The 5T approach in asthma: Triple Therapy Targeting Treatable Traits

Cazzola, Mario; Braido, Fulvio; Calzetta, Luigino; Matera, Maria Gabriella; Piraino, Alessio; Rogliani, Paola; Scichilone, Nicola

doi:10.1016/j.rmed.2022.106915

Cited by 14 publications

(9 citation statements)

References 149 publications

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“…As a result, the addition of a LAMA to the standard treatment with ICS + LABA probably reduces the risk of moderate and/or severe asthma exacerbations and should be used in cases wheredual treatment is inadequate in the prevention of the asthma exacerbations [ 21 , 36 ].…”

Section: Discussionmentioning

confidence: 99%

“…To sum up, the addition of LAMA to the standard ICS + LABA treatment regimen undoubtedly significantly improves lung function in patients with inadequately controlled asthma [ 21 , 36 ].…”

Section: Discussionmentioning

confidence: 99%

“…Some asthma traits that might be predictive ofbetter response to treatment with LAMA could be a previous smoking history and fixed airway obstruction [ 36 ]. The role of other recognizable disease traits is still under investigation [ 21 ].…”

Section: Discussionmentioning

confidence: 99%

“…LAMAs were recently studied for the management of asthma; despite the different pathogenetic mechanisms between asthma and COPD, based on the common cardinal pathophysiological characteristic of bronchoconstriction [ 17 , 18 ], the bronchodilator action of LAMAs [ 19 ] and the effectiveness of SAMAs in asthma exacerbation treatment [ 20 ]. Furthermore, a few trials focused on identifying patients that could specifically benefit from LAMA treatment initiation based on disease traits and various biomarkers [ 21 ].…”

Section: Introductionmentioning

confidence: 99%

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Open and Closed Triple Inhaler Therapy in Patients with Uncontrolled Asthma

Kotoulas

Tsiouprou

Domvri

et al. 2023

ARM

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Long-acting muscarinic antagonists (LAMAs) are a class of inhalers that has recently been included as add-on therapy in the GINA guidelines, either in a single inhaler device with inhaled corticosteroids plus long-acting β2-agonists (ICS + LABA) (closed triple inhaler therapy) or in a separate one (open triple inhaler therapy). This review summarizes the existing evidence on the addition of LAMAs in patients with persistently uncontrolled asthma despite ICS + LABA treatment based on clinical efficacy in the reduction of asthma symptoms and exacerbations, the improvement in lung function, and its safety profile.

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Section: Discussionmentioning

confidence: 99%

“…To sum up, the addition of LAMA to the standard ICS + LABA treatment regimen undoubtedly significantly improves lung function in patients with inadequately controlled asthma [ 21 , 36 ].…”

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Open and Closed Triple Inhaler Therapy in Patients with Uncontrolled Asthma

Kotoulas

Tsiouprou

Domvri

et al. 2023

ARM

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“…Airway remodeling can affect both large and small airways [ 47 ]. Ach’s potential to facilitate remodeling suggests that it is appropriate to target the damaging actions of ACh on ASM and the persistent inflammatory airway insult caused by immune/inflammatory cells, which means using an LAMA and an ICS + LABA combination at the same time [ 48 ]. Noteably, this therapeutic approach also benefits from the decreased ACh release that comes with LABA + LAMA combination [ 23 ].…”

Section: Use Of Lamas Considering Treatable Traitsmentioning

confidence: 99%

Might It Be Appropriate to Anticipate the Use of Long-Acting Muscarinic Antagonists in Asthma?

Cazzola

Rogliani

Matera

2023

Drugs

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A growing number of clinical trials are documenting that adding a long-acting muscarinic antagonist (LAMA) to established asthma treatment with an inhaled corticosteroid (ICS) and a long-acting β 2 -agonist (LABA) is a treatment option that improves the health of patients with uncontrolled severe asthma even when therapy is optimized. These favorable results are the reason why the leading guidelines recommend triple therapy with ICS + LABA + LAMA in patients with asthma uncontrolled by medium- to high-dose ICS-LABA. However, we suggest adding LAMAs to ICS-LABAs at an earlier clinical stage. Such action could positively influence airflow limitation, exacerbations, and eosinophilic inflammation, conditions that are associated with acetylcholine (ACh) activity. It could also interrupt the vicious cycle related to a continuous release of ACh leading to the progressive expansion of neuronal plasticity resulting in small airway dysfunction. The utility of an earlier use of triple therapy in asthma should, in any case, be confirmed by statistically powered trials.

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