Efficacy of non-invasive intelligent volume assured pressure support (iVAPS) and pressure support ventilation (PSV) in clinical practice.

AIMS OF THE STUDY: Noninvasive ventilation (NIV) is a well-established treatment option for hypercapnic respiratory failure; however, the best mode of ventilation remains unknown. The aim of this retrospective study was to compare patients’ adherence to NIV using either pressure support ventilation (PSV) or intelligent volume-assured pressure support (iVAPS). PATIENTS AND METHODS: In this retrospective cohort study, we assessed in- and outpatients suffering from hypercapnic respiratory failure of various aetiologies (chronic obstructive pulmonary disease [COPD], obese COPD [body mass index >30 kg/m2], obesity hypoventilation syndrome and other diseases such as amyotrophic lateral sclerosis or interstitial lung disease) after NIV initiation with PSV or iVAPS. Adherence to treatment was compared between these modes using the Wilcoxon test. Within-group differences were tested using linear regression models. Mortality and emergency hospital readmission rates were modelled using Kaplan-Meier estimates and Cox proportional hazards models. RESULTS: Adherence to treatment was similar in both groups throughout the observation period – after 6 weeks: PSV 363 min/night (interquartile range [IQR] 200–448), iVAPS 369 min/night (IQR 310–468) (p = 0.619); after 1 year: PSV 423 (323–500), iVAPS 429 (298–475) (p = 0.901); at the last follow up: PSV 481 (395–586), iVAPS 426 (391–565) (p = 0.284). NIV reduced PaCO2 significantly compared with baseline at all follow-ups: PSV −1.29/−1.49/−1.49 kPa, iVAPS −1.47/−1.23/−1.24 kPa, p <0.001 each, PSV vs iVAPS: p = 0.250, 0.756 and 0.352, respectively. Median survival time (PSV 5.06 years, iVAPS median not reached; p = 0.800) and time to first readmission (PSV 3.6 years, iVAPS 7.33 years, p = 0.200) did not differ between groups. Obese COPD patients had a longer time to hospital readmission than lean COPD patients (3.8 vs 1.5 years, hazard ratio (HR) 0.39, 95% confidence interval [CI] 0.16–0. 74; p = 0.007). Good adherence (>4 h/night and >80% nightly usage) was associated with a lower mortality rate (HR 0.34, 95% CI 0.15–0.77; p = 0.010). CONCLUSION: In a real-world setting of a mixed population with hypercapnic respiratory failure, iVAPS and PSV seem to be similarly effective in improving gas exchange and demonstrate excellent adherence to treatment. A longer survival was noted in NIV-adherent patients. Randomised controlled studies are necessary to identify patients who might benefit more from hybrid ventilation modes.

Diagnostic precision and identification of rare diseases is dependent on distance of residence relative to tertiary medical facilities.

BACKGROUND: Diagnostic precision and the identification of rare diseases is a daily challenge, which needs specialized expertise. We hypothesized, that there is a correlation between the distance of residence to the next tertiary medical facility with highly specialized care and the diagnostic precision, especially for rare diseases. RESULTS: Using a nation-wide hospitalization database, we found a negative association between diagnostic diversity and travel time to the next tertiary referral hospital when including all cases throughout the overall International Classification of Diseases version 10 German Modification (ICD-10-GM) diagnosis codes. This was paralleled with a negative association of standardized incidence rates in all groups of rare diseases defined by the Orphanet rare disease nomenclature, except for rare teratologic and rare allergic diseases. CONCLUSION: Our findings indicate a higher risk of being mis-, under- or late diagnosed especially in rare diseases when living more distant to a tertiary medical facility. Greater distance to the next tertiary medical facility basically increases the chance for hospitalization in a non-comprehensive regional hospital with less diagnostic capacity, and, thus, impacts on adapted health care access. Therefore, solutions for overcoming the distance to specialized care as an indicator of health care access are a major goal in the future.

Nocturnal Cough and Sleep Quality to Assess Asthma Control and Predict Attacks.

INTRODUCTION: Objective markers for asthma, that can be measured without extra patient effort, could mitigate current shortcomings in asthma monitoring. We investigated whether smartphone-recorded nocturnal cough and sleep quality can be utilized for the detection of periods with uncontrolled asthma or meaningful changes in asthma control and for the prediction of asthma attacks. METHODS: We analyzed questionnaire and sensor data of 79 adults with asthma. Data were collected in situ for 29 days by means of a smartphone. Sleep quality and nocturnal cough frequencies were measured every night with the Pittsburgh Sleep Quality Index and by manually annotating coughs from smartphone audio recordings. Primary endpoint was asthma control assessed with a weekly version of the Asthma Control Test. Secondary endpoint was self-reported asthma attacks. RESULTS: Mixed-effects regression analyses showed that nocturnal cough and sleep quality were statistically significantly associated with asthma control on a between- and within-patient level (p < 0.05). Decision trees indicated that sleep quality was more useful for detecting weeks with uncontrolled asthma (balanced accuracy (BAC) 68% vs 61%; Δ sensitivity -12%; Δ specificity -2%), while nocturnal cough better detected weeks with asthma control deteriorations (BAC 71% vs 56%; Δ sensitivity 3%; Δ specificity -34%). Cut-offs using both markers predicted asthma attacks up to five days ahead with BACs between 70% and 75% (sensitivities 75 - 88% and specificities 57 - 72%). CONCLUSION: Nocturnal cough and sleep quality have useful properties as markers for asthma control and seem to have prognostic value for the early detection of asthma attacks. Due to the limited study duration per patient and the pragmatic nature of the study, future research is needed to comprehensively evaluate and externally validate the performance of both biomarkers and their utility for asthma self-management.

Characteristics of Asthma-related Nocturnal Cough: A Potential New Digital Biomarker.

INTRODUCTION: The nature of nocturnal cough is largely unknown. It might be a valid marker for asthma control but very few studies characterized it as a basis for better defining its role and its use as clinical marker. This study investigated prevalence and characteristics of nocturnal cough in asthmatics over the course of four weeks. METHODS: In two centers, 94 adult patients with physician-diagnosed asthma were recruited. Patient-reported outcomes and nocturnal sensor data were collected by a smartphone with a chat-based study app. RESULTS: Patients coughed in 53% of 2212 nights (range: 0-345 coughs/night). Median coughs per hour were 0 (IQR 0-1). Nocturnal cough rates showed considerable inter-individual variance. The highest counts were measured in the first 30 min in bed (4.5-fold higher than rest of night). Eighty-six percent of coughs were part of a cough cluster. Clusters consisted of a median of two coughs (IQR 2-4). Nocturnal cough was persistent within patient. CONCLUSION: To the best of the authors' knowledge, this study is the first to describe prevalence and characteristics of nocturnal cough in asthma over a period of one month, demonstrating that it was a prevalent symptom with large variance between patients and high persistence within patients. Cough events in asthmatics were 4.5 times more frequent within the first 30 min in bed indicating a potential role of positional change, and not more frequent during the early morning hours. An important next step will investigate the association between nocturnal cough and asthma control.

Longitudinal change of COPD assessment test (CAT) in a telehealthcare cohort is associated with exacerbation risk.

BACKGROUND: There are only scarce data regarding the evolution of the chronic obstructive pulmonary disease (COPD) assessment test (CAT) over time. Our aim was to investigate the evolution of the CAT in a telehealthcare (THC) cohort and to evaluate its potential to predict exacerbations. PATIENTS AND METHODS: The CAT was measured weekly over up to 1 year in 40 COPD patients undergoing a THC intervention. The evolution of the CAT was analyzed using linear regression. The association between this evolution and the occurrence of exacerbations was evaluated using the Andersen-Gill formulation of the Cox proportional hazards model for the analysis of recurrent time-to-event data with time-varying predictors. RESULTS: The median CAT at inclusion was 17 (interquartile range 13-22) points. During the study, 25% of patients had a significant negative slope (median -7 points per year [ppy]), 38% were stable (median +0 ppy) and 38% had a significant positive slope (median +6 ppy). The median slope of the CAT in the overall cohort was +1 (interquartile range -3 to +6) ppy. A significant positive association was found between the change in CAT scores and the risk of exacerbations (hazard ratio =1.08, 95% CI: 1.03-1.13; p<0.001). There was an 8% increase of the risk of exacerbation per unit increase in CAT. We detected a significant learning effect in filling out the CAT in 18.4% of patients with a median learning phase of five filled questionnaires. CONCLUSION: Sixty-three percent of the COPD patients monitored by THC experienced a stable or improved CAT during 1-year follow-up. We found a significant positive association between the evolution of the CAT over time and the risk of exacerbations. In about one-fifth of patients, there was a significant learning effect in filling out the CAT, before reliable results could be obtained. The evolution of the CAT could help to assess the risk for future exacerbations.

Multimodel inference applied to oxygen recovery kinetics after 6-min walk tests in patients with chronic obstructive pulmonary disease.

6-min walk tests (6MWT) are routinely performed in patients with chronic obstructive pulmonary disease (COPD). Oxygen uptake ([Formula: see text]) kinetics during 6MWT can be modeled and derived parameters provide indicators of patients' exercise capacity. Post-exercise [Formula: see text] recovery also provides important parameters of patients' fitness which has not been extensively investigated in COPD. Several nonlinear regression models with different underlying biological assumptions may be suitable for describing recovery kinetics. Multimodel inference (model averaging) can then be used to capture the uncertainty in considering several models. Our aim was to apply multimodel inference in order to better understand the physiological underpinnings of [Formula: see text] recovery after 6MWT in patients with COPD. 61 patients with COPD (stages 2 to 4) were included in this study. Oxygen kinetics during 6MWT were modeled using nonlinear regression. Three statistical approaches (mixed-effects, meta-analysis and weighted regression) were compared in order to summarize estimates obtained from multiple kinetics. The recovery phase was modeled using 3 distinct equations (log-logistic, Weibull 1 and Weibull 2). Three models were fitted to the set of 61 kinetics. A significant model-averaged difference of 40.39 sec (SE = 17.1) in the time to half decrease of [Formula: see text] level ([Formula: see text]) was found between stage 2 and 4 (p = 0.0178). In addition, the Weibull 1 model characterized by a steeper decrease at the beginning of the recovery phase showed some improvement of goodness of fit when fitted to the kinetics of patients with stage 2 COPD in comparison with the 2 other models. Multimodel inference was successfully used to model [Formula: see text] recovery after 6MWT in patients with COPD. Significant model-averaged differences in [Formula: see text] were found between moderate and very severe COPD patients. Furthermore, specific patterns of [Formula: see text] recovery could be identified across COPD stages.

NIV by an interdisciplinary respiratory care team in severe respiratory failure in the emergency department limited to day time hours.

Non-invasive ventilatory support is frequently used in patients with severe respiratory failure (SRF), but is often limited to intensive care units (ICU). We hypothesized that an instantaneous short course of NIV (up to 2 h), limited to regular working hours as an additional therapy on the emergency department (ED) would be feasible and could improve patient´s dyspnoea measured by respiratory rate and Borg visual dyspnea scale. NIV was set up by an interdisciplinary respiratory care team. Outside these predefined hours NIV was performed in the ICU. This is an observational cohort study over 1 year in the ED in a non-university hospital. Fifty-one % of medical emergencies arrived during regular working hours (5475 of 10,718 patients). In total, 63 patients were treated with instantaneous NIV. Door to NIV in the ED was 56 (31-97) min, door to ICU outside regular working hours was 84 (57-166) min. Within 1 h of NIV, the respiratory rate decreased from 30/min (25-35) to 19/min (14-24, p < 0.001), the Borg dyspnoea scale improved from 7 (5-8) to 2 (0-3, p < 0.001). In hypercapnic patients, the blood-pH increased from 7.29 (7.24-7.33) to 7.35 (7.29-7.40) and the pCO2 dropped from 8.82 (8.13-10.15) to 7.45 (6.60-8.75) kPa. In patients with SRF of varying origin, instantaneous NIV in the ED during regular working hours was feasible in a non-university hospital setting, and rapidly and significantly alleviated dyspnoea and reduced respiratory rate. This approach proved to be useful as a bridge to the ICU as well as an efficient palliative dyspnoea treatment.

Transcutaneous versus blood carbon dioxide monitoring during acute noninvasive ventilation in the emergency department - a retrospective analysis.

QUESTIONS UNDER STUDY: Transcutaneous measurement of carbon dioxide (PtCO2) has been suggested as an alternative to invasively obtained PaCO2 for the monitoring of patients with hypercapnic respiratory failure during noninvasive ventilation (NIV). Current data on monitoring in hypoxaemic respiratory failure are scarce and show conflicting results in hypercapnic patients in the emergency department. METHODS AND SETTING: We performed a retrospective comparison of real-time PtCO2 (SenTec Digital Monitor) and arterial/venous carbon dioxide tension (PaCO2/PvCO2) measurements in patients with severe hypoxaemic and/or hypercapnic respiratory failure during NIV. Agreement between PtCO2 and PaCO2/PvCO2 was the primary endpoint. Bland-Altman analysis and linear regression were used. RESULTS: 102 patients had at least one matched measurement of PtCO2 and PaCO2/PvCO2. For patients with arterial blood gas analysis, the mean difference was 0.46 kPa at baseline (95% confidence interval [CI] 0.23 to 0.60, limits of agreement 95% CI -0.54 to 1.45) and 0.12 kPa after NIV (95% CI -0.04 to 0.29, limits of agreement 95% CI: -0.61 to 0.86). The linear regression analysis found a correlation R2 of 0.88 (p <0.001) at baseline and an R2 of 0.99 (p <0.001) after initiating NIV. For patients with venous blood gas analysis, the mean difference was 0.64 kPa at baseline (95% CI 0.04 to 1.24, limits of agreement 95% CI -0.72 to 2) and 0.80 kPa after NIV (95% CI 0.51 to 1.10, limits of agreement 95% CI 0.29 to 1.32), R2 0.78 (p <0.001) at baseline and R2 0.91 (p <0.001) after initiating NIV. A PaCO2/PvCO2 >8 kPa was associated with a lesser degree of agreement between the levels of PtCO2 and PaCO2/PvCO2 (p <0.001). CONCLUSION: Transcutaneous PCO2 monitoring shows a good concordance with PaCO2 and is a reliable, feasible, patient-friendly and safe alternative to repeated blood gas analysis for patients with severe hypoxaemic and/or hypercapnic respiratory failure receiving emergency NIV in the emergency department. An initial blood gas analysis to evaluate the respiratory and metabolic state and to rule out a significant discrepancy compared with the transcutaneous measurement is recommended.

The outcome of community-acquired pneumonia in patients with chronic lung disease: a case-control study.

BACKGROUND: The impact of chronic lung diseases on outcome in community-acquired pneumonia (CAP) is not well established. We aimed to investigate the outcome of adult CAP-patients with underlying chronic obstructive pulmonary disease (COPD), asthma or interstitial lung disease (ILD) in a case-control study. METHODS: We used a nationwide database including all hospitalisations in Switzerland from 2002 to 2010. Endpoints were the incidence of lung abscess, parapneumonic pleural effusion, empyema, acute respiratory distress syndrome, in-hospital mortality and length of stay. RESULTS: We found less disease-related complications of CAP in COPD (n = 17,075) and asthma (n = 2700) patients compared with their controls. This difference was mainly related to a lower incidence of pleural effusion (COPD: 4.3% vs 4.9%, p = 0.011; asthma: 3.4% vs 5.2%, p <0.001). In-hospital mortality was lower in the COPD and - much more pronounced - asthma cohorts (COPD: 5.8% vs 6.7%, p <0.001; asthma: 1.4% vs 4.8%, p <0.001). For ILD (n = 916), the complication rate was similar as compared to the control group, whereas in-hospital mortality was markedly higher (16.3% vs 6.8%, p <0.001). CONCLUSIONS: These rather unexpected results should be viewed as hypothesis generating, with various possible explanations for our findings. These include the possible influence of inhaled corticosteroid therapy, a possibly higher awareness of general practitioners and hospital physicians while treating patients with chronic lung diseases, a different infective agent spectrum or a different immune response.