Therapeutic Bronchoalveolar Lavage Research Articles

ЛЕГЕНЕВИЙ АЛЬВЕОЛЯРНИЙ ПРОТЕЇНОЗ: ВИПАДОК СУБТОТАЛЬНОГО УРАЖЕННЯ ПАРЕНХІМИ ЛЕГЕНЬ)

Pulmonary alveolar proteinosis (PAP) is a rare pulmonary disease, characterized by the intraalveolar accumulation of surfactant-like lipoprotein substance. There are three forms of the disease: autoimmune (formerly known as idiopathic), secondary and congenital PAP. The disturbances of surfactant metabolism (protein-lipoid complex secreted by type II pneumocytes) play the crucial role in the development of the disease. Surfactant decreases a surface tension of alveoli and prevents its collapse at the end of the expiration and takes part in protection against infections as well. Surfactant is inactivated through the transformation into the surface-inactive aggregates, which are mainly absorbed by type II pneumocytes. The rest of surfactant are catabolized by alveolar macrophages (AM). This process is regulated by cytokines, especially granulocyte-macrophage colony-stimulating factor (GM-CSF) being the most important of them. Disturbances of interrelation between GM-CSF and cellular receptors blocks the signals to effector cells for surfactant deactivation. This is resulted in excessive accumulation of surfactant in alveoli. General lavage of the lung is a standard method of symptomatic management of PAP. Contemporary pathogenesis treatment uses two approaches — increasing the clearance of surfactant by means of exogenous GM-CSF administration and decreasing the level of GM-CSF antibodies using the rituximab and plasmapheresis. Due to the use of broncho-alveolar lavage (BAL) 5-year survival rate of th patients reaches 95 %. The mortality depends on the area of lung lesion and reversely correlated with the timely diagnosis and treatment. We report the case of subtotal lung parenchyma lesion associated with severe respiratory failure in 46 years old patient. Three series of BAL (5 procedures in each with 1-2 months interval) were performed using the limited volume of lavage fluid due to the severity of the patient’s condition. The results was an improvement of clinical condition, resolution of respiratory failure, significant reduction of the size of the lesions, improved lung transparency on CT scan, restoration of lung diffusion and total lung capacity. Conclusion. Therapeutic BAL is an effective method of PAP management. The outcome of clinical case presented and our many years experience confirm not only the effectiveness of conventional BAL with reduced lavage volume application but also a safety of fiberoptic bronchoscopy, especially in patients with subtotal involvement of lung parenchyma. Key words: pulmonary alveolar proteinosis, subtotal pulmonary parenchyma involvement, pulmonary bronchoalveolar lavage, efficiency.

Optimization strategy for the early timing of bronchoalveolar lavage treatment for children with severe mycoplasma pneumoniae pneumonia

BackgroundEarly evaluation of severe mycoplasma pneumoniae pneumonia (SMPP) and the prompt utilization of fiberoptic bronchoscopic manipulation can effectively alleviate complications and restrict the progression of sequelae. This study aim to establish a nomogram forecasting model for SMPP in children and explore an optimal early therapeutic bronchoalveolar lavage (TBAL) treatment strategy.MethodsThis retrospective study included children with mycoplasma pneumoniae pneumonia (MPP) from January 2019 to December 2021. Multivariate logistic regression analysis was used to screen independent risk factors for SMPP and establish a nomogram model. The bootstrap method was employed and a receiver operator characteristic (ROC) curve was drawn to evaluate the accuracy and robustness of the model. Kaplan–Meier analysis was used to assess the effect of lavage and hospitalization times.ResultsA total of 244 cases were enrolled in the study, among whom 68 with SMPP and 176 with non-SMPP (NSMPP). A prediction model with five independent risk factors: left upper lobe computed tomography (CT) score, sequential organ failure assessment (SOFA) score, acute physiology and chronic health assessment (APACHE) II score, bronchitis score (BS), and c-reactive protein (CRP) was established based on the multivariate logistic regression analysis. The ROC curve of the prediction model showed the area under ROC curve (AUC) was 0.985 (95% confidence interval (CI) 0.972–0.997). The Hosmer–Lemeshow goodness-of-fit test results showed that the nomogram model predicted the risk of SMPP well (χ2 = 2.127, P = 0.977). The log-rank result suggested that an early BAL treatment could shorten MPP hospitalization time (P = 0.0057).ConclusionThis nomogram model, based on the left upper lobe CT score, SOFA score, APACHE II score, BS, and CRP level, represents a valuable tool to predict the risk of SMPP in children and optimize the timing of TBAL.

The effect of therapeutic bronchoalveolar lavage in combination with glucocorticoids on children with acute exogenous lipoid pneumonia.

Exogenous lipoid pneumonia (ELP) is a rare disease caused by the inhalation of oily materials in the alveoli with the pathological characterization by the presence of laden-lipid macrophages in the respiratory specimens. At present, the treatment norm for ELP has not well defined, and so the aim of this study is to evaluate the effect of bronchoalveolar lavage in combination with glucocorticoids on children with ELP. We retrospectively reviewed 17 children with a confirmed history of exogenous oily materials aspiration, admitted to the First Affiliated Hospital of Guangzhou Medical University from June 2012 to December 2021. Clinical features, blood investigations, tomographic evaluations, therapeutic bronchoalveolar lavage and glucocorticoids use were carried out at the beginning of therapy and throughout a follow-up period. The included children are the median age of 2 years. Fever, dypnea and tachypnea were the most common symptoms. The most common radiological features were airspace consolidations (15, 93.75%). Chest CT scans showed areas of consolidation with air bronchogram (15, 93.75%), poorly defined centrilobular nodules (13, 81.25%), areas of ground-glass attenuation (11, 68.75%) and 'crazy-paving' pattern (6, 37.5%) in the both lower, right middle lung lobes. Neutrophil percentage of peripheral blood and bronchoalveolar lavage fluid exhibited a significantly higher than the normal range. After treatment with multiple bronchoalveolar lavages and local administration of budesonide during the hospital stay, taken by oral prednisolone (1 ~ 2 mg/kg) after discharge, all of children became asymptomatic and presented normal radiological imagings in the follow-up period. The most frequently findings in the CT scan of ELP were consolidations and ground-glass attenuation in the both lower and right middle lung lobes. Multiple bronchoalveolar lavages in combination with oral prednisolone for children who had a confirmed history of exogenous oily substances ingestion were an efficient and safe for the clearance of oily materials from the lung and the prevention of fibrosis. This strategy contributed to reducing the damage of ELP in children patients.

Monitoring bronchoalveolar lavage with electrical impedance tomography: first experience in a patient with COVID-19

Objective: Patients with the novel coronavirus disease (COVID-19) often have airway secretions that severely compromise ventilation. This study investigates electrical impedance tomography (EIT) monitoring of a therapeutic bronchoalveolar lavage (BAL) in a patient with COVID-19. Approach: A patient with COVID-19 developed acute respiratory distress syndrome requiring mechanical ventilation. He received regional BAL to remove mucus in the small airways (20 ml × 5). Regional ventilation changes before BAL, 30 min after and in the following days, were monitored with EIT. Main results: Regional ventilation worsened shortly after BAL and improved in the following days. The improvement of the oxygenation did not exactly match the ventilation improvement, which indicated a possible ventilation/perfusion mismatch. Significance: Therapeutic BAL might improve regional ventilation for COVID-19 and EIT could be a useful tool at the bedside to monitor the ventilation treatment of COVID-19.

Effects of Surfactant Lavage Combined With Intratracheal Budesonide Instillation on Meconium-Injured Piglet Lungs.

To evaluate the combined effects of surfactant lavage and intratracheally instillation of budesonide on meconium-injured piglet lungs. A prospective, randomized, animal model study. An experimental laboratory. Twenty-four anesthetized and mechanically ventilated newborn piglets. Human meconium slurry was intratracheally instilled into piglet lungs to induce lung injury. The injured piglets were randomly assigned to either the sham treatment group (control) or one of the three therapeutic groups: the intratracheally instilled budesonide (Bud) group, the bronchoalveolar lavage with diluted surfactant (dsBAL) group, and the combination therapy of Bud and dsBAL (dsBAL + Bud) group. Cardiopulmonary profiles were measured hourly. Proinflammatory cytokine (interleukin-1β, interleukin-6, and interleukin-8) levels in bronchoalveolar lavage fluid were measured. Finally, the pulmonary histology of the experimental subjects was examined at the end of experiments. Both of the lavaged groups (dsBAL and dsBAL + Bud) showed significantly better oxygenation than those that had not undergone lavage (control and Bud) (p < 0.05). The dsBAL + Bud group showed a significantly higher lung compliance and required a significantly lower peak inspiratory pressure during the experimental periods than the other three groups (p < 0.05). All treatment groups had significantly lower concentrations of interleukin-1β concentration in the bronchoalveolar lavage fluid than the control group (p < 0.05). The dsBAL + Bud group also had a significantly lower interleukin-6 concentration in the bronchoalveolar lavage fluid (p< 0.05), as well as a significantly lower lung injury score based on pulmonary histology than the control group (p < 0.05). Therapeutic bronchoalveolar lavage with diluted surfactant followed by intratracheal instillation of budesonide has a synergistic and beneficial effect when treating severe meconium-injured newborn piglet lungs.

A Case of Lipoid Pneumonia From Mineral Oil Aspiration With Delayed-Onset ARDS

SESSION TITLE: Lung Pathology Student/Resident Case Report Posters SESSION TYPE: Student/Resident Case Report Poster PRESENTED ON: Tuesday, October 27, 2015 at 01:30 PM - 02:30 PM INTRODUCTION: Hydrocarbons may facilitate aspiration via inhibition of the cough reflex. Very few observational studies have been performed to investigate the evolution and outcomes of hydrocarbon aspiration. CASE PRESENTATION: A 17-month-old boy presented to a local Emergency Department with signs of respiratory distress and concern for aspiration of baby oil. Initial chest radiograph showed bilateral perihilar and lower lobe infiltrates and antibiotic therapy was initiated. Within 24 hours of aspiration, the patient developed tachypnea and hypoxia with confirmed radiographic evolution of infiltrates. He was initiated on oxygen therapy and antibiotic coverage was broadened to treat lipoid aspiration pneumonia with superimposed bacterial pneumonia. In spite of combined therapy with antimicrobials and systemic steroids, he continued to be hypoxemic and ultimately required invasive ventilatory support for respiratory embarrassment. Initial bronchoalveolar lavage performed two weeks into his course showed opaque fluid with numerous inflammatory cells. Following his second therapeutic bronchoalveolar lavage, the patient was extubated and discharged home on supplemental oxygen therapy. DISCUSSION: This rare case depicts delayed-onset acute respiratory distress syndrome secondary to evolution of injury from hydrocarbon inhalation. The performance of multiple bronchoalveolar lavages within months of suspected aspiration has been shown to improve clinical outcomes and radiographic disease amongst children with lipoid aspiration. In our case, steroids may have decreased inflammation, but did not prevent lung injury. CONCLUSIONS: Very few observational studies have been performed describing the natural history of lipoid aspiration pneumonia, particularly among children. Most clinical outcomes are favorable, as in the case of our patient, but some children will develop pulmonary fibrosis. The utility of steroids remains controversial and warrants further investigation. This case emphasizes the importance of conversations regarding household safety at preventive health visits. Reference #1: Marchiori, E., Zanetti, G., Mano, C.M., Hochhegger, B. “Exogenous lipoid pneumonia. Clinical and radiological manifestations.” Respiratory Medicine. 2011. 105, 659-666. Reference #2: de Azevedo Sias, S.M., Ferreira, A.S., Daltro, P.A., Caetano, R.L., da Silva Moreira, J., Quirico-Santos, T. “Evolution of exogenous lipoid pneumonia in children: clinical aspects, radiological aspects and the role of bronchoalveolar lavage.” J Bras Pneumol. 2009. 35(9): 839-845. Reference #3: Sias, S.M.A, Daltro, P.A., Marchiori, E., Ferreira, A.S., Caetano, R.L., Silva, C.S., Muller, N.L., Moreira, J., Quirico-Santo, T. “Clinic and Radiological Improvement of Lipoid Pneumonia With Multiple Bronchoalveolar Lavages.” Pediatric Pulmonology. 2009. 44, 309-315. DISCLOSURE: The following authors have nothing to disclose: Ashley Devonshire, Sonal Malhotra, Mary Nevin No Product/Research Disclosure Information

Therapeutic bronchoalveolar lavage with conventional treatment in allergic bronchopulmonary aspergillosis.

To establish the role of therapeutic bronchoalveolar lavage in addition to conventional treatment among two groups, with allergic bronchopulmonary aspergillosis, in terms of regression in serum IgE levels and clinical recurrence at 3 and 6 months of follow-up. Aquasi-experimental study. Department of Pulmonology, Fauji Foundation Hospital, Rawalpindi, from July 2010 to December 2013. The study was carried out on 132 patients who fulfilled the Greenberger and Patterson criteria and underwent a chest X-ray, an HRCT chest and classified radiologically as with Central Bronchiectasis (CB), High Attenuation Mucus (HAM) or Other Radiological Features (ORF). Baseline serum IgE levels were noted. All patients were given treatment including prednisolone and antifungal agent itraconazole for 4 months. Patients with ORF on HRCTchest and just received the medical treatment were labeled as conventional group. Those patients who had CB or HAM radiological features also underwent bronchoscopy with therapeutic Bronchoalveolar Lavage (BAL), labeled as BALgroup. Clinical recurrence and serum IgE levels were noted at 3 and 6 months. Values were compared using chi-square and Mann-Whitney tests respectively. Around 78 (59.1%) of patients underwent bronchoscopy with therapeutic bronchoalveolar lavage to remove the mucus plugs. The mean serum IgE levels at baseline were 3312.04 ± 2526.217 and 3486.15 ± 2528.324 IU/ml in the BAL and conventional groups respectively. There was a statistically significant reduction in the mean serum IgE levels at 3 (p < 0.00) and 6 months (p < 0.001) of follow-up in BALas compared to conventional group. There was no significant difference in the clinical recurrence rate in both the groups (p=0.078 at 3 and 0.343 at 6 months respectively). Therapeutic bronchoalveolar lavage may be a useful adjunct to treatment in patients with allergic bronchopulmonary aspergillosis, serum in terms of IgE level reduction.

Surfactant lavage decreases systemic interleukin‐1β production in meconium aspiration syndrome

Surfactant lavage has been used to remove meconium debris in meconium aspiration syndrome (MAS), but the influence of surfactant lavage on pro-inflammatory cytokines and cellular apoptosis is unclear. The aim of this study was to investigate the response of pro-inflammatory cytokine and the influence on alveolar cellular apoptosis using therapeutic bronchoalveolar lavage with diluted surfactant to treat MAS. Twelve newborn piglets were anesthetized, intubated via tracheostomy, and artificially ventilated. MAS was induced by intratracheal instillation of 3-5 mL/kg of 20% human meconium. The piglets were then randomly assigned to a surfactant lavage group (n= 6) or a control group (n= 6). Piglets in the lavage group received bronchoalveolar lavage with 30 mL/kg diluted surfactant (5 mg/mL) in two aliquots. Cardiopulmonary parameters were monitored continuously. Serum was obtained hourly to measure concentrations of pro-inflammatory cytokines, including interleukin (IL)-I beta, IL-6, and tumor necrosis factor alpha. Lung tissue was histologically examined after experiments, and terminal deoxynucleotidyl transferase-mediated nick-end labeling assay for apoptotic cell death was also performed. The animals in the lavage group displayed significantly better gas exchange and lower serum concentrations of IL-1 beta than the animals in the control group (P < 0.05). The number of apoptotic cells in lung tissues was significantly lower in the lavage group than the control group, and also in the nondependent than the dependent site. Therapeutic surfactant lavage improves oxygenation, decreases production of systemic pro-inflammatory cytokine IL-1 beta, and alleviates the severity of lung cell apoptosis in newborn piglets with experimentally-induced MAS.

SP-D counteracts GM-CSF-mediated increase of granuloma formation by alveolar macrophages in lysinuric protein intolerance

BackgroundPulmonary alveolar proteinosis (PAP) is a syndrome with multiple etiologies and is often deadly in lysinuric protein intolerance (LPI). At present, PAP is treated by whole lung lavage or with granulocyte/monocyte colony stimulating factor (GM-CSF); however, the effectiveness of GM-CSF in treating LPI associated PAP is uncertain. We hypothesized that GM-CSF and surfactant protein D (SP-D) would enhance the clearance of proteins and dying cells that are typically present in the airways of PAP lungs.MethodsCells and cell-free supernatant of therapeutic bronchoalveolar lavage fluid (BALF) of a two-year-old patient with LPI were isolated on multiple occasions. Diagnostic BALF samples from an age-matched patient with bronchitis or adult PAP patients were used as controls. SP-D and total protein content of the supernatants were determined by BCA assays and Western blots, respectively. Cholesterol content was determined by a calorimetic assay or Oil Red O staining of cytospin preparations. The cells and surfactant lipids were also analyzed by transmission electron microscopy. Uptake of Alexa-647 conjugated BSA and DiI-labelled apoptotic Jurkat T-cells by BAL cells were studied separately in the presence or absence of SP-D (1 μg/ml) and/or GM-CSF (10 ng/ml), ex vivo. Specimens were analyzed by light and fluorescence microscopy.ResultsHere we show that large amounts of cholesterol, and large numbers of cholesterol crystals, dying cells, and lipid-laden foamy alveolar macrophages were present in the airways of the LPI patient. Although SP-D is present, its bioavailability is low in the airways. SP-D was partially degraded and entrapped in the unusual surfactant lipid tubules with circular lattice, in vivo. We also show that supplementing SP-D and GM-CSF increases the uptake of protein and dying cells by healthy LPI alveolar macrophages, ex vivo. Serendipitously, we found that these cells spontaneously generated granulomas, ex vivo, and GM-CSF treatment drastically increased the number of granulomas whereas SP-D treatment counteracted the adverse effect of GM-CSF.ConclusionsWe propose that increased GM-CSF and decreased bioavailability of SP-D may promote granuloma formation in LPI, and GM-CSF may not be suitable for treating PAP in LPI. To improve the lung condition of LPI patients with PAP, it would be useful to explore alternative therapies for increasing dead cell clearance while decreasing cholesterol content in the airways.

Effective Lavage Volume of Diluted Surfactant Improves the Outcome of Meconium Aspiration Syndrome in Newborn Piglets

Meconium aspiration syndrome (MAS) is one of the top causes of severe respiratory failure in neonates. This study was designed to investigate the effective volume of therapeutic bronchoalveolar lavage (BAL) with diluted surfactant in the treatment of MAS in newborn piglets. Human meconium was instilled in 24 piglets to induce MAS, and the piglets were randomly divided into four groups: 1) control, no lavage; 2) lavage-10, BAL with diluted surfactant (5 mg/mL, Survanta) 10 mL/kg in two aliquots; 3) lavage-20, 20 mL/kg in two aliquots; 4) lavage-30, 30 mL/kg in two aliquots. Cardiopulmonary parameters were monitored, and the lung tissue was histologically examined after experiments. The changes in oxygenation and lung compliance of lavage-20 and lavage-30 groups were significantly better than control and lavage-10 groups (p < 0.05), but there was no significant difference between lavage-20 and lavage-30 groups. The lung injury scores were significantly lower in the dependent site of lavage-20 and lavage-30 groups than the other two groups. In conclusion, using 20 mL/kg diluted surfactant in two aliquots to perform therapeutic BAL was as effective as 30 mL/kg in improving the pathophysiological outcomes in MAS and may warrant consideration clinically in treating MAS.

Effects of therapeutic bronchoalveolar lavage and partial liquid ventilation on meconium-aspirated newborn piglets

To investigate the therapeutic effects of bronchoalveolar lavage (BAL) with either diluted surfactant (SBAL) or perfluorochemical liquid (PBAL), followed by either conventional mechanical ventilation (CMV) or partial liquid ventilation (PLV), on lung injury and proinflammatory cytokine production induced by meconium aspiration in newborn piglets. A prospective, randomized, experimental study. An animal research laboratory at a medical center. Anesthetized and mechanically ventilated newborn piglets (n = 27). The animals were instilled with 3-5 mL/kg 25% human meconium via an endotracheal tube to induce meconium aspiration syndrome (MAS). After stabilization, animals were randomly assigned to either CMV group (no BAL) or one of the treatment groups (SBAL-CMV, SBAL-PLV, PBAL-CMV, and PBAL-PLV). Cardiopulmonary variables were monitored, and interleukin-1beta and interleukin-6 content of the serum and lung tissue was measured. The animals without any treatment (CMV group) displayed the worst outcome; the animals in the PBAL-PLV group had the best gas exchange, lung compliance, and least pulmonary damage; and the SBAL-CMV, PBAL-CMV, and SBAL-PLV groups had intermediate effects. The serum interleukin-1beta concentration of the CMV group was significantly higher than all other groups over time (p < .05), and interleukin-6 concentration was significantly higher than the PBAL-PLV group (p < .05). The tissue interleukin-1beta and interleukin-6 contents were also highest in the CMV group and lowest in the PBAL-PLV group. Initial therapeutic BAL and therapeutic BAL followed by PLV with the same perfluorochemical liquid provided significant therapeutic effects in treating an animal model with severe MAS and therefore warrant consideration in cases that are intractable to other therapies.

[Improvement in alveolar macrophage function after therapeutic lung lavage in pulmonary alveolar proteinosis].

Alveolar macrophage (AM) function was investigated in 4 cases of pulmonary alveolar proteinosis (PAP). Therapeutic bronchoalveolar lavage (BAL) with a flexible bronchofiberscope was done 7-13 times during periods of 4-24 weeks. In the initial BAL, the total cell count was only 0.18-0.92 x 10(5)/ml. Also low AM, lymphocytosis and eosinophilia values were noted. The phagocytic activity of AM was only 3-14% and nitroblue tetrazonium (NBT) reduction of AM was under 5% before therapeutic BAL. However, the phagocytic activity was from 25-63% and NBT reduction from 15-35% after therapeutic BAL, AM function with periods of remission of PAP was normal but AM function decreased during relapse and exacerbation of PAP. After therapeutic BAL, two patients have been in remission for three years, one patient with incomplete restoration of AM function relapsed after one year, and one patient without restoration of AM function showed further deterioration after developing pulmonary tuberculosis. These findings indicate that the defect in AM function found in PAP is reversible with therapeutic BAL, and that the severity of PAP is closely associated with AM function.

Therapeutic Use of Bronchoalveolar Lavage in a Very Difficult Asthmatic: A Case Report

A patient with severe chronic asthma, who had become refractory to conventional antiasthma drugs, is described. As a last resort, therapeutic bronchoalveolar lavage was performed using beta-stimulant, steroid, and mucolytic solutions. The patient, who had had asthmatic attacks almost every day prior to lavage, showed a dramatic and sustained improvement in his condition. It is suggested that therapeutic bronchoalveolar lavage may be useful in chronic asthmatics who have become refractory to conventional treatment because of mucus plugging of their bronchi.