Methimazole-Induced ANCA Vasculitis: A Case Report

Rapidly progressive glomerulonephritis (RPGN) is a syndrome which presents rapid loss of renal function. Vasculitis represents one of the major causes, often related to anti-neutrophil cytoplasmic antibodies (ANCA). Herein, we report a case of methimazole-induced ANCA-associated vasculitis. A 35-year-old woman complained of weight loss and fatigue for 2 weeks and attended the emergency room with alveolar hemorrhage. She had been diagnosed with Graves’ disease and had been taking methimazole in the past 6 months. Her physical examination showed pulmonary wheezing, hypertension and signs of respiratory failure. Laboratory tests revealed urea 72 mg/dL, creatinine 2.65 mg/dL (eGFR CKD-EPI: 20 mL/min/1.73 m2), urine analysis with >100 red blood cells per high-power field, 24 h-proteinuria: 1.3 g, hemoglobin 6.6 g/dL, white-cell count 7700/mm3, platelets 238,000/mm3, complement within the normal range, negative viral serological tests and ANCA positive 1:80 myeloperoxidase pattern. Chest tomography showed bilateral and diffuse ground-glass opacities, and bronchial washing confirming alveolar hemorrhage. A renal biopsy using light microscopy identified 27 glomeruli (11 with cellular crescentic lesions), focal disruption in glomerular basement membrane and fibrinoid necrosis areas, tubulitis and mild interstitial fibrosis. Immunofluorescence microscopy showed IgG +2/+3, C3 +3/+3 and Fibrinogen +3/+3 in fibrinoid necrosis sites. She was subsequently diagnosed with crescentic pauci-immune glomerulonephritis, mixed class, in the setting of a methimazole-induced ANCA vasculitis. The patient was treated with methimazole withdrawal and immunosuppressed with steroids and cyclophosphamide. Four years after the initial diagnosis, she is currently being treated with azathioprine, and her exams show creatinine 1.30 mg/dL (eGFR CKD-EPI: 52 mL/min/1.73 m2) and negative p-ANCA.

Diagnostic efficacy cell block method of transthoracic fine needle aspiration in diagnosis of lung cancer

BackgroundLung cancer is still the main cause of cancer deaths. The high lung cancer mortality rate is caused by a diagnosis factor or therapy selection. The cell block cytology technique using fine needle aspiration (FNA) samples can provide immunocytochemical material that plays an important role in the differential diagnosis of lung cancer subtypes and in determining immunotherapy administration. This study aimed to determine the sensitivity and specificity of transthoracic FNA (TTFNA) cell block cytology in comparison with bronchial washing smears and TTFNA smears in diagnosing lung cancer. MethodsThis was a cross-sectional diagnostic study involving 26 subjects. All subjects had undergone bronchial washing and CT scan-guided fine needle aspiration followed by cell block preparation. Both direct FNA smears and cell blocks are useful in the diagnostic work-up of patients. Comparative statistical analysis of TTFNA cell block versus bronchial washing smear and TTFNA smear cytology was carried out using the McNemar test. ResultsLung cancer was found in 15 patients (57.7%) using the TTFNA cell block technique. The sensitivity and specificity of the TTFNA cell block technique were 85.7% and 75%, respectively. There was no difference in the positivity value between TTFNA cell block technique of bronchial wash smear technique, and TTFNA smear on lung cancer diagnosis (p>0.05). ConclusionsTransthoracic fine-needle aspiration in combination with the cell block technique has good sensitivity and specificity. The TTFNA can be used for immunocytochemical examinations in lung cancer diagnosis and therapy. This approach is valuable for providing individualized treatment and prognostic evaluations.

Bronchial Brushing and Diagnosis of Pulmonary Nontuberculous Mycobacteria Infection

<b><i>Background:</i></b> The optimal bronchoscopy procedure for diagnosis of pulmonary nontuberculous mycobacteria (NTM) infection is unclear. <b><i>Objective:</i></b> This study investigated the usefulness of bronchial brushing in bronchoscopy for diagnosis of pulmonary NTM infection in patients with suspected NTM lung disease and nodular bronchiectasis on chest computed tomography (CT) images. <b><i>Methods:</i></b> Bronchoscopy was prospectively performed for 69 patients with clinically suspected pulmonary NTM infection on chest CT from December 2017 through December 2019. Before and after bronchial brushing, bronchial washing was performed with 20 or 40 mL of normal sterile saline at the same segmental or subsegmental bronchi. Before and after bronchial brushing, samples of the washing fluid (pre- and postbrushing samples) and brush deposits (brush samples) were obtained and cultured separately. <b><i>Results:</i></b> NTM was detected in 37 of the 69 (53.6%) patients (<i>Mycobacterium avium</i> in 27, <i>Mycobacterium intracellulare</i> in 7, <i>M. abscessus</i> in 2, and <i>M. kansasii</i> in 2). NTM was detected in 34 (49.3%) prebrushing samples, in 27 (39.1%) postbrushing samples, and in 20 (29.0%) brush samples from the 69 patients. In 2 (2.9%) patients, NTM was detected only in postbrushing samples; in 1 (1.4%) patient, NTM was detected only in a brush sample. As compared with bronchial washing only, additional bronchial brushing increased the NTM culture-positive rate by 4.3% (3/69). Bronchial brushing caused bleeding, requiring hemostasis in 5 (7.2%) patients. <b><i>Conclusion:</i></b> Additional bronchial brushing increased the NTM culture-positive rate by only 4.3% (3/69), as compared with bronchial washing alone. Thus, the usefulness of brushing appears to be limited.

Identifying Genomic Alterations in Small Cell Lung Cancer Using the Liquid Biopsy of Bronchial Washing Fluid

Objective: With the rapid development of cancer genomics and immunomics, some new treatments of small cell lung cancer (SCLC) are emerging. However, there are limitations to the clinical use of tumor tissue. Our study aimed to evaluate the potential use of bronchial washing fluid (BWF) in the liquid biopsy of SCLC.Methods: Twenty-one extensive SCLC (ES-SCLC) patients were enrolled in this study. For all patients, four sample types, BWF supernatant (BWFs), BWF precipitate (BWFp), plasma and tumor tissue, were collected before receiving chemotherapy, and one type, plasma, was collected after chemotherapy. All samples were conducted to NGS using the 1021-gene panel. The concordance rates of genomic profiling using NGS in the four types of samples were evaluated. Multiple clinical information was analyzed for correlation.Results: We successfully tested 20 BWFs samples, 21 BWFp samples, 21 tumor tissue samples, 20 pre-treatment plasma, and 13 post-treatment plasma of these 21 patients. The detectability of somatic mutations was 100% for BWFs, BWFp, tumor tissues, and post-treatment plasma, and only one pre-treatment plasma was absent with any mutation. Matched tumor tissue, BWFs, BWFp, and pre-treatment plasma samples were subsistent for 19 patients. For these patients, 204 genomic alterations were identified in tissue samples, while 189 (92.6%), 175 (85.5%), and 163 (79.9%) alterations were detected in the matched BWFs, BWFp, and pre-treatment plasma, respectively. Moreover, we found that the three tumor markers associated with SCLC have a lower sensitivity than genomic alterations. The endocrine resistance pathway was found enriched in hyponatremia patients which may be related to the hyponatremia. The TMBs of BWF, BWFp, and pre-treatment plasma samples all had a strong correlation with that of tissue samples. Both the VAF and the MVAF of mutations in post-treatment plasma were less than those in pre-treatment plasma, which was in accordance with the evaluation of curative effect.Conclusions: For ES-SCLC patients, the liquid biopsy of BWF showed a highly potential advantage to identify DNA alterations, which suggested that genomic analysis of BWF liquid biopsy may have clinical value as a supplement for tissue and blood detection. Through the restricted validation, it can be widely used in routine clinical practice.

Flexible bronchoscopy in a tertiary healthcare facility: a review of indications and outcomes

Objectives: Flexible Fibreoptic bronchoscopy (FFB) is a major diagnostic and therapeutic tool employed largely in respiratory medicine but its use in our country has been quite limited. We performed a retrospective review of the indications, overall diagnostic yield and safety of FFB at the Korle-Bu Teaching Hospital (KBTH).Study Design: Retrospective studyStudy Setting: Cardiothoracic Unit, Korle-Bu Teaching HospitalStudy Participants: All bronchoscopy records from January 2017 - December 2018Interventions: Eight-five bronchoscopy reports generated over a 2-year period were reviewed. Using a data extraction form, patient’s demographic details, indications for FFB, sedation given, specimen obtained and results of investigation, and complications encountered were recorded and entered into SPSS version 22. Descriptive analysiswas performed and presented as means and percentages.Results: Suspected lung cancer was the predominant indication for bronchoscopy requests (55.3%). Diagnostic yield of endobronchial biopsy was 86.7% increased to 93.3% when biopsy was combined with bronchial washing cytology. Bronchial washing geneXpert was positive in 20.8% of sputum negative cases, and 20.7% of patients with unresolved pneumonia and bronchiectasis had a positive microbial yield. Overall mild complications occurred in 5.9% of patients with no mortality.Conclusion: Flexible bronchoscopy has a significantly high diagnostic yield, particularly in evaluating lung cancers and undiagnosed lung infections with minimal associated complications, hence increasing its availability in the country and widening the diagnostic scope at the cardiothoracic unit of the Korle-Bu Teaching Hospital.

Bronchial Washing Fluid Versus Plasma and Bronchoscopy Biopsy Samples for Detecting Epidermal Growth Factor Receptor Mutation Status in Lung Cancer

BackgroundBronchial washing fluid (BWF) is a common specimen collected during bronchoscopy and has been suggested to contain both tumor cells and cell-free DNA. However, there is no consensus on the feasibility of BWF in epidermal growth factor receptor (EGFR) genetic analysis because of the limited sample size and varying results in previous studies. This study compared the feasibility, sensitivity, and specificity of detecting EGFR mutation using BWF, bronchoscopy biopsy, and plasma samples in patients with lung cancer (LC).Materials and MethodsA total of 144 patients (110 with LC and 34 without LC) were enrolled in the study. During diagnostic bronchoscopy for suspected LC lesions, bronchial washing with saline was performed directly or through a guide sheath. BWF was collected as well as paired bronchoscopy biopsy and plasma samples, and EGFR mutation testing was performed via highly sensitive blocker polymerase chain reaction. The EGFR mutation status of histologic samples was set as the standard reference.ResultsCompared with the histologic samples, the sensitivity, specificity, and concordance rate of EGFR mutation detected in BWF samples were 92.5%, 100%, and 97.9%, respectively. Moreover, BWF showed a higher sensitivity in EGFR mutation testing than both plasma (100% [8/8] vs. 62.5% [5/8], p = 0.095) and bronchoscopy biopsy samples (92.5% [37/40] vs. 77.5% [31/40], p = 0.012) and identified EGFR mutations in 6 cases whose biopsy failed to establish an LC diagnosis. The diameter of the target lesion and its contact degree with BWF were positive predictive factors for EGFR testing results.ConclusionsBWF yields a high sensitivity in EGFR mutation testing, having high concordance with histologic samples, and presenting the benefit of rapid EGFR mutation detection in LC patients.

The lung microbiota in Korean patients with non-tuberculous mycobacterial pulmonary disease

Background The microbiota of the lower respiratory tract in patients with non-tuberculous mycobacterial pulmonary disease (NTM-PD) has not been fully evaluated. We explored the role of the lung microbiota in NTM-PD by analyzing protected specimen brushing (PSB) and bronchial washing samples from patients with NTM-PD obtained using a flexible bronchoscope. Results Bronchial washing and PSB samples from the NTM-PD group tended to have fewer OTUs and lower Chao1 richness values compared with those from the control group. In both bronchial washing and PSB samples, beta diversity was significantly lower in the NTM-PD group than in the control group (P = 2.25E-6 and P = 4.13E-4, respectively). Principal component analysis showed that the PSBs and bronchial washings exhibited similar patterns within each group but differed between the two groups. The volcano plots indicated differences in several phyla and genera between the two groups. Conclusions The lower respiratory tract of patients with NTM-PD has a unique microbiota distribution that is low in richness/diversity.