In this article, I talked about the recent approaches to the management of asthma and COPD. The newly approved agents plus the families of drugs that are being studied and devices.

2. Contents
1. Introduction.................................................................................................................3
2. New advances in the therapeutic agents (approved and under studies)................3
2.1 Renefenacin (YUPELRI®)......................................................................................3
2.2 Fluticasone propionate/salmeterol (ADVAIR®).....................................................3
2.3 Muscarinic antagonist-ẞ-agonist............................................................................4
2.4 Non-selective selective glucocorticoid receptor agonists (SEGRA).....................4
2.5 Phosphodiesterase-4-inhibitos (PDE4)..................................................................4
2.6 Kinase inhibitors......................................................................................................5
2.6.1 p38 Mitogen-Activation Protein Kinase (p38-MAPK) inhibitors.......................5
2.6.2 Phosphoinostide-3-kinase (PI3k) inhibitors .....................................................5
2.6.3 Janus-kinase inhibitors (JAKinibs) ...................................................................5
3. New Pulmonary Delivering Devices..........................................................................6
4. Other Dosage Forms of Drugs Approved by the FDA .............................................7
Anti-immunoglobulin E drugs .................................................................................7
4.2 Interleukin-5 targeting agents.................................................................................7
5. Conclusion..................................................................................................................8
6. References used........................................................................................................8

3. 1. Introduction
Asthma and chronic obstructive pulmonary disease (COPD) are the most common pulmonary
related disorder, that require chronic and acute management. Current treatments are known to
be less than optimal for which new drugs are greatly needed. The pharmaceutical industry has
gotten better in providing medicines that satisfy the needs of patients with these disorders.
Besides the therapeutic choice, one more thing should be taken into consideration and that is
the choice of inhaler device. For over than 4000 years, the Indians started using aerosol drug
delivery, and since then approach gained the interest for treating both pulmonary and non-
pulmonary diseases. And now the voice of patients and clinician is being heard, leading
technologists to come up with a safer, more economic, and easy to use inhaler devices.
In this report I will cover some of the recent advances in the management of asthma and COPD
drugs and inhaler devices.
2. New advances in the therapeutic agents (approved and under studies)
2.1 Renefenacin(YUPELRI®)
Is a long-acting muscarinic antagonist (LAMA), that has been approved since
2018 for the management of COPD for patients older than 4 years.
It blocks the action of acetylcholine at muscarinic receptors (M1-M5) in the
bronchial airway leading to bronchodilation. It is orally inhaled using a
standard jet nebulizer connected to air compressor. Available as 175 mcg/3ml
vial and taken once daily (preferably at the same time each day)
2.2 Fluticasone propionate/salmeterol(ADVAIR®)
Is a combination of inhaled corticosteroid (ICS) and long acting ẞ-agonist (LABA),
that has been approved since 2019 in three strengths (100mcg/50mcg,
250mcg/50mcg and 500mcg/50mcg).
For asthma (4 years and older, twice daily) and for COPD (reduces exacerbation).
Not for acute relief.

4. 2.3 Muscarinic antagonist-ẞ-agonist
Bi-functional muscarinic antagonist, ẞ-agonist (MABA), dual bronchodilator therapy for the use in stable
moderate-to-severe COPD patients is a good pharmacological approach for those who cannot control
the symptoms by ultra-long-acting ẞ-agonist monotherapy. The advantages of this approach include,
delivering fixed ratio into every region of the lung thus decreasing the complexity of combinational
therapy, and providing a single pharmacokinetic profile. The one issue that is worth mentioning is the
minimal flexibility of the dose.
An example of this formulation is batefenterol which is still under development by GSK for COPD
management. The drug has both muscarinic receptor M2 and M3 blocking effect, and a ẞ2-antagnosim
effect.
2.4 Non-selective selective glucocorticoid receptoragonists (SEGRA)
Since ICS shown some pulmonary and systemic adverse reactions when chronically used, the search
for new glucocorticoid (GC) receptor (GR) modulators was essential. These group of agents activate
specific GR mechanisms and alter GR-mediated gene expression. GCs therapeutic profile can be
improved by enhancing the genomic mechanisms mediated by transpression, which is responsible for
several anti-inflammatory and immunomodulatory actions by inhibiting the expression of cytokines and
other pro-inflammatory molecules rather than transactivation which causes most of the GC-associated
adverse effects.
These agents are still being studied and evaluated for their effects and side effects, one example is
AZD7594; developed by AstraZeneca, which is in clinical trials for the use in COPD patients, it is a non-
steroidal, inhaled, selective GR modulator.
2.5 Phosphodiesterase-4-inhibitos (PDE4)
PDE is responsible for the mobilizing the intracellular second messenger cAMP and cGMP, PDE4 is a
subfamily of this enzyme that has four genes (A-D). the expression pf PDE4 has been demonstrated in
many inflammatory cells relevant to asthma and COPD; which makes it a therapeutic strategy for
inflammatory respiratory diseases. They inhibit the hydrolysis of cAMP, thereby increasing cAMP
concentration, and activate the downstream of phosphorylation cascade, and just like that it will relax
the airway smooth muscle and inhibit inflammation. They also reduce the exacerbation in patients with
severe COPD.

5. This group of agents are still under development. For example, CHF6001 and ensifentrine, the latter is
a dual PDE3 and 4 inhibitor that causes the airway smooth muscle to relax and suppress inflammation
(it began final-stage clinical evaluation in 2020 for COPD patients).
2.6 Kinase inhibitors
Kinase signaling pathway is responsible for the activation of pro-inflammatory transcription factors such
as nuclear factor-kB (NF-kB) and activator protein 1 (AP1) in asthma which is mostly derived by an
allergen, and COPD that is also mediated by multiple interacting kinase pathways.
Kinase is an enzyme that transfer ɣ-phosphate of ATP to hydrolysis-bearing substrates, thus the
phosphorylation of proteins, lipids, and sugar. And by this, it will activate the enzymes that cause cellular
translocation or interacting with other proteins causing signal transduction.
Since kinase inhibitors are used for several types of inflammation and for cancer, it was necessary to
come up with an inhaled delivery which may reduce the risk of systemic effects.
2.6.1 p38 Mitogen-Activation Protein Kinase (p38-MAPK)inhibitors
There is considerable evidence that p38 MAPK is activated in asthma and COPD, and that plays an
important role in driving chronic inflammation and in corticosteroid insensitivity.
An example of these inhibitors is CHF6297, is a new p38 MAPK inhibitor that has recently entered
phase 2 clinical trials for the evaluation of its safety and efficacy in COPD
2.6.2 Phosphoinostide-3-kinase (PI3k)inhibitors
Another subfamily of the kinase enzyme that is lipophilic and generates lipid second messengers, that
regulate cellular events such as innate and adaptive immune responses, growth, differentiation, cell
motility and survival. Evidence have shown that PI3K plays a key role in asthma and COPD through
the activation of inflammation, corticosteroid resistance and cellular senescence which accelerate
aging.
Examples of this group are GSK2269557 which completed phase 2 clinical trials and is progression to
phase 2b for COPD. And CHF6523 which is currently in phase 1 also for COPD.
2.6.3 Janus-kinase inhibitors (JAKinibs)
It regulates multiple fundamental biological processes, inflammatory and immune proteins and has
been implicated in many inflammatory diseases. Which makes it a good candidate to manage asthma
and COPD. They are still under development.

6. 3. New Pulmonary Delivering Devices
Inhaler devices are the most appropriate medical device used for delivering medications into the lungs.
The choice of the inhaler is just as important as the choice of the device.
BREO® ELLIPTA®
• It is a fixed dose combination of ICS fluticasone and LABA vilanterol
• Given as ellipta dry powder inhaler for asthma
• Approved in 2015, developed by GSK
BEVESPI AEROSPHERETM
• A combination of two long-acting bronchodilators (Glycopyrrolate and formoterol)
• Not a rescue inhaler
• Approved in 2016, developed by AstraZenca
Wixela® Inhub®
• The first generic version of Advair Diskus.
• Approved in 2019
Monaghan Aerobika OPEP and Versa PAP
• They are used as positive airway pressure device and a positive expiratpry
pressure device
• Approved in 2020

7. 4. Other Dosage Forms of Drugs Approved by the FDA
Anti-immunoglobulin E drugs
4.2 Interleukin-5 targeting agents
FasenraTM (benralizumab) is IL-5 receptor alpha chain monoclonal
antibody, which is approved as a treatment for severe eosinophilic
asthma and COPD. Used as a maintenance therapy for patients from
12 and older.

8. 5. Conclusion
To conclude, science till now is working to come up with a way that can reverse the damage on the
lung, or slow the progression. Which is the main driving force to discover new drugs and new
methods to deliver these drugs and this is what we have seen in the newly studied agents which
directly act on the inflammation processes.
The pulmonary agents and the delivery process to the lung is a whole science that still lacks sufficient
information and still has a lot to be added and discovered in the upcoming years.
6. References used
1) Arzu Ari & James B Fink (2020): Recent advances in aerosol devices for the delivery of inhaled medications,
Expert Opinion on Drug Delivery, DOI: 10.1080/17425247.2020.1712356
2) Amy E Defnet, Jeffery D Hasday, Paul Shapiro, Kinase inhibitors in the treatment of obstructive pulmonary
diseases, Current Opinion in Pharmacology, Volume 51, 2020, Pages 11-18, ISSN 1471-4892,
https://doi.org/10.1016/j.coph.2020.03.005.
3) Peter J. Barnes Pharmacological Reviews, Kinase Inhibitors in Airway Disease July 1, 2016, 68 (3) 788-815; DOI:
https://doi.org/10.1124/pr.116.012518
4) Federica Lo Bello , Philip M. Hansbro , Chantal Donovan , Irene Coppolino , Sharon Mumby , Ian M. Adcock &
Gaetano Caramori (2020): New drugs under development for COPD, Expert Opinion on Emerging Drugs, DOI:
10.1080/14728214.2020.1819982
5) Gross NJ, Barnes PJ. New Therapies for Asthma and Chronic Obstructive Pulmonary Disease. Am J Respir Crit
Care Med. 2017 Jan 15;195(2):159-166. doi: 10.1164/rccm.201610-2074PP. PMID: 27922751.
6) Cazzola, M., Lopez-Campos, J.-L., & Puente-Maestu, L. (2013). The MABA approach: a new option to improve
bronchodilator therapy. European Respiratory Journal, 42(4), 885–887. doi:10.1183/09031936.00067013
7) Shakshuki, A., & Agu, R. U. (2017). Improving the Efficiency of Respiratory Drug Delivery: A Review of Current
Treatment Trends and Future Strategies for Asthma and Chronic Obstructive Pulmonary Disease. Pulmonary
Therapy, 3(2), 267–281. doi:10.1007/s41030-017-0046-2
8) Phillips JE(2019) Inhaled Phosphodiesterase 4 (PDE4) Inhibitors for Inflammatory Respiratory Diseases. Front.
Pharmacol. 11:259. doi:10.3389/fphar.2020.00259
9) Jonathan Corren, New Targeted Therapies for Uncontrolled Asthma, The Journal of Allergy and Clinical
Immunology: In Practice, Volume 7, Issue 5, 2019, Pages 1394-1403, ISSN 2213-2198,
https://doi.org/10.1016/j.jaip.2019.03.022.
10) Constantinos Potamitis, Dimitra Siakouli, Konstantinos D. Papavasileiou, Athina Boulaka, Vassiliki Ganou, Marina
Roussaki, Theodora Calogeropoulou, Panagiotis Zoumpoulakis, Michael N. Alexis, Maria Zervou, Dimitra J.
Mitsiou, Discovery of New non-steroidal selective glucocorticoid receptor agonists, The Journal of Steroid
Biochemistry and Molecular Biology, Volume 186, 2019, Pages 142-153, ISSN 0960-0760,
https://doi.org/10.1016/j.jsbmb.2018.10.007.
11) Akshay Chandel, Amit K. Goyal, Goutam Ghosh, Goutam Rath, Recent advances in aerosolised drug delivery,
Biomedicine & Pharmacotherapy, Volume 112, 2019, 108601, ISSN 0753-3322,
https://doi.org/10.1016/j.biopha.2019.108601.
12) Rogliani P, Ritondo BL, Puxeddu E, Pane G, Cazzola M, Calzetta L. Experimental Glucocorticoid Receptor
Agonists for the Treatment of Asthma: A Systematic Review. J Exp Pharmacol. 2020;12:233-253
https://doi.org/10.2147/JEP.S237480
13) Philippe Rogueda & Daniela Traini (2016): The future of inhalers: how can we improve drug delivery in asthma
and COPD?, Expert Review of Respiratory Medicine, DOI: 10.1080/17476348.2016.1227246
14) AstraZenca, Bevespi Aerosphere™ approved by the US FDA for patients with COPD, 2016
https://www.astrazeneca.com/media-centre/press-releases/2016/bevespi-aerosphere-approved-by-the-us-fda-for-
patients-with-copd-25042016.html
15) Jill Murphy, Assistant Editor, Pharmacy Times, FDA Approves Budesonide/Glycopyrrolate/Formoterol Fumarate
for Treatment of Patients With COPD, 2020
https://www.pharmacytimes.com/news/fda-approves-budesonideglycopyrrolateformoterol-fumarate-for-treatment-
of-patients-with-copd?sp_url=copd