The Pulmonary Microbiome in Cystic Fibrosis

The chronic colonisation of the lower airways by bacterial pathogens is the leading cause of morbidity and mortality in patients with cystic fibrosis (CF). The use of novel culture-independent techniques such as next-generation sequencing (NGS) to analyse the lungs has allowed us to further understand the diversity, the complexity, the effects of acute exacerbations and the use of antibiotics on the bacterial communities. The understanding of the CF microbiome to airway disease remains a fascinating area of research; it presents new opportunities for disease management in CF and has the potential to explore the effects of cystic fibrosis transmembrane conductance regulator (CFTR) modulators. It also allows further appreciation regarding the roles played by anaerobic organisms within the CF airways. It is also of interest that a number of studies have demonstrated that the fluctuations of microbiome are not necessarily associated with the patient’s clinical status. Despite the available evidence, there remain many challenges that must be overcome if microbiome profiling is going to influence future clinical practice. The effects of fungus and the emergence of nontuberculous mycobacteria in CF are also briefly discussed in this chapter

Case Report: First report of <i>Elizabethkingia miricola</i> infection in a patient with cystic fibrosis.

Elizabethkingia miricola is a rare non-fermenting Gram-negative rod that has previously been reported to be associated with blood stream and pulmonary abscess infections, but never before in cystic fibrosis (CF). Here we present the first reported case of Elizabethkingia miricola infection in a patient with CF and discuss the management options. We describe a patient with CF in whom we observed clinical and spirometric evidence of pulmonary exacerbation with the associated growth of E. miricola in sputum culture. The period of clinical instability was observed to coincide with the obtainment of four sputum samples from which E. miricola was cultured; improvement was seen following treatment with ciprofloxacin and the subsequent eradication of E. miricola. We conclude that E. miricola is able to survive in the CF lung and in this case was associated with pulmonary exacerbation. Empirical treatment with fluoroquinolones is appropriate, based on our experience

Antibiotic therapy for chronic infection with Burkholderia cepacia complex in people with cystic fibrosis

BACKGROUND:Cystic fibrosis (CF) a life-limiting inherited disease affecting a number of organs, but classically associated with chronic lung infection and progressive loss of lung function. Chronic infection by Burkholderia cepacia complex (BCC) is associated with increased morbidity and mortality and therefore represents a significant challenge to clinicians treating people with CF. This review examines the current evidence for long-term antibiotic therapy in people with CF and chronic BCC infection. OBJECTIVES:The objective of this review is to assess the effects of long-term oral and inhaled antibiotic therapy targeted against chronic BCC lung infections in people with CF. The primary objective is to assess the efficacy of treatments in terms of improvements in lung function and reductions in exacerbation rate. Secondary objectives include quantifying adverse events, mortality and changes in quality of life associated with treatment. SEARCH METHODS:We searched the Cochrane Cystic Fibrosis Trials Register, compiled from electronic database searches and handsearching of journals and conference abstract books. We also searched online trial registries and the reference lists of relevant articles and reviews.Date of last search: 29 May 2019. SELECTION CRITERIA:Randomised controlled trials (RCTs) of long-term antibiotic therapy in people with CF and chronic BCC infection. DATA COLLECTION AND ANALYSIS:Two authors independently extracted data, assessed risk of bias and assessed the quality of the evidence using GRADE. MAIN RESULTS:We included one RCT (100 participants) which lasted 52 weeks comparing continuous inhaled aztreonam lysine (AZLI) and placebo in a double-blind RCT for 24 weeks, followed by a 24-week open-label extension and a four-week follow-up period. The average participant age was 26.3 years, 61% were male and average lung function was 56.5% predicted.Treatment with AZLI for 24 weeks was not associated with improvement in forced expiratory volume in one second (FEV1), mean difference 0.91% (95% confidence interval (CI) -3.15 to 4.97) (moderate-quality evidence). The median time to the next exacerbation was 75 days in the AZLI group compared to 51 days in the placebo group, but the difference was not significant (P = 0.27) (moderate-quality evidence). Similarly, the number of participants hospitalised for respiratory exacerbations showed no difference between groups, risk ratio (RR) 0.88 (95% CI 0.53 to 1.45) (moderate-quality evidence). Overall adverse events were similar between groups, RR 1.08 (95% CI 0.98 to 1.19) (moderate-quality evidence). There were no significant differences between treatment groups in relation to mortality (moderate-quality evidence), quality of life or sputum density.In relation to methodological quality, the overall risk of bias in the study was assessed to be unclear to low risk. AUTHORS' CONCLUSIONS:We found insufficient evidence from the literature to determine an effective strategy for antibiotic therapy for treating chronic BCC infection

Effects of postpartum mobile phone‐based education on maternal and infant health in Ecuador

ObjectiveTo evaluate the effects of a mobile phone‐based intervention on postnatal maternal health behavior and maternal and infant health in a middle‐income country.MethodsA prospective evaluation enrolled consecutive postpartum women at two public hospitals in Quito, Ecuador, between June and August 2012. Inclusion criteria were live birth, no neonatal intensive care admission, and Spanish speaking. Intervention and control groups were assigned via random number generation. The intervention included a telephone‐delivered educational session and phone/text access to a nurse for 30 days after delivery. Maternal and infant health indicators were recorded at delivery and 3 months after delivery via chart review and written/telephone‐administered survey.ResultsOverall, 102 women were assigned to the intervention group and 76 to the control group. At 3 months, intervention participants were more likely to attend the infant’s postnatal check‐up (P = 0.022) and to breastfeed exclusively (P = 0.005), and less likely to feed formula (P = 0.016). They used more effective forms of contraception (more implants P = 0.023; fewer condoms P = 0.036) and reported fewer infant illnesses (P = 0.010). There were no differences in maternal acute illness or check‐up attendance.ConclusionMobile phone‐based postnatal patient education is a promising strategy for improving breastfeeding, contraceptive use, and infant health in low‐resource settings; different strategies are needed to influence postpartum maternal health behavior.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/135151/1/ijgo93.pd

The long-term effects of insulin use in incident cystic fibrosis-related diabetes: a target trial emulated using longitudinal national registry data.

Introduction: Cystic fibrosis-related diabetes (CFRD) is a common complication of cystic fibrosis and is associated with deleterious clinical outcomes. Insulin is recommended as a treatment by international guidelines. However, there are scarce clinical trial data to support the use of insulin, and little is known about the long-term outcomes of treatment. The aim of this study was to compare the long-term impacts of insulin use versus non-use in CFRD. Methods: We used data from the national UK Cystic Fibrosis Registry and adopted a target trial framework. Eligible individuals included those 12 years and older with a new diagnosis of CFRD. Outcomes were change in % predicted forced expiratory volume in 1 s (FEV1 %) and body mass index z-scores (BMI) over a 5-year follow-up period. Treatment strategies were to receive insulin or not for the duration of follow-up. Treatment effect estimates were obtained using two methods to control for confounding: inverse-probability-of-treatment weighted estimation of marginal structural models and the G-formula. Results: We identified 1613 individuals diagnosed with CFRD between 2008 and 2016 and included 1196 and 1192 in the FEV1 % and BMI outcome analyses respectively. We found no evidence of an effect of insulin on FEV1 % over the 5-year study period. Similarly, we found no overall effect of insulin on BMI; however, there was some evidence for a positive treatment effect in patients with lower baseline BMI. Conclusion: Using well-established national registry data, we found no evidence of long-term treatment effects for insulin on FEV1 % or BMI in people with incident CFRD

Case Report: Haemolytic anaemia with ceftazidime use in a patient with cystic fibrosis.

Drug-induced Immune Haemolytic Anaemia (DIIHA) is a rare but serious complication of cephalosporin use. Ceftazidime is recognized to be a rare cause of DIIHA. We report and discuss a case of DIIHA in a person with cystic fibrosis who developed severe haemolytic anaemia following use of ceftazidime in the management of an acute pseudomonal pulmonary exacerbation

The utility of established prognostic scores in COVID-19 hospital admissions: a multi-centre prospective evaluation of CURB-65, NEWS2, and qSOFA

AbstractIntroductionThe COVID-19 pandemic is ongoing yet, due to the lack of a COVID-19 specific tool, clinicians must use pre-existing illness severity scores for initial prognostication. However, the validity of such scores in COVID-19 is unknown.MethodsThe North West Collaborative Organization for Respiratory Research (NW-CORR) performed a multi-centre prospective evaluation of adult patients admitted to hospital with confirmed COVID-19 during a two-week period in April 2020. Clinical variables measured as part of usual care at presentation to hospital were recorded, including the CURB-65, NEWS2, and qSOFA scores. The primary outcome of interest was 30-day mortality.ResultsData were collected for 830 people with COVID-19 admitted across 7 hospitals. By 30 days, a total of 300 (36.1%) had died and 142 (17.1%) had been in ICU. All scores underestimated mortality compared to their original validation in non-COVID-19 populations, and overall prognostic performance was generally poor. Among the ‘low risk’ categories (CURB-65&lt;2, NEWS2&lt;5, qSOFA&lt;2) 30-day mortality was 16.7%, 32.9% and 21.4%, respectively. Multivariable logistic regression identified features of respiratory compromise rather than circulatory collapse as most relevant prognostic variables.ConclusionAll existing prognostic scores evaluated here underestimated adverse outcomes and performed sub-optimally in the COVID-19 setting. New prognostic tools including a focus on features of respiratory compromise rather than circulatory collapse are needed. We provide a baseline set of variables which are relevant to COVID-19 outcomes and may be used as a basis for developing a bespoke COVID-19 prognostication tool.Key MessagesWhat is the key question?Do well-established illness severity scores have prognostic value in COVID-19?What is the bottom line?All scores appeared to underestimate mortality in COVID-19 and prognostic performance was generally poor, and importantly could not discriminate those patients at very low risk of death within 30 days.Why read on?In this multi-centre prospective evaluation of CURB-65, NEWS2 and qSOFA we comprehensively evaluate score performance and also identify variables which may be of use in COVID-19 prognostication.</jats:sec

Continuous glucose monitoring systems for monitoring cystic fibrosis-related diabetes

Objectives: This is a protocol for a Cochrane Review (intervention). The objectives are as follows:. To establish the impact of insulin therapy guided by continuous glucose monitoring compared to insulin therapy guided by other forms of glucose data collection on the lives of people with cystic fibrosis-related diabetes (pwCFRD)