Does PaCO2 correction have an impact on survival of patients with chronic respiratory failure and long-term non-invasive ventilation?

Background and objective: Non-invasive ventilation (NIV) improves survival of patients with chronic respiratory failure (CRF). Most often, pressure settings are made to normalize arterial blood gases. However, this objective is not always achieved due to intolerance to increased pressure or poor compliance. Few studies have assessed the effect of persistent hypercapnia on ventilated patients' survival. Data from the Pays de la Loire Respiratory Health Research Institute cohort were analyzed to answer this question. Study design and methods: NIV-treated adults enrolled between 2009 and 2019 were divided into 5 subgroups: obesity-hypoventilation syndrome (OHS), COPD, obese COPD, neuromuscular disease (NMD) and chest wall disease (CWD). PaCO2 correction was defined as the achievement of a PaCO2 < 6 kPa or a 20% decrease in baseline PaCO2 in COPD patients. The endpoint was all-cause mortality. Follow-up was censored in case of NIV discontinuation. Results: Data from 431 patients were analyzed. Median survival was 103 months and 148 patients died. Overall, PaCO2 correction was achieved in 74% of patients. Bivariate analysis did not show any survival difference between patients who achievedPaCO2 correction and those who remained hypercapnic: overall population: p = 0.74; COPD: p = 0.97; obese COPD: p = 0.28; OHS: p = 0.93; NMD: p = 0.84; CWD: p = 0.28. Conclusion: Moderate residual hypercapnia under NIV does not negatively impact survival in CRF patients. In individuals with poor tolerance of pressure increases, residual hypercapnia can therefore be tolerated under long-term NIV. Larger studies, especially with a higher number of patients with residual PaCO2 > 7 kPa, are needed to confirm these results.

Contribution of Transcutaneous PCO2 in Obesity Hypoventilation Syndrome.

BACKGROUND: More and more patients have obesity-hypoventilation syndrome (OHS) because of the increasing prevalence of obesity. The accuracy of transcutaneous PCO2 (PtcCO2 ) has recently been validated. However, no study evaluated the interest of measuring systematically nocturnal PtcCO2 in the follow-up of patients with OHS and home mechanical ventilation to detect residual nocturnal hypoventilation. We aimed to evaluate the contribution of nocturnal PtcCO2 to assess nocturnal hypoventilation compared with current routine examinations, that is, daytime arterial blood gases and nocturnal pulse oximetry. METHODS: A prospective monocentric pilot study was conducted from August 2018 to November 2019. Patients with stable OHS and who were treated with home noninvasive ventilation for at least 6 months were eligible to participate. After oral consent, we performed both diurnal arterial blood gases and combined home oximetry and capnography. The primary end point was the presence of residual nocturnal hypoventilation, defined as PaCO2 > 45 mm Hg or bicarbonate ≥ 27 mmol/L, SpO2 < 90% for ≥ 10% of the night, or PtcCO2 > 49 mm Hg for ≥ 10% of the night. RESULTS: A total of 32 subjects were included. Twenty-nine subjects with nocturnal PtcCO2 were analyzed. Eighteen of the 29 subjects showed residual nocturnal hypoventilation. The association of diurnal arterial blood gases and nocturnal pulse oximetry revealed nocturnal hypoventilation in only 9 subjects. Among the 19 subjects with both normal blood gases and normal nocturnal pulse oximetry, 11 had nocturnal hypoventilation with transcutaneous capnography. Only one subject presented with hypoventilation symptoms (asthenia). CONCLUSIONS: The assessment of PtcCO2 in comparison with nocturnal pulse oximetry and arterial blood gases provides important information for the diagnosis of residual nocturnal hypoventilation in the subjects with OHS who were ventilated at home.

Diagnosis and management of Becker muscular dystrophy: the French guidelines.

Becker muscular dystrophy (BMD) is one of the most frequent among neuromuscular diseases, affecting approximately 1 in 18,000 male births. It is linked to a genetic mutation on the X chromosome. In contrast to Duchenne muscular dystrophy, for which improved care and management have changed the prognosis and life expectancy of patients, few guidelines have been published for management of BMD. Many clinicians are inexperienced in managing the complications of this disease. In France, a committee of experts from a wide range of disciplines met in 2019 to establish recommendations, with the goal of improving care of patients with BMD. Here, we present the tools to provide diagnosis of BMD as quickly as possible and for differential diagnoses. Then, we describe the multidisciplinary approach essential for optimum management of BMD. We give recommendations for the initial assessment and follow-up of the neurological, respiratory, cardiac, and orthopedic consequences of males who present with BMD. Finally, we describe the optimal therapeutic management of these complications. We also provide guidance on cardiac management for female carriers.

Obstructive sleep apnea, chronic obstructive pulmonary disease and NAFLD: an individual participant data meta-analysis.

RATIONALE: Chronic intermittent hypoxia occurring in obstructive sleep apnea (OSA) is independently associated with nonalcoholic fatty liver disease (NAFLD). Chronic obstructive pulmonary disease (COPD) has also been suggested to be linked with liver disease. OBJECTIVE: In this individual participant data meta-analysis, we investigated the association between liver damage and OSA and COPD severity. METHODS AND MEASUREMENTS: Patients suspected of OSA underwent polysomnography (PSG) or home sleep apnea testing (HSAT). Non-invasive tests were used to evaluate liver steatosis (Hepatic Steatosis Index) and fibrosis (Fibrotest or FibroMeter). An individual participant data meta-analysis approach was used to determine if the severity of OSA/COPD affects the type and severity of liver disease. Results were confirmed by multivariate and causal mediation analysis. Sub-group analyses were performed to investigate specific populations. MAIN RESULTS: Among 2120 patients, 1584 had steatosis (75%). In multivariable analysis, risk factors for steatosis were an apnea-hypopnea index (AHI) > 5/h, body mass index (BMI) > 26 kg/m2, age, type 2 diabetes (all p-values <0.01) and male gender (p = 0.02). Concerning fibrosis, among 2218 patients 397 had fibrosis (18%). Risk factors associated with fibrosis were BMI>26 kg/m2, age, male gender, and type 2 diabetes (all p-values <0.01). AHI severity was not associated with fibrosis. A combination of AHI >30/h and COPD stage 1 was associated with an increased risk of steatosis. CONCLUSION: This meta-analysis confirms the strong association between steatosis and the severity of OSA. The relation between OSA and fibrosis is mainly due to BMI as shown by causal mediation analysis.

Noninvasive Ventilation in Obese Subjects After Acute Respiratory Failure.

INTRODUCTION: Noninvasive ventilation (NIV) has been widely used to treat acute respiratory failure in obese patients. Criteria that could help clinicians to decide whether they should continue to use NIV after such an initial episode remain unclear. Our retrospective study aims to analyze characteristics of subjects receiving long-term NIV after an initial hospitalization for acute respiratory failure. METHODS: From January 2011 to December 2012, 77 obese adults were admitted in the ICU of the respiratory disease department in Nantes University Hospital in France. After discharge, adherence, body mass index (BMI), and arterial blood gases were assessed or measured at 6 months and 12 months. RESULTS: In all, 53 subjects were analyzed, including 62% who were admitted for idiopathic acute hypercapnic respiratory failure. Mean BMI was 42 ± 11 kg/m2. Failure of NIV occurred in 10% cases in the ICU. At the end of the hospital stay, 34 subjects were discharged with NIV at home. They had higher BMI and higher initial inspiratory positive airway pressure than those who were not ventilated at home. During follow-up, BMI, PaCO2 , and bicarbonate rate significantly decreased. At 12 months, 4 subjects were not ventilated anymore after a mean duration of 6 ± 4.2 months of ventilation. Adherence was correct in 86%, with a mean use of 7 ± 3.1 h/d. Adherent subjects had better adherence at 1 month, a lower forced vital capacity, a higher bicarbonate rate, and a higher NIV breathing frequency when compared to subjects with poor adherence. CONCLUSIONS: Subjects with the most severe obesity or who experienced the most difficult initial ventilation were more likely to receive long-term NIV after initial management of acute respiratory failure in the ICU. In those subjects, long-term NIV at home was effective and well tolerated.

Home Non-Invasive Ventilation Fails to Improve Quality of Life in the Elderly: Results from a Multicenter Cohort Study.

BACKGROUND: Home non-invasive ventilation (NIV) is a widely used treatment for chronic hypoventilation but little is known on its impact in the elderly. In a multicenter prospective cohort study, we studied tolerance and efficacy of domiciliary NIV in patients aged 75 or more compared to younger ones. METHODS AND RESULTS: 264 patients with at least a six-month follow-up were analyzed. Among them, 82 were elderly. In the elderly and the younger, we found an improvement of arterial blood gas, the Epworth sleepiness scale and the Pittsburgh sleep quality index at 6 months. Mean daily use of NIV at 6 months was 7 hours and the rate of non-adherent patients was similar in both group. Health-related quality of life (HRQL) assessed by SF-36 questionnaires did not change significantly after NIV initiation in the elderly whereas HRQL improved in the less than 75. On univariate analysis, we found that diabetes was a predictive factor for non-adherence in the elderly (Odds ratio: 3.95% confidence interval: 1.06-8.52). CONCLUSION: NIV was efficient in the elderly while evaluation at 6 months showed a good adherence but failed to improve HRQL.

Cytokeratin 19 fragments in patients with acute lung injury: a preliminary observation.

OBJECTIVE: Cytokeratin 19 (CK19) is a specific cytoskeletal structure for alveolar epithelium. We hypothesized that the levels of CK19 fragments in bronchoalveolar lavage (BAL) fluid could serve as an index of epithelial injury and as a prognosis marker in patients with acute lung injury (ALI) or acute respiratory distress syndrome (ARDS). The aims of our study were, in patients with ALI/ARDS: (1) to measure CK19 fragments concentrations in BAL fluid, (2) to assess its prognostic value, and (3) to identify the cellular source of CK19 in the alveolar space. DESIGN: Prospective preliminary study. SETTING: University hospital surgical ICU. PATIENTS: Twenty-two mechanically ventilated patients with ALI/ARDS and 10 non-ventilated control patients. Plasma samples were obtained for 11 ALI/ARDS patients. MEASUREMENTS AND RESULTS: The concentration of BAL CK19 fragments was higher in patients (median 4916 pg/ml, 25th-75th percentile 2717-10533) than in controls (2208 pg/ml. 767-3923; p =0.05), and higher in 10 non-survivors (7051 pg/ml, 4372-13371) than in 12 survivors (2888 pg/ml, 1315-5639; p =0.03 among ALI/ARDS patients). BAL CK19 fragment concentration did not correlate with simplified acute physiologic score, lung injury score or PaO(2)/FIO(2) ratio, but correlated positively with BAL albumin concentration (p =0.002) and with number of BAL macrophages (p=0.0001). Plasma CK19 fragment concentrations were 10 times lower than those in BAL. Immunohistochemical staining for CK19 showed a strong labelling of injured detached epithelial cells and hyperplastic epithelium in ALI/ARDS lung samples. CONCLUSION: CK19 fragment concentrations were found to be elevated in BAL fluid in ALI/ARDS patients compared with control subjects. High BAL CK19 fragment levels were associated with a poor prognosis.

Hospital-acquired pneumonia: risk factors for antimicrobial-resistant causative pathogens in critically ill patients.

STUDY OBJECTIVES: To determine factors associated with antimicrobial-resistant hospital-acquired pneumonia (AR-HAP), to build an algorithm evaluating the risk for such a pneumonia, and to test this algorithm. DESIGN: Combined observational and validation cohorts over two periods: January 1994 to December 1999, and January 2000 to March 2001. SETTING: One ICU from a university-affiliated urban teaching hospital. PATIENTS: One hundred twenty-four patients in the observational cohort and 26 patients in the validation cohort exhibiting bacteriologically documented hospital-acquired pneumonia (HAP). INTERVENTIONS: Prospective data collection and multivariate analysis using the chi(2) automatic interaction and detection technique. RESULTS: In the observational cohort, 39 antimicrobial-resistant bacteria were incriminated in 37 patients (30%). Multivariate analysis identified four independent variables allowing a binary stratification of risk. According to the presence or absence of prior antimicrobial treatment, neurologic disturbances on ICU admission, aspiration on ICU admission, and time elapsed between ICU admission and the onset of pneumonia, we were able to identify and separate patients at high, low, or even no risk for acquiring AR-HAP. In the validation cohort, nine antimicrobial-resistant bacteria were incriminated in nine patients (34.6%). In this cohort, the algorithm performed well allowing the identification of null risk categories: the absence of prior antimicrobial treatment, the presence of prior antimicrobial treatment with neurologic disturbances on ICU admission and an early-onset pneumonia, and the presence of prior antimicrobial treatment without neurologic disturbances but with aspiration on ICU admission were always associated with antimicrobial-susceptible HAP. CONCLUSION: We developed and tested a binary algorithm allowing the identification of patients at low risk for acquiring AR-HAP. An antibiotic strategy including an initial antimicrobial treatment guided by such an algorithm, followed, if possible, by a de-escalation when antimicrobial data are available, could increase the administration of adequate initial antimicrobial treatment and help prevent the emergence of antibiotic resistance in the ICU.

Differential role of neutrophils and alveolar macrophages in hepatocyte growth factor production in pulmonary fibrosis.

Neutrophils may participate in the development of lung fibrosis. Hepatocyte growth factor (HGF), a growth factor for type II pneumocytes, is produced by neutrophils. We measured the production of HGF by blood and alveolar neutrophils from patients with either idiopathic pulmonary fibrosis (n = 11) or connective tissue disease-associated pulmonary fibrosis (n = 10) and from control patients (n = 10). HGF secretion by alveolar macrophages and the expression of the HGF receptor by alveolar epithelial cells in pulmonary fibrosis were also evaluated. HGF was not detected in bronchoalveolar lavage fluid from controls. HGF concentration in the epithelial lining fluid from patients was 4-fold higher than in plasma, suggesting a local production within the alveolar space. Alveolar neutrophils secreted HGF in vitro. Basal HGF secretion by alveolar neutrophils positively correlated with HGF in the epithelial lining fluid (p = 0.05, rho = 0.582). HGF secretion by alveolar neutrophils could not be further stimulated with lipopolysaccharide, whereas HGF secretion by blood neutrophils doubled with lipopolysaccharide. Alveolar macrophages did not secrete HGF in vitro. The expression of the HGF receptor was greatly increased in the fibrotic lung, supporting the local function of HGF secreted by neutrophils. We conclude that neutrophils are a source of HGF in patients with pulmonary fibrosis.

Hepatocyte growth factor is produced by blood and alveolar neutrophils in acute respiratory failure.

We tested the novel hypothesis that neutrophils in the lung or the airspaces may produce hepatocyte growth factor (HGF) in ventilated patients with acute respiratory failure. Neutrophils were purified from blood and bronchoalveolar lavage (BAL) fluid samples from 16 mechanically ventilated patients who underwent BAL for a diagnostic workup of ventilator-acquired pneumonia. Most of the patients had pneumonia (n = 11). Ten nonventilated patients served as controls. Both blood and BAL neutrophils released HGF in vitro. Basal HGF secretion by blood neutrophils from controls was 823 (666) pg x ml(-1) x 10(-7) neutrophils (median, 25th-75th percentile) and doubled to 1,730 (1,684-2,316) pg x ml(-1) x 10(-7) neutrophils (P = 0.001) with lipopolysaccharide (LPS) stimulation. Basal HGF secretion by blood neutrophils from patients was similar [956 (655-2,140) pg x ml(-1) x 10(-7) neutrophils, P = 0.4] and doubled with LPS stimulation [2,767 (2,165-3,688) pg x ml(-1) x 10(-7) neutrophils, P < 0.0001 vs. controls]. Alveolar neutrophils released HGF in vitro [653 (397-1,209) pg x ml(-1) x 10(-7) neutrophils]. LPS stimulation did not significantly increase the HGF release from alveolar neutrophils [762 (434-1,305) pg x ml(-1) x 10(-7) neutrophils]. BAL HGF positively correlated with the BAL neutrophil count (P = 0.01, R = 0.58). We conclude that blood and alveolar neutrophils from patients with acute respiratory failure can produce HGF, a mitogenic factor that may enhance the alveolar repair process.