Host-Response Subphenotypic Classification with A Parsimonious Model Offers Prognostic Information in Patients with Acute Respiratory Failure: A Prospective Cohort Study.

2020 ◽  
Author(s):  
Callie M. Drohan ◽  
S. Mehdi Nouraie ◽  
William Bain ◽  
Faraaz A. Shah ◽  
John Evankovich ◽  
...  
Keyword(s):  
Respiratory Failure ◽  
Acute Respiratory Failure ◽  
Regression Model ◽  
Clinical Outcomes ◽  
Host Response ◽  
Latent Class ◽  
Validation Cohort ◽  
Prognostic Information ◽  
Derivation Cohort ◽  
Parsimonious Model

Abstract Background: Recent research in patients with ARDS has consistently shown the presence of two distinct subphenotypes of host-responses (hyper- and hypo-inflammatory) with markedly different outcomes and responses to therapies. However, inherent uncertainty in reaching the diagnosis of ARDS creates considerable biological and clinical overlap with other broadly-defined syndromes of acute respiratory failure, such as patients with risk factors (e.g. sepsis or pneumonia) for ARDS (at-risk for ARDS [ARFA]) or patients with decompensated congestive heart failure (CHF). Limited data are available for the presence of subphenotypes in such broader critically-ill populations. Methods: We enrolled mechanically-ventilated patients with acute respiratory failure (ARDS, ARFA, and CHF) and measured 11 plasma biomarkers at baseline. We applied latent class analysis (LCA) methods to determine optimal subphenotypic classifications in this inclusive patient cohort by considering clinical variables and biomarkers. We then derived a parsimonious logistic regression model for subphenotype predictions and compared clinical outcomes between subphenotypes.Results: We included 334 patients (123 [37%] ARDS, 177 [53%] ARFA, 34 [10%] CHF) in a derivation cohort and 36 patients in a temporally-independent validation cohort. A two-class LCA model was found to be optimal, classifying 29% of patients in the hyper-inflammatory subphenotype, consistent with prior findings. A 4-variable parsimonious model (angiopoietin-2, soluble tumor necrosis factor receptor-1, procalcitonin and bicarbonate) for subphenotype prediction offered excellent classification (area under the curve = 0.98) compared to LCA classifications. For both LCA- and regression model classifications, hyper-inflammatory patients had higher severity of illness by Sequential Organ Failure Assessment scores, fewer ventilator-free days and higher 30- and 90-day mortality (all p<0.01) compared to the hypo-inflammatory group. Subphenotype predictions in the validation cohort revealed consistent trends for clinical outcomes and higher levels of inflammatory biomarkers in the hyper-inflammatory group (22%). Conclusions: Host-response subphenotypes are observable in broader and heterogeneous patient populations beyond just patients with ARDS, and subphenotypic classifications offer prognostic information on clinical outcomes. Accurate subphenotyping is possible with the use of a simple predictive model to improve clinical applicability.

scholarly journals Association of time-to-treatment with outcomes of Pneumocystis pneumonia with respiratory failure in HIV-negative patients

2019 ◽  
Vol 20 (1) ◽  
Author(s):  
Ryoung-Eun Ko ◽  
Soo Jin Na ◽  
Kyungmin Huh ◽  
Gee Young Suh ◽  
Kyeongman Jeon
Keyword(s):  
Logistic Regression ◽  
Respiratory Failure ◽  
Hospital Mortality ◽  
Regression Model ◽  
Clinical Outcomes ◽  
Logistic Regression Model ◽  
Pneumocystis Pneumonia ◽  
Definitive Treatment ◽  
Hypoxemic Respiratory Failure ◽  
Hiv Negative

Abstract Background The prevalence of pneumocystis pneumonia (PCP) and associated hypoxic respiratory failure is increasing in human immunodeficiency virus (HIV)-negative patients. However, no prior studies have evaluated the effect of early anti-PCP treatment on clinical outcomes in HIV-negative patient with severe PCP. Therefore, this study investigated the association between the time to anti-PCP treatment and the clinical outcomes in HIV-negative patients with PCP who presented with hypoxemic respiratory failure. Methods A retrospective observational study was performed involving 51 HIV-negative patients with PCP who presented in respiratory failure and were admitted to the intensive care unit between October 2005 and July 2018. A logistic regression model was used to adjust for potential confounding factors in the association between the time to anti-PCP treatment and in-hospital mortality. Results All patients were treated with appropriate anti-PCP treatment, primarily involving trimethoprim/sulfamethoxazole. The median time to anti-PCP treatment was 58.0 (28.0–97.8) hours. Thirty-one (60.8%) patients were treated empirically prior to confirmation of the microbiological diagnosis. However, the hospital mortality rates were not associated with increasing quartiles of time until anti-PCP treatment (P = 0.818, test for trend). In addition, hospital mortality of patients received early empiric treatment was not better than those of patients received definitive treatment after microbiologic diagnosis (48.4% vs. 40.0%, P = 0.765). In a multiple logistic regression model, the time to anti-PCP treatment was not associated with increased mortality. However, age (adjusted OR 1.07, 95% CI 1.01–1.14) and failure to initial treatment (adjusted OR 13.03, 95% CI 2.34–72.65) were independently associated with increased mortality. Conclusions There was no association between the time to anti-PCP treatment and treatment outcomes in HIV-negative patients with PCP who presented in hypoxemic respiratory failure.

scholarly journals Association between low body mass index and increased 28-day mortality of severe sepsis in Japanese cohorts

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Takehiko Oami ◽  
◽  
Satoshi Karasawa ◽  
Tadanaga Shimada ◽  
Taka-aki Nakada ◽  
...  
Keyword(s):  
Body Mass Index ◽  
Severe Sepsis ◽  
Clinical Outcomes ◽  
Body Mass ◽  
Validation Cohort ◽  
Univariate Analysis ◽  
University Hospital ◽  
Primary Analysis ◽  
Derivation Cohort ◽  
Asian Populations

AbstractCurrent research regarding the association between body mass index (BMI) and altered clinical outcomes of sepsis in Asian populations is insufficient. We investigated the association between BMI and clinical outcomes using two Japanese cohorts of severe sepsis (derivation cohort, Chiba University Hospital, n = 614; validation cohort, multicenter cohort, n = 1561). Participants were categorized into the underweight (BMI < 18.5) and non-underweight (BMI ≥ 18.5) groups. The primary outcome was 28-day mortality. Univariate analysis of the derivation cohort indicated increased 28-day mortality trend in the underweight group compared to the non-underweight group (underweight 24.4% [20/82 cases] vs. non-underweight 16.0% [85/532 cases]; p = 0.060). In the primary analysis, multivariate analysis adjusted for baseline imbalance revealed that patients in the underweight group had a significantly increased 28-day mortality compared to those in the non-underweight group (p = 0.031, adjusted odds ratio [OR] 1.91, 95% confidence interval [CI] 1.06–3.46). In a repeated analysis using a multicenter validation cohort (underweight n = 343, non-underweight n = 1218), patients in the underweight group had a significantly increased 28-day mortality compared to those in the non-underweight group (p = 0.045, OR 1.40, 95% CI 1.00–1.97). In conclusion, patients with a BMI < 18.5 had a significantly increased 28-day mortality compared to those with a BMI ≥ 18.5 in Japanese cohorts with severe sepsis.

scholarly journals Derivation and External Validation of a Simple Prediction Rule for the Development of Respiratory Failure in Hospitalized Patients With Influenza

2022 ◽  
Author(s):  
Blanca Ayuso ◽  
Antonio Lalueza ◽  
Estibaliz Arrieta ◽  
Eva Maria Romay ◽  
Álvaro Marchán-López ◽  
...  
Keyword(s):  
Respiratory Failure ◽  
Lactate Dehydrogenase ◽  
Respiratory Rate ◽  
Validation Cohort ◽  
Influenza Infection ◽  
External Validation ◽  
Prediction Rule ◽  
Influenza Viruses ◽  
Chronic Obstructive ◽  
Derivation Cohort

Abstract BACKGROUND: Influenza viruses cause seasonal epidemics worldwide with a significant morbimortality burden. Clinical spectrum of Influenza is wide, being respiratory failure (RF) one of its most severe complications. This study aims to elaborate a clinical prediction rule of RF in hospitalized Influenza patients.METHODS: a prospective cohort study was conducted during two consecutive Influenza seasons (December 2016 - March 2017 and December 2017 - April 2018) including hospitalized adults with confirmed A or B Influenza infection. A prediction rule was derived using logistic regression and recursive partitioning, followed by internal cross-validation. External validation was performed on a retrospective cohort in a different hospital between December 2018 - May 2019. RESULTS: Overall, 707 patients were included in the derivation cohort and 285 in the validation cohort. RF rate was 6.8% and 11.6%, respectively. Chronic obstructive pulmonary disease, immunosuppression, radiological abnormalities, respiratory rate, lymphopenia, lactate dehydrogenase and C-reactive protein at admission were associated with RF. A four category-grouped seven point-score was derived including radiological abnormalities, lymphopenia, respiratory rate and lactate dehydrogenase. Final model area under the curve was 0.796 (0.714-0.877) in the derivation cohort and 0.773 (0.687-0.859) in the validation cohort (p<0.001 in both cases). The predicted model showed an adequate fit with the observed results (Fisher’s test p>0.43). CONCLUSION: we present a simple, discriminating, well-calibrated rule for an early prediction of the development of RF in hospitalized Influenza patients, with proper performance in an external validation cohort. This tool can be helpful in patient´s stratification during seasonal Influenza epidemics.

scholarly journals Impact of exposure time in awake prone positioning on clinical outcomes of patients with COVID-19-related acute respiratory failure treated with high-flow nasal oxygen: a multicenter cohort study

Critical Care ◽  
2022 ◽  
Vol 26 (1) ◽  
Author(s):  
Mariano Esperatti ◽  
Marina Busico ◽  
Nora Angélica Fuentes ◽  
Adrian Gallardo ◽  
Javier Osatnik ◽  
...  
Keyword(s):  
Cohort Study ◽  
Respiratory Failure ◽  
Hospital Mortality ◽  
Acute Respiratory Failure ◽  
Clinical Outcomes ◽  
Endotracheal Intubation ◽  
High Flow ◽  
Secondary Outcome ◽  
Prone Positioning ◽  
Multicenter Cohort Study

Abstract Background In patients with COVID-19-related acute respiratory failure (ARF), awake prone positioning (AW-PP) reduces the need for intubation in patients treated with high-flow nasal oxygen (HFNO). However, the effects of different exposure times on clinical outcomes remain unclear. We evaluated the effect of AW-PP on the risk of endotracheal intubation and in-hospital mortality in patients with COVID-19-related ARF treated with HFNO and analyzed the effects of different exposure times to AW-PP. Methods This multicenter prospective cohort study in six ICUs of 6 centers in Argentine consecutively included patients > 18 years of age with confirmed COVID-19-related ARF requiring HFNO from June 2020 to January 2021. In the primary analysis, the main exposure was awake prone positioning for at least 6 h/day, compared to non-prone positioning (NON-PP). In the sensitivity analysis, exposure was based on the number of hours receiving AW-PP. Inverse probability weighting–propensity score (IPW-PS) was used to adjust the conditional probability of treatment assignment. The primary outcome was endotracheal intubation (ETI); and the secondary outcome was hospital mortality. Results During the study period, 580 patients were screened and 335 were included; 187 (56%) tolerated AW-PP for [median (p25–75)] 12 (9–16) h/day and 148 (44%) served as controls. The IPW–propensity analysis showed standardized differences < 0.1 in all the variables assessed. After adjusting for other confounders, the OR (95% CI) for ETI in the AW-PP group was 0.36 (0.2–0.7), with a progressive reduction in OR as the exposure to AW-PP increased. The adjusted OR (95% CI) for hospital mortality in the AW-PP group ≥ 6 h/day was 0.47 (0.19–1.31). The exposure to prone positioning ≥ 8 h/d resulted in a further reduction in OR [0.37 (0.17–0.8)]. Conclusion In the study population, AW-PP for ≥ 6 h/day reduced the risk of endotracheal intubation, and exposure ≥ 8 h/d reduced the risk of hospital mortality.

Frailty subtypes and recovery in older survivors of acute respiratory failure: a pilot study

Thorax ◽  
2020 ◽  
pp. thoraxjnl-2020-214998
Author(s):  
Matthew R Baldwin ◽  
Lauren R Pollack ◽  
Richard A Friedman ◽  
Simone P Norris ◽  
Azka Javaid ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Respiratory Failure ◽  
Acute Respiratory Failure ◽  
Hospital Discharge ◽  
Recovery Rate ◽  
Latent Class ◽  
Free Testosterone ◽  
Clinical Frailty Scale ◽  
Frailty Phenotype ◽  
Anabolic Hormone

BackgroundIdentifying subtypes of acute respiratory failure survivors may facilitate patient selection for post-intensive care unit (ICU) follow-up clinics and trials.MethodsWe conducted a single-centre prospective cohort study of 185 acute respiratory failure survivors, aged ≥65 years. We applied latent class modelling to identify frailty subtypes using frailty phenotype and cognitive impairment measurements made during the week before hospital discharge. We used Fine-Gray competing risks survival regression to test associations between frailty subtypes and recovery, defined as returning to a basic Activities of Daily Living disability count less than or equal to the pre-hospitalisation count within 6 months. We characterised subtypes by pre-ICU frailty (Clinical Frailty Scale score ≥5), the post-ICU frailty phenotype, and serum inflammatory cytokines, hormones and exosome proteomics during the week before hospital discharge.ResultsWe identified five frailty subtypes. The recovery rate decreased 49% across each subtype independent of age, sex, pre-existing disability, comorbidity and Acute Physiology and Chronic Health Evaluation II score (recovery rate ratio: 0.51, 95% CI 0.41 to 0.63). Post-ICU frailty phenotype prevalence increased across subtypes, but pre-ICU frailty prevalence did not. In the subtype with the slowest recovery, all had cognitive impairment. The three subtypes with the slowest recovery had higher interleukin-6 levels (p=0.03) and a higher prevalence of ≥2 deficiencies in insulin growth factor-1, dehydroepiandrostersone-sulfate, or free-testosterone (p=0.02). Exosome proteomics revealed impaired innate immunity in subtypes with slower recovery.ConclusionsFrailty subtypes varied by prehospitalisation frailty and cognitive impairment at hospital discharge. Subtypes with the slowest recovery were similarly characterised by greater systemic inflammation and more anabolic hormone deficiencies at hospital discharge.

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