1851-1913: The history of asthma sputum

Okay, so few of us want to talk about it.  If you mention it at the dinner table your mother, or grandmother, may send you to your room.  Yet people taking care of the sick people over the years, especially sick people with breathing trouble — i.e. asthmatics, had no choice but to pay attention to it.  Some even devised speculations and theories explaining its appearance.

Originally all shortness of breath, and all causes of excessive sputum production, were defined as asthma.  And since sputum was so often associated with such dyspnea, ancient physicians may have surmised the sputum was caused by evil spirits, and expectoration of sputum was associated with the expectoration of evil spirits.  Such speculation most likely satiated ancient sufferers and their families.

Actually, such speculations may have satiated sufferers of asthma and their families even through the middle of the 19th century, as most people continued to be ignorant about such things.  And when your physician told you one thing, you tended to believe it.  Ditto can be said of wive’s tales: when your mother tells you something, you tend to believe it.

As time went by physicians and scientists came up with other more carefully thought out theories about asthma sputum, some speculating it was the cause, others the effect.  Although, in the end, most of these theories weren’t any better than ancient speculation.

In a report on the experiments of  Charles J.B. Williams (the man who proved the spasmotic theory of asthma), J. Lotvall notes that “the main theory about asthma in the 18th century was that it was a disease of excess mucus, and in the 19th century it was recognized that airflow obstruction may also be due to airway smooth muscle contraction.”  So we see that was very common to speculate asthma was caused in some way by the sputum.  (1)

A good example here is the theory postulated by  Dr. Robert Bree in 1798.  He guessed that sputum was the main component of asthma.  He believed some irritating or peccant matter entered the lungs, and it was this matter that triggered the asthmatic response.  The attack didn’t end until the irritating matter was expectorated in a wad of sputum.  (2)

Bree gained a lot of respect by the medical community for his theory, although during the 1850s Dr. Henry Hyde Salter would reject this theory and bring the spasmotic and nervous theories to the forefront of the medical community.  Regardless, many physicians continued believe sputum had a significant role in asthma.

In 1851 Dr. Beau and his assistant Cozart insisted asthma was caused by increased sputum in the lungs that was capable of blocking the air passages with mucus plugs.  In 1878, J.B. Berkart wrote about a Dr. Beau who worked with his pupil Beau to come up with his observation that asthma attacks end with a spit of sputum.  They believed asthma was caused by increased sputum and resolved when sputum breaks up with a coughing fit. (3, page 31)

Berkart explained that Beau basically believed asthma was a disease of chronic catarrh, or inflammation of the air passages.  He believed this sputum was capable of obstructing the air passages, and this is what caused the symptoms of asthma, “as well as the sonorous and sibilant rhonchi — their ‘rales vibrants.”  (3, page 31)

Thus, Berkart wrote, “with the displacement of the mucous plug into the larger bronchus, or on its expulsion by means of a fit of coughing, the dyspnea ceases, and with it also the rales disappear.  This form of bronchitis is, in their (Beau and Crozants) opinion, due partly to an idiosyncrasy of the patient, partly to exciting causes, which greatly vary in different individuals.”

Tiny crystals were first observed in sputum in 1851 by Jean Martin Charcot, but it wasn’t until 1872 that the crystals were linked to asthma by Ernst Victor von Leyden. So history has given credit for this discovery to both men by calling the crystals Charcot-Leyden crystals.

Leyden, whose asthma theories were similar to Bree’s theory, believed Charcot-Leyden crystals caused asthma by irritating “the peripheral extremities of the vagus nerve, and produce reflex spasm of the bronchial muscle.”   The asthma attack, therefore, ended when these were coughed up.  (4, page 14-15

In 1878 Dr. John Charles Thorowgood explains that subsequent experiments disproved Leyden’s theory, and this was further disproved when Charcot-Leyden crystals were also found in the sputum produced from patients with “ordinary catarrh and croupus bronchitis.” (4, page 15)

Of course Thorowgood also describes that “the asthmatic patient while in a fit presents abundance of symptoms distressing enough to endure or to witness; and yet, when things seem to be at their worse, and yet when things seem to be at their worst, and the patient well-nigh at his last gasp, a remission comes on, the spasm yields, air enters the lungs, and the attack subsides, coincidentally often with access of cough and mucous expectoration.” (4, page 16)(9, page 1,2)

I added italics for emphasis.

In 1879 bacteriologist Paul Erlich discovered the eosinophil, and it was soon discovered that elevated levels of eosinophils (eosinophilia) was commonly found in asthmatics. (5)

In 1882 Heinrich Curshmann observed other spirals in asthma sputum and believed they were associated with causing asthma. He believed since Leyden’s crystals didn’t cause asthma, perhaps his crystals did. (5)

Later Curshmann’s crystals were determined to be fragments of mucus plugs associated with asthma, and Leyden crystals were determined to be fragments of eosinophils. Eosinophils were later learned to be a type of white blood cell that, along with mast cells, are involved in the allergic reaction.

In 1911 Hermann Sahli described eosinophils in asthmatic sputum. Yet Sahli noted another author from 1891 who described eosinophils in asthmatic blood, and he concluded that these must be pathological with asthma. Yet he also noted that neither the cause of the eosinophils nor their origin was known. (7)

Sahli could isolate the area where the sputum came from based on epithelial cells in it, yet he did not understand the mechanisms of its production as we do today. (7)

Dr. James Adams describes asthma sputum in 1913: (8)

“Asthmatic sputum varies. Often there is none till the end of the attack; then it is in the typical form of small, tough pellets expelled by laborious coughing. The attack may then cease, or it may go on till a more free and profuse expectoration occurs.”

He also wrote:  (8)

“The sputum does not readily decompose, and is said to be wonderfully free from microbes; but this is not always so, as I have occasionally found it teeming with them.”

The true purpose of sputum is to ball up microbes inside the lungs and haul them out, and in this way the lungs stay sterile.  Surely asthma can be caused by inhaling a microbe, such as a bacteria, but it’s also caused by asthma triggers (dust mites, smoke, fumes, chemicals, pollution, animal dander) that are innocuous to most people, and non infecting agents.

Backing up a moment, in 1906 Australian pediatrician Clemons van Pirquet coined the term allergy when he observed that some of his patients were hypersensitive to substances that did not bother other people (what we now refer to as allergens, or asthma triggers).  This was the first time asthma was linked with allergies.

By 1910 Histamine was discovered and found to be a major component in the allergic response.  So some went on to speculate that finding a way to block histamine would cure both allergies and asthma. By 1946 antihystamines hit the market, and within a decade they were among the most commonly prescribed medicines.

Yet as time went by, it was learned that there was more to asthma and allergies than just histamine.  It was learned that asthmatic and allergic immune systems respond irrationally to allergens and asthma triggers by increasing production of eosinophils and  this spearheads inflammation of the bronchial muscles. Another weapon of the immune are mast cells that line the respiratory tract and eyes, and these were discovered in 1953.  .

In 1967 Immunoglobulin E antibodies (IgE) were discovered.  It was later learned IgE have a significant role in the asthmatic and the allergic response.  The first time an asthmatic, for example, is exposed to an asthma trigger (allergen), say dust mites, his immune system develops dust mite IgE antibodies that attach to mast cells that line the epithelial layer of the skin or respiratory tract.

The second time that person is exposed to that allergen (dust mites in this case), a mast cell that
has a dust mite IgE antibody attached to it explodes and releases its contents:  the mediators of inflammation.  Other mediators eventually discovered include histamine (discovered in 1910), cytokines and leukotrienes (discovered in the 1970s).

These mediators cause inflammation of the respiratory tract that starts the asthmatic response.  In the allergic person, they can also cause inflammation of the upper respiratory tract, which includes the back of the throat and nose.  The offending substance (dust in our case) becomes is recognized by the immune system, trapped in the mucus layer, absorbed by the mucus, balled up by the mucus, and sent on it’s way up the respiratory track to be coughed up.

What can compound this problem is that asthmatic lungs tend to produce an abnormal number of goblet cells, so mucus production during an asthma attack can become exorbitant. Some of this may make it’s way to the upper respiratory tract, although much of it can become trapped inside already spasming air passages.

When the fit ends, when the air passages relax and dilate, the patient will probably expectorate this sputum, which is usually (if no bacteria or virus is present) be white and sterile.  It will also have IgE and eosinophils in it, hence your Charcot-Leyden and Curshmann crystals.

So it’s easy to understand how this production of sputum at the end of an attack could be misinterpreted as the cause, rather than the effect.

References:

1. Lotval, J.,  ”Contractility of Lungs and air tubes: experiments performed in 1840 by Charles J.B. Williams, European Respiratory Journal, 1994, (7) pages 592-595


2. Bree, Robert, “A Practical Inquiry into Disordered Respiration Distinguishing the Species of Convulsive Asthma, their Causes and Indication for a Cure,” 4th ed, 1810, London, page pages 117-118


3. Berkart, J.B., “On Asthma: Its Pathology and Treatment,” 1878


4. Thorowgood, John C., “Asthma and Chronic Bronchitis: A New Edition of Notes on Asthma and Bronchial Asthma,” 1894, London, Bailliere, Tyndall, & Cox


5. Lipkowitz, Myron, Tova Navarra, “Encyclopedia of Allergies,” 2001


6. Brenner, Barry E, “Emergency Medicine, 1998, page 10


7. Sahli, Hermann, “A treatise on diagnostic methods of examination,” 1911


8. Adams, James, Asthma and it’s Radical Treatment, 1913


9. Thorowgood, John C., “Notes on Asthma,” 1878, 3rd edition, London, J & A Churchill