Predictors of Mortality in Pulmonary Hypertension-Associated Chronic Lung Disease.

Background/Objectives: Pulmonary hypertension (PH) often accompanies chronic lung diseases. Several chronic lung diseases with PH portends unfavorable outcomes. We investigated which variables in this cohort of patients with chronic lung disease and PH predicts mortality. Methods: This is a retrospective analysis of patients with chronic lung disease and PH at a single tertiary, academic center. The underlying lung disease included were COPD, IPF, other fibrotic ILD, non-fibrotic ILD, fibrotic sarcoidosis, and CPFE. All patients had right heart catheterization diagnostic of PH as well as pulmonary function testing data including 6 min walk testing. Univariable and multivariate Cox regression was performed to identify variables associated with mortality. Results: We identified 793 patients with chronic lung disease and PH. In total, 144 patients died prior to potential lung transplant. In multivariable Cox regression IPF, other fibrotic ILD, non-fibrotic ILD, and CPFE were significantly associated with an increased risk of mortality. Severe PH (PVR > 5 WU), FEV1 < 30% predicted, FVC < 40% predicted, 6 min walk distance < 150 m were also significantly associated with an increased risk of mortality. Conclusions: Carrying a diagnosis of IPF, CPFE, fibrotic ILD, or non-fibrotic ILD with PH has an increased risk of mortality as compared to COPD with PH. Hemodynamic, PVR > 5 WU, 6 min walk test less than 150 m, as well as spirometric data including FEV1 < 30% and FVC < 40% predicted were independently associated with an increased risk of death.

Pulmonary Vasodilator Therapy Is Associated with Decreased Mortality in Patients with Chronic Lung Disease and Severe Pulmonary Hypertension.

The mortality benefit of PAH-specific therapy for patients with pulmonary hypertension (PH) associated with lung disease is not clear. Our aim was to determine whether pulmonary arterial hypertension (PAH)-specific therapy is associated with reduced mortality among all patients with PH associated with lung disease and in patients with chronic lung disease and severe PH. This was a retrospective cohort study of patients at our institution with chronic lung disease and PH. Survival analysis was performed by comparing patients who received PAH-specific therapy with patients who did not receive pulmonary vasodilators in the entire cohort and in a subgroup of patients with severe PH defined as PVR > 5 WU. We identified 783 patients with chronic lung disease and PH; 246 patients met the new criteria for severe PH. In the entire cohort, a similar survival probability was seen between the treated and untreated PH groups (logrank p = 0.67). In the severe PH subgroup, patients treated with PAH-specific therapy had increased survival probability (logrank p = 0.03). PAH-specific therapy was independently and significantly associated with decreased mortality in severe PH (HR 0.31, 95% CI 0.11-0.88, p = 0.03). PAH-specific therapy may confer a mortality benefit in patients with chronic lung disease and severe PH, which is now defined as PVR > 5 WU, similarly to those with pulmonary arterial hypertension.

Critical Care Management of Severe Asthma Exacerbations.

Severe asthma exacerbations, including near-fatal asthma (NFA), have high morbidity and mortality. Mechanical ventilation of patients with severe asthma is difficult due to the complex pathophysiology resulting from severe bronchospasm and dynamic hyperinflation. Life-threatening complications of traditional ventilation strategies in asthma exacerbations include the development of systemic hypotension from hyperinflation, air trapping, and pneumothoraces. Optimizing pharmacologic techniques and ventilation strategies is crucial to treat the underlying bronchospasm. Despite optimal pharmacologic management and mechanical ventilation, the mortality rate of patients with severe asthma in intensive care units is 8%, suggesting a need for advanced non-pharmacologic therapies, including extracorporeal life support (ECLS). This review focuses on the pathophysiology of acute asthma exacerbations, ventilation management including non-invasive ventilation (NIV) and invasive mechanical ventilation (IMV), the pharmacologic management of acute asthma, and ECLS. This review also explores additional advanced non-pharmacologic techniques and monitoring tools for the safe and effective management of critically ill adult asthmatic patients.

Elevated pulmonary vascular resistance is associated with increased lung transplant waitlist mortality among patients with chronic obstructive pulmonary disease and pulmonary hypertension: a retrospective cohort analysis.

BACKGROUND: The latest European Society of Cardiology and European Respiratory Society guidelines have changed the definition of both pre-capillary pulmonary hypertension (PH) and severe PH in chronic lung disease. The clinical significance of these new criteria are unclear among patients with chronic obstructive pulmonary disease (COPD)-PH. We aim to examine the clinical significance of the new PH definitions with regards to lung transplant waitlist mortality amongst patients with COPD-PH. METHODS: This was a retrospective cohort study of adult patients with COPD-PH listed for lung transplantation. Kaplan-Meier survival analyses were performed comparing patients with newly defined pre-capillary PH to those without pre-capillary PH and comparing patients with severe PH, defined as pulmonary vascular resistance (PVR) > 5 WU, to those without severe PH. Both mean pulmonary artery pressure (mPAP) and PVR were analyzed for potential cut-off points associated with increased waitlist mortality. Predictors of waitlist mortality were identified via Cox regression. RESULTS: Among 6495 patients with COPD-PH listed for lung transplantation, pre-capillary PH was not associated with increased waitlist mortality (logrank p = 0.43), while severe PH was (logrank p < 0.001). Both severe PH (HR 1.79, 95% CI 1.22-2.60, p = 0.003) and PVR > 3.9 WU (HR 1.49, 95% CI 1.14-1.95, p = 0.004) were independently and significantly associated with increased waitlist mortality. CONCLUSIONS: PVR may serve as a strong predictor of lung transplant waitlist mortality among patients with COPD-PH as compared to other pulmonary hemodynamic parameters when predicting transplant waitlist mortality.

Pulmonary hemodynamics and transplant-free survival in sarcoidosis-associated pulmonary hypertension: Results from an international registry.

Pulmonary hypertension (PH) is a risk factor for mortality in patients with sarcoidosis. Severe PH in chronic lung disease has previously been defined as mean pulmonary arterial pressure (mPAP) ≥ 35 mmHg or mPAP 25 ≥ mmHg with cardiac index (CI) ≤ 2 L/min/m2. However, there is no clear definition denoting severity of sarcoidosis-associated PH (SAPH). We aimed to determine pulmonary hemodynamic cut-off values where transplant-free survival was worse among patients with SAPH. This was a retrospective cohort analysis of the Registry of SAPH database focusing on pulmonary hemodynamic predictors of transplant-free survival among patients with precapillary SAPH. Cox regression was performed to determine which pulmonary hemodynamic values predicted death or lung transplantation. Kaplan-Meier survival analysis was performed on statistically significant predictors to determine pulmonary hemodynamic cut-off values where transplant-free survival was decreased. Decreased transplant-free survival occurred among SAPH patients with mPAP ≥ 40 mmHg and SAPH patients with pulmonary vascular resistance (PVR) ≥ 5 Woods units (WU). Transplant-free survival was not decreased in patients who fulfilled prior criteria of severe PH in chronic lung disease. We identified new cut-offs with decreased transplant-free survival in the SAPH population. Neither cut-off of mPAP ≥ 40 mmHg nor PVR ≥ 5 WU has previously been shown to be associated with decreased transplant-free survival in SAPH. These values could suggest a new definition of severe SAPH. Our PVR findings are in line with the most recent European Society of Cardiology/European Respiratory Society guideline definition of severe PH in chronic lung disease.

Sarcoidosis lung transplantation waitlist mortality, a national registry database study.

Background: The Lung Allocation Score (LAS) prioritises lung transplantation candidates, balancing waitlist mortality and post-transplant survival. The score groups sarcoidosis candidates based on mean pulmonary artery pressure: those with ≤30 mmHg (sarcoidosis A) are grouped with COPD and those with >30 mmHg (sarcoidosis D) with idiopathic pulmonary fibrosis (IPF). We hypothesise that sarcoidosis candidates have a higher waitlist mortality than other candidates within their LAS grouping. Methods: This is a retrospective cohort study of consecutive lung transplantation candidates from the Scientific Registry of Transplant Recipients database from May 2005 to May 2019. We included candidates aged ≥18 years diagnosed with sarcoidosis, COPD or IPF. Univariate, multivariate and survival estimate analyses were performed. Results: We identified 385 sarcoidosis A, 642 sarcoidosis D, 7081 COPD and 10 639 IPF lung transplantation candidates. 17.3% of sarcoidosis D, 14.8% of IPF, 14.3% of sarcoidosis A and 9.8% of COPD candidates died awaiting transplant. Sarcoidosis A was an independent risk factor for waitlist mortality. Sarcoidosis A had a lower waitlist survival probability compared to COPD. Sarcoidosis D had the highest waitlist mortality. IPF candidates had lower waitlist survival probability than sarcoidosis D in the first 60 days after listing. Conclusion: Based on our results, the grouping of candidates with sarcoidosis in allocation systems should be revised to mitigate waitlist mortality disparity.

Pulmonary vasodilator therapy in sarcoidosis-associated pulmonary hypertension may decrease lung function decline and mortality.

The efficacy of treating sarcoidosis-associated pulmonary hypertension (SAPH) with pulmonary vasodilator therapy is unclear. The INCREASE trial showed improvement in 6-minute walk distance (6MWD) and in decline in functional vital capacity (FVC) in patients with interstitial lung disease and pulmonary hypertension. We hypothesize that patients with SAPH treated with pulmonary vasodilators have reduced decline in FVC. We retrospectively analyzed patients with SAPH who underwent lung transplantation evaluation. The primary objective was to compare change in FVC between patients with SAPH who received pulmonary vasodilators (treated) and those who did not (untreated). Secondary objectives were to compare the change in 6MWD, change in oxygen requirement, transplant rates, and mortality between treated and untreated SAPH patients. We identified 58 patients with SAPH; 38 patients received pulmonary vasodilator therapy, and 20 patients did not. Treated SAPH patients had significantly less decline in FVC than untreated SAPH patients (+54 mL vs. -357 mL, p < 0.01). Treated SAPH patients had significantly higher survival than untreated SAPH patients. Receiving PH therapy was significantly associated with a change in FVC (estimate 0.36 ± 0.07, p < 0.01) and decreased mortality (hazard ratio 0.29, confidence interval 0.12-0.67, p < 0.01). Among patients with SAPH, those who received pulmonary vasodilator therapy had significantly less decline in FVC and increased survival. Receiving pulmonary vasodilator therapy was significantly associated with FVC change and decreased mortality. These study findings point towards potential benefit of pulmonary vasodilator therapy in SAPH patients. Further prospective studies are required to fully elucidate the benefits of pulmonary vasodilator therapy in SAPH.

Pulmonary Point-of-Care Ultrasonography in the Intensive Care Unit.

Pulmonary point-of-care ultrasonography (POCUS) is a quick and essential tool in the diagnosis of various pulmonary pathologies. Pulmonary POCUS can aid in the detection of pneumothorax, pleural effusion, pulmonary edema, and pneumonia, with sensitivity and specificity comparable, if not superior, to those of chest radiograph and chest computed tomography. Knowledge of anatomy and scanning of both lungs in multiple positions is essential for effective pulmonary POCUS. In addition to identifying pertinent anatomic structures such as the diaphragm, liver, spleen, and pleura and identifying specific ultrasonography findings such as A-lines, B-lines, lung sliding, and dynamic air bronchograms, POCUS helps detect pleural and parenchymal abnormalities. Proficiency in pulmonary POCUS is an attainable and essential skill in the care and management of the critically ill patient.

Predictors of hospitalization for respiratory failure among patients with sarcoidosis-associated pulmonary hypertension.

Pulmonary hypertension leads to significant morbidity and mortality in patients with sarcoidosis. In this study, we examined clinical factors associated with the risk of respiratory failure-related hospitalization in 58 patients with sarcoidosis-associated pulmonary hypertension. Pulmonary vasodilator therapy and spirometry were associated with reduced risk of hospitalization in this cohort.

Lung Transplantation Waitlist Mortality Among Sarcoidosis Patients by Lung Allocation Score Grouping.

BACKGROUND: The Lung Allocation Score (LAS) system was designed to equalize and minimize waitlist mortality among candidiates for lung transplantation. The LAS stratifies sarcoidosis patients by mean pulmonary arterial pressure (mPAP) into group A (mPAP ≤30 mm Hg) and group D (mPAP >30 mm Hg). In this study, we aimed to analyze the effect of diagnostic grouping and patient characteristics on waitlist mortality among sarcoidosis patients. METHODS: This was a retrospective review of sarcoidosis lung transplantation candidates since LAS implementation in May 2005 through May 2019 in the Scientific Registry of Transplant Recipients database. We compared baseline characteristics, LAS variables, and waitlist outcomes between sarcoidosis groups A and D. We performed Kaplan-Meier survival analysis and multivariable regression to determine associations with waitlist mortality. RESULTS: We identified 1027 sarcoidosis candidates since LAS implementation. Of these, 385 had mPAP ≤30 mm Hg and 642 had mPAP >30 mm Hg. Waitlist mortality was 18% in sarcoidosis group D and 14% in sarcoidosis group A. Kaplan-Meier curve showed lower waitlist survival probability for sarcoidosis group D than group A (log-rank P = .0049). Functional status, oxygen requirement, and sarcoidosis group D were associated with increased waitlist mortality. Cardiac output ≥4 L/min was associated with decreased waitlist mortality. CONCLUSION: Sarcoidosis group D had lower waitlist survival than group A. Decreased survival appears driven by mPAP; sarcoidosis group D, functional status, oxygen requirement, and cardiac output had significant associations with waitlist mortality. These findings suggest that the current LAS grouping does not adequately reflect the risk for waitlist mortality among sarcoidosis group D patients.

Unexpected pulmonary mechanics during positive pressure mechanical ventilation in fibrotic lung disease with concomitant flail chest.

Understanding of pulmonary mechanics is essential to understanding mechanical ventilation. Typically, clinicians are mindful of peak and plateau pressures displayed on the ventilator and lung compliance, which is decreased in lung disease such as idiopathic pulmonary fibrosis (IPF). Decreased lung compliance leads to elevated peak and plateau pressures. We present a patient with IPF undergoing mechanical ventilation after cardiac arrest. Despite low lung compliance, he had normal peak and plateau pressures due to the presence of flail chest and increased chest wall compliance. This case highlights the role chest wall compliance plays in total respiratory system compliance and pulmonary mechanics.

Microscopic Examination of Clots from Percutaneous Mechanical Embolectomies in Pulmonary Embolism.

Pulmonary embolism (PE) is a very common clinical entity with clinical symptoms that range from no symptom to complete hemodynamic collapse, sometimes with similar-appearing clot burden on computed tomographic pulmonary angiogram. Given highly variable clinical presentation, the authors wanted to investigate if there is clinical correlation based on the age of a clot with microscopic examination to clinical presentation. Thirteen thrombectomy aspirates from patients with an acute PE were microscopically analyzed. The goal was to age the thrombus based on histologic features and correlate it to clinical course.

Single-institution experience of extracorporeal membrane oxygenation for near-fatal asthma.

Near-fatal asthma (NFA) is the most severe presentation of asthma. It is characterized by hypoxemic and hypercapnic respiratory failure requiring ventilatory assistance, including non-invasive ventilation and mechanical ventilation. However, NFA has a high mortality rate despite conventional therapy. Extracorporeal membrane oxygenation (ECMO) is a treatment modality that is increasingly being utilized as rescue therapy in patients with NFA that is refractory to mechanical ventilation. Prior analyses of the international Extracorporeal Life Support Organization (ELSO) registry data showed a survival rate of over 83% in patients placed on venovenous (VV) ECMO for NFA, but with notable rate of hemorrhagic complications. We report seven cases of adults with NFA requiring ECMO support at our large quaternary care institution between the years 2019 and 2022. All seven patients presented with respiratory failure in the setting of asthma exacerbation that progressed despite standard pharmacotherapy and mechanical ventilation. All patients survived to hospital discharge after ECMO support without hemorrhagic complications, highlighting the effectiveness and safety of ECMO when appropriately used in this population.

Contemporary practice patterns and outcomes of systemic thrombolysis in acute pulmonary embolism.

OBJECTIVE: Although systemic thrombolysis (ST) is the standard of care in the treatment of high-risk pulmonary embolism (PE), large variations in real-world usage exist, including its use to treat intermediate-risk PE. A paucity of data is available to define the outcomes and practice patterns of the ST dose, duration, and treatment of presumed and imaging-confirmed PE. METHODS: We performed a multicenter retrospective study to evaluate the real-world practice patterns of ST use in the setting of acute PE (presumed vs imaging-confirmed intermediate- and high-risk PE). Patients who had received tissue plasminogen activator for PE between 2017 and 2019 were included. We compared the baseline clinical characteristics, tissue plasminogen activator practice patterns, and outcomes for patients with confirmed vs presumed PE. RESULTS: A total of 104 patients had received ST for PE: 52 with confirmed PE and 52 with presumed PE. Significantly more patients who had been treated for presumed PE had experienced cardiac arrest (n = 47; 90%) compared with those with confirmed PE (n = 23; 44%; P < .01). Survival to hospital discharge was 65% for the patients with confirmed PE vs 6% for those with presumed PE (P < .01). The use of ST was contraindicated for 56% of the patients with confirmed PE, with major bleeding in 26% but no intracranial hemorrhage. CONCLUSIONS: The in-hospital mortality of patients with confirmed acute PE has remained high (35%) in contemporary practice for those treated with ST. A large proportion of these patients had had contraindications to ST, and the rates of major bleeding were significant. Those with confirmed PE had had a higher survival rate compared with those with presumed PE, including those with cardiac arrest. This observation suggests a limited role for empiric thrombolysis in cardiac arrest situations.

Malignant Pleural Effusion: Presentation, Diagnosis, and Management.

Malignant pleural effusions are common in patients with cancer. Most malignant pleural effusions are secondary to metastases to the pleura, most often from lung or breast cancer. The presence of malignant effusion indicates advanced disease and poor survival; in lung cancer, the presence of malignant effusion upstages the cancer to stage 4. Usually presenting as a large, unilateral exudative effusion, most patients with malignant pleural effusion experience dyspnea. Prior to intervention, diagnosis of malignant pleural effusion and exclusion of infection should be made. Thoracic imaging is typically performed, with computed tomography considered by many to be the gold standard. Thoracic ultrasound is also useful, particularly if diaphragmatic or pleural thickening and nodularity can be identified. Cytology should then be obtained; this is typically done via pleural fluid aspiration or pleural biopsy. Treatment focuses on palliation and relief of symptoms. Numerous interventions are available, ranging from drainage with thoracentesis or indwelling pleural catheter to more definitive, invasive options such as pleurodesis. There is no clear best approach, and a patient-centered approach should be taken.

Nasopharyngolaryngoscopy as a Triage Tool for Airway Compromise in Angioedema: A Retrospective Cohort Study.

Background Airway compromise and respiratory failure are feared complications of angioedema leading to intensive care unit (ICU) admission. However, few of these patients decompensate. There is a paucity of tools that predict airway compromise in patients with angioedema, and it is unclear if automatic triage to the ICU is warranted. We analyzed patients admitted to our tertiary center ICU with angioedema for "airway watch" to find a way to triage those at greatest risk of respiratory decompensation. Methods We performed a retrospective review of patients with angioedema admitted to our ICU between 2017 and 2020. Data collected included demographics, comorbidities, nasopharyngolaryngoscopy (NPL) findings, need for intubation, and length of stay. Descriptive analysis and subsequent ANOVA or T-test statistical analysis was performed to determine the relationships between individual variables and outcomes. Categorical variables were compared using Pearson's Chi-squared test or Fisher's exact test where applicable. Continuous variables were compared using a Mann-Whitney U test. Results Of 134 patients admitted to our ICU, 63 (47%) required intubation, primarily in the emergency department (92.1%). Of those who required intubation, 61.9% had abnormal NPL findings in contrast to 25.35% of patients who did not require intubation (p<0.0001). Normal NPL findings had a negative predictive value for requiring intubation of 86.5%. Abnormal NPL findings had a positive predictive value for requiring intubation of 68.4%. Conclusion While airway compromise is a serious complication of angioedema, there is scant evidence to support triage to the ICU for those not intubated immediately. The majority of patients with angioedema who required intubation had abnormal NPL findings, and the majority of those with normal NPL findings did not require intubation. This suggests that NPL findings in patients with angioedema can help with triage to the ICU.

Changes in Lung Perfusion in Patients Treated with Percutaneous Mechanical Thrombectomy for Intermediate-Risk Pulmonary Embolism.

BACKGROUND: Current pulmonary embolism treatment options rely heavily on anatomical clot location. However, anatomical location does not necessarily determine adverse outcomes; rather, clinical severity is secondary to the degree of perfusion impairment. Dual-energy computed tomography pulmonary angiogram (DE-CTPA) can map perfusion at the time of pulmonary embolism diagnosis. Single-photon emission computed tomography ventilation-perfusion scans allow for perfusion tracking similar to DE-CTPA. METHODS: We present 3 patients with intermediate-risk pulmonary embolism treated with mechanical thrombectomy using the Inari FlowTriever System (Inari Medical, Irvine, Calif). Lung perfusion scoring was applied to pre-procedure and post-procedure imaging. We graded perfusion of each lobe in 3 planes. If the entire lobe was perfused, a score of 3 was assigned. If lung perfusion is normal, total perfusion score is 15. All patients had pre-procedure and follow-up transthoracic echocardiograms. RESULTS: All 3 patients were diagnosed with pulmonary embolism via DE-CTPA that showed right ventricle strain and had deep venous thrombosis. Following mechanical thrombectomy, patients immediately experienced improvement in perfusion score; scores continued to improve at follow-up. All patients also had improvement in right ventricle size or function on follow-up echocardiogram. DISCUSSION: Intermediate-risk pulmonary embolism often has large initial clot burden that predicts residual pulmonary vascular obstruction. Residual pulmonary vascular obstruction is associated with increased risk of death, recurrent thrombus, and chronic thromboembolic pulmonary hypertension. Clot removal via thrombectomy may decrease the prevalence of residual pulmonary vascular obstruction by improving lung perfusion. We found that mechanical thrombectomy increased lung perfusion immediately and at follow-up assessments.

Granulomatosis with polyangiitis: The trigger cannot be long hidden.

Granulomatosis with polyangiitis, or GPA, is a form of vasculitis that affects multiple organs especially the respiratory tract and the kidneys. The diagnosis is suspected with the clinical presentation and elevated serum titer of antineutrophil cytoplasmic antibodies and confirmed with the biopsy of the affected organ. Viral infection has been described as one of the triggers of the immune system in developing GPA. In this report, we describe a rare case of GPA that developed following cytomegalovirus infection in a patient with unknown immunocompromised medical condition.

Vitamin C Deficiency-Induced Pulmonary Arterial Hypertension.

We report a case of a man in his 60s who developed pulmonary arterial hypertension (PAH) in association with profound vitamin C deficiency. Decreased availability of endothelial nitric oxide and activation of the hypoxia-inducible family of transcription factors, both consequences of vitamin C deficiency, are believed to be mechanisms contributing to the pathogenesis of the pulmonary hypertension. The PAH resolved following vitamin C supplementation. The current case highlights the importance of testing for vitamin C deficiency in patients with PAH in the proper clinical setting.

CDC Group EO-4 and Candida tropicalis Peritonitis in a Patient on Peritoneal Dialysis after Upper Endoscopy, Colonoscopy and Coil Embolization of the Gastroduodenal Artery.

Peritoneal dialysis (PD) is an excellent form of renal replacement therapy for many patients with end-stage renal disease (ESRD). Over 10,000 patients receive PD in the United States [United States Renal Data System: 2015 USRDS Annual Data Report: Epidemiology of Kidney Disease in the United States, 2015]. PD has superior outcomes compared to hemodialysis in the first 2 years of ESRD [Sinnakirouchenan and Holley: Adv Chronic Kidney Dis 2011;18: 428-432]. However, peritonitis is a known complication and may result in significant morbidity and necessitate transition to hemodialysis, which increases medical costs [Holley and Piraino: Semin Dial 1990;3: 245-248]. We report the first case of a PD patient who underwent endoscopy, colonoscopy and CT angiogram with coil embolization for gastrointestinal bleeding without antibiotic prophylaxis and subsequently developed CDC group EO-4 organism and fungal peritonitis.