Immunohistology and remodeling in fatal pediatric and adolescent asthma

Kristiina Malmström,Merja Kajosaari,Seppo Sarna,Antti Sajantila,Frode L Jahnsen,Jouko Lohi,Mika J Mäkelä

doi:10.1186/s12931-017-0575-0

Kristiina Malmström, Merja Kajosaari + Show 5 more

Open Access

https://doi.org/10.1186/s12931-017-0575-0

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Abstract

BackgroundThickening of reticular basement membrane, increased airway smooth muscle mass and eosinophilic inflammation are found in adult fatal asthma. At the present study the histopathology of fatal paediatric and adolescent asthma is evaluated.MethodsPost-mortem lung autopsies from 12 fatal asthma cases and 8 non-asthmatic control subjects were examined. Thickness of reticular basement membrane (RBM) and percentage of airway smooth muscle (ASM%) mass area were measured and inflammatory cells were counted. Patient records were reviewed for clinical history.ResultsThe age range of the cases was from 0.9 to 19.5 years, eight were males and five had received inhaled corticosteroids. Thickened RBM was detected in majority of the cases without any correlation to treatment delay, age at onset of symptoms or diagnosis. In the large airways ASM was clearly increased in one third of the cases whereas the median ASM% did not differ from that in healthy controls (14.0% vs. 14.0%). In small airways no increase of ASM was found, instead mucous plugs were seen in fatal asthma. The number of eosinophils, plasmacytoid dendritic cells, macrophages, and B-cells were significantly increased in fatal asthma cases compared with controls and the two latter correlated with the length of the fatal exacerbation.ConclusionsThe findings highlight the strong presence of eosinophils and mucous plugs even in small airways in children and adolescents with fatal asthma. Thickened RBM was obvious in majority of the patients. Contrary to our hypothesis, increased ASM% was detected in only one third of the patients.

Highlights

Thickening of reticular basement membrane, increased airway smooth muscle mass and eosinophilic inflammation are found in adult fatal asthma
Remodelling is characterized by epithelial injury, thickening of reticular basement membrane (RBM), airway smooth muscle (ASM), goblet cell hypertrophy and hyperplasia, and angiogenesis, whereas the inflammation is merely eosinophilic [2]
As anticipated, thickened RBM was found in fatal asthma but contrary to our hypothesis, ASM% was increased only 1/3 of fatal asthma cases, exclusively in large airways

Summary

Introduction

Thickening of reticular basement membrane, increased airway smooth muscle mass and eosinophilic inflammation are found in adult fatal asthma. Remodelling is characterized by epithelial injury, thickening of reticular basement membrane (RBM), airway smooth muscle (ASM), goblet cell hypertrophy and hyperplasia, and angiogenesis, whereas the inflammation is merely eosinophilic [2]. Thickened RBM was detected in school children with moderate and severe asthma [4,5,6,7,8,9], Increased thickness of ASM is seen in severe adult asthmatics especially in large airways [11, 12] and both ASM hyperplasia and hypertrophy contribute [13, 14]. ASM hyperplasia and hypertrophy in large airways were present even in moderate-to-severe asthma in children 7–16 years of age [15]

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