Using intra-breath oscillometry in obesity hypoventilation syndrome to detect tidal expiratory flow limitation: a potential marker to optimize CPAP therapy.

BACKGROUND: Continuous positive airway pressure (CPAP) therapy has profound effects in obesity hypoventilation syndrome (OHS). Current therapy initiation focuses on upper airway patency rather than the assessment of altered respiratory mechanics due to increased extrapulmonary mechanical load. METHODS: We aimed to examine the viability of intra-breath oscillometry in optimizing CPAP therapy for OHS. We performed intra-breath oscillometry at 10 Hz in the sitting and supine positions, followed by measurements at increasing CPAP levels (none-5-10-15-20 cmH2O) in awake OHS patients. We plotted intra-breath resistance and reactance (Xrs) values against flow (V') and volume (V) to identify tidal expiratory flow limitation (tEFL). RESULTS: Thirty-five patients (65.7% male) completed the study. We found a characteristic looping of the Xrs vs V' plot in all patients in the supine position revealing tEFL: Xrs fell with decreasing flow at end-expiration. Intra-breath variables representing expiratory decrease of Xrs became more negative in the supine position [end-expiratory Xrs (mean ± SD): -1.9 ± 1.8 cmH2O·s·L- 1 sitting vs. -4.2 ± 2.2 cmH2O·s·L- 1 supine; difference between end-expiratory and end-inspiratory Xrs: -1.3 ± 1.7 cmH2O·s·L- 1 sitting vs. -3.6 ± 2.0 cmH2O·s·L- 1 supine, p < 0.001]. Increasing CPAP altered expiratory Xrs values and loop areas, suggesting diminished tEFL (p < 0.001). 'Optimal CPAP' value (able to cease tEFL) was 14.8 ± 4.1 cmH2O in our cohort, close to the long-term support average of 13.01(± 2.97) cmH2O but not correlated. We found no correlation between forced spirometry values, patient characteristics, apnea-hypopnea index and intra-breath oscillometry variables. CONCLUSIONS: tEFL, worsened by the supine position, can be diminished by stepwise CPAP application in most patients. Intra-breath oscillometry is a viable method to detect tEFL during CPAP initiation in OHS patients and tEFL is a possible target for optimizing therapy in OHS patients.

Exploring red cell distribution width as a biomarker for treatment efficacy in home mechanical ventilation.

BACKGROUND: With the growing practice of home mechanical ventilation, there is a need to identify biological markers for adequate follow-up. Red cell distribution width (RDW) is a promising candidate because it is convenient, objective and may reflect treatment effect over a long period of time. The aim of this study was to explore the possible role of RDW as a marker for home mechanical ventilation in real-life, unselected chronic respiratory patient populations. METHODS: First, we identified characteristic RDW values for mixed case, unselected chronic respiratory failure and home mechanical ventilated patients through retrospective review within our institutional database. Next, we conducted a prospective observational study to identify RDW changes during the first six months of optimized home mechanical ventilation treatment. Adult patients starting home mechanical ventilation were included. Factors affecting RDW change during the first 6 months of treatment were analysed. RESULTS: RDW was elevated in both chronic respiratory failure and home mechanical ventilation patients compared to healthy individuals in the retrospective review. In the prospective study of 70 patients, we found that 55.4% of patients starting home mechanical ventilation have abnormal RDW values which are reduced from 14.7 (IQR = 13.2-16.2)% to 13.5 (IQR = 13.1-14.6)% during the first 6 months of HMV treatment (p < 0.001). RDW improvement correlates with improvement in self-reported health-related quality of life and sleepiness scale scores, as well as physical functional status during the same time frame. RDW proved to be a comparable marker to other parameters traditionally used to evaluate treatment efficacy. CONCLUSIONS: RDW is elevated in chronic respiratory failure patients and is significantly reduced in the first six months of optimized home mechanical ventilation. Although further research is needed to verify if RDW change reflects outcome and how comorbidities influence RDW values, our results suggest that RDW is a promising marker of home mechanical ventilation efficacy. Trial registration This study was approved by and registered at the ethics committee of Semmelweis University (TUKEB 250/2017 and TUKEB 250-1/2017, 20th of December 2017 and 1st of October 2019).

Decreased ERCC1 Expression After Platinum-Based Neoadjuvant Chemotherapy in non-Small Cell Lung Cancer.

We have already demonstrated in a small cohort of 17 non-small cell lung cancer patients that ERCC1 (excision repair cross-complementation group 1) protein expression decreased after platinum-based treatment, however, certain clinicopathological parameters, such as histologic subtypes, ERCC1 expression scores, chemotherapeutic combinations, response rate, gender and smoking history were not analyzed. The aim of our present study was to extend the studied cohort and analyze those parameters. ERCC1 protein expression was examined in 46 patients treated with neoadjuvant chemotherapy. 46 bronchoscopic biopsy samples (27 squamous cell carcinomas /SCC/ and 19 adenocarcinomas /ADC/) together with their corresponding surgical biopsies were studied. ERCC1 immunohistochemistry was performed on formalin-fixed, paraffin-embedded tissues. Staining scores were calculated by multiplying the percentage of positive tumor cells (0-100) by the staining intensity (0-3). 24/27 bronchoscopic SCC tissues expressed ERCC1. Thirteen of these cases became negative after neoadjuvant therapy and the expression differences between pre- and postchemotherapy samples were highly significant (p < 0.001). 11/19 bronchoscopic ADC tissues expressed ERCC1. Six of these cases became negative after neoadjuvant therapy and the expression differences were significant (p < 0.010). There was no newly expressed ERCC1 postoperatively. Comparison of staining score changes revealed more pronounced decrease in SCC (p = 0.032). We observed no correlation between initial ERCC1 level or ERCC1 decrease and overall survival, but we demonstrated correlations between decrease in ERCC1 expression and histologic subtypes of tumors and gender. We could confirm our previous data in a larger cohort that platinum-based chemotherapy affects the ERCC1 expression probably referring to an induction of tumor cell selection.