Dyspnoea in patients with advanced cancer: Incidence, causes and treatments

Cancer Treatment Reviews

Volumn 24, Issue 1, 1998, Pages 69-80

  Ripamonti, C ^a,b   Fulfaro, F ^a   Bruera, E ^b  

^a NATIONAL CANCER INSTITUTE   (Italy)

^b UNIVERSITY OF ALBERTA   (Canada)

Author keywords

[No Author keywords available]

Indexed keywords

BRONCHODILATING AGENT; CORTICOSTEROID; OPIATE; PSYCHOTROPIC AGENT;

ADVANCED CANCER; DYSPNEA; HUMAN; OXYGEN THERAPY; REVIEW; TERMINAL CARE;

EID: 0031919265     PISSN: 03057372     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0305-7372(98)90072-X     Document Type: Article

References (153)

1. Baines M. Control of other symptoms. In: Saunders CM, ed, The Management of Terminal Disease. Chicago: Year Book, 1978.
2. Ventafridda V, De Conno F, Ripamonti C, Gamba A, Tamburini M. Quality of life assessment during a palliative care programme. Ann Oncol 1990; 1: 415-420.
3. Higginson I, McCarthy M. Measuring symptoms in terminal cancer: are pain and dyspnoea controlled? J Royal Soc Med 1989; 82: 264-267.
4. Grond S, Zech D, Diefenbach C, Bischoff A. Prevalence and pattern of symptoms in patients with cancer pain: a prospective evaluation of 1635 cancer patients referred to a pain clinic. J Pain Symptom Manag 1994; 9: 372-382.
5. Donnelly S, Walsh D. The symptoms of advanced cancer: identification of clinical and research priorities by assessment of prevalence and severity. J Palliat Care 1995; 11: 27-32.
6. Curtis EB, Krech R, Walsh TD. Common symptoms in patients with advanced cancer. J Palliat Care 1991; 7: 25-29.
7. Heyse-Moore LH, Ross V, Mullee MA. How much of a problem is dyspnea in advanced cancer? Palliat Med 1991; 5: 20-26.
8. Ventafridda V, Ripamonti C, De Conno F, Tamburini M, Cassileth BR. Symptom prevalence and control during cancer patient's last days of life. J Palliat Care 1990; 6: 7-11.
9. Twycross RG, Lack SA. Control of Alimentary Symptoms in Far Advanced Cancer. London: Churchill Livingstone, 1986; 1-11.
10. Muers MF. Palliation of symptoms in non-small cell lung cancer: a study by the Yorkshire Regional Cancer Organization Thoracic Group. Thorax 1993; 48: 339-343.
11. Saunders C. The Management of Terminal Malignant Disease, second edition. London: Edward Arnold, 1984; 113-119.
12. Reuben DB, Mor V. Dyspnea in terminally ill cancer patients. Chest 1986; 89: 234-236.
13. Desbiens NA, Mueller-Rizner N, Connors AF, Wenger NS. The relationship of nausea and dyspnea to pain in seriously ill patients. Pain 1997; 71: 149-156.
14. Krech RL, Walsh D. Symptoms of pancreatic cancer. J Pain Symptom Manag 1991; 6: 360-367.
15. Hardy JR, Turner R, Saunders M, A'Hern R. Prediction of survival in a Hospital-based Continuing Care Unit. Eur J Cancer 1994; 30A: 284-288.
16. Maltoni M, Pirovano M, Scarpi E et al. Prediction of survival of patients terminally ill with cancer. Cancer 1995; 75: 2613-2622.
17. Escalante CP, Martin CG, Elting LS et al. Dyspnea in Cancer Patients. Etiology, Resource Utilization, and Survival. Implications in a managed care world. Cancer 1996; 78: 1314-1319.
18. Ripamonti C, Bruera E. Dyspnea: pathophysiology and assessment. J Pain Symptom Manag 1997; 13: 220-232.
19. Ahmedzai S. Palliation of respiratory symptoms. In: Doyle D, Hanks GWC, MacDonald N, eds, Oxford Textbook of Palliative Medicine. Oxford: Oxford University Press, 1993; 349-378.
20. Congleton J, Muers MF. The incidence of airflow obstruction in bronchial carcinoma, its relation to breathlessness, and response to bronchodilator therapy. Respir Med 1995; 89: 291-296.
21. Bruera E, Fainsinger RL. Clinical management of cachexia and anorexia. In: Doyle D, Hanks GWC, MacDonald N, eds, Oxford Textbook of Palliative Medicine. Oxford: Oxford Medical Publications, 1993; 330-337.
22. Palange P, Forte S, Felli A, Galassetti P, Serra P, Carlone S. Nutritional state and exercise tolerance in patients with COPD. Chest 1995; 107: 1206-1212.
23. Kongragunta VR, Druz WS, Sharp JT. Dyspnea and diaphragmatic fatigue in patients with chronic obstructive pulmonary disease. Am Rev Respir Dis 1988; 137: 662-667.
24. Arora NS, Rochester DF. Respiratory muscle strength and maximal voluntary ventilation in undernourished patients. Am Rev Respir Dis 1982; 126: 5-8.
25. Clark AL, Sparrow JL, Coats AJS. Muscle fatigue and dyspnoea in chronic heart failure: two sides of the same coin? Eur Heart J 1995; 16: 49-52.
26. Mahler DA, Rosiello RA, Harver A, Lentine T, McGovern JF, Daubenspeck JA. Comparison of clinical dyspnea ratings and psychophysical measurements of respiratory sensation in obstructive airway disease. Am Rev Respir Dis 1987; 135: 1229-1233.
27. Stoller JK, Ferranti R, Feinstein AR. Further specification and evaluation of a new clinical index for dyspnea. Am Rev Respir Dis 1986; 134: 1129-1134.
28. Burns BH, Howell JBL. Disproportionately severe breathlessness in chronic bronchitis. Quart J Med 1969; 151: 277-294.
29. Burdon JGW, Pain MCF, Rubinfeld AR, Nana A. Chronic lung disease and the perception of breathlessless: a clinical perspective. Eur Respir J 1994; 7: 1342-1349.
30. Medical Research Council, by its Lung Cancer Working Party. Inoperable non-small cell lung cancer (NSCLC): a Medical Research Council randomised trial of palliative radiotherapy with two fractions or ten fractions. Br J Cancer 1991; 63: 265-270.
31. Cullen MH. The MIC regimen in non-small cell lung cancer. Lung Cancer 1993; 9 (Suppl. 2): 81-89.
32. Hardy JR, Noble T, Smith IE. Symptom relief with moderate dose chemotherapy (mitomycin-C, vinblastine and cisplatin) in advanced non-small cell lung cancer. Br J Cancer 1989; 60: 764-766.
33. Fernandez C, Rosell R, Abad-Esteve A et al. Quality of life during chemotherapy in non-small cell lung cancer patients. Acta Oncolog 1989; 28: 29-33.
34. Thatcher N, Anderson H, Betticher DC, Ranson M. Symptomatic benefit from gemcitabine and other chemotherapy in advanced non-small cell lung cancer: changes in performance status and tumor-related symptoms. Anti-Cancer Drugs 1995; 6 (Suppl. 6): 39-48.
35. Nelson R, Tarassoff P. Dyspnea with gemcitabine is commonly seen, often disease related, transient and rarely severe. Eur J Cancer 1995; 31(A) (Suppl. 5): 197-198.
36. Kaye SB. Gemcitabine: current status of phase I and II trials. J Clin Oncol 1994; 12: 1527-1531.
37. Pavlakis N, Bell DR, Millward MJ, Levi JA. Fatal pulmonary toxicity resulting from treatment with gemcitabine. Cancer 1997; 80: 286-291.
38. Anderson BS, Cogan BM, Keating MJ, Estey EH, McCreadie KB, Freireich EJ. Subacute pulmonary failure complicating therapy with high dose ara-C in acute leukemia. Cancer 1985; 56: 2181-2184.
39. Shearer P, Katz J, Bozeman P et al. Pulmonary insufficiency complicating therapy with high dose cytosine arabinoside in five paedriatic patients with relapsed acute myelogenous leukemia. Cancer 1994; 74: 1953-1958.
40. Rivera MP, Kris MG, Gralla RJ, White DA. Syndrome of acute dyspnea related to combined mitomycin plus vinca alkaloid chemotherapy. Am J Clin Oncol 1995; 18/3: 245-250.
41. Varricchio C. Clinical management of superior vena cava syndrome. Heart Lung 1985; 14: 411-416.
42. Adelstein DJ, Hines JD, Carter SG, Sacco D. Thromboembolic events in patients with malignant superior vena cava syndrome and the role of anticoagulation. Cancer 1988; 62: 2258-2262.
43. Smith MJ, Spiro DG. Respiratory complications of malignant disease. In: Kay SB, Rankin EM, eds, Medical Complications of Malignant Disease. London: Bailliere Tindall, 1988; 319-346.
44. Sculier JP, Feld R. Superior vena cava obstruction syndrome: recommendations for management. Cancer Treat Rev 1985; 15: 165-181.
45. Lequaglie C, Alloisio M, Muscolino G et al. Malignant obstruction of the superior vena cava and its palliation. J Exp Clin Cancer Res 1997; 16/2 (Suppl.): 16.
46. Stock KW, Jacob AL, Proske M, Bolliger CT, Rochlitz C, Steinbrich W. Treatment of malignant obstruction of the superior vena cava with the self-expanding Wallstent. Thorax 1995; 50: 1151-1156.
47. Miche O, Prott FJ, Schafer U, Wagner W, Potter R, Willich N. Endoluminal HDR brachytherapy in the palliative treatment of patients with the recurrence of a non-small-cell bronchial carcinoma after prior radiotherapy. Strahlenther Onkol 1995; 171: 554-559.
48. Huber RM, Fischer R, Hautmann H et al. Palliative endobronchial brachytherapy for central lung tumors. A prospective, randomized comparison of two fractionation schedules. Chest 1995; 107: 463-470.
49. Cavaliere S, Venuta F, Foccoli P, Toninelli C, La Face B. Endoscopic treatment of malignant airway obstructions in 2,008 patients. Chest 1996; 110: 1536-1542.
50. Aygun C, Blum JE. Treatment of unresectable lung cancer with brachytherapy. World J Surg 1995; 19: 823-827.
51. Ninane V. Endoscopic management of acute respiratory failure related to tracheobronchial malignancies. Support Care Cancer 1995; 3: 418-421.
52. Macha HN, Wahlers B, Reichle C, von-Zwenl D. Endobronchial radiation therapy for obstructing malignancies: ten years' experience with iridium-192 high-dose radiation brachytherapy afterloading technique in 365 patients. Lung 1995; 173: 271-280.
53. Spinelli P, Meroni E, Cerrai FG. A new technique of endoscopic implantation of self-expanding mesh stents for inoperable traceho-bronchial malignancies. End Surg 1993; 1: 82-84.
54. Wilson GE, Walshaw MJ, Ilind CR. Treatment of large airway obstruction in lung cancer using expandable metal stents inserted under direct vision via the fibreoptic bronchoscope. Thorax 1996; 51: 248-252.
55. Brutinel WM, Cortese DA, McDougall JG, Gillio RG, Berstrahl EJ. A two year experience with the neodymium-YAG laser in endobronchial carcinoma. Chest 1987; 91: 159-165.
56. Petrou M, Goldstraw P. The management of tracheobronchial obstruction: a review of endoscopic techniques. Eur J Cardiothorac Surg 1994; 8: 436-441.
57. Mestitz H, Pierce RJ, Holmes PW. Intrathoracic manifestation of disseminated prostatic adenocarcinoma. Respir Med 1989; 83: 161-166.
58. Sahn SA. Malignant pleural effusions. Seminars Respir Med 1987; 9: 43-52.
59. Chernow B, Sahn SA. Carcinomatous involvement of the pleura: an analysis of 96 patients. Am J Med 1977; 63: 695-702.
60. Miles DW, Knight RK. Diagnosis and management of malignant pleural effusion. Cancer Treat Rev 1993; 19: 151-168.
61. Estenne MC, Vernault JC, De Troyer A. Mechanism of relief of dyspnea after thoracocentesis in patients with pleural effusions. Am J Med 1983; 74: 813-819.
62. Walker-Renard PB, Vaughan LM, Sahn SA. Chemical pleurodesis for malignant pleural effusions. Ann Intern Med 1994; 120: 56-64.
63. Viallat J-R, Rey F, Astoul P, Boutin C. Thoracoscopic talc pudrage pleurodesis for malignant effusions. A review of 360 cases. Chest 1996; 110: 1387-1393.
64. Boniface E, Guerin JC. Interet du talcage par thoracoscopie dans le traitment symptomatique des pleuresies recidivantes a propos de 302 cas. Rev Mal Respir 1989; 6: 133-139.
65. Canto A, Rivas J, Moya J et al. Pleural effusion of malignant etiology: thoracoscopic use of talc as an effective method of pleurodesis. Med Clin 1985; 84: 806-808.
66. Ladjimi S, M'raihi L, Djemel A et al. Resultats du talcage pleural sous thoracoscopie au cours des pleuresies neoplasiques. Rev Mal Respir 1989; 6: 147-150.
67. Sanchez-Armengol A, Rodriguez-Panadero F. Survival and talc pleurodesis in metastatic pleural carcinoma revisited: report of 125 cases. Chest 1993; 104: 1482-1485.
68. Weissberg D, Ben-Zeev I. Talc pleurodesis: experience with 360 patients. J Thorac Cardiovasc Surg 1993; 106: 689-695.
69. Petrou M, Kaplan D, Goldstraw P. Management of recurrent malignant pleural effusions. The complementary role talc pleurodesis and pleuroperitoneal shunting. Cancer 1995; 75: 801-805.
70. Ponn RB, Blancaflor J, D'Agostino RS, Kiernan ME, Toole AL, Stern H. Pleuroperitoneal shunting for intractable pleural effusions. Ann Thorac Surg 1991; 51: 605-609.
71. Tsang V, Fernando HC, Goldstraw P. Pleuroperitoneal shunt for recurrent malignant pleural effusions. Thorax 1990; 45: 369-372.
72. Little AG, Kadowaki MH, Ferguson MK, Staszek VM, Skinner DB. Pleuroperitoneal shunting. Ann Surg 1988; 208: 443-450.
73. Roukema JA, Lobach HJC, van der Werken Chr. Ascites after pleuroperitoneal shunting. Cancer 1990; 66: 675-676.
74. Findlay IN. Cardiac complications of malignant disease. In: Kay SB, Rankin EM, eds, Medical Complications of Malignant Disease. London: Bailliere Tindall, 1988; 283-317.
75. Press OW, Livingston R. Management of malignant pleural effusion and tamponade. J Am Med Assoc 1987; 257: 1088-1092.
76. Mauch PM, Ullmann JE. Treatment of malignant pericardial effusions. In: De Vita VT, Hellman S, Rosenberg SA, eds, Cancer, Principles and Practice of Oncology. Philadelphia: JB Lippincott, 1985; 2141-2144.
77. Wilding G, Green HL, Longo DL, Urba WJ. Tumours of the heart and pericardium. Cancer Treat Rev 1988; 15: 165-181.
78. Kvale PA. Editorial. The cancer patient with dyspnea: unusual cause? Mayo Clin Proc 1991; 66: 215-218.
79. Anderlini P, Benjamin RS, Wong FC et al. Idarubicin cardiotoxicity: a retrospective study in acute myeloid leukemia and myelodysplasia. J Clin Oncol 1995; 13: 2827-2834.
80. Yano S, Shimada K. Vasospastic angina after chemotherapy by with carboplatin and etoposide in a patient with lung cancer. Jpn Circ J 1996; 60: 185-188.
81. Shan K, Lincoff AM, Young JB. Anthracycline-induced cardiotoxicity. Ann Intern Med 1996; 125: 47-58.
82. Lund MB, Kongerud J, Boe J et al. Cardiopulmonary sequelae after treatment for Hodgkin's disease: increased risk in females? Ann Oncol 1996; 7: 257-264.
83. Ford PA, Arbuck SG, Minniti C, Miller LL, DeMaria D, O'Dwyer PJ. Phase I trial etoposide, doxorubicina and cisplatin (EAP) in combination with GM-CSF. Eur J Cancer 1996; 32A: 631-635.
84. Dreicer R, Propert KJ, Roth BJ, Einhorn LH, Loehrer PJ. Vinblastine, isofosfamide, and gallium nitrate - an active new regimen in patients with advanced carcinoma of the urothelium. A phase II trial of the Eastern Cooperative Oncology Group. Cancer 1997; 79: 110-114.
85. Pizzo PA, Meyers J, Freifeld AG et al. Infections in the cancer patient. In: De Vita VT, Hellman S, Rosenberg SA, eds, Cancer, Principles and Practice of Oncology, fourth edition. Philadelphia: JB Lippincott Company 1993; 2: 2292-2337.
86. Bruera E, de Stoutz N, Velasco-Leiva A, Schoeller T, Hanson J. The effects of oxygen on the intensity of dyspnea in hypoxemic terminal cancer patients. Lancet 1993; 342: 13-14.
87. Bruera E, Schoeller T, MacEachern T. Symptomatic benefit of supplemental oxygen in hypoxemic patients with terminal cancer: the use of the N of 1 randomized controlled trial. J Pain Symptom Manag 1992; 7: 365-368.
88. Booth S, Kelly MJ, Cox NP, Adams L, Guz A. Does oxygen help dyspnea in patients with cancer? Am J Respir Crit Care Med 1996; 153: 1515-1518.
89. Restrick LJ, Davies SW, Noone L, Wedzicha JA. Ambulatory oxygen in chronic heart failure. Lancet 1992; 340: 1192-1193.
90. Moore DP, Weston AR, Hughes JMB, Oakley LM, Cleland JGF. Effects of increased inspired oxygen concentrations on exercise performance in chronic heart failure. Lancet 1992; 339: 850-853.
91. Swinburn CR, Mould H, Stone TN, Corris PA, Gibson GJ. Symptomatic benefit of supplemental oxygen in hypoxemic patients with chronic lung disease. Am Rev Respir Dis 1991; 143: 913-915.
92. Davidson AC, Leach R, George RJD, Geddes DM. Supplemental oxygen and exercise ability in chronic obstructive airways disease. Thorax 1988; 43: 965-971.
93. Woodcock AAS, Gross ER, Geddes DM. Oxygen relieves breathlessness in "pink puffers". Lancet 1981: 907-909.
94. Dean NC, Brown JK, Himelman RB, Doherty JJ, Gold WM, Stulbarg MS. Oxygen may improve dyspnea and endurance in patients with chronic obstructive pulmonary disease and only mild hypoxemia. Am Rev Respir Dis 1992; 146: 941-945.
95. Liss HP, Grant BJB. The effect of nasal flow on breathlessness in patients with chronic obstructive pulmonary disease. Am Rev Respir Dis 1988; 137: 1285-1288.
96. Doll DC, Weiss RB. Neoplasia and the erythron. J Clin Oncol 1985; 3: 429-446.
97. Case DC, Bukowski M, Carey RW et al. Recombinant human erythropoietin therapy for anemic patients on combination chemotherapy. J Natl Cancer 1993; 85: 801-806.
98. Henry DH, Abels RI. Recombinant human erythropoietin in the treatment of cancer and chemotherapy-induced anemia: results of double-blind and open-label follow-up studies. Semin Oncol 1994; 21: 21-28.
99. Del Mastro L, Venturini M, Lionetto R et al. Randomized Phase III trial evaluating the role of erythropoietin in the prevention of chemotherapy-induced anemia. J Clin Oncol 1997; 15: 2715-2721.
100. Ludwig H, Sundal E, Pecherstorfer M et al. Recombinant human erythropoietin for the correction of cancer associated anemia with a without concomitant cytotoxic chemotherapy. Cancer 1995; 76(11): 2319-2329.
101. Monti M, Castellani L, Berlusconi A, Cunietti E. Use of red blood cell transfusions in terminally ill cancer patients admitted to a Palliative Care Unit. J Pain Symptom Manag 1996; 12: 18-22.
102. Gleeson C, Spencer D. Blood transfusion and its benefits in palliative care. Palliative Medicine 1995; 9: 307-313.
103. Mozes B, Epstein M, Ben-Bassat I, Modan B, Halkin H. Evaluation of the appropriateness of blood and blood product transfusion using preset criteria. Transfusion 1989; 29: 473-476.
104. Elwood PC. Evluation of the clinical importance of anemia. Am J Clin Nutr 1973; 26: 958-964.
105. Viteri FE, Torun B. Anaemia and physical work capacity. Clin Haematol 1974; 3: 609-626.
106. Wachtel TJ, Mor V. The use of transfusion in terminal cancer patients. Hospice versus conventional care setting. Transfusion 1985; 25: 278-279.
107. Frew AJ, Holgate ST. Clinical pharmacology of asthma. Implications for treatment. Drugs 1993; 46: 847-862.
108. Ziment I. Pharmacologic therapy of obstructive airway disease. Clin Chest Med 1990; 11: 461-468.
109. Celli BR, Snider GL, Heffner J. Comprehensive outpatient management of COPD. Am J Respir Crit Care Med 1995; 152: S84-S120.
110. Thompson WH, Nielson CP, Carvalho P, Charan NB, Crowley JJ. Controlled trial of oral prednisone in outpatient with acute COPD exacerbation. Am J Respir Crit Care Med 1996; 154: 407-412.
111. Ferguson GT, Irvin CG, Cherniak RM. Effect of corticosteroids on respiratory muscle histopathology. Am Rev Respir Dis 1990; 142: 1047-1052.
112. Mahler DA, Matthay RA, Snyder PE, Well CK, Loke J. Sustained-release theophylline reduced dyspnea in non-reversible obstructive airway disease. Am Rev Respir Dis 1985; 131: 22-25.
113. Aubier M, De Troyer A, Sampson M, Macklem PT, Roussos C. Aminophylline improves diaphragmatic contractility. N Engl J Med 1981; 305: 249-252.
114. Wittmann TA, Kelsen SG. The effect of caffeine on diaphragmatic muscle force in normal hamsters. Am Rev Respir Dis 1982; 126: 499-504.
115. Murciano D, Aubier M, Lecocguic Y, Pariente R. Effects of theophylline on diaphragmatic strength and fatigue in patients with chronic obstructive pulmonary disease. N Engl J Med 1984; 311: 349-353.
116. Bruera E, MacEachern T, Ripamonti C, Hanson J. Subcutaneous morphine for dyspnea in cancer patients. Annals Int Med 1993; 119: 906-907.
117. Bruera E, Macmillan K, Pither J, MacDonald RN. The effects of morphine on the dyspnea of terminal cancer patients. J Pain Symptom Manag 1990; 5: 341-344.
118. Cohen MH, Johnston Anderson A, Krasnow SH et al. Continuous intravenous infusion of morphine for severe dyspnea. Southern Med J 1991; 84: 229-234.
119. Ventafridda V, Spoldi E, De Conno F. Control of dyspnea in advanced cancer patients. Letter to the Editor. Chest 1990; 98: 1544-1545.
120. Browning I, D'Alonzo GE, Tobin MJ. Effect of hydrocodone on dyspnea, respiratory drive and exercise performance in adult patients with cystic fibrosis. Am Rev Respir Dis 1988; 137: 305 (abstract).
121. Woodcock AA, Gross ER, Gellert A, Shah S, Johnson M, Geddes DM. Effects of dihydrocodeine, alcohol, and caffeine on breathlessness and exercise tolerance in patients with chronic obstructive lung disease and normal blood gases. N Engl J Med 1981; 305: 1611-1616.
122. Johnson MA, Woodcock AA, Geddes DM. Dihydrocodeine for breathlessness in "pink puffers". Br Med J 1983; 286: 675-677.
123. Robin ED, Burke CM. Risk-benefit analysis in chest medicine. Single-patient randomization clinical trial. Opiates for intractable dyspnea. Chest 1986; 90: 889-892.
124. Light RW, Muro JR, Sato RI, Stansburry DW, Fisher CE, Brown SE. Effects of oral morphine on breathlessness and exercise tolerance in patients with chronic obstructive pulmonary disease. Am Rev Respir Dis 1989; 139: 126-133.
125. Rice KL, Kronenberg RS, Hedemark LL, Niewoehner DE. Effects of chronic administration of codeine and promethazine on breathlessness and exercise tolerance in patients with chronic airflow obstruction. Br J Dis Chest 1987; 81: 287-292.
126. Eiser N, Denman WT, West C, Luce P. Oral diamorphine: lack of effect on dyspnoea and exercise tolerance in the "pink puffer" syndrome. Eur Respir J 1991; 4: 926-931.
127. Lane DJ. The clinical presentation of chest disease, In: Weatherall DJ, Ledingham JGG, Warrel DA, eds, The Oxford Textbook of Medicine. Oxford: Oxford University Press, 1983; 1539-1552.
128. Santiago V, Edelman NH. Opioids and breathing. J Appl Physiol 1985; 59: 1675-1685.
129. Florez J, Pazos A, Hurle MA, Mediavilla A. Focusing on the respiratory actions of opioids. Trends Pharmacol Sci 1983; 4: 470-472.
130. Hughes J. Peripheral opioid receptor mechanisms. Trends Pharmacol Sci 1981; 2: 21-24.
131. McQueen DS. Opioid peptide interactions with respiratory and circulatory systems. Br Med Bull 1983; 39: 77-82.
132. Johansson IGM, Grundstom N, Andersson RGG. Modulation of the airways excitatory neuronal pathways via alpha2 adrenoceptors and opioid receptors. Acta Physiol Scand 1988; 134 (Suppl. 575): 29.
133. Belvisi MG, Stretton CD, Barnes PJ. Modulation of cholinergic neurotransmission in guinea-pig airways by opioids. Br J Pharmacol 1990; 100: 131-137.
134. Bellofiore S, Di Maria GU, Privitera S, Sapienza S, Milic-Emili J, Mistretta A. Endogenous opioids modulate the increase in ventilatory output and dyspnea during severe acute broncho-constriction. Am Rev Respir Dis 1990; 142: 812-816.
135. Rogers DF, Barnes PG. Opioid inhibition of neurally mediated mucous secretion in human bronchi. Lancet 1989; 1: 930-931.
136. Davis CL, Lam W, Butcher M et al. Low systemic bioavailability of nebulized morphine: potential therapeutic role for the relieve of dyspnea (meeting abstract). Proc Ann Meet Am Soc Clin Oncol 1992; 11: A359.
137. Masood AR, Thomas SHL. Systemic absorption of nebulized morphine compared with oral morphine in healthy subjects. Br J Clin Pharmacol 1996; 41: 250-252.
138. Farncombe M, Chater S, Gillin A. The use of nebulized opioids for breathlessness: a chart review. Palliat Med 1994; 8: 306-312.
139. Davis CL, Penn K, A'Hern R, Daniels J, Slevin M. Single dose randomized controlled trial of nebulized morphine in patients with cancer related breathlessness (Abstract). Palliat Med 1996; 10: 64.
140. Young IH, Daviskas E, Keena VA. Effect of low dose nebulised morphine on exercise endurance in patients with chronic lung disease. Thorax 1989; 44: 387-390.
141. Weil JV, McCullough RE, Kline JS, Sodal IE. Diminished ventilatory response to hypoxia and hypercapnia after morphine in normal man. N Engl J Med 1975; 292: 1103-1106.
142. Bourke DL, Warley A. The steady state and rebreathing methods compared during morphine administration in humans. J Physiol 1989; 419: 509-517.
143. Santiago TV, Johnson J, Riley DJ, Edelman NH. Effects of morphine on ventilatory response to exercise. J Appl Physiol 1979; 47: 112-118.
144. Davis CL, Hodder C, Love S, Shah R, Slevin M, Wedzicha J. Effect of nebulised morphine and morphine-6-glucuronide on exercise endurance in patients with chronic obstructive pulmonary disease. Thorax 1994; 49: 393 (Abstract).
145. Masood AR, Reed JW, Thomas SHL. Lack of effect of inhaled morphine on exercise-induced breathlessness in chronic obstructive pulmonary disease. Thorax 1995; 50: 629-634.
146. Beauford W, Saylor TT, Stansbury DW, Avalos K, Light RW. Effects of nebulized morphine sulfate on the exercise tolerance on the ventilatory limited COPD patient. Chest 1993; 104: 175-178.
147. Craven J, Sutherland A. Buspirone for anxiety disorders in patients with severe lung disease. Lancet 1991; 338: 249.
148. Stark RD, Gambles SA, Lewis JA. Methods to assess breath-lessness in healthy subjects: a critical evaluation and application to analyse the acute effects of diazepam and promethazine on breathlessness induced by exercise or by exposure to raised levels of carbon dioxide. Clin Sci 1981; 61: 429-439.
149. O'Neill PA, Morton PB, Stark RD. Chlorpromazine - a specific effect on breathlessness? Br J Clin Pharmac 1985; 19: 793-797.
150. Woodcock AA, Gross ER, Geddes DM. Drug treatment of breathlessness: contrasting effects of diazepam and promethazine in pink puffers. Br Med J 1981; 283: 343-346.
151. Man GCW, Sproule BJ. Effect of alprazolam on exercise and dyspnea in patients with chronic obstructive pulmonary disease. Chest 1986; 90: 832-836.
152. Mitchell-Heggs P, Murphy K, Minty K et al. Diazepam in the treatment of dyspnoea in the "pink puffer" syndrome. Quart J Med New Series 1980; XLIX(193): 9-20.
153. Light RW, Stansbury DW, Webster JS. Effect of 30 mg of morphine alone or with promethazine or prochlorperazine on the exercise capacity of patients with COPD. Chest 1996; 109: 975-981.