502
M. Rashid et al.
9.1.1 NMR Based Metabolomics in Acute Respiratory Distress
Syndrome (ARDS):
Since half of the century since ARDS first got described, [41, 42] it has been challenging to manage the disease with a survival of as low as 40%. The patient of ARDS
are kept under observation in intensive care unit and even after recovery the quality
of life is drastically affected making patients suffer with co-morbidity even after
recovery [43].
The only factor which could weigh in to increase the survival rate is early diagnosis
of this disease, however it has been really challenging to search for early biomarkers
owing to broad range of causative factors for the disease ranging from sepsis, injury,
trauma, ventilator associated changes to pneumonia [44]. In many patients suffering
from ARDS the lung alveoli are filled with liquid and the patients have difficulty
in breathing due to reduction of available air space. The fluid inside alveoli and
nearby are called as bronchoalveolar lavage fluid (BALF) and mini-bronchoalveolar
lavage fluid (mBALF) respectively [42]. Both mBALF and BALF can be used as
samples for metabolomics studies in patients of ARDS, It has been shown that a total
50 metabolites could be detected in mBALF from human lung [45–47]. In order to
search for early biomarkers ideally suited sample would be Bronchoalveolar lavage
fluid (BALF).
However, Rai et al. and Singh et al. have proved that the fluid present near
alveoli which is also called mBALF and is as effective as BALF for the purpose of
metabolomics studies [44–47]. Precautions should be taken while extracting the fluid
using catheter as it can cause contamination of unwanted SMWM if not done carefully
[46]. Pioneer study by Rai et al. using
1 H NMR based metabolomics of mBALF from
30 ARDS patients could differentiate Acute Lung Injury (ALI) from ARDS patients.
ALI is less severe and the categorization used to be based on P/F ratio (P—partial pressure of oxygen/F-fraction of inspired oxygen) [44]. Similar results were obtained by
metabolomics profiling where untargeted LC–MS metabolomics of bronchoalveolar
lavage fluid differentiated ARDS from health, here 37 metabolomics were identified
[48]. Figure 25 Elaborates the steps taken in the process of metabolomics studies of
ARDS from body fluids.
As mBALF sample requires a lot of expertise, as well as is costly Singh et al.,
performed
1 H NMR based metabolomics and the results showed that non ARDS
(NARDS) control samples could be separated from ARDS patients [43]. The key
molecules responsible for this differentiation between ARDS and NARDS were Nacetylglycoproteins (NAC), acetoacetate, lactate, creatinine, histidine, formate and
aromatic amino acids. Another study by Viswan et al., focused to narrow down
the number of SMWM responsible for different ARDS substages to 6, proline,
lysine/arginine, taurine, threonine and glutamate [49] using partial least squares
discriminant analysis (PLSDA) as major classifier. Most of these reports were based
on smaller sample size as its very difficult to collect ARDS patient samples. Furthermore, in this search of biomarkers differentiating different subtypes of ARDS which
got evolved from ALI/ARDS grouping to Mild, moderate and severe ARDS groups
based of P/F ratio.
M. Rashid et al.
9.1.1 NMR Based Metabolomics in Acute Respiratory Distress
Syndrome (ARDS):
Since half of the century since ARDS first got described, [41, 42] it has been challenging to manage the disease with a survival of as low as 40%. The patient of ARDS
are kept under observation in intensive care unit and even after recovery the quality
of life is drastically affected making patients suffer with co-morbidity even after
recovery [43].
The only factor which could weigh in to increase the survival rate is early diagnosis
of this disease, however it has been really challenging to search for early biomarkers
owing to broad range of causative factors for the disease ranging from sepsis, injury,
trauma, ventilator associated changes to pneumonia [44]. In many patients suffering
from ARDS the lung alveoli are filled with liquid and the patients have difficulty
in breathing due to reduction of available air space. The fluid inside alveoli and
nearby are called as bronchoalveolar lavage fluid (BALF) and mini-bronchoalveolar
lavage fluid (mBALF) respectively [42]. Both mBALF and BALF can be used as
samples for metabolomics studies in patients of ARDS, It has been shown that a total
50 metabolites could be detected in mBALF from human lung [45–47]. In order to
search for early biomarkers ideally suited sample would be Bronchoalveolar lavage
fluid (BALF).
However, Rai et al. and Singh et al. have proved that the fluid present near
alveoli which is also called mBALF and is as effective as BALF for the purpose of
metabolomics studies [44–47]. Precautions should be taken while extracting the fluid
using catheter as it can cause contamination of unwanted SMWM if not done carefully
[46]. Pioneer study by Rai et al. using
1 H NMR based metabolomics of mBALF from
30 ARDS patients could differentiate Acute Lung Injury (ALI) from ARDS patients.
ALI is less severe and the categorization used to be based on P/F ratio (P—partial pressure of oxygen/F-fraction of inspired oxygen) [44]. Similar results were obtained by
metabolomics profiling where untargeted LC–MS metabolomics of bronchoalveolar
lavage fluid differentiated ARDS from health, here 37 metabolomics were identified
[48]. Figure 25 Elaborates the steps taken in the process of metabolomics studies of
ARDS from body fluids.
As mBALF sample requires a lot of expertise, as well as is costly Singh et al.,
performed
1 H NMR based metabolomics and the results showed that non ARDS
(NARDS) control samples could be separated from ARDS patients [43]. The key
molecules responsible for this differentiation between ARDS and NARDS were Nacetylglycoproteins (NAC), acetoacetate, lactate, creatinine, histidine, formate and
aromatic amino acids. Another study by Viswan et al., focused to narrow down
the number of SMWM responsible for different ARDS substages to 6, proline,
lysine/arginine, taurine, threonine and glutamate [49] using partial least squares
discriminant analysis (PLSDA) as major classifier. Most of these reports were based
on smaller sample size as its very difficult to collect ARDS patient samples. Furthermore, in this search of biomarkers differentiating different subtypes of ARDS which
got evolved from ALI/ARDS grouping to Mild, moderate and severe ARDS groups
based of P/F ratio.