The Use of Blood Cell Count for Asthma Phenotype Identification

Despite the significant advances made in asthma diagnosis and management in recent years, the need for an accurate and easily accessible test for identifying airway inflammation remains.

Previously, the identification of airway inflammation, and therefore asthma phenotypes and appropriate courses of treatment, had been done by sputum induction. In effort to establish a less complicated approach for measuring airway inflammation, several biomarkers such as complete blood cell count have been examined.

Andriana Papaioannou, MD, PhD, further discusses the relationship between airway inflammation, asthma phenotypes, and the potential future use of the complete blood cell count in asthma diagnosis and management. Dr Papaioannou is a consultant in respiratory medicine at Attikon University Hospital in Athens, Greece.

Consultant360: To begin, could you discuss why identifying asthma phenotypes is an important consideration in the diagnosis and management of patients with asthma?

Andriana Papaioannou, MD, PhD: Asthma is characterized as severe when adequate control cannot be achieved by high-dose treatment with inhaled corticosteroids and additional controllers, by oral corticosteroid treatment, or when adequate control is lost when the treatment is reduced. Although clinical manifestations may be similar among patients, severe asthma is a heterogeneous and complex disease with variable responses to standard treatment and thus, can be distinguished in different phenotypes based on measurable characteristics, such as age of onset, degree of airway obstruction, comorbidities, and inflammatory characteristics. To date, a novel approach (known as “precision medicine”) has been proposed for the management of patients and aims to offer individuals the best intervention, which will lead to the best therapeutic result. Precision medicine is based on the identification of different phenotypes of asthma and offers specific therapeutic approaches targeting genetic, immunological, environmental, and/or lifestyle factors in individual patients.

C360: Your commentary notes that complete blood count is not only more accessible than other airway inflammation tests for asthma, such as sputum induction, but may provide an estimation on the type of airway inflammation present through airway eosinophils. Why is this an important consideration for health care providers?

Dr Papaioannou: Sputum induction has been used as the gold standard for the identification of airway inflammation for many years. Although we must admit that it is the most specific test for this purpose, it is also a test requiring experienced and trained personnel and expensive laboratory equipment. Sputum induction is also a semi-invasive procedure and in rare cases might be related to adverse events, especially in patients with severe disease. On the contrary, complete blood cell count is affordable, simple, and a widely available test, which can be performed in almost all health care utilities. Since it has been shown that complete blood cell count can provide an estimation of airway inflammation in patients with asthma, health care providers can use this test to phenotype their patients to offer them the most appropriate treatment.

C360: How may an individual’s circulating eosinophil number and/or airway eosinophils aid or alter the diagnosis and management of various asthma phenotypes, such as eosinophilic asthma or allergic asthma?

Dr Papaioannou: It cannot, per se. The physician must also consider several clinical characteristics of the patient, including other symptoms, comorbidities, and other disease manifestations. However, if all the above have been considered, the number of eosinophils in the complete blood cell count may help inform the final decision for the most appropriate therapeutic intervention, especially regarding biological treatments.

C360: Could you further discuss the relationship between eosinophils and neutrophils in individuals with asthma, and how this may impact treatment?

Dr Papaioannou: Most of the available therapies for severe asthma are effective on the so-called T-helper type 2-high inflammatory phenotype. This phenotype is most often characterized by increased eosinophils. In this regard, the identification of a high number of eosinophils in an individual with severe asthma provides information that this patient will probably benefit from the administration of biological treatment. The absence of eosinophils in a well-controlled patient probably means that the patient has been adequately treated.

The presence of increased neutrophils without increased eosinophils in a patient with uncontrolled asthma is the most difficult phenotype, and to date no special therapeutic intervention has been effective. However, other factors of systemic inflammation and/or medication use has been shown to be related with the elevated number of neutrophils and should be also considered.

Finally, some patients without elevated eosinophils nor neutrophils remain uncontrolled. In this subgroup of patients, it is likely that other not yet recognized inflammatory factors might be related to asthma and these patients are candidates for the development of novel therapeutic interventions.

C360: What do you believe are next steps for research concerning blood cell count, inflammatory pathways, and asthma phenotypes?

Dr Papaioannou: Although there seems to be a relation between blood cell count and airway inflammation in asthma, this correlation is quite weak. Of course, blood cell count can provide information on the possibility a patient may benefit from a biological agent. However, the identification of easily accessible and affordable biomarkers in blood, sputum, or exhaled air is essential for the recognition of different asthma phenotypes which would allow a better disease management and control.

Reference:

Papaioannou A, Loukides S, Bakakos P. Identification of asthma phenotypes using blood cell counts. EBioMedicine. 2022;77:103907. doi:10.1016/j.ebiom.2022.103907