Prospective Detection of Early Lung Cancer in Patients With COPD in Regular Care by Electronic Nose Analysis of Exhaled Breath.

BACKGROUND: Patients with COPD are at high risk of lung cancer developing, but no validated predictive biomarkers have been reported to identify these patients. Molecular profiling of exhaled breath by electronic nose (eNose) technology may qualify for early detection of lung cancer in patients with COPD. RESEARCH QUESTION: Can eNose technology be used for prospective detection of early lung cancer in patients with COPD? STUDY DESIGN AND METHODS: BreathCloud is a real-world multicenter prospective follow-up study using diagnostic and monitoring visits in day-to-day clinical care of patients with a standardized diagnosis of asthma, COPD, or lung cancer. Breath profiles were collected at inclusion in duplicate by a metal-oxide semiconductor eNose positioned at the rear end of a pneumotachograph (SpiroNose; Breathomix). All patients with COPD were managed according to standard clinical care, and the incidence of clinically diagnosed lung cancer was prospectively monitored for 2 years. Data analysis involved advanced signal processing, ambient air correction, and statistics based on principal component (PC) analysis, linear discriminant analysis, and receiver operating characteristic analysis. RESULTS: Exhaled breath data from 682 patients with COPD and 211 patients with lung cancer were available. Thirty-seven patients with COPD (5.4%) demonstrated clinically manifest lung cancer within 2 years after inclusion. Principal components 1, 2, and 3 were significantly different between patients with COPD and those with lung cancer in both training and validation sets with areas under the receiver operating characteristic curve of 0.89 (95% CI, 0.83-0.95) and 0.86 (95% CI, 0.81-0.89). The same three PCs showed significant differences (P < .01) at baseline between patients with COPD who did and did not subsequently demonstrate lung cancer within 2 years, with a cross-validation value of 87% and an area under the receiver operating characteristic curve of 0.90 (95% CI, 0.84-0.95). INTERPRETATION: Exhaled breath analysis by eNose identified patients with COPD in whom lung cancer became clinically manifest within 2 years after inclusion. These results show that eNose assessment may detect early stages of lung cancer in patients with COPD.

The use of oximetry and a questionnaire in primary care enables exclusion of a subsequent obstructive sleep apnea diagnosis.

PURPOSE: The study aims to prospectively validate the prognostic value of oximetry alone or combined in a two-step strategy with a questionnaire for the exclusion of obstructive sleep apnea (OSA) in primary care. METHODS: A total of 140 subjects with suspected OSA were included from 54 participating primary care practices. All subjects completed the Philips questionnaire and underwent one night of oximetry prior to referral to a sleep center. The prognostic value of two strategies was evaluated against the diagnosis of the sleep center as the gold standard: (1) assume OSA and subsequently refer to a sleep center if the oxygen desaturation index (ODI) is ≥ 5 and (2) assume OSA and refer to a sleep center if the Philips questionnaire score is ≥ 55% (regardless of the ODI) or if the Philips questionnaire score is < 55% and the ODI is ≥ 5. RESULTS: OSA was diagnosed in the sleep centers in 100 (71%) of the included subjects. Using ODI ≥ 5 alone resulted in a sensitivity of 99.0%, a specificity of 50.0%, a negative predictive value of 95.2%, and a positive predictive value 83.2%. Using the two-step strategy, oximetry would be performed on 39% of the subjects. This strategy resulted in a sensitivity of 100%, a specificity of 35.0%, a negative predictive value of 100%, and a positive predictive value of 79.4%. CONCLUSIONS: In a Dutch primary care population with a clinical suspicion of OSA and low frequency of cardiovascular comorbidities, the use of oximetry alone or combined in a two-step strategy with a questionnaire enables exclusion of a sleep center diagnosis of OSA.

Validation of the oxygen desaturation index in the diagnostic workup of obstructive sleep apnea.

INTRODUCTION: Obstructive sleep apnea (OSA) is common, and diagnosis requires expensive and laborious testing to assess the apnea hypopnea index (AHI). We performed an analysis to explore the relationship between the oxygen desaturation index (ODI) as measured with pulse oximetry and the AHI in our large portable monitoring (PM) database to find an optimal cutoff value for the ODI in order to be able to exclude AHI ≥ 5 on PM. METHODS: Three thousand four hundred thirteen PM recordings were randomly divided into a training set (N = 2281) and a test set (N = 1132). The optimal cutoff for the ODI to exclude an AHI ≥ 5 on PM was determined in the training set and subsequently validated in the test set. RESULTS: Area under the curve of the ODI to exclude an AHI ≥ 5 on PM was 0.997 in the training set and 0.996 in the test set. In the training set, the optimal cutoff to predict an AHI < 5 was an ODI < 5. Using this cutoff in the test set provided a sensitivity of 97.7%, a specificity of 97.0%, a positive predictive value of 99.2%, and a negative predictive value of 91.4%. CONCLUSION: An ODI < 5 predicts an AHI < 5 with high sensitivity and specificity when measured simultaneously using the same oximeter during PM recording.

Retrospective validation of a new volumetric capnography parameter for the exclusion of pulmonary embolism at the emergency department.

Volumetric capnography might be used to exclude pulmonary embolism (PE) without the need for computed tomography pulmonary angiography. In a pilot study, a new parameter (CapNoPE) combining the amount of carbon dioxide exhaled per breath (carbon dioxide production (V CO2 )), the slope of phase 3 of the volumetric capnogram (slope 3) and respiratory rate (RR) showed promising diagnostic accuracy (where CapNoPE=(V CO2 ×slope 3)/RR). To retrospectively validate CapNoPE for the exclusion of PE, the volumetric capnograms of 205 subjects (68 with PE) were analysed, based on a large multicentre dataset of volumetric capnograms from subjects with suspected PE at the emergency department. The area under the curve (AUC) of the receiver operating characteristic (ROC) curve and diagnostic accuracy of the in-pilot established threshold (1.90 Pa·min) were calculated. CapNoPE was 1.56±0.97 Pa·min in subjects with PE versus 2.51±1.67 Pa·min in those without PE (p<0.001). The AUC of the ROC curve was 0.714 (95% CI 0.64-0.79). For the cut-off of ≥1.90 Pa·min, sensitivity was 64.7%, specificity was 59.9%, the negative predictive value was 77.4% and the positive predictive value was 44.4%. The CapNoPE parameter is decreased in patients with PE but its diagnostic accuracy seems too low to use in clinical practice.

Reproducibility of hypercapnic ventilatory response measurements with steady-state and rebreathing methods.

In this study, the hypercapnic ventilatory response (HCVR) was measured, defined as the ventilation response to carbon dioxide tension (PCO2 ). We investigated which method, rebreathing or steady-state, is most suitable for measurement of the HCVR in healthy subjects, primarily based on reproducibility. Secondary outcome parameters were subject experience and duration. 20 healthy adults performed a rebreathing and steady-state HCVR measurement on two separate days. Subject experience was assessed using numeric rating scales (NRS). The intraclass correlation coefficient (ICCs) of the sensitivity to carbon dioxide above the ventilatory recruitment threshold and the projected apnoea threshold were calculated to determine the reproducibility of both methods. The ICCs of sensitivity were 0.89 (rebreathing) and 0.56 (steady-state). The ICCs of the projected apnoea threshold were 0.84 (rebreathing) and 0.25 (steady-state). The steady-state measurement was preferred by 16 out of 20 subjects; the differences in NRS scores were small. The hypercapnic ventilatory response measured using the rebreathing setup provided reproducible results, while the steady-state method did not. This may be explained by high variability in end-tidal PCO2 . Differences in subject experience between the methods are small.

The TL,NO /TL,CO ratio cannot be used to exclude pulmonary embolism.

BACKGROUND: The existing screening modalities for pulmonary embolism (PE), such as D-dimer and clinical prediction rules, have low positive predictive values. With its capability to indicate pulmonary vascular abnormalities, the ratio of the transfer factor of the lungs for nitric oxide and the transfer factor of the lungs for carbon monoxide (TL,NO /TL,CO ) might be an additional discriminating parameter. METHODS: Carbon monoxide/Nitric oxide diffusion measurements were performed on unselected patients seen on the emergency department for which due to suspected PE a computed tomography pulmonary angiogram (CTPA) was ordered. RESULTS: A total of 28 patients were included, PE was found in 12 on CTPA. Median TL,NO /TL,CO ratio was 4·09 (interquartile range (IQR) 3·83-4·40) in the no PE group versus 4·00 (IQR 3·78-4·32) in the PE group (P = 0·959). Median alveolar volume was 77·1% of predicted in the no PE group versus 71·0% of predicted in the PE group (P = 0·353). Median TL,CO was 75·8% of predicted in the no PE group versus 68·8% of predicted in the PE group (P = 0·120). Median TL,NO was 69·3% of predicted in the no PE group versus 60·5% of predicted in the PE group (P = 0·078). CONCLUSION: The presented data indicate that the TL,NO /TL,CO ratio cannot be used to exclude PE.

Volumetric capnography in the exclusion of pulmonary embolism at the emergency department: a pilot study.

The analysis of the [Formula: see text] in expired air as a function of the exhaled volume (volumetric capnography) might result in a more specific exclusion tool for pulmonary embolism (PE) in addition to the Wells-score and D-dimer. A novel combination of volumetric capnography parameters ([Formula: see text]) should be decreased in PE and could possibly be used to decrease the number of requested computed tomography pulmonary angiograms (CTPA). Volumetric capnography measurements were performed on consecutive patients seen in the emergency department for which, due to suspected PE (due to increased D-dimer level or Wells-score), a CTPA was ordered. A total of 30 subjects were included, of which in 13 PE was seen on CTPA. Median [Formula: see text] was 4.36 kPa (IQR 3.92-4.88) in the no PE group versus 4.07 kPa (IQR 3.37-4.39) in the PE group (p = 0.086). Median of the novel parameter [Formula: see text] was 1.85 min.kPa dl-1 (IQR 1.21-3.00) in the no PE group versus 1.18 min.kPa dl-1 (IQR 0.61-1.38) in the PE group (p = 0.006). Using a threshold for the new parameter of 1.90 min.kPa dl-1 or higher to exclude PE resulted in a negative predictive value of 100% (95% CI: 77%-100%) and would have potentially excluded PE in 47% (95% CI: 26%-69%) of the no PE group without the need for CTPA. This pilot study introduces a novel parameter [Formula: see text] which is significantly decreased in PE subjects. Future studies regarding validation and addressing aspects such as reproducibility and normalization after treatment are needed to confirm its usability in excluding PE in the emergency department.

Electroanatomical Mapping of the Urinary Bladder.

A noncontact mapping system (EnSite) was used for electroanatomical mapping of the bladder simultaneously with pressure flow study in three women with lower urinary tract symptoms. We selected the periods of obvious detrusor activity. Data were processed to remove baseline drift, and an envelope of electrovesicography (EVG) data was created. The correlation coefficient for the correlation between between the EVG envelope and the detrusor pressure (Pdet) was calculated. Bladder geometry was successfully created in all 3 patients. Simultaneous recording of EVG and pressure flow data was successful in 1 patient. Scatter plots were made of the highest correlation coefficient, showing a positive correlation between the Pdet and the envelope, and negative correlation between abdominal pressure (Pabd) and the envelope. Minimal electrical activity could be observed. Significant weak to moderate correlation coefficients were found for the correlations between Pdet and EVG and between Pabd and EVG.