The airway microbiome in COPD, bronchiectasis and bronchiectasis‐COPD overlap

Tiew, Pei Yee; Jaggi, Tavleen Kaur; Chan, Louisa; Chotirmall, Sanjay H.

doi:10.1111/crj.13294

Cited by 45 publications

(41 citation statements)

References 111 publications

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“…In particular, our cohort of CF adults had more advanced lung disease and a microbial community which was much less diverse (median SDI 1.21 (IQR 0.5-1.8)and thus less likely to experience significant perturbations [37,38]. It is possible a younger cohort of individuals with CF with more diverse microbial communitiesmore in keeping with those of asthma, COPD, and nCFB [39,40] may be more likely to demonstrate a change. However, other studies focusing on classical CF methods have also found that azithromycin treatment had no major impact on microbiological outcomes in a CF pediatric cohort with early P. aeruginosa infection [11] or in sputum bioburden [9].…”

Section: Discussionmentioning

confidence: 92%

Azithromycin and the microbiota of cystic fibrosis sputum

et al. 2021

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Background Azithromycin is commonly prescribed drug for individuals with cystic fibrosis (CF), with demonstrated benefits in reducing lung function decline, exacerbation occurrence and improving nutrition. As azithromycin has antimicrobial activity against components of the uncultured microbiome and increasingly the CF microbiome is implicated in disease pathogenesis – we postulated azithromycin may act through its manipulation. Herein we sought to determine if the CF microbiome changed following azithromycin use and if clinical benefit observed during azithromycin use associated with baseline community structure. Results Drawing from a prospectively collected biobank we identified patients with sputum samples prior to, during and after initiating azithromycin and determined the composition of the CF microbial community by sequencing the V3-V4 region of the 16S rRNA gene. We categorized patients as responders if their rate of lung function decline improved after azithromycin initiation. Thirty-eight adults comprised our cohort, nine who had not utilized azithromycin in at least 3 years, and 29 who were completely naïve. We did not observe a major impact in the microbial community structure of CF sputum in the 2 years following azithromycin usage in either alpha or beta-diversity metrics. Seventeen patients (45%) were classified as Responders – demonstrating reduced lung function decline after azithromycin. Responders who were naïve to azithromycin had a modest clustering effect distinguishing them from those who were non-Responders, and had communities enriched with several organisms including Stenotrophomonas, but not Pseudomonas. Conclusions Azithromycin treatment did not associate with subsequent large changes in the CF microbiome structure. However, we found that baseline community structure associated with subsequent azithromycin response in CF adults.

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Section: Discussionmentioning

confidence: 92%

Azithromycin and the microbiota of cystic fibrosis sputum

et al. 2021

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“…Fungi play an important role in the human microbiome ( Huseyin et al, 2017 ; Perez et al, 2021 ; Tiew et al, 2021 ). In this review, we have focused on genetic predisposition to human fungal infections and discussed the link that exists between ancestry and susceptibility to IFIs.…”

Section: Discussionmentioning

confidence: 99%

Genetic Susceptibility to Fungal Infections and Links to Human Ancestry

et al. 2021

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Over the ages, fungi have associated with different parts of the human body and established symbiotic associations with their host. They are mostly commensal unless there are certain not so well-defined factors that trigger the conversion to a pathogenic state. Some of the factors that induce such transition can be dependent on the fungal species, environment, immunological status of the individual, and most importantly host genetics. In this review, we discuss the different aspects of how host genetics play a role in fungal infection since mutations in several genes make hosts susceptible to such infections. We evaluate how mutations modulate the key recognition between the pathogen associated molecular patterns (PAMP) and the host pattern recognition receptor (PRR) molecules. We discuss the polymorphisms in the genes of the immune system, the way it contributes toward some common fungal infections, and highlight how the immunological status of the host determines fungal recognition and cross-reactivity of some fungal antigens against human proteins that mimic them. We highlight the importance of single nucleotide polymorphisms (SNPs) that are associated with several of the receptor coding genes and discuss how it affects the signaling cascade post-infection, immune evasion, and autoimmune disorders. As part of personalized medicine, we need the application of next-generation techniques as a feasible option to incorporate an individual’s susceptibility toward invasive fungal infections based on predisposing factors. Finally, we discuss the importance of studying genomic ancestry and reveal how genetic differences between the human race are linked to variation in fungal disease susceptibility.

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“…Proteobacteria dysbiosis of the microbiome is associated with more severe disease and worse clinical outcomes. 6,65,[111][112][113] P. aeruginosa is the most commonly identified pathogen in bronchiectasis patients worldwide and has been associated with increased exacerbation frequency, reduced quality of life, and increased mortality. 112,114,115 The frequency of P. aeruginosa colonization is likely due to its ability to evade killing by inflammatory cells and antimicrobial peptides.…”

Section: Airway Infection Bacterial Infectionmentioning

confidence: 99%

Pathophysiology of Bronchiectasis

Keir

Chalmers

2021

Semin Respir Crit Care Med

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Bronchiectasis is a complex, heterogeneous disorder defined by both a radiological abnormality of permanent bronchial dilatation and a clinical syndrome. There are multiple underlying causes including severe infections, mycobacterial disease, autoimmune conditions, hypersensitivity disorders, and genetic conditions. The pathophysiology of disease is understood in terms of interdependent concepts of chronic infection, inflammation, impaired mucociliary clearance, and structural lung damage. Neutrophilic inflammation is characteristic of the disease, with elevated levels of harmful proteases such as neutrophil elastase associated with worse outcomes. Recent data show that neutrophil extracellular trap formation may be the key mechanism leading to protease release and severe bronchiectasis. Despite the dominant of neutrophilic disease, eosinophilic subtypes are recognized and may require specific treatments. Neutrophilic inflammation is associated with elevated bacterial loads and chronic infection with organisms such as Pseudomonas aeruginosa. Loss of diversity of the normal lung microbiota and dominance of proteobacteria such as Pseudomonas and Haemophilus are features of severe bronchiectasis and link to poor outcomes. Ciliary dysfunction is also a key feature, exemplified by the rare genetic syndrome of primary ciliary dyskinesia. Mucus symptoms arise through goblet cell hyperplasia and metaplasia and reduced ciliary function through dyskinesia and loss of ciliated cells. The contribution of chronic inflammation, infection, and mucus obstruction leads to progressive structural lung damage. The heterogeneity of the disease is the most challenging aspect of management. An understanding of the pathophysiology of disease and their biomarkers can help to guide personalized medicine approaches utilizing the concept of “treatable traits.”

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The airway microbiome in COPD, bronchiectasis and bronchiectasis‐COPD overlap

Cited by 45 publications

References 111 publications

Azithromycin and the microbiota of cystic fibrosis sputum

Azithromycin and the microbiota of cystic fibrosis sputum

Genetic Susceptibility to Fungal Infections and Links to Human Ancestry

Pathophysiology of Bronchiectasis

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