Overcoming barriers to a successful transition from pediatric to adult care

As life expectancy for people with cystic fibrosis (CF) has increased dramatically, so has the need for a guided, structured transition from pediatric to adult-focused care. A formalized transition program allows for seamless transfer of patients between providers, helping to ensure continuity of care, and avoid potential declines associated with inconsistent medical care. New CF Center guidelines issued by the CFF strongly recommend that each center establish a transition program for age-appropriate transition to an adult CF clinic. In this article, we explore the remaining barriers to establishing a transition program in a CF Center and offer examples of several successful models. We describe CFF-sponsored and other initiatives that exist to support centers in establishing a transition program and discuss the need for ongoing research in this area

Breathing easier: Addressing the challenges of aerosolizing medications to infants and preschoolers

An increasing number of patients are dependent on aerosolized therapy to manage pulmonary diseases, including asthma, cystic fibrosis, and pulmonary arterial hypertension. An aerosol therapy is only useful if it can be appropriately and consistently delivered in the desired dose to the lower respiratory tract. Many factors affect this deposition in young children, including anatomical and physiologic differences between adults and children, patient-mask interface issues, the challenge of administering medication to uncooperative children, and behavioral adherence. Moreover, the techniques used to assess aerosol delivery to pediatric patients need to be carefully evaluated as new therapies and drug-device combinations are tested. In this review, we will address some of the challenges of delivering aerosolized medications to pediatric patients

Eosinophilic esophagitis in cystic fibrosis: A case series and review of the literature

Patients with cystic fibrosis (CF) frequently experience gastrointestinal symptoms including nausea, emesis, malnutrition and indigestion; diseases such as gastroesophageal reflux disease (GERD), distal intestinal obstructive syndrome, and cholelithiasis are commonly implicated. We have recently diagnosed eosinophilic esophagitis (EoE) in three patients with CF. EoE is a TH-2 driven, allergen-mediated disease which causes esophageal eosinophilia and presents with symptoms of nausea, feeding intolerance, regurgitation, and dysphagia. EoE is diagnosed when esophageal biopsies reveal greater than 15 eosinophils per high power field in the setting of the appropriate clinical scenario and after exclusion of other causes of esophageal eosinophilia. Although described with increasing frequently in the gastrointestinal literature, there have been no prior cases documenting the co-existence of EoE and CF. We speculate that this is related to lack of familiarity with EoE symptoms by CF providers. We present three patients with CF diagnosed with EoE and review the current literature regarding diagnosis and management, focusing on management issues in patients with CF

Dynamic Perfluorinated Gas MRI Shows Improved Lung Ventilation in People with Cystic Fibrosis after Elexacaftor/Tezacaftor/Ivacaftor: An Observational Study

The availability of highly effective CFTR modulators is revolutionizing the treatment of cystic fibrosis (CF) and drastically improving outcomes. MRI-based imaging modalities are now emerging as highly sensitive endpoints, particularly in the setting of mild lung disease. Adult CF patients were recruited from a single center prior to starting treatment with E/T/I. The following studies were obtained before and after one month on treatment: spirometry, multiple breath nitrogen washout (MBW), 1H UTE MRI (structural images) and 19F MRI (ventilation images). Changes between visits were calculated, as were correlations between FEV1, lung clearance index (LCI), MRI structural scores, and MRI-based ventilation descriptors. Eight subjects had complete datasets for evaluation. Consistent with prior clinical trials, FEV1 and LCI improved after 28 days of E/T/I use. 1H UTE MRI detected improvements in bronchiectasis/airway wall thickening score and mucus plugging score after 28 days of therapy. 19F MRI demonstrated improvements in fractional lung volume with slow gas washout time (FLV↑tau2) and ventilation defect percentage (VDP). Improvements in FLV↑tau2 and VDP correlated with improvement in FEV1 (r = 0.81 and 0.86, respectively, p < 0.05). This observational study establishes the ability of 19F MRI and 1H UTE MRI to detect improvements in lung structure and function after E/T/I treatment. This study supports further development of 19F MRI and 1H UTE MRI as outcome measures for cystic fibrosis research and drug development

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Intrapleural hemorrhage after administration of tPA: a case report and review of the literature

Objective: Intrapleural fibrinolytic enzymes have been used for over 60 years in the treatment of complicated pleural effusions to lyse loculations and promote resolution. Despite this extensive history of use, however, little is known about complications that may arise with the use of this therapy. Here we discuss a patient with chronic renal failure on hemodialysis who developed an intrapleural hemorrhage after the administration of intrapleural tPA to treat a complicated parapneumonic effusion. A review of the literature examines the efficacy and safety of this therapy, focusing on bleeding complications. Specific attention is paid to patients who have underlying coagulopathies or who are receiving anticoagulation. Data sources: A review of the literature, as indexed in PubMed, was undertaken using the following search terms in combination: tPA, pleural effusion, complications of thrombolytics, and intrapleural hemorrhage. The search was inclusive of patients under the age of 18, but was limited by English language and human subjects. Study selection/data extraction: All relevant articles identified during the search were reviewed. Those studies that reported on bleeding complications, or lack thereof, were included in this review. Limitations of each article are noted in the text. Conclusions: Multiple studies, including a 2000 ACP consensus statement and a 2008 Cochrane review, indicate the need for further investigations to evaluate the safety and efficacy of intrapleural thrombolytics for the treatment of complicated pleural effusions and empyemas. Limited studies specifically address bleeding complications, especially in subpopulations of patients receiving concurrent anticoagulant therapy