Tyvaso DPI is a drug-device combination therapy comprised of a small, portable, reusable, breath-powered, dry powder inhaler (DPI) for the delivery of treprostinil. It is approved for the treatment of pulmonary arterial hypertension and pulmonary hypertension associated with interstitial lung disease. Tyvaso DPI utilizes single-use prefilled cartridges to ensure proper dosing. Unlike nebulizer devices, administration of Tyvaso DPI is passive and does not require coordination with the device. The low-flow rate design results in targeted delivery to the peripheral lungs due to minimal drug loss from impaction in the oropharynx. The inert fumaryl diketopiperazine (FDKP) excipient forms microparticles that carry treprostinil into the airways, with a high fraction of the particles in the respirable range. In a clinical study in patients with pulmonary arterial hypertension, Tyvaso DPI had similar exposure and pharmacokinetics, low incidence of adverse events, and high patient satisfaction compared with nebulized treprostinil solution. Tyvaso DPI may be considered as a first prostacyclin agent or for those that do not tolerate other prostacyclin formulations, patients with pulmonary comorbidities, patients with mixed Group 1 and Group 3 pulmonary hypertension, or those that prefer an active lifestyle and need a portable, non-invasive treatment. Tyvaso DPI is a patient-preferred, maintenance-free, safe delivery option that may improve patient compliance and adherence.

Abstract Hereditary hemorrhagic telangiectasia (HHT) is a rare autosomal dominant hereditary disorder characterized by recurrent spontaneous epistaxis, mucocutaneous telangiectasias, and solid organ arteriovenous malformations (AVMs). Pulmonary hypertension (PH) is an increasingly recognized complication in patients with HHT, most often precipitated by high‐output heart failure in the presence of hepatic AVMs as well as pulmonary arterial hypertension in the form of a proliferative vasculopathy. The presence of PH in patients with HHT is associated with significant elevations in rates of morbidity and mortality. Additionally, there is growing recognition of a thromboembolic propensity in this population that increases the risk of chronic thromboembolic PH, posing unique clinical considerations regarding the use of anticoagulation. Patients with HHT are also at risk of PH due to disorders commonly seen in the general population, including left‐sided heart and lung disease. The etiology of PH in HHT is multifaceted and complex; the diagnostic approach and treatment strategies must consider the underlying pathophysiology of HHT. This comprehensive review summarizes current knowledge of PH in HHT, detailing the pathogenesis of known etiologies, diagnostic evaluation, and suggested treatment modalities as well as emerging therapies that may be of future interest.

Background Severe acute respiratory syndrome caused by a novel coronavirus 2 (SARS-CoV-2) has infected more than 18 million people worldwide. The activation of endothelial cells is a hallmark of signs of SARS-CoV-2 infection that includes altered integrity of vessel barrier and endothelial inflammation. Objectives Pulmonary endothelial activation is suggested to be related to the profound neutrophil elastase (NE) activity, which is necessary for sterilization of phagocytosed bacterial pathogens. However, unopposed activity of NE increases alveolocapillary permeability and extracellular matrix degradation. The uncontrolled protease activity of NE during the inflammatory phase of lung diseases might be due to the resistance of exosome associated NE to inhibition by alpha-1 antitrypsin. Method 31 subjects with a diagnosis of SARS-CoV2 infection were recruited in the disease group and samples from 30 voluntaries matched for age and sex were also collected for control. Results We measured the plasma levels of exosome-associated NE in SARS-CoV-2 patients which, were positively correlated with sign of endothelial damage in those patients as determined by plasma levels of LDH. Notably, we also found strong correlation with plasma levels of alpha-1 antitrypsin and exosome-associated NE in SARS-CoV-2 patients. Using macrovascular endothelial cells, we also observed that purified NE activity is inhibited by purified alpha-1 antitrypsin while, NE associated with exosomes are resistant to inhibition and show less sensitivity to alpha-1 antitrypsin inhibitory activity, in vitro. Conclusions Our results point out the role of exosome-associated NE in exacerbation of endothelial injury in SARS-CoV-2 infection. We have demonstrated that exosome-associated NE could be served as a new potential therapeutic target of severe systemic manifestations of SARS-CoV-2 infection.

A term hypotonic female infant was born to a primigravida mother. The infant required mechanical ventilation from birth until death at 5 weeks of age. An elevated serum creatine kinase of 1300 IU l-(1) lead to a quadriceps muscle biopsy at 3 days of age. The biopsy showed numerous intranuclear inclusions on light microscopy. Electron microscopy revealed the inclusions to be rod (nemaline) bodies and were located in 80% of the muscle nuclei. Cytoplasmic rod bodies were also present in 50% of the muscle fibers, often arising from Z discs. The intranuclear rods were more than ten times larger than the cytoplasmic rods. There have been eight reported cases of abundant intranuclear rods in nemaline myopathy: three adult onset; one childhood onset; and four neonatal (including this case). Six of the cases (all of the neonatal and two adult onset) died due to respiratory failure and pneumonia. While intranuclear rods are unusual in nemaline myopathy, they occur in both adult and neonatal cases, and their presence is often associated with a fatal outcome.

We read with interest the article by Gao et al. [[1]Gao M. Yang L. Chen X. Deng Y. Yang S. Xu H. Chen Z. Gao X. A study on infectivity of asymptomatic SARS-CoV-2 carriers.Respir. Med. 2020; 169: 106026Abstract Full Text Full Text PDF PubMed Scopus (97) Google Scholar], "A study on infectivity of asymptomatic severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) carriers." This case is certainly an important assessment within the context of the current global pandemic. In this study, 455 contacts of an asymptomatic patient were tested. This cohort comprised 224 health care workers (HCW), 196 family members, and 35 patients, all of whom subsequently tested negative. The authors concluded that the infectivity of asymptomatic SARS-CoV2 carriers may be weak. The authors speculated that this was likely due to a low viral load in asymptomatic patients. This article came to our attention once it began disseminating through social media platforms such as Twitter and Facebook by various "truther," "anti-vaxxer," and conspiracy-focused accounts, in addition to (we presume) well-meaning individuals with questions about the infectivity of SARS-CoV2, or the necessity of social distancing and protective equipment protocols. The authors should have taken steps to ensure that their findings not be misconstrued as "proof" that SARS-CoV2 is poorly, or non-, infective. Further, we have several major concerns regarding the study methodology. We strongly disagree with their conclusion that the infectivity of SARS-CoV2 is weak. Indeed, recent, and more methodologically sound, studies have suggested the opposite. Ruiyun et al. used dynamic metapopulation modeling and Bayesian inference and concluded that an extremely high (79–85%) percentage of all infections in China during late January and early February 2020 were undocumented. Many of these individuals were likely poorly symptomatic or asymptomatic [[2]Li R. Pei S. Chen B. et al.Substantial undocumented infection facilitates the rapid dissemination of novel coronavirus (SARS-CoV-2).Science. 2020; 368: 489-493https://doi.org/10.1126/science.abb3221Crossref PubMed Scopus (2209) Google Scholar]. The authors' methods, as reported, do not support their assertion of poor infectivity. First, at the time of testing, the patient may have been only carrying inactive viral particles. It is well known that a positive polymerase chain reaction (PCR) only indicates the presence of viral RNA and not necessarily viable virus [[3]Wölfel R. Corman V.M. Guggemos W. et al.Virological assessment of hospitalized patients with COVID-2019.Nature. 2020; 581: 465-469https://doi.org/10.1038/s41586-020-2196-xCrossref PubMed Scopus (4578) Google Scholar]. In this case, the patient was tested on hospital day 26. Furthermore, her respiratory symptoms were present for one month prior to admission. Therefore, the patient was tested almost 56 days after her initial symptom onset. Given that the patient had a month of symptoms prior to admission, she could well have had SARS-CoV2 initially and cleared the infection by the time of admission. Thus, the positive test could well have detected non-viable viral particles only. Secondly, if the authors considered the patient to have an active infection at the time of testing, they should have reported the viral cycle threshold (Ct), which is the number of replication cycles required to produce a signal. Although we recognize that this testing isn't universally accessible, we are curious to know if it was something the authors considered and, in any case, this should have been presented as a limitation. In general, a Ct value of less than 40 is considered positive, but this information is unknown [[4]Sethuraman N. Jeremiah S.S. Ryo A. Interpreting diagnostic tests for SARS-CoV-2.J. Am. Med. Assoc. 2020; https://doi.org/10.1001/jama.2020.8259Crossref Scopus (1057) Google Scholar]. Thirdly, the authors defined infectiousness yet failed to obtain a positive viral culture. This would have been particularly useful given that the patient was tested long after she initially had respiratory symptoms. Wölfel et al. [[2]Li R. Pei S. Chen B. et al.Substantial undocumented infection facilitates the rapid dissemination of novel coronavirus (SARS-CoV-2).Science. 2020; 368: 489-493https://doi.org/10.1126/science.abb3221Crossref PubMed Scopus (2209) Google Scholar] were unable to isolate the virus in a culture obtained from the nasopharynx eight days after illness onset. In this case, the patient's specimen was obtained from the nasopharynx and we therefore cannot know if the patient can be considered infectious in this setting. Lastly, they reached their conclusion from exposure to one case which is, by no means, generalizable. The authors acknowledge that their findings stem from a single case. In fact, this was the only limitation they present. However, they then proceed to state that these same findings are "representative to some extent." We question the veracity of this statement and, given the methodological issues mentioned above, also question its appropriateness. We appreciate the authors' effort to answer a very important question about the infectiousness of SARS-CoV2. However, their methodology is severely flawed. Further, their conclusion can, and is, being easily misinterpreted by the lay public. Such misinterpretation may carry dangerous consequences. This is particularly true when social anxiety is high, when clear directives from leading governmental and public health officials are frequently contradictory, and when quarantine and social distancing measures are being relaxed. We welcome any additional insights the authors can offer. None. None.

SESSION TITLE: Monday Abstract Posters SESSION TYPE: Original Investigation Posters PRESENTED ON: 10/21/2019 02:30 PM - 03:15 PM PURPOSE: Pulmonary arterial hypertension (PAH) diagnosis is established by obtaining pulmonary hemodynamics by right heart catheterization (RHC). During RHC, aspirate samples from the pulmonary artery are obtained to measure the mixed venous oxygen saturation. As part of some practices, aspirate blood in the wedged position is also obtained to confirm an accurate wedge position by evaluating the pulmonary wedge oxygen saturation. In some cases, despite adequate positioning, it is not possible to aspirate blood while in a wedge position. This may represent more severe pulmonary vascular bed disease. We evaluated whether the inability to aspirate blood in the wedge position correlates with worse pulmonary hemodynamics and clinical outcomes and if it may serve as a marker of worse prognosis. METHODS: A retrospective study of patients with a diagnosis of PAH at the University of Florida from 2009 to 2017 was done. We reviewed 197 patients who had initial RHC performed at our institute for PAH. After analysis, 93 patients were included in the analysis based on the clinical team’s ability or inability to aspirate blood in the wedged position. RESULTS: Blood was aspirated from a wedged position in 69 patients (74%), while in 24 patients (26%) no blood could be aspirated from a wedge position. There was no difference in patient demographics and clinical characteristics between the two groups. We observed a significantly higher average mPAP (56.7+12.7 vs 45.3+13.8, p=0.001), PVR (11.9+8.0 vs 8.3+5.0, p=0.01), and lower DLCO (39.9+19.4 vs 52.0+19.4, p=0.05) in the unable to aspirate group. A significantly higher proportion of deaths was observed in the unable to aspirate group (33% vs 14%; p=0.04) as well as a higher trend of patients requiring triple therapy (58% vs 36%; p=0.06). A 10-year Kaplan-Meier survival analysis showed a trend towards an association between the inability to aspirate in the wedge position status and worsened survival (p= 0.075). CONCLUSIONS: These findings support the hypothesis that the inability to aspirate blood in the wedged position is likely due to greater disease burden in the pulmonary vasculature bed as evident by the higher means in the mPAP, PVR and lower DLCO measurements. This population of patients had a higher proportion of deaths. Study limitations include that this was a small, retrospective, single center study. These findings should be further confirmed in larger prospective studies. CLINICAL IMPLICATIONS: An accurate wedge position is important during RHC to confirm pre-capillary pulmonary hypertension. A blood wedge aspirate can be easily performed not only to confirm an accurate wedge position but may help in patient prognostication. The inability to aspirate blood in the wedge position may indicate worse pulmonary hemodynamics and worse clinical outcomes. DISCLOSURES: no disclosure on file for Hassan Alnuaimat; No relevant relationships by Ali Ataya, source=Web Response no disclosure on file for Christina Eagan; No relevant relationships by Dana Kay, source=Web Response No relevant relationships by Raju Reddy, source=Web Response