Airway Remodeling in Preschool Children with Severe Recurrent Wheeze

Lezmi, Guillaume; Gosset, Philippe; Deschildre, A.; Abou‐Taam, Rola; Mahut, Bruno; Beydon, Nicole; Blic, J. de

doi:10.1164/rccm.201411-1958oc

Cited by 77 publications

(100 citation statements)

References 48 publications

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“…Pre-school children with severe wheezing that developed asthma only had significantly more ASM in their endobronchial biopsies at pre-school age compared with those wheezers that did not develop asthma, while tissue eosinophilia or RBM thickness were not predictors [36]. In addition, increased ASM was the only change associated with atopy in severe pre-school wheezers [31]. Thus, early abnormalities in ASM function may determine asthma development.…”

Section: Airway Smooth Musclementioning

confidence: 93%

“…Moreover, even younger pre-school children (median age 3 years) with severe recurrent wheezing have evidence of increased RBM thickness and tissue eosinophilic inflammation [5]. Interestingly, a recent biopsy study in pre-school children with severe wheeze has shown the presence of several features of remodelling, including increased RBM thickness, ASM, vascularity and mucus gland area, but no relationship between inflammatory cell counts in biopsies and remodelling [31]. A limitation of human studies, especially paediatric studies, is the relative difficulty in obtaining repeated invasive biopsies to assess longitudinal changes in pathology over time.…”

Section: Limitations Of Therapy Targeted At Inflammationmentioning

confidence: 99%

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Novel concepts in airway inflammation and remodelling in asthma

2015

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The hallmark pathological features of asthma include airway eosinophilic inflammation and structural changes (remodelling) which are associated with an irreversible loss in lung function that tracks from childhood to adulthood. In parallel with changes in function, pathological abnormalities occur early, during the pre-school years, are established by school age and subsequently remain (even though symptoms may remit for periods during adulthood). Given the equal importance of inflammation and remodelling in asthma pathogenesis, there is a significant disparity in studies undertaken to investigate the contribution of each. The majority focus on the role of inflammation, and although novel therapeutics such as those targeted against T-helper cell type 2 (Th2) mediators have arisen, it is apparent that targeting inflammation alone has not allowed disease modification. Therefore, unless airway remodelling is addressed for future therapeutic strategies, it is unlikely that we will progress towards a cure for asthma. Having acknowledged these limitations, the focus of this review is to highlight the gaps in our current knowledge about the mechanisms underlying airway remodelling, the relationships between remodelling, inflammation and function, remodelling and clinical phenotypes, and the importance of utilising innovative and realistic pre-clinical models to uncover effective, disease-modifying therapeutic strategies. @ERSpublications We discuss mechanisms of airway inflammation and remodelling in asthma to uncover effective therapeutic strategies http://ow.ly/SsXiO

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Section: Airway Smooth Musclementioning

confidence: 93%

Section: Limitations Of Therapy Targeted At Inflammationmentioning

confidence: 99%

Novel concepts in airway inflammation and remodelling in asthma

2015

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“…Despite the generally accepted notion of airway inflammation guiding airway remodeling, this association has been disputed based on studies conducted in both children and adults. A study involving pre-school children failed to detect any association between airway inflammation and airway remodeling [96]. In a different study in adults, while allergen exposure induced airway inflammation, bronchoconstriction and airway remodeling, methacholine challenge induced bronchoconstriction and airway remodeling but no airway inflammation [97].…”

Section: Beneficial and Adverse Effects Of Neutrophils In The Asthmatmentioning

confidence: 99%

Neutrophilic Inflammation in Asthma and Association with Disease Severity

Ray

Kolls

2017

Trends in Immunology

388

307

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Asthma is a chronic inflammatory disorder of the airways. While the local infiltration of eosinophils and mast cells, and their role in the disease, have long been recognized, neutrophil infiltration has also been assessed in many clinical studies. In these studies, airway neutrophilia was associated with asthma severity. Importantly, neutrophilia also correlates with asthma that is refractory to corticosteroids, the mainstay of asthma treatment. However, it is now increasingly recognized that neutrophils are a heterogeneous population, and a more precise phenotyping of these cells may help delineate different subtypes of asthma. Here, we review the current knowledge on the role of neutrophils in asthma and highlight future avenues of research in this field.

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“…59 Taken together, these findings indicate that airway histopathologic changes and alterations consistent with airway remodeling occur by 3 years of age in children who are destined to have persistent asthma by school age. 60 …”

Section: Airway Physiologic Alterationsmentioning

confidence: 99%

Lessons learned from birth cohort studies conducted in diverse environments

Jackson

Gern

Lemanske

2017

Journal of Allergy and Clinical Immunology

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Birth cohort studies have produced significant advances toward understanding how genetic and environmental factors contribute to the inception of asthma and related allergic diseases. Histopathologic, physiologic, microbiologic, and immunologic findings indicate that critical developmental windows exist in which these various factors either alone or in concert induce the expression of the childhood asthma phenotype. The microbiome in early life clearly influences immune development and asthma. Early environmental exposures, including those related to the home, parents, siblings, pets, and pests, are all likely to influence patterns of microbial colonization and also might shape immune responses to allergens and viruses. As with other contributing factors, there appear to be windows of opportunity in early life when microbial exposures have the greatest effect on these processes. Recent studies of bacterial metabolic products and their effects might suggest new strategies for immune modulation in early life.

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Airway Remodeling in Preschool Children with Severe Recurrent Wheeze

Cited by 77 publications

References 48 publications

Novel concepts in airway inflammation and remodelling in asthma

Novel concepts in airway inflammation and remodelling in asthma

Neutrophilic Inflammation in Asthma and Association with Disease Severity

Lessons learned from birth cohort studies conducted in diverse environments

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