Predicting response to oxygen therapy in obstructive sleep apnoea patients using a 10-minute daytime test.

There is no satisfactory treatment for obstructive sleep apnoea (OSA). Supplemental low-flow oxygen therapy (LFO2) has been shown to reduce hypoxaemia and is well tolerated by patients with OSA. However, oxygen therapy may be beneficial only to certain subsets of patients with OSA. In this study, we evaluated a 10-min awake ventilatory chemoreflex test in predicting individual OSA response to 2 months of LFO2 therapy.At baseline, patients with OSA underwent ventilatory chemoreflex testing in the afternoon, prior to the overnight polysomnography. Subjects were reassessed with polysomnography after 2 months of nocturnal oxygen treatment.20 patients with OSA completed the study. After 2 months of O2 treatment, changes in the apnoea-hypopnoea index (AHI) were significantly correlated with baseline CO2 ventilatory response threshold (VRT) and chemosensitivity (p<0.05). In predicting a fall in AHI, the area under the receiver operating characteristic curve (AUC) was 0.79 for VRT and 0.89 for chemosensitivity. When these two variables were combined in a logistic regression model, the prediction effect became stronger with an AUC of 0.97, sensitivity of 0.92 and specificity of 0.83.Our awake ventilatory chemoreflex test could be considered a simple potential clinical tool to predict individual OSA response to oxygen therapy. It could provide a novel personalised medicine approach to OSA treatment.

Diagnostic accuracy of transbronchial lung cryobiopsy for interstitial lung disease diagnosis (COLDICE): a prospective, comparative study.

BACKGROUND: Transbronchial lung cryobiopsy (TBLC) is a novel technique for sampling lung tissue for interstitial lung disease diagnosis. The aim of this study was to establish the diagnostic accuracy of TBLC compared with surgical lung biopsy (SLB), in the context of increasing use of TBLC in clinical practice as a less invasive biopsy technique. METHODS: COLDICE was a prospective, multicentre, diagnostic accuracy study investigating diagnostic agreement between TBLC and SLB, across nine Australian tertiary hospitals. Patients with interstitial lung disease aged between 18 and 80 years were eligible for inclusion if they required histopathological evaluation to aid diagnosis, after detailed baseline evaluation. After screening at a centralised multidisciplinary discussion (MDD), patients with interstitial lung disease referred for lung biopsy underwent sequential TBLC and SLB under one anaesthetic. Each tissue sample was assigned a number between 1 and 130, allocated in a computer-generated random sequence. Encoded biopsy samples were then analysed by masked pathologists. At subsequent MDD, de-identified cases were discussed twice with either TBLC or SLB along with clinical and radiological data, in random non-consecutive order. Co-primary endpoints were agreement of histopathological features in TBLC and SLB for patterns of definite or probable usual interstitial pneumonia, indeterminate for usual interstitial pneumonia, and alternative diagnosis; and for agreement of consensus clinical diagnosis using TBLC and SLB at MDD. Concordance and κ values were calculated for each primary endpoint. This study is registered with the Australian New Zealand Clinical Trials Registry, ACTRN12615000718549. FINDINGS: Between March 15, 2016, and April 15, 2019, we enrolled 65 patients (31 [48%] men, 34 [52%] women; mean age 66·1 years [SD 9·3]; forced vital capacity 83·7% [SD 14·2]; diffusing capacity for carbon monoxide 63·4% [SD 12·8]). TBLC (7·1 mm, SD 1·9) and SLB (46·5 mm, 14·9) samples were each taken from two separate ipsilateral lobes. Histopathological agreement between TBLC and SLB was 70·8% (weighted κ 0·70, 95% CI 0·55-0·86); diagnostic agreement at MDD was 76·9% (κ 0·62, 0·47-0·78). For TBLC with high or definite diagnostic confidence at MDD (39 [60%] of 65 cases), 37 (95%) were concordant with SLB diagnoses. In the 26 (40%) of 65 cases with low-confidence or unclassifiable TBLC diagnoses, SLB reclassified six (23%) to alternative high-confidence or definite MDD diagnoses. Mild-moderate airway bleeding occurred in 14 (22%) patients due to TBLC. The 90-day mortality was 2% (one of 65 patients), following acute exacerbation of idiopathic pulmonary fibrosis. INTERPRETATION: High levels of agreement between TBLC and SLB for both histopathological interpretation and MDD diagnoses were shown. The TBLC MDD diagnoses made with high confidence were particularly reliable, showing excellent concordance with SLB MDD diagnoses. These data support the clinical utility of TBLC in interstitial lung disease diagnostic algorithms. Further studies investigating the safety profile of TBLC are needed. FUNDING: University of Sydney, Hunter Medical Research Institute, Erbe Elektromedizin, Medtronic, Cook Medical, Rymed, Karl-Storz, Zeiss, and Olympus.

Cryobiopsy versus open lung biopsy in the diagnosis of interstitial lung disease (COLDICE): protocol of a multicentre study.

Introduction: Transbronchial lung cryobiopsy (TBLC) is a novel, minimally invasive technique for obtaining lung tissue for histopathological assessment in interstitial lung disease (ILD). Despite its increasing popularity, the diagnostic accuracy of TBLC is not yet known. The COLDICE Study (Cryobiopsy versus Open Lung biopsy in the Diagnosis of Interstitial lung disease allianCE) aims to evaluate the agreement between TBLC and surgical lung biopsy sampled concurrently from the same patients, for both histopathological and multidisciplinary discussion (MDD) diagnoses. Methods and analysis: This comparative, multicentre, prospective trial is enrolling patients with ILD requiring surgical lung biopsy to aid with their diagnosis. Participants are consented for both video-assisted thoracoscopic surgical (VATS) biopsy and TBLC within the same anaesthetic episode. Specimens will be blindly assessed by three expert pathologists both individually and by consensus. Each tissue sample will then be considered in conjunction with clinical and radiological data, within a centralised MDD. Each patient will be presented twice in random order, once with TBLC data and once with VATS data. Meeting participants will be blinded to the method of tissue sampling. The accuracy of TBLC will be assessed by agreement with VATS at (1) histopathological analysis and (2) MDD diagnosis. Data will be collected on interobserver agreement between pathologists, interobserver agreement between MDD participants, and detailed clinical and procedural characteristics. Ethics and dissemination: The study is being conducted in accordance with the International Conference on Harmonisation Guideline for Good Clinical Practice and Australian legislation for the ethical conduct of research. Trial registration number: ACTRN12615000718549.

Influence of sleep state on frequency of swallowing, apnea, and arousal in human infants.

Apnea and arousal are modulated with sleep stage, and swallowing may interfere with respiratory rhythm in infants. We hypothesized that swallowing itself would display interaction with sleep state. Concurrent polysomnography and measurement of swallowing allowed time-matched analysis of 3,092 swallows, 482 apneas, and 771 arousals in 17 infants aged 1-34 wk. The mean rates of swallowing, apnea, and arousal were significantly different, being 23.3 +/- 8.5, 9.4 +/- 8.8, and 15.5 +/- 10.6 h(-1), respectively (P < 0.001 ANOVA). Swallows occurred before 25.2 +/- 7.9% and during 74.8 +/- 6.3% of apneas and before 39.8 +/- 6.0% and during 60.2 +/- 6.0% of arousals. The frequencies of apneas and arousals were both strongly influenced by sleep state (active sleep > indeterminate > quiet sleep, P < 0.001), whether or not the events coincided with swallowing, but swallowing rate showed minimal independent interaction with sleep state. Interactions between swallowing and sleep state were predominantly influenced by the coincidence of swallowing with apnea or arousal.