Etiology and Outcomes of Pulmonary and Extrapulmonary Acute Lung Injury/ARDS in a Respiratory ICU in North India

doi:10.1378/chest.130.3.724

Chest

Volume 130, Issue 3, September 2006, Pages 724-729

https://doi.org/10.1378/chest.130.3.724 Get rights and content

Objective

Outcomes in patients with ARDS/acute lung injury (ALI) may be dependent on the underlying cause. We describe the case mix, clinical behavior, and outcomes of patients with ALI/ARDS resulting from pulmonary causes (ALI/ARDSp) and extrapulmonary causes (ALI/ARDSexp).

Design

Retrospective study conducted between January 2001 and June 2005.

Setting

Respiratory ICU (RICU) of a tertiary care hospital in northern India.

Patients

All patients fulfilling the criteria for ALI/ARDS and requiring mechanical ventilation for > 24 h.

Measurements and results

Of the 180 patients (ARDS, 140 patients; ALI, 40 patients), 123 patients had ALI/ARDSp, whereas 57 patients had ALI/ARDSexp. The most common cause of ALI/ARDSp was infective pneumonia, whereas the most common cause of ALI/ARDSexp was sepsis. At ICU admission, although patients with ALI/ARDSexp were sicker than those with ALI/ARDSp, there was no difference between the two groups of patients in the development of new organ dysfunction/failure (δ sequential organ failure assessment [SOFA] scores) or the time to develop the first organ dysfunction/failure (assessed by SOFA scores). The median length of RICU stay was similar in the two groups (5 days [interquartile range (IQR), 6 days] vs 5 days [IQR, 9.5 days], respectively, in patients with ALI/ARDSp and ALI/ARDSexp; p = 0.4). The hospital mortality rate was 47.8% and was not significantly different between the two groups (ALI/ARDSp group, 43.1%; ALI/ARDSexp group, 57.9%; p = 0.06). Multivariate analysis showed the following risk factors for death in the ICU: female gender (odds ratio [OR], 0.49; 95% confidence interval [CI], 0.25 to 0.94); SOFA scores (OR, 1.18; 95% CI, 1.07 to 1.3); and δSOFA scores (OR, 1.24; 95% CI, 1.09 to 1.41). There was no significant effect of the category of ARDS on outcome (OR, 1.6; 95% CI, 0.8 to 3.2).

Conclusions

Although patients with ALI/ARDSexp are sicker on ICU admission, the underlying cause of ARDS does not affect the length of ICU stay or hospital survival time.

Section snippets

MATERIALS AND METHODS

This was a retrospective study conducted in the RICU of the Postgraduate Institute of Medical Education and Research between January 2001 and June 2005. All data in the RICU are entered prospectively into a computer program that is specifically designed for this purpose, with a continuous process of monitoring its completeness and correcting entries. Data are registered on RICU admission and every 24 h thereafter, using the lowest daily values for all variables of interest. Day 0 is defined as

RESULTS

During the study period, a total of 209 patients were admitted to the RICU with a diagnosis of ALI/ARDS; 180 patients (ARDS, 140 patients; ALI, 40 patients; ALI/ARDSp, 123 patients; ALI/ARDSexp, 57 patients) were included for further analysis. Twenty-nine patients were excluded from the analysis for one of the following reasons: survival for < 24 h; ambiguity in the diagnosis and etiology of lung injury; and the presence of insufficient information. The most common cause of ALI/ARDSp was

DISCUSSION

Only a few studies have investigated the prevalence of ALI/ARDSp and ALI/ARDSexp and the mortality of patients with those conditions. However, in the majority of available studies, as in the present study, the prevalence of ARDSp was higher compared to ARDSexp,3, 12, 13 although, in the most recent retrospective analysis of patients enrolled in the ARDS Network trial¹⁴ of low-tidal volume ventilation, roughly an equal proportion of ARDSp and ARDSexp patients were identified. In two studies,15,

REFERENCES (22)

MR Suchyta et al.
The adult respiratory distress syndrome: a report of survival and modifying factors
Chest
(1992)
MD Diodato et al.
Gender differences in the inflammatory response and survival following haemorrhage and subsequent sepsis
Cytokine
(2001)
SK Jindal et al.
Adult respiratory distress syndrome in the tropics
Clin Chest Med
(2002)
LB Ware et al.
The acute respiratory distress syndrome
N Engl J Med
(2000)
P Pelosi et al.
Pulmonary and extrapulmonary forms of acute respiratory distress syndrome
Semin Respir Crit Care Med
(2001)
L Gattinoni et al.
Acute respiratory distress syndrome caused by pulmonary and extrapulmonary disease: different syndromes?
Am J Respir Crit Care Med
(1998)
P Pelosi et al.
Pulmonary and extrapulmonary acute respiratory distress syndrome are different
Eur Respir J Suppl
(2003)
G Suntharalingam et al.
Influence of direct and indirect etiology on acute outcome and 6-month functional recovery in acute respiratory distress syndrome
Crit Care Med
(2001)
SJ Kim et al.
Recovery from lung injury in survivors of acute respiratory distress syndrome: difference between pulmonary and extrapulmonary subtypes
Intensive Care Med
(2004)
D Gupta et al.
Assessment of factors predicting outcome of acute respiratory distress syndrome in North India
Respirology
(2001)

GR Bernard et al.

Report of the American-European consensus conference on ARDS: definitions, mechanisms, relevant outcomes and clinical trial coordination: The Consensus Committee

Intensive Care Med

(1994)

Cited by (85)

Machine learning for the early prediction of acute respiratory distress syndrome (ARDS) in patients with sepsis in the ICU based on clinical data
2024, Heliyon
Acute respiratory distress syndrome (ARDS) is a fatal outcome of severe sepsis. Machine learning models are helpful for accurately predicting ARDS in patients with sepsis at an early stage.
We aim to develop a machine-learning model for predicting ARDS in patients with sepsis in the intensive care unit (ICU).
The initial clinical data of patients with sepsis admitted to the hospital (including population characteristics, clinical diagnosis, complications, and laboratory tests) were used to predict ARDS, and screen out the crucial variables. After comparing eight different algorithms, namely, XG boost, logistic regression, light GBM, random forest, Gaussian NB, complement NB, support vector machine (SVM), and K nearest neighbors (KNN), rebuilding a prediction model with the best one. When remodeling with the best algorithm, 10% was randomly selected to test, and the remaining was trained for cross-validation. Using the area under the curve (AUC), sensitivity, accuracy, specificity, positive and negative predictive value, F1 score, kappa value, and clinical decision curve to evaluate the model's performance. Eventually, the application in the model illustrated by the SHAP package.
Ten critical features were screened utilizing the lasso method, namely, PaO₂/PAO₂, A-aDO₂, PO₂(T), CRP, gender, PO₂, RDW, MCH, SG, and chlorine. The prior ranking of variables demonstrated that PaO₂/PAO₂ was the most significant variable. Among the eight algorithms, the performance of the Gaussian NB algorithm was significantly better than that of the others. After remodeling with the best algorithm, the AUC in the training and validation sets were 0.777 and 0.770, respectively, and the algorithm performed well in the test set (AUC = 0.781, accuracy = 78.6%, sensitivity = 82.4%, F1 score = 0.824). A comparison of the overlap factors with those of previous models revealed that the model we developed performs better.
Sepsis-associated ARDS can be accurately predicted early via a machine learning model based on existing clinical data. These findings are helpful for accurate identification and improvement of the prognosis in patients with sepsis-associated ARDS.
Potential therapeutic interventions of plant–derived isoflavones against acute lung injury
2021, International Immunopharmacology
Acute lung injury (ALI) is a life-threatening syndrome that possibly leads to high morbidity and mortality as no therapy exists. Several natural ingredients with negligible adverse effects have recently been investigated to possibly inhibit the inflammatory pathways associated with ALI at the molecular level. Isoflavones, as phytoestrogenic compounds, are naturally occurring bioactive compounds that represent the most abundant category of plant polyphenols (Leguminosae family). A broad range of therapeutic activities of isoflavones, including antioxidants, chemopreventive, anti-inflammatory, antiallergic and antibacterial potentials, have been extensively documented in the literature. Our review exclusively focuses on the possible anti-inflammatory, antioxidant role of botanicals’-derived isoflavones against ALI and their immunomodulatory effect in experimentally induced ALI. Despite the limited scope covering their molecular mechanisms, isoflavones substantially contributed to protecting from ALI via inhibiting toll-like receptor 4 (TLR4)/Myd88/NF-κB pathway and subsequent cytokines, chemokines, and adherent proteins. Nonetheless, future research is suggested to fill the gap in elucidating the protective roles of isoflavones to alleviate ALI concerning antioxidant potentials, inhibition of the inflammatory pathways, and associated molecular mechanisms.
Oxygen-mediated lung injury in mice lacking the gene for NRF2: Rescue with the cytochrome P4501A-inducer, beta-naphthoflavone (BNF), and differential sex-specific effects
2020, Free Radical Biology and Medicine
Acute respiratory distress syndrome (ARDS) leads to progressive lung injury, which significantly impacts patient morbidity and mortality but may differ clinically between the sexes. Cytochrome P450 (CYP) 1A enzymes are protective against hyperoxic lung injury and may contribute to sex-dependent pathology. NRF2 is a critical transcriptional regulator of antioxidants and loss of NRF2 leads to severe hyperoxic lung injury and mortality in mice. NRF2 deficiencies and polymorphisms have been observed in patients with pulmonary diseases such as chronic obstructive pulmonary disease and severe asthma. No prior studies have evaluated whether there are sex-specific differences in oxygen-mediated lung injury in Nrf2^−/− mice and there are few rescue studies.
To test the hypothesis that hyperoxia induces greater lung injury and inflammation in Nrf2^−/− mice compared to wild type (WT) that differs between sexes, and that this phenotype will be rescued by the administration of the cytochrome P450 (CYP) 1A inducer beta-naphthoflavone (BNF).
Male and female 8-10-week-old WT or Nrf2^−/− C57BL/6 mice were pre-treated with BNF (40 mg/kg) or corn oil control and exposed to hyperoxia (95% O₂) for 68 h. Survival, pulmonary edema, neutrophil recruitment, and lung injury scores were evaluated. Gene expression of phase II detoxification enzymes, pulmonary cytokines, and Cyp1a1/2 was quantified. CYP1A1/2 protein expression and catalytic activities were also measured.
Hyperoxia exposure greatly reduced survival in Nrf2^−/− mice, particularly in females. BNF treatment improved survival by 182.8% in Nrf2^−/− females and by 41.4% in Nrf2^−/− males as well as in WT females by 85.7%. Females had greater pulmonary edema as measured by lung weight to body weight ratios but was attenuated in all groups except Nrf2^−/− females by BNF. Neutrophils doubled in Nrf2^−/− lungs compared to WT in hyperoxia but were decreased in BNF-treated females of both genotypes. Pulmonary cytokine gene expression including Il-6 and Tnf-α increased in hyperoxia especially in Nrf2^−/− mice and was unaffected by BNF. Pulmonary and hepatic Nqo1 gene expression w-as decreased in Nrf2^−/− mice and was largely unaffected by BNF; however pulmonary Ho-1 did not vary significantly between the genotypes and was decreased in WT animals treated with BNF. Activities and protein expression of pulmonary and hepatic CYP1A1/2 were induced via BNF across all groups. Although hepatic Cyp1a2 gene expression was higher in Nrf2^−/− males, the catalytic activity was higher in Nrf2^−/− females.
Hyperoxia augmented lung injury in Nrf2^−/− mice, and pre-treatment with BNF was protective against mortality and injury, eliminating the sex-dependent survival difference in both genotypes. Our results support the hypothesis that NRF2 protects mice against lung injury, and the fact that BNF rescues the lung injury phenotype in Nrf2^−/− mice suggests that augmented CYP1A expression by BNF may contribute to the beneficial effects. Further studies could lead to the development of BNF and other flavonoids for the prevention/treatment of hyperoxic lung injury, particularly in vulnerable patients with relative NRF2 deficiency, regardless of sex.
17b-estradiol, a potential ally to alleviate SARS-CoV2 infection
2020, Clinics
Considering that female sexual hormones may modulate the inflammatory response and also exhibit direct effects on the cells of the immune system, herein, we intend to discuss the sex differences and the role of estradiol in modulating the lung and systemic inflammatory response, focusing on its possible application as a treatment modality for SARS-CoV-2 patients. COVID-19 patients develop severe hypoxemia early in the course of the disease, which is silent most of the time. Small fibrinous thrombi in pulmonary arterioles and a tumefaction of endothelial were observed in the autopsies of fatal COVID-19 cases. Studies showed that the viral infection induces a vascular process in the lung, which included vasodilation and endothelial dysfunction. Further, the proportions of CD4+ T and CD8+ T lymphocytes were strongly reduced in patients with severe SARS-CoV-2 infection. Estradiol is connected with CD4+ T cell numbers and increases T-reg cell populations, affecting immune responses to infection. It is known that estradiol exerts a protective effect on endothelial function, activating the generation of nitric oxide (NO) via endothelial nitric oxide synthase. Estrogen attenuates the vasoconstrictor response to various stimuli and induces vasodilation in the pulmonary vasculature during stress situations like hypoxia. It exerts a variety of rapid actions, which are initiated after its coupling with membrane receptors, which in turn, may positively modulate vascular responses in pulmonary disease and help to maintain microvascular flow. Direct and indirect mechanisms underlying the effects of estradiol were investigated, and the results point to a possible protective effect of estradiol against COVID-19, indicating that it may be considered as an adjuvant therapeutic element for the treatment of patients affected by the novel coronavirus.
Epidemiology and clinical outcomes of invasive mould infections in Indian intensive care units (FISF study)
2019, Journal of Critical Care
Due to limited data on invasive mould infections (IMIs) in the intensive care units (ICUs) of developing countries, we ascertain epidemiology and management of IMIs at 11 ICUs across India.
Consecutive patients with proven or probable/putative IMIs were enrolled during the study period. Subjects were categorized into classical (neutropenia, malignancy, transplant recipients on immunosuppression) and non-classical (chronic obstructive pulmonary disease, diabetes, liver disease and glucocorticoids) risk groups. We analyzed the demographic, laboratory variables and outcomes of these patients.
398 patients with IMIs (96 proven, 302 probable) were identified, amounting to a prevalence of 9.5 cases/1000 ICU admissions. The mean ± SD age of the participants was 45.6 ± 21.9 years. The mean ± SD APACHE II score was 14.3 ± 11.4. The IMIs were diagnosed at a median of 4 days after ICU admission. There were 145 and 253 subjects with classical and non-classical risk groups, respectively. Although Aspergillus spp. were the commonest (82.1%) isolates, Mucorales were detected in 14.4% subjects. A high APACHE II score and IMI due to mucormycosis were significant predictors of mortality.
The study highlights the distinct epidemiology of IMIs in India ICUs with high burden, new susceptible patient groups and considerable number of non-Aspergillus mould infections. [clinicaltrials.gov: NCT02683642].
Epidemiology, lung mechanics and outcomes of ARDS: A comparison between pregnant and non-pregnant subjects
2019, Journal of Critical Care
Citation Excerpt :
Depending on the severity of ARDS, the hospital mortality varies between 35% and 46% [2]. Based on the mechanism of injury, ARDS has been classified as pulmonary (injury to the alveolar epithelium) or extrapulmonary (injury to the vascular endothelium) [3,4]. Although the mortality is similar in both forms of ARDS, they behave differently, with the latter responding better to higher positive end expiratory pressure (PEEP) [5].
We describe the epidemiology, lung mechanics and outcomes of acute respiratory distress syndrome (ARDS) complicating pregnancy. We also compare the outcomes of ARDS in pregnant and non-pregnant females.
Retrospective observational study of all women admitted with ARDS.
211 women with ARDS were admitted, which included 27 (12.8%) pregnant subjects. All were ventilated with a low tidal volume strategy. Most pregnant females presented during the third trimester. There was no difference in the lung compliance, the applied PEEP and the plateau pressures across trimesters. The pregnant females had a lower median age (25 [[22], [23], [24], [25], [26], [27], [28]] vs. 32 [22–42] years, p = 0.003), higher proportion of severe ARDS (40.8% vs. 10.3%, p < 0.0001), and higher driving pressure (18.2 vs. 15.5 cm H₂O, p = 0.03) compared to non-pregnant females. The maternal (18.5%) and perinatal (37%) mortality was high. However, the mortality was not different between pregnant and non-pregnant subjects with ARDS. On a multivariate logistic regression analysis, the baseline APACHE II score, driving pressure and the delta SOFA score were independent predictors of mortality.
ARDS complicating pregnancy is severe and is associated with high perinatal mortality. However, the outcomes of ARDS in pregnant females were similar to non-pregnant females.

View all citing articles on Scopus

The authors have reported to the ACCP that no significant conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article.

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (www.chestjournal.org/misc/reprints.shtml).

View full text

Chest

Original Research: Critical Care MedicineEtiology and Outcomes of Pulmonary and Extrapulmonary Acute Lung Injury/ARDS in a Respiratory ICU in North India

Objective

Design

Setting

Patients

Measurements and results

Conclusions

Section snippets

MATERIALS AND METHODS

RESULTS

DISCUSSION

Chest

Cytokine

Clin Chest Med

The acute respiratory distress syndrome

N Engl J Med

Pulmonary and extrapulmonary forms of acute respiratory distress syndrome

Semin Respir Crit Care Med

Acute respiratory distress syndrome caused by pulmonary and extrapulmonary disease: different syndromes?

Am J Respir Crit Care Med

Pulmonary and extrapulmonary acute respiratory distress syndrome are different

Eur Respir J Suppl

Influence of direct and indirect etiology on acute outcome and 6-month functional recovery in acute respiratory distress syndrome

Crit Care Med

Recovery from lung injury in survivors of acute respiratory distress syndrome: difference between pulmonary and extrapulmonary subtypes

Intensive Care Med

Assessment of factors predicting outcome of acute respiratory distress syndrome in North India

Respirology

Report of the American-European consensus conference on ARDS: definitions, mechanisms, relevant outcomes and clinical trial coordination: The Consensus Committee

Intensive Care Med

Original Research: Critical Care Medicine
Etiology and Outcomes of Pulmonary and Extrapulmonary Acute Lung Injury/ARDS in a Respiratory ICU in North India