Extended-culture and culture-independent molecular analysis of the airway microbiota in cystic fibrosis following CFTR modulation with ivacaftor

Einarsson, G.G.; Ronan, N.J.; Mooney, D.; McGettigan, Clodagh; Mullane, D.; NíChróinín, Muireann; Shanahan, Fergus; Murphy, Desmond M.; McCarthy, M.; McCarthy, Yvonne; Eustace, Joseph A.; Gilpin, D.F.; Elborn, J.S.; Plant, Barry J.; Tunney, Michael

doi:10.1016/j.jcf.2020.12.023

Cited by 31 publications

(24 citation statements)

References 32 publications

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“…However, P. aeruginosa density rebounded after ∼1 year, and P. aeruginosa strains present pretreatment were found to persist for ∼6 years of follow-up ( 4 ). Epidemiological studies analyzing patient registry data ( 5 – 9 ) and studies using DNA-based methods ( 5 , 10 , 11 ) also indicate that chronic infections usually persist in modulator-treated patients. Persistent infection is likely to be detrimental, so strategies that eradicate infections in modulator-treated patients could markedly increase the health benefits from these drugs.…”

Section: Introductionmentioning

confidence: 99%

Combining Ivacaftor and Intensive Antibiotics Achieves Limited Clearance of Cystic Fibrosis Infections

Durfey

Pipavath

et al. 2021

mBio

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Section: Introductionmentioning

confidence: 99%

Combining Ivacaftor and Intensive Antibiotics Achieves Limited Clearance of Cystic Fibrosis Infections

Durfey

Pipavath

et al. 2021

mBio

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“…Non-induced sputum was collected at inclusion, and an extended microbiological culture was performed, as previously described ( Sherrard et al, 2019 ; Einarsson et al, 2021 ). Sputum quality assessment was performed for each sputum according to the Bartlett score ( Bartlett et al, 1998 ).…”

Section: Methodsmentioning

confidence: 99%

Extended Bacteria Culture-Based Clustering Identifies a Phenotype Associating Increased Cough and Enterobacterales in Stable Chronic Obstructive Pulmonary Disease

et al. 2021

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Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory lung disease characterized by airflow limitation. This chronic respiratory disease represents the third leading cause of death worldwide. Alteration of the airway microbiota has been reported to be associated with exacerbation frequency in COPD, but its role on the symptoms in patients at stable state is still incompletely described. This study aimed to determine whether bacteria isolated in sputum can be associated with the clinical features of COPD patients within stable state. Our study highlights, for the first time, that altered microbiota with Enterobacterales is associated with pejorative clinical symptoms in stable COPD patients. The airway microbiota of 38 patients was analyzed using an extended culture approach and mass spectrometry identification. Cluster analysis by principal coordinate analysis of the bacterial communities showed that the patients could be classified into three distinct clusters in our cohort. The clusters showed no differences in proportions of the phylum, but one of them was associated with a high prevalence of Enterobacterales (71.4% in cluster 1 vs. 0% in cluster 3), loss of microbiota diversity, and higher bacterial load (107 vs. 105 CFU/ml, respectively) and characterized by predominant cough and impact on mental health. These novel findings, supported by further studies, could lead to modifying the processing of COPD sputum in the everyday practice of clinical microbiology laboratories.

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“…Investigations about the effects of CFTR modulators on the airway microbiome have so far focused on single-modulator ivacaftor treatment for patients with at least one G551D allele, and only one recent study investigated the effects of lumacaftorivacaftor on airway microbiome in F508del-homozygous individuals. In Table 1, we have summarized the studies addressing the effects of modulator therapies on microbial features (Rowe et al, 2014;Bernarde et al, 2015;Heltshe et al, 2015;Hisert et al, 2017;Peleg et al, 2018;Ronan et al, 2018;Harris et al, 2019;Einarsson et al, 2021;Graeber et al, 2021). Effects of ivacaftor therapy on P. aeruginosa sputum level and other clinical parameters have been assessed in 133 patients of age 6 and older in a longitudinal cohort study (Rowe et al, 2014).…”

Section: How Cftr Modulator Therapies Affect the Airway Microbiomementioning

confidence: 99%

“…Here a change in antibiotic exposure was defined as any escalation or deescalation in antibiotic use in the two weeks prior to sputum sample collection (Peleg et al, 2018). In another one-year study with 14 patients, with a combination of culture and cultureindependent approaches, it has been shown that microbial community richness and diversity of sputum microbiota increased after ivacaftor treatment, which was correlated with lower levels of the main markers of inflammation (Ronan et al, 2018;Einarsson et al, 2021). Interestingly, the relative abundance of streptococci increased, while the relative abundance of Pseudomonas spp.…”

Section: How Cftr Modulator Therapies Affect the Airway Microbiomementioning

confidence: 99%

Changes in the Cystic Fibrosis Airway Microbiome in Response to CFTR Modulator Therapy

Dalpke

Boutin

2021

Front. Cell. Infect. Microbiol.

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The development of CFTR modulator therapies significantly changed the treatment scheme of people with cystic fibrosis. However, CFTR modulator therapy is still a life-long treatment, which is not able to correct the genetic defect and cure the disease. Therefore, it becomes crucial to understand the effects of such modulation of CFTR function on the airway physiology, especially on airway infections and inflammation that are currently the major life-limiting factors in people with cystic fibrosis. In this context, understanding the dynamics of airway microbiome changes in response to modulator therapy plays an essential role in developing strategies for managing airway infections. Whether and how the newly available therapies affect the airway microbiome is still at the beginning of being deciphered. We present here a brief review summarizing the latest information about microbiome alterations in light of modern cystic fibrosis modulator therapy.

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Extended-culture and culture-independent molecular analysis of the airway microbiota in cystic fibrosis following CFTR modulation with ivacaftor

Cited by 31 publications

References 32 publications

Combining Ivacaftor and Intensive Antibiotics Achieves Limited Clearance of Cystic Fibrosis Infections

Combining Ivacaftor and Intensive Antibiotics Achieves Limited Clearance of Cystic Fibrosis Infections

Extended Bacteria Culture-Based Clustering Identifies a Phenotype Associating Increased Cough and Enterobacterales in Stable Chronic Obstructive Pulmonary Disease

Changes in the Cystic Fibrosis Airway Microbiome in Response to CFTR Modulator Therapy

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