Daily Respiratory Research Analysis
Analyzed 97 papers and selected 3 impactful papers.
Summary
Three impactful respiratory studies stand out today: a randomized human challenge trial shows PCV13 confers clade-specific protection against pneumococcal serotype 3 colonization and sustained protection against serotype 6B; a meta-analysis finds dry powder and soft mist inhalers match pressurized MDIs in efficacy and safety, supporting lower-carbon device switches; and multicenter neonatal models accurately predict pulmonary hypertension in infants with bronchopulmonary dysplasia using routine clinical data.
Research Themes
- Vaccine-induced prevention of pneumococcal colonization and clade-specific effects
- Equivalence of inhaler device types enabling low-carbon respiratory care
- Machine learning risk prediction for pulmonary hypertension in BPD
Selected Articles
1. The effect of pneumococcal conjugate vaccine and pneumococcal polysaccharide vaccine on nasopharyngeal colonisation following human infection challenge with serotype 3 and serotype 6B (PREVENTING PNEUMO 2): a double-masked, randomised, controlled, phase 4 trial.
In this double-masked randomized human challenge study, PCV13 reduced serotype 3 colonization risk overall non-significantly (16%) but showed significant protection against clade II (29%), with no protection against clade Iα. At 6 months, PCV13 reduced serotype 6B colonization risk by 60%, whereas PPV23 did not protect against clade Iα. No severe adverse events occurred.
Impact: Provides robust, clade-resolved, randomized evidence on pneumococcal vaccine effects on colonization, a key driver of transmission and herd protection, and clarifies sustained protection for serotype 6B.
Clinical Implications: Supports continued use of PCV13 for direct adult protection where serotype 3 disease persists, with awareness of clade heterogeneity; PPV23 may not prevent serotype 3 clade Iα colonization. Findings argue for adult vaccination strategies rather than relying solely on pediatric herd effects for serotype 3.
Key Findings
- Overall, PCV13 reduced Spn3 colonization acquisition by 16% versus placebo (RR 0.84; 95% CI 0.70–1.01; p=0.068).
- PCV13 conferred significant protection against Spn3 clade II (RR 0.71; 95% CI 0.54–0.91; p=0.009) but not clade Iα (RR 1.01; 95% CI 0.77–1.32; p=0.95).
- PPV23 showed no protection against Spn3 clade Iα (RR 0.84; 95% CI 0.63–1.11; p=0.22).
- At 6 months, PCV13 reduced Spn6B colonization acquisition by 60% (RR 0.40; 95% CI 0.22–0.69; p=0.002).
- No severe or life-threatening adverse events were observed.
Methodological Strengths
- Double-masked randomized controlled human challenge with clade-stratified assignment and modified ITT analysis.
- Prospective registration and masked laboratory assessment across sizable cohorts (n=407 Spn3; n=243 Spn6B).
Limitations
- Healthy adults (18–50 years) limit generalizability to older adults, children, and high-risk populations.
- Colonization endpoints rather than clinical disease; PPV23 was evaluated against clade Iα only.
Future Directions: Define immune correlates of clade-specific protection, assess effectiveness in older/high-risk adults, and inform next-generation pneumococcal vaccines targeting serotype 3 heterogeneity.
BACKGROUND: Although evidence suggests some direct protection from the 13-valent pneumococcal conjugate vaccine (PCV13) against Streptococcus pneumoniae serotype 3 (Spn3), Spn3 remains a frequent cause of pneumococcal disease in the UK, potentially due to lower vaccine effect on colonisation, shorter duration of protection, or the emergence of more successful Spn3 clades. To test these hypotheses, we compared PCV13 and 23-valent pneumococcal polysaccharide vaccine (PPV23) protection against prevalent Spn3 clades. Additionally, we assessed the long-term protection offered by pneumococcal vaccines against colonisation using S pneumoniae serotype 6B (Spn6B), a serotype PCV13 protects against in the short term. METHODS: This double-masked, randomised, controlled, phase 4 trial recruited healthy participants aged 18-50 years in Liverpool, UK, and assigned them (2:1:2) to PCV13, PPV23, or placebo (0·9% NaCl). Participants assigned to the PPV23 group were challenged with clade Iα, and participants in PCV13 and placebo groups were subsequently randomly assigned to receive clade Iα or II Spn3. Nasal challenge with Spn3 was at 1 month and with Spn6B in a subgroup at 6 months after vaccination. Selection for this subgroup was conducted on a first-come-first-served basis, with participants who enrolled earliest being offered participation in both challenges. Recruitment for the second challenge was discontinued once the target number of participants was reached. The primary outcome was the acquisition risk of the challenge strain as detected by nasal wash culture at 2 days, 7 days, 14 days, or 23 days in the vaccine versus the placebo groups. The analysis was performed in a modified intention-to-treat population, defined as all participants who received vaccination, underwent challenge, and had at least one nasal wash sample collected after the challenge. Randomisation used a computer-generated schedule that only the unmasked team could access. The unmasked team performed vaccinations and did not perform the nasal challenges or nasal washes. The laboratory staff and participants were masked to the vaccination status. This study was prospectively registered with the EU Drug Regulating Authorities Clinical Trials Database, 2019-004742-15, the International Standard Randomised Controlled Trial Number registry, ISRCTN15728847, and ClinicalTrials.gov, NCT04974294, and is complete.
2. Efficacy and safety of different inhaler types for asthma and chronic obstructive pulmonary disease. a systematic review and meta-analysis.
Across 44 randomized trials (24,710 participants), DPIs and SMIs demonstrated efficacy and safety comparable to pMDIs for both asthma and COPD, with no clinically meaningful differences across assessed outcomes. These findings support switching to non-propellant devices without compromising disease control, enabling climate-conscious respiratory care.
Impact: Directly informs prescribing and stewardship by demonstrating device equivalence, removing a key barrier to decarbonizing inhaler use in asthma/COPD care.
Clinical Implications: Clinicians can consider transitioning suitable patients from pMDIs to DPIs/SMIs to reduce environmental impact without sacrificing efficacy or safety, with shared decision-making and inhaler technique training.
Key Findings
- Forty-four randomized trials with 24,710 participants showed no statistically significant or clinically important differences between pMDIs, DPIs, and SMIs across outcomes.
- For asthma maintenance, peak expiratory flow mean difference was 1.07 L/min (95% CI -0.93 to 3.06), indicating equivalence.
- Moderate-certainty evidence supported comparable efficacy and safety for COPD as well.
Methodological Strengths
- Comprehensive systematic review and meta-analysis of randomized controlled trials with large aggregate sample size.
- Consistent null differences across multiple clinical endpoints, supporting robustness.
Limitations
- Between-trial heterogeneity in drug formulations and devices; environmental outcomes (carbon footprint) not directly measured.
- Long-term adherence and real-world technique effects are not fully captured by RCTs.
Future Directions: Pragmatic trials and implementation studies to assess real-world switching strategies, adherence, technique training, and quantified environmental impact.
Pressurised metered dose inhalers (pMDIs) contain propellant gases with high global warming potential yet remain a cornerstone of management for asthma and chronic obstructive pulmonary disease (COPD). The aim of this study was to determine whether non-propellant alternatives of dry powder inhalers (DPIs) and soft mist inhalers (SMIs) had similar efficacy and safety. A systematic review was performed finding 44 randomised trials (24,710 participants) and moderate certainty evidence for most outcomes. No statistically significant or clinically important differences were found between inhaler types for any assessed measure. For asthma maintenance, the mean difference in peak expiratory flow rate between groups was 1.07 L/min (95% confidence interval [CI] -0.93 to 3.06). For COPD, the mean difference in FEV
3. Predicting pulmonary hypertension in infants with bronchopulmonary dysplasia.
Using a large multicenter neonatal cohort, logistic regression and LSTM models accurately predicted pulmonary hypertension risk at 33 and 36 weeks PMA using routinely collected variables. Birth weight and contemporaneous respiratory support/FiO2 were the most informative predictors, with strong temporal validation performance.
Impact: Offers validated, timepoint-specific risk stratification tools for BPD infants using readily available clinical data, enabling earlier surveillance and targeted echocardiography.
Clinical Implications: Neonatal teams can use routine variables at 33 and 36 weeks PMA to identify infants at highest PH risk to guide timely echocardiography, oxygen/ventilation optimization, and referral.
Key Findings
- At 33 weeks PMA (N=2,849), FiO2 and birth weight were the top predictors in LR models.
- At 36 weeks PMA (N=20,173), current respiratory support and birth weight dominated predictive importance.
- Both LR and LSTM models showed strong performance in temporal validation (2021–2022 discharges) at both timepoints.
Methodological Strengths
- Large multicenter cohort with two clinically relevant timepoints and temporal external validation.
- Comparison of interpretable LR with sequence-aware LSTM using routinely available variables.
Limitations
- Observational design with potential residual confounding; PH ascertainment details not provided in abstract.
- Generalizability outside participating NICUs and different practice patterns requires further validation.
Future Directions: Prospective validation with standardized PH diagnostics, integration into EHR clinical decision support, and evaluation of impact on outcomes and resource utilization.
OBJECTIVE: Develop and validate predictive models for pulmonary hypertension (PH) in high-risk infants. STUDY DESIGN: We trained logistic regression (LR) and long short-term memory (LSTM) models using a multicenter cohort study of infants 22-28 weeks gestational age discharged from neonatal intensive care units from 2008 to 2020, at two timepoints: 33 weeks post-menstrual age (PMA) for infants receiving mechanical ventilation at that time, and 36 weeks PMA for infants receiving any respiratory support at that time. RESULTS: At 33 weeks PMA (N = 2849), top LR model predictors were current fraction of inspired oxygen and birth weight. At 36 weeks (N = 20,173), top LR model predictors were current respiratory support and birth weight. Both LR and LSTM models had strong performance in the temporal validation cohort (infants discharged 2021-2022) for both timepoints. CONCLUSION: Using available clinical variables, we developed and validated predictive models that may identify infants most at risk for PH at two timepoints.