Airway Hyperresponsiveness in Asthma: A Better Understanding Yet to Yield Clinical Benefit

Seminal and ongoing research has made it clear that the molecular signature of asthma is not unique.

The molecular abnormalities that have been described in asthma are rather heterogeneous, and those that lead to asthma symptoms also differ between affected individuals.

This is not surprising, owing to the plethora of environmental factors that can trigger asthma. More than 500 individual triggers have been identified, including allergens, viruses, bacteria, pollutants, exercise, as well as occupational irritants and sensitizers.

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P-Selectin is a Key Molecule Underlying the Pathophysiology of Aspirin- Exacerbated Respiratory Disease

Recently, the evidence for platelet association with allergic diseases has been established by many researches. Activated platelets contribute to airway hyper reactivity, bronchoconstriction, airway inflammation and airway remodeling in asthmatic patients.

We aimed to clarify platelet activation and key molecules on platelets, which are mainly associated with the mechanism underlying aspirin-exacerbated respiratory disease.

Aspirin-exacerbated respiratory disease (AERD) is characterized by the triad of asthma, nasal polyposis, and hypersensitivity to aspirin and other cyclooxygenase (COX)-1 inhibitors.

Urinary leukotriene (LT) E4 (uLTE4) levels are 3-4 fold higher in AERD patients than in ATA patients, which further increase after aspirin-induced reaction in AERD patients.

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P-Selectin is a Key Molecule Underlying the Pathophysiology of Aspirin

Aspirin-exacerbated respiratory disease (AERD) is characterized by the triad of asthma, nasal polyposis, and hypersensitivity to aspirin and other cyclooxygenase (COX)-1 inhibitors. Aspirin intolerance is one of the risk factors for severe asthma, particularly in patients with persistent airflow limitation (PAFL).

 The overproduction of cysteinyl leukotriene (cysLT) is the biochemical hallmark of AERD. Urinary leukotriene levels are 3-4 fold higher in AERD patients than in ATA patients, which further increase after aspirin-induced reaction in AERD patients. Decreased levels of prostaglandin E2 (PGE2) were also a characteristic feature of AERD patients. Impaired E prostanoid 2 (EP2) expression and resistance to PGE2 were detected in nasal polyp fibroblasts from AERD patients. However, the mechanism underlying the development of AERD has not been clarified in detail.

In addition to their role in hemostasis, platelets have the capacity to mediate immune responses during inflammation and to facilitate granulocyte recruitment into airways. Platelet activation has been detected in several allergic diseases, including asthma. Platelets play an important role in asthma, which contributes to airway hyper reactivity (AHR), bronchoconstriction, airway inflammation and airway remodeling. Recently, Laidlaw and Boyce have demonstrated that platelet activity is strongly associated with the pathophysiology of AERD.

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