Increased risk of respiratory events during endobronchial ultrasound examination in patients with reduced forced expiratory volume: a prospective observational study

BackgroundThe incidence of adverse events during endobronchial ultrasound is low. Nevertheless, it is unclear, whether patients with impaired pulmonary function have an increased risk of respiratory events during the intervention.MethodsA monocentric prospective observational study was performed at the Department of Respiratory Medicine, University Hospital Frankfurt/Main, Germany. Adult patients undergoing an endobronchial ultrasound examination with propofol-sedation were included. Pre-interventional screening included pulmonary function testing, laboratory tests and electrocardiogram. The occurrence of hypercapnia >55 mmHg or reduced oxygen saturation <85% was defined as a respiratory event was recorded and compared between patients with normal and impaired pulmonary function tests.ResultsIn total, 126 patients were included. Pulmonary function testing revealed a median FEV1 of 2.2 l (range 0.4–6.04l) and a predicted FEV1 of 79.5% (range 20–127.8%) respectively. The median FVC was 3.0 l (range 0.87–7.28l), the median predicted FVC was 82% (range 31.4–128.4%). In 72 examinations (60%) pCO2 levels >55 mmHg were measured. Transient oxygen desaturation <85% occurred in 31 cases (25.8%). The Mann Whitney U-test showed a significantly lower FEV1 (% predicted value) in patients with respiratory events (p = 0.007). ROC analysis identified a predicted FEV1 of 78.5% as the optimal cut-off with a sensitivity of 58% and a specificity of 71%. Using Z-score instead of predicted values, there was no significant association between a lower Z- score of FEV or FVC and hypercapnic or hypoxic events. However, both a lower absolute value of FEV1/FVC and a lower Z-score of the FEV1/FVC index were associated with the occurrence of respiratory events. In binary logistic regression analysis, we could not demonstrate any association with other relevant parameters (age, BMI, sedation dosage, sedation duration, or ASA-score).ConclusionsAn impaired forced expiratory volume is associated with the frequency of respiratory events during endobronchial ultrasound examination under propofol-sedation

Primary Ciliary Dyskinesia in Adult Bronchiectasis:Data from the German Bronchiectasis Registry PROGNOSIS

Background: Primary ciliary dyskinesia (PCD) is a rare genetic disorder caused by the malfunction of motile cilia and a specific etiology of adult bronchiectasis of unknown prevalence. A better understanding of the clinical phenotype of adults with PCD is needed to identify individuals for referral to diagnostic testing. Research Question: What is the frequency of PCD among adults with bronchiectasis; how do people with PCD differ from those with other etiologies; and which clinical characteristics are independently associated with PCD? Study Design and Methods: We investigated the proportion of PCD among the participants of the Prospective German Non-CF-Bronchiectasis Registry (PROGNOSIS) study; applied multiple imputation to account for missing data in 64 (FEV1), 58 (breathlessness), 26 (pulmonary exacerbations), and two patients (BMI), respectively; and identified predictive variables from baseline data using multivariate logistic regression analysis. Results: We consecutively recruited 1,000 patients from 38 centers across all levels of the German health care system. Overall, PCD was the fifth most common etiology of bronchiectasis in 87 patients (9%) after idiopathic, postinfective, COPD, and asthma. People with PCD showed a distinct clinical phenotype. In multivariate regression analysis, the chance of PCD being the etiology of bronchiectasis increased with the presence of upper airway disease (chronic rhinosinusitis and/or nasal polyps; adjusted OR [aOR], 6.3; 95% CI, 3.3-11.9; P &lt;.001), age &lt; 53 years (aOR, 5.3; 95% CI, 2.7-10.4; P &lt;.001), radiologic involvement of any middle and lower lobe (aOR, 3.7; 95% CI, 1.3-10.8; P =.016), duration of bronchiectasis &gt; 15 years (aOR, 3.6; 95% CI, 1.9-6.9; P &lt;.001), and a history of Pseudomonas aeruginosa isolation from respiratory specimen (aOR, 2.4; 95% CI, 1.3-4.5; P =.007). Interpretation: Within our nationally representative cohort, PCD was a common etiology of bronchiectasis. We identified few easy-to-assess phenotypic features, which may promote awareness for PCD among adults with bronchiectasis. Clinical Trial Registration: ClinicalTrials.gov; No.: NCT02574143; URL: www.clinicaltrials.gov</p

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Hypercapnic Failure in Acute Exacerbated COPD Patients: Severe Airflow Limitation as an Early Warning Signal

Background: Hypercapnic failure is a severe complication of COPD disease progression, which is associated with a high morbidity and mortality. The aim of this study was to examine the association of comorbidity and clinical risk factors with the development of hypercapnia in acute exacerbated COPD patients. Methods: In this retrospective monocentric cohort study, we examined the influence of the clinical parameters and the comorbidity of hospitalized patients with the acute exacerbation of COPD on the development of hypercapnia by performing multivariate logistic regression and a receiver operating characteristic analysis. Results: In total, 275 patient cases with COPD exacerbation were enrolled during the period from January 2011 until March 2015, where 104 patients (37.8%) with hypercapnia were identified. The logistic regression analysis revealed severe airflow limitation (decreased FEV1) as the main factor associated with the development of hypercapnia. In the ROC analysis, we determined an FEV1 of 42.12%, which was predicted with a sensitivity of 82.6% and specificity of 55%, and an absolute value of FEV1 of 0.8 L, with a sensitivity of 0.62 and specificity of 0.79 as the cut off points, respectively. We could not verify an association with the patient&rsquo;s condition or the laboratory surrogate parameters of organ failure. Conclusion: Severe airflow limitation is an important risk factor that is associated with hypercapnic failure in acute exacerbated COPD patients. Validation in prospective cohorts is warranted and should focus on more intensive monitoring of these at-risk patients

Präoperative Vorbereitung: Optimierung pulmonaler Erkrankungen

ZusammenfassungLungenerkrankungen wie COPD oder Asthma sind bedeutende Risikofaktoren perioperativer pulmonaler Komplikationen. Die Optimierung dieser Erkrankungen ist deshalb wichtiger Bestandteil des präoperativen Managements. Das Wissen um die Pathophysiologie und medikamentöse Therapie ist dabei essenziell.</jats:p

Retrospective cohort study of adult patients with cystic fibrosis supported with venovenous extracorporeal membrane oxygenation (VV ECMO) at a large German cystic fibrosis center

Abstract Background Severe respiratory failure in patients with cystic fibrosis (CF) requiring invasive mechanical ventilation is associated with poor clinical outcomes. The purpose of this study was to evaluate the role of extracorporeal membrane oxygenation (ECMO) in this clinical setting. Methods In this descriptive retrospective monocentric cohort study, we collected data by using electronic medical records from all patients with CF who received ECMO therapy during the period 2012–2021. Setting A monocentric setting at the non-surgical intensive care unit of the University Hospital of Frankfurt, Germany (tertiary care level center and nationally certified CF center). Results During the study period 72 cases of CF patients with intensive care treatment were detected. Of these, 46 cases required mechanical ventilation. Nine patients received ECMO therapy for severe respiratory failure due to pulmonary exacerbation. Eight of the nine patients died in the hospital. This corresponds to an in-hospital mortality rate of 88.9%. None of the patients underwent lung transplantation. The most common CF mutation was the p.Phe508del homo- or heterozygous genotype. Pseudomonas aeruginosa colonization was significantly associated with the in-hospital mortality. Conclusions ECMO support in CF patients and severe hypoxemic failure is associated with high mortality and its use must take into account the increased risk and poor patient outcome in this clinical setting. Clinical trial number This was a retrospective, unregistered analysis. A clinical trial number is not applicable

Hypercapnic Failure in Acute Exacerbated COPD Patients: Severe Airflow Limitation as an Early Warning Signal

Background: Hypercapnic failure is a severe complication of COPD disease progression, which is associated with a high morbidity and mortality. The aim of this study was to examine the association of comorbidity and clinical risk factors with the development of hypercapnia in acute exacerbated COPD patients. Methods: In this retrospective monocentric cohort study, we examined the influence of the clinical parameters and the comorbidity of hospitalized patients with the acute exacerbation of COPD on the development of hypercapnia by performing multivariate logistic regression and a receiver operating characteristic analysis. Results: In total, 275 patient cases with COPD exacerbation were enrolled during the period from January 2011 until March 2015, where 104 patients (37.8%) with hypercapnia were identified. The logistic regression analysis revealed severe airflow limitation (decreased FEV1) as the main factor associated with the development of hypercapnia. In the ROC analysis, we determined an FEV1 of 42.12%, which was predicted with a sensitivity of 82.6% and specificity of 55%, and an absolute value of FEV1 of 0.8 L, with a sensitivity of 0.62 and specificity of 0.79 as the cut off points, respectively. We could not verify an association with the patient’s condition or the laboratory surrogate parameters of organ failure. Conclusion: Severe airflow limitation is an important risk factor that is associated with hypercapnic failure in acute exacerbated COPD patients. Validation in prospective cohorts is warranted and should focus on more intensive monitoring of these at-risk patients.</jats:p