Citations

ABSTRACT Pulmonary hypertension (PH) is a common complication in interstitial lung disease (ILD), but the additional burden it imposes on patients and healthcare systems is not well characterized. This retrospective analysis of claims data from the US Merative MarketScan database assessed hospitalization rates and costs over 2 years in patients with connective tissue disease‐related ILD (CTD‐ILD) and non‐CTD‐ILD with or without PH (between January 2017 and December 2019). Index was the date of first ILD claim; baseline was the 12‐month preindex period. In total, 16,129 patients with non‐CTD‐ILD (1502 [9%] with PH) and 4545 patients with CTD‐ILD (663 [15%] with PH) were identified. A higher proportion of patients with non‐CTD‐ILD with PH, compared with patients without PH, had all‐cause and heart failure (HF)‐related hospitalizations during baseline (all‐cause, 37.0% vs. 22.3%; HF‐related, 14.2% vs. 3.1%), 0–12 months (62.4% vs. 43.0%; 29.0% vs. 7.0%), and 13–24 months (44.7% vs. 18.3%; 21.5% vs. 3.2%) follow‐up ( p < 0.0001 for all). A significantly higher proportion of patients with CTD‐ILD with PH, compared with patients without PH, had all‐cause and HF‐related hospitalizations during baseline (all‐cause: 30.0% vs. 20.6%; HF‐related: 9.1% vs. 1.9%), 0–12 months (41.9% vs. 29.1%; 15.5% vs. 3.9%), and 13–24 months (37.9% vs. 18.9%; 13.9% vs. 2.5%) follow‐up ( p < 0.0001 for all). In both cohorts, total all‐cause and HF‐related costs were significantly higher in patients with PH at baseline, 0–12 months, and 13–24 months follow‐up ( p < 0.05 for all). PH substantially increased hospitalization risks and costs in both types of ILD, underscoring the importance of improving outcomes in patients with ILD‐PH.

ABSTRACT Background Treating Mycobacterium avium complex (MAC) infection pre‐lung transplant (LT) can be challenging to treat, given prolonged therapy and side effects. The impact of pre‐transplant MAC treatment on recurrence and outcomes post‐LT remains unclear, especially in patients with interstitial lung disease (ILD) who have a median survival of less than 2 years. Methods We performed a retrospective cohort study of adult LT patients at the Mayo Clinic who had positive MAC sputum cultures pre‐LT. The cohort was stratified and compared based on the type of treatment (complete, partial, or no treatment) for MAC pulmonary infection. The primary outcome was MAC recurrence post‐LT, and secondary outcomes were mortality, FEV‐1, and FVC at 1‐year post‐LT. Results Among the cohort of 47 patients, 9 (19.1%) were partially treated and 11 (23.4%) were completely treated for MAC infection pre‐LT. Post‐transplant MAC pulmonary infection recurrence occurred in eight (17%) of the total cohort, with four (14.8%) in the non‐treated, four (44.4%) in the partially‐treated, and none (0%) in the completely treated patients ( p = 0.026). There was no difference in mortality in patients who had MAC recurrence post‐transplantation (13% vs. 9.7%, p > 0.9) and those who were completely or partially treated, compared to non‐treated (0% vs. 13% vs. 13%, p > 0.9). The FEV1 and FVC at 1‐year post‐LT did not differ by the pre‐transplant treatment or post‐transplant MAC recurrence status. Conclusion The role of treatment for MAC infection pre‐transplant is questionable, especially in patients with diseases like ILD who may not have enough wait time to complete therapy.

Background: Lung cancer is classified into small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC – including adenocarcinoma, squamous cell, and large cell carcinoma). The incidence of major adverse cardiovascular events (MACE)—defined as acute myocardial infarction, acute coronary syndrome/ischemic heart disease requiring revascularization, stroke, and cardiovascular death—have not been well defined in lung cancer patients following treatment. Coronary artery calcifications (CAC) and aortic calcifications (CA) are known cardiovascular risk markers in non-cancer populations. Purpose: To determine whether the presence of CAC or CA, as identified on baseline PET-CT (Positron Emission Tomography–Computed Tomography) or chest CT imaging, is predictive of MACE and all-cause mortality (ACM) in patients with lung cancer. Methods: We conducted a retrospective cohort study of patients diagnosed with SCLC or NSCLC who received chemotherapy, between January 1, 2010, and December 31, 2024. The baseline PET-CT or chest CT scans were reviewed for the presence of CAC and/or CA. Patients were excluded if they lacked baseline imaging or had experienced a MACE before treatment. Univariate and multivariate adjusted Cox regression models were employed to assess associations between CAC/CA and MACE or ACM. The Kaplan-Meier survival analyses was performed to evaluate event-free survival. Results: A total of 385 patients were included (mean age: 74 years, IQR: 67–79), predominantly female (158 [55%]) and white (279 [96.2%]). NSCLC was found in 255 (88%) and SCLC in 35 (12%). CAC was identified in 172 (60%) and CA in 87 (30%). Among patients with NSCLC, the presence of CAC was significantly associated with MACE (HR: 2.84 [95% CI: 1.6–4.8], p=0.0001) (Fig. a), particularly in those with adenocarcinoma (Fig. b). In SCLC, (HR: 1.56 [95% CI: 0.1–14.0], p=ns). On multivariable analysis, CAC remained the strongest predictor of MACE after adjusting for age, hypertension, diabetes, dyslipidemia, and smoking status (HR: 2.6 [95% CI: 1.5–4.4], p=0.0008) (Fig. d). No significant association was found between CA and MACE in either group (p>0.05). ACM was similar for SCLC, squamous cell, and NSCLC (Fig. c). Conclusion: In patients with NSCLC especially lung adenocarcinoma, the presence of CAC in the baseline PET/CT was an independent predictor of MACE. This finding supports the value of CAC as a non-invasive cardiovascular risk marker.

Abstract Understanding tumor cell dynamics can improve prognosis and treatment but remains limited for lung adenocarcinoma in people who have never smoked (NS-LUAD). With RNA sequencing data from 684 NS-LUAD cases and validation in an independent dataset, we identified three subtypes with distinct phenotypic traits and cell compositions. Additional genomic and histologic data further characterized the subtypes. “Steady,” marked by low proliferation, high alveolar cell fraction, moderate-to-well differentiation, and fewer driver gene alterations, is linked to prolonged survival and low immune evasion. “Proliferative” shows high proliferation markers, TP53 mutations, and gene fusions. “Chaotic,” with high epithelial-to-mesenchymal transition markers, has the worst prognosis, even within stage I tumors. Lacking known molecular or histologic characteristics, this aggressive subtype is solely identified by transcriptomic data. A 60-gene signature recapitulates the classification and predicts survival even within subgroups based on tumor stage or known genomic features, emphasizing its potential for improving early-stage NS-LUAD prognostication in clinical settings. Significance: The transcriptome of 684 NS-LUAD identifies three subtypes with different cellular dynamics and genomic and morphologic features. A 60-gene signature accurately stratifies subjects for mortality risk, even in stage I, offering a potential clinically applicable tool for treatment decision-making in patients with NS-LUAD. See related commentary by Azizi et al., p. 423

BACKGROUND: The optimal antithrombotic treatment after transcatheter left atrial appendage closure (LAAC) remains to be determined. The objective of this trial was to compare anticoagulation and antiplatelet therapy for preventing device-related thrombosis (DRT) after LAAC. METHODS: This was a prospective multicenter international randomized trial comparing 2 different antithrombotic strategies for preventing DRT after LAAC in patients with nonvalvular atrial fibrillation. Patients were randomized (1:1) to receive direct oral anticoagulants (DOACs) or dual antiplatelet therapy (DAPT; aspirin+clopidogrel) for 60 days. Patients underwent transesophageal echocardiography at 60 days, and the images were analyzed in a central echocardiography laboratory by experienced echocardiographers blinded to the allocated treatment. The primary outcome was DRT as determined by transesophageal echocardiography 60 days after LAAC in patients receiving the allocated treatment at the time of transesophageal echocardiography (per-protocol analysis). The safety outcome included all-cause mortality, stroke, bleeding, or site-reported DRT within 60 days after LAAC in all randomized patients (intention-to-treat analysis). RESULTS: A total of 510 patients (mean age 77±9 years, 35% women) were included between October 2018 and May 2025, and 253 and 257 patients were randomized to the DOAC and DAPT groups, respectively. Of these, 399 patients underwent transesophageal echocardiography and were receiving the allocated treatment at 60 days after LAAC. The primary outcome occurred in 3 patients (1.5%) in the DOAC group compared with 8 patients (4.1%) in the DAPT group (difference, −2.7% [95% CI, −6.0% to 0.6%]; P =0.110). The safety outcome occurred in 52 patients (22.5%) in the DOAC group compared with 82 patients (34.9%) in the DAPT group (difference, −12.4% [95% CI, −20.6% to −4.2%]; P =0.003), and differences were mainly driven by a lower rate of bleeding events in the DOAC group (44 patients [17.4%] versus 64 patients [24.9%]; difference, −7.5% [95% CI, −14.6% to −0.4%]; P =0.038). CONCLUSIONS: The use of DOACs after LAAC failed to reduce DRT compared with DAPT, but it was associated with an improved safety profile. The results of this study should be interpreted with caution because of statistical power issues related to the narrower-than-expected between-group differences and will need confirmation in future larger studies. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03568890.

ABSTRACT Background The impact of psychosocial health and socioeconomic status (SES) on long‐term lung transplant survival remains unclear. Methods We conducted a single‐center, retrospective 2:1 matched case‐control study of adult lung transplant recipients (1999–2019). Cases survived ≥6 years post‐transplant; controls survived <6 years. Matching was based on transplant year (±5 years) and indication. Psychosocial health and SES were assessed using the Psychosocial Assessment of Candidates for Transplant (PACT) score, Mayo Clinic Housing‐Based Socioeconomic Status (HOUSES) index, and Area Deprivation Index (ADI). Secondary covariates included insurance, marital status, employment, caregiver relationship, and proximity to the transplant center. Conditional logistic regression adjusted for age and gender was used. Results Among 189 patients (63 cases, 126 controls), PACT score, HOUSES index, and ADI were not significantly associated with long‐term survival. Patients with non‐family caregivers had lower odds of survival compared to those with a spouse or partner (OR = 0.16, p = 0.022). Regional residents had lower odds of long‐term survival compared to local recipients (OR = 0.55, p = 0.001). Conclusions Pre‐transplant psychosocial and SES measures were not significantly associated with long‐term survival. Caregiver relationships and geographic proximity may have a greater impact on outcomes, highlighting the importance of support systems and access to care.

Data from the current study support the hypothesis that the pressure-generating capacity of the diaphragm at high lung volume is compromised primarily due to a mechanism that involves a combined mechanical effect of hyperinflation and substantial muscle contraction rather than a significant loss of its muscle fiber curvature.

Abstract The sections in this article are: Regulation of the Upper Airway During Exercise Anatomy and Physiology of the Upper Airway Contractile Properties and Endurance of Upper Airway Muscles Changes in Upper Airway Flow Resistance During Exercise Upper Airway Muscle Activities during Exercise Oronasal Distribution of Respiratory Airflow Effects of Exercise on Passive Respiratory Mechanics Elastic Properties Total Lung Capacity Expiratory Flow Rates, Vital Capacity, and Residual Volume Breathing Pattern During Exercise Mechanical Breathing Pattern Methods of Assessment of Respiratory Muscle Contraction Pattern of Respiratory Muscle Contraction Influence of Sensory Feedback on Breathing Pattern Influence of Respiratory Mechanics on Breathing Pattern Influence of Duration of Exercise on Breathing Pattern Influence of Mode of Exercise on Breathing Pattern Breathing Pattern during Recovery from Exercise Physiological Implications of Exercise Breathing Pattern Importance of Respiratory Load in Regulation of Exercise Hyperpnea Helium‐Oxygen Unloading Unloading with Pressure Assist Conclusion Locomotor‐Respiration Interdependence Entrainment—the Most Obvious Locomotor‐Respiratory Interaction How Does Entrainment Effect Ventilation? Is there Stronger Evidence to Support a Significant Biomechanical Effect of Locomotion on Respiration in Dogs? Are Biomechanical Effects Important in Entrainment in Humans? Locomotory: Respiratory Interactions, Independent of Entrainment Conclusion Respiratory Muscle Perfusion and Energetics Oxygen Cost of Hyperpnea Respiratory Muscle Blood Flow Exercise‐Induced Respiratory Muscle Fatigue Respiratory System Design Assessment of Diaphragm Fatigue in Animal Models Glycogen Depletion Fiber Type Recruitment Definition of Fatigue Task Failure vs. Objective Assessment of Fatigue Contractile Changes with Fatigue Predicting Respiratory Muscle Fatigue During Exercise Application of Resting Tests to Respiratory Muscle Function During Exercise Assessment of Respiratory Muscle Fatigue in Humans Volitional Tests Volitional Tests Applied to Exercise Nonvolitional Tests Bilateral Phrenic Nerve Stimulation ( BPNS ) Characteristics of Diaphragm Fatigue High‐ vs. Low‐Frequency Fatigue Sites and Mechanisms of Respiratory Muscle Fatigue Central Fatigue in Humans Neurotransmission Fatigue Bilateral Phrenic Nerve Stimulation Applied to Exercise Short‐Term Exercise Endurance Exercise Factors Contributing to the Decline in Twitch Pdi Following Exercise Role of Diaphragmatic Force Output in Fatigue Consequences of Exercise‐Induced Diaphragmatic Fatigue Fatigue vs. Task Failure Does Training of Respiratory Muscles Affect Exercise Performance? Altered Respiratory Muscle Recruitment with Fatigue Physical Training Effects on Respiratory Muscles Respiratory Muscle Morphology and Contractile Properties Whole‐Body Training: Effects on Rodent Respiratory Muscles Whole‐Body Exercise: Effects on Human Respiratory Muscle Performance Specific Respiratory Muscle Training Respiratory Sensation During Exertion Mechanisms of Respiratory Sensations during Exercise Methods of Assessing Respiratory Sensations Respiratory Movements An Urge to Breathe A Sense of Respiratory Effort Respiratory Sensation as a Respiratory Controller during Exercise Respiratory Sensation as a Limiting Factor during Exercise Conclusions Summary—Pulmonary System Limitations and Their Effects on Exercise Performance Absence of Pulmonary System Limitations in the Normally Fit Contrasting Adaptabilities: Demand vs. Capacity Alveolar Capillary Diffusion Surface of the Lung Ventilatory Limitations/Constraints Inadequate Alveolar Ventilation and Limitations Endurance Exercise Performance Special Circumstances Favoring Pulmonary Limitations to Exercise Performance in Health Hypoxia of High Altitudes Aging Effects on Pulmonary Limitations