Frequency of Screening and Spontaneous Breathing Trial Techniques: A Randomized Clinical Trial.

Importance: The optimal screening frequency and spontaneous breathing trial (SBT) technique to liberate adults from ventilators are unknown. Objective: To compare the effects of screening frequency (once-daily screening vs more frequent screening) and SBT technique (pressure-supported SBT with a pressure support level that was >0-≤8 cm H2O and a positive end-expiratory pressure [PEEP] level that was >0-≤5 cm H2O vs T-piece SBT) on the time to successful extubation. Design, Setting, and Participants: Randomized clinical trial with a 2 × 2 factorial design including critically ill adults who were receiving invasive mechanical ventilation for at least 24 hours, who were capable of initiating spontaneous breaths or triggering ventilators, and who were receiving a fractional concentration of inspired oxygen that was 70% or less and a PEEP level of 12 cm H2O or less. Recruitment was between January 2018 and February 2022 at 23 intensive care units in North America; last follow-up occurred October 18, 2022. Interventions: Participants were enrolled early to enable protocolized screening (more frequent vs once daily) to identify the earliest that patients met criteria to undergo pressure-supported or T-piece SBT lasting 30 to 120 minutes. Main Outcome and Measures: Time to successful extubation (time when unsupported, spontaneous breathing began and was sustained for ≥48 hours after extubation). Results: Of 797 patients (198 in the once-daily screening and pressure-supported SBT group, 204 in once-daily screening and T-piece SBT, 195 in more frequent screening and pressure-supported SBT, and 200 in more frequent screening and T-piece SBT), the mean age was 62.4 (SD, 18.4) years and 472 (59.2%) were men. There were no statistically significant differences by screening frequency (hazard ratio [HR], 0.88 [95% CI, 0.76-1.03]; P = .12) or by SBT technique (HR, 1.06 [95% CI, 0.91-1.23]; P = .45). The median time to successful extubation was 2.0 days (95% CI, 1.7-2.7) for once-daily screening and pressure-supported SBT, 3.1 days (95% CI, 2.7-4.8) for once-daily screening and T-piece SBT, 3.9 days (95% CI, 2.9-4.7) for more frequent screening and pressure-supported SBT, and 2.9 days (95% CI, 2.0-3.1) for more frequent screening and T-piece SBT. An unexpected interaction between screening frequency and SBT technique required pairwise contrasts that revealed more frequent screening (vs once-daily screening) and pressure-supported SBT increased the time to successful extubation (HR, 0.70 [95% CI, 0.50-0.96]; P = .02). Once-daily screening and pressure-supported SBT (vs T-piece SBT) did not reduce the time to successful extubation (HR, 1.30 [95% CI, 0.98-1.70]; P = .08). Conclusions and Relevance: Among critically ill adults who received invasive mechanical ventilation for more than 24 hours, screening frequency (once-daily vs more frequent screening) and SBT technique (pressure-supported vs T-piece SBT) did not change the time to successful extubation. However, an unexpected and statistically significant interaction was identified; protocolized more frequent screening combined with pressure-supported SBTs increased the time to first successful extubation. Trial Registration: ClinicalTrials.gov Identifiers: NCT02399267 and NCT02969226.

Serum Immunoglobulin G Levels Are Associated with Risk for Exacerbations: An Analysis of SPIROMICS.

RATIONALE: Serum Immunoglobulin G (IgG) deficiency is associated with morbidity in chronic obstructive pulmonary disease (COPD) but it is unclear whether concentrations in the lower end of the normal range still confer risk. OBJECTIVES: To determine if levels above traditional cutoffs for serum IgG deficiency are associated with exacerbations among current and former smokers with or at risk for COPD. MEASUREMENTS AND MAIN RESULTS: Former and current smokers in SPIROMICS (n=1,497) were studied, n=1,026 with and n=471 at risk for COPD. In a subset (n=1,031), IgG subclasses were measured. Associations between total IgG or subclasses and prospective exacerbations were evaluated with multivariable models adjusting for demographics, current smoking, smoking history, FEV1% predicted, inhaled corticosteroids, and serum IgA. RESULTS: The 35th percentile (1225 mg/dL in this cohort) of IgG was the best cutoff by Akaike Information Criterion (AIC). Below this, there was increased exacerbation risk (IRR 1.28, 95% CI 1.08-1.51). Among subclasses, IgG1 and IgG2 below 35th percentile (354 and 105 mg/dL, respectively) were both associated with increased risk of severe exacerbation (IgG1: IRR 1.39, 95% CI 1.06-1.84; IgG2: IRR 1.50, 95% CI 1.14-1.1.97). These associations remained significant when additionally adjusting for history of exacerbations. CONCLUSIONS: Lower serum IgG is prospectively associated with exacerbations in individuals with or at risk for COPD. Among subclasses, lower IgG1 and IgG2 are prospectively associated with severe exacerbations. The optimal IgG cutoff was substantially higher than traditional cutoffs for deficiency, suggesting subtle impairment of humoral immunity may be associated with exacerbations.

A Single-center Experience With >200 Lung Transplant Recipients With COVID-19 Infection.

Background: Although COVID-19 is no longer a declared global health emergency, data remain limited on the impact of COVID-19 in lung transplant recipients. Methods: We identified lung transplant recipients who were diagnosed with COVID-19 from March 2020 through August 2022 in our institutional database and investigated clinical outcomes. We then analyzed outcomes based on date of COVID-19 diagnosis (first wave March 2020-October 2020; second wave November 2020-2021; third wave December 2021-September 2022) and compared these results. Results: Of the 210 lung transplant recipients (median age 67; 67% men) enrolled, 140 (67%) required hospital admission. Among admitted recipients, 35 (25%) were intubated and 7 (5%) were placed on extracorporeal membrane oxygenation. Overall survival was 67.1% at 1 y and 59.0% at 2 y post-COVID-19 diagnosis. COVID-19 led to mortality in all 5 patients diagnosed during their index admission for lung transplantation. Although overall survival was significantly better in recipients with COVID-19 during the third wave, in-hospital mortality remained high (first wave 28%, second wave 38%, and 28% third wave). Vaccination (partially vaccinated versus none and fully vaccinated versus none) was the only significant protective factor for hospital admission, and age 70 y and older and partially vaccinated (versus none or fully vaccinated) were independent risk factors for in-hospital mortality. Conclusions: Overall survival after COVID-19 infection in lung transplant recipients continues to improve; however, in-hospital mortality remains remarkably high. Vaccination appears to have been impactful in preventing hospital admission, but its impact on in-hospital mortality is still unclear. Further research is needed to better identify lung transplant recipients at high risk for mortality from COVID-19.

Clinical Review of Non-invasive Ventilation.

Noninvasive ventilation (NIV) is the mainstay to treat patients who need augmentation of ventilation for acute and chronic forms of respiratory failure. The last several decades has witnessed an extension of the indications for NIV to a variety of acute and chronic lung diseases. Evolving advancements in technology and personalised approaches to patient care make it feasible to prioritise patient centered care models that deliver home-based management using telemonitoring and telemedicine systems support. These trends may improve patient outcomes, reduce healthcare costs, and improve the quality of life for patients who suffer from chronic diseases that precipitate respiratory failure.

Unraveling the spectrum of airway complications following lung transplantation: a comprehensive overview.

PURPOSE OF REVIEW: This review delves into the intricate landscape of airway complications post lung transplantation. With the rising prevalence of end-stage lung disease and the increasing number of lung transplantation worldwide, understanding and effectively managing airway complications are crucial. Given the nuanced nature of these complications and the array of treatment options available, this review aims to provide a comprehensive overview of how to identify, classify, mitigate risk factors for, and manage these complications. RECENT FINDINGS: Several donor, recipient, and surgical risk factors are associated with the increased risk of airway complications. In managing these complications, bronchoscopic interventions, notably balloon dilation and stenting, are pivotal. Although self-expanding metallic stents offer versatility, silicone stents are preferred in certain scenarios for their durability. Emerging techniques such as biodegradable stents and advancing imaging modalities show promise in mitigating complications and improving outcomes. SUMMARY: These findings underscore the significance of a multidisciplinary approach and personalized treatment algorithms in managing airway complications post lung transplantation. By elucidating specific indications and complications of treatment modalities, this review serves as a valuable resource for optimally managing airway complications. Ongoing research into novel interventions holds promise for further enhancing outcomes in this challenging clinical setting.

Predictors of Residual Pulmonary Vascular Obstruction after Acute Pulmonary Embolism Based on Patient Variables and Treatment Modality.

Background: Residual Pulmonary Vascular Obstruction (RPVO) is an area of increasing focus in patients with acute pulmonary embolism (PE) due to its association with long-term morbidity and mortality. The predictive factors and the effect catheter-directed therapies (CDT) have on RPVO are still under investigation. Methods: This is a single-center retrospective review between April 2017 and July 2021. Patients with intermediate risk of PE were included. Patient variables associated with RPVO were analyzed and the degree of clot burden was quantified using the Qanadli score. Results: A total of 551 patients with acute PE were identified, 288 were intermediate risk and 53 had RPVO based on CT or V/Q scan three months post-PE. Baseline clot burden was higher in patients who received CDT compared to those who received anticoagulation alone (Qanadli score 45.88% vs. 31.94% p < 0.05). In univariate analysis, treatment with CDT showed a HR of 0.32 (95% CI 0.21-0.50, p < 0.001) when compared with anticoagulation alone. Patient variables including intermediate-high risk, sPESI ≥ 1, elevated biomarkers, RV dysfunction on imaging, malignancy, history of or concurrent DVT were also significantly associated with development of RPVO in univariate analysis. In multivariable analysis, only baseline Qanadli score (HR 13.88, 95% CI 1.42-135.39, p = 0.02) and concurrent DVT (HR 2.53, 95% CI 1.01-6.40, p = 0.04) were significantly associated with the development of RPVO. Conclusions: Catheter-directed therapy may be associated with a reduced risk of RPVO at 3 months; however, quantitative clot burden scores, such as the Qanadli score, may be stronger predictors of the risk of developing RPVO at 3 months. Further prospective studies are required.

Respiratory Assist Devices in Pulmonary Rehabilitation.

Patients with advanced lung disease, especially patients with COPD, suffer from dyspnea at rest that worsens during the performance of even limited physical activities. The causes of dyspnea are multifactorial and are related to structural changes found in the parenchymal compartment of the lung as well as the airway and pulmonary vasculature. Alterations in any of the lung compartments may have negative consequences for the physiological performance of exercise. Respiratory assist devices that attenuate the pathophysiological derangements induced by the underlying lung disease, and/or unload the increased work of breathing, can enhance the performance of exercise, and help to produce more robust training effects in patients with lung disease. Herein we review the data that examines these approaches using respiratory assist devices to improve exercise outcomes in patients with COPD.

Lung volume reduction surgery is safe and leads to functional improvement in patients who fail or cannot undergo bronchoscopic lung volume reduction.

Background: Bronchoscopic lung volume reduction (BLVR) has supplanted surgery in the treatment of patients with advanced emphysema, but not all patients qualify for it. Our study aimed to investigate the outcomes of lung volume reduction surgery (LVRS) among patients who either failed BLVR or were not candidates for it. Methods: We conducted a retrospective analysis of patients who underwent LVRS for upper lobe-predominant emphysema at a single tertiary center between March 2018 and December 2022. The main outcomes measures were preoperative and postoperative respiratory parameters, perioperative morbidity, and mortality. Results: A total of 67 LVRS recipients were evaluated, including 10 who had failed prior valve placement. The median patient age was 69 years, and 35 (52%) were male. All procedures were performed thoracoscopically, with 36 patients (53.7%) undergoing bilateral LVRS. The median hospital length of stay was 7 days (interquartile range, 6-11 days). Prolonged air leak (>7 days) occurred in 20 patients. There was one 90-day mortality from a nosocomial pneumonia (non-COVID-related) and no further deaths at 12 months. There were mean improvements of 10.07% in forced expiratory volume in 1 second and 4.74% in diffusing capacity of the lung for carbon monoxide, along with a mean decrease 49.2% in residual volume (P < .001 for all). The modified Medical Research Council dyspnea scale was improved by 1.84 points (P < .001). Conclusions: LVRS can be performed safely in patients who are not candidates for BLVR and those who fail BLVR and leads to significant functional improvement. Long-term follow-up is necessary to ensure the sustainability of LVRS benefits in this patient population.

ß-Blocker Use and Clinical Outcomes in Patients With COPD Following Acute Myocardial Infarction.

Importance: While ß-blockers are associated with decreased mortality in cardiovascular disease (CVD), exacerbation-prone patients with chronic obstructive pulmonary disease (COPD) who received metoprolol in the Beta-Blockers for the Prevention of Acute Exacerbations of Chronic Obstructive Pulmonary Disease (BLOCK-COPD) trial experienced increased risk of exacerbations requiring hospitalization. However, the study excluded individuals with established indications for the drug, raising questions about the overall risk and benefit in patients with COPD following acute myocardial infarction (AMI). Objective: To investigate whether ß-blocker prescription at hospital discharge is associated with increased risk of mortality or adverse cardiopulmonary outcomes in patients with COPD and AMI. Design, Setting, and Participants: This prospective, longitudinal cohort study with 6 months of follow-up enrolled patients aged 35 years or older with COPD who underwent cardiac catheterization for AMI at 18 BLOCK-COPD network hospitals in the US from June 2020 through May 2022. Exposure: Prescription for any ß-blocker at hospital discharge. Main Outcomes and Measures: The primary outcome was time to the composite outcome of death or all-cause hospitalization or revascularization. Secondary outcomes included death, hospitalization, or revascularization for CVD events, death or hospitalization for COPD or respiratory events, and treatment for COPD exacerbations. Results: Among 3531 patients who underwent cardiac catheterization for AMI, prevalence of COPD was 17.1% (95% CI, 15.8%-18.4%). Of 579 total patients with COPD and AMI, 502 (86.7%) were prescribed a ß-blocker at discharge. Among the 562 patients with COPD included in the final analysis, median age was 70.0 years (range, 38.0-94.0 years) and 329 (58.5%) were male; 553 of the 579 patients (95.5%) had follow-up information. Among those discharged with ß-blockers, there was no increased risk of the primary end point of all-cause mortality, revascularization, or hospitalization (hazard ratio [HR], 1.01; 95% CI, 0.66-1.54; P = .96) or of cardiovascular events (HR, 1.11; 95% CI, 0.65-1.92; P = .69), COPD-related or respiratory events (HR, 0.75; 95% CI, 0.34-1.66; P = .48), or treatment for COPD exacerbations (rate ratio, 1.01; 95% CI, 0.53-1.91; P = .98). Conclusions and Relevance: In this cohort study, ß-blocker prescription at hospital discharge was not associated with increased risk of adverse outcomes in patients with COPD and AMI. These findings support use of ß-blockers in patients with COPD and recent AMI.

Optimizing clinical outcomes for bronchoscopic lung volume reduction with Zephyr® valves.

Bronchoscopic lung volume reduction treatment with Zephyr one-way valves is an effective guideline-based treatment option for patients with severe emphysema and hyperinflation. However, in some cases the treatment response is less than anticipated or there might be a loss of initial treatment effect. Reasons for the lack of response can include incorrect assessment of collateral ventilation, improper valve placement, or patient related factors. Loss of initial benefit can be due to granulation tissue formation and subsequent valve dysfunction, or there may be side effects such as excessive coughing or infectious problems. Careful follow-up after treatment with valves is important and evaluation with a CT scan and/or bronchoscopy is helpful if there is no improvement after treatment or loss of initial benefit. This paper aims to describe the most important causes and provide a strategy of how to approach and manage these patients.

Computational Deconvolution of Cell Type-Specific Gene Expression in COPD and IPF Lungs Reveals Disease Severity Associations.

RATIONALE: Chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF) are debilitating diseases associated with divergent histopathological changes in the lungs. At present, due to cost and technical limitations, profiling cell types is not practical in large epidemiology cohorts (n>1000). Here, we used computational deconvolution to identify cell types in COPD and IPF lungs whose abundances and cell type-specific gene expression are associated with disease diagnosis and severity. METHODS: We analyzed lung tissue RNA-seq data from 1026 subjects (COPD, n=465; IPF, n=213; control, n=348) from the Lung Tissue Research Consortium. We performed RNA-seq deconvolution, querying thirty-eight discrete cell-type varieties in the lungs. We tested whether deconvoluted cell-type abundance and cell type-specific gene expression were associated with disease severity. RESULTS: The abundance score of twenty cell types significantly differed between IPF and control lungs. In IPF subjects, eleven and nine cell types were significantly associated with forced vital capacity (FVC) and diffusing capacity for carbon monoxide (DLCO), respectively. Aberrant basaloid cells, a rare cells found in fibrotic lungs, were associated with worse FVC and DLCO in IPF subjects, indicating that this aberrant epithelial population increased with disease severity. Alveolar type 1 and vascular endothelial (VE) capillary A were decreased in COPD lungs compared to controls. An increase in macrophages and classical monocytes was associated with lower DLCO in IPF and COPD subjects. In both diseases, lower non-classical monocytes and VE capillary A cells were associated with increased disease severity. Alveolar type 2 cells and alveolar macrophages had the highest number of genes with cell type-specific differential expression by disease severity in COPD and IPF. In IPF, genes implicated in the pathogenesis of IPF, such as matrix metallopeptidase 7, growth differentiation factor 15, and eph receptor B2, were associated with disease severity in a cell type-specific manner. CONCLUSION: Utilization of RNA-seq deconvolution enabled us to pinpoint cell types present in the lungs that are associated with the severity of COPD and IPF. This knowledge offers valuable insight into the alterations within tissues in more advanced illness, ultimately providing a better understanding of the underlying pathological processes that drive disease progression.

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.

Design of the STRIVE-IPF Trial- Study of Therapeutic Plasma Exchange, Rituximab, and Intravenous Immunoglobulin for Acute Exacerbations of Idiopathic Pulmonary Fibrosis.

Background: Acute exacerbations of idiopathic pulmonary fibrosis (AE-IPF) affect a significant proportion of patients with IPF. There are limited data to inform therapeutic strategies for AEIPF, despite its high mortality. We discuss the rationale and design of STRIVE-IPF, a randomized, multi-center, open-label Phase IIb clinical trial to determine the efficacy of combined therapeutic plasma exchange (TPE), rituximab, and intravenous immunoglobulin (IVIG), in comparison to treatment as usual (TAU), among patients with acute IPF exacerbations. Methods: The STRIVE-IPF trial will randomize 51 patients among five sites in the United States. The inclusion criteria have been designed to select a study population with AE-IPF, as defined by American Thoracic Society criteria, while excluding patients with an alternative cause for a respiratory decompensation. The primary endpoint of this trial is six-month survival. Secondary endpoints include supplement oxygen requirement and six-minute walk distance which will be assessed immediately prior to treatment and after completion of therapy on day 19, as well as at periodic subsequent visits. Discussion: The experimental AE-IPF therapy proposed in this clinical trial was adapted from treatment regimens used in other antibody-mediated diseases. The regimen is initiated with TPE, which is expected to rapidly reduce circulating autoantibodies, followed by rituximab to reduce B-cells and finally IVIG, which likely has multiple effects, including affecting feedback inhibition of residual B-cells by Fc receptor occupancy. We have reported potential benefits of this experimental therapy for AE-IPF in previous anecdotal reports. This clinical trial has the potential to profoundly affect current paradigms and treatment approaches to patients with AE-IPF.Trial Registration ClinicalTrials.gov identifier: NCT03286556.

Design of the STRIVE-IPF trial- study of therapeutic plasma exchange, rituximab, and intravenous immunoglobulin for acute exacerbations of idiopathic pulmonary fibrosis.

BACKGROUND: Acute exacerbations of idiopathic pulmonary fibrosis (AE-IPF) affect a significant proportion of patients with IPF. There are limited data to inform therapeutic strategies for AE-IPF, despite its high mortality. We discuss the rationale and design of STRIVE-IPF, a randomized, multi-center, open-label Phase IIb clinical trial to determine the efficacy of combined therapeutic plasma exchange (TPE), rituximab, and intravenous immunoglobulin (IVIG), in comparison to treatment as usual (TAU), among patients with acute IPF exacerbations. METHODS: The STRIVE-IPF trial will randomize 51 patients among five sites in the United States. The inclusion criteria have been designed to select a study population with AE-IPF, as defined by American Thoracic Society criteria, while excluding patients with an alternative cause for a respiratory decompensation. The primary endpoint of this trial is six-month survival. Secondary endpoints include supplement oxygen requirement and six-minute walk distance which will be assessed immediately prior to treatment and after completion of therapy on day 19, as well as at periodic subsequent visits. DISCUSSION: The experimental AE-IPF therapy proposed in this clinical trial was adapted from treatment regimens used in other antibody-mediated diseases. The regimen is initiated with TPE, which is expected to rapidly reduce circulating autoantibodies, followed by rituximab to reduce B-cells and finally IVIG, which likely has multiple effects, including affecting feedback inhibition of residual B-cells by Fc receptor occupancy. We have reported potential benefits of this experimental therapy for AE-IPF in previous anecdotal reports. This clinical trial has the potential to profoundly affect current paradigms and treatment approaches to patients with AE-IPF. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03286556.

The Effect of Chronic Altitude Exposure on COPD Outcomes in the SPIROMICS Cohort.

RATIONALE: Individuals with COPD have airflow obstruction and maldistribution of ventilation. For those living at high altitude, any gas exchange abnormality is compounded by reduced partial pressures of inspired oxygen. OBJECTIVES: Does residence at higher-altitude exposure affect COPD outcomes, including lung function, imaging characteristics, symptoms, health status, functional exercise capacity, exacerbations, or mortality? METHODS: From the SPIROMICS cohort, we identified individuals with COPD living below 1,000 ft (305 m) elevation (n= 1,367) versus above 4,000 ft (1,219 m) elevation (n= 288). Multivariable regression models were used to evaluate associations of exposure to high altitude with COPD-related outcomes. MEASUREMENTS AND MAIN RESULTS: Living at higher altitude was associated with reduced functional exercise capacity as defined by 6MWD (-32.3 m, (-55.7 to -28.6)). There were no differences in patient-reported outcomes as defined by symptoms (CAT, mMRC), or health status (SGRQ). Higher altitude was not associated with a different rate of FEV1 decline. Higher altitude was associated with lower odds of severe exacerbations (IRR 0.65, (0.46 to 0.90)). There were no differences in small airway disease, air trapping, or emphysema. In longitudinal analyses, higher altitude was associated with increased mortality (HR 1.25, (1.0 to 1.55)); however, this association was no longer significant when accounting for air pollution. CONCLUSIONS: Chronic altitude exposure is associated with reduced functional exercise capacity in individuals with COPD, but this did not translate into differences in symptoms or health status. Additionally, chronic high-altitude exposure did not affect progression of disease as defined by longitudinal changes in spirometry.

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.