Asthma Subgroups: The basics of Neutrophilic Asthma?
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Neutrophilic Asthma is yet another subgroup of asthma. This one is generally diagnosed in the 10-15% of asthmatics who already have a diagnosis of severe asthma. It has an adult onset, is intrinsic, and features neutrophilia. Unlike Eosinophilic Asthma, very little is known about it. Based on the few articles written on this subject, here is what I have learned.

Let’s begin with some basic definitions.

Severe asthma

It’s an asthma subgroup defined as asthma that responds poorly to corticosteroids, and therefore requiring two or more asthma medicines to obtain any degree of asthma control. They generally require the highest doses of inhaled corticosteroids, and frequent boosts of systemic corticosteroids, to obtain minimal asthma control.

Neutrophils

They are a type of white blood cell (leukocyte) that are made in the bone marrow. When they mature, half stay in the bloodstream and half are in tissues. At any one time, they consist of 50-80% of circulating leukocytes, although live for only a few hours. When they receive a signal, they migrate to sites of injury (trauma to cells) or infections (bacteria or fungus).1

They are intended as a first line of defense against bacterial and fungal infections.2 Researchers understand that they are also involved in the allergy and asthma responses, although their roles here are not well defined.3

Apoptosis

This is when cells die. Neutrophil apoptosis occurs after only 1-2 days, although they may live slightly longer during infections.2 A theory suggests that corticosteroids might contribute to neutrophil activation and prevent their apoptosis. So, it’s possible the same medicines used to obtain asthma control may contribute to worsening asthma in a small percentage of asthmatics.3

Phagocytic

This means that they engulf (eat) bacteria. When there is a large infection, they can be used up quite fast.1

Granulocytes

They also contain granules. These granules contain proteins, such as the mediators of inflammation (histamine, leukotrienes, and cytokines). When activated during the immune response, these contents are released.

Mediators of Inflammation

These are proteins responsible for inflammation. In our case, they attach to cells lining the respiratory tract making their membranes permeable. This causes airway cells to give up some of their fluid, resulting in inflammation. The purpose of this is to trap pathogens. This is good during infections, although bad during the allergy and asthma responses.

Storage

To prevent you from running out of neutrophils, your bone marrow has some stored up just in case of a severe infection.1

Neutrophilia

This is when you have an abnormally elevated level of neutrophils in your blood or sputum. This normally occurs during an infection and allergy and asthma attacks. However, it’s abnormal for them to be chronically elevated.

Researchers have known that it can result from chronic diseases such as certain cancers. However, they have only recently begun to suspect their role in allergies and asthma. They believe this occurs when certain environmental factors (such as cigarette smoke or air pollution) activate certain asthma genes.

Neutrophilic Asthma

Neutrophils are commonly elevated in asthmatic airway tissues and sputum during acute asthma episodes, although they usually decline to near normal levels between episodes. However, in severe asthma, they continue to stay elevated, particularly when asthma is treated with daily inhaled corticosteroids.2,3

Neutrophilia in lung tissue is thought to be responsible for chronic inflammation that is thought to cause scarring of cells lining airways. This makes airway walls thicker. Thicker airway walls make the air passages narrower than normal. This causes airway obstructions that allows air to get in but not out (air trapping). Because such scarring is permanent, diminished lung function and asthma symptoms are only partially reversible with treatment. This means that some shortness of breath may occur even on good asthma days.3

Triggers

 Since their asthma is generally non-allergic, their main asthma triggers are chemicals in cigarette smoke and air pollution, along with viral infections (colds).

Diagnosis

Once severe asthma is diagnosed, the quest should be ongoing to establish the specific asthma subgroup responsible. Neutrophilic asthma can be diagnosed by counting the number of neutrophils in a blood or sputum sample.

Comorbidity

 Neutrophilic asthma may exist on its own, although it may also coexist with other asthma subgroups, such as eosinophilic asthma. When neutrophilic and eosinophilic asthma co-exist, this is considered the most severe form of asthma. Their asthma is generally refractory (does not respond) to corticosteroids. This spotlights the complexity of severe asthma.3,4,5

Treatment

At the present time, there are no guidelines, and no specific treatment options, approved for this asthma subgroup. The quest to obtain good asthma control involves working with asthma doctors and trialing non-traditional asthma medicines, such as those that are new to the market or experimental.

Conclusion

The identification of this asthma subgroup should prove to be a godsend to those who have it, as researchers are working overtime to better understand it, and to come up with effective treatment options. What they think causes it, and what are the current and potential future treatment options, will be the topics of my next two posts. So, stay tuned!

view references
  1. Neutrophil, Encyclopedia Britannica, https://www.britannica.com/science/neutrophil, accessed 10/31/16
  2. Monteseirin, J., “Neutrophils and Asthma,” Journal of Investigational Allergology and Clinical Immunolog, 2009, http://www.jiaci.org/issues/vol19issue5/1.pdf, accessd 11/2/16
  3. enzel, Sally, “Asthma phenotypes: the evolution from clinical to molecular approaches,” Nature Medicine, 2012, May, Vol. 18, No. 5, pages 716-725, http://www.healthylungs.com.au/resources/WenzelAstham-Phenotypes.pdf, accessed 10/31/16
  4. Lockey, Richard F., "Defining Phenotypes: Expanding our Understanding of Asthma Challenges in Treating Respiratory Disease," National Heart Lung and Blood Institute, slideshow for World Asthma Day, http://www.worldallergy.org/UserFiles/file/NHLBI%20Asthma%20Phenotypes-Lockey.pdf, accessed 1/1/16,
  5. Chesne, Julie, "IL17 in severe asthma: Where do we stand?" American Journal of Respiratory and Critical Care Medicine," May 13, 2014, vol. 190, no. 10, http://www.atsjournals.org/doi/full/10.1164/rccm.201405-0859PP, accessed 1/1/16
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