Lung Microbiota Signature and Corticosteroid Responses in Pneumonia-Associated Acute Respiratory Distress Syndrome in Hematological Patients

Figures & data

Figure 1 Study design and distribution of ΔPO₂/FiO₂ for all included patients. (A) Schematic diagram of study design. (B) Distribution of ΔPO₂/FiO₂ of all included patients.

Abbreviation: PEEP, Positive End Expiratory Pressure.

Table 1 Characteristics of Corticosteroid Non-Responders and Responders

	Non-Responders (n=28)	Responders (n=22)	P
Age (y)	37 (24–49)	34 (20–53)	0.167
Female sex (%)	16 (57.14)	9 (54.5)	0.254
BMI, Kg/m^2	20.65 (18.23–22.42)	21.48 (19.27–23.42)	0.315
Primary Malignancy			0.982
AML/CML/MDS	11 (39.29)	9 (40.91)
ALL	5 (17.86)	3 (13.64)
Lymphoma	4 (14.28)	4 (18.18)
MM	6 (21.43)	5 (22.72)
Others	2 (7.14)	1 (4.55)
Time from the diagnosis of pneumonia to BAL, hours	42 (36–94)	39 (32–78)	0.072
SOFA score	7 (4–8)	6 (4–9)	0.263
Prothrombin Time, s	11.3 (10.2–13.5)	10.8 (10.5–11.3)	0.364
Lactate, mmol/L	2.3 (1.5–2.8)	1.9 (1.3–2.5)	0.762
Creatine, μmol/L	97 (59–99)	95 (68–105)	0.624
Tmax, °C	38.4 (36.8–38.9)	38.6 (37.2–38.6)	0.532
WBC, ×10^9/L	7.62 (1.82–10.57)	6.23 (2.21–9.63)	0.152
Lymphocyte count, ×10^9/L	0.42 (0.19–0.58)	0.33 (0.24–0.69)	0.055
C-reactive protein, mg/L	87.21 (35.75–111.60)	58.32 (22.73–75.13)	0.027
Procalcitonin, ng/mL	0.47 (0.13–1.49)	0.51 (0.11–1.45)	0.258
Cytokines
IL-6, pg/mL	62.52 (12.26–93.11)	220.30 (96.37–371.01)	<0.001
IL-8, pg/mL	18.44 (13.22–20.56)	114.27 (67.55–240.22)	<0.001
IFN-γ, pg/mL	29.17 (16.64–44.87)	32.53 (12.10–37.98)	0.158
TNF-α, pg/mL	11.54 (10.22–26.42)	118.27 (87.63–142.45)	<0.001
BNP, pg/mL	273 (150–570)	316 (189–624)	0.158
PO2/FiO2, mmHg	175 (88.5–193.2)	169 (96.1–188.4)	0.041
ΔPO2/FiO2, mmHg	73.52 (29.63–86.55)	165 (111.03–195.52)	<0.001
PCO2, mmHg	37 (32–42)	35 (33–44)	0.381
PEEP, cmH2O	10 (8–12)	10 (8–12)	0.856
pH	7.37 (7.34–7.51)	7.39 (7.35–7.49)	0.733
Respiratory rate, breath/mins	24 (22–31)	22 (19–29)	0.188
Tidal volume, mL/Kg	7.3 (6.6–8.5)	6.8 (6.2–7.9)	0.522
Adjunctive therapies of ARDS			0.505
ECMO	0	1
Neuro-muscular blocking	2	1
Prone positioning	5	6

Abbreviations: BMI, Body Mass Index; BNP, Brain Natriuretic Peptide; ECMO, Extra Corporal Membrane Oxygenation; FiO₂, Fraction of inspired oxygen; LRTI, Lower Respiratory Tract Infection; PaO₂, Partial pressure of Oxygen; PCO₂, Partial pressure of Carbon Dioxide; PEEP, Positive End Expiratory Pressure; SOFA, Sequential Organ Failure Assessment; WBC, White Blood Cell.

Figure 2 Alpha diversity and beta diversity of lung microbiota for the non-responders and responders. (A and B) The non-responders and responders had no difference in the richness of species (evaluated with ACE index and chao1 index). (C and D) The responders had lower diversity in lung microbiota than the non-responders (evaluated with Shannon index and Simpson index). (E) The beta diversity was evaluated with Bray-Curtis Dissimilarity metric plotted in a principal coordinate analysis (PCoA), revealing an apparent pattern of clustering.

Abbreviation: ACE, Abundance-based Coverage Estimators.

Figure 3 Constitution of microorganisms in the lung microbiota of non-responders and responders. (A) The relative abundance of top 20 families in the BAL samples of included patients. (B) The relative abundances of the top 20 families within the groups of non-responders and responders.

Figure 4 Taxonomic difference of lung microbiota in non-responders and responders. (A) Cladogram using the LEfSe method indicating the phylogenetic distribution of lung microbiota of non-responders and responders, only the units with difference s were presented. (B) LDA effect size analysis revealed significant microbial differences in the two groups. LDA score (log10 >2) and p< 0.05 are presented.

Abbreviations: LDA, linear discriminant analysis; LEfSe, LDA effect size analysis.

Figure 5 The etiological microbiome, clinical course and outcomes of non-responders and responders. (A) The primary and secondary etiological species of non-responders and responders. (B) Clinical courses of non-responders and responders. (C) The Kaplan-Meier survival curve of non-responders and responders (Log-rank p = 0.073). (D) The Kaplan-Meier survival curve of non-responders with or without coinfection and responders (Log-rank p = 0.028).

Table 2 Outcomes of Corticosteroid Non-Responders and Responders

	Non-Responders (n=28)	Responders (n=22)	P
30-day mortality	15 (53.5%)	7 (31.8%)	0.124
Invasive Mechanical Ventilation after the first 24 hours	8 (28.6%)	5 (22.7%)	0.640
ICU length of stay	17 (12–22)	16 (10–21)	0.416
Ventilator free days (at day 28)	4 (0–6)	6 (0–10)	0.034
Ventilator free days in survivors (at day 28)	5 (3–6)	8 (3–10)	0.012
New-onset viremia or bacteremia	2 (7.14%)	1 (4.15%)	0.701