Three groups of biomedical researchers recently discovered that CFTR, cystic fibrosis mutation gene, is triggered by low levels of oxygen in body cells. Exercise with oral respiration causes reduction in arterial CO2 and nasal NO absorption making exercise almost useless and even dangerous since it can lead to reduced body oxygen levels. This problems are solved if all exercise workouts are done with nosy breathing only (inhalations and exhalations).
Three groups of biomedical researchers recently discovered that CFTR (cystic fibrosis transmembrane conductance regulator), the cystic fibrosis mutation gene, is triggered by low levels of oxygen in body cells. The key chemical that controls CFTR expression is HIF-1 (hypoxia-inducible factor-1 representing oxygen availability in body cells). These studies were conducted in the Department of Medicine at the University of Alabama in Birmingham, USA (Bebök et al, 2001); Department of Genetics and Fleming James Cystic Fibrosis Research Center at University of Alabama at Birmingham in Alabama, USA (Guimbellot et al, 2008), and Department of Gastroenterology, Hepatology, and Endocrinology at the Hanover Medical High School in Germany (Zheng et al, 2009).
Hypoxia controls CFTR and ions’ transport
According to these studies, HIF-1 regulates, in dose-dependent manner, transport of ions (such as Na+, Cl-, and H2O) across epithelial membranes and abnormalities in this transport. Bear in mind that CFTR expression leads to increased viscosity of mucus causing inability of mucosal secretions to suppress pathogens. That results in frequent infections in airways, GI problems and development of other symptoms of cystic fibrosis.
Exercise and body oxygen levels
How could it relate to physical exercise and breathing routes during exercise? As a first step, one needs to realize that oxygen transport to body cells depends on our automatic breathing patterns. and our breathing is mainly regulated by CO2 levels in the arterial blood.
We have normal levels of oxygen in tissues, when our breathing parameters are normal. When we breathe more that the medical norm, we get less oxygen in body cells. The effect is due to reduced CO2 that causes hypocapnic vasoconstriction and the suppressed Bohr effect. (When people develop ventilation-perfusion mismatch due to problems in the lungs, low alveolar CO2 prevents healing of lung tissue and modulates bronchospasm and worsened lung function results. )
What about breathing parameters in cystic fibrosis?
|Normal breathing||6 L/min||-||Medical textbooks|
|Healthy subjects||6-7 L/min||>400||Results of 14 studies|
|Cystic fibrosis||15 L/min||15||Fauroux et al, 2006|
|Cystic fibrosis*||13 (±2) L/min||10||Bell et al, 1996|
|Cystic fibrosis||10 L/min||11||Browning et al, 1990|
|Cystic fibrosis||11-14 L/min||6||Tepper et al, 1983|
|Cystic fibrosis*||10 L/min||10||Ward et al, 1999|
|CF and diabetes*||10 L/min||7||Ward et al, 1999|
|Cystic fibrosis||16 L/min||7||Dodd et al, 2006|
|Cystic fibrosis||18 L/min||9||McKone et al, 2005|
This table proves that people with cystic fibrosis have increased minute ventilation at rest (chronic hyperventilation) that is the cause of their tissue hypoxia and CFTR expression.
Mouth breathing vs nose breathing exercise
Finally, we can consider effects of exercise. When we exercise with oral respiration, we generally have less CO2 in the arterial blood. As a result, this exercise is causes reduction in arterial CO2. Low CO2 immediately reduces oxygen transport to cells and also causes increased heart rate during exercise. The breathing center adapts to low CO2 and later, after exercise, breathing remains heavy (deep and fast) promoting symptoms of cystic fibrosis.
In addition, mouth breathing prevents nasal NO (nitric oxide) absorption making exercise almost useless and even dangerous since NO is dangerously low in lungs of people with cystic fibrosis. (Nasal NO is generated in sinuses, and it prevents infections in airways due to its powerful antimicrobial and antiviral properties.)
What are the benefits of nose breathing during physical exercise for cystic fibrosis? Nasal breathing increases arterial CO2 levels during exercise. This causes adaptation of the respiratory center to higher CO2 values. Hence, such exercise improves oxygen content in body cells. In addition, nasal respiration delivers nasal NO to other parts of airways.
Gradual transition to nose breathing exercise
However, for people with heavy breathing at rest, intensive exercise with nose breathing is impossible. They need to slow down their intensity to accommodate strictly nasal breathing. Later, day after day it is possible to increase intensity, but do it very gradually. When the results of the body oxygen test are above 20 seconds, most people are able to exercise with nose breathing in and out.
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Bebök Z, Tousson A, Schwiebert LM, Venglarik CJ, Improved oxygenation promotes CFTR maturation and trafficking in MDCK monolayers, Am J Physiol Cell Physiol. 2001 Jan;280(1):C135-45.
Guimbellot JS, Fortenberry JA, Siegal GP, Moore B, Wen H, Venglarik C, Chen YF, Oparil S, Sorscher EJ, Hong JS, Role of oxygen availability in CFTR expression and function, Am J Respir Cell Mol Biol. 2008 Nov;39(5):514-21
Zheng W, Kuhlicke J, Jäckel K, Eltzschig HK, Singh A, Sjöblom M, Riederer B, Weinhold C, Seidler U, Colgan SP, Karhausen J, Hypoxia inducible factor-1 (HIF-1)-mediated repression of cystic fibrosis transmembrane conductance regulator (CFTR) in the intestinal epithelium, FASEB J. 2009 Jan;23(1):204-13.
References for the Table
Fauroux B, Nicot F, Boelle PY, Boulé M, Clément A, Lofaso F, Bonora M, Mechanical limitation during CO2 rebreathing in young patients with cystic fibrosis, Respir Physiol Neurobiol. 2006 Oct 27;153(3):217-25.
Bell SC, Saunders MJ, Elborn JS, Shale DJ, Resting energy expenditure and oxygen cost of breathing in patients with cystic fibrosis, Thorax 1996 Feb; 51(2): 126-131.
Browning IB, D’Alonzo GE, Tobin MJ, Importance of respiratory rate as an indicator of respiratory dysfunction in patients with cystic fibrosis, Chest. 1990 Jun;97(6):1317-21.
Tepper RS, Skatrud B, Dempsey JA, Ventilation and oxygenation changes during sleep in cystic fibrosis, Chest 1983; 84; p. 388-393.
Ward SA, Tomezsko JL, Holsclaw DS, Paolone AM, Energy expenditure and substrate utilization in adults with cystic fibrosis and diabetes mellitus, Am J Clin Nutr. 1999 May;69(5):913-9.
Dodd JD, Barry SC, Barry RB, Gallagher CG, Skehan SJ, Masterson JB, Thin-section CT in patients with cystic fibrosis: correlation with peak exercise capacity and body mass index, Radiology. 2006 Jul;240(1):236-45.
McKone EF, Barry SC, Fitzgerald MX, Gallagher CG, Role of arterial hypoxemia and pulmonary mechanics in exercise limitation in adults with cystic fibrosis, J Appl Physiol. 2005 Sep;99(3):1012-8. Epub 2005 Apr 28.