Machine learning classifier is associated with mortality in interstitial lung disease: a retrospective validation study leveraging registry data.

BACKGROUND: Mortality prediction in interstitial lung disease (ILD) poses a significant challenge to clinicians due to heterogeneity across disease subtypes. Currently, forced vital capacity (FVC) and Gender, Age, and Physiology (GAP) score are the two most utilized metrics in prognostication. Recently, a machine learning classifier system, Fibresolve, designed to identify a variety of computed tomography (CT) patterns associated with idiopathic pulmonary fibrosis (IPF), was demonstrated to have a significant association with mortality across multiple subtypes of ILD. The purpose of this follow-up study was to retrospectively validate these findings in a large, external cohort of patients with ILD. METHODS: In this multi-center validation study, Fibresolve was applied to chest CT scans of patients with confirmed ILD that had available follow-up data. Fibresolve scores categorized by tertile were analyzed using Cox regression analysis adjusted for tobacco use and modified GAP (mGAP) score. RESULTS: Of 643 patients included, 446 (69.3%) died over a median follow-up time of 144 [1-821] weeks. The median [range] mGAP score was 5 [3-7]. In multivariable analysis, Fibresolve score categorized by tertile was significantly associated with mortality (Tertile 2 HR 1.47, 95% CI 0.82-2.37, p = 0.11; Tertile 3 HR 3.12, 95% CI 1.98-4.90, p < 0.001). Subgroup analyses revealed significant associations amongst those with non-IPF ILDs (Tertile 2 HR 1.95, 95% CI 1.28-2.97, Tertile 3 HR 4.66, 95% CI 2.94-7.38) and severe disease, defined by a FVC ≤ 75% (Tertile 2 HR 2.29, 95% CI 1.43-3.67, Tertile 3 HR 4.80, 95% CI 2.93-7.86). CONCLUSIONS: Fibresolve is independently associated with mortality in ILD, particularly amongst patients with non-IPF ILDs and in those with severe disease.

Risk Factors for Hospital Readmission in Patients With Interstitial Lung Disease.

BACKGROUND: Little is known about the rates, causes, or risk factors for hospital readmission among patients with interstitial lung disease (ILD). We investigated the prevalence, features, and comorbidities of subjects hospitalized with ILD and their subsequent re-hospitalizations in this retrospective study. METHODS: A retrospective analysis of subjects enrolled in the University of Chicago ILD Natural History registry was conducted. Demographic data, comorbidities, and timing and cause of subsequent hospitalizations were collected from the medical record. The primary outcome was time to first readmission via a cause-specific Cox hazards model with a sensitivity analysis with the Fine-Gray cumulative hazard model; the secondary outcome was the number of hospitalizations per subject via a Poisson multivariable model. RESULTS: Among 1,796 patients with ILD, 443 subjects were hospitalized, with 978 total hospitalizations; 535 readmissions were studied, 282 (53%) for a respiratory indication. For the outcome of time to readmission, Black race was the only subject characteristic associated with an increased hazard of readmission in the Cox model (hazard ratio 1.50, P = .03) while Black race, hypersensitivity pneumonitis, and sarcoidosis were associated with increased hazard of readmission in the Fine-Gray model. Black race, female sex, atrial fibrillation, obstructive lung disease, and pulmonary hypertension were associated with an increased number of hospitalizations in the Poisson model. CONCLUSIONS: We demonstrated that hospital readmission from any cause was a common occurrence in subjects with ILD. Further efforts to improve quality of life among these subjects could focus on risk scores for readmission, mitigating racial health disparities, and treatment of comorbidities.

Computer-Aided Pulmonary Fibrosis Detection Leveraging an Advanced Artificial Intelligence Triage and Notification Software.

Background: Improvement in recognition and referral of pulmonary fibrosis (PF) is vital to improving patient outcomes within interstitial lung disease. We determined the performance metrics and processing time of an artificial intelligence triage and notification software, ScreenDx-LungFibrosis™, developed to improve detection of PF. Methods: ScreenDx-LungFibrosis™ was applied to chest computed tomography (CT) scans from multisource data. Device output (+/- PF) was compared to clinical diagnosis (+/- PF), and diagnostic performance was evaluated. Primary endpoints included device sensitivity and specificity > 80% and processing time < 4.5 min. Results: Of 3,018 patients included, PF was present in 22.9%. ScreenDx-LungFibrosis™ detected PF with a sensitivity and specificity of 91.3% (95% confidence interval (CI): 89.0-93.3%) and 95.1% (95% CI: 94.2-96.0%), respectively. Mean processing time was 27.6 s (95% CI: 26.0 - 29.1 s). Conclusions: ScreenDx-LungFibrosis™ accurately and reliably identified PF with a rapid per-case processing time, underscoring its potential for transformative improvement in PF outcomes when routinely applied to chest CTs.

Tobacco smoking is associated with combined pulmonary fibrosis and emphysema and worse outcomes in interstitial lung disease.

Tobacco smoking is an established cause of pulmonary disease whose contribution to interstitial lung disease (ILD) is incompletely characterized. We hypothesized that compared with nonsmokers, subjects who smoked tobacco would differ in their clinical phenotype and have greater mortality. We performed a retrospective cohort study of tobacco smoking in ILD. We evaluated demographic and clinical characteristics, time to clinically meaningful lung function decline (LFD), and mortality in patients stratified by tobacco smoking status (ever vs. never) within a tertiary center ILD registry (2006-2021) and replicated mortality outcomes across four nontertiary medical centers. Data were analyzed by two-sided t tests, Poisson generalized linear models, and Cox proportional hazard models adjusted for age, sex, forced vital capacity (FVC), diffusion capacity of the lung for carbon monoxide (DLCO), ILD subtype, antifibrotic therapy, and hospital center. Of 1,163 study participants, 651 were tobacco smokers. Smokers were more likely to be older, male, have idiopathic pulmonary fibrosis (IPF), coronary artery disease, CT honeycombing and emphysema, higher FVC, and lower DLCO than nonsmokers (P < 0.01). Time to LFD in smokers was shorter (19.7 ± 20 mo vs. 24.8 ± 29 mo; P = 0.038) and survival time was decreased [10.75 (10.08-11.50) yr vs. 20 (18.67-21.25) yr; adjusted mortality HR = 1.50, 95%CI 1.17-1.92; P < 0.0001] compared with nonsmokers. Smokers had 12% greater odds of death for every additional 10 pack yr of smoking (P < 0.0001). Mortality outcomes remained consistent in the nontertiary cohort (HR = 1.51, 95%CI = 1.03-2.23; P = 0.036). Tobacco smokers with ILD have a distinct clinical phenotype strongly associated with the syndrome of combined PF and emphysema, shorter time to LFD, and decreased survival. Smoking prevention may improve ILD outcomes.NEW & NOTEWORTHY Smoking in ILD is associated with combined pulmonary fibrosis and emphysema and worse clinical outcomes.

Antigenic responses are hallmarks of fibrotic interstitial lung diseases independent of underlying etiologies.

Interstitial lung diseases (ILD) are heterogeneous conditions that may lead to progressive fibrosis and death of affected individuals. Despite diversity in clinical manifestations, enlargement of lung-associated lymph nodes (LLN) in fibrotic ILD patients predicts worse survival. Herein, we revealed a common adaptive immune landscape in LLNs of all ILD patients, characterized by highly activated germinal centers and antigen-activated T cells including regulatory T cells (Tregs). In support of these findings, we identified serum reactivity to 17 candidate auto-antigens in ILD patients through a proteome-wide screening using phage immunoprecipitation sequencing. Autoantibody responses to actin binding LIM protein 1 (ABLIM1), a protein highly expressed in aberrant basaloid cells of fibrotic lungs, were correlated with LLN frequencies of T follicular helper cells and Tregs in ILD patients. Together, we demonstrate that end-stage ILD patients have converging immune mechanisms, in part driven by antigen-specific immune responses, which may contribute to disease progression.

Critical Care Pharmacist Attitudes and Perceptions of Neuromuscular Blocker Infusions in ARDS.

BACKGROUND: Current critical care pharmacist (CCP) practices and perceptions related to neuromuscular infusion (NMBI) use for acute respiratory distress syndrome (ARDS) maybe different with the COVID-19 pandemic and the publication of 2020 NMBI practice guidelines. OBJECTIVE: To evaluate CCP practices and perceptions regarding NMBI use for patients with moderate-severe ARDS. METHODS: We developed, tested, and electronically administered a questionnaire (7 parent-, 42 sub-questions) to 409 American College of Clinical Pharmacy (ACCP) Critical Care Practice and Research Network members in 12 geographically diverse states. The questionnaire focused on adults with moderate-severe ARDS (PaO2:FiO2<150) whose causes of dyssynchrony were addressed. Two reminders were sent at 10-day intervals. RESULTS: Respondents [131/409 (32%)] primarily worked in a medical intensive care unit (ICU) 102 (78%). Compared to COVID-negative(-) ARDS patients, COVID positive(+) ARDS patients were twice as likely to receive a NMBI (34 ± 18 vs.16 ± 17%; P < 0.01). Respondents somewhat/strongly agreed a NMBI should be reserved until after trials of deep sedation (112, 86%) or proning (92, 81%) and that NMBI reduced barotrauma (88, 67%), dyssynchrony (87, 66%), and plateau pressure (79, 60%). Few respondents somewhat/strongly agreed that a NMBI should be initiated at ARDS onset (23, 18%) or that NMBI reduced 90-day mortality (12, 10%). Only 2/14 potential NMBI risks [paralysis awareness (101, 82%) and prolonged muscle weakness (84, 68%)] were frequently reported to be of high/very high concern. Multiple NMBI titration targets were assessed as very/extremely important including arterial pH (109, 88%), dyssynchrony (107, 86%), and PaO2: FiO2 ratio (82, 66%). Train-of-four (55, 44%) and BIS monitoring (36, 29%) were deemed less important. Preferred NMBI discontinuation criteria included absence of dysschrony (84, 69%) and use ≥48 hour (72, 59%). CONCLUSIONS AND RELEVANCE: Current critical care pharmacists believe NMBI for ARDS patients are best reserved until after trials of deep sedation or proning; unique considerations exist in COVID+ patients. Our results should be considered when ICU NMBI protocols are being developed and bedside decisions regarding NMBI use in ARDS are being formulated.

Physicians' attitudes and perceptions of neuromuscular blocker infusions in ARDS.

PURPOSE: The perceptions and practices of ICU physicians regarding initiating neuromuscular blocker infusions (NMBI) in acute respiratory distress syndrome (ARDS) may not be evidence-based amidst the surge of severe ARDS during the SARS-CoV-2 pandemic and new practice guidelines. We identified ICU physicians' perspectives and practices regarding NMBI use in adults with moderate-severe ARDS. MATERIALS AND METHODS: After extensive development and testing, an electronic survey was distributed to 342 ICU physicians from three geographically-diverse U.S. health systems(n = 12 hospitals). RESULTS: The 173/342 (50.5%) respondents (75% medical) somewhat/strongly agreed a NMBI should be reserved until: after a trial of deep sedation (142, 82%) or proning (59, 34%) and be dose-titrated based on train-of-four monitoring (107, 62%). Of 14 potential NMBI risks, 2 were frequently reported to be of high/very high concern: prolonged muscle weakness with steroid use (135, 79%) and paralysis awareness due to inadequate sedation (114, 67%). Absence of dyssychrony (93, 56%) and use ≥48 h (87, 53%) were preferred NMBI stopping criteria. COVID-19 + ARDS patients were twice as likely to receive a NMBI (56 ± 37 vs. 28 ± 19%, p < 0.01). CONCLUSIONS: Most intensivists agreed NMBI in ARDS should be reserved until after a deep sedation trial. Stopping criteria remain poorly defined. Unique considerations exist regarding the role of paralysis in COVID-19+ ARDS.

Geotrichum infection in an immunocompetent host with SARS-CoV-2 infection.

There has been increasing reports of secondary bacterial and fungal infections associated with COVID-19. Following the initial reports of infection with Aspergillus spp., and Candida spp. there has been a significant rise in infections with Mucorales spp. In this case report, we present a case of Geotrichum spp. infection in an immunocompetent host with COVID-19. To our knowledge, this is the first case of Geotrichum infection in COVID-19. Geotrichum is a rare emerging pathogen that causes invasive disease, termed geotrichosis, which occurs in immunocompromised adult hosts with neutropenia. The development of invasive fungal infection such as Geotrichum in patients with SARS-CoV-2 infection requires a high degree of clinical suspicion and should be considered particularly in those who have an underlying immunocompromised state and those receiving corticosteroids or other immunosuppressive agents.

Association between acute respiratory failure requiring mechanical ventilation and the production of advanced glycation end products.

Patients with acute respiratory failure often have hyperglycemia. Elevated glucose levels could cause acute lung injury through the production of advanced glycation end products. We measured glucose, advanced glycation end products, glycated albumin, circulating glycated hemoglobin, and soluble receptor for advanced glycation end product (sRAGE) levels on admission, at 24 hours, and at 72 hours in 40 patients with acute respiratory failure requiring mechanical ventilation. We compared these values with healthy control subjects. The mean age was 63.3±11.2 years. Fifty percent of the patients were women. Thirteen patients (32.5%) died during this hospitalization. The mean maximum glucose level on the day of admission was 215.7±171.1 mg/dL. Compared with control subjects, there was a significant reduction in advanced glycation end product levels (p=0.0001) in the patients at all 3 time points. Circulating glycated hemoglobin levels were significantly higher in patients compared with control subjects. We also observed a moderate increase in glycated albumin levels on admission and at 24 hours when compared with the control samples. Overall sRAGE levels were similar to controls, but patients with dense infiltrates on chest X-ray had increased levels compared with patients who did not have these dense infiltrates on the day of admission. Patients with acute respiratory failure requiring mechanical ventilation have decreased levels of advanced glycation end products and increased levels of circulating glycated hemoglobin. The results from this pilot study suggest that the acute stress associated with respiratory failure might create glycated proteins which could contribute to disease pathogenesis.

Advanced glycation end products and glycosaminoglycans in patients with diabetic ketoacidosis.

In some patients diabetic ketoacidosis (DKA) causes acute endothelial injury and multiorgan failure. Measurement of glycosaminoglycan (GAG) and advanced glycation end products (AGE) could provide information to help understand the biochemical events associated with poor outcomes in these patients. This study included 37 patients with DKA admitted to an intensive care unit. Blood was collected from these patients during the first day of hospitalization, 24 hours after the first sample, and 72 hours after the first sample when possible. ELISA-based assays were used to measure glucose, hemoglobin A1c, AGE, glycated albumin, and GAG levels in serum. Twenty healthy control subjects with no history of diabetes donated 1 blood sample. Control subjects had a mean age of 36.3±12.1 years; patients with DKA had a mean age of 38.1±18.5 years. Admission laboratory tests in patients with DKA included glucose 546±296 mg/dL, bicarbonate 10.1±5.5 mEq/L, anion gap 31.8±7.8 mEq/L, and creatinine 1.1±1.0 mg/dL. Patients with DKA had significantly higher level glucose and free glycated hemoglobin. Control subjects had significantly higher levels of AGE and glycated albumin. There were no differences in soluble receptor for AGE levels or GAG levels between the control subjects and patients with DKA. Patients with DKA had lower circulating levels of AGE and glycated albumin than control subjects. These results may reflect absorption of these proteins to damaged capillary surfaces or loss of proteins into interstitial spaces secondary to increased endothelial permeability.

The Complexity of Characteristics, Diagnoses and Treatment of Older Patients With Pulmonary Hypertension.

BACKGROUND: Older patients with pulmonary hypertension (PH) are more likely to have complex comorbidity than younger patients with pulmonary arterial hypertension (PAH). The best approach to the evaluation and management of these patients is unclear. METHODS: We, retrospectively, reviewed the clinical records of patients older than 60 years referred for evaluation for PAH. We recorded patient demographics, comorbidity, functional classification (FC), right heart catheterization data, echocardiographic data, chest radiographic images and pulmonary function results. We recorded the final diagnoses according to World Health Organization (WHO) subgroups and treatment outcomes based on changes in FC. RESULTS: Ninety-seven records were reviewed in detail. The mean age was 71.2 ± 7.5 years with 66% women. Cardiovascular disease was the most frequent comorbidity. Mean PA pressure by catheterization was 39.5 ± 12.2mmHg (n = 65). The overall distribution after evaluation included 21 (21.6%) Group 1, 35 (36.1%) Group 2, 16 (16.5%) Group 3, 18 (18.6%) mixed Group 2 and 3, 6 (6.2%) Group 4 and 1 (1%) Group 5 patients. Group 1 patients were treated with PAH specific drug, and 12 patients had an improvement in FC with treatment. CONCLUSIONS: Older patients with suspected PH often have significant cardiovascular and respiratory comorbidity. Comprehensive evaluations are needed to determine the severity of PH and associated diseases and to initiate treatment focused on FC. Patients in WHO Group 2 and mixed Group 2 and 3 were frequently identified and constituted a diagnostic and treatment challenge in this study. Older patients with PAH may benefit from PAH specific drugs.

Characteristics of Patients With Congestive Heart Failure or Chronic Obstructive Pulmonary Disease Readmissions Within 30 Days Following an Acute Exacerbation.

BACKGROUND: The Hospital Readmissions Reduction Program targets Medicare patients with congestive heart failure (CHF) and chronic obstructive pulmonary disease (COPD) and penalizes hospitals that have increased 30-day readmission rates for these patients. The main goals of this study were to determine the clinical explanations for readmissions within 30 days, to identify possible deficiencies in patient care, and to identify typical characteristics of patients who were readmitted to the hospital. METHODS: The medical records department at University Medical Center in Lubbock, Texas, generated a list of patients with a primary discharge diagnosis of either acute exacerbation of CHF or an acute exacerbation of COPD who were readmitted within 30 days of discharge. Data collected from the electronic medical records included demographic information, clinical information, laboratory data, electrocardiographic information, echocardiographic results, and radiographic information for the index admission and readmission hospitalization. The indication for readmission was determined after review of all clinical data. RESULTS: The final study cohorts included 58 admission-readmission events for acute exacerbations of CHF (47 patients) and 27 admission-readmission events for acute exacerbations of COPD (16 patients). Patients in both cohorts had significant comorbidity and frequent admissions during the 12 months prior to their index admissions. Patients with COPD had predominantly an emphysematous phenotype. Chest radiographs in patients with CHF showed cardiomegaly, pulmonary edema, and pleural effusions. Patients with CHF were discharged with suboptimal medication regimens. Referral to outpatient rehabilitation programs was low in both groups. CONCLUSIONS: Patients with acute exacerbations of COPD or CHF who require readmission within 30 days have complex comorbidity. They appear to have typical clinical profiles (emphysematous-type COPD patients and CHF patients with fluid overload), are frequently discharged with suboptimal medication regimens, and are not referred to outpatient rehabilitation. These patients had frequent hospitalizations prior to index hospitalizations. This information provides the basis for a focused review of patients admitted to the hospital to identify factors that might contribute to readmission.

Glucose Levels in Patients With Acute Respiratory Failure Requiring Mechanical Ventilation.

BACKGROUND: Recent studies suggest that patients with acute exacerbations of chronic obstructive pulmonary disease (COPD) frequently develop hyperglycemia, which has been linked to adverse outcomes. METHODS: We retrospectively collected information about patient demographics, admission diagnosis, comorbidities, use of insulin, and glucose levels and related tests in 174 patients who required mechanical ventilation for acute respiratory failure. RESULTS: These patients had a mean age of 57.8 ± 16.8 years, a mean Acute Physiology and Chronic Health Evaluation (APACHE II) score of 13.8 ± 6.1, and an overall mortality of 32.2%. The mean number of ventilator days was 7.5 ± 7.1. The mean highest glucose level was 239.3 ± 88.9 mg/dL in patients with COPD (n = 41) and 259.1 ± 131.7 mg/dL in patients without COPD (n =133). Patients with diabetes had higher glucose levels than patients without this diagnosis ( P < .05). Patients receiving corticosteroids did not have increased glucose levels ( P > .05). The mortality rate was higher in patients with glucose levels >140 mg/dL than in patients below 140 mg/dL (35.1% vs 10.5%, P < .05 unadjusted analysis). CONCLUSION: In this study, hyperglycemia occurred in 89% of the patients with acute respiratory failure requiring mechanical ventilation. The most important risk factor for this was a premorbid diagnosis of diabetes.

Complications and Resource Utilization Associated With Mechanical Ventilation in a Medical Intensive Care Unit in 2013.

INTRODUCTION: Evolving strategies for ventilator management could reduce the frequency of complications, but there is limited information about complications in contemporary intensive care units. METHODS: We retrospectively collected information about patient demographics, chest x-ray abnormalities, complications, including pneumothoraces, ventilator-associated events, self-extubation, and resource utilization in 174 patients who required mechanical ventilation in 2013. RESULTS: The mean age was 57.8 ± 16.8 years, the number of ventilator days was 7.5 ± 7, and the overall in-hospital mortality was 32.2%. The mean fluid balance per day during the mechanical ventilation period was 1539 ± 1721 mL. Three (1.7%) patients developed pneumothoraces, and 5 patients required chest tubes. Twenty-five (14.4%) patients had ventilator-associated events. Ten patients had episodes of self-extubation, and 11 had episodes of failed extubation. Chest X-rays showed new or increasing infiltrates in 113 (64.9%) patients and new or increasing pleural effusions in 29 (16.7%) patients. These patients had 1.2 ± 0.4 X-rays per day on the ventilator, and they had 10.0 ± 9.4 arterial blood gases and 0.7 ± 0.7 central lines. CONCLUSION: The frequency of ventilator-associated complications was low in this study. However, these patients frequently developed increasing infiltrates, and these outcomes need attention during patient management and are a potential focus for future studies.

Making of a Successful Early Mobilization Program for a Medical Intensive Care Unit.

OBJECTIVES: To provide a guideline for intensive care unit (ICU) early mobilization program development and implementation and to describe the patient characteristics and endpoints for those who participated in our hospital's early mobilization program. METHODS: An ICU early mobilization program was developed with five guiding principles: analgesia/sedation optimization, sedation minimization, protocol of progressive mobility, physical therapy and occupational therapy recruitment, and nursing education. This program began in April 2014, and the initial 32 patients who ambulated while receiving mechanical ventilation were retrospectively assessed and their characteristics described. RESULTS: After program implementation, more than 50 mechanically ventilated patients ambulated in the first year following early mobilization initiation. Patients with an FiO2 as high as 1.0 and on nonconventional modes of mechanical ventilation successfully ambulated without adverse events. The mean ambulation distance was 102 ± 152 f. and usually required three ICU staff members with 5 to 10 minutes of preparation before ambulation. After implementation, a retrospective analysis revealed a decrease in the average length of ICU stay, from 4.8 to 4.1 days. CONCLUSIONS: Addressing analgesia and sedation practices, along with instituting a progressive mobility protocol and recruiting physical and occupational therapy, may serve as a guide to the creation of a successful early mobilization program. This study provides additional supportive evidence that early mobilization in the ICU is safe and effective.