Bronchodilators for Airway Disease

Cazzola, Mario; Matera, Maria Gabriella

doi:10.1016/b978-0-08-102723-3.00043-3

Cited by 3 publications

(4 citation statements)

References 111 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Airway tone is mainly controlled by the vagus nerve 5,6 . Indeed, the parasympathetic fibres of the vagus nerve are tonically active, producing a stable and easily reversible basal tone of airway smooth muscle (ASM).…”

Section: The Pharmacological Rationale For Dual Bronchodilationmentioning

confidence: 99%

“…Airway tone is mainly controlled by the vagus nerve. 5,6 Indeed, the parasympathetic fibres of the vagus nerve are tonically active, producing a stable and easily reversible basal tone of airway smooth muscle (ASM). Mechanical or chemical airway stimuli can activate vagal afferents that release acetylcholine (Ach).…”

Section: The Pharmacological Rationale For Dual Bronchodilationmentioning

confidence: 99%

See 1 more Smart Citation

Dual bronchodilation for the treatment of COPD: From bench to bedside

Cazzola

Page

Rogliani

et al. 2022

Brit J Clinical Pharma

Self Cite

View full text Add to dashboard Cite

Because there is a solid pharmacological rationale based on positive interactions between long-acting muscarinic receptor antagonists (LAMAs) and long-acting β-agonists (LABAs) for their ability to relax human airway smooth muscle in vitro alongside several randomised controlled trials (RCTs) and real-world observational studies that support the use of LAMA/LABA fixed-dose combinations (FDCs) for the treatment of patients with chronic obstructive pulmonary disease (COPD), in this narrative review we discuss the preclinical and clinical proofs supporting the use of LAMA + LABA therapy in COPD and why this therapeutic approach optimises bronchodilation. Robust evidence indicates that all LAMA/LABA FDCs are consistently more effective than LAMA or LABA administered alone in improving lung function, dyspnoea, quality of life and exercise capacity in patients with COPD. However, the ability of dual bronchodilation with FDCs of LAMA/LABA to prevent or reduce the risk of COPD exacerbations remains unclear due to conflicting data from large RCTs, despite several mechanisms explaining why such combinations should be of value in decreasing the frequency of COPD exacerbations. Both LABAs and LAMAs mechanistically can affect the cardiovascular system, but from clinical studies to date, LAMA/LABA FDCs have an acceptable cardiovascular safety profile, at least in the COPD population enrolled in RCTs. Indirect evidence suggests that some FDCs may even exert a protective role against serious cardiovascular adverse events compared to monotherapies. Consequently, several LAMA/LABA FDCs have been developed and approved for clinical use as treatments for patients with COPD. However, to date, there are unfortunately very few head-to-head studies comparing the safety and efficacy of different LAMA/LABA FDCs, making it difficult to choose the most appropriate combination, although the use of meta-analyses has provided some information in this regard.Endurance time Exercise time until exhaustion measured by a standard endurance test. Inspiratory capacityThe maximum volume of air that can be inspired after reaching the end of a normal, quiet expiration. It is the sum of the tidal volume and the inspiratory reserve volume. St George's Respiratory Questionnaire (SGRQ) A tool to measure health status in patients with respiratory disease. It has three domains: symptoms, activity and

show abstract

Section: The Pharmacological Rationale For Dual Bronchodilationmentioning

confidence: 99%

Section: The Pharmacological Rationale For Dual Bronchodilationmentioning

confidence: 99%

Dual bronchodilation for the treatment of COPD: From bench to bedside

Cazzola

Page

Rogliani

et al. 2022

Brit J Clinical Pharma

Self Cite

View full text Add to dashboard Cite

show abstract

“…LABAs differ substantially in key pharmacological parameters, such as selectivity for and residence time on the β 2 -AR, potency, intrinsic efficacy (namely the extent to which they activate the receptor), and lipophilicity. 32 , 33 These differences are critical in characterizing the pharmacological profile (primarily the onset and duration of action, but also the loss of responsiveness to chronic LABA therapy) and, consequently, the clinical effect of each LABA. It should be noted, however, that apparently, slow receptor dissociation is not a key factor in the duration of action of LABAs whereas partitioning of the drug into lipophilic compartments after inhalation is the key determinant of their long duration of action.…”

Section: Pharmacological and Clinical Evidence Supporting Triple Therapymentioning

confidence: 99%

“…Regarding LAMAs, there are substantial differences in their pharmacological profiles. 33 , 34 Their onset of action probably differs somewhat in the different time taken to reach equilibrium at the M 3 mAChR. Their offsets of action duration and potency also differ significantly.…”

Section: Pharmacological and Clinical Evidence Supporting Triple Therapymentioning

confidence: 99%

Beyond Dual Bronchodilation – Triple Therapy, When and Why

Cazzola¹,

Rogliani²,

Laitano³

et al. 2022

COPD

Self Cite

View full text Add to dashboard Cite

Although pharmacological treatment of COPD is codified in different guidelines and strategy documents, there is abundant evidence of discrepancy between what they suggest and what health professionals prescribe, especially in low-risk groups where there is widespread overprescription of triple therapy. It is therefore necessary to clarify when the use of triple therapy is indicated in COPD patients and when it is preferable to maintain treatment with dual bronchodilation. In this article, we discuss our views based on our experience and what is reported in the literature and try to give answers to these two questions. The evidence generated by pivotal RCTs supports the use of triple therapy in patients who present for the first time and have severe airway obstruction, are symptomatic, have had frequent moderate or severe exacerbations in the previous year, and have peripheral eosinophilia. However, it is difficult to determine whether step-up is useful in all other cases because the available data are quite conflicting. It is likely that the inconsistency in the information generated by the various available studies may explain the prescribing behaviour of many physicians who do not adhere to recommendations of guidelines and strategies. However, it is necessary to establish whether and when the addition of an ICS to the LAMA/LABA combination is effective, to determine whether triple therapy can induce an additional clinical benefit over dual bronchodilation, irrespective of a preventive effect on COPD exacerbations, to establish its value, and to examine whether cost differences can support the use of triple therapy over combined LAMA/LABA therapy in real life.

show abstract