Acute Exacerbation of Chronic Obstructive Pulmonary Disease – Clinical Presentation and Predictors of Outcome
Main Article Content
Abstract
Background and Objectives: Chronic Obstructive Pulmonary Disease (COPD) is a common, costly and preventable disease and is at present the fourth leading cause of death globally. To study the outcome of patients with acute exacerbation of COPD and to analyse the risk factors predicting adverse outcomes in patients with acute exacerbation of COPD.
Patients and Methods: A Prospective study was conducted over a period of one year, from December 2021 to December 2022, Minimum of 50 patients, both male and female with AECOPD getting admitted to a Tertiary care centre were included in this study.
Results: Of the 50 patients studied, 42 were males; all of them were smokers (84%). The mean age was 64.34 ± 10.47 years. The mean duration of the disease was 10.04±6 years. All patients presented with cough, recent worsening of Dyspnea and increased sputum purulence/volume. 70% patients had one or more associated co-morbid illness, majority had hypertension (40%). Of 32 patients with Respiratory failure on admission 17(53.12%) patients had Type II and 15(46.28%) had Type I failure. 44 patients received medical management and 6 patients required invasive mechanical ventilation (IMV). Overall mortality was 5 (10%). 20 variables were compared between survivors and non-survivors. Univariate sensitivity analysis revealed that presence of altered sensorium (P=0.001), Hypotension (P=0.02), cyanosis (P=0.00463), pedal edema (P=0.02), presence of infection (P=0.024) Severe Acidosis (P=0.012), Hypercapnia (P=0.016), cor pulmonale (P=0.04), at the time of admission and need for invasive mechanical ventilation (P<0.001) as predictors of mortality.
Conclusions: 64% of AECOPD presented with respiratory failure, majority were type II. Overall mortality was 10%. Altered Sensorium, pedal edema, presence of infection, cyanosis, hypotension, severe acidosis, hypercapnia and presence of cor pulmonale at the time of admission predict adverse outcome. Those who need invasive mechanical ventilation had high mortality. Survivors had less hospital stay.
Keywords:
COPD, Cor pulmonale, Respiratory failure, Mechanical ventilation
Article Details
How to Cite
S, Gautam; ANTIN, Guruprasad; PUJAR, Kirankumar.
Acute Exacerbation of Chronic Obstructive Pulmonary Disease – Clinical Presentation and Predictors of Outcome.
Medical Research Archives, [S.l.], v. 11, n. 7.1, july 2023.
ISSN 2375-1924.
Available at: <https://esmed.org/MRA/mra/article/view/4032>. Date accessed: 21 nov. 2024.
doi: https://doi.org/10.18103/mra.v11i7.1.4032.
Section
Research Articles
The Medical Research Archives grants authors the right to publish and reproduce the unrevised contribution in whole or in part at any time and in any form for any scholarly non-commercial purpose with the condition that all publications of the contribution include a full citation to the journal as published by the Medical Research Archives.
References
1. World Health Organization; Chronic obstructive pulmonary disease Available from: URL: http://www.who.int/respiratory/copd/en/Accessed on 10th April 2023.
2. Murray CJL, Lopez AD. Evidence-based health policy: lessons from the Global Burden of Disease Study. Science l996; 274:740-3.
3. The global burden of disease; World Health Organization; Available from URL: http://www.who.int/respiratory/copd/burden/en/index.html Accessed on 10th April 2023.
4. Hurd SS. International Efforts Directed at attacking the Problem of COPD Chest 2000; 117:336S-338S.
5. Executive summary. Global initiative for chronic obstructive lung disease. National Institutes of Health, National Heart, Lung and Blood Institute. Available from URL: http://goldcopd.com/Guideline. Accessed on 14th April 2023.
6. Tobacco or Health: A Global Status Report. Country profiles by region. Southeast Asia. India. Available at: http://www.cdc.gov/tobacco/who/india.htmI
India Inhales. Available at: http://www.tve.org/lifeonline/index.cfm?aid=l 143 Accessed on 10th April 2023.
7. Snow V, Lascher S, Mottur-Pilson C. Joint Expert Panel on COPD of the American College of Chest Physicians and the American College of Physicians-American Society of Internal Medicine. The evidence base for the management of acute exacerbation of COPD. Clinical practice guideline, Part 1. Chest 2001; 119:1185-9.
8. Connors AF Jr, Dawson NV, Thomas C, Harrell FE Jr, Desbiens N, Fulkerson WJ, et al. Outcomes following acute exacerbation of severe chronic obstructive lung disease. The SUPPORT investigators (Study to Understand Prognoses and Preferences for Outcomes and Risks of Treatments). Am J Respir Crit Care Med 1996; 154:959-67.
9. Standards for the diagnosis and care of patients with chronic obstructive pulmonary disease. American Thoracic Society. Am J Respir Crit Care Med 1995; 152:S77-S121.
10. Randall E Harris, epidemiology of chronic disease-2013, Chapter- 30, Epidemiology of chronic obstructive pulmonary disease; 347-350.
11. V.K. Vijayan Vallabhbhai Patel Chest Institute, University of Delhi, Delhi, India Chronic obstructive pulmonary disease, November 6, 2012; Indian J Med Res 137, February 2013, pp 251-269.
12. Jindal SK, Agarwal AN, Gupta D. A review of population studies from India to estimate national burden of chronic obstructive pulmonary disease and its association with smoking. Indian J Chest Dis Allied Sci 2001; 43: 139-47.
13. Data monitor research store; Epidemiology – Chronic obstructive pulmonary disease in India- Aging, population growth and increased survival will drive a marked increase in prevalent of cases of COPD over next ten years; 01/04/2011.
14. Sundeep Salvi1 Etall Prevalence of COPD in a rural population in India ERJ 2011 September;38(55):295.
15. Douglas Seaton, Anthony Seaton : Crofton and Douglass Respiratory Diseases : Blackwell science : Fifth Edition 2000; Chapter 23 Chronic bronchitis & Emphysema; 616 - 695.
16. Malson JL, Sims K, Murty R, Pickworth WB. Comparison of the nicotine content of tobacco used in beedis and conventional cigarettes. Tobacco Control 2001; 10:181-3.
17. Malik SK, Chronic bronchitis in beedi smokers, Indian J Chest Dis 1974; 16:94-9.
18. Chabbra SK, Rajpal S, Gupta R. Patterns of smoking in Delhi and comparison of chronic respiratory morbidity among beedi and cigarette smokers. Indian J Chest Dis Allied Sci 2001; 43:19-26.
19. Voelkel NF, Tuder R COPD exacerbation. Chest 2000; 117:376S-379S.
20. Sullivan SD, Ramsey SD, Lee TA. The economic burden of COPD. Chest 2000; 117(2Suppl):5S-9S.
21. BTS guidelines for the management of chronic obstructive pulmonary disease The COPD Guidelines Group of the Standards of Care Committee of the BTS. Thorax 1997; 52(Suppl5): Sl-28.
22. Siafakas NM, Vermeire P, Pride NB, Paoletti P, Gibson J, Howard P, et al. Optimal assessment and management of chronic obstructive pulmonary disease (COPD). The European Respiratory Society task Force. Eur Respir J 1995; 8:1398-420.
23. Rodriguez-Roisin R. Toward a consensus definition for COPD exacerbations. Chest 2000; 117(5 Suppl2): 398S-401S.
24. ATS COPD exacerbation definition: available at LTRL:
http://www-test.thoracic.org/COPD/13/definition.asp
25. McCrory DC, Brown C, Gelfand SE, Bach PB. Management of acute exacerbations of COPD: a summary and appraisal of published evidence. Chest 2001;119:1190-209.
26. Sethi S. Infectious etiology of acute exacerbations of chronic bronchitis. Chest 2000;117:380S-385S.
27. Alfred P Fishman, Fishman’s Pulmonary diseases and disorders, McGraw hill, 4th edition,2008; Volume 2, Chapter 120, Acute exacerbation of chronic obstructive lung disease; 2115-2120.
28. Garmendia J1, Morey P, Bengoechea JA, Impact of cigarette smoke exposure on host-bacterial pathogen interactions. Eur respir journal.2012 Feb;39(2):467-77.
29. Soler N, Torres A, Ewig s, et al. Bronchial microbial patterns in severe exacerbations of chronic obstructive pulmonary disease (COPD) requiring mechanical ventilation. Am J Respir Crit Care Med 1998; 157:1498-505.
30. Monso. E, Ruiz J, Rosell A, et al. Bacterial infection in chronic obstructive pulmonary disease; a study of stable and exacerbated outpatients using the protected specimen brush, Am J P.espir Crit Care Med 1995; 152:1316-20.
31. Fagon J-Y, Chastre J, Trouillet J-L, et al. Characterization of distal bronchial micro flora during acute exacerbation of chronic bronchitis. Am Rev Respir Dis 1990;142:1004-8.
32. Pela R, Marchesani FF, Agostinelli C, et al. Airways microbial flora in COPD patients in stable clinical conditions and during exacerbations: a bronchoscopic investigation. Monaldi Arch Chest Dis 1998; 53:262-7.
33. Lieberman D, Lieberman D, Ben-Yaakov M, Lazarovich Z, Hoffman S, Ohana B, et al. Infectious etiologies in acute exacerbation of COPD. Diagn Microbiol Infect Dis 2001; 40:95-102.
34. S L Gorbach, J W Mayhew, J G Bartlett, H Thadepalli, and AB Onderdonk Rapid diagnosis of anaerobic infections by direct gas-liquid chromatography of clinical speciments. Clin Invest. Feb 1976;57(2): 478–484.
35. Arora N, Daga MK, Mahajan R, Prakash SK, Gupta N. Microbial pattern of acute infective exacerbation of chronic obstructive airway disease in a hospital based study. Indian J Chest Dis Allied Sci 2001; 43:157-162.
36. Alfred P Fishman, Fishman’s Pulmonary diseases and disorders, McGraw hill, 4th edition,2008; Volume 2, Chapter 120, Acute exacerbation of chronic obstructive lung disease; 2117-2120
37. JeanAnn Fitzgerald, Chronic Dehydration Part 10 – It Triggers Breathing Problems, Healthy beginnings lifestyle magazine.
38. Richard C Boucher, MD, University of North Carolina, Chapel Hill; Mucus Dehydration and Evolution of Chronic Obstructive Pulmonary Disease (COPD) Lung Disease, clinical trials.gov.
39. Management of COPD exacerbation: ATS guidelines available at URl.:http://www-test.thoracic.org/COPD/exacerbation.asp.
40. Belman MJ, Botnick WC, Shin JW. Inhaled bronchodilators reduce dynamic hyperinflation during exercise in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med 1996; 153:967-75.
41. Braun SR, McKenzie WN, Copeland C, et al. A comparison of the effect of ipratropium and albuterol in the treatment of chronic obstructive airway disease. Arch Intern Med 1989; 149:544-7.
42. McCrory DC, Brown CD. Anticholinergic bronchodilators versus beta2- sympatho mimetic agents for acute exacerbations of chronic obstructive pulmonary disease (Cochrane methodology review). The Cochrane Library. Issue 4 2003;Chichester, UK: John Wiley & Sons.
43. Turner MO, Patel A, Ginsburg S, et al. Bronchodilator delivery in acute airflow obstruction. A meta-analysis. Arch Intern Med 1997;157:1736- 44.
44. Turner MO, Gafni A, Swan D, et al A review and economic evaluation of bronchodilator delivery methods in hospitalized patients. Arch Intern Med 1996;156:2113-18.
45. Levitt MA, Gambrioli EF, Fink JB. Comparative trial of continuous nebulization versus metered-dose inhaler in the treatment of acute bronchospasm. Ann Emerg Med 1995;26:273-7.
46. Saetta M, Di Stefano A, Maestrelli P, et al. Airway eosinophilia in chronic bronchitis during exacerbations. Am J Respir Crit Care Med 1994; 150:1646-52.
47. Bhowmik A, Seemungal TAR, Sapsford RJ, et al. Relation of sputum inflammatory markers to symptoms and lung function changes in COPD exacerbations. Thorax 2000;55:114-20.
48. Singh JM, Palda VA, Stanbrook MB, et al. Corticosteroid therapy for patients with acute exacerbations of chronic obstructive pulmonary disease. A systematic review. Arch Intern Med 2002;162:2527-36.
49. Wood-Baker R, Walters EH, Gibson P. Oral corticosteroids for acute exacerbations of chronic obstructive pulmonary disease (Cochrane methodology review). The Cochrane Library. Issue 4 2003;Chichester, UK: John Wiley & Sons.
50. Anthonisen NR, Manfreda J, Warren CP, et al. Antibiotic therapy in exacerbations of chronic obstructive pulmonary disease. Ann Intern Med 1987;106:196-204.
51. Stockley RA, O'Brien C, Pye A, et al. Relationship of sputum color to nature and outpatient management of acute exacerbations of COPD. Chest 2000;117:1638-45.
52. Sachs APE, Koeter GH, Groenier KH, et al. Changes in symptoms, peak expiratory flow, and sputum flora during treatment with antibiotics of exacerbations in patients with chronic obstructive pulmonary disease in general practice. Thorax 1995;50:758-63.
53. Saint S, Bent S, Vittinghoff E, et al. Antibiotics in chronic obstructive pulmonary disease exacerbations. A meta-analysis JAMA 1995;273:957- 60.
54. National Institute for Clinical Excellence. Chronic obstructive pulmonary disease (COPD): management of chronic obstructive pulmonary disease in primary and secondary care. Thorax 2004;59 (suppl) :il-i232.
55. Andrés Canut1, Jose E. Martín-Herrero, Alicia Labora1 and Hiart Maortua1; What are the most appropriate antibiotics for the treatment of acute exacerbation of chronic obstructive pulmonary disease? A therapeutic outcomes model; Oxford Journals Medicine & Health Journal of Antimicrobial Chemotherapy 60(Issue 3): 605-612.
56. Barr RG, Rowe BH, Camargo CA Jr. Methylxanthines for exacerbations of chronic obstructive pulmonary disease: meta-analysis of randomised trials. BMJ 2003;327:643-6.
57. Peter J. Barnes. Theophylline. 2010 Mar; 3(3): 725–747.
58. Douglas Seaton, Anthony Seaton: Crofton and Douglass Respiratory Diseases: Chapter-9, Drugs in lung diseases. 5th Ed. Blackwell Science; 2000 p.252-256.
59. Barbera JA, Roca J, Ferrer A, et at Mechanisms of worsening gas exchange during acute exacerbations of chronic obstructive pulmonary disease. Eur Respir J 1997;10:1285-91.
60. Plant PK, Owen J, Elliot MW. One year period prevalence study of respiratory acidosis in acute exacerbation of COPD: implications for the provision of non-invasive ventilation and oxygen administration. Thorax 2000;55:550-4.
61. Robinson TD, Freiberg DB, Regnis JA, et al The role of hypoventilation and ventilation-perfusion redistribution in oxygen-induced hypercapnia during acute exacerbations of chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2000;161:1524-9.
62. Farokh Erach Udwadia. Principles of Respiratory medicine; Oxford Section 10, Chapter 37. Acute exacerbation of chronic obstructive pulmonary diseases; 402-404.
63. Moloney ED, Kiely JL, McNichoIas WT. Controlled oxygen therapy and carbon dioxide retention during exacerbations of chronic obstructive pulmonary disease. Lancet 2001;357:526-8.
64. Costello RW, Liston R, McNichoIas WT. Compliance at night with low flow oxygen therapy: a comparison of nasal cannulae and Venturi face masks. Thorax 1995;50:405-6.
65. Agusti AGN, Carrera M, Barbe F, et al. Oxygen therapy during exacerbations of chronic obstructive pulmonary disease. Eur Respir J 1999;14:934-9.
66. Alfred P Fishman, Fishman’s Pulmonary diseases and disorders, McGraw hill, 4th Ed., Vol.2, Chapter-120, Acute exacerbation of chronic obstructive lung disease. 2008 p.2122-2123.
67. Bott J, Carroll MP, Conway JH, et al. Randomised controlled trial of nasal ventilation in acute ventilatory failure due to chronic obstructive airways disease. Lancet 1993;341:l555-7.
68. Brochard L, Mancebo J, Wysocki M, et al Noninvasive ventilation for acute exacerbations of chronic obstructive pulmonary disease. TV Engl J Med 1995;333:817-22.
69. Kramer N, Meyer TJ, Meharg J, et al. Randomized, prospective trial of noninvasive positive pressure ventilation in acute respiratory failure. Am J Respir Crit Care Med 1995;151:1799-806.
70. Plant PK, Owen JL, Elliott MW. Early use of non-invasive ventilation for acute exacerbations of chronic obstructive pulmonary disease on general respiratory wards: a multicentre randomised controlled trial. Lancet 2000;355:1931-5.
71. Lightowler JV, Wedzicha JA, Elliott MW, et al. Non-invasive positive pressure ventilation to treat respiratory failure resulting from exacerbations of COPD: Cochrane systematic review and meta-analysis. BMJ 2003;326:185-7.
72. Keenan SP, Gregor J, Sibbald WJ, et al. Noninvasive positive pressure ventilation in the setting of severe, acute exacerbations of chronic obstructive pulmonary disease: more effective and less expensive. Crit Care Med 2000;28:2094-102.
73. Plant PK, Owen JL, Parrott S, et al Cost effectiveness of ward based non-invasive ventilation for acute exacerbations of chronic obstructive pulmonary disease: economic analysis of randomised controlled trial. BMJ 2003;326:956-9.
74. ATS guidelines for Invasive mechanical ventilation for COPD exacerbation, available at URL;
http://www-test.thoracic.org/COPD/15/invasive ventilation asp
75. Roberts CM, Lowe D, Bucknall CE, Ryland I, Kelly Y, Pearson MG. Clinical audit indicators of outcome following admission to hospital with acute exacerbation of chronic obstructive pulmonary disease. Thorax 2002;57:137-41.
76. Seneff MG, Wagner DP, Wagner RP, Zimmerman JE, Knaus WA. Hospital and 1- year survival of patients admitted to intensive care units with acute exacerbation of chronic obstructive pulmonary disease. JAMA 1995;274:1852-7.
77. Fuso L, Incalzi RA, Pistelli R, Muzzolon R, Valente S, Pagliari G, et al.
78. Predicting mortality of patients hospitalized for acutely exacerbated Chronic obstructive pulmonary disease. Am J Med 1995; 98:272-7.
79. Jeffrey AA, Warren PM, Flenley DC. Acute hypercapnic respiratory failure in patients with chronic obstructive lung disease: risk factors and use of guidelines for management. Thorax 1992; 47:34-40.
80. Portier F, Defouilloy C, Muir JF, Determinations of immediate survival among chronic respiratory insufficiency patients admitted to an intensive care unit for acute respiratory failure. A prospective multicenter study. The French Task Group for Acute Respiratory Failure in Chronic Respiratory insufficiency. Chest 1992;101:204-10.
81. Prediction and course of symptoms and lung function around an exacerbation in Chronic Obstructive Pulmonary Disease Respiratory Research 2012;13:44.
82. Alladi Mohan, Raya Premanand, Lebaka Narayana Reddy, Mangu H Rao, Surendra K Sharma, Ranjit Kamity and Srinivas Bollineni1. Clinical presentation and predictors of outcome in patients with severe acute exacerbation of chronic obstructive pulmonary disease requiring admission to intensive care unit http://www.biomedcentral.com/1471- 2466/6/27. Published: 19 December 2006 BMC Pulmonary Medicine 2006, 6:27 doi: 10.1186/1471-2466-6-27.
83. Ramakrishna R. Madakala,; Vijaya Bhaskar,; Vijai R. Kumar, Acute exacerbation of chronic obstructive pulmonary disease: predictors of outcome–single-center prospective study from India CHEST. 2006; 130. (4_MeetingAbstracts):172S-a-172S.
84. Heuser MD, Case LD, Ettinger WH. Mortality in intensive care patients with respiratory diseases. Is age important? Arch Intern med 1992; 152:1683-8.
85. Burk RH, George RB. Acute respiratory failure in chronic obstructive pulmonary disease. Immediate and long-term prognosis. Arch Intern Med 1973;132:865-8.
86. Warren PM, Flenley DC, Millar JS, Avery A. Respiratory failure revisited: acute exacerbations of chronic bronchitis between 1961-68 and 1970 - 76. Lancet 1980; 1:467-70.
87. Pedro Almagro, Esther Calbo, MD, Anna Ochoa de Echagiien, MD; et al Mortality after Hospitalization for COPD Chest 2002; 121:1441-1448.
88. JJ Soler - Cataluna, M A Martinez-Garcia, P Roman Sanchez, E Salcedo, et al -Severe acute exacerbations and mortality in patients with chronic obstructive pulmonary disease Thorax 2005;60:925-931.
89. H Gunen, S.S. Hacievhyagil, F. Kosar, et al ; Factors affecting survival of hospitalized patients with COPD ERS Journal 2005;26:234-241.
90. Maarten van den Berge1, Wim CJ Hop, Thys van der Molen, Jan A van Noord, Jacques PHM Creemers, Ad JM Schreurs, Emiel FM Wouters and Dirkje S Postma1 for the COSMIC (COPD and Seretide: a Multi- Center Intervention and Characterization) study group; Prediction and course of symptoms and lung function around an exacerbation in chronic obstructive pulmonary disease; Research 2012, 13:44 http://respiratoryresearch.com/content/13/1/44
91. Michael L.Nvins, MD and Scott K et al Predictors of outcome for patients with COPD requiring invasive mechanical ventilation. Chest 2001; 119:1840-1849.
92. R. Antenolli Incalzi, L. Fuso, M De Rosa, F. Forastiere, E. Rapiti et al Co-morbidity contributes to predict mortality of patients with chronic obstructive pulmonary disease. Eur Respir J 1997;10:2794-2800.
93. Sherman S, Skoney JA, Ravikrishnan K. Routine chest radiographs in exacerbation of chronic obstructive pulmonary disease; diagnostic value. Arch Intern Med 1989; 149:2493-3496.
94. Tsai TW, Gallagher EJ, Lombardi G, et al. Guidelines for the selective ordering of admission chest radiography in adult obstructive airway disease. Ann Eer4-1858g Med 1993; 22:18.
95. Emerman CL Cydulka RK. Evaluation of high-yield criteria for chest radiography in acute exacerbation of chronic obstructive pulmonary disease. Ann Emerg Med 1993;22:680-684.
96. S. Kumar et al, Dept of internal medicine PGI Chandigarh; Predictors of requirement of mechanical ventilation in patients with Chronic obstructive lung disease with acute respiratory failure. Lung India, 2013 Sept; 30(Issue 3): 178-181.
97. Steer J, GJ. Gibson, and SC. Bourke. Predicting outcomes following hospitalization for acute exacerbations of COPD, Q J Med 2010; 103: 817–829.
98. Ian G. Stiell, Catherine M. Clement RN, Shawn D. Aaron, Brian H. Rowe, Jeffrey J. Perry, Robert J. Brison, et al. Clinical characteristics associated with adverse events in patients with exacerbation of chronic obstructive pulmonary disease: a prospective cohort study. CMAJ, 2014 April;186(6): CMAJ 2014. DOI:10.1503 /cmaj.130968
2. Murray CJL, Lopez AD. Evidence-based health policy: lessons from the Global Burden of Disease Study. Science l996; 274:740-3.
3. The global burden of disease; World Health Organization; Available from URL: http://www.who.int/respiratory/copd/burden/en/index.html Accessed on 10th April 2023.
4. Hurd SS. International Efforts Directed at attacking the Problem of COPD Chest 2000; 117:336S-338S.
5. Executive summary. Global initiative for chronic obstructive lung disease. National Institutes of Health, National Heart, Lung and Blood Institute. Available from URL: http://goldcopd.com/Guideline. Accessed on 14th April 2023.
6. Tobacco or Health: A Global Status Report. Country profiles by region. Southeast Asia. India. Available at: http://www.cdc.gov/tobacco/who/india.htmI
India Inhales. Available at: http://www.tve.org/lifeonline/index.cfm?aid=l 143 Accessed on 10th April 2023.
7. Snow V, Lascher S, Mottur-Pilson C. Joint Expert Panel on COPD of the American College of Chest Physicians and the American College of Physicians-American Society of Internal Medicine. The evidence base for the management of acute exacerbation of COPD. Clinical practice guideline, Part 1. Chest 2001; 119:1185-9.
8. Connors AF Jr, Dawson NV, Thomas C, Harrell FE Jr, Desbiens N, Fulkerson WJ, et al. Outcomes following acute exacerbation of severe chronic obstructive lung disease. The SUPPORT investigators (Study to Understand Prognoses and Preferences for Outcomes and Risks of Treatments). Am J Respir Crit Care Med 1996; 154:959-67.
9. Standards for the diagnosis and care of patients with chronic obstructive pulmonary disease. American Thoracic Society. Am J Respir Crit Care Med 1995; 152:S77-S121.
10. Randall E Harris, epidemiology of chronic disease-2013, Chapter- 30, Epidemiology of chronic obstructive pulmonary disease; 347-350.
11. V.K. Vijayan Vallabhbhai Patel Chest Institute, University of Delhi, Delhi, India Chronic obstructive pulmonary disease, November 6, 2012; Indian J Med Res 137, February 2013, pp 251-269.
12. Jindal SK, Agarwal AN, Gupta D. A review of population studies from India to estimate national burden of chronic obstructive pulmonary disease and its association with smoking. Indian J Chest Dis Allied Sci 2001; 43: 139-47.
13. Data monitor research store; Epidemiology – Chronic obstructive pulmonary disease in India- Aging, population growth and increased survival will drive a marked increase in prevalent of cases of COPD over next ten years; 01/04/2011.
14. Sundeep Salvi1 Etall Prevalence of COPD in a rural population in India ERJ 2011 September;38(55):295.
15. Douglas Seaton, Anthony Seaton : Crofton and Douglass Respiratory Diseases : Blackwell science : Fifth Edition 2000; Chapter 23 Chronic bronchitis & Emphysema; 616 - 695.
16. Malson JL, Sims K, Murty R, Pickworth WB. Comparison of the nicotine content of tobacco used in beedis and conventional cigarettes. Tobacco Control 2001; 10:181-3.
17. Malik SK, Chronic bronchitis in beedi smokers, Indian J Chest Dis 1974; 16:94-9.
18. Chabbra SK, Rajpal S, Gupta R. Patterns of smoking in Delhi and comparison of chronic respiratory morbidity among beedi and cigarette smokers. Indian J Chest Dis Allied Sci 2001; 43:19-26.
19. Voelkel NF, Tuder R COPD exacerbation. Chest 2000; 117:376S-379S.
20. Sullivan SD, Ramsey SD, Lee TA. The economic burden of COPD. Chest 2000; 117(2Suppl):5S-9S.
21. BTS guidelines for the management of chronic obstructive pulmonary disease The COPD Guidelines Group of the Standards of Care Committee of the BTS. Thorax 1997; 52(Suppl5): Sl-28.
22. Siafakas NM, Vermeire P, Pride NB, Paoletti P, Gibson J, Howard P, et al. Optimal assessment and management of chronic obstructive pulmonary disease (COPD). The European Respiratory Society task Force. Eur Respir J 1995; 8:1398-420.
23. Rodriguez-Roisin R. Toward a consensus definition for COPD exacerbations. Chest 2000; 117(5 Suppl2): 398S-401S.
24. ATS COPD exacerbation definition: available at LTRL:
http://www-test.thoracic.org/COPD/13/definition.asp
25. McCrory DC, Brown C, Gelfand SE, Bach PB. Management of acute exacerbations of COPD: a summary and appraisal of published evidence. Chest 2001;119:1190-209.
26. Sethi S. Infectious etiology of acute exacerbations of chronic bronchitis. Chest 2000;117:380S-385S.
27. Alfred P Fishman, Fishman’s Pulmonary diseases and disorders, McGraw hill, 4th edition,2008; Volume 2, Chapter 120, Acute exacerbation of chronic obstructive lung disease; 2115-2120.
28. Garmendia J1, Morey P, Bengoechea JA, Impact of cigarette smoke exposure on host-bacterial pathogen interactions. Eur respir journal.2012 Feb;39(2):467-77.
29. Soler N, Torres A, Ewig s, et al. Bronchial microbial patterns in severe exacerbations of chronic obstructive pulmonary disease (COPD) requiring mechanical ventilation. Am J Respir Crit Care Med 1998; 157:1498-505.
30. Monso. E, Ruiz J, Rosell A, et al. Bacterial infection in chronic obstructive pulmonary disease; a study of stable and exacerbated outpatients using the protected specimen brush, Am J P.espir Crit Care Med 1995; 152:1316-20.
31. Fagon J-Y, Chastre J, Trouillet J-L, et al. Characterization of distal bronchial micro flora during acute exacerbation of chronic bronchitis. Am Rev Respir Dis 1990;142:1004-8.
32. Pela R, Marchesani FF, Agostinelli C, et al. Airways microbial flora in COPD patients in stable clinical conditions and during exacerbations: a bronchoscopic investigation. Monaldi Arch Chest Dis 1998; 53:262-7.
33. Lieberman D, Lieberman D, Ben-Yaakov M, Lazarovich Z, Hoffman S, Ohana B, et al. Infectious etiologies in acute exacerbation of COPD. Diagn Microbiol Infect Dis 2001; 40:95-102.
34. S L Gorbach, J W Mayhew, J G Bartlett, H Thadepalli, and AB Onderdonk Rapid diagnosis of anaerobic infections by direct gas-liquid chromatography of clinical speciments. Clin Invest. Feb 1976;57(2): 478–484.
35. Arora N, Daga MK, Mahajan R, Prakash SK, Gupta N. Microbial pattern of acute infective exacerbation of chronic obstructive airway disease in a hospital based study. Indian J Chest Dis Allied Sci 2001; 43:157-162.
36. Alfred P Fishman, Fishman’s Pulmonary diseases and disorders, McGraw hill, 4th edition,2008; Volume 2, Chapter 120, Acute exacerbation of chronic obstructive lung disease; 2117-2120
37. JeanAnn Fitzgerald, Chronic Dehydration Part 10 – It Triggers Breathing Problems, Healthy beginnings lifestyle magazine.
38. Richard C Boucher, MD, University of North Carolina, Chapel Hill; Mucus Dehydration and Evolution of Chronic Obstructive Pulmonary Disease (COPD) Lung Disease, clinical trials.gov.
39. Management of COPD exacerbation: ATS guidelines available at URl.:http://www-test.thoracic.org/COPD/exacerbation.asp.
40. Belman MJ, Botnick WC, Shin JW. Inhaled bronchodilators reduce dynamic hyperinflation during exercise in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med 1996; 153:967-75.
41. Braun SR, McKenzie WN, Copeland C, et al. A comparison of the effect of ipratropium and albuterol in the treatment of chronic obstructive airway disease. Arch Intern Med 1989; 149:544-7.
42. McCrory DC, Brown CD. Anticholinergic bronchodilators versus beta2- sympatho mimetic agents for acute exacerbations of chronic obstructive pulmonary disease (Cochrane methodology review). The Cochrane Library. Issue 4 2003;Chichester, UK: John Wiley & Sons.
43. Turner MO, Patel A, Ginsburg S, et al. Bronchodilator delivery in acute airflow obstruction. A meta-analysis. Arch Intern Med 1997;157:1736- 44.
44. Turner MO, Gafni A, Swan D, et al A review and economic evaluation of bronchodilator delivery methods in hospitalized patients. Arch Intern Med 1996;156:2113-18.
45. Levitt MA, Gambrioli EF, Fink JB. Comparative trial of continuous nebulization versus metered-dose inhaler in the treatment of acute bronchospasm. Ann Emerg Med 1995;26:273-7.
46. Saetta M, Di Stefano A, Maestrelli P, et al. Airway eosinophilia in chronic bronchitis during exacerbations. Am J Respir Crit Care Med 1994; 150:1646-52.
47. Bhowmik A, Seemungal TAR, Sapsford RJ, et al. Relation of sputum inflammatory markers to symptoms and lung function changes in COPD exacerbations. Thorax 2000;55:114-20.
48. Singh JM, Palda VA, Stanbrook MB, et al. Corticosteroid therapy for patients with acute exacerbations of chronic obstructive pulmonary disease. A systematic review. Arch Intern Med 2002;162:2527-36.
49. Wood-Baker R, Walters EH, Gibson P. Oral corticosteroids for acute exacerbations of chronic obstructive pulmonary disease (Cochrane methodology review). The Cochrane Library. Issue 4 2003;Chichester, UK: John Wiley & Sons.
50. Anthonisen NR, Manfreda J, Warren CP, et al. Antibiotic therapy in exacerbations of chronic obstructive pulmonary disease. Ann Intern Med 1987;106:196-204.
51. Stockley RA, O'Brien C, Pye A, et al. Relationship of sputum color to nature and outpatient management of acute exacerbations of COPD. Chest 2000;117:1638-45.
52. Sachs APE, Koeter GH, Groenier KH, et al. Changes in symptoms, peak expiratory flow, and sputum flora during treatment with antibiotics of exacerbations in patients with chronic obstructive pulmonary disease in general practice. Thorax 1995;50:758-63.
53. Saint S, Bent S, Vittinghoff E, et al. Antibiotics in chronic obstructive pulmonary disease exacerbations. A meta-analysis JAMA 1995;273:957- 60.
54. National Institute for Clinical Excellence. Chronic obstructive pulmonary disease (COPD): management of chronic obstructive pulmonary disease in primary and secondary care. Thorax 2004;59 (suppl) :il-i232.
55. Andrés Canut1, Jose E. Martín-Herrero, Alicia Labora1 and Hiart Maortua1; What are the most appropriate antibiotics for the treatment of acute exacerbation of chronic obstructive pulmonary disease? A therapeutic outcomes model; Oxford Journals Medicine & Health Journal of Antimicrobial Chemotherapy 60(Issue 3): 605-612.
56. Barr RG, Rowe BH, Camargo CA Jr. Methylxanthines for exacerbations of chronic obstructive pulmonary disease: meta-analysis of randomised trials. BMJ 2003;327:643-6.
57. Peter J. Barnes. Theophylline. 2010 Mar; 3(3): 725–747.
58. Douglas Seaton, Anthony Seaton: Crofton and Douglass Respiratory Diseases: Chapter-9, Drugs in lung diseases. 5th Ed. Blackwell Science; 2000 p.252-256.
59. Barbera JA, Roca J, Ferrer A, et at Mechanisms of worsening gas exchange during acute exacerbations of chronic obstructive pulmonary disease. Eur Respir J 1997;10:1285-91.
60. Plant PK, Owen J, Elliot MW. One year period prevalence study of respiratory acidosis in acute exacerbation of COPD: implications for the provision of non-invasive ventilation and oxygen administration. Thorax 2000;55:550-4.
61. Robinson TD, Freiberg DB, Regnis JA, et al The role of hypoventilation and ventilation-perfusion redistribution in oxygen-induced hypercapnia during acute exacerbations of chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2000;161:1524-9.
62. Farokh Erach Udwadia. Principles of Respiratory medicine; Oxford Section 10, Chapter 37. Acute exacerbation of chronic obstructive pulmonary diseases; 402-404.
63. Moloney ED, Kiely JL, McNichoIas WT. Controlled oxygen therapy and carbon dioxide retention during exacerbations of chronic obstructive pulmonary disease. Lancet 2001;357:526-8.
64. Costello RW, Liston R, McNichoIas WT. Compliance at night with low flow oxygen therapy: a comparison of nasal cannulae and Venturi face masks. Thorax 1995;50:405-6.
65. Agusti AGN, Carrera M, Barbe F, et al. Oxygen therapy during exacerbations of chronic obstructive pulmonary disease. Eur Respir J 1999;14:934-9.
66. Alfred P Fishman, Fishman’s Pulmonary diseases and disorders, McGraw hill, 4th Ed., Vol.2, Chapter-120, Acute exacerbation of chronic obstructive lung disease. 2008 p.2122-2123.
67. Bott J, Carroll MP, Conway JH, et al. Randomised controlled trial of nasal ventilation in acute ventilatory failure due to chronic obstructive airways disease. Lancet 1993;341:l555-7.
68. Brochard L, Mancebo J, Wysocki M, et al Noninvasive ventilation for acute exacerbations of chronic obstructive pulmonary disease. TV Engl J Med 1995;333:817-22.
69. Kramer N, Meyer TJ, Meharg J, et al. Randomized, prospective trial of noninvasive positive pressure ventilation in acute respiratory failure. Am J Respir Crit Care Med 1995;151:1799-806.
70. Plant PK, Owen JL, Elliott MW. Early use of non-invasive ventilation for acute exacerbations of chronic obstructive pulmonary disease on general respiratory wards: a multicentre randomised controlled trial. Lancet 2000;355:1931-5.
71. Lightowler JV, Wedzicha JA, Elliott MW, et al. Non-invasive positive pressure ventilation to treat respiratory failure resulting from exacerbations of COPD: Cochrane systematic review and meta-analysis. BMJ 2003;326:185-7.
72. Keenan SP, Gregor J, Sibbald WJ, et al. Noninvasive positive pressure ventilation in the setting of severe, acute exacerbations of chronic obstructive pulmonary disease: more effective and less expensive. Crit Care Med 2000;28:2094-102.
73. Plant PK, Owen JL, Parrott S, et al Cost effectiveness of ward based non-invasive ventilation for acute exacerbations of chronic obstructive pulmonary disease: economic analysis of randomised controlled trial. BMJ 2003;326:956-9.
74. ATS guidelines for Invasive mechanical ventilation for COPD exacerbation, available at URL;
http://www-test.thoracic.org/COPD/15/invasive ventilation asp
75. Roberts CM, Lowe D, Bucknall CE, Ryland I, Kelly Y, Pearson MG. Clinical audit indicators of outcome following admission to hospital with acute exacerbation of chronic obstructive pulmonary disease. Thorax 2002;57:137-41.
76. Seneff MG, Wagner DP, Wagner RP, Zimmerman JE, Knaus WA. Hospital and 1- year survival of patients admitted to intensive care units with acute exacerbation of chronic obstructive pulmonary disease. JAMA 1995;274:1852-7.
77. Fuso L, Incalzi RA, Pistelli R, Muzzolon R, Valente S, Pagliari G, et al.
78. Predicting mortality of patients hospitalized for acutely exacerbated Chronic obstructive pulmonary disease. Am J Med 1995; 98:272-7.
79. Jeffrey AA, Warren PM, Flenley DC. Acute hypercapnic respiratory failure in patients with chronic obstructive lung disease: risk factors and use of guidelines for management. Thorax 1992; 47:34-40.
80. Portier F, Defouilloy C, Muir JF, Determinations of immediate survival among chronic respiratory insufficiency patients admitted to an intensive care unit for acute respiratory failure. A prospective multicenter study. The French Task Group for Acute Respiratory Failure in Chronic Respiratory insufficiency. Chest 1992;101:204-10.
81. Prediction and course of symptoms and lung function around an exacerbation in Chronic Obstructive Pulmonary Disease Respiratory Research 2012;13:44.
82. Alladi Mohan, Raya Premanand, Lebaka Narayana Reddy, Mangu H Rao, Surendra K Sharma, Ranjit Kamity and Srinivas Bollineni1. Clinical presentation and predictors of outcome in patients with severe acute exacerbation of chronic obstructive pulmonary disease requiring admission to intensive care unit http://www.biomedcentral.com/1471- 2466/6/27. Published: 19 December 2006 BMC Pulmonary Medicine 2006, 6:27 doi: 10.1186/1471-2466-6-27.
83. Ramakrishna R. Madakala,; Vijaya Bhaskar,; Vijai R. Kumar, Acute exacerbation of chronic obstructive pulmonary disease: predictors of outcome–single-center prospective study from India CHEST. 2006; 130. (4_MeetingAbstracts):172S-a-172S.
84. Heuser MD, Case LD, Ettinger WH. Mortality in intensive care patients with respiratory diseases. Is age important? Arch Intern med 1992; 152:1683-8.
85. Burk RH, George RB. Acute respiratory failure in chronic obstructive pulmonary disease. Immediate and long-term prognosis. Arch Intern Med 1973;132:865-8.
86. Warren PM, Flenley DC, Millar JS, Avery A. Respiratory failure revisited: acute exacerbations of chronic bronchitis between 1961-68 and 1970 - 76. Lancet 1980; 1:467-70.
87. Pedro Almagro, Esther Calbo, MD, Anna Ochoa de Echagiien, MD; et al Mortality after Hospitalization for COPD Chest 2002; 121:1441-1448.
88. JJ Soler - Cataluna, M A Martinez-Garcia, P Roman Sanchez, E Salcedo, et al -Severe acute exacerbations and mortality in patients with chronic obstructive pulmonary disease Thorax 2005;60:925-931.
89. H Gunen, S.S. Hacievhyagil, F. Kosar, et al ; Factors affecting survival of hospitalized patients with COPD ERS Journal 2005;26:234-241.
90. Maarten van den Berge1, Wim CJ Hop, Thys van der Molen, Jan A van Noord, Jacques PHM Creemers, Ad JM Schreurs, Emiel FM Wouters and Dirkje S Postma1 for the COSMIC (COPD and Seretide: a Multi- Center Intervention and Characterization) study group; Prediction and course of symptoms and lung function around an exacerbation in chronic obstructive pulmonary disease; Research 2012, 13:44 http://respiratoryresearch.com/content/13/1/44
91. Michael L.Nvins, MD and Scott K et al Predictors of outcome for patients with COPD requiring invasive mechanical ventilation. Chest 2001; 119:1840-1849.
92. R. Antenolli Incalzi, L. Fuso, M De Rosa, F. Forastiere, E. Rapiti et al Co-morbidity contributes to predict mortality of patients with chronic obstructive pulmonary disease. Eur Respir J 1997;10:2794-2800.
93. Sherman S, Skoney JA, Ravikrishnan K. Routine chest radiographs in exacerbation of chronic obstructive pulmonary disease; diagnostic value. Arch Intern Med 1989; 149:2493-3496.
94. Tsai TW, Gallagher EJ, Lombardi G, et al. Guidelines for the selective ordering of admission chest radiography in adult obstructive airway disease. Ann Eer4-1858g Med 1993; 22:18.
95. Emerman CL Cydulka RK. Evaluation of high-yield criteria for chest radiography in acute exacerbation of chronic obstructive pulmonary disease. Ann Emerg Med 1993;22:680-684.
96. S. Kumar et al, Dept of internal medicine PGI Chandigarh; Predictors of requirement of mechanical ventilation in patients with Chronic obstructive lung disease with acute respiratory failure. Lung India, 2013 Sept; 30(Issue 3): 178-181.
97. Steer J, GJ. Gibson, and SC. Bourke. Predicting outcomes following hospitalization for acute exacerbations of COPD, Q J Med 2010; 103: 817–829.
98. Ian G. Stiell, Catherine M. Clement RN, Shawn D. Aaron, Brian H. Rowe, Jeffrey J. Perry, Robert J. Brison, et al. Clinical characteristics associated with adverse events in patients with exacerbation of chronic obstructive pulmonary disease: a prospective cohort study. CMAJ, 2014 April;186(6): CMAJ 2014. DOI:10.1503 /cmaj.130968