Airway Microbiota and Pathogen Abundance in Age-Stratified Cystic Fibrosis Patients

Bacterial communities in the airways of cystic fibrosis (CF) patients are, as in other ecological niches, influenced by autogenic and allogenic factors. However, our understanding of microbial colonization in younger versus older CF airways and the association with pulmonary function is rudimentary at best. Using a phylogenetic microarray, we examine the airway microbiota in age stratified CF patients ranging from neonates (9 months) to adults (72 years). From a cohort of clinically stable patients, we demonstrate that older CF patients who exhibit poorer pulmonary function possess more uneven, phylogenetically-clustered airway communities, compared to younger patients. Using longitudinal samples collected form a subset of these patients a pattern of initial bacterial community diversification was observed in younger patients compared with a progressive loss of diversity over time in older patients. We describe in detail the distinct bacterial community profiles associated with young and old CF patients with a particular focus on the differences between respective “early” and “late” colonizing organisms. Finally we assess the influence of Cystic Fibrosis Transmembrane Regulator (CFTR) mutation on bacterial abundance and identify genotype-specific communities involving members of the Pseudomonadaceae, Xanthomonadaceae, Moraxellaceae and Enterobacteriaceae amongst others. Data presented here provides insights into the CF airway microbiota, including initial diversification events in younger patients and establishment of specialized communities of pathogens associated with poor pulmonary function in older patient populations

Partitioning core and satellite taxa from within cystic fibrosis lung bacterial communities

Cystic fibrosis (CF) patients suffer from chronic bacterial lung infections that lead to death in the majority of cases. The need to maintain lung function in these patients means that characterising these infections is vital. Increasingly, culture-independent analyses are expanding the number of bacterial species associated with CF respiratory samples; however, the potential significance of these species is not known. Here, we applied ecological statistical tools to such culture-independent data, in a novel manner, to partition taxa within the metacommunity into core and satellite species. Sputa and clinical data were obtained from 14 clinically stable adult CF patients. Fourteen rRNA gene libraries were constructed with 35 genera and 82 taxa, identified in 2139 bacterial clones. Shannon–Wiener and taxa-richness analyses confirmed no undersampling of bacterial diversity. By decomposing the distribution using the ratio of variance to the mean taxon abundance, we partitioned objectively the species abundance distribution into core and satellite species. The satellite group comprised 67 bacterial taxa from 33 genera and the core group, 15 taxa from 7 genera (including Pseudomonas (1 taxon), Streptococcus (2), Neisseria (2), Catonella (1), Porphyromonas (1), Prevotella (5) and Veillonella (3)], the last four being anaerobes). The core group was dominated by Pseudomonas aeruginosa. Other recognised CF pathogens were rare. Mantel and partial Mantel tests assessed which clinical factors influenced the composition observed. CF transmembrane conductance regulator genotype and antibiotic treatment correlated with all core taxa. Lung function correlated with richness. The clinical significance of these core and satellite species findings in the CF lung is discussed

An appraisal of respiratory system compliance in mechanically ventilated covid-19 patients

BackgroundHeterogeneous respiratory system static compliance (CRS) values and levels of hypoxemia in patients with novel coronavirus disease (COVID-19) requiring mechanical ventilation have been reported in previous small-case series or studies conducted at a national level.MethodsWe designed a retrospective observational cohort study with rapid data gathering from the international COVID-19 Critical Care Consortium study to comprehensively describe CRS—calculated as: tidal volume/[airway plateau pressure-positive end-expiratory pressure (PEEP)]—and its association with ventilatory management and outcomes of COVID-19 patients on mechanical ventilation (MV), admitted to intensive care units (ICU) worldwide.ResultsWe studied 745 patients from 22 countries, who required admission to the ICU and MV from January 14 to December 31, 2020, and presented at least one value of CRS within the first seven days of MV. Median (IQR) age was 62 (52–71), patients were predominantly males (68%) and from Europe/North and South America (88%). CRS, within 48 h from endotracheal intubation, was available in 649 patients and was neither associated with the duration from onset of symptoms to commencement of MV (p = 0.417) nor with PaO2/FiO2 (p = 0.100). Females presented lower CRS than males (95% CI of CRS difference between females-males: − 11.8 to − 7.4 mL/cmH2O p RS was marginal (p = 0.139). Ventilatory management varied across CRS range, resulting in a significant association between CRS and driving pressure (estimated decrease − 0.31 cmH2O/L per mL/cmH20 of CRS, 95% CI − 0.48 to − 0.14, p RS (+ 10 mL/cm H2O) was only associated with being discharge from the ICU within 28 days (HR 1.14, 95% CI 1.02–1.28, p = 0.018).ConclusionsThis multicentre report provides a comprehensive account of CRS in COVID-19 patients on MV. CRS measured within 48 h from commencement of MV has marginal predictive value for 28-day mortality, but was associated with being discharged from ICU within the same period. Trial documentation: Available at https://www.covid-critical.com/study.Trial registration: ACTRN12620000421932

A multi-country analysis of COVID-19 hospitalizations by vaccination status

Background: Individuals vaccinated against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), when infected, can still develop disease that requires hospitalization. It remains unclear whether these patients differ from hospitalized unvaccinated patients with regard to presentation, coexisting comorbidities, and outcomes. Methods: Here, we use data from an international consortium to study this question and assess whether differences between these groups are context specific. Data from 83,163 hospitalized COVID-19 patients (34,843 vaccinated, 48,320 unvaccinated) from 38 countries were analyzed. Findings: While typical symptoms were more often reported in unvaccinated patients, comorbidities, including some associated with worse prognosis in previous studies, were more common in vaccinated patients. Considerable between-country variation in both in-hospital fatality risk and vaccinated-versus-unvaccinated difference in this outcome was observed. Conclusions: These findings will inform allocation of healthcare resources in future surges as well as design of longer-term international studies to characterize changes in clinical profile of hospitalized COVID-19 patients related to vaccination history. Funding: This work was made possible by the UK Foreign, Commonwealth and Development Office and Wellcome (215091/Z/18/Z, 222410/Z/21/Z, 225288/Z/22/Z, and 220757/Z/20/Z); the Bill & Melinda Gates Foundation (OPP1209135); and the philanthropic support of the donors to the University of Oxford's COVID-19 Research Response Fund (0009109). Additional funders are listed in the "acknowledgments" section