Nebuliser hygiene in cystic fibrosis: evidence-based recommendations.

Breathe (Sheff). 2020 Jun;16(2):190328

Authors: Bell J, Alexander L, Carson J, Crossan A, McCaughan J, Mills H, O'Neill D, Moore JE, Millar BC

Abstract
Nebulised therapies are extensively used in the daily therapeutic management of cystic fibrosis both for mucociliary clearance and for the management of chronic infections. Extensive developments have been made in relation to nebulised drug delivery mechanisms and drug formulations, and guidelines have been prepared that have addressed the appropriate use of such therapies. However, due to these developments, a plethora of nebuliser devices and drug chambers exist, and frequently, the limited guidance provided in relation to nebuliser hygiene is to follow manufacturers' instructions. Such instructions are inconsistent and at times confusing, translating to an increase in the burden associated with nebuliser maintenance. An evidence-based universal guideline relating to nebuliser care and hygiene is urgently required that is applicable to both at-home use and inpatient use. This article reviews the scientific literature in order to propose an evidence-based approach to nebuliser hygiene to ensure optimum drug delivery, and infection prevention and control.
Educational aims: To understand the reasons why nebuliser hygiene is important.To give an overview of the current nebuliser care instructions that have been described by manufacturers, societies and the scientific literature.To outline the current nebuliser hygiene practices used by persons with cystic fibrosis in the home and hospital settings.To highlight areas that need further evaluation to promote optimum nebuliser care.To establish an evidence-based guideline for nebuliser hygiene in relation to cystic fibrosis.

PMID: 32684992 [PubMed]

Ivacaftor or lumacaftor/ivacaftor treatment does not alter the core CF airway epithelial gene response to rhinovirus.

J Cyst Fibros. 2020 Jul 17;:

Authors: De Jong E, Garratt LW, Looi K, Lee AHY, Ling KM, Smith ML, Falsafi R, Sutanto EN, Hillas J, Iosifidis T, Martinovich KM, Shaw NC, Montgomery ST, Kicic-Starcevich E, Lannigan FJ, Vijayasekaran S, Hancock REW, Stick SM, Kicic A, WAERP, Arest CF

Abstract
BACKGROUND: Aberrant responses by the cystic fibrosis airway epithelium during viral infection may underly the clinical observations. Whether CFTR modulators affect antiviral responses by CF epithelia is presently unknown. We tested the hypothesis that treatment of CF epithelial cells with ivacaftor (Iva) or ivacaftor/lumacaftor (Iva/Lum) would improve control of rhinovirus infection.
METHODS: Nineteen CF epithelial cultures (10 homozygous for p.Phe508del as CFTR Class 2, 9 p.Phe508del/p.Gly551Asp as Class 3) were infected with rhinovirus 1B at multiplicity of infection 12 for 24 h. Culture RNA and supernatants were harvested to assess gene and protein expression respectively.
RESULTS: RNA-seq analysis comparing rhinovirus infected cultures to control identified 796 and 629 differentially expressed genes for Class 2 and Class 3, respectively. This gene response was highly conserved when cells were treated with CFTR modulators and were predicted to be driven by the same interferon-pathway transcriptional regulators (IFNA, IFNL1, IFNG, IRF7, STAT1). Direct comparisons between treated and untreated infected cultures did not yield any differentially expressed genes for Class 3 and only 68 genes for Class 2. Changes were predominantly related to regulators of lipid metabolism and inflammation, aspects of epithelial biology known to be dysregulated in CF. In addition, CFTR modulators did not affect viral copy number, or levels of pro-inflammatory cytokines produced post-infection.
CONCLUSIONS: Though long-term clinical data is not yet available, results presented here suggest that first generation CFTR modulators do not interfere with core airway epithelial responses to rhinovirus infection. Future work should investigate the latest triple modulation therapies.

PMID: 32684439 [PubMed - as supplied by publisher]

[Emerging bacteria in cystic fibrosis and non-cystic fibrosis bronchiectasis from a microbiologist's perspective].

Rev Mal Respir. 2020 Jul 16;:

Authors: Menetrey Q, Dupont C, Chiron R, Marchandin H

Abstract
INTRODUCTION: Common major pathogens like Pseudomonas aeruginosa are identified in the airways of patients with cystic fibrosis (CF) and non-CF bronchiectasis. However, other opportunistic bacterial pathogens like Achromobacter xylosoxidans complex, Stenotrophomonas maltophilia and non-tuberculous mycobacteria are currently emerging in CF and are also reported in non-CF bronchiectasis.
BACKGROUND: The emergence of opportunistic bacterial pathogens has been recognized in CF through annual national reports of sputum microbiology data. Despite common factors driving the emergence of bacteria identified in CF and non-CF bronchiectasis patients, bronchiectasis registries have been created more recently and no longitudinal analysis of recorded microbiological data is currently available in the literature, thereby preventing the recognition of emerging bacteria in patients with non-CF bronchiectasis.
OUTLOOK: A longitudinal follow-up of microbiological data is still needed in non-CF bronchiectasis to identify emerging opportunistic bacterial pathogens. Homogeneity in practice of sputum microbiological examination is also required to allow comparative analysis of data in CF and non-CF bronchiectasis.
CONCLUSION: Bacterial pathogens recognized as emerging in CF have to be more carefully monitored in non-CF bronchiectasis in view of their association with deterioration of the lung disease.

PMID: 32684338 [PubMed - as supplied by publisher]

The outcome of pregnancy in women with cystic fibrosis: a UK population based descriptive study.

BJOG. 2020 Jul 19;:

Authors: Ashcroft A, Chapman SJ, Mackillop L

Abstract
OBJECTIVE: To estimate the incidence of cystic fibrosis in pregnancy, and explore and obstetric and neonatal outcomes.
DESIGN: A population-based descriptive study using the methodology of the UK Obstetric Surveillance System (UKOSS).
SETTING: All consultant-led maternity units within the UK.
POPULATION: All pregnant women with a diagnosis of cystic fibrosis who booked for antenatal care in a UK obstetric unit between March 2015 and February 2017.
METHODS: Prospective case collection identified using UKOSS monthly notification.
MAIN OUTCOME MEASURES: Incidence, maternal morbidity, maternal mortality, gestation at delivery, neonatal mortality, neonatal morbidity.
RESULTS: We report 71 pregnancies over a two-year period. There was one early miscarriage, four terminations and three sets of twins, resulting in the live birth of 69 infants. There were no maternal deaths. One infant died following spontaneous pre-term birth at 29 weeks gestation. The mean gestation at delivery was 36.2 completed weeks. The mean birthweight centile for gestational age was the 61st centile. We report a positive correlation between both maternal lung function (FEV1) and mean gestation at delivery, and between FEV1 and mean birthweight centile for gestational age.
CONCLUSIONS: Pregnancy outcomes are generally good in women with cystic fibrosis. Successful pregnancy is possible even in those women with FEV1 <60% predicted although such women have higher chance of preterm delivery and a smaller baby.

PMID: 32683738 [PubMed - as supplied by publisher]

Strategies for dose reduction with specific clinical indications during computed tomography.

Radiography (Lond). 2020 Jul 15;:

Authors: Joyce S, O'Connor OJ, Maher MM, McEntee MF

Abstract
Increasing integration of computed tomography (CT) into routine patient care has escalated concerns regarding associated radiation exposure. Specific patient cohorts, particularly those with cystic fibrosis (CF) and Crohn's disease, have repeat exposures and thus have an increased risk of high lifetime cumulative effective dose exposures. Thoracic CT is the gold standard imaging method in the diagnosis, assessment and management of pulmonary disease. In the setting of CF, CT demonstrates increased sensitivity compared with pulmonary function tests and chest radiography. Furthermore, in specific cases of Crohn's disease, CT demonstrates diagnostic superiority over magnetic resonance imaging (MRI) for radiological evaluation. Low dose CT protocols have proven beneficial in the evaluation of CF, Crohn's disease and renal calculi, and in the follow up of testicular cancer patients. For individuals with chronic conditions warranting frequent radiological follow up, the focus must continue to be the incorporation of appropriate CT use into patient care. This is of particular importance for the paediatric population who are most susceptible to potential radiation induced malignancy. CT technological developments continue to focus on radiation dose optimisation. This article aims to highlight these advancements, which prioritise the acquisition of diagnostically satisfactory images with the least amount of radiation possible.

PMID: 32682731 [PubMed - as supplied by publisher]

Evaluating assumptions of definition-based pulmonary exacerbation endpoints in cystic fibrosis clinical trials.

J Cyst Fibros. 2020 Jul 15;:

Authors: VanDevanter DR, Hamblett NM, Simon N, McIntosh J, Konstan MW

Abstract
BACKGROUND: Cystic fibrosis (CF) pulmonary exacerbations can be serious respiratory events and reduction in exacerbation rate or risk are important efficacy endpoints for CF therapeutic trials. Variability in exacerbation diagnoses and treatment have led drug developers to employ "objective" exacerbation definitions combining antimicrobial treatment (AT) and the presence of ≥4 of 12 respiratory criteria (first published by Fuchs et al. [NEJM 1994;331(10):637-42]). Assumptions underlying this approach have yet to be formally evaluated.
METHODS: Respiratory events (RE) observed during a 48-week trial of ataluren (NCT02139306), a read-through agent for premature nonsense codons, were compared across six exacerbation definitions: any AT, intravenous AT (IVAT), ≥4 Fuchs criteria present, AT plus ≥4 Fuchs criteria, IVAT plus ≥4 Fuchs criteria, and investigator assessment. Fuchs definitions were evaluated by assessing missingness of individual criteria and associations between criteria presence and clinician exacerbation assessment.
RESULTS: Among 751 RE, more than one third had ≥4 Fuchs criteria present but were not assessed as exacerbations by investigators. Data for ≥1 and for 4 Fuchs criteria, respectively, were missing for ~ 90% and >30% of RE. Only 6/12 Fuchs criteria were present more often when investigators assessed RE as exacerbations than when they did not.
CONCLUSIONS: "Objective" definitions have shortcomings inconsistent with their purpose of optimizing exacerbation capture in clinical trials : 1) they capture events clinicians do not consider exacerbations, 2) are prone to data missingness which can bias the likelihood of meeting the definition, and 3) employ criteria that are not associated with investigator assessment of exacerbation.

PMID: 32682670 [PubMed - as supplied by publisher]

Assessment of Quality of Life Among Patients After Lung Transplantation: A Single-Center Study.

Transplant Proc. 2020 Jul 15;:

Authors: Stącel T, Jaworska I, Zawadzki F, Wajda-Pokrontka M, Tatoj Z, Urlik M, Nęcki M, Latos M, Szywacz W, Szczerba A, Antończyk R, Pióro A, Przybyłowskia P, Zembala M, Ochman M

Abstract
INTRODUCTION: Lung transplantation (LTx) is the only effective method of treatment to improve the health and quality of life (QoL) of patients with end-stage lung diseases. After LTx, medical examination accompanied by quality of life assessment should be performed on routine follow-up visits. The aim of the study was to assess the QoL of patients after LTx.
MATERIAL AND METHODS: The study group consisted of 60 patients (29 women and 31 men); 20 patients received single lung transplantation (SLT), and 40 received double lung transplantation (DLT). To determine the patient's QoL, the General Health Questionnaire (GHQ), the World Health Organization Quality of Life Test-BREF (WHOQOL-BREF), and the Saint George Respiratory Questionnaire (SGRQ) were used. Spirometry and the 6-minute walk test were analyzed to examine efficiency of transplanted organs.
RESULTS: In SGRQ there are differences between patients with cystic fibrosis and interstitial lung disease in symptom domain (20.28% vs 39.26%, P = .025) and total score (19.38% vs 32.47%, P = .028). As reported in the GHQ, men had worse overall results than women in sten scale (5.22 points vs 4.69 points). Patients after SLT achieved similar scores in every questionnaire.
CONCLUSION: Studies assessing QoL should be an important addition to lung function tests and an integral part of control during postoperative follow-up visits. This study is one of the important contributions to understanding of how essential QoL is after LTx. The authors of this study realize that their work does not cover the whole issue, and further studies in this area are warranted.

PMID: 32682577 [PubMed - as supplied by publisher]

Emerging Technologies for Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) Restoration in all People with CF.

Pediatr Pulmonol. 2020 Jul 18;:

Authors: Egan ME

Abstract
2019 will be remembered as a landmark year for the Cystic Fibrosis (CF) community because it marks the year when effective modulator therapy became available for most CF patients[1-3]. effective modulator therapy has the potential to change the trajectory of patients' health and long-term outcomes. These therapies optimize the function of the patients' endogenous mutant Cystic Fibrosis Transmembrane Conductance Regulator (CFTR), which results in return of CFTR channel function [1,2,4-6]. Although the combination of high throughput screening of small molecule libraries and medicinal chemistry have resulted in amazing new effective modulator therapies for many, it is unlikely that this approach will provide a game changing therapy for all. In part because the response to even the most promising modulator therapy is variable and an area of active investigation. Also, there are about 10% of patients with CF who don't produce a mutant protein to modulate, potentiate or optimize and for these patients such therapies are unlikely to be of significant benefit. Efforts to develop small molecule therapy to promote protein production in patients with nonsense mutations such as PTC124 has proved to be far more challenging than predicted [7]. There is a need to develop new therapeutic approaches that can work for this patient population. These new therapies will be genetic-based therapies that include ribonucleic acid (RNA) therapies, deoxyribonucleic acid (DNA) therapies and gene editing technologies. Each approach will result in functional CFTR expression in CF affected cells. Ideally, these approaches would require less frequent dosing than effective modulators, which are given daily. For instance, RNA based treatments could be given periodically. Ultimately, treatment with certain gene-altering treatments could be given once in a lifetime and lead to a permanent cure (Figure 1). In this review which is based on Plenary 1 from the North American Cystic Fibrosis Conference in 2019 which is based on Plenary 1 from the North American Cystic Fibrosis Conference in 2019 we will examine the potential of RNA therapies, gene transfer therapies and gene editing therapies for the treatment of CF[8-13], as well as the challenges that will need to be faced as we harness the power of these emerging therapies towards a one-time cure. This article is protected by copyright. All rights reserved.

PMID: 32681713 [PubMed - as supplied by publisher]

Inflammasome inhibition under physiological and pharmacological conditions.

Genes Immun. 2020 Jul 17;:

Authors: Caseley EA, Poulter JA, Rodrigues F, Immunome Project Consortium for Autoinflammatory Disorders (ImmunAID), McDermott MF

Abstract
Inflammasomes are key regulators of the host response against microbial pathogens, in addition to limiting aberrant responses to sterile insults, as mediated by environmental agents such as toxins or nanoparticles, and also by endogenous danger signals such as monosodium urate, ATP and amyloid-β. To date at least six different inflammasome signalling platforms have been reported (Bauernfeind & Hornung, EMBO Mol Med. 2013;5:814-26; Broz & Dixit, Nat Rev Immunol. 2016;16:407). This review focuses on the complex molecular machinery involved in activation and regulation of the best characterised inflammasome, NLRP3 (NOD-, LRR- and pyrin domain-containing protein 3), and the development of molecular agents to modulate NLRP3 inflammasome function. Activation of the NLRP3 inflammasome induces inflammation via secretion of interleukin-1β (IL-1β) and interleukin-18 (IL-18) proinflammatory cytokines, with orchestration of pyroptotic cell death, to eliminate invading microbial pathogens. This field has gradually moved from an emphasis on monogenic autoinflammatory conditions, such as cryopyrin-associated periodic syndromes (CAPS), to the broad spectrum of innate immune-mediated disease. NLRP3 inflammasome activation is also linked to a range of common disorders in humans including type 2 diabetes (Krainer et al., J Autoimmun. 2020:102421), cystic fibrosis (Scambler et al., eLife. 2019;8), myocardial infarction, Parkinson's disease, Alzheimer's disease (Savic et al., Nat Rev Rheumatol. 2020:1-16) and cancers such as mesotheliomas and gliomas (Moossavi et al., Mol Cancer. 2018;17:158). We describe how laboratory-based assessment of NLRP3 inflammasome activation is emerging as an integral part of the clinical evaluation and treatment of a range of undifferentiated systemic autoinflammatory disorders (uSAID) (Harrison et al., JCI Insight. 2016;1), where a DNA-based diagnosis has not been possible. In addition, this review summarises the current literature on physiological inhibitors and features various pharmacological approaches that are currently being developed, with potential for clinical translation in autoinflammatory and immune-mediated conditions. We discuss the possibilities of rational drug design, based on detailed structural analyses, and some of the challenges in transferring exciting preliminary results from trials of small-molecule inhibitors of the NLRP3 inflammasome, in animal models of disease, to the clinical situation in human pathology.

PMID: 32681062 [PubMed - as supplied by publisher]

Sodium Status and Replacement in Children and Adults Living with Cystic Fibrosis: A Narrative Review.

J Acad Nutr Diet. 2020 Jul 14;:

Authors: Declercq D, Van Braeckel E, Marchand S, Van Daele S, Van Biervliet S

Abstract
Patients with cystic fibrosis (CF) have a two- to four-fold higher sodium chloride sweat content compared with healthy controls. This high sweat salt loss increases the risk for electrolyte disturbances, associated with subacute or chronic complications. Sodium status therefore needs to be adequately monitored and salt intake adjusted to individual needs. The lack of current evidence to formulate specific recommendations and assess sodium status is reflected in a variability of recommendations in international guidelines. This narrative review presents an overview of the current evidence. Infants with CF in particular are at risk for severe sodium deficiency, potentially leading to metabolic alkalosis due to low intake and high sweat losses. More research on the assessment of sodium status and efficacy of sodium chloride supplements in the population of patients with CF, especially given the changing era of CF transmembrane conductance regulator modulatory treatment, is warranted.

PMID: 32680818 [PubMed - as supplied by publisher]

The SPLUNC1-βENaC complex prevents Burkholderia cenocepacia invasion in normal airway epithelia.

Respir Res. 2020 Jul 17;21(1):190

Authors: Ahmad S, Kim CSK, Tarran R

Abstract
Cystic fibrosis (CF) patients are extremely vulnerable to Burkholderia cepacia complex (Bcc) infections. However, the underlying etiology is poorly understood. We tested the hypothesis that short palate lung and nasal epithelial clone 1 (SPLUNC1)-epithelial sodium channel (ENaC) interactions at the plasma membrane are required to reduce Bcc burden in normal airways. To determine if SPLUNC1 was needed to reduce Bcc burden in the airways, SPLUNC1 knockout mice and their wild-type littermates were infected with B. cenocepacia strain J2315. SPLUNC1 knockout mice had increased bacterial burden in the lungs compared to wild-type littermate mice. SPLUNC1-knockdown primary human bronchial epithelia (HBECs) were incubated with J2315, which resulted in increased bacterial burden compared to non-transduced HBECs. We next determined the interaction of the SPLUNC1-ENaC complex during J2315 infection. SPLUNC1 remained at the apical plasma membrane of normal HBECs but less was present at the apical plasma membrane of CF HBECs. Additionally, SPLUNC1-βENaC complexes reduced intracellular J2315 burden. Our data indicate that (i) secreted SPLUNC1 is required to reduce J2315 burden in the airways and (ii) its interaction with ENaC prevents cellular invasion of J2315.

PMID: 32680508 [PubMed - as supplied by publisher]

Kv7 Channels in Lung Diseases.

Front Physiol. 2020;11:634

Authors: Mondejar-Parreño G, Perez-Vizcaino F, Cogolludo A

Abstract
Lung diseases constitute a global health concern causing disability. According to WHO in 2016, respiratory diseases accounted for 24% of world population mortality, the second cause of death after cardiovascular diseases. The Kv7 channels family is a group of voltage-dependent K+ channels (Kv) encoded by KCNQ genes that are involved in various physiological functions in numerous cell types, especially, cardiac myocytes, smooth muscle cells, neurons, and epithelial cells. Kv7 channel α-subunits are regulated by KCNE1-5 ancillary β-subunits, which modulate several characteristics of Kv7 channels such as biophysical properties, cell-location, channel trafficking, and pharmacological sensitivity. Kv7 channels are mainly expressed in two large groups of lung tissues: pulmonary arteries (PAs) and bronchial tubes. In PA, Kv7 channels are expressed in pulmonary artery smooth muscle cells (PASMCs); while in the airway (trachea, bronchus, and bronchioles), Kv7 channels are expressed in airway smooth muscle cells (ASMCs), airway epithelial cells (AEPs), and vagal airway C-fibers (VACFs). The functional role of Kv7 channels may vary depending on the cell type. Several studies have demonstrated that the impairment of Kv7 channel has a strong impact on pulmonary physiology contributing to the pathophysiology of different respiratory diseases such as cystic fibrosis, asthma, chronic obstructive pulmonary disease, chronic coughing, lung cancer, and pulmonary hypertension. Kv7 channels are now recognized as playing relevant physiological roles in many tissues, which have encouraged the search for Kv7 channel modulators with potential therapeutic use in many diseases including those affecting the lung. Modulation of Kv7 channels has been proposed to provide beneficial effects in a number of lung conditions. Therefore, Kv7 channel openers/enhancers or drugs acting partly through these channels have been proposed as bronchodilators, expectorants, antitussives, chemotherapeutics and pulmonary vasodilators.

PMID: 32676036 [PubMed]

Prone and lateral positioning in spontaneously breathing patients with COVID-19 pneumonia undergoing non-invasive helmet CPAP treatment.

Chest. 2020 Jul 14;:

Authors: Retucci M, Aliberti S, Ceruti C, Santambrogio M, Tammaro S, Cuccarini F, Carai C, Grasselli G, Oneta AM, Saderi L, Sotgiu G, Privitera E, Blasi F

PMID: 32679237 [PubMed - as supplied by publisher]

Macrophage dysfunction in cystic fibrosis: Nature or nurture?

J Leukoc Biol. 2020 Jul 17;:

Authors: Turton KB, Ingram RJ, Valvano MA

Abstract
Mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) affect the homeostasis of chloride flux by epithelial cells. This has deleterious consequences, especially in respiratory epithelia, where the defect results in mucus accumulation distinctive of cystic fibrosis. CFTR is, however, also expressed in phagocytic cells, like macrophages. Immune cells are highly sensitive to conditioning by their environment; thus, CFTR dysfunction in epithelia influences macrophages by affecting the lung milieu, but the mutations also appear to be directly consequential for intrinsic macrophage functions. Particular mutations can alter CFTR's folding, traffic of the protein to the membrane and function. As such, understanding the intrinsic effects of CFTR mutation requires distinguishing the secondary effects of misfolded CFTR on cell stress pathways from the primary defect of CFTR dysfunction/absence. Investigations into CFTR's role in macrophages have exploited various models, each with their own advantages and limitations. This review summarizes these methodologic approaches, discussing their physiological correspondence and highlighting key findings. The controversy surrounding CFTR-dependent acidification is used as a case study to highlight difficulties in commensurability across model systems. Recent work in macrophage biology, including polarization and host-pathogen interaction studies, brought into the context of CFTR research, offers potential explanations for observed discrepancies between studies. Moreover, the rapid advancement of novel gene editing technologies and new macrophage model systems makes this assessment of the field's models and methodologies timely.

PMID: 32678926 [PubMed - as supplied by publisher]

Clinical Outcomes Associated with Burkholderia cepacia Complex Infection in Patients with Cystic Fibrosis.

Ann Am Thorac Soc. 2020 Jul 17;:

Authors: Somayaji R, Yau YCW, Tullis E, LiPuma JJ, Ratjen F, Waters V

Abstract
RATIONALE: Little is known in contemporary CF cohorts about the outcomes following new Burkholderia species infections.
OBJECTIVES: Evaluate the changing epidemiology and clinical outcomes associated with Burkholderia species infections in persons with cystic fibrosis.
METHODS: A cohort study of children and adults with CF was conducted from 1997 - 2018 in Toronto, Canada. Patients were characterised as having no history of Burkholderia species infection and those who were culture-positive for Burkholderia spp. for the first time in this time frame, categorized by species (B. gladioli, B. cenocepacia, B. multivorans or other) and strain (B. cenocepacia ET-12). Cox models were used to estimate risk of death or transplantation. Mixed effects models were used to assess impact of Burkholderia species on odds of pulmonary exacerbations (PEx) and effect on lung function (FEV1% predicted).
RESULTS: A total of 1196 patients were followed over 20 years; 88 patients (7.4%) had ≥ 1 culture positive for Burkholderia species. Patients with ET-12 infection had a median time to death of 1.95 years compared to 5.30-6.72 years for those with other Burkholderia infections. ET-12 infection was associated with a greater risk of death or transplantation compared to patients with no history of Burkholderia infection in a univariate model (HR 3.92, 95% CI 2.25 - 6.81) but was no longer significant after adjusting for confounders. PEx were more common in those with Burkholderia infections and remained significant in the ET-12 group after adjusting for confounders (OR 2.96 (1.17 - 7.53)). No differences were noted in baseline FEV1% or the rate of FEV1% decline between the groups with and without Burkholderia species infection.
CONCLUSION: With the exception of ET-12, acquisition of Burkholderia species infection did not appear to worsen clinical outcomes compared to those with no history of infection. Given this, prognosis, management and clinical trial inclusion protocols may need to be re-evaluated for persons with Burkholderia infection.

PMID: 32678679 [PubMed - as supplied by publisher]

Sustained recovery of exocrine pancreatic function in a teenager with cystic fibrosis treated with ivacaftor.

Pediatr Pulmonol. 2020 Jul 17;:

Authors: Smith H, Rayment JH

PMID: 32678518 [PubMed - as supplied by publisher]

Palliative care and cystic fibrosis: Opportunities for growth.

Pediatr Pulmonol. 2020 Jul 17;:

Authors: Waldman E, Quinn M

PMID: 32678474 [PubMed - as supplied by publisher]

Clinical characteristics and outcomes in adult cystic fibrosis patients with severe lung disease in Porto Alegre, southern Brazil.

BMC Pulm Med. 2020 Jul 16;20(1):194

Authors: Silva GF, J Simmonds N, Roth Dalcin PT

Abstract
BACKGROUND: Advanced lung disease in adult cystic fibrosis (CF) drives most clinical care requirements. The aim was to evaluate outcome (time to death while in the study) in a cohort of adult CF patients with severe lung disease, and to determine the association among baseline patient characteristics and outcome.
METHODS: A retrospective cohort study was performed and clinical records between 2000 and 2015 were reviewed. Severe lung disease was defined as forced expiratory volume in the first second (FEV1) < 30% of predicted. Outcomes of all patients, including their date of death or transplantation, were determined till January 1st, 2016. Clinical data were recorded at the entry date.
RESULTS: Among 39 subjects included in the study, 20 (51.3%) died, 16 (41.0%) underwent bilateral lung transplantation, and 3 were alive at the end of the study period. Two variables were independently associated with death: body mass index (BMI ≥ 18.5 kg/m2) (HR = 0.78, 95% CI = 0.64-0.96 and p = 0.017) and use of tobramycin inhalation therapy (HR = 3.82, 95% CI = 1.38-10.6 and p = 0.010). Median survival was 37 (95% CI = 16.4-57.6) months. The best cut-off point for BMI was 18.5 kg/m2. Median survival in patients with BMI < 18.5 kg/m2 was 36 months (95% CI = 18.7-53.3).
CONCLUSION: Median survival of CF subjects with FEV1 < 30% was 37 months. BMI and tobramycin inhalation therapy were independently associated with death. Median survival in patients with BMI < 18.5 kg/m2 was significantly lower than in patients with BMI ≥ 18.5 kg/m2. The association of tobramycin inhalation with death was interpreted as confounding by severity (use was reserved for advanced lung disease).

PMID: 32677921 [PubMed - as supplied by publisher]

Improved outcomes in cystic fibrosis using modified Re-Education of Airway Clearance Technique (REACT) programme.

BMJ Open Qual. 2020 Jul;9(3):

Authors: Reamer C, O'Malley C, Nufer J, Savant A

Abstract
BACKGROUND AND OBJECTIVES: Cystic fibrosis (CF) is known to reduce lung function as measured by per cent predicted for the forced expiratory volume in the first second (ppFEV1) over time. Our paediatric CF programme demonstrated significant gaps in benchmarked ppFEV1 predicted compared with the national median. Our objective was to assess whether the implementation of a modified Re-Education of Airway Clearance Techniques (REACT) programme could lead to an improvement in lung function as measured by ppFEV1.
METHODS: This 2-year prospective quality improvement study at Lurie Children's CF Center for children aged >6 years used improvement methodology to implement a modified REACT programme. Outcome measures were assessed for our entire programme via the CF Foundation Patient Registry (CFFPR) and statistical process control. Comparisons were also made before and after REACT for outcome measures.
RESULTS: By the end of implementation, monthly participation rate achieved 100%. Using CFFPR data and SPC, median ppFEV1 increased by 3.9%, whereas only body mass index (BMI) as a secondary outcome increased. Comparison of pre and post REACT showed improvements in average ppFEV1 (95% vs 96%, p<0.0001), FEF25%-75% (82% vs 83%, p=0.0590), rate of ppFEV1 decline (+2% vs -4%, p=0.0262) and BMI percentile (57% vs 60%, p<0.0001).
CONCLUSIONS: Implementation of a modified REACT at Lurie Children's paediatric CF programme led to an increase in ppFEV1, FEF25%-75% and BMI percentile.

PMID: 32675178 [PubMed - in process]

Predicting the course of nutrition and lung disease in infants and children with cystic fibrosis.

J Cyst Fibros. 2020 Jul 14;:

Authors: McColley SA

PMID: 32674985 [PubMed - as supplied by publisher]