Respirology | APSR Respiratory Medicine Journal
Review: Unclear Whether Eosinophilic COPD Contributes To Pathogenesis Of COPD
The role that eosinophilic chronic obstructive pulmonary disease (COPD) plays in the pathogenesis of COPD is not well understood, given the lack of evidence about the subject.
A review focusing on the mechanisms of eosinophilia in chronic obstructive pulmonary disease (COPD), the utility and specificity of eosinophilia in this patient population, and the data currently available that might validate an approach to eosinophilic COPD determined that the evidence that eosinophilic COPD constitutes a distinct subset of COPD remains unclear.
Observations from the review were published in Lung.
Eosinophils come from CD34+ precursor cells, which are the common precursor for eosinophils and basophils. In the blood, eosinophils have a circulatory time of 8 to 18 hours before being incorporated into a variety of tissues including the gastrointestinal tract, the uterus, thymus, and, in some disease states, lung.
A variety of definitions of peripheral blood eosinophilia have been used in the context of COPD, including the currently accepted definition of having an eosinophil count greater than 2% of total cells or more than 150 total cells/mcL.
Past research has demonstrated that as a single variable, eosinophilia is associated with poorer outcomes in COPD. The relationship between eosinophilia in COPD and response to corticosteroids could be an important determinant as to whether a distinct population of COPD patients can be defined by the presence of eosinophilia, as previous research has shown that the association of poorer outcomes in eosinophilic asthma appears strong for patients who are clinically resistant to corticosteroids.
Studies involving anti–interleukin (IL)-5 therapies demonstrated that they were effective in significantly reducing the number of eosinophils in blood and sputum in patients with asthma but were ineffective in improving asthma outcomes. Past data regarding anti–IL-5 therapy may suggest that with proper patient selection, a highly specific group of patients with COPD might benefit from anti–IL-5 therapy or that the number needed to treat for IL-5 therapies in COPD is quite high such that individual studies had insufficient power to detect a difference.
Although proven to be successful in reducing eosinophilia, the failure of anti–IL-5 therapies to affect COPD exacerbation rate in most individual studies weakens the idea that eosinophilia plays an integral role in the morbidity of COPD.
Dupilumab, a fully human immunoglobulin G4 monoclonal antibody directed against the IL-4 R-alpha subunit, has been shown to significantly improve asthma control, airflow, and symptom improvement in patients with asthma regardless of the presence of baseline peripheral blood eosinophilia. A pivotal study to assess the efficacy, safety, and tolerability of dupilumab in patients with moderate to severe COPD with type 2 inflammation is underway.
Unlike asthma, in which the immunologic mechanisms of atopic disease and eosinophilia are linked with an increasing eosinophil count and poor control of the disease, there is little evidence to determine that eosinophilia contributes to the pathogenesis of severe COPD, authors concluded.
Reference
Weissler JC, Adams TN. Eosinophilic chronic obstructive pulmonary disease. Lung. 2021;199(6):589-595. Doi:10.1007/s00408-021-00492-0
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GATA3 Innate Lymphoid Cells Associated With Sputum Eosinophilia In COPD
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What Causes Eosinophilia?
Eosinophilia is classified as primary or secondary, in addition to the hypereosinophilic syndromes.
Primary EosinophiliaPrimary eosinophilia is a rise in the peripheral eosinophil count without any underlying condition to account for it. It is subclassified into clonal and idiopathic types.
Clonal primary eosinophilia is the type of eosinophilia that is due to proliferation of a clone of eosinophils in the bone marrow, and is found in leukemias or other myeloproliferative disorders.
Idiopathic primary eosinophilia is a term used to refer to peripheral blood eosinophilia without any detectable cause.
Secondary EosinophiliaSecondary eosinophilia is the result of other disorders not associated with bone marrow proliferation, such as atopy, asthma, and most commonly helminthic infestations.
Hypereosinophilic SyndromesHypereosinophilic syndromes are disorders which are characterized by eosinophilia above 1500/µL persisting for at least 6 months, with no underlying disease condition, but associated with organ dysfunction due to eosinophil recruitment into tissues which suffer resulting damage. These include the syndromes of pulmonary eosinophilic infiltrate with eosinophilia, such as:
The following simple classification may help to understand the manifold conditions which may give rise to secondary eosinophilia.
Allergic conditions, especially of the skin and the respiratory tract, such as;
Connective tissue disorders such as;
Immune disorders such as;
Certain tumors, such as Hodgkin's disease, also result in eosinophilia. Others include
Invasive parasite infestations result in a rise in the number of peripheral blood eosinophils, such as
With regard to parasitosis, a sustained rise in eosinophils is usually seen when the parasites migrate into tissues and come into contact with patrolling immune cells. Once the parasite is walled off within a cyst, or is dormant, eosinophilia tends to fade. Only if the cyst leaks and parasite products again become exposed to immune effector cells (T-lymphocytes) does eosinophilia again appear. Parasites which remain within the lumen of the gut during their whole lifecycle rarely cause persistent eosinophilia.
Again, protozoal infection is not usually a cause of a raised eosinophil count. However, ectoparasites such as the scabies mite are associated with eosinophilia.
Non-parasitic infestations such as:
Skin disorders due to hypersensitivity reactions:
Asymptomatic drug-induced eosinophilia
Eosinophilia associated with pulmonary infiltrates
Eosinophilia associated with hepatitis
Eosinophilia associated with interstitial nephritis
Other conditions that may be found in eosinophilia include:
Last Updated: Feb 26, 2019
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