An international, multicenter study of intravenous bevacizumab for bleeding in hereditary hemorrhagic telangiectasia: the InHIBIT-Bleed study

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,

Incidence of SARS-CoV-2 in people with cystic fibrosis in Europe between February and June 2020

Background Viral infections can cause significant morbidity in cystic fibrosis (CF). The current Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) pandemic could therefore have a serious impact on the health of people with CF (pwCF). Methods We used the 38-country European Cystic Fibrosis Society Patient Registry (ECFSPR) to collect case data about pwCF and SARS-CoV-2 infection. Results Up to 30 June 2020, 16 countries reported 130 SARS-CoV-2 cases in people with CF, yielding an incidence of 2.70/1000 pwCF. Incidence was higher in lung-transplanted patients (n=23) versus non-transplanted patients (n=107) (8.43 versus 2.36 cases/1000). Incidence was higher in pwCF versus the age-matched general population in the age groups <15, 15-24, and 25-49 years (p<0.001), with similar trends for pwCF with and without lung transplant. Compared to the general population, pwCF (regardless of transplantation status) had significantly higher rates of admission to hospital for all age groups with available data, and higher rates of intensive care, although not statistically significant. Most pwCF recovered (96.2%), however 5 died, of whom 3 were lung transplant recipients. The case fatality rate for pwCF (3.85%, 95% CI: 1.26-8.75) was non-significantly lower than that of the general population (7.46%; p=0.133). Conclusions SARS-CoV-2 infection can result in severe illness and death for pwCF, even for younger patients and especially for lung transplant recipients. PwCF should continue to shield from infection and should be prioritized for vaccination

Exercise testing in children with lung diseases

Exercise is an important aspect of health and development in children. By placing the pulmonary system under stress, exercise testing may reveal subtle dynamic abnormalities that are not apparent on conventional static pulmonary function tests. Furthermore, exercise testing assesses the functional impact of respiratory disease on children. Exercise testing has been used in children with a variety of respiratory diseases such as exercise induced bronchoconstriction, asthma, cystic fibrosis and bronchopulmonary dysplasia to assess the severity of disease as well as response to various interventions. Furthermore, there is good evidence that exercise testing is a useful tool to help determine prognosis in patients with cystic fibrosis. In addition to the clinical utility, exercise testing is also becoming an increasingly important outcome measure in research studies

Topical propranolol improves epistaxis in patients with hereditary hemorrhagic telangiectasia - a preliminary report

Abstract Background Severe epistaxis is often difficult to control in patients with hereditary hemorrhagic telangiectasia (HHT). Propranolol has been shown to have antiangiogenic properties in vitro and in vivo and is commonly used to treat hemangiomas. We present our experience with topical nasal propranolol for the treatment of moderate to severe epistaxis in patients with HHT. Methods Retrospective case series. Six patients with HHT were treated with 0.5 cm3 of 1.5% propranolol gel, applied to each nostril twice daily for at least 12 weeks. Outcome measures were epistaxis severity score (ESS), hemoglobin level, and number of blood transfusions prior to and while on treatment. Local and systemic side effects were recorded. Results The mean duration of treatment was 30 ± 5.6 weeks. A significant improvement in the ESS was found in all patients, with a mean decrease from 6.4 ± 2.1 at treatment onset to 3.5 ± 1.7 at 12 weeks (p = 0.028). Hemoglobin level increased significantly from 8.4 ± 3.1 to 11.0 ± 1.8 g/dL at 12 weeks (p = 0.043). The mean number of blood transfusions decreased from 4.5 ± 4.9 before treatment to 2.5 ± 2.9 at 12 weeks and 0.3 ± 0.8 at 24 weeks, but the difference did not reach statistical significance (p = 0.109 for both). No significant side effects of treatment were recorded. Conclusions These preliminary results suggest that topical propranolol may be effective for the treatment of epistaxis in patients with HHT. A prospective controlled trial is required to confirm our findings

Changing epidemiology of the respiratory bacteriology of patients with cystic fibrosis&#8211;data from the European cystic fibrosis society patient registry

Background: Monitoring changes in the epidemiology of cystic fibrosis (CF) pathogens is essential for clinical research, quality improvement, and clinical management. Methods: We analyzed data reported to the European Cystic Fibrosis Society Patient Registry (ECFSPR) from 2011 to 2016 to determine the overall and the age-specific annual prevalence and incidence of selected CF pathogens and their trends during these years. The ECFSPR collects data on three chronic infections: Pseudomonas aeruginosa (PsA), Burkholderia cepacia complex Species (BCC) and Staphylococcus aureus (SA), as well as on the occurrence of non-tuberculous mycobacteria (NTM) and Stenotrophomonas maltophilia (SM). The same analyses were performed for different country groups, according to their gross national income (GNI). Results: The pathogens with the highest prevalence were SA and PsA, with prevalence, in 2016, equal to 38.3% and 29.8% respectively, followed by SM (8.1%). The pathogens with the lowest prevalence were NTM (3.3%) and BCC (3.1%). The overall prevalence and incidence significantly decreased for PsA; they also decreased for BCC, while they increased significantly for SA. The overall prevalence of NTM and SM increased significantly. The most considerable prevalence changes were observed for PsA, which decreased across all income country groups and all age strata (with the exception of 0\u20131 years) The prevalence and incidence of pathogens differed significantly according to GNI. Conclusions: The epidemiology of CF pathogens in Europe has changed; epidemiologic data differ significantly among countries with different socio-economic status. The causes of these observations are multifactorial and include improvements in clinical care and infection control

Thoracoscopic resection of pulmonary lesions in Israel: The mentorship approach

Background: Most congenital pulmonary airway malformations (CPAMs) are detected antenatally. The majority of newborns are asymptomatic. Patients are prone to subsequent respiratory complications and to a lesser extent malignant transformation remains concerning. In Israel, until 2013, pediatric surgeries were performed by thoracotomy. To minimize its morbidity, we introduced thoracoscopy using a mentorship approach. We present our experience with thoracoscopic resections coordinated by the mentorship of a pediatric worldwide leader in his field and compare our results with resections performed by thoracotomy. Materials and Methods: A retrospective review of records of children operated between 2013 and 2020 was conducted. Data were compared using t-test for quantitative variables. Results: Fifty patients were operated by thoracoscopy with a median age of 4 years, a thoracoscopic lobectomy performed in 68%. There was no conversion with a median length of stay (LOS) of 3½ days. Thirty patients were operated by thoracotomy by a thoracic surgeon with a median age of 3.5 years. A lobectomy was performed in 87% with a median LOS of 7 days. Conclusions: Thoracoscopic lobectomy is a technically demanding procedure with a long learning curve, strongly related to the low volume of cases. The role of a mentorship program in acquiring those surgical skills is crucial through standardization of the technique applied and supervised by the mentor. Early thoracoscopy for congenital pulmonary lesions at an early age can be achieved with a low conversion rate and minimal complications creating a change in the paradigm of practice when considering surgery for CPAM in Israel

Dynamic Hyperinflation While Exercising—A Potential Predictor of Pulmonary Deterioration in Cystic Fibrosis

Background: Lung function deterioration in cystic fibrosis (CF) is typically measured by a decline in the forced expiratory volume in one second (FEV1%), which is thought to be a late marker of lung disease. Dynamic hyperinflation (DH) is seen in obstructive lung diseases while exercising. Our aim was to assess whether DH could predict pulmonary deterioration in CF; a secondary measure was the peak VO2. Methods: A retrospective study was conducted of people with CF who performed cardiopulmonary exercise tests (CPETs) during 2012–2018. The tests were classified as those demonstrating DH non-DH. Demographic, genetic, and clinical data until 12.2022 were extracted from patient charts. Results: A total of 33 patients aged 10–61 years performed 41 valid CPETs with valid DH measurements; sixteen (39%) demonstrated DH. At the time of the CPETs, there was no difference in the FEV1% measurements between the DH and non-DH groups (median 83.5% vs. 87.6%, respectively; p = 0.174). The FEV1% trend over 4 years showed a decline in the DH group compared to the non-DH group (p = 0.009). A correlation was found between DH and the lung clearance index (LCI), as well as the FEV1% (r = 0.36 and p = 0.019 and r = −0.55 and p = 0.004, respectively). Intravenous (IV) antibiotic courses during the 4 years after the CPETs were significantly more frequent in the DH group (p = 0.046). The peak VO2 also correlated with the FEV1% and LCI (r = 0.36 and p = 0.02 and r = −0.46 and p = 0.014, respectively) as well as with the IV antibiotic courses (r = −0.46 and p = 0.014). Conclusions: In our cohort, the DH and peak VO2 were both associated with lung function deterioration and more frequent pulmonary exacerbations. DH may serve as a marker to predict pulmonary deterioration in people with CF

Disease severity of people with cystic fibrosis carrying residual function mutations: Data from the ECFS Patient Registry

RATIONAL: People with cystic fibrosis carrying residual function (RF) mutations are considered to have a mild disease course. This may influence caregivers and patients on how intensive the treatments should be. OBJECTIVES: Characterize disease severity of patients carrying RF mutations, using the European CF Society Patient Registry (ECFSPR) data. METHODS: Demographic, clinical characteristics, lung function and death probability of patients carrying at least one RF mutation were analyzed and compared to patients homozygous to minimal function mutations (MF). MAIN RESULTS: Of the 44,594 eligible patients (median age 19.5 years, IQR 10-29.8), 6,636 (14.6%) carried RF mutations, and 37,958 (85.1%) MF mutations. Patients carrying RF mutations were older, diagnosed at a later age, had lower sweat chloride at diagnosis and better FEV1pp at each age group. However, their FEV1pp declined with age and rates of chronic Pseudomonas aeruginosa increased with age. A significant number of patients with RF had FEV1pp similar to patients with MF at each age group. 4.5% of RF patients were treated with oxygen and 2.61% had a lung transplant. With increasing age, 26.6% of RF patients were treated with pancreatic enzymes associated with a more severe lung disease. RF patients had shortened life spans, with mortality starting around the age of 20 years. CONCLUSIONS: Patients carrying an RF mutations experience a decline of pulmonary function with age, leading to life-shortening. Standard of care therapies and augmenting CFTR function may improve their survival and quality of life

Cystic fibrosis related diabetes in Europe: Prevalence, risk factors and outcome; Olesen et al

BACKGROUND Cystic fibrosis related diabetes (CFRD) has implications for morbidity and mortality with several risk factors identified. We studied the epidemiology of CFRD in the large dataset of the European Cystic Fibrosis Society Patient registry. METHODS Data on CF patients were investigated for the prevalence of CFRD as well as for any association with suggested risk factors and effects. RESULTS CFRD increased by approximately ten percentage points every decade from ten years of age. Prevalence was higher in females in the younger age groups. CFRD was associated with severe CF genotypes (OR = 3.11, 95%CI: 2.77-3.48), pancreatic insufficiency (OR = 1.46, 95%CI: 1.39-1.53) and female gender (OR = 1.28, 95%CI: 1.21-1.34). Patients with CFRD had higher odds of being chronically infected with Pseudomonas aeruginosa, Burkholderia cepacia complex and Stenotrophomonas maltophilia than patients without CFRD, higher odds of having FEV1% of predicted <40% (OR = 1.82, 95%CI: 1.70-1.94) and higher odds of having BMI SDS ≤-2 than patients without CFRD (OR = 1.24, 95%CI: 1.15-1.34). CONCLUSIONS Severe genotype, pancreatic insufficiency and female gender remain considerable intrinsic risk factors for early acquisition of CFRD. CFRD is associated with infections, lower lung function and poor nutritional status. Early diagnosis and aggressive treatment of CFRD are more important than ever with increasing life span

Risk factors for forced expiratory volume in 1 s decline in European patients with cystic fibrosis: data from the European Cystic Fibrosis Society Patient Registry

Aim To examine the trajectory of forced expiratory volume in 1 s (FEV1) 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 FEV1 decline. Methods The study population included patients with a confirmed diagnosis of cystic fibrosis recorded in the ECFPR (2008–2016). The evolution of FEV1 % predicted (%FEV1) with age, and the yearly change in %FEV1 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 FEV1 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 %FEV1, but a higher yearly %FEV1 loss between the ages of 15 and 25 years. We showed stabilisation and even improvement in %FEV1 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 %FEV1 was found in patients from low-income countries compared to a similar %FEV1 evolution in patients from middle- and high-income countries. Conclusions These longitudinal FEV1 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