A critical review of definitions used to describe Pseudomonas aeruginosa microbiological status in patients with cystic fibrosis for application in clinical trials.

J Cyst Fibros. 2019 Sep 13;:

Authors: Taccetti G, Denton M, Hayes K, ECFS-CTN Microbiology Group, Drevinek P, Sermet-Gaudelus I

Abstract
BACKGROUND: Definition of Pseudomonas aeruginosa (Pa) microbiological status is essential for patients' inclusion in clinical trials. The aim of this study was to agree on the definitions of Pa infection status for initial infection, eradication and chronic infection to be used in clinical trials and to propose additional future study areas.
METHODS: An exhaustive literature search was performed. The clinimetric properties of different definitions of Pa microbiological status were evaluated.
RESULTS: Historical studies have mostly used culture-based definitions, although some have also involved complementary anti-Pa antibodies. Clinimetric analysis showed great variability in the definitions used, leading to differences in reliability, validity, responsiveness to treatment and correlation with outcome measures. Use of serology for initial Pa infection and successful Pa eradication introduced a greater level of complexity as antibody tests are not standardised. Moreover, the chronology of the immune response to Pa antigenic determinants was not completely clear. Chronic Pa infection was characterized by high levels of antibodies and good concordance between culture results and serology.
CONCLUSIONS: Microbiological monitoring, regular sampling from the airways and standardization of culture methods remain essential requisites for microbiological definitions. Despite limitations, serology should be incorporated in the definitions of initial infection and eradication used in clinical trials to better classify patients at enrolment, mainly in non-expectorating children. This requires standardization of serological testing.

PMID: 31526710 [PubMed - as supplied by publisher]

Influence of sex gap on muscle strength and functional mobility in patients with cystic fibrosis.

Appl Physiol Nutr Metab. 2019 Sep 17;:

Authors: Martínez-García MDM, Rodríguez-Juan JJ, Ruiz-Cárdenas JD

Abstract
The aims were to determine whether there were differences in handgrip strength and functional mobility between cystic fibrosis (CF) patients and healthy controls with regard to sex, and to ascertain whether these differences were related to lung function. Thirty-eight CF patients (twenty-one women) aged 18-65 and thirty-eight healthy controls were included. Muscle weakness and functional mobility were assessed through handgrip strength; walking speed; time, velocity and power derived from a single sit-to-stand (STS) test. CF patients showed differences for STS variables and walking speed but not for handgrip strength, compared to healthy controls. Considering sex differences, female patients showed differences for all variables analyzed while CF males only exhibited differences for STS variables, compared to healthy controls. CF females showed moderate relationship between muscle weakness, functional mobility, and lung function (|r| = 0.45 - 0.49; p ≤ 0.05) whereas no relationships were observed for CF males. The influence of chronic infection with Pseudomonas aeruginosa and pancreatic insufficiency on muscle weakness and functional mobility was similar in both sexes. Differences in muscle strength and functional mobility were predominantly observed in CF females. These results suggest an important effect of sex gap on muscle weakness and functional mobility in CF patients. NCT03524859 ●The influence of sex gap on muscle weakness in cystic fibrosis (CF) has been shown. ●Muscle weakness was predominantly observed in CF females.

PMID: 31526325 [PubMed - as supplied by publisher]

Cystic Fibrosis Mutation Spectrum in North Macedonia: A Step Toward Personalized Therapy.

Balkan J Med Genet. 2019 Jun;22(1):35-40

Authors: Terzic M, Jakimovska M, Fustik S, Jakovska T, Sukarova-Stefanovska E, Plaseska-Karanfilska D

Abstract
The most prevalent "rare" disease worldwide, cystic fibrosis (CF), is an autosomal recessive multisystem disease, caused by mutations in the CFTR gene. The knowledge of CFTR mutations present in certain population is important for designing a simple, fast and cost-effective genetic testing approach, also for better management of CF patients, including the administration of novel targeted therapies. Here, we present genetic results of 158 unrelated CF patients from the National CF Registry of the Republic of North Macedonia. Initially, patients were screened for the 11 most common CF mutations. Additional CF mutations and large deletions/duplications in the CFTR gene were analyzed using commercial kits. If the genotype was undetermined, all CFTR exons were analyzed using Sanger DNA sequencing or next generation sequencing (NGS) (since 2014). The most common CF mutation, c.l521_ 1523del (legacy name F508del), was found with an overall incidence of 75.9%. Additionally, 26 other pathogenic variants and three large deletions were identified in the CFTR gene as a genetic cause of CF. Two of these, c.1070 C>T (p.Ala357Val) and c.2779_2788dup CTTGCTATGG (p.Gly930AlafsTer48), were novel. According to the distribution and prevalence of the pathogenic variants detected in our patients, a fast and cost-effective method, based on a single base extension was designed as a first-line CF genetic test with a 90.0% detection rate within our population. Furthermore, the knowledge of CFTR mutation classes in our CF patients represents the first step toward personalized therapy for CF in our country.

PMID: 31523618 [PubMed]

A Novel Tool to Evaluate the Accuracy of Predicting Survival and Guiding Lung Transplantation in Cystic Fibrosis.

Epidemiology (Sunnyvale). 2019;9(2):

Authors: Bansal A, Mayer-Hamblett N, Goss CH, Chan LN, Heagerty PJ

Abstract
Background: Effective transplantation recommendations in cystic fibrosis (CF) require accurate survival predictions, so that high-risk patients may be prioritized for transplantation. In practice, decisions about transplantation are made dynamically, using routinely updated assessments. We present a novel tool for evaluating risk prediction models that, unlike traditional methods, captures classification accuracy in identifying high-risk patients in a dynamic fashion.
Methods: Predicted risk is used as a score to rank incident deaths versus patients who survive, with the goal of ranking the deaths higher. The mean rank across deaths at a given time measures time-specific predictive accuracy; when assessed over time, it reflects time-varying accuracy.
Results: Applying this approach to CF Registry data on patients followed from 1993-2011, we show that traditional methods do not capture the performance of models used dynamically in the clinical setting. Previously proposed multivariate risk scores perform no better than forced expiratory volume in 1 second as a percentage of predicted normal (FEV1%) alone. Despite its value for survival prediction, FEV1% has a low sensitivity of 45% over time (for fixed specificity of 95%), leaving room for improvement in prediction. Finally, prediction accuracy with annually-updated FEV1% shows minor differences compared to FEV1% updated every 2 years, which may have clinical implications regarding the optimal frequency of updating clinical information.
Conclusions: It is imperative to continue to develop models that accurately predict survival in CF. Our proposed approach can serve as the basis for evaluating the predictive ability of these models by better accounting for their dynamic clinical use.

PMID: 31523488 [PubMed]

Revealing the molecular signaling pathways of mucus stasis in cystic fibrosis.

J Clin Invest. 2019 Sep 16;:

Authors: Birket SE, Rowe SM

Abstract
Mucus obstruction is a hallmark of cystic fibrosis (CF) airway disease, leading to chronic infection, dysregulated inflammation, and progressive lung disease. As mucus hyperexpression is a key component in the initiation and perpetuation of airway obstruction, the triggers underlying mucin release must be identified and understood. In this issue of the JCI, Chen et al. sought to delineate the mechanisms that allow IL-1α/IL-1β to perpetuate the mucoinflammatory environment characteristic of the CF airway. The authors demonstrated that IL-1α and IL-1β stimulated non-CF human bronchial epithelial (HBE) cells to upregulate and secrete both MUC5B and MUC5AC in a dose-dependent manner, an effect that was neutralized by the inhibition of the IL-1α/IL-1β receptor (IL-1R1). Further experiments using mouse models and excised lung tissue identified contributors that drive a vicious feedback cycle of hyperconcentrated mucus secretions and persistent inflammation in the CF airway, factors that are likely at the nidus of progressive lung disease.

PMID: 31524633 [PubMed - as supplied by publisher]

IL-1β dominates the promucin secretory cytokine profile in cystic fibrosis.

J Clin Invest. 2019 Sep 16;:

Authors: Chen G, Sun L, Kato T, Okuda K, Martino MB, Abzhanova A, Lin JM, Gilmore RC, Batson BD, O'Neal YK, Volmer AS, Dang H, Deng Y, Randell SH, Button B, Livraghi-Butrico A, Kesimer M, Ribeiro CM, O'Neal WK, Boucher RC

Abstract
Cystic fibrosis (CF) lung disease is characterized by early and persistent mucus accumulation and neutrophilic inflammation in the distal airways. Identification of the factors in CF mucopurulent secretions that perpetuate CF mucoinflammation may provide strategies for novel CF pharmacotherapies. We show that IL-1β, with IL-1α, dominated the mucin prosecretory activities of supernatants of airway mucopurulent secretions (SAMS). Like SAMS, IL-1β alone induced MUC5B and MUC5AC protein secretion and mucus hyperconcentration in CF human bronchial epithelial (HBE) cells. Mechanistically, IL-1β induced the sterile α motif-pointed domain containing ETS transcription factor (SPDEF) and downstream endoplasmic reticulum to nucleus signaling 2 (ERN2) to upregulate mucin gene expression. Increased mRNA levels of IL1B, SPDEF, and ERN2 were associated with increased MUC5B and MUC5AC expression in the distal airways of excised CF lungs. Administration of an IL-1 receptor antagonist (IL-1Ra) blocked SAMS-induced expression of mucins and proinflammatory mediators in CF HBE cells. In conclusion, IL-1α and IL-1β are upstream components of a signaling pathway, including IL-1R1 and downstream SPDEF and ERN2, that generate a positive feedback cycle capable of producing persistent mucus hyperconcentration and IL-1α and/or IL-1β-mediated neutrophilic inflammation in the absence of infection in CF airways. Targeting this pathway therapeutically may ameliorate mucus obstruction and inflammation-induced structural damage in young CF children.

PMID: 31524632 [PubMed - as supplied by publisher]

Methicillin-Resistant Staphylococcus aureus Infection and Treatment Options.

Methods Mol Biol. 2020;2069:229-251

Authors: Chalmers SJ, Wylam ME

Abstract
Methicillin-resistant Staphylococcus aureus (MRSA) is a leading cause of infection worldwide, including a wide array of both hospital- and community-acquired infections-most commonly bacteremia, upper and lower respiratory tract infection, skin and soft-tissue infection, osteomyelitis, and septic arthritis. This chapter describes the epidemiology of MRSA infection, its ability to confer antibiotic resistance and produce a wide array of virulence factors, and its pivotal role in human infection, especially cystic fibrosis. It also provides an introduction to the strategies for treatment of both chronic and acute MRSA infections.

PMID: 31523777 [PubMed - in process]

Identification of Virulence Determinants During Host-Pathogen Interaction Using Tn-Seq Technology.

Methods Mol Biol. 2020;2069:155-175

Authors: Peek CT, Ibberson CB, Cassat JE

Abstract
Transposon sequencing (Tn-seq) is a powerful genetic tool that enables the detection of essential genes within a given environment. The application of Tn-seq to Staphylococcus aureus has generated transposon libraries in numerous strains with inactivation of virtually every nonessential gene in the genome. This exciting technology coupled with increasingly available computational tools has been deployed in animal models of infection to identify essential S. aureus genes within specific host environments. In this chapter, we describe the application of Tn-seq to a murine model of osteomyelitis as a paradigm for using this powerful technology to elucidate mechanisms of bacterial pathogenesis.

PMID: 31523773 [PubMed - in process]

Multilocus Sequence Typing of Staphylococcus aureus.

Methods Mol Biol. 2020;2069:95-102

Authors: Liu Y, Ji Y

Abstract
Multilocus sequence typing (MLST) has been successfully used to differentiate and trace the bacterial species and pathogens that cause outbreaks or epidemics of infectious diseases. MLST provides a powerful solution for molecular epidemiological characterization of bacterial strains, including Staphylococcus aureus, by using the sequences of the internal region of seven housekeeping genes. In previous studies, we utilized MLST to analyze the genotypes of S. aureus isolates from pediatric patients with cystic fibrosis and revealed three prevalent ST types, including ST5, ST30, and ST8 in these isolates. In this chapter, we describe a detailed procedure of MLST for genotyping S. aureus.

PMID: 31523768 [PubMed - in process]

Unwarranted use of intravenous aminoglycosides at UK paediatric cystic fibrosis centres.

J Cyst Fibros. 2019 Sep 12;:

Authors: Ditchfield N, Carroll WD, Gilchrist FJ

PMID: 31522925 [PubMed - as supplied by publisher]

A smartphone application for reporting symptoms in adults with cystic fibrosis improves the detection of exacerbations: Results of a randomised controlled trial.

J Cyst Fibros. 2019 Sep 12;:

Authors: Wood J, Jenkins S, Putrino D, Mulrennan S, Morey S, Cecins N, Bear N, Hill K

Abstract
BACKGROUND: Respiratory exacerbations impair lung function and health-related quality of life in people with CF, with delayed identification of exacerbations often resulting in worse outcomes. We developed a smartphone application (app) for adults with CF to report symptoms to the CF team, and investigated its impact on antibiotic use and other outcomes.
METHODS: Participants were randomised to intervention (use of the app weekly or sooner if symptoms had worsened) or control (usual care). The app comprised questions relating to symptoms suggestive of an exacerbation. If worsening symptoms were reported, the participant was contacted by the nurse practitioner. The primary outcome measure was the number of courses and days of intravenous (IV) antibiotics.
RESULTS: Sixty participants (29 female, aged [mean ± SD] 31 ± 9 years, FEV1 60 ± 18% predicted) were recruited, with 29 (48%) allocated to the intervention group. Over the 12-month follow-up, there was no clear effect of the app on the number of courses of IV antibiotics (incidence rate ratio [IRR] 1; 95% confidence interval [CI] 0.6 to 1.7), however number of courses of oral antibiotics increased (IRR 1.5; 95% CI 1.0 to 2.2). The median [IQR] time to detection of exacerbation requiring oral or IV antibiotics was shorter in the intervention group compared with the control group (70 [123] vs. 141 [140] days; p = .02). No between-group differences were observed in other outcomes.
CONCLUSION: The use of an app reduced time to detect respiratory exacerbations that required antibiotics, however did not demonstrate a clear effect on the number of courses of IV antibiotics.

PMID: 31522924 [PubMed - as supplied by publisher]

Geometry-Dependent Spectroscopic Contrast in Deep Tissues.

iScience. 2019 Aug 29;19:965-975

Authors: Ge X, Tang H, Wang X, Liu X, Chen S, Wang N, Ni G, Yu X, Chen S, Liang H, Bo E, Wang L, Braganza CS, Xu C, Rowe SM, Tearney GJ, Liu L

Abstract
Nano-structures of biological systems can produce diverse spectroscopic effects through interactions with broadband light. Although structured coloration at the surface has been extensively studied, natural spectroscopic contrasts in deep tissues are poorly understood, which may carry valuable information for evaluating the anatomy and function of biological systems. Here we investigated the spectroscopic characteristics of an important geometry in deep tissues at the nanometer scale: packed nano-cylinders, in the near-infrared window, numerically predicted and experimentally proved that transversely oriented and regularly arranged nano-cylinders could selectively backscatter light of the long wavelengths. Notably, we found that the spectroscopic contrast of nanoscale fibrous structures was sensitive to the pressure load, possibly owing to the changes in the orientation, the degree of alignment, and the spacing. To explore the underlying physical basis, we further developed an analytical model based on the radial distribution function in terms of their radius, refractive index, and spatial distribution.

PMID: 31522119 [PubMed - as supplied by publisher]

Estimated Ventricular Size, Asthma Severity and Exacerbations: The SARP III Cohort.

Chest. 2019 Sep 12;:

Authors: Ash SY, Vegas Sanchez-Ferrero G, Schiebler ML, Rahaghi FN, Rai A, Come CE, Ross JC, Colon AG, Cardet JC, Bleecker ER, Castro M, Fahy JV, Fain SB, Gaston BM, Hoffman EA, Jarjour NN, Lempel JK, Mauger DT, Tattersall MC, Wenzel SE, Levy BD, Washko GR, Israel E, San Jose Estepar R, SARP Investigators

Abstract
BACKGROUND: Relative enlargement of the pulmonary artery (PA) on chest computed tomography (CT) is associated with respiratory exacerbations in patients with chronic obstructive pulmonary disease or cystic fibrosis. We sought to determine if similar findings were present in patients with asthma and if they were explained by differences in ventricular size.
METHODS: We measured the PA and aorta diameters in 233 individuals from the Severe Asthma Research Program III cohort. We also estimated right, left and total epicardial cardiac ventricular volume indices (eERVVI, eELVVI and eETVVI respectively). Associations between the cardiac and PA measures (PA to aorta ratio (PA/A), eERVVI to eELVVI ratio (eRV/eLV), eERVVI, eELVVI, eETVVI) and clinical measures of asthma severity were assessed using Pearson correlation, and associations with asthma severity and exacerbation rate were evaluated using multivariable linear and zero-inflated negative binomial regression.
RESULTS: Asthma severity was associated with smaller ventricular volumes. For example, those with severe asthma had 36.1 mL/m2 smaller eETVVI than healthy controls (p=0.003) and 14.1 mL/m2 smaller eETVVI than those with mild/moderate disease (p=0.011). Smaller ventricular volumes were also associated with a higher rate of asthma exacerbations, both retrospectively and prospectively. For example, those with an eETVVI less than the median had a 57% higher rate of exacerbations during follow up than those with eETVVI greater than the median (p=0.020). Neither PA/A nor eRV/eLV were associated with asthma severity or exacerbations.
CONCLUSIONS: In asthmatics, smaller cardiac ventricular size may be associated with more severe disease and a higher rate of asthma exacerbations.

PMID: 31521672 [PubMed - as supplied by publisher]

Proximal small bowel obstruction in a patient with cystic fibrosis: a case report.

Surg Case Rep. 2019 Sep 13;5(1):143

Authors: Alattar Z, Thornley C, Behbahaninia M, Sisley A

Abstract
BACKGROUND: As advancements are made in the management of cystic fibrosis (CF), survival of the CF patient into adulthood has increased, leading to the discovery of previously unknown CF complications. Though gastrointestinal complications of CF, such as distal intestinal obstruction syndrome, are common, this case demonstrates a variant presentation of small bowel obstruction in this population.
CASE PRESENTATION: We describe a 42-year-old male with CF who presented with 2 days of worsening upper abdominal pain, emesis, and loss of bowel function. The patient had no history of any prior abdominal surgeries; however, imaging was concerning for high-grade mechanical small bowel obstruction possibly related to internal hernia. Given leukocytosis and diffusely tender abdomen found on further workup, the decision was made to proceed with diagnostic laparoscopy after a brief period of intravenous fluid resuscitation. Intraoperatively, the transition point was found in the mid-jejunum and was noted to be due to kinking of the bowel causing vascular congestion in the proximal portion. Surgical manipulation of the bowel was required for return of normal perfusion and patency.
CONCLUSION: Though the exact mechanism cannot be definitively delineated, we speculate that the increased viscosity and prolonged intestinal transit time, characteristic of CF, resulted in inspissated fecal content in the proximal small bowel, which then acted as a lead point for obstruction. Thus, though small bowel obstruction in patients with CF is often attributed to distal intestinal obstruction syndrome, a broader differential must be considered. Early surgical intervention may be necessary to prevent bowel ischemia and subsequent small bowel resection in a patient presenting with concerning clinical and image findings, as was seen in this patient.

PMID: 31520190 [PubMed]

Scotland strikes deal to offer cystic fibrosis drugs.

BMJ. 2019 Sep 13;366:l5556

Authors: Christie B

PMID: 31519651 [PubMed - in process]

Bone Health in Children and Youth with Cystic Fibrosis: A Systematic Review and Meta-Analysis of Matched Cohort Studies.

J Pediatr. 2019 Sep 10;:

Authors: Ubago-Guisado E, Cavero-Redondo I, Alvarez-Bueno C, Vlachopoulos D, Martínez-Vizcaíno V, Gracia-Marco L

Abstract
OBJECTIVE: To assess the evidence regarding the differences in areal bone mineral density (aBMD) between children and adolescents with cystic fibrosis (CF) compared with their healthy peers, based on data from longitudinal studies.
STUDY DESIGN: We searched MEDLINE, SPORTDiscus, the Cochrane Library, PEDro (Physiotherapy Evidence Database), and Embase databases. Observational studies addressing the change of aBMD in children with CF and healthy children and adolescents were eligible. The DerSimonian and Laird method was used to compute pooled estimates of effect sizes (ES) and 95% CIs for the change of whole body (WB), lumbar spine (LS), and femoral neck (FN) aBMD.
RESULTS: Six studies with participants with CF and 26 studies with healthy participants were included in the systematic review and meta-analysis. For the analysis in children with CF, the pooled ES for the change of WB aBMD was 0.29 (95% CI -0.15 to 0.74), for the change of LS aBMD was 0.13 (95% CI -0.16 to 0.41), and for the change of FN aBMD was 0.09 (95% CI -0.39 to 0.57). For the analysis in healthy children, the pooled ES for the change of WB aBMD was 0.37 (95% CI 0.26-0.49), for the change of LS aBMD was 0.13 (95% CI -0.16 to 0.41), and for the change of FN aBMD was 0.52 (95% CI 0.19-0.85).
CONCLUSIONS: aBMD development might not differ between children and adolescents with CF receiving medical care compared with their healthy peers. Further longitudinal studies in a CF population during growth and development are required to confirm our findings.

PMID: 31519442 [PubMed - as supplied by publisher]

Clinical Adoption of mHealth Technology to Support Pediatric Cystic Fibrosis Care in Sweden: Qualitative Case Study.

JMIR Pediatr Parent. 2018 Dec 10;1(2):e11080

Authors: Longacre M, Grande S, Hager A, Montan M, Bergquist RP, Martensson M, Kotzbauer G

Abstract
BACKGROUND: Mobile health (mHealth) technologies have potential to improve self-management and care co-ordination of pediatric chronic diseases requiring complex care, such as cystic fibrosis (CF). Barriers to implementation include the lack of support and infrastructure to use mHealth in the clinical microsystem. Coproducing mHealth technology with patients, clinicians, and designers may increase the likelihood of successful integration into the clinical setting.
OBJECTIVE: This study explored the development, adoption, and integration of a new, co-produced mHealth platform (Genia) for the management of pediatric CF in Sweden.
METHODS: A retrospective, qualitative case study approach was used. The case was defined as the process of introducing and using Genia at the Pediatric Cystic Fibrosis Center at Skåne University Hospital in Lund, Sweden. Data sources included interviews, presentations, meeting notes, and other archival documents created between 2014 and 2017. To be included, data sources must have described or reflected upon the Genia adoption process. Iterative content analysis of data source materials was conducted by 2 qualitatively trained researchers to derive themes characterizing the mHealth clinical adoption process.
RESULTS: In total, 4 core themes characterized successful clinical integration of Genia in Lund: cultural readiness to use mHealth; use of weekly huddles to foster momentum and rapid iteration; engagement in incremental "Genia Talk" to motivate patient adoption; and co-design approach toward pediatric chronic care.
CONCLUSIONS: Principles of quality improvement, relational co-ordination, user-centered design, and coproduction can facilitate the integration of mHealth technology into clinical care systems for pediatric CF care.

PMID: 31518297 [PubMed]

Assessing the Perceptions of Inspiratory Muscle Training in Children With Cystic Fibrosis and Their Multidisciplinary Team: Mixed-Methods Study.

JMIR Pediatr Parent. 2018 Oct 25;1(2):e11189

Authors: McCreery JL, Mackintosh KA, Cox NS, McNarry MA

Abstract
BACKGROUND: Little is known about the opinions or perceived benefits of an inspiratory muscle training intervention in patients with cystic fibrosis and their multidisciplinary team.
OBJECTIVE: The aim of this qualitative study was to examine patients' and multidisciplinary teams' views on inspiratory muscle training to inform and tailor future interventions.
METHODS: Individual, semistructured interviews were conducted to evaluate participants' perspectives of a 4-week inspiratory muscle training intervention. In this study, 8 of 13 individuals involved in the inspiratory muscle training program (5 children aged 11-14 years; 2 physiotherapists; and 1 respiratory physician) participated. Interviews were transcribed verbatim, analyzed using thematic analyses, and then coded into relevant themes.
RESULTS: Four key themes emerged: acceptability, facilitators, barriers, and recommendations. While fun, enjoyment, and improved perceived physical ability were reported by children and their multidisciplinary team following the inspiratory muscle training program, the multidisciplinary team identified factors such as time and cost as key barriers.
CONCLUSIONS: A short inspiratory muscle training program was perceived to have positive effects on the physical ability and psychosocial health of children with cystic fibrosis. These findings highlight the importance of obtaining participants' and multidisciplinary teams' perceptions and recommendations to ensure the efficacy and optimal design of future inspiratory muscle training protocols.

PMID: 31518290 [PubMed]

Bronchoscopic instillation of DNase to manage refractory lobar atelectasis in a lung cancer patient.

Ann Transl Med. 2019 Aug;7(15):363

Authors: Assallum H, Song TY, DeLorenzo L, Harris K

Abstract
Lobar atelectasis is a common complication in lung cancer. It can be caused by direct endobronchial tumorous seeding or indirectly by mucus plugs due to bacterial lung infections. Treatment is usually conservative, with or without therapeutic bronchoscopy. Dornase alfa is a recombinant human deoxyribonuclease I (rhDNase), an enzyme that selectively cleaves DNA, thus reducing mucous viscosity. rhDNase has been used as a mucolytic agent in cystic fibrosis (CF) patients. Though bronchoscopically instilled rhDNase has been reported as a treatment for persistent lobar atelectasis in newborn and pediatric populations, its use in adults has not been well established.

PMID: 31516909 [PubMed]

Mycophenolate mofetil as an alternative treatment in sarcoidosis.

Pulm Pharmacol Ther. 2019 Sep 10;:101840

Authors: Papiris S, Stagaki E, Papadaki G, Kolilekas L, Korbila I, Apollonatou V, Kallieri M, Gialafos H, Chatziioannou S, Papaioannou AI, Manali ED

Abstract
INTRODUCTION: In sarcoidosis although no better drug therapy than corticosteroids (CS) has emerged, alternative immunosuppressive agents are used when indicated. Mycophenolate mofetil (MMF) presents rapid action, a considerable safety profile and absence of lung toxicity. Few data exist so far on its use in patients with sarcoidosis. This is a retrospective study on the effectiveness and safety of MMF in patients with sarcoidosis.
MATERIALS AND METHODS: All patients with biopsy proven sarcoidosis treated for at least 1 year with MMF from 2008 to 2017 in our department are evaluated.
RESULTS: Eight patients with both pulmonary and extrapulmonary disease are included in the analysis. During follow-up, symptoms and chest radiological findings improved in all. A statistically significant improvement of FEV1 and FVC is reported (p = 0.010 and p = 0.021 respectively). Cardiac and renal disease resolved during treatment while dermal disease significantly improved. MMF permitted CS dose reduction from 15.0 (10.0, 35.0) to 2.5 (0.0, 5.0) mg prednisolone (or equivalent), p = 0.016. All patients but one, tolerated well MMF.
CONCLUSION: MMF as an alternative drug in systemic sarcoidosis, proved safe and effective, permitting the reduction of the dose of oral CS and leading to clinical, functional and radiological improvement.

PMID: 31518648 [PubMed - as supplied by publisher]