Asthma and Cardiovascular Diseases: Navigating Mutual Pharmacological Interferences.


Journal

Drugs
ISSN: 1179-1950
Titre abrégé: Drugs
Pays: New Zealand
ID NLM: 7600076

Informations de publication

Date de publication:
26 Sep 2024
Historique:
accepted: 14 08 2024
medline: 27 9 2024
pubmed: 27 9 2024
entrez: 26 9 2024
Statut: aheadofprint

Résumé

Asthma and cardiovascular disease (CVD) often co-exist. When a patient has both conditions, management requires an approach that addresses the unique challenges of each condition separately, while also considering their potential interactions. However, specific guidance on the management of asthma in patients with CVD and on the management of CVD in patients with asthma is still lacking. Nevertheless, health care providers need to adopt a comprehensive approach that includes both respiratory and CVD health. The management of CVD in patients with asthma requires a delicate balance between controlling respiratory symptoms and minimising potential cardiovascular (CV) risks. In the absence of specific guidelines for the management of patients with both conditions, the most prudent approach would be to follow established guidelines for each condition independently. Careful selection of asthma medications is essential to avoid exacerbation of CV symptoms. In addition, optimal management of CV risk factors is essential. However, close monitoring of these patients is important as there is evidence that some asthma medications may have adverse effects on CVD and, conversely, that some CVD medications may worsen asthma symptoms. On the other hand, there is also increasing evidence of the potential beneficial effects of asthma medications on CVD and, conversely, that some CVD medications may reduce the severity of asthma symptoms. We aim to elucidate the potential risks and benefits associated with the use of asthma medications in patients with CVD, and the potential pulmonary risks and benefits for patients with asthma who are prescribed CVD medications.

Identifiants

pubmed: 39327397
doi: 10.1007/s40265-024-02086-5
pii: 10.1007/s40265-024-02086-5
doi:

Types de publication

Journal Article Review

Langues

eng

Sous-ensembles de citation

IM

Informations de copyright

© 2024. The Author(s).

Références

Aggarwal K, Bansal V, Mahmood R, et al. Asthma and cardiovascular diseases: uncovering common ground in risk factors and pathogenesis. Cardiol Rev. 2023. https://doi.org/10.1097/CRD.0000000000000600 .
doi: 10.1097/CRD.0000000000000600 pubmed: 37643208
Guo J, Zhang Y, Liu T, et al. Allergic asthma is a risk factor for human cardiovascular diseases. Nat Cardiovas Res. 2022;1(5):417–30. https://doi.org/10.1038/s44161-022-00067-z .
doi: 10.1038/s44161-022-00067-z
Dodd KE, Blackley DJ, Mazurek JM. Cardiovascular disease among adults with work-related asthma, 2012–2017. Am J Prev Med. 2023;64(2):194–203. https://doi.org/10.1016/j.amepre.2022.09.010 .
doi: 10.1016/j.amepre.2022.09.010 pubmed: 36371324
Cazzola M, Hanania NA, Rogliani P, et al. Cardiovascular disease in asthma patients: from mechanisms to therapeutic implications. Kardiol Pol. 2023;81(3):232–41. https://doi.org/10.33963/KP.a2023.0038 .
doi: 10.33963/KP.a2023.0038 pubmed: 36739655
Wen LY, Ni H, Li KS, et al. Asthma and risk of stroke: a systematic review and meta-analysis. J Stroke Cerebrovasc Dis. 2016;25(3):497–503. https://doi.org/10.1016/j.jstrokecerebrovasdis.2015.11.030 .
doi: 10.1016/j.jstrokecerebrovasdis.2015.11.030 pubmed: 26803721
Wang L, Gao S, Yu M, Sheng Z, Tan W. Association of asthma with coronary heart disease: a meta analysis of 11 trials. PLoS ONE. 2017;12(6): e0179335. https://doi.org/10.1371/journal.pone.0179335 .
doi: 10.1371/journal.pone.0179335 pubmed: 28609456 pmcid: 5469478
Zhang B, Li ZF, An ZY, et al. Association between asthma and all-cause mortality and cardiovascular disease morbidity and mortality: a meta-analysis of cohort studies. Front Cardiovasc Med. 2022;9: 861798. https://doi.org/10.3389/fcvm.2022.861798 .
doi: 10.3389/fcvm.2022.861798 pubmed: 35369308 pmcid: 8968068
Cepelis A, Brumpton BM, Laugsand LE, et al. Asthma, asthma control and risk of acute myocardial infarction: HUNT study. Eur J Epidemiol. 2019;34(10):967–77. https://doi.org/10.1007/s10654-019-00562-x .
doi: 10.1007/s10654-019-00562-x pubmed: 31512117
Hekking PP, Amelink M, Wener RR, Bouvy ML, Bel EH. Comorbidities in difficult-to-control asthma. J Allergy Clin Immunol Pract. 2018;6(1):108–13. https://doi.org/10.1016/j.jaip.2017.06.008 .
doi: 10.1016/j.jaip.2017.06.008 pubmed: 28734857
Rogliani P, Laitano R, Ora J, Beasley R, Calzetta L. Strength of association between comorbidities and asthma: a meta-analysis. Eur Respir Rev. 2023;32(167): 220202. https://doi.org/10.1183/16000617.0202-2022 .
doi: 10.1183/16000617.0202-2022 pubmed: 36889783 pmcid: 10032614
Pollevick ME, Xu KY, Mhango G, et al. The relationship between asthma and cardiovascular disease: an examination of the Framingham Offspring Study. Chest. 2021;159(4):1338–45. https://doi.org/10.1016/j.chest.2020.11.053 .
doi: 10.1016/j.chest.2020.11.053 pubmed: 33316236
Choi HG, Kwon MJ, Kim JH, et al. Association between asthma and cardiovascular diseases: a longitudinal follow-up study using a national health screening cohort. World Allergy Organ J. 2024;17(6): 100907. https://doi.org/10.1016/j.waojou.2024.100907 .
doi: 10.1016/j.waojou.2024.100907 pubmed: 38873616 pmcid: 11170141
Schanen JG, Iribarren C, Shahar E, et al. Asthma and incident cardiovascular disease: the Atherosclerosis Risk in Communities Study. Thorax. 2005;60(8):633–8. https://doi.org/10.1136/thx.2004.026484 .
doi: 10.1136/thx.2004.026484 pubmed: 16061703 pmcid: 1747501
Cazzola M, Calzetta L, Bettoncelli G, et al. Cardiovascular disease in asthma and COPD: a population-based retrospective cross-sectional study. Respir Med. 2012;106(2):249–56. https://doi.org/10.1016/j.rmed.2011.07.021 .
doi: 10.1016/j.rmed.2011.07.021 pubmed: 21856140
Valencia-Hernández CA, Del Greco MF, Sundaram V, Portas L, Minelli C, Bloom CI. Asthma and incident coronary heart disease: an observational and Mendelian randomisation study. Eur Respir J. 2023;62(5):2301788. https://doi.org/10.1183/13993003.01788-2023 .
doi: 10.1183/13993003.01788-2023 pubmed: 37945032 pmcid: 10695770
Cazzola M, Calzetta L, Bettoncelli G, Novelli L, Cricelli C, Rogliani P. Asthma and comorbid medical illness. Eur Respir J. 2011;38(1):42–9. https://doi.org/10.1183/09031936.00140310 .
doi: 10.1183/09031936.00140310 pubmed: 21177843
Wang S, Liu H, Yang P, et al. Exploring the genetic association of allergic diseases with cardiovascular diseases: a bidirectional Mendelian randomization study. Front Immunol. 2023;14:1175890. https://doi.org/10.3389/fimmu.2023.1175890 .
doi: 10.3389/fimmu.2023.1175890 pubmed: 37334359 pmcid: 10272545
Kreslová M, Kirchnerová O, Rajdl D, et al. Bronchial asthma as a cardiovascular risk factor: a prospective observational study. Biomedicines. 2022;10(10):2614. https://doi.org/10.3390/biomedicines10102614 .
doi: 10.3390/biomedicines10102614 pubmed: 36289876 pmcid: 9599703
Tattersall MC, Dasiewicz AS, McClelland RL, et al. Persistent asthma is associated with carotid plaque in MESA. J Am Heart Assoc. 2022;11(23): e026644. https://doi.org/10.1161/JAHA.122.026644 .
doi: 10.1161/JAHA.122.026644 pubmed: 36416156 pmcid: 9851438
Cazzola M, Page CP, Matera MG, et al. Revisiting asthma pharmacotherapy: where do we stand and where do we want to go? Eur Respir J. 2023;62(2):2300700. https://doi.org/10.1183/13993003.00700-2023 .
doi: 10.1183/13993003.00700-2023 pubmed: 37474159
Hung MJ, Mao CT, Hung MY, Chen TH. Impact of asthma on the development of coronary vasospastic angina: a population-based cohort study. Medicine (Baltimore). 2015;94(42): e1880. https://doi.org/10.1097/MD.0000000000001880 .
doi: 10.1097/MD.0000000000001880 pubmed: 26496346
Sakata Y, Komamura K, Hirayama A, et al. Elevation of the plasma histamine concentration in the coronary circulation in patients with variant angina. Am J Cardiol. 1996;77(12):1121–6. https://doi.org/10.1016/s0002-9149(96)00147-6 .
doi: 10.1016/s0002-9149(96)00147-6 pubmed: 8644672
Bazan-Socha S, Wójcik K, Olchawa M, et al. Increased oxidative stress in asthma-relation to inflammatory blood and lung biomarkers and airway remodeling indices. Biomedicines. 2022;10(7):1499. https://doi.org/10.3390/biomedicines10071499 .
doi: 10.3390/biomedicines10071499 pubmed: 35884804 pmcid: 9312921
Incalza MA, D’Oria R, Natalicchio A, et al. Oxidative stress and reactive oxygen species in endothelial dysfunction associated with cardiovascular and metabolic diseases. Vascul Pharmacol. 2018;100:1–19. https://doi.org/10.1016/j.vph.2017.05.005 .
doi: 10.1016/j.vph.2017.05.005 pubmed: 28579545
Chen E, Miller GE. Stress and inflammation in exacerbations of asthma. Brain Behav Immun. 2007;21(8):993–9. https://doi.org/10.1016/j.bbi.2007.03.009 .
doi: 10.1016/j.bbi.2007.03.009 pubmed: 17493786 pmcid: 2077080
Hoshide S, Mogi M, Kario K. Sympathetic nervous activation and hypertension. Hypertens Res. 2023;46(7):1636–7. https://doi.org/10.1038/s41440-023-01319-6 .
doi: 10.1038/s41440-023-01319-6 pubmed: 37402815
Cazzola M, Rogliani P, Calzetta L, et al. Bronchodilators in subjects with asthma-related comorbidities. Respir Med. 2019;151:43–8. https://doi.org/10.1016/j.rmed.2019.04.001 .
doi: 10.1016/j.rmed.2019.04.001 pubmed: 31047116
Ora J, Cavalli F, Cazzola M. Management of patients with asthma or COPD and cardiovascular disease: risks versus benefits. In: Martínez-García MA, Pépin J-L, Cazzola M, editors. Cardiovascular complications of respiratory disorders (ERS Monograph). Sheffield: European Respiratory Society; 2020. p. 66–81. https://doi.org/10.1183/2312508X.10027419 .
doi: 10.1183/2312508X.10027419
Levy ML, Bacharier LB, Bateman E, et al. Key recommendations for primary care from the 2022 Global Initiative for Asthma (GINA) update. NPJ Prim Care Respir Med. 2023;33(1):7. https://doi.org/10.1038/s41533-023-00330-1 .
doi: 10.1038/s41533-023-00330-1 pubmed: 36754956 pmcid: 9907191
Agache I, Akdis CA, Akdis M, et al. EAACI biologicals guidelines-recommendations for severe asthma. Allergy. 2021;76(1):14–44. https://doi.org/10.1111/all.14425 .
doi: 10.1111/all.14425 pubmed: 32484954
Ora J, Calzetta L, Matera MG, et al. Advances with glucocorticoids in the treatment of asthma: state of the art. Expert Opin Pharmacother. 2020;21(18):2305–16. https://doi.org/10.1080/14656566.2020.1807514 .
doi: 10.1080/14656566.2020.1807514 pubmed: 32808828
Varas-Lorenzo C, Rodriguez LA, Maguire A, Castellsague J, Perez-Gutthann S. Use of oral corticosteroids and the risk of acute myocardial infarction. Atherosclerosis. 2007;192(2):376–83. https://doi.org/10.1016/j.atherosclerosis.2006.05.019 .
doi: 10.1016/j.atherosclerosis.2006.05.019 pubmed: 16787647
Lefebvre P, Duh MS, Lafeuille MH, et al. Acute and chronic systemic corticosteroid-related complications in patients with severe asthma. J Allergy Clin Immunol. 2015;136(6):1488–95. https://doi.org/10.1016/j.jaci.2015.07.046 .
doi: 10.1016/j.jaci.2015.07.046 pubmed: 26414880
Ekström M, Nwaru BI, Hasvold P, et al. Oral corticosteroid use, morbidity and mortality in asthma: a nationwide prospective cohort study in Sweden. Allergy. 2019;74(11):2181–90. https://doi.org/10.1111/all.13874 .
doi: 10.1111/all.13874 pubmed: 31095758
Ng MK, Celermajer DS. Glucocorticoid treatment and cardiovascular disease. Heart. 2004;90(8):829–30. https://doi.org/10.1136/hrt.2003.031492 .
doi: 10.1136/hrt.2003.031492 pubmed: 15253942 pmcid: 1768346
Suissa S, Assimes T, Brassard P, et al. Inhaled corticosteroid use in asthma and the prevention of myocardial infarction. Am J Med. 2003;115(5):377–81. https://doi.org/10.1016/s0002-9343(03)00393-0 .
doi: 10.1016/s0002-9343(03)00393-0 pubmed: 14553873
Ayodele OA, Cabral HJ, McManus DD, et al. Glucocorticoids and risk of venous thromboembolism in asthma patients aged 20–59 years in the United Kingdom’s CPRD 1995–2015. Clin Epidemiol. 2022;14:83–93. https://doi.org/10.2147/CLEP.S341048 .
doi: 10.2147/CLEP.S341048 pubmed: 35082533 pmcid: 8786344
Camargo CA, Barr RG, Chen R, et al. Prospective study of inhaled corticosteroid use, cardiovascular mortality, and all-cause mortality in asthmatic women. Chest. 2008;134(3):546–51. https://doi.org/10.1378/chest.07-3126 .
doi: 10.1378/chest.07-3126 pubmed: 18641096
Podgórski M, Kupczyk M, Grzelak P, et al. Inhaled corticosteroids in asthma: promoting or protecting against atherosclerosis? Med Sci Monit. 2017;23:5337–44. https://doi.org/10.12659/msm.904469 .
doi: 10.12659/msm.904469 pubmed: 29120994 pmcid: 5691568
Daley-Yates PT. Inhaled corticosteroids: potency, dose equivalence and therapeutic index. Br J Clin Pharmacol. 2015;80(3):372–80. https://doi.org/10.1111/bcp.12637 .
doi: 10.1111/bcp.12637 pubmed: 25808113 pmcid: 4574823
Ye Q, He XO, D’Urzo A. A review on the safety and efficacy of inhaled corticosteroids in the management of asthma. Pulm Ther. 2017;3:1–18. https://doi.org/10.1007/s41030-017-0043-5 .
doi: 10.1007/s41030-017-0043-5
Matera MG, Rinaldi B, Calzetta L, Rogliani P, Cazzola M. Pharmacokinetics and pharmacodynamics of inhaled corticosteroids for asthma treatment. Pulm Pharmacol Ther. 2019;58: 101828. https://doi.org/10.1016/j.pupt.2019.101828 .
doi: 10.1016/j.pupt.2019.101828 pubmed: 31349002
Raissy HH, Kelly HW, Harkins M, Szefler SJ. Inhaled corticosteroids in lung diseases. Am J Respir Crit Care Med. 2013;187(8):798–803. https://doi.org/10.1164/rccm.201210-1853PP .
doi: 10.1164/rccm.201210-1853PP pubmed: 23370915 pmcid: 3707369
Rossi GA, Cerasoli F, Cazzola M. Safety of inhaled corticosteroids: room for improvement. Pulm Pharmacol Ther. 2007;20(1):23–35. https://doi.org/10.1016/j.pupt.2005.10.008 .
doi: 10.1016/j.pupt.2005.10.008 pubmed: 16359896
Rogliani P, Ora J, Cavalli F, Cazzola M, Calzetta L. Comparing the efficacy and safety profile of triple fixed-dose combinations in COPD: a meta-analysis and IBiS score. J Clin Med. 2022;11(15):4491. https://doi.org/10.3390/jcm11154491 .
doi: 10.3390/jcm11154491 pubmed: 35956108 pmcid: 9369741
Moore CD, Roberts JK, Orton CR, et al. Metabolic pathways of inhaled glucocorticoids by the CYP3A enzymes. Drug Metab Dispos. 2013;41(2):379–89. https://doi.org/10.1124/dmd.112.046318 .
doi: 10.1124/dmd.112.046318 pubmed: 23143891 pmcid: 3558858
Sevrioukova I. Interaction of human drug-metabolizing CYP3A4 with small inhibitory molecules. Biochemistry. 2019;58(7):930–9. https://doi.org/10.1021/acs.biochem.8b0122 .
doi: 10.1021/acs.biochem.8b0122 pubmed: 30676743
Macie C, Wooldrage K, Manfreda J, et al. Cardiovascular morbidity and the use of inhaled bronchodilators. Int J Chron Obstruct Pulmon Dis. 2008;3(1):163–9. https://doi.org/10.2147/copd.s1516 .
doi: 10.2147/copd.s1516 pubmed: 18488440 pmcid: 2528211
Dinenno FA, Jones PP, Seals DR, et al. Age-associated arterial wall thickening is related to elevations in sympathetic activity in healthy humans. Am J Physiol Heart Circ Physiol. 2000;278(4):H1205–10. https://doi.org/10.1152/ajpheart.2000.278.4.H1205 .
doi: 10.1152/ajpheart.2000.278.4.H1205 pubmed: 10749715
Lee CJ, Hwang J, Kang CY, et al. Asthma and increased risk of myocardial infarction and mortality among hypertensive Korean patients. Hypertens Res. 2023;46(7):1694–704. https://doi.org/10.1038/s41440-023-01257-3 .
doi: 10.1038/s41440-023-01257-3 pubmed: 36991063
Cazzola M, Page CP, Rogliani P, et al. β2-agonist therapy in lung disease. Am J Respir Crit Care Med. 2013;187(7):690–6. https://doi.org/10.1164/rccm.201209-1739PP .
doi: 10.1164/rccm.201209-1739PP pubmed: 23348973
Moore LE, Kapoor K, Byers BW, et al. Acute effects of salbutamol on systemic vascular function in people with asthma. Respir Med. 2019;155:133–40. https://doi.org/10.1016/j.rmed.2019.07.018 .
doi: 10.1016/j.rmed.2019.07.018 pubmed: 31349187
Snyder EM, Wong EC, Foxx-Lupo WT, et al. Effects of an inhaled β2-agonist on cardiovascular function and sympathetic activity in healthy subjects. Pharmacotherapy. 2011;31(8):748–56. https://doi.org/10.1592/phco.31.8.748 .
doi: 10.1592/phco.31.8.748 pubmed: 21923601
Matera MG, Martuscelli E, Cazzola M. Pharmacological modulation of β-adrenoceptor function in patients with coexisting chronic obstructive pulmonary disease and chronic heart failure. Pulm Pharmacol Ther. 2010;23(1):1–8. https://doi.org/10.1016/j.pupt.2009.10.001 .
doi: 10.1016/j.pupt.2009.10.001 pubmed: 19833222
Bristow MR, Ginsburg R, Umans V, et al. Beta 1- and beta 2-adrenergic-receptor subpopulations in nonfailing and failing human ventricular myocardium: coupling of both receptor subtypes to muscle contraction and selective beta 1-receptor down-regulation in heart failure. Circ Res. 1986;59(3):297–309. https://doi.org/10.1161/01.res.59.3.297 .
doi: 10.1161/01.res.59.3.297 pubmed: 2876788
Matera MG, Calzetta L, Cazzola M. β-Adrenoceptor modulation in chronic obstructive pulmonary disease: present and future perspectives. Drugs. 2013;73(15):1653–63. https://doi.org/10.1007/s40265-013-0120-5 .
doi: 10.1007/s40265-013-0120-5 pubmed: 24127222
Brodde OE, Michel MC. Adrenergic and muscarinic receptors in the human heart. Pharmacol Rev. 1999;51(4):651–90.
pubmed: 10581327
Matera MG, Panettieri RA Jr. β
doi: 10.1183/2312508X.10028519
Hanania NA, Dickey BF, Bond RA. Clinical implications of the intrinsic efficacy of beta-adrenoceptor drugs in asthma: full, partial and inverse agonism. Curr Opin Pulm Med. 2010;16(1):1–5. https://doi.org/10.1097/MCP.0b013e328333def8 .
doi: 10.1097/MCP.0b013e328333def8 pubmed: 19887938 pmcid: 2855430
Chan WL, Yang KP, Chao TF, et al. The association of asthma and atrial fibrillation—a nationwide population-based nested case–control study. Int J Cardiol. 2014;176(2):464–9. https://doi.org/10.1016/j.ijcard.2014.07.087 .
doi: 10.1016/j.ijcard.2014.07.087 pubmed: 25127961
Salpeter SR, Ormiston TM, Salpeter EE. Cardiovascular effects of beta-agonists in patients with asthma and COPD: a meta-analysis. Chest. 2004;125(6):2309–21. https://doi.org/10.1378/chest.125.6.2309 .
doi: 10.1378/chest.125.6.2309 pubmed: 15189956
Thottathil P, Acharya J, Moss AJ, et al. Risk of cardiac events in patients with asthma and long-QT syndrome treated with β
doi: 10.1016/j.amjcard.2008.05.029 pubmed: 18805113 pmcid: 4005827
Mohammad HA, Abdulfttah MT, Abdulazez AO, et al. A study of electrolyte disturbances in patients with chronic stable asthma and with asthma attacks. Egypt J Chest Dis Tuberc. 2014;63(3):529–34. https://doi.org/10.1016/j.ejcdt.2014.03.010 .
doi: 10.1016/j.ejcdt.2014.03.010
Zhang B, de Vries F, Setakis E, van Staa TP. The pattern of risk of myocardial infarction in patients taking asthma medication: a study with the General Practice Research Database. J Hypertens. 2009;27(7):1485–92. https://doi.org/10.1097/HJH.0b013e32832af68d .
doi: 10.1097/HJH.0b013e32832af68d pubmed: 19491706
Clausen T. Hormonal and pharmacological modification of plasma potassium homeostasis. Fundam Clin Pharmacol. 2010;24(5):595–605. https://doi.org/10.1111/j.1472-8206.2010.00859.x .
doi: 10.1111/j.1472-8206.2010.00859.x pubmed: 20618871
Skogestad J, Aronsen JM. Hypokalemia-induced arrhythmias and heart failure: new insights and implications for therapy. Front Physiol. 2018;9:1500. https://doi.org/10.3389/fphys.2018.01500 .
doi: 10.3389/fphys.2018.01500 pubmed: 30464746 pmcid: 6234658
Poelzing S, Veeraraghavan R. Heterogeneous ventricular chamber response to hypokalemia and inward rectifier potassium channel blockade underlies bifurcated T wave in guinea pig. Am J Physiol Heart Circ Physiol. 2007;292(6):H3043–51. https://doi.org/10.1152/ajpheart.01312.2006 .
doi: 10.1152/ajpheart.01312.2006 pubmed: 17307991
Weiss JN, Qu Z, Shivkumar K. Electrophysiology of hypokalemia and hyperkalemia. Circ Arrhythm Electrophysiol. 2017;10(3): e004667. https://doi.org/10.1161/CIRCEP.116.004667 .
doi: 10.1161/CIRCEP.116.004667 pubmed: 28314851 pmcid: 5399982
Daubert GP, Mabasa VH, Leung VW, et al. Acute clenbuterol overdose resulting in supraventricular tachycardia and atrial fibrillation. J Med Toxicol. 2007;3(2):56–60. https://doi.org/10.1007/BF03160909 .
doi: 10.1007/BF03160909 pubmed: 18072161 pmcid: 3550084
Zheng B, Yadav K. Acute salbutamol toxicity in the emergency department: a case report. World J Emerg Med. 2021;12(1):73–5. https://doi.org/10.5847/wjem.j.1920-8642.2021.01.012 .
doi: 10.5847/wjem.j.1920-8642.2021.01.012 pubmed: 33505554 pmcid: 7790705
Cepelis A, Brumpton BM, Malmo V, et al. Associations of asthma and asthma control with atrial fibrillation risk: results from the Nord-Trøndelag Health Study (HUNT). JAMA Cardiol. 2018;3(8):721–8. https://doi.org/10.1001/jamacardio.2018.1901 .
doi: 10.1001/jamacardio.2018.1901 pubmed: 29998294 pmcid: 6143075
Au DH, Curtis JR, Every NR, et al. Association between inhaled β-agonists and the risk of unstable angina and myocardial infarction. Chest. 2002;121(3):846–51. https://doi.org/10.1378/chest.121.3.846 .
doi: 10.1378/chest.121.3.846 pubmed: 11888971
Lee CH, Choi S, Jang EJ, et al. Inhaled bronchodilators and acute myocardial infarction: a nested case–control study. Sci Rep. 2017;7(1):17915. https://doi.org/10.1038/s41598-017-17890-1 .
doi: 10.1038/s41598-017-17890-1 pubmed: 29263396 pmcid: 5738390
Robin ED, McCauley R. Sudden cardiac death in bronchial asthma, and inhaled beta-adrenergic agonists. Chest. 1992;101(6):1699–702. https://doi.org/10.1378/chest.101.6.1699 .
doi: 10.1378/chest.101.6.1699 pubmed: 1350972
Squire I. Shortness of breath, prescription of bronchodilators and the risk of myocardial infarction. J Hypertens. 2009;27(7):1358–9. https://doi.org/10.1097/HJH.0b013e32832c4e06 .
doi: 10.1097/HJH.0b013e32832c4e06 pubmed: 19542987
Rossinen J, Partanen J, Stenius-Aarniala B, et al. Salbutamol inhalation has no effect on myocardial ischaemia, arrhythmias and heart-rate variability in patients with coronary artery disease plus asthma or chronic obstructive pulmonary disease. J Intern Med. 1998;243(5):361–6. https://doi.org/10.1046/j.1365-2796.1998.00291.x .
doi: 10.1046/j.1365-2796.1998.00291.x pubmed: 9651558
Uddin MJ, Groenwold RH, de Boer A, et al. Evaluating different physician’s prescribing preference based instrumental variables in two primary care databases: a study of inhaled long-acting beta2-agonist use and the risk of myocardial infarction. Pharmacoepidemiol Drug Saf. 2016;25(Suppl 1):132–41. https://doi.org/10.1002/pds.3860 .
doi: 10.1002/pds.3860 pubmed: 27038359
Au DH, Udris EM, Curtis JR, et al. Association between chronic heart failure and inhaled β-2-adrenoceptor agonists. Am Heart J. 2004;148(5):915–20. https://doi.org/10.1016/j.ahj.2004.03.048 .
doi: 10.1016/j.ahj.2004.03.048 pubmed: 15523327
Li Z, Ling Y, Chen Q, et al. Inhaled beta2-agonists increase in-hospital mortality in ICU patients with heart failure. Int Heart J. 2021;62(5):1076–82. https://doi.org/10.1536/ihj.20-825 .
doi: 10.1536/ihj.20-825 pubmed: 34544969
Sengstock DM, Obeidat O, Pasnoori V, et al. Asthma, β-agonists, and development of congestive heart failure: results of the ABCHF study. J Card Fail. 2002;8(4):232–8. https://doi.org/10.1054/jcaf.2002.127771 .
doi: 10.1054/jcaf.2002.127771 pubmed: 12397571
Bermingham M, O’Callaghan E, Dawkins I, et al. Are beta2-agonists responsible for increased mortality in heart failure? Eur J Heart Fail. 2011;13(8):885–91. https://doi.org/10.1093/eurjhf/hfr063 .
doi: 10.1093/eurjhf/hfr063 pubmed: 21791542
Maak CA, Tabas JA, McClintock DE. Should acute treatment with inhaled beta agonists be withheld from patients with dyspnea who may have heart failure? J Emerg Med. 2011;40(2):135–45. https://doi.org/10.1016/j.jemermed.2007.11.056 .
doi: 10.1016/j.jemermed.2007.11.056 pubmed: 18572345
Minasian AG, van den Elshout FJ, Dekhuijzen PN, et al. Bronchodilator responsiveness in patients with chronic heart failure. Heart Lung. 2013;42(3):208–14. https://doi.org/10.1016/j.hrtlng.2012.11.007 .
doi: 10.1016/j.hrtlng.2012.11.007 pubmed: 23273658
Burggraaf J, Westendorp RG, in’t Veen JC, et al. Cardiovascular side effects of inhaled salbutamol in hypoxic asthmatic patients. Thorax. 2001;56(7):567–9. https://doi.org/10.1136/thorax.56.7.567 .
doi: 10.1136/thorax.56.7.567 pubmed: 11413357 pmcid: 1746095
Amegadzie JE, Gamble JM, Farrell J, et al. Association between inhaled β-agonists initiation and risk of major adverse cardiovascular events: a population-based nested case–control study. Int J Chron Obstruct Pulmon Dis. 2022;17:1205–17. https://doi.org/10.2147/COPD.S35892 .
doi: 10.2147/COPD.S35892 pubmed: 35645559 pmcid: 9130098
Stolz D, Cazzola M. Characterising the cardiovascular safety profile of inhaled muscarinic receptor antagonists. In: Martínez-García MA, Pépin J-L, Cazzola M, editors. Cardiovascular complications of respiratory disorders (ERS Monograph). Sheffield: European Respiratory Society; 2020. p. 238–50. https://doi.org/10.1183/2312508X.10028619 .
doi: 10.1183/2312508X.10028619
Matera MG, Cazzola M. Muscarinic receptor antagonists. Handb Exp Pharmacol. 2017;237:41–62. https://doi.org/10.1007/164_2016_68 .
doi: 10.1007/164_2016_68 pubmed: 27787709
Patanè S. M3 muscarinic acetylcholine receptor in cardiology and oncology. Int J Cardiol. 2014;177(2):646–9. https://doi.org/10.1016/j.ijcard.2014.09.178 .
doi: 10.1016/j.ijcard.2014.09.178 pubmed: 25449471
Hang P, Zhao J, Qi J, et al. Novel insights into the pervasive role of M
doi: 10.2174/138945013804998963 pubmed: 23317008
Saternos HC, Almarghalani DA, Gibson HM, et al. Distribution and function of the muscarinic receptor subtypes in the cardiovascular system. Physiol Genomics. 2018;50(1):1–9. https://doi.org/10.1152/physiolgenomics.00062.2017 .
doi: 10.1152/physiolgenomics.00062.2017 pubmed: 29093194
Cazzola M, Page CP, Calzetta L, et al. Pharmacology and therapeutics of bronchodilators. Pharmacol Rev. 2012;64(3):450–504. https://doi.org/10.1124/pr.111.004580 .
doi: 10.1124/pr.111.004580 pubmed: 22611179
Lehrer PM, Hochron SM, Rausch L, et al. Effects of aerosol ipratropium bromide on cardiac vagal tone. Chest. 1994;105(6):1701–4. https://doi.org/10.1378/chest.105.6.1701 .
doi: 10.1378/chest.105.6.1701 pubmed: 8205863
Adimadhyam S, Schumock GT, Walton S, et al. Risk of arrhythmias associated with ipratropium bromide in children, adolescents, and young adults with asthma: a nested case–control study. Pharmacotherapy. 2014;34(4):315–23. https://doi.org/10.1002/phar.1336 .
doi: 10.1002/phar.1336 pubmed: 23918239
Kerstjens HA, Engel M, Dahl R, et al. Tiotropium in asthma poorly controlled with standard combination therapy. N Engl J Med. 2012;367(13):1198–207. https://doi.org/10.1056/NEJMoa1208606 .
doi: 10.1056/NEJMoa1208606 pubmed: 22938706
Kerstjens HA, Casale TB, Bleecker ER, et al. Tiotropium or salmeterol as add-on therapy to inhaled corticosteroids for patients with moderate symptomatic asthma: two replicate, double-blind, placebo-controlled, parallel-group, active-comparator, randomised trials. Lancet Respir Med. 2015;3(5):367–76. https://doi.org/10.1016/S2213-2600(15)00031-4 .
doi: 10.1016/S2213-2600(15)00031-4 pubmed: 25682232
Ohta K, Ichinose M, Tohda Y, et al. Long-term once-daily tiotropium Respimat
doi: 10.1371/journal.pone.0124109 pubmed: 25894430 pmcid: 4404354
Matera MG, Calzetta L, Rogliani P, et al. Cardiovascular events with the use of long-acting muscarinic receptor antagonists: an analysis of the FAERS database 2020–2023. Lung. 2024. https://doi.org/10.1007/s00408-024-00677-3 .
doi: 10.1007/s00408-024-00677-3 pubmed: 38321329 pmcid: 11009752
Li X, Obeidat M, Zhou G, et al. Responsiveness to ipratropium bromide in male and female patients with mild to moderate chronic obstructive pulmonary disease. EBioMedicine. 2017;19:139–45. https://doi.org/10.1016/j.ebiom.2017.04.020 .
doi: 10.1016/j.ebiom.2017.04.020 pubmed: 28461224 pmcid: 5440622
Calzetta L, Puxeddu E, Rogliani P. Gender-related responsiveness to the pharmacological treatment of COPD: a first step towards the personalized medicine. EBioMedicine. 2017;19:14–5. https://doi.org/10.1016/j.ebiom.2017.04.035 .
doi: 10.1016/j.ebiom.2017.04.035 pubmed: 28473238 pmcid: 5440626
Rogliani P, Cavalli F, Chetta A, et al. Potential drawbacks of ICS/LABA/LAMA triple fixed-dose combination therapy in the treatment of asthma: a quantitative synthesis of safety profile. J Asthma Allergy. 2022;15:565–77. https://doi.org/10.2147/JAA.S283489 .
doi: 10.2147/JAA.S283489 pubmed: 35573127 pmcid: 9091690
Bittar G, Friedman HS. The arrhythmogenicity of theophylline. A multivariate analysis of clinical determinants. Chest. 1991;99(6):1415–20. https://doi.org/10.1378/chest.99.6.1415 .
doi: 10.1378/chest.99.6.1415 pubmed: 2036824
Cazzola M, Page CP, Calzetta L, Rogliani P, Matera MG. Doxofylline: advancing and empowering equitable asthma and COPD management beyond tradition. Adv Ther. 2024. https://doi.org/10.1002/adtp.202400103 .
doi: 10.1002/adtp.202400103
Calzetta L, Hanania NA, Dini FL, et al. Impact of doxofylline compared to theophylline in asthma: a pooled analysis of functional and clinical outcomes from two multicentre, double-blind, randomized studies (DOROTHEO 1 and DOROTHEO 2). Pulm Pharmacol Ther. 2018;53:20–6. https://doi.org/10.1016/j.pupt.2018.09.007 .
doi: 10.1016/j.pupt.2018.09.007 pubmed: 30219705
Bäck M. Leukotriene signaling in atherosclerosis and ischemia. Cardiovasc Drugs Ther. 2009;23(1):41–8. https://doi.org/10.1007/s10557-008-6140-9 .
doi: 10.1007/s10557-008-6140-9 pubmed: 18949546
Capra V, Bäck M, Barbieri SS, et al. Eicosanoids and their drugs in cardiovascular diseases: focus on atherosclerosis and stroke. Med Res Rev. 2013;33(2):364–438. https://doi.org/10.1002/med.21251 .
doi: 10.1002/med.21251 pubmed: 22434418
Eaton A, Nagy E, Pacault M, et al. Cysteinyl leukotriene signaling through perinuclear CysLT
doi: 10.1007/s00109-012-0904-1 pubmed: 22527886
Muluhie M, Castiglioni L, Rzemieniec J, et al. Montelukast, an available and safe anti-asthmatic drug, prevents maladaptive remodelling and maintains cardiac functionality following myocardial infarction. Sci Rep. 2024;14(1):3371. https://doi.org/10.1038/s41598-024-53936-x .
doi: 10.1038/s41598-024-53936-x pubmed: 38337010 pmcid: 10858037
Zhou X, Cai J, Liu W, et al. Cysteinyl leukotriene receptor type 1 (CysLT1R) antagonist zafirlukast protects against TNF-α-induced endothelial inflammation. Biomed Pharmacother. 2019;111:452–9. https://doi.org/10.1016/j.biopha.2018.12.064 .
doi: 10.1016/j.biopha.2018.12.064 pubmed: 30594784
Ingelsson E, Yin L, Bäck M. Nationwide cohort study of the leukotriene receptor antagonist montelukast and incident or recurrent cardiovascular disease. J Allergy Clin Immunol. 2012;129(3):702-707.e2. https://doi.org/10.1016/j.jaci.2011.11.052 .
doi: 10.1016/j.jaci.2011.11.052 pubmed: 22244598
Hoxha M, Tedesco CC, Quaglin S, et al. Montelukast use decreases cardiovascular events in asthmatics. Front Pharmacol. 2021;11: 611561. https://doi.org/10.3389/fphar.2020.611561 .
doi: 10.3389/fphar.2020.611561 pubmed: 33519477 pmcid: 7838535
Allayee H, Hartiala J, Lee W, et al. The effect of montelukast and low-dose theophylline on cardiovascular disease risk factors in asthmatics. Chest. 2007;132(3):868–74. https://doi.org/10.1378/chest.07-0831 .
doi: 10.1378/chest.07-0831 pubmed: 17646220
Altawalbeh SM, Thorpe CT, Zgibor JC, et al. Antileukotriene agents versus long-acting beta-agonists in older adults with persistent asthma: a comparison of add-on therapies. J Am Geriatr Soc. 2016;64(8):1592–600. https://doi.org/10.1111/jgs.14235 .
doi: 10.1111/jgs.14235 pubmed: 27351988 pmcid: 7961814
Reddel HK, Bacharier LB, Bateman ED, et al. Global Initiative for Asthma Strategy 2021: executive summary and rationale for key changes. Eur Respir J. 2022;59:2102730. https://doi.org/10.1183/13993003.02730-2021 .
doi: 10.1183/13993003.02730-2021 pubmed: 34667060 pmcid: 8719459
Ray WA, Murray KT, Hall K, Arbogast PG, Stein CM. Azithromycin and the risk of cardiovascular death. N Engl J Med. 2012;366(20):1881–90. https://doi.org/10.1056/NEJMoa1003833 .
doi: 10.1056/NEJMoa1003833 pubmed: 22591294 pmcid: 3374857
Albert RK, Schuller JL, COPD Clinical Research Network. Macrolide antibiotics and the risk of cardiac arrhythmias. Am J Respir Crit Care Med. 2014;189(10):1173–80. https://doi.org/10.1164/rccm.201402-0385CI .
doi: 10.1164/rccm.201402-0385CI pubmed: 24707986 pmcid: 4061901
Food and Drug Administration. FDA Drug Safety Communication: azithromycin (Zithromax or Zmax) and the risk of potentially fatal heart rhythms. 2013. http://www.fda.gov/drugs/drugsafety/ucm341822.htm . Accessed 30 Mar 2024.
Smith D, Du Rand IA, Addy C, et al. British Thoracic Society guideline for the use of long-term macrolides in adults with respiratory disease. BMJ Open Respir Res. 2020;7(1): e000489. https://doi.org/10.1136/bmjresp-2019-000489 .
doi: 10.1136/bmjresp-2019-000489 pubmed: 32332022 pmcid: 7204798
Kounis NG, Hahalis G. Serum IgE levels in coronary artery disease. Atherosclerosis. 2016;251:498–500. https://doi.org/10.1016/j.atherosclerosis.2016.05.045 .
doi: 10.1016/j.atherosclerosis.2016.05.045 pubmed: 27288268
Iribarren C, Rahmaoui A, Long AA, et al. Cardiovascular and cerebrovascular events among patients receiving omalizumab: results from EXCELS, a prospective cohort study in moderate to severe asthma. J Allergy Clin Immunol. 2017;139(5):1489–95. https://doi.org/10.1016/j.jaci.2016.07.038 .
doi: 10.1016/j.jaci.2016.07.038 pubmed: 27639934
Oblitas CM, Galeano-Valle F, Vela-De La Cruz L, et al. Omalizumab as a provoking factor for venous thromboembolism. Drug Target Insights. 2019;13:1177392819861987. https://doi.org/10.1177/1177392819861987 .
doi: 10.1177/1177392819861987 pubmed: 31320796 pmcid: 6611017
Quinta JB, Montastruc F, Sommet A, et al. Cardiovascular adverse effects of anti-IL-5/IL-5Rα therapies: a real-world study. J Allergy Clin Immunol Pract. 2021;9(3):1411–3. https://doi.org/10.1016/j.jaip.2020.12.031 .
doi: 10.1016/j.jaip.2020.12.031 pubmed: 33412311
Iribarren C, Rothman KJ, Bradley MS, et al. Cardiovascular and cerebrovascular events among patients receiving omalizumab: pooled analysis of patient-level data from 25 randomized, double-blind, placebo-controlled clinical trials. J Allergy Clin Immunol. 2017;139(5):1678–80. https://doi.org/10.1016/j.jaci.2016.12.953 .
doi: 10.1016/j.jaci.2016.12.953 pubmed: 28108337
Bleecker ER, Al-Ahmad M, Bjermer L, et al. Systemic corticosteroids in asthma: a call to action from World Allergy Organization and Respiratory Effectiveness Group. World Allergy Organ J. 2022;15(12): 100726. https://doi.org/10.1016/j.waojou.2022.100726 .
doi: 10.1016/j.waojou.2022.100726 pubmed: 36582404 pmcid: 9761384
Dorscheid DR, Lee JK, Ramesh W, et al. Guidance for administering biologics for severe asthma and allergic conditions. Can Respir J. 2022;2022:9355606. https://doi.org/10.1155/2022/9355606 .
doi: 10.1155/2022/9355606 pubmed: 36124286 pmcid: 9482537
Alton P, Hughes DM, Zhao SS. Cardiovascular safety of genetically proxied interleukin-5 inhibition: a Mendelian randomization study. Respir Investig. 2023;61(2):149–52. https://doi.org/10.1016/j.resinv.2022.12.004 .
doi: 10.1016/j.resinv.2022.12.004 pubmed: 36682083
Knutsson A, Björkbacka H, Dunér P, et al. Associations of interleukin-5 with plaque development and cardiovascular events. JACC Basic Transl Sci. 2019;4(8):891–902. https://doi.org/10.1016/j.jacbts.2019.07.002 .
doi: 10.1016/j.jacbts.2019.07.002 pubmed: 31909299 pmcid: 6939009
Kader HA, Azeem M, Jwayed SA, et al. Current insights into immunology and novel therapeutics of atopic dermatitis. Cells. 2021;10(6):1392. https://doi.org/10.3390/cells10061392 .
doi: 10.3390/cells10061392 pubmed: 34200009 pmcid: 8226506
Kakinuma T, Nakamura K, Wakugawa M, et al. Thymus and activation-regulated chemokine in atopic dermatitis: serum thymus and activation-regulated chemokine level is closely related with disease activity. J Allergy Clin Immunol. 2001;107(3):535–41. https://doi.org/10.1067/mai.2001.113237 .
doi: 10.1067/mai.2001.113237 pubmed: 11240957
Döring Y, van der Vorst EPC, Yan Y, et al. Identification of a non-canonical chemokine-receptor pathway suppressing regulatory T cells to drive atherosclerosis. Nat Cardiovasc Res. 2024;3:221–42. https://doi.org/10.1038/s44161-023-00413-9 .
doi: 10.1038/s44161-023-00413-9 pubmed: 39044999 pmcid: 7616283
Kataoka Y. Thymus and activation-regulated chemokine as a clinical biomarker in atopic dermatitis. J Dermatol. 2014;41(3):221–9. https://doi.org/10.1111/1346-8138.12440 .
doi: 10.1111/1346-8138.12440 pubmed: 24628072
Villani AP, Pavel AB, Wu J, et al. Vascular inflammation in moderate-to-severe atopic dermatitis is associated with enhanced Th2 response. Allergy. 2021;76(10):3107–21. https://doi.org/10.1111/all.14859 .
doi: 10.1111/all.14859 pubmed: 33866573
He H, Olesen CM, Pavel AB, et al. Tape-strip proteomic profiling of atopic dermatitis on dupilumab identifies minimally invasive biomarkers. Front Immunol. 2020;11:1768. https://doi.org/10.3389/fimmu.2020.01768 .
doi: 10.3389/fimmu.2020.01768 pubmed: 32849633 pmcid: 7423990
Chaplin S. Tezepelumab as add-on treatment for severe asthma. Prescriber. 2023;34(3):13–4. https://doi.org/10.1002/psb.2050 .
doi: 10.1002/psb.2050
Schonck WAM, Stroes ESG, Hovingh GK, Reeskamp LF. Long-term efficacy and tolerability of PCSK9 targeted therapy: a review of the literature. Drugs. 2024;84(2):165–78. https://doi.org/10.1007/s40265-024-01995-9 .
doi: 10.1007/s40265-024-01995-9 pubmed: 38267805 pmcid: 10981656
Baker JG, Wilcox RG. β-Blockers, heart disease and COPD: current controversies and uncertainties. Thorax. 2017;72(3):271–6. https://doi.org/10.1136/thoraxjnl-2016-208412 .
doi: 10.1136/thoraxjnl-2016-208412 pubmed: 27927840
Morales DR, Jackson C, Lipworth BJ, et al. Adverse respiratory effect of acute β-blocker exposure in asthma: a systematic review and meta-analysis of randomized controlled trials. Chest. 2014;145(4):779–86. https://doi.org/10.1378/chest.13-1235 .
doi: 10.1378/chest.13-1235 pubmed: 24202435
Morales DR, Lipworth BJ, Donnan PT, et al. Respiratory effect of beta-blockers in people with asthma and cardiovascular disease: population-based nested case control study. BMC Med. 2017;15(1):18. https://doi.org/10.1186/s12916-017-0781-0 .
doi: 10.1186/s12916-017-0781-0 pubmed: 28126029 pmcid: 5270217
Loth DW, Brusselle GG, Lahousse L, et al. β-Adrenoceptor blockers and pulmonary function in the general population: the Rotterdam study. Br J Clin Pharmacol. 2014;77(1):190–200. https://doi.org/10.1111/bcp.12181 .
doi: 10.1111/bcp.12181 pubmed: 23772842
Baker JG. The selectivity of β-adrenoceptor antagonists at the human β
doi: 10.1038/sj.bjp.0706048 pubmed: 15655528 pmcid: 1576008
Salpeter S, Ormiston T, Salpeter E. Cardioselective beta-blockers for reversible airway disease. Cochrane Database Syst Rev. 2002;1:CD002992. https://doi.org/10.1002/14651858.CD002992 .
doi: 10.1002/14651858.CD002992
Huang KY, Tseng PT, Wu YC, et al. Do beta-adrenergic blocking agents increase asthma exacerbation? A network meta-analysis of randomized controlled trials. Sci Rep. 2021;11(1):452. https://doi.org/10.1038/s41598-020-79837-3 .
doi: 10.1038/s41598-020-79837-3 pubmed: 33432057 pmcid: 7801657
Bennett M, Chang CL, Tatley M, et al. The safety of cardioselective β
doi: 10.1183/23120541.00801-2020 pubmed: 33681344 pmcid: 7917232
Parra S, Bond RA. Inverse agonism: from curiosity to accepted dogma, but is it clinically relevant? Curr Opin Pharmacol. 2007;7(2):146–50. https://doi.org/10.1016/j.coph.2006.10.005 .
doi: 10.1016/j.coph.2006.10.005 pubmed: 17284360
Walker JK, Penn RB, Hanania NA, et al. New perspectives regarding β
doi: 10.1111/j.1476-5381.2010.01178.x pubmed: 21175591 pmcid: 3085865
Rosendorff C, Lackland DT, Allison M, et al. Treatment of hypertension in patients with coronary artery disease: a scientific statement from the American Heart Association, American College of Cardiology, and American Society of Hypertension. J Am Coll Cardiol. 2015;65(18):1998–2038. https://doi.org/10.1016/j.jacc.2015.02.038 .
doi: 10.1016/j.jacc.2015.02.038 pubmed: 25840655
Hanania NA, Singh S, El-Wali R, et al. The safety and effects of the beta-blocker, nadolol, in mild asthma: an open-label pilot study. Pulm Pharmacol Ther. 2008;21(1):134–41. https://doi.org/10.1016/j.pupt.2007.07.002 .
doi: 10.1016/j.pupt.2007.07.002 pubmed: 17703976
Hanania NA, Mannava B, Franklin AE, et al. Response to salbutamol in patients with mild asthma treated with nadolol. Eur Respir J. 2010;36(4):963–5. https://doi.org/10.1183/09031936.00003210 .
doi: 10.1183/09031936.00003210 pubmed: 20889466
Bennett MR, Chang CL, Tuffery C, et al. The impact of regular bisoprolol on the response to salbutamol in asthma: a double-blind randomized placebo-controlled crossover trial. Respirology. 2021;26(3):225–32. https://doi.org/10.1111/resp.13955 .
doi: 10.1111/resp.13955 pubmed: 33043552
Matera MG, Rogliani P, Calzetta L, Cazzola M. An overview of the efficacy and safety of β
doi: 10.1080/14740338.2024.2362817 pubmed: 38813912
Tiotiu A, Novakova P, Kowal K, et al. Beta-blockers in asthma: myth and reality. Expert Rev Respir Med. 2019;13(9):815–22. https://doi.org/10.1080/17476348.2019.1649147 .
doi: 10.1080/17476348.2019.1649147 pubmed: 31352857
Oehme S, Mittag A, Schrödl W, et al. Agonist-induced β
doi: 10.1016/j.pupt.2014.05.007 pubmed: 24915152
Rinaldi B, Capuano A, Gritti G, et al. Effects of chronic administration of β-blockers on airway responsiveness in a murine model of heart failure. Pulm Pharmacol Ther. 2014;28(2):109–13. https://doi.org/10.1016/j.pupt.2014.04.005 .
doi: 10.1016/j.pupt.2014.04.005 pubmed: 24769100
Cheung D, Timmers MC, Zwinderman AH, et al. Long-term effects of a long-acting beta 2-adrenoceptor agonist, salmeterol, on airway hyperresponsiveness in patients with mild asthma. N Engl J Med. 1992;327(17):1198–203. https://doi.org/10.1056/NEJM199210223271703 .
doi: 10.1056/NEJM199210223271703 pubmed: 1357550
Lin R, Peng H, Nguyen LP, et al. Changes in β
doi: 10.1016/j.pupt.2007.06.003 pubmed: 17689122
Rinaldi B, Donniacuo M, Sodano L, et al. Effects of chronic treatment with the new ultra-long-acting β
doi: 10.1111/bph.13148 pubmed: 25825265 pmcid: 4507164
Taddei S, Bortolotto L. Unraveling the pivotal role of bradykinin in ACE inhibitor activity. Am J Cardiovasc Drugs. 2016;16(5):309–21. https://doi.org/10.1007/s40256-016-0173-3 .
doi: 10.1007/s40256-016-0173-3 pubmed: 27260014
Christiansen SC, Zuraw BL. Treatment of hypertension in patients with asthma. N Engl J Med. 2019;381(11):1046–57. https://doi.org/10.1056/NEJMra1800345 .
doi: 10.1056/NEJMra1800345 pubmed: 31509675
Lunde H, Hedner T, Samuelsson O, et al. Dyspnoea, asthma, and bronchospasm in relation to treatment with angiotensin converting enzyme inhibitors. BMJ. 1994;308(6920):18–21. https://doi.org/10.1136/bmj.308.6920.18 .
doi: 10.1136/bmj.308.6920.18 pubmed: 8298346 pmcid: 2539116
Christiansen SC, Schatz M, Yang SJ, et al. Hypertension and asthma: a comorbid relationship. J Allergy Clin Immunol Pract. 2016;4(1):76–81. https://doi.org/10.1016/j.jaip.2015.07.009 .
doi: 10.1016/j.jaip.2015.07.009 pubmed: 26342745
Morales DR, Lipworth BJ, Donnan PT, et al. Intolerance to angiotensin converting enzyme inhibitors in asthma and the general population: a UK population-based cohort study. J Allergy Clin Immunol Pract. 2021;9(9):3431–9. https://doi.org/10.1016/j.jaip.2021.04.055 .
doi: 10.1016/j.jaip.2021.04.055 pubmed: 33965593 pmcid: 8443840
Packard KA, Wurdeman RL, Arouni AJ. ACE inhibitor-induced bronchial reactivity in patients with respiratory dysfunction. Ann Pharmacother. 2002;36(6):1058–67. https://doi.org/10.1345/aph.1A332 .
doi: 10.1345/aph.1A332 pubmed: 12022909
Song WJ, Niimi A. Angiotensin-converting enzyme inhibitors, asthma, and cough: relighting the torch. J Allergy Clin Immunol Pract. 2021;9(9):3440–1. https://doi.org/10.1016/j.jaip.2021.07.002 .
doi: 10.1016/j.jaip.2021.07.002 pubmed: 34507711
Caldeira D, David C, Sampaio C. Tolerability of angiotensin-receptor blockers in patients with intolerance to angiotensin-converting enzyme inhibitors: a systematic review and meta-analysis. Am J Cardiovasc Drugs. 2012;12(4):263–77. https://doi.org/10.1007/BF03261835 .
doi: 10.1007/BF03261835 pubmed: 22587776
Myou S, Fujimura M, Kamio Y, et al. Effect of losartan, a type 1 angiotensin II receptor antagonist, on bronchial hyperresponsiveness to methacholine in patients with bronchial asthma. Am J Respir Crit Care Med. 2000;162(1):40–4. https://doi.org/10.1164/ajrccm.162.1.9907127 .
doi: 10.1164/ajrccm.162.1.9907127 pubmed: 10903217
Tan WSD, Liao W, Zhou S, et al. Targeting the renin-angiotensin system as novel therapeutic strategy for pulmonary diseases. Curr Opin Pharmacol. 2018;40:9–17. https://doi.org/10.1016/j.coph.2017.12.002 .
doi: 10.1016/j.coph.2017.12.002 pubmed: 29288933
Santos RAS, Sampaio WO, Alzamora AC, et al. The ACE2/angiotensin-(1–7)/MAS axis of the renin-angiotensin system: focus on angiotensin-(1–7). Physiol Rev. 2018;98(1):505–53. https://doi.org/10.1152/physrev.00023.2016 .
doi: 10.1152/physrev.00023.2016 pubmed: 29351514
Matera MG, Calzetta L, Rinaldi B, et al. Treatment of COPD: moving beyond the lungs. Curr Opin Pharmacol. 2012;12(3):315–22. https://doi.org/10.1016/j.coph.2012.04.001 .
doi: 10.1016/j.coph.2012.04.001 pubmed: 22552103
Magalhães GS, Gregório JF, Cançado Ribeiro ATP, et al. Oral formulation of angiotensin-(1–7) promotes therapeutic actions in a model of eosinophilic and neutrophilic asthma. Front Pharmacol. 2021;12: 557962. https://doi.org/10.3389/fphar.2021.557962 .
doi: 10.3389/fphar.2021.557962 pubmed: 33762930 pmcid: 7982577
Gregório JF, Rodrigues-Machado MDG, Santos RAS, et al. Asthma: role of the angiotensin-(1–7)/Mas (MAS1) pathway in pathophysiology and therapy. Br J Pharmacol. 2021;178(22):4428–39. https://doi.org/10.1111/bph.15619 .
doi: 10.1111/bph.15619 pubmed: 34235725
Hui Q, Hao Y, Ye F, et al. Genetically high angiotensin-converting enzyme concentrations causally increase asthma risk: a meta-analysis using Mendelian randomization. Front Med (Lausanne). 2022;9: 941944. https://doi.org/10.3389/fmed.2022.941944 .
doi: 10.3389/fmed.2022.941944 pubmed: 36419791 pmcid: 9676456
Liu G, Chen Y, Wang Y, et al. Angiotensin II enhances group 2 innate lymphoid cell responses via AT1a during airway inflammation. J Exp Med. 2022;219(3): e20211001. https://doi.org/10.1084/jem.20211001 .
doi: 10.1084/jem.20211001 pubmed: 35044462 pmcid: 8932533
Millar EA, Nally JE, Thomson NC. Angiotensin II potentiates methacholine-induced bronchoconstriction in human airway both in vitro and in vivo. Eur Respir J. 1995;8(11):1838–41. https://doi.org/10.1183/09031936.95.08111838 .
doi: 10.1183/09031936.95.08111838 pubmed: 8620948
Sakai H, Nishizawa Y, Nishimura A, et al. Angiotensin II induces hyperresponsiveness of bronchial smooth muscle via an activation of p42/44 ERK in rats. Pflugers Arch. 2010;460(3):645–55. https://doi.org/10.1007/s00424-010-0844-y .
doi: 10.1007/s00424-010-0844-y pubmed: 20495822
Li N, Cai R, Niu Y, et al. Inhibition of angiotensin II-induced contraction of human airway smooth muscle cells by angiotensin-(1–7) via downregulation of the RhoA/ROCK2 signaling pathway. Int J Mol Med. 2012;30(4):811–8. https://doi.org/10.3892/ijmm.2012.1080 .
doi: 10.3892/ijmm.2012.1080 pubmed: 22842919
US Preventive Services Task Force, Bibbins-Domingo K, Grossman DC, et al. Statin use for the primary prevention of cardiovascular disease in adults: US preventive services task force recommendation statement. JAMA. 2016;316(19):1997–2007. https://doi.org/10.1001/jama.2016.15450 .
doi: 10.1001/jama.2016.15450
Andreikos D, Karampitsakos T, Tzouvelekis A, et al. Statins’ still controversial role in pulmonary fibrosis: what does the evidence show? Pulm Pharmacol Ther. 2022;77: 102168. https://doi.org/10.1016/j.pupt.2022.102168 .
doi: 10.1016/j.pupt.2022.102168 pubmed: 36195297
Jang HJ, Lee DY, Loloci G, et al. Association between the use of statins and risk of interstitial lung disease/idiopathic pulmonary fibrosis: time-dependent analysis of population-based nationwide data. Eur Respir J. 2023;62(1):2300291. https://doi.org/10.1183/13993003.00291-2023 .
doi: 10.1183/13993003.00291-2023 pubmed: 37202155
Zeki AA, Elbadawi-Sidhu M. Innovations in asthma therapy: is there a role for inhaled statins? Expert Rev Respir Med. 2018;12(6):461–73. https://doi.org/10.1080/17476348.2018.1457437 .
doi: 10.1080/17476348.2018.1457437 pubmed: 29575963 pmcid: 6018057
Cazzola M, Calzetta L, Rinaldi B, et al. Management of chronic obstructive pulmonary disease in patients with cardiovascular diseases. Drugs. 2017;77(7):721–32. https://doi.org/10.1007/s40265-017-0731-3 .
doi: 10.1007/s40265-017-0731-3 pubmed: 28349353
Naing C, Ni H. Statins for asthma. Cochrane Database Syst Rev. 2020;7(7):CD013268. https://doi.org/10.1002/14651858.CD013268.pub2 .
doi: 10.1002/14651858.CD013268.pub2 pubmed: 32668027
Kim JH, Wee JH, Choi HG, et al. Association between statin medication and asthma/asthma exacerbation in a national health screening cohort. J Allergy Clin Immunol Pract. 2021;9(7):2783–91. https://doi.org/10.1016/j.jaip.2021.04.014 .
doi: 10.1016/j.jaip.2021.04.014 pubmed: 33894391
Park C, Jang JH, Kim C, et al. Real-world effectiveness of statin therapy in adult asthma. J Allergy Clin Immunol Pract. 2024;12(2):399–408. https://doi.org/10.1016/j.jaip.2023.10.029 .
doi: 10.1016/j.jaip.2023.10.029 pubmed: 37866433
Sunata K, Kabata H, Kuno T, et al. The effect of statins for asthma. A systematic review and meta-analysis. J Asthma. 2022;59(4):801–10. https://doi.org/10.1080/02770903.2021.1879850 .
doi: 10.1080/02770903.2021.1879850 pubmed: 33504228
Zhang QX, Zhang HF, Lu XT, et al. Statins improve asthma symptoms by suppressing inflammation: a meta-analysis based on RCTs. Eur Rev Med Pharmacol Sci. 2022;26(22):8401–10. https://doi.org/10.26355/eurrev_202211_30376 .
doi: 10.26355/eurrev_202211_30376 pubmed: 36459023
Thomson NC, Charron CE, Chaudhuri R, et al. Atorvastatin in combination with inhaled beclometasone modulates inflammatory sputum mediators in smokers with asthma. Pulm Pharmacol Ther. 2015;31:1–8. https://doi.org/10.1016/j.pupt.2015.01.001 .
doi: 10.1016/j.pupt.2015.01.001 pubmed: 25595138
Maneechotesuwan K, Ekjiratrakul W, Kasetsinsombat K, et al. Statins enhance the anti-inflammatory effects of inhaled corticosteroids in asthmatic patients through increased induction of indoleamine 2, 3-dioxygenase. J Allergy Clin Immunol. 2010;126(4):754–62. https://doi.org/10.1016/j.jaci.2010.08.005 .
doi: 10.1016/j.jaci.2010.08.005 pubmed: 20920765
Maneechotesuwan K, Kasetsinsombat K, Wamanuttajinda V, et al. Statins enhance the effects of corticosteroids on the balance between regulatory T cells and Th17 cells. Clin Exp Allergy. 2013;43(2):212–22. https://doi.org/10.1111/cea.12067 .
doi: 10.1111/cea.12067 pubmed: 23331562
Bellosta S, Corsini A. Statin drug interactions and related adverse reactions: an update. Expert Opin Drug Saf. 2018;17(1):25–37. https://doi.org/10.1080/14740338.2018.1394455 .
doi: 10.1080/14740338.2018.1394455 pubmed: 29058944
Crisan E, Patil VK. Neuromuscular complications of statin therapy. Curr Neurol Neurosci Rep. 2020;20(10):47. https://doi.org/10.1007/s11910-020-01064-0 .
doi: 10.1007/s11910-020-01064-0 pubmed: 32839913
Owczarek J, Jasińska M, Orszulak-Michalak D. Drug-induced myopathies. An overview of the possible mechanisms. Pharmacol Rep. 2005;57(1):23–34.
pubmed: 15849374
Ponziani MC, Karamouzis I, Mele C, et al. Baseline glucose homeostasis predicts the new onset of diabetes during statin therapy: a retrospective study in real life. Hormones (Athens). 2017;16(4):396–404. https://doi.org/10.14310/horm.2002.1760 .
doi: 10.14310/horm.2002.1760 pubmed: 29518760
Price DB, Voorham J, Brusselle G, et al. Inhaled corticosteroids in COPD and onset of type 2 diabetes and osteoporosis: matched cohort study. NPJ Prim Care Respir Med. 2019;29(1):38. https://doi.org/10.1038/s41533-019-0150-x .
doi: 10.1038/s41533-019-0150-x pubmed: 31659161 pmcid: 6817865
Sullivan PJ, Jafar ZH, Harbinson PL, et al. Platelet dynamics following allergen challenge in allergic asthmatics. Respiration. 2000;67(5):514–7. https://doi.org/10.1159/000067466 .
doi: 10.1159/000067466 pubmed: 11070455
Yue M, Hu M, Fu F, et al. Emerging roles of platelets in allergic asthma. Front Immunol. 2022;13: 846055. https://doi.org/10.3389/fimmu.2022.846055 .
doi: 10.3389/fimmu.2022.846055 pubmed: 35432313 pmcid: 9010873
Luo L, Zhang J, Lee J, et al. Platelets, not an insignificant player in development of allergic asthma. Cells. 2021;10(8):2038. https://doi.org/10.3390/cells10082038 .
doi: 10.3390/cells10082038 pubmed: 34440807 pmcid: 8391764
Chebbo M, Duez C, Alessi MC, et al. Platelets: a potential role in chronic respiratory diseases? Eur Respir Rev. 2021;30(161): 210062. https://doi.org/10.1183/16000617.0062-2021 .
doi: 10.1183/16000617.0062-2021 pubmed: 34526315 pmcid: 9488457
Badimon L, Vilahur G, Rocca B, et al. The key contribution of platelet and vascular arachidonic acid metabolism to the pathophysiology of atherothrombosis. Cardiovasc Res. 2021;117(9):2001–15. https://doi.org/10.1093/cvr/cvab003 .
doi: 10.1093/cvr/cvab003 pubmed: 33484117
Li KL, Lee AY, Abuzeid WM. Aspirin exacerbated respiratory disease: epidemiology, pathophysiology, and management. Med Sci (Basel). 2019;7(3):45. https://doi.org/10.3390/medsci7030045 .
doi: 10.3390/medsci7030045 pubmed: 30884882
Laidlaw TM, Boyce JA. Updates on immune mechanisms in aspirin-exacerbated respiratory disease. J Allergy Clin Immunol. 2023;151(2):301–9. https://doi.org/10.1016/j.jaci.2022.08.021 .
doi: 10.1016/j.jaci.2022.08.021 pubmed: 36184313
Rajan JP, Wineinger NE, Stevenson DD, et al. Prevalence of aspirin-exacerbated respiratory disease among asthmatic patients: a meta-analysis of the literature. J Allergy Clin Immunol. 2015;135(3):676–81. https://doi.org/10.1016/j.jaci.2014.08.020 .
doi: 10.1016/j.jaci.2014.08.020 pubmed: 25282015
Jenkins C, Costello J, Hodge L. Systematic review of prevalence of aspirin induced asthma and its implications for clinical practice. BMJ. 2004;328(7437):434. https://doi.org/10.1136/bmj.328.7437.434 .
doi: 10.1136/bmj.328.7437.434 pubmed: 14976098 pmcid: 344260
Thakker RA, Salazar L, Jazar DA, et al. Coronary artery disease and aspirin intolerance: background and insights on current management. Cardiol Ther. 2022;11(2):175–83. https://doi.org/10.1007/s40119-022-00255-9 .
doi: 10.1007/s40119-022-00255-9 pubmed: 35344187 pmcid: 9135937
Lussana F, Di Marco F, Terraneo S, et al. Effect of prasugrel in patients with asthma: results of PRINA, a randomized, double-blind, placebo-controlled, cross-over study. J Thromb Haemost. 2015;13(1):136–41. https://doi.org/10.1111/jth.12779 .
doi: 10.1111/jth.12779 pubmed: 25387888
Butler K, Maya J, Teng R. Effect of ticagrelor on pulmonary function in healthy elderly volunteers and asthma or chronic obstructive pulmonary disease patients. Curr Med Res Opin. 2013;29(5):569–77. https://doi.org/10.1185/03007995.2013.781502 .
doi: 10.1185/03007995.2013.781502 pubmed: 23448616
Trinh HKT, Nguyen TVT, Choi Y, et al. The synergistic effects of clopidogrel with montelukast may be beneficial for asthma treatment. J Cell Mol Med. 2019;23(5):3441–50. https://doi.org/10.1111/jcmm.14239 .
doi: 10.1111/jcmm.14239 pubmed: 30905080 pmcid: 6484307
Arkless KL, Pan D, Shankar-Hari M, et al. Stimulation of platelet P2Y
doi: 10.1111/bph.16039 pubmed: 36694432
Dogné JM, de Leval X, Benoit P, et al. Therapeutic potential of thromboxane inhibitors in asthma. Expert Opin Investig Drugs. 2002;11(2):275–81. https://doi.org/10.1517/13543784.11.2.275 .
doi: 10.1517/13543784.11.2.275 pubmed: 11829716
Magazine R, Surendra VU, Chogtu B. Comparison of oral montelukast with oral ozagrel in acute asthma: a randomized, double-blind, placebo-controlled study. Lung India. 2018;35(1):16–20. https://doi.org/10.4103/lungindia.lungindia_226_17 .
doi: 10.4103/lungindia.lungindia_226_17 pubmed: 29319028 pmcid: 5760861
Hernandez JM, Janssen LJ. Revisiting the usefulness of thromboxane-A2 modulation in the treatment of bronchoconstriction in asthma. Can J Physiol Pharmacol. 2015;93(2):111–7. https://doi.org/10.1139/cjpp-2014-0364 .
doi: 10.1139/cjpp-2014-0364 pubmed: 25581104
Godfraind T. Calcium channel blockers in cardiovascular pharmacotherapy. J Cardiovasc Pharmacol Ther. 2014;19(6):501–15. https://doi.org/10.1177/1074248414530508 .
doi: 10.1177/1074248414530508 pubmed: 24872348
Hirota S, Helli P, Janssen LJ. Ionic mechanisms and Ca
doi: 10.1183/09031936.00147706 pubmed: 17601970
Twiss MA, Harman E, Chesrown S, et al. Efficacy of calcium channel blockers as maintenance therapy for asthma. Br J Clin Pharmacol. 2002;53(3):243–9. https://doi.org/10.1046/j.0306-5251.2001.01560.x .
doi: 10.1046/j.0306-5251.2001.01560.x
Chiu KY, Li JG, Lin Y. Calcium channel blockers for lung function improvement in asthma: a systematic review and meta-analysis. Ann Allergy Asthma Immunol. 2017;119(6):518–23. https://doi.org/10.1016/j.anai.2017.08.013 .
doi: 10.1016/j.anai.2017.08.013 pubmed: 29032888
Tsuzuki R, To M, Yamawaki S, et al. Inhibitory effect of calcium channel blockers on the deterioration of lung function in adult-onset asthma. Ann Allergy Asthma Immunol. 2021;126(6):731–3. https://doi.org/10.1016/j.anai.2021.02.029 .
doi: 10.1016/j.anai.2021.02.029 pubmed: 33705916
Martinez Manzano JM, Lo KB, Jarrett SA, et al. Angioedema associated with the use of dihydropyridine calcium channel blockers. A case series. Ann Allergy Asthma Immunol. 2022;128(2):228–9. https://doi.org/10.1016/j.anai.2021.10.030 .
doi: 10.1016/j.anai.2021.10.030 pubmed: 34732378
Lipworth BJ, McDevitt DG, Struthers AD. Prior treatment with diuretic augments the hypokalemic and electrocardiographic effects of inhaled albuterol. Am J Med. 1989;86(6 Pt 1):653–7. https://doi.org/10.1016/0002-9343(89)90438-5 .
doi: 10.1016/0002-9343(89)90438-5 pubmed: 2729315
Chandy D, Aronow WS, Banach M. Current perspectives on treatment of hypertensive patients with chronic obstructive pulmonary disease. Integr Blood Press Control. 2013;6:101–9. https://doi.org/10.2147/IBPC.S33982 .
doi: 10.2147/IBPC.S33982 pubmed: 23901294 pmcid: 3724277
Kardalas E, Paschou SA, Anagnostis P, et al. Hypokalemia: a clinical update. Endocr Connect. 2018;7(4):R135–46. https://doi.org/10.1530/EC-18-0109 .
doi: 10.1530/EC-18-0109 pubmed: 29540487 pmcid: 5881435
Vasileiadis I, Alevrakis E, Ampelioti S, et al. Acid-base disturbances in patients with asthma: a literature review and comments on their pathophysiology. J Clin Med. 2019;8(4):563. https://doi.org/10.3390/jcm8040563 .
doi: 10.3390/jcm8040563 pubmed: 31027265 pmcid: 6518237
Tamargo J, Segura J, Ruilope LM. Diuretics in the treatment of hypertension. Part 2: loop diuretics and potassium-sparing agents. Expert Opin Pharmacother. 2014;15(5):605–21. https://doi.org/10.1517/14656566.2014.879117 .
doi: 10.1517/14656566.2014.879117 pubmed: 24456327
Rutten FH, Cramer MJ, Lammers JW, et al. Heart failure and chronic obstructive pulmonary disease: An ignored combination? Eur J Heart Fail. 2006;8(7):706–11. https://doi.org/10.1016/j.ejheart.2006.01.010 .
doi: 10.1016/j.ejheart.2006.01.010 pubmed: 16531114
Palmer BF. A physiologic-based approach to the evaluation of a patient with hyperkalemia. Am J Kidney Dis. 2010;56(2):387–93. https://doi.org/10.1053/j.ajkd.2010.01.020 .
doi: 10.1053/j.ajkd.2010.01.020 pubmed: 20493606
Tang Z, Jiang L, Peng J, et al. PCSK9 siRNA suppresses the inflammatory response induced by oxLDL through inhibition of NF-κB activation in THP-1-derived macrophages. Int J Mol Med. 2012;30(4):931–8. https://doi.org/10.3892/ijmm.2012.1072 .
doi: 10.3892/ijmm.2012.1072 pubmed: 22825241
Xu Y, Li Y. Association between lipid-lowering drugs and allergic diseases: a Mendelian randomization study. World Allergy Organ J. 2024;17(4): 100899. https://doi.org/10.1016/j.waojou.2024.100899 .
doi: 10.1016/j.waojou.2024.100899 pubmed: 38623319 pmcid: 11017355
Liang L, Chung SI, Guon TE, Park KH, Lee JH, Park JW. Statin administration or blocking PCSK9 alleviates airway hyperresponsiveness and lung fibrosis in high-fat diet-induced obese mice. Respir Res. 2024;25(1):213. https://doi.org/10.1186/s12931-024-02842-x .
doi: 10.1186/s12931-024-02842-x pubmed: 38762465 pmcid: 11102611
Xie W, Li J, Du H, Xia J. Causal relationship between PCSK9 inhibitor and autoimmune diseases: a drug target Mendelian randomization study. Arthritis Res Ther. 2023;25(1):148. https://doi.org/10.1186/s13075-023-03122-7 .
doi: 10.1186/s13075-023-03122-7 pubmed: 37580807 pmcid: 10424393

Auteurs

Mario Cazzola (M)

Unit of Respiratory Medicine, Department of Experimental Medicine, University of Rome 'Tor Vergata', Rome, Italy. mario.cazzola@uniroma2.it.

Clive P Page (CP)

Institute of Pharmaceutical Science, King's College London, London, UK.

Nicola A Hanania (NA)

Section of Pulmonary and Critical Care Medicine, Baylor College of Medicine, Houston, TX, USA.

Luigino Calzetta (L)

Department of Medicine and Surgery, Respiratory Disease and Lung Function Unit, University of Parma, Parma, Italy.

Maria Gabriella Matera (MG)

Unit of Pharmacology, Department of Experimental Medicine, University of Campania 'Luigi Vanvitelli', Naples, Italy.

Paola Rogliani (P)

Unit of Respiratory Medicine, Department of Experimental Medicine, University of Rome 'Tor Vergata', Rome, Italy.

Classifications MeSH