Daily Respiratory Research Analysis
Three impactful respiratory studies stood out today: lung virome convergence that precedes hospital-acquired pneumonia in intubated ICU patients, genotype-stratified responses to elexacaftor–tezacaftor–ivacaftor in cystic fibrosis, and evidence that nocturnal hypoxaemia nadir does not increase intraoperative fentanyl ventilatory sensitivity in children with obstructive sleep apnoea. Together, these works advance infection prediction, precision therapy, and perioperative safety.
Summary
Three impactful respiratory studies stood out today: lung virome convergence that precedes hospital-acquired pneumonia in intubated ICU patients, genotype-stratified responses to elexacaftor–tezacaftor–ivacaftor in cystic fibrosis, and evidence that nocturnal hypoxaemia nadir does not increase intraoperative fentanyl ventilatory sensitivity in children with obstructive sleep apnoea. Together, these works advance infection prediction, precision therapy, and perioperative safety.
Research Themes
- Critical care viromics and infection prediction
- CFTR modulator precision medicine in cystic fibrosis
- Perioperative opioid safety in pediatric obstructive sleep apnoea
Selected Articles
1. Lung virome convergence precedes hospital-acquired pneumonia in intubated critically ill patients.
In intubated ICU patients, the lung virome converged toward a bacteriophage-dominant, lower beta-diversity state 4–5 days before hospital-acquired pneumonia onset. This signature was externally validated and in silico causal inference implicated bacteriophages linked to Streptococcus and Prevotella as regulators of HAP risk.
Impact: Reveals a preclinical virome signal preceding HAP, opening avenues for early risk stratification and microbiome-targeted prevention in critical care.
Clinical Implications: If validated prospectively with interventional studies, serial virome profiling could identify patients at imminent HAP risk to guide prophylaxis timing and antimicrobial stewardship.
Key Findings
- Viral beta-diversity decreased and converged toward a bacteriophage-dominant signature 4–5 days before HAP onset.
- The virome signature and its convergence were validated in an external cohort, with 18% of the bacteriophage signature conserved.
- A distinct viral–bacterial interactome preceded HAP, and causal inference highlighted Streptococcus- and Prevotella-associated phages as key regulators.
- The endotracheal virome was dominated by Caudoviricetes across patients.
Methodological Strengths
- Longitudinal sampling with temporal proximity to HAP onset
- External validation cohort and registered discovery/validation studies
- In silico causal inference linking phages to bacterial taxa
Limitations
- Observational design limits causal confirmation and clinical translation
- Moderate sample size and single-specimen source (endotracheal aspirates) may affect generalizability
- Potential confounding from antibiotics and ICU interventions
Future Directions: Prospective interventional trials should test virome-guided prophylaxis or microbiome modulation to prevent HAP and evaluate integration with bacterial microbiome and host immune profiling.
2. Sweat chloride and lung function responses to elexacaftor-tezacaftor-ivacaftor in people with cystic fibrosis with two versus one responsive CFTR variants: an analysis of two real-world observational studies.
Across 1266 people with cystic fibrosis, those with two ETI-responsive CFTR variants achieved lower post-initiation sweat chloride (median 36 mmol/L) and were more likely to reach SCC <30 mmol/L than those with one responsive variant. Genotype count predicted CFTR correction in sweat glands, whereas ppFEV1 responses were less strongly differentiated.
Impact: Provides genotype-stratified, real-world evidence that refines expectations for CFTR modulator efficacy and supports precision counseling and trial design.
Clinical Implications: Clinicians can counsel patients that two responsive variants increase the likelihood of deep sweat chloride correction with ETI, while lung function gains remain variable and should not be inferred from sweat chloride alone.
Key Findings
- Among 1266 participants, 834 had two responsive variants and 432 had one.
- Median post-ETI sweat chloride was 36 mmol/L (IQR 24–50) with two responsive variants vs 53 mmol/L (26–72) with one (p<0.0001).
- SCC <30 mmol/L occurred in 36% with two responsive variants vs 15% with one (significant by chi-square).
- ppFEV1 improvements were not as distinctly predicted by the count of responsive variants compared with sweat chloride.
Methodological Strengths
- Large sample size across two real-world cohorts
- Objective biomarkers (sweat chloride, ppFEV1) with genotype stratification
Limitations
- Observational design with potential confounding and heterogeneity in care
- Follow-up timing and prior treatments may differ between cohorts
- Sweat chloride–lung function dissociation limits surrogate inference
Future Directions: Prospective studies should evaluate genotype-informed ETI initiation and escalation strategies, integrating airway biomarkers to better predict lung function response.
3. Association of preoperative nocturnal hypoxaemia nadir and fentanyl ventilatory sensitivity in children with obstructive sleep apnoea undergoing general anaesthesia: a multicentre clinical cohort study.
In 90 children aged 2–8 years with OSA undergoing adenotonsillectomy, single-dose fentanyl ventilatory effects during sevoflurane anaesthesia were not associated with the preoperative nocturnal hypoxaemia nadir. Fentanyl dosing should not be determined by sleep study SpO2 nadir.
Impact: Addresses a prevalent perioperative safety concern and provides negative evidence against hypoxaemia-nadir–based fentanyl dose reduction strategies in pediatric OSA.
Clinical Implications: Standard pediatric fentanyl dosing can be considered in children with OSA without adjusting solely for nocturnal SpO2 nadir; clinicians should instead rely on multimodal monitoring and risk stratification.
Key Findings
- Multicentre cohort (n=90) with in-cohort fentanyl dose randomisation in children 2–8 years with OSA undergoing adenotonsillectomy.
- No association between preoperative nocturnal SpO2 nadir and fentanyl-induced ventilatory effects during sevoflurane anaesthesia.
- Trial registered (NCT05051189), supporting methodological transparency.
- Findings argue against basing intraoperative fentanyl dosing on sleep study hypoxaemia nadir alone.
Methodological Strengths
- Prospective multicentre design with in-cohort dose randomisation
- Objective ventilatory assessments under standardized anaesthesia conditions
- Clinical trial registration
Limitations
- Single intraoperative dose and anaesthetic context may limit generalizability to other settings or opioid regimens
- Abstracted data do not detail full sleep study metrics beyond SpO2 nadir
- Short-term intraoperative outcomes without postoperative respiratory events assessment
Future Directions: Evaluate broader OSA severity metrics and postoperative respiratory outcomes across different opioid regimens and anaesthesia types to refine dosing guidance.