Advanced airway management and respiratory care in decompensated pulmonary hypertension.

Meticulous risk stratification is essential when considering intubation of a patient with decompensated pulmonary hypertension (dPH). It is paramount to understand both the pathophysiology of dPH (and associated right ventricular failure) and the complications related to a high-risk intubation before attempting the procedure. There are few recommendations in this area and the literature, guiding these recommendations, is limited to expert opinion and very few case reports/case series. This review will discuss the complex pathophysiology of dPH, the complications associated with intubation, the debates surrounding induction agents, and the available options for the intubation procedure, with specific emphasis on the emerging role for awake fiberoptic intubation. All patients should be evaluated for candidacy for veno-arterial extracorporeal membrane oxygen as a bridge to recovery, lung transplantation, or pulmonary endarterectomy prior to intubation. Only an experienced proceduralist who is both comfortable with high-risk intubations and the pathophysiology of dPH should perform these intubations.

Breathing variability predicts the suggested need for corrective intervention due to the perceived severity of patient-ventilator asynchrony during NIV.

Patient-ventilator asynchrony is associated with intolerance to noninvasive ventilation (NIV) and worsened outcomes. Our goal was to develop a tool to determine a patient needs for  intervention by a practitioner due to the presence of patient-ventilator asynchrony. We postulated that a clinician can determine when a patient needs corrective intervention due to the perceived severity of patient-ventilator asynchrony. We hypothesized a new measure, patient breathing variability, would indicate when corrective intervention is suggested by a bedside practitioner due to the perceived severity of patient-ventilator asynchrony. With IRB approval data was collected on 78 NIV patients. A panel of experts reviewed retrospective data from a development set of 10 NIV patients to categorize them into one of the three categories. The three categories were; "No to mild asynchrony-no intervention needed", "moderate asynchrony-non-emergent corrective intervention required", and "severe asynchrony-immediate intervention required". A stepwise regression with a F-test forward selection criterion was used to develop a positive linear logic model predicting the expert panel's categorizations of the need for corrective intervention. The model was incorporated into a software tool for clinical implementation. The tool was implemented prospectively on 68 NIV patients simultaneous to a bedside practitioner scoring the need for corrective intervention due to the perceived severity of patient-ventilator asynchrony. The categories from the tool and the practitioner were compared with the rate of agreement, sensitivity, specificity, and receiver operator characteristic analyses. The rate of agreement in categorizing the suggested need for clinical intervention due to the perceived presence of patient-ventilator asynchrony between the tool and experienced bedside practitioners was 95% with a Kappa score of 0.85 (p < 0.001). Further analysis found a specificity of 84% and sensitivity of 99%. The tool appears to accurately match the suggested need for corrective intervention by a bedside practitioner. Application of the tool allows for continuous, real time, and non-invasive monitoring of patients receiving NIV, and may enable early corrective interventions to ameliorate potential patient-ventilator asynchrony.

Progressive Dyspnea on Exertion in an 82-Year-Old.

An older patient with hereditary hemorrhagic telangiectasia and right lower lobe segmental pulmonary embolism presented with dyspnea that had worsened over 5 years; physical examination and laboratory testing showed jugular venous distension, a cardiac systolic murmur, right ventricular heave, bilateral lower extremity edema to the knees, and elevated brain-type natriuretic peptide level. What is the diagnosis and what would you do next?

Alpha1-antitrypsin Deficiency-Increased Knowledge and Diagnostic Testing after Viewing Short Instructional Video.

Many individuals with Alpha-1 Antitrypsin Deficiency (AATD) are unaware of their diagnosis. In the absence of an AATD diagnosis, irreversible damage continues, and incorrect care is provided. Research demonstrates low levels of knowledge about AATD among health care providers. To address this ongoing issue, a short educational video was developed for health care providers with the goal of increasing knowledge and testing for AATD. A five-question test on the video material was developed. Invitations to participate in the study were sent via email to providers at both public teaching hospitals and private practices across the country. Respondents completed three parts online: pre-test, video, and post-test. To confirm retention of knowledge gained, providers who completed all three were invited to take the same test 3-6 months later. There were 683 providers who responded, and 213 completed all three portions; 105 of those providers completed the 3-6-months of follow-up testing. The average pre-test score of the 213 providers was 54.6% (std. dev. = 26.2%). The average post-test score immediately following the video viewing was 74.7% (std. dev. = 27.7%). The average follow-up test score 3-6 months later was 63.2% (std. dev. = 22.0%). During the follow-up period, 11 providers reported testing for AATD for the first time. This short educational video demonstrated both immediate and sustained improvement in knowledge and an increase in testing for AATD. Short digital videos may provide an effective platform for the ongoing effort to identify individuals with AATD.

Transitioning from parenteral to inhaled prostacyclin therapy in pulmonary arterial hypertension.

BACKGROUND: Parenteral prostacyclin therapy for PAH has allowed for improvements in functional status, quality of life and mortality. Parenteral therapies however carry an increased risk of line-associated complications. Inhaled prostacyclins are an attractive alternative therapy; however, limited data exists supporting the safety and outcomes after transition. METHODS: We describe a retrospective observational analysis of adults with PAH who were transitioned from a parenteral prostacyclin to inhaled treprostinil at our institution. Endpoints include duration of transition, hospital length of stay, adverse effects during transition, and cardiopulmonary function post transition. RESULTS: Eight patients were included, all of which were on triple therapy. Seven patients receiving intravenous prostacyclin therapy were transitioned in an ICU setting, while one patient was transitioned from subcutaneous treprostinil as an outpatient. The average ICU and hospital length of stay was 4.1 ± 0.7 days. Patient preference was the most common reason for transition (n = 5), followed by line complication (n = 2), and intolerance to parenteral therapy (n = 1). One adverse event was observed while initiating inhaled treprostinil that only required slowing of the transition process. On follow-up (19.6 ± 11.1 months) functional class did not change, and non-parametric test showed no change in 6MWD after transition (p = 0.62). One patient failed inhaled therapy necessitating transition back to intravenous therapy. CONCLUSION: Transitioning patients from parenteral to inhaled prostacyclin therapy can be safely accomplished in specialized centers over a 48-72 h period. Patient preference was overwhelming the most prevalent reason for transition.

A perfectly imperfect engine: Utilizing the digital twin paradigm in pulmonary hypertension.

Pulmonary hypertension (PH) is a severe medical condition with a number of treatment options, the majority of which are introduced without consideration of the underlying mechanisms driving it within an individual and thus a lack of tailored approach to treatment. The one exception is a patient presenting with apparent pulmonary arterial hypertension and shown to have vaso-responsive disease, whose clinical course and prognosis is significantly improved by high dose calcium channel blockers. PH is however characterized by a relative abundance of available data from patient cohorts, ranging from molecular data characterizing gene and protein expression in different tissues to physiological data at the organ level and clinical information. Integrating available data with mechanistic information at the different scales into computational models suggests an approach to a more personalized treatment of the disease using model-based optimization of interventions for individual patients. That is, constructing digital twins of the disease, customized to a patient, promises to be a key technology for personalized medicine, with the aim of optimizing use of existing treatments and developing novel interventions, such as new drugs. This article presents a perspective on this approach in the context of a review of existing computational models for different aspects of the disease, and it lays out a roadmap for a path to realizing it.

Unsupervised Exercise in Interstitial Lung Disease: A Delphi Study to Develop a Consensus Preparticipation Screening Tool for Lymphangioleiomyomatosis.

BACKGROUND: Little research is available to provide practical guidance to health care providers for exercise preparticipation screening and referral of patients with interstitial lung diseases (ILD), including lymphangioleiomyomatosis (LAM), to participate in remote, unsupervised exercise programs. RESEARCH QUESTION: What exercise preparticipation screening steps are essential to determine whether a patient with LAM is medically appropriate to participate in a remote, unsupervised exercise program? STUDY DESIGN AND METHODS: Sixteen experts in LAM and ILD participated in a two-round modified Delphi study, ranking their level of agreement for ten statements related to unsupervised exercise training in LAM, with an a priori definition of consensus. Additionally, 60 patients with LAM completed a survey of the perceived risks and benefits of remote exercise training in LAM. RESULTS: Seven of the 10 statements reached consensus among experts. Experts agreed that an in-person clinical exercise test is indicated to screen for exercise-induced hypoxemia and prescribe supplemental oxygen therapy as indicated prior to initiating a remote exercise program. Patients with recent pneumothorax should wait to start an exercise program for at least 4 weeks until after resolution of pneumothorax and clearance by a physician. Patients with high cardiovascular risk for event during exercise, severe resting pulmonary hypertension, or risk for falls may be more appropriate for referral to a rehabilitation center. A LAM-specific remote exercise preparticipation screening tool was developed from the consensus statements and agreed upon by the panelists. INTERPRETATION: A modified Delphi study approach was useful to develop disease-specific recommendations for safety and preparticipation screening prior to unsupervised, remotely administered exercise in LAM. The primary product of this study is a clinical decision aid for providers to use when medically screening patients prior to participation in the newly launched LAMFit remote exercise program. FUNDING: This work was funded by an Established Investigator Award (LAM0130PB07-18) to MBB from The LAM Foundation.

Practical management of oral treprostinil in patients with pulmonary arterial hypertension: Lessons from ADAPT, EXPEDITE, and expert consensus.

BACKGROUND: Oral treprostinil is a prostacyclin analogue approved to treat pulmonary arterial hypertension (PAH) by delaying disease progression and improving exercise capacity. Higher doses of oral treprostinil correlate with increased treatment benefit. Titrations may be challenging due to common side effects of prostacyclin-class therapies. STUDY DESIGN AND METHODS: The multicenter, prospective, real-world, observational ADAPT Registry study followed adult patients with PAH for up to 78 weeks after initiating oral treprostinil (NCT03045029). Dosing, titration, and transitions of oral treprostinil were at the discretion of the prescriber. Patient-reported incidence and treatment of common side effects were collected to understand side effect management and tolerability. Insights from literature and expert recommendations were added to provide a consolidated resource for oral treprostinil use. RESULTS: In total, 139 participants in ADAPT completed ≥1 weekly survey; (median age 60.0 years, 76 % female). Median treatment duration of oral treprostinil was 13.1 months. During early therapy (Months 1-5), 62 % (78/126) of patients reported headache and diarrhea, and 40 % (50/126) reported nausea. At Month 6, many patients who reported side effects during early therapy reported an improvement (61 % headache, 44 % diarrhea, 70 % nausea). Common side effect treatments, including acetaminophen, loperamide, and ondansetron, were effective. Approximately one-quarter of patients reporting the most common side effects were untreated at Month 6. CONCLUSION: Patient selection for, and initiation and titration of, oral treprostinil should be individualized and may include parenteral treprostinil induction-transition for faster titration. Assertive side effect management may help patients reach higher and more efficacious doses of oral treprostinil.