The Microbiome and the Pathophysiology of Asthma

Sullivan, Ashley F.; Hunt, Eoin; MacSharry, John; Murphy, Desmond M.

doi:10.1186/s12931-016-0479-4

Cited by 60 publications

(54 citation statements)

References 103 publications

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“…It may mean that bacterial lower airway inflammation acts as a complicating factor in patients with poorly controlled asthma as it was suggested previously. 22 An interesting finding of our study was the absence of a correlation between GI symptoms and food allergies with presence of esophageal eosinophils (with the exception of children with EoE), which emphasizes the importance of EsB in children with SUA even in the absence of clinical features suggestive of esophagitis. Emergence of aerodigestive medicine has been associated with the introduction of combined aerodigestive endoscopy in pediatric practice.…”

Section: Discussionsupporting

confidence: 46%

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Airway and esophageal eosinophils in children with severe uncontrolled asthma

Erkman¹,

Vaynblat

Thomas

et al. 2018

Pediatric Pulmonology

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Aim Children with severe uncontrolled asthma (SUA) have a high burden of symptoms and increased frequency of asthma exacerbations. Reflux esophagitis and eosinophilic esophagitis are important co‐morbid factors for SUA. Both are associated with the presence of eosinophils in esophageal mucosa. We hypothesized that esophageal eosinophils are frequently present and correlate with the presence of airway eosinophils in children with SUA. Method We performed a retrospective analysis of a prospective database of children who underwent “triple endoscopy” (sleep laryngoscopy, bronchoscopy with bronchoalveolar lavage [BAL] and endobronchial biopsy [EBB], and esophagogastroduodenoscopy with esophageal biopsy [EsB]) at our Aerodigestive Center for evaluation of SUA. Children with known cystic fibrosis, primary ciliary dyskinesia, and aspiration‐related lung disease were excluded. Result Twenty‐four children (21 males) ages 2‐16 years were studied. Elevated BAL eosinophils were found in 10 (42%) patients, endobronchial eosinophils in 16 (67%); 7 (29%) had endobronchial eosinophils without elevated BAL eosinophils. Esophageal eosinophils were found in 11 (46%) patients. There was a correlation between the amount of eosinophils in BAL and EBB (R = 0.43, P = 0.05) airway eosinophils, defined as elevated BAL and/or EBB eosinophils, correlated with esophageal eosinophils (R = 0.41, P = 0.047). Conclusion We concluded that airway and esophageal eosinophils are frequently present in children with SUA.

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Section: Discussionsupporting

confidence: 46%

“…More than half of our study, patients were found to have bacterial bronchitis with positive BAL cultures. It may mean that bacterial lower airway inflammation acts as a complicating factor in patients with poorly controlled asthma as it was suggested previously …”

Section: Discussionmentioning

confidence: 89%

Airway and esophageal eosinophils in children with severe uncontrolled asthma

Erkman¹,

Vaynblat

Thomas

et al. 2018

Pediatric Pulmonology

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“…5 Recent microbiome studies on the basis of culture-independent techniques, such as massive sequencing or microarrays, have shown that the lung is not sterile as previously thought. 6 Furthermore, it has been highlighted the role of bacteria residing in the human lung in the development of asthma and the severity of the disease, 7 and how bacteria interact with the airways in asthma susceptibility. 8 In addition, it has been shown that there is a connection between the inflammation of the airways and early environmental exposures in life, being those children who have had contact with animals and other allergens during their first period of life the ones less prone to develop the disease.…”

Section: Introductionmentioning

confidence: 99%

Bacterial salivary microbiome associates with asthma among african american children and young adults

Espuela‐Ortiz

Lorenzo-Díaz

Baez‐Ortega

et al. 2019

Pediatric Pulmonology

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Several studies have shown that the airways of asthma patients contain higher diversity of bacteria and are enriched in pathogenic species. However, sampling the airways in children is challenging. Here we aimed to identify differences in the salivary bacterial composition between African Americans children with and without asthma. Saliva samples from 57 asthma cases and 57 healthy controls were analyzed by means of 16S ribosomal RNA amplicon profiling. Measurements of bacterial diversity and genus relative abundance were compared between cases and controls using the nonparametric Wilcoxon test and multivariate regression models. A total of five phyla and a mean of 56 genera were identified. Among them, 15 genera had a relative abundance greater than 1%, being Prevotella, Haemophilus, Streptococcus, and Veillonella the most abundant genera. Differences between cases and controls were found in terms of diversity, as well as in relative abundance for Streptococcus genus (13.0% in cases vs 18.3% in controls; P = .003) and Veillonella genus (11.1% in cases vs 8.0% in controls; P = .002). These differences remained significant after correction for multiple comparisons and when potential confounders were taken into account in logistic regression models. In conclusion, we identified changes in the salivary microbiota associated with asthma among African Americans.

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“…The relatively recent increase in asthma is attributed to the "hygiene hypothesis" of reduced exposure to microorganisms, a result of improved hygiene during infancy and early adulthood [4,5]. Reduced exposure to microorganisms during these vulnerable periods contributes to the development of lymphocytes with a T helper 2 (Th2) phenotype, i.e., lymphocytes known to promote asthmatic symptoms by producing Th2 cytokines, along with the induced accumulation of leukocytes.…”

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confidence: 99%

Therapeutic Role for TSP-2 Antibody in a Murine Asthma Model

Huang²,

Zhu

et al. 2018

Int Arch Allergy Immunol

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Background: Specific immunotherapy, including agonists for Toll-like receptor 2 (TLR2), have been shown to protect from allergies and to have a high immunomodulatory capacity. Methods: A new antibody, TSP-2, reactive against an epitope of the extracellular domain of TLR2, was identified. The effect of the antibody on dendritic cells was assessed by immunohistochemistry, Western blot, and flow cytometric analysis. The effect of TSP-2 in a murine asthma model induced with ovalbumin (OVA) was assessed. The model is a form of airway hyperresponsiveness (AHR) and was analyzed by whole-body plethysmography, the measurement of Th1/Th2 cytokines in bronchial alveolar lavage fluid (BALF) and serum by ELISA, and the CCK-8 assay for lymphocyte proliferation. The effect of TSP-2 on the maturation of bone marrow-derived dendritic cells (BMDCs) was assessed by flow cytometric analysis. Results: TSP-2 promoted the maturation of dendritic cells and the proliferation of lymphocyte in vitro and in vivo. The effect of TSP-2 on T helper 1 (Th1)/Th2 cytokine secretion was slightly more powerful than that of Pam₃CSK₄. TSP-2 antibody reduced AHR and OVA-specific IgE levels in allergic asthma. TSP-2 antibody also reduced lung inflammation and decreased leukocyte numbers in an OVA-sensitized and challenged asthma model. TSP-2 antibody increased OVA-stimulated I-A, CD80, CD86, and MHC-II levels on BMDCs. Conclusions: This study identifies a novel therapeutic strategy for AHR, which uses antibodies reactive against TLR2. It also provides theoretical evidence for the control of allergic asthma by targeting TLR2.

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The Microbiome and the Pathophysiology of Asthma

Cited by 60 publications

References 103 publications

Airway and esophageal eosinophils in children with severe uncontrolled asthma

Airway and esophageal eosinophils in children with severe uncontrolled asthma

Bacterial salivary microbiome associates with asthma among african american children and young adults

Therapeutic Role for TSP-2 Antibody in a Murine Asthma Model

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