Daily Ards Research Analysis
A multicenter randomized trial protocol (PIONEER) will test pirfenidone to reduce fibroproliferation and increase ventilator-free days in ARDS. A 502,409-participant UK Biobank cohort links hospital-treated infections to long-term musculoskeletal disorders, with risks persisting beyond 10 years. A national prospective neonatal cohort in Türkiye reveals substantial variability in surfactant use among late preterm infants with respiratory distress.
Summary
A multicenter randomized trial protocol (PIONEER) will test pirfenidone to reduce fibroproliferation and increase ventilator-free days in ARDS. A 502,409-participant UK Biobank cohort links hospital-treated infections to long-term musculoskeletal disorders, with risks persisting beyond 10 years. A national prospective neonatal cohort in Türkiye reveals substantial variability in surfactant use among late preterm infants with respiratory distress.
Research Themes
- Antifibrotic therapy in ARDS
- Long-term sequelae of severe infections
- Variability in neonatal respiratory management
Selected Articles
1. Pirfenidone to prevent fibrosis in acute respiratory distress syndrome: The PIONEER study protocol.
This ongoing multicenter, double-blind RCT will randomize 130 invasively ventilated ARDS patients to pirfenidone versus placebo for up to 28 days, with ventilator-free days at day 28 as the primary outcome. Secondary endpoints include ICU/hospital-free days, mortality, HRCT fibroproliferation markers, and quality of life.
Impact: If positive, this trial could introduce the first antifibrotic strategy specifically targeting ARDS-related fibroproliferation, potentially shortening ventilation and improving outcomes.
Clinical Implications: Clinicians should be aware of ongoing enrollment and avoid off-trial pirfenidone use; if efficacy is demonstrated, early antifibrotic therapy may become part of ARDS management, guided by HRCT and clinical endpoints.
Key Findings
- First multicenter, double-blind, placebo-controlled RCT testing pirfenidone in ARDS (N=130).
- Primary outcome: ventilator-free days at day 28; secondary outcomes include ICU/hospital-free days and mortality.
- Fibroproliferation assessed by HRCT at ICU discharge; trial registered (NCT05075161) with intention-to-treat analysis.
Methodological Strengths
- Randomized, double-blind, multicenter design with intention-to-treat analysis.
- Pre-registered protocol with clearly defined primary and secondary endpoints.
Limitations
- Protocol paper: no clinical results yet; actual effect size and safety are unknown.
- Modest sample size (N=130) may limit power for mortality and subgroup analyses; ARDS heterogeneity may dilute treatment effect.
Future Directions: If efficacy signals emerge, proceed to larger phase III trials, enrich for fibroproliferative phenotypes using imaging/biomarkers, and explore timing, dosing, and combination strategies with lung-protective ventilation.
BACKGROUND: Pulmonary fibrosis is a major complication of the Acute Respiratory Distress Syndrome (ARDS). Pirfenidone is an approved treatment for idiopathic pulmonary fibrosis. It may attenuate ARDS-related fibrosis and decrease the need for prolonged ventilation. Accordingly, we aimed to evaluate the effect of pirfenidone on ventilator-free days in patients with ARDS. METHODS: In a multi-center, randomized, double-blind, placebo-controlled trial, we plan to randomly assign 130 adults invasively ventilated for ARDS to receive pirfenidone or placebo for up to 28 days. The primary outcome is days alive and ventilator free at 28 days. Secondary outcomes include ICU-free days, hospital free days all at 28 day, ICU mortality and hospital mortality. We will also assess fibroproliferative changes on high-resolution CT scans at ICU discharge and quality of life. Data analysis will be on an intention-to-treat basis. DISCUSSION: The trial is ongoing and currently recruiting. It will be the first randomized controlled study to investigate whether, compared to placebo, pirfenidone increases the number of days alive and ventilator-free in patients with ARDS. Its double-blind multicenter design will provide internal validity, minimal bias, and a degree of external validity. If our hypothesis is confirmed, this treatment would justify larger trials of this intervention. TRIAL REGISTRATION: This trial was registered on ClinicalTrials.gov with the trial identification NCT05075161.
2. Hospital-Treated Infections and 15-year Incidence of Musculoskeletal Disorders: A Large Population-Based Cohort Study.
In 502,409 UK Biobank participants, prior hospital-treated infections were associated with higher risks of six musculoskeletal disorders, strongest for osteoporosis (HR 1.55) and rheumatoid arthritis (HR 1.53). Associations were similar for bacterial and viral infections, strengthened with more frequent/severe infections, and persisted beyond 10 years.
Impact: This large, well-balanced cohort provides population-level evidence linking severe infections to diverse long-term musculoskeletal sequelae, informing surveillance and preventive strategies.
Clinical Implications: Patients with a history of hospital-treated infections may benefit from long-term MSK health monitoring, including bone health assessment and early rheumatologic evaluation, especially when infections are frequent or severe.
Key Findings
- Prior hospital-treated infections increased risks of all six MSK disorders; strongest associations for osteoporosis (HR 1.55) and rheumatoid arthritis (HR 1.53).
- Risks were similar across bacterial and viral infections and were higher with more frequent/severe infections, suggesting a systemic effect.
- Associations persisted even when excluding incident cases within the first 5 and 10 years post-baseline, indicating long-term risk.
Methodological Strengths
- Very large sample (N=502,409) with propensity score matching (1:5) and multi-source outcome ascertainment.
- Sensitivity analyses excluding early events (5- and 10-year windows) to reduce reverse causality.
Limitations
- Residual confounding and misclassification of infection severity/pathogens are possible in observational data.
- Generalizability beyond the UK Biobank population may be limited; outpatient-treated infections were not the primary exposure.
Future Directions: Mechanistic studies to elucidate immune-bone crosstalk post-infection and intervention trials testing bone/rheumatic surveillance and prevention strategies in high-risk post-infection populations.
BACKGROUND: Basic science evidence reveals interactions between the immune and bone systems. However, population studies linking infectious diseases and musculoskeletal (MSK) disorders are limited and inconsistent. We aimed to examine the risk of six main MSK disorders (osteoarthritis, rheumatoid arthritis, osteoporosis, gout, low back pain, and neck pain) following hospital-treated infections in a large cohort with long follow-up periods. METHODS: We analysed data from 502,409 UK Biobank participants. Participants free of specific MSK disorders at baseline were included in each analysis. Hospital-treated infections before baseline were identified using national inpatient data, while incident MSK outcomes were ascertained from inpatient records, primary care, and death registers. Participants with prior infections were propensity score matched (1:5) with those without. Hazard ratios (HRs) and absolute rate differences (ARDs) with 95% confidence intervals (CIs) were calculated using Cox proportional hazards models. To assess potential reverse causality due to delayed diagnosis of preexisting illness, analyses were repeated excluding MSK disorder cases that occurred within the first 5 and 10 years post-baseline. RESULTS: A hospital-treated infection was associated with increased risks of all six MSK disorders, with particularly strong associations for osteoporosis (HR, 1.55 [1.48-1.63]; ARD, 1.48 [95% CI 1.29-1.68] per 1000 person-years) and rheumatoid arthritis (HR, 1.53 [1.41-1.65]; ARD, 0.58 [0.46-0.71] per 1000 person-years), while other disorders showed HRs of 1.28-1.32. Bacterial and viral infections showed similar associations, with MSK infections (generally stronger risk) and other locations both linked to increased risks. Associations remained significant even for incident cases that occurred more than 10 years post-baseline. CONCLUSION: Hospital-treated infections are associated with long-term MSK disorder risks, regardless of pathogen type or disorder nature (inflammatory or degenerative). Long-term monitoring and care for MSK health in patients with prior hospital-treated infections are recommended. Recent studies have revealed intimate interactions between immune and bone cells. However, population studies on the link between infection and musculoskeletal (MSK) disorders are limited. In this large-scale study with balanced covariates and over 15 years of follow-up, we found that people who had hospital-treated infections had a higher risk of developing MSK conditions, including those related to bone metabolism (osteoporosis), inflammation (eg, rheumatoid arthritis, gout), and degenerative processes (eg, osteoarthritis). This increased risk was not specific to a particular infection and grew with more frequent and severe infections, suggesting a systemic rather than pathogen-specific effect. The risk persists beyond 10 years, highlighting the need for long-term MSK care for individuals with a history of severe infections.
3. Surfactant Therapy in Late Preterm Infants with Respiratory Distress in Türkiye: An Observational, Prospective, Multicenter Study.
Among 3327 late preterm NICU admissions in 2022, 1866 had respiratory distress and 288 received surfactant. Indications were heterogeneous—RDS (54.8%), congenital pneumonia (27.4%), and TTN (11.1%)—demonstrating substantial variability in use beyond classic neonatal RDS.
Impact: Provides national, prospective real-world data revealing practice variability and off-RDS indications for surfactant in late preterm infants, informing guideline refinement and quality improvement.
Clinical Implications: Hospitals should review local criteria for surfactant use in late preterm infants, harmonize protocols, and prioritize evidence generation (e.g., RCTs) to clarify benefits in non-RDS indications like congenital pneumonia and TTN.
Key Findings
- Of 3327 late preterm NICU admissions, 1866 had respiratory distress and 288 received surfactant.
- Indications: RDS 54.8% (n=158), congenital pneumonia 27.4% (n=79), TTN 11.1% (n=32).
- Marked variability in surfactant administration practices across centers.
Methodological Strengths
- Prospective, multicenter observational design with national coverage (16 NICUs, 20 neonatologists).
- Clear enumeration of indications and denominators enabling practice variation assessment.
Limitations
- Descriptive observational study without comparative outcomes or adjustment for confounding.
- Follow-up limited to the hospitalization period; no assessment of efficacy or safety by indication.
Future Directions: Conduct randomized trials to test surfactant efficacy in non-RDS indications (e.g., congenital pneumonia, TTN) and develop standardized criteria to reduce unwarranted practice variation.
Objective: Surfactant therapy (ST) is commonly used in late preterm (LPT) infants with respiratory distress despite a lack of definitive recommendation for these infants. Our aim was to establish a national prospective database to evaluate the use of surfactants in LPT infants. Materials and Methods: A multicenter, prospective observational cohort study was conducted among LPT infants treated with surfactant between January 1, 2022, and December 31, 2022. Twenty neonatologists from 16 neonatal intensive care units (NICUs) participated in the study. Results: During the study period, a total of 3327 LPT infants were admitted to the participating NICUs. Among them, 1866 infants experienced respiratory distress, and 288 received surfactant treatment. In this study, respiratory distress syndrome (RDS) was the most common indication for surfactant administration, affecting 158 infants (54.8%), followed by congenital pneumonia in 79 infants (27.4%) and transient tachypnea of the newborn (TTN) in 32 infants (11.1%). Conclusion: We demonstrated that ST is administered with significant variability among LPT infants experiencing respiratory distress. Additionally, respiratory issues in LPT infants beyond RDS, such as congenital pneumonia and TTN, are also frequently treated with surfactant.