Daily Respiratory Research Analysis
Analyzed 179 papers and selected 3 impactful papers.
Summary
Analyzed 179 papers and selected 3 impactful articles.
Selected Articles
1. Development of a rapid ex vivo tumor platform for drug response prediction in lung cancer.
A prospective multicenter study demonstrated that a rapid ex vivo 3D tumor replica platform can be established from routine lung cancer biopsies in 65% of cases and predicts clinical drug response with 73% sensitivity and 92% positive predictive value. Results are available in a median of 12 days, aligning with real-world treatment decision windows and externally validated.
Impact: Introduces a scalable, patient-derived functional assay that bridges the gap between genomics and real-time treatment selection in lung cancer. This platform could reduce exposure to ineffective therapies and accelerate personalized care.
Clinical Implications: Clinicians could integrate ex vivo testing alongside molecular profiling to prioritize effective regimens within two weeks, especially when actionable genomic targets are lacking or multiple options exist.
Key Findings
- Tumor replicas were established from routine biopsies in 65% of 129 treatment-naïve lung cancer patients.
- Ex vivo drug responses were available at a median of 12 days and concordant with patient and PDX responses.
- Clinical validation showed 73% sensitivity and 92% positive predictive value; external validation confirmed feasibility.
Methodological Strengths
- Prospective multicenter cohort with external validation
- Functional assay using small routine biopsies with rapid turnaround
Limitations
- Culture establishment rate was 65%, limiting applicability to all patients
- Non-randomized validation; potential selection bias and limited therapy panels in some cases
Future Directions: Increase establishment rates, expand drug panels (including immunotherapies), and test utility in prospective interventional trials that randomize treatment selection based on ex vivo results.
Despite advances in systemic therapies for patients with (locally) advanced stage lung cancer, response rates remain poor, underscoring the urgent need for predictive models to guide therapy selection. Patient-derived ex vivo models are promising, however, their clinical utility is restricted by the need for surgical biopsies, low establishment rates, and culture durations exceeding the clinically-relevant therapeutic decision-making window. Here, we developed and clinically validated a rapid, high-throughput ex vivo 3D tumor replica platform that enables functional drug testing from small diagnostic biopsies. In this prospective multicenter cohort study of 129 treatment-naïve lung cancer patients, tumor replicas were successfully established in 65% of biopsies. These cultures retained their original morphological, genetic, and immunophenotypic features. Ex vivo drug responses to chemotherapy and targeted agents were generated within a median of 12 days from biopsy acquisition. The ex vivo drug responses were in concordance with the treatment responses in patient-derived xenografts and lung cancer patients. In the clinical study, the ex vivo platform demonstrated a sensitivity of 73% and a positive predictive value of 92%. External validation confirmed the feasibility and reproducibility of the platform. In conclusion, this platform enables rapid patient-specific drug response assessment from routine biopsies within a clinically relevant time-frame.
2. USP4 controls neutrophil spreading through stabilising IQGAP1 during lung inflammation.
This study identifies USP4 as a regulator of neutrophil spreading via stabilization of IQGAP1 during acute lung inflammation. USP4 was upregulated in leukocytes from ARDS patients and ALI mice, and pharmacologic targeting of the USP4–IQGAP1 axis (Vialinin A) is proposed as a therapeutic strategy.
Impact: It uncovers a druggable proteostasis pathway linking USP4 to neutrophil-driven tissue damage in ARDS, bridging human data with mechanistic models and nominating a tractable small-molecule approach.
Clinical Implications: USP4–IQGAP1 modulation may represent a new anti-inflammatory strategy to attenuate neutrophil-mediated injury in ARDS (acute respiratory distress syndrome), warranting translational studies of Vialinin A or selective USP4 inhibitors.
Key Findings
- USP4 expression is increased in blood and pulmonary leukocytes from ARDS patients and in ALI mice, while decreased in mouse lung parenchyma after LPS challenge.
- USP4 controls neutrophil spreading by stabilizing IQGAP1, linking protein homeostasis to inflammatory cell recruitment.
- Pharmacologic targeting of the USP4–IQGAP1 axis with Vialinin A is proposed as a therapeutic strategy for ARDS secondary to severe pneumonia.
Methodological Strengths
- Integration of human ARDS samples with mechanistic mouse ALI models.
- Molecular pathway mapping implicating USP4 stabilization of IQGAP1, with pharmacologic modulation (Vialinin A).
Limitations
- Human sample size and detailed cohort characteristics are not specified in the abstract.
- Translational efficacy and safety of Vialinin A or USP4 inhibition in humans remain untested.
Future Directions: Quantify USP4/IQGAP1 pathway activity across ARDS endotypes; test selective USP4 inhibitors and Vialinin A analogs in large-animal models; develop pharmacodynamic biomarkers of neutrophil spreading.
BACKGROUND: Protein availability critically influences innate immune reactivity and the extent of immune-mediated tissue injury. A key unresolved question is how specific protein homeostasis networks within immune cells such as neutrophils can be modulated to mitigate the detrimental outcomes of acute inflammation. METHODS: We established an acute lung injury (ALI) model in immune-specific ubiquitin-specific peptidase 4 (USP4) knockout chimeric (BM-Usp4 RESULTS: USP4 expression was upregulated in blood and pulmonary leucocytes from patients with ARDS and ALI mice (p=0.049, p=0.0086), but downregulated in mouse lung parenchyma (lipopolysaccharide vs control, p=0.0019). BM-Usp4 CONCLUSION: USP4 links protein homeostasis to neutrophil recruitment during inflammation. Targeting the USP4-IQGAP1 axis with Vialinin A represents a promising therapeutic strategy for patients with ARDS secondary to severe pneumonia.
3. In-hospital and post-discharge mortality among infants with respiratory syncytial virus in rural Kenya: a 25-year retrospective cohort study.
Across 25 RSV seasons in rural Kenya, in-hospital mortality among RSV-positive infants remained unchanged, with most deaths occurring within 7 days. Congenital heart disease, severe undernutrition (weight-for-age Z score), and hypoxemia independently predicted death at admission.
Impact: It provides long-term, large-scale evidence from an LMIC setting, identifying modifiable nutritional and clinical risk factors that can guide triage and targeted interventions where RSV burden is greatest.
Clinical Implications: Prioritize pulse oximetry and oxygen therapy, screen for congenital heart disease, and implement targeted nutritional support for RSV-infected infants at admission to reduce early in-hospital mortality.
Key Findings
- Among 2,745 RSV-positive infants, in-hospital mortality was 2.4%, with 76% of deaths occurring within 7 days.
- Independent predictors of mortality: congenital heart disease (OR 3.51), severe undernutrition (per 1-unit lower WAZ: OR 1.59), and hypoxemia (per 1% lower SpO2: OR 1.05).
- No sustained decline in RSV-associated in-hospital mortality or improvement in anthropometrics over 25 years.
Methodological Strengths
- 25-year surveillance with laboratory-confirmed RSV and WHO pneumonia definitions.
- Use of both random-forest and multivariable logistic regression to identify predictors.
Limitations
- Single-center retrospective design may limit generalizability and introduce unmeasured confounding.
- Predominance of post-neonatal infants; limited detail on post-discharge outcomes within abstract.
Future Directions: Prospective risk-stratified care bundles integrating nutrition, cardiac screening, and oxygen access; evaluate effects of maternal and infant RSV immunization alongside nutrition programs.
BACKGROUND: Respiratory syncytial virus (RSV) is the leading cause of hospital admission for lower respiratory infection in infants worldwide, with more than 95% of deaths occurring in low-income and middle-income countries. Predictors of adverse outcomes following RSV hospitalisation remain poorly defined. We aimed to identify clinical and anthropometric predictors of mortality among infants admitted with RSV pneumonia and to assess changes in mortality over a 25-year surveillance period. METHODS: In this retrospective cohort study, we analysed 25 years of paediatric surveillance at Kilifi County Hospital, Kilifi, Kenya, spanning 25 successive RSV seasons. Neonates (aged <28 days) and post-neonatal infants (aged 28 days to 12 months) admitted with WHO-defined pneumonia were tested for RSV and demographic, anthropometric, and clinical data were recorded at admission. The primary outcome was in-hospital death among infants admitted with RSV pneumonia. Predictors of mortality were identified using random-forest and multivariable logistic regression, and temporal trends in mortality and anthropometric status were examined. FINDINGS: Of 75 482 admissions of infants to Kilifi County Hospital between Jan 1, 2001, and July 13, 2025, 19 299 (25·6%) met WHO pneumonia criteria and 2745 (22·7%) had RSV. Of these infants, 2390 (87·1%) were post-neonatal, of whom 58 (2·4%) died in hospital with 44 (76%) deaths within 7 days of admission. Mortality was independently associated with congenital heart disease (odds ratio 3·51 [95% CI 1·37-8·97]), severe undernutrition (per 1-unit reduction in weight-for-age Z score: 1·59 [1·28-1·99]), and hypoxaemia (per 1% decrease in peripheral oxygen saturation: 1·05 [1·03-1·08]). 38 (70·4%) of 54 infants with RSV who died in hospital had a mid-upper arm circumference below the severe acute malnutrition threshold of 11·5 cm. There was no evidence of a sustained decline in RSV-associated in-hospital mortality or improvement in anthropometric status over the 25-year study period. INTERPRETATION: RSV mortality in Kenyan infants remains high and has not declined over 25 years. Severe undernutrition and congenital heart disease identify infants with RSV who are at the highest risk of in-hospital death. These findings highlight the role of chronic anthropometric deficits in RSV outcomes and support targeted nutritional interventions to reduce mortality. FUNDING: Bill & Melinda Gates Foundation and Wellcome.