Cytopathological Findings in Bronchoalveolar Lavage from Patients with COVID-19.

Information on cellular analysis of bronchoalveolar lavage (BAL) in patients with COVID-19 is limited. Some studies have described an increase in lymphocyte percentage or exuberant plasmacytosis. Some reports addressed the importance of molecular testing on BAL samples to confirm COVID-19 pneumonia, in clinically highly suspected patients with consecutive negative nasopharyngeal swab results. In addition to atypical lymphocytes in the peripheral blood, morphologic findings of atypical lymphocytes in BAL were also reported in a few patients. The objective of this study was to describe the cytopathic characteristics identified, any data presented here are descriptives and intended to trigger further research. Three general aspects have been evaluated in each sample: reactive changes, virus-related pathological changes, and differential leukocyte count. Seventeen samples were collected. All samples were negative for malignancy, with an inflammatory background, predominantly lymphohistiocytic in 5 samples, histiocytic in 9, and 3 with predominantly neutrophilic. Hemosiderin-laden macrophages were observed in 12/17. Nonspecific reactive cell changes were identified in 4 samples, including bronchial, alveolar, and reserve cell hyperplasia. Virus-related pathological changes were observed in 14 samples, such as loss of nuclear chromatin pattern, lymphocytes with atypical nuclei, nuclear and cytoplasmic inclusions, multinucleations in bronchial cells and macrophages, or multinucleated giant cells. The identification of multinucleated giant cells could represent a cytopathic effect induced by the virus, at the same time the nuclear clearance of pneumocytes as a possible direct effect. BAL is a procedure aimed at obtaining cells from the respiratory tract that can provide valuable and rapid information. It is important to collect and describe as many cytopathological findings as possible, which can provide relevant information for future studies.

Acute Dyspnea and Hemoptysis in an 84-Year-Old Man With Multiple Comorbidities.

CASE PRESENTATION: An 84-year-old man with an active smoking habit presented to the ED with dyspnea, hemoptysis, and thick phlegm that was difficult to clear. He reported no weight loss, no fever, and no chest pain or dysphonia. He denied both international travel and previous contact with confirmed cases of TB or SARS-CoV-2. He had no known occupational exposures. The patient's personal history included a resolved complete atrioventricular block that required a permanent pacemaker, moderate-to-severe COPD, rheumatoid arthritis (treated with oral prednisone, 2.5 mg/d) and B-chronic lymphocytic leukemia (treated with methotrexate and prophylactic oral supplements of ferrous sulfate). Moreover, he was in medical follow up because of a peptic ulcer, atrophic gastritis, and colonic diverticulosis. The patient also had a history of thoracic surgery after an episode of acute mediastinitis from an odontogenic infection, which required ICU management and temporal tracheostomy.

Bronchoalveolar lavage in suspected COVID-19 cases with a negative nasopharyngeal swab: a retrospective cross-sectional study in a high-impact Northern Italy area.

COVID-19 diagnosis relies on molecular testing for SARS-CoV-2 via nasopharyngeal swab in the presence of suggestive clinical, radiological and laboratory findings. Since bronchoalveolar lavage liquid (BAL) collected during fibrobronchoscopy may increase test sensitivity compared to nasopharyngeal swabs, it was performed during the 2020 pandemic in clinically or radiologically suspected cases. Our aim was to determine whether clinical features, chest computed tomography (CT) findings or laboratory tests may predict patients testing positive for SARS-CoV-2 at BAL after a negative nasopharyngeal swab. We performed a retrospective cross-sectional study with multivariable analysis of suspected patients who were tested for SARS-CoV-2 at BAL after at least one negative nasopharyngeal swab. Univariable logistic regression for odds ratio and multivariate models was calculated to determine clinical, radiological and laboratory predictors. 32/198 (16%) patients had BAL positive for SARS-CoV-2, while 65/198 tested positive for other pathogens at BAL. Of the 32 patients positive for COVID, 4 had a coinfection at BAL, being thus positive both for COVID as well as for another pathogen while the remaining 105 patients were negative for COVID and other pathogens at BAL. COVID-19 patients had more often highly suggestive CT findings, higher number of involved lobes, more often ground glass opacity of more than 50% of lung parenchyma, and less frequently other radiologically suspected infections. At multivariate model, temperature also predicted BAL positivity. The procedure was well tolerated-with only one desaturation episode-while no healthcare worker was infected. In conclusion, when nasopharyngeal swabs are negative but there is clinical or imaging suspicion of COVID-19, BAL represents a complementary diagnostic tool, particularly in conjunction with suggestive/more extensive lung involvement at CT scan. The procedure did not carry increased risks for patients nor for operators, while allowing to free hospital resources, avoiding unnecessary isolations.

Alveolar compartmentalization of inflammatory and immune cell biomarkers in pneumonia-related ARDS.

BACKGROUND: Biomarkers of disease severity might help individualizing the management of patients with the acute respiratory distress syndrome (ARDS). Whether the alveolar compartmentalization of biomarkers has a clinical significance in patients with pneumonia-related ARDS is unknown. This study aimed at assessing the interrelation of ARDS/sepsis biomarkers in the alveolar and blood compartments and explored their association with clinical outcomes. METHODS: Immunocompetent patients with pneumonia-related ARDS admitted between 2014 and 2018 were included in a prospective monocentric study. Bronchoalveolar lavage (BAL) fluid and blood samples were obtained within 48 h of admission. Twenty-two biomarkers were quantified in BAL fluid and serum. HLA-DR+ monocytes and CD8+ PD-1+ lymphocytes were quantified using flow cytometry. The primary clinical endpoint of the study was hospital mortality. Patients undergoing a bronchoscopy as part of routine care were included as controls. RESULTS: Seventy ARDS patients were included. Hospital mortality was 21.4%. The BAL fluid-to-serum ratio of IL-8 was 20 times higher in ARDS patients than in controls (p < 0.0001). ARDS patients with shock had lower BAL fluid-to-serum ratio of IL-1Ra (p = 0.026), IL-6 (p = 0.002), IP-10/CXCL10 (p = 0.024) and IL-10 (p = 0.023) than others. The BAL fluid-to-serum ratio of IL-1Ra was more elevated in hospital survivors than decedents (p = 0.006), even after adjusting for SOFA and driving pressure (p = 0.036). There was no significant association between alveolar or alveolar/blood monocytic HLA-DR or CD8+ lymphocytes PD-1 expression and hospital mortality. CONCLUSIONS: IL-8 was the most compartmentalized cytokine and lower BAL fluid-to-serum concentration ratios of IL-1Ra were associated with hospital mortality in patients with pneumonia-associated ARDS.

Safe and Efficient Practice of Bronchoscopic Sampling from Mechanically Ventilated Patients: A Structured Evaluation of the Ambu Bronchosampler-Ascope 4 Integrated System.

BACKGROUND: Bronchoscopic sampling of bronchoalveolar fluid (BAL) should be safe and effective. Current sampling practice risks loss of sample to the attached negative flow, aerosolisation, or spillage, due to repeated circuit breaks, when replacing sample containers. Such concerns were highlighted during the recent coronavirus pandemic. OBJECTIVES: Evaluation of an alternative integrated sampling solution, with the Ambu Bronchosampler with aScope 4, by an experienced bronchoscopist in ICU. METHODS: An observational study of 20 sequential bronchoscopic diagnostic sampling procedures was performed on mechanically ventilated patients with suspected ventilator-associated pneumonia. Mixed methods assessment was done. The predefined outcome measures were (1) ease of set up, (2) ease of specimen collection, (3) ease of protecting specimen from loss or spillage, and (4) overall workflow. The duration of the procedure and the % volume of sample retrieved were recorded. RESULTS: The mean (±standard deviation [SD]) time for collecting 1 sample was 2.5 ± 0.8 min. The mean (±SD) specimen yield for instilled miniBAL was 54.2 ± 17.9%. Compared with standard sampling, the set-up was much easier in 18 (90%), or easier in 2 (10%) of procedures, reducing the connection steps. It was much more intuitive to use in 14 (70%), more intuitive in 4 (20%), and no more intuitive to use in 2 (10%). The overall set-up and workflow was much easier in 69% of the 13 intraprocedural connections and easier or as easy in the remaining 31% procedures. All procedures where pre connection was established were much easier (7, 100%). The Ambu Bronchosampler remained upright in all procedures with no loss or spillage of sample. Obtaining a sample was much easier in 60%, easier in 10%, no different in 20%, and worse in 10%. The ability to protect a sample from start to finish compared to standard procedures was much easier in 80%, easier in 15%, and no different in 5% of procedures. Overall workflow was much easier in 14 (70%), easier in 4 (20%), and no different in 2 (10%) of procedures. CONCLUSIONS: The Ambu Bronchosampler unit was a reliable, effective, and possibly safer technique for diagnostic sampling in ICU. It may improve safety standards during the coronavirus pandemic. A randomized control trial against the standard sampling technique is warranted.

Clinical performance of the GenMark Dx ePlex respiratory pathogen panels for upper and lower respiratory tract infections.

The GenMark Dx ePlex Respiratory Pathogen Panel (RP) is a multiplexed nucleic acid test for the qualitative detection of common viral and a few bacterial causes of respiratory tract infections. The ePlex RP has received FDA clearance for nasopharyngeal swab (NPS) specimens collected in viral transport media. In this study, we evaluated the performance of the ePlex RP panel in comparison to the NxTAG Respiratory Pathogen Panel (NxTAG-RPP) from Luminex in use in our laboratory, not only for NPS but also for bronchoalveolar lavage specimens (BAL). We also evaluated the impact of implementing the ePlex RP on the test turn-around time (TAT). The newest panel from GenMark Dx, the ePlex Respiratory Pathogen Panel 2 (RP2), which added the SARS-CoV-2 target to the RP was also evaluated for NPS. Verification of the performance of the ePlex RP for both NPS and BAL showed 93.3 % and 84.9 % total agreement with the NxTAG-RPP respectively. An overall comparison of the TAT after implementing the ePlex RP as compared to the NxTAG-RPP assay showed an average decrease of almost seven-fold.

COVID-19 Diagnosis in Case of Two Negative Nasopharyngeal Swabs: Association between Chest CT and Bronchoalveolar Lavage Results.

See also the editorial by Little in this issue.

Experience of N-acetylcysteine airway management in the successful treatment of one case of critical condition with COVID-19: A case report.

RATIONALE: The new coronavirus pneumonia Corona Virus Disease 2019 (COVID-19) has become a global pandemic. Patients with critically COVID-19 usually require invasive respiratory support, and the airway management is particularly important and the prognosis is poor. PATIENT CONCERNS: A 64-year-old man with an anastomotic fistula after radical treatment of esophageal cancer and right-side encapsulated pyopneumothorax was admitted with cough and dyspnea. DIAGNOSIS: The patient was diagnosed with novel coronavirus pneumonia and right-side encapsulated pyopneumothorax by pharyngeal swab nucleic acid test in combination with chest computed tomography (CT). INTERVENTIONS: The patient was treated with antibiotics, antiviral and antibacterial medications, respiratory support, expectorant nebulization, and nutritional support. But he expressed progressive deterioration. Endotracheal intubation and mechanical ventilation were performed since the onset of the type - respiratory failure on the 13th day of admission. The patient had persistent refractory hypercapnia after mechanical ventilation. Based on the treatment mentioned above, combined with repeated bronchoalveolar lavage by using N-acetylcysteine (NAC) inhalation solution, the patients refractory hypercapnia was gradually improved. OUTCOMES: The patient was cured and discharged after being given the mechanical ventilation for 26 days as well as 46 days of hospitalization, currently is surviving well. LESSONS: Patients with severe conditions of novel coronavirus pneumonia often encounter bacterial infection in their later illness-stages. They may suffer respiratory failure and refractory hypercapnia that is difficult to improve due to excessive mucus secretion leading to small airway obstruction. This study provided a new insight on the proper treatment severe COVID-19 patients. The use of reasonable antibiotics and symptomatic respiratory support and other treatment, timely artificial airway and repeated bronchoalveolar NAC inhalation solution lavage, expectorant and other airway management are essential for such patients.

Bronchoalveolar lavage-based COVID-19 testing in patients with cancer.

OBJECTIVE/BACKGROUND: A few case reports in the setting of coronavirus disease 2019 (COVID-19) and multiplex polymerase chain reaction (PCR)-based assays for common respiratory pathogens have shown a higher yield of bronchoalveolar lavage (BAL) samples than upper airway specimens in immunocompromised patients. METHODS: A retrospective study was conducted reviewing patients diagnosed with COVID-19 at the Medical College of Wisconsin (Milwaukee, WI, USA) between March 13, 2020 and June 11, 2020. All patients tested positive for SARS-CoV-2 via real-time reverse transcriptase PCR (RT-PCR), through a nasopharyngeal or a bronchoscopy specimen. RESULTS: During the study period, 53 bronchoscopy procedures were performed at the institution, of which five patients tested positive for COVID-19. Of the five patients, three underwent BAL testing based on high clinical suspicion for COVID-19 after the nasopharyngeal (NP) swab(s) was negative. All three patients had underlying cancers and had lymphopenia for a considerable duration prior to being diagnosed with COVID-19. Two patients had better outcomes that could be attributed to earlier BAL specimen testing resulting in timely medical intervention. CONCLUSION: This study underscores the need for early lower respiratory tract sampling, whenever possible, in patients with cancer and prolonged lymphopenia. High clinical suspicion ought to supersede false-negative NP reverse transcriptase-PCR as early bronchoscopic evaluation in cancer patients, who are either receiving active treatment or are immunosuppressed, can allow timely institution of efficacious treatment, enrollment into clinical trials, as well as effective infection control. In the apt clinical setting in patients with cancer, presumptive treatment may also be considered to minimize exposure to healthcare providers and proceduralists.

The value of flexible bronchoscopy in pulmonary infections of immunosuppressed children.

OBJECTIVES: To demonstrate the value of flexible bronchoscopy (FB) and bronchoalveolar lavage (BAL) when determining causes of lung infection in immunocompromised children; to investigate differences in causes and radiological features of lung infections following bone marrow transplantation (BMT) compared to other immunosuppressive conditions; to evaluate the reliability of radiological findings when predicting the pathogen. METHODS: We retrospectively evaluated 132 immunosuppressed children who underwent FB and BAL because pulmonary complications between January 1999 and May 2014 at the Hacettepe University Hospital Pediatric Pulmonology Unit. Two groups, Group I (n = 106) and Group II (n = 26), consisted of patients who had primary or secondary immunodeficiency and those who were immunosuppressed because BMT, respectively. Radiological findings before FB and macroscopic and microscopic findings of the procedure were evaluated. RESULTS: FB and BAL were diagnostic in 86/132 patients (65.1%) and the antimicrobial treatment changed for 75/132 patients (56.8%). The most common pathogen was bacteria (Streptococcus pneumoniae was the leading one). Bacteria were more frequent in Group I than Group II (P = .008). No significant difference in radiological findings between Groups I and II was found. Considering all patients, a significant association was detected between viral pathogens and radiologically interstitial infiltration and a ground-glass appearance (P = .003). However, no significant association was detected between bacterial and fungal pathogens and the radiological findings. CONCLUSION: In immunosuppressed patients, FB and BAL should be evaluated early for clarifying the causative agents. Then, appropriate treatments can be utilised and the side effects and high cost of unnecessary treatment may be mitigated.

Common respiratory viral infections: Bilateral versus unilateral bronchoalveolar lavage versus endotracheal aspiration.

Data about the diagnostic efficiency of bilateral bronchoalveolar lavage (BAL) samples and endotracheal aspirates (EA) testing for common viral respiratory infections are scarce. We analyzed data from 167 cases, where bilateral BAL samples were tested, and from 101 cases, where BAL samples and EA were tested. Multiplex polymerase chain reaction (PCR) was performed with the fast track diagnostics viral respiratory panel, producing data on the adenovirus, coronavirus, enterovirus, human metapneumovirus, bocavirus, influenza virus, parainfluenza virus, rhinovirus, and respiratory syncytial virus status of patients with respiratory disease symptoms. In the bilateral BAL cohort, 46 (27.5%) cases were positive for at least one of the viruses mentioned above in both samples. Discrepant results (virus not detected on one side) were seen in six (3.6%) cases. In the BAL versus EA cohort, 12 (11.9%) cases were positive in both materials, discrepant results (only one material being positive) were observed in 11 (10.9%) cases, with seven (63.6%) BAL samples, and four (36.4%) EA being positive. Bilateral sampling does not significantly improve the diagnostic efficiency of BAL for the detection of common respiratory viral pathogens via PCR. The diagnostic quality of EA and BAL samples for the detection of common viral respiratory pathogens is comparable.

Monitoring bronchoalveolar lavage with electrical impedance tomography: first experience in a patient with COVID-19.

OBJECTIVE: Patients with the novel coronavirus disease (COVID-19) often have airway secretions that severely compromise ventilation. This study investigates electrical impedance tomography (EIT) monitoring of a therapeutic bronchoalveolar lavage (BAL) in a patient with COVID-19. APPROACH: A patient with COVID-19 developed acute respiratory distress syndrome requiring mechanical ventilation. He received regional BAL to remove mucus in the small airways (20 ml × 5). Regional ventilation changes before BAL, 30 min after and in the following days, were monitored with EIT. MAIN RESULTS: Regional ventilation worsened shortly after BAL and improved in the following days. The improvement of the oxygenation did not exactly match the ventilation improvement, which indicated a possible ventilation/perfusion mismatch. SIGNIFICANCE: Therapeutic BAL might improve regional ventilation for COVID-19 and EIT could be a useful tool at the bedside to monitor the ventilation treatment of COVID-19.