Scanning Electron and Atomic Force Microscopic Analysis of Erythrocytes in a Cohort of Atopic Asthma Patients—A Pilot Study

Background: Non-communicable diseases are often associated with chronic inflammation, placing patients suffering from these conditions at a higher risk of thrombosis and other complications. The pathophysiology of asthma and/or atopic asthma is also linked to chronic inflammation, which consequently may alter blood parameters including erythrocyte structure and function. Methodology: The objective of this study was to evaluate differences in erythrocytes between patients with atopic asthma (n = 30) and healthy individuals (n = 30) by evaluating routine haematological parameters; structures and axial ratios of erythrocytes using light microscopy; erythrocyte membrane elasticity using atomic force microscopy; and erythrocyte ultrastructure using scanning electron microscopy. Results: The haematological findings of healthy participants and patients suffering from asthma were within normal clinical ranges together with significantly higher levels of circulating monocytes (p = 0.0066), erythrocytes (p = 0.0004), haemoglobin (p = 0.0057), and haematocrit (p = 0.0049) in asthma patients. The analysis of eosin-stained erythrocytes by light microscopy showed more echinocytes, acanthocytes, and ovalocytes compared to controls and a significant difference in axial ratios (p < 0.0001). Atomic force microscopy findings showed reduced erythrocyte membrane elasticity in asthmatic erythrocytes (p = 0.001). Ultrastructural differences in erythrocytes were visible in the asthma group compared to controls. Conclusion: Altered erythrocyte ultrastructural morphology and a significant change in the haematological profile are evident in atopic asthma and may influence common complications associated with asthma. The impact of these changes on the physiological mechanisms of coagulation and the pathophysiology of asthma needs to be further elucidated.

[1]  M. Jeebhay,et al.  Work-related allergy and asthma associated with cleaning agents in health workers in Southern African tertiary hospitals. , 2022, American journal of industrial medicine.

[2]  T. Müller,et al.  Red Blood Cell Stiffness and Adhesion Are Species-Specific Properties Strongly Affected by Temperature and Medium Changes in Single Cell Force Spectroscopy , 2021, Molecules.

[3]  A. Doctor,et al.  Red Blood Cell Contribution to Hemostasis , 2021, Frontiers in Pediatrics.

[4]  Y. Zhi,et al.  Prevalence of Comorbid Asthma and Related Outcomes in COVID-19: A Systematic Review and Meta-Analysis , 2020, The Journal of Allergy and Clinical Immunology: In Practice.

[5]  F. Regateiro,et al.  The diverse roles of T cell subsets in asthma. , 2020, European annals of allergy and clinical immunology.

[6]  F. Kelly,et al.  Air Pollution and Asthma: Critical Targets for Effective Action , 2020, Pulmonary Therapy.

[7]  K. Nadeau,et al.  Advances and novel developments in mechanisms of allergic inflammation , 2020, Allergy.

[8]  Eun Sug Park,et al.  Global burden of 369 diseases and injuries in 204 countries and territories, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019 , 2020, Lancet.

[9]  Arife Zeybek,et al.  Does asthma affect outcomes of patients with COVID-19 infections? , 2020, The Journal of Allergy and Clinical Immunology: In Practice.

[10]  N. Scichilone,et al.  Prioritizing care for severe asthma during SARS-CoV-2 pandemic , 2020, Pulmonology.

[11]  G. Canonica,et al.  COVID‐19 in Severe Asthma Network in Italy (SANI) patients: Clinical features, impact of comorbidities and treatments , 2020, Allergy.

[12]  M. Plebanski,et al.  The Key Role of TNF-TNFR2 Interactions in the Modulation of Allergic Inflammation: A Review , 2018, Front. Immunol..

[13]  E. Pretorius,et al.  The inflammatory effects of TNF-α and complement component 3 on coagulation , 2018, Scientific Reports.

[14]  T. Assi,et al.  Allergic diseases, smoking, and environmental exposure among university students in Lebanon , 2018, The Journal of asthma : official journal of the Association for the Care of Asthma.

[15]  A. Sureda,et al.  Recent advances in the search for novel 5-lipoxygenase inhibitors for the treatment of asthma. , 2017, European journal of medicinal chemistry.

[16]  E. Pretorius,et al.  Characterizing pathology in erythrocytes using morphological and biophysical membrane properties: Relation to impaired hemorheology and cardiovascular function in rheumatoid arthritis. , 2017, Biochimica et biophysica acta. Biomembranes.

[17]  J. Weisel,et al.  Role of red blood cells in haemostasis and thrombosis , 2017, ISBT science series.

[18]  E. Pretorius,et al.  Effects of IL-1β, IL-6 and IL-8 on erythrocytes, platelets and clot viscoelasticity , 2016, Scientific Reports.

[19]  E. Pretorius,et al.  Erythrocytes and their role as health indicator: Using structure in a patient-orientated precision medicine approach. , 2016, Blood reviews.

[20]  Eva Rönmark,et al.  Is asthma prevalence still increasing? , 2016, Expert review of respiratory medicine.

[21]  S. Saglani,et al.  Novel concepts in airway inflammation and remodelling in asthma , 2015, European Respiratory Journal.

[22]  M. Papi,et al.  Mapping viscoelastic properties of healthy and pathological red blood cells at the nanoscale level. , 2015, Nanoscale.

[23]  E. Nwose,et al.  Association of abnormal erythrocyte morphology with oxidative stress and inflammation in metabolic syndrome. , 2015, Blood cells, molecules & diseases.

[24]  Sehyun Shin,et al.  Advances in the measurement of red blood cell deformability: A brief review , 2015 .

[25]  G. Tomaiuolo.  Biomechanical properties of red blood cells in health and disease towards microfluidics. , 2014, Biomicrofluidics.

[26]  J. Jaworska,et al.  Environmental tobacco smoke exposure and risk of allergic sensitisation in children: a systematic review and meta-analysis , 2014, Archives of Disease in Childhood.

[27]  D. Kell,et al.  Diagnostic morphology: biophysical indicators for iron-driven inflammatory diseases. , 2014, Integrative biology : quantitative biosciences from nano to macro.

[28]  S. Jerez,et al.  The role of oxidative stress in alterations of hematological parameters and inflammatory markers induced by early hypercholesterolemia. , 2013, Life sciences.

[29]  E. Pretorius,et al.  Changes in red blood cell membrane structure in type 2 diabetes: a scanning electron and atomic force microscopy study , 2013, Cardiovascular Diabetology.

[30]  M. Socol,et al.  Full dynamics of a red blood cell in shear flow , 2012, Proceedings of the National Academy of Sciences.

[31]  S. Vigmostad,et al.  Red blood cell flow in the cardiovascular system: a fluid dynamics perspective. , 2012, Critical reviews in biomedical engineering.

[32]  C. Saldanha,et al.  Erythrocyte as a biological sensor. , 2012, Clinical hemorheology and microcirculation.

[33]  Carole Ober,et al.  The genetics of asthma and allergic disease: a 21st century perspective , 2011, Immunological reviews.

[34]  D. Cho,et al.  Hemorheology and Microvascular Disorders , 2011, Korean circulation journal.

[35]  M. Targosz-Korecka,et al.  Effect of selected drugs used in asthma treatment on morphology and elastic properties of red blood cells , 2011, International journal of nanomedicine.

[36]  Subra Suresh,et al.  Shape and Biomechanical Characteristics of Human Red Blood Cells in Health and Disease , 2010, MRS bulletin.

[37]  D. Vercelli.  Gene–environment interactions in asthma and allergy: the end of the beginning? , 2010, Current opinion in allergy and clinical immunology.

[38]  Gabriel Popescu,et al.  Measurement of red blood cell mechanics during morphological changes , 2010, Proceedings of the National Academy of Sciences.

[39]  Q. Hamid,et al.  Airway remodelling in asthma: from benchside to clinical practice. , 2010, Canadian respiratory journal.

[40]  J. Weisel,et al.  Fibrin network structure and clot mechanical properties are altered by incorporation of erythrocytes , 2009, Thrombosis and Haemostasis.

[41]  P. Jani,et al.  Inflammatory mechanisms in the lung , 2008, Journal of inflammation research.

[42]  J. Chung,et al.  Lysophosphatidic Acid Induces Thrombogenic Activity Through Phosphatidylserine Exposure and Procoagulant Microvesicle Generation in Human Erythrocytes , 2006, Arteriosclerosis, thrombosis, and vascular biology.

[43]  J. Delaunay.  The molecular basis of hereditary red cell membrane disorders. , 2007, Blood reviews.

[44]  Y. Missirlis,et al.  Red blood cell deformability in patients with sepsis: a marker for prognosis and monitoring of severity. , 2007, Clinical hemorheology and microcirculation.

[45]  R. Mukhopadhyay,et al.  Stomatocyte–discocyte–echinocyte sequence of the human red blood cell: Evidence for the bilayer– couple hypothesis from membrane mechanics , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[46]  R. Plomin,et al.  Genes and environment in asthma: a study of 4 year old twins , 2001, Archives of disease in childhood.

[47]  H. Nelson,et al.  The importance of allergens in the development of asthma and the persistence of symptoms. , 2001, Disease-a-month : DM.

[48]  M. Telen.  Red blood cell surface adhesion molecules: their possible roles in normal human physiology and disease. , 2000, Seminars in hematology.

[49]  T Sigsgaard,et al.  Genetic and environmental influence on asthma: a population-based study of 11,688 Danish twin pairs. , 1999, The European respiratory journal.

[50]  N. Mohandas,et al.  Red blood cell deformability, membrane material properties and shape: regulation by transmembrane, skeletal and cytosolic proteins and lipids. , 1993, Seminars in hematology.