Flexible bronchoscopy in pediatric lung transplantation.

Pediatric lung transplantation represents a treatment option for children with advanced lung disease or pulmonary vascular disorders who are deemed an appropriate candidate. Pediatric flexible bronchoscopy is an important and evolving field that is highly relevant in the pediatric lung transplant population. It is thus important to advance our knowledge to better understand how care for children after lung transplant can be maximally optimized using pediatric bronchoscopy. Our goals are to continually improve procedural skills when performing bronchoscopy and to decrease the complication rate while acquiring adequate samples for diagnostic evaluation. Attainment of these goals is critical since allograft assessment by bronchoscopic biopsy is required for histological diagnosis of acute cellular rejection and is an important contributor to establishing chronic lung allograft dysfunction, a common complication after lung transplant. Flexible bronchoscopy with bronchoalveolar lavage and transbronchial lung biopsy plays a key role in lung transplant graft assessment. In this article, we discuss the application of bronchoscopy in pediatric lung transplant evaluation including historical approaches, our experience, and future directions not only in bronchoscopy but also in the evolving pediatric lung transplantation field. Pediatric flexible bronchoscopy has become a vital modality for diagnosing lung transplant complications in children as well as assessing therapeutic responses. Herein, we review the value of flexible bronchoscopy in the management of children after lung transplant and discuss the application of novel techniques to improve care for this complex pediatric patient population and we provide a brief update about new diagnostic techniques applied in the growing lung transplantation field.

Experience of flexible bronchoscopy in the pediatric pulmonary diseases clinic.

Introduction: Flexible bronchoscopy is a valuable method in the diagnosis and treatment of respiratory tract diseases in children. This study aimed to examine the indications for and results of flexible bronchoscopy in children. Materials and Methods: The study included patients aged 0-18 years who underwent flexible bronchoscopy between 1 January 2017 and 31 December 2022. The patients were evaluated for demographic characteristics, indications for bronchoscopy, comorbidities, bronchoscopy findings, and the results of bronchoalveolar lavage. Result: During the defined study period, a total of 410 flexible bronchoscopy procedures were performed. 51.9% of the patient population were male, and 48.1% were female, with a mean age of 96.93 ± 63.45 months. The most common indication for flexible bronchoscopy was recurrent lower respiratory tract infection (26.8%), followed by chronic cough (19.1%). The bronchoalveolar lavage culture results showed that the most commonly isolated microorganisms were H. influenzae non-type b (7.8%) followed by M. catarrhalis (7.3%). Mucus obstruction and secretion (33.0%) constituted the most common bronchoscopic findings, while the flexible bronchoscopy examination was normal in 27% of patients. No serious complications occurred in any patient during or after the procedure. Conclusions: The results of this study demonstrated that the most common indication for flexible bronchoscopy was recurrent lower respiratory tract infection and the most common bronchoscopy finding was purulent secretion with mucus obstruction. Flexible bronchoscopy is an important diagnostic and treatment tool for patients with recurrent respiratory symptoms. It is a highly valuable method as it enables direct visualization of the airways and facilitates the collection of bronchoalveolar lavage samples.

Effect of acyclovir therapy on the outcome of mechanically ventilated patients with lower respiratory tract infection and detection of herpes simplex virus in bronchoalveolar lavage: protocol for a multicentre, randomised controlled trial (HerpMV).

INTRODUCTION: Herpes simplex virus (HSV) is frequently detected in the respiratory tract of mechanically ventilated patients and is associated with a worse outcome. The aim of this study is to determine whether antiviral therapy in HSV-positive patients improves outcome. METHODS AND ANALYSIS: Prospective, multicentre, open-label, randomised, controlled trial in parallel-group design. Adult, mechanically ventilated patients with pneumonia and HSV type 1 detected in bronchoalveolar lavage (≥105 copies/mL) are eligible for participation and will be randomly allocated (1:1) to receive acyclovir (10 mg/kg body weight every 8 hours) for 10 days (or until discharge from the intensive care unit if earlier) or no intervention (control group). The primary outcome is mortality measured at day 30 after randomisation (primary endpoint) and will be analysed with Cox mixed-effects model. Secondary endpoints include ventilator-free and vasopressor-free days up to day 30. A total of 710 patients will be included in the trial. ETHICS AND DISSEMINATION: The trial was approved by the responsible ethics committee and by Germany's Federal Institute for Drugs and Medical Devices. The clinical trial application was submitted under the new Clinical Trials Regulation through CTIS (The Clinical Trials Information System). In this process, only one ethics committee, whose name is unknown to the applicant, and Germany's Federal Institute for Drugs and Medical Devices are involved throughout the entire approval process. Results will be published in a journal indexed in MEDLINE and CTIS. With publication, de-identified, individual participant data will be made available to researchers. TRIAL REGISTRATION NUMBER: NCT06134492.

Microbiological Rapid On-Site Evaluation for Pulmonary Infectious Diseases.

The prompt initiation of empirical anti-infective therapy is crucial in patients presenting with unexplained pulmonary infection. Although imaging acquisition is relatively straightforward in clinical practice, its lack of specificity often necessitates additional time-consuming tests such as sputum culture, bronchoalveolar-lavage fluid culture, or genetic sequencing to identify the underlying etiology of the disease accurately. Moreover, the limited efficacy of empirical anti-infective treatment may contribute to antibiotic misuse. Recent advancements in interpreting microbial background on rapid on-site evaluation (ROSE) slides have enabled clinicians to promptly obtain samples through bronchoscopy (e.g., alveolar lavage, mucosal brushing, tissue clamp), facilitating bedside staining and interpretation that provides essential microbial background information. Consequently, this establishes a foundation for developing targeted anti-infection treatment and individualized drug therapy plans. With a better understanding of which pathogens are causing infections in real-time, physicians can avoid unnecessary broad-spectrum antibiotics contributing to antibiotic resistance. Establishing a rapid and standardized M-ROSE workflow within respiratory medicine departments or intensive care units will greatly assist physicians in formulating accurate treatment strategies for patients, which holds significant clinical implications.

Three-minute nebulization of gentamicin in healthy dogs results in therapeutic concentrations in bronchoalveolar lavage fluid while remaining below the toxic range values in blood.

OBJECTIVE: To determine and compare the concentration of gentamicin in the lower airways and serum of healthy spontaneously breathing dogs after nebulization with 5% undiluted gentamicin during 3 versus 10 minutes. ANIMALS: 10 healthy experimental Beagles. METHODS: This was a prospective crossover study. A standardized bronchoalveolar lavage (BAL) procedure was performed in each dog after 1 week of administration of each of 2 different gentamicin nebulization protocols separated by a 1-week washout period. The 2 protocols consisted of nebulization of 5% undiluted gentamicin (50 mg/mL) twice daily either during 10 minutes per session (± 95 mg; 10-minute protocol) or 3 minutes per session (± 28 mg; 3-minute protocol). BAL fluid (BALF) was obtained under general anesthesia using a bronchoscope within 15 minutes after administration of the last nebulization. Blood was collected within 5 minutes after BALF collection. BALF and serum gentamicin concentrations were determined by particle-enhanced turbidimetric inhibition immunoassay. Concentrations between protocols were compared using a paired t test. RESULTS: Both BALF and serum gentamicin concentrations were higher after the 10-minute protocol compared with the 3-minute protocol (mean ± SD: 2.41 ± 0.87 mg/L vs 1.25 ± 0.31 mg/L, P = .001; and 1.02 ± 0.59 mg/L vs 0.31 ± 0.24 mg/L, P < .0001 in BALF and serum, respectively), while the BALF-to-serum ratio did not differ between the protocols (3.75 [1.37 to 5.75] (median [IQR]) in the 3-minute protocol vs 2.48 [2.02 to 2.67] in the 10-minute protocol; P = .754). CLINICAL RELEVANCE: A 3-minute nebulization of gentamicin seems to achieve sufficient concentrations of gentamicin in the BALF to have good efficacy against aminoglycoside-sensitive bacteria while remaining below the toxic range values in blood.

Ten-year experience of whole lung lavage in pediatric Pulmonary Alveolar Proteinosis.

BACKGROUND: Pulmonary Alveolar Proteinosis (PAP) is extremely rare and can be caused by hereditary dysfunction of the granulocyte macrophage colony-stimulating factor receptor (GM-CSF) receptor, autoantibodies against GM-CSF, or other diseases leading to alveolar macrophage (AM) dysfunction. This leads to protein accumulation in the lung and severe dyspnea and hypoxemia. Whole lung lavage (WLL) is the first line treatment strategy. METHODS: Here, we present data from more than ten years of WLL practice in pediatric PAP. WLL performed by the use of a single lumen or double lumen tube (SLT vs. DLT) were compared for technical features, procedure time, and adverse events. RESULTS: A total of n=57 procedures in six PAP patients between 3.5 and 14.3 years of age were performed. SLT based WLL in smaller children was associated with comparable rates of adverse events but with longer intervention times and postprocedural intensive care treatment when compared to DLT based procedures. DISCUSSION: Our data shows that WLL is feasible even in small children. DLT based WLL seems to be more effective, and our data supports the notion that it should be considered as early as possible in pediatric PAP. CONCLUSION: WLL lavage is possible in small PAP patients but should performed in close interdisciplinary cooperation and with age appropriate protocols.

Lipoid Pneumonia Caused by Esophageal Achalasia.

A 59-year-old man presented with esophageal achalasia complicated by lipoid pneumonia. Dysphagia and diffuse ground-glass shadows on computed tomography led to the diagnosis of esophageal achalasia. An analysis of bronchoalveolar lavage (BAL) revealed yellow BAL fluid, with two distinct layers. Oil droplets were observed in the upper layer. Macrophages that phagocytosed lipids were also observed. He was diagnosed with lipoid pneumonia secondary to esophageal achalasia. His lipoid pneumonia improved after peroral endoscopic myotomy because of the reduction in aspiration risk.

Impact of bronchoalveolar lavage on the management of immunocompromised hosts.

BACKGROUND: Respiratory infections are an important cause of morbidity and mortality in immunocompromised individuals. Fiberoptic bronchoscopy with bronchoalveolar lavage (BAL) is an important tool to detect infectious agents in immunocompromised patients with low respiratory tract infections (LRTI). RESEARCH QUESTION: BAL changes the management of immunocompromised patients with suspected LRTI. STUDY DESIGN AND METHODS: Immunocompromised patients with a suspicion of LRTI underwent diagnostic BAL. The primary composite outcome consisted of pre-defined modifications in the management of the immunocompromised patients following BAL. We quantified the impact of bronchoscopy up to 30 days after the procedure. RESULTS: A total of 2666 visits from 1301 patients were included in the study and immunosuppression was classified as haematological (n = 1040; 544 patients), solid organ transplantation (n = 666; 107 patients) and other causes (n = 960; 650 patients). BAL led to a change in management in 52.36% (n = 1396) of all cases. This percentage, as well as the 30-day mortality differed significantly amongst the three groups. Age, C-reactive protein and aetiology of infection determined significantly the risk of 30-day mortality in all patients. In 1.89% (n = 50) of all cases, a combination of 2 respiratory viral agents was identified and 24.23% (n = 646) were diagnosed with a single respiratory viral agent. INTERPRETATION: BAL leads to changes in management in the majority of immunosuppressed patients. There is a high prevalence of multimicrobial infections and respiratory viral infections in immunocompromised patients with respiratory symptoms. Individual virus infection is associated with diverse risk of a negative outcome.

Impacto de la evaluación pulmonar ecográfica durante un lavado pulmonar total: caso pediátrico de proteinosis alveolar pulmonar / The impact of lung ultrasound assessment during a whole lung lavage: a paediatric case of pulmonary alveolar proteinosis

El lavado pulmonar total (LPT) es la principal terapia para la proteinosis alveolar pulmonar (PAP). Formulamos la hipótesis de la aplicabilidad de la ecografía pulmonar (EP) para guiar el alcance de la inundación alveolar en un varón de 15 años. El LPT de cada pulmón consistió en la instilación de solución salina, seguida de quinesioterapia y drenaje de líquidos. En el primer LPT, el proceso se repitió hasta observar el aclaramiento macroscópico progresivo del líquido de lavado, con visualización simultánea de las fases de aireación pulmonar mediante EP. En la segunda etapa, se utilizó un patrón de EP para guiar la extensión del lavado. La aparición del patrón de tipo tisular mediante broncograma del fluido definió la terminación temprana de la infusión salina. En conclusión, la EP contribuyó a monitorizar las fases de la desaireación pulmonar a lo largo del LPT, y redujo la cantidad total de solución salina instilada, con el fin de minimizar sus complicaciones inherentes.(AU)

Whole lung lavage (WLL) is the first-line treatment for pulmonary alveolar proteinosis. We hypothesized that lung ultrasound (LUS) would guide flooding during treatment in a 15-year-old boy. WLL of each lung consisted of instillation of saline followed by kinesiotherapy and fluid drainage. In the first WLL, the lung was repeatedly flooded until the lavage fluid was clear on macroscopic examination. During this process, LUS was used to visualise lung aeration. In the second WLL, we used LUS signs to guide the lavage volume. The appearance of the fluid bronchogram sign showed that saline infusion could be stopped earlier than in the first lavage. In conclusion, LUS helped monitor the different stages of controlled lung de-aeration during WLL and reduce the total amount of saline used. This technique will also reduce the risk of WLL-related complications.(AU)

Cytokine release syndrome after bronchoalveolar lavage.

BACKGROUND: Immunosuppressed bone marrow transplant patients with pulmonary infiltrates routinely undergo bronchoscopy with bronchoalveolar lavage (BAL) to investigate potential etiologies. Cytokine release syndrome after BAL is unreported in the literature in general and in this patient population. CASE PRESENTATION: We report on an allogeneic bone marrow transplant patient with non-infectious organizing pneumonia of the lungs who developed delayed and rapidly progressive shock and hypoxia post-procedure over the course of 12 h resulting in intensive care unit admission for supportive care. BAL was characterized by a marked lymphocytic, cytotoxic T cell infiltrate on pathology and flow cytometry without clear evidence of infection. The patient's clinical status improved quickly only after the initiation of high dose intravenous steroids and returned to baseline as an outpatient. CONCLUSION: The patient's clinical data and course suggest a cytotoxic T cell response from the lung and BAL as the etiology. With an increasing number of cellular therapies for cancer entering the clinic, the potential for unusual but morbid complications from routine bronchoscopy should be considered.

[One case of severe exogenous lipoid pneumonia complicated with lung abscess caused by diesel inhalation].

Exogenous lipoid pneumonia is an inflammatory response to the lungs caused by inhaled lipid substances, which is prone to secondary bacterial infection, resulting in the formation of local abscesses, which can be life-threatening in severe cases. This paper reports a case of a 55-year-old patient with diesel aspiration, secondary to Klebsiella pneumoniae (ESBL positive) and Candida glabrata infection resulting in lung abscess formation. He was treated with a variety of antibacterial drugs for anti-infection, non-invasive ventilator ventilation, bronchoalveolar lavage, glucocorticoids, phlegm and other medical treatments. Finally, he underwent middle lobectomy for improvement and was discharged from the hospital, and he recovered well with regular follow-up.

The impact of lung ultrasound assessment during a whole lung lavage: A paediatric case of pulmonary alveolar proteinosis.

Whole lung lavage (WLL) is the first-line treatment for pulmonary alveolar proteinosis. We hypothesized that lung ultrasound (LUS) would guide flooding during treatment in a 15-year-old boy. WLL of each lung consisted of instillation of saline followed by kinesiotherapy and fluid drainage. In the first WLL, the lung was repeatedly flooded until the lavage fluid was clear on macroscopic examination. During this process, LUS was used to visualise lung aeration. In the second WLL, we used LUS signs to guide the lavage volume. The appearance of the fluid bronchogram sign showed that saline infusion could be stopped earlier than in the first lavage. In conclusion, LUS helped monitor the different stages of controlled lung de-aeration during WLL and reduce the total amount of saline used. This technique will also reduce the risk of WLL-related complications.

Extrinsic lipoid pneumonia due to chronic polyethylene glycol consumption: A case report.

Extrinsic lipoid pneumonia (ELP) results from the aspiration of lipid-containing substances. Tissue or cell histopathology after Oil-Red-O staining can confirm the diagnosis, which requires proper tissue handling and preparation during bronchoscopy. Here, we report a case of ELP in a quadriplegic patient with a long history of dysphagia and polyethylene glycol consumption. Computed tomography (CT) of the chest revealed multiple, progressively enlarging, fat-attenuated, nodular pulmonary lesions. Bronchoscopy with bronchoalveolar lavage (BAL) and a transbronchial forceps biopsy confirmed the diagnosis of lipoid pneumonia. We discuss the clinical, radiological, and pathological features of ELP and highlight the preparatory steps required for obtaining a successful diagnosis.

The impact of bronchoalveolar lavage on the diagnosis of undifferentiated interstitial lung disease alongside a multidisciplinary discussion.

BACKGROUND AND OBJECTIVE: Cellular analysis of bronchoalveolar lavage (BAL) fluid may aid diagnosis in patients with undifferentiated interstitial lung disease (ILD). The utility of this test in the diagnostic process in conjunction with a multidisciplinary discussion (MDD) is not known. We aim to assess and compare interobserver agreement and diagnostic confidence before and after presenting BAL results in an ILD-MDD. METHODS: Patients undergoing investigations for ILD at Waikato Hospital were recruited. At the ILD-MDD two respiratory physicians and one respiratory radiologist participated in the discussion, and their diagnosis and diagnostic confidence were assessed at four sequential time points. Assessors were blinded to each others diagnosis and diagnostic confidence scores. The four sequential time points were (1) after clinical and radiology presentation; (2) after subsequent MDD; (3) after reviewing BAL results; (4) after final MDD with all results. Interobserver agreements were calculated using Fleiss κ statistic. RESULTS: 36 patients were recruited, and 77.8% were male. In the first step, the interobserver agreement was substantial κ = 0.622 (95% CI 0.47-0.77), improving in step 2 following MDD to κ = 0.78 (95% CI 0.624-0.935), in step 3 κ = 0.776 (95% CI 0.614-0.937) and step 4 achieved almost perfect agreement of κ = 0.969 (95% CI 0.828-1.11). The diagnostic confidence for individual and group diagnosis increased with the presentation of BAL with and without multidisciplinary MDD. CONCLUSION: We found that BAL cellular analysis improves interobserver agreement and confidence in diagnosis following MDD, thus aiding decision-making in cases with undifferentiated ILD.

Biofire pneumonia panel in lung donors: faster detection but limited pathogens.

BACKGROUND: Culture of bronchoalveolar lavage (BAL) specimens takes time to report. We tested whether a molecular diagnostic test could accelerate donor lung assessment and treatment. METHODS: We compared BioFire Film Array Pneumonia Panel (BFPP) with standard of care (SOC) tests on lung allograft samples at three time points: (1) donor BAL at organ recovery, (2) donor bronchial tissue and airway swab at implantation, and (3) first recipient BAL following lung implantation. Primary outcomes were the difference in time to result (Wilcoxon signed-ranked tests) and the agreement in results between BFPP and SOC assays (Gwet's agreement coefficient). RESULTS: We enrolled 50 subjects. In donor lung BAL specimens, BFPP detected 52 infections (14 out of 26 pathogens in the panel). Viral and bacterial BFPP results were reported 2.4 h (interquartile range, IQR 2.0-6.4) following BAL versus 4.6 h (IQR 1.9-6.0, p = 0.625) for OPO BAL viral SOC results and 66 h (IQR 47-87, p < .0001) for OPO BAL bacterial SOC results. Although there was high overall agreement of results between BAL-BFPP versus OPO BAL-SOC tests (Gwet's AC p < .001 for all), the level of agreement differed among 26 pathogens designed in BFPP and differed by types of specimens. BFPP could not detect many infections identified by SOC assays. CONCLUSIONS: BFPP decreased time to detection of lung pathogens among donated lungs, but it cannot replace SOC tests due to the limited number of pathogens in the panel.

Association between one-session bilateral whole-lung lavage and periprocedural complications in patients with pulmonary alveolar proteinosis: a retrospective cohort study.

BACKGROUND: Whole lung lavage (WLL) has been recognized as the most effective therapy of severe pulmonary alveolar proteinosis (PAP). Most centers perform the lavage of each lung in two sessions under general anesthesia at an interval of several days to weeks. Compared with two-session WLL, one-session bilateral sequential WLL only requires general anesthesia once. However, the safety of one-session WLL in PAP patients has not been assessed by large cohort studies. In this study, we aimed to investigate the association between the mode of WLL procedure (one-session or two-session) and the risk of periprocedural complications in PAP patients. METHODS: In this single-center retrospective cohort study, we included adult patients who were diagnosed as PAP and had undergone WLL procedures under general anesthesia from 2000 to 2022. Patients requiring extra-corporeal oxygenation during WLL were excluded. Since some patients received multiple WLL procedures, we considered each procedure in one-session or two-session group as a unique unit in our analysis. The primary outcome was the occurrence of any complications during hospitalization, including termination of WLL procedure due to fluid leakage or refractory hypoxemia, bronchospasm, delayed endotracheal extubation, cardiovascular event, pneumothorax, and fever. RESULTS: We included a total of 175 WLL procedures (118 patients), with 48 in the two-session group and 127 in the one-session group. Periprocedural complications occurred in 17 (35.4%) and 39 (30.7%) procedures in the two-session and the one-session groups, respectively. The risk of periprocedural complications did not differ significantly between groups, after adjusting the unbalanced confounders in a multivariable model (odds ratio 0.95, 95% confidence interval 0.34 to 2.69, P 0.929) or by inverse probability of treatment weighting (odds ratio 0.70, 95% confidence interval 0.30 to 1.54, P 0.379). Compared with the two-session WLL group, the one-session WLL group had a shorter postprocedural length of hospitalization and comparable decrease in alveolar-arterial oxygen tension gradient from baseline. CONCLUSIONS: One-session bilateral WLL was not associated with an increased risk of periprocedural complications compared with two-session WLL in PAP patients. Experienced physicians may consider performing one-session WLL in view of the comparable safety and efficacy and potential advantages of saving time.

22q11.2 deletion syndrome complicated with pulmonary alveolar proteinosis in a child: a case report.

BACKGROUND: To analyze the clinical data and next generation sequencing (NGS) results from a child with 22q11.2 deletion syndrome (22q11DS) complicated with pulmonary alveolar proteinosis (PAP) who was admitted to the Department of Pediatrics of Fuyang People's Hospital and to present a review of the literature. CASE PRESENTATION: A 9-year-old male child, whose face had a small mandible and high-arched palate, but lacked a cleft palate, had repeated respiratory tract infections and bronchiectasis. Clinical examination, computer tomography, and electronic bronchoscopy were performed. Genetic testing via NGS was undertaken. PAP was confirmed by Periodic Acid Schiff staining of milky white alveolar lavage fluid isolated by electronic bronchoscopy. A deletion of approximately 2.46 Mbp on chromosome 22q11.2 was confirmed by NGS. During hospitalization, anti-infection, nebulization, alveolar lavage, and regular application of thymosin were administered to the patient. The condition of the patient stabilized following treatment. CONCLUSIONS: 22q11DS and PAP are both rare diseases, and the manifestation of 22q11DS combined with PAP has not been previously reported. The diagnosis and treatment of this case will be a reference for future clinical work.

[Nontuberculous mycobacteria infection and pulmonary alveolar proteinosis in a patient with hematopoietic defects].

A 28-year-old male with a history of leukopenia was admitted with complaints of fever, cough, and dyspnea for 3 months. Initial work-up identified reduced circulating levels of granulocytes, monocytes, lymphocytes, and NK cells. Computed tomography revealed bilateral reticulonodular opacities and mediastinal lymph node enlargement. Peripheral blood culture and mediastinal lymph node aspiration yielded Mycobacterium avium. Genetic testing revealed a heterozygous germline GATA2 mutation (c.1187G>A, R396Q). Despite standard anti-mycobacterial therapy, the patient's dyspnea worsened and subsequent imaging studies revealed diffuse ground-glass opacification. A transbronchial lung biopsy confirmed the development of pulmonary alveolar proteinosis. Bone marrow transplantation had not been performed due to the unavailability of suitable donors. The disease progressed after whole lung lavage, and the patient died at the age of 31 years from respiratory failure. The current case report emphasized the importance of raising awareness about the rare GATA2 deficiency, which is characterized by hematologic abnormalities, primary immunodeficiency, and pulmonary alveolar proteinosis.