Interventional Pulmonology: Extending the Breadth of Thoracic Care.

Interventional pulmonary medicine has developed as a subspecialty focused on the management of patients with complex thoracic disease. Leveraging minimally invasive techniques, interventional pulmonologists diagnose and treat pathologies that previously required more invasive options such as surgery. By mitigating procedural risk, interventional pulmonologists have extended the reach of care to a wider pool of vulnerable patients who require therapy. Endoscopic innovations, including endobronchial ultrasound and robotic and electromagnetic bronchoscopy, have enhanced the ability to perform diagnostic procedures on an ambulatory basis. Therapeutic procedures for patients with symptomatic airway disease, pleural disease, and severe emphysema have provided the ability to palliate symptoms. The combination of medical and procedural expertise has made interventional pulmonologists an integral part of comprehensive care teams for patients with oncologic, airway, and pleural needs. This review surveys key areas in which interventional pulmonologists have impacted the care of thoracic disease through bronchoscopic intervention.

Externalized histones fuel pulmonary fibrosis via a platelet-macrophage circuit of TGFß1 and IL-27.

Externalized histones erupt from the nucleus as extracellular traps, are associated with several acute and chronic lung disorders, but their implications in the molecular pathogenesis of interstitial lung disease are incompletely defined. To investigate the role and molecular mechanisms of externalized histones within the immunologic networks of pulmonary fibrosis, we studied externalized histones in human and animal bronchoalveolar lavage (BAL) samples of lung fibrosis. Neutralizing anti-histone antibodies were administered in bleomycin-induced fibrosis of C57BL/6 J mice, and subsequent studies used conditional/constitutive knockout mouse strains for TGFß and IL-27 signaling along with isolated platelets and cultured macrophages. We found that externalized histones (citH3) were significantly (P < 0.01) increased in cell-free BAL fluids of patients with idiopathic pulmonary fibrosis (IPF; n = 29) as compared to healthy controls (n = 10). The pulmonary sources of externalized histones were Ly6G+CD11b+ neutrophils and nonhematopoietic cells after bleomycin in mice. Neutralizing monoclonal anti-histone H2A/H4 antibodies reduced the pulmonary collagen accumulation and hydroxyproline concentration. Histones activated platelets to release TGFß1, which signaled through the TGFbRI/TGFbRII receptor complex on LysM+ cells to antagonize macrophage-derived IL-27 production. TGFß1 evoked multiple downstream mechanisms in macrophages, including p38 MAPK, tristetraprolin, IL-10, and binding of SMAD3 to the IL-27 promotor regions. IL-27RA-deficient mice displayed more severe collagen depositions suggesting that intact IL-27 signaling limits fibrosis. In conclusion, externalized histones inactivate a safety switch of antifibrotic, macrophage-derived IL-27 by boosting platelet-derived TGFß1. Externalized histones are accessible to neutralizing antibodies for improving the severity of experimental pulmonary fibrosis.

Fibrotic progression from acute cellular rejection is dependent on secondary lymphoid organs in a mouse model of chronic lung allograft dysfunction.

Chronic lung allograft dysfunction (CLAD) remains one of the major limitations to long-term survival after lung transplantation. We modified a murine model of CLAD and transplanted left lungs from BALB/c donors into B6 recipients that were treated with intermittent cyclosporine and methylprednisolone postoperatively. In this model, the lung allograft developed acute cellular rejection on day 15 which, by day 30 after transplantation, progressed to severe pleural and peribronchovascular fibrosis, reminiscent of changes observed in restrictive allograft syndrome. Lung transplantation into splenectomized B6 alymphoplastic (aly/aly) or splenectomized B6 lymphotoxin-ß receptor-deficient mice demonstrated that recipient secondary lymphoid organs, such as spleen and lymph nodes, are necessary for progression from acute cellular rejection to allograft fibrosis in this model. Our work uncovered a critical role for recipient secondary lymphoid organs in the development of CLAD after pulmonary transplantation and may provide mechanistic insights into the pathogenesis of this complication.

Circulating monocytes decrease significantly following disease-directed therapy and may reflect disease expansion in Langerhans Cell Histiocytosis.

We aimed to examine the association between relative monocytosis and the recurrence of pulmonary Langerhans Cell Histiocytosis. Clinical, laboratory, radiographic and treatment data for 86 patients with a histopathological diagnosis of Langerhans Cell Histiocytosis over a 20-year duration. Parameters such as biological sex, age at diagnosis, time to diagnosis, molecular diagnostic data and imaging were collected. Treatment responses were assessed predominantly through radiography, with RECIST 1.1 criteria applied to MRI or CT scans and PERCIST utilized for serial PET imaging. Investigators also assessed peripheral blood absolute monocyte count at various time points, including initial diagnosis and the most recently available value. While peripheral blood absolute monocyte count between the earliest assessed timepoint and latest value did not differ, the mean value on progression (0.94 K/µL), however, was significantly higher than that following re-institution of therapy (0.31, p = 0.000794. Our observation of relative monocytosis on LCH disease progression may be related to an increase in circulating LCH on disease progression or from increased monocyte production for later differentiation into mature dendritic cells that participate in MHC Class 1 upregulation. This trend is especially evident in pulmonary LCH which is incited by tissue trauma and irritation by environmental factors. The phenomena observed in our study parallel other non-LCH cohorts, specifically in published findings from our own group in patients with Rosai Dorfman and Erdheim Chester Disease. To further elucidate the molecular underpinnings of LCH and explore the etiology of this monocyte trend, expanded integrated genomic-transcriptomic sequencing analyses to evaluate the molecular character of LCH and ultimately clarify the origin of this monocyte trend are in progress. These studies are poised to offer invaluable insight to the molecular mechanisms underlying LCH, specifically as they pertain to monocyte signaling and differentiation.

Improving Asthma Control Test completion rates across a multi-site pediatric pulmonary clinic network: a quality improvement initiative.

OBJECTIVE: Assessing asthma control is an essential part of the outpatient management of children with asthma and can be performed through validated questionnaires such as the Asthma Control Test (ACT). Systematic approaches to incorporating the ACT in outpatient visits are often lacking, contributing to inconsistent completion rates. We conducted a quality improvement initiative to increase the proportion of visits where the ACT is completed for children with asthma in our multi-site pediatric pulmonary clinic network. METHODS: We developed an intervention of sending the ACT questionnaire to patients and caregivers through the electronic patient portal to complete prior to their visits. This strategy was first piloted at one clinic beginning in July 2020 and then expanded to 5 other clinics in the network in October 2020. Our outcome measure was average monthly proportion of visits with a completed ACT, tracked using statistical process control charts. The process measure was method of ACT completion tracked using run charts. RESULTS: At the pilot clinic, average monthly completion rate rose within 3 months of the intervention from 27% to 72% and was sustained more than 22 months. Completion across all clinics increased from 57% pre-intervention to 76% post-intervention. Importantly, the intervention did not rely on clinic staff to administer the questionnaire and did not interfere with existing clinic flow. CONCLUSION: An intervention of delivering the ACT electronically to patients and caregivers for completion prior to visits led to a rapid and sustained improvement in ACT completion rates across a large, pediatric pulmonary clinic network.

Pediatric chest radiograph interpretation in a real-life setting.

Chest radiography is a frequently used imaging modality in children. However, only fair to moderate inter-observer agreement has been reported between chest radiograph interpreters. Most studies were not performed in real-world clinical settings. Our aims were to examine the agreement between emergency department pediatricians and board-certified radiologists in a pediatric real-life setting and to identify clinical risk factors for the discrepancies. Included were children aged 3 months to 18 years who underwent chest radiography in the emergency department not during the regular hours of radiologist interpretation. Every case was reviewed by an expert panel. Inter-observer agreement between emergency department pediatricians and board-certified radiologists was assessed by Cohen's kappa; risk factors for disagreement were analyzed. Among 1373 cases, the level of agreement between emergency department pediatricians and board-certified radiologists was "moderate" (k = 0.505). For radiographs performed after midnight, agreement was only "fair" (k = 0.391). The expert panel identified clinically relevant disagreements in 260 (18.9%) of the radiographs. Over-treatment of antibiotics was identified in 121 (8.9%) of the cases and under-treatment in 79 (5.8%). In a multivariable logistic regression, the following parameters were found to be significantly associated with disagreements: neurological background (p = 0.046), fever (p = 0.001), dyspnea (p = 0.014), and radiographs performed after midnight (p = 0.007). CONCLUSIONS: Moderate agreement was found between emergency department pediatricians and board-certified radiologists in interpreting chest radiographs. Neurological background, fever, dyspnea, and radiographs performed after midnight were identified as risk factors for disagreement. Implementing these findings could facilitate the use of radiologist expertise, save time and resources, and potentially improve patient care. WHAT IS KNOWN: • Only fair to moderate inter-observer agreement has been reported between chest radiograph interpreters. • Most studies were not performed in real-world clinical settings. Clinical risk factors for disagreements have not been reported. WHAT IS NEW: • In this study, which included 1373 cases at the emergency department, the level of agreement between interpreters was only "moderate." • The major clinical parameters associated with interpretation discrepancies were neurological background, fever, dyspnea, and interpretations conducted during the night shift.

Neonatal diagnosis of primary ciliary dyskinesia in a high consanguinity population: a single tertiary center experience.

Though PCD usually presents after birth in term neonates, diagnosing PCD during the neonatal and infancy stages is uncommon, particularly in children who do not exhibit laterality defects. We report our recent experience with the diagnosis of PCD in the neonatal and early infantile period in a highly consanguine population. This was achieved by implementing a novel genetic-based diagnostic approach based on direct testing for recognized regional genetic variants. We conducted a retrospective analysis of children diagnosed with PCD at Soroka University Medical Center during the neonatal or early infantile period between 2020 and 2023. We included children under 3 months of age who had a genetic confirmation of PCD, as evidenced by the presence of two pathogenic variants in recognized genes. Genetic testing targeted regional genetic variants in previously identified PCD genes. Eight patients were included. The median age at diagnosis was 12.5 days. Three (38%) were born prematurely < 34 weeks gestational age. All patients were presented with respiratory distress and hypoxemia after birth. The median duration of oxygen support was 23 days, and upper lobe atelectasis was present in five patients (63%). Congenital cardiac malformation was present in four patients. Organ laterality defects were present in four patients. Genetic mutations identified were in the DNAAF5, DNAL1, DNAAF3, and DNAH1 genes.     Conclusion: Neonatal diagnosis of PCD is uncommon, especially in atypical presentations such as children without laterality defects or preterms. Focusing on a genetic diagnosis of the local tribal pathogenic variants promotes a potential cost-efficient test leading to earlier diagnosis. There is a need for a standardized protocol for earlier diagnosis of PCD in high-consanguinity areas. What is Known: • Primary ciliary dyskinesia (PCD) typically presents after birth in term neonates. • Diagnosing PCD during neonatal and infancy stages is challenging, particularly in children without laterality defects. What is New: • A novel genetic-based diagnostic approach was implemented on the neonatal population in a highly consanguine community, focusing on direct testing for regional genetic variants, leading to early and rapid diagnosis of PCD.

Therapeutic bronchoscopy for malignant central airway obstructions caused by non-bronchogenic cancers: Results from the EpiGETIF registry.

BACKGROUND AND OBJECTIVE: Little is known about malignant central airway obstruction (MCAO) complicating the metastatic spread of non-bronchogenic solid cancers (NBC) and their bronchoscopic management. This study aimed to describe the epidemiology of this population and determine prognostic factors before therapeutic bronchoscopy (TB). METHODS: In this multicenter study using the EpiGETIF registry, we analysed patients treated with TB for MCAO caused by NBC between January 2019 and December 2022. RESULTS: From a database of 2389 patients, 436 patients (18%) with MCAO and NBC were identified. After excluding patients with direct local invasion, 214 patients (8.9%) were analysed. The main primaries involved were kidney (17.8%), colon (16.4%), sarcoma (15.4%), thyroid (8.9%) and head and neck (7.9%) cancers. Most patients (63.8%) had already received one or more lines of systemic treatment. Obstructions were purely intrinsic in 58.2%, extrinsic in 11.1% and mixed in 30.8%. Mechanical debulking was used in 73.4% of cases, combined with thermal techniques in 25.6% of cases. Airway stenting was required in 38.4% of patients. Median survival after TB was 11.2 months, influenced by histology (p = 0.002), performance status (p = 0.019), initial hypoxia (HR 1.45 [1.01-2.18]), prior oncologic treatment received (HR 1.82 [1.28-2.56], p < 0.001) and assessment of success at the end of the procedure (HR 0.66 [0.44-0.99], p < 0.001). Complications rate was 8.8%, mostly mild, with no procedure-related mortality. CONCLUSION: TB for MCAO caused by a NBC metastasis provides rapid improvement of symptoms and prolonged survival. Patients should be promptly referred by medical oncologists for bronchoscopic management based on the prognostic factors identified.

Low bleeding rates following transbronchial lung cryobiopsy in unclassifiable interstitial lung disease.

BACKGROUND AND OBJECTIVE: Bronchoscopic transbronchial lung cryobiopsy (TBLC) is a guideline-endorsed alternative to surgical lung biopsy for tissue diagnosis in unclassifiable interstitial lung disease (ILD). The reported incidence of post-procedural bleeding has varied widely. We aimed to characterize the incidence, severity and risk factors for clinically significant bleeding following TBLC using an expert-consensus airway bleeding scale, in addition to other complications and diagnostic yield. METHODS: A retrospective cohort study of consecutive adult outpatients with unclassifiable ILD who underwent TBLC following multidisciplinary discussion at a single centre in the UK between July 2016 and December 2021. TBLC was performed under general anaesthesia with fluoroscopic guidance and a prophylactic endobronchial balloon. RESULTS: One hundred twenty-six patients underwent TBLC (68.3% male; mean age 62.7 years; FVC 86.2%; DLCO 54.5%). Significant bleeding requiring balloon blocker reinflation for >20 min, admission to ICU, packed red blood cell transfusion, bronchial artery embolization, resuscitation or procedural abandonment, occurred in 10 cases (7.9%). Significant bleeding was associated with traction bronchiectasis on HRCT (OR 7.1, CI 1.1-59.1, p = 0.042), a TBLC histological pattern of UIP (OR 4.0, CI 1.1-14, p = 0.046) and the presence of medium-large vessels on histology (OR 37.3, CI 6.5-212, p < 0.001). BMI ≥30 (p = 0.017) and traction bronchiectasis on HRCT (p = 0.025) were significant multivariate predictors of longer total bleeding time (p = 0.017). Pneumothorax occurred in nine cases (7.1%) and the 30-day mortality was 0%. Diagnostic yield was 80.6%. CONCLUSION: TBLC has an acceptable safety profile in experienced hands. Radiological traction bronchiectasis and obesity increase the risk of significant bleeding following TBLC.

Effective Radiation Dose from Cone-Beam Computed Tomography Guidance during Bronchoscopic Tumour Ablation.

INTRODUCTION: Endobronchial radiofrequency ablation (RFA) is a novel minimally invasive approach to management of peripheral non-small-cell lung cancer (NSCLC) in medically inoperable patients. Minimally invasive ablative techniques are generally delivered with cone-beam computed tomography (CBCT) guidance. CBCT requires a significant number of two dimensional imaging projections to be acquired which is then reconstructed as a three-dimensional cone-beam image. The objective of this study was to determine the radiation dosimetry consequent to use of CBCT guidance for bronchoscopic RFA. METHODS: Post hoc analysis of data following bronchoscopic RFA of stage I biopsy-confirmed NSCLC performed with CBCT. Effective dose estimates for these patients were calculated using PCXMC2.0 software. RESULTS: Ten patients underwent bronchoscopic RFA, with a median 3 (range 2-4) CBCT spins per procedure. Mean dose area product (DAP) per procedure was 7,778 µGy.m2 (±4,743) with an effective dose of 11.6 mSv (±7.4). The DAP per spin for these 10 patients varied from 83.8 to 8,625.6 µGy.m2 (effective dose range 0.15-13.81 mSv). CONCLUSION: This is the first study to report radiation dosimetry consequent to CT guidance for bronchoscopic RFA procedures. Effective doses appear comparable to other CT fluoroscopic procedures.

Bronchial Cryo-Denervation for Severe Asthma: A Pilot Study.

INTRODUCTION: Targeting the parasympathetic nervous system innervating the airway with pharmacologic products has been proved to improve the clinical outcomes of severe asthma. Bronchial cryo-denervation (BCD) is a novel non-pharmacologic treatment for severe asthma using an endobronchial cryo-balloon administered via bronchoscopy to denervate parasympathetic pulmonary nerves. Preclinical studies have demonstrated that BCD significantly disrupted vagal innervation in the lung. METHODS: A total of 15 patients with severe asthma were enrolled in this prospective, single-center pilot study. Patients underwent bifurcated BCD treatment at a 30-day interval after baseline assessment. Follow-up through 12 months included assessment of adverse events, technical feasibility, and changes in pulmonary function; asthma control questionnaire-7 (ACQ-7); and asthma control test (ACT). RESULTS: BCD was performed on all 15 severe asthma patients, with technical feasibility of 96.7%. There were no device-related and 2 procedure-related serious adverse events through 12 months, which resolved without sequelae. The most frequent nonserious procedure-related adverse event was increased cough in 60% (9 of 15) patients. Pulmonary function remained unchanged, and significant improvements from baseline ACQ-7 (mean, -1.19, p = 0.0032) and ACT (mean, 3.18, p = 0.0011) scores were observed since the first month's follow-up after a single lung airway treatment, with similar trends till the end of the 12-month follow-up. CONCLUSION: This study provides the first clinical evidence of the safety, feasibility, and initial efficacy of BCD in patients with severe asthma.

High risk and low incidence diseases: Massive hemoptysis.

BACKGROUND: Massive hemoptysis (MH) is a serious condition that carries with it a high rate of morbidity and mortality. OBJECTIVE: This review highlights the pearls and pitfalls of massive hemoptysis, including presentation, diagnosis, and management in the emergency department (ED) based on current evidence. DISCUSSION: MH is a rare but deadly condition. It is defined clinically as any bleeding from the tracheobronchial tree that compromises respiratory or circulatory function. The bronchial artery system is the primary source in the majority of cases of MH. The most common cause is tuberculosis worldwide, but bronchiectasis, bronchogenic carcinoma, and mycetoma are more common causes in the U.S. Patients with MH require rapid assessment and management, as decompensation can be rapid. Patients with altered mental status, inability to clear their sections, respiratory distress, or hemodynamic compromise require emergent airway intervention. The imaging modality of choice is computed tomography angiography with pulmonary arterial phase contrast. A reasonable order or sequence of management includes initial stabilization; assessment for the need for airway intervention; reversal of any coagulopathy; advanced imaging; and emergent consultation of pulmonary, cardiothoracic surgery, and interventional radiology. Ongoing resuscitation including blood products may be required in some patients with MH until definitive hemostasis is achieved. CONCLUSIONS: An understanding of MH can assist emergency clinicians in diagnosing and managing this dangerous disease. Providing a prompt evaluation, obtaining intravenous access, pursuing advanced imaging, providing reversal of coagulopathy, supporting hemodynamics, and appropriate consultation are key interventions in MH.

Pleural line slope in point of care ultrasound assessment of paediatric wheeze may reflect respiratory effort.

AIM: Asthma scoring systems rely on physical examination findings. Point of care ultrasound may provide an objective means to document improvement in the work of breathing in paediatric lower airway obstruction. METHODS: Thirty children with wheeze on physical examination (cases) and 15 children presenting with abdominal pain (controls) were studied. Using point-of-care ultrasound, m-mode tracing of lung was recorded above the right hemidiaphragm at the midclavicular line. Pleural line slope and excursion were measured before and after treatment. RESULTS: Twenty patients had a final slope measurement under 20°, and only three were admitted-one for hypoxia that resolved prior to ascending to the ward and another for poor compliance. Average decrease in pleural line slope after treatment was 43% and average decrease in pleural line excursion was 32%. Of the 10 children admitted, 8 had measurements over 25°. The correlation coefficient between pleural slope and pleural excursion was 0.67. All controls had a horizontal m-mode tracing at the pleural line. CONCLUSION: Oscillation of the m-mode line at the pleura is seen in children with lower airway obstruction and is absent in controls. There appears to be a correlation between beta-agonist therapy and decreased pleural line slope and excursion.

[On the formation of Russian pulmonology: the development of the doctrine of lung diseases (first half of the 20th century)].

The articles on the history of Russian pulmonology presented in the historical, medical and therapeutic literature contain materials for this history, but their authors did not solve the problem of its consistent presentation, highlighting the stages of formation and founders. The authors of this study critically reviewed the literary and archival primary sources, for the first time proposed the identification of three stages in the development of Russian pulmonology and indicated eight of its founders at these stages. The abundance of material did not allow us to present it in one article. This article is devoted to the 1st stage of the history of pulmonology - the formation of the doctrine of lung diseases. The second (development of pulmonology as an independent scientific direction in internal diseases) and the third (organizational design of pulmonology as a new independent clinical scientific and educational discipline and medical specialty, i.e. its institutionalization) stages will be discussed in the next articles.

Thoracoabdominal asynchrony in a virtual preterm infant: computational modeling and analysis.

Thoracoabdominal asynchrony (TAA), the asynchronous volume changes between the rib cage and abdomen during breathing, is associated with respiratory distress, progressive lung volume loss, and chronic lung disease in the newborn infant. Preterm infants are prone to TAA risk factors such as weak intercostal muscles, surfactant deficiency, and a flaccid chest wall. The causes of TAA in this fragile population are not fully understood and, to date, the assessment of TAA has not included a mechanistic modeling framework to explore the role these risk factors play in breathing dynamics and how TAA can be resolved. We present a dynamic compartmental model of pulmonary mechanics that simulates TAA in the preterm infant under various adverse clinical conditions, including high chest wall compliance, applied inspiratory resistive loads, bronchopulmonary dysplasia, anesthesia-induced intercostal muscle deactivation, weakened costal diaphragm, impaired lung compliance, and upper airway obstruction. Sensitivity analyses performed to screen and rank model parameter influence on model TAA and respiratory volume outputs show that risk factors are additive so that maximal TAA occurs in a virtual preterm infant with multiple adverse conditions, and addressing risk factors individually causes incremental changes in TAA. An abruptly obstructed upper airway caused immediate nearly paradoxical breathing and tidal volume reduction despite greater effort. In most simulations, increased TAA occurred together with decreased tidal volume. Simulated indices of TAA are consistent with published experimental studies and clinically observed pathophysiology, motivating further investigation into the use of computational modeling for assessing and managing TAA.NEW & NOTEWORTHY A novel model of thoracoabdominal asynchrony incorporates literature-derived mechanics and simulates the impact of risk factors on a virtual preterm infant. Sensitivity analyses were performed to determine the influence of model parameters on TAA and respiratory volume. Predicted phase angles are consistent with prior experimental and clinical results, and influential parameters are associated with clinical scenarios that significantly alter phase angle, motivating further investigation into the use of computational modeling for assessing and managing thoracoabdominal asynchrony.

Subphenotypes of frailty in lung transplant candidates.

Heterogeneous frailty pathobiology might explain the inconsistent associations observed between frailty and lung transplant outcomes. A Subphenotype analysis could refine frailty measurement. In a 3-center pilot cohort study, we measured frailty by the Short Physical Performance Battery, body composition, and serum biomarkers reflecting causes of frailty. We applied latent class modeling for these baseline data. Next, we tested class construct validity with disability, waitlist delisting/death, and early postoperative complications. Among 422 lung transplant candidates, 2 class model fit the best (P = .01). Compared with Subphenotype 1 (n = 333), Subphenotype 2 (n = 89) was characterized by systemic and innate inflammation (higher IL-6, CRP, PTX3, TNF-R1, and IL-1RA); mitochondrial stress (higher GDF-15 and FGF-21); sarcopenia; malnutrition; and lower hemoglobin and walk distance. Subphenotype 2 had a worse disability and higher risk of waitlist delisting or death (hazards ratio: 4.0; 95% confidence interval: 1.8-9.1). Of the total cohort, 257 underwent transplant (Subphenotype 1: 196; Subphenotype 2: 61). Subphenotype 2 had a higher need for take back to the operating room (48% vs 28%; P = .005) and longer posttransplant hospital length of stay (21 days [interquartile range: 14-33] vs 18 days [14-28]; P = .04). Subphenotype 2 trended toward fewer ventilator-free days, needing more postoperative extracorporeal membrane oxygenation and dialysis, and higher need for discharge to rehabilitation facilities (P ≤ .20). In this early phase study, we identified biological frailty Subphenotypes in lung transplant candidates. A hyperinflammatory, sarcopenic Subphenotype seems to be associated with worse clinical outcomes.

Endovascular transatrial stenting of pulmonary vein stenosis after lung transplantation.

Pulmonary vein stenosis (PVS) and pulmonary vein occlusion (PVO) represent rare complications after lung transplantation (LTx), with limited therapeutic options and a high risk of graft loss. We present 2 cases of successful endovascular transatrial stenting following double LTx. A 60-year-old woman with chronic obstructive pulmonary disease who underwent double lobar LTx was diagnosed at postoperative day 72 with a high-grade PVS on the left side. A 22-year-old woman with idiopathic pulmonary arterial hypertension who underwent double LTx was diagnosed 9 days later with PVO of the left upper lobe vein. To avoid surgical reintervention, endovascular transatrial dilatation and stenting were performed successfully in both cases. Transatrial endovascular stenting of PVS or PVO after LTx seems an effective and safe treatment option that should be considered for these life-threatening complications and executed with care.

Donor and recipient human leukocyte antigen-G polymorphisms modulate the risk of adverse immunologic events following lung transplantation.

The long-term benefits of lung transplantation (LTx) are limited by pathogenic alloimmune responses that drive injury, inflammation, and chronic dysfunction. Human leukocyte antigen-G (HLA-G) plays a key role in the modulation of these pathways. This study assesses the impact of the HLA-G genotype on immunologic risk and survival following LTx. This retrospective cohort study included 289 bilateral LTx. Recipient and donor HLA-G genotypes were analyzed to identify associations with de novo donor-specific antibodies, acute rejection, chronic lung allograft dysfunction, and allograft survival. We further assessed these associations, both individually and in paired analysis, based on a grouped haplotype classification of HLA-G expression. Donor HLA-G single nucleotide polymorphisms were associated with allograft injury, the onset of chronic lung allograft dysfunction following injury, and allograft survival. Recipient HLA-G single nucleotide polymorphisms were associated with allograft injury, cellular rejection, and donor-specific antibody formation. "Low HLA-G expression" donor haplotypes were associated with impaired allograft survival, as were "low HLA-G expression" donor-recipient haplotype pairs. This study provides compelling evidence for the role of HLA-G in modulating immunologic risk after LTx. Our results highlight the importance of both donor and recipient HLA-G genotypes on the overall risk profile and underscore the lasting influence of donor genotype on lung transplant outcomes.

Preemptive treatment of de novo donor-specific antibodies in lung transplant patients reduces subsequent risk of chronic lung allograft dysfunction or death.

The development of donor-specific antibodies after lung transplantation is associated with downstream acute cellular rejection, antibody-mediated rejection (AMR), chronic lung allograft dysfunction (CLAD), or death. It is unknown whether preemptive (early) treatment of de novo donor-specific antibodies (dnDSAs), in the absence of clinical signs and symptoms of allograft dysfunction, reduces the risk of subsequent CLAD or death. We performed a multicenter, retrospective cohort study to determine if early treatment of dnDSAs in lung transplant patients reduces the risk of the composite endpoint of CLAD or death. In the cohort of 445 patients, 145 patients developed dnDSAs posttransplant. Thirty patients received early targeted treatment for dnDSAs in the absence of clinical signs and symptoms of AMR. Early treatment of dnDSAs was associated with a decreased risk of CLAD or death (hazard ratio, 0.36; 95% confidence interval, 0.17-0.76; P < .01). Deferring treatment until the development of clinical AMR was associated with an increased risk of CLAD or death (hazard ratio, 3.00; 95% confidence interval, 1.46-6.18; P < .01). This study suggests that early, preemptive treatment of donor-specific antibodies in lung transplant patients may reduce the subsequent risk of CLAD or death.

Miscalibration of lung allocation models leads to inaccurate waitlist mortality predictions.

The importance of waitlist (WL) mortality risk estimates will increase with the adoption of the US Composite Allocation Score (CAS) system. Calibration is rarely assessed in clinical prediction models, yet it is a key factor in determining access to lung transplant. We assessed the calibration of the WL-lung allocation score (LAS)/CAS models and developed alternative models to minimize miscalibration. Scientific Registry of Transplant Recipients data from 2015 to 2020 were used to assess the calibration of the WL model and for subgroups (age, sex, diagnosis, and race/ethnicity). Three recalibrated models were developed and compared: (1) simple recalibration model (SRM), (2) weighted recalibration model 1 (WRM1), and (3) weighted recalibration model 2 (WRM2). The current WL-LAS/CAS model underestimated risk for 78% of individuals (predicted mortality risk, <42%) and overpredicted risk for 22% of individuals (predicted mortality risk, ≥42%), with divergent results among subgroups. Error measures improved in SRM, WRM1, and WRM2. SRM generally preserved candidate rankings, whereas WRM1 and WRM2 led to changes in ranking by age and diagnosis. Differential miscalibration occurred in the WL-LAS/CAS model, which improved with recalibration measures. Further inquiry is needed to develop mortality models in which risk predictions approximate observed data to ensure accurate ranking and timely access to transplant. IMPACT: With changes to the lung transplant allocation system planned in 2023, evaluation of the accuracy and precision of survival models used to rank candidates for lung transplant is important. The waitlist model underpredicts risk for 78% of US transplant candidates with an unequal distribution of miscalibration across subgroups leading to inaccurate ranking of transplant candidates. This work will serve to inform future efforts to improve modeling efforts in the US lung transplant allocation system.