Acute Asthma attacks: When breathing is part of the problem

Cells need balanced acid levels (measured by its pH) within and without the cell. Uncontrolled acidification of the cell's environment causes dysfunction and can lead to cell death (2, 4).

A lung's primary function is to get rid of CO2 from the blood. Interestingly, even though lung cells generate a lot of acid-containing molecules, the pH of exhaled breath in normal people is slightly alkaline (~ 7.65). In fact, exhaled breath of people with controlled asthma is in the same range. 

Unfortunately, people with acute exacerbations of asthma don't seem to be able to control the acid level of their exhaled air. During an acute exacerbation, asthmatics have been found to have 250 times more acid in the water of their exhaled breath than has been found in control subjects (pH 5.23  versus pH 7.65, respectively) (3).

Thus, during an acute asthma attack, alveolar and bronchial cells are bathed in moisture that is acidic. Some acidification is beneficial as it has antimicrobial effects. But too much acid is harmful (4).

Both inhaled and exhaled acidic breath cause problems.

In cities where the fog is acidic (for example with a pH of 5), the low pH increases the sensitivity of the lungs to the fog pollutants. Of course, the acid itself is irritating to the airways. For example, typical symptoms of an asthma attack (cough, wheezing, broncho-constriction, dyspnea) are induced by chlorine gas inhalation. The symptoms will immediately disappear with the use of a nebulized alkaline solution (for example, sodium bicarbonate) (2).

Chronic gastro-esophageal acid reflux can also worsen asthma. Micro-aspiration of minute amounts of acid into the trachea (experimentally, just 0.05 ml or 1% of a teaspoon) can cause 4 x worsening of airway resistance (2).

The same symptoms that take place when the moisture of inhaled breath is highly acidic ensue when the pH of exhaled breath is in the low 5's (1, 2).

The acidic water in inhaled or exhaled breath has a lot of protons. These positively charged ions cause problems through: 

• Causing death of cells, particularly eosinophils
• Releasing inflammatory proteins from sensory nerves
• Inducing the formation of reactive oxygen species, nitrous oxide, and peroxides; all are strong cellular irritants
• Activating muscle fibers to cause broncho-constriction
• stimulating thick mucus production causing mucus plugging
• decreasing cilia beating

In fact, as noted above, all the symptoms of an acute asthma attack can be reproduced by breathing in acidified air, and then abated when a nebulized alkaline solution is administered (1, 2, 3).

People without asthma and people with controlled asthma clearly have normal (or alkaline) levels of pH in their exhaled breath  (2, 3). Why is the pH of exhaled air during an acute asthma attack so low?

Lung cells have several mechanisms to ensure that the pH of their exhaled air is within normal limits. One of the major ways of doing that is having the cells take up glutamine (a non-essential amino acid from the blood). Interestingly, glutamine is the most abundant amino acid in the body (5).

To prevent damage to the lung from the acid, cells take up glutamine from the blood and break it down into glutamate and ammonia (NH3) (1). The ammonia is secreted into the airway lumen neutralizing the excess acid. Normal airway cells are able to respond to increased acid in the milieu by revving up ammonia production.

Unfortunately, during an acute asthma attack, the lung cells seem to have a problem revving up the breakdown of glutamine in their cells. This results in a lower level of ammonia in their breath. Thus, the exhaled moisture in the breath stays acidic.  

Many factors play a role, but the key seems to be an inability to break down glutamine to produce ammonia through the use of an enzyme called glutaminase. Several factors block glutaminase from working properly. 

Stress, inflammatory proteins, and viruses.  When glutaminase is not working properly, the pH in the exhaled air becomes more acidic. This causes the cascade of effects noted above. In particular, destruction of eosinophils and stimulating sensory nerve endings is a sure way to release increasing amounts of inflammatory proteins (cytokines). This creates a snowball effect. The cytokines further suppress the enzymatic breakdown of glutamine (1). This, of course, worsens the acid levels in the airways because there is less production of ammonia. The worsened acid levels generate more inflammation and more noxious radicals, perpetuating the vicious cycle.

Corticosteroids help normalize the pH in asthma. A study of hospitalized patients receiving steroids showed that their exhaled air pH improved from ~5.23 --> 7.4 after 48 hours (3).

Steroids do several things to break an acute asthma attack (1, 6, 7): 

1. They suppress release of cytokines from inflammatory cells

2. They enhance the production of glutaminase

3. They reduce eosinophil counts in the sputum

4. They reduce airway swelling

5. They up-regulate the beta2-adrenergic receptors (allowing drugs like Salmeterol to improve their efficacy in promoting broncho-dilatation)

Basically, steroids work to reduce the inflammatory component of asthma. In so doing, the lung cells are better able to generate glutaminase. This leads to more ammonia  and a normalization of pH in the exhaled breath.

There is marked dysregulation of the components in exhaled breath in an acute asthma attack. The breath is more acidic, has higher levels of noxious molecules,  has an exaggerated inflammatory cascade as well as destruction of eosinophils, and has depressed ammonia levels.

All together, it is no wonder that an acute asthmatic attack is characterized by significant symptoms and distress. The change from a relatively normal pH in exhaled air to a very acidic one wreaks havoc.