Antibiotic treatment for Burkholderia cepacia complex in people with cystic fibrosis experiencing a pulmonary exacerbation.

Cochrane Database Syst Rev. 2020 Apr 02;4:CD009529

Authors: Lord R, Jones AM, Horsley A

Abstract
BACKGROUND: Chronic pulmonary infection is a hallmark of lung disease in cystic fibrosis. Infections dominated by organisms of the Burkholderia cepacia complex, a group of at least 18 closely-related species of gram-negative bacteria, are particularly difficult to treat. These infections may be associated with a fulminant necrotising pneumonia. Burkholderia cepacia complex bacteria are resistant to many common antibiotics and able to acquire resistance against many more. Following patient segregation in cystic fibrosis medical care, the more virulent epidemic strains are not as frequent, and new infections are more likely to be with less virulent environmentally-acquired strains. Although evidence-based guidelines exist for treating respiratory exacerbations involving Pseudomonas aeruginosa, these cannot be extended to Burkholderia cepacia complex infections. This review, which is an update of a previous review, aims to assess the available trial evidence for the choice and application of treatments for these infections.
OBJECTIVES: To assess the effectiveness and safety of different antibiotic regimens in people with cystic fibrosis experiencing an exacerbation and chronically infected with organisms of the Burkholderia cepacia complex.
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 the reference lists of relevant articles and reviews. Date of latest search: 29 May 2019.
SELECTION CRITERIA: Randomised and quasi-randomised controlled trials of treatments for exacerbations of pulmonary symptoms in people with cystic fibrosis chronically infected with organisms of the Burkholderia cepacia complex.
DATA COLLECTION AND ANALYSIS: No relevant trials were identified.
MAIN RESULTS: No trials were included in this review.
AUTHORS' CONCLUSIONS: Burkholderia cepacia complex infections present a significant challenge for people with cystic fibrosis and their clinicians. The incidence is likely to increase as the cystic fibrosis population ages; and managing and treating these infections will become more important. There is a lack of trial evidence to guide decision making and no conclusions can be drawn from this review about the optimal antibiotic regimens for people with cystic fibrosis who have chronic Burkholderia cepacia complex infections. Clinicians must continue to assess each person individually, taking into account in vitro antibiotic susceptibility data, previous clinical responses and their own experience. Multicentre randomised clinical trials are needed to assess the effectiveness of different antibiotic regimens in people with cystic fibrosis infected with organisms of the Burkholderia cepacia complex.

PMID: 32239690 [PubMed - as supplied by publisher]

Obstructive sleep apnea in pediatric obesity and the effects of sleeve gastrectomy.

Semin Pediatr Surg. 2020 Feb;29(1):150887

Authors: Kanney ML, Harford KL, Raol N, Leu RM

Abstract
The prevalence of severe pediatric obesity is rising and poses many adverse health risks. Children with obesity are at increased risk of several cardiovascular and metabolic diseases. They are also more likely to have obstructive sleep apnea (OSA), which increases the risk of cardiovascular and metabolic problems. In this review, we examine the relationship between OSA and obesity, improvements in OSA after non-surgical and surgical weight loss, and explore potential directions for future research.

PMID: 32238281 [PubMed - as supplied by publisher]

Lung function and microbiota diversity in cystic fibrosis.

Microbiome. 2020 Apr 02;8(1):45

Authors: Cuthbertson L, Walker AW, Oliver AE, Rogers GB, Rivett DW, Hampton TH, Ashare A, Elborn JS, De Soyza A, Carroll MP, Hoffman LR, Lanyon C, Moskowitz SM, O'Toole GA, Parkhill J, Planet PJ, Teneback CC, Tunney MM, Zuckerman JB, Bruce KD, van der Gast CJ

Abstract
BACKGROUND: Chronic infection and concomitant airway inflammation is the leading cause of morbidity and mortality for people living with cystic fibrosis (CF). Although chronic infection in CF is undeniably polymicrobial, involving a lung microbiota, infection surveillance and control approaches remain underpinned by classical aerobic culture-based microbiology. How to use microbiomics to direct clinical management of CF airway infections remains a crucial challenge. A pivotal step towards leveraging microbiome approaches in CF clinical care is to understand the ecology of the CF lung microbiome and identify ecological patterns of CF microbiota across a wide spectrum of lung disease. Assessing sputum samples from 299 patients attending 13 CF centres in Europe and the USA, we determined whether the emerging relationship of decreasing microbiota diversity with worsening lung function could be considered a generalised pattern of CF lung microbiota and explored its potential as an informative indicator of lung disease state in CF.
RESULTS: We tested and found decreasing microbiota diversity with a reduction in lung function to be a significant ecological pattern. Moreover, the loss of diversity was accompanied by an increase in microbiota dominance. Subsequently, we stratified patients into lung disease categories of increasing disease severity to further investigate relationships between microbiota characteristics and lung function, and the factors contributing to microbiota variance. Core taxa group composition became highly conserved within the severe disease category, while the rarer satellite taxa underpinned the high variability observed in the microbiota diversity. Further, the lung microbiota of individual patient were increasingly dominated by recognised CF pathogens as lung function decreased. Conversely, other bacteria, especially obligate anaerobes, increasingly dominated in those with better lung function. Ordination analyses revealed lung function and antibiotics to be main explanators of compositional variance in the microbiota and the core and satellite taxa. Biogeography was found to influence acquisition of the rarer satellite taxa.
CONCLUSIONS: Our findings demonstrate that microbiota diversity and dominance, as well as the identity of the dominant bacterial species, in combination with measures of lung function, can be used as informative indicators of disease state in CF. Video Abstract.

PMID: 32238195 [PubMed - as supplied by publisher]

Allergic bronchopulmonary aspergillosis without asthma or cystic fibrosis.

Paediatr Int Child Health. 2020 Apr 02;:1-3

Authors: Kaur P, Kumar P, Randev S, Guglani V

Abstract
Allergic bronchopulmonary aspergillosis (ABPA) is an immunological disease complicating asthma or cystic fibrosis. An 8-year-old girl with no previous respiratory morbidity was diagnosed with ABPA on the basis of a raised eosinophil count and total and specific serum IgE levels combined with a positive skin-prick test for aspergillus and typical CT images of finger-in-glove hilar opacities and hyperattenuating mucous. She responded to treatment with itraconazole and corticosteroids and remains well. As far as we are aware, she is only the second child to be diagnosed with ABPA without asthma or cystic fibrosis.

PMID: 32238049 [PubMed - as supplied by publisher]

Improvements in frailty contribute to substantial improvements in quality of life after lung transplantation in patients with cystic fibrosis.

Pediatr Pulmonol. 2020 Apr 01;:

Authors: Perez AA, Hays SR, Soong A, Gao Y, Greenland JR, Leard LE, Shah RJ, Golden J, Kukreja J, Venado A, Kleinhenz ME, Singer JP

Abstract
BACKGROUND: While lung transplantation (LTx) improves health-related quality of life (HRQL) in cystic fibrosis (CF), the determinants of this improvement are unknown. In other populations, frailty-a syndrome of vulnerability to physiologic stressors-is associated with disability and poor HRQL. We hypothesized that improvements in frailty would be associated with improved disability and HRQL in adults with CF undergoing LTx.
METHODS: In a single-center prospective cohort study from 2010 to 2017, assessments of frailty, disability, and HRQL were performed before and at 3- and 6-months after LTx. We assessed frailty by the short physical performance battery (SPPB). We assessed disability with the Lung Transplant Valued Life Activities scale (LT-VLA) and HRQL by the Medical Outcomes Study Short Form Physical and Mental Component Summary scales (SF12-PCS, -MCS), the Airway Questionnaire 20-Revised (AQ20R), and the Euroqol 5D (EQ5D). We tested the association of concurrent changes in frailty and lung function on disability and HRQL by linear mixed-effects models adjusted for sex and body mass index.
RESULTS: Among 23 participants with CF, improvements in frailty and lung function were independently associated with improved disability and some HRQL measures. For example, each 1-point improvement in SPPB or 200 mL improvement in FEV1 was associated with improved LT-VLA disability by 0.14 (95%CI: 0.08-0.20) and 0.07 (95%CI: 0.05-0.09) points and improved EQ5D by 0.05 (95%CI: 0.03 to 0.07) and 0.02 (95%CI: 0.01-0.03) points, respectively.
CONCLUSION: Improvement in frailty is a novel determinant of improved disability and HRQL in adults with CF undergoing LTx.

PMID: 32237273 [PubMed - as supplied by publisher]

Cathelicidin-inspired antimicrobial peptides as novel antifungal compounds.

Med Mycol. 2020 Apr 01;:

Authors: van Eijk M, Boerefijn S, Cen L, Rosa M, Morren MJH, van der Ent CK, Kraak B, Dijksterhuis J, Valdes ID, Haagsman HP, de Cock H

Abstract
Fungal infections in humans are increasing worldwide and are currently mostly treated with a relative limited set of antifungals. Resistance to antifungals is increasing, for example, in Aspergillus fumigatus and Candida auris, and expected to increase for many medically relevant fungal species in the near future. We have developed and patented a set of cathelicidin-inspired antimicrobial peptides termed 'PepBiotics'. These peptides were initially selected for their bactericidal activity against clinically relevant Pseudomonas aeruginosa and Staphylococcus aureus isolates derived from patients with cystic fibrosis and are active against a wide range of bacteria (ESKAPE pathogens). We now report results from studies that were designed to investigate the antifungal activity of PepBiotics against a set of medically relevant species encompassing species of Aspergillus, Candida, Cryptococcus, Fusarium, Malassezia, and Talaromyces. We characterized a subset of PepBiotics and show that these peptides strongly affected metabolic activity and/or growth of a set of medically relevant fungal species, including azole-resistant A. fumigatus isolates. PepBiotics showed a strong inhibitory activity against a large variety of filamentous fungi and yeasts species at low concentrations (≤1 μM) and were fungicidal for at least a subset of these fungal species. Interestingly, the concentration of PepBiotics required to interfere with growth or metabolic activity varied between different fungal species or even between isolates of the same fungal species. This study shows that PepBiotics display strong potential for use as novel antifungal compounds to fight a large variety of clinically relevant fungal species.

PMID: 32236485 [PubMed - as supplied by publisher]

Respiratory physiotherapy in patients with COVID-19 infection in acute setting: a Position Paper of the Italian Association of Respiratory Physiotherapists (ARIR).

Monaldi Arch Chest Dis. 2020 Mar 26;90(1):

Authors: Lazzeri M, Lanza A, Bellini R, Bellofiore A, Cecchetto S, Colombo A, D'Abrosca F, Del Monaco C, Gaudiello G, Paneroni M, Privitera E, Retucci M, Rossi V, Santambrogio M, Sommariva M, Frigerio P

Abstract
Respiratory physiotherapy in patients with COVID-19 infection in acute setting: a Position Paper of the Italian Association of Respiratory Physiotherapists (ARIR) On February 2020, Italy, especially the northern regions, was hit by an epidemic of the new SARS-Cov-2 coronavirus that spread from China between December 2019 and January 2020. The entire healthcare system had to respond promptly in a very short time to an exponential growth of the number of subjects affected by COVID-19 (Coronavirus disease 2019) with the need of semi-intensive and intensive care units.

PMID: 32236089 [PubMed - indexed for MEDLINE]

TMEM16A: An Alternative Approach to Restoring Airway Anion Secretion in Cystic Fibrosis?

Int J Mol Sci. 2020 Mar 30;21(7):

Authors: Danahay H, Gosling M

Abstract
The concept that increasing airway hydration leads to improvements in mucus clearance and lung function in cystic fibrosis has been clinically validated with osmotic agents such as hypertonic saline and more convincingly with cystic fibrosis transmembrane conductance regulator (CFTR) repair therapies. Although rapidly becoming the standard of care in cystic fibrosis (CF), current CFTR modulators do not treat all patients nor do they restore the rate of decline in lung function to normal levels. As such, novel approaches are still required to ensure all with CF have effective therapies. Although CFTR plays a fundamental role in the regulation of fluid secretion across the airway mucosa, there are other ion channels and transporters that represent viable targets for future therapeutics. In this review article we will summarise the current progress with CFTR-independent approaches to restoring mucosal hydration, including epithelial sodium channel (ENaC) blockade and modulators of SLC26A9. A particular emphasis is given to modulation of the airway epithelial calcium-activated chloride channel (CaCC), TMEM16A, as there is controversy regarding whether it should be positively or negatively modulated. This is discussed in light of a recent report describing for the first time bona fide TMEM16A potentiators and their positive effects upon epithelial fluid secretion and mucus clearance.

PMID: 32235608 [PubMed - in process]

Abstracts from the 25th Italian Congress of Cystic Fibrosis and the 15th National Congress of Cystic Fibrosis Italian Society : Assago, Milan. 10 - 12 October 2019.

Ital J Pediatr. 2020 Apr 01;46(Suppl 1):32

Authors:

PMID: 32234058 [PubMed - in process]

Bacterial Community Variability: Outliers May Be Leading Us Astray.

Ann Am Thorac Soc. 2019 12;16(12):1499-1501

Authors: Hahn A, Zemanick ET

PMID: 31774321 [PubMed - indexed for MEDLINE]

Gene Therapy: Current Applications and Future Possibilities.

Adv Pediatr. 2019 08;66:37-54

Authors: Steffin DHM, Hsieh EM, Rouce RH

PMID: 31230699 [PubMed - indexed for MEDLINE]

Long-term effects of ivacaftor on nonpulmonary outcomes in individuals with cystic fibrosis, heterozygous for a S1251N mutation.

Pediatr Pulmonol. 2020 Mar 31;:

Authors: Burghard MM, Berkers GG, Ghijsen SS, Hollander-Kraaijeveld FF, de Winter-de Groot KK, van der Ent CK, Heijerman HH, Takken TT, Hulzebos HE

Abstract
OBJECTIVES: To describe the long-term effects of ivacaftor (Kalydeco®) in individuals with cystic fibrosis (CF) on body mass index (BMI), body composition (BC), pulmonary function (PF), resting energy expenditure (REE), and exercise capacity (EC) after ≥12 months of treatment.
WORKING HYPOTHESIS: BMI, lean and fat mass, PF, and EC will increase and REE will decrease after treatment.
STUDY DESIGN: Observational study.
METHODOLOGY: Seven individuals with CF (mean age 15.4 ± 5.8 years) heterozygous for S1251N mutation, starting with ivacaftor, were included. Paired t tests were performed to assess the effects of ivacaftor. Height and weight were used to calculate BMI and BMI Z-scores. Dual-energy X-ray absorptiometry was used to assess BC. Spirometry and body plethysmography were used to assess PF. Indirect calorimetry was used to measure REE and cardiopulmonary exercise testing (CPET) was used to measure oxygen uptake (VO2peak ), peak work rate (Wpeak ), and other CPET variables.
RESULTS: After a median of 15 (interquartile range: 13-16) months of treatment, BMI increased significantly (P = .03), but not BMI Z-score (P = .23) or BC. Significant improvements were found for several PF variables, especially measures of hyperinflation (P = .02). Absolute VO2peak (P = .01), VO2peak related to body weight (P = .00), and oxygen cost of work (P = .01) decreased. Absolute Wpeak (P = .59) and Wpeak related to body weight (P = .31) remained stable.
CONCLUSIONS: The results showed that long-term treatment of ivacaftor is associated with improvement of BMI and PF, but not of BC and REE. Oxygen uptake reduced after treatment, which may be due to a decrease in work of breathing.

PMID: 32233113 [PubMed - as supplied by publisher]

Semaglutide in Cystic Fibrosis-Related Diabetes.

J Clin Endocrinol Metab. 2020 Mar 31;:

Authors: Gnanapragasam H, Mustafa N, Bierbrauer M, Andrea Providence T, Dandona P

Abstract
CONTEXT AND OBJECTIVE: In spite of the evidence that inadequately controlled glycemia is associated with worse clinical outcomes, CFRD is not well controlled in a majority of patients. The objective of this report is to demonstrate the effect of the addition of semaglutide, a GLP-1RA, to basal insulin to control glycemia in one such patient.
DESIGN, INTERVENTION AND THE MAIN OUTCOME MEASURES: The replacement of rapidly acting prandial insulin with semaglutide weekly with continuation of basal insulin. HbA1c was measured and continuous glucose monitoring was conducted.
RESULTS: There was a significant improvement in glycemic control, reduction in HbA1c from 9.1% to 6.7% and stable euglycemic pattern on CGM (mean glucose: 142 mg/dL and SD of 51) within 3 month of starting treatment. There was no increase in plasma pancreatic enzyme concentrations.
CONCLUSIONS: Semaglutide at a small dose was able to replace prandial insulin and control glycemia to perfection in combination with basal insulin.

PMID: 32232400 [PubMed - as supplied by publisher]

Hardy-Weinberg Equilibrium in the Large Scale Genomic Sequencing Era.

Front Genet. 2020;11:210

Authors: Abramovs N, Brass A, Tassabehji M

Abstract
Hardy-Weinberg Equilibrium (HWE) is used to estimate the number of homozygous and heterozygous variant carriers based on its allele frequency in populations that are not evolving. Deviations from HWE in large population databases have been used to detect genotyping errors, which can result in extreme heterozygote excess (HetExc). However, HetExc might also be a sign of natural selection since recessive disease causing variants should occur less frequently in a homozygous state in the population, but may reach high allele frequency in a heterozygous state, especially if they are advantageous. We developed a filtering strategy to detect these variants and applied it on genome data from 137,842 individuals. The main limitations of this approach were quality of genotype calls and insufficient population sizes, whereas population structure and inbreeding can reduce sensitivity, but not precision, in certain populations. Nevertheless, we identified 161 HetExc variants in 149 genes, most of which were specific to African/African American populations (∼79.5%). Although the majority of them were not associated with known diseases, or were classified as clinically "benign," they were enriched in genes associated with autosomal recessive diseases. The resulting dataset also contained two known recessive disease causing variants with evidence of heterozygote advantage in the sickle-cell anemia (HBB) and cystic fibrosis (CFTR). Finally, we provide supporting in silico evidence of a novel heterozygote advantageous variant in the chromodomain helicase DNA binding protein 6 gene (CHD6; involved in influenza virus replication). We anticipate that our approach will aid the detection of rare recessive disease causing variants in the future.

PMID: 32231685 [PubMed]

Pulmonary Pathogens Adapt to Immune Signaling Metabolites in the Airway.

Front Immunol. 2020;11:385

Authors: Riquelme SA, Wong Fok Lung T, Prince A

Abstract
A limited number of pulmonary pathogens are able to evade normal mucosal defenses to establish acute infection and then adapt to cause chronic pneumonias. Pathogens, such as Pseudomonas aeruginosa or Staphylococcus aureus, are typically associated with infection in patients with underlying pulmonary disease or damage, such as cystic fibrosis (CF) or chronic obstructive pulmonary disease (COPD). To establish infection, bacteria express a well-defined set of so-called virulence factors that facilitate colonization and activate an immune response, gene products that have been identified in murine models. Less well-understood are the adaptive changes that occur over time in vivo, enabling the organisms to evade innate and adaptive immune clearance mechanisms. These colonizers proliferate, generating a population sufficient to provide selection for mutants, such as small colony variants and mucoid variants, that are optimized for long term infection. Such host-adapted strains have evolved in response to selective pressure such as antibiotics and the recruitment of phagocytes at sites of infection and their release of signaling metabolites (e.g., succinate). These metabolites can potentially function as substrates for bacterial growth and but also generate oxidant stress. Whole genome sequencing and quantified expression of selected genes have helped to explain how P. aeruginosa and S. aureus adapt to the presence of these metabolites over the course of in vivo infection. The serial isolation of clonally related strains from patients with cystic fibrosis has provided the opportunity to identify bacterial metabolic pathways that are altered under this immune pressure, such as the anti-oxidant glyoxylate and pentose phosphate pathways, routes contributing to the generation of biofilms. These metabolic pathways and biofilm itself enable the organisms to dissipate oxidant stress, while providing protection from phagocytosis. Stimulation of host immune signaling metabolites by these pathogens drives bacterial adaptation and promotes their persistence in the airways. The inherent metabolic flexibility of P. aeruginosa and S. aureus is a major factor in their success as pulmonary pathogens.

PMID: 32231665 [PubMed - in process]

The Iron-chelator, N,N'-bis (2-hydroxybenzyl) Ethylenediamine-N,N'-Diacetic acid is an Effective Colistin Adjunct against Clinical Strains of Biofilm-Dwelling Pseudomonas aeruginosa.

Antibiotics (Basel). 2020 Mar 27;9(4):

Authors: Mettrick K, Hassan K, Lamont I, Reid D

Abstract
Targeting the iron requirement of Pseudomonas aeruginosa may be an effective adjunctive for conventional antibiotic treatment against biofilm-dwelling P. aeruginosa. We, therefore, assessed the anti-biofilm activity of N,N'-bis (2-hydroxybenzyl) ethylenediamine-N,N'-diacetic acid (HBED), which is a synthetic hexadentate iron chelator. The effect of HBED was studied using short-term (microtitre plate) and longer-term (flow-cell) biofilm models, under aerobic, anaerobic, and microaerobic (flow-cell) conditions and in combination with the polymyxin antibiotic colistimethate sodium (colistin). HBED was assessed against strains of P. aeruginosa from patients with cystic fibrosis and the reference strain PAO1. HBED inhibited growth and biofilm formation of all clinical strains under aerobic and anaerobic conditions, but inhibitory effects against PAO1 were predominantly exerted under anaerobic conditions. PA605, which is a clinical strain with a robust biofilm-forming phenotype, was selected for flow-cell studies. HBED significantly reduced biomass and surface coverage of PA605, and, combined with colistin, HBED significantly enhanced the microcolony killing effects of colistin to result in almost complete removal of the biofilm. HBED combined with colistin is highly effective in vitro against biofilms formed by clinical strains of P. aeruginosa.

PMID: 32230813 [PubMed]

Glibenclamide inhibits BK polyomavirus infection in kidney cells through CFTR blockade.

Antiviral Res. 2020 Mar 27;:104778

Authors: Panou MM, Antoni M, Morgan EL, Loundras EA, Wasson CW, Welberry-Smith M, Mankouri J, Macdonald A

Abstract
BK polyomavirus (BKPyV) is a ubiquitous pathogen in the human population that is asymptomatic in healthy individuals, but can be life-threatening in those undergoing kidney transplant. To-date, no vaccines or anti-viral therapies are available to treat human BKPyV infections. New therapeutic strategies are urgently required. In this study, using a rational pharmacological screening regimen of known ion channel modulating compounds, we show that BKPyV requires cystic fibrosis transmembrane conductance regulator (CFTR) activity to infect primary renal proximal tubular epithelial cells. Disrupting CFTR function through treatment with the clinically available drug glibenclamide, the CFTR inhibitor CFTR172, or CFTR-silencing, all reduced BKPyV infection. Specifically, time of addition assays and the assessment of the exposure of VP2/VP3 minor capsid proteins indicate a role for CFTR during BKPyV transport to the endoplasmic reticulum, an essential step during the early stages of BKPyV infection. We thus establish CFTR as an important host-factor in the BKPyV life cycle, and reveal CFTR modulators as potential anti-BKPyV therapies.

PMID: 32229236 [PubMed - as supplied by publisher]

Place of Death for Individuals with Chronic Lung Disease: Trends and Associated Factors from 2003 to 2017 in the United States.

Chest. 2020 Mar 27;:

Authors: Cross SH, Ely EW, Kavalieratos D, Tulsky JA, Warraich HJ

Abstract
BACKGROUND: Chronic lung disease is a common cause of mortality, yet little is known about where individuals with chronic lung disease die.
RESEARCH QUESTION: What are the trends and factors associated with place of death among individuals with chronic lung disease?
STUDY DESIGN AND METHODS: We conducted a cross-sectional analysis of natural deaths using the Centers for Disease Control and Prevention Wide-ranging OnLine Data for Epidemiologic Research from 2003 to 2017 for which chronic obstructive pulmonary disease (COPD), interstitial lung disease (ILD), or cystic fibrosis (CF) was the underlying cause. Place of death was categorized as hospital, home, nursing facility, hospice facility, and other.
RESULTS: From 2003 to 2017, more than 2.2. million deaths were primarily attributed to chronic lung disease (51.6% female, 92.4% white). Most were attributed to COPD (88.9%), followed by ILD (10.8.%), and CF (0.3%). Hospital and nursing facility deaths declined from 44.4% (n= 59,470) and 22.6% (n= 30,285) to 28.3% (n= 49,6555) and 19.7% (n= 34,495) while home and hospice facility deaths increased from 23.3% (n=31,296) and 0.1% (n=192) to 34.7% (n=60851) and 9.0% (n=15,861) respectively. Male sex, being married, and having some college education were associated with increased odds of home death while non-white race and Hispanic ethnicity were associated with increased odds of hospital death. Compared to decedents with COPD, individuals with ILD and CF had increased odds of hospital death and reduced odds of home, nursing facility or hospice facility death.
INTERPRETATION: Home deaths are increasing among decedents from chronic lung disease increasing the need for quality end-of-life care in this setting. Further research should explore the end-of-life needs and preferences of these patients and their caregivers with particular attention paid to patients with ILD and CF who continue to have high rates of hospital death.

PMID: 32229227 [PubMed - as supplied by publisher]

Respiratory viruses: What is their role in acute exacerbations in children with cystic fibrosis?

Pediatr Pulmonol. 2020 Mar 30;:

Authors: Hizal M, Yalcin E, Alp A, Ozden M, Karakaya J, Eryilmaz Polat S, Tugcu G, Dogru D, Ozcelik U, Kiper N

Abstract
BACKGROUND: Respiratory viruses (RVs) are frequently present in the airways of patients with cystic fibrosis (CF) during pulmonary exacerbations (PEx).
METHOD AND OBJECTIVES: This prospective, longitudinal study was performed to examine the role of RVs in acute exacerbations in children with CF. Sputum samples or additional midturbinate swabs were tested from all children using a polymerase chain reaction panel. The primary aims of the study were to determine the prevalence and etiologic role of RVs in exacerbations of CF and to compare changes with RV-positive and RV-negative infections. The secondary aims were to determine the predictive factors for RV-related exacerbations.
RESULTS: From 50 patients with PEx, 23 (48.9%) sputum samples were virus-positive. With a combination of sputum and swab, viral positivity increased to 56%. The virus-positive group presented more frequently with hypoxia (oxygen saturation <93%) than the virus-negative group (P = .048). Virus-positive exacerbations were not associated with an increase in colonization rates or greater lung function decline over 12 months.
CONCLUSIONS: RVs frequently present during PEx of CF. However, predicting viral infections is difficult in this group. Only the presence of hypoxia may raise the suspicion of an accompanying viral agent. The combination of sputum and nasal swab samples increases the diagnostic yield in viral infections of CF. Despite their high frequency, the presence of RVs had no impact on clinical outcomes, such as a decline in lung function and increased colonization rates.

PMID: 32227679 [PubMed - as supplied by publisher]

Physical therapies for postural abnormalities in people with cystic fibrosis.

Cochrane Database Syst Rev. 2020 Mar 30;3:CD013018

Authors: Oliveira VH, Mendonça KM, Monteiro KS, Silva IS, Santino TA, Nogueira PAM

Abstract
BACKGROUND: Cystic fibrosis (CF) is the most common life-threatening, inherited disease in white populations which causes several dysfunctions, including postural abnormalities. Physical therapy may help in some consequences of these postural abnormalities, such as pain, trunk deformity and quality of life.
OBJECTIVES: To determine the effects of a range of physical therapies for managing postural abnormalities in people with cystic fibrosis, specifically on quality of life, pain and trunk deformity.
SEARCH METHODS: We searched the Cochrane Cystic Fibrosis Trials Register, compiled from electronic database searches, hand-searched journals and conference abstract books. We also searched the reference lists of relevant articles and reviews. Additional searches were conducted on ClinicalTrials.gov and on the WHO International Clinical Trials Registry Platform for any planned, ongoing and unpublished studies. Date of the last search: 19 March 2020.
SELECTION CRITERIA: Randomised controlled trials examining any modality of physical therapy considered relevant for treating postural disorders compared with each other, no physical therapy, sham treatment or usual care in people with CF (of any age or disease severity).
DATA COLLECTION AND ANALYSIS: Two review authors independently selected eligible trials, assessed the risk of bias in each trial and extracted the data. We contacted trial authors to obtain missing or additional information. We assessed the quality of the evidence using the GRADE criteria.
MAIN RESULTS: Two trials, involving a total of 50 participants with CF and postural abnormalities, were included in this review. One was in people with stable disease (lasting three months) and one in hospital inpatients experiencing an exacerbation (20 days). Both trials compared manual therapy comprising mobilizations to the rib cage and thoracic spine, treatment of specific muscle dysfunction or tight muscle groups; and postural awareness and education versus medical usual care. The age of participants ranged from 17 years to 58 years. Both trials were conducted in the UK. The following outcomes were measured: change in quality of life, change in pain, change in trunk deformity and change in pulmonary function. Manual therapy may make little or no difference to the change in trunk deformity compared to usual care (low-quality evidence). No results could be analysed for quality of life (very low-quality evidence) and pain outcomes (very low-quality evidence) because of the high heterogeneity between trials. It is uncertain whether the intervention improves lung function: forced vital capacity (very low-quality evidence); forced expiratory volume in one second (very low-quality evidence); or Tiffeneau's index (ratio of forced expiratory volume at one second (FEV1) and forced vital capacity (FVC)). Only one trial (15 participants) measured functional capacity, and the change in walked distance seemed to favour intervention over usual care, but with the possibility of no effect due to wide confidence intervals. The same trial also reported that six participants in the intervention group had positive comments about the intervention and no adverse events were mentioned.
AUTHORS' CONCLUSIONS: Due to methodological limitations in the included trials, and in addition to the very low to low quality of the current evidence, there is limited evidence about the benefits of physical therapies on postural abnormalities in people with CF. Therefore, further well-conducted trials with robust methodologies are required considering a prior inclusion criterion to identify the participants who have postural abnormalities.

PMID: 32227599 [PubMed - in process]