Search

Aim: To examine the trajectory of forced expiratory volume in 1 s (FEV 1 ) using data from the European Cystic Fibrosis Society patient registry (ECFPR) collected from 2008 to 2016, i.e. the era before highly effective modulator therapy (HEMT). We evaluated risk factors for FEV 1 decline., Methods: The study population included patients with a confirmed diagnosis of cystic fibrosis recorded in the ECFPR (2008-2016). The evolution of FEV 1 % predicted (%FEV 1 ) with age, and the yearly change in %FEV 1 were evaluated. Risk factors considered were cystic fibrosis transmembrane conductance regulator ( -CFTR ) mutation class, gender, age at diagnosis, neonatal screening, meconium ileus, sweat chloride concentration at diagnosis and country's income level., Results: We used 199 604 FEV 1 recordings from 38 734 patients. The fastest decline was seen during puberty and in patients diagnosed before the age of 10 years. Males had a higher %FEV 1 , but a higher yearly %FEV 1 loss between the ages of 15 and 25 years. We showed stabilisation and even improvement in %FEV 1 over age in adults with a class III CFTR mutation, but a steady decline in patients homozygous for F508del or with both mutations of classes I/II. A faster decline in %FEV 1 was found in patients from low-income countries compared to a similar %FEV 1 evolution in patients from middle- and high-income countries., Conclusions: These longitudinal FEV 1 data reflect the reality of cystic fibrosis across Europe in the era pre-HEMT, and can serve as baseline for comparison with the post-HEMT era. The similar evolution in middle- and high-income countries underlines opportunities for low-income countries., Competing Interests: Conflict of interest: The authors declare no conflict of interest., (Copyright ©The authors 2023.)

Hereditary hemorrhagic telangiectasia (HHT, Osler-Weber-Rendu disease) is a rare multisystem vascular disorder causing chronic gastrointestinal bleeding, epistaxis, and severe anemia. Bevacizumab, an anti-vascular endothelial growth factor antibody, may be effective to treat bleeding in HHT. This international, multicenter, retrospective study evaluated the use of systemic bevacizumab to treat HHT-associated bleeding and anemia at 12 HHT treatment centers. Hemoglobin, epistaxis severity score, red cell units transfused, and intravenous iron infusions before and after treatment were evaluated using paired means testing and mixed-effects linear models. 238 HHT patients received bevacizumab for a median of 12 (range, 1-96) months. Compared with pretreatment, bevacizumab increased mean hemoglobin by 3.2 g/dL (95% CI, 2.9-3.5 g/dL) [mean hemoglobin 8.6 (8.5, 8.8) g/dL versus 11.8 (11.5, 12.1) g/dL, p<0.0001)] and decreased the epistaxis severity score (ESS) by 3.4 (3.2-3.7) points [mean ESS 6.8 (6.6-7.1) versus 3.4 (3.2-3.7), P<0.0001] during the first year of treatment. Compared with 6 months pretreatment, RBC units transfused decreased by 82% [median of 6.0 (IQR 0.0-13.0) units versus 0 (IQR, 0.0-1.0) units, P<0.0001] and iron infusions decreased by 70% [median of 6.0 (1.0-18.0) infusions versus 1.0 (0.0-4.0) infusions, P<0.0001] during the first 6 months of bevacizumab treatment. Outcomes were similar regardless of underlying pathogenic mutation. Following initial induction infusions, continuous/scheduled bevacizumab maintenance achieved higher hemoglobin and lower ESS than intermittent/as needed maintenance but with more drug exposure. Bevacizumab was well tolerated: hypertension, fatigue, and proteinuria were the most common adverse events. Venous thromboembolism occurred in 2% of patients. In conclusion, systemic bevacizumab was safe and effective to manage chronic bleeding and anemia in HHT.

Description: Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant disease with an estimated prevalence of 1 in 5000 that is characterized by the presence of vascular malformations (VMs). These result in chronic bleeding, acute hemorrhage, and complications from shunting through VMs. The goal of the Second International HHT Guidelines process was to develop evidence-based consensus guidelines for the management and prevention of HHT-related symptoms and complications., Methods: The guidelines were developed using the AGREE II (Appraisal of Guidelines for Research and Evaluation II) framework and GRADE (Grading of Recommendations Assessment, Development and Evaluation) methodology. The guidelines expert panel included expert physicians (clinical and genetic) in HHT from 15 countries, guidelines methodologists, health care workers, health care administrators, patient advocacy representatives, and persons with HHT. During the preconference process, the expert panel generated clinically relevant questions in 6 priority topic areas. A systematic literature search was done in June 2019, and articles meeting a priori criteria were included to generate evidence tables, which were used as the basis for recommendation development. The expert panel subsequently convened during a guidelines conference to conduct a structured consensus process, during which recommendations reaching at least 80% consensus were discussed and approved., Recommendations: The expert panel generated and approved 6 new recommendations for each of the following 6 priority topic areas: epistaxis, gastrointestinal bleeding, anemia and iron deficiency, liver VMs, pediatric care, and pregnancy and delivery (36 total). The recommendations highlight new evidence in existing topics from the first International HHT Guidelines and provide guidance in 3 new areas: anemia, pediatrics, and pregnancy and delivery. These recommendations should facilitate implementation of key components of HHT care into clinical practice.

Objective: To evaluate the effect of allergic bronchopulmonary aspergillosis (ABPA) on FEV 1 percent predicted in children and adolescents with cystic fibrosis., Design: Longitudinal data analysis (2008-2010)., Setting: Patients participating in the European Cystic Fibrosis Society Patient Registry., Participants: 3350 patients aged 6-17 years., Main Outcome Measure: FEV 1 percent predicted was the main outcome measure (one measurement per year per child). To describe the effect of ABPA (main explanatory variable) on FEV 1 while controlling for other prognostic factors, a linear mixed effects regression model was applied., Results: In 2008, the mean (±SD) FEV 1 percent predicted was 78.6 (±20.6) in patients with ABPA (n=346) and 88 (±19.8) in those without ABPA (n=2806). After considering other variables, FEV 1 in subjects with ABPA on entry to the study was 1.47 percentage points lower than FEV 1 in patients of similar age without ABPA (p=0.003). There was no FEV 1 decline associated with ABPA over the subsequent study years as the interaction of ABPA with age was not significant (p>0.05). For patients aged 11.82 years (population mean age), poor body mass index had the greatest impact on FEV 1 in 2008, followed by high-risk genotype (two severe mutations), female gender, diabetes mellitus, chronic Pseudomonas aeruginosa infection and ABPA in descending order of effect size., Conclusions: In contrast to the common clinical belief of ABPA having a serious impact on lung function, the difference in FEV 1 between young patients with and without the complication was found to be modest when the effect of other prognostic factors was considered., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Background: The forced oscillation technique is a noninvasive and effort-independent technique that is well suited for lung function measurement in young children. FOT employs small-amplitude pressure oscillations superimposed on normal breathing. Therefore, it has the advantage over conventional lung function techniques in that it does not require patient cooperation for conducting respiratory maneuvers., Objectives: To test the feasibility of the FOT test in preschool children and to compare the results to the commonly used spirometry before and after the administration of bronchodilator therapy., Methods: Forty-six children (median age 4.9 years, range 1.8-18.3) attending the pulmonary clinic at Schneider Children's Medical Center tried to perform FOT and routine spirometry. Results were retrospectively analyzed., Results: Of the 46 children 40 succeeded in performing FOT and only 29 succeeded in performing simple spirometry. All but one of the 32 children aged 4 years and above (97%) could perform both tests. Nine of 14 children (64%) aged 4 and less could perform the FOT but only 3 (21%) could perform spirometry. Baseline values of respiratory resistance measured at 6 Hz (R6) negatively correlated with body length (r2 = 0.68, P < 0.005). Twenty-four children performed both tests before and after bronchodilator therapy. A significant concordance was found between the measured responses to bronchodilators by FOT and spirometry (P < 0.01). Only one child had a negative response by FOT but a positive response by spirometry., Conclusions: The FOT is a simple, non-invasive technique that does not require subject cooperation and thus can be utilized for measuring lung function in children as young as 2 years old. Furthermore, the FOT was shown to reliably measure response to bronchodilator therapy.

Osler-Weber-Rendu Syndrome or Hereditary Hemorrhagic Telangiectasia (HHT) is an autosomal dominant inherited disease. It is more common than previously estimated, with a prevalence of 1:5,000-10,000. It was described mainly in adults, however recent studies suggest a similar presentation in children. The clinical characteristics include epistaxis, skin and mucosal telangiectases and visceral arteriovenous malformations (AVMs), and diagnostic criteria for this disease have been established. Epistaxis and telangiectases appear in most patients. Epistaxis can be massive and difficult to treat. Pulmonary AVMs are present in 30% of patients and can result in right to left shunt, with dyspnea, cyanosis and polycythemia. The shunt, bypassing the pulmonary capillary bed, can also result in paradoxical emboli to the brain, strokes and brain abscesses. Different screening methods have been suggested for pulmonary AVMs, preferably high resolution chest CT and bubble echocardiography. Definite diagnosis is made by pulmonary angiography. The recommended treatment is pulmonary embolization and recent studies show excellent results in adults and children. Cerebral AVMs appear in 5% of patients and can result in cerebral hemorrhage. MRI is the recommended screening test. There is a debate as to whether to treat asymptomatic patients with cerebral AVMs. Mutations in two genes have been shown to cause 2 types of this disease. Both genes encode proteins, endoglin and ALK-1, which are components of the TGF-beta receptor. Mutations in these genes cause HHT1 and HHT2, respectively. Screening family members of patients for pulmonary AVMs is recommended, and children should probably be included.