Bronchodilator and Best Bronchodilators: CO2 and NO

Woman coughing A bronchodilator is a substance that relaxes smooth muscles or airways and causes dilation of bronchi and bronchioles. Bronchodilators reduce resistance in the respiratory tract and improve airflow to the alveoli of the lungs. Bronchodilators are divided on endogenous bronchodilators (originating naturally within the human body), or they may be medical drugs that are used for treatment of breathing problems in people with COPD, asthma, cystic fibrosis and other respiratory conditions. In order to find best bronchodilators, consider the cause of bronchospasm in these people.

CO2: the chief bronchodilator

Minute ventilation rates (chronic diseases)

Condition	Minute ventilation	Number of people	All references or click below for abstracts
Normal breathing	6 l/min	-	Medical textbooks
Healthy Subjects	6-7 l/min	>400	Results of 14 studies
COPD	14 (±2) l/min	12	Palange et al, 2001
COPD	12 (±2) l/min	10	Sinderby et al, 2001
COPD	14 l/min	3	Stulbarg et al, 2001
Asthma	13 (±2) l/min	16	Chalupa et al, 2004
Asthma	15 l/min	8	Johnson et al, 1995
Asthma	14 (±6) l/min	39	Bowler et al, 1998
Asthma	13 (±4) l/min	17	Kassabian et al, 1982
Asthma	12 l/min	101	McFadden & Lyons, 1968
Cystic fibrosis	15 L/min	15	Fauroux et al, 2006
Cystic fibrosis	10 L/min	11	Browning et al, 1990
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
Cystic fibrosis*	13 (±2) l/min	10	Bell et al, 1996
Cystic fibrosis	11-14 l/min	6	Tepper et al, 1983

CO2 is a powerful natural bronchodilator

We see that those sick people who suffer from bronchoconstriction have heavy breathing or they breathe too much air. Therefore, they have too low levels of CO2 in airways. What are the effects?

Carbon dioxide is probably the most powerful among all bronchodilators since it is the most potent relaxant of smooth muscles and vasodilator (see links to studies below). Hence, normal breathing parameters include 40 mm Hg CO2 pressure in the alveoli of the lungs to keep these air passages open wide (see on the left) due to bronchodilation, while hypocapnia (CO2 deficiency) in airways leads to bronchoconstriction or bronchospasm.

"Agents that tend to dilate airways include increased CO2 (hypoventilation or inspired CO2)..." Normal C. Straub, Sr., Professor Emeritus, University of California at San Francisco School of Medicine; Textbook on physiology: Straub NC, Section V, The Respiratory System, in Physiology, eds. RM Berne & MN Levy, 4-th edition, Mosby, St. Louis, 1998.

Carbon dioxide is listed in this medical textbook as Number 1 bronchodilator. When the CO2 level in the lungs is low, the bronchi constrict (the right picture below: bronchoconstriction), causing wheezing, feelings of breathlessness, and difficulty breathing. These effects are particularly known to asthmatics, patients with bronchitis, emphysema, and COPD. Hence, bronchodilation is another carbon dioxide effect that is crucial for normal health. Note that since ordinary people breathe about 2 times more air than the medical norm (visit Hyperventilation: Present in Over 90% of Normal People: 24 medical publications), bronchoconstriction is a normal effect present in most people these days. It is especially damaging in asthma and COPD due to excessive mucus production and inflammation.

In 1968, in his research article The mechanism of bronchoconstriction due to hypocapnia in man (“hypocapnia” means abnormally low CO2 concentrations) Sterling explained that carbon dioxide deficiency leads to an excited state of the cholinergic nerve (Sterling, 1968). Since this nerve is responsible for the tone or relaxation of the smooth muscles in bronchi, its excited state prevents bronchodilation. CO2 is a powerful natural bronchodilator

Dr. Herxheimer was probably the first scientist who proposed that CO2 causes bronchodilation, while low CO2 is the cause of bronchial asthma. His articles Hyperventilation asthma and The late bronchial reaction in induced asthma were published in 1946 and 1952 (see references below).

Soviet Doctor K Buteyko independently proposed this link in the 1950’s (his first publication was in 1964) when he discovered the central roles of CO2 in bronchodilation and overbreathing in the development and degree of COPD and asthma (Buteyko, 1964).

He and his colleagues also found that asthma patients got immediate relief from their asthma attack symptoms, if they practiced reduced breathing exercise which is the main exercise of the Buteyko breathing therapy. Indeed, as soon as a person with bronchoconstriction starts to breathe less, their carbon dioxide level in the alveoli rises, and this leads to bronchodilation. Read more about this Emergency Procedure (How to stop an asthma attack using a simple breathing exercise).

Correction of causes of hyperventilation is also necessary in order to permanently normalize one's breathing and alveolar carbon dioxide levels to ensure natural bronchodilation. This is the most logical and natural treatment and relief from asthma.

Hence, hypocapnic bronchoconstriction or bronchospasm is the law of physiology, while CO2 is a powerful natural bronchodilator.

Nasal nitric oxide is bronchodilator if you are a nose breather

Nitric oxide is also a bronchodilator (see the study done in the Harvard Medical School Bronchodilator Action of Inhaled Nitric Oxide in Guinea Pigs). NO (nitric oxide) is another substance that is produced in different parts of the human body including sinus passages. Mouth breathing prevents absorption of nasal nitric oxide and causes additional problems due to spread of pathogens since nitric oxide has powerful antiviral and anti-bacterial properties.

More information about asthma, its symptoms, mechanism, and treatment options

References: CO2 Effects Web Pages
Vasodilation: CO2 expands arteries and arterioles facilitating perfusion (or blood supply) to all vital organs
The Bohr effect How and why oxygen is released by red blood cells in tissues
Cell Oxygen Levels and oxygen transport are controlled by alveolar CO2 and breathing
Oxygen Transport depends on breathing and these two effects (Vasoconstriction-Vasodilation and the Bohr effect) are parts of two diagrams that summarize influences of hypocapnia (low CO2 content in the blood and cells) on circulation and O2 delivery
Free Radical Generation takes place due to anaerobic cell respiration caused by cell hypoxia. Hence, antioxidant defenses of the human body are also regulated by CO2 and breathing
Inflammatory Response is controlled by breathing since hypoxia leads to or intensifies chronic inflammation through over-expression of the hypoxia-inducible factor 1, while normal breathing reduces these processes
Nerve stabilization takes place due to calmative or sedative effects of carbon dioxide in neurons or nerve cells
Muscle relaxation or relaxation of muscle cells is normal at high CO2, while hypocapnia causes muscular tension, poor posture and, sometimes, aggression and violence
Brochodilation - dilation of airways (bronchi and bronchioles) by carbon dioxide, and their constriction due to hypocapnia
CO2: Best Natural Cough Suppressant and "home remedy" since it calms urge-to-cough nerve receptors located in the tracheobronchial tree and larynx
Blood pH regulation and regulation of other bodily fluids
CO2: Lung Damage Healer: Elevated carbon dioxide prevents injury and promotes healing of lung tissues
CO2: Skin and Tissue Healer
Synthesis of Glutamine in the Brain, CO2 fixation, and other chemical reactions
CO2 myth "CO2 is a toxic waste gas" myth
Breathing control How is our breathing regulated? Why hypocapnia makes breathing uneven and erratic?

Reference Web Pages: Breathing norms, Medical Graphs and Tables about Breathing Rates (Minute Ventilation) and Body Oxygen in Healthy, Normal and Sick People
Breathing norms Parameters, graph, and description of the normal breathing pattern
6 breathing myths 6 myths about breathing and body oxygenation (prevalence: over 90%)
Hyperventilation Definitions of hyperventilation: their advantages and weak points
Hyperventilation Syndrome in the Sick. Table 1. Western scientific evidence about prevalence of CHV (chronic hyperventilation) in patients with various chronic conditions (34 medical studies)
Normal Minute Ventilation in Healthy Subjects: Easy and Light Breathing (14 Studies)
Hyperventilation Prevalence Present in Over 90% of Normal People (24 medical publications)
HV and hypoxia How and why deep breathing reduces oxygenation of cells and tissues of all vital organs
Body oxygen test How to measure your own breathing and body oxygenation (a simple DIY test)
Body oxygen in healthy Table 4. CP (body oxygen level) in healthy people (27 medical studies)
Body oxygen in sick Table 5. CP (body oxygen level) in sick people (14 medical studies)
Buteyko Table of Health Zones with clinical description of most common zones
Morning HV Morning hyperventilation effect or how and why critically ill people are most likely to die during early morning hours

References

Buteyko KP, An Instruction for VBN Therapy for Bronchial Asthma, Angina Pectoris, High Blood Pressure and Obliterating Endarteritis: Preprint. - Novosibirsk, 1964.

Herxheimer H, Hyperventilation asthma, Lancet 1946, 6385: p. 83-87.

Herxheimer H, The late bronchial reaction in induced asthma, Int Arch Allergy Appl Immunol 1952; 3: p. 323-328.

Sterling GM, The mechanism of bronchoconstriction due to hypocapnia in man, Clin Sci 1968 Apr; 34(2): 277-285.

Straub NC, Section V, The Respiratory System, in Physiology, eds. RM Berne & MN Levy, 4-th edition, Mosby, St. Louis, 1998.

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* Illustrations by Victor Lunn-Rockliffe