A placebo-controlled, crossover trial to investigate the efficacy of tiotropium bromide or placebo added to usual care in stable symptomatic post-hematopoietic stem cell transplantation (HSCT) bronchiolitis obliterans syndrome (BOS).

BACKGROUND: Despite the fundamental progress in hematopoietic stem cell transplant, this treatment is also associated with complications. Graft-versus-host disease is a possible complication of HSCT. Bronchiolitis obliterans syndrome (BOS) is the pulmonary form of this syndrome. Due to the high morbidity and mortality rate of BOS, various studies have been conducted in the field of drug therapy for this syndrome, although no standard treatment has yet been proposed. According to the hypotheses about the similarities between BOS and chronic obstructive pulmonary disease, the idea of using tiotropium bromide as a bronchodilator has been proposed. METHOD/DESIGN: A randomized, double-blind, placebo-controlled, and crossover clinical trial is being conducted to evaluate the efficacy of tiotropium in patients with BOS. A total of 20 patients with BOS were randomly assigned (1:1) to receive a once-daily inhaled capsule of either tiotropium bromide (KP-Tiova Rotacaps 18 mcg, Cipla, India) or placebo for 1 month. Patients will receive tiotropium bromide or placebo Revolizer added to usual standard care. Measurements will include spirometry and a 6-min walking test. ETHICS/DISSEMINATION: This study was approved by the Research Ethics Committees of Imam Khomeini Hospital Complex, Tehran University of Medical Science. Recruitment started in September 2022, with 20 patients randomized. The treatment follow-up of participants with tiotropium is currently ongoing and is due to finish in April 2024. The authors will disseminate the findings in peer-reviewed publications, conferences, and seminar presentations. TRIAL REGISTRATION: Iranian Registry of Clinical Trial (IRCT) IRCT20200415047080N3. Registered on 2022-07-12, 1401/04/21.

[Paraneoplastic pemphigus with underlying Castleman's disease in a 16-year-old girl]. / Morbus Castleman-assoziierter paraneoplastischer Pemphigus bei einer 16-jährigen Patientin.

Paraneoplastic pemphigus is a rare, life-threatening autoimmune disease that is clinically characterized by mostly extensive and refractory mucosal erosions and polymorphous skin lesions. We report here on a 16-year-old girl with isolated oral erosions, in whom mucosal pemphigoid was initially suspected and after treatment with prednisolone and dapsone marked improvement was achieved. However, a few months later the patient developed massive respiratory insufficiency as a result of bronchiolitis obliterans, so that a lung transplant was planned. As part of the preparatory diagnostic workup, unicentric, abdominally localized Castleman's disease was diagnosed, which ultimately led to the diagnosis of paraneoplastic pemphigus as evidenced by envoplakin autoantibodies. Tumor resection and subsequent lung transplantation achieved good results with sustained mucocutaneous remission.

A review of the therapeutic potential of the cysteinyl leukotriene antagonist Montelukast in the treatment of bronchiolitis obliterans syndrome following lung and hematopoietic-stem cell transplantation and its possible mechanisms.

Lung and hematopoietic stem cell transplantation are therapeutic modalities in chronic pulmonary and hematological diseases, respectively. One of the complications in these patients is the development of bronchiolitis obliterans syndrome (BOS). The efficacy and safety of available treatment strategies in BOS remain a challenge. A few mechanisms have been recognized for BOS in lung transplant and graft-versus-host disease (GVHD) patients involving the TH-1 and TH-2 cells, NF-kappa B, TGF-b, several cytokines and chemokines, and cysteinyl leukotrienes (CysLT). Montelukast is a highly selective CysLT receptor antagonist that has been demonstrated to exert anti-inflammatory and anti-fibrotic effects in abundant experiments. One area of interest for the use of montelukast is lung transplants or GVHD-associated BOS. Herein, we briefly review data regarding the mechanisms involved in BOS development and montelukast administration as a treatment modality for BOS, and finally, the possible relationship between CysLTs antagonism and BOS improvement will be discussed.

A review of the therapeutic potential and possible mechanism of Montelukast in the treatment of bronchiolitis obliterans syndrome following lung and hematopoietic stem cell transplantationLung and bone marrow transplantation are therapeutic modalities in chronic diseases of the lungs and the blood, respectively. One of the complications in these patients is the development of Bronchiolitis obliterans syndrome (BOS). The efficacy and safety of available treatment strategies in BOS remain a challenge. A few mechanisms for BOS in lung transplant and graft-versus-host disease (GVHD) patients involving many immune components have been recognized. Cysteinyl leukotrienes are products of plasma membrane phospholipids that increase smooth muscle contraction, microvascular permeability, and airway mucus secretion. Montelukast is a highly selective cysteinyl leukotriene receptor blocker demonstrated to exert anti-inflammatory and anti-fibrotic effects. One area of interest for the use of montelukast is in lung transplant- or GVHD-associated BOS. In this article, we briefly review data regarding the mechanisms involved in BOS development and montelukast administration as a treatment modality for BOS. Finally, the possible relationship between cysteinyl leukotriene inhibition and BOS improvement will be discussed.

Bronquiolitis obliterante posinfecciosa secundaria a adenovirus / Post-infectious bronchiolitis obliterans secondary to adenovirus

La bronquiolitis obliterante es una rara enfermedad respiratoria obstructiva crónica, secundaria a una agresión de las vías respiratorias inferiores que provoca inflamación y obliteración, parcial o total, de las mismas. Existen diferentes causas que la provocan, siendo la infecciosa la más frecuente en Pediatría, principalmente, por adenovirus. Se presenta el caso de un lactante varón de 18 meses de edad, con el antecedente de ingreso a los 8 meses en la unidad de cuidados intensivos pediátricos por bronquitis secundaria a virus respiratorio sincitial y adenovirus. Posteriormente a este episodio, presenta de forma persistente dificultad respiratoria y auscultación pulmonar patológica. La tomografía computarizada pulmonar de alta resolución muestra patrón en mosaico con áreas de atrapamiento aéreo y disminución del calibre vascular en las zonas afectas, hallazgos sugestivos de bronquiolitis obliterante. (AU)

Bronchiolitis obliterans is a rare chronic obstructive respiratory disease secondary to damage of the lower respiratory tract causing inflammation and partial or total obliteration of it. There are different causes, being infectious the most frequent in pediatrics, mainly due to adenovirus. We present the case of an 18-month-old male infant with a history of admission to the Pediatric Intensive Care Unit at 8 months of age due to bronchitis secondary to respiratory syncytial virus and adenovirus. After this episode, he presented persistent respiratory distress and pathological pulmonary auscultation. High resolution pulmonary computed tomography showed a mosaic pattern with areas of air trapping and decreased vascular caliber in the affected areas, findings suggestive of bronchiolitis obliterans. (AU)

IL-27 Levels in Bronchoalveolar Lavage Fluid in Children with Post-infectious Bronchiolitis Obliterans.

Background: Pulmonary neutrophils may play a crucial role in the development of bronchiolitis obliterans (BO) following measles virus infection. IL-27 could potentially have a negative regulatory effect on the release of reactive oxygen species and cytotoxic granules in neutrophils. Objective: To investigate the levels of IL-27 in the bronchoalveolar lavage fluid (BALF) of children with post-infectious bronchiolitis obliterans (PIBO) and analyze the relationship between IL-27 levels and neutrophil proportions. Methods: A total of 24 children with PIBO were recruited for the experimental group, while 23 children with bronchial foreign bodies were included in the control group. Bronchoscopic alveolar lavage was performed in both groups. The levels of IL-27 in BALF were measured using enzyme-linked immunosorbent assay (ELISA). The proportions of neutrophils in BALF were determined by smear staining. The relationship between the levels of IL-27 in BALF and the neutrophil proportions was analyzed by the Pearson test. Results: The levels of IL-27 in BALF were significantly lower in children with PIBO compared to children with bronchial foreign bodies (p<0.05). Additionally, the proportions of neutrophils in BALF were significantly higher in children with PIBO compared to children with bronchial foreign bodies (p<0.05). The levels of IL-27 were negatively correlated with the neutrophil proportions in BALF in children with PIBO (p<0.05), but not in children with bronchial foreign bodies (p>0.05). Conclusion: The present study suggests that a decrease in IL-27 may be associated with an increase in neutrophils in BALF and may contribute to the pathogenesis of PIBO.

Ventilatory capacity in CLAD is driven by dysfunctional airway structure.

BACKGROUND: Chronic lung allograft dysfunction (CLAD) encompasses three main phenotypes: bronchiolitis obliterans syndrome (BOS), restrictive allograft syndrome (RAS) and a Mixed phenotype combining both pathologies. How the airway structure in its entirety is affected in these phenotypes is still poorly understood. METHODS: A detailed analysis of airway morphometry was applied to gain insights on the effects of airway remodelling on the distribution of alveolar ventilation in end-stage CLAD. Ex vivo whole lung µCT and tissue-core µCT scanning of six control, six BOS, three RAS and three Mixed explant lung grafts (9 male, 9 female, 2014-2021, Leuven, Belgium) were used for digital airway reconstruction and calculation of airway dimensions in relation to luminal obstructions. FINDINGS: BOS and Mixed explants demonstrated airway obstructions of proximal bronchioles (starting at generation five), while RAS explants particularly had airway obstructions in the most distal bronchioles (generation >12). In BOS and Mixed explants 76% and 84% of bronchioles were obstructed, respectively, while this was 22% in RAS. Bronchiolar obstructions were mainly caused by lymphocytic inflammation of the airway wall or fibrotic remodelling, i.e. constrictive bronchiolitis. Proximal bronchiolectasis and imbalance in distal lung ventilation were present in all CLAD phenotypes and explain poor lung function and deterioration of specific lung function parameters. INTERPRETATION: Alterations in the structure of conducting bronchioles revealed CLAD to affect alveolar ventilatory distribution in a regional fashion. The significance of various obstructions, particularly those associated with mucus, is highlighted. FUNDING: This research was funded with the National research fund Flanders (G060322N), received by R.V.

Restrictive Allograft Syndrome After COVID-19 Pneumonia: A Case Report.

Chronic lung allograft dysfunction (CLAD) continues to be the leading cause of death in the long term after lung transplantation (LTx). CLAD has the following two main subtypes: bronchiolitis obliterans syndrome (BOS) and restrictive allograft syndrome (RAS). BOS features obstructive lung dysfunction, while RAS features restrictive lung dysfunction. Overall, RAS has a worse prognosis. The pathophysiology of CLAD is not fully understood; however, pulmonary infections can trigger CLAD, including coronavirus disease 2019 (COVID-19) pneumonia. Here, we describe a case of a 55-year-old female who received LTx about seven years ago and developed RAS after COVID-19 pneumonia. RAS was ultimately diagnosed based on the clinical course and imaging findings. Steroid pulse therapy and empirical antimicrobial therapy were initiated, but respiratory failure progressed, and the patient died 139 days after COVID-19 diagnosis, and 83 days after dyspnea progression. Clinicians should be aware of unusual stair-step clinical courses and imaging features in a given setting of pulmonary infection including COVID-19 to suspect CLAD in lung transplant patients.

Association between cytomegalovirus viremia and long-term outcomes in lung transplant recipients.

Although cytomegalovirus (CMV) viremia/DNAemia has been associated with reduced survival after lung transplantation, its association with chronic lung allograft dysfunction (CLAD) and its phenotypes is unclear. We hypothesized that, in a modern era of CMV prophylaxis, CMV DNAemia would still remain associated with death, but also represent a risk factor for CLAD and specifically restrictive allograft syndrome (RAS)/mixed phenotype. This was a single-center retrospective cohort study of all consecutive adult, first, bilateral-/single-lung transplants done between 2010-2016, consisting of 668 patients. Risks for death/retransplantation, CLAD, or RAS/mixed, were assessed by adjusted cause-specific Cox proportional-hazards models. CMV viral load (VL) was primarily modeled as a categorical variable: undetectable, detectable to 999, 1000 to 9999, and ≥10 000 IU/mL. In multivariable models, CMV VL was significantly associated with death/retransplantation (≥10 000 IU/mL: HR = 2.65 [1.78-3.94]; P < .01), but was not associated with CLAD, whereas CMV serostatus mismatch was (D+R-: HR = 2.04 [1.30-3.21]; P < .01). CMV VL was not associated with RAS/mixed in univariable analysis. Secondary analyses with a 7-level categorical or 4-level ordinal CMV VL confirmed similar results. In conclusion, CMV DNAemia is a significant risk factor for death/retransplantation, but not for CLAD or RAS/mixed. CMV serostatus mismatch may have an impact on CLAD through a pathway independent of DNAemia.

Detection of Bronchiolitis Obliterans Syndrome Using Nitrogen Multiple Breath Washout in Children Posthemopoietic Stem Cell Transplant.

Bronchiolitis obliterans syndrome (BOS) is a severe complication following hemopoietic stem cell transplantation (HSCT) and is often undetected until there is significant deterioration in pulmonary function. Lung clearance index (LCI2.5) derived from the nitrogen multiple breath washout (N2MBW) test may be more feasible and sensitive than spirometry, which is currently used for surveillance and detection of BOS. We aimed to examine the feasibility of performing surveillance N2MBW in children post-HSCT, and in an exploratory analysis, determine if LCI2.5 led to earlier detection of BOS when compared to spirometric indices. Participants aged 5 to 17 years were recruited prior to receiving HSCT into a prospective, single-center, feasibility study at the Royal Children's Hospital, Melbourne. N2MBW and spirometry were performed within the month prior to transplant and repeated at 3, 6, 9, and 12 months post-transplant. Data were also collected on the presence of graft-versus-host (GVHD) disease in any organ, including the lungs. Twenty-one (12 male) children with a mean age of 13.4 (range 9.2 to 17.1) years at recruitment participated in this study. Prior to HSCT, all participants had normal LCI2.5, while 16 (76%) demonstrated normal forced expiratory volume in 1 second (FEV1). Ninety-nine percent of N2MBW tests were technically acceptable, compared with 66% of spirometry tests. Three participants developed BOS, while 2 participants died of other respiratory complications. At 6 and 12 months post-transplant, the BOS group had increases in LCI2.5 ranging from 3 to 5 units and mean reductions in FEV1 % predicted of 40% to 53% relative to pre HSCT values, respectively. In those who developed BOS, post-HSCT LCI2.5 values were significantly worse when compared with the no BOS group (P < .001). Relative changes in LCI2.5 and FEV1 were both predictive of BOS at 6 months post HSCT. This study demonstrates that N2MBW is a more feasible test compared with spirometry in children post HSCT. However, in an exploratory analysis, LCI2.5 did not lead to earlier detection of BOS, when compared to spirometry.

Single-cell resolution of human airway epithelial cells exposed to bronchiolitis obliterans-associated chemicals.

Bronchiolitis obliterans (BO) is a fibrotic lung disease characterized by progressive luminal narrowing and obliteration of the small airways. In the nontransplant population, inhalation exposure to certain chemicals is associated with BO; however, the mechanisms contributing to disease induction remain poorly understood. This study's objective was to use single-cell RNA sequencing for the identification of transcriptomic signatures common to primary human airway epithelial cells after chemical exposure to BO-associated chemicals-diacetyl or nitrogen mustard-to help explain BO induction. Primary airway epithelial cells were cultured at air-liquid interface and exposed to diacetyl, nitrogen mustard, or control vapors. Cultures were dissociated and sequenced for single-cell RNA. Differential gene expression and functional pathway analyses were compared across exposures. In total, 75,663 single cells were captured and sequenced from all exposure conditions. Unbiased clustering identified 11 discrete phenotypes, including 5 basal, 2 ciliated, and 2 secretory cell clusters. With chemical exposure, the proportion of cells assigned to keratin 5+ basal cells decreased, whereas the proportion of cells aligned to secretory cell clusters increased compared with control exposures. Functional pathway analysis identified interferon signaling and antigen processing/presentation as pathways commonly upregulated after diacetyl or nitrogen mustard exposure in a ciliated cell cluster. Conversely, the response of airway basal cells differed significantly with upregulation of the unfolded protein response in diacetyl-exposed basal cells, not seen in nitrogen mustard-exposed cultures. These new insights provide early identification of airway epithelial signatures common to BO-associated chemical exposures.NEW & NOTEWORTHY Bronchiolitis obliterans (BO) is a devastating fibrotic lung disease of the small airways, or bronchioles. This original manuscript uses single-cell RNA sequencing for identifying common signatures of chemically exposed airway epithelial cells in BO induction. Chemical exposure reduced the proportion of keratin 5+ basal cells while increasing the proportion of keratin 4+ suprabasal cells. Functional pathways contributory to these shifts differed significantly across exposures. These new results highlight similarities and differences in BO induction across exposures.

Risk factors and prediction models for bronchiolitis obliterans after severe adenoviral pneumonia.

Severe adenoviral pneumonia (SAP) can cause post-infectious bronchiolitis obliterans (PIBO) in children. We aimed to investigate the relevant risk factors for PIBO and develop a predictive nomogram for PIBO in children with SAP. This prospective study analysed the clinical data of hospitalised children with SAP and categorised them into the PIBO and non-PIBO groups. Least absolute shrinkage and selection operator (LASSO) regressions were applied to variables that exhibited significant intergroup differences. Logistic regression was adopted to analyse the risk factors for PIBO. Additionally, a nomogram was constructed, and its effectiveness was assessed using calibration curves, C-index, and decision curve analysis. A total of 148 hospitalised children with SAP were collected in this study. Among them, 112 achieved favourable recovery, whereas 36 developed PIBO. Multivariable regression after variable selection via LASSO revealed that aged < 1 year (OR, 2.38, 95% CI, 0.82-6.77), admission to PICU (OR, 24.40, 95% CI, 7.16-105.00), long duration of fever (OR, 1.16, 95% CI, 1.04-1.31), and bilateral lung infection (OR, 8.78, 95% CI, 1.32-195.00) were major risk factors for PIBO. The nomogram model included the four risk factors: The C-index of the model was 0.85 (95% CI, 0.71-0.99), and the area under the curve was 0.85 (95% CI, 0.78-0.92). The model showed good calibration with the Hosmer-Lemeshow test (χ2 = 8.52, P = 0.38) and was useful in clinical settings with decision curve analysis. CONCLUSION: Age < 1 year, PICU admission, long fever duration, and bilateral lung infection are independent risk factors for PIBO in children with SAP. The nomogram model may aid clinicians in the early diagnosis and intervention of PIBO. WHAT IS KNOWN: • Adenoviruses are the most common pathogens associated with PIBO. • Wheezing, tachypnoea, hypoxemia, and mechanical ventilation are the risk factors for PIBO. WHAT IS NEW: • Age < 1 year, admission to PICU, long duration of fever days, and bilateral lung infection are independent risk factors for PIBO in children with SAP. • A prediction model presented as a nomogram may help clinicians in the early diagnosis and intervention of PIBO.

Sleep and quality of life characteristics in a pediatric population with chronic obstructive respiratory diseases.

PURPOSE: To describe sleep and quality of life of pediatric patients with chronic obstructive respiratory diseases and to ascertain whether or not sleep quality correlates with quality of life in this population. METHODS: Participants aged 5 to 18 years with cystic fibrosis (CF), severe asthma, or postinfectious bronchiolitis obliterans (PIBO) receiving regular follow-up at a pediatric respiratory medicine center were recruited. Two questionnaires were used: the Brazilian version of the Sleep Disturbance Scale for Children (SDSC) and the Pediatric Quality of Life Inventory (Peds-QL). RESULTS: A total of 46 individuals were included: 30 with CF, 9 with severe asthma, and 7 with PIBO. Almost two-thirds of the patients and their parents or guardians scored at least 39 points on the SDSC, suggesting poor sleep quality. Significantly higher overall median scores were observed in those with severe asthma. Patients and their parents or guardians scored a median of 77 and 80 points respectively on the Peds-QL, with parents of patients with CF scoring higher than any other group. There was a moderate inverse correlation between sleep disorders and quality of life (r = - 0.532 for patients and r = - 0.606 for parents; p < 0.001). CONCLUSION: Children and adolescents with chronic obstructive respiratory diseases experience impairment in their sleep quality and quality of life. Sleep disorders and quality of life have a moderate negative correlation.

Castleman disease of plasma cell type accompanied with bronchiolitis obliterans: a case report and review of the literature.

BACKGROUND: Castleman disease, also known as giant lymph node hyperplasia or angiofollicular lymph node hyperplasia, is a highly heterogeneous clinicopathological entity that belongs to the family lymphoproliferative disorders. Castleman disease accompanied by bronchiolitis obliterans is uncommon and often poses a great diagnostic challenge, which is easily confused with respiratory diseases and impeding the correct diagnosis and treatment. The main aim in presenting such rare case studies is to raise awareness and expand the diagnostic horizon of clinicians for appropriate management. CASE PRESENTATION: Here, we present a 69-year-old Chinese male who was admitted to our hospital due to right chest pain for 6 months, accompanied by cough, expectoration, and fever. Laboratory examinations revealed elevated immunoglobulin G and C-reactive protein, and normal serum levels of tumor markers and interleukin-6. Computed tomography scan detected diffuse bronchial wall thickening and patchy area of air trapping consistent with small airway disease. Pulmonary function test showed mild small airway obstructive ventilation dysfunction and moderate decrease in diffusion capacity. The pathological result of the right axillary lymph node was consistent with the plasma cell type Castleman disease. According to the above examinations, the patient was finally diagnosed with the plasma cell type Castleman disease accompanied with bronchiolitis obliterans. He received immunosuppressive medication after surgery and has been followed up for 11 months. Now the patient is currently in stable condition without recurrence. CONCLUSION: Castleman disease is a rare lymphoproliferative disorder with a variety of symptoms. At present, the treatment of Castleman disease accompanied with bronchiolitis obliterans is mostly based on experiences or previous case reports, and there is no standard treatment. Here, we report an uncommon case of Castleman disease accompanied with bronchiolitis obliterans in which the patient received immunosuppressive medication after surgery and has been followed up for 11 months without experiencing a recurrence, which may deepen and extend our understanding of this disease.

Short-term outcomes after third-time lung transplantation: A single institution experience.

BACKGROUND: Reoperative lung transplantation (LTx) survival has improved over time such that a growing number of patients may present for third-time LTx (L3Tx). To understand the safety of L3Tx, we evaluated perioperative outcomes and 3-year survival after L3Tx at a high-volume US LTx center. METHODS: This retrospective study included all patients who underwent bilateral L3Tx at our institution. Using an optimal matching technique, a primary LTx (L1Tx) cohort was matched 1:2 and a second-time LTx (L2Tx) cohort 1:1. Recipient, operative, and donor characteristics, perioperative outcomes, and 3-year survival were compared among L1Tx, L2Tx, and L3Tx groups. RESULTS: Eleven L3Tx, 11 L2Tx, and 22 L1Tx recipients were included. Among L3Tx recipients, median age at transplant was 37 years and most (73%) had cystic fibrosis. L3Tx was performed median 6.0 and 10.6 years after L2Tx and L1Tx, respectively. Compared to L1Tx and L2Tx recipients, L3Tx recipients had greater intraoperative transfusion requirements, a higher incidence of postoperative complications, and a higher rate of unplanned reoperation. Rates of grade 3 primary graft dysfunction at 72 hours, extracorporeal membrane oxygenation at 72 hours, reintubation, and in-hospital mortality were similar among groups. There were no differences in 3-year patient (log-rank p = 0.61) or rejection-free survival (log-rank p = 0.34) after L1Tx, L2Tx, and L3Tx. CONCLUSIONS: At our institution, L3Tx was associated with similar perioperative outcomes and 3-year patient survival compared to L1Tx and L2Tx. L3Tx represents the only safe treatment option for patients with allograft failure after L2Tx; however, further investigation is needed to understand the long-term survival and durability of L3Tx.

Bronchiolitis Obliterans With Recurrent Pneumothorax After Allogeneic Bone Marrow Transplantation.

Bronchiolitis obliterans syndrome (BOS) is a non-infectious pulmonary complication that can occur in patients who have undergone allogeneic bone marrow transplantation (BMT). BOS is characterized by the irreversible narrowing and obstruction of bronchi, resulting in severe respiratory distress and poor outcomes. This case report focuses on the complex management of a patient with a multifaceted medical history. A 20-year-old man was initially diagnosed with precursor B lymphoblastic lymphoma and subsequently underwent allogeneic BMT. Nine months later, the patient was diagnosed with bronchiolitis obliterans with graft-versus-host disease, resulting in the development of BOS. Remarkably, 12 years after BMT, the patient was registered for lung transplantation. However, one year after registration, the patient developed a left pneumothorax. Despite rigorous efforts, including continuous thoracic drainage and autologous pleurodesis, the pneumothorax did not respond to treatment and required video-assisted thoracic surgery (VATS) bullectomy. The preoperative assessment revealed a challenging clinical finding characterized by the need for home oxygen therapy (5 L/min with a nasal cannula), severe Hugh-Jones classification IV-V, and marked hypercapnia (partial pressure of carbon dioxide (pCO2), 76 mmHg). Imaging studies, including high-resolution computed tomography and chest radiography, revealed hyperinflation, emphysematous changes, and bronchiectasis across all lung lobes, further complicating the patient's condition. Intraoperative management had the unique challenges of persistent hypoxia (P/F ratio 65-80), positive end-expiratory pressure of 5 cmH2O, and low tidal volumes (1.6-2.0 mL/kg) during one-lung ventilation. To address these problems, both-lung ventilation had to be performed intermittently. However, hyperventilation remained unmanageable, with maximum pCO2 values reaching 140 mmHg. Following surgery, the patient had to be admitted to the intensive care unit in an intubated state. Fortunately, the following day, the patient's condition improved markedly, his state of consciousness was clear (Glasgow Coma Scale 15) and his pCO2 level improved (66 mmHg) with spontaneous breath. This course of events allowed extubation and the patient was discharged to the general ward only two days after surgery. This case highlights the critical importance of a comprehensive preoperative assessment, including advanced imaging, when managing patients with BOS and complex pulmonary complications. Furthermore, it highlights the complexity and difficulty of perioperative respiratory management in such cases.

Postinfectious bronchiolitis obliterans in children: case series at a pediatric hospital in Peru.

BACKGROUND: Postinfectious bronchiolitis obliterans is a rare lung disease; there are limited reports in South America. CASE REPORT: We report 10 patients with this disease diagnosed at the Instituto Nacional de Salud del Niño-Breña (Lima-Peru). The median age at diagnosis was 19 months and all patients had a history of severe acute respiratory infection. The most frequent symptoms were cough, respiratory distress, wheezing, and hypoxemia. The mosaic attenuation pattern was the most frequent on the tomography. All the patients had positive serology for adenovirus. The treatment received was methylprednisolone pulses, azithromycin, hydroxychloroquine, and inhaled corticosteroids. No patient died during the follow-up. CONCLUSIONS: In previously healthy children with a history of severe acute respiratory infection and persistent bronchial obstructive symptoms, the diagnosis of postinfectious bronchiolitis obliterans should be considered. This is the first report in Peru with a therapeutic regimen adapted to our institution.

INTRODUCCIÓN: La bronquiolitis obliterante postinfecciosa es una enfermedad pulmonar poco frecuente; existen limitados reportes en Sudamérica. CASO CLÍNICO: En esta serie se reportan 10 pacientes con esta enfermedad diagnosticados en el Instituto Nacional de Salud del Niño-Breña (Lima-Perú). La mediana de edad al diagnóstico fue de 19 meses. Todos los pacientes presentaron el antecedente de infección respiratoria aguda grave. Los síntomas más frecuentes fueron tos, dificultad respiratoria, sibilancias e hipoxemia; el patrón de atenuación en mosaico fue la característica más frecuente en la tomografía. Todos tenían serología positiva para adenovirus. Se administró tratamiento con pulsos de metilprednisolona, azitromicina, hidroxicloroquina y corticoides inhalados. Ningún paciente falleció durante el seguimiento. CONCLUSIONES: En los niños previamente sanos con antecedente de infección respiratoria aguda grave y sintomatología obstructivo bronquial persistente se debe considerar el diagnóstico de bronquiolitis obliterante postinfecciosa. Este es el primer reporte en Perú con un régimen terapéutico adaptado a nuestra institución.

Chronic Lung Allograft Dysfunction Is Associated with Significant Disability after Lung Transplantation-A Burden of Disease Analysis in 1025 Cases.

BACKGROUND: Chronic lung allograft dysfunction (CLAD) is the leading cause of death after the first postoperative years of lung transplantation (LTx). OBJECTIVE: To assess the number of disability-adjusted life years (DALYs) per patient with severe CLAD. METHODS: The clinical and demographic data of patients who received their lung transplantation between 2010 and 2020 in the Hanover Medical School (Germany) were evaluated. RESULTS: A total of 1025 lung transplant patients were followed for a median of 51 months (4.25 years); the median age at transplantation was 52.8 (interquartile range (IQR) 19) years. More than a quarter of transplant patients (271/1025 or 26.4%) developed CLAD, mostly (60%) of the bronchiolitis obliterans syndrome (BOS) phenotype. Of the CLAD patients, 99, or 36.5%, suffered from significant disability, which on average occurred after 2 years (IQR 2.55). The survival of CLAD patients with disability after transplantation was significantly lower compared to that of patients without CLAD (median 4.04 versus 5.41 years). Adjusted to the DALY estimation approach, CLAD patients lost 1.29 life years (YLL) and lived for 0.8 years with their disability (YLD), adding up to 2.09 DALYs (range 1.99-2.72) per patient. CONCLUSIONS: CLAD after lung transplantation is a major public health problem and is associated with substantial disability and costs. Further work is needed to develop therapeutic interventions that reduce its development.

Monitoring regulatory T cells as a prognostic marker in lung transplantation.

Lung transplantation is the major surgical procedure, which restores normal lung functioning and provides years of life for patients suffering from major lung diseases. Lung transplant recipients are at high risk of primary graft dysfunction, and chronic lung allograft dysfunction (CLAD) in the form of bronchiolitis obliterative syndrome (BOS). Regulatory T cell (Treg) suppresses effector cells and clinical studies have demonstrated that Treg levels are altered in transplanted lung during BOS progression as compared to normal lung. Here, we discuss levels of Tregs/FOXP3 gene expression as a crucial prognostic biomarker of lung functions during CLAD progression in clinical lung transplant recipients. The review will also discuss Treg mediated immune tolerance, tissue repair, and therapeutic strategies for achieving in-vivo Treg expansion, which will be a potential therapeutic option to reduce inflammation-mediated graft injuries, taper the toxic side effects of ongoing immunosuppressants, and improve lung transplant survival rates.

Bronquiolitis obliterante postinfecciosa en niños: serie de casos en un hospital pediátrico de Perú / Postinfectious bronchiolitis obliterans in children: case series at a pediatric hospital in Peru

Resumen Introducción: La bronquiolitis obliterante postinfecciosa es una enfermedad pulmonar poco frecuente; existen limitados reportes en Sudamérica. Caso clínico: En esta serie se reportan 10 pacientes con esta enfermedad diagnosticados en el Instituto Nacional de Salud del Niño-Breña (Lima-Perú). La mediana de edad al diagnóstico fue de 19 meses. Todos los pacientes presentaron el antecedente de infección respiratoria aguda grave. Los síntomas más frecuentes fueron tos, dificultad respiratoria, sibilancias e hipoxemia; el patrón de atenuación en mosaico fue la característica más frecuente en la tomografía. Todos tenían serología positiva para adenovirus. Se administró tratamiento con pulsos de metilprednisolona, azitromicina, hidroxicloroquina y corticoides inhalados. Ningún paciente falleció durante el seguimiento. Conclusiones: En los niños previamente sanos con antecedente de infección respiratoria aguda grave y sintomatología obstructivo bronquial persistente se debe considerar el diagnóstico de bronquiolitis obliterante postinfecciosa. Este es el primer reporte en Perú con un régimen terapéutico adaptado a nuestra institución.

Abstract Background: Postinfectious bronchiolitis obliterans is a rare lung disease; there are limited reports in South America. Case report: We report 10 patients with this disease diagnosed at the Instituto Nacional de Salud del Niño-Breña (Lima-Peru). The median age at diagnosis was 19 months and all patients had a history of severe acute respiratory infection. The most frequent symptoms were cough, respiratory distress, wheezing, and hypoxemia. The mosaic attenuation pattern was the most frequent on the tomography. All the patients had positive serology for adenovirus. The treatment received was methylprednisolone pulses, azithromycin, hydroxychloroquine, and inhaled corticosteroids. No patient died during the follow-up. Conclusions: In previously healthy children with a history of severe acute respiratory infection and persistent bronchial obstructive symptoms, the diagnosis of postinfectious bronchiolitis obliterans should be considered. This is the first report in Peru with a therapeutic regimen adapted to our institution.