Cancer Treatment Reviews
Volume 24, Issue 1 , Pages 69-80 , February 1998

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

  • C. Ripamonti

      Affiliations

    • Corresponding Author InformationCorrespondence: C. Ripamonti, Adjunct Clinical Professor of Oncology, Alberta University, Edmonton, Canada; Pain Therapy & Palliative Care Division, National Cancer Institute, via Venezian, 1, 20133 Milano, Italy.
    • Pain Therapy and Palliative Care Division, National Cancer Institute, Milan, Italy
  • ,
  • F. Fulfaro

      Affiliations

    • Pain Therapy and Palliative Care Division, National Cancer Institute, Milan, Italy
  • ,
  • E. Bruera

      Affiliations

    • Division of Palliative Care Medicine, University of Alberta, Palliative Care Program, Grey Nuns Community Health Centre, Edmonton, Canada

References 

  1. Baines M. Control of other symptoms. In:  Saunders CM editors. 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. In: London: Churchill Livingstone; 1986;p. 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. In: second edition. London: Edward Arnold; 1984;p. 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. In: Etiology, Resource Utilization, and Survival. fourth edition. Cancer. 78:1996;p. 1314–1319 Implications in a managed care world
  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,  GWC Hanks,  MacDonald N editor. Oxford Textbook of Palliative Medicine. Oxford: Oxford University Press; 1993;p. 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 anorexia. In:  Doyle D,  GWC Hanks,  MacDonald N editor. Oxford Textbook of Palliative Medicine. Oxford: Oxford Medical Publications; 1993;p. 330–337
  22. Palange P, Forte S, Felli A, Galassetti P, Serra P, Carlone S. National state and exercise tolerance in patients with COPD. In: fourth edition. Chest. 107:1995;p. 1206–1212
  23. Kongragunta VR, Druz WS, Sharp JT. Dyspnea and diaphragmatic fatigue in patients with chronic obstructive pulmonary disease. Nutritional state and exercise tolerance in patients with COPD. Chest. 1995;107:1206–1212
  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, AJS Coats. 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 . Inoperable non-small cell lung cancer (NSCLC): a Medical Research Council randomised trial of palliative radiotherapy with two fractions or ten fractions. by its Lung Cancer Working Party. 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 editor. Medical Complications of Malignant Disease. London: Bailliere Tindall; 1988;p. 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;16/2:16; (Suppl.)
  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. In: A prospective, randomized comparison of two fractionation schedules. fourth edition. Chest. 107:1995;p. 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-Zwehl 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. In: fourth edition. Seminars Respir Med. 9:1987;p. 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. In: A review of 360 cases. fourth edition. Chest. 110:1996;p. 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. In: The complementary role talc pleurodesis and pleuroperitoneal shunting. fourth edition. Cancer. 75:1995;p. 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 editor. Medical Complications of Malignant Disease. London: Bailliere Tindall; 1988;p. 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 editor. Cancer, Principles and Practice of Oncology. Philadelphia: JB Lippincott; 1985;p. 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. The cancer patient with dyspnea: unusual cause?. Editorial 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. In: A phase II trial of the Eastern Cooperative Oncology Group. fourth edition. Cancer. 79:1997;p. 110–114
  85. Pizzo PA, Meyers J, Freifeld AG, et al.  Infections in the cancer patient. In: fourth edition.  De Vita VT,  Hellman S,  Rosenberg SA editor. Cancer, Principles and Practice of Oncology. 2:Philadelphia: JB Lippincott Company; 1993;p. 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. In: Hospice versus conventional care setting. Transfusion. 25:1985;p. 278–279
  107. Frew AJ, Holgate ST. Clinical pharmacology of asthma. In: Implications for treatment. Drugs. 46:1993;p. 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 nonreversible 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. In: Single-patient randomization clinical trial. Chest. 90:1986;p. 889–892 Opiates for intractable dyspnea
  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,  JGG Ledingham,  Warrel DA editor. The Oxford Textbook of Medicine. Oxford: Oxford University Press; 1983;p. 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 bronchoconstriction. 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) In: Proc Ann Meet Am Soc Clin Oncol. 11:1992;p. 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 breathlessness 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

PII: S0305-7372(98)90072-X

Cancer Treatment Reviews
Volume 24, Issue 1 , Pages 69-80 , February 1998