Coenzyme Q10 (CoQ10) has potential as an antioxidant treatment for asthma. Studies have shown lower levels of CoQ10 in asthma patients compared to healthy controls. As a mitochondria-targeted antioxidant, CoQ10 can protect against oxidative damage to mitochondria, which plays a role in asthma pathophysiology. Administration of CoQ10 in animal studies of asthma attenuated airway inflammation, reduced oxidative stress markers, and downregulated inflammatory pathways. CoQ10 supplementation may help restore antioxidant balance and reduce corticosteroid dependency in asthma patients. More research is still needed but CoQ10 shows promise as a therapeutic agent for its antioxidant and anti-inflammatory effects in asthma.

1. Coenzyme Q10 in Asthma: An
Unexplored Oppotunity
dr. ……

2. Asthma
• Asthma is a long-term inflammatory and allergic airway pathology caused by
infiltration of immune cells such as neutrophils, lymphocytes and macrophages into
the lung tissues.
• The mechanism underlying the pathology of asthma encompasses elevated mucus
secretion, hyper-allergic response and constriction, and airway inflammation.
• The other clinical factors involved in asthma are high concentrations of IgE,
infiltration of mast cells as a result of inflammation, and aggravated release of
cytokines and chemokines.
• These factors result in accumulation of the inflammatory cells in the airway area,
leading to generation of toxic free radicals. The free radicals reduce pulmonary
antioxidant defense system and modify the structure of vital biomolecules
1. Robb CT, Regan KH, Dorward DA, Rossi AG. Key mechanisms governing resolution of lung inflammation. Semin Immunopathol 2016; 38(4): 425-448.
2. Mishra V, Banga J, Silveyra P. Oxidative stress and cellular pathways of asthma and inflammation: Therapeutic strategies and pharmacological targets. Pharmacol Ther 2018; 181: 169-182.
3. Peng, Jingwei & Ma, Jilong & Zhang, Lan & Lu, Banghao. (2020). Coenzyme Q10 attenuates airway inflammation and oxidative stress in neonatal asthmatic rats. Tropical Journal of
Pharmaceutical Research. 19. 1969-1975. 10.4314/tjpr.v19i9.24.

3. Asthma in Indonesia
• Based on data from the Ministry of Health for 2020, Asthma is one of the
most common types of disease in Indonesian people.
• Until the end of 2020, the number of asthma sufferers in Indonesia is 4.5
percent of the total population of Indonesia or as many as 12 million
more.
• According to BPJS Kesehatan data, during the 2018-2022 period, the
budget covered for respiratory diseases has increased every year.
• Pneumonia costs Rp. 8.7 trillion, Rp. 5.2 trillion for tuberculosis, Rp. 1.8
trillion for COPD, Rp. 1.4 trillion for asthma, and Rp. 766 billion for lung
cancer.
1. National Institute of Health. 2020. National Heart, Lung, and Blood Institute. Asthma
2. BPJS Kesehatan, 2022

4. Pathophysiology Of
Asthma
• Asthma is a complex interaction
between cells, cytokines and
chemokines. There are two effector
cell responses, neutrophilic, and
eosinophilic.
• The eosinophilic response is the
most frequent, mediated by the
synthesis of a Th2 cytokine profile
(IL-5, IL-4, and IL-13) and histamine
released when there is an IgE-
mediated allergic response; or by
alarmins (TSLP, IL-25, and IL-33) in
the case of a non-allergic one.
• Neutrophilic response is less
understood and maybe a transition
from early Th2 or be a
consequence of early Th1/Th17
secondary to macrophage
activation and IL-8 release.
Pavón-Romero GF, Serrano-Pérez NH, García-Sánchez L, Ramírez-Jiménez F and Terán LM (2021) Neuroimmune Pathophysiology in Asthma.
Front. Cell Dev. Biol. 9:663535. doi: 10.3389/fcell.2021.663535

5. Athari, S.S. Targeting cell signaling in allergic asthma. Sig Transduct Target Ther 4, 45 (2019). https://doi.org/10.1038/s41392-019-0079-0

6. • Epithelial, goblet, smooth muscle, and immune cells are influenced in asthma.
• Mitochondria of airway cells are involved in asthma pathophysiology and have main roles
in the health of the respiratory system, especially in bronchia, by influencing airway
remodeling, fibrosis, eosinophilic inflammation, and cell apoptosis, necrosis, and
autophagy, which can be regulated by both cellular and mitochondrial signaling pathways
Qian L, Mehrabi Nasab E, Athari SM, et al Mitochondria signaling pathways in allergic asthma Journal of Investigative Medicine 2022;70:863-
882.
Mitochondria and Asthma

7. Mitochondria and Asthma
• The accumulation of dysmorphic mitochondria is related with asthma
and airway remodeling and will be done with increased ASM mass and
fibroblast dysfunction.
• TGF-β induces PRMT1 expression in lung fibroblasts and can regulate
post-translational arginine methylation which play important roles in
signal transduction and events in the extracellular milieu
• Arginine methylation displays a novel protein modification which is
implicated in the intracellular signaling, DNA repair and processing,
protein–protein interaction, and gene expression regulation. PRMT1
upregulates extracellular matrix deposition through ERK1/2-STAT1
signaling.
• The TGF-β- activated signal pathway augments PRMT1 expression and
caused mitochondria dysfunction through the SMAD2/3, C/EBPb,
PRMT1, PGC-1a signaling sequence.
• The TGF-β1 and C/EBPb are upstream of PGC-1a and PRMT1 expression.
• In the alveolar macrophages and epithelial cells, TGF-β1 overexpression
induces mitochondria dysfunction that leads to remodeling of bronchi.
Qian L, Mehrabi Nasab E, Athari SM, et al Mitochondria signaling pathways in allergic asthma Journal of Investigative Medicine 2022;70:863-882.

8. Oxidative Stress in Asthma
• Interplay between intrinsic and
extrinsic factors leads to the
production of reactive oxygen species
(ROS) and in certain conditions, due
to the imbalance between the
production of ROS and antioxidant
defense, oxidative stress and
modification of biomolecules
develops.
• Due to the modifications of various
biomolecules with different functions,
particular components of chronic
inflammation lead to asthma
development and clinical symptoms
onset.
• Non-controlled or partially controlled
and regulated inflammation is
another important source of ROS,
which closes the vicious circle.
Jesenak M, Zelieskova M and Babusikova E (2017) Oxidative Stress and Bronchial Asthma in Children—Causes or Consequences? Front. Pediatr.
5:162. doi: 10.3389/fped.2017.00162

9. • An increase in air pollution, an increased use of oxidant
medication, and a decreased intake of antioxidants account
for increased airway oxidative stress, which can cause
immunity and airway inflammation.
• Another explanation for the recent increase in the
development of asthma may be associated with individual
variations in the cellular machineries that handle
intracellular antioxidants.
• A partial deficiency in the intracellular antioxidant defense
system may critically affect oxidants when the level of
increased oxidative stress goes beyond the capability of the
system.
• Increased oxidative stress in the environment may
contribute to allergic airway inflammation by inducing a
break in immune tolerance in genetically predisposed
individuals whose antioxidant systems are unable to handle
the oxidative stress burden imposed on immune cells.
• It is assumed that a higher severity of asthma is also closely
related to a lower ability to control oxidative stress in
genetically predisposed patients.
Cho YS, Moon HB. The role of oxidative stress in the pathogenesis of asthma. Allergy, Asthma & Immunology Research.
2010 Jul;2(3):183-187. DOI: 10.4168/aair.2010.2.3.183. PMID: 20592917; PMCID: PMC2892050.

10. J Thorac Dis 2019;11(Suppl 17):S2129-S2140
Classification of Asthma Severity

11. Treatment of Asthma
• In the new guidelines from GINA, the preferred line of treatment, which includes all
asthma patients regardless of their severity, recommends inhaled corticosteroids
(ICS) in combination with a long-acting 2-agonist (LABA) as reliever therapy.
• Based on asthma severity, this treatment can also be used as maintenance therapy
(MART).
• When choosing a LABA in the combination treatment, GINA recommends the use of
formoterol due to its long and rapid onset of action.
• A meta-analysis by O’Shea et al. from 2021 updated the evidence on the safety
profile and risk assessment of the combination of formoterol and ICS versus the
combination of salmeterol and ICS, and found no evidence of safety issues that
could affect the choice between salmeterol and formoterol in combination inhalers
used for regular maintenance therapy by adults and children with asthma.
• Finally, GINA does not recommend asthma patients being treated with short-acting
2-agonists (SABAs) in monotherapy
1. Global Initiative for Asthma. Global Strategy for Asthma Management and Prevention. 2022. Available online: https://ginasthma. org/wp-
content/uploads/2022/07/GINA-Main-Report-2022-FINAL-22-07-01-WMS.pdf (accessed on 1 December 2022).
2. Global Initiative for Asthma. Global Strategy for Asthma Management and Prevention. 2019. Available online: https://ginasthma.org/wp-
content/uploads/2019/06/GINA-2019-main-report-June-2019-wms.pdf (accessed on 1 December 2022).
3. O’Shea, O.; Stovold, E.; Cates, C.J. Regular treatment with formoterol and an inhaled corticosteroid versus regular treatment with salmeterol
and an inhaled corticosteroid for chronic asthma: Serious adverse events. Cochrane Database Syst. Rev. 2021, 4,CD007694. [PubMed]

12. A summary of the GINA Guidelines from 2018
compared with the GINA guidelines from 2022.
Holst, S.S.; Sabedin, E.; Sabedin, E.; Vermehren, C. A Shift in Asthma Treatment According to New Guidelines: An Evaluation of Asthma Patients’ Attitudes towards Treatment Change.
Int. J. Environ. Res. Public Health 2023, 20, 3453. https://doi.org/10.3390/ijerph20043453

13. Antioxidant in Asthma
• Epidemiological data suggest that antioxidants have a
significant effect on the incidence and severity of asthma.
• It was shown that asthma and airflow limitation are
associated with deficiency of various antioxidants, such
as carotenoids, retinol, coenzyme Q10, and vitamin C, D,
and E.
• In many studies, total antioxidant status of the serum in
asthmatics was lower when compared with healthy
controls.
Jesenak M, Zelieskova M and Babusikova E (2017) Oxidative Stress and Bronchial Asthma in Children—Causes or Consequences? Front. Pediatr. 5:162. doi: 10.3389/fped.2017.00162

14. CoQ10 Levels in Asthma
• Coenzyme Q10 (ubichinone), a vitamin-like substance, represents an
important member of the antioxidative potential in humans.
• This substance plays a decisive role in the production of cell energy and in
the scavenger activity of free oxygen radicals.
• Most concentrations of CoQ10 represent tissues and organs with a high
need of energy consumption.
• Gazdik et al, demonstrated significantly decreased concentrations of
CoQ10, both in plasma and whole blood, in patients with allergic asthma
in comparison with healthy controls.
Gazdík F, Gvozdjáková A, Nádvorníková R, et al. Decreased levels of coenzyme Q(10) in patients with bronchial asthma. Allergy. 2002 Sep;57(9):811-814. DOI: 10.1034/j.1398-9995.2002.23747.x.
PMID: 12169177.

15. CoQ10 as an Antioxidant in Asthma
• Mitochondrial-directed therapeutics are relatively new, and understanding their
role in asthma treatment needs more studies.
• Mitochondria are sources of ROS and susceptible to oxidative damage (ie, the
oxidation of mtDNA, proteins, Coenzyme Q reductase (complex I), and other
respiratory complexes), resulting in impaired electron transport chain and
increased production of mtROS.
• Antioxidants can particularly protect mitochondria against oxidative damage.
• CoQ10 as a mitochondria-targeted antioxidant composed of ubiquinone covalently
linked to a cationic moiety, has promised a highly effective therapeutic agent and is
able to selectively accumulate within the MIM of negatively charged mitochondria.
• However, mitochondria signaling has important effects in asthma pathophysiology
and using Co-Q10 can control asthma and allergic rhinitis symptoms.
• Studies suggest that mitochondrial-directed therapies can alleviate lung
remodeling
1. Qian L, Mehrabi Nasab E, Athari SM, et al Mitochondria signaling pathways in allergic asthma Journal of Investigative Medicine 2022;70:863-882.
2. Peng, Jingwei & Ma, Jilong & Zhang, Lan & Lu, Banghao. (2020). Coenzyme Q10 attenuates airway inflammation and oxidative stress in neonatal asthmatic rats. Tropical Journal of
Pharmaceutical Research. 19. 1969-1975. 10.4314/tjpr.v19i9.24.

16. CoQ10 as an Antioxidant in Asthma
• Co-Q10, which is structurally similar to vitamin K, has three biological
functions. It enhances mitochondrial ATP for energy production, provides
antioxidant effects, and enhances cell membrane stabilization.
• Co-Q10 also known as ubiquinol-10, is an endogenous enzyme cofactor in
mitochondria and lysosomes that catalyzes proton/electron translocation
and protects mitochondria from free radical damage may play a role in
preventing programmed cell death or apoptosis.
• CoQ10-induced anti-allergic effects were mediated by up-regulation of
Nrf2 and the induction of antiinflammation defense mechanisms.
• CoQ10 quenches ROS, including superoxide and peroxynitrite, and
protects mitochondria against oxidative damage.
• Coenzyme Q10 restores eNOS activity and reduces free-radical formation.
1. Qian L, Mehrabi Nasab E, Athari SM, et al Mitochondria signaling pathways in allergic asthma Journal of Investigative Medicine 2022;70:863-882.
2. Peng, Jingwei & Ma, Jilong & Zhang, Lan & Lu, Banghao. (2020). Coenzyme Q10 attenuates airway inflammation and oxidative stress in neonatal asthmatic rats. Tropical Journal of
Pharmaceutical Research. 19. 1969-1975. 10.4314/tjpr.v19i9.24.

17. CoQ10 as an Antioxidant in Asthma
• Results: coenzyme Q10 supplementation significantly decreased lipid peroxidation, and reduced
inflammatory cells and IgE levels, while the antioxidant levels were enhanced (p < 0.05). Moreover, coenzyme
Q10 reduced the levels of Th2 cytokines and downregulated the expressions of NF-κB, TNF-α, IL-6, and iNOS
in the neonatal asthmatic rats (p < 0.05).
• Conclusion: Coenzyme Q10 attenuates airway inflammation and oxidative stress in neonatal asthmatic rats.
Thus, coenzyme Q10 has promising therapeutic potential in the management of asthma.

18. CoQ10 as an Antioxidant in Asthma
Results: Co-Q10 with two supplementation (Mg-S and O-3) modulate MRC, BALf eosinophils, eosinophilic-
inflammation related genes (eotaxin, CCL11 and CCL24), peribronchial and perivascular inflammation, EPO, type 2
cytokines (IL-4, 5 and 13), IgE, histamine, Cyc-LT and LTB4 as main allergic bio-factors. Importantly, Co-Q10
treatment increased Nrf2 expression and Nrf2 induced antioxidant genes, glutathione redox and inhibited
inflammation, oxidative stress injury, Th2 cytokines production and attenuated allergic inflammatory responses.

19. CoQ10 as an Antioxidant in Asthma
• The patients were divided into two groups, one group receiving standard antiasthmatic therapy and clinically
stabilized, and the second group receiving, in addition, antioxidants consisting of CoQ10 (120 mg) + 400 mg
α-tocopherol + 250 mg vitamin C a day. The groups were crossed over at 16 weeks for a total duration of 32
weeks.
• Results and conclusions: Data show that patients with corticosteroid-dependent bronchial asthma have low
plasma CoQ10 concentrations that may contribute to their antioxidant imbalance and oxidative stress. A
reduction in the dosage of corticosteroids required by the patients following antioxidant supplementation
was observed, indicating lower incidence of potential adverse effects of the drugs, decreased oxidative
stress.

20. Thankyou