For pediatric rare diseases, the number of patients available to support traditional research methods is often inadequate. However, patients who have similar diseases cluster "virtually" online via social media. This study aimed to (1) determine whether patients who have the rare diseases Fontan-associated protein losing enteropathy (PLE) and plastic bronchitis (PB) would participate in online research, and (2) explore response patterns to examine social media' s role in participation compared with other referral modalities. A novel, internetbased survey querying details of potential pathogenesis, course, and treatment of PLE and PB was created. The study was available online via web and Facebook portals for 1 year. Apart from 2 study-initiated posts on patient-run Facebook pages at the study initiation, all recruitment was driven by study respondents only. Response patterns and referral sources were tracked. A total of 671 respondents with a Fontan palliation completed a valid survey, including 76 who had PLE and 46 who had PB. Responses over time demonstrated periodic, marked increases as new online populations of Fontan patients were reached. Of the responses, 574 (86%) were from the United States and 97 (14%) were international. The leading referral sources were Facebook, internet forums, and traditional websites. Overall, social media outlets referred 84% of all responses, making it the dominant modality for recruiting the largest reported contemporary cohort of Fontan patients and patients who have PLE and PB. The methodology and response patterns from this study can be used to design research applications for other rare diseases. Pediatrics 2014;133:e1345-e1353 AUTHORS:

Plastic bronchitis (PB) is a rare disease that often occurs in patients with congenital heart disease (CHD) who have undergone staged single ventricle palliation. It is characterized by the formation of rubbery “casts” in the airways. PB treatment frequently includes inhaled tPA. However, the efficacy of tPA to reduce cast burden is unknown. This is further complicated by our lack of knowledge of cast composition. We obtained spontaneously expectorated PB casts from children (n=4) with CHD and one adult patient with idiopathic PB. Pathological assessment was made from paraffin-preserved samples. Casts were treated with phosphate-buffered saline (PBS) or tPA. Cast response to tPA was assessed by changes in cast weight and the production of fibrin D-dimer. Independent of dose, tPA reduced cast weight compared with PBS-treatment (p=0.001) and increased D-dimer levels. Histological staining showed that PB casts from all patients were comprised of fibrin and contained notable numbers of lymphocytes. Cast composition did not change over time. Collectively, these data support that in our PB patients, casts are comprised of fibrin and are responsive to tPA treatment. This makes inhaled tPA a potentially viable option for symptomatic relief of PB while we work to unravel the complexity of PB pathogenesis.

Plastic bronchitis (PB) is a poorly understood disease that can complicate any underlying pulmonary disease. However, it appears to most often occur in patients with surgically palliated congenital heart disease, particularly after the Fontan procedure. Few data exist about the prevalence and etiology of PB in this population. In an effort to establish data about prevalence, we conducted a retrospective study of an existing Fontan surgery database (n = 654) comprised of data, including sex, age at date of surgery, alive/dead status, New York Heart Association classification at last follow-up, right-ventricular end-diastolic pressure and pulmonary artery pressure before Fontan surgery, and the presence of a Fontan fenestration. An initial medical record review of 173 patients in the database who were followed at the University of Michigan identified seven patients with PB resulting in an estimated prevalence of 4 %. Subsequently, 14 % of 211 surveyed patients reported that they presently expectorate mucus or fibrin plugs (casts). Demographic and clinical variables did not differ between patients with or without possible PB. Collectively, these findings suggest that Fontan patients presently with PB may range from 4 to 14 %, indicating potential under-diagnosis of the disease. There were no remarkable physical or hemodynamic indicators that differentiated patients with or without possible PB. These data also highlight the need for more elaborate, prospective studies to improve our understanding of PB pathogenesis so that more definitive diagnostic criteria for this devastating disease can be established and its prevalence more accurately determined.

Objective Characterize the medical history, disease progression, and treatment of current-era patients with the rare diseases Fontan-associated protein losing enteropathy (PLE) and plastic bronchitis (PB). Study Design A novel survey that queried demographics, medical details, and treatment information was piloted and placed online via a Facebook portal allowing social media to power the study. Participation regardless of PLE or PB diagnosis was allowed. Case control analyses compared patients with PLE and PB to uncomplicated control Fontan patients. Results The survey was completed by 671 subjects including 76 with PLE, 46 with PB, and 7 with both. Median PLE diagnosis was 2.5 years post-Fontan. Hospitalization for PLE occurred in 71% with 41% hospitalized ≥ 3 times. Therapy varied significantly. PLE patients more commonly had hypoplastic left ventricle (62% vs 44% control; OR 2.8, 95% CI 1.4–5.5), chylothorax (66% vs 41%; OR 3.0, CI 1.6–5.3), and cardiothoracic surgery in addition to staged palliation (17% vs 5%; OR 4.3, CI 1.6, 11.2). Median PB diagnosis was 2 years post-Fontan. Hospitalization for PB occurred in 91% with 61% hospitalized ≥3 times. Therapy was very diverse. PB patients more commonly had chylothorax at any surgery (72% vs 51%; OR 2.5, CI 1.2–5.1) and seasonal allergies (52% vs 36%; OR 2.0, CI 1.0–3.9). Conclusions Patient-specific factors are associated with diagnoses of PLE or PB. Treatment strategies are diverse without clear patterns. These results provide a foundation upon which to design future therapeutic studies and identify a clear need for forming consensus approaches to treatment.

Pediatric pharmacotherapy is often challenging due to the paucity of available clinical data on the safety and efficacy of medications that are commonly used in children. This quandary is even more prevalent in children with rare diseases. Although extrapolations for dosing and administration are often made from available adult data with similar disease states, this translation becomes even more problematic in rare pediatric diseases. Understanding of disease pathophysiology is typically poor, and few, if any, effective therapies have been studied and identified. One condition that illustrates these issues is plastic bronchitis, a rare, most often pediatric disease that is characterized by the production of obstructive bronchial airway casts. This illness primarily occurs in children with congenital heart disease, often after palliative surgery. Plastic bronchitis is a highly clinically relevant and therapeutically challenging problem with a high mortality rate, and, to date, a generally accepted effective pharmacotherapy regimen has not been identified. Furthermore, the disease is ill defined, which makes timely identification and treatment of children with plastic bronchitis difficult. The pharmacotherapies currently used to manage this disease are largely anecdotal and vary between the use of macrolide antibiotics, mucolytics, bronchodilators, and inhaled fibrinolytics in a myriad of combinations. The purpose of this review is twofold: first, to highlight the dilemma of treating plastic bronchitis, and second, to bring attention to the continuing need for studies of drug therapies used in children so that safe and effective drug regimens can be established, particularly for rare diseases, which often have no treatment options.

Inhaled nitric oxide (iNO) is considered standard therapy for pediatric postcardiac surgical pulmonary hypertension (PH). Limited data suggest that inhaled iloprost (inIlo), an aerosolized prostacyclin, may be a feasible and more affordable therapeutic alternative. The goal of this study was to determine if significant hemodynamic change or adverse events would occur in postoperative congenital heart surgery (CHS) patients with PH after their transition from iNO to inIlo. This retrospective review investigated CHS patients with postoperative PH (mean pulmonary artery pressure [mPAP] >25 mmHg) between January 1, 2010 and December 31, 2011 who transitioned from iNO to inIlo. By protocol, CHS patients receiving stable doses of iNO were gradually transitioned to inIlo. After full transition, the patients received inIlo every 2 h, with a final dosing range of 1.25-5 μg/dose. Both PAP and systemic arterial pressure (SAP) were invasively measured during the transition period. Seven patients ages 10 days to 1.5 years completed the protocol. Measurements of mPAP (p = 0.27) and systolic PAP (p = 0.25) did not differ between iNO and inIlo therapy alone. No serious adverse events or complications (bleeding or thrombocytopenia) occurred. The ratio of systolic PAP to SAP decreased in all patients receiving inIlo alone (p = 0.03). Pulmonary hypertension in postoperative CHS patients can be managed successfully with inIlo, and the measured hemodynamics with this agent are similar to those observed with iNO. For the management of postoperative PH, inIlo may be a reasonable alternative, thus reducing the need for costly iNO. Larger confirmatory studies would more robustly facilitate its integration into standard care.

Extemporaneously compounded suspensions of clopidogrel, 5 mg/mL, in a 1:1 mixture of Ora-Plus and Ora-Sweet were stable for at least 60 days when stored in amber plastic bottles at room temperature and under refrigeration.

An extemporaneously prepared suspension of tadalafil 5 mg/mL in a 1:1 mixture of Ora-Plus and Ora-Sweet was stable for at least 91 days when stored in amber plastic bottles at room temperature.