Daily Respiratory Research Analysis
Analyzed 62 papers and selected 3 impactful papers.
Summary
A phase 3 RCT (TACTIC) shows that adding an indwelling pleural catheter at medical thoracoscopy for malignant pleural effusion does not shorten hospital stay or improve dyspnea versus poudrage alone, but it markedly reduces subsequent invasive procedures. Nationwide targeted sequencing directly from respiratory specimens enabled detection of macrolide-resistant Bordetella pertussis (≈4%) and high-resolution lineage tracking, strengthening diagnostic surveillance. In critically ill patients on kidney replacement therapy, incident hypophosphatemia was independently associated with fewer ventilator‑free days.
Research Themes
- Optimizing malignant pleural effusion management strategies
- Culture-independent genomic surveillance for respiratory pathogens
- Electrolyte dysregulation and respiratory outcomes in critical care
Selected Articles
1. Medical thoracoscopy with talc poudrage and indwelling pleural catheter insertion versus medical thoracoscopy with talc poudrage alone for patients with symptomatic malignant pleural effusion (TACTIC): a randomised, controlled phase 3 trial.
In 124 patients with malignant pleural effusion, adding an indwelling pleural catheter at medical thoracoscopy with talc poudrage did not reduce 4‑week hospital time or improve dyspnea versus poudrage alone, but it markedly reduced additional invasive pleural procedures by 12 weeks. Safety profiles were similar between groups, with three related serious adverse events in the intervention arm.
Impact: This pragmatic phase 3 RCT delivers practice‑informing, negative evidence: routine IPC insertion at thoracoscopy does not improve primary outcomes but can reduce re‑interventions, guiding personalized procedural choices in malignant pleural effusion.
Clinical Implications: For symptomatic malignant pleural effusion undergoing medical thoracoscopy with poudrage, IPC should be considered when patient priorities include minimizing subsequent invasive procedures or facilitating ambulatory management, but not with the expectation of shorter hospitalization or better dyspnea in the first 4 weeks.
Key Findings
- No significant difference in total 4‑week hospital time between IPC+poudrage and poudrage alone (median 1 vs 2 days; p=0.26).
- No significant difference in average dyspnea VAS over 4 weeks (p=0.26).
- Fewer additional invasive pleural procedures by 12 weeks in the IPC group (3% vs 34%, p<0.0001).
- Similar overall trial‑related adverse event rates; three related serious adverse events occurred in the intervention arm.
Methodological Strengths
- Phase 3, multicenter randomized controlled design with centralized web-based randomization
- Co-primary outcomes with modified intention-to-treat analysis and clinically meaningful endpoints
Limitations
- Unblinded design may introduce performance bias
- Modest sample size; three serious adverse events limited to the intervention arm; generalizability beyond UK centers uncertain
Future Directions: Cost‑effectiveness analyses, patient‑reported outcomes beyond 4 weeks, and stratified strategies (e.g., by tumor type, trapped lung, pleural elastance) to identify subgroups who benefit most from IPC at thoracoscopy.
BACKGROUND: Patients with suspected malignant pleural effusions (MPE) are often in need of both a confirmatory diagnosis and symptom control. Therapeutic options include talc pleurodesis via chest drain, poudrage during medical thoracoscopy, or alternatively an indwelling pleural catheter (IPC). Combining the diagnostic and therapeutic efficacy of medical thoracoscopy and poudrage with the ambulatory benefits of an IPC has not been studied within a randomised controlled trial. The aim of the TACTIC trial was to determine whether this approach resulted in a reduced length of hospital stay and improvements in dyspnoea. METHODS: This unblinded, phase 3, randomised controlled trial was undertaken in 11 UK hospitals. Patients with MPE and confirmed malignancy (during medical thoracoscopy or beforehand) received talc poudrage and were randomly assigned by a centralised web-based system to an IPC at the time of medical thoracoscopy or usual care (ie, medical thoracoscopy, poudrage, and admission with large bore tube). Co-primary outcomes were time in hospital (including initial admission for trial procedure and any subsequent readmissions over 4 weeks post procedure) and average breathlessness assessed with visual analogue scale dyspnoea scores, measuring severity of dyspnoea from 0 mm to 100 mm, over a 4-week period. All randomised patients in whom an outcome was available were included in the analysis on a modified intention-to-treat basis. TACTIC was registered with ISRCTN on Aug 8, 2021 (ISRCTN11058680). FINDINGS: Participants were recruited from between Dec 15, 2021, and Jan 3, 2024. 124 participants were randomised: 62 to the intervention and 62 to standard care. Leading diagnoses were pleural mesothelioma (46%), lung cancer (28%), and breast cancer (10%). Co-primary outcome data were available for 102 patients for total length of hospital stay (52 in intervention group vs 50 in standard care group) and 108 patients for breathlessness (57 vs 51). Median time in hospital was 1 day (IQR 1-3, 95% CI 1-2) in the intervention group versus 2 days (IQR 1-3, 95% CI 1-2) in standard care group (p=0·26). Median visual analogue scale dyspnoea scores did not differ between groups: 14·0 mm (IQR 8·8-32·4) in the intervention group versus 19·6 mm (8·1-38·7) in standard care group (p=0·26). Participants in the intervention group required fewer additional invasive pleural procedures by 12 weeks (two [3%] of 60 vs 19 [34%] of 56, p<0·0001) Trial related adverse events rates were similar in both groups (46 [74%] of 62 vs 44 [71%] of 62, p=0·84). Three related serious adverse events were recorded, all occurring in the intervention group. INTERPRETATION: The combination of medical thoracoscopy, poudrage, and IPC did not result in shorter hospital stay but was safe and resulted in similar dyspnoea control compared with standard care. For patients with symptomatic MPE undergoing medical thoracoscopy for pleurodesis who prioritise minimising the length of hospital stay or the need for further invasive pleural procedures, the addition of an IPC alongside poudrage might help to achieve this goal. FUNDING: National Institute of Health Research, Research for Patient Benefit.
2. Characterisation of Bordetella pertussis virulence and macrolide resistance in Australia by targeted culture-independent sequencing: a genomic epidemiology study.
Targeted sequencing directly from 255 RT‑PCR‑positive respiratory specimens recovered near‑complete Bordetella pertussis genomes in 58% of cases, resolving seven co‑circulating lineages and identifying eight dispersed macrolide‑resistant cases (23S rRNA 2037A→G; ≈4% prevalence). The approach complemented PCR, enabling resistance mutation detection and fine‑scale phylogenetics in a single workflow.
Impact: By enabling culture‑independent recovery of near‑complete genomes and resistance mutations directly from clinical specimens, this study provides an implementable framework for real‑time genomic surveillance of pertussis and antimicrobial stewardship.
Clinical Implications: Diagnostic laboratories and public health programs can integrate tNGS to detect macrolide resistance and track lineages directly from respiratory samples, informing appropriate macrolide use and outbreak investigations when culture is unavailable or slow.
Key Findings
- Near-complete B. pertussis genomes were recovered from 58% (148/255) of RT‑PCR‑positive respiratory specimens using tNGS.
- Seven co-circulating lineages were documented, including two linked to macrolide resistance.
- Eight epidemiologically unrelated, geographically dispersed macrolide‑resistant cases with 23S rRNA 2037A→G were identified and confirmed; estimated resistance prevalence ≈4%.
- tNGS performance correlated with RT‑PCR Ct values and complemented PCR-based surveillance.
Methodological Strengths
- Nationwide, multi-jurisdiction sampling with both retrospective and prospective accrual
- Orthogonal confirmation with whole-genome sequencing and phenotypic testing for a subset
Limitations
- Near-complete genome recovery in 58% indicates variable yield; performance dependent on pathogen load (Ct)
- Not all states/territories included; mix of retrospective and prospective sampling may introduce bias
Future Directions: Prospective integration of tNGS into routine diagnostics with standardized Ct thresholds, cost‑effectiveness analyses, and linkage to clinical outcomes to assess impact on treatment and transmission control.
BACKGROUND: Bordetella pertussis continues to circulate globally despite widespread vaccination, with a notable epidemic in 2024. Its resurgence is confounded by the emergence of pertactin-deficient, macrolide-resistant B pertussis strains in Asia and Europe, which are under-recognised by conventional diagnostics. We aimed to apply targeted culture-independent next-generation sequencing (tNGS) of respiratory specimens to improve global B pertussis diagnostic capability and genomic surveillance. METHODS: We did a nationwide genomic epidemiology study of B pertussis RT-PCR-positive respiratory specimens that were retrospectively and prospectively collected by diagnostic and public health laboratories in six of seven states and territories of Australia. Specimens underwent tNGS and macrolide-resistant B pertussis-specific PCR, and an opportunistic subset from New South Wales and Queensland were cultured for confirmatory susceptibility testing and whole-genome sequencing. Sequencing data were analysed for genome recovery, virulence profiles, and macrolide resistance mutations, and were compared with international macrolide-resistant B pertussis genomes and ancestral Australian genomes. The performance of the tNGS approach was assessed with logistic regression relative to RT-PCR cycle threshold values, and sensitivity and specificity values were calculated. FINDINGS: 255 respiratory specimens positive for B pertussis were included in the study. 64 (25%) were retrospectively collected between Jan 12, 2012, and Dec 31, 2023, and 191 (75%) were prospectively collected between Jan 1 and Oct 28, 2024. Of these 255 specimens, 148 (58%) yielded near-complete B pertussis genomes through tNGS. Seven co-circulating lineages of B pertussis were documented, including two associated with macrolide-resistance. Eight epidemiologically unrelated and geographically dispersed cases of macrolide-resistant B pertussis with a 23S rRNA 2037A→G mutation were identified by tNGS and confirmed by whole-genome sequencing. Three of these were further validated by phenotypic testing. The estimated prevalence of macrolide resistance among Australian cases positive for B pertussis was 4% (eight of 188). INTERPRETATION: tNGS can recover near-complete B pertussis genomes directly from clinical specimens, enabling identification of macrolide resistance mutations and high-resolution phylogenetic analysis. These findings show that tNGS complements PCR-based surveillance by providing genome-wide assessment of resistance, virulence, and genomic diversity in a single workflow. FUNDING: NSW Health Prevention Research Support Program.
3. Hypophosphatemia During Kidney Replacement Therapy and Ventilator-Free Days: A Post-Hoc Analysis of the STARRT-AKI Trial.
In a post‑hoc analysis of 1,942 STARRT‑AKI participants, incident hypophosphatemia during kidney replacement therapy occurred in 33% and was independently associated with fewer ventilator‑free days at 28 days; severe hypophosphatemia showed a stronger association. No association was observed with 90‑day mortality or KRT dependence.
Impact: Links a modifiable biochemical abnormality during KRT to an important patient‑centered respiratory outcome, supporting proactive phosphate monitoring/repletion strategies in the ICU.
Clinical Implications: Implement routine phosphate monitoring and protocols for timely repletion during KRT—especially CKRT and accelerated starts—to potentially improve ventilator liberation; consider integrating targets into ICU electrolyte bundles.
Key Findings
- Incident hypophosphatemia occurred in 32.6% and severe hypophosphatemia in 9.9% of KRT recipients.
- Hypophosphatemia and severe hypophosphatemia were independently associated with fewer ventilator‑free days at 28 days (both p<0.001).
- Risk factors included female sex, lower body weight, lower baseline phosphate, CKRT modality, and accelerated KRT initiation.
- No association with 90‑day mortality or KRT dependence.
Methodological Strengths
- Large sample size from a randomized trial cohort with rigorous post‑hoc modeling (IPW zero‑inflated negative binomial, win‑ratio)
- Clear exposure and outcome definitions with clinically meaningful endpoints
Limitations
- Post‑hoc observational design subject to selection bias and residual confounding
- Phosphate measurement timing/frequency may vary; causality cannot be inferred
Future Directions: Prospective interventional studies testing phosphate‑supplementation protocols during KRT with ventilator weaning outcomes; exploration of mechanism (diaphragmatic weakness, ventilatory drive).
RATIONALE & OBJECTIVE: Critically ill patients receiving kidney replacement therapy (KRT), especially continuous KRT (CKRT), have a high risk of hypophosphatemia due to extracorporeal losses, which may contribute to muscle weakness and prolonged respiratory failure. This study evaluated the relationship between incident hypophosphatemia and respiratory function in these patients. STUDY DESIGN: Post hoc observational study of STARRT-AKI trial participants. SETTING & PARTICIPANTS: Eligible trial participants 1) received continuous kidney replacement therapy (CKRT) >24 hours or intermittent hemodialysis (IHD) or sustained low-efficiency dialysis (SLED) for >1 session, 2) had a serum phosphate ≥0.5 mmol/L on the day of KRT initiation, and 3) had ≥1 serum phosphate measurement during KRT. EXPOSURES: Hypophosphatemia (<0.7 mmol/L) and severe hypophosphatemia (<0.5 mmol/L) during KRT. OUTCOMES: Primary outcome was ventilator-free days (VFD) at 28 days of follow-up. Secondary outcomes included mortality and KRT dependence at 90 days. ANALYTICAL APPROACH: A truncated hurdle model was fit to describe clinical characteristics associated with hypophosphatemia. Adjusted analyses of VFD utilized an inverse probability weighted zero-inflated negative binomial model and a win-ratio analysis. Secondary outcomes were assessed with logistic regression. RESULTS: 1,942 trial participants were studied. Among them, 634 (32.6%) developed hypophosphatemia, and 192 (9.9%) developed severe hypophosphatemia. Clinical factors independently associated with incident hypophosphatemia during KRT were female sex, lower body weight, lower serum phosphate levels at KRT initiation, CKRT as the initial KRT modality, and randomization to accelerated KRT initiation. Incident hypophosphatemia and severe hypophosphatemia were associated with fewer VFD at 28 days (β 0.91, 95% CI: 0.87, 0.95 and β 0.87, 95% CI: 0.82, 0.93, respectively, p<0.001 for both). By win-ratio for any random pair of patients, those with incident hypophosphatemia and severe hypophosphatemia had a 27% and 25% lower likelihood of combined 28-day survival and fewer days on the ventilator, respectively. There was no association between hypophosphatemia and 90-day mortality or KRT dependence. LIMITATIONS: Selection bias and unmeasured confounding. CONCLUSIONS: Incident hypophosphatemia during KRT was independently associated with fewer VFD at 28 days.