Cancer: the more they breathe, the sooner they die

Respiratory rate (breathing frequency) of cancer patients is an independent predictor of their survival (Chiang et al, 2009; de Miguel Sanchez et al, 2006; Groeger et al, 1998). Those, who breathe more frequently, have poor prognosis.

Last year the Journal of Applied Physiology published a study done in the Department of Medicine, Queen's University (Kingston, Ontario, Canada). It was found that 40 patients with cancer breathed about 12 litres of air per minute at rest (Travers et al, 2008), instead of 6 l/min, which is the medical norm. Breathing frequency of these cancer patients was 20 breaths per minute (the norm is only 12 breaths per min at rest).

What else is known about respiratory parameters of cancer patients at rest? Just a few titles and some quotes are sufficient to realize what is going on with breathing of terminally ill cancer patients.
---------
Reuben DB, Mor V, Dyspnea in terminally ill cancer patients, Chest 1986; 89: p. 234–236.

Dudgeon DJ, Lertzman M, Dyspnea in the advanced cancer patient, J Pain Symptom Management 1998 Oct; 16(4): p.212-219.

Coyne PJ, Viswanathan R, Smith TJ, Nebulized fentanyl citrate improves patients' perception of breathing, respiratory rate, and oxygen saturation in dyspnea, J Pain Symptom Manage 2002; 23: p. 157–160.
“Dyspnea is exceedingly common. Ruben and Mor found that 70% of 1500 cancer patients suffered dyspnea during their last four weeks of life.”

Bruera E, MacEachern T, Ripamonti C, Hanson J, Subcutaneous morphine for dyspnea in cancer patients, Ann Intern Med. 1993; 119: p. 906-907.

Travers J, Dudgeon DJ, Amjadi K, McBride I, Dillon K, Laveneziana P, Ofir D, Webb KA, O'Donnell DE, Mechanisms of exertional dyspnea in patients with cancer, J Appl Physiol 2008 Jan; 104(1): p.57-66.

Reuben DB, Mor V, How much of a problem is dyspnoea in advanced cancer? Palliat Med 1991; 5: 20–26.
“Introduction. Although a number of articles on dyspnoea in terminal cancer have appeared, [1-8] in terms of publications, this symptom remains a poor relation when compared with pain. Anyone, however, who has looked after dying people will be aware that dyspnoea is a common and often distressing symptom, particularly if severe. In such cases patients may feel that they may die from lack of air - even pain does not have this connotation. This is demonstrated in Comroe’s definition of dyspnoea as ’difficult, laboured, uncomfortable breathing; it is an unpleasant type of breathing, though it is not painful in the usual sense of the word. It is subjective, and, like pain, it involves both perception of the sensation by the patient and his reaction to the sensation.”

Ripamonti C. Management of dyspnea in advanced cancer patients. Support Care Cancer. 1999; 7: p. 233-243.
"Dyspnea has been defined as an “uncomfortable awareness of breathing”"
(End of quotes.)
---------
But normal breathing is invisible, inaudible, and imperceptible, because it is tiny in tidal volume and very slow in frequency. Moreover, according to physiological laws, normal breathing provides humans with superior tissue oxygenation. Hence, healthy people do not feel their breath at all. These cancer patients breathe at least 3-4 times more than the norm in order to be uncomfortably aware about their breathing.

What is the typical breathing frequency in cancer patients with dyspnea? US doctors from the Massey Cancer Center of Virginia Commonwealth University (Richmond, Virginia, USA) tested 35 cancer patients (of the 35 patients, 34 were using oxygen) and found that their average respiratory rate was 28.4 breaths/minute (Coyne et al, 2002). A 1993 study done by Italian and Canadian doctors revealed the respiratory rate of 23 breathes per minute (Bruera et al, 1993) in a group of terminal cancer patients with dispnea. A Swiss study conducted in the Division of Palliative Care, University Hospital, Lausanne found 26 breaths per minute in elderly patients with advanced cancer (Mazzocato et al, 1999).

In 2 recent German studies (Department of Anaesthesiology, Intensive Care Medicine, Bonn), average breathing rates in 2 groups of cancer patients were stunning 42 and 39 breaths per minute (Clemens et al, 2007; Clemens et al, 2008). It is indeed physiologically shocking numbers since the normal respiratory frequency is only 12 breaths per minute. (Old medical textbooks suggest 8-10 breaths per minute as normal.)

What are the known effects of overbreathing or breathing too much/too? When we breathe more air at rest, our arterial blood cannot get more oxygen since haemoglobin O2 saturation is about 98% for miniscule normal breathing. Hence, the immediate physiological effect is arterial CO2 deficiency. Since CO2 is a vasodilator, arteries and arterioles immediately constrict and we get less blood supply (reduced perfusion) in all vital organs. This effect was confirmed by dozens of physiological studies. The next effect makes hypoxia even worse since oxygen release in tissues is governed by the Bohr law (the higher the CO2 in tissues, the more O2 is released). Hence, overbreathing leads to reduced oxygenation of the brain, kidneys, liver, pancreas, stomach, and all other organs. But cancer patients breathe so heavy that doctors can see and comment on it! It is not a surprise then that cancer patients have very low body oxygenation.

What are the effects of reduced tissue oxygenation on tumors? Here are again just a few titles:
-----
Ryan H, Lo J, Johnson RS, The hypoxia inducible factor-1 gene is required for embryogenesis and solid tumor formation, EMBO J 1998, 17: p. 3005-3015.

Ryan HE, Poloni M, McNulty W, Elson D, Gassmann M, Arbeit JM, Johnson RS, Hypoxia-inducible factor-1 is a positive factor in solid tumor growth, Cancer Res, August 1, 2000; 60(15): p. 4010 - 4015.

Harris AL, Hypoxia: a key regulatory factor in tumour growth, Nat Rev Cancer 2002 Jan; 2(1): p. 38-47.

Evans SM & Koch CJ, Prognostic significance of tumor oxygenation in humans, Cancer Lett 2003 May 30; 195(1): p. 1-16.
------
Hence, cancer prevention should be based on learning how to breathe less. The goal of the Buteyko breathing method, developed in the 1960s by leading Soviet physiologist Konstantin Buteyko, is to normalize one’s respiratory parameters.

(Other) references

Chiang JK, Lai NS, Wang MH, Chen SC, Kao YH, A proposed prognostic 7-day survival formula for patients with terminal cancer, BMC Public Health. 2009 Sep 29; 9(1): p.365.

Clemens KE, Klaschik E, Effect of hydromorphone on ventilation in palliative care patients with dyspnea, Support Care Cancer. 2008 Jan; 16(1): p.93-99. Epub 2007 Oct 11.

Clemens KE, Klaschik E, Symptomatic therapy of dyspnea with strong opioids and its effect on ventilation in palliative care patients, J Pain Symptom Management 2007 Apr; 33(4): p.473-481.

de Miguel Sanchez C, Elustondo SG, Estirado A, Sanchez FV, de la Rasilla Cooper CG, Romero AL, Otero A, Olmos LG, Palliative Performance Status, Heart Rate and Respiratory Rate as Predictive Factors of Survival Time in Terminally Ill Cancer Patients, J Pain Symptom Managem. June 2006; 31(6), p. 485-492.

Groeger JS, Lemeshow S, Price K, Nierman DM, White P Jr, Klar J, Granovsky S, Horak D, Kish SK, Multicenter outcome study of cancer patients admitted to the intensive care unit: a probability of mortality model, J Clin Oncol. 1998 Feb; 16(2): p.761-770.

Mazzocato C, Buclin T, Rapin CH, The effects of morphine on dyspnea and ventilatory function in elderly patients with advanced cancer: a randomized double-blind controlled trial, Annals of Oncology. 1999 Dec; 10(12): p.1511-1514.
Division of Palliative Care, University Hospital, Lausanne, Switzerland. Tweet