SARS-CoV2 disrupts clinical research - the role of a rare disease-specific trial network.

Eur Respir J. 2020 Aug 06;:

Authors: van Koningsbruggen-Rietschel S, Dunlevy F, Bulteel V, Downey D, Dupont L

PMID: 32764115 [PubMed - as supplied by publisher]

Complete Genome Sequence of Stenotrophomonas maltophilia Strain CF13, Recovered from Sputum from an Australian Cystic Fibrosis Patient.

Microbiol Resour Announc. 2020 Aug 06;9(32):

Authors: Hamidian M, Lazenby J, To J, Hartstein R, Soares J, McNamara S, Whitchurch CB

Abstract
Stenotrophomonas maltophilia isolate CF13 is a multidrug-resistant isolate that was recovered in Sydney, Australia, in 2011, from a sputum sample from an individual with cystic fibrosis. The genome sequence of CF13 was completed using long- and short-read technologies.

PMID: 32763931 [PubMed - as supplied by publisher]

COVID-19 in a complex obstetric patient with cystic fibrosis.

Infect Dis Health. 2020 Jul 23;:

Authors: Walczak A, Wilks K, Shakhovskoy R, Baird T, Schlebusch S, Taylor C, Reid D, Choong K

Abstract
We report the first case of COVID-19 in a pregnant patient with cystic fibrosis. We describe the diagnosis, clinical course and management of the patient and their family with regards to clinical, social and infection control measures around delivery. This case highlights the importance of the cooperation of multidisciplinary teams to achieve good clinical outcomes in complex patients with COVID-19.

PMID: 32763024 [PubMed - as supplied by publisher]

Trikafta and Psychopathology in Cystic Fibrosis: A Case Report.

Psychosomatics. 2020 Jul 02;:

Authors: Tindell W, Su A, Oros SM, Rayapati AO, Rakesh G

PMID: 32763020 [PubMed - as supplied by publisher]

Cystic fibrosis drug approved for patients aged 6-11 years worked well in clinical practice.

Acta Paediatr. 2020 Aug 06;:

Authors: Loukou I, Petrocheilou A, Moustaki M, Katsagoni CN, Douros K

Abstract
Ivacaftor (IVA) and lumacaftor (LUM) modulate the cystic fibrosis (CF) transmembrane conductance regulator protein. IVA targets gating defects and LUM improves the conformational stability of the F508del mutation. This combined drug was approved for homozygous F508del CF patients aged 12 years or more in 2015 and was extended to children aged 6-11 in 2018.

PMID: 32762058 [PubMed - as supplied by publisher]

Pseudo-Bartter Syndrome in Chinese Children with Cystic Fibrosis: Clinical Features and Genotypic Findings.

Pediatr Pulmonol. 2020 Aug 06;:

Authors: Yuelin S, Xiaolei T, Jinrong L, Huiming L, Shunying Z

Abstract
OBJECTIVES: To characterize the clinical and genotypic features of Cystic fibrosis-associated pseudo-Bartter syndrome (CF-PBS) in Chinese children.
METHODS: We recruited and characterized the clinical manifestations of 12 Chinese children with CF-PBS. Sweat test, blood and urinary analysis, sputum culture, chest and sinus computed tomography, and abdominal ultrasonography were obtained. Whole-exome sequencing, bioinformatics analysis, and sanger sequencing validation were performed to define the genotypes.
RESULTS: CF-PBS was accompanied by recurrent and/or persistent pneumonia (91.7%), pancreatitis (83.3%), vomiting and/or diarrhea (66.7%), failure to thrive and liver disease (58.3% respectively) among our patients. The predominant organisms found in the airways were Pseudomonas aeruginosa (83.3%) and Staphylococcus aureus (75.0%). The mean concentrations of blood gas and electrolytes were: pH 7.58, bicarbonate 40.8 mmol/L, sodium 125.9 mmol/L, chloride 77.5 mmol/L, and potassium 2.6 mmol/L. A high recurrence rate (50.0%) of CF-PBS was observed despite continued electrolyte supplementation during follow up. 19 different variants of CFTR gene were identified, and 10 of these were found to be novel observations (c.262_266delTTATA[p.L88FfsX21], c.579+2insACAT, c.1210-3C>G, c.1733T>C[p.L578P], c.2236_2246delGAGGCGATACTinsAAAAATC[p.E746KfsX8], c.3068T>G [p.I1023R], c.3635delT[p.V1212AfsX16], c.3859delG[p.G1287EfsX2], c.3964-7A>G and ΔE23 [c.3718-?_3873+?del]). The c.2909G>A[p.G970D] was the most common variant, with an allele frequency of 16.6%. A homozygous genotype of c.1521_1523delCTT[p.F508del] was discovered for the first time in patients of Chinese origin.
CONCLUSIONS: In China, CF-PBS usually presents early and recurs frequently in infancy, accompanied by multiple comorbidities. Recurrence of CF-PBS in school-going patients does occur but is rare. The p.G970D is the most frequent variant, with a significant ethnic tendency of Chinese origin. This article is protected by copyright. All rights reserved.

PMID: 32761997 [PubMed - as supplied by publisher]

Lung Function Deterioration in School Children with Cystic Fibrosis.

Pediatr Pulmonol. 2020 Aug 06;:

Authors: Walicka-Serzysko K, Postek M, Milczewska J, Sands D

Abstract
INTRODUCTION: Lung disease in cystic fibrosis (CF) begins early in life but the capabilities for detecting abnormalities of pulmonary dysfunction in children remain limited.
OBJECTIVES: The study aimed to evaluate the early progression of lung function by the analysis of pulmonary hyperinflation, ventilation inhomogeneity (VI), trapped gas and airway obstruction with age.
METHODS: One hundred CF children aged 7-18, divided into two groups aged 7-12 (n=40) and 13-18 (n=60), were enrolled. Patients performed MBNW tests and plethysmography for measurements of lung clearance index (LCI), functional residual capacity (FRCpleth , FRCMBNW ), volume of trapped gas (VT ), total resistance (Rtot ), and effective and specific effective airway resistance (Reff , sReff ).
RESULTS: We obtained a positive correlation of FRCpleth , FRCMBNW , and LCI with age. A linear correlation between FRCMBNW and FRCpleth (p<0.0001) was observed. Ventilation inhomogeneity was higher in the group of older patients (9.79 in the group aged 7-12 and 11.67 in the group aged 13-18). An increased effective specific airway resistance (sReff >2 z-score) was present in 58% of all subjects (50%, 63.3% respectively). Pulmonary hyperinflation (FRCpleth >2 z-score) was observed in 33% of all patients: 25%, 36.6 % respectively. Trapped gas (VT >2 z-score) was present in 18% of all children: 30%, 10% respectively.
CONCLUSIONS: A gradual decline in lung function is associated with an increase in ventilation inhomogeneity, airway obstruction, pulmonary hyperinflation and development of trapped gas. In children who cannot perform either spirometry or plethysmography, MBNW can deliver a measurement of LCI connecting with VI as well as FRCMBNW to indicate indirectly the increase of hyperinflation. This article is protected by copyright. All rights reserved.

PMID: 32761970 [PubMed - as supplied by publisher]

Rituximab for treating inhibitors in people with inherited severe hemophilia.

Cochrane Database Syst Rev. 2020 Aug 03;8:CD010810

Authors: Jiang L, Liu Y, Zhang L, Santoro C, Rodriguez A

Abstract
BACKGROUND: Hemophilia A and B are inherited coagulation disorders characterized by a reduced or absent level of factor VIII or factor IX respectively. The severe form is characterized by a factor level less than 0.01 international units (IU) per milliliter. The development of inhibitors in hemophilia is the main complication of treatment, because the presence of these antibodies, reduces or even nullifies the efficacy of replacement therapy, making it very difficult to control the bleeding. People with inhibitors continue to have significantly higher risks of morbidity and mortality, with considerable treatment costs. Given the wide 'off-label' use of rituximab for treating people with hemophilia and inhibitors, its efficacy and safety need to be evaluated. This is an update of a previously published Cochrane Review.
OBJECTIVES: To assess the efficacy and safety of rituximab for treating inhibitors in people with inherited severe hemophilia A or B.
SEARCH METHODS: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Coagulopathies Trials Register, complied from electronic database searches and handsearching of journals and conference abstract books. We searched the reference lists of relevant articles and reviews and also searched for ongoing or unpublished studies. We also undertook further searches of other bibliographic databases and trial registries. Date of last search of the Cochrane Cystic Fibrosis and Genetic Disorders Group's Coagulopathies Trials Register: 19 March 2020.
SELECTION CRITERIA: Randomized controlled trials and controlled clinical trials investigating the efficacy and safety of rituximab for treating inhibitors in people with hemophilia.
DATA COLLECTION AND ANALYSIS: No randomized controlled trials matching the selection criteria were eligible for inclusion.
MAIN RESULTS: No randomized controlled trials on rituximab for treating inhibitors in people with hemophilia were identified.
AUTHORS' CONCLUSIONS: We were unable to identify any relevant trials on the efficacy and safety of rituximab for treating inhibitors in people with hemophilia. The research evidence available is from case reports and case series. Randomized controlled trials are needed to evaluate the efficacy and safety of rituximab for this condition. However, prior to the publication of any possible future randomized controlled trials, meta-analysis of case reports and case series may provide some evidence.

PMID: 32761818 [PubMed - in process]

Pancreatic enzyme replacement therapy for people with cystic fibrosis.

Cochrane Database Syst Rev. 2020 Aug 05;8:CD008227

Authors: Somaraju URR, Solis-Moya A

Abstract
BACKGROUND: Most people with cystic fibrosis (CF) (80% to 90%) need pancreatic enzyme replacement therapy (PERT) to prevent malnutrition. Enzyme preparations need to be taken whenever food is taken, and the dose needs to be adjusted according to the food consumed. A systematic review on the efficacy and safety of PERT is needed to guide clinical practice, as there is variability between centres with respect to assessment of pancreatic function, time of commencing treatment, dose and choice of supplements. This is an updated version of a published review.
OBJECTIVES: To evaluate the efficacy and safety of PERT in children and adults with CF and to compare the efficacy and safety of different formulations of PERT and their appropriateness in different age groups. Also, to compare the effects of PERT in CF according to different diagnostic subgroups (e.g. different ages at introduction of therapy and different categories of pancreatic function).
SEARCH METHODS: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register comprising references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings. Most recent search: 07 November 2019. We also searched an ongoing trials website and the websites of the pharmaceutical companies who manufacture pancreatic enzyme replacements for any additional trials. Most recent search: 26 December 2019.
SELECTION CRITERIA: Randomised and quasi-randomised controlled trials in people of any age, with CF and receiving PERT, at any dosage and in any formulation, for a period of not less than four weeks, compared to placebo or other PERT preparations.
DATA COLLECTION AND ANALYSIS: Two authors independently assessed trials and extracted outcome data. They also assessed the risk of bias and quality of the evidence (GRADE) of the trials included in the review.
MAIN RESULTS: 14 trials were included in the review (641 children and adults with CF), two of these were parallel trials and 12 were cross-over trials. Interventions included different enteric and non-enteric-coated preparations of varying formulations in comparison to each other. The number of participants in each trial varied between 14 and 129. 13 trials were for a duration of four weeks and one trial lasted seven weeks. The majority of the trials had an unclear risk of bias from the randomisation process as the details of this were not given; they also had a high risk of attrition bias and reporting bias. The quality of the evidence ranged from moderate to very low. We mostly could not combine data from the trials as they compared different formulations and the findings from individual trials provided insufficient evidence to determine the size and precision of the effects of different formulations.
AUTHORS' CONCLUSIONS: There is limited evidence of benefit from enteric-coated microspheres when compared to non-enteric coated pancreatic enzyme preparations up to one month. In the only comparison where we could combine any data, the fact that these were cross-over trials is likely to underestimate the level of inconsistency between the results of the trials due to over-inflation of CIs from the individual trials.There is no evidence on the long-term effectiveness and risks associated with PERT. There is also no evidence on the relative dosages of enzymes needed for people with different levels of severity of pancreatic insufficiency, optimum time to start treatment and variations based on differences in meals and meal sizes. There is a need for a properly designed trial that can answer these questions.

PMID: 32761612 [PubMed - in process]

[Clinical presentation of lung disease in cystic fibrosis].

Radiologe. 2020 Aug 06;:

Authors: Stahl M

Abstract
Although cystic fibrosis (CF) is a multiorgan disease, the extent of CF lung disease is decisive for the course and survival of patients. The optimization of symptomatic therapies has led to a significant improvement in the life expectancy of those affected in recent decades. Regular monitoring of the course of CF lung disease with microbiological, pulmonary function, and imaging examinations is essential for early detection of problems and individualized therapy. With new, causal therapy options in the form of cystic fibrosis transmembrane conductance regulator (CFTR) modulators and early diagnosis through newborn screening, a further normalization of life expectancy and quality of life of CF patients can be expected.

PMID: 32761355 [PubMed - as supplied by publisher]

Targeting the Heme Oxygenase 1/Carbon Monoxide Pathway to Resolve Lung Hyper-Inflammation and Restore a Regulated Immune Response in Cystic Fibrosis.

Front Pharmacol. 2020;11:1059

Authors: Di Pietro C, Öz HH, Murray TS, Bruscia EM

Abstract
In individuals with cystic fibrosis (CF), lung hyper-inflammation starts early in life and is perpetuated by mucus obstruction and persistent bacterial infections. The continuous tissue damage and scarring caused by non-resolving inflammation leads to bronchiectasis and, ultimately, respiratory failure. Macrophages (MΦs) are key regulators of immune response and host defense. We and others have shown that, in CF, MΦs are hyper-inflammatory and exhibit reduced bactericidal activity. Thus, MΦs contribute to the inability of CF lung tissues to control the inflammatory response or restore tissue homeostasis. The non-resolving hyper-inflammation in CF lungs is attributed to an impairment of several signaling pathways associated with resolution of the inflammatory response, including the heme oxygenase-1/carbon monoxide (HO-1/CO) pathway. HO-1 is an enzyme that degrades heme groups, leading to the production of potent antioxidant, anti-inflammatory, and bactericidal mediators, such as biliverdin, bilirubin, and CO. This pathway is fundamental to re-establishing cellular homeostasis in response to various insults, such as oxidative stress and infection. Monocytes/MΦs rely on abundant induction of the HO-1/CO pathway for a controlled immune response and for potent bactericidal activity. Here, we discuss studies showing that blunted HO-1 activation in CF-affected cells contributes to hyper-inflammation and defective host defense against bacteria. We dissect potential cellular mechanisms that may lead to decreased HO-1 induction in CF cells. We review literature suggesting that induction of HO-1 may be beneficial for the treatment of CF lung disease. Finally, we discuss recent studies highlighting how endogenous HO-1 can be induced by administration of controlled doses of CO to reduce lung hyper-inflammation, oxidative stress, bacterial infection, and dysfunctional ion transport, which are all hallmarks of CF lung disease.

PMID: 32760278 [PubMed]

Investigation of Stenotrophomonas maltophilia epidemiology in a French cystic fibrosis center.

Respir Med Res. 2020 Apr 18;78:100757

Authors: Capaldo C, Beauruelle C, Saliou P, Rault G, Ramel S, Héry-Arnaud G

Abstract
BACKGROUND: Stenotrophomonas maltophilia is an emerging opportunistic pathogen. The increasing incidence is of particular concern in patients with cystic fibrosis (CF). Since 2012, the Western France has witnessed high annual prevalence of S. maltophilia colonization/infection. This retrospective cohort study investigated the epidemiology of S. maltophilia emergence in the CF center of Roscoff, Western France, a region of high prevalence of CF in Europe.
METHODS: All CF patients with S. maltophilia isolated in respiratory samples between December 2013 and February 2017 were included. For each patient the colonization status with S. maltophilia was determined. The epidemiological and microbiological characteristics collected were compared between colonization statuses.
RESULTS: S. maltophilia was isolated in 90 patients (42 males, 48 females). Mean age at first colonization was 24.4±13.5 years. Annual prevalence since 2013 was high (16-17.9%), but stable. This high prevalence is mainly due to a high rate of intermittent colonization. Only 2.8% of CF patients showed chronic colonization, with significantly more frequent co-colonization by methicillin-susceptible Staphylococcus aureus (P<0.0001) and Pseudomonas aeruginosa (P<0.05). During chronic colonization, S. maltophilia acquired resistance to cotrimoxazole and β-lactams. Interestingly, there were cases of decolonization.
CONCLUSION: This is the first epidemiological report of S. maltophilia in a French CF center. Prevalence was stable but above the national average. Most cases were intermittent; chronic colonization was rare.

PMID: 32759054 [PubMed - as supplied by publisher]

A comparison of the CFHH criteria against the Leeds criteria in determining the Pseudomonas aeruginosa status among adults with cystic fibrosis.

Respir Med. 2020 Jul 28;171:106103

Authors: Hoo ZH, Hitchcock L, Curley R, Wildman MJ

Abstract
BACKGROUND: Pseudomonas aeruginosa (PA) status influences management decisions in cystic fibrosis (CF) but diagnostic approaches vary. We evaluated the ability of the CFHealthHub (CFHH) criteria, which consist of two major and four minor statements, in diagnosing chronic PA infection among adults with CF.
METHODS: In this retrospective cross-sectional analysis, we compared the CFHH criteria against the Leeds criteria. Data were collected between 1st January and 31st December 2016 from all adults with CF receiving care at Sheffield, excluding those with lung transplantation (n = 7) or on ivacaftor (n = 13). The CFHH criteria PA status were cross-tabulated against the Leeds criteria, and clinical outcomes between chronic PA vs non chronic PA for both criteria were compared.
RESULTS: This analysis included 186 adults with CF (90 females, median age 27 years, median baseline FEV1 78.5%). The CFHH criteria diagnosed more cases of chronic PA (116/186, 62.4% vs 79/186, 42.5%), and 37/107 cases of non-chronic PA according to the Leeds criteria were deemed chronic PA by the CFHH criteria. The magnitude of difference in %FEV1 decline between chronic PA vs non chronic PA was slightly greater for the CFHH criteria (-0.6%, 95% CI -1.8 to 0.6%) compared to the Leeds criteria (-0.2%, 95% CI -1.3 to 1.0%).
CONCLUSIONS: The CFHH criteria detected more chronic PA cases yet still retained similar levels of discrimination for health outcomes in comparison to the Leeds criteria. These findings provide preliminary evidence for the validity of the CFHH criteria among adults with CF.

PMID: 32758991 [PubMed - as supplied by publisher]

Clinical and genetic characterization of patients with cystic fibrosis and functional assessment of the chloride channel with the pathogenic variant c.831G> A (p.Trp277*), described for the first time.

Gene. 2020 Aug 03;:145023

Authors: Kondratyeva E, Efremova A, Melyanovskaya Y, Petrova N, Satsuk N, Bulatenko N, Bukharova T, Zodbinova A, Sherman V, Kashirskaya N, Zinchenko R, Kutsev S, Goldstein D

Abstract
The clinical pictures of the disease of two Russian patients with cystic fibrosis with a rare nonsense variant c.831G>A (p.Trp277*) are described. The first case is a patient with the genotype comprising variant c.54-5940_273+10250del21kb (CFTRdele2,3), and the genotype of the second case included variant c.1521_1523delCTT (F508del). Patient 1, whose genotype had two class I genetic variants, revealed severe violations of CFTR synthesis based on the intestinal current measurements (ICM) and results obtained in the intestinal organoids. In both cases of patients with genetic variant c.831G>A, a severe course of cystic fibrosis was observed.

PMID: 32758581 [PubMed - as supplied by publisher]

Heat acclimation improves sweat gland function and lowers sweat sodium concentration in an adult with cystic fibrosis.

J Cyst Fibros. 2020 Aug 02;:

Authors: Willmott AGB, Holliss R, Saynor Z, Corbett J, Causer AJ, Maxwell NS

Abstract
We present novel data concerning the time-course of adaptations and potential benefits of heat acclimation for people with cystic fibrosis (pwCF), who are at greater risk of exertional heat illness. A 25-year-old male (genotype: delta-F508 and RH117, forced expiratory volume in 1-second: 77% predicted and baseline sweat [Na+]: 70 mmol·L - 1), who had previously experienced muscle cramping during exercise in ambient heat, underwent 10-sessions of heat acclimation (90-min at 40°C and in 40% relative humidity). Adaptations included; lower resting core temperature (-0.40°C) and heart rate (-6 beats·min-1), plasma volume expansion (+6.0%) and, importantly, increased sweat loss (+370 mL) and sweat gland activity (+12 glands·cm2) with decreased sweat [Na+] (-18 mmol·L - 1). Adaptations were maintained for at least 7-days, with no evidence of cramping during follow-up exercise-heat stress testing. These data suggest pwCF may benefit from heat acclimation to induce sudomotor function improvements, particularly reductions in sweat [Na+], however, further research is required.

PMID: 32758394 [PubMed - as supplied by publisher]

Cystic fibrosis gene mutations and polymorphisms in Saudi men with infertility.

Ann Saudi Med. 2020 Jul-Aug;40(4):321-329

Authors: AlMaghamsi T, Iqbal N, Al-Esaei NA, Mohammed M, Eddin KZ, Ghurab F, Moghrabi N, Heaphy E, Junaid I

Abstract
BACKGROUND: Some mutations of the cystic fibrosis transmembrane regulator (CFTR) gene may impair spermatogenesis or cause a congenital absence of the vas deferens that manifests as isolated male infertility.
OBJECTIVE: Assess the frequency and analyze the spectrum of CFTR gene variations in Saudi men with primary infertility.
DESIGN: Prospective, cross-sectional.
SETTING: Tertiary care specialist hospital in Jeddah.
PATIENTS AND METHODS: Genomic DNA was extracted from peripheral blood samples of Saudi men who presented with primary infertility to the outpatient andrology clinic with either azoospermia or oligoasthenoteratozoospermia. Polymerase chain reaction and direct sequencing were used to identify all variants of the CFTR gene.
MAIN OUTCOME MEASURES: Proportion of the patients with a mutant CFTR gene and the spectrum of CFTR gene variations.
SAMPLE SIZE: 50 infertile Saudi men.
RESULTS: This study identified 10 CFTR gene variants in 7 (14%) subjects (100 chromosomes). The detected variants and polymorphisms were: c.1408G>A, c.4389G>A, c.2562T>G, c.869+11C>T, c.2909-92G>A, c.3469-65C>A, c.1210-6delT, c.1210-6T>A, c.2988+1G>A, and c.1210-13GT>TG.
CONCLUSION: We demonstrated that 14% of the study subjects had one or more CFTR mutations and these were compounded in most of the affected patients. The spectrum of CFTR gene mutations in these subjects was similar to the mutations reported in other studies throughout the world.
LIMITATIONS: Small sample size and the lack of a control group.
CONFLICTS OF INTEREST: None.

PMID: 32757986 [PubMed - in process]

APPEAL-2: a pan-European qualitative study to explore the burden of peanut-allergic children, teenagers, and their caregivers.

Clin Exp Allergy. 2020 Aug 05;:

Authors: DunnGalvin A, Gallop K, Acaster S, Timmermans F, Regent L, Schnadt S, Podestà M, Sánchez A, Ryan R, Couratier P, Feeney M, Hjorth B, Fisher HR, Blumchen K, Vereda A, Fernández-Rivas M

Abstract
BACKGROUND: Allergy to Peanuts ImPacting Emotions And Life (APPEAL-1) was a recent European multi-country questionnaire survey that highlighted the negative impacts of peanut allergy (PA) on quality of life. A follow-on qualitative study, APPEAL-2, further assessed the burden of PA and associated coping strategies through semi-structured interviews.
OBJECTIVE: To gain qualitative insight on the strategies used to cope with and manage PA and the impact of these strategies on the quality of life of children, teenagers, and caregivers.
METHODS: This cross-sectional qualitative study was conducted in eight European countries: the United Kingdom, France, Germany, Ireland, Spain, Italy, Denmark, and the Netherlands. Semi-structured interviews were conducted with children (aged 8-12 years) and teenagers (aged 13-17 years) with self-/proxy-reported moderate or severe PA and with parents/caregivers of children or teenagers (aged 4-17 years) with moderate or severe PA. Data were analyzed using thematic analysis; data saturation was assessed. Two conceptual models were developed to illustrate the impacts of PA and coping strategies used to manage them for (1) individuals with PA and (2) parents/caregivers of children with PA.
RESULTS: 107 participants were interviewed: 24 children, 39 teenagers, and 44 caregivers. The conceptual models illustrated themes related to coping and control, driven by the fear of PA reactions, and the associated emotional, social, relationship, and work impacts. Factors moderating these impacts included social attitudes and support, child-caregiver relationship, and coping strategies used.
CONCLUSIONS AND CLINICAL RELEVANCE: The APPEAL-2 results substantiate the findings of APPEAL-1; the results also suggest that the severity of experience with PA may not correlate with perception of its overall burden and show variable impacts by country.

PMID: 32757478 [PubMed - as supplied by publisher]

Host Adaptation Predisposes Pseudomonas aeruginosa to Type VI Secretion System-Mediated Predation by the Burkholderia cepacia Complex.

Cell Host Microbe. 2020 Jul 24;:

Authors: Perault AI, Chandler CE, Rasko DA, Ernst RK, Wolfgang MC, Cotter PA

Abstract
Pseudomonas aeruginosa and Burkholderia cepacia complex (Bcc) species are opportunistic lung pathogens of cystic fibrosis (CF) patients. While P. aeruginosa can initiate long-term infections in younger CF patients, Bcc infections only arise in teenagers and adults. Both P. aeruginosa and Bcc use type VI secretion systems (T6SSs) to mediate interbacterial competition. Here, we show P. aeruginosa isolates from teenage and adult CF patients, but not those from young CF patients, are outcompeted by the epidemic Bcc isolate Burkholderia cenocepacia strain AU1054 in a T6SS-dependent manner. The genomes of susceptible P. aeruginosa isolates harbor T6SS-abrogating mutations, the repair of which, in some cases, rendered the isolates resistant. Moreover, seven of eight Bcc strains outcompeted P. aeruginosa strains isolated from the same patients. Our findings suggest certain mutations that arise as P. aeruginosa adapts to the CF lung abrogate T6SS activity, making P. aeruginosa and its human host susceptible to potentially fatal Bcc superinfection.

PMID: 32755549 [PubMed - as supplied by publisher]

Clinical impact of depression and anxiety in patients with non-cystic fibrosis bronchiectasis.

Tuberk Toraks. 2020 Jul;68(2):103-111

Authors: Bekir M, Kocakaya D, Balcan B, Olguz Yıldızeli Ş, Eryüksel E, Ceyhan B

Abstract
Introduction: Bronchiectasis is a chronic suppurative disease characterized by abnormal bronchial dilatation. The nature of bronchiectasis may have negative impact on psychological status, however it is poorly studied in relation to clinical indices, particularly the severity of disease. Primary aim of this study is to detect depression and anxiety in patients with non-cystic fibrosis bronchiectasis and to evaluate its relationship with disease severity indexes.
Materials and Methods: Ninety (male/female= 37/53; median age 45 years) stable non-cystic fibrosis bronchiectatic adult patients were enrolled into this study. Dyspnea scores, number of exacerbations and hospital admissions within the last year, body-mass index, pulmonary function tests, sputum cultures, bronchiectasis disease severity indexes (BSI and FACED) were assessed. Anxiety and depression were evaluated by using the Turkish version of the hospital anxiety and depression scale questionaire.
Result: Anxiety was diagnosed in 30% of patients and depression was diagnosed in 41% of the participants. Female participants had significantly higher rates of depression (55% vs. 22%; p= 0.002). Exacerbation rates within the last year were higher among the subjects with anxiety, moreover, patients with depression had shorter duration of disease. BSI and FACED severity indexes increased with longer duration of disease (5.6 ± 5.0 yrs in mild group vs. 10.1 ± 9.2 yrs in moderate-to-severe group, p= 0.035 and 5.7 ± 5.4 yrs in mild group vs. 12.1 ± 9.7 yrs in moderate-to-severe group, p= 0.001, respectively), however, anxiety and depression were not related with BSI and FACED severity indexes.
Conclusions: Patients with non-cystic fibrosis bronchiectasis have an increased risk for depression and anxiety. Duration of disease and higher exacerbation rate are related with psychological status and indexes increased with longer duration of disease. Early detection and taking the necessary measures to improve the psychological state is necessary for the overall management of these patients.

PMID: 32755109 [PubMed - in process]

Development and Validation of the AdT-Physio Scale: A Tool to Assess Adherence and Perception of Physical Therapist Intervention in Patients With Cystic Fibrosis.

Phys Ther. 2020 Aug 05;:

Authors: Del Corral T, La Touche R, Cebrià I Iranzo MÀ, Olmos R, Blanco-Royano F, López-de-Uralde-Villanueva I

Abstract
OBJECTIVE: The purpose of this study was to develop a scale to measure patient adherence to physical therapist intervention and to report psychometric properties in patients with cystic fibrosis (CF).
METHODS: This observational, multicenter, qualitative, and cross-sectional study was divided into 2 phases: development of scale items (content validity) and assessment of psychometric properties (construct validity, reliability, and convergent/discriminant validity). Recruited were 121 patients with CF (aged ≥16 y). Sociodemographic characteristics, lung function testing, Coping with Stress Self-Efficacy (EAEAE), brief Coping Orientation to Problems Experienced inventory (COPE-28), and the AdT-Physio scale were evaluated.
RESULTS: The final version of the AdT-Physio scale consists of 15 items distributed across 2 subscales: compliance and beliefs about treatment/therapist. The scale showed high internal consistency (Cronbach α = 0.897; 95% CI = 0.868-0.922) and subscales above 0.800. The 2-factor confirmatory factor analysis model fitted the data reasonably well: χ2 (76) = 111.96, comparative fit index = 0.982, Tucker-Lewis index = 0.978, root mean square error of approximation = 0.063, 95% CI = 0.036 to 0.086, weighted root mean square residual = 0.720. No floor or ceiling effects were identified. There was a positive, significant, and moderate-low magnitude correlation with the total COPE-28 (r = .360) and EAEAE subscale efficacy expectations scores (r = .304). For discriminant validity, there was a positive, significant, and moderate correlation between the total and the age of the patients (r = .354).
CONCLUSION: The AdT-Physio scale is psychometrically valid and reliable for use in the clinic for the assessment of adherence to physiotherapy in patients with CF.
IMPACT: Ultimately, the authors propose this documentary instrument to assess the evaluation of the therapeutic alliance in a valid and objective manner. The AdT-Physio scale provides us with a greater degree of understanding of the problems behind noncompliance with treatment to advance person-centered decisions in physical therapy and thereby enhance the effectiveness of care.

PMID: 32754747 [PubMed - as supplied by publisher]