Daily Respiratory Research Analysis
Analyzed 212 papers and selected 3 impactful papers.
Summary
Three high-impact studies shape respiratory medicine today: a multicentre diagnostic study shows tongue-swab PCR is a highly accurate, non-invasive alternative for pulmonary TB in sputum-scarce patients; two large, masked RCTs in extremely preterm infants (AZTEC azithromycin prophylaxis and Baby-OSCAR selective early ibuprofen for large PDA) report no improvement in survival without chronic lung disease, guiding de-implementation of routine prophylaxis and early PDA treatment. Together, these results refine diagnostic pathways and neonatal respiratory care.
Research Themes
- Non-invasive, accurate diagnostics for pulmonary tuberculosis in sputum-scarce patients
- High-quality negative neonatal RCTs refining prevention/treatment strategies (azithromycin for BPD, early ibuprofen for PDA)
- Implementation impact: de-implementation and pathway redesign in respiratory and neonatal care
Selected Articles
1. Accuracy of rapid quantitative PCR on tongue swabs for pulmonary tuberculosis in sputum-scarce patients: a prospective multicentre diagnostic study.
In a prospective multicentre cohort of 625 sputum-scarce presumptive TB patients, tongue-swab PCR achieved 79.9% sensitivity/99.5% specificity versus BALF microbiological reference and 81.7%/97.6% versus BALF Xpert. Modeling suggests tongue-swab PCR outperforms sputum-only Xpert when sputum-scarce cases exceed 10%, supporting integration into diagnostic pathways.
Impact: Provides robust, non-invasive diagnostic accuracy data and operational modeling for a scalable TB diagnostic strategy in sputum-scarce settings, directly addressing a major bottleneck in case detection.
Clinical Implications: Tongue-swab PCR can be incorporated as a front-line option for sputum-scarce or sputum-negative adults, potentially improving case detection, accelerating treatment initiation, and reducing transmission; programs should pilot workflows and QA for sampling to optimize sensitivity in low-burden disease.
Key Findings
- Sensitivity/specificity versus BALF microbiological reference standard: 79.9% (95% CI 73.9–84.8)/99.5% (95% CI 98.0–99.9).
- Sensitivity/specificity versus BALF Xpert MTB/RIF: 81.7% (95% CI 75.7–86.6)/97.6% (95% CI 95.5–98.8).
- Simulation showed tongue-swab PCR outperforms sputum-only Xpert when sputum-scarce patients exceed 10% of the tested population.
- Non-invasive collection with preserved high specificity supports programmatic deployment.
Methodological Strengths
- Prospective multicentre design with paired tongue swab and BALF specimens.
- Comparison against both microbiological reference standard and Xpert MTB/RIF with predefined accuracy metrics and simulation modeling.
Limitations
- Conducted in hospital settings in China; generalizability to primary care or different epidemiology requires validation.
- Sensitivity may be lower in paucibacillary disease; sampling protocols and assay optimization are needed.
Future Directions: Prospective implementation studies in primary care and high-burden settings, cost-effectiveness analyses, and protocol refinements to improve sensitivity in low-bacillary-load disease.
BACKGROUND: The diagnosis of pulmonary tuberculosis (TB) remains challenging in sputum-scarce and sputum-negative patients. Tongue swabs represent a promising non-invasive alternative specimen type that could overcome this diagnostic limitation. This study aimed to evaluate the performance of molecular detection of Mycobacterium tuberculosis (Mtb) from tongue swabs in this clinically challenging population. METHODS: In this study, We enrolled 625 sputum scarce individuals with presumptive TB from four Chinese TB hospitals. For each participant, paired tongue swab and bronchoalveolar lavage fluid (BALF) specimens were collected. Tongue swab specimens were analyzed using MTB-specific PCR assay, while BALF specimens underwent comprehensive evaluation using both microbiological reference standard (MRS) and Xpert MTB/RIF assay. RESULTS: Tongue swab testing demonstrated high diagnostic accuracy with 79.9% sensitivity (95% CI: 73.9-84.8) and 99.5% specificity (95% CI: 98.0-99.9) against the MRS, and 81.7% sensitivity (95% CI: 75.7-86.6) with 97.6% specificity (95% CI: 95.5-98.8) against Xpert MTB/RIF. Notably, simulation modeling revealed that when the proportion of sputum-scarce patients exceeded 10%, the tongue swab PCR strategy outperformed conventional sputum-only Xpert MTB/RIF testing in overall case detection rates. CONCLUSIONS: Tongue swab-based PCR represents a non-invasive, accurate, and highly specific diagnostic approach for tuberculosis, particularly in sputum-scarce or sputum-negative individuals. While this study demonstrates its superior performance in such populations, further optimization of sampling protocols and molecular assays is needed to improve detection sensitivity in cases with low bacillary loads. Integrating tongue swab testing into routine TB diagnostic algorithms could enhance case detection, strengthen drug resistance surveillance, and contribute to reducing transmission.
2. Azithromycin therapy for prevention of chronic lung disease of prematurity (AZTEC): a randomised placebo-controlled trial.
In 796 extremely/very preterm infants requiring early respiratory support, 10 days of intravenous azithromycin did not increase survival without physiologically defined moderate/severe chronic lung disease at 36 weeks’ PMA compared with placebo (42.1% vs 44.5%; adjusted OR 0.84, 95% CI 0.55–1.29). The trial reports a high-quality negative result to guide de-implementation of prophylactic macrolides.
Impact: A large, CONSORT-compliant, multicentre RCT provides definitive evidence against routine azithromycin prophylaxis to prevent chronic lung disease of prematurity.
Clinical Implications: Routine prophylactic azithromycin to prevent BPD in very/extremely preterm infants on early respiratory support should not be used; stewardship efforts should redirect away from macrolide prophylaxis while focusing on proven lung-protective strategies.
Key Findings
- Primary outcome (survival without physiologically defined moderate/severe CLD at 36 weeks PMA): 42.1% azithromycin vs 44.5% placebo; adjusted OR 0.84 (95% CI 0.55–1.29).
- Randomisation across 30 neonatal units with median GA 27.0 weeks ensured external validity.
- Preplanned follow-up at 1 and 2 years underway to assess medium-term effects.
Methodological Strengths
- Multicentre, double-blind, randomised, placebo-controlled design with physiologic CLD definition.
- Adequate power planning and masked allocation across 30 neonatal units.
Limitations
- Some missed oxygen reduction tests and incomplete respiratory support data reduce granularity of secondary analyses.
- Lower-than-anticipated baseline sampling limits mechanistic subgroup evaluations.
Future Directions: Complete 1–2 year follow-up, biomarker analyses (e.g., cytokines), and targeted trials in biomarker-selected subgroups rather than blanket prophylaxis.
BACKGROUND: Systematic reviews have reported conflicting evidence to confirm if macrolides reduce rates of chronic lung disease of prematurity in at-risk preterm-born infants, including in those colonised with pulmonary METHODS: Infants recruited from 30 neonatal units (median gestational age 27.0 weeks, interquartile range 25.3-28.6) requiring respiratory support within 72 hours of birth were randomised to intravenous azithromycin 20 mg/kg/day for 3 days followed by 10 mg/kg for 7 days or to placebo. Primary outcome was survival without development of physiologically defined moderate/severe chronic lung disease of prematurity at 36 weeks' postmenstrual age. A total of 796 infants were required to detect 12% improvement in survival without development of moderate or severe chronic lung disease of prematurity, including 10% dropout, with two-sided FINDINGS: After three withdrawals, 796 randomised infants were included in the final analyses. Survivors without physiologically defined moderate/severe chronic lung disease of prematurity were: 166/394 (42.1%) and 179/402 (44.5%) in the intervention and placebo groups, respectively (adjusted odds ratio 0.84; 95% confidence interval 0.55 to 1.29; INTERPRETATION: Prophylactic use of azithromycin did not improve survival without development of physiologically defined chronic lung disease of prematurity regardless of FUTURE WORK: Follow-up at ages 1 and 2 years will assess the medium-term effects. Investigating whether treatment modulated proinflammatory cytokine concentrations, including whether this was more prevalent in the LIMITATIONS: Limitations include the (limited) missed oxygen reduction tests, inadequate collection of respiratory support data and lower-than-anticipated baseline sampling. FUNDING: This synopsis presents independent research funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme as award number 16/111/106. Many premature babies will develop a disease called chronic lung disease of prematurity during their stay in hospital. Chronic lung disease of prematurity develops due to the impact of additional oxygen and breathing support given to help the babies’ lungs, which are too immature to work independently. We and several research groups have shown that infection and inflammation are increased in babies who develop chronic lung disease of prematurity. Chronic lung disease of prematurity can lead to more hospital admissions in infancy and breathing problems during childhood and beyond. Azithromycin is an antibiotic which has been shown to treat both lung infections (particularly a bacteria called
3. Outcome after Selective early treatment for Closure of patent ductus ARteriosus in preterm babies, a multicentre, masked, randomised placebo-controlled parallel group trial (Baby-OSCAR trial).
In 653 extremely preterm infants with echocardiographically large PDA, early ibuprofen (≤72 h) did not reduce death or moderate/severe BPD at 36 weeks’ PMA (69.2% vs 63.5%; adjusted RR 1.09, 95% CI 0.98–1.20) or improve 24-month neurodevelopmental or respiratory outcomes. Crossover and later dosing may have diluted effects but results argue against routine early selective PDA closure.
Impact: A rigorous multicentre, masked RCT demonstrates no clinical benefit of early selective ibuprofen for large PDA in extremely preterm infants, informing practice and reducing potentially unnecessary exposure.
Clinical Implications: Routine early ibuprofen treatment for echocardiographically large PDA should not be used solely to prevent BPD or improve survival; management should prioritize individualized criteria, conservative support, and participation in targeted trials for persistent, symptomatic PDA beyond 7 days.
Key Findings
- Primary composite (death or moderate/severe BPD at 36 weeks PMA): no reduction with early ibuprofen (adjusted RR 1.09, 95% CI 0.98–1.20).
- No improvement in survival without moderate/severe neurodevelopmental impairment or without respiratory morbidity at 24 months.
- Open-label PDA therapy occurred in 29.8% of placebo infants; first dose median at 61 hours could attenuate treatment contrast.
Methodological Strengths
- Multicentre, masked, randomised, placebo-controlled design with long-term follow-up and health economics.
- Clear echocardiographic eligibility and physiologic BPD endpoint increase clinical relevance.
Limitations
- High rate of open-label PDA therapy in placebo arm may bias towards null.
- First dosing at median 61 h post-birth later than some trials; under-recruitment relative to original target.
Future Directions: Trials in symptomatic PDA non-closers beyond 7 days, IPD meta-analysis, and extended developmental follow-up (8–10 years) to assess late outcomes.
BACKGROUND: In extremely preterm babies, born before 28 weeks' gestation, a large (≥ 1.5 mm in diameter) patent ductus arteriosus present beyond 3 days of age is associated with higher mortality and morbidity than infants without a patent ductus arteriosus. The cyclooxygenase inhibitor ibuprofen may be used to treat patent ductus arteriosus. Whether selective early treatment of a large patent ductus arteriosus with ibuprofen improves health and developmental outcomes is not known. METHODS: We conducted a multicentre, randomised, double-blind, placebo-controlled trial evaluating early treatment (≤ 72 hours after birth) with ibuprofen for a large patent ductus arteriosus in extremely preterm infants. The primary outcome was a composite of death or moderate or severe bronchopulmonary dysplasia at 36 weeks' of post menstrual age. The short-term secondary outcomes included complications of prematurity, patent ductus arteriosus closure and side effects of treatment. The main long-term outcome was survival without moderate or severe neurodevelopmental impairment, using parent report or classified by blinded end-point review committee at 24 months of corrected age. Other secondary outcomes included survival without respiratory morbidity and duration of oxygen supplementation. A health economic evaluation was undertaken. RESULTS: A total of 326 infants were randomised to ibuprofen and 327 to placebo. The primary outcome occurred in 220/318 infants (69.2%) in the ibuprofen group and in 202/318 infants (63.5%) in the placebo group (adjusted risk ratio 1.09, 95% confidence interval 0.98 to 1.20; CONCLUSION: The risk of death or moderate or severe bronchopulmonary dysplasia at 36 weeks of post menstrual age was not statistically significantly lower for extremely preterm infants randomised to early treatment with ibuprofen compared to placebo. There was no evidence of an improvement in survival without moderate to severe neurodevelopmental impairment or survival without respiratory morbidity at 24 months' corrected age, after selective early treatment of a large patent ductus arteriosus with ibuprofen in children born extremely preterm. FUTURE WORK: Future work required includes a trial in babies who are clinically symptomatic and fail to close the patent ductus arteriosus beyond 7 days of age; an individual patient data meta-analysis; follow-up of babies in Baby-OSCAR at 8-10 years of age. LIMITATIONS: Open-label therapy was received by 29.8% of infants in the placebo group, potentially increasing the percentage of infants with patent ductus arteriosus closure in this group. The first dose of trial treatment was administered at a median of 61 hours after birth, later than in other trials. FUNDING: This synopsis presents independent research funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme as award number 11/92/15.