Progression of the Radiologic Severity Index predicts mortality in patients with parainfluenza virus-associated lower respiratory infections

Sheshadri, Ajay; Shah, Dimpy P.; Godoy, Myrna C.B.; Erasmus, Jeremy J.; Song, Juhee; Li, Liang; Evans, Scott E.; Chemaly, Roy F.; Dickey, Burton F.; Ost, David

doi:10.1371/journal.pone.0197418

Cited by 20 publications

(38 citation statements)

References 49 publications

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“…Treatment was well tolerated, and we believe we reached the upper plateau of the dose-response curve based upon small rises in blood neutrophils and C-reactive protein levels resembling the small sigmoidal-shaped plots of rises in blood IL-6 levels in mice (15). Next steps in development of the drug include viral challenge studies in subjects with airway disease (44)(45)(46), followed by natural infection preemption studies in subjects with airway disease or immune compromise (20,38,47,48). O/P showed reductions in acute SeV lung burden and chronic asthma phenotypes comparable to those seen with aerosolized IFN-β in mice (Fig.…”

Section: Discussionmentioning

confidence: 99%

Aerosolized TLR Agonists Suppress Acute Sendai Virus Lung Infection and Chronic Airway Disease in Mice

Goldblatt

Gonzalez

et al. 2019

Preprint

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These authors contributed equally to this work.One Sentence Summary: Respiratory viral infections can induce chronic airway disease, and we find that stimulating innate immunity within the lungs of mice reduces the severity of acute infection and development of a chronic asthma phenotype.Abstract: Respiratory viral infections play central roles in the initiation, exacerbation and progression of asthma in humans. An acute paramyxoviral infection in mice can cause a chronic lung disease that resembles human asthma. We sought to determine whether reduction of Sendai virus lung burden in mice by stimulating innate immunity with aerosolized Toll-like receptor (TLR) agonists could attenuate the severity of chronic asthma-like lung disease. Treatment with 1 µM oligodeoxynucleotide (ODN) M362, an agonist of the TLR9 homodimer, and 4 µM Pam2CSK4 (Pam2), an agonist of the TLR2/6 heterodimer, within a few days before or after Sendai virus challenge, resulted in a ~75% reduction in lung Sendai virus burden five days after challenge. The reduction in acute lung virus burden was associated with marked reductions 49 days after viral challenge in eosinophilic and lymphocytic lung inflammation, airway mucous metaplasia, lumenal mucus occlusion, and hyperresponsiveness to methacholine.Mechanistically, ODN/Pam2 treatment attenuated the chronic asthma phenotype by suppressing IL-33 production by type 2 pneumocytes, both by reducing the severity of acute infection and by downregulating Type 2 (allergic) inflammation. These data suggest that treatment of susceptible human hosts with aerosolized ODN and Pam2 at the time of a respiratory viral infection might attenuate the severity of the acute infection and reduce progression of asthma.

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Section: Discussionmentioning

confidence: 99%

Aerosolized TLR Agonists Suppress Acute Sendai Virus Lung Infection and Chronic Airway Disease in Mice

Goldblatt

Gonzalez

et al. 2019

Preprint

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“…Radiologic severity is an attractive endpoint because it is generally attributable to infection in the absence of hypervolemia or pre‐existing interstitial lung disease. We previously showed that in longitudinal models of time‐varying radiologic severity, each 1‐point increase in RSI was associated with a 13% increase in the hazard for mortality at 30 days after parainfluenza virus LRTI . Reliability among readers was excellent, and explanatory models of peak‐RSI and delta‐RSI showed that increasing RSI was associated with higher rates of mortality and respiratory failure.…”

Section: Discussionmentioning

confidence: 97%

“…Delta‐RSI was calculated by subtracting baseline‐RSI from peak‐RSI. Table illustrates how RSI is calculated . Briefly, chest radiographs were divided into three zones: upper (above carina), middle (below carina, above inferior pulmonary vein), and lower (below inferior pulmonary vein) in both lungs.…”

Section: Methodsmentioning

confidence: 99%

“…Although immunodeficiency scores can estimate mortality risks based on baseline characteristics, they are not suitable to measure the disease severity of RSV LRTI because they are estimates of the severity of immunodeficiency and not the LRTI itself. We previously developed a semi‐quantitative tool of radiologic severity, the Radiologic Severity Index (RSI), which was the strongest predictor of mortality after parainfluenza virus LRTI . Longitudinal measurement of RSI can measure the evolving severity of LRTI.…”

Section: Introductionmentioning

confidence: 99%

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Refinement of estimates of mortality risk using the Radiologic Severity Index in hematologic malignancy patients with respiratory syncytial virus infection

Sheshadri

Karimipour

Vakil

et al. 2019

Transplant Infectious Dis

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Background: Immunocompromised hematologic malignancy (HM) patients experience high mortality after respiratory syncytial virus (RSV) lower respiratory tract infection (LRTI). We measured radiologic severity to determine whether it could improve the performance of 60-day mortality models based only upon immunodeficiency severity. Methods:We studied 155 HM patients, including 84 hematopoietic cell transplant recipients, who developed RSV LRTI from 2001 to 2013. We measured immunodeficiency using lymphopenia (lymphocyte count <200 cells/mm 3 ), Immunodeficiency Severity Index (ISI), and Severe Immunodeficiency (SID) criteria. Radiologic severity was measured by the Radiologic Severity Index (RSI, range 0-72) at time of LRTI (baseline-RSI) and peak severity (peak-RSI). Delta-RSI was defined as the difference between baseline-RSI and peak-RSI. We used logistic regression models to measure the association of immunodeficiency and RSI with 60-day all-cause mortality, and measured model discrimination using areas under the receiver-operating characteristics curves, calibration using Brier scores, and explained variance using pseudo-R 2 values.Results: Forty-one patients died within 60 days of RSV LRTI. Severe immunodeficiency was associated with higher mortality. Peak-RSI (odds ratio [OR] 1.06/point, 95% confidence interval [CI] 1.04-1.08), and delta-RSI (OR 1.07/point, 95% CI 1.05-1.10) were associated with 60-day mortality after RSV LRTI, but not baseline-RSI. Addition of peak-RSI or delta-RSI to baseline immunodeficiency improved the discrimination, calibration, and explained variance (P < 0.001) of 60-day mortality models. Conclusions:Although baseline immunodeficiency in HM patients helps predict 60day mortality after RSV LRTI, mortality risk estimates can be further refined by also measuring LRTI progression using RSI. RSI is well-suited as a marker of LRTI severity in RSV infection.

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“…It has been previously shown that clinicians who make diagnostic and treatment decisions based solely on their clinical judgment lack predictive accuracy regarding death risk in human H7N9 infection cases and are, therefore, unable to increase the survival probability in these cases. [5][6][7] An accurate assessment of survival probability would help tailor treatment in human H7N9 infection cases. Unfortunately, the vast majority of published studies 8,9 on the topic focus on risk factors of H7N9 infection and case fatalities.…”

Section: Introductionmentioning

confidence: 99%

<p>Nomogram for the Individualized Prediction of Survival Among Patients with H7N9 Infection</p>

Cheng

Zhou

Zhao

et al. 2020

RMHP

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These authors contributed equally to this work Background: Until recently, almost all of these studies have identified multiple risk factors but did not offer practical instruments for routine use in predicting individualized survival in human H7N9 infection cases. The objective of this study is to create a practical instrument for use in predicting an individualized survival probability of H7N9 patients. Methods: A matched case-control study (1:2 ratios) was performed in Zhejiang Province between 2013 and 2019. We reviewed specific factors and outcomes regarding patients with H7N9 virus infection (VI) to determine relationships and developed a nomogram to calculate individualized survival probability. This tool was used to predict each individual patient's probability of survival based on results obtained from the multivariable Cox proportional hazard regression analysis. Results: We examined 227 patients with H7N9 VI enrolled in our study. Stepwise selection was applied to the data, which resulted in a final model with 8 independent predictors [including initial PaO 2 /FiO 2 ratio ≤300 mmHg, age ≥60 years, chronic diseases, poor hand hygiene, time from illness onset to the first medical visit, incubation period ≤5 days, peak C-reactive protein ≥120 mg/L], and initial bilateral lung infection. The concordance index of this nomogram was 0.802 [95% confidence interval (CI): 0.694-0.901] and 0.793 (95% CI: 0.611-0.952) for the training and validation sets, respectively, which indicates adequate discriminatory power. The calibration curves for the survival showed optimal agreement between nomogram prediction and actual observation in the training and validation sets, respectively. Conclusion: We established and validated a novel nomogram that can accurately predict the survival probability of patients with H7N9 VI. This nomogram can serve an important role in counseling patients with H7N9 VI and guide treatment decisions.

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Progression of the Radiologic Severity Index predicts mortality in patients with parainfluenza virus-associated lower respiratory infections

Cited by 20 publications

References 49 publications

Aerosolized TLR Agonists Suppress Acute Sendai Virus Lung Infection and Chronic Airway Disease in Mice

Aerosolized TLR Agonists Suppress Acute Sendai Virus Lung Infection and Chronic Airway Disease in Mice

Refinement of estimates of mortality risk using the Radiologic Severity Index in hematologic malignancy patients with respiratory syncytial virus infection

<p>Nomogram for the Individualized Prediction of Survival Among Patients with H7N9 Infection</p>

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