Tiotropium add-on therapy is safe and reduces seasonal worsenings in paediatric asthma patients.

Eur Respir J. 2019 May 16;:

Authors: Vogelberg C, Szefler SJ, Vrijlandt EJLE, Boner AL, Engel M, Azzi GE, Vulcu SD, Moroni-Zentgraf PM, Eickmeier O, Hamelmann EH

Abstract
There remains an unmet need for effective, well tolerated therapeutic options in paediatric patients with not fully controlled asthma, for whom safety is of paramount importance.Data were pooled from five randomised, double-blind, placebo-controlled studies evaluating tiotropium 5 or 2.5 µg versus placebo add-on therapy in patients with symptomatic asthma aged 1-17 years. Analysis included adverse events (AEs) and serious AEs (SAEs) reported throughout and for 30 days following treatment.Of 1691 patients treated, 1119 received tiotropium. Reporting of AEs was low and comparable across all groups: tiotropium 5 µg (51%), 2.5 µg (51%) and placebo (54%). Reporting of drug-related AEs, those leading to discontinuation and SAEs was also low and balanced between treatment groups, irrespective of age, disease severity or gender. The number of AEs related to asthma symptoms and exacerbations was lower with tiotropium (5 µg) than with placebo, particularly during the seasonal peaks of these AEs.This comprehensive analysis of a large safety database allowed subgroup analyses that are often impractical with individual trials and provides further support for the safety of once-daily tiotropium Respimat® add-on therapy in paediatric patients with symptomatic asthma.Clinical Trial Registration: NinoTinA-asthma® (NCT01634113), CanoTinA-asthma® (NCT01634139), VivaTinA-asthma® (NCT01634152), RubaTinA-asthma® (NCT01257230), PensieTinA-asthma® (NCT01277523).

PMID: 31097514 [PubMed - as supplied by publisher]

Predictors and reproducibility of exercise-induced bronchoconstriction in cold air.

BMC Pulm Med. 2019 May 16;19(1):94

Authors: Dreßler M, Friedrich T, Lasowski N, Herrmann E, Zielen S, Schulze J

Abstract
BACKGROUND: Physical activity is an important part of life, and hence exercise-induced bronchoconstriction (EIB) can reduce the quality of life. A standardized test is needed to diagnose EIB. The American Thoracic Society (ATS) guidelines recommend an exercise challenge in combination with dry air. We investigated the feasibility of a new, ATS guidelines conform exercise challenge in a cold chamber (ECC) to detect EIB. The aim of this study was to investigate the surrogate marker reaction to methacholine, ECC and exercise challenge in ambient temperature for the prediction of a positive reaction and to re-evaluate the reproducibility of the response to an ECC.
METHODS: Seventy-eight subjects aged 6 to 40 years with suspected EIB were recruited for the study. The subjects performed one methacholine challenge, two ECCs, and one exercise challenge at an ambient temperature. To define the sensitivity and specificity of the predictor, a receiver-operating characteristic curve was plotted. The repeatability was evaluated using the method described by Bland and Altman (95% Limits of agreement).
RESULTS: The following cut-off values showed the best combination of sensitivity and specificity: the provocation dose causing a 20% decrease in the forced expiratory volume in 1 s (PD20FEV1) of methacholine: 1.36 mg (AUC 0.69, p < 0.05), the maximal decrease in FEV1 during the ECC: 8.5% (AUC 0.78, p < 0.001) and exercise challenges at ambient temperatures: FEV1 5.2% (AUC 0.64, p = 0.13). The median decline in FEV1 was 14.5% (0.0-64.2) during the first ECC and 10.7% (0.0-52.5) during the second ECC. In the comparison of both ECCs, the Spearman rank correlation of the FEV1 decrease was r = 0.58 (p < 0.001). The 95% limits of agreement (95% LOAs) for the FEV1 decrease were - 17.7 to 26.4%.
CONCLUSIONS: The surrogate markers PD20FEV1 of methacholine and maximal decrease in FEV1 during ECC can predict a positive reaction in another ECC, whereas the maximal FEV1 decrease in an exercise challenge at an ambient temperature was not predictive. Compared with previous studies, we can achieve a similar reproducibility with an ECC.
CLINICAL TRIAL REGISTRATION: NCT02026492 (retrospectively registered 03/Jan/2014).

PMID: 31097027 [PubMed - in process]

Relations between air pollution and vascular development in 5-year old children: a cross-sectional study in the Netherlands.

Environ Health. 2019 May 16;18(1):50

Authors: Ntarladima AM, Vaartjes I, Grobbee DE, Dijst M, Schmitz O, Uiterwaal C, Dalmeijer G, van der Ent C, Hoek G, Karssenberg D

Abstract
BACKGROUND: Air pollution has been shown to promote cardiovascular disease in adults. Possible mechanisms include air pollution induced changes in arterial wall function and structure. Atherosclerotic vascular disease is a lifelong process and childhood exposure may play a critical role. We investigated whether air pollution is related to arterial wall changes in 5-year old children. To this aim, we developed an air pollution exposure methodology including time-weighted activity patterns improving upon epidemiological studies which assess exposure only at residential addresses.
METHODS: The study is part of an existing cohort study in which measurements of carotid artery intima-media thickness, carotid artery distensibility, elastic modulus, diastolic and systolic blood pressure have been obtained. Air pollution assessments were based on annual average concentration maps of Particulate Matter and Nitrogen Oxides at 5 m resolution derived from the European Study of Cohorts for Air Pollution Effects. We defined children's likely primary activities and for each activity we calculated the mean air pollution exposure within the assumed area visited by the child. The exposure was then weighted by the time spent performing each activity to retrieve personal air pollution exposure for each child. Time spent in these activities was based upon a Dutch mobility survey. To assess the relation between the vascular status and air pollution exposure we applied linear regressions in order to adjust for potential confounders.
RESULTS: Carotid artery distensibility was consistently associated with the exposures among the 733 5-years olds. Regression analysis showed that for air pollution exposures carotid artery distensibility decreased per standard deviation. Specifically, for NO2, carotid artery distensibility decreased by - 1.53 mPa- 1 (95% CI: -2.84, - 0.21), for NOx by - 1.35 mPa- 1 (95% CI: -2.67, - 0.04), for PM2.5 by - 1.38 mPa- 1 (95% CI: -2.73, - 0.02), for PM10 by - 1.56 mPa- 1 (95% CI: -2.73, - 0.39), and for PM2.5absorbance by - 1.63 (95% CI: -2.30, - 0.18). No associations were observed for the rest outcomes.
CONCLUSIONS: The results of this study support the view that air pollution exposure may reduce arterial distensibility starting in young children. If the reduced distensibility persists, this may have clinical relevance later in life. The results of this study further stress the importance of reducing environmental pollutant exposures.

PMID: 31096974 [PubMed - in process]

[Vitamin D and pediatrics respiratory diseases].

Rev Chil Pediatr. 2019;90(1):94-101

Authors: Cepeda S J, Zenteno A D, Fuentes S C, Bustos B R

Abstract
The better understanding of the global activity of vitamin D has led to an intense search for its involvement in non-skeletal diseases. This article presents an updated review of the relationship between vitamin D and pediatric respiratory pathology. A literature search was performed in PUBMED using free terms and MESH terms: vitamin D, asthma, respiratory system diseases, and bronchiolitis. Stu dies in human patients younger than 18 years and animals, published in English and Spanish until 2017 were included. 507 articles were found, of which 43 were included. Indirect evidence suggests a role of vitamin D and fetal lung maturation. In relation to pediatric pulmonary pathology, studies are scarce and inconclusive. Recent meta-analyses performed with individualized evaluation of the participants shows an important protective role of vitamin D supplementation in the prevention of severe asthma exacerbations and acute viral infections. In bronchiolitis, the results are contradictory, with no clear relationship between plasma levels and severity. There is not enough evidence to assess the benefits of vitamin D supplementation in cystic fibrosis and tuberculosis. A direct relationship between the severity of sleep-related breathing disorders and vitamin D plasma levels has recently been proposed, although the exact mechanisms involved in this association are unknown. Current information suggests that vitamin D supplementation may represent a cost-effective strategy in redu cing important causes of infant morbidity and mortality.

PMID: 31095224 [PubMed - in process]

[Neutropenia associated with the use of cefepime in pediatric patients with cystic fibrosis].

Rev Chilena Infectol. 2019 Feb;36(1):112-114

Authors: Hernández R, Delpiano L, Amador J, Arias M, Carrasco Delgado J

Abstract
Pulmonary exacerbations of infectious cause are one of the major complications in patients with cystic fibrosis (CF). These are associated with a progressive increase in morbidity and mortality. The treatment depending on the isolated microorganism. The β-lactam antibiotics are generally used which are not exempt from adverse reactions. Next, two report of neutropenia cases are described after prolonged use of cefepime in CF patients.

PMID: 31095211 [PubMed - in process]

Imaging Evaluation of Lung Transplantation Patients: A Time and Etiology-based Approach to High-resolution Computed Tomography Interpretation.

J Thorac Imaging. 2019 May 13;:

Authors: Amadi CC, Galizia MS, Mortani Barbosa EJ

Abstract
Lung transplantation is an established therapeutic option for patients with irreversible end-stage pulmonary disease limiting life expectancy and quality of life. Common indications for lung transplantation include chronic obstructive pulmonary disease, idiopathic pulmonary fibrosis, cystic fibrosis, pulmonary arterial hypertension, and alpha-1 antitrypsin deficiency. Complications of lung transplantation can be broadly divided etiologically into surgical, infectious, immunologic, or neoplastic. Moreover, specific complications often occur within a certain time interval following surgery, which can be broadly classified as early (<6 wk), intermediate (6 wk to 6 mo), and late (>6 mo). Thus, each group of complications can further be categorized on the basis of the time continuum from transplantation. Imaging, primarily by high-resolution computed tomography, plays a critical role in early diagnosis of complications after lung transplantation. Early recognition of complications by the radiologist, and initiation of therapy, contributes to improved morbidity and mortality. However, accurate diagnosis is only feasible if one has a thorough understanding of the major etiologic categories of complications and how they relate to the time course since transplantation. We review imaging manifestations of lung transplant complications via a framework that includes the following major etiologic categories: surgical; infectious; immunologic; and neoplastic; and the following time frames: surgery to 6 weeks; 6 weeks to 6 months; and beyond 6 months. We propose this approach as a logical, evidence-based algorithm to construct a narrow, optimal differential diagnosis of lung transplantation complications.

PMID: 31094899 [PubMed - as supplied by publisher]

Therapeutic delivery: industry update covering January 2019.

Ther Deliv. 2019 May 16;:

Authors: Simpson I

Abstract
This Industry Update covers the period from 1 to 31 January 2019 and is based on information sourced from company press releases, scientific literature, patents and various news websites. Bristol-Myers Squibb (NY, USA) and Celgene (NJ, USA) announced a merger to create one of the largest oncology-focused pharmaceutical businesses. Also, with a focus on oncology, Lilly (IN, USA) announced it is acquiring Loxo Oncology (CT, USA). Alphabet's life sciences business, Verily (CA, USA), announced it had raised new funds to invest in new business opportunities and acquisitions. Talee Bio (PA, USA) and Agenus (MA, USA) announced that they had won grants to support their work in cystic fibrosis and vaccine development, respectively. Biogen (MA, USA) established two new collaborations aimed at expanding its neuroscience pipeline and Voyager Therapeutics (MA, USA) and Neurocrine Biosciences (CA, USA) agreed a collaboration to develop and commercialize gene therapy treatments also in neuroscience. In digital health, Proteus Digital Health (CA, USA) continued the development of digital pill technology, with the initiation of a study in oncology and Otsuka (Tokyo, Japan) agreed a collaboration with Click Therapeutics (NY, USA) to develop digital therapies to treat major depressive disorder. This month also finally saw the approval of Mylan's (PA, USA) generic version of GSK's (Brentford, UK) blockbuster inhaled drug, ADVAIR. Several developments in novel drug delivery methods were reported including the use of microneedles to deliver contraceptives, inhaled delivery of mRNA and a study supporting the use of peptoids to deliver gene therapies into cells. A publication from the Salk Institute (CA, USA) suggested a cellular mechanism might be important in reducing the risk of cancer, and a study by a team at Washington University (MO, USA) supported the possibility of gene therapy to treat neuropathy.

PMID: 31094291 [PubMed - as supplied by publisher]

Challenges with optimizing nutrition in cystic fibrosis.

Expert Rev Respir Med. 2019 May 16;:1-12

Authors: Colombo C, Nobili RM, Alicandro G

Abstract
INTRODUCTION: Optimizing nutrition remains the cornerstone of therapy for patients with cystic fibrosis (CF) since it is associated with better pulmonary function and survival. However, a significant proportion of patients still fail to achieve normal growth and nutritional status. Areas covered. This review describes the current challenges in providing effective nutritional therapy in CF with a focus on the current issues related to energy imbalance, dietary composition, adherence to nutritional recommendations, pancreatic enzyme replacement therapy, and the effects of modulators of the CF transmembrane conductance regulator. Expert opinion. CF is a multisystemic disease that requires a personalized nutritional approach with accurate evaluation of energy balance. There is an urgent need for evidence-based recommendations on the dietary composition, in consideration of the increasing prevalence of overweight, diabetes and the potential effects of fatty acids on inflammation and immune response. More research into new pancreatic enzyme formulations is also required.

PMID: 31094240 [PubMed - as supplied by publisher]

Species distribution and clinical features of infection and colonisation with non-tuberculous mycobacteria in a tertiary care centre, central Germany, 2006-2016.

Infection. 2019 May 15;:

Authors: Wetzstein N, Hügel C, Wichelhaus TA, Hogardt M, Eickmeier O, Küpper-Tetzel CP, Kann G, Just-Nübling G, Stephan C, Wolf T

Abstract
PURPOSE: NTM are ubiquitous bacteria that can cause colonisation and infection in immunocompetent and compromised hosts. The aim of this study was to elucidate the epidemiology of infection or colonisation with NTM for the metropolitan region of Frankfurt, Germany.
METHODS: All patients from whom NTM were isolated within the period from 2006 to 2016 were included in this retrospective analysis. Patient data were retrieved using the local patient data management system. Different groups were formed according to clinical manifestations, underlying diseases and mycobacterial species. They were compared in regard to mortality, duration of infection/colonisation and their geographical origins.
RESULTS: A total of 297 patients with a median of 28 new patients each year were included. Most patients suffered from lung infection or colonisation (72.7%, n = 216), followed by disseminated mycobacteriosis (12.5%, n = 37). The majority were HIV-positive, suffering from malignoma or cystic fibrosis (29.3%, n = 87, 16.2%, n = 48, and 13.8%, n = 41, respectively). 17.2% of patients showed no predisposing condition (n = 51). Mycobacterium avium complex (MAC) species were most frequently isolated (40.7%, n = 121). Infection/colonisation was longest in CF patients (median of 1094 days). The mortality was highest in malignoma patients (52.4%), while CF patients had the lowest overall mortality rate (5.3%). But mortality analysis showed non-significant results within different mycobacterial species and clinical manifestations.
CONCLUSION: NTM remain rare but underestimated pathogens in lung and disseminated disease. MAC were the species most frequently isolated. Depending on species and underlying predispositions, the duration of infection/colonisation can be unexpectedly long.

PMID: 31093923 [PubMed - as supplied by publisher]

Progressive Scoliosis in a Child with Cystic Fibrosis.

Case Rep Pediatr. 2019;2019:1471879

Authors: Castner LM, Nasr SZ, Arteta M

Abstract
We discuss an adolescent female with cystic fibrosis, asthma, and scoliosis who had a rapid decline in her pulmonary function despite typical treatment for a cystic fibrosis exacerbation. Ultimately, she had a fixed airway obstruction likely due to her progressive scoliosis, which improved following surgical intervention.

PMID: 31093403 [PubMed]

RNA Sequencing: A Potentiator of Discovery-Based Research.

Am J Respir Cell Mol Biol. 2019 May 15;:

Authors: Alexander M, Reyfman PA

PMID: 31091961 [PubMed - as supplied by publisher]

Highlights from the 2018 North American cystic fibrosis conference.

Pediatr Pulmonol. 2019 May 15;:

Authors: Martiniano SL, Daines CL, Dellon EP, Esther CR, Muhlebach MS, Ong T, Rabinowitz EC, Toprak D, Zemanick ET

Abstract
The 32nd annual North American Cystic Fibrosis Conference was held in Denver, CO on Oct. 18 to 20, 2018. This review highlights presentations in several topic areas, including the pathophysiology and basic science of cystic fibrosis lung disease, clinical trials, clinical care, and quality improvement. Citations from the conference are by first author and abstract or symposium number, as designated in the previously published supplement.

PMID: 31091021 [PubMed - as supplied by publisher]

BODY MASS INDEX AND ALBUMIN LEVELS ARE ASSOCIATED WITH PULMONARY FUNCTION PARAMETERS IN PEDIATRIC SUBJECTS WITH CYSTIC FIBROSIS.

Rev Paul Pediatr. 2019 May 09;:

Authors: Simon MISDS, Paulo GCF, Marostica JC

Abstract
OBJECTIVE: To evaluate the association of body mass index (BMI) and albumin with pulmonary function in cystic fibrosis (CF) pediatric subjects.
METHODS: This is a cross-sectional study with clinically stable CF's subjects. Clinical (pulmonary function) and nutritional evaluation (body mass index and albumin) were performed. Univariate analysis was performed using simple linear correlations. Regression analysis was performed using an exit level of p<0.05.
RESULTS: Seventy-eight CF's subjects (mean age 12.8±3.8 years) with mean albumin 4.2±0.4 mg/dL, predicted forced expiratory volume in 1 second (FEV1%) 80.8±22.6 and BMI median percentile 51.2 (1.3-97.7). In the multiple regression models, albumin, age and BMI percentile were associated with pulmonary function. Subjects with lower than 25 BMI percentile had 12.2% lower FEV1%. An albumin increase of 0.1 mg was associated with 2.7% increase in predicted FEV1%, and one year increase in age was associated with reduction in 1.2% of predicted FEV1%.
CONCLUSIONS: BMI percentile, albumin and age were independently associated with predicted FEV1% in a tertiary referral hospital.

PMID: 31090852 [PubMed - as supplied by publisher]

Serum IgE and IgG reactivity to Aspergillus recombinant antigens in patients with cystic fibrosis.

J Med Microbiol. 2019 May 15;:

Authors: Alghamdi NS, Barton R, Wilcox M, Peckham D

Abstract
PURPOSE: The diagnosis of aspergillosis in cystic fibrosis (CF) patients remains a challenge due to overlapping features of both diseases. This is further complicated by inconsistent antibody reactivity to the currently used crude antigen, which has led a more focused evaluation of the efficacy of IgE response to a number of pure Aspergillus fumigatus recombinant proteins in patients with CF and asthma. In this study, we dissected the IgE and IgG responses to multiple A. fumigatus recombinant antigens in CF patients with different Aspergillus diseases.
METHODOLOGY: Serum IgE and IgG antibodies were measured in 12 CF patients with allergic bronchopulmonary aspergillosis (ABPA), 12 with Aspergillus sensitization (AS) and 12 with Aspergillus bronchitis (AB) against recombinant antigens Asp f1, f2, f3, f4 and f6.
RESULTS: The ABPA group showed significantly greater IgE reactivity to Asp f1, f2, f3 and f4 compared to patients with AS. Patients with AB expressed higher IgG positivity to Asp f1 and Asp f2 compared with those with ABPA. There were very low IgE antibody levels against all recombinant antigens in patients with AS. Aspf1 IgG reactivity in ABPA patients correlated with positive culture.
CONCLUSION: The use of multiple recombinant antigens may improve the diagnostic accuracy in CF complicated with ABPA or AB. Asp f1 reactivity may relate to the presence of actively growing Aspergillus spp., which might be a useful marker for guiding antifungal therapy in ABPA.

PMID: 31090534 [PubMed - as supplied by publisher]

Image quality comparison between model-based iterative reconstruction and adaptive statistical iterative reconstruction chest computed tomography in cystic fibrosis patients.

J Med Imaging Radiat Oncol. 2019 May 15;:

Authors: Lin S, Lin M, Lau KK

Abstract
INTRODUCTION: Cystic fibrosis (CF) predominantly affects young adults. Accurate radiological assessment of pulmonary disease is vital for predicting exacerbations, one of the leading causes of morbidity and mortality. We evaluated the image quality of model-based iterative reconstruction (MBIR) ultra-low-dose CT chest (ULD-CT) in CF evaluation.
METHODS: We compared ULD-CT with standard adaptive statistical iterative reconstruction (ASIR) low-dose CT (LD-CT). Subjective assessment of contrast and noise were performed for each study. Background noise, signal to noise ratio (SNR) and contrast to noise ratio (CNR) were calculated and compared between the CT studies. Conspicuity of major structures was assessed. These aspects of image quality were compared to determine whether ULD-CT was superior to LD-CT in assessment of CF.
RESULTS: The ULD-CT achieved median effective dose of 0.073 mSv, comparable to one standard chest radiograph and significantly lower than the median LD-CT dose of 1.22 mSv. ULD-CT had lower subjective contrast and higher subjective noise when compared to LD-CT. Objectively measured background noise was lower in ULD-CT (16.33 HU vs 38.53 HU, P < 0.0001) compared to LD-CT. ULD-CT had higher median CNR (52.65 vs 22.09, P < 0.0001) and SNR in lung (9.08 vs 7.29, P = 0.002) compared to LD-CT. ULD-CT was equal to LD-CT in identification of trachea, bronchi, pleural and pericardium. Interobserver reliability showed agreement of 80-92%.
CONCLUSIONS: The image quality of ULD-CT is similar to LD-CT, at 1/16th the dose. MBIR constructed ULD-CT is an effective imaging modality for CF surveillance, with potential applications in other disease settings.

PMID: 31090256 [PubMed - as supplied by publisher]

Lung infection caused by Pseudomonas aeruginosa in a CD26/DPP4 deficient F344 rat model.

Inflamm Res. 2019 May 14;:

Authors: Neuhaus M, Munder A, Schipke J, Schmiedl A

Abstract
BACKGROUND: Pseudomonas aeruginosa (PA) is the most important opportunistic pathogen in causing nosocomial infections and, furthermore, poses a permanent threat for severe chronic infections in patients with cystic fibrosis or COPD. The transmembrane protein CD26 with dipeptidyl peptidase-4 (DPP4) activity shows an increased expression in inflamed tissue. We tested whether CD26/DPP4 deficiency leads to reduced inflammation and decreased structural damage when infected with PA.
METHODS: CD26/DPP4+ and CD26/DPP4- rats were instilled intratracheally with NaCl (controls) or with PA. Six hours later, bacterial distribution was detected with the in vivo imaging system 200 (IVIS). Lungs were then processed for molecular biology, light and electron microscopy and analyzed qualitatively, quantitatively and stereologically. Bacterial numbers were determined in homogenized lungs.
RESULTS: Compared to saline treated controls, in both infected groups (1) the acinar airspace was significantly increased, (2) the volume density of the alveolar epithelium was significantly decreased, (3) the septal thickness was significantly reduced, (4) more than 40% of the alveolar epithelial surface was damaged, and up to 36% of the epithelial surface was covered with edema. In infected CD26- rats, the increase in lung weight was significantly less pronounced, the portion of edematous alveolar airspace was significantly lower and the part of edema interspersed with PA was decreased significantly.
CONCLUSIONS: CD26/DPP4 deficiency resulted in reduced pulmonary edema under sublethal PA infection, implicating a role for CD26 in infection progression. The partly pronounced structural damage may mask further possible influences of CD26 on the inflammatory response.

PMID: 31089745 [PubMed - as supplied by publisher]

Correction: Sequencing as a first-line methodology for cystic fibrosis carrier screening.

Genet Med. 2019 May 15;:

Authors: Beauchamp KA, Taber KAJ, Grauman PV, Spurka L, Lim-Harashima J, Svenson A, Goldberg JD, Muzzey D

Abstract
The original version of this Article contained an error in Figure 3. Specifically, the result "3 (67%) TOP" should read "2 (67%) TOP." This has now been corrected in both the PDF and HTML versions of the Article.

PMID: 31089271 [PubMed - as supplied by publisher]

IL-1β, IL-23, and TGF-β drive plasticity of human ILC2s towards IL-17-producing ILCs in nasal inflammation.

Nat Commun. 2019 May 14;10(1):2162

Authors: Golebski K, Ros XR, Nagasawa M, van Tol S, Heesters BA, Aglmous H, Kradolfer CMA, Shikhagaie MM, Seys S, Hellings PW, van Drunen CM, Fokkens WJ, Spits H, Bal SM

Abstract
Innate lymphoid cells (ILCs) are crucial for the immune surveillance at mucosal sites. ILCs coordinate early eradication of pathogens and contribute to tissue healing and remodeling, features that are dysfunctional in patients with cystic fibrosis (CF). The mechanisms by which ILCs contribute to CF-immunopathology are ill-defined. Here, we show that group 2 ILCs (ILC2s) transdifferentiated into IL-17-secreting cells in the presence of the epithelial-derived cytokines IL-1β, IL-23 and TGF-β. This conversion is abrogated by IL-4 or vitamin D3. IL-17 producing ILC2s induce IL-8 secretion by epithelial cells and their presence in nasal polyps of CF patients is associated with neutrophilia. Our data suggest that ILC2s undergo transdifferentiation in CF nasal polyps in response to local cytokines, which are induced by infectious agents.

PMID: 31089134 [PubMed - in process]

Focus on echocardiographic right ventricular strain analysis in cystic fibrosis adults without cardiovascular risk factors: a case-control study.

Intern Emerg Med. 2019 May 14;:

Authors: Sciatti E, Vizzardi E, Bonadei I, Valentini F, Menotti E, Prati F, Dallapellegrina L, Berlendis M, Poli P, Padoan R, Metra M

Abstract
Strain echocardiography is able to detect subclinical ventricular systolic and diastolic dysfunction. Prolonged survival to cystic fibrosis favors heart and vessel involvement. The purpose of the present study was to compare clinically stable adult patients affected by cystic fibrosis without overt pulmonary hypertension with controls to evaluate right ventricular (RV) systolic and diastolic function by means of strain and tissue Doppler imaging (TDI), respectively. 22 adults affected by cystic fibrosis and 24 healthy volunteers matched for age and sex were enrolled. None had known cardiovascular risk factors or overt pulmonary hypertension. All people underwent blood pressure measurement and transthoracic echocardiography. Cystic fibrosis patients showed higher sPAP [median 25 (IQR 21-30) vs 22 (22-22) mmHg; p = 0.02] and more frequent RV diastolic dysfunction (p < 0.001). Among cases, some RV systolic parameters were significantly altered than controls, such as TAPSE [20 (18-24) vs. 23 (21-28) mm; p = 0.001], FAC [34 (26-44) vs. 49 (48-50)%; p < 0.001], midwall tissue strain [- 25.0 (- 31.3 to - 22.8) vs. - 30.5 (- 31.8 to - 29.3)%; p = 0.03], apical tissue strain [- 22 (- 29.3 to - 19.0) vs. - 30.5 (- 32.8 to - 28.3)%; p = 0.001] and 2D strain [- 22.0 (- 25.1 to - 19.0) vs. - 29.5 (- 31.8 to - 27.3)%; p < 0.001]. Finally, 2D strain correlated with spirometric FEV1 (ρ = - 0.463, p = 0.03) and nearly with FEF25-75% (ρ = - 0.393, p = 0.07). Our study confirmed a RV subclinical systo-diastolic dysfunction in clinically stable patients affected by cystic fibrosis without overt pulmonary hypertension nor cardiovascular risk factors. This may be due to systemic inflammation and temporary recurrent pulmonary hypertension. We retain that RV 2D strain and TDI echocardiography could become an important tool in the follow-up of these patients.

PMID: 31087253 [PubMed - as supplied by publisher]

Bruising as the first sign of exocrine pancreatic insufficiency in infancy.

Med Pharm Rep. 2019 Apr;92(2):200-204

Authors: Szabo CE, Man OI, Şerban RS, Kiss E, Lazăr CF

Abstract
Exocrine pancreatic insufficiency is an important cause of chronic malnutrition, secondary to maldigestion-malabsorption, which can be caused in children especially by cystic fibrosis, but also by other much rarer diseases. The case of a 6 months and 3 weeks old male pediatric patient is reported, who was admitted to the clinic for head and forearms bruising. Laboratory findings identified vitamin K deficiency as the cause of the cutaneous hemorrhagic syndrome. Further investigations revealed association of steatorrhea (which is a marker of fat malabsorption), iron-deficiency anemia and hypovitaminosis D, which had been produced by nutritional deficiencies caused by malabsorption syndrome. From the numerous disorders that could be associated with pancreatic insufficiency in children, the following conditions had been excluded: cystic fibrosis (mucoviscidosis), cow's milk protein intolerance, gluten-sensitive enteropathy (coeliac disease), Shwachman-Diamond syndrome, abetalipoproteinemia, etc. Based upon decreased levels of stool pancreatic elastase in repeated measurements, together with low serum lipase, the final diagnosis of exocrine pancreatic insufficiency was established. Treatment of this case consisted mainly in pancreatic enzyme replacement therapy, but also oral iron supplementation and dietary supplements with fat-soluble vitamins (A, D, E, K). The outcome was favorable, characterized by normalization of intestinal passage, ascending growth curve and normalization of the majority of laboratory tests values that were modified between the time of patient admission to our clinic and initiation of specific therapy (serum level of vitamin K, vitamin D and lipase, coagulation profile, hemoglobin and red blood cell indexes), as well as higher value of fecal pancreatic elastase.

PMID: 31086851 [PubMed]