Severity of chronic asthma

Woolcock, Ann J.; Dusser, Daniel; Fajac, Isabelle

doi:10.1136/thx.53.6.442

Cited by 10 publications

(5 citation statements)

References 32 publications

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“…Furthermore, rhinovirus, RSV, and influenza can exacerbate established asthma ( Mikhail and Grayson, 2019 ), which can also become steroid-insensitive. Irrespective of the endotype or phenotype of asthma, the severity of asthma can be associated with increased potency of bronchoconstrictors but also an increase in the maximum contraction of ASM that can lead to complete airway closure in fatal asthma ( Woolcock et al, 1998 ). Therefore, improving outcomes for patients requires an understanding of the mechanisms controlling airway reactivity and the influence of inflammatory mediators.…”

Section: Asthma Epidemiology and Pathophysiologymentioning

confidence: 99%

Advances in respiratory physiology in mouse models of experimental asthma

et al. 2023

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Recent advances in mouse models of experimental asthma coupled with vast improvements in systems that assess respiratory physiology have considerably increased the accuracy and human relevance of the outputs from these studies. In fact, these models have become important pre-clinical testing platforms with proven value and their capacity to be rapidly adapted to interrogate emerging clinical concepts, including the recent discovery of different asthma phenotypes and endotypes, has accelerated the discovery of disease-causing mechanisms and increased our understanding of asthma pathogenesis and the associated effects on lung physiology. In this review, we discuss key distinctions in respiratory physiology between asthma and severe asthma, including the magnitude of airway hyperresponsiveness and recently discovered disease drivers that underpin this phenomenon such as structural changes, airway remodeling, airway smooth muscle hypertrophy, altered airway smooth muscle calcium signaling, and inflammation. We also explore state-of-the-art mouse lung function measurement techniques that accurately recapitulate the human scenario as well as recent advances in precision cut lung slices and cell culture systems. Furthermore, we consider how these techniques have been applied to recently developed mouse models of asthma, severe asthma, and asthma-chronic obstructive pulmonary disease overlap, to examine the effects of clinically relevant exposures (including ovalbumin, house dust mite antigen in the absence or presence of cigarette smoke, cockroach allergen, pollen, and respiratory microbes) and to increase our understanding of lung physiology in these diseases and identify new therapeutic targets. Lastly, we focus on recent studies that examine the effects of diet on asthma outcomes, including high fat diet and asthma, low iron diet during pregnancy and predisposition to asthma development in offspring, and environmental exposures on asthma outcomes. We conclude our review with a discussion of new clinical concepts in asthma and severe asthma that warrant investigation and how we could utilize mouse models and advanced lung physiology measurement systems to identify factors and mechanisms with potential for therapeutic targeting.

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Section: Asthma Epidemiology and Pathophysiologymentioning

confidence: 99%

Advances in respiratory physiology in mouse models of experimental asthma

et al. 2023

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“…Measurement of exhaled nitric oxide may also be used to monitor the effects of corticosteroids on the underlying inflammation, although the usefulness of this measure is uncertain 1112 It has been suggested that assessment of bronchial hyperresponsiveness (methacholine or histamine challenge) is the single most useful test of asthma severity,13 but in practice it is rarely useful in children.…”

Section: Confirming the Severitymentioning

confidence: 99%

Difficult asthma: beyond the guidelines

Balfour‐Lynn

1999

Archives of Disease in Childhood

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“…Asthma is characterized by inflammation, airway wall remodeling, and airway hyperresponsiveness (AHR), whereby airways are more sensitive to a variety of stimuli and subsequently contract too easily and too much [2]. …”

Section: Introductionmentioning

confidence: 99%

“…Asthma is a chronic inflammatory lung disease affecting over 300 million people worldwide, with 250,000 deaths per year attributed to the disease [ 1 ]. Asthma is characterized by inflammation, airway wall remodeling, and airway hyperresponsiveness (AHR), whereby airways are more sensitive to a variety of stimuli and subsequently contract too easily and too much [ 2 ].…”

Section: Introductionmentioning

confidence: 99%

PPARγLigands Regulate Noncontractile and Contractile Functions of Airway Smooth Muscle: Implications for Asthma Therapy

2012

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In asthma, the increase in airway smooth muscle (ASM) can contribute to inflammation, airway wall remodeling and airway hyperresponsiveness (AHR). Targetting peroxisome proliferator-activated receptor γ (PPARγ), a receptor upregulated in ASM in asthmatic airways, may provide a novel approach to regulate these contributions. This review summarises experimental evidence that PPARγ ligands, such as rosiglitazone (RGZ) and pioglitazone (PGZ), inhibit proliferation and inflammatory cytokine production from ASM in vitro. In addition, inhaled administration of these ligands reduces inflammatory cell infiltration and airway remodelling in mouse models of allergen-induced airways disease. PPARγ ligands can also regulate ASM contractility, with acute treatment eliciting relaxation of mouse trachea in vitro through a PPARγ-independent mechanism. Chronic treatment can protect against the loss of bronchodilator sensitivity to β 2-adrenoceptor agonists and inhibit the development of AHR associated with exposure to nicotine in utero or following allergen challenge. Of particular interest, a small clinical trial has shown that oral RGZ treatment improves lung function in smokers with asthma, a group that is generally unresponsive to conventional steroid treatment. These combined findings support further investigation of the potential for PPARγ agonists to target the noncontractile and contractile functions of ASM to improve outcomes for patients with poorly controlled asthma.

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Severity of chronic asthma

Cited by 10 publications

References 32 publications

Advances in respiratory physiology in mouse models of experimental asthma

Advances in respiratory physiology in mouse models of experimental asthma

Difficult asthma: beyond the guidelines

PPARγLigands Regulate Noncontractile and Contractile Functions of Airway Smooth Muscle: Implications for Asthma Therapy

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