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.

Imbalance between alpha-1-antitrypsin and interleukin 6 is associated with in-hospital mortality and thrombosis during COVID-19.

Thrombosis is a hallmark of severe COVID-19. Alpha-1-antitrypsin (AAT), an inflammation-inducible serpin with anti-inflammatory, tissue protective and anticoagulant properties may be involved in severe COVID-19 pathophysiology including thrombosis onset. In this study, we examined AAT ability to predict occurrence of thrombosis and in-hospital mortality during COVID-19. To do so, we performed a monocentric cross-sectional study of 137 hospitalized patients with COVID-19 of whom 56 (41%) were critically ill and 33 (22.4%) suffered from thrombosis during hospitalization. We measured AAT and IL-6 plasma levels in all patients and phenotyped AAT in a subset of patients with or without thrombosis paired for age, sex and COVID-19 severity. We observed that AAT levels at admission were higher in both non-survivors and thrombosis patients than in survivors and non-thrombosis patients. AAT: IL-6 ratio was lower in non-survivors and thrombosis patients. In a logistic regression multivariable analysis model adjusted on age, BMI and D-dimer levels, a higher AAT: IL-6 was a protective factor of both in-hospital mortality (Odds ratio, OR: 0.07 95%CI [0.02-0.25], p < 0.001) and thrombosis (OR 0.36 95%CI [0.14-0.82], p = 0.02). AAT phenotyping did not show a higher proportion of AAT abnormal variants in thrombosis patients.Our findings suggest an insufficient production of AAT regarding inflammation intensity during severe COVID-19. AAT appeared as a powerful predictive marker of severity, mortality and thrombosis mirroring the imbalance between harmful inflammation and protective counter-balancing mechanism in COVID-19. Restoring the balance between AAT and inflammation could offer therapeutic opportunities in severe COVID-19.

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.

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.

Transesophageal echocardiography-associated tracheal microaspiration and ventilator-associated pneumonia in intubated critically ill patients: a multicenter prospective observational study.

BACKGROUND: Microaspiration of gastric and oropharyngeal secretions is the main causative mechanism of ventilator-associated pneumonia (VAP). Transesophageal echocardiography (TEE) is a routine investigation tool in intensive care unit and could enhance microaspiration. This study aimed at evaluating the impact of TEE on microaspiration and VAP in intubated critically ill adult patients. METHODS: It is a four-center prospective observational study. Microaspiration biomarkers (pepsin and salivary amylase) concentrations were quantitatively measured on tracheal aspirates drawn before and after TEE. The primary endpoint was the percentage of patients with TEE-associated microaspiration, defined as: (1) ≥ 50% increase in biomarker concentration between pre-TEE and post-TEE samples, and (2) a significant post-TEE biomarker concentration (> 200 µg/L for pepsin and/or > 1685 IU/L for salivary amylase). Secondary endpoints included the development of VAP within three days after TEE and the evolution of tracheal cuff pressure throughout TEE. RESULTS: We enrolled 100 patients (35 females), with a median age of 64 (53-72) years. Of the 74 patients analyzed for biomarkers, 17 (23%) got TEE-associated microaspiration. However, overall, pepsin and salivary amylase levels were not significantly different between before and after TEE, with wide interindividual variability. VAP occurred in 19 patients (19%) within 3 days following TEE. VAP patients had a larger tracheal tube size and endured more attempts of TEE probe introduction than their counterparts but showed similar aspiration biomarker concentrations. TEE induced an increase in tracheal cuff pressure, especially during insertion and removal of the probe. CONCLUSIONS: We could not find any association between TEE-associated microaspiration and the development of VAP during the three days following TEE in intubated critically ill patients. However, our study cannot formally rule out a role for TEE because of the high rate of VAP observed after TEE and the limitations of our methods.

Multiplex targeted high-throughput sequencing in a series of 352 patients with congenital limb malformations.

Congenital limb malformations (CLM) comprise many conditions affecting limbs and more than 150 associated genes have been reported. Due to this large heterogeneity, a high proportion of patients remains without a molecular diagnosis. In the last two decades, advances in high throughput sequencing have allowed new methodological strategies in clinical practice. Herein, we report the screening of 52 genes/regulatory sequences by multiplex high-throughput targeted sequencing, in a series of 352 patients affected with various CLM, over a 3-year period of time. Patients underwent a clinical triage by expert geneticists in CLM. A definitive diagnosis was achieved in 35.2% of patients, the yield varying considerably, depending on the phenotype. We identified 112 single nucleotide variants and 26 copy-number variations, of which 52 are novel pathogenic or likely pathogenic variants. In 6% of patients, variants of uncertain significance have been found in good candidate genes. We showed that multiplex targeted high-throughput sequencing works as an efficient and cost-effective tool in clinical practice for molecular diagnosis of congenital limb malformations. Careful clinical evaluation of patients may maximize the yield of CLM panel testing.

Impact of nutrition route on microaspiration in critically ill patients with shock: a planned ancillary study of the NUTRIREA-2 trial.

BACKGROUND: Microaspiration of gastric and oropharyngeal secretions is the main mechanism of entry of bacteria into the lower respiratory tract in intubated critically ill patients. The aim of this study is to determine the impact of enteral nutrition, as compared with parenteral nutrition, on abundant microaspiration of gastric contents and oropharyngeal secretions. METHODS: Planned ancillary study of the randomized controlled multicenter NUTRIREA2 trial. Patients with shock receiving invasive mechanical ventilation were randomized to receive early enteral or parenteral nutrition. All tracheal aspirates were collected during the 48 h following randomization. Abundant microaspiration of gastric contents and oropharyngeal secretions was defined as the presence of significant levels of pepsin (> 200 ng/ml) and salivary amylase (> 1685 UI/ml) in > 30% of tracheal aspirates. RESULTS: A total of 151 patients were included (78 and 73 patients in enteral and parenteral nutrition groups, respectively), and 1074 tracheal aspirates were quantitatively analyzed for pepsin and amylase. Although vomiting rate was significantly higher (31% vs 15%, p = 0.016), constipation rate was significantly lower (6% vs 21%, p = 0.010) in patients with enteral than in patients with parenteral nutrition. No significant difference was found regarding other patient characteristics. The percentage of patients with abundant microaspiration of gastric contents was significantly lower in enteral than in parenteral nutrition groups (14% vs 36%, p = 0.004; unadjusted OR 0.80 (95% CI 0.69, 0.93), adjusted OR 0.79 (0.76, 0.94)). The percentage of patients with abundant microaspiration of oropharyngeal secretions was significantly higher in enteral than in parenteral nutrition groups (74% vs 54%, p = 0.026; unadjusted OR 1.21 (95% CI 1.03, 1.44), adjusted OR 1.23 (1.01, 1.48)). No significant difference was found in percentage of patients with ventilator-associated pneumonia between enteral (8%) and parenteral (10%) nutrition groups (HR 0.78 (0.26, 2.28)). CONCLUSIONS: Our results suggest that enteral and parenteral nutrition are associated with high rates of microaspiration, although oropharyngeal microaspiration was more common with enteral nutrition and gastric microaspiration was more common with parenteral nutrition. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03411447 . Registered 18 July 2017. Retrospectively registered.

Impact of subglottic secretion drainage on microaspiration in critically ill patients: a prospective observational study.

BACKGROUND: Microaspiration is a major factor in ventilator-associated pneumonia (VAP) pathophysiology. Subglottic secretion drainage (SSD) aims at reducing its incidence. METHODS: Single-center prospective observational study, performed in a French intensive care unit (ICU) from March 2012 to April 2013, including adult patients mechanically ventilated for at least 24 hours divided in two groups: patients in the SSD group intubated using tracheal tubes allowing SSD and patients in the control group intubated with standard tracheal tubes. Pepsin and salivary amylase concentrations were measured for 24 hours in all tracheal aspirates. Primary objective was to determine the impact of SSD on gastric or oropharyngeal microaspiration using pepsin or amylase concentration in tracheal aspirates. RESULTS: Fifty-five patients were included in the SSD group and 45 in the control group. No difference was found between groups regarding the incidence of microaspiration defined as at least one tracheal aspirate positive for either pepsin or amylase [49 (89%) vs. 37 (82%), P=0.469]. Percentage of patients with VAP [16 (29%) vs. 11 (24%), P=0.656], ventilator-associated tracheobronchitis (VAT) [7 (13%) vs. 4 (9%), P=0.750] or early airway colonization [15 (35%) vs. 8 (18%), P=0.219] were not significantly different in study groups. CONCLUSIONS: SSD did not reduce the incidence of microaspiration, VAP, VAT or airway colonization in this observational study.

Description of 22 new alpha-1 antitrypsin genetic variants.

Alpha-1 antitrypsin deficiency is an autosomal co-dominant disorder caused by mutations of the highly polymorphic SERPINA1 gene. This genetic disorder still remains largely under-recognized and can be associated with lung and/or liver injury. The laboratory testing for this deficiency typically comprises serum alpha-1 antitrypsin quantification, phenotyping according to the isoelectric focusing pattern and genotyping if necessary. To date, more than 100 SERPINA1 variants have been described and new genetic variants are frequently discovered. Over the past 10 years, 22 new genetic variants of the SERPINA1 gene were identified in the daily practice of the University Medical laboratories of Lille and Lyon (France). Among these 22 variants, seven were Null alleles and one with a M1 migration pattern (M1Cremeaux) was considered as deficient according to the clinical and biological data and to the American College of Medical Genetics and Genomics (ACMG) criteria. Three other variants were classified as likely pathogenic, three as variants of uncertain significance while the remaining ones were assumed to be neutral. Moreover, we also identified in this study two recently described SERPINA1 deficient variants: Trento (p.Glu99Val) and SDonosti (p.Ser38Phe). The current data, together with a recent published meta-analysis, represent the most up-to-date list of SERPINA1 variants available so far.

Alpha1 antitrypsin deficiency due to an homozygous PI* Null Q0Cairo mutation: Early onset of pulmonary manifestations and variability of clinical expression.

Alpha-1 antitrypsin deficiency is an autosomal, codominant disorder caused by mutations of the SERPINA1 gene. This genetic disorder is mainly associated with development of pulmonary emphysema and/or chronic liver disease and cirrhosis. Here we report a very rare alpha-1 antitrypsin Null Q0cairo homozygous mutation characterized by a complete absence of alpha-1 antitrypsin in the plasma, in a non-consanguineous Moroccan family. This mutation has been previously described in heterozygosis in only three cases worldwide: an Italian/Egyptian family and two Italian families (Zorzetto et al., 2005). The main clinical features in two members of this Moroccan family were the severity and precocity of bronchiectasis, quickly spreading and seriously limiting respiratory function and physical activity by the second decade of age. Moreover, the index case presented with many episodes of pulmonary infections concomitant with severe neutropenia. The third member of the family presented with ankylosing spondyloarthritis and developed panniculitis later but had no respiratory symptoms. The presence of this alpha-1-antitrypsin Q0cairo homozygous mutation could explain the severity of clinical manifestations. Moreover, our observations highlight a great variability of clinical expression for the same mutation: early severe bronchiectasis, panniculitis, rheumatologic manifestations. This study further underlines the importance of genotyping by whole SERPINA1 gene sequencing in addition to serum alpha-1 antitrypsin determination, to enable detection of alpha-1 antitrypsin deficiency due to rare genotypes.

Efficiency of an electronic device in controlling tracheal cuff pressure in critically ill patients: a randomized controlled crossover study.

BACKGROUND: Despite intermittent control of tracheal cuff pressure (P cuff) using a manual manometer, cuff underinflation (<20 cmH2O) and overinflation (>30 cmH2O) frequently occur in intubated critically ill patients, resulting in increased risk of microaspiration and tracheal ischemic lesions. The primary objective of our study was to determine the efficiency of an electronic device in continuously controlling P cuff. The secondary objective was to determine the impact of this device on the occurrence of microaspiration of gastric or oropharyngeal secretions. METHODS: Eighteen patients requiring mechanical ventilation were included in this prospective randomized controlled crossover study. They randomly received either continuous control of P cuff with Mallinckrodt® device for 24 h, followed by discontinuous control with a manual manometer for 24 h, or the reverse sequence. During the 48 h after randomization, P cuff was continuously recorded, and pepsin and alpha amylase were quantitatively measured in tracheal aspirates. P cuff target was 25 cmH2O. RESULTS: Clinical characteristics were similar during the two study periods, as well as mean airway pressure. Percentage of time spent with cuff overinflation or underinflation was significantly lower during continuous control compared with routine care period [median (IQR) 0.8 (0.1, 2) vs 20.9 (3.1, 40.1), p = 0.0009]. No significant difference was found in pepsin [median (IQR) 230 (151, 300) vs 259 (134, 368), p = 0.95] or in alpha amylase level [median (IQR) 1475 (528, 10,333) vs 2400 (1342, 15,391), p = 0.19] between continuous control and routine care periods, respectively. CONCLUSIONS: The electronic device is efficient in controlling P cuff, compared with routine care using a manometer. Further studies are needed to evaluate the impact of this device on intubation-related complications. Trial registration ClinicalTrials.gov Identifier: NCT01965821.

Tapered-cuff Endotracheal Tube Does Not Prevent Early Postoperative Pneumonia Compared with Spherical-cuff Endotracheal Tube after Major Vascular Surgery: A Randomized Controlled Trial.

BACKGROUND: Patients undergoing major vascular surgery often develop postoperative pneumonia that impacts their outcomes. Conflicting data exist concerning the potential benefit of tapered-shaped cuffs on tracheal sealing. The primary objective of this study was to assess the efficiency of a polyvinyl chloride tapered-cuff endotracheal tube at reducing the postoperative pneumonia rate after major vascular surgery. Secondary objectives were to determine its impact on microaspiration, ventilator-associated pneumonia rate, and inner cuff pressure. METHODS: This prospective randomized controlled study included 109 patients who were randomly assigned to receive either spherical- (standard cuff) or taper-shaped (tapered cuff) endotracheal tubes inserted after anesthesia induction and then admitted to the intensive care unit after major vascular surgery. Cuff pressure was continuously recorded over 5 h. Pepsin and α-amylase concentrations in tracheal aspirates were quantified on postoperative days 1 and 2. The primary outcome was the early postoperative pneumonia frequency. RESULTS: Comparing the tapered-cuff with standard-cuff group, respectively, postoperative pneumonia rates were comparable (42 vs. 44%, P = 0.87) and the percentage (interquartile range) of cuff-pressure time with overinflation was significantly higher (16.1% [1.5 to 50] vs. 0.6% [0 to 8.3], P = 0.01), with a 2.5-fold higher coefficient of variation (20.2 [10.6 to 29.4] vs. 7.6 [6.2 to 10.2], P < 0.001). Although microaspiration frequencies were high, they did not differ between groups. CONCLUSION: For major vascular surgery patients, polyvinyl chloride tapered-cuff endotracheal tubes with intermittent cuff-pressure control did not lower the early postoperative pneumonia frequency and did not prevent microaspiration.

Health-related quality of life in patients with alpha-1 antitrypsin deficiency: the French experience.

The French registry of patients with alpha-1 antitrypsin deficiency (AATD)-associated emphysema was launched in 2006. Here, we aimed to report on the baseline characteristics of these patients, their health-related quality of life (HRQoL) and factors associated with HRQoL. Another goal was to survey the practices of French physicians regarding augmentation therapy. We included 273 patients with AATD, emphysema, obstructive-pattern [forced expiratory volume in 1 sec/forced volume capacity (FEV1/FVC) < 0.7], FEV1 ≤ 80% predicted. Mean (SD) age was 51.8 (11.1) years, 240 (87.9%) of patients were smokers or ex-smokers, mean (SD) FEV1 was 40.5% (15.7) predicted. Mean (SD) SGRQ score was 49.0 (20.0) and was higher for females than males (52.7 [20.7] vs 46.8 [18.2]; p = 0.01). Dyspnea showed the strongest association with SGRQ score (r = 0.65; p < 0.0001), followed by chronic bronchitis (r = 0.33; p < 0.0001) and wheezing (r = 0.32; p < 0.0001). Number of exacerbations in the year before inclusion was also significantly associated with SGRQ score (r = 0.36; p < 0.0001). The SGRQ score was associated with the 6-min walking distance (r = -0.53, p < 0.0001), FEV1 (% predicted, r = -0.53, p < 0.0001) and DLCO (% predicted, r = -0.52, p < 0.0001). It was also associated with the GOLD 2006 (r = 0.53; p < 0.0001) and GOLD 2011 (r = 0.63; p< 0.0001) classifications and with the BODE index (r = 0.37; p < 0.0001). Age, history of tobacco smoking or current smoking did not show any association with SGRQ total scores. On multivariate analysis, a model including age, chronic bronchitis, dyspnea (MRC scale), diffusing lung capacity and 6-min walking distance explained 57% of the variation in the score. The French registry provides important insights into the clinical characteristics of French patients with AATD-related emphysema.

[Development of a laboratory test on dried blood spots for facilitating early diagnosis of alpha-1-antitrypsin deficiency]. / Diagnostic biologique du déficit en alpha-1-antitrypsine : développement d'un test simplifié sur goutte de sang recueillie sur papier-filtre.

Alpha- 1-antitrypsin (A1AT) deficiency is a hereditary autosomal codominant genetic disorder resulting in low circulating levels of A1AT and leading to lung and/or liver disease. It remains underdiagnosed and only 5 to 10% of PIZZ patients, the most common form of severe A1AT deficiency, would be actually identified in France. Facilitating early diagnosis of A1AT deficiency would allow a better management of this disease; therefore we have developed and standardized in three laboratories involved in this study, a diagnostic test on dried blood spots (DBS) including quantitative A1AT measurement, phenotyping by IEF electrophoresis and, if necessary, genotyping by SERPINA1 gene sequencing. We performed a quantitative assay on 90 DBS samples by immunoturbidimetric or immunonephelometric methods. We demonstrated that both methods were suitable for this type of sampling and the results obtained were highly correlated (R(2)>0.9) between the three laboratories: for a target value of 1.00 g/L, the results obtained from the three laboratories were between 1.00 and 1.02 g/L. Phenotyping and genotyping were performed under redefined operating conditions and adapted to the analysis of DBS samples. The results were comparable with those obtained for venous blood samples. Following this work, it becomes possible to provide pulmonologists with a reliable kit to perform a capillary blood sampling on filter paper which would allow a large-scale screening of A1AT deficiency in the population particularly affected by this genetic condition.

Accuracy of alpha amylase in diagnosing microaspiration in intubated critically-ill patients.

OBJECTIVES: Amylase concentration in respiratory secretions was reported to be a potentially useful marker for aspiration and pneumonia. The aim of this study was to determine accuracy of α-amylase in diagnosing microaspiration in critically ill patients. METHODS: Retrospective analysis of prospectively collected data collected in a medical ICU. All patients requiring mechanical ventilation for at least 48 h, and included in a previous randomized controlled trial were eligible for this study, provided that at least one tracheal aspirate was available for α-amylase measurement. As part of the initial trial, pepsin was quantitatively measured in all tracheal aspirates during a 48-h period. All tracheal aspirates were frozen, allowing subsequent measurement of α-amylase for the purpose of the current study. Microaspiration was defined as the presence of at least one positive tracheal aspirate for pepsin (>200 ng.mL-1). Abundant microaspiration was defined as the presence of pepsin at significant level in >74% of tracheal aspirates. RESULTS: Amylase was measured in 1055 tracheal aspirates, collected from 109 patients. Using mean α-amylase level per patient, accuracy of α-amylase in diagnosing microaspiration was moderate (area under the receiver operator curve 0.72±0.05 [95%CI 0.61-0.83], for an α-amylase value of 1685 UI.L-1). However, when α-amylase levels, coming from all samples, were taken into account, area under the receiver operator curve was 0.56±0.05 [0.53-0.60]. Mean α-amylase level, and percentage of tracheal aspirates positive for α-amylase were significantly higher in patients with microaspiration, and in patients with abundant microaspiration compared with those with no microaspiration; and similar in patients with microaspiration compared with those with abundant microaspiration. α-amylase and pepsin were significantly correlated (r2 = 0.305, p = 0.001). CONCLUSION: Accuracy of mean α-amylase in diagnosing microaspiration is moderate. Further, when all α-amylase levels were taken into account, α-amylase was inaccurate in diagnosing microaspiration, compared with pepsin.

Performance of the BODE index in patients with α1-antitrypsin deficiency-related COPD.

The BODE (body mass index, airflow obstruction, dyspnoea and exercise capacity) index is used to decide on referral and transplantation of patients with chronic obstructive pulmonary disease (COPD). The BODE index has not been validated in patients with α1-antitrypsin deficiency, who account for 15% of COPD patients undergoing lung transplantation. We sought to validate the BODE index in α1-antitrypsin deficiency-related COPD. We assessed the prognostic value of the BODE index in 191 patients followed from 2006 to 2012 in a French prospective cohort of patients with α1-antitrypsin deficiency. 20 patients died during follow-up and 22 underwent lung transplantation. Survival (95% CI) was 93.0% (91.7-94.3%) at 3 years and 76.0% (72.9-79.1%) at 5 years. The 3-year survival was 97.4% (96.6-98.2%), 98.0% (96.7-99.3%), 87.7% (84.5-90.9%) and 75.3% (66.0-84.6%) for patients with BODE index 0-2, 3-4, 5-6 and 7-10, respectively. Survival discrimination of the BODE index was better than with both forced expiratory volume in 1 s and Global Initiative for Chronic Obstructive Lung Disease classification. Regarding calibration, expected survival by BODE index was noticeably lower than observed survival. The BODE index showed very good survival discrimination in patients with α1-antitrypsin deficiency-related COPD. Larger studies are needed to support its use to drive patient referral for lung transplantation.

Efficiency of a pneumatic device in controlling cuff pressure of polyurethane-cuffed tracheal tubes: a randomized controlled study.

BACKGROUND: The primary objective of this study was to determine the efficiency of a pneumatic device in controlling cuff pressure (Pcuff) in patients intubated with polyurethane-cuffed tracheal tubes. Secondary objectives were to determine the impact of continuous control of Pcuff, and cuff shape on microaspiration of gastric contents. METHODS: Prospective randomized controlled study. All patients requiring intubation and mechanical ventilation ≥48 h were eligible. The first 32 patients were intubated with tapered polyurethane-cuffed, and the 32 following patients were intubated with cylindrical polyurethane-cuffed tracheal tubes. Patients randomly received 24 h of continuous control of Pcuff using a pneumatic device (Nosten®), and 24 h of routine care of Pcuff using a manometer. Target Pcuff was 25 cmH2O. Pcuff was continuously recorded, and pepsin was quantitatively measured in all tracheal aspirates during these periods. RESULTS: The pneumatic device was efficient in controlling Pcuff (med [IQ] 26 [24, 28] vs 22 [20, 28] cmH2O, during continuous control of Pcuff and routine care, respectively; p = 0.017). In addition, percentage of patients with underinflation (31% vs 68%) or overinflation (53% vs 100%) of tracheal cuff, and percentage of time spent with underinflation (0.9 [0, 17] vs 14% [4, 30]) or overinflation (0 [0, 2] vs 32% [9, 54]) were significantly (p < 0.001) reduced during continuous control of Pcuff compared with routine care.No significant difference was found in microaspiration of gastric content between continuous control of Pcuff compared with routine care, or between patients intubated with tapered compared with cylindrical polyurethane-cuffed tracheal tubes. CONCLUSION: The pneumatic device was efficient in controlling Pcuff in critically ill patients intubated with polyurethane-cuffed tracheal tubes. TRIAL REGISTRATION: The Australian New Zealand Clinical Trials Registry (NCT01351259).

Continuous control of tracheal cuff pressure and microaspiration of gastric contents in critically ill patients.

RATIONALE: Underinflation of the tracheal cuff frequently occurs in critically ill patients and represents a risk factor for microaspiration of contaminated oropharyngeal secretions and gastric contents that plays a major role in the pathogenesis of ventilator-associated pneumonia (VAP). OBJECTIVES: To determine the impact of continuous control of tracheal cuff pressure (P(cuff)) on microaspiration of gastric contents. METHODS: Prospective randomized controlled trial performed in a single medical intensive care unit. A total of 122 patients expected to receive mechanical ventilation for at least 48 hours through a tracheal tube were randomized to receive continuous control of P(cuff) using a pneumatic device (intervention group, n = 61) or routine care of P(cuff) (control group, n = 61). MEASUREMENTS AND MAIN RESULTS: The primary outcome was microaspiration of gastric contents as defined by the presence of pepsin at a significant level in tracheal secretions collected during the 48 hours after randomization. Secondary outcomes included incidence of VAP, tracheobronchial bacterial concentration, and tracheal ischemic lesions. The pneumatic device was efficient in controlling P(cuff). Pepsin was measured in 1,205 tracheal aspirates. Percentage of patients with abundant microaspiration (18 vs. 46%; P = 0.002; OR [95% confidence interval], 0.25 [0.11-0.59]), bacterial concentration in tracheal aspirates (mean ± SD 1.6 ± 2.4 vs. 3.1 ± 3.7 log(10) cfu/ml, P = 0.014), and VAP rate (9.8 vs. 26.2%; P = 0.032; 0.30 [0.11-0.84]) were significantly lower in the intervention group compared with the control group. However, no significant difference was found in tracheal ischemia score between the two groups. CONCLUSIONS: Continuous control of P(cuff) is associated with significantly decreased microaspiration of gastric contents in critically ill patients.