Airway pepsinogen A4 identifies lung transplant recipients with microaspiration and predicts chronic lung allograft dysfunction.

BACKGROUND: Aspiration is a known risk factor for adverse outcomes post-lung transplantation. Airway bile acids are the gold-standard biomarker of aspiration; however, they are released into the duodenum and likely reflect concurrent gastrointestinal dysmotility. Previous studies investigating total airway pepsin have found conflicting results on its relationship with adverse outcomes post-lung transplantation. These studies measured total pepsin and pepsinogen in the airways. Certain pepsinogens are constitutively expressed in the lungs, while others, such as pepsinogen A4 (PGA4), are not. We sought to evaluate the utility of measuring airway PGA4 as a biomarker of aspiration and predictor of adverse outcomes in lung transplant recipients (LTRs) early post-transplant. METHODS: Expression of PGA4 was compared to other pepsinogens in lung tissue. Total pepsin and PGA4 were measured in large airway bronchial washings and compared to preexisting markers of aspiration. Two independent cohorts of LTRs were used to assess the relationship between airway PGA4 and chronic lung allograft dysfunction (CLAD). Changes to airway PGA4 after antireflux surgery were assessed in a third cohort of LTRs. RESULTS: PGA4 was expressed in healthy human stomach but not lung. Airway PGA4, but not total pepsin, was associated with aspiration. Airway PGA4 was associated with an increased risk of CLAD in two independent cohorts of LTRs. Antireflux surgery was associated with reduced airway PGA4. CONCLUSIONS: Airway PGA4 is a marker of aspiration that predicts CLAD in LTRs. Measuring PGA4 at surveillance bronchoscopies can help triage high-risk LTRs for anti-reflux surgery.

Presence of Gastric Pepsinogen in the Trachea Is Associated with Altered Inflammation and Microbial Composition.

Gastroesophageal reflux is a common gastrointestinal issue that can lead to aspiration and contribute to respiratory problems. Little is known about how reflux can alter the respiratory microenvironment. We aimed to determine if the presence of gastric pepsinogen in the trachea was associated with changes in the microbial and inflammatory microenvironment. A pediatric cohort at high risk of reflux aspiration was prospectively recruited, and the tracheal microenvironment was examined. Pepsinogen A3 (PGA3) and cytokines were measured. The microbiome (bacterial and fungal) was profiled using 16S rRNA and internal transcribed spacer 2 (ITS2) amplicon sequencing. Increased bacterial richness and an altered composition driven by an enrichment of Prevotella correlated with high PGA3 levels. Fungal richness increased with PGA3, with higher Candida relative abundances observed in a subset of samples with high PGA3 levels. Source tracking of tracheal microbial taxa against taxa from matched oral and gastric samples revealed a significantly greater contribution of oral than of gastric taxa with higher PGA3 levels. Tracheal cytokines were differentially produced when stratified according to PGA3, with higher levels of interleukin-1 (IL-1)-related cytokines and IL-8 being associated with high PGA3 levels. Network analysis across cytokine and microbiome measures identified relationships between IL-1-related proteins and microbial taxa, with the presence of respiratory issues associated with higher levels of IL-1ß, IP-10, and Prevotella In conclusion, PGA3 levels in the trachea are correlated with increases in specific microbial taxa and inflammatory molecules, with an increase in oral microbes with increasing PGA3.

A New Modified Evans Blue Dye Test as Screening Test for Aspiration in Tracheostomized Patients.

OBJECTIVE: The authors assessed the diagnostic accuracy of a new modified Evans blue dye test (MEBDT) as a screening test for aspiration in tracheostomized patients. DESIGN: Monocentric retrospective study performed between October 2013 and December 2015. SETTING: Anesthesia and Intensive Care Unit, Second University of Naples. PARTICIPANTS: Among 62 eligible patients, 5 were excluded. The authors' study population included 57 patients. INTERVENTIONS: Patients underwent both fiberoptic endoscopic examination of the swallow (FEES) and MEBDT to evaluate swallow. The MEBDT results were compared with those of FEES and the diagnostic accuracy of MEBDT was calculated using the FEES as the gold standard. MEASUREMENTS AND MAIN RESULTS: The authors found that both FEES and MEBDT were positive for aspiration in 40 patients (true-positive MEBDT); FEES and MEBDT were negative in 10 (true-negative MEBDT). On the other hand, FEES was positive with an MEBDT negative in 7 patients (false-negative MEBDT), and there were no FEES negative and MEBDT positive (false-positive MEBDT). MEBDT had a sensitivity, specificity, positive, and negative predicted value of 85%, 100%, 100%, and 58.82%, respectively. CONCLUSIONS: MEBDT could be a supplementary diagnostic test for aspiration. Patients with positive MEBDT should not undergo oral feeding, while patients with negative MEBDT should undergo FEES before starting oral feeding.

Lung hyperinflation by mechanical ventilation versus isolated tracheal aspiration in the bronchial hygiene of patients undergoing mechanical ventilation.

OBJECTIVE: To determine the efficacy of lung hyperinflation maneuvers via a mechanical ventilator compared to isolated tracheal aspiration for removing secretions, normalizing hemodynamics and improving lung mechanics in patients on mechanical ventilation. METHODS: This was a randomized crossover clinical trial including patients admitted to the intensive care unit and on mechanical ventilation for more than 48 hours. Patients were randomized to receive either isolated tracheal aspiration (Control Group) or lung hyperinflation by mechanical ventilator (MVH Group). Hemodynamic and mechanical respiratory parameters were measured along with the amount of aspirated secretions. RESULTS: A total of 50 patients were included. The mean age of the patients was 44.7 ± 21.6 years, and 31 were male. Compared to the Control Group, the MVH Group showed greater aspirated secretion amount (3.9g versus 6.4g, p = 0.0001), variation in mean dynamic compliance (-1.3 ± 2.3 versus -2.9 ± 2.3; p = 0.008), and expired tidal volume (-0.7 ± 0.0 versus -54.1 ± 38.8, p = 0.0001) as well as a significant decrease in peak inspiratory pressure (0.2 ± 0.1 versus 2.5 ± 0.1; p = 0.001). CONCLUSION: In the studied sample, the MVH technique led to a greater amount of aspirated secretions, significant increases in dynamic compliance and expired tidal volume and a significant reduction in peak inspiratory pressure.

Hiperinsuflação pulmonar com ventilador mecânico versus aspiração traqueal isolada na higiene brônquica de pacientes submetidos à ventilação mecânica / Lung hyperinflation by mechanical ventilation versus isolated tracheal aspiration in the bronchial hygiene of patients undergoing mechanical ventilation

RESUMO Objetivo: Determinar a eficácia da manobra de hiperinsuflação pulmonar com o ventilador mecânico, em comparação à aspiração traqueal isolada, para remover secreções, normalizar a hemodinâmica e melhorar a mecânica pulmonar em pacientes em ventilação mecânica. Métodos: Ensaio clínico randomizado cruzado incluindo pacientes em ventilação mecânica por mais de 48 horas internados na unidade de terapia intensiva. Os pacientes foram randomizados para receber a aspiração traqueal isolada (Grupo Controle) e hiperinsuflação pulmonar por meio do ventilador mecânico (Grupo HVM). Mensuraram-se parâmetros hemodinâmicos e de mecânica respiratória, assim como a quantidade de secreção aspirada. Resultados: Foram incluídos 50 pacientes. A média de idade dos pacientes foi de 44,7 ± 21,6 anos, sendo 31 do sexo masculino. O Grupo HVM apresentou maior quantidade de secreção aspirada (3,9g versus 6,4g; p = 0,0001), variação na média da complacência dinâmica (-1,3 ± 2,3 versus -2,9 ± 2,3; p = 0,008), volume corrente expirado (-0,7 ± 0,0 versus -54,1 ± 38,8; p = 0,0001) e diminuição significativa da pressão inspiratória de pico (0,2 ± 0,1 versus 2,5 ± 0,1; p = 0,001), em comparação com o Grupo Controle. Conclusão: Na amostra estudada, a técnica de HVM apresentou maior quantidade de secreção aspirada, aumento significativo da complacência dinâmica e volume corrente expirado, além de diminuição significativa da pressão de pico inspiratória.

ABSTRACT Objective: To determine the efficacy of lung hyperinflation maneuvers via a mechanical ventilator compared to isolated tracheal aspiration for removing secretions, normalizing hemodynamics and improving lung mechanics in patients on mechanical ventilation. Methods: This was a randomized crossover clinical trial including patients admitted to the intensive care unit and on mechanical ventilation for more than 48 hours. Patients were randomized to receive either isolated tracheal aspiration (Control Group) or lung hyperinflation by mechanical ventilator (MVH Group). Hemodynamic and mechanical respiratory parameters were measured along with the amount of aspirated secretions. Results: A total of 50 patients were included. The mean age of the patients was 44.7 ± 21.6 years, and 31 were male. Compared to the Control Group, the MVH Group showed greater aspirated secretion amount (3.9g versus 6.4g, p = 0.0001), variation in mean dynamic compliance (-1.3 ± 2.3 versus -2.9 ± 2.3; p = 0.008), and expired tidal volume (-0.7 ± 0.0 versus -54.1 ± 38.8, p = 0.0001) as well as a significant decrease in peak inspiratory pressure (0.2 ± 0.1 versus 2.5 ± 0.1; p = 0.001). Conclusion: In the studied sample, the MVH technique led to a greater amount of aspirated secretions, significant increases in dynamic compliance and expired tidal volume and a significant reduction in peak inspiratory pressure.

Oropharyngeal aspiration of bleomycin: An alternative experimental model of pulmonary fibrosis developed in Swiss mice.

OBJECTIVE: Pulmonary fibrosis (PF) is a progressive and predominantly lethal form of several interstitial lung diseases with limited current therapeutics; it is, therefore, essential to develop a simple, homogeneous, and noninvasive disease model to investigate possible anti-fibrotic approaches. The present study is designed to develop oropharyngeal aspiration (OPA) model of bleomycin (BLM)-induced PF as a simple and alternative to intratracheal (IT) administration of BLM in Swiss mice strain. MATERIALS AND METHODS: Mice were divided into two groups, BLM-treated and normal control. BLM via OPA (2 IU/kg) was used to induce PF. Water for injection was used as a vehicle in control animals. Body weights were measured once in a week, and the study was continued for 21 days. At the end of the study, animals were euthanized and bronchoalveolar lavage fluid was collected and subjected to lymphocytes count, estimation of albumin and protein levels. Lung tissues were collected, and various biochemical assays (malondialdehyde, glutathione, nitric oxide, hydroxyproline) and molecular techniques including ELISA and Western blot were performed to investigate the effect of OPA-BLM. Further, histopathology and Masson's trichrome staining techniques were performed in lung sections. RESULTS: OPA administration of BLM in Swiss mice significantly induced PF, evident from lung index and morphology. Several oxidative stress parameters and hydroxyproline assay revealed the significant (P < 0.05) induction of PF. Further results obtained from histopathology, Masson's trichrome staining, ELISA, and Western blot confirmed the significant induction of PF via OPA-BLM. CONCLUSION: BLM administration by OPA route in Swiss mice can be used as a simple, homogeneous, and noninvasive model of inducing PF and to investigate the effect of various anti-fibrotic agents as an alternative to IT-BLM.

The Role of Phosphorylated Cx43 on PKC Mediated Ser368 in Lung Injury Induced by Seawater Inhalation.

Seawater aspiration may result in acute lung injury/acute respiratory distress syndrome (ALI/ARDS), which is characterized by pulmonary inflammation and lung edema that closely related to pulmonary barrier dysfunction and intracellular communication. The aim of the present research was to explore the role of connexion 43 (Cx43) in seawater aspiration-induced ALI/ARDS. The results from in vivo experiments showed that seawater inhalation led to increased expression of p-PKC and phosphorylated Cx43 (p-Cx43), which were followed by protein rich fluid leakage and TNF-α and IL-1ß secretion. Besides, the results from in vitro tests proved that the expression of p-PKC directly influenced phosphorylation state of Cx43 and its function, which could further affect the inflammatory factors secretion and intercellular communication. In conclusion, seawater aspiration causes p-Cx43 expression by PKC pathway, which is involved in the on come and development of pulmonary inflammation and lung edema.

Participation of autophagy in acute lung injury induced by seawater.

Seawater drowning can lead to acute lung injury (ALI). However, the molecular and cellular mechanisms underlying this phenomenon remain elusive. The overall aim of this study is to clarify the role of autophagy in seawater-induced ALI, by which we can further understand the molecular mechanism and develop new methods for prevention and treatment of seawater-induced ALI. In this study, electron microscopy, western blot analysis, and RT-PCR were used to detect autophagy in lung tissues. Moreover, arterial blood gas analysis, lung weight coefficient, TNF-α, IL-8 in bronchoalveolar fluid (BALF), histopathology were used to detect the lung injury of seawater exposure. An inhibitor of autophagy (3-Methyladenine, 3-MA) was injected intraperitoneally before seawater exposure to further explore the role of autophagy in ALI. Electron microscopy revealed increasing autophagosomes in alveolar epithelial cell in seawater group compared with the control. The transcription and expression levels (mRNA and protein levels) of the LC3 II significantly increased in lung tissue of seawater group compared with those in control group. Furthermore, the alterations of autophage were basically consistent with the changes in arterial blood gas, lung weight coefficient, TNF-α, IL-8 in BALF and morphologic findings. In addition, inhibition of autophagy by 3-MA partly ameliorated seawater-induced ALI, as indicated by reduced lung weight coefficient and TNF-α in BALF, as well as increased PaO2. In conclusion, seawater aspiration triggered autophagy, and autophagy may be a scathing factor responsible for ALI induced by seawater.

Aspiration, localized pulmonary inflammation, and predictors of early-onset bronchiolitis obliterans syndrome after lung transplantation.

BACKGROUND: We hypothesized that immune mediator concentrations in the bronchoalveolar fluid (BALF) are predictive of bronchiolitis obliterans syndrome (BOS) and demonstrate specific patterns of dysregulation, depending on the presence of acute cellular rejection, BOS, aspiration, and timing of lung transplantation. STUDY DESIGN: We prospectively collected 257 BALF samples from 105 lung transplant recipients. The BALF samples were assessed for absolute and differential white blood cell counts and 34 proteins implicated in pulmonary immunity, inflammation, fibrosis, and aspiration. RESULTS: There were elevated BALF concentrations of interleukin (IL)-15, IL-17, basic fibroblast growth factor, tumor necrosis factor-α, and myeloperoxidase, and reduced concentrations of α1-antitrypsin, which were predictive of early-onset BOS. Patients with BOS had an increased percentage of BALF lymphocytes and neutrophils, with a reduced percentage of macrophages (p < 0.05). The BALF concentrations of IL-1ß; IL-8; interferon-γ-induced protein 10; regulated upon activation, normal T-cell expressed and secreted; neutrophil elastase; and pepsin were higher in patients with BOS (p < 0.05). Among those with BOS, BALF concentrations of IL-1RA; IL-8; eotaxin; interferon-γ-induced protein 10; regulated upon activation, normal T-cell expressed and secreted; myeloperoxidase; and neutrophil elastase were positively correlated with time since transplantation (p < 0.01). Those with worse grades of acute cellular rejection had an increased percentage of lymphocytes in their BALF (p < 0.0001) and reduced BALF concentrations of IL-1ß, IL-7, IL-9, IL-12, granulocyte colony-stimulating factor, granulocyte-macrophage colony-stimulating factor, interferon-γ, and vascular endothelial growth factor (p ≤ 0.001). Patients with aspiration based on detectable pepsin had increased percentage of neutrophils (p < 0.001) and reduced BALF concentrations of IL-12 (p < 0.001). CONCLUSIONS: The BALF levels of IL-15, IL-17, basic fibroblast growth factor, tumor necrosis factor-α, myeloperoxidase, and α1-antitrypsin at 6 to 12 months after lung transplantation are predictive of early-onset BOS, and those with BOS and aspiration have an augmented chemotactic and inflammatory balance of pulmonary leukocytes and immune mediators. These data justify the surgical prevention of aspiration and argue for the refinement of antirejection regimens.

Airway pepsin levels in otherwise healthy surgical patients receiving general anesthesia with endotracheal intubation.

BACKGROUND: Airway pepsin has been increasingly used as a potentially sensitive and quantifiable biomarker for gastric-to-pulmonary aspiration, despite lack of validation in normal control subjects. This study attempts to define normal levels of airway pepsin in adults and distinguish between pepsin A (exclusive to stomach) and pepsin C (which can be expressed by pneumocytes). METHODS: We performed a prospective study of 51 otherwise healthy adult patients undergoing elective extremity orthopedic surgery at a single tertiary-care academic medical center. Lower airway samples were obtained immediately following endotracheal intubation and just prior to extubation. Total pepsin and pepsin A concentrations were directly measured by an enzymatic activity assay, and pepsin C was subsequently derived. Pepsinogen/pepsin C was confirmed by Western blot analyses. Baseline characteristics were secondarily compared. RESULTS: In all, 11 (22%; 95% CI = 9.9%-33%) had detectable airway pepsin concentrations. All 11 positive specimens had pepsin C, without any detectable pepsin A. Pepsinogen/pepsin C was confirmed by Western blot analyses. In a multivariate logistic regression, men were more likely to have airway pepsin (OR, 12.71, P = .029). CONCLUSIONS: Enzymatically active pepsin C, but not the gastric-specific pepsin A, is frequently detected in the lower airways of patients who otherwise have no risk for aspiration. This suggests that nonspecific pepsin assays should be used and interpreted with caution as a biomarker of gastropulmonary aspiration, as pepsinogen C potentially expressed from pneumocytes may be detected in airway samples.

Bronchoalveolar lavage pepsin in acute exacerbation of idiopathic pulmonary fibrosis.

Some patients with idiopathic pulmonary fibrosis experience acute exacerbations in their respiratory status leading to substantial morbidity and mortality. Occult aspiration of gastric contents has been proposed as one possible mechanism leading to these acute exacerbations. We sought to determine whether pepsin, a marker of gastric aspiration, is elevated in bronchoalveolar lavage fluid obtained from patients during acute exacerbation of idiopathic pulmonary fibrosis, compared with that obtained in stable disease. Lavage samples were obtained in a case-control study of well-characterised patients. Acute exacerbation was defined using standard criteria. Levels of lavage pepsin were compared in cases and controls, and were correlated with clinical features and disease course. 24 cases with acute exacerbations and 30 stable controls were identified. There were no significant differences in baseline demographics between the two groups. Pepsin level was an indicator of acute exacerbation status (p=0.04). On average, pepsin appeared higher in patients with acute exacerbations compared with stable controls. This difference was driven by a subgroup of eight patients (33%) with pepsin levels ≥70 ng·mL(-1). Pepsin level was not an independent predictor of survival time. These results suggest occult aspiration may play a role in some cases of acute exacerbation of idiopathic pulmonary fibrosis.

Gastric residual volumes in critical illness: what do they really mean?

The practice of measuring gastric residual volumes (GRVs) has become a routine part of enteral feeding protocols in the critical care setting. However, little scientific evidence indicates that their use improves patient outcomes. The use of GRVs is more of a tradition, which unfortunately guides the delivery of enteral nutrition (EN). The practice of GRVs is predicated on several flawed assumptions. Using GRVs in hospitalized patients assumes that the practice is well standardized, that GRVs reliably and accurately measure gastric contents, and that they sufficiently distinguish normal from abnormal emptying. The practice also assumes that GRVs are easy to interpret, that a tight correlation exists between GRVs and aspiration, and that continuing EN after a high value for GRV is obtained leads to pneumonia and adverse patient outcomes. And finally, clinicians assume that GRVs are an inexpensive "poor man's test" for determining tolerance of EN. This article reviews studies showing the fallacies of these assumptions. Although clinicians are unlikely to stop using GRVs, interpretation of these must be modified so as not to interrupt the delivery of EN. Using a protocol that directs appropriate responses to elevated GRVs should promote the delivery of EN and improve patient outcome.

Biomarkers in the diagnosis of aspiration syndromes.

Recognizing and managing the different types of aspiration events remain a challenging task due to the lack of distinguishing clinical or laboratory characteristics. Numerous biomarkers in serum, sputum and bronchoalveolar lavage have been studied, and their role in the recognition of aspiration remains controversial at this time. Recent animal investigations using an array of biomarkers based on distinct pathogenic features of each aspiration event have produced promising results; however, they have not been validated in humans. Newer markers are being introduced as diagnostic and prognostic tools in conditions such as community-acquired pneumonia and sepsis, but they have not been examined in aspiration. The present review summarizes the different biomarkers that have been studied in aspiration and those who might have a potential clinical use in the future.

Pepsin measured in induced sputum--a test for pulmonary aspiration in children?

PURPOSE: The purpose of this study was to investigate if pepsin measured in sputum is a useful marker of pulmonary aspiration secondary to gastroesophageal reflux (GER) in children. It is possible that the induced sputum procedure could cause GER and invalidate the results. The hypothesis stated that healthy children (those without history of respiratory or gastroesophageal symptoms) would not have pepsin detected in induced sputum. METHODS: Children attending surgical outpatients in the Royal Belfast Hospital for Sick Children (Belfast, Northern Ireland) were recruited. After spirometry, sputum was obtained by induction with hypertonic 3% saline. Spirometry was repeated, and complications were noted. An "in-house" enzyme-linked immunosorbent assay was used to measure pepsin concentration in sputum. The lower limit of detection of pepsin was 1.19 ng/mL. RESULTS: Children (n = 21) aged 4 to 16 years were recruited. Twenty children completed the study. No adverse effects were reported. Pepsin was detected in 17 (85%) of 20 sputum samples. CONCLUSIONS: The act of sputum induction appears to induce physiologic GER in a healthy childhood population. The analysis of pepsin in sputum obtained by sputum induction is therefore not useful in the investigation of reflux-related respiratory disease.

Effects of Nigella sativa seed extract on ameliorating lung tissue damage in rats after experimental pulmonary aspirations.

Aspiration of gastric contents can cause serious lung injury, although the mechanisms of pulmonary damage are still not clear and means of amelioration of the pulmonary damage have been little investigated. The black cumin seed, Nigella sativa L. (NS) has been shown to have specific health benefits and the aim of the current study was to investigate the possible beneficial effects of NS on experimental lung injury in male Wistar rats after pulmonary aspiration of different materials. The rats were randomly allotted into one of six experimental groups (n=7 per group): (1) saline control, (2) saline+NS treated, (3) Pulmocare (a specialized nutritional supplement given to pulmonary patients), (4) Pulmocare+NS treated, (5) hydrochloric acid, (6) hydrochloric acid+NS treated. The saline, Pulmocare and hydrochloric acid were injected into the lungs in a volume of 2 ml/kg. The rats received daily oral doses of NS volatile oil (400mg/kg body weight) by means of intragastric intubation for 7 days starting immediately after the pulmonary aspiration of the materials. After 7 days, the rats were sacrificed and tissue samples from both lungs were taken for histopathological investigation. To date, no similar study investigating the potential for NS treatment to protect against lung injury after pulmonary aspiration of materials has been reported. Our study showed that NS treatment inhibits the inflammatory pulmonary responses, reducing significantly (p<0.05) peribronchial inflammatory cell infiltration, alveolar septal infiltration, alveolar edema, alveolar exudate, alveolar macrophages, interstitial fibrosis, granuloma and necrosis formation in different pulmonary aspiration models. Our data indicate a significant reduction in the activity of inducible nitric oxide synthase (iNOS) and a rise in surfactant protein D in lung tissue of different pulmonary aspiration models after NS therapy. Based on our results, we conclude that NS treatment might be beneficial in lung injury and have potential clinical use.

Lung contusion: inflammatory mechanisms and interaction with other injuries.

This article reviews current animal models and laboratory studies investigating the pathophysiology of lung contusion (LC), a common and severe condition in patients with blunt thoracic trauma. Emphasis is on studies elucidating cells, mediators, receptors, and processes important in the innate pulmonary inflammatory response that contribute to LC injury. Surfactant dysfunction in the pathogenesis of LC is also discussed, as is the potential role of epithelial cell or neutrophil apoptosis. Studies examining combination injuries where LC is exacerbated by secondary insults such as gastric aspiration in trauma patients are also noted. The need for continuing mechanism-based research to further clarify the pathophysiology of LC injury, and to define and test potential therapeutic interventions targeting specific aspects of inflammation or surfactant dysfunction to improve clinical outcomes in patients with LC, is also emphasized.

Airway colonization and gastric aspiration after lung transplantation: do birds of a feather flock together?

BACKGROUND: Both gastroesophageal reflux and airway colonization with Pseudomonas aeruginosa (P aeruginosa) are common in lung transplantation (LTx) recipients. There is mounting evidence that, due to their interaction with the epithelium, both may be involved in chronic allograft dysfunction/bronchiolitis obliterans syndrome (BOS) after LTx. We investigated whether gastric aspiration and airway colonization with P aeruginosa after LTx are associated. METHODS: In this retrospective, cross-sectional, case-control study, 24 stable double (SS) LTx recipients were included. Markers of gastroesophageal reflux (pepsin, bile acids) and airway inflammation (neutrophilia and interleukin-8 (IL-8)) were evaluated in bronchoalveolar lavage (BAL) samples of post-operatively colonized (n = 12) and non-colonized matched-control LTx recipients (n = 12). RESULTS: BAL bile acid levels, but not pepsin levels, as well as neutrophilia and IL-8 protein levels were significantly elevated in colonized compared with non-colonized patients. Furthermore, bile acid levels, but not pepsin levels, correlated positively with BAL neutrophilia and IL-8 protein levels. CONCLUSIONS: Bile acid aspiration and airway colonization by P aeruginosa after LTx seem to be associated. This relationship between reflux and airway colonization and their role in the development of chronic allograft dysfunction/BOS after LTx should be further elucidated; nevertheless, induction of IL-8-mediated neutrophilic airway inflammation may be a putative mechanism.

Assessment of the prevalence of microaspiration by gastric pepsin in the airway of ventilated children.

AIM: Mechanically ventilated patients are at risk for aspiration of gastric contents. The aim of this observational study was to determine the prevalence of micro-aspiration in children with cuffed and uncuffed endotracheal (ET) tubes and with tracheostomies and to assess the effect of feeding status on aspiration. Micro-aspiration was determined by measuring gastric pepsin in tracheal aspirates. METHODS: We studied 27 children on ventilators in paediatric intensive care unit (PICU) and 10 children undergoing elective surgeries for various indications. Tracheal aspirates were collected from children on ventilatory support in the intensive care unit during medically indicated suctioning and from the group of children undergoing elective surgery in the operation room. Pepsin was detected by enzymatic assay. RESULTS: Overall 70% of cases in PICU were positive for pepsin in at least one of the aspirates. Pepsin positivity was significantly lower in the cuffed group than in the uncuffed and tracheostomy groups. Tube feedings did not significantly influence the prevalence of pepsin positivity. CONCLUSIONS: Measurement of gastric pepsin in tracheobronchial fluid is a sensitive tool to detect aspirations in mechanically ventilated children and to assess the efficacy of preventive measures in PICU settings.