Markers Of Asthma - An Overview Of This Respiratory Disease
Knowing the markers of asthma - the measurable indicators that help identify the presence, severity, or progression of this disease - aids in better understanding it.
Author:Suleman ShahReviewer:Han JuSep 08, 20241.4K Shares146.4K Views
Some of those genes have a protective effect and otherscontribute to the disease pathogenesis, with each gene having its own tendency to be influenced by the environment.
Allergic asthmais a chronic respiratory disease that affects 300 million people throughout the world.
Its prevalence has increased in the world over the last 25 years.
Asthma is common [chronic] inflammatory diseaseof the [airways] characterized by variable and attacks of cough and breathlessness, usually precipitated by an environmental trigger, such as:
- air pollution
- cold
- dry air
- smoke
The sequence of immunopathogenesis is unclear but there is clearly a genetic predisposition.
Methods
By the end of 2010, 100 genes had been associated with asthma in six or more separate populations, including:
A. Interleukins (IL)
| Shortened Term | Long Term |
| IL-1α | interleukin 1-alpha |
| IL-1β | interleukin-1 beta |
| IL-3, 4, 5, 9, 10, 12, 13, 18 | interleukin-3, 4, 5, 9, 10, 12, 13, 18 |
| IL-1R1 | interleukin 1 receptor, type I |
| IRAK-3 | interleukin-1 receptor-associated kinase 3 |
| IL-1RN | interleukin-1 receptor antagonist protein |
| IL-8Rα | interleukin 8 receptor, alpha |
B. Other genes (first batch)
| Shortened Term | Long Term |
| A3AR | A3 adenosine receptor |
| ACE | angiotensin-converting enzyme |
| ADAM33 | a disintegrin and metalloprotease 33 |
| ARG1 | arginase 1 |
| CBR1 | carbonyl reductase 1 |
| CC16 | Clara cell secretory protein |
| CCR2 | C-C motif chemokine receptor 2 |
| CD24 | cluster of differentiation 24 |
| CD69 | cluster of differentiation 69 |
| CHIA | chitinase acidic |
C. Other genes (second batch)
| Shortened Term | Long Term |
| CLCA1 | calcium-activated chloride channel regulator 1 |
| CTLA4 | cytotoxic T-lymphocyte-associated antigen 4; or |
| -- | cytotoxic T-lymphocyte associated protein 4 |
| CMA1 | chymase 1 |
| EGFR | epidermal growth factor receptor |
| EGR-1 | early growth response protein 1 |
| eNOS | endothelial nitric oxide synthase |
| GPRA | G protein‐coupled receptor for asthma susceptibility |
| GSTM1 | glutathione S-transferase mu 1 |
| iNOS | inducible nitric oxide synthase |
D. Other genes (third batch)
| Shortened Term | Long Term |
| LELP1 | late cornified envelope-like proline-rich 1 |
| LTC4S | leukotriene C4 synthase |
| MUC-2 | mucin 2 |
| NAT2 | N-acetyltransferase 2 |
| NOS3 | nitric oxide synthase 3 |
| PAF-2 | peroxisome assembly factor-2 |
| PHF11 | plant homeodomain finger protein 11 |
| PIM1 | provirus integration site for Moloney murine leukemia virus 1 |
| PTGER3 | prostaglandin E receptor 3 |
| SLP-76 | SH2 domain-containing leukocyte phosphoprotein of 76 kDa |
E. Other genes (fourth batch)
| Shortened Term | Long Term |
| SOD1 | superoxide dismutase 1 |
| SOD2 | superoxide dismutase 2 |
| SPINK5 | serine protease inhibitor Kazal type-5 |
| STAT6 | signal transducer and activator of transcription 6 |
| TCRc | T-cell receptor gamma |
| TGFβ1 | transforming growth factor beta 1 |
| TNF-α | tumor necrosis factor alpha |
| VAMP-7, aka SYBL-1 | vesicle-associated membrane protein 7 |
| V-CAM 1 | vascular cell adhesion protein 1 |
| VDR | vitamin D receptor |
Another one is the human FcεRIβ gene, a beta subunit of the high-affinity immunoglobulin E (IgE) receptor.
Some of these genes may also be involved with other phenotypes, such as:
| cardiovascular diseases | hyperparathyroidism |
| chronic hepatitis B infection | insulin-dependent diabetes mellitus |
| chronic obstructive pulmonary disease (COPD) | leprosy |
| congenital thrombotic thrombocytopenia | prostate cancer |
| Crohn’s disease (ADAM33) | renal cell carcinoma |
| helminthic infections (FcεRIβ and IL-4) | tuberculosis |
Results
Current treatment consists in administering corticoids that treat the symptoms and temporarily relieve the disorder, but without curing it.
An alternative, long-lasting treatment for allergic asthma is based on a specific immunotherapeutic protocol commonly known as desensitization.
Repeated, increased doses of the allergen are administered in order to decrease the hypersensitivity and reduce the symptoms in the event of subsequent exposure.
However, the efficiency of this protocol is limited and varies greatly from one patient to another.
The researchers first tried proving the efficiency of this DNA-based vaccination against the specific allergen Derf1, using a relevant animal model developed by the Bronchial and Allergic Pathologies team led by Antoine O. Magnan, M.D., a professor of respiratory medicine in France.
In Europe and the Mediterranean region of Turkey, Dermatophagoides farinae 1 (Derf1) is a very common allergen carried by Dermatophagoides farinae (house dust mite).
More than half of patients presenting allergies to house dust mites produce specific immunoglobulin E (IgE) type antibodies (Derf1) against this substance that are characteristic of asthma.
In practice, the researchers associated useful genetic sequences of the allergen Derf1 with a nanovector consisting of a synthetic polymer.
This DNA sequence, transported by a sort of “molecular taxi” into the muscle cells that ensure protein synthesis of the allergen, modulated the allergic response in asthmatic animals.
In a study conducted in the Mediterranean region of Turkey, the prevalence of the following was detected:
- asthma - 8.2%
- allergic rhinitis- 10.8%
- allergic eye disease - 7.5%
In our previous study, we showed that as the wind speed, pollination, and temperature increased, the symptoms of the disease increased, too.
Skin prick test (SPT) positivity for the common hazel (Corylus avellana) was significant in the age group of >40 years old.
SPT positivity for the following was significant in patients younger than 40 years old:
- the plant ribwort plantain (Plantago lanceolata)
- a species of fungus with the scientific name of Aspergillus fumigatus
- house dust mite (Dermatophagoides pteronyssinus or D. pteronyssinus)
The sensitivity for the grass, barley, weed, and tree allergen mixtures of SPT was significantly increased in May and June.
During the month of May, air pollination of grass (Poaceae, formerly Gramineae) also increased.
Mainstays of the treatment of difficult to control allergic severe persistent asthma include avoidance of allergens and other exacerbating factors and control of common coexisting conditions, such as:
- postnasal drip
- sleep apnea
- rhinosinusitis
- gastroesophageal reflux disease (GERD)
Persistent allergic asthma that is refractory to usual treatment continues to be a challenge, but new biological therapies offer hope to improve the quality of lifeand long-term prognosis of severe persistent allergic asthmatics.
They include:
- omalizumab (brand name Xolair)
- benralizumab (brand name Fasenra)
- mepolizumab (brand name Nucala)
Since the discovery of immunoglobulin E (IgE) in 1967, the mechanisms of immediate-type hypersensitivity and allergy have been increasingly unraveled.
IgE binds to the high-affinity IgE Fc receptor (FcεRI) on mast cells and basophils mediates inflammatory cascades of the allergic response.
Discussion
Allergic asthma is critically dependent on a series of cell adhesion molecule-mediated interactions between vascular endothelium and leukocytes, and elevation in total serum immunoglobulin E (IgE).
Omalizumab, a humanized monoclonal antibody (mAb) that binds to the CH3 domain near the binding site for the high-affinity type-I IgE Fc receptors of human IgE, can neutralize free IgE and inhibit the IgE allergic pathway without sensitizing mast cell and basophils.
Omalizumab is also a humanized recombinant anti-IgE monoclonal antibody approved for therapeutic use both in adults and in children.
The clinical benefit of omalizumab has been established in several large clinical trials.
We demonstrated that prior and after onset of treatment, there were significant changes in the following, giving evidence for a good therapeutic effect:
| IL-1β | eosinophil cationic peptid |
| CXCL8 | 25-hydroxyvitamin-D |
| IL10 | homocysteine |
| D-dimer | ceruloplasmin oxidase activity |
| soluble OX-2 | fractional exhaled nitric oxide |
| s TRAIL (sApo 2L) | pulmonary function tests |
| total IgE | asthma control test |
Blood samples were taken in May or June during the highest air pollination.
Vitamin D has several effects on the innate and adaptive immune systems that might be relevant in the:
- primary prevention of asthma
- protection against or reduction of asthma morbidity
- modulation of the severity of asthma exacerbations
Cross-sectional data indicate that low 25-hydroxyvitamin-D levels in patients with mild to moderate asthma are correlated with:
- poor asthma control
- reduced lung function
- reduced glucocorticoid response
- more frequent exacerbations
- consequent increased steroid use
The hormone calcifediol, aka 25-hydroxyvitamin-D, has effects on the innate and adaptive immune system. Its are associated with:
- poor asthma control
- reduced pulmonary function
- increased medication intake and exacerbations
Little is known about 25-hydroxyvitamin-D in adult asthma patients or its association with asthma severity.
More than that, 25-hydroxyvitamin-D triggers a homocysteine metabolizing enzyme, and data from the Longitudinal Aging Study Amsterdam (LASA) suggested a correlation between 25-hydroxyvitamin-D status and homocysteine levels.
In our previous study, we demonstrated that the increase in homocysteine concentrations and decrease in 25-hydroxyvitamin-D supports the possible allergic inflammationmechanism.
Alternatively, the development of atopy may also be a direct effect of elevated homocysteine or some of its metabolites, which appears to exert a number of diverse effects on immune function.
In addition, total homocysteine has been shown to increase in response to immune activation and cell proliferation during a non-allergic Th1-type immune response.
Although much less is known about the healtheffects of sustained post-load homocysteine concentrations, there is evidence that it has negative effects on:
- platelet aggregation
- endothelial function
A number of studies have indicated that homocysteine may contribute to the development and progression of atherosclerosis, a risk factor for cardiovascular diseases.
However, the mechanisms by which homocysteine can induce vascular dysfunction are not fully understood.
In conventional thinking the involvement of immunoglobulin E (IgE) in mast cell activation requires the cross-linking of FcεRI-bound IgE by antigen or anti-IgE antibodies.
In a transcriptome analysis of 8,793 genes, sensitization of mast cells with monoclonal IgE alone was found to upregulate 58 genes more than 2-fold compared with their levels in unsensitized mast cells.
These genes included those for:
- cytokines (IL-1β, IL-6, colony-stimulating factor 1)
- chemokines (CXCL8, CCL7, CCL4)
- chemokine receptors
Conclusion
Asthma is one of the most serious and intriguing allergic diseases.
Asthma aggregates within families and is a complex multifactorial disease with the involvement of environment and genetic components.
The mechanism of action of Anti-IgE monoclonal antibody in the treatment of allergic disorders is believed to be multifactorial and includes effects mediated through altered production of redox metabolite, such as:
- total antioxidant capacity
- hydrogen peroxide
- malondialdehyde
- total nitric oxide
More studies are needed to determine the markers of asthma and the exact function of these genes and gene-environment interactions, which are undoubtedly complex and remain elusive for the time being even with whole genome-wide association studies.
Suleman Shah
Author
Suleman Shah is a researcher and freelance writer. As a researcher, he has worked with MNS University of Agriculture, Multan (Pakistan) and Texas A & M University (USA). He regularly writes science articles and blogs for science news website immersse.com and open access publishers OA Publishing London and Scientific Times. He loves to keep himself updated on scientific developments and convert these developments into everyday language to update the readers about the developments in the scientific era. His primary research focus is Plant sciences, and he contributed to this field by publishing his research in scientific journals and presenting his work at many Conferences.
Shah graduated from the University of Agriculture Faisalabad (Pakistan) and started his professional carrier with Jaffer Agro Services and later with the Agriculture Department of the Government of Pakistan. His research interest compelled and attracted him to proceed with his carrier in Plant sciences research. So, he started his Ph.D. in Soil Science at MNS University of Agriculture Multan (Pakistan). Later, he started working as a visiting scholar with Texas A&M University (USA).
Shah’s experience with big Open Excess publishers like Springers, Frontiers, MDPI, etc., testified to his belief in Open Access as a barrier-removing mechanism between researchers and the readers of their research. Shah believes that Open Access is revolutionizing the publication process and benefitting research in all fields.
Han Ju
Reviewer
Hello! I'm Han Ju, the heart behind World Wide Journals. My life is a unique tapestry woven from the threads of news, spirituality, and science, enriched by melodies from my guitar. Raised amidst tales of the ancient and the arcane, I developed a keen eye for the stories that truly matter. Through my work, I seek to bridge the seen with the unseen, marrying the rigor of science with the depth of spirituality.
Each article at World Wide Journals is a piece of this ongoing quest, blending analysis with personal reflection. Whether exploring quantum frontiers or strumming chords under the stars, my aim is to inspire and provoke thought, inviting you into a world where every discovery is a note in the grand symphony of existence.
Welcome aboard this journey of insight and exploration, where curiosity leads and music guides.
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