Reversibility of Hypercapnia after an Acute Exacerbation of COPD.

BACKGROUND: After an episode of hypercapnic AECOPD, some patients show reversible, prolonged or persistent hypercapnic respiratory failure. However, at the time of patient discharge, it is uncertain whether patients will remain hypercapnic or may return to a physiologic gas status. METHODS: Data were retrospectively collected from COPD patients with an acute hypercapnic exacerbation (AECOPD). Out of 143 total COPD inpatients, complete data set was available for 82 patients in stable condition. According to the first available capillary or arterial pCO2, patients were divided into those with persistent hypercapnia (PHG) and those with reversible hypercapnia. RESULTS: In this study, 51% of patients with acute hypercapnic AECOPD and follow-up (FUP) visits developed normocapnia after a time period of several weeks. These patients were characterized by lower carbon dioxide partial pressure (PaCO2), HCO3-, and BE levels prior to the AECOPD event, at discharge and at FUP. pH was higher at discharge and FUP in this group. Greater disease severity and lower forced vital capacity were prominent in patients with PHG. Binary logistic regression revealed GOLD D and higher PaCO2 at discharge as predicting factors for PHG. CONCLUSIONS: A large percentage of patients has prolonged hypercapnia following acute hypercapnic COPD exacerbation. The risk profile of patients with irreversible hypercapnia should be carefully evaluated following AECOPD in order to choose selected patients for home-noninvasive ventilation.

Effectiveness of nasal highflow in hypercapnic COPD patients is flow and leakage dependent.

BACKGROUND: Nasal Highflow (NHF) delivers a humidified and heated airflow via nasal prongs. Current data provide evidence for efficacy of NHF in patients with hypoxemic respiratory failure. Preliminary data suggest that NHF may decrease hypercapnia in hypercapnic respiratory failure. The aim of this study was to evaluate the mechanism of NHF mediated PCO2 reduction in patients with chronic obstructive pulmonary disease (COPD). METHODS: In 36 hypercapnic COPD patients (PCO2 > 45 mmHg), hypercapnia was evaluated by capillary gas sampling 1 h after NHF breathing under four conditions A to D with different flow rates and different degrees of leakage (A = 20 L/min, low leakage, two prongs, both inside; B = 40 L/min, low leakage, two prongs, both inside; C = 40 L/min, high leakage, two prongs, one outside and open; D = 40 L/min, high leakage, two prongs, one outside and closed). Under identical conditions, mean airway pressure was measured in the hypopharynx of 10 COPD patients. RESULTS: Hypercapnia significantly decreased in all patients. In patients with capillary PCO2 > 55 mmHg (n = 26), PCO2 additionally decreased significantly by increased leakage and/or flow rate in comparison to lower leakage/ flow rate conditions (A = 94.2 ± 8.2%; B = 93.5 ± 4.4%; C = 90.5 ± 7.2%; D = 86.8 ± 3.8%). The highest mean airway pressure was observed in patients breathing under condition B (2.3 ± 1.6 mbar; p < 0.05). CONCLUSIONS: This study demonstrates effective PCO2 reduction with NHF therapy in stable hypercapnic COPD patients. This effect does not correlate with an increase in mean airway pressure but with increased leakage and airflow, indicating airway wash out and reduction of functional dead space as important mechanisms of NHF therapy. These results may be useful when considering NHF treatment in hypercapnic COPD patients. TRIAL REGISTRATION: Clinical Trials: NCT02504814; First posted July 22, 2015.

Impact of socio-economic position on cancer stage at presentation: Findings from a large hospital-based study in Germany.

We explored the relationship between socio-economic characteristics and cancer stage at presentation. Patients admitted to a university hospital for diagnosis and treatment of cancer provided data on their education, vocational training, income, employment, job, health insurance and postcode. Tumor stage was classified according to the Union International Contre le Cancer (UICC). To analyze disparities in the likelihood of late-stage (UICC III/IV vs. I/II) diagnoses, logistic regression models adjusting for age and gender were used. Out of 1,012 patients, 572 (59%) had late-stage cancer. Separately tested, increased odds of advanced disease were associated with post-compulsory education compared to college degrees, with apprenticeship and no vocational training, with unemployment, disability pension, jobs with a low hierarchy level, blue collar jobs and with low income. Health insurance and community size were not related with late-stage cancer. Jointly modelled, there was evidence for an independent effect of unemployment (odds ratio (OR) 1.7, CI 1.0-2.8), disability pension (OR 1.8, CI 1.0-3.2) and very low income (OR 2.6, CI 1.1-6.1) on the likelihood of advanced disease stage. It is of great concern that these socio-economic gradients occur even in systems with equal access to health care.

Effect of Nasal High Flow (NHF) on Right Heart Function in Stable Patients with Pulmonary Hypertension of Different WHO Classes.

Background: Nasal high flow (NHF) has various effects on the respiratory system in acute and chronic conditions. There are initial reports that NHF is also able to influence cardiac function in acute decompensation. This study was designed to clarify whether NHF has an influence on the right heart in stable patients with chronic pulmonary hypertension. Methods: Forty-one stable patients from different pulmonary hypertension (PH) WHO classes were recruited. Most patients were assigned to WHO classes 1 and 3. All received a right heart catheterization and blood gas analysis. Oxygenation was kept constant. The mean pulmonary arterial pressure (mPAP), wedge pressure (PC), cardiac output (CO), diastolic pulmonary gradient (DPG), pulmonary arterial resistance (PVR) and other parameters were determined. The patients then used NHF at 35 L/min for 20 min, after which the right heart catheter measurements were repeated with ongoing NHF therapy. Results: In the entire cohort and in the subgroups, there were no changes in right heart function or cardiac ejection fraction. The blood gases did not change either. Conclusions: Thus, there is no effect of NHF on right heart function in stable patients with PH.

Effects of nasal high flow on ventilation in volunteers, COPD and idiopathic pulmonary fibrosis patients.

BACKGROUND: A high flow of air applied by large bore nasal cannulae has been suggested to improve symptoms of chronic respiratory insufficiency. In pediatric patients, nasal high-flow (nHF) ventilation was similarly effective compared to noninvasive ventilation with a face mask. OBJECTIVES: The aim of this study was to describe changes in respiratory parameters. METHODS: We measured pressure amplitudes during the respiratory cycle and mean pressures in patients with idiopathic pulmonary fibrosis (IPF) and COPD. In order to achieve tidal volume and minute volume measurements, we used a polysomnography device. Capillary blood was taken for blood gas analysis before and after nHF breathing (8 h). RESULTS: nHF led to an increase in pressure amplitude and mean pressure in healthy volunteers and in patients with COPD and IPF in comparison with spontaneous breathing. In COPD, nHF increased tidal volume, while no difference in tidal volume was observed in patients with IPF. Interestingly, tidal volume decreased in healthy volunteers. Breathing rates and minute volumes were reduced in all groups. Capillary pCO2 decreased in patients with IPF and COPD. CONCLUSIONS: nHF resulted in significant effects on respiratory parameters in patients with obstructive and restrictive pulmonary diseases. The rise in pressure amplitude and mean pressure and the decrease in breathing rate and minute volume will support inspiratory efforts, helps to increase effectiveness of ventilation and will contribute to a reduction in the work of breathing. A CO2 wash-out effect in the upper airway part of the anatomical dead space may contribute to the beneficial effects of the nHF instrument.

Nasal High-Flow (NHF) Improves Ventilation in Patients with Interstitial Lung Disease (ILD)-A Physiological Study.

INTRODUCTION: Acute hypercapnic respiratory failure has a poor prognosis in patients with interstitial lung disease (ILD). Recent data demonstrated a positive effect of nasal high-flow (NHF) in patients with acute hypoxemic respiratory failure. Preliminary data also show benefits in several hypercapnic chronic lung diseases. OBJECTIVES: The aim of this study was to characterize flow-dependent changes in mean airway pressure, breathing volumes, and breathing frequency and decreases in PCO2. METHODS: Mean airway pressure was measured in the nasopharyngeal space. To evaluate breathing volumes, a polysomnographic device was used (16 patients). All subjects received 20, 30, 40, and 50 L/min and-to illustrate the effects-nCPAP and nBiPAP. Capillary blood gas analyses were performed in 25 hypercapnic ILD subjects before and 5 h after the use of NHF. Additionally, comfort and dyspnea during the use of NHF were surveyed. RESULTS: NHF resulted in a small flow-dependent increase in mean airway pressure. Tidal volume was unchanged and breathing rate decreased. The calculated minute volume decreased by 20 and 30 L/min NHF breathing. In spite of this fact, hypercapnia decreased at a flow rate of 24 L/min. Additionally, an improvement in dyspnea was observed. CONCLUSIONS: NHF leads to a reduction in paCO2. This is most likely achieved by a washout of the respiratory tract and a reduction in functional dead space. NHF enhances the effectiveness of breathing in ILD patients by the reduction in respiratory rate. In summary, NHF works as an effective ventilatory support device in hypercapnic ILD patients.

Comparison of SARS-CoV-2 antigen testing to RT-PCR in a real-world setting-an observational cohort study.

A total of 2978 patients with validated paired results (SARS-CoV2-antigen and PCR) were identified. Our results show that only 45 antigen tests from 90 patients with positive validated PCR were correctly identified by antigen testing (sensitivity 50%). Roughly 50% of these patients had ongoing respiratory symptoms.

Nasal high-flow compared to non-invasive ventilation in treatment of acute acidotic hypercapnic exacerbation of chronic obstructive pulmonary disease-protocol for a randomized controlled noninferiority trial (ELVIS).

BACKGROUND: Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) have a major negative impact on health status, rates of hospitalization, readmission, disease progression and mortality. Non-invasive ventilation (NIV) is the standard therapy for hypercapnic acidotic respiratory failure in AECOPD. Despite its beneficial effects, NIV is often poorly tolerated (11-34 % failure rate). An increasing number of studies have documented a beneficial effect of nasal high-flow (NHF) in acute hypercapnia. We designed a prospective, randomized, multi-centre, open label, non-inferiority trial to compare treatment failure in nasal NHF vs NIV in patients with acidotic hypercapnic AECOPD. METHODS: The study will be conducted in about 35 sites in Germany. Patients with hypercapnic AECOPD with respiratory acidosis (pH < 7.35) will be randomized 1:1 to NIV or NHF. The primary outcome is the combined endpoint of intubation, treatment failure or death at 72 h. The switch from one to the other device marks a device failure but acts as a rescue treatment in absence of intubation criteria. A sample size of 720 was calculated to have 80% power for showing that NHF is non-inferior to NIV with a margin of 8 percentage points. Linear regression will be used for the confirmatory analysis. DISCUSSION: If NHF is shown to be non-inferior to NIV in acidotic hypercapnic AECOPD, it could become an important alternative treatment. TRIAL REGISTRATION: ClinicalTrials.gov , NCT04881409 , Registered on May 11, 2021.

Use of nasal high flow oxygen during acute respiratory failure.

Nasal high flow (NHF) has gained popularity among intensivists to manage patients with acute respiratory failure. An important literature has accompanied this evolution. In this review, an international panel of experts assessed potential benefits of NHF in different areas of acute respiratory failure management. Analyses of the physiological effects of NHF indicate flow-dependent improvement in various respiratory function parameters. These beneficial effects allow some patients with severe acute hypoxemic respiratory failure to avoid intubation and improve their outcome. They require close monitoring to not delay intubation. Such a delay may worsen outcome. The ROX index may help clinicians decide when to intubate. In immunocompromised patients, NHF reduces the need for intubation but does not impact mortality. Beneficial physiological effects of NHF have also been reported in patients with chronic respiratory failure, suggesting a possible indication in acute hypercapnic respiratory failure. When intubation is required, NHF can be used to pre-oxygenate patients either alone or in combination with non-invasive ventilation (NIV). Similarly, NHF reduces reintubation alone in low-risk patients and in combination with NIV in high-risk patients. NHF may be used in the emergency department in patients who would not be offered intubation and can be better tolerated than NIV.

Nasal high-flow versus noninvasive ventilation in patients with chronic hypercapnic COPD.

Background: Despite the encouraging results of noninvasive ventilation (NIV) in chronic hypercapnic COPD patients, it is also evident that some patients do not tolerate NIV or do not benefit from it. We conducted a study in which COPD patients with stable, chronic hypercapnia were treated with NIV and nasal high-flow (NHF) to compare effectiveness. Methods: In a multi-centered, randomized, controlled, cross-over design, patients received 6 weeks of NHF ventilation followed by 6 weeks of NIV ventilation or vice-versa (TIBICO) between 2011 and 2016. COPD patients with stable daytime hypercapnia (pCO2≥50 mmHg) were recruited from 13 German centers. The primary endpoint was pCO2 changes from baseline blood gas, lung function, quality of life (QoL), the 6 min walking test, and duration of device use were secondary endpoints. Results: A total of 102 patients (mean±SD) age 65.3±9.3 years, 61% females, body mass index 23.1±4.8 kg/m2, 90% GOLD D, pCO2 56.5±5.4 mmHg were randomized. PCO2 levels decreased by 4.7% (n=94; full analysis set; 95% CI 1.8-7.5, P=0.002) using NHF and 7.1% (95% CI 4.1-10.1, P<0.001) from baseline using NIV (indistinguishable to intention-to-treat analysis). The difference of pCO2 changes between the two devices was -1.4 mmHg (95% CI -3.1-0.4, P=0.12). Both devices had positive impact on blood gases and respiratory scores (St. George's Respiratory Questionnaire, Severe Respiratory Insufficiency Questionnaire). Conclusions: NHF may constitute an alternative to NIV in COPD patients with stable chronic hypercapnia, eg, those not tolerating or rejecting NIV with respect to pCO2 reduction and improvement in QoL.

Oral Versus Nasal High-Flow Bronchodilator Inhalation in Chronic Obstructive Pulmonary Disease.

BACKGROUND: Nasal high flow (NHF) alters breathing patterns, stabilizes fraction of inspired oxygen (FiO2) during respiratory distress, helps to keep up hemostasis in the airways, and washes out the upper airways. Particularly the support of inspiratory flow and decrease in functional dead space are interesting mechanisms of action with regard to aerosol delivery. Several laboratory investigations have studied aerosol delivery via the nasal route by using NHF, whereas clinical benefits are poorly evaluated. METHODS: Thirty patients with stable chronic obstructive pulmonary disease Gold D were recruited. In a randomized order, they inhaled a salbutamol 2.5 mg/ipratropium bromide 500 µg solution oral or NHF adapted on the second study day. A jet nebulizer was used as aerosol delivery device. The chosen flow rate was 35 L/min. RESULTS: Four patients refused to repeat the procedure, for example, for inconvenience or fear of delayed discharge, and were not included in the intention-to-treat analysis. All remaining patients tolerated both inhalation systems well. Forced vital capacity (FVC), forced expiratory volume in 1 second (FEV1), airway resistance (Rtot), and residual volume (RV) were significantly altered after bronchodilator inhalation with each of the both devices. The two different ways of combined bronchodilator inhalation resulted in very comparable changes in FVC, FEV1, relative 1 second-capacity (FEV1%FVC), Rtot, total lung capacity (TLC), RV, and residual volume expressed as percent of TLC (RV%TLC). However, in between devices, no difference was observed on comparing the postinhalational measurements of FVC, FEV1, Rtot, and RV. CONCLUSIONS: We conclude from this proof-of-principle kind of study that inhalation of combined bronchodilators adapted to an NHF device is similarly effective to inhalation with a standard oral aerosol nebulizer. (Clinical Trails NCT02885103).

Nasal highflow eliminates CO2 from lower airways.

INTRODUCTION: Nasal highflow (NHF) has a growing evidence in treatment of hypoxemic respiratory failure. There are preliminary data available about use in acute and chronic type-II-respiratory failure. Unfortunately underlying mechanisms of NHF are not well understood. Increase in airway pressure seems too small to explain the observed reduction in hypercapnia. Most interesting effects are wash-out of upper airways and reduction of functional dead space. There are no data available about a wash-out of lower airways. METHODS: We established a sheep lung model to evaluate CO2-wash-out in lower airways. Therefore we placed measuring and insufflation catheter in maximal expanded lung. The lung was not ventilated in order to minimize influence of CO2 rebreathing and increase in airway pressure. Airway pressure and CO2 values were measured in lower airways and in tracheal space. RESULTS: CO2 was decreased by NHF in lower airways and in tracheal space. Changes in CO2 were flow dependent. There was also an increase in airway pressure in these settings. CONCLUSIONS: NHF is able to decrease CO2 in lower airways in a flow-dependent manner. This effect is independent of an increase in airway pressure and CO2-rebreathing. So wash-out is an important reason for efficiency of NHF in decreasing hypercapnia.

Nasal highflow improves ventilation in patients with COPD.

BACKGROUND: Nasal highflow (NHF) provides a warmed and humidified air stream up to 60 L/min. Recent data demonstrated a positive effect in patients with acute hypoxemic respiratory failure, especially when caused by pneumonia. Preliminary data show a decrease in hypercapnia in patients with COPD. Therefore, NHF should be evaluated as a new ventilatory support device. This study was conducted to assess the impact of different flow rates on ventilatory parameters in patients with COPD. MATERIALS AND METHODS: This interventional clinical study was performed with patients suffering from severe COPD. The aim was to characterize flow-dependent changes in mean airway pressure, breathing volumes, breathing frequency, and decrease in partial pressure of CO2 (pCO2). Mean airway pressure was measured in the nasopharyngeal space (19 patients). To evaluate breathing volumes, we used a polysomnographic device (18 patients). All patients received 20 L/min, 30 L/min, 40 L/min, and 50 L/min and - to illustrate the effects - nasal continuous positive airway pressure and nasal bilevel positive airway pressure. Capillary blood gas analyses were performed in 54 patients with hypercapnic COPD before and two hours after the use of NHF. We compared the extent of decrease in pCO2 when using 20 L/min and 30 L/min. Additionally, comfort and dyspnea during the use of NHF were surveyed. RESULTS: NHF resulted in a minor flow dependent increase in mean airway pressure. Tidal volume increased, and breathing rate decreased. The calculated minute volume decreased under NHF breathing. In spite of this fact, hypercapnia decreased with increasing flow (20 L/min vs 30 L/min). Additionally, an improvement in dyspnea was observed. The rapid shallow breathing index shows a decrease when using NHF. CONCLUSION: NHF leads to a flow-dependent reduction in pCO2. This is most likely achieved by a washout of the respiratory tract and a functional reduction in dead space. In summary, NHF enhances effectiveness of breathing in patients with COPD, reduces pCO2, the work of breathing, and rapid shallow breathing index as an indicator of respiratory work load.

[Nasal Highflow - Treatment option in severe hypoxaemia?]. / Nasaler Highflow - Bessere Alternative der Sauerstoffapplikation bei schwerer Hypoxie?

Nasal High Flow (NHF) provides a warmed and humidified air stream. In pediatrics, this method is already in widespread use and is increasingly replacing the CPAP. New studies show success in treating adults. Currently the acute hypoxemic insufficiency cause of pneumoniae is a secured area of use. NHF is not inferior in comparison to other oxygen delivery systems. At this juncture effectiveness of this easy to use method is not clear. Preliminary reports describe an improvement in ventilation by the NHF. Here, a wash-out of the airways and improved alveolar ventilation seem to be the main operating principles.

Nasal High-flow versus non-invasive ventilation in stable hypercapnic COPD: a preliminary report.

BACKGROUND: There are no data available about effectiveness of Nasal High-flow (NHF)in chronic respiratory insufficiency. METHODS: Eleven COPD patients with stable hypercapnia were adjusted to NHF-system with a flow of 20 l/min. After six weeks patients were switched to non-invasive ventilation (NIV) for another six weeks period. RESULTS: NHF led to significant decreases in resting pCO2. Between the devices we found no differences in pCO2 levels. CONCLUSIONS: NHF may thus be an alternative treatment device in stable hypercapnic COPD patients.

Diffuse Interstitial Pulmonary Infiltrates in Malignant Melanoma.

Only a few cases of sarcoidosis-like reaction to a pharmacologic compound have been reported in patients with melanoma in the literature. Long-term treatment with interferon alpha may be assumed. We report a case of a 25-y-old man who presented to our department with diffuse interstitial pulmonary infiltrates and slightly enlarged mediastinal lymph nodes as determined by computed tomography. He had a history of malignant melanoma with 18 months of interferon alpha-2 therapy. Histological analysis of a transbronchial biopsy revealed sarcoidosis-like reactions.

Candidate genes upregulated in density dependent growth inhibition of lung cancer cells.

Prognosis of lung cancer remains poor despite the recent development of new chemotherapeutic agents. Novel therapeutic strategies therefore need to be developed. The search for factors inhibiting tumor growth in a paracrine/autocrine fashion might result in a well-tolerated adjuvant tumor therapy. In this study we aimed to identify candidate genes for such inhibitors of tumor cell growth. Native and heat-inactivated supernatants of confluent, slow growing H460 tumor cell cultures and of sparse (non-confluent), fast growing H460 tumor cell cultures were tested in proliferation assays. We observed that native supernatant of confluent H460 and A549 cells contain proteins inhibiting tumor cell growth of NSCLC cell lines. Microarray gene expression analysis of sparse and confluent H460 cells exhibited overexpression of 7 candidate genes in confluent, slow growing cells. The products of these genes possess cell growth inhibitory function and also exist in the extracellular compartment. The increased expression level of these genes was verified using real-time RT-PCR analysis. Our results show that especially components of IGF pathway appear to be involved in exogenous growth inhibition of confluent cells. Further investigations of these factors may result in the identification of autocrine/paracrine tumor cell growth inhibitory proteins for future use in clinical applications.