Lumacaftor/ivacaftor in patients with cystic fibrosis and advanced lung disease homozygous for F508del-CFTR.

J Cyst Fibros. 2017 Nov 07;:

Authors: Taylor-Cousar JL, Jain M, Barto TL, Haddad T, Atkinson J, Tian S, Tang R, Marigowda G, Waltz D, Pilewski J, VX14-809-106 Investigator Group

Abstract
OBJECTIVE: Evaluation of the safety, tolerability, and efficacy of lumacaftor/ivacaftor in patients with cystic fibrosis (CF) with severe lung disease.
METHODS: Patients with CF 12 years of age and older, homozygous for F508del-CFTR, with percent predicted forced expiratory volume in 1 second (ppFEV1) <40 received lumacaftor 400 mg/ivacaftor 250mg every 12h (full dose) for 24weeks in an open-label, prospective study (NCT02390219). Dose modification to half dose for 1-2weeks (including at initiation) was permitted. Safety and tolerability were the primary outcome measures; clinical outcomes were also assessed.
RESULTS: Of 46 patients (initiated on full dose: n=28; initiated on half dose: n=18), 35 (76%) completed 24weeks of treatment. The most common adverse events included infective pulmonary exacerbation, abnormal respiration, cough, and dyspnea. Compared with patients initiating on full dose, patients initiating at half dose had less frequent respiratory events (56% vs 71%) of shorter median duration (4 vs 9days). No dose modifications or discontinuations as a result of respiratory events occurred in patients initiating on half dose who were then increased to the full dose over 2weeks (versus three each for patients on full dose). Following an initial reduction, ppFEV1 was similar to baseline from week 4 throughout the remainder of the study (least squares mean [95% confidence interval] at week 24: -0.4 [-1.9, 1.1]; p=0.6249). Compared with the 24weeks prior to study, the annualized hospitalization rate was lower (rate ratio: 0.41; p=0.00026) and the duration of intravenous antibiotics was shorter (mean [standard deviation] difference: -8.52 [24.91] days; p=0.0369) through study week 24.
CONCLUSIONS: Compared with patients with higher lung function, respiratory events were more common in patients with ppFEV1<40; aside from these events, the lumacaftor/ivacaftor safety profile was consistent with previous studies. Results suggest that patients with ppFEV1<40 may benefit from treatment initiation at a lower dose with augmented monitoring before increasing to the full dose.

PMID: 29126871 [PubMed - as supplied by publisher]

Post-exposure immunization by capsid-modified AdC7 vector expressing Pseudomonas aeruginosa OprF clears P. aeruginosa respiratory infection.

Vaccine. 2017 Nov 07;:

Authors: Gomi R, Sharma A, Wu W, Sung B, Worgall S

Abstract
Respiratory infections with Pseudomonas aeruginosa are major health problems, particularly in patients with cystic fibrosis (CF). No vaccine against P. aeruginosa is yet available. A vaccine that controls colonization of the respiratory tract with P. aeruginosa could be useful to prevent chronic infection and exacerbations. Replication-deficient adenoviral (Ad) vectors based on non-human serotypes are attractive vaccine platforms as they can circumvent the problem of pre-existing anti-Ad immunity in humans. The primate-based AdC7 vector AdC7OprF.RGD that expresses the outer membrane protein F (OprF) of P. aeruginosa (AdC7OprF) and that displays an integrin-binding arginine-glycine-aspartic acid (RGD) sequence is a potent inducer of lung mucosal and protective immunity. Here, we investigated the efficacy of immunization with AdC7OprF.RGD to clear an already established P. aeruginosa respiratory infection in mice (wild-type and CF) and rats. Intratracheal administration of the clinical P. aeruginosa strain RP73 embedded in agar beads was used to establish persistent infection. Subsequent intranasal immunization with AdC7OprF.RGD induced robust P. aeruginosa-specific systemic and mucosal, humoral and cellular immune responses. Importantly, the AdC7OprF.RGD immunized mice effectively cleared P. aeruginosa from the lungs. Likewise, immunization with AdC7OprF.RGD of CF mice and Sprague Dawley rats with established P. aeruginosa respiratory infection showed enhanced anti-Pseudomonas immune responses and increased clearance of P. aeruginosa from the lungs. These data suggest that AdC7OprF.RGD can be effective as a post-exposure vaccine and may be useful in clinical settings in particular for patients with CF who frequently harbor the bacteria over prolonged periods.

PMID: 29126807 [PubMed - as supplied by publisher]

Evaluation of spina bifida transitional care practices in the United States.

J Pediatr Rehabil Med. 2017 Oct 20;:

Authors: Kelly MS, Thibadeau J, Struwe S, Ramen L, Ouyang L, Routh J

Abstract
PURPOSE: Recent studies have revealed that the lack of continuity in preparing patients with spina bifida to transition into adult-centered care may have detrimental health consequences. We sought to describe current practices of transitional care services offered at spina bifida clinics in the US.
METHODS: Survey design followed the validated transitional care survey by the National Cystic Fibrosis center. Survey was amended for spina bifida. Face validity was completed. Survey was distributed to registered clinics via the Spina Bifida Association. Results were analyzed via descriptive means.
RESULTS: Total of 34 clinics responded. Over 90 characteristics were analyzed per clinic. The concept of transition is discussed with most patients. Most clinics discuss mobility, bowel and bladder management, weight, and education plans consistently. Most do not routinely evaluate their process or discuss insurance coverage changes with patients. Only 30% communicate with the adult providers. Sexuality, pregnancy and reproductive issues are not readily discussed in most clinics. Overall clinics self-rate themselves as a 5/10 in their ability to provide services for their patients during transition.
CONCLUSIONS: Characteristics of current transitional care services and formal transitional care programs at US clinics show wide variances in what is offered to patients and families.

PMID: 29125516 [PubMed - as supplied by publisher]

Asthma and Allergy "Epidemic" and the Role of Vitamin D Deficiency.

Adv Exp Med Biol. 2017;996:169-183

Authors: Douros K, Boutopoulou B, Fouzas S, Loukou I

Abstract
The increase in asthma and allergies prevalence that has been recorded in many countries during the last decades, and the reemergence of vitamin D (VD) deficiency in many populations worldwide, renders fairly plausible the assumption of an underlying association between these two conditions and justifies the research effort invented in this issue. Indeed, there is growing body of evidence from epidemiological, laboratory, and clinical studies, suggesting that such an association does exist. The hypothesis of low levels of VD leading to compromised fetal programming and impairment of various immune functions involved in asthma and allergic disorders, stands as the most credible explanation of this presumed association. However, the evidence is not yet definite and there are some conflicting results among studies. As a consequence, no safe conclusions can be drawn yet, and more research is required in order to fully clarify the involvement of VD deficiency in the pathogenesis of asthma and allergies, and decide if VD has a role to play in the prevention and therapy of these disorders.

PMID: 29124699 [PubMed - in process]

Thirty Years of Sweat Chloride Testing at One Referral Center.

Front Pediatr. 2017;5:222

Authors: Faria AG, Marson FAL, Gomez CCS, Servidoni MF, Ribeiro AF, Ribeiro JD

Abstract
Objective: To conduct a descriptive analysis of the sweat test (ST), associating ST results with epidemiological data, CFTR (cystic fibrosis transmembrane conductance regulator) mutations and reasons to indicate the ST, as well as correlating sweat sodium and sweat chloride concentrations in subjects.
Methods: Retrospective survey and descriptive analysis of 5,721 ST at a university referral center.
Results: The inclusion of the subjects was based on clinical data related with cystic fibrosis (CF) phenotype. The samples were grouped by (i) sweat chloride concentrations (mEq/L): <30: 3,249/5,277 (61.6%); ≥30 to <60: 1,326/5,277 (25.1%); ≥60: 702/5,277 (13.3%) and (ii) age: (Group A--GA) 0 to <6 months; (Group B--GB) ≥6 months to <18 years; (Group C--GC) ≥18 years. Digestive symptoms showed higher prevalence ratio for the CF diagnosis as well as association between younger age and higher values of sweat chloride, sweat sodium, and chloride/sodium ratio. The indication of ST due to respiratory symptoms was higher in GB and associated with greater age, lower values of sweat chloride, sweat sodium, and chloride/sodium ratio. There was higher prevalence of ST with sweat chloride levels <30 mEq/L in GB, ≥60 mEq/L in GC, and with borderline level in GB. There was positive correlation between sweat sodium and sweat chloride. Sweat chloride/sweat sodium and sweat sodium-sweat chloride indexes showed association with sex, reason for ST indication, and CFTR mutations. Sex alters some values presented in the ST. The number of ST/year performed before and after the newborn screening implementation was the same; however, we observed a higher number of borderlines values. A wide spectrum of CFTR mutation was found. Severe CFTR mutations and F508del/F508del genotype were associated with highest probability of ST chloride levels ≥60 mEq/L, and the absence of CFTR mutations identified was associated with borderline ST and respiratory symptoms.
Conclusions: ST data showed wide variability dependent on age, sex, reason for examination indication, CFTR mutations, and weight of the collected sweat sample. Sweat sodium concentration is directly correlated with sweat chloride levels and it could be used as a quality parameter.

PMID: 29124052 [PubMed]

Janus-Faced Neutrophil Extracellular Traps in Periodontitis.

Front Immunol. 2017;8:1404

Authors: Vitkov L, Hartl D, Minnich B, Hannig M

Abstract
Periodontitis is characterized by PMN infiltration and formation of neutrophil extracellular traps (NETs). However, their functional role for periodontal health remains complex and partially understood. The main function of NETs appears to be evacuation of dental plaque pathogen-associated molecular patterns. The inability to produce NETs is concomitant with aggressive periodontitis. But in cases with exaggerated NET production, NETs are unable to maintain periodontal health and bystander damages occur. This pathology can be also demonstrated in animal models using lipopolysaccharide as PMN activator. The progress of periodontitis appears to be a consequence of the formation of gingival pockets obstructing the evacuation of both pathogen-associated and damage-associated molecular patterns, which are responsible for the self-perpetuation of inflammation. Thus, besides the pathogenic effects of the periodontal bacteria, the dysregulation of PMN activation appears to play a main role in the periodontal pathology. Consequently, modulation of PMN activation might be a useful approach to periodontal therapy.

PMID: 29123528 [PubMed]

Airway surface liquid pH is not acidic in children with cystic fibrosis.

Nat Commun. 2017 Nov 10;8(1):1409

Authors: Schultz A, Puvvadi R, Borisov SM, Shaw NC, Klimant I, Berry LJ, Montgomery ST, Nguyen T, Kreda SM, Kicic A, Noble PB, Button B, Stick SM

Abstract
Modulation of airway surface liquid (ASL) pH has been proposed as a therapy for cystic fibrosis (CF). However, evidence that ASL pH is reduced in CF is limited and conflicting. The technical challenges associated with measuring ASL pH in vivo have precluded accurate measurements in humans. In order to address this deficiency, ASL pH was measured in vivo in children using a novel luminescent technology integrated with fibre-optic probes. Here we show that ASL pH in children with CF is similar to that of children without CF. Findings were supported by highly controlled direct pH measurements in primary human airway epithelial cell culture models, which also suggest that the potential ASL pH gradient produced by defective apical ion transport is balanced out by paracellular shunting of acid/base. Thus, reduced baseline ASL pH is unlikely to be an important pathobiological factor in early CF lung disease.

PMID: 29123085 [PubMed - in process]

Elucidating progression of early cystic fibrosis lung disease.

Eur Respir J. 2017 Nov;50(5):

Authors: Ramsey K, Ratjen F, Latzin P

PMID: 29122922 [PubMed - in process]

Elevated lung clearance index in infants with cystic fibrosis shortly after birth.

Eur Respir J. 2017 Nov;50(5):

Authors: Kieninger E, Yammine S, Korten I, Anagnostopoulou P, Singer F, Frey U, Mornand A, Zanolari M, Rochat I, Trachsel D, Mueller-Suter D, Moeller A, Casaulta C, Latzin P, and the SCILD, and BILD study groups

Abstract
It is not known at what age lung function impairment may arise in children with cystic fibrosis (CF). We assessed lung function shortly after birth in infants with CF diagnosed by newborn screening.We performed infant lung function measurements in a prospective cohort of infants with CF and healthy controls. We assessed lung clearance index (LCI), functional residual capacity (FRC) and tidal breathing parameters. The primary outcome was prevalence and severity of abnormal lung function (±1.64 z-scores) in CF.We enrolled 53 infants with CF (mean age 7.8 weeks) and 57 controls (mean age 5.2 weeks). Compared to controls, LCI and FRC were elevated (mean difference 0.30, 95% CI 0.02-0.60; p=0.034 and 14.5 mL, 95% CI 7.7-21.3 mL; p<0.001, respectively), while ratio of time to peak tidal expiratory flow to expiratory time was decreased in infants with CF. In 22 (41.5%) infants with CF, either LCI or FRC exceeded 1.64 z-scores; three infants had both elevated LCI and FRC.Shortly after birth, abnormal lung function is prevalent in CF infants. Ventilation inhomogeneity or hyperinflation may serve as noninvasive markers to monitor CF lung disease and specific treatment effects, and could thus be used as outcome parameters for future intervention studies in this age group.

PMID: 29122915 [PubMed - in process]

Pulmonary function deficits in newborn screened infants with cystic fibrosis managed with standard UK care are mild and transient.

Eur Respir J. 2017 Nov;50(5):

Authors: Davies G, Stocks J, Thia LP, Hoo AF, Bush A, Aurora P, Brennan L, Lee S, Lum S, Cottam P, Miles J, Chudleigh J, Kirkby J, Balfour-Lynn IM, Carr SB, Wallis C, Wyatt H, Wade A, London Cystic Fibrosis Collaboration (LCFC)

Abstract
With the advent of novel designer molecules for cystic fibrosis (CF) treatment, there is huge need for early-life clinical trial outcomes, such as infant lung function (ILF). We investigated the degree and tracking of ILF abnormality during the first 2 years of life in CF newborn screened infants.Forced expiratory volume in 0.5 s (FEV0.5), lung clearance index (LCI) and plethysmographic functional residual capacity were measured at ∼3 months, 1 year and 2 years in 62 infants with CF and 34 controls.By 2 years there was no significant difference in FEV0.5 z-score between CF and controls, whereas mean LCI z-score was 0.81 (95% CI 0.45-1.17) higher in CF. However, there was no significant association between LCI z-score at 2 years with either 3-month or 1-year results. Despite minimal average group changes in any ILF outcome during the second year of life, marked within-subject changes occurred. No child had abnormal LCI or FEV0.5 on all test occasions, precluding the ability to identify "high-risk" infants in early life.In conclusion, changes in lung function are mild and transient during the first 2 years of life in newborn screened infants with CF when managed according to a standardised UK treatment protocol. Their potential role in tracking disease to later childhood will be ascertained by ongoing follow-up.

PMID: 29122914 [PubMed - in process]

Vitamin D₃ deficiency and its association with nasal polyposis in patients with cystic fibrosis and patients with chronic rhinosinusitis.

Am J Rhinol Allergy. 2017 Nov 01;31(6):395-400

Authors: Konstantinidis I, Fotoulaki M, Iakovou I, Chatziavramidis A, Mpalaris V, Shobat K, Markou K

Abstract
BACKGROUND: Currently vitamin D3 (VD3) or cholecalciferol is considered an immunomodulator that may be implicated in nasal polyposis (NP) pathophysiology.
OBJECTIVES: This study aimed to investigate if deficiency of VD3 is associated with the presence of NP in patients with cystic fibrosis (CF) and patients with chronic rhinosinusitis (CRS).
METHODS: In total, 152 adult participants were included in five phenotypic groups: CF with NP (CFwNP) (n = 27), CF without NP (CFsNP) (n = 31), CRS with NP (CRSwNP) (n = 32), CRS without NP (CRSsNP) (n = 30), and controls (n = 32). The serum levels of 25(OH)-VD3 < 20 ng/mL are considered as a deficiency, 21-29 ng/mL as insufficiency, and >30 ng/mL as sufficiency. Endoscopic and imaging staging of the mucosal disease performed with the Lund-Kennedy (LK) and Lund-Mackay (LM) scoring systems, respectively. The genotype of the patients with CF and the nasal microbial colonization of the patients with CF and patients with CRS were also recorded.
RESULTS: The patients with CFwNP had the lowest percentage of sufficiency in VD3 and the highest percentage in insufficiency among all the groups. The LM imaging scores were inversely correlated with the VD3 levels in both arms of the study (CF and CRS). Moreover, the LK endoscopic scores had a similar correlation in the CF groups; however, this was not the case with the CRS groups. The genotype of the patients with CF was not correlated with the VD3 serum levels. The patients with positive microbial colonization (mainly Pseudomonas and Staphylococcus aureus) had significantly lower VD3 serum levels in both the CF and CRS process.
CONCLUSION: VD3 deficiency seemed to be associated with the presence of nasal polyps in the patients with CRS and in the patients with CF in a similar manner. The lower the level of serum VD3, the more severe the mucosal disease was found in the imaging studies and the more frequent microbial colonization of the patients with CF and the patients with CRS.

PMID: 29122084 [PubMed - in process]

Management of an outbreak of Exophiala dermatitidis bloodstream infections at an outpatient oncology clinic.

Clin Infect Dis. 2017 Nov 07;:

Authors: Vasquez AM, Zavasky D, Chow NA, Gade L, Zlatanic E, Elkind S, Litvintseva AP, Pappas PG, Perfect JR, Revankar SG, Lockhart SR, Chiller TM, Ackelsberg J, Vallabhaneni S

Abstract
Exophiala (Wangiella) dermatitidis is a dematiaceous fungus that can grow in yeast or mold forms and is typically found in decaying organic matter. It can cause central nervous system disease, particularly in immunocompromised patients, and has been implicated as a respiratory pathogen in cystic fibrosis patients [1,2]. It has also been identified as a colonizer in the gastrointestinal tract [3]. However, bloodstream infections with this organism are exceedingly rare.

PMID: 29121235 [PubMed - as supplied by publisher]

Developing selective media for quantification of multispecies biofilms following antibiotic treatment.

PLoS One. 2017;12(11):e0187540

Authors: Vandeplassche E, Coenye T, Crabbé A

Abstract
The lungs of cystic fibrosis (CF) patients are chronically colonized by a polymicrobial biofilm community, leading to difficult-to-treat infections. To combat these infections, CF patients are commonly treated with a variety of antibiotics. Understanding the dynamics of polymicrobial community composition in response to antibiotic therapy is essential in the search for novel therapies. Culture-dependent quantification of individual bacteria from defined multispecies biofilms is frequently carried out by plating on selective media. However, the influence of the selective agents in these media on quantitative recovery before or after antibiotic treatment is often unknown. In the present study we developed selective media for six bacterial species that are frequently co-isolated from the CF lung, i.e. Pseudomonas aeruginosa, Staphylococcus aureus, Streptococcus anginosus, Achromobacter xylosoxidans, Rothia mucilaginosa, and Gemella haemolysans. We show that certain supplementations to selective media strongly influence quantitative recovery of (un)treated biofilms. Hence, the developed media were optimized for selectivity and quantitative recovery before or after treatment with antibiotics of four major classes, i.e. ceftazidime, ciprofloxacin, colistin, or tobramycin. Finally, in a proof of concept experiment the novel selective media were applied to determine the community composition of multispecies biofilms before and after treatment with tobramycin.

PMID: 29121069 [PubMed - in process]

Improving transition to adult healthcare for young people with cystic fibrosis: A systematic review.

J Child Health Care. 2017 Sep;21(3):312-330

Authors: Coyne I, Sheehan AM, Heery E, While AE

Abstract
As survival increases worldwide, large numbers of young people will need to transition from child to adult cystic fibrosis (CF) services. Little is known about the best method for transitioning patients with CF and which transition programmes yield better outcomes. This paper provides a systematic review of the empirical literature on the outcomes and experiences of transition for young people with CF. Outcomes data were subject to a narrative synthesis and a thematic synthesis of experiences data. Structured transition programmes were associated with increased satisfaction, discussions about transition, self-care and self-advocacy skills, more independence, lower anxiety, and increased self-management and parent management of physiotherapy and nutritional supplementation. Young people's concerns included leaving behind previous caregivers, differences in care provision and infection risks. Lack of preparation was a consistent theme. The two most useful aspects of transition programmes were meeting the adult doctors/CF specialist nurse/team and visiting the adult centre. Young people want education about the differences between services, implications of their condition and self-care management. Structured transition programmes appear to impact positively on experiences but the contribution of the different components of transition programmes is unclear. The absence of high-quality studies indicates the need for more well-designed research.

PMID: 29119815 [PubMed - in process]

Uneven distribution of professors and instructors in medical disciplines dealing with the four main chronic non-communicable diseases: the case of the Italian Universities.

Multidiscip Respir Med. 2017;12:27

Authors: Viegi G, Centanni S, Blasi F

Abstract
Background: Chronic (non-communicable) diseases (NCD) -- principally cardiovascular diseases, cancer, chronic respiratory diseases, and diabetes -- are leading causes of death and disability. There is the need to adopt a core University curriculum which let students be taught by teachers who are experts of the four main NCD, for reaching the public health goals proposed by the UN and the WHO.
Methods: Our aim was to assess whether all medical students, regardless of the Italian university of enrolment, have an equal opportunity to be educated by an expert teacher in each of the four NCD. We have used the search engine http://cercauniversita.cineca.it/php5/docenti/cerca.php.
Results: In January 2016, for each of the 43 universities with a school of medicine, we have assessed the presence of professors / instructors for each of the four academic disciplines corresponding to the four NCD: a) Respiratory medicine; b) Cardiovascular medicine; c) Oncology; d) Endocrinology. Comparing university personnel between Respiratory medicine and each of the other NCD academic sectors, there were negative differences, much wider with the sector Cardiovascular medicine, regarding individual (number of professors/instructors) and collective indicators (number of Universities with various kinds of professors/instructors).
Conclusions: Both national societies and ERS should promote periodic analyses of the academic situation of respiratory medicine in the European countries for advocating the EU in order to have recommendations/suggestions for the Member States to get the proper recognition of respiratory medicine, at the same level as the other disciplines involved in preventing and managing the four main NCD.

PMID: 29118982 [PubMed]

Proton Pump Inhibitor Use Is Associated With an Increased Frequency of Hospitalization in Patients With Cystic Fibrosis.

Gastroenterology Res. 2017 Oct;10(5):288-293

Authors: Ayoub F, Lascano J, Morelli G

Abstract
Background: Proton pump inhibitors (PPIs) are among the most commonly prescribed medications in clinical practice. PPI use has been associated with the development of community-acquired pneumonia. With a reported prevalence of gastroesophageal reflux disease (GERD) and PPI use that is higher than the general population, patients with cystic fibrosis (CF) are particularly vulnerable to PPI adverse effects. We sought to explore whether PPI use was associated with a higher number of hospitalizations for CF pulmonary exacerbation.
Methods: We conducted a longitudinal retrospective review in an academic outpatient setting. Patients > 18 years of age with a diagnosis of CF and at least 1 year of follow-up were eligible for inclusion. Baseline characteristics, PPI use, and details of hospitalization through 1 year of follow-up were collected.
Results: One hundred fourteen patients met inclusion criteria. Fifty-nine patients (51.7%) were hospitalized at least once in the follow-up year, mean number of hospitalizations was 2.17 (± 1.9). At least 6 months of PPI use was observed in 59 patients (51.7%). In univariate analysis, PPI use was associated with a significantly higher mean number of hospitalizations (0.9 vs. 1.4, P = 0.009). In a multi-variable regression model, PPI use remained significantly associated with a higher number of hospitalizations (P = 0.03), while controlling for risk factors traditionally associated with increased pulmonary exacerbations.
Conclusion: PPI use is highly prevalent in CF patients. Exposure to PPI therapy is independently associated with a higher number of hospitalizations for pulmonary exacerbation in CF patients.

PMID: 29118869 [PubMed]

A novel cystic fibrosis gene mutation c.2490insT in a Palestinian patient: A case report and review of the literature.

Ann Thorac Med. 2017 Oct-Dec;12(4):290-293

Authors: Chami H, Arbid SA, Badra R, Farra C

Abstract
We report the case of a 19-year-old male patient of Palestinian descent, who presented with a 1-year history of recurrent Pseudomonas aeruginosa respiratory infections, weight loss, chronic diarrhea, and a normal chloride sweat test. A panel for common cystic fibrosis transmembrane conductance regulator (CFTR) gene mutations test was also negative. Cystic fibrosis (CF) was still clinically suspected thus, full CFTR gene sequencing was performed, which revealed a homozygous unreported mutation c.2490insT (GenBank accession number: BankIt2019289 seq1 MF167456). Both parents were also found to be heterozygous for this mutation. This case highlights the importance of clinical evaluation and the need for extensive genetic investigation when dealing with a genetic disease with wide variability in a clinical presentation such as CF.

PMID: 29118863 [PubMed]

Salvage therapy with topical posaconazole in lung transplant recipients with invasive scedosporium infection.

Am J Transplant. 2017 Nov 08;:

Authors: Solé A, García-Robles AA, Jordá C, Viedma EC, Mancheño N, Poveda-Andrés JL, Mezquida JPR, Pemán J

Abstract
Scedosporium is an important pathogen in cystic fibrosis (CF) and post-transplant, but it rarely causes invasive infection. Treatment remains challenging, particularly due to the inherent resistance to multiple antifungal agents. We present three complicated invasive tracheobronchial and lung Scedosporium apiospermum infections following lung transplant. In two of three cases, the infection was clinically and radiologically cured with frequent cleansing bronchoscopies, combining triazole with terbinafine therapy and nebulized posaconazole. These cases highlight the importance of adjunctive nebulized therapy in addition to prolonged triazole treatment to manage complex invasive Scedosporium infections in immunosuppressed patients. Posaconazole (PSZ) was delivered during the bronchoscopy procedure through intrabronchial administration, whereas an eFlow rapid(®) device was used for nebulized therapy. Topical posaconazole was well tolerated in two patients, with only a slight cough during administrations; the third patient suffered local irritation with poor tolerance, which led to its withdrawal. This is the first report on compassionate use of topical posaconazole as salvage therapy for resistant mold infections in lung transplantation recipients. These three cases represent the entire experience using this approach; no additional patients have received this therapy due to not having received any additional cases of Scedosporium tracheobronchitis. This article is protected by copyright. All rights reserved.

PMID: 29116676 [PubMed - as supplied by publisher]

Monocytes from patients with Primary Ciliary Dyskinesia show enhanced inflammatory properties and produce higher levels of pro-inflammatory cytokines.

Sci Rep. 2017 Nov 07;7(1):14657

Authors: Cockx M, Gouwy M, Ruytinx P, Lodewijckx I, Van Hout A, Knoops S, Pörtner N, Ronsse I, Vanbrabant L, Godding V, De Boeck K, Van Damme J, Boon M, Struyf S

Abstract
Patients with Primary Ciliary Dyskinesia (PCD) suffer from recurrent upper and lower airway infections due to defects in the cilia present on the respiratory epithelium. Since chronic inflammatory conditions can cause changes in innate immune responses, we investigated whether monocytes isolated from the peripheral blood of pediatric PCD patients respond differently to inflammatory stimuli, compared to monocytes from healthy children and adults. The receptor for C5a (C5aR) was upregulated in PCD, whereas expression levels of the leukocyte chemoattractant receptors CCR1, CCR2, CCR5, BLT1 and FPR1 on PCD monocytes were similar to those on monocytes from healthy individuals. Also in vitro migration of PCD monocytes towards the ligands of those receptors (CCL2, fMLP, C5a and LTB4) was normal. Compared to healthy children, PCD patients had a higher percentage of the non-classic monocyte subset (CD14+CD16++) in circulation. Finally, PCD monocytes produced higher levels of pro-inflammatory cytokines (IL-1β and TNF-α) and chemokines (CCL3, CCL5, CCL18 and CCL22) in response to LPS, peptidoglycan and/or dsRNA stimulation. These data suggest that monocytes might exacerbate inflammatory reactions in PCD patients and might maintain a positive feedback-loop feeding the inflammatory process.

PMID: 29116124 [PubMed - in process]

The First Successful Lung Transplantation in a Korean Child with Cystic Fibrosis.

J Korean Med Sci. 2017 Dec;32(12):2073-2078

Authors: Noh SR, Lee E, Yoon J, Jung S, Yang SI, Yu J, Hong SJ

Abstract
Cystic fibrosis (CF) is an autosomal recessive inherited multisystem disorder caused by mutations of the gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR) protein. Respiratory failure remains the most frequent cause of morbidity and mortality. Lung transplantation is the only option to treat end-stage lung disease. Very few cases of CF occur in Koreans. We report the case of a 12-year-old girl with respiratory failure due to CF who underwent lung transplantation. She had been diagnosed with CF 8 years previously after being treated for recurrent Pseudomonas aeruginosa pneumonia and malnutrition based on sweat chloride concentrations and the CFTR protein gene mutation test. Progression to end-stage lung disease and respiratory failure led to registration with the Korean Network for Organ Sharing. She underwent successful double lung transplantation in 2014. Although she has diabetes mellitus and chronic kidney disease, she has a better quality of life and a prolonged life expectancy.

PMID: 29115094 [PubMed - in process]