Digital image comparison of cellular yield in bronchial brushing, pre- and post-biopsy lavage cytology.

Background Bronchoscopy is a useful diagnostic tool capable of performing core biopsy, forceps biopsy, bronchoalveolar lavage, and bronchial brushing. This study compares the cellularity of bronchial cytology including pre- and post-biopsy lavage by digital image analysis, aiming to increase diagnostic and tumor yield by optimizing the sequence and combination of bronchial biopsy and cytology. Methods Alveolar macrophage, bronchial epithelium, and tumor cell cellularity from liquid-based cytology preparations of bronchial brushing and pre-biopsy and post-biopsy bronchoalveolar lavage were annotated on digitized whole-slide images and compared. Secondary analysis on the relationship of tumor cell and non-lesional cell yield was performed. Results 118 cytology specimens from 43 patients were retrieved in total. Bronchial epithelium count was higher in pre-biopsy than post-biopsy lavage (p<0.01) but not for alveolar macrophages nor tumor cell (p>0.05). Tumor cell count was higher for bronchial brushing cytology samples than lavage (p=0.018). The alveolar macrophage count was higher in post-biopsy lavage than bronchial brushing (p=0.033), otherwise brushing showed consistently higher bronchial epithelium and tumor cell counts. There were 33 false negative (tumor cell absent) specimens, and the combination of bronchial brushing and pre-biopsy lavage yielded the lowest false negative cases. Correlation between bronchial epithelium and alveolar macrophage counts with tumor cell count were weak (correlation coefficient=-0.168-0.203) except for post-biopsy lavage (correlation coefficient=0.412-0.479, p<0.05). Conclusion Bronchial brushing yields a greater amount of tumor cell than lavage, and timing lavage before or after core biopsy does not affect tumor cell yield. Combining bronchial brushing and pre-biopsy lavage results in the lowest false negative rate.

Comparison of the 12-month impact of COVID-19 and SARS on physiological capacity and health-related quality of life.

BACKGROUND: Little is known about the differences in medium to long-term recovery on spirometry, 6-minute walking distance (6MWD) and health-related quality of life (HRQoL) between COVID-19 and SARS. METHODS: We performed a 12-month prospective study on COVID-19 survivors. The changes in dynamic lung volumes at spirometry (%predicted FEV1, %predicted FVC), 6MWD and HRQoL at 1-3, 6 to 12 months were compared against a historical cohort of SARS survivors using the same study protocol. The residual radiological changes in HRCT in COVID-19 survivors were correlated with their functional capacity. RESULTS: 108 COVID-19 survivors of various disease severity (asymptomatic 2.9%, mild 33.3%, moderate 47.2%, severe 8.3%, critical 8.3%) were recruited. When compared with 97 SARS survivors, 108 COVID-19 survivors were older (48.1 ± 16.4 vs. 36.1 ± 9.5 years, p < 0.001) and required less additional support during hospitalization; with lower dynamic lung volumes, shorter 6MWD and better physical component score. Both groups of survivors had comparable changes in these parameters at subsequent follow-ups. Both COVID-19 and SARS survivors had similar mental component score (MCS) at 6 and 12 months. COVID-19 survivors initially experienced less (between-group difference, -3.1, 95% confidence interval [CI] -5.5 to -0.7, p = 0.012) and then more improvement (between-group difference 2.9, 95%, CI 0.8 to 5.1, p = 0.007) than SARS survivors in the MCS at 1-3 to 6 months and 6 to 12 months respectively. Forty (44.0%) out of 91 COVID-19 survivors had residual abnormalities on HRCT at 12 months, with a negative correlation between the severity scores of parenchymal changes and 6MWD (r=-0.239, p < 0.05). CONCLUSIONS: COVID-19 survivors demonstrated a similar recovery speed in dynamic lung volumes and exercise capacity, but different paces of psychological recovery as SARS survivors in the convalescent phase. The severity of parenchymal changes in HRCT is negatively correlated with the 6MWD of COVID-19 survivors. TRIAL REGISTRATION: This prospective study was registered at ClinicalTrials.gov on 2 November 2020 (Identifier: NCT04611243).

1-Year Prospective Study of the Relationship of Serial Exhaled Nitric Oxide Level and Asthma Control.

Background and Objective: Previous studies found that the fractional nitric oxide concentration in exhaled breath (FeNO) levels in healthy Chinese adults was higher than in White adults. More understanding of serial changes of FeNO levels with asthma control in a real-life clinical setting would be important to explore the utility of this biomarker in routine asthma management. This study assessed the FeNO levels of Chinese asthma subjects with different levels of asthma control and the serial changes with respect to the changes in asthma control over 1 year. Methods: A 12-month prospective study (subjects recruited between November 2019 and January 2021) with serial measurement of FeNO levels at baseline, 4, 8 and 12 months. Asthma control was assessed by the Global Initiative for Asthma classification, Asthma Control Test (ACT) and Asthma Control Questionnaire (ACQ). Results: Altogether, 136 subjects (mean age 51.51±15.09 years, 46[33.8%] male) had successful baseline FeNO measurements. At baseline, the FeNO levels did not show a statistically significant difference for controlled, partly controlled and uncontrolled asthma according to GINA classification, ACT and ACQ. FeNO levels decreased with improving asthma control and stayed at similar levels with unchanged or worsening asthma control for all subjects. For subjects with baseline blood eosinophil levels ≥300 cells/µL(n=59), FeNO levels decreased with improving asthma control, stayed similar without change for asthma control and increased with worsening asthma control. Receiver operating characteristic (ROC) analysis with the highest area under curve (AUC) for changes in FeNO levels for improving asthma control was between ≤ -10 to -25 ppb at various time points in the 12-month study. Conclusion: Changes in FeNO levels over time were associated with changes in clinical asthma control, particularly in those with higher blood eosinophil count and are likely more useful than a single time point measurement in managing asthma.