Pulmonary corticosteroids and mast cell inhibitors

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Pulmonary corticosteroids and mast cell inhibitors

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A 12-year-old girl comes to the office of her pulmonologist with her parent after a recent asthma exacerbation that required hospitalization. The parent is concerned that the patient continues to wheeze and cough multiple nights per week. The patient takes multiple inhaled and systemic medications. The patient reports that she uses the restroom to urinate multiple times a day despite no change in her diet. A review of systems is otherwise unremarkable. Temperature is 37°C (98.6°F), pulse is 75/min, respirations are 20/min, and blood pressure is 110/65 mmHg. Physical examination reveals scattered expiratory wheezes in both lungs. Fingerstick glucose is 246 mg/dl. The physician stops the systemic corticosteroids and adds omalizumab to the treatment regimen. Which of the following is the most likely site of action of this new medication? 

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In obstructive lung diseases like asthma, where individuals suffer from reversible narrowing of the airways, medications like bronchodilators are helpful in keeping the airways open.

But, most of the times, narrowing of the airways actually occurs as a result of inflammation and excessive release of various inflammatory chemical mediators like leukotrienes and prostaglandins.

So, to effectively manage the disease, it’s important to give medications that will control the inflammation.

So, if we take a look at the lungs, you’ve got the trachea, which branches off into right and left bronchi, and then continues to branch into thousands of bronchioles.

In the bronchioles you’ve got the lumen, the mucosa, which includes the inner lining of epithelial cells, as well as the lamina propria which contains many cells like the type 2 helper cells, B cells, and mast cells.

Surrounding the lamina propria, there is a layer of smooth muscles and submucosa.

The submucosal layer contains mucus-secreting glands and blood vessels.

Now, the molecular pathway that leads to asthma is actually pretty complex, but it is often initiated by an environmental trigger.

Allergens from environmental triggers, like air pollutants or cigarette smoke, are picked up by dendritic cells which, present them to a type 2 helper cell or Th2 cell in the lamina propria.

These cells then produce cytokines like IL-4 and IL-5 which causes the inflammatory response.

IL-4 is especially important because it leads to the production of IgE antibodies by B-cells, and these antibodies bind to FcεR1 receptors on mast cells to activate them.

These mast cells use an enzyme called phospholipase A2 to take membrane phospholipids and make a 20 carbon polyunsaturated fatty acid called arachidonic acid.

Summary

Pulmonary corticosteroids and mast cell inhibitors are medications used to treat certain lung disorders. Corticosteroids are a class of drugs that reduce inflammation and swelling in the lungs, making it easier to breathe. They are often used to treat conditions such as asthma, chronic obstructive pulmonary disease (COPD), and certain types of lung infections. Mast cell inhibitors, also known as mast cell stabilizers, are a class of drugs that prevent the release of inflammatory mediators from mast cells in the lungs. They are often used to prevent symptoms of asthma and allergic rhinitis. They are less potent than corticosteroids but are generally well-tolerated with fewer side effects.

Sources

  1. "Katzung & Trevor's Pharmacology Examination and Board Review,12th Edition" McGraw-Hill Education / Medical (2018)
  2. "Rang and Dale's Pharmacology" Elsevier (2019)
  3. "Goodman and Gilman's The Pharmacological Basis of Therapeutics, 13th Edition" McGraw-Hill Education / Medical (2017)
  4. "Update on Clinical Aspects of Chronic Obstructive Pulmonary Disease" New England Journal of Medicine (2019)
  5. "Triple therapy in COPD: new evidence with the extrafine fixed combination of beclomethasone dipropionate, formoterol fumarate, and glycopyrronium bromide" International Journal of Chronic Obstructive Pulmonary Disease (2017)
  6. "Omalizumab for Severe Asthma: Beyond Allergic Asthma" BioMed Research International (2018)
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