Development and Evaluation of a Small Airway Disease Index Derived From Modeling the Late-Expiratory Flattening of the Flow-Volume Loop.

Excessive decrease in the flow of the late expiratory portion of a flow volume loop (FVL) or "flattening", reflects small airway dysfunction. The assessment of the flattening is currently determined by visual inspection by the pulmonary function test (PFT) interpreters and is highly variable. In this study, we developed an objective measure to quantify the flattening. We downloaded 172 PFT reports in PDF format from the electronic medical records and digitized and extracted the expiratory portion of the FVL. We located point A (the point of the peak expiratory flow), point B (the point corresponding to 75% of the expiratory vital capacity), and point C (the end of the expiratory portion of the FVL intersecting with the x-axis). We did a linear fitting to the A-B segment and the B-C segment. We calculated: 1) the AB-BC angle (∠ABC), 2) BC-x-axis angle (∠BCX), and 3) the log ratio of the BC slope over the vertical distance between point A and x-axis [log (BC/A-x)]. We asked an expert pulmonologist to assess the FVLs and separated the 172 PFTs into the flattening and the non-flattening groups. We defined the cutoff value as the mean minus one standard deviation using data from the non-flattening group. ∠ABC had the best concordance rate of 80.2% with a cutoff value of 149.7°. We then asked eight pulmonologists to evaluate the flattening with and without ∠ABC in another 168 PFTs. The Fleiss' kappa was 0.320 (lower and upper confidence intervals [CIs]: 0.293 and 0.348 respectively) without ∠ABC and increased to 0.522 (lower and upper CIs: 0.494 and 0.550) with ∠ABC. There were 147 CT scans performed within 6 months of the 172 PFTs. Twenty-six of 55 PFTs (47.3%) with ∠ABC <149.7° had CT scans showing small airway disease patterns while 44 of 92 PFTs (47.8%) with ∠ABC ≥149.7° had no CT evidence of small airway disease. We concluded that ∠ABC improved the inter-rater agreement on the presence of the late expiratory flattening in FVL. It could be a useful addition to the assessment of small airway disease in the PFT interpretation algorithm and reporting.

Participation in pulmonary hypertension support group improves patient-reported health quality outcomes: a patient and caregiver survey.

Support group participation has been shown to be effective in many chronic medical conditions. The evidence for integrating support group into pulmonary hypertension care and its effect on quality of life, physical and psychological well-being is limited. We sought to assess the effect of support group participation on quality of life in patients diagnosed with pulmonary hypertension and their caregivers. The emPHasis-10 questionnaire (a tool validated for quality of life assessment in pulmonary hypertension) was used to evaluate the effect of support group participation. Additional demographic and health-related quality measures were examined. Results showed that 165 subjects were enrolled in the study; 122 (74.4%) were patients with pulmonary hypertension, 41 (25.0%) were their caregivers, and 2 (0.02%) did not respond. The cohort was predominantly female (n = 128, 78%), Caucasian (n = 10, 61%), and the principal self-reported classification of pulmonary hypertension was World Health Organization Group 1 (n = 85, 51.8%) and the self-reported New York Heart Association Functional Class was II and III (n = 43, 57.3%). Most participants (n = 118, 71.5%) attended support groups and of them, a majority (n = 107, 90.6%) stated it helped them. There was no difference in quality of life as assessed by emPHasis-10 scores with support group participation (median score 30 vs 32, p = 0.387). There was self-reported improvement in understanding condition better including procedures such as right heart catheterization, medication compliance, and confidence in self-care (p < 0.05). Using multivariate logistic regression, baseline variables that were independently associated with emPHasis-10 scores for the entire cohort included knowledge of New York Heart Association Functional Class (odds ratio: 1.919, 95% CI: 1.004-3.67, p = 0.04) and greater distance traveled to visit pulmonary hypertension physician (odds ratio: 1.391, 95% CI: 0.998--1.94, p = 0.05). In conclusion, support group participation does not improve quality of life as assessed by emPHasis-10 scores but improves other meaningful health-related quality outcomes.

Application of Machine Learning in Pulmonary Function Assessment Where Are We Now and Where Are We Going?

Analysis of pulmonary function tests (PFTs) is an area where machine learning (ML) may benefit clinicians, researchers, and the patients. PFT measures spirometry, lung volumes, and carbon monoxide diffusion capacity of the lung (DLCO). The results are usually interpreted by the clinicians using discrete numeric data according to published guidelines. PFT interpretations by clinicians, however, are known to have inter-rater variability and the inaccuracy can impact patient care. This variability may be caused by unfamiliarity of the guidelines, lack of training, inadequate understanding of lung physiology, or simply mental lapses. A rules-based automated interpretation system can recapitulate expert's pattern recognition capability and decrease errors. ML can also be used to analyze continuous data or the graphics, including the flow-volume loop, the DLCO and the nitrogen washout curves. These analyses can discover novel physiological biomarkers. In the era of wearables and telehealth, particularly with the COVID-19 pandemic restricting PFTs to be done in the clinical laboratories, ML can also be used to combine mobile spirometry results with an individual's clinical profile to deliver precision medicine. There are, however, hurdles in the development and commercialization of the ML-assisted PFT interpretation programs, including the need for high quality representative data, the existence of different formats for data acquisition and sharing in PFT software by different vendors, and the need for collaboration amongst clinicians, biomedical engineers, and information technologists. Hurdles notwithstanding, the new developments would represent significant advances that could be the future of PFT, the oldest test still in use in clinical medicine.

Significance of autoimmune disease in severe pulmonary hypertension complicating extensive pulmonary fibrosis: a prospective cohort study.

The association of autoimmune disease (AI) with transplant-free survival in the setting of severe Group 3 pulmonary hypertension and extensive pulmonary fibrosis remains unclear. We report cases of severe pulmonary hypertension (mean pulmonary artery pressure ≥35 mmHg and right ventricular dysfunction) and extensive pulmonary fibrosis after pulmonary arterial hypertension-specific therapy. We used multivariate regression to determine the clinical variables associated with transplant-free survival. Of 286 screened patients, 55 demonstrated severe pulmonary hypertension and extensive pulmonary fibrosis and were treated with parenteral prostacyclin therapy. The (+)AI subgroup (n = 34), when compared to the (-)AI subgroup (n = 21), was more likely to be female (77% versus 19%) and younger (58.7 ± 12.1 versus 66.0 ± 10.7 years), and revealed lower forced vital capacity (absolute) (1.9 ± 0.7 versus 2.9 ± 1.1 L), higher DLCO (% predicted) (31.1 ± 15.2 versus 23.2 ± 8.0), and increased unadjusted transplant-free survival (1 year (84.6 ± 6.3% versus 45 ± 11.1%)), 3 years (71 ± 8.2% versus 28.6 ± 11.9%), and 5 years (47.6 ± 9.6% versus 6.4 ± 8.2%); (p = 0.01)). Transplant-free survival was unchanged after adjusting for age and gender. The pulmonary hemodynamic profiles improved after parenteral prostacyclin therapy, independent of AI status. The baseline variables associated with mortality included age at pulmonary hypertension diagnosis (heart rate (HR) 1.23 (confidence interval (CI) 1.03-1.47); p = 0.02) and presence of AI (HR 0.26 (confidence interval (CI) 0.10-0.70); p < 0.01). Gas exchange was not adversely affected by parenteral prostacyclin therapy. In the setting of severe Group 3 pulmonary hypertension and extensive pulmonary fibrosis treated with pulmonary arterial hypertension-specific therapy, AI is independently associated with increased transplant-free survival. Pulmonary hypertension/pulmonary fibrosis associated with AI should be considered in future clinical trials of pulmonary arterial hypertension-specific therapy in Group 3 pulmonary hypertension.

Pulmonary tumor thrombotic microangiopathy presenting as recurrent syncope.

Pulmonary tumor thrombotic microangiopathy is a rare condition in which embolization of tumor cells to the pulmonary arterioles causes fibrocellular intimal thickening and activation of the coagulation cascade resulting in pulmonary hypertension and right heart failure. Herein, we highlight a young 35-year-old male with no known past medical history who presented with recurrent syncope and dyspnea, and was found to have severe right heart failure and pulmonary hypertension. He developed sudden clinical deterioration and died after a cardiac arrest. Autopsy revealed poorly differentiated gastric adenocarcinoma and pulmonary tumor thrombotic microangiopathy. New onset severe pulmonary hypertension and right heart failure without any other obvious etiology should encourage the reader to evaluate for pulmonary tumor thrombotic microangiopathy and undergo a diligent search for underlying malignancy. This case highlights recurrent syncope as a rare presentation of this rapidly fatal disease.

A Physiologic Approach to Hemodynamic Monitoring and Optimizing Oxygen Delivery in Shock Resuscitation.

The approach to shock resuscitation focuses on all components of oxygen delivery, including preload, afterload, contractility, hemoglobin, and oxygen saturation. Resuscitation focused solely on preload and fluid responsiveness minimizes other key elements, resulting in suboptimal patient care. This review will provide a physiologic and practical approach for the optimization of oxygen delivery utilizing available hemodynamic monitoring technologies. Venous oxygen saturation (SvO2) and lactate will be discussed as indicators of shock states and endpoints of resuscitation within the framework of resolving oxygen deficit and oxygen debt.

Long-Term High-Altitude Hypoxia and Alpha Adrenoceptor-Dependent Pulmonary Arterial Contractions in Fetal and Adult Sheep.

Autonomic innervation of the pulmonary vasculature triggers vasomotor contractility predominately through activation of alpha-adrenergic receptors (α-ARs) in the fetal circulation. Long-term hypoxia (LTH) modulates pulmonary vasoconstriction potentially through upregulation of α1-AR in the vasculature. Our study aimed to elucidate the role of α-AR in phenylephrine (PE)-induced pulmonary vascular contractility, comparing the effects of LTH in the fetal and adult periods on α-AR subtypes and PE-mediated Ca2+ responses and contractions. To address this, we performed wire myography, Ca2+ imaging, and mRNA analysis of pulmonary arteries from ewes and fetuses exposed to LTH or normoxia. Postnatal maturation depressed PE-mediated contractile responses. α2-AR activation contracted fetal vessels; however, this was suppressed by LTH. α1A- and α1B-AR subtypes contributed to arterial contractions in all groups. The α1D-AR was also important to contractility in fetal normoxic vessels and LTH mitigated its function. Postnatal maturity increased the number of myocytes with PE-triggered Ca2+ responses while LTH decreased the percentage of fetal myocytes reacting to PE. The difference between myocyte Ca2+ responsiveness and vessel contractility suggests that fetal arteries are sensitized to changes in Ca2+. The results illustrate that α-adrenergic signaling and vascular function change during development and that LTH modifies adrenergic signaling. These changes may represent components in the etiology of pulmonary vascular disease and foretell the therapeutic potential of adrenergic receptor antagonists in the treatment of pulmonary hypertension.

Inhaled Fasudil Lacks Pulmonary Selectivity in Thromboxane-Induced Acute Pulmonary Hypertension in Newborn Lambs.

INTRODUCTION: Pulmonary hypertension (PH) is a potentially deadly disease for infants and adults with few existing medical interventions and no cure. In PH, increased blood pressure in the pulmonary artery eventually leads to heart failure. Fasudil, an antagonist of Rho-kinase, causes vasodilation leading to decreased systemic artery pressure and pulmonary artery pressure (PAP). This study compared the effects of fasudil administered as either an intravenous infusion or inhaled aerosol in newborn lambs. HYPOTHESIS: Inhaled aerosol delivery of fasudil will provide selective pulmonary vasodilation when compared with intravenous administration. METHODS: Newborn lambs (∼11 days) were surgically instrumented and mechanically ventilated under anesthesia. A pulmonary artery catheter and ultrasonic flow probe were inserted to measure hemodynamics. Acute PH was pharmaceutically induced via continuous intravenous infusion of thromboxane. After achieving a 2- to 3-fold elevation of PAP, fasudil was administered either as intravenous infusion (2.5 mg/kg) or inhaled aerosol (100 mg of fasudil in 2 mL of saline). Changes in PAP, mean systemic arterial pressure (MABP), pulmonary vascular resistance (PVR), systemic vascular resistance (SVR), cardiac output, and heart rate were assessed. In addition, plasma concentrations of fasudil were measured. RESULTS: Both routes of fasudil delivery produced significant decreases in PAP and PVR but also produced similar decreases in MABP and SVR. The Cmax for intravenous fasudil was greater than that for inhaled fasudil. CONCLUSIONS: These results suggest inhaled fasudil lacks pulmonary selectivity when compared with intravenous fasudil.

Developing a percutaneous dilatational tracheostomy service by medical intensivists: experience at one academic institution.

PURPOSE: Percutaneous dilatational tracheostomy (PDT) is increasingly becoming the preferred method, compared with open surgical tracheostomy, for patients requiring chronic ventilatory assistance. Little is known regarding the process involved to incorporate PDT as a standard service in the medical intensive care unit. In this report, we describe our experience developing a "PDT service" led by medical intensivists. MATERIALS AND METHODS: With support from our leadership and surgical colleagues, we developed a credentialing and training process for medical intensivists, formulated a bedside team to perform PDT, refined our technique, and maintained a patient data registry for quality improvement. RESULTS: To date, our service includes 4 medical intensivists with PDT privileges. Over a 4-year period, we performed 171 PDTs for patients in the medical intensive care unit after 12.1 ± 8.2 days of mechanical ventilation. Our procedure-related complication rates are similar to other reports. No patient required emergent open surgical tracheostomy, and there were no deaths related to PDT. We required minimal to no backup support from our surgical colleagues in performing PDT. CONCLUSIONS: We successfully developed a medical intensivist-driven PDT service, sharing our unique successes and challenges, to facilitate the care of our patients requiring prolonged ventilator support.

Impact of a 2-Day Critical Care Ultrasound Course during Fellowship Training: A Pilot Study.

Objectives. Despite the increasing utilization of point-of-care critical care ultrasonography (CCUS), standards establishing competency for its use are lacking. The purpose of this study was to evaluate the effectiveness of a 2-day CCUS course implementation on ultrasound-naïve critical care medicine (CCM) fellows. Methods. Prospective evaluation of the impact of a two-day CCUS course on eight CCM fellows' attitudes, proficiency, and use of CCUS. Ultrasound competency on multiple organ systems was assessed including abdominal, pulmonary, vascular, and cardiac systems. Subjects served as self-controls and were assessed just prior to, within 1 week after, and 3 months after the course. Results. There was a significant improvement in CCM fellows' written test scores, image acquisition ability, and pathologic image interpretation 1 week after the course and it was retained 3 months after the course. Fellows also had self-reported increased confidence and usage of CCUS applications after the course. Conclusions. Implementation of a 2-day critical care ultrasound course covering general CCUS and basic critical care echocardiography using a combination of didactics, live models, and ultrasound simulators is effective in improving critical care fellows' proficiency and confidence with ultrasound use in both the short- and long-term settings.

Ischemic preconditioning improves oxygen saturation and attenuates hypoxic pulmonary vasoconstriction at high altitude.

Exposure to hypoxic environments is associated with decreased arterial oxygen saturation and increased pulmonary artery pressures. Ischemic preconditioning of an extremity (IPC) is a procedure that stimulates vasoactive and inflammatory pathways that protect remote organ systems from ongoing or future ischemic injury. To test the effects of IPC on oxygen saturation and pulmonary artery pressures at high altitude, 12 healthy adult volunteers were evaluated in a randomized cross-over trial. IPC was administered utilizing a standardized protocol. IPC or placebo was administered daily for 5 days prior to ascent to altitude. All participants were evaluated twice at 4342 m altitude (placebo and IPC conditions separated by 4 weeks, randomized). The pulmonary artery systolic pressure (PASP) at 4342 m was significantly lower in the IPC condition than the placebo condition (36 ± 6.0 mmHg vs. 38.1 ± 7.6 mmHg, respectively, p = 0.035). Oxygen saturation at 4342 m was significantly higher with IPC compared to placebo (80.3 ± 8.7% vs. 75.3 ± 9.6%, respectively, p = 0.003). Prophylactic IPC treatment is associated with improved oxygen saturation and attenuation of the normal hypoxic increase in pulmonary artery pressures following ascent to high altitude.

Pre-condicionamiento isquémico mejora saturación de oxígeno y atenúa vasoconstricción pulmonar por hipoxia a gran altura / Ischemic pre-conditioning improves oxygen saturation and attenuates pulmonary vasoconstriction due to high-altitude hypoxia

La exposición a ambientes de hipoxia, está asociada con una disminución de la saturación arterial de oxígeno y el aumento de las presiones de la arteria pulmonar. El pre-condicionamiento isquémico de una extremidad (IPC Ischemic Preconditioning), es un procedimiento que estimula las vías vasoactiva e inflamatoria, que protegen los sistemas de órganos remotos, de daño isquémico. Para evaluar los efectos de IPC, en la saturación de oxígeno y presiones de la arteria pulmonar, a gran altura; fueron evaluados 12 voluntarios adultos sanos, en un ensayo aleatorio randomizado cruzado (randomized cross-over trial). El IPC fue realizado, utilizando un protocolo estandarizado. Se realizó IPC o placebo diariamente, durante 5 días previos al ascenso a gran altura. Todos los participantes fueron evaluados dos veces a 4243 m de altura (en condiciones de IPC y placebo, con un intervalo de 4 semanas, aleatorizados). La presión sistólica de la arteria pulmonar (PASP) a 4342 m fue significativamente menor en condiciones de IPC, que en condiciones de placebo (36±6.0 mmHg vs. 38.1±7.6 mmHg, respectivamente, p=0.0035). La saturación de oxígeno a 4342 m fue significativamente más elevada en IPC en comparación con placebo (80.3±8.7 por ciento vs. 75.3±9.6 por ciento, respectivamente, p-0.003). IPC como tratamiento profiláctico está asociado con una saturación de oxígeno mayor y atenuación del incremento normal de la presión de arteria pulmonar por hipoxia, seguida al ascenso a gran altura.