Daily Respiratory Research Analysis
Analyzed 204 papers and selected 3 impactful papers.
Summary
A mechanistic study in Cell Metabolism shows that a ketogenic diet mitigates septic lung injury via a gut–lung microbial axis producing azelaic acid that reshapes innate immune responses. A multicenter European Heart Journal cohort demonstrates that echocardiography-derived right ventricular phenotypes add prognostic value at first follow-up in pulmonary arterial hypertension. A clinical study finds nanopore targeted sequencing markedly improves detection of pulmonary pathogens, especially fungi and mixed infections, versus conventional tests.
Research Themes
- Microbiome-mediated modulation of lung injury in sepsis
- Right ventricular echocardiographic phenotyping to refine PAH risk
- Rapid genomics for pulmonary infection diagnosis
Selected Articles
1. Ketogenic diet alleviates septic lung injury via microbial gut-lung axis.
This mechanistic study demonstrates that a ketogenic diet reshapes the gut microbiota to enrich strains expressing an FMO that converts dietary oleic acid into azelaic acid, which then traffics to the lung during sepsis. Azelaic acid promotes neutrophil apoptosis and expansion of MerTK+ reparative macrophages, attenuating septic lung injury. Findings link diet, microbiota-derived metabolites, and innate immune reprogramming along the gut–lung axis.
Impact: It uncovers a specific metabolite (azelaic acid) and enzyme (FMO) pathway by which diet–microbiome interactions modulate lung injury in sepsis, suggesting tractable targets. The cross-species evidence elevates its translational potential.
Clinical Implications: While preclinical, these data suggest that modulating the gut microbiome or delivering azelaic acid (or mimetics) could serve as adjunctive strategies to reduce lung injury in sepsis/ARDS. KD safety and feasibility in septic patients require careful evaluation.
Key Findings
- Ketogenic diet enriched Limosilactobacillus reuteri and Lactiplantibacillus plantarum in mice and humans.
- Specific strains expressed a flavin-dependent monooxygenase that converted oleic acid into azelaic acid.
- Azelaic acid translocated to the lung during sepsis, promoting neutrophil apoptosis and expansion of MerTK+ macrophages, mitigating lung injury.
Methodological Strengths
- Integrates dietary, microbial, enzymatic, and immunologic mechanisms across gut–lung axis.
- Cross-species evidence (mice and humans) supporting microbiome shifts induced by ketogenic diet.
Limitations
- Preclinical study; no randomized clinical evaluation of ketogenic diet or azelaic acid in sepsis.
- Potential safety and metabolic risks of ketogenic diet in critically ill patients are not addressed.
Future Directions: Test azelaic acid or pathway agonists as therapeutics in sepsis models; pilot clinical trials to evaluate safety/feasibility of microbiome or metabolite-based adjuncts in septic ARDS; mechanistic mapping of AZA signaling in lung immune cells.
Sepsis is characterized by impaired immunity to infection, leading to multi-organ dysfunction, with the lung being the most vulnerable organ. Here, we show that ketogenic diet (KD) alleviates sepsis-induced lung injury through a microbial-gut-lung axis. KD alters the gut microbiota in mice and humans, enriching Limosilactobacillus reuteri and Lactiplantibacillus plantarum. Specific strains of these species produce a flavin-dependent monooxygenase (FMO) that converts oleic acid in KD into azelaic acid (AZA). During sepsis, AZA translocates to the lung, where it promotes neutrophil apoptosis and expands MerTK
2. Pulmonary arterial hypertension: right ventricular phenotyping to improve risk assessment at follow-up.
In a prospective multicenter cohort of PAH patients re-evaluated 6–12 months after diagnosis, four echocardiographic RV phenotypes reflecting RV size and RV–PA coupling stratified prognosis independently of ESC/ERS and REVEAL 2.0 risk groups. Patients with severe dilation and poor RV–PA coupling (phenotype-4) had the worst outcomes, while mildly dilated with preserved coupling (phenotype-1) had the best survival in intermediate risk.
Impact: Provides a pragmatic, echocardiography-based phenotyping schema that augments established risk tools and could guide intensity of follow-up and therapy in PAH. Multicenter prospective design and mortality endpoint strengthen applicability.
Clinical Implications: Incorporating RV phenotypes at first follow-up can refine prognostic counseling and identify high-risk patients (severe dilation with poor RV–PA coupling) for closer monitoring and escalation of therapy.
Key Findings
- Defined four RV phenotypes combining RV dilatation and RV–PA coupling from echocardiography.
- Phenotype-4 (severe dilatation with poor RV–PA coupling ± moderate/severe TR) identified patients with poorest survival across risk strata.
- Phenotype-1 (mild dilatation with preserved coupling) flagged better survival within intermediate-risk groups, independent of ESC/ERS and REVEAL 2.0 risk scores.
Methodological Strengths
- Prospective multicenter cohort with standardized echocardiographic phenotyping.
- Hard clinical endpoint (all-cause mortality) with median 3.7-year follow-up.
Limitations
- Phenotype assignments depend on echocardiographic measurements and operator variability.
- Generalizability outside specialized PAH centers requires further validation.
Future Directions: Validate phenotypes in external cohorts, integrate with biomarkers/hemodynamics, and test phenotype-guided treatment escalation strategies.
BACKGROUND AND AIMS: The aim of this study was to evaluate whether echocardiography-derived phenotypes describing different degrees of right ventricular (RV) remodelling and dysfunction add prognostic information to that of current risk stratification tools in patients with pulmonary arterial hypertension (PAH) at first follow-up. METHODS: In 11 centres of the Italian Pulmonary Hypertension NETwork (IPHNET), data were prospectively collected from patients with PAH who underwent re-evaluation between 6 and 12 months after diagnosis. Echocardiographic variables were combined a priori to define four phenotypes representing different degrees of RV dilatation and right ventricular-pulmonary arterial (RV-PA) coupling: a mildly dilated right ventricle with preserved RV-PA coupling defined phenotype-1; a mildly dilated right ventricle with poor RV-PA coupling defined phenotype-2; a severely dilated right ventricle with preserved RV-PA coupling defined phenotype-3; a severely dilated right ventricle with poor RV-PA coupling, either with or without tricuspid regurgitation of moderate degree or more, defined phenotype-4. Patients were followed up for all-cause death for a median of 3.7 years. RESULTS: These echocardiographic phenotypes were present in all European Society of Cardiology/European Respiratory Society or REVEAL 2.0 risk groups except for the high-risk groups, which included only phenotype-3 and phenotype-4. In each risk group, RV phenotype-4 identified patients with a poorer prognosis; RV phenotype-1 identified patients with better survival in intermediate risk groups. CONCLUSIONS: Echocardiography-derived phenotypes describing different degrees of RV remodelling and dysfunction provide prognostic information which is independent of and additional to the clinically defined risk in PAH patients at first follow-up.
3. Assessing Nanopore Targeted Sequencing for the Diagnosis of Pulmonary Infections: A Comparative Multidisease Approach.
In 284 patients with suspected lower respiratory tract infection, nanopore targeted sequencing significantly outperformed conventional microbiological tests, with 91.85% sensitivity overall and marked gains for fungi and mixed infections. Pathogen spectra differed across clinical subgroups, and patients with hypertension had more fungal/mixed infections where NTS excelled at detecting opportunists.
Impact: Demonstrates real-world diagnostic gains of nanopore targeted sequencing for pulmonary infections, addressing major gaps in polymicrobial and fungal detection. It provides actionable subgroup insights that can inform deployment in high-risk populations.
Clinical Implications: NTS can be considered to complement or replace conventional testing in suspected lower respiratory tract infections, especially in immunocompromised or comorbid patients where fungal or mixed etiologies are likely. It may expedite targeted therapy.
Key Findings
- Overall sensitivity of NTS was 91.85% versus 74.81% for conventional microbiological tests.
- Marked improvements for fungal (81.7%) and mixed infections (99.65%) using NTS.
- Hypertensive patients exhibited higher fungal and mixed infection rates; NTS was effective in detecting opportunistic pathogens in this subgroup.
Methodological Strengths
- Head-to-head comparison against conventional testing in a real-world cohort.
- Subgroup analyses illuminating heterogeneous pathogen distributions across clinical contexts.
Limitations
- Single-center study limits generalizability; no randomized diagnostic strategy trial.
- Turnaround time, cost-effectiveness, and impact on patient outcomes were not fully evaluated.
Future Directions: Prospective multicenter trials to assess clinical impact, turnaround time, antimicrobial stewardship benefits, and cost-effectiveness of NTS-guided management.
Pulmonary infections remain a significant global health burden, particularly in immunocompromised individuals and patients with chronic respiratory or systemic diseases. Conventional microbiological tests (CMTs), though widely used, often have limited sensitivity and delayed results, especially in polymicrobial or atypical infections. This study evaluated the diagnostic performance of nanopore targeted sequencing (NTS) in 284 patients with suspected lower respiratory tract infections at Chifeng Municipal Hospital, using CMTs and clinical diagnosis as references. NTS demonstrated markedly higher sensitivity (91.85%) compared to CMTs (74.81%), with substantial improvements in detecting fungal (81.7%) and mixed infections (99.65%). A total of 259 pathogens were detected. Among them, bacteria were the most frequently identified pathogens (69.5%), followed by fungi (15.44%) and viruses (14.28%). Pathogen distribution varied by clinical subgroup, such as community-acquired pneumonia and chronic obstructive pulmonary disease, reflecting infection heterogeneity. Patients with hypertension (HBP) showed a higher incidence of fungal and mixed infections than non-HBP patients. NTS was particularly effective in detecting opportunistic pathogens in the HBP group, suggesting an association between cardiovascular comorbidity and altered pathogen susceptibility.