Novel Therapeutic Strategies in Asthma-Chronic Obstructive Pulmonary Disease Overlap

Heaney L.G. Busby J. Hanratty C.E. et al.

Composite type-2 biomarker strategy versus a symptom-risk-based algorithm to adjust corticosteroid dose in patients with severe asthma: a multicentre, single-blind, parallel group, randomised controlled trial.

Lancet Respir Med. 9: 57-68George L. Brightling C.E.

Eosinophilic airway inflammation: role in asthma and chronic obstructive pulmonary disease.

Ther Adv Chronic Dis. 7: 34-51Normansell R. Walker S. Milan S.J. et al.

Omalizumab for asthma in adults and children.

Cochrane Database Syst Rev. 1: CD003559Putcha N. Fawzy A. Matsui E.C. et al.

Clinical Phenotypes of Atopy and Asthma in COPD: A Meta-analysis of SPIROMICS and COPDGene.

Chest. 158: 2333-2345Stoll P. Bähker A. Ulrich M. et al.

The dendritic cell high-affinity IgE receptor is overexpressed in both asthma and severe COPD.

Clin Exp Allergy. 46: 575-583Hanania N.A. Chipps B.E. Griffin N.M. et al.

Omalizumab effectiveness in asthma-COPD overlap: Post hoc analysis of PROSPERO.

J Allergy Clin Immunol. 143: 1629-1633.e2Maltby S. Gibson P.G. Powell H. et al.

Omalizumab Treatment Response in a Population With Severe Allergic Asthma and Overlapping COPD.

Chest. 151: 78-89Hanania N.A. Fortis S. Haselkorn T. et al.

Omalizumab in Asthma with Fixed Airway Obstruction: Post Hoc Analysis of EXTRA.

J Allergy Clin Immunol Pract. 10: 222-228Pavord I.D. Korn S. Howarth P. et al.

Mepolizumab for severe eosinophilic asthma (DREAM): a multicentre, double-blind, placebo-controlled trial.

Lancet. 380: 651-659Bel E.H. Wenzel S.E. Thompson P.J. et al.

Oral glucocorticoid-sparing effect of mepolizumab in eosinophilic asthma.

N Engl J Med. 371: 1189-1197Ortega H.G. Liu M.C. Pavord I.D. et al.

Mepolizumab treatment in patients with severe eosinophilic asthma.

N Engl J Med. 371: 1198-1207Castro M. Zangrilli J. Wechsler M.E. et al.

Reslizumab for inadequately controlled asthma with elevated blood eosinophil counts: results from two multicentre, parallel, double-blind, randomised, placebo-controlled, phase 3 trials.

Lancet Respir Med. 3: 355-366Bleecker E.R. FitzGerald J.M. Chanez P. et al.

Efficacy and safety of benralizumab for patients with severe asthma uncontrolled with high-dosage inhaled corticosteroids and long-acting beta2-agonists (SIROCCO): a randomised, multicentre, placebo-controlled phase 3 trial.

Lancet. 388: 2115-2127FitzGerald J.M. Bleecker E.R. Nair P. et al.

Benralizumab, an anti-interleukin-5 receptor alpha monoclonal antibody, as add-on treatment for patients with severe, uncontrolled, eosinophilic asthma (CALIMA): a randomised, double-blind, placebo-controlled phase 3 trial.

Lancet. 388: 2128-2141Nair P. Wenzel S. Rabe K.F. et al.

Oral Glucocorticoid-Sparing Effect of Benralizumab in Severe Asthma.

N Engl J Med. 376: 2448-2458Bafadhel M. McCormick M. Saha S. et al.

Profiling of sputum inflammatory mediators in asthma and chronic obstructive pulmonary disease.

Respiration. 83: 36-44Brightling C.E. Bleecker E.R. Panettieri Jr., R.A. et al.

Benralizumab for chronic obstructive pulmonary disease and sputum eosinophilia: a randomised, double-blind, placebo-controlled, phase 2a study.

Lancet Respir Med. 2: 891-901Criner G.J. Celli B.R. Brightling C.E. et al.

Benralizumab for the Prevention of COPD Exacerbations.

N Engl J Med. 381: 1023-1034Criner G.J. Celli B.R. Singh D. et al.

Predicting response to benralizumab in chronic obstructive pulmonary disease: analyses of GALATHEA and TERRANOVA studies.

Lancet Respir Med. 8: 158-170

Acute Exacerbations Treated With BenRAlizumab (The ABRA Study) (ABRA).

() ()Pavord I.D. Chanez P. Criner G.J. et al.

Mepolizumab for Eosinophilic Chronic Obstructive Pulmonary Disease.

N Engl J Med. 377: 1613-1629

Mepolizumab as Add-on Treatment IN Participants With COPD Characterized by Frequent Exacerbations and Eosinophil Level (MATINEE).

() ()

Mepolizumab for COPD Hospital Eosinophilic Admissions Pragmatic Trial (COPD-HELP).

() ()Hanania N.A. Korenblat P. Chapman K.R. et al.

Efficacy and safety of lebrikizumab in patients with uncontrolled asthma (LAVOLTA I and LAVOLTA II): replicate, phase 3, randomised, double-blind, placebo-controlled trials.

Lancet Respir Med. 4: 781-796Panettieri Jr., R.A. Sjöbring U. Péterffy A. et al.

Tralokinumab for severe, uncontrolled asthma (STRATOS 1 and STRATOS 2): two randomised, double-blind, placebo-controlled, phase 3 clinical trials.

Lancet Respir Med. 6: 511-525Yousuf A. Ibrahim W. Greening N.J. et al.

T2 Biologics for Chronic Obstructive Pulmonary Disease.

J Allergy Clin Immunol Pract. 7: 1405-1416Castro M. Corren J. Pavord I.D. et al.

Dupilumab Efficacy and Safety in Moderate-to-Severe Uncontrolled Asthma.

N Engl J Med. 378: 2486-2496

Pivotal Study to Assess the Efficacy, Safety and Tolerability of Dupilumab in Patients With Moderate-to-severe COPD With Type 2 Inflammation (BOREAS).

() ()Aneas I. Decker D.C. Howard C.L. et al.

Asthma-associated genetic variants induce IL33 differential expression through an enhancer-blocking regulatory region.

Nat Commun. 12: 6115Ketelaar M.E. Portelli M.A. Dijk F.N. et al.

Phenotypic and functional translation of IL33 genetics in asthma.

J Allergy Clin Immunol. 147: 144-157Wechsler M.E. Ruddy M.K. Pavord I.D. et al.

Efficacy and Safety of Itepekimab in Patients with Moderate-to-Severe Asthma.

N Engl J Med. 385: 1656-1668Kim S.W. Rhee C.K. Kim K.U. et al.

Factors associated with plasma IL-33 levels in patients with chronic obstructive pulmonary disease.

Int J Chron Obstruct Pulmon Dis. 12: 395-402Rabe K.F. Celli B.R. Wechsler M.E. et al.

Safety and efficacy of itepekimab in patients with moderate-to-severe COPD: a genetic association study and randomised, double-blind, phase 2a trial.

Lancet Respir Med. 9: 1288-1298Kelsen S.G. Agache I.O. Soong W. et al.

Astegolimab (anti-ST2) efficacy and safety in adults with severe asthma: A randomized clinical trial.

J Allergy Clin Immunol. 148: 790-798Yousuf A.J. Mohammed S. Carr L. et al.

Late Breaking Abstract - Astegolimab, an anti-ST2, in chronic obstructive pulmonary disease - COPD-ST2OP: a phase IIa, placebo-controlled trial.

Eur Respir J. 58: RCT206Diver S. Khalfaoui L. Emson C. et al.

Effect of tezepelumab on airway inflammatory cells, remodelling, and hyperresponsiveness in patients with moderate-to-severe uncontrolled asthma (CASCADE): a double-blind, randomised, placebo-controlled, phase 2 trial.

Lancet Respir Med. 9: 1299-1312Menzies-Gow A. Colice G. Griffiths J.M. et al.

NAVIGATOR: a phase 3 multicentre, randomized, double-blind, placebo-controlled, parallel-group trial to evaluate the efficacy and safety of tezepelumab in adults and adolescents with severe, uncontrolled asthma.

Respir Res. 21: 266

ClinicalTrials.gov. Tezepelumab COPD Exacerbation Study (COURSE).

() ()Brightling C.E. Brusselle G. Altman P.

The impact of the prostaglandin D(2) receptor 2 and its downstream effects on the pathophysiology of asthma.

Allergy. 75: 761-768Gonem S. Berair R. Singapuri A. et al.

Fevipiprant, a prostaglandin D2 receptor 2 antagonist, in patients with persistent eosinophilic asthma: a single-centre, randomised, double-blind, parallel-group, placebo-controlled trial.

Lancet Respir Med. 4: 699-707Castro M. Kerwin E. Miller D. et al.

Efficacy and safety of fevipiprant in patients with uncontrolled asthma: Two replicate, phase 3, randomised, double-blind, placebo-controlled trials (ZEAL-1 and ZEAL-2).

EClinicalMedicine. 35: 100847Brightling C.E. Gaga M. Inoue H. et al.

Effectiveness of fevipiprant in reducing exacerbations in patients with severe asthma (LUSTER-1 and LUSTER-2): two phase 3 randomised controlled trials.

Lancet Respir Med. 9: 43-56Snell N. Foster M. Vestbo J.

Efficacy and safety of AZD1981, a CRTH2 receptor antagonist, in patients with moderate to severe COPD.

Respir Med. 107: 1722-1730Bowen H. Kelly A. Lee T. et al.

Control of cytokine gene transcription in Th1 and Th2 cells.

Clin Exp Allergy. 38: 1422-1431Krug N. Hohlfeld J.M. Kirsten A.M. et al.

Allergen-induced asthmatic responses modified by a GATA3-specific DNAzyme.

N Engl J Med. 372: 1987-1995Greulich T. Hohlfeld J.M. Neuser P. et al.

A GATA3-specific DNAzyme attenuates sputum eosinophilia in eosinophilic COPD patients: a feasibility randomized clinical trial.

Respir Res. 19: 55Jang H.Y. Gu S. Lee S.M. et al.

Overexpression of sirtuin 6 suppresses allergic airway inflammation through deacetylation of GATA3.

J Allergy Clin Immunol. 138: 1452-1455.e13Ma K. Lu N. Zou F. et al.

Sirtuins as novel targets in the pathogenesis of airway inflammation in bronchial asthma.

Eur J Pharmacol. 865: 172670Panch S.R. Bozik M.E. Brown T. et al.

Dexpramipexole as an oral steroid-sparing agent in hypereosinophilic syndromes.

Blood. 132: 501-509Laidlaw T.M. Prussin C. Panettieri R.A. et al.

Dexpramipexole depletes blood and tissue eosinophils in nasal polyps with no change in polyp size.

Laryngoscope. 129: E61-E66

Dexpramipexole Dose-Ranging Biomarker Study in Subjects With Eosinophilic Asthma (AS201).

() ()Herath S.C. Normansell R. Maisey S. et al.

Prophylactic antibiotic therapy for chronic obstructive pulmonary disease (COPD).

Cochrane Database Syst Rev. 10: Cd009764

Global Initiative for Asthma. Global Strategy for Asthma Management and Prevention. Scientific Report 2021. Available at: https://ginasthma.org/gina-reports/.

Holguin F. Cardet J.C. Chung K.F. et al.

Management of severe asthma: a European Respiratory Society/American Thoracic Society guideline.

Eur Respir J. 55: 1900588Taylor S.L. Leong L.E.X. Mobegi F.M. et al.

Long-Term Azithromycin Reduces Haemophilus influenzae and Increases Antibiotic Resistance in Severe Asthma.

Am J Respir Crit Care Med. 200: 309-317Brusselle G.G. Vanderstichele C. Jordens P. et al.

Azithromycin for prevention of exacerbations in severe asthma (AZISAST): a multicentre randomised double-blind placebo-controlled trial.

Thorax. 68: 322-329Gibson P.G. Yang I.A. Upham J.W. et al.

Effect of azithromycin on asthma exacerbations and quality of life in adults with persistent uncontrolled asthma (AMAZES): a randomised, double-blind, placebo-controlled trial.

Lancet. 390: 659-668Taylor S.L. Ivey K.L. Gibson P.G. et al.

Airway abundance of Haemophilus influenzae predicts response to azithromycin in adults with persistent uncontrolled asthma.

Eur Respir J. 56: 2000194Haldar K. Bafadhel M. Lau K. et al.

Microbiome balance in sputum determined by PCR stratifies COPD exacerbations and shows potential for selective use of antibiotics.

PLoS One. 12: e0182833

Airway microbial dysbiosis in asthmatic patients: A target for prevention and treatment?.

J Allergy Clin Immunol. 139: 1071-1081Hua J.L. Hu W.P. Zuo Y.H. et al.

Prevention of Acute Exacerbation in Subjects with Moderate-to-very Severe COPD by Modulating Lower Respiratory Microbiome: Protocol of a Prospective, Multicenter, Randomized Controlled Trial.

Int J Chron Obstruct Pulmon Dis. 15: 2985-2990

Preclinical data and safety assessment of phage therapy in humans.

Curr Opin Biotechnol. 68: 310-317van Rijn A.L. van Boheemen S. Sidorov I. et al.

The respiratory virome and exacerbations in patients with chronic obstructive pulmonary disease.

PLoS One. 14: e0223952Choi S. Sohn K.H. Jung J.W. et al.

Lung virome: New potential biomarkers for asthma severity and exacerbation.

J Allergy Clin Immunol. 148: 1007-1015.e9Waters E.M. Neill D.R. Kaman B. et al.

Phage therapy is highly effective against chronic lung infections with Pseudomonas aeruginosa.

Thorax. 72: 666-667Djukanovic R. Harrison T. Johnston S.L. et al.

The effect of inhaled IFN-beta on worsening of asthma symptoms caused by viral infections. A randomized trial.

Am J Respir Crit Care Med. 190: 145-154Gielen V. Johnston S.L. Edwards M.R.

Azithromycin induces anti-viral responses in bronchial epithelial cells.

Eur Respir J. 36: 646-654Vermeersch K. Gabrovska M. Aumann J. et al.

Azithromycin during Acute Chronic Obstructive Pulmonary Disease Exacerbations Requiring Hospitalization (BACE). A Multicenter, Randomized, Double-Blind, Placebo-controlled Trial.

Am J Respir Crit Care Med. 200: 857-868Johnston S.L. Szigeti M. Cross M. et al.

Azithromycin for Acute Exacerbations of Asthma : The AZALEA Randomized Clinical Trial.

JAMA Intern Med. 176: 1630-1637Leung J.M. Tiew P.Y. Mac Aogáin M. et al.

The role of acute and chronic respiratory colonization and infections in the pathogenesis of COPD.

Respirology. 22: 634-650O'Driscoll B.R. Powell G. Chew F. et al.

Comparison of skin prick tests with specific serum immunoglobulin E in the diagnosis of fungal sensitization in patients with severe asthma.

Clin Exp Allergy. 39: 1677-1683Agbetile J. Bourne M. Fairs A. et al.

Effectiveness of voriconazole in the treatment of Aspergillus fumigatus-associated asthma (EVITA3 study).

J Allergy Clin Immunol. 134: 33-39

Novel Therapies to Inhibit Mucus Synthesis and Secretion in Airway Hypersecretory Diseases.

Pharmacology. 97: 84-100Woodruff P.G. Wolff M. Hohlfeld J.M. et al.

Safety and efficacy of an inhaled epidermal growth factor receptor inhibitor (BIBW 2948 BS) in chronic obstructive pulmonary disease.

Am J Respir Crit Care Med. 181: 438-445Alevy Y.G. Patel A.C. Romero A.G. et al.

IL-13-induced airway mucus production is attenuated by MAPK13 inhibition.

J Clin Invest. 122: 4555-4568Van As A. Kraft M. Hanania N.A. et al.Inhibition of airway mucus hypersecretion and inflammation with bio-11006, A novel dual action drug, results in improvement of indices of bronchitis and lung function in chronic obstructive pulmonary disease (COPD). 2011. American Thoracic Society Congress, ()Garner J.L. Shaipanich T. Hartman J.E. et al.

A prospective safety and feasibility study of metered cryospray for patients with chronic bronchitis in COPD.

Eur Respir J. 56: 2000556Valipour A. Fernandez-Bussy S. Ing A.J. et al.

Bronchial Rheoplasty for Treatment of Chronic Bronchitis. Twelve-Month Results from a Multicenter Clinical Trial.

Am J Respir Crit Care Med. 202: 681-689Dunican E.M. Watchorn D.C. Fahy J.V.

Autopsy and Imaging Studies of Mucus in Asthma. Lessons Learned about Disease Mechanisms and the Role of Mucus in Airflow Obstruction.

Ann Am Thorac Soc. 15: S184-S191Liu G. Philp A.M. Corte T. et al.

Therapeutic targets in lung tissue remodelling and fibrosis.

Pharmacol Ther. 225: 107839Baraldo S. Turato G. Badin C. et al.

Neutrophilic infiltration within the airway smooth muscle in patients with COPD.

Thorax. 59: 308-312Saunders R. Kaul H. Berair R. et al.

Fevipiprant reduces airway smooth muscle mass in asthmatics via PGD2 receptor antagonism.

Eur Respir J. 50: OA283Chachi L. Diver S. Kaul H. et al.

Computational modelling prediction and clinical validation of impact of benralizumab on airway smooth muscle mass in asthma.

Eur Respir J. 54: 1900930Delgado-Eckert E. James A. Meier-Girard D. et al.

Lung function fluctuation patterns unveil asthma and COPD phenotypes unrelated to type 2 inflammation.

J Allergy Clin Immunol. 148: 407-419Castro M. Rubin A.S. Laviolette M. et al.

Effectiveness and safety of bronchial thermoplasty in the treatment of severe asthma: a multicenter, randomized, double-blind, sham-controlled clinical trial.

Am J Respir Crit Care Med. 181: 116-124Wechsler M.E. Laviolette M. Rubin A.S. et al.

Bronchial thermoplasty: Long-term safety and effectiveness in patients with severe persistent asthma.

J Allergy Clin Immunol. 132: 1295-1302Chernyavsky I.L. Russell R.J. Saunders R.M. et al.

In vitro, in silico and in vivo study challenges the impact of bronchial thermoplasty on acute airway smooth muscle mass loss.

Eur Respir J. 51: 1701680Hu S.Y. Long F. Long L. et al.

[Analysis of the clinical efficacy and safety of bronchial thermoplasty in the treatment of patients with severe asthma and asthma-chronic obstructive pulmonary disease overlap].

Zhonghua Yi Xue Za Zhi. 101: 1071-1076Otoshi R. Baba T. Aiko N. et al.

Effectiveness and Safety of Bronchial Thermoplasty in the Treatment of Severe Asthma with Smoking History: A Single-Center Experience.

Int Arch Allergy Immunol. 181: 522-528Slebos D.J. Klooster K. Koegelenberg C.F. et al.

Targeted lung denervation for moderate to severe COPD: a pilot study.

Thorax. 70: 411-419Valipour A. Asadi S. Pison C. et al.

Long-term safety of bilateral targeted lung denervation in patients with COPD.

Int J Chron Obstruct Pulmon Dis. 13: 2163-2172Slebos D.J. Shah P.L. Herth F.J.F. et al.

Safety and Adverse Events after Targeted Lung Denervation for Symptomatic Moderate to Severe Chronic Obstructive Pulmonary Disease (AIRFLOW). A Multicenter Randomized Controlled Clinical Trial.

Am J Respir Crit Care Med. 200: 1477-1486Slebos D.J. Degano B. Valipour A. et al.

Design for a multicenter, randomized, sham-controlled study to evaluate safety and efficacy after treatment with the Nuvaira® lung denervation system in subjects with chronic obstructive pulmonary disease (AIRFLOW-3).

BMC Pulm Med. 20: 41Zakarya R. Chan Y.L. Rutting S. et al.

BET proteins are associated with the induction of small airway fibrosis in COPD.

Thorax. 76: 647-655Tian B. Hosoki K. Liu Z. et al.

Mucosal bromodomain-containing protein 4 mediates aeroallergen-induced inflammation and remodeling.

J Allergy Clin Immunol. 143: 1380-1394.e9Cazzola M. Rogliani P. Matera M.G.

The future of bronchodilation: looking for new classes of bronchodilators.

Eur Respir Rev. 28Wenzel S.E. Barnes P.J. Bleecker E.R. et al.

A randomized, double-blind, placebo-controlled study of tumor necrosis factor-alpha blockade in severe persistent asthma.

Am J Respir Crit Care Med. 179: 549-558Rennard S.I. Fogarty C. Kelsen S. et al.

The safety and efficacy of infliximab in moderate to severe chronic obstructive pulmonary disease.

Am J Respir Crit Care Med. 175: 926-934Pascoe S. Kanniess F. Bonner J. et al.

A monoclonal antibody to IL-1B attenuates the late asthmatic response to antigen challenge in patients with mild asthma.

Suppl. 50. 28. Eur Respir J, : 752 ()Calverley P.M.A. Sethi S. Dawson M. et al.

A randomised, placebo-controlled trial of anti-interleukin-1 receptor 1 monoclonal antibody MEDI8968 in chronic obstructive pulmonary disease.

Respir Res. 18: 153Rogliani P. Calzetta L. Ora J. et al.

Canakinumab for the treatment of chronic obstructive pulmonary disease.

Pulm Pharmacol Ther. 31: 15-27Osei E.T. Brandsma C.A. Timens W. et al.

Current perspectives on the role of interleukin-1 signalling in the pathogenesis of asthma and COPD.

Eur Respir J. 55Oronsky B. Reid T.R. Larson C. et al.

REPLATINUM Phase III randomized study: RRx-001 + platinum doublet versus platinum doublet in third-line small cell lung cancer.

Future Oncol. 15: 3427-3433Williams E.J. Negewo N.A. Baines K.J.

Role of the NLRP3 inflammasome in asthma: Relationship with neutrophilic inflammation, obesity, and therapeutic options.

J Allergy Clin Immunol. 147: 2060-2062Revez J.A. Bain L.M. Watson R.M. et al.

Effects of interleukin-6 receptor blockade on allergen-induced airway responses in mild asthmatics.

Clin Transl Immunol. 8: e1044Busse W.W. Holgate S. Kerwin E. et al.

Randomized, double-blind, placebo-controlled study of brodalumab, a human anti-IL-17 receptor monoclonal antibody, in moderate to severe asthma.

Am J Respir Crit Care Med. 188: 1294-1302

Study of Efficacy and Safety of Brodalumab Compared With Placebo in Inadequately Controlled Asthma Subjects With High Bronchodilator Reversibility.

() ()

Study to Assess the Efficacy and Safety of CJM112 in Patients With Inadequately Controlled Severe Asthma.

() ()Eich A. Urban V. Jutel M. et al.

A Randomized, Placebo-Controlled Phase 2 Trial of CNTO 6785 in Chronic Obstructive Pulmonary Disease.

COPD. 14: 476-483Whitehead G.S. Kang H.S. Thomas S.Y. et al.

Therapeutic suppression of pulmonary neutrophilia and allergic airway hyperresponsiveness by a RORγt inverse agonist.

JCI Insight. 5: e125528Brightling C.E. Nair P. Cousins D.J. et al.

Risankizumab in Severe Asthma - A Phase 2a, Placebo-Controlled Trial.

N Engl J Med. 385: 1669-1679O'Byrne P.M. Metev H. Puu M. et al.

Efficacy and safety of a CXCR2 antagonist, AZD5069, in patients with uncontrolled persistent asthma: a randomised, double-blind, placebo-controlled trial.

Lancet Respir Med. 4: 797-806Rennard S.I. Dale D.C. Donohue J.F. et al.

CXCR2 Antagonist MK-7123. A Phase 2 Proof-of-Concept Trial for Chronic Obstructive Pulmonary Disease.

Am J Respir Crit Care Med. 191: 1001-1011Mahler D.A. Huang S. Tabrizi M. et al.

Efficacy and safety of a monoclonal antibody recognizing interleukin-8 in COPD: a pilot study.

Chest. 126: 926-934Uddin M. Watz H. Malmgren A. et al.

NETopathic Inflammation in Chronic Obstructive Pulmonary Disease and Severe Asthma.

Front Immunol. 10: 47Khindri S. Cahn A. Begg M. et al.

A Multicentre, Randomized, Double-Blind, Placebo-Controlled, Crossover Study To Investigate the Efficacy, Safety, Tolerability, and Pharmacokinetics of Repeat Doses of Inhaled Nemiralisib in Adults with Persistent, Uncontrolled Asthma.

J Pharmacol Exp Ther. 367: 405-413Cahn A. Hamblin J.N. Begg M. et al.

Safety, pharmacokinetics and dose-response characteristics of GSK2269557, an inhaled PI3Kδ inhibitor under development for the treatment of COPD.

Pulm Pharmacol Ther. 46: 69-77Cahn A. Hamblin J.N. Robertson J. et al.

An Inhaled PI3Kδ Inhibitor Improves Recovery in Acutely Exacerbating COPD Patients: A Randomized Trial.

Int J Chron Obstruct Pulmon Dis. 16: 1607-1619Fahy W.A. Homayoun-Valiani F. Cahn A. et al.

Nemiralisib in Patients with an Acute Exacerbation of COPD: Placebo-Controlled, Dose-Ranging Study.

Int J Chron Obstruct Pulmon Dis. 16: 1637-1646Braithwaite I.E. Cai F. Tom J.A. et al.

Inhaled JAK inhibitor GDC-0214 reduces exhaled nitric oxide in patients with mild asthma: A randomized, controlled, proof-of-activity trial.

J Allergy Clin Immunol. 148: 783-789Li S. Hui Y. Yuan J. et al.

Syk-Targeted, a New 3-Arylbenzofuran Derivative EAPP-2 Blocks Airway Inflammation of Asthma-COPD Overlap in vivo and in vitro.

J Inflamm Res. 14: 2173-2185Ramis I. Otal R. Carreño C. et al.

A novel inhaled Syk inhibitor blocks mast cell degranulation and early asthmatic response.

Pharmacol Res. 99: 116-124Watz H. Barnacle H. Hartley B.F. et al.

Efficacy and safety of the p38 MAPK inhibitor losmapimod for patients with chronic o

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