key: cord-0877499-j4m7k4s1
authors: Baron, Audrey; Hachem, Mouna; Tran Van Nhieu, Jeanne; Botterel, Françoise; Fourati, Slim; Carteaux, Guillaume; De Prost, Nicolas; Maitre, Bernard; Mekontso-Dessap, Armand; Schlemmer, Frédéric
title: Bronchoalveolar Lavage in Patients with COVID-19 with Invasive Mechanical Ventilation for Acute Respiratory Distress Syndrome
date: 2021-04-03
journal: Ann Am Thorac Soc
DOI: 10.1513/annalsats.202007-868rl
sha: 976129d0e63263c063e564942d32607831de53aa
doc_id: 877499
cord_uid: j4m7k4s1

nan

To the Editor:

Bronchoalveolar lavage (BAL) is a routine bronchoscopic procedure that may provide significant information for the management of pneumonia. In critically ill patients, including those with severe acute respiratory distress syndrome (ARDS), bronchoscopy and BAL safety have been demonstrated (1, 2) . However, early after the coronavirus disease (COVID-19) pandemic spread, guidelines converged in recommending limiting the use of bronchoscopy and considered known or suspected COVID-19 to be a relative contraindication to bronchoscopy, as the risk of contamination to healthcare workers may be increased by this aerosol-generating procedure (3, 4) . During the first wave of the pandemic, we rapidly observed, as highlighted by others (5, 6) , an increased need for bronchoscopy in patients with COVID-19-associated ARDS requiring mechanical ventilation, mainly for bronchoaspiration but also, in some cases, to perform BAL for microbiological sampling. The ability of BAL to confirm COVID-19 was also demonstrated, in case of previous negative nasopharyngeal swab(s) in patients, intubated or not, with clinical concern for this diagnosis (6) (7) (8) . Nevertheless, the value of BAL has not been evaluated so far for further microbiological workup after noninvasive diagnostic tests were exhausted.

For this purpose, and because data on BAL performed on patients with COVID-19-associated ARDS remain scarce, we herein describe our single-center experience at the Henri Mondor University Hospital on 28 consecutive BALs performed between March 31 and June 3, 2020, on 24 patients with COVID-19 (4 patients had two BALs) treated with invasive mechanical ventilation for moderate to severe ARDS. The median time from intubation to BAL was 16 (interquartile range [IQR], 10-21) days, and the median ratio of arterial oxygen pressure to fraction of inspired oxygen (Pa O 2 /FI O 2 ), FI O 2 , and positive end-expiratory pressure (H 2 O cm) before BAL were, respectively, 122 (IQR, 74-148), 0.8 (IQR, 0.4-1), and 8 (IQR, 5-10).

BALs were performed for a microbiological purpose in all cases: to confirm severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (n = 2; 7%), after one and three negative reverse transcriptase-polymerase chain reactions on nasopharyngeal swab, for a suspicion of ventilator-associated pneumonia (n = 11; 39%) or a suspicion of invasive aspergillosis (n = 4, 14%) and/or to rule out a superinfection before starting a corticosteroid course (n = 12; 43%). Results of routine noninvasive microbiological tests (blood cultures, protected distal aspiration for bacterial culture, tracheal aspiration for fungal culture and Aspergillus and Pneumocystis polymerase chain reaction (PCR), serum galactomannan and b-D-glucan detection, and nasopharyngeal swab for SARS-CoV-2 genome detection) were always considered before deciding whether to perform BAL.

Cytological analysis was available in most of the cases (n = 26, 93%). BAL fluid was frequently rich in mucus (n = 23, 82%), with a mean (range) BAL cellularity of 702 cells/ml (30-4,554), higher than what we usually observe in patients with ARDS without COVID-19 (personal data). Subcellular differential count is presented in Table 1 . As usually observed in patients with ARDS without COVID-19 (9), BAL fluid was predominantly neutrophilic in 24 cases (92%). BAL lymphocytosis exceeded 10% in eight cases (31%), and exceeded 20% in four of these cases (15%), all respectively performed at ,14 days and <10 days after intubation. Activated lymphocytes (AL) of various types, often with atypical pattern, were frequently observed (n = 14; 54%), especially if BAL was performed <10 days after intubation (Table 1 ). AL were scored either "rare-to-occasional" (n = 6) or "frequent-to-prominent" (n = 8) based on whether the lymphocyte proportion exceeded a threshold of 25%. When AL score was "frequent-to-prominent," SARS-CoV-2 reverse transcriptase-polymerase chain reaction was positive, either on BAL (n = 7) or on the last nasopharyngeal swab 48 hours before BAL in the case it was not performed on BAL. According to SARS-CoV-2 genome detection on BAL, AL were found in 9/11 positive cases (82%), versus 4/11 (36%) in negatives (P = 0.08).

BAL microbiological analysis revealed at least one pathogen in 24 cases (86%) ( Table 1) . When considering the results of previous less invasive microbiological tests, BAL revealed at least one previously undetected pathogen in 13 cases (46%) in culture and/or by PCR: nine bacteria, eight viruses (one cytomegalovirus, four herpes simplex virus-1, one rhinovirus, two SARS-CoV-2), and three Aspergillus. Results and final interpretation of mycological tests (9) (10) (11) (12) , including those obtained before BAL, are shown in Table 2 .

Overall, BAL had an impact on medical decision-making in 20 cases (71%), with introduction (n = 6), continuation (n = 3), switch (n = 2), or withdrawal (n = 4) of antimicrobial therapy in 14 cases (50%) and/or decision to start (n = 6; 21%), or not (n = 6, 21%), corticosteroids therapy.

No immediate complication of BAL procedures occurred, but one patient experienced a significant deterioration of his condition 24 hours after BAL, requiring venovenous extracorporeal membrane oxygenation. The day after BAL, the median ratio of arterial oxygen tension/pressure to FI O 2 was 150 (IQR, 61 to 174), not significantly different from the baseline value (P = 0.15), with a median change of 122 (IQR, 254 to 133). Six patients (23%) died during follow-up, with a median time from intubation to BAL of 19 (IQR, 12 to 20) days and a median time from BAL to death of 4 x Introduction, switch, prolongation, or withdrawal of antibiotics; modifications of antibiotics due to last PDA results were excluded. k Introduction, continuation (only considered if diagnostic criteria of pulmonary aspergillosis were not obtained before BAL), or withdrawal of antifungal therapy (see Table 2 for details). (10) and revised by Schauwvlieghe and colleagues (11) .

x Diagnosis of probable Aspergillus tracheobronchitis was based on the presence of airway plaque and pseudomembrane associated with microbial criteria, as recently proposed for influenzaassociated pulmonary aspergillosis (12 Concerning safety issues for the staff in charge, all procedures were alternatively performed by two trained pulmonologists, assisted by one out of three dedicated nurses. All of them carefully followed current guidelines for bronchoscopy in patients with COVID-19 (3) and remained COVID-19-free as assessed by a recent serological anti-SARS-CoV-2 immunoglobulin G testing (Architect; Abbott).

In conclusion, cytological analysis of BAL performed in patients with moderate to severe COVID-19-related ARDS typically shows a high cellularity, with neutrophilic alveolitis that could be linked to bacterial or fungal superinfections often observed in our population and/or be a hallmark of moderate to severe SARS-CoV-2-related ARDS itself. It may also reveal lymphocytosis, with a marked proportion of activated lymphocytes, especially when patients still carry the virus, at the early stage of the disease. In our series, although BAL was performed after a systematic noninvasive microbiological workup, it had a nonnegligible diagnostic yield and impact on medical decisions. BAL may therefore be considered as a complementary tool to noninvasive microbiological tests in selected patients with COVID-19-associated ARDS.

Author disclosures are available with the text of this letter at www.atsjournals.org.

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