ADAM9: A Damaging Player in Chronic Obstructive Pulmonary Disease.

Am J Respir Crit Care Med. 2018 12 15;198(12):1465-1466

Authors: Russell DW, Gaggar A

PMID: 29986153 [PubMed - indexed for MEDLINE]

Isolation and identification of Pandoraea spp. From bronchoalveolar lavage of cystic fibrosis patients in Iran.

Ital J Pediatr. 2019 Sep 02;45(1):118

Authors: Tabatabaei M, Dastbarsar M, Moslehi MA

Abstract
BACKGROUND: Pandoraea species are gram negative, motile, non-spore forming, rod shaped and oxidase positive, obligate aerobes bacteria, and have one polar flagellum. Most of Pandoraea species are associated with lung infections in cystic fibrosis patients. Cystic fibrosis is the most prevalent autosomal recessive hereditary disease in the world that affects various organs of the body. The main important cause of death in these patients is lung involvement. This study was conducted to isolate and identify Pandoraea bacterium from bronchoalveolar lavage and sputum samples of cystic fibrosis patients in Shiraz, Iran.
METHODS: In this research 31 samples of bronchoalveolar lavage and sputum were examined by culture and PCR method. Then confirmed isolates were evaluated for susceptibility to different antibiotics and ability to produce biofilm.
RESULTS: The results of this study after cultivation, purification and DNA extraction led to the isolation of 4 Pandoraea bacterium by PCR using specific primers. Antibiotic susceptibility test were indicated all isolates were resistant to gentamicin, amikacin and imipenem and susceptible to ciprofloxacin, trimethoprim-sulfumethoxazole, piperacillin and tetracycline. Ability to create biofilm was indicated by some of Pandoraea isolates. According to findings of this study, ability to synthesis biofilm by Pandoraea isolates and resistance to some antibiotics are very important.
CONCLUSIONS: Our study notes the role of P. pnomenusa as an emerging pathogen that can cause chronic lung colonization in CF patients. Identification tools need to be accurate and must be based on molecular techniques. Also our findings should raise awareness about antibiotic resistance in cystic fibrosis patients in Iran and ability of including bacterial agents to produce biofilm is an alarm for public health. Thus clinicians should exercise caution about finding of clinical relevance of this pathogen to the infection and prescribing antibiotics, especially in cases of children infections.

PMID: 31477148 [PubMed - in process]

Reduced expression of the Ion channel CFTR contributes to airspace enlargement as a consequence of aging and in response to cigarette smoke in mice.

Respir Res. 2019 Sep 02;20(1):200

Authors: Wellmerling JH, Chang SW, Kim E, Osman WH, Boyaka PN, Borchers MT, Cormet-Boyaka E

Abstract
Chronic Obstructive Pulmonary Disease (COPD) is a complex disease resulting in respiratory failure and represents the third leading cause of global death. The two classical phenotypes of COPD are chronic bronchitis and emphysema. Owing to similarities between chronic bronchitis and the autosomal-recessive disease Cystic Fibrosis (CF), a significant body of research addresses the hypothesis that dysfunctional CF Transmembrane Conductance Regulator (CFTR) is implicated in the pathogenesis of COPD. Much less attention has been given to emphysema in this context, despite similarities between the two diseases. These include early-onset cellular senescence, similar comorbidities, and the finding that CF patients develop emphysema as they age. To determine a potential role for CFTR dysfunction in the development of emphysema, Cftr+/+ (Wild-type; WT), Cftr+/- (heterozygous), and Cftr-/- (knock-out; KO) mice were aged or exposed to cigarette smoke and analyzed for airspace enlargement. Aged knockout mice demonstrated increased alveolar size compared to age-matched wild-type and heterozygous mice. Furthermore, both heterozygous and knockout mice developed enlarged alveoli compared to their wild-type counterparts following chronic smoke exposure. Taken into consideration with previous findings that cigarette smoke leads to reduced CFTR function, our findings suggest that decreased CFTR expression sensitizes the lung to the effects of cigarette smoke. These findings may caution normally asymptomatic CF carriers against exposure to cigarette smoke; as well as highlight emphysema as a future challenge for CF patients as they continue to live longer. More broadly, our data, along with clinical findings, may implicate CFTR dysfunction in a pathology resembling accelerated aging.

PMID: 31477092 [PubMed - in process]

EFSUMB Gastrointestinal Ultrasound (GIUS) Task Force Group: Celiac sprue and other rare gastrointestinal diseases ultrasound features.

Med Ultrason. 2019 Aug 31;21(3):299-315

Authors: Dietrich CF, Hollerweger A, Dirks K, Higginson A, Serra C, Calabrese E, Dong Y, Hausken T, Maconi G, Mihmanli I, Nürnberg D, Nylund K, Pallotta N, Ripollés T, Romanini L, Săftoiu A, Sporea I, Wüstner M, Maaser C, Gilja OH

Abstract
Transabdominal gastrointestinal ultrasound (GIUS) is unique in its capacity to examine the bowel non-invasively and in its physiological condition, including extra-intestinal features such as the splanchnic vessels, mesentery, omentum and lymph nodes- even at the bedside. Despite this, and its extensive documentation for its usefulness, it has only been fully implemented in a few European countries and expert centres. Therefore, the European Federation of Societies for Ultrasound in Medicine and Biology (EFSUMB) established a GIUS Task Force Group in 2014 consisting of international experts from 9 European countries with the objectives to standardize and promote the use of GIUS in a clinical setting. This is achieved by publishing clinical guidelines and recommendations on indications and use of GIUS and so far,4 guidelines have been published: first on "examination techniques and normal findings", second on "inflammatory bowel disease", third on "acute appendicitis and diverticulitis" and fourth on "transrectal and perineal ultrasound".This paper describes the ultrasound features of miscellaneous disorders such as celiac disease, cystic fibrosis, omental infarction, Meckel's diverticle, endometriosis, intestinal neoplasia, mucocele, amyloidosis, GVHD, foreign bodies, vasculitis, and pneumatosis cystoides intestinalis. Bowel ultrasound can be indicated in most of these conditions to investigate intestinal symptoms but in other cases the alterations of the bowel can be also an incidental finding that suggest other examinations which finally help to discover an unknown pathological condition.

PMID: 31476211 [PubMed - in process]

Children with bronchiectasis have poorer lung function than those with cystic fibrosis and do not receive the same standard of care.

Pediatr Pulmonol. 2019 Sep 01;:

Authors: Prentice BJ, Wales S, Doumit M, Owens L, Widger J

Abstract
BACKGROUND: Children with cystic fibrosis (CF) are routinely managed in a multidisciplinary clinic at tertiary pediatric centers. However, children with bronchiectasis may not be managed in the same way. We sought to compare the management model and clinical outcomes of children with bronchiectasis with children diagnosed with CF, in a single pediatric center.
METHODS: We identified patients with bronchiectasis from hospital medical records at an urban tertiary pediatric hospital and identified a sex- and age-matched CF patient at the same center to compare lung function, nutritional status, frequency of physiotherapy and respiratory physician visits, and number of microbiological samples taken for bacterial culture.
RESULTS: Twenty-two children with bronchiectasis were identified, mean (standard deviation [SD]) age was 11 (3) years. The most common known etiology for bronchiectasis was postinfective (6 of 22) but was unknown in 8 of 22. The cohort with bronchiectasis had poorer lung function (FEV1 mean [SD] percent predicted 78.6 [20.5] vs 94.5 [14.7], P = .005) and had less outpatient reviews by the respiratory physician (P < .001) and respiratory physiotherapist (P < .001) when compared to those with CF. Nutritional parameters did not differ between the groups. Many children (10 of 22, 45%) with bronchiectasis did not have any microbiological respiratory tract samples taken for evaluation.
CONCLUSION: Children with bronchiectasis at this institution have poorer lung function than children with CF, and are deserving of improved multidisciplinary care.

PMID: 31475469 [PubMed - as supplied by publisher]

Deciphering multivalent glycocluster-lectin interactions through AFM characterization of the self-assembled nanostructures.

Soft Matter. 2019 Sep 02;:

Authors: Zuttion F, Sicard D, Dupin L, Vergoten G, Girard-Bock C, Madaoui M, Chevolot Y, Morvan F, Vidal S, Vasseur JJ, Souteyrand E, Phaner-Goutorbe M

Abstract
Pseudomonas aeruginosa is a human opportunistic pathogen responsible for lung infections in cystic fibrosis patients. The emergence of resistant strains and its ability to form a biofilm seem to give a selective advantage to the bacterium and thus new therapeutic approaches are needed. To infect the lung, the bacterium uses several virulence factors, like LecA lectins. These proteins are involved in bacterial adhesion due to their specific interaction with carbohydrates of the host epithelial cells. The tetrameric LecA lectin specifically binds galactose residues. A new therapeutic approach is based on the development of highly affine synthetic glycoclusters able to selectively link with LecA to interfere with the natural carbohydrate-LecA interaction. In this study, we combined atomic force microscopy imaging and molecular dynamics simulations to visualize and understand the arrangements formed by LecA and five different glycoclusters. Our glycoclusters are small scaffolds characterized by a core and four branches, which terminate in a galactose residue. Depending on the nature of the core and the branches, the glycocluster-lectin interaction can be modulated and the affinity increased. We show that glycocluster-LecA arrangements highly depend on the glycocluster architecture: the core influences the rigidity of the geometry and the directionality of the branches, whereas the nature of the branch determines the compactness of the structure and the ease of binding.

PMID: 31475271 [PubMed - as supplied by publisher]

Whole-blood transcriptomic responses to lumacaftor/ivacaftor therapy in cystic fibrosis.

J Cyst Fibros. 2019 Aug 29;:

Authors: Kopp BT, Fitch J, Jaramillo L, Shrestha CL, Robledo-Avila F, Zhang S, Palacios S, Woodley F, Hayes D, Partida-Sanchez S, Ramilo O, White P, Mejias A

Abstract
BACKGROUND: Cystic fibrosis (CF) remains without a definitive cure. Novel therapeutics targeting the causative defect in the cystic fibrosis transmembrane conductance regulator (CFTR) gene are in clinical use. Lumacaftor/ivacaftor is a CFTR modulator approved for patients homozygous for the CFTR variant p.Phe508del, but there are wide variations in treatment responses preventing prediction of patient responses. We aimed to determine changes in gene expression related to treatment initiation and response.
METHODS: Whole-blood transcriptomics was performed using RNA-Seq in 20 patients with CF pre- and 6 months post-lumacaftor/ivacaftor (drug) initiation and 20 non-CF healthy controls. Correlation of gene expression with clinical variables was performed by stratification via clinical responses.
RESULTS: We identified 491 genes that were differentially expressed in CF patients (pre-drug) compared with non-CF controls and 36 genes when comparing pre-drug to post-drug profiles. Both pre- and post-drug CF profiles were associated with marked overexpression of inflammation-related genes and apoptosis genes, and significant under-expression of T cell and NK cell-related genes compared to non-CF. CF patients post-drug demonstrated normalized protein synthesis expression, and decreased expression of cell-death genes compared to pre-drug profiles, irrespective of clinical response. However, CF clinical responders demonstrated changes in eIF2 signaling, oxidative phosphorylation, IL-17 signaling, and mitochondrial function compared to non-responders. Top overexpressed genes (MMP9 and SOCS3) that decreased post-drug were validated by qRT-PCR. Functional assays demonstrated that CF monocytes normalized calcium (increases MMP9 expression) concentrations post-drug.
CONCLUSIONS: Transcriptomics revealed differentially regulated pathways in CF patients at baseline compared to non-CF, and in clinical responders to lumacaftor/ivacaftor.

PMID: 31474496 [PubMed - as supplied by publisher]

Ensifentrine (RPL554): an investigational PDE3/4 inhibitor for the treatment of COPD.

Expert Opin Investig Drugs. 2019 Sep 01;:1-7

Authors: Cazzola M, Calzetta L, Rogliani P, Matera MG

Abstract
Introduction: A compound that simultaneously inhibits PDE3 and PDE4 should increase airway caliber by relaxing the smooth muscle and, simultaneously, suppress airway inflammatory responses. Ensifentrine (RPL554) is considered a PDE3/4 inhibitor, although its affinity for PDE3 is 3,440 times higher than that for PDE4, that is under clinical development for the treatment of asthma and COPD and, potentially, cystic fibrosis. Areas covered: We analyze the development of this molecule from its basic pharmacology to the present clinical Phase II studies. Expert opinion: Ensifentrine is an interesting drug but there is a lack of solid studies that still does not allow us to correctly allocate this molecule in the current COPD and even asthma therapeutic armamentarium. Furthermore, apparently ensifentrine has not yet entered Phase III clinical development and, in any case, there is no reliable evidence of its ability to elicit an anti-inflammatory activity in patients with COPD or asthma. Therefore, the real anti-inflammatory profile of ensifentrine must be clarified with new studies of basic pharmacology and adequate clinical studies specifically designed. However, at present the most intriguing perspective is linked to its possible use in the treatment of cystic fibrosis, also considering the lack of valid therapeutic options for this disease.

PMID: 31474120 [PubMed - as supplied by publisher]

Associations between demographic characteristics and unmet supportive care needs in adults with cystic fibrosis.

BMJ Support Palliat Care. 2019 Aug 31;:

Authors: Obregon LL, Jeong K, Hoydich ZP, Yabes J, Pilewski J, Richless C, Moreines LT, Dellon EP, Goss CH, Arnold RM, Kavalieratos D

Abstract
CONTEXT: Patients living with cystic fibrosis (CF) report impaired quality of life. Little is known about unmet supportive care needs among adults living with CF and how they are associated with demographic characteristics.
OBJECTIVES: The primary objective of this study was to identify associations between demographic variables and unmet supportive care needs regarding anxiety, sadness, pain and uncertainty about the future of living with CF.
METHODS: We recruited 165 adults with CF from a single academic medical centre to complete a brief demographic survey and the Supportive Care Needs Survey (SCNS-34), a validated self-reported needs assessment that measures the prevalence of and preferences for support for 34 needs that commonly occur in patients with serious illness.
RESULTS: Approximately half of the participant sample was male, with a median age of 29 years, varying income levels and a range of lung disease severity. We found statistically significant associations between insufficient income and increased odds of reporting need for support regarding anxiety (OR: 6.48; 95% CI 2.08 to 20.2), sadness (OR: 6.15; 95% CI 2.04 to 18.5), pain (OR: 7.06; 95% CI 2.22 to 22.4) and worries surrounding uncertainty about the future (OR: 3.43; 95% CI 1.18 to 9.99).
CONCLUSION: Adults with CF report significant unmet needs for support in several physical and emotional domains. Many of these domains were associated with demographic characteristics, most notably, income. Our findings underscore the importance of developing treatment approaches that are sensitive to patient demographics when addressing unmet supportive care needs among adults with CF.

PMID: 31473650 [PubMed - as supplied by publisher]

Generation of a CFTR knock-in reporter cell line (MHHi006-A-1) from a human induced pluripotent stem cell line.

Stem Cell Res. 2019 Aug 20;40:101542

Authors: Engels L, Olmer R, de la Roche J, Göhring G, Ulrich S, Haller R, Martin U, Merkert S

Abstract
CFTR encodes for a chloride ion channel expressed primarily in secretory epithelia in the airways, intestine, liver and other tissues. Mutations in the CFTR gene have been identified in people suffering from Cystic Fibrosis. Here, we established a CFTR knock-in reporter cell line from a human iPSC line (MHHi006-A) using TALEN technology. The reporter enables the monitoring and optimization of the differentiation of pluripotent stem cells into CFTR expressing epithelia on a single cell level, as well as the enrichment of CFTR positive cells, which represent an excellent tool for Cystic Fibrosis disease modelling, drug screening and ultimately cellular therapies.

PMID: 31473565 [PubMed - as supplied by publisher]

Nutritional assessment in adults with cystic fibrosis.

Nutrition. 2019 Jun 12;67-68:110518

Authors: Schönenberger KA, Reber E, Bally L, Geiser T, Lin D, Stanga Z

Abstract
OBJECTIVES: Clinical experience with patients with cystic fibrosis (CF) suggests a nutritional risk in this population. In addition to the lung pathology, a main pathophysiologic concern is the viscous mucus blocking pancreatic ducts, leading to reduced production of pancreatic enzymes. Therefore, maldigestion and consequently malabsorption (particularly fat and fat-soluble vitamins) occur, resulting in steatorrhea, vitamin deficiencies, and subsequently manifest malnutrition. The aim of this study was to investigate the nutritional status and determine the prevalence of malnutrition in an adult Swiss CF cohort.
METHODS: This was an observational cohort study in which the nutritional status and dietary habits of patients with CF and healthy controls were compared. Assessment was based on the nutritional risk screening (NRS-2002), dietary habits (7-d dietary record), body composition (bioelectrical impedance analysis), anthropometrics, resting energy expenditure (REE; indirect calorimetry), and physical or mental function (hand-grip strength, Short Form-36 v2).
RESULTS: Nineteen patients (15 men, mean age 32 y) and 15 controls (8 men, mean age 49 y) were included. Eight patients (42%) were at nutritional risk (NRS-2002 ≥3). Patients had higher energy intake/body weight (P = 0.021) with lower body fat percentage (P < .001), body mass index (P = 0.030), and physical/mental health scores (P < 0.001) than controls. Energy intake was higher than REE in patients (P = 0.003), but not in controls (P = 0.373).
CONCLUSIONS: Prevalence of malnutrition was high in this CF cohort, coinciding with low body fat percentage and low body mass index despite high energy and protein intake. Energy requirements of patients with CF should be estimated as approximately twice the Harris-Benedict REE and 1.7 times indirect calorimetry REE, while ensuring adequate intake of pancreatic enzymes.

PMID: 31473521 [PubMed - as supplied by publisher]

Case Report of Nursing Care for a Pregnant Woman With Cystic Fibrosis.

J Obstet Gynecol Neonatal Nurs. 2019 Aug 29;:

Authors: Stayer DL, Culver ED, Brosius HM, Stamm JA

Abstract
Life expectancy for individuals with cystic fibrosis (CF) has significantly increased during the last few decades, and subsequently, more women with CF are considering pregnancy. A detailed understanding of the management of pregnancy, specific pulmonary treatments, and necessary medications is essential to provide specialized care for women with CF. In this article, we present the physical and psychosocial aspects of care for pregnant women with CF and describe a case involving the planned pregnancy of a nulliparous woman with CF. We suggest vigilant monitoring for adequate nutrition, weight gain, and pulmonary function throughout pregnancy as implications for nursing care.

PMID: 31473148 [PubMed - as supplied by publisher]

Practical Approach to Genetic Testing for Primary Immunodeficiencies.

Ann Allergy Asthma Immunol. 2019 Aug 28;:

Authors: Chinen J, Lawrence M, Dorsey M, Kobrynski LJ

PMID: 31472268 [PubMed - as supplied by publisher]

Evaluation of TD test for analysis of persistence or tolerance in clinical isolates of Staphylococcus aureus.

J Microbiol Methods. 2019 Aug 28;:105705

Authors: Hana K, Marie C, Irena L, Jan T, Libor F, Jana B, Oto M

Abstract
Besides natural and acquired mechanisms of resistance, bacteria can cope with presence of antibiotics by using complex mechanisms such as persistence or tolerance. The main purpose of this study was to evaluate the suitability of newly developed Tolerance Disk Test (TDtest) (Gefen et al., 2017) to detect persistent or tolerant bacterial cells in clinical isolates of Staphylococcus aureus. The principle of the test is to resuscitate the subpopulation of persistent or tolerant bacterial cells following a disk diffusion test by glucose. Results of the TDtest were evaluated using time killing experiments for three pairs of consecutive S. aureus isolates from lower respiratory airway samples of three cystic fibrosis patients with chronic staphylococcal infections. TDtest enabled semi-quantitative detection of persistent or tolerant bacterial populations in all analyzed isolates for oxacillin, vancomycin, and ciprofloxacin to which isolates studied were susceptible. Therefore, TDtest is a promising method for rapidly determining persistence/tolerance in clinical isolates of S. aureus.

PMID: 31472196 [PubMed - as supplied by publisher]

Addressing the burden of illness in adults with cystic fibrosis with screening and triage: An early intervention model of palliative care.

J Cyst Fibros. 2019 Aug 27;:

Authors: Dhingra L, Walker P, Berdella M, Plachta A, Chen J, Fresenius A, Balzano J, Barrett M, Bookbinder M, Wilder K, Glajchen M, Langfelder-Schwind E, Portenoy RK

Abstract
BACKGROUND: Novel models that improve generalist-level palliative care for cystic fibrosis (CF) are needed to address the burden of this illness. A screening-and-triage model has the potential to identify clinical problems requiring immediate follow-up by CF professionals. This study describes such a model and its immediate impact on care delivery for CF patients during a two-year period.
METHODS: Eligible adults completed monthly online screening for sources of distress. If results revealed one or more "indicators of concern" on two consecutive screenings, this triggered an attempted triage by a social worker. Completed triages led to prompt follow-up by CF professionals for clinical problems, if indicated. Process data were summarized and generalized linear mixed models were used to evaluate baseline patient characteristics (symptom distress, quality of life, and sociodemographics) associated with the need for prompt follow-up.
RESULTS: A total of 1,015 monthly surveys were completed by 74 patients; 634 (66 patients) had >1 indicators of concern; and 164 surveys (46 patients) had >1 indicators for two consecutive surveys (e.g., global distress, pain, dyspnea, and psychological symptoms). The 164 attempted triages yielded 84 completed triages (51.2%), of which 39 (46.4%) required prompt follow-up. In multivariable analyses, older patients and those with higher symptom distress at baseline were more likely to require prompt follow-up (p < .05).
CONCLUSIONS: Web-based screening that assesses varied domains of distress or burden can identify a subset of CF patients whose clinical problems may benefit from immediate medical or psychological attention. Additional investigations should improve screening efficiency.

PMID: 31471264 [PubMed - as supplied by publisher]

Impaired intestinal farnesoid X receptor signaling in cystic fibrosis mice.

Cell Mol Gastroenterol Hepatol. 2019 Aug 27;:

Authors: Ikpa PT, Doktorova M, Meijsen KF, Nieuwenhuijze NDA, Verkade HJ, Jonker JW, de Jonge HR, Bijvelds MJC

Abstract
BACKGROUND & AIMS: The bile acid (BA)-activated farnesoid X receptor (FXR) controls hepatic BA synthesis and cell proliferation via the intestinal hormone fibroblast growth factor 19 (FGF19). Because cystic fibrosis (CF) is associated with intestinal dysbiosis, anomalous BA handling and biliary cirrhosis, we investigated FXR signaling in CF.
METHODS: Intestinal and hepatic expression of FXR target genes and inflammation markers was assessed in Cftr null mice and controls. Localization of the apical sodium-dependent BA transporter (ASBT) was assessed, and BAs in gastrointestinal tissues were analyzed. The CF microbiota was characterized and FXR signaling was investigated in intestinal tissue and organoids.
RESULTS: Ileal Fgf15 (murine FGF19 ortholog) expression was strongly reduced in CF mice, compared to controls. Luminal BA levels and localization of ASBT was not affected, and BAs induced Fgf15 up to normal levels in CF ileum, ex vivo, and CF organoids. CF mice displayed a dysbiosis, which was associated with a marked upregulation of genes involved in host-microbe interactions, including those involved in mucin glycosylation, anti-microbial defense, and Toll-like receptor signaling. Antibiotic treatment reversed the up-regulation of inflammatory markers and restored intestinal FXR-signaling in CF mice. Conversely, FXR-dependent gene induction in ileal tissue and organoids was repressed by bacterial lipopolysaccharide (LPS) and pro-inflammatory cytokines, respectively. Loss of intestinal FXR activity was associated with a markedly blunted hepatic trophic response to oral BA supplementation, and with impaired repression of Cyp7a1, the gene encoding the rate-limiting enzyme in BA synthesis.
CONCLUSIONS: In CF mice, the gut microbiota represses intestinal FXR activity, and, consequently, FXR-dependent hepatic cell proliferation and feedback control of BA synthesis.

PMID: 31470114 [PubMed - as supplied by publisher]

Impact of a Reduction in Susceptibility Testing for Pseudomonas aeruginosa in a Cystic Fibrosis Program.

Am J Respir Crit Care Med. 2019 Aug 30;:

Authors: Ponce MC, Svendsen E, Steed L, Flume PA

PMID: 31469583 [PubMed - as supplied by publisher]

Screening for Cystic Fibrosis-Related Diabetes and Pre-diabetes: Evaluating 1,5-Anhydroglucitol, Fructosamine, Glycated Albumin, and Hemoglobin A1c.

Pediatr Diabetes. 2019 Aug 30;:

Authors: Tommerdahl KL, Brinton JT, Vigers T, Nadeau KJ, Zeitler PS, Chan CL

Abstract
OBJECTIVE: Dysglycemia is prevalent in cystic fibrosis (CF) but screening with annual oral glucose tolerance tests (OGTT) can be burdensome. We investigated alternate glycemic markers - hemoglobin A1c (HbA1c), 1,5-anhydroglucitol (1,5AG), fructosamine (FA), and glycated albumin (GA) - as screening tests for CF-related diabetes (CFRD) and pre-diabetes (CFPD) in youth with CF as defined by the gold-standard OGTT 2-hour glucose (2hG).
METHODS: Youth 10-18 years with CF had a 1,5AG, FA, GA, HbA1c, and 2-hour OGTT collected. Correlations between all glycemic markers and 2hG were evaluated. Area under the Receiver Operative Characteristic (ROC-AUC) curves were generated. Optimal cut points for predicting CFPD (2hG ≥ 140 mg/dL) and CFRD (2hG ≥ 200 mg/dL) were determined.
RESULTS: Fifty-eight youth with CF were included (2hG <140, n = 16; CFPD, n = 33; CFRD, n = 9; 41% male, mean ± SD age 14.2 ± 3.6 years, BMI z-score 0.0 ± 0.8, % predicted forced expiratory volume in 1 second [FEV1] 89.9 ± 15.1, % predicted forced vital capacity [FVC] 103.2 ± 14.6). ROC-AUC's for all alternate markers were low for CFPD (0.52-0.67) and CFRD (0.56-0.61). At a cut point of 5.5%, HbA1c had 78% sensitivity (95% CI: 0.45-0.94) and 41% specificity (95% CI: 0.28-0.55) for identifying CFRD, correlating to a ROC-AUC of 0.61 (95% CI: 0.42-0.8).
CONCLUSIONS: All alternate markers tested demonstrate poor diagnostic accuracy for identifying CFRD by 2hG. This article is protected by copyright. All rights reserved.

PMID: 31469470 [PubMed - as supplied by publisher]

Caregiver burden in children with cystic fibrosis and primary ciliary dyskinesia.

Pediatr Pulmonol. 2019 Aug 29;:

Authors: Keniş Coşkun Ö, Gençer Atalay K, Erdem E, Karadag-Saygi E, Gökdemir Y, Karadağ B

Abstract
INTRODUCTION: Caregiver burden impacts both the social and economic framework of society. Cystic fibrosis (CF) causes significant caregiver burden, but the current data is scarce. In the case of primary ciliary dyskinesia (PCD), even less is known. This study aims to compare the caregiver burden of the parents of patients with CF and PCD.
METHODS: Patients with CF and PCD between the ages of 6 to 13 and their parents were included. Patients' clinical information and parents' demographics were recorded. Caregiver burden was measured with Zarit Caregiver Burden Scale (ZCB), while the quality of life (QOL) was measured with CFQOL-revised (CFQOL-R) and PCD QOL questionnaire as the patients' age and diagnosis indicated.
RESULTS: A total of 63 patients, 44 with CF (69%) and 85 caregivers (35 mothers, 6 fathers, and 22 mother-father dyads) participated in the study. Caregiver burden was significantly higher in mothers of the CF group with a mean ZCB of 30.5 ± 10.7 when compared to the PCD group with a mean ZCB of 21.93 ± 8.26 (P = .006). This was similar in fathers with mean ZCB of 27.5 ± 9.21 in the CF group and 20.36 ± 7.43 in the PCD group (P = .03). In correlation analyses, mothers' caregiver burden moderately and inversely correlated with CFQOL-R subscales in the CF population.
CONCLUSION: Caregiver burden is significantly higher in the CF population when compared to PCD. It is correlated with pulmonary functions and QOL in patients with CF.

PMID: 31468736 [PubMed - as supplied by publisher]

The bridging bronchus: A comprehensive review of a rare, potentially life-threatening congenital airway anomaly associated with cardiovascular defects.

Pediatr Pulmonol. 2019 Aug 29;:

Authors: Henry BM, Cheruiyot I, Wong LM, Keet K, Mutua V, Chhapola V, Tubbs RS

Abstract
The bridging bronchus is a rare congenital airway anomaly in which the right upper lobe of the lung is supplied by the right main bronchus while the right lower lobe, and often the right middle lobe is supplied by an aberrant bronchus arising from the left main bronchus. The aberrant bronchus crosses (bridges) the lower part of the mediastinum, hence the term bridging bronchus (BB). This potentially life-threatening condition, usually accompanied by diffuse or focal airway stenosis, commonly presents with signs and symptoms related to large airway obstruction, such as respiratory distress, apnea, wheezing, stridor, and recurrent respiratory tract infections. Diagnosis of the BB is often challenging because the associated signs and symptoms mimic those of common conditions such as bacterial and viral bronchiolitis, bronchial asthma, cystic fibrosis, and foreign body aspiration. The BB is also often accompanied by congenital cardiovascular anomalies, including left pulmonary artery sling, atrial, and ventricular septal defects, tetralogy of Fallot, patent ductus arteriosus, and coarctation of the aorta. Patients presenting with the above signs and symptoms who are not responsive to standard treatment modalities, and have accompanying cardiovascular congenital anomalies should, therefore, be investigated for the BB. Herein, we review the anatomy, embryology, clinical presentation, differential diagnosis, imaging techniques and surgical management of the BB.

PMID: 31468716 [PubMed - as supplied by publisher]