secreting cells proliferate, replacing surfactant-secreting club cells.7 Phagocytes enter the airways, and smooth muscle hypertrophy can occur. All of these abnormalities cause narrowing of the airway lumen with fibrosis, excess mucus, edema, and cellular infiltration. Reduction of surfactant can increase surface tension, causing collapse. The inflammatory cell collection causes proteolytic destruction of elastic fibers in the bronchioles and alveolar ducts, where fibers are concentrated as rings around the entrance to alveoli.7


Emphysema includes destruction of lung parenchyma. The walls of these structures become perforated and coalesce into small air spaces into abnormal and much larger air spaces. Many macrophages, neutrophils, and T lymphocytes collect in the bronchioles of smokers. The macrophages cause release of proteinases that result in tissue destruction.


Emphysema is classified into types based on the location of the pathologic findings within the pulmonary acinus.7 The types are centriacinar (also known as centrilobular), panacinar (also known as panlobular), and localized emphysema (also known as paraseptal). Centriacinar emphysema is associated with cigarette smoking and occurs in the upper lobes and superior segments of the lower lobes.7 Panacinar emphysema is uniformly distributed within the pulmonary acinus and occurs in basal lung areas. Localized emphysema occurs in isolated areas and is usually found in the apex of the upper lobe.7,8


Pathophysiologic outcomes

Airflow obstruction. Airflow during forced expiration is the result of the balance between the elastic recoil of the lungs promoting flow and the resistance of the airways limiting flow. Normally, the flow decreases toward the end of expiration as the lungs empty out because of decreased elastic recoil. In COPD, the flow decreases even further earlier in expiration because of airway collapse. Spirometry measures are FEV1 and the total volume of air produced during expiratory maneuver, or forced vital capacity (FVC).7 These volumes are low in COPD. The ratio of FEV1 to FVC (FEV1/FVC) is also low in COPD.7


Hyperinflation. Occurring in COPD to preserve expiratory airflow because it decreases airway resistance, hyperinflation pushes the diaphragm into a flattened position.7 This can affect the application of abdominal pressure to the chest wall during inspiration. The shortened diaphragm muscle fibers are less able to generate inspiratory pressures, and the flattened diaphragm has to generate greater tension for the transpulmonary pressure to produce tidal breathing.7


Impaired gas exchange. The partial pressure of oxygen (PaO2) in arterial blood remains near normal until the FEV1 is less than 50% of predicted. Arterial carbon dioxide does not elevate until the FEV1 is less than 25%.7 Ventilation can vary in different areas of the lung due to compliance and airway resistance. Ventilation-perfusion mismatching is the cause of hypoxemia with minimal shunting.7


Supplemental oxygen is usually sufficient to treat hypoxemia. If supplemental oxygen does not correct the hypoxemia, pathophysiologic problems other than COPD are likely present.7


Signs and symptoms of COPD

Dyspnea. The best known symptom of COPD, dyspnea is a major cause of disability.13 Individuals with COPD describe dyspnea in many different ways: breathlessness, increased effort to breathe, chest heaviness, air hunger, or gasping.14 Dyspnea is caused by respiratory diseases such as COPD resulting from hyperinflation and bronchoconstriction that often lead to hypoxemia and hypercapnia.15


Disorders of the ventilatory pump (respiratory muscles) that increase the work of breathing or a sense of increased effort to breathe are associated with an increase in airway resistance or decreased compliance.15 Chemoreceptors in the carotid bodies are activated by hypoxemia, acute hypercapnia, and acidemia.7 Stimulation of these receptors and other chemoreceptors leads to an increase in ventilation, which can cause the sensation of air hunger. Other receptors include the mechanoreceptors in the lungs stimulated by bronchoconstriction, which give the sensation of chest tightness. J-receptors are sensitive to interstitial edema and pulmonary vasculature, and are activated by acute changes in pulmonary artery pressure. Hyperinflation makes it difficult to take a deep or satisfying breath, and increases the work of breathing.15


Assessing dyspnea requires determining the quality of the discomfort. Scales such as a Modified Borg Dyspnea Scale or visual analogue can measure dyspnea at rest or immediately after an activity.15 More extensive dyspnea scales are available to determine intensity during many different activities and can determine the extent of disability.15


Cough. Often the first symptom, cough in COPD may occur occasionally, every day, or several times each day. Cough in COPD may be productive or unproductive.16


Sputum. Individuals with COPD often expectorate tenacious sputum with a cough. Cough with the production of sputum regularly over 3 or more months in 2 consecutive years is a classic definition of chronic bronchitis, but this definition may not reflect all sputum production in COPD.5,17 Purulent sputum often indicates an increase in inflammatory mediators.18,19


Wheezing and chest tightness. Presence of wheezing and chest tightness varies among days and on the same day. Wheezing may vary and be audible without a stethoscope, and inspiratory and expiratory wheezes may be heard during auscultation. Not all individuals with COPD experience wheezing or chest tightness.5

Table COPD airflow l... - Click to enlarge in new windowTable COPD airflow limitation severity

Other signs and symptoms. Fatigue, weight loss, and anorexia occur in individuals with severe and very severe COPD.20-22 These symptoms have prognostic significance and need to be investigated. Symptoms of depression and anxiety need to be assessed in individuals with COPD and can be caused by acute exacerbations.23



Spirometry. Measuring FEV1 and FVC, spirometry calculates the ratio of these two measurements (FEV1/FVC).5 Spirometry measurements are compared with reference values based on age, height, gender, and race.5 The spirometric criterion for diagnosis of airflow limitation or COPD is a postbronchodilator fixed ratio of FEV1/FVC less than 0.70.5 See COPD airflow limitation severity for the Global Initiative for Obstructive Lung Disease (GOLD) classifications.5


Imaging. Chest X-rays cannot establish a diagnosis of COPD but can exclude other respiratory diagnoses.5 Changes in the chest X-ray of a patient with COPD include signs of lung hyperinflation (flattened diaphragm, increase in volume of retrosternal air space), hyperlucency of the lungs, and rapid tapering of the vascular markings.5 Computed tomography of the chest is not recommended to assist in a diagnosis of COPD.


Lung volume and diffusing capacity. Gas trapping in COPD may be recognized in lung plethysmography and can help determine the severity of COPD, but it may not be helpful in managing the patient. Diffusing capacity measurement may help determine the functional impact of emphysema in COPD not related to airflow limitation.5


Oximetry and ABGs. Pulse oximetry is used to determine arterial oxygen saturation and need for supplemental oxygen. It should be used in patients with clinical signs of acute respiratory failure. If peripheral arterial oxygen saturation is less than 92%, ABGs should be assessed.24,25

Table Acute respirat... - Click to enlarge in new windowTable Acute respiratory failure categories for acute exacerbations of COPD

Exercise testing and physical activity assessment. Exercise impairment related to the effects of COPD can be assessed with self-paced walking distances.26,27 For example, the 6-minute walk test can be used to stratify patients with COPD for clinical trials and interventions aimed at mitigating exacerbations, hospitalizations, or death.27


Exacerbations and acute respiratory failure

COPD exacerbations are an acute worsening of respiratory symptoms that result in the need for additional therapy.5 Mild exacerbations are treated with short-acting bronchodilators; moderate exacerbations are treated with short-acting bronchodilators plus antibiotics for bacterial infection and/or oral corticosteroids; and severe exacerbations require treatment in the ED or hospitalization. Severe exacerbations may be associated with acute respiratory failure.5 Exacerbations usually occur with respiratory viral infections, although bacterial infections, pollution, and ambient temperature may also initiate these events.5,28 Viral infections are associated with severe, long-lasting exacerbations and often require hospitalization.5


Sputum production can increase in COPD exacerbation, and purulent sputum suggests increased bacteria in the sputum.5 Eosinophils are increased in the airways, lung, and blood in many patients with COPD. Eosinophils increase with neutrophils and other inflammatory cells during exacerbations of COPD. In exacerbations associated with increases in sputum and blood eosinophils may respond to systemic corticosteroids.29


GOLD guidelines recommend that hospitalized patients with COPD have the severity of their acute respiratory failure classified.5 These severity classes include no acute respiratory failure; acute respiratory failure, non-life-threatening; and acute respiratory failure, life-threatening. See Acute respiratory failure categories for acute exacerbations of COPD for comparisons of the clinical signs among the three classes.5


Management of non-life-threatening COPD exacerbations with respiratory failure includes assessing the severity of signs and symptoms, supplemental oxygen, use of short-acting bronchodilators and a muscarinic antagonist, and long-acting bronchodilators when the patient is stable.5 Providers should consider treatment with oral corticosteroids, antibiotics for bacterial infection, and noninvasive ventilation (NIV).30-38 See Pharmacologic treatments for acute exacerbations.5


Supplemental oxygen should be titrated to improve to a target saturation of 88% to 92%.5 NIV should be the first mode of ventilation used in patients with COPD who have acute respiratory failure because it improves gas exchange, reduces work of breathing and the need for intubation, decreases hospitalization duration, and improves survival.5,39-46 NIV is the standard of care for acute exacerbations of COPD with concomitant administration of appropriate antibiotics, corticosteroids, and bronchodilators.47 The use of NIV to manage patients with acute exacerbations of COPD has been associated with a 35% reduction in mortality; a 35% reduction in hospital-acquired pneumonia; an 18% reduction in hospital length of stay; a 30% reduction in costs; and 78%, 55%, and 29% reductions in mortality in patients with low, moderate, and high comorbidity burdens, respectively, compared with patients managed with invasive mechanical ventilation.48


Indications for NIV include at least one of the following: respiratory acidosis with hypercapnia, severe dyspnea, and persistent hypoxemia in spite of supplemental oxygen therapy.5 NIV should provide mandatory rates up to 30 breaths/minute, inspiratory pressures up to 30 cm H2O, positive end-expiratory pressure (PEEP) or expiratory positive airway pressure up to 15 cm H2O; and inspiratory flow rates of up to 180 L/minute at 20 cm H2O.49 To effectively manage patients receiving NIV, the bedside team of nurses, acute care NPs, respiratory therapists, and physicians must collaborate and coordinate their efforts.


Nursing care of patients with acute exacerbations of COPD who receive NIV includes continuous assessment of the patient and monitoring of the noninvasive ventilators. See Monitoring and care of patients receiving NIV.50,51

Table Pharmacologic ... - Click to enlarge in new windowTable Pharmacologic treatments for acute exacerbations

When invasive mechanical ventilation is needed, these patients will require intensive care. Other indications for intensive care include severe dyspnea that does not respond to treatment, changes in mental status, and persistent or worsening hypoxemia or acidosis with a pH under 7.25 despite supplemental oxygen. See Monitoring and care of patients receiving invasive mechanical ventilation.52,53


Case study conclusion

After treatment with albuterol, Mr. B is placed on NIV with a face mask interface at a rate of 24 breaths/minute, inspiratory pressures of 25 cm H2O, PEEP of 10 cm H2O, and inspiratory flow rates of up to 160 L/minute at 20 cm H2O and 40% FiO2. His pulmonologist orders azithromycin I.V. infusion and oral prednisolone.


After 2 hours of treatment on NIV, Mr. B's ABGs are now pH 7.33, PaCO2 50 mm Hg, HCO3 30 mEq/L, and PaO2 59 mm Hg. His SaO2 is 86% with slight buccal cyanosis. Hemodynamics include a heart rate, 112 beats/minute, and BP, 154/90 mm Hg. Mr. B is still coughing and expectorating yellow sputum. No changes are made to his ventilator settings.


If Mr. B's pH had initially been less than 7.25 and/or his PaO2 less than 40 mm Hg with changes in mental status, a decision to intubate with an endotracheal tube and placement on invasive mechanical ventilation would have been considered. In addition, if his ABGs worsened (particularly increased acidosis), or he developed reduced pulse oximetry saturations, other oxygenation indices, and/or dyspnea, it could warrant intubation and invasive mechanical ventilation.


By the next morning, Mr. B's ABGs improved to: pH, 7.37; PaCO2, 49 mm Hg; HCO3, 30 mEq/L; PaO2, 65 mm Hg; and SaO2, 90%. He had a heart rate of 92 beats/minute and BP of 140/84 mm Hg. NIV was continued with the same initial settings, including a respiratory rate of 24 breaths/minute. He responded appropriately to commands and questions.

Table Monitoring and... - Click to enlarge in new windowTable Monitoring and care of patients receiving NIV

Mr. B was taken off NIV 48 hours after admission. His ABG values were within normal ranges for him and his COPD. His SpO2 varied between 90% and 92%. Supplemental oxygen was discontinued. However, he remained in the hospital for 2 more days to continue his I.V. infusion antibiotics and glucocorticoids, to mobilize, and to begin pulmonary rehabilitation. He was discharged on day 5 and continued on pulmonary rehabilitation on an outpatient basis for 4 more weeks.


Mr. B was prescribed a bronchodilator p.r.n. for dyspnea/chest tightness and an inhaled corticosteroid twice a day, and was continued on oral azithromycin for 5 more days. He remained on captopril for his hypertension. He was scheduled for a visit to his pulmonologist 2 weeks after hospital discharge.



Many patients with COPD have acute exacerbations that lead to acute respiratory failure and require hospitalization. It is important to understand the pathophysiology of COPD and what leads to acute respiratory failure in these patients. Nurses must learn appropriate management techniques for these patients so they make appropriate clinical judgments. In addition, nurses must take an interactive and team approach to the care and management of patients with COPD who have acute respiratory failure. Partnering with a healthcare team that includes physicians, clinical nurses, acute care NPs, clinical nurse specialists, respiratory therapists, pharmacists, physical therapists, and dietitians is key to appropriate and quality care.




1. Adeloye D, Chua S, Lee C, et al Global and regional estimates of COPD prevalence: systematic review and meta-analysis. J Glob Health. 2015;5(2):020415. [Context Link]


2. Global Burden of Disease Study Collaborators. Global, regional, and national age-sex specific all-cause and cause-specific mortality for 240 causes of death, 1990-2013: a systematic analysis for the global burden of disease study 2013. Lancet. 2015;385(9963):117-171. [Context Link]


3. Imperial College London. Burden of Obstructive Lung Disease Initiative.[Context Link]


4. Lamprecht B, McBurnie MA, Vollmer WM, et al COPD in never smokers: results from the population-based burden of obstructive lung disease study. Chest. 2011;139(4):752-763. [Context Link]


5. Global Initiative for Chronic Obstructive Lung Disease. GOLD report 2017.[Context Link]


6. Tan WC, Sin DD, Bourbeau J, et al Characteristics of COPD in never-smokers and ever-smokers in the general population: results from the CanCOLD study. Thorax. 2015;70(9):822-829. [Context Link]


7. Reilly JJ, Silverman EK, Shapiro SD. Chronic obstructive pulmonary disease. In: Loscalzo J, ed. Harrison's Pulmonary and Critical Care Medicine. 2nd ed. New York, NY: McGraw Hill Education Medical; 2013. [Context Link]


8. Strayer D, Rubin E, eds. Rubin's Pathology: Clinicopathologic Foundations of Medicine. 7th ed. Philadelphia, PA: Wolters Kluwer; 2015. [Context Link]


9. Omland O, Wurtz ET, Aasen TB, et al Occupational chronic obstructive pulmonary disease: a systematic literature review. Scand J Work Environ Health. 2014;40(1):19-35. [Context Link]


10. Stocks J, Sonnappa S. Early life influences on the development of chronic obstructive pulmonary disease. Ther Adv Respir Dis. 2013;7(3):161-173. [Context Link]


11. Brostrom EB, Akre O, Katz-Salamon M, Jaraj D, Kaijser M. Obstructive pulmonary disease in old age among individuals born preterm. Eur J Epidemiol. 2013;28(1):79-85. [Context Link]


12. Bush A. Lung development and aging. Ann Am Thorac Soc. 2016;13(suppl 5):S438-S446. [Context Link]


13. Miravitlles M, Worth H, Soler Cataluna JJ, et al Observational study to characterise 24-hour COPD symptoms and their relationship with patient-reported outcomes: results from the ASSESS study. Respir Res. 2014;15:122. [Context Link]


14. Scioscia G, Blanco I, Arismendi E, et al Different dyspnoea perception in COPD patients with frequent and infrequent exacerbations. Thorax. 2017;72(2):117-121. [Context Link]


15. Schwartzkein RM. Dyspnea. In: Harrison's Pulmonary and Critical Care Medicine. Loscalzo J, ed. 2nd ed. New York, NY: McGraw Hill Education Medical; 2013. [Context Link]


16. Cho SH, Lin HC, Ghoshal AG, et al Respiratory disease in the Asia-Pacific region: cough as a key symptom. Allergy Asthma Proc. 2016;37(2):131-140. [Context Link]


17. Allinson JP, Hardy R, Donaldson GC, Shaheen SO, Kuh D, Wedzicha JA. The presence of chronic mucus hypersecretion across adult life in relation to chronic obstructive pulmonary disease development. Am J Respir Crit Care Med. 2016;193(6):662-672. [Context Link]


18. Soler N, Esperatti M, Ewig S, Huerta A, Agusti C, Torres A. Sputum purulence-guided antibiotic use in hospitalised patients with exacerbations of COPD. Eur Respir J. 2012;40(6):1344-1353. [Context Link]


19. Brusse-Keizer MG, Grotenhuis AJ, Kerstjens HA, et al Relation of sputum colour to bacterial load in acute exacerbations of COPD. Respir Med. 2009;103(4):601-606. [Context Link]


20. von Haehling S, Anker SD. Cachexia as a major underestimated and unmet medical need: facts and numbers. J Cachexia Sarcopenia Muscle. 2010;1(1):1-5. [Context Link]


21. Pothirat C, Chaiwong W, Phetsuk N, et al The relationship between body composition and clinical parameters in chronic obstructive pulmonary disease. J Med Assoc Thai. 2016;99(4):386-393.


22. Rutten EP, Calverley PM, Casaburi R, et al Changes in body composition in patients with chronic obstructive pulmonary disease: do they influence patient-related outcomes. Ann Nutr Metab. 2013;63(3):239-247. [Context Link]


23. Hanania NA, Mullerova H, Locantore NW, et al Determinants of depression in the ECLIPSE chronic obstructive pulmonary disease cohort. Am J Respir Crit Care Med. 2011;183(5):604-611. [Context Link]


24. Amalakanti S, Pentakota MR. Pulse oximetry overestimates oxygen saturation in COPD. Respir Care. 2016;61(4):423-427. [Context Link]


25. Garcia-Gutierrez S, Unzurrunzaga A, Arostegui I, et al The use of pulse oximetry to determine hypoxemia in acute exacerbations of COPD. COPD. 2015;12(6):613-620. [Context Link]


26. Durheim MT, Smith PJ, Babyak MA, et al Six-minute-walk distance and accelerometry predict outcomes in chronic obstructive pulmonary disease independent of Global Initiative for Chronic Obstructive Lung Disease 2011 Group. Ann Am Thorac Soc. 2015;12(3):349-356. [Context Link]


27. Celli B, Tetzlaff K, Criner G, et al The 6-minute-walk distance test as a chronic obstructive pulmonary disease stratification tool. Insights from the COPD Biomarker Qualification Consortium. Am J Respir Crit Care Med. 2016;194(12):1483-1493. [Context Link]


28. Djamin RS, Uzun S, Snelders E, et al Occurrence of virus-induced COPD exacerbations during four seasons. Infect Dis (Lond). 2015;47(2):96-100. [Context Link]


29. Bafadhel M, McKenna S, Terry S, et al Acute exacerbations of chronic obstructive pulmonary disease: identification of biologic clusters and their biomarkers. Am J Respir Crit Care Med. 2011;184(6):662-671. [Context Link]


30. National Institute for Health and Care Excellence. COPD overview. 2017. [Context Link]


31. Hatipoglu US, Aboussouan LS. Treating and preventing acute exacerbations of COPD. Cleve Clin J Med. 2016;83(4):289-300.


32. Emami Ardestani M, Kalantary E, Samaiy V, Taherian K. Methyl prednisolone vs dexamethasone in management of COPD exacerbation: a randomized clinical trial. Emerg (Tehran). 2017;5(1):e35.


33. Donohue JF. Another choice for prevention of COPD exacerbations. N Engl J Med. 2016;374(23):2284-2286.


34. Vestbo J, Leather D, Diar Bakerly N, et al Effectiveness of Fluticasone Furoate-Vilanterol for COPD in clinical practice. N Engl J Med. 2016;375(13):1253-1260.


35. Perrone V, Sangiorgi D, Buda S, Degli Esposti L. Comparative analysis of budesonide/formoterol and fluticasone/salmeterol combinations in COPD patients: findings from a real-world analysis in an Italian setting. Int J Chron Obstruct Pulmon Dis. 2016;11:2749-2755.


36. Ceviker Y, Sayiner A. Comparison of two systemic steroid regimens for the treatment of COPD exacerbations. Pulm Pharmacol Ther. 2014;27(2):179-183.


37. Alia I, de la Cal MA, Esteban A, et al Efficacy of corticosteroid therapy in patients with an acute exacerbation of chronic obstructive pulmonary disease receiving ventilatory support. Arch Intern Med. 2011;171(21):1939-1946.


38. Wilson R, Anzueto A, Miravitlles M, et al. Moxifloxacin versus amoxicillin/clavulanic acid in outpatient acute exacerbations of COPD: MAESTRAL results. Eur Respir J. 2012;40(1):17-27. [Context Link]


39. Stefan MS, Shieh MS, Pekow PS, Hill N, Rothberg MB, Lindenauer PK. Trends in mechanical ventilation among patients hospitalized with acute exacerbations of COPD in the United States, 2001 to 2011. Chest. 2015;147(4):959-968. [Context Link]


40. Hess DR. Noninvasive ventilation for acute respiratory failure. Respir Care. 2013;58(6):950-972.


41. Nava S. Behind a mask: tricks, pitfalls, and prejudices for noninvasive ventilation. Respir Care. 2013;58(8):1367-1376.


42. Chandra D, Stamm JA, Taylor B, et al Outcomes of noninvasive ventilation for acute exacerbation of chronic obstructive pulmonary disease in the United States, 1998-2008. Am J Respir Crit Care Med. 2012;185(2):152-159.


43. Ramsay M, Hart N. Current opinions on non-invasive ventilation as a treatment for chronic obstructive pulmonary disease. Curr Opin Pulm Med. 2013;19(6):626-630.


44. Schnell D, Timsit JF, Darmon M, et al Noninvasive mechanical ventilation in acute respiratory failure: trends in use and outcomes. Intensive Care Med. 2014;40(4):582-591.


45. Ouanes I, Ouanes-Besbes L, Ben Abdallah S, Dachraoui F, Abroug F. Trends in use and impact on outcome of empiric antibiotic therapy and non-invasive ventilation in COPD patients with acute exacerbation. Ann Intensive Care. 2015;5(1):30.


46. Moxon A, Lee G. Non-invasive ventilation in the emergency department for patients in type II respiratory failure due to COPD exacerbations. Int Emerg Nurs. 2015;23(3):232-236. [Context Link]


47. Osadnik CR, Tee VS, Carson-Chahhoud KV, Picot J, Wedzicha JA, Smith BJ. Non-invasive ventilation for the management of acute hypercapnic respiratory failure due to exacerbation of chronic obstructive pulmonary disease. Cochrane Database Syst Rev. 2017;7:CD004104. [Context Link]


48. Lindenauer PK, Stefan MS, Shieh MS, Pekow PS, Rothberg MB, Hill NS. Outcomes associated with invasive and noninvasive ventilation among patients hospitalized with exacerbations of chronic obstructive pulmonary disease. JAMA Intern Med. 2014;174(12):1982-1993. [Context Link]


49. Williams PF. Noninvasive ventilation. In: Kacmarek RM, Stoller JK, Heuer AJ, eds. Egan's Fundamentals of Respiratory Care. 10th ed. St. Louis, MO: Elsevier Mosby; 2013. [Context Link]


50. Frazier SK. Noninvasive positive ventilation: continuous positive airway pressure (CPAP) and bilevel positive airway pressure (BiPAP). In: Weigand DL, ed. AACN Procedure Manual for High Acuity, Progressive, and Critical Care. 7th ed. St. Louis, MO: Elsevier; 2017. [Context Link]


51. Bulechek GM, Butcher HK, Dochterman JM, Wagner CM. Mechanical Ventilation Management: Noninvasive. St. Louis, MO: Elsevier Mosby; 2013. [Context Link]


52. Gallagher J. Invasive mechanical ventilation (through an artificial airway): volume and pressure modes. In: Weigand DL, ed. AACN Procedure Manual for High Acuity, Progressive, and Critical Care. 7th ed. St. Louis, MO: Elsevier; 2017. [Context Link]


53. Bulechek GM, Butcher HK, Dochterman JM, Wagner CM. Mechanical Ventilation Management: Invasive. St. Louis, MO: Elsevier Mosby; 2013. [Context Link]