Hospital staff practical skills and theoretical knowledge in inhaled aerosol therapy: a single centre cross-sectional observational study.

Monaldi Arch Chest Dis. 2021 Jan 25;91(1):

Authors: Santambrogio M, Lazzeri M, Bonitta G, Guarise R, Simonetta E, Blasi F, Privitera E

Abstract
Inhaled therapy is widely used for treatment of many respiratory disorders. Drug delivery in lungs is dependent on the correct use of aerosol devices and patients' training is vital for a correct therapy administration. Therefore, is very important to assess the skills of professionals involved in training patients to the correct use of inhaler devices. The aim of this study was to check the practical skills and the theoretical knowledge of health care personnel in our University Hospital in using aerosol therapy and to determine differences among professional figures in the management of inhaler devices. Three hundred and fifteen (315) volunteers including physicians, residents, nurses and respiratory physiotherapists were enrolled; an independent professional, not working in our University Hospital, assessed their theoretical knowledge related to aerosol throughout a questionnaire. Practical skills were assessed through placebo simulation with the devices that participants declared to use frequently with patients. None of the respondents correctly answered all questions evaluating theoretical knowledge on the proper use of aerosol therapy. Respiratory physiotherapists obtained significantly better results with 17.2 (1.3) average points compared to 10.3 (3.7) obtained by doctors, 9.0 (3.0) by nurses and 9.1 (4.5) by residents. Analysing in detail physicians' results, pneumologists showed better theoretical knowledge than other specialists. Concerning the practical skills, about 80% of those stating they knew how to use metered dose inhalers, made mistakes in the basic steps for proper inhalation technique and over 50% of respondents were unable to properly simulate placebo administration of dry powder inhalers. Also here, respiratory physiotherapists and pneumologists had significant better performances, when compared to other health professionals. Our data are in line with those published in the literature in other international clinical settings, noting inadequate practical and theoretical knowledge of the available devices for aerosol therapy.

PMID: 33501819 [PubMed - in process]

Molecular mechanism mediating enteric bacterial translocation after severe burn: the role of cystic fibrosis transmembrane conductance regulator.

Burns Trauma. 2020;8:tkaa042

Authors: Liu X, Chen Y, You B, Peng Y, Chen Y, Yang Z, Zhang Y, Chen J

Abstract
Background: Gut ischemia and hypoxia post severe burn leads to breakdown of intestinal epithelial barrier and enteric bacterial translocation (EBT), resulting in serious complications, such as systemic inflammatory response syndrome, sepsis and multiple organ failure. Cystic fibrosis transmembrane conductance regulator (CFTR) is known to be downregulated by hypoxia and modulate junctional complexes, which are crucial structures maintaining the intestinal barrier. This study aimed to investigate whether CFTR plays a role in both regulating the intestinal barrier and mediating EBT post severe burn, as well as the signaling pathways involved in these processes.
Methods: An in vitro Caco-2 cell model subjected to hypoxic injury and an in vivo mouse model with a 30% total body surface area full-thickness dermal burn were established. DF 508 mice (mice with F508del CFTR gene mutation) were used as an in vivo model to further demonstrate the role of CFTR in maintaining normal intestinal barrier function. QRT-PCR, western blot, ELISA, TER assay and immunofluorescence staining were used to detect the expression and localization of CFTR and tight junction proteins, as well as the function of tight junctions.
Results: Our data indicated that, in Caco-2 cells, the hypoxia condition significantly reduced CFTR expression; activated extracellular signal-regulated kinase and nuclear factor-κB signaling; elevated secretion of inflammatory factors (tumor necrosis factor-α, interleukin-1β and interleukin-8); downregulated zonula occludens-1, occludin and E-cadherin expression; decreased transepithelial electrical resistance values; and led to a cellular mislocation of ZO-1. More importantly, knockdown of CFTR caused similar alterations. The upregulation of inflammatory factors and downregulation of tight junction proteins (ZO-1 and occludin) induced by knockdown of CFTR could be reversed by specific extracellular signal-regulated kinase or nuclear factor-κB inhibition. In support of the in vitro data, exuberant secretion of pro-inflammatory mediators and EBT was observed in the intestine of severely burnt mice in vivo. EBT occurred in DF508 mice (mice with the F508del CFTR gene mutation), accompanied by augmented tumor necrosis factor-α, interleukin-1β and interleukin-8 levels in the ileum compared to wildtype mice. In addition, vitamin D3 was shown to protect the intestinal epithelial barrier from hypoxic injury.
Conclusions: Collectively, the present study illustrated that CFTR and downstream signaling were critical in modulating the intestinal epithelial junction and EBT post severe burn.

PMID: 33501367 [PubMed]

Cystic fibrosis-related diabetes onset can be predicted using biomarkers measured at birth.

Genet Med. 2021 Jan 26;:

Authors: Lin YC, Keenan K, Gong J, Panjwani N, Avolio J, Lin F, Adam D, Barrett P, Bégin S, Berthiaume Y, Bilodeau L, Bjornson C, Brusky J, Burgess C, Chilvers M, Consunji-Araneta R, Côté-Maurais G, Dale A, Donnelly C, Fairservice L, Griffin K, Henderson N, Hillaby A, Hughes D, Iqbal S, Itterman J, Jackson M, Karlsen E, Kosteniuk L, Lazosky L, Leung W, Levesque V, Maille É, Mateos-Corral D, McMahon V, Merjaneh M, Morrison N, Parkins M, Pike J, Price A, Quon BS, Reisman J, Smith C, Smith MJ, Vadeboncoeur N, Veniott D, Viczko T, Wilcox P, van Wylick R, Cutting G, Tullis E, Ratjen F, Rommens JM, Sun L, Solomon M, Stephenson AL, Brochiero E, Blackman S, Corvol H, Strug LJ

Abstract
PURPOSE: Cystic fibrosis (CF), caused by pathogenic variants in the CF transmembrane conductance regulator (CFTR), affects multiple organs including the exocrine pancreas, which is a causal contributor to cystic fibrosis-related diabetes (CFRD). Untreated CFRD causes increased CF-related mortality whereas early detection can improve outcomes.
METHODS: Using genetic and easily accessible clinical measures available at birth, we constructed a CFRD prediction model using the Canadian CF Gene Modifier Study (CGS; n = 1,958) and validated it in the French CF Gene Modifier Study (FGMS; n = 1,003). We investigated genetic variants shown to associate with CF disease severity across multiple organs in genome-wide association studies.
RESULTS: The strongest predictors included sex, CFTR severity score, and several genetic variants including one annotated to PRSS1, which encodes cationic trypsinogen. The final model defined in the CGS shows excellent agreement when validated on the FGMS, and the risk classifier shows slightly better performance at predicting CFRD risk later in life in both studies.
CONCLUSION: We demonstrated clinical utility by comparing CFRD prevalence rates between the top 10% of individuals with the highest risk and the bottom 10% with the lowest risk. A web-based application was developed to provide practitioners with patient-specific CFRD risk to guide CFRD monitoring and treatment.

PMID: 33500570 [PubMed - as supplied by publisher]

Animal Models and Their Role in Understanding the Pathophysiology of Cystic Fibrosis-Associated Gastrointestinal Lesions.

Annu Rev Pathol. 2021 Jan 24;16:51-67

Authors: Gibson-Corley KN, Engelhardt JF

Abstract
The life expectancy of cystic fibrosis (CF) patients has greatly increased over the past decade, and researchers and clinicians must now navigate complex disease manifestations that were not a concern prior to the development of modern therapies. Explosive growth in the number of CF animal models has also occurred over this time span, clarifying CF disease pathophysiology and creating opportunities to understand more complex disease processes associated with an aging CF population. This review focuses on the CF-associated pathologies of the gastrointestinal system and how animal models have increased our understanding of this complex multisystemic disease. Although CF is primarily recognized as a pulmonary disease, gastrointestinal pathology occurs very commonly and can affect the quality of life for these patients. Furthermore, we discuss how next-generation genetic engineering of larger animal models will impact the field's understanding of CF disease pathophysiology and the development of novel therapeutic strategies.

PMID: 33497264 [PubMed - as supplied by publisher]

Peripheral muscle strength is associated with aerobic fitness and use of antibiotics in patients with cystic fibrosis.

Int J Clin Pract. 2021 Jan 26;:e14050

Authors: Vendrusculo FM, Bueno GS, Gheller MF, Campos NE, Schiwe D, de Almeida IS, Becker NA, Heinzmann-Filho JP, Fagundes Donadio MV

Abstract
AIMS: Individuals with cystic fibrosis (CF) may develop muscle abnormalities, although little is known on its clinical and functional impact. This study aimed to evaluate the association of peripheral muscle strength with aerobic fitness, habitual physical activity, lung function and the use of antibiotics (ATB) in patients with CF.
METHODS: A Cross-sectional study where individuals aged ≥ 6 years underwent peripheral muscle strength evaluation (biceps, quadriceps and hamstrings) and performed a cardiopulmonary exercise test. Demographic, anthropometric, genetic, lung function, and total days of ATB use within one year of tests were also collected.
RESULTS: Correlation was found for biceps (r=0.45; p=0.002) strength with the peak oxygen consumption (VO2 peak). Muscle strength (biceps and quadriceps) also correlated with the ventilatory equivalent for oxygen consumption (VE /VO2 ) at anaerobic threshold (AT) and with the ventilatory equivalent for carbon dioxide production (VE /VCO2 ) both at AT and peak exercise. Negative correlations were found for quadriceps (r=-0.39) and hamstrings (r=-0.42) with the total days of ATB use in the following year. Patients needing to use ATB presented lower biceps strength (p=0.05) and individuals with VO2 peak lower than 37 mL.kg-1 .min-1 presented lower muscle strength for both biceps (p=0.01) and quadriceps (p=0.02).
CONCLUSIONS: The results have shown that peripheral muscle strength is associated with aerobic fitness and the use of antibiotics in patients with CF.

PMID: 33497024 [PubMed - as supplied by publisher]

A Mobile Health Platform for Self-Management of Pediatric Cystic Fibrosis: Qualitative Study of Adaptation to Stakeholder Needs and Integration in Clinical Settings.

JMIR Form Res. 2021 Jan 26;5(1):e19413

Authors: Rutland SB, Bergquist RP, Hager A, Geurs R, Mims C, Gutierrez HH, Oates GR

Abstract
BACKGROUND: Cystic fibrosis (CF) is an inherited chronic condition that requires extensive daily care and quarterly clinic visits with a multidisciplinary care team. The limited exchange of information outside of the quarterly clinic visits impedes optimal disease self-management, patient engagement, and shared decision making.
OBJECTIVE: The aim of this study is to adapt a mobile health (mHealth) app originally developed in Sweden to the needs of patients, families, and health care providers in a CF center in the United States and to test it as a platform for sharing patient-generated health data with the CF health care team.
METHODS: Focus groups with health care providers of patients with CF, adolescents with CF, and caregivers of children with CF were conducted to determine what modifications were necessary. Focus group data were analyzed using a thematic analysis, and emergent themes were ranked according to desirability and technical feasibility. The mHealth platform was then modified to meet the identified needs and preferences, and the flow of patient-generated health data to a secure Research Electronic Data Capture database was tested. Protocols for data management and clinical follow-up were also developed.
RESULTS: A total of 5 focus groups with 21 participants were conducted. Recommended modifications pertained to all functionalities of the mHealth platform, including tracking of symptoms, treatments, and activities of daily care; creating and organizing medication lists and setting up reminders; generating reports for the health care team; language and presentation; sharing and privacy; and settings and accounts. Overall, health care providers recommended changes to align the mHealth platform with US standards of care, people with CF and their caregivers requested more tracking functionalities, and both groups suggested the inclusion of a mental health tracker as well as more detailed response options and precise language. Beta testers of the modified platform reported issues related to translatability to US environment and various bugs.
CONCLUSIONS: This study demonstrated the importance of identifying the needs and preferences of target users and stakeholders before adopting existing mHealth solutions. All relevant perspectives, including those of clinicians, patients, and caregivers, should be thoroughly considered to meet both end users' needs and evidence-based practice recommendations.

PMID: 33496667 [PubMed - as supplied by publisher]

Overcoming the Limits of Reconditioning: Seventeen Hours of Ex-Vivo Lung Perfusion (EVLP) with Successful Transplantation from Uncontrolled Circulatory Death Donor.

Transplantation. 2021 Jan 25;:

Authors: Palleschi A, Rosso L, Ruggeri GM, Croci GA, Rossetti V, Citerio G, Grasselli G, Nosotti M, Zanella A

Abstract
BACKGROUND: Uncontrolled donors after circulatory death (DCD) are an extraordinary resource to increase the number of lungs available for transplantation. However, the risk of the warm ischemia resulting from cardiac arrest to irreversibly damage the organs is considerable. Moreover, graft preservation issues and organizational problems often worsen the dangerous effects of warm ischemia. Ex-Vivo Lung Perfusion (EVLP) enables to evaluate and recondition lungs whose functionality is doubtful, as well as to overcome the difficulties related to time and logistics.
METHODS: We report the case of uncontrolled DCD lungs successfully treated with an exceptionally prolonged EVLP. Since the donor's blood count and liver biopsy showed signs of a possible leukaemia, EVLP was protracted up to seventeen hours while waiting for immunohistochemical analyses to rule out this diagnosis; eventually, the results came back negative and lungs were judged suitable for transplantation.
RESULTS: The recipient was a 32-year old male with cystic fibrosis, colonized by Pandoraea pnomenusa. Bilateral transplantation required central extracorporeal membrane oxygenation. The patient was extubated after 36 hours and was discharged 21 days after the operation. Despite early re-colonization by Pandoraea pnomenusa and airway complications requiring pneumatic dilatation, he is alive and has a satisfactory respiratory function 15 months after transplantation.
CONCLUSIONS: Uncontrolled DCD represents a challenge due to both logistical issues and the complexity of grafts evaluation before procurement: EVLP with cellular perfusate could be a valuable tool to overcome these limits. Nonetheless, caution should be exercised when interpreting the effects of this technique on airway healing.

PMID: 33496562 [PubMed - as supplied by publisher]

[Portuguese Newborn Screening Program.]

Rev Esp Salud Publica. 2021 Jan 26;95:

Authors: Rocha H, Marcão A, Sousa C, Fonseca H, Lopes L, Carvalho I, Vilarinho L

Abstract
The Portuguese Newborn Screening Program is a public health program that started in 1979, screening for PKU, being totally supported by public funds. It's a non-mandatory well implemented program that testes about 99.9% of Portuguese newborns. In the actual screening panel encompasses 26 disorders, including inborn errors of metabolism, congenital hypothyroidism and cystic fibrosis. Sample collection is advised to be made at 3rd day of life and treatment begins in average by the 10th day. Every testes are performed in one single national laboratory, that processes about 88,000 samples/year. In the 41 years of program existence, more than 3,800,000 newborns were screened and 2,130 affected newborns detected, reflecting the positive impact of the Program in the population. Future perspectives include the increase of program value in terms of public health by optimizing the screening of the disorders already screened and evaluation the possibility of adding others.

PMID: 33496269 [PubMed - in process]

"Test-retest reliability and minimal detectable change in TGlittre-P test in children and adolescents with cystic fibrosis".

Disabil Rehabil. 2021 Jan 26;:1-7

Authors: Scalco JC, Martins R, Almeida ACDS, Caputo F, Schivinski CIS

Abstract
OBJECTIVE: to provide test-retest reliability for the TGlittre-P in children and adolescents with cystic fibrosis (CFG) and healthy controls (HCG), to establish the minimal detectable change for time in TGlittre-P and comparing the performance in the TGlittre-P test between these populations.
METHOD: A cross-sectional study evaluated 36 children and adolescents aged 6 to 13. Anthropometric and spirometric evaluation was performed, as well as, on the same day, two TGlittre-P tests with a 30-minute interval between them.
RESULTS: TGlittre-P time test-retest reliability was excellent for both groups (CFG: intraclass correlation coefficient [ICC] = 0.849, p < 0.001 and HCG: ICC = 0.913, p < 0.001). As concerning absolute reliability, the time spent presented a small variability with a standard error of measurement of 8.4 s (s) to CFG and 5.3 s to HCG. The minimal detectable change at 95% confidence level (MDC95) was 23.2 s and 14.6 s, respectively. There was no difference between the groups regarding performance in the TGlittre-P test (CFG 179.1 s ± 25.7 s vs. HCG 174.7 s ± 22.3 s) p = 0.589.
CONCLUSION: The TGlittre-P is a reliable tool in children and adolescents with CF and healthy controls. The TGlittre-P appears not to be sensitive enough to discriminate a group of children and adolescents with mild cystic fibrosis from healthy counterparts. IMPLICATIONS FOR REHABILITATION TGlittre-P is a multitasking test that has been used to assess the functional capacity of children and adolescents with chronic diseases. TGlittre-P has excellent reliability in children and adolescents with and without CF. TGlittre-P differences time greater than 12% could indicate changes in the functional capacity of children and adolescents with CF. Other functional capacity tests may be preferred to detect continuous increases in functional capacity through rehabilitation or training, whether children and adolescents obtain performance values close to 100% of predicted.

PMID: 33496210 [PubMed - as supplied by publisher]

The proteostatic network chaperome is downregulated in F508del homozygote cystic fibrosis.

J Cyst Fibros. 2021 Jan 22;:

Authors: Sala MA, Alexander M, Khuder B, Politanska Y, Abdala-Valencia H, Budinger GRS, Liu J, Jain M, Reyfman PA

Abstract
BACKGROUND: CF patients demonstrate clinical heterogeneity and much remains unknown about how to risk stratify individuals for disease progression.  The most common cystic fibrosis mutation, F508del, is a protein folding mutation that has been shown in vitro to negatively affect proteostasis and CFTR transcription. Since CFTR is expressed in the nasal epithelium, we hypothesized that by using unbiased transcriptomics we could gain clinically relevant insights about differential gene expression and heterogeneity in CF patients as well as assess proteostatic dysfunction in the nasal epithelium.
METHODS: Using nasal curettage and RNA-seq we assessed differential gene expression in F508del homozygotes compared to healthy volunteers. Gene set enrichment analysis was performed using a list of known chaperones. Pilot and validation cohorts were studied.
RESULTS: PCA analysis and gene expression heatmaps exhibited greater heterogeneity among CF than healthy volunteers. Differentially expressed genes were enriched for the downregulation of ciliary/microtubular genes and the upregulation of inflammatory/immune response genes in F508del homozygotes compared to healthy volunteers. Gene set analysis identified negative enrichment for chaperone genes and decreased CFTR transcription in the F508del homozygotes. We also found preliminary evidence for the recently identified ionocyte in the nasal specimens.
CONCLUSION: CF patients homozygous for F508del demonstrate heterogeneous gene expression profiles, proteostatic dysregulation, and reduced CFTR transcription. Larger studies are needed to determine whether nasal epithelial gene transcription profiles can be leveraged for insights into disease heterogeneity.

PMID: 33495079 [PubMed - as supplied by publisher]

Prolonged Treatment With Inhaled Ampicillin in Children With Non-cystic Fibrosis Bronchiectasis.

Arch Bronconeumol. 2020 Dec 25;:

Authors: Pérez-Torres Lobato MR, Mejías Trueba M, Rodríguez Ramallo H, Álvarez Del Vayo Benito C, Iglesias Aguilar MDC, Gaboli M

PMID: 33494941 [PubMed - as supplied by publisher]

Synthesis of Tetravalent Thio- and Selenogalactoside-Presenting Galactoclusters and Their Interactions with Bacterial Lectin PA-IL from Pseudomonas aeruginosa.

Molecules. 2021 Jan 21;26(3):

Authors: Illyés TZ, Malinovská L, Rőth E, Tóth B, Farkas B, Korsák M, Wimmerová M, Kövér KE, Csávás M

Abstract
Synthesis of tetravalent thio- and selenogalactopyranoside-containing glycoclusters using azide-alkyne click strategy is presented. Prepared compounds are potential ligands of Pseudomonas aeruginosa lectin PA-IL. P. aeruginosa is an opportunistic human pathogen associated with cystic fibrosis, and PA-IL is one of its virulence factors. The interactions of PA-IL and tetravalent glycoconjugates were investigated using hemagglutination inhibition assay and compared with mono- and divalent galactosides (propargyl 1-thio- and 1-seleno-β-d-galactopyranoside, digalactosyl diselenide and digalactosyl disulfide). The lectin-carbohydrate interactions were also studied by saturation transfer difference NMR technique. Both thio- and seleno-tetravalent glycoconjugates were able to inhibit PA-IL significantly better than simple d-galactose or their intermediate compounds from the synthesis.

PMID: 33494330 [PubMed - in process]

Metabotypes of Pseudomonas aeruginosa Correlate with Antibiotic Resistance, Virulence and Clinical Outcome in Cystic Fibrosis Chronic Infections.

Metabolites. 2021 Jan 21;11(2):

Authors: Moyne O, Castelli F, Bicout DJ, Boccard J, Camara B, Cournoyer B, Faudry E, Terrier S, Hannani D, Huot-Marchand S, Léger C, Maurin M, Ngo TD, Plazy C, Quinn RA, Attree I, Fenaille F, Toussaint B, Le Gouëllec A

Abstract
Pseudomonas aeruginosa (P.a) is one of the most critical antibiotic resistant bacteria in the world and is the most prevalent pathogen in cystic fibrosis (CF), causing chronic lung infections that are considered one of the major causes of mortality in CF patients. Although several studies have contributed to understanding P.a within-host adaptive evolution at a genomic level, it is still difficult to establish direct relationships between the observed mutations, expression of clinically relevant phenotypes, and clinical outcomes. Here, we performed a comparative untargeted LC/HRMS-based metabolomics analysis of sequential isolates from chronically infected CF patients to obtain a functional view of P.a adaptation. Metabolic profiles were integrated with expression of bacterial phenotypes and clinical measurements following multiscale analysis methods. Our results highlighted significant associations between P.a "metabotypes", expression of antibiotic resistance and virulence phenotypes, and frequency of clinical exacerbations, thus identifying promising biomarkers and therapeutic targets for difficult-to-treat P.a infections.

PMID: 33494144 [PubMed]

Therapeutic peptides for the treatment of cystic fibrosis: Challenges and perspectives.

Eur J Med Chem. 2021 Jan 16;213:113191

Authors: Sala V, Cnudde SJ, Murabito A, Massarotti A, Hirsch E, Ghigo A

Abstract
Cystic fibrosis (CF) is the most common amongst rare genetic diseases, affecting more than 70.000 people worldwide. CF is characterized by a dysfunctional chloride channel, termed cystic fibrosis conductance regulator (CFTR), which leads to the production of a thick and viscous mucus layer that clogs the lungs of CF patients and traps pathogens, leading to chronic infections and inflammation and, ultimately, lung damage. In recent years, the use of peptides for the treatment of respiratory diseases, including CF, has gained growing interest. Therapeutic peptides for CF include antimicrobial peptides, inhibitors of proteases, and modulators of ion channels, among others. Peptides display unique features that make them appealing candidates for clinical translation, like specificity of action, high efficacy, and low toxicity. Nevertheless, the intrinsic properties of peptides, together with the need of delivering these compounds locally, e.g. by inhalation, raise a number of concerns in the development of peptide therapeutics for CF lung disease. In this review, we discuss the challenges related to the use of peptides for the treatment of CF lung disease through inhalation, which include retention within mucus, proteolysis, immunogenicity and aggregation. Strategies for overcoming major shortcomings of peptide therapeutics will be presented, together with recent developments in peptide design and optimization, including computational analysis and high-throughput screening.

PMID: 33493828 [PubMed - as supplied by publisher]

Manifesto on United Airways Diseases (UAD): An Interasma (Global Asthma Association - GAA) document.

J Asthma. 2021 Jan 25;:1-33

Authors: Tiotiu A, Novakova P, Baiardini I, Bikov A, Chong-Neto HJ, Correia-de-Sousa J, Emelyanov A, Heffler E, Fogelbach GG, Kowal K, Labor M, Mihaicuta S, Nedeva D, Novakova S, Steiropoulos P, Ansotegui IJ, Bernstein JA, Boulet LP, Canonica GW, DuBuske L, Nunes C, Ivancevich JC, Santus P, Rosario N, Perazzo T, Braido F

Abstract
The large amount of evidence and the renewed interest on upper and lower airways involvement in infectious and inflammatory diseases has led Interasma (Global Asthma Association) to take a position on United Airways Diseases (UAD). Starting from an extensive literature review, Interasma excecutive committee discussed and approved this Manifesto developed by Interasma scientific network (INES) members. The manifesto describes the evidence gathered to date and defines, states, advocates, and proposes issues on UAD (rhinitis, rhinosinusitis and nasal polyposis), and concomitant/comorbid lower airways disorders (asthma, chronic obstructive pulmonary disease, bronchiectasis, cystic fibrosis, obstructive sleep apnoea) with the aim of challenging assumptions, fostering commitment, and bringing about change. UAD refer to clinical pictures characterized by the coexistence of upper and lower airways involvement, driven by a common pathophysiological mechanism, leading to a greater burden on patient's health status and requiring an integrated diagnostic and therapeutic plan. The high prevalence of UAD must be taken into account. Upper and lower airways diseases influence disease control and patient's quality of life. Patients with UAD need to have a timely and adequate diagnosis, treatment, and, when recommended, referral for management in a specialized center. Diagnostic testing including skin prick or serum specific IgE, lung function, fractional exhaled nitric oxide (FeNO), polysomnography, allergen-specific immunotherapies, biological therapies and homebased continuous positive airway pressure (CPAP) whenever these are recommended, should be part of the management plan for UAD. Education of medical students, physicians, health professionals, patients and caregivers on the UAD is needed.

PMID: 33492196 [PubMed - as supplied by publisher]

Analysis of national coverage of neonatal cystic fibrosis screening in Brazil from 2008 to 2017.

J Matern Fetal Neonatal Med. 2021 Jan 24;:1-6

Authors: Sadigurschi G, Vaz Micherino B, Assunção Mendes da Cunha MB, Antão Paiva CL, da Silva E Sá GR

Abstract
INTRODUCTION: The Brazilian neonatal screening program established in 2001 included the investigation of cystic fibrosis (CF) in the phase III of the program. For this purpose, the immunoreactive trypsin (IRT) measurement was added to the newborn screening test. The purpose of National Neonatal Screening Program is to reach 100% of live births in Brazil. The aim of this study was to analyze the coverage of neonatal Screening for Cystic Fibrosis (CF) in Brazil from 2008 to 2017.
MATERIALS AND METHODS: This is an ecological study design based on data collected from the Brazilian Outpatient Information System regarding the detection of IRT as a component of the heel stick test from 2008 to 2017. Moreover, we gathered data from the Brazilian Live Birth Information System referring to live births from 2008 to 2017. We calculated the coverage of IRT measurement for every 100 live births, using the number of IRT measurement procedures as the numerator and the number of live births stratified by federative units (states), as well as by the Brazilian regions as the denominator. These regions correspond to the divisions of the national territory based on criteria such as natural, social, cultural and economic aspects.
RESULTS: From 2008 to 2017, the regions presented the following coverage medians: South (84.1%), Southeast (71.4%), Midwest (47.3%) Northeast (12.3%) and North (10.9%). In the analysis of federative units, in the years 2013 to 2017, Paraná and Distrito Federal presented the highest median of coverage (100%), while the states with the lowest median were Rio Grande do Norte (12.1%), Amazonas (16.8%) and Paraíba (27.5%). Highest coverage was found in the South region, where are located most of the states with high socioeconomic development and high supply of health services, while the lowest coverage was found in the North region, where are located manly the states with low socioeconomic development and low supply of health services. According to data from the Brazilian Ministry of Health, the universalization of neonatal screening for cystic fibrosis occurred in 2013, however, at the end of this year, most states in the North and Northeast regions had not registered IRT measurements in the Outpatient Information System.
CONCLUSION: Although the coverage of neonatal screening for CF has improved nationwide over the years of the study, the disparity in the coverage of IRT measurements at the interregional and interstate levels is notable. Systematic implementation of neonatal screening for cystic fibrosis with equity and access to the entire population is suggested, leading to a greater number of children benefiting from treatment and a better quality of life.

PMID: 33491525 [PubMed - as supplied by publisher]

Preoperative evaluation for lung resection in patients with bronchiectasis: should we rely on standard lung function evaluation?

Eur J Cardiothorac Surg. 2021 Jan 25;:

Authors: Mariani AW, Vallilo CC, de Albuquerque ALP, Salge JM, Augusto MC, Suesada MM, Pêgo-Fernandes PM, Terra RM

Abstract
OBJECTIVES: The scant data about non-cystic fibrosis bronchiectasis, including tuberculosis sequelae and impairment of lung function, can bias the preoperative physiological assessment. Our goal was to evaluate the changes in lung function and exercise capacity following pulmonary resection in these patients; we also looked for outcome predictors.
METHODS: We performed a non-randomized prospective study evaluating lung function changes in patients with non-cystic fibrosis bronchiectasis treated with pulmonary resection. Patients performed lung function tests and cardiopulmonary exercise tests preoperatively and 3 and 9 months after the operation. Demographic data, comorbidities, surgical data and complications were collected.
RESULTS: Forty-four patients were evaluated for lung function. After resection, the patients had slightly lower values for spirometry: forced expiratory volume in 1 s preoperatively: 2.21 l ± 0.8; at 3 months: 1.9 l ± 0.8 and at 9 months: 2.0 l ± 0.8, but the relationship between the forced expiratory volume in 1 s and the forced vital capacity remained. The gas diffusion measured by diffusing capacity for carbon monoxide did not change: preoperative value: 23.2 ml/min/mmHg ± 7.4; at 3 months: 21.5 ml/min/mmHg ± 5.6; and at 9 months: 21.7 ml/min/mmHg ± 8.2. The performance of general exercise did not change; peak oxygen consumption preoperatively was 20.9 ml/kg/min ± 7.4; at 3 months: 19.3 ml/kg/min ± 6.4; and at 9 months: 20.2 ml/kg/min ± 8.0. Forty-six patients were included for analysis of complications. We had 13 complications with 2 deaths. To test the capacity of the predicted postoperative (PPO) values to forecast complications, we performed several multivariate and univariate analyses; none of them was a significant predictor of complications. When we analysed other variables, only bronchoalveolar lavage with positive culture was significant for postoperative complications (P = 0.0023). Patients who had a pneumonectomy had a longer stay in the intensive care unit (P = 0.0348).
CONCLUSIONS: The calculated PPO forced expiratory volume in 1 s had an excellent correlation with the measurements at 3 and 9 months; but the calculated PPO capacity for carbon monoxide and the PPO peak oxygen consumption slightly underestimated the 3- and 9-month values. However, none of them was a predictor for complications. Better tools to predict postoperative complications for patients with bronchiectasis who are candidates for lung resection are needed.
CLINICAL TRIAL REGISTRATION NUMBER: Clinicaltrials.gov: NCT01268475.

PMID: 33491053 [PubMed - as supplied by publisher]

The fractional excretion of sodium in patients with cystic fibrosis treated with oral sodium chloride.

Am J Clin Exp Urol. 2020;8(6):185-190

Authors: Keivanfar M, Daris S, Reisi M, Mehrkesh M

Abstract
Background: Cystic Fibrosis (CF) is a chronic disease associated with low sodium status. The patients are usually treated with oral sodium chloride to control the side effects of low sodium status. Therefore, the fractional excretion of sodium (FENa) was assessed in patients with cystic fibrosis (CF) treated with oral sodium chloride (NaCl). Methods: This was a prospective cross-sectional study that was conducted on forty children with cystic fibrosis who were under treatment with oral NaCl and were referred to Imam Hossein Hospital-Isfahan-Iran between 2017 to 2019. The patients were under treated with 2-4 mEq/kg per day oral NaCl and urinary and plasma sodium and creatinine, as well as FENa, were assessed after three months of taking NaCl. Also the patients were compared in terms of efficacy of treatment based on sodium level (between 135 and 145 mmol/L) and acceptable FENa level (between 0.5% and 1.5%). The sensitivity and specificity of FeNa and plasma sodium were assessed with ROC curve test. Results: Plasma sodium was normal in 65% of treated patients, and FENa was also normal range in 47.5% of treated patients. The treatment also was desirable for 35% of the patients. The sensitivity and specificity of FeNa were 42.9% and 57.7%, respectively, and the sensitivity and specificity of plasma sodium were 85.7% and 26.9%, respectively. Conclusion: Using of plasma sodium had higher sensitivity than FeNa and FeNa had higher specificity than plasma sodium to follow up of patients with CF.

PMID: 33490307 [PubMed]

A narrative review of electrical impedance tomography in lung diseases with flow limitation and hyperinflation: methodologies and applications.

Ann Transl Med. 2020 Dec;8(24):1688

Authors: Sang L, Zhao Z, Lin Z, Liu X, Zhong N, Li Y

Abstract
Electrical impedance tomography (EIT) is a functional radiation-free imaging technique that measures regional lung ventilation distribution by calculating the impedance changes in the corresponding regions. The aim of the present review was to summarize the current literature concerning the methodologies and applications of EIT in lung diseases with flow limitation and hyperinflation. PubMed was searched up to May 2020 to identify studies investigating the use of EIT in patients with asthma, bronchiectasis, bronchitis, bronchiolitis, chronic obstructive pulmonary disease, and cystic fibrosis. The extracted data included study design, EIT methodologies, interventions, validation and comparators, population characteristics, and key findings. Of the 44 included studies, seven were related to simulation, animal experimentation, or reconstruction algorithm development with evaluation on patients; 27 studies had the primary objective of validating EIT technique and measures including regional ventilation distribution, regional EIT-spirometry parameters, end-expiratory lung impedance, and regional time constants; and 10 studies had the primary objective of applying EIT to monitor the response to therapeutic interventions, including various ventilation supports, patient repositioning, and airway suctioning. In pediatric and adult patients, EIT has been successfully validated for assessing spatial and temporal ventilation distribution, measuring changes in lung volume and flow, and studying regional respiratory mechanics. EIT has also demonstrated potential as an alternative or supplement to well-established measurement modalities (e.g., conventional pulmonary function testing) to monitor the progression of obstructive lung diseases, although the existing literature lacks prediction values as references and lacks clinical outcome evidence.

PMID: 33490200 [PubMed]

Radiological evaluation of a case of chronic intestinal pseudo-obstruction (CIPO).

Radiol Case Rep. 2021 Mar;16(3):651-655

Authors: Trimarchi R, Visalli C, Quartararo C, Lucanto MC, Nardo GD, Turiaco N, Salamone I

Abstract
Chronic intestinal pseudo-obstruction (CIPO) is a severe form of gastrointestinal dysmotility (often due to derangement of the innervation and/or smooth muscle and/or interstitial cells of Cajal) with recurrent episodes of intestinal sub-occlusion. We describe a clinical setting and radiological features of CIPO in an 11-year-old girl with periodic relapses. Our attention was focused firstly on surgical causes, leading to a delay in the diagnosis; thus, is important detecting equivocal symptoms and considering the possible correlation to the CIPO for an early diagnosis and related prevention of acute episodes improving prognosis and quality of life of pediatric patients.

PMID: 33488892 [PubMed]