Validating Methylated HOXA9 in Bronchial Lavage as a Diagnostic Tool in Patients Suspected of Lung Cancer

Diagnosing lung cancer requires invasive procedures with high risk of complications. Methylated tumor DNA in bronchial lavage has previously shown potential as a diagnostic biomarker. We aimed to develop and validate methylated HOXA9 in bronchial lavage as a diagnostic biomarker of lung cancer. Participants were referred on suspicion of lung cancer. Ten mL lavage fluid was collected at bronchoscopy for analysis of methylated HOXA9 based on droplet digital PCR according to our previously published method. HOXA9 status was compared with the final diagnosis. The Discovery and Validation cohorts consisted of 101 and 95 consecutively enrolled participants, respectively. In the discovery cohort, the sensitivity and specificity were 73.1% (95% CI 60.9–83.2%) and 85.3% (95% CI 68.9–95.0%), respectively. In the validation cohort, the values were 80.0% (95% CI 66.3–90.0%) and 75.6% (95% CI 60.5–87.1%), respectively. A multiple logistic regression model including age, smoking status, and methylated HOXA9 status resulted in an AUC of 84.9% (95% CI 77.3–92.4%) and 85.9% (95% CI 78.4–93.4%) for the Discovery and Validation cohorts, respectively. Methylated HOXA9 in bronchial lavage holds potential as a supplementary tool in the diagnosis of lung cancer with a clinically relevant sensitivity and specificity. It remained significant when adjusting for age and smoking status.

Bronchoscopic biopsies with radial endobronchial ultrasonographic navigation in the diagnosis of tuberculosis and mycobacteriosis in patients with peripheral lung masses

The objective of the study: to evaluate the effectiveness of diagnosis of tuberculosis and mycobacteriosis in bronchobiopsy specimens obtained during navigation by radial endobronchial ultrasonography (rEBUS) in patients with peripheral lung lesions without bacterial excretion.Subjects and methods. A retrospective analysis of the diagnostic effectiveness of bronchoscopic examination with biopsies was carried out in 179 patients (75 men and 104 women) suffering from pulmonary tuberculosis or mycobacteriosis without bacterial excretion; peripheral lung lesions had been visualized by computed tomography (CT). The patients were divided into two groups: 93 underwent bronchoscopy with biopsies with rEBUS navigation, 86 underwent bronchoscopy with classical biopsies and preliminary CT navigation. Each patient underwent multiple biopsies, at least one fluid biopsy (bronchoalveolar lavage or bronchial lavage), and one tissue biopsy (transbronchial lung biopsy or brush biopsy). Specimens collected by all types of bronchobiopsy were sent for microbiological and cytological tests, specimens of pulmonary transbronchial biopsy were additionally sent for histological examination.Results. The diagnosis of tuberculosis was verified by bronchobiopsy in 106 (67.5%) of 158 patients with tuberculosis, but statistically significantly more often in the group with rEBUS navigation versus the group without it – 81.9% (68/83) versus 50.7% (38/75), respectively (pχ2 < 0.01). The diagnosis of non-tuberculous mycobacteriosis was verified by bronchobiopsy in 13 (61.9%) of 21 patients, in the group with rEBUS navigation – in 80.0% (8/10) patients, in the group without it – in 45.5% (5/11) (pφ > 0.05). The use of rEBUS navigation while collecting bronchobiopsy specimens made it possible to increase the etiological verification of tuberculosis using the following microbiological methods: microscopy – from 14.7 to 49.4% (pχ2 < 0.01), molecular genetic – from 41.3 to 72.3% ( pχ2 < 0.01), culture (Bactec MGIT960) – from 44.0 to 67.5% (pχ2 < 0.01) The greatest enhancement of diagnostic effectiveness was achieved in the specimens of bronchoalveolar lavage and bronchial lavage – from 33.3 to 71.1% (pχ2 < 0.01) and in brush biopsy specimens – from 25.6 to 57.6% (pχ2 < 0.01).

Successful treatment of severe pneumonia, pyopneumothorax with severe acute respiratory distress syndrome, and septic shock: a case report

Background This article reports a patient who survived severe pneumonia, pyopneumothorax with acute respiratory distress syndrome (ARDS), and septic shock, which is very difficult to treat. Case presentation Antibiotics, continuous renal replacement therapy (CRRT), bronchial lavage and other treatments were used to treat a patient with pneumonia, pyopneumothorax, severe ARDS and septic shock. After comprehensive treatment, the patient was successfully treated and survived for a long time. Conclusions There is a low successful clinical treatment rate for patients with pneumonia, pyopneumothorax with severe ARDS and septic shock. The successful treatment of this patient benefited from early and effective empirical therapy, targeted drug selection in the later stage, adequate closed thoracic drainage, repeated bronchial lavage, early CRRT, an appropriate respiratory support mode and parameter setting, immunotherapy and nutritional support therapy. This paper proposes a reference diagnosis and treatment solution for similar cases.

Validation of tumor DNA in bronchial lavage as a diagnostic tool in lung cancer.

9020 Background: Diagnosing lung cancer requires invasive procedures with risk of complications for the patient. The HOXA9 gene is highly methylated in lung cancer, and methylated tumor DNA (meth-tDNA) in bronchial lavage has previously shown potential as a diagnostic biomarker. The aim of the present study was to validate these preliminary results. Methods: Patients were referred by the general practitioner on suspicion of lung cancer. The Danish diagnostic package includes chest and abdominal CT scan, bronchoscopy, blood tests, and histopathological or cytological verification. Twelve ml lavage fluid was collected at bronchoscopy for analysis of meth-tDNA based on droplet digital PCR according to our published method. A positive test was defined as ≥ 4 droplets containing meth-tDNA and a ratio between HOXA9 and Albumin of > 0.15%. The analysis was performed blinded to clinical data and meth-tDNA status was compared with the final diagnosis. Results: The study population was 204 consecutively enrolled patients. The material consisted of a discovery cohort (n = 105, presented at ASCO 2019) used for establishing the cut-points, and a validation cohort (n = 99). Six were excluded from analysis due to malignancy other than lung cancer and one due to failed analysis. In the discovery cohort, the sensitivity was 68.7% (95% CI 56.2-79.4%), specificity 88.2% (95% CI 72.6-96.7%), and positive predictive value (PPV) 92.0% (95% CI 80.8-97.8%). In the validation cohort, the same values were 76.9% (95% CI 63.2-87.5%), 77.3% (95% CI 62.2-88.5%), and 80.0% (95% CI 66.3-90.0%), respectively. Analyzing the entire patient material (n = 197) the sensitivity, specificity, and PPV were 72.3% (95% CI 63.3-80.1%), 82.1% (95% CI 71.7-89.8%), and 86.0% (95% CI 77.6-92.1%), respectively. The false positive samples were equally distributed among patients with cryptogenic organizing pneumonia, granulomatous inflammation, and acute inflammatory disease. The false negative samples were mainly from patients with peripheral tumor, no radiologically detectable tumor, and mesothelioma. Conclusions: Meth-tDNA in bronchial lavage holds potential as a supplementary tool in the diagnosis of lung cancer with a clinically relevant sensitivity and specificity. Routine clinical application awaits further validation in a clinical trial. [Table: see text]

Bronchial lavage under fiberoptic bronchoscopy in the treatment of severe pulmonary infection

Objective: To investigate the clinical efficacy of bronchial lavage under fiberoptic bronchoscopy in the treatment of severe pulmonary infection. Methods: One hundred forty eight patients with severe pulmonary infection who were admitted to our hospital from October 2016 to December 2017 were included in this study. According to the random number table method, they were divided into a control group and an observation group with 79 patients each. The control group was given conventional treatment, while the observation group was given bronchoalveolar lavage with fiberoptic bronchoscopy on the basis of the treatment in the control group. The clinical efficacy of the two groups was compared, the duration of mechanical ventilation, antibiotic use and symptoms improvement of the two groups were recorded, and the respiratory mechanics parameters, serum procalcitonin (PCT) and transforming growth factor β (TGF-β) level were measured before and after treatment. Results: The duration of mechanical ventilation, antibiotic use, respiratory failure correction, body temperature decline and white blood cell recovery in the observation group were significantly shorter than those in the control group (P<0.05). The total efficacy of the observation group was significantly higher than that of the control group (92.4% vs. 74.7%). The respiratory mechanics parameters of the two groups after treatment were higher than those before treatment (P<0.05) and the increase of the observation group was more obvious than that of the control group (P<0.05). The serum PCT and TGF-β levels of the two groups after treatment were lower than those before treatment (P<0.05), and the decrease level in the observation group was more obvious (P<0.05). Conclusion: Bronchial lavage under fiberoptic bronchoscopy can improve the clinical efficacy, accelerate the improvement of clinical symptoms and respiratory mechanics parameters, significantly reduce the PCT and TGF-β levels, and promote the rapid recovery of patients in the treatment of severe pulmonary infection. doi: https://doi.org/10.12669/pjms.36.3.1539 How to cite this:Zhao Y, Dai X, Ji J, Cheng P. Bronchial lavage under fiberoptic bronchoscopy in the treatment of severe pulmonary infection. Pak J Med Sci. 2020;36(3):---------. doi: https://doi.org/10.12669/pjms.36.3.1539 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.