The role of NTHi colonization and infection in the pathogenesis of neutrophilic asthma

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The role of NTHi colonization and infection in the pathogenesis of neutrophilic asthma Jing Zhang1,2 , Zhenxing Zhu3, Xu Zuo2, He Pan2, Yinuo Gu2, Yuze Yuan2, Guoqiang Wang2, Shiji Wang1, Ruipeng Zheng2,4, Zhongmin Liu1, Fang Wang2 and Jingtong Zheng2,5*

Abstract Asthma is a complex heterogeneous disease. The neutrophilic subtypes of asthma are described as persistent, more severe and corticosteroid-resistant, with higher hospitalization and mortality rates, which seriously affect the lives of asthmatic patients. With the development of high-throughput sequencing technology, an increasing amount of evidence has shown that lower airway microbiome dysbiosis contributes to the exacerbation of asthma, especially neutrophilic asthma. Nontypeable Haemophilus influenzae is normally found in the upper respiratory tract of healthy adults and is one of the most common strains in the lower respiratory tract of neutrophilic asthma patients, in whom its presence is related to the occurrence of corticosteroid resistance. To understand the pathogenic mechanism by which nontypeable Haemophilus influenzae colonization leads to the progression of neutrophilic asthma, we reviewed the previous literature on nontypeable Haemophilus influenzae colonization and subsequent aggravation of neutrophilic asthma and corticosteroid resistance. We discussed nontypeable Haemophilus influenzae as a potential therapeutic target to prevent the progression of neutrophilic asthma. Keywords: Neutrophilic asthma, Nontypeable Haemophilus influenzae (NTHi), Oxidative stress, Th17/Treg imbalance, Corticosteroid-resistant

Background Asthma is a complex airway inflammatory disease. It has been reported that there are more than 300 million asthma patients worldwide. The incidence of asthma varies greatly among different countries and regions. In recent decades, the mortality rate of asthma has declined significantly worldwide (Fig. 1a), mainly due to the widespread use of inhaled corticosteroids (ICS). However, the number of new cases of asthma is still increasing (Fig. 1b). According to a prediction from the Global Initiative for Asthma (GINA), 400 million people worldwide will suffer from asthma by 2025. Asthma is considered to be

* Correspondence: [email protected] 2 Department of Pathogen Biology, College of Basic Medical Sciences, Jilin University, Changchun 130021, China 5 Key Laboratory of Zoonosis, Ministry of Education, College of Veterinary Medicine, Jilin University, Changchun 130062, China Full list of author information is available at the end of the article

a major cause of disability, substantial medical expenditures and preventable death. In the past, asthma was too often viewed as a monolithic entity and was known as a type 1 hypersensitivity disease with eosinophilic bronchitis. The Th2 response plays a significant role in asthma, leading to interleukin4 (IL-4), IL-5, and IL-13 production, IgE-mediated responses, mucus secretion and airway hyperreactivity (AHR) [1]. These are classical explanations of asthma. The view o