Role of alveolar nitric oxide in gastroesophageal reflux-associated cough: prospective observational study.

BACKGROUND: Fractional exhaled nitric oxide (FeNO) measured at multiple exhalation flow rates can be used as a biomarker to differentiate central and peripheral airway inflammation. However, the role of alveolar nitric oxide (CaNO) indicating peripheral airway inflammation remains unclear in gastroesophageal reflux-associated cough (GERC). OBJECTIVES: We aimed to characterize the changes in alveolar nitric oxide (CaNO) and determine its clinical implication in GERC. DESIGN: This is a single-center prospective observational study. METHODS: FeNOs at exhalation flow rates of 50 and 200 ml/s were measured in 102 patients with GERC and 134 patients with other causes of chronic cough (non-GERC). CaNO was calculated based on a two-compartment model and the factors associated with CaNO were analyzed. The effect of anti-reflux therapy on CaNO was examined in 26 GERC patients with elevated CaNO. RESULTS: CaNO was significantly elevated in GERC compared with that in non-GERC (4.6 ± 4.4 ppb versus 2.8 ± 2.3 ppb, p < 0.001). GERC patients with high CaNO (>5 ppb) had more proximal reflux events (24 ± 15 versus 9 ± 9 episodes, p = 0.001) and a higher level of pepsin (984.8 ± 492.5 versus 634.5 ± 626.4 pg/ml, p = 0.002) in sputum supernatant than those with normal CaNO. More GERC patients with high CaNO required intensified anti-reflux therapy (χ2 = 3.963, p = 0.046), as predicted by a sensitivity of 41.7% and specificity of 83.3%. Cough relief paralleled a significant improvement in CaNO (8.3 ± 3.0 versus 4.8 ± 2.6 ppb, p < 0.001). CONCLUSION: Peripheral airway inflammation can be assessed by CaNO measurement in GERC. High CaNO indicates potential micro-aspiration and may predict a necessity for intensified anti-reflux therapy.

Role of CaNO in GERCWhy was the study done? This study aimed to investigate the role of concentration of alveolar nitric oxide (CaNO) as a biomarker for peripheral airway inflammation in patients with gastroesophageal reflux-associated cough (GERC). The evaluation of airway inflammation in GERC has not been widely practiced in clinical settings, and the potential of CaNO as a biomarker remained unclear.What did the researchers do? The researchers conducted a prospective study involving patients diagnosed with GERC and compared the changes in CaNO levels between GERC patients and those with cough due to other causes. The study also identified potential factors contributing to elevated CaNO levels in GERC patients relative to the normal range. Additionally, CaNO level changes were evaluated in a subgroup of GERC patients with initially elevated CaNO levels (n = 26).What did the researchers find? The study found that CaNO levels were significantly increased in GERC patients. Using a reference value for normal CaNO, the GERC patients were divided into a high CaNO cohort and a normal CaNO cohort. More proximal reflux episodes and higher level of pepsin in sputum supernatant were observed in the high CaNO cohort. Moreover, CaNO demonstrated moderate predictive value for the therapeutic efficacy of intensified anti-reflux therapy in GERC patients. After several weeks of anti-reflux therapy, CaNO levels significantly decreased along with the resolution of cough. These findings further confirmed the predictive value of CaNO for anti-reflux therapy.What do the findings mean? The findings suggest that CaNO may have the potential to be used as a non-invasive biomarker for detecting peripheral airway inflammation in GERC patients. Increased CaNO may be associated with potential micro-aspiration. Furthermore, high CaNO may predict the need for intensified anti-reflux therapy.

Effect of trans-nasal humidified rapid insufflation ventilatory exchange on reflux and microaspiration in patients undergoing laparoscopic cholecystectomy during induction of general anesthesia: a randomized controlled trial.

Background: Reflux aspiration is a rare but serious complication during induction of anesthesia. The primary aim of this study is to compare the incidence of reflux and microaspiration in patients undergoing laparoscopic cholecystectomy during induction of general anesthesia using either a facemask or trans-nasal humidified rapid insufflation ventilatory exchange. Methods: We conducted a single-center, randomized, controlled trial. Thirty patients were allocated to either a facemask or a trans-nasal humidified rapid insufflation ventilatory exchange (THRIVE) group. Pre-oxygenation for 5 min with a facemask or THRIVE, positive pressure ventilation for 2 min or THRIVE for 2 min after anesthesia induction was followed. Before endotracheal intubation, the secretion above and below the glottis was collected to measure pepsin content and analyze blood gas. The ELISA assay for supra- and subglottic human pepsin content was used to detect the presence of reflux and microaspiration. The primary outcome was the incidence of reflux and microaspiration. Secondary outcomes were apnea time, PaO2 before tracheal intubation, and the end-expiratory carbon dioxide partial pressure. Results: Patients in the THRIVE group had a significantly longer apnea time (379.55 ± 94.12 s) compared to patients in the facemask group (172.96 ± 58.87 s; p < 0.001). There were no differences observed in PaO2 between the groups. A significant difference in gastric insufflation, reflux, and microaspiration was observed between the groups. Gastric insufflation was 6.9% in the THRIVE group vs. 28.57% kPa in the facemask group (p = 0.041); reflux was 10.34% in the THRIVE group vs. 32.14% kPa in the facemask group (p = 0.044); and microaspiration was 0% in the THRIVE group vs. 17.86% kPa in the facemask group (p = 0.023). Conclusion: The application of THRIVE during induction of general anesthesia reduced the incidence of reflux and microaspiration while ensuring oxygenation and prolonged apnea time in laparoscopic cholecystectomy patients. THRIVE may be an optimal way to administer oxygen during the induction of general anesthesia in laparoscopic cholecystectomy patients. Clinical trial registration: Chinese Clinical Trial Registry, No: ChiCTR2100054086, https://www.chictr.org.cn/indexEN.html.

Does Dysphagia Predict Inpatient Morbidity and Mortality in Geriatric Patients Admitted for Aspiration Pneumonia?

Background Aspiration pneumonia is common in older adults admitted for community-acquired pneumonia and is associated with significant morbidity and mortality. Factors that put this population at higher risk of aspiration include cognitive impairment, neuromuscular dysfunction, and dysphagia. This study aimed to determine whether a concurrent diagnosis of dysphagia conferred a higher risk of complications in the elderly admitted for aspiration pneumonia. Methods The National Inpatient Sample 2001-2013 database was queried for patients, aged 65 or older, with a diagnosis of aspiration pneumonia using International Classification of Diseases, Ninth Revision (ICD-9) codes. Sepsis, respiratory failure, and intubation were identified with their respective ICD-9 codes. A chi-square test and binary logistic regression analysis were used to examine socio-demographic and complication variables, with a significance level of α <0.001. Results A total of 1,097,325 patients were admitted for aspiration pneumonia, of which 349,861 (24.2%) had dysphagia. After incorporating socio-demographic variables, the dysphagia group had a significantly lower likelihood of having sepsis (OR=0.72), respiratory failure (OR=0.92), intubation (OR=0.52), and inpatient mortality (OR = 0.59). Patients with dysphagia had a significantly higher likelihood of increased length of stay (OR=1.24). Conclusions Elderly patients admitted with aspiration pneumonia with a co-diagnosis of dysphagia were less likely to have inpatient morbidity and mortality compared to their counterparts. This may be due to improved speech evaluation and treatment in patients with dysphagia allowing for better control of macro and micro aspiration. Future research is needed to examine if universal speech therapy can reduce hospitalization and long-term mortality for such patients.

Oral Care Associated With Less Microaspiration in Ventilated Cardiac Patients.

Aspiration is common in mechanically ventilated patients and may predispose patients to aspiration pneumonia, chemical pneumonitis, and chronic lung damage. Pepsin A is a specific marker of gastric fluid aspiration and is often detected in ventilated pediatric patients. We investigated the effect of oral care and throat suctioning in the detection of pepsin A in tracheal aspirates (TAs) up to 4 hours after these procedures. Methods: Twelve pediatric patients between age 2 weeks to 14 years who underwent intubation for cardiac surgery were enrolled in this study. Six of the 12 patients were consented before their surgery with initial specimen collected at the time of intubation and last one shortly before extubation (intubation duration < 24 hours). The remaining 6 patients were consented after cardiac surgery. All specimens were collected per routine care per respiratory therapy protocol and shortly before extubation (intubation duration > 24 hours). Tracheal fluid aspirates were collected every 4 to 12 hours in the ventilated patients. Enzymatic assay for gastric pepsin A and protein determination were performed. The time of oral care and throat suctioning within 4 hours prior was recorded prospectively. Results: A total of 342 TA specimens were obtained from the 12 intubated pediatric patients during their course of hospitalization; 287 (83.9%) showed detectable total pepsin (pepsin A and C) enzyme activity (> 6 ng/mL) and 176 (51.5%) samples had detectable pepsin A enzyme levels (>6 ng/mL of pepsin A). Only 29 samples of 76 samples (38.2%) had evidence of microaspiration after receiving oral care, while 147 of 266 (55.3%) samples were pepsin A positive when no oral care was provided. Odds ratio is 0.50 (Cl 0.30-0.84), and the number needed to treat is 5.8 (Confidence interval 3.4-22.3). Testing air filters for pepsin was not beneficial. Conclusion: Oral care is a highly effective measure to prevent microaspiration of gastric fluid in ventilated pediatric patients. The number needed to treat (5.8) suggests this is a very effective prevention strategy. Our study suggests that pepsin A is a useful and sensitive biomarker that allows identification of gastric aspiration.

Airway ultrasound to detect subglottic secretion above endotracheal tube cuff.

BACKGROUND: Subglottic secretion had been proven as one of the causes of microaspiration and increased risk of ventilator-associated pneumonia (VAP). The role of ultrasound to detect subglottic secretion has not yet been established. PURPOSE: The purpose of this study is to determine the sensitivity and specificity of upper airway ultrasound (US) in the detection of subglottic secretions as compared to computed tomography (CT) scanning. MATERIAL AND METHODS: A prospective observational study was carried out in adult trauma patients requiring mechanical ventilation and cervical CT scan. All patients had an endotracheal tube cuff-pressure maintained between 20 and 30 cm H2O. Airway US was performed at the bedside immediately before the patient was transferred to the CT scan suite. The sensitivity, specificity, and positive/negative predictive values (PPV, NPV) of the upper airway US detection of subglottic secretions were then calculated and compared with CT findings. RESULTS: Fifty participants were consecutively included. Subglottic secretions were detected in 31 patients using upper airway US. The sensitivity and specificity of upper airway US in detecting subglottic secretion were 96.7% and 90%, respectively (PPV 93.5%, NPV 94.7%). 18 (58%) patients with subglottic secretions developed VAP during their ICU stay (p = 0.01). The area under the receiver operating curve (AUROC) was 0.977 (95% CI 0.936-1.00). CONCLUSIONS: Upper airway US is a useful tool for detecting subglottic secretions with high sensitivity and specificity. CLINICAL IMPLICATIONS: This study shows: 1. Upper airway US may aid in detecting subglottic secretions, which are linked to VAP. 2. Detecting subglottic secretions at the bedside aids in determining the best frequency of subglottic aspiration to clean the subglottic trachea. 3. Upper airway US may also aid in detecting the correct ETT position. Trial registration Clinicaltrials.gov. CLINICALTRIALS: gov identifier NCT04739878 Date of registration 2nd May 2021 URL of trial registry record https://clinicaltrials.gov/ct2/show/NCT04739878 .

Bronchoalveolar lavage (BAL) amylase and pepsin levels as potential biomarkers of aspiration pneumonia.

BACKGROUND AND OBJECTIVE: There are currently no established markers for aspiration pneumonia. We hypothesized that bronchoalveolar lavage (BAL) amylase and pepsin might be candidate biomarkers for aspiration pneumonia. METHODS: This cross-sectional study reviewed consenting adults who underwent clinically-indicated bronchoscopy at Aizu Medical Center. BAL samples were obtained using standardized methods. Amylase levels were measured in our clinical laboratory, and pepsin levels were assessed by ELISA. RESULTS: Aspiration pneumonia was clinically diagnosed based on the guidelines of the Japanese Respiratory Society in 48 of the 327 participants. Median BAL salivary amylase and pepsin levels in this group were 702.0 U/L and 12.7 ng/ml respectively, which were significantly higher than in non-aspiration pneumonia patients. BAL amylase ≥204 U/L had 77.1% sensitivity and 84.2% specificity as a diagnostic index, and the area under the receiver operating characteristic (ROC) curve was 0.859 (95% confidence interval (CI), 0.803-0.915). Similarly, BAL pepsin levels of ≥7.45 ng/ml had 87.2% sensitivity and 59.9% specificity for identifying aspiration, and the area under the ROC curve was 0.757 (95% CI, 0.688-0.826). Multivariate regression demonstrated that BAL amylase ≥204 U/L and BAL pepsin ≥7.45 ng/ml were associated with significantly higher odds for aspiration pneumonia (odds ratio (OR) 10.0, 95% CI, 4.51-22.2, and OR 8.81 95% CI, 3.32-23.4, respectively). There were no significant associations between risk factors for aspiration pneumonia and BAL amylase and pepsin levels. CONCLUSION: BAL amylase and pepsin might be useful biomarkers for suggesting aspiration pneumonia, and could be objective markers without relying on known risk factors for aspiration.

Use of an innovative cuff pressure control and subglottic secretions drainage system in COVID-19 ARDS patients undergoing pronation.

We conducted a proof of concept study where Anapnoguard endotracheal tubes and its control unit were used in 15 patients with COVID-19 acute respiratory distress syndrome. Anapnoguard system provides suction, venting, rinsing of subglottic space and controls cuff pressure detecting air leakage through the cuff. Alpha-amylase and pepsin levels, as oropharyngeal and gastric microaspiration markers, were assessed from 85 tracheal aspirates in the first 72 h after connection to the system. Oropharyngeal microaspiration occurred in 47 cases (55%). Episodes of gastric microaspiration were not detected. Patient positioning, either prone or supine, did not affect alpha-amylase and pepsin concentration in tracheal secretions. Ventilator-associated pneumonia (VAP) rate was 40%. The use of the AG system provided effective cuff pressure control and subglottic secretions drainage. Despite this, no reduction in the incidence of VAP has been demonstrated, compared to data reported in the current COVID-19 literature. The value of this new technology is worth of being evaluated for the prevention of ventilator-associated respiratory tract infections.

Snoring may transmit infectious aerosols from the upper to the lower respiratory tract.

Migration to the lungs of an initial upper airway infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or other respiratory pathogens can lead to pneumonia, associated with progression from mild to severe symptoms. Chemical pneumonitis or bacterial pneumonia may be caused by the 'macroaspiration' of large volumes of oropharyngeal or gastroesophageal secretions into the lower respiratory tract. 'Microaspiration', i.e., a similar mechanism but involving much smaller amounts of oropharyngeal secretions, is considered the pathogenetic mechanism for most pneumonias, including that associated with COVID-19. Here, we hypothesize an alternative mechanism: Rather than by microaspiration, these fluids enter the lungs as microdroplets that are generated by snoring and then carried by the inspired airstream. Laboratory measurements indicate that snoring generates (a) comparable numbers and sizes of oral fluid droplets as loud speaking and (b) total fluid quantities that are similar to those reported for microaspiration. Snoring propensity is strongly correlated to known risk factors for severe COVID-19, including male gender, age, obesity, diabetes, obstructive sleep apnea, and pregnancy. Therefore, more research is urgently needed to determine if various methods that decrease snoring can prevent progression to pneumonia after initial infection of the upper airways.

Are Cirrhotic Patients Receiving Invasive Mechanical Ventilation at Risk of Abundant Microaspiration.

Previous studies have identified cirrhosis as a risk factor for ventilator-associated pneumonia (VAP). The aim of our study was to determine the relationship between cirrhosis and abundant gastric-content microaspiration in intubated critically ill patients. We performed a matched cohort study using data from three randomized controlled trials on abundant microaspiration in patients under mechanical ventilation. Each cirrhotic patient was matched with three to four controls for gender, age ± 5 years and simplified acute physiology score II (SAPS II) ± 5 points. Abundant microaspiration was defined by significant levels of pepsin and alpha-amylase in >30% of tracheal aspirates. All tracheal aspirates were collected for the first 48 h of the study period. The percentage of patients with abundant gastric-content microaspiration was the primary outcome. The abundant microaspiration of oropharyngeal secretions, VAP incidence, the duration of mechanical ventilation, length of intensive care unit (ICU) stay and mortality were the secondary outcomes. A. total of 39 cirrhotic patients were matched to 138 controls. The percentage of patients with abundant gastric-content microaspiration did not differ between the two groups (relative risk: 0.91 (95% CI: 0.75 to 1.10)). There was no significant difference between the two groups in terms of the abundant microaspiration of oropharyngeal secretions, VAP, the duration of mechanical ventilation, the length of ICU stay and mortality. Our results suggest that cirrhosis is not associated with abundant gastric-content microaspiration.

Association of enteral feeding with microaspiration in critically ill adults.

AIM: This study explored relationships between enteral feeding and tracheal pepsin A. BACKGROUND: Mechanically ventilated (MV) patients receiving enteral feeding are at risk for microaspiration. Tracheal pepsin A, an enzyme specific to gastric cells, was a proxy for microaspiration of gastric secretions. METHODS: Secondary analysis of RCT data from critically ill, MV adults was conducted. Microaspiration prevention included elevated head of bed, endotracheal tube cuff pressure management, and regular oral care. Tracheal secretions for pepsin A were collected every 12 h. Microaspiration was defined as pepsin A ≥ 6.25 ng/mL. Positive pepsin A in >30 % of individual tracheal samples was defined as abundant microaspiration (frequent aspirator). Chi-squared, Fisher's Exact test, and generalized linear model (GLM) were used. RESULTS: Tracheal pepsin A was present in 111/283 (39 %) mechanically ventilated patients and 48 (17 %) had abundant microaspiration. Enteral feeding was associated with tracheal pepsin A, which occurred within 24 h of enteral feeding. Of the patients who aspirated, the majority received some enteral feeding 96/111 (86 %), compared to only 15/111 (14 %) who received no feeding. A greater number of positive pepsin A events occurred with post-pyloric feeding tube location (55.6 %) vs. gastric (48.6 %), although significant only at the event-level. Frequent aspirators (abundant pepsin A) had higher pepsin A levels compared to infrequent aspirators. CONCLUSIONS: Our findings confirmed the stomach as the microaspiration source. Contrary to other studies, distal feeding tube location did not mitigate microaspiration. Timing for first positive pepsin A should be studied for possible association with enteral feeding intolerance.

The Association Between Gastroesophageal Reflux Disease and Non-Small Cell Lung Cancer: A Retrospective Case-Control Study.

Background: Lung cancer is a leading cause of mortality in the USA. Non-small cell lung cancer (NSCLC) contributes to 85% of all lung cancers. It is the most prevalent subtype amongst non-smokers, and its incidence has risen in the last 20 years. In addition, gastroesophageal reflux disease (GERD) has been associated with several lung pathologies, namely idiopathic pulmonary fibrosis and asthma. We aimed to investigate the association between GERD and NSCLC by performing a retrospective, multicenter, case-control study. This is the first study of this nature to be carried out in the USA. Methods: Data were retrieved from 17 Northwell health care facilities in the New York area between the years 2010 and 2018. Inclusion criteria were patients > 18 years of age with NSCLC (large cell, adenocarcinoma, and squamous cell). They were appropriately matched with controls based on age, gender, weight, comorbidities, and medication use. Our exposure group had a diagnosis of GERD based on the International Classification of Diseases, Ninth/10th Revision (ICD 9/10) codes and endoscopic, in addition to histological evidence if present. We excluded patients with secondary lung cancers, esophageal adenocarcinoma, other primary malignancies, Barrett's esophagus, and smokers. Logistic regression was conducted to determine the adjusted odds ratio (OR) and corresponding 95% confidence interval (CI) for the association between NSCLC and GERD. Results: A total of 1,083 subjects were included in our study: 543 (50%) patients were diagnosed with NSCLC. In this population, GERD was twice as prevalent compared to controls (20.4% vs. 11.6%, P < 0.001). Multivariate analysis demonstrated that GERD was associated with a higher risk of NSCLC compared to matched controls (OR = 1.86, 95% CI = 1.26 - 2.73). In addition, GERD patients treated with either antihistamines or proton pump inhibitors did not demonstrate an overall reduced risk of NSCLC (OR = 1.01, 95% CI = 0.48 - 2.12). Conclusions: Our study demonstrates that GERD is associated with a higher risk of NSCLC, irrespective of GERD treatment. We postulate that GERD patients suffer from chronic micro-aspirations leading to a prolonged inflammatory state within the lung parenchyma, triggering specific proliferative signaling pathways that may lead to malignant transformation.

Utility of bile acids in large airway bronchial wash versus bronchoalveolar lavage as biomarkers of microaspiration in lung transplant recipients: a retrospective cohort study.

BACKGROUND: Bronchoalveolar lavage (BAL) is a key tool in respiratory medicine for sampling the distal airways. BAL bile acids are putative biomarkers of pulmonary microaspiration, which is associated with poor outcomes after lung transplantation. Compared to BAL, large airway bronchial wash (LABW) samples the tracheobronchial space where bile acids may be measurable at more clinically relevant levels. We assessed whether LABW bile acids, compared to BAL bile acids, are more strongly associated with poor clinical outcomes in lung transplant recipients. METHODS: Concurrently obtained BAL and LABW at 3 months post-transplant from a retrospective cohort of 61 lung transplant recipients were analyzed for taurocholic acid (TCA), glycocholic acid (GCA), and cholic acid by mass spectrometry and 10 inflammatory proteins by multiplex immunoassay. Associations between bile acids with inflammatory proteins and acute lung allograft dysfunction were assessed using Spearman correlation and logistic regression, respectively. Time to chronic lung allograft dysfunction and death were evaluated using multivariable Cox proportional hazards and Kaplan-Meier methods. RESULTS: Most bile acids and inflammatory proteins were higher in LABW than in BAL. LABW bile acids correlated with inflammatory proteins within and between sample type. LABW TCA and GCA were associated with acute lung allograft dysfunction (OR = 1.368; 95%CI = 1.036-1.806; P = 0.027, OR = 1.064; 95%CI = 1.009-1.122; P = 0.022, respectively). No bile acids were associated with chronic lung allograft dysfunction. Adjusted for risk factors, LABW TCA and GCA predicted death (HR = 1.513; 95%CI = 1.014-2.256; P = 0.042, HR = 1.597; 95%CI = 1.078-2.366; P = 0.020, respectively). Patients with LABW TCA in the highest tertile had worse survival compared to all others. CONCLUSIONS: LABW bile acids are more strongly associated than BAL bile acids with inflammation, acute lung allograft dysfunction, and death in lung transplant recipients. Collection of LABW may be useful in the evaluation of microaspiration in lung transplantation and other respiratory diseases.

Effect of invasive mechanical ventilation on the diversity of the pulmonary microbiota.

Pulmonary microbial diversity may be influenced by biotic or abiotic conditions (e.g., disease, smoking, invasive mechanical ventilation (MV), etc.). Specially, invasive MV may trigger structural and physiological changes in both tissue and microbiota of lung, due to gastric and oral microaspiration, altered body posture, high O2 inhalation-induced O2 toxicity in hypoxemic patients, impaired airway clearance and ventilator-induced lung injury (VILI), which in turn reduce the diversity of the pulmonary microbiota and may ultimately lead to poor prognosis. Furthermore, changes in (local) O2 concentration can reduce the diversity of the pulmonary microbiota by affecting the local immune microenvironment of lung. In conclusion, systematic literature studies have found that invasive MV reduces pulmonary microbiota diversity, and future rational regulation of pulmonary microbiota diversity by existing or novel clinical tools (e.g., lung probiotics, drugs) may improve the prognosis of invasive MV treatment and lead to more effective treatment of lung diseases with precision.

Biomechanical responses of encysted zoospores of the oomycete Achlya bisexualis to hyperosmotic stress are consistent with an ability to turgor regulate.

Zoospores are motile, asexual reproductive propagules that enable oomycete pathogens to locate and infect new host tissue. While motile, they have no cell wall and maintain tonicity with their external media using water expulsion vacuoles. Once they locate host tissue, they encyst and form a cell wall, enabling the generation of turgor pressure that will provide the driving force for germination and invasion of the host. It is not currently known how these spores respond to the osmotic stresses that might arise due to different environments on and around their hosts that have different osmotic strengths. We have made microaspiration (MA) measurements on > 800 encysted zoospores and atomic force microscopy (AFM) measurements on 12 encysted zoospores to determine their mechanical properties and how these change after hyperosmotic stress. Two types of encysted zoospores (Type A and Type B) were produced from the oomycete Achlya bisexualis, that differed in their morphology and response. With a small hyperosmotic stress (using 0.1 and 0.2 M sorbitol to give media osmolality changes of 155.4 and 295.6 mOsmol/kg), Type A zoospores initially became stiffer, with an increase in the Young's modulus (E) over 30 mins from 0.16 MPa to 0.25 and 0.22 MPa respectively. E then returned to its original value after 120 min. With a greater osmotic stress (using 0.3, 0.4 and 0.5 M sorbitol to give media osmolality changes of 438.2, 587.2 and 787.6 mOsmol/kg) the reverse occurred, with an initial decrease in E over 30 - 60 mins to values of 0.1, 0.08 and 0.09 MPa respectively, before recovery to the original value after 120 min. In 0.5 M sorbitol this recovery was only observed with AFM, but not with MA. Type B zoospores, which may be primary/secondary spores about to release secondary/tertiary spores, or else spores that were damaged during encystment, initially stiffened in response to the lower hyperosmotic stresses with a slight increase in E (from 0.077 to 0.1 MPa after 15 min (with both 0.1 and 0.2 M sorbitol) before recovering to the original value after 60 min. These spores showed no change in response to the higher osmotic stresses. The responses of the Type A spores are consistent with rapid changes in cell wall thickness and a turgor regulation mechanism. Turgor regulation is further supported by microscopic observations of the Type A spores showing protoplast retraction from the cell wall followed by deplasmolysis, coupled with measurements of spore volume. As far as we are aware this is the first demonstration of turgor regulation, not just in encysted zoospores, but in oomycetes in general.

The current definition, epidemiology, animal models and a novel therapeutic strategy for aspiration pneumonia.

In the 21st century, aspiration pneumonia (ASP) is very common in older patients, and has a high mortality rate. ASP is diagnosed following confirmation of inflammatory findings in the lungs and overt aspiration or the existence of dysphagia. It is dominant in hospitalized community-acquired pneumonia (CAP), nursing and healthcare-associated pneumonia (NHCAP), and hospital-acquired pneumonia (HAP). The incidence of ASP is increasing every year. The human and experimental animal data revealed that micro-aspiration due to dysphagia during the night is the central mechanism of ASP. Therefore, the precise assessment of swallowing function is the key to diagnose ASP. From a therapeutic point of view, an appropriate administration of antibiotics, as well as a comprehensive approach for dysphagia plays a pivotal role in the prognosis and recovery from ASP. The non-pharmacologic approach, including swallowing rehabilitation and oral care, and a pharmacologic approach including ACE inhibitors and bronchodilators, are essential modalities for treatment and prevention of ASP. The clinical data of NHCAP provides us with a promising treatment strategy for ASP.

Positive bronchoalveolar lavage pepsin assay associated with viral and fungal respiratory infections in children with chronic cough.

OBJECTIVE: To assess the association between commonly obtained endoscopic and serologic data and bronchoalveolar lavage pepsin assay (BAL) results in children with chronic cough. STUDY DESIGN: We performed a retrospective chart review of 72 children with a BAL pepsin obtained through our Aerodigestive Center over an 18-month period. BAL outcomes include evidence of viral, bacterial, or fungal infection, presence of lipid-laden macrophages, and cytology (eosinophils, neutrophils, and lymphocytes). Gastrointestinal outcomes include esophagogastroduodenoscopy (EGD) and pH impedance probe findings. Other characteristics include serum eosinophils, neutrophils, and lymphocytes; spirometry; FeNO; and IgE. RESULTS: Seventy-two patients underwent BAL pepsin testing. Median age was 4.9 years, 30.6% had severe persistent asthma, and 59.2% were on reflux medication. There was an association between positive BAL pepsin assay and positive viral panel (p = .002) or fungal culture (p = .027). No significant association found between positive BAL bacterial culture; BAL cytology; the presence of BAL lipid-laden macrophages; IgE; spirometry; FeNO; CBC neutrophil, eosinophil, or lymphocytes; pH impedance testing parameters; or EGD pathology. CONCLUSIONS: BAL pepsin is associated with a positive BAL viral PCR or fungal culture. Lack of correlation between pepsin-positivity and pH-impedance parameters or EGD pathology suggests microaspiration may be due to an acute event (such as a respiratory infection) rather than chronic gastroesophageal reflux disease. This may be especially true in the presence of a positive viral panel or fungal culture when a BAL pepsin is obtained.

Relationship Between Obesity and Ventilator-Associated Pneumonia: A Post Hoc Analysis of the NUTRIREA2 Trial.

BACKGROUND: Patients with obesity are at higher risk for community-acquired and nosocomial infections. However, no study has specifically evaluated the relationship between obesity and ventilator-associated pneumonia (VAP). RESEARCH QUESTION: Is obesity associated with an increased incidence of VAP? STUDY DESIGN AND METHODS: This study was a post hoc analysis of the Impact of Early Enteral vs Parenteral Nutrition on Mortality in Patients Requiring Mechanical Ventilation and Catecholamines (NUTRIREA2) open-label, randomized controlled trial performed in 44 French ICUs. Adults receiving invasive mechanical ventilation and vasopressor support for shock and parenteral nutrition or enteral nutrition were included. Obesity was defined as BMI ≥ 30 kg/m2 at ICU admission. VAP diagnosis was adjudicated by an independent blinded committee, based on all available clinical, radiologic, and microbiologic data. Only first VAP episodes were taken into account. Incidence of VAP was analyzed by using the Fine and Gray model, with extubation and death as competing risks. RESULTS: A total of 699 (30%) of the 2,325 included patients had obesity; 224 first VAP episodes were diagnosed (60 and 164 in obese and nonobese groups, respectively). The incidence of VAP at day 28 was 8.6% vs 10.1% in the two groups (hazard ratio, 0.85; 95% CI 0.63-1.14; P = .26). After adjustment on sex, McCabe score, age, antiulcer treatment, and Sequential Organ Failure Assessment at randomization, the incidence of VAP remained nonsignificant between obese and nonobese patients (hazard ratio, 0.893; 95% CI, 0.66-1.2; P = .46). Although no significant difference was found in duration of mechanical ventilation and ICU length of stay, 90-day mortality was significantly lower in obese than in nonobese patients (272 of 692 [39.3%] patients vs 718 of 1,605 [44.7%]; P = .02). In a subgroup of patients (n = 123) with available pepsin and alpha-amylase measurements, no significant difference was found in rate of abundant microaspiration of gastric contents, or oropharyngeal secretions between obese and nonobese patients. INTERPRETATION: Our results suggest that obesity has no significant impact on the incidence of VAP.

A new diagnostic paradigm for laryngopharyngeal reflux disease: correlation of impedance-pH monitoring and digital reflux scintigraphy results.

PURPOSE: No gold-standard investigation exists for laryngopharyngeal reflux (LPR). Multichannel intraluminal impedance (MII)-pH testing has uncertain utility in LPR. Meanwhile, reflux scintigraphy allows immediate and delayed visualisation of tracer reflux in the esophagus, pharynx, and lungs. The present study aimed to correlate MII-pH and scintigraphic reflux results in patients with primary LPR. METHODS: Consecutive patients with LPR underwent MII-pH and scintigraphic reflux studies. Abnormal values for MII-pH results were defined from existing literature. MII-pH and scintigraphic data were correlated. RESULTS: 105 patients with LPR [31 males (29.5%), median age 60 years (range 20-87)] were studied. Immediate scintigraphic reflux was seen in the pharynx in 94 (90.4%), and in the proximal esophagus in 94 (90.4%). Delayed scintigraphic contamination of the pharynx was seen in 101 patients (96.2%) and in the lungs of 56 patients (53.3%). For MII-pH, abnormally frequent reflux was seen in the distal esophagus in 12.4%, proximal esophagus in 25.7%, and in the pharynx in 82.9%. Patients with poor scintigraphic clearance had higher Demeester scores (p = 0.043), more proximal reflux episodes (p = 0.046), more distal acid reflux episodes (p = 0.023), and more prolonged bolus clearance times (p = 0.002). CONCLUSION: Reflux scintigraphy has a high yield in LPR patients. Scintigraphic time-activity curves correlated with validated MII-pH results. A high rate of pulmonary microaspiration was found in LPR patients. This study demonstrated a high level of pharyngeal contamination by scintigraphy and MII-pH, which supports the use of digital reflux scintigraphy in diagnosing LPR.

Is COPD associated with increased risk for microaspiration in intubated critically ill patients?

BACKGROUND: Although COPD patients are at higher risk for aspiration when breathing spontaneously, no information is available on the risk for microaspiration in invasively ventilated COPD patients. The aim of our study was to determine the relationship between COPD and abundant microaspiration in intubated critically ill patients. METHODS: This was a retrospective analysis of prospectively collected data, provided by 3 randomized controlled trials on microaspiration in critically ill patients receiving invasive mechanical ventilation for more than 48 h. Abundant microaspiration was defined as the presence of pepsin and or alpha-amylase at significant levels in tracheal aspirates. In all study patients, pepsin and alpha-amylase were quantitatively measured in all tracheal aspirates collected during a 48-h period. COPD was defined using spirometry criteria. RESULTS: Among the 515 included patients, 70 (14%) had proven COPD. Pepsin and alpha-amylase were quantitatively measured in 3873 and 3764 tracheal aspirates, respectively. No significant difference was found in abundant microaspiration rate between COPD and non-COPD patients (62 of 70 patients (89%) vs 366 of 445 (82%) patients, p = 0.25). Similarly, no significant difference was found in abundant microaspiration of gastric contents (53% vs 45%, p = 0.28), oropharyngeal secretions (71% vs 71%, p = 0.99), or VAP (19% vs 22%, p = 0.65) rates between the two groups. No significant difference was found between COPD and non-COPD patients in duration of mechanical ventilation, ICU length of stay, or ICU mortality. CONCLUSIONS: Our results suggest that COPD is not associated with increased risk for abundant microaspiration in intubated critically ill patients.

The risk of microaspiration during oral care in mechanically ventilated patients: A randomised cross-over study comparing two different suction protocols.

OBJECTIVES: To assess whether optimised oral care including subglottic suction could reduce microaspiration in comparison with a routine oral care. RESEARCH METHODOLOGY/DESIGN: An open prospective study comparing optimized¼versus a routine oral care procedure in two randomised crossover consecutive periods of one day each. Optimised oral care consisted of suction via the subglottic suction port before and after a 10 seconds chlorhexidine oral care, compared with no use of the port during routine care. SETTING: Single-centre inclusion of critically ill patients ventilated for ≥48 hours with a subglottic suction endotracheal tube, no curare, Ramsay score not <3, and semi-quantitative assessments of tracheal secretions ≥ ++. MAIN OUTCOME MEASURES: Amylase being a relevant surrogate for oropharyngeal content, microaspirations were defined by tracheal/oral amylase ratio. RESULTS: 21 patients (11 and 10 with routine and optimised care in the first day respectively) with no baseline difference in risk of microaspiration. Neither difference in tracheal amylase amount or in tracheal/oral amylase ratio (1.5% (0.7%-16%) and 2.3% (0.6%-6%), p = 0.37) was observed indicating that microaspirations were not significantly decreased after optimized versus routine oral care. CONCLUSION: Suctioning by the subglottic port of endotracheal tubes may not decrease the risk of microaspiration during oral care of ventilated patients.