Mucus hypersecretion in asthma is associated with rhinosinusitis, polyps and exacerbations

Martínez‐Rivera, Carlos; Crespo, Astrid; Pinedo-Sierra, Celia; García-Rivero, Juan Luis; Pallarés-Sanmartín, Abel; Marina-Malanda, Nuria; Pascual-Erquicia, Silvia; Padilla, Alicia; Mayoralas-Alises, Sagrario; Plaza, Vicente; López-Viña, Antolín; Picado, César

doi:10.1016/j.rmed.2017.12.013

Cited by 36 publications

(26 citation statements)

References 31 publications

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“…Our ndings point to clinical characteristics that differentiate patients with and without mucus hypersecretion, mainly that hypersecretors are older, have severer asthma, greater bronchial obstruction and poorer asthma control, have lower peripheral blood albumin and lower IgE levels, have lower induced sputum lymphocyte levels, are less likely to have prick test-positive asthma and, nally, needed more short-term oral glucocorticoid treatments in the previous year. Our results corroborate those of Martínez-Rivera et al (28), who reported that hypersecretion, common in patients with asthma, was associated with greater airway obstruction, poorer asthma control and more exacerbation episodes. Another European prospective respiratory health study followed up over 9 years reported that one determinant of asthma severity was airway mucus hypersecretion (29).…”

Section: Discussionsupporting

confidence: 92%

Association of the CFTR Gene With Asthma and Airway Mucus Hypersecretion

Crespo‐Lessmann

Bernal

Río

et al. 2020

Preprint

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IntroductionAirway mucus hypersecretion is an undercharacterized phenotype of asthma. Objectives(1) To determine the presence of genetic variants of the CFTR gene in patients with asthma with and without airway mucus hypersecretion. (2) To identify the characteristics of the asthma phenotype with airway mucus hypersecretion.MethodComparative cross-sectional multicentre study including 39 hypersecretors and 61 non-hypersecretors asthma patients. Asthmatic hypersecretion was defined as the presence of cough productive of sputum on most days for at least three months in two successive years. Spirometry, fractional exhaled nitric oxide, induced sputum cell count, blood test and questionnaires were performed. Blood DNA samples were sequenced using a MiSeq sequencer and the Illumina platform was used for the CFTR gene analysis.ResultsGenetic differences were observed in the c.1680-870T>A genetic variant of the CFTR gene, significantly more evident in hypersecretors than in non-hypersecretors: 78.94% vs. 59.32% in the majority allele and 21.05% vs. 40.67% in the minority allele (p=0.036). Asthma hypersecretors were older (57.4 years vs. 49.4 years; p=0.004) and had greater asthma severity (58.9% vs. 23.7%; p=0.005), greater airway obstruction (FEV1/FVC% 64.3 vs. 69.5; p=0.041), poorer asthma control (60% vs. 29%; p=0.021), and lower IgE levels (126.4 IU/mL vs. 407.6 IU/mL; p=0.003).ConclusionPatients with asthma and with mucus hypersecretion may have a different disease mechanism produced by an intronic genetic variant in the CFTR gene (NM_000492.3:c.1680-870T>A). They present a more severe disease, poorer asthma control and a non-allergic inflammatory phenotype.

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Section: Discussionsupporting

confidence: 92%

Association of the CFTR Gene With Asthma and Airway Mucus Hypersecretion

Crespo‐Lessmann

Bernal

Río

et al. 2020

Preprint

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“…One of the important features of asthma is the mucus deposition and alterations in bronchial epithelia. Moreover, mucus production usually affects nasal epithelia and it is known that rhinitis is strongly associated to the development and the worsening of asthma symptoms [45]. OVA inhalation induces mucus deposition in airway epithelial cells, which is positively correlated with the reduction in lung function [46].…”

Section: Discussionmentioning

confidence: 99%

Inhibition of MAPK and STAT3-SOCS3 by Sakuranetin Attenuated Chronic Allergic Airway Inflammation in Mice

Santana

Silva

Grecco

et al. 2019

Mediators of Inflammation

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Asthma allergic disease is caused by airway chronic inflammation. Some intracellular signaling pathways, such as MAPK and STAT3-SOCS3, are involved in the control of airway inflammation in asthma. The flavonoid sakuranetin demonstrated an anti-inflammatory effect in different asthma models. Our aim was to clarify how sakuranetin treatment affects MAPK and STAT3-SOCS3 pathways in a murine experimental asthma model. Mice were submitted to an asthma ovalbumin-induction protocol and were treated with vehicle, sakuranetin, or dexamethasone. We assayed the inflammatory profile, mucus production, and serum antibody, STAT3-SOCS3, and MAPK levels in the lungs. Morphological alterations were also evaluated in the liver. LPS-stimulated RAW 264.7 cells were used to evaluate the effects of sakuranetin on nitric oxide (NO) and cytokine production. In vivo, sakuranetin treatment reduced serum IgE levels, lung inflammation (eosinophils, neutrophils, and Th2/Th17 cytokines), and respiratory epithelial mucus production in ovalbumin-sensitized animals. Considering possible mechanisms, sakuranetin inhibits the activation of ERK1/2, JNK, p38, and STAT3 in the lungs. No alterations were found in the liver for treated animals. Sakuranetin did not modify in vitro cell viability in RAW 264.7 and reduced NO release and gene expression of IL-1β and IL-6 induced by LPS in these cells. In conclusion, our data showed that the inhibitory effects of sakuranetin on eosinophilic lung inflammation can be due to the inhibition of Th2 and Th17 cytokines and the inhibition of MAPK and STAT3 pathways, reinforcing the idea that sakuranetin can be considered a relevant candidate for the treatment of inflammatory allergic airway disease.

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“…In patients with asthma, mucous hypersecretion is associated with more symptoms, more obstruction, and more exacerbations. 61 Furthermore, in this case, roflumilast has revealed improvement of symptoms and lung function in asthmatics when added to montelukast, in comparison to this drug used in monotherapy. 62 …”

Section: Therapeutic Goals and Treatable Traits In Cadmentioning

confidence: 72%

<p>A Proposed Approach to Chronic Airway Disease (CAD) Using Therapeutic Goals and Treatable Traits: A Look to the Future</p>

Llano¹,

Miravitlles²,

Golpe³

et al. 2020

COPD

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Chronic airflow obstruction affects a wide range of airway diseases, the most frequent of which are asthma, COPD, and bronchiectasis; they are clearly identifiable in their extremes, but quite frequently overlap in some of their pathophysiological and clinical characteristics. This has generated the description of new mixed or overlapping disease phenotypes with no clear biological grounds. In this special article, a group of experts provides their perspective and proposes approaching the treatment of chronic airway disease (CAD) through the identification of a series of therapeutic goals (TG) linked to treatable traits (TT)-understood as clinical, physiological, or biological characteristics that are quantifiable using biomarkers. This therapeutic approach needs validating in a clinical trial with the strategy of identification of TG and treatment according to TT for each patient independently of their prior diagnosis.

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Mucus hypersecretion in asthma is associated with rhinosinusitis, polyps and exacerbations

Abstract: Mucus hypersecretion is frequent in patients with asthma, and is associated with chronic upper airways disease, airway obstruction, poor asthma control and more exacerbations.

Cited by 36 publications

References 31 publications

Association of the CFTR Gene With Asthma and Airway Mucus Hypersecretion

Association of the CFTR Gene With Asthma and Airway Mucus Hypersecretion

Inhibition of MAPK and STAT3-SOCS3 by Sakuranetin Attenuated Chronic Allergic Airway Inflammation in Mice

<p>A Proposed Approach to Chronic Airway Disease (CAD) Using Therapeutic Goals and Treatable Traits: A Look to the Future</p>

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