Daily Respiratory Research Analysis
Three studies advanced respiratory science and care. A meta-analysis showed broad cardiopulmonary exercise impairments among survivors of preterm birth. A prospective model identified alveolar exhaled nitric oxide (CaNO) as a noninvasive marker to help diagnose checkpoint inhibitor-related pneumonitis. A large multicenter cohort found chronic pulmonary aspergillosis independently worsens prognosis in nontuberculous mycobacterial pulmonary disease.
Summary
Three studies advanced respiratory science and care. A meta-analysis showed broad cardiopulmonary exercise impairments among survivors of preterm birth. A prospective model identified alveolar exhaled nitric oxide (CaNO) as a noninvasive marker to help diagnose checkpoint inhibitor-related pneumonitis. A large multicenter cohort found chronic pulmonary aspergillosis independently worsens prognosis in nontuberculous mycobacterial pulmonary disease.
Research Themes
- Long-term cardiopulmonary sequelae after preterm birth
- Noninvasive diagnostics for immune checkpoint inhibitor-related pneumonitis
- Impact of fungal coinfection on outcomes in nontuberculous mycobacterial lung disease
Selected Articles
1. Physiological responses to exercise in survivors of preterm birth: a meta-analysis.
This PROSPERO-registered meta-analysis of 47 cohorts found that survivors of preterm birth have broad impairments on cardiopulmonary exercise testing, including lower peak VO2, work rate, ventilation, tidal volume, oxygen pulse, heart rate, and anaerobic threshold, with worse gas exchange efficiency versus term-born controls. Findings support prioritizing lifetime interventions to improve cardiorespiratory fitness in those born preterm.
Impact: Quantifies multi-system exercise impairments after preterm birth across large cohorts, providing robust targets for rehabilitation and surveillance. The synthesis informs policy and clinical programs for a growing adult preterm survivor population.
Clinical Implications: Clinicians should anticipate reduced aerobic capacity and broad cardiopulmonary limitations in preterm-born patients; structured exercise rehabilitation and tailored cardiopulmonary surveillance may be warranted from adolescence into adulthood.
Key Findings
- Meta-analysis of 47 cohorts (n=2149 preterm, n=1650 term) showed lower peak VO2 (SMD −0.39) and work rate (SMD −0.53) in preterm-born individuals.
- Preterm-born participants had lower minute ventilation, tidal volume, oxygen pulse, heart rate, and anaerobic threshold at peak exercise.
- Gas exchange efficiency was worse (SMD 0.22), indicating broader respiratory, cardiovascular, and metabolic impairments.
Methodological Strengths
- Pre-registered protocol (PROSPERO) and systematic multi-database search
- Random-effects meta-analysis across 47 cohorts with matched term-born controls
Limitations
- Heterogeneity in exercise protocols and outcome definitions across cohorts
- Potential publication bias and limited data on longitudinal change
Future Directions: Define dose–response to exercise training, assess longitudinal trajectories into older age, and develop precision rehabilitation targeting specific respiratory, cardiovascular, and metabolic deficits in preterm-born individuals.
RATIONALE: Survivors of preterm birth (<37 weeks' gestation) have low peak oxygen uptake, a global measure of aerobic fitness and an established predictor of increased morbidity and mortality. However, little is known about other cardiopulmonary outcome measures in this population. We addressed the hypothesis that preterm birth is associated with abnormal respiratory, cardiovascular and metabolic responses to exercise, as assessed by cardiopulmonary exercise testing, METHODS: Six databases were systematically searched up to 29 November 2024 (PROSPERO: CRD42022320775). Studies reporting cardiopulmonary outcome measures obtained during a standardised exercise test were included if they had preterm-born participants and matched term-born controls. The standardised mean difference (SMD) between pooled preterm-born and term-born cohorts was calculated using random-effects models for the meta-analysis. RESULTS: Of the 12 143 records identified, 47 cohorts were included in the final meta-analysis. At peak exercise, the preterm-born cohort (n=2149) demonstrated lower oxygen uptake (SMD -0.39, 95% CI -0.52 to -0.26), work rate (SMD -0.53, 95% CI -0.70 to -0.35), minute ventilation (SMD -0.43, 95% CI -0.60 to -0.26), tidal volume (SMD -0.38, 95% CI -0.62 to -0.15), oxygen pulse (SMD -0.47, 95% CI -0.75 to -0.19), heart rate (SMD -0.18, 95% CI -0.28 to -0.07), anaerobic threshold (SMD -0.29, 95% CI -0.49 to -0.08) and gas exchange efficiency (SMD 0.22, 95% CI 0.04 to 0.41), compared to the term-born cohort (n=1650). CONCLUSIONS: In addition to a reduced peak oxygen uptake, survivors of preterm birth have impairments in the respiratory, cardiovascular and metabolic domains during cardiopulmonary exercise testing. Given that reduced aerobic capacity is associated with increased morbidity and mortality, exercise interventions that target cardiorespiratory fitness should be prioritised across the lifespan in those born preterm.
2. Construction of a checkpoint inhibitor-related pneumonia diagnostic model based on exhaled nitric oxide: a prospective observational study.
In this prospective observational study of lung cancer patients on ICIs, the alveolar NO concentration (CaNO) was significantly higher in those with checkpoint inhibitor-related pneumonitis. Elevated CaNO, prior thoracic radiotherapy, CT-reported emphysema, small pleural effusion, and lower peripheral lymphocyte count independently associated with CIP, enabling an internally validated multi-indicator diagnostic model.
Impact: Introduces a noninvasive, physiologically grounded biomarker (CaNO) for CIP and integrates it into a clinically usable diagnostic model with internal validation.
Clinical Implications: CaNO measurement could augment early recognition of CIP in ICI-treated patients, guiding timely imaging, treatment interruption, and corticosteroid initiation while reducing diagnostic uncertainty.
Key Findings
- Alveolar NO (CaNO) was significantly elevated in CIP compared with non-CIP ICI-treated patients.
- Independent CIP risk factors: increased CaNO, prior chest radiotherapy, CT-reported emphysema, small pleural effusion, and lower peripheral lymphocyte count.
- A multi-indicator diagnostic model incorporating CaNO achieved internal validation for identifying CIP.
Methodological Strengths
- Prospective biomarker assessment with physiologically partitioned eNO (airway vs alveolar) and ROC-derived cut-off
- Multivariable logistic modeling with internal validation of a multi-indicator diagnostic model
Limitations
- Single-center design with unspecified sample size may limit generalizability
- Model lacked external validation and prospective impact analysis on clinical decision-making
Future Directions: Externally validate CaNO thresholds and the multi-indicator model across centers and cancer types; assess clinical impact on time-to-diagnosis, treatment safety, and outcomes.
BACKGROUND: Checkpoint inhibitor-related pneumonia (CIP) is a complication of immune checkpoint inhibitors (ICIs) with high mortality. There is still a lack of effective biomarkers to identify CIP. Exhaled nitric oxide (eNO), an airway inflammatory marker, can be obtained by non-invasive methods, but its value in CIP is unknown. The purpose of this study was to investigate the value of eNO in CIP. METHODS: Lung cancer patients who received ICIs were included at Nanfang Hospital, Southern Medical University. Fractional eNO at expiratory flow rates of 50 and 200 mL/s (FeNO50 and FeNO200) were measured. The alveolar concentration of nitric oxide (CaNO) was calculated based on the two-compartment model of airway and alveoli. The optimal CaNO cut-off value was determined by the receiver operating characteristic (ROC) curve. eNO, clinical characteristics, and laboratory tests were analyzed to find out the risk factors for CIP by logistic regression analysis. A multi-indicator model based on best risk factors for CIP was developed and internally validated. RESULTS: CaNO was significantly elevated in the CIP group [8.1±5.0 CONCLUSIONS: CaNO may be a new marker for identifying CIP. Increased CaNO, pre-existing radiotherapy and emphysema reported on chest CT, a small amount of pleural effusion reported on chest CT, and lower count of lymphocyte cell in peripheral blood are independently associated with CIP.
3. Risk Factors and Long-Term Prognosis for Coinfection of Nontuberculous Mycobacterial Pulmonary Disease and Chronic Pulmonary Aspergillosis: A Multicentre Observational Study in Japan.
In a multicenter cohort of 1304 NTM-PD patients, 3.5% had CPA, predominantly chronic progressive disease. Male sex, COPD, oral corticosteroids, and cavitary lesions were risk factors for coinfection. CPA conferred significantly higher mortality (adjusted HR 1.59) after propensity score matching, establishing CPA as an independent adverse prognostic factor in NTM-PD.
Impact: Defines clear clinical risk factors and quantifies the independent mortality impact of CPA in NTM-PD using propensity matching, directly informing screening and management strategies.
Clinical Implications: NTM-PD patients—especially males with COPD, on oral corticosteroids, and with cavitary disease—should be actively screened for CPA; early antifungal evaluation and integrated management may improve outcomes.
Key Findings
- CPA occurred in 3.5% (45/1304) of NTM-PD patients; 42 were chronic progressive pulmonary aspergillosis.
- Risk factors for CPA coinfection: male sex, COPD, oral corticosteroid use, and cavitary lesions.
- CPA independently increased all-cause mortality (adjusted HR 1.59) after propensity score matching.
Methodological Strengths
- Large multicenter cohort with detailed clinical, radiologic, and survival data
- Multivariable modeling and propensity score matching to address confounding
Limitations
- Retrospective design; potential residual confounding and selection bias
- Low absolute number of CPA cases (n=45) may limit subgroup analyses
Future Directions: Prospective screening strategies for CPA in NTM-PD, evaluation of antifungal therapy impact on survival, and development of predictive tools integrating clinical and imaging features.
BACKGROUND: Nontuberculous mycobacterial pulmonary disease (NTM-PD) is a chronic respiratory infection with increasing prevalence and mortality worldwide. Coinfection with chronic pulmonary aspergillosis (CPA) is a significant complication of NTM-PD, often complicating treatment and resulting in poor prognosis. OBJECTIVE: In this multicentre, retrospective cohort study, we examined the epidemiology, comorbidities, risk factors for CPA coinfection and long-term prognosis of patients with NTM-PD infected with CPA in Japan. METHODS: Patients aged ≥ 18 years with newly diagnosed NTM-PD who visited 18 hospitals between 2010 and 2017 in Kyushu, Japan, were included. Medical records were reviewed for patient characteristics, mycobacterial species, laboratory data, radiological features, Aspergillus coinfection and all-cause mortality rates. Risk factors for CPA coinfection were analysed using multiple logistic regression, and survival analysis was performed before and after propensity score matching with risk factors. RESULTS: Among 1304 patients with NTM-PD, 45 (3.5%) were diagnosed with CPA, including 42 with chronic progressive pulmonary aspergillosis. The risk factors for CPA coinfection included male sex, chronic obstructive pulmonary disease, oral corticosteroid use and cavity formation. All-cause mortality was significantly higher in patients with NTM-PD with CPA than in those without CPA (log-rank test, p < 0.001; crude hazard ratio [HR], 3.98). Survival analysis after propensity score matching suggested CPA was an independent poor prognostic factor (log-rank test, p = 0.036; adjusted HR, 1.59). CONCLUSION: CPA is an independent poor prognostic factor in patients with NTM-PD. Clinicians must consider CPA when treating patients with NTM-PD, particularly those with high-risk factors, to ensure timely diagnosis and management.