Reduction of post-bronchoscopy pneumonia by working channel irrigation with sterile saline before diagnostic procedures

Reduction of post-bronchoscopy pneumonia by working channel irrigation with sterile saline before diagnostic procedures | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Reduction of post-bronchoscopy pneumonia by working channel irrigation with sterile saline before diagnostic procedures Satoshi Nagaoka, Masaki Yamamoto, Sachi Takakura, Shunsuke Okazaki, and 12 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6100467/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 20 May, 2025 Read the published version in BMC Pulmonary Medicine → Version 1 posted 4 You are reading this latest preprint version Abstract Background/Question After transbronchial biopsy with flexible bronchoscopy, pneumonia sometimes occurs as a complication. The goal of our study was to determine whether irrigation of the working channel before diagnostic procedures can reduce the frequency of post-bronchoscopy pneumonia. Methods Initially, we examined the effect of working channel irrigation with 100 mL of sterile saline to reduce the number of bacteria attached to the working channel. Subsequently, we compared the frequency of post-bronchoscopy pneumonia in patients who underwent or did not undergo working channel irrigation before bronchoscopic biopsy or lavage fluid collection. Results A significant reduction in bacterial colonies was observed in the irrigated channel-flush samples. Of the 242 enrolled participants, 109 were in the exploratory group, whereas 133 were in the control group. The frequency of post-bronchoscopy pneumonia was 2.8% (n = 3) and 3.8% (n = 5) in the exploratory and control groups, respectively. Conclusions/Answer to the question Irrigation by suctioning 100 mL of sterile saline significantly reduced the number of bacteria in the flexible bronchoscopy working channel. To confirm the practical significance of irrigation in reducing post-bronchoscopy pneumonia and post-bronchoscopy fever, further evaluation with additional cases from other institutions is required. Flexible bronchoscopy post-bronchoscopy pneumonia Figures Figure 1 Figure 2 Figure 3 Key messages After transbronchial biopsy with flexible bronchoscopy, pneumonia sometimes occurs as a complication. Although prophylactic antimicrobials may prevent post-bronchoscopy pneumonia in patients with tracheobronchial stenosis, the effect of irrigation of the working channel before diagnostic procedures was unknown. This study added that irrigation by suctioning 100 mL of sterile saline significantly reduced the number of bacteria in the flexible bronchoscopy working channel. This study might decrease the rates of post-bronchoscopy pneumonia. Introduction Backgrounds Flexible bronchoscopy (FB) is the standard diagnostic procedure used to obtain specimens from the lower respiratory tract for various respiratory diseases, especially malignant conditions [ 1 ]. Among complications that can occur after transbronchial biopsy with FB [ 2 – 4 ], post-bronchoscopy pneumonia (PBP) [ 5 – 11 ] sometimes leads to abscess formation [ 12 ] within a tumor. Since long-term antimicrobial therapy is required for abscesses, evaluation and treatment of the malignant disease must be postponed, which may lead to disease progression or missed opportunities for definitive treatment. Therefore, prophylactic antibacterial administration has been examined but has generally failed to show effectiveness in the general population [ 13 ]. Risk factors have been investigated [ 14 ], and a retrospective, single-center, age- and sex-matched case-control study from Japan reported that tracheobronchial stenosis was an independent risk factor for PBP, according to multivariate analysis [ 15 ]. Although prophylactic antimicrobials may prevent PBP in patients with tracheobronchial stenosis, no prospective study has yet demonstrated efficacy in these patients [ 8 , 16 – 18 ]. Most importantly, prophylactic methods that do not involve antimicrobials are ideal, adhering to general principles of antimicrobial stewardship. The development of an infectious disease depends on both the virulence and the quantity of pathogens, as well as the host's immunological status. In some patients with chronic respiratory diseases, gram-negative organisms may be present as colonizers. However, in most cases of PBP, no particularly virulent bacteria are identified. Instead, bacteria from the oropharyngeal flora are typically found in lower respiratory tract samples collected during the procedure, which contribute to the development of PBP. Therefore, bacterial load, rather than virulence, is an essential factor in PBP development. Upper respiratory tract secretions can adhere to the FB working channel, leading to contamination of the lower respiratory tract. When biopsy forceps pass through the contaminated working channel and inoculate bacteria into the lesion, PBPs can develop. The increasing amount of tumor tissues required for genetic mutation testing and other purposes has led to a rise in the number of biopsy procedures, which may also be related. Objectives Accordingly, we hypothesized that irrigating the working channel before diagnostic procedures could reduce the frequency of PBP. First, we examined the efficacy of working channel irrigation with 100 mL of sterile saline suctioning and observed a significant reduction in bacterial colonies in channel-flush samples after irrigation. Subsequently, we compared the frequency of PBP after FB examinations with and without irrigation in clinical practice. Patients and methods Setting Patients who underwent bronchoscopic examination at Yokohama City University Medical Center between June 2023 and March 2024 as participants in the exploratory group and between June 2022 and March 2023 as participants in the control group were enrolled. We utilized FB made in Olympus, product number BF-1TH1200, BF-1T260, BF-P290, BF-P260F and BF-F260. Bronchoscopes and radial EBUS probes (Olympus UM-S20-17S and UM-S20-20R-3) were reprocessed with an automated endoscope reprocessor (Olympus OER-2) and orthophthalaldehyde (DISOPA™ Solution 0.55%) according to the instruction manuals. To obtain specimens, disposable covered sheath, biopsy forceps and cytology brushes were used. There was no change in the reprocessing and disinfection methods during study periods. Participants Patients were usually admitted to the hospital on the day of the bronchoscopic examination and discharged the next day if they had no complications. The procedures were conducted at an endoscopy unit. Patients were sedated with propofol and dexmedetomidine. They were intubated and breathed spontaneously with oxygen supplementation. Patients prescribed antibiotics during a bronchoscopic examination or received a bronchoscopic examination for the diagnosis of infectious diseases were excluded. Patients who underwent EBUS-TBNA were also excluded because the FBs were replaced from a standard FB to an FB for EBUS-TBNA after intubation and observation in our facility. The following items were collected from medical records: age, sex, ECOG (Eastern Cooperative Oncology Group) performance status, smoking history, inhaled medication, past medical history, diagnosis before and after FB, types of bronchoscopic examination, and use of prophylactic antibiotics after FB. The use of antibiotics after FB examinations was allowed and left to the discretion of the attending physicians. Microbiological evaluation To evaluate the efficacy of the working channel irrigation, working channel flushing samples were obtained at four points during FB examinations: 1) Before FB examinations; 2) After bronchoscopy-guided intubation, when the tip of the bronchoscope passes through the upper airway tract and reaches the lower respiratory tract, and before irrigation; 3) After working channel irrigation and before endotracheal observation; and 4) After endotracheal observation and before the intended procedure (observation with radial endobronchial ultrasound, bronchial brushing, forceps biopsy, or saline injection for BAL) to obtain specimens for clinical evaluation. Between points two and three, the working channel was irrigated with 100 mL of sterile saline via antegrade suction. Saline and air (5 mL) were flushed into the working channel and collected from the FB at each of the four steps. The sediments of collected samples were separated with a centrifuge at 420×g for 5 min and resuspended in 50 µL of sterile saline. Ten microliters of the resuspended sediment were inoculated onto chocolate agar and blood agar plates. The number of colonies on each plate was counted after 48 h of incubation. Evaluation of PBP In this study, PBP was defined as an increase in white blood cells and/or C-reactive protein with newly appearing opacities on chest radiography or computed tomography within 14 d of the FB examination. We monitored the frequency of PBP after FB examination in the exploratory group (with irrigation). This was retrospectively evaluated in the control group (without irrigation). Statistical methods Groups of categorical data were compared using Fisher’s exact test, and average values were compared using the Wilcoxon rank-sum test. Statistical analyses were performed using JMP Pro 17.2.0 (JMP Statistical Discovery LLC, CA, USA). Statistical significance was set at p < 0.05. Results Participants A total of 267 patients underwent FB examinations (excluding EBUS-TBNA) between June 2022 and March 2023 and between June 2023 and March 2024 (Fig. 1 ). Fourteen patients were excluded because of antibiotic administration after the examinations (seven in the exploratory group and seven in the control group). Ten patients were excluded because they were diagnosed with infectious disease after FB from exploratory group. One patient from the exploratory group withdrew consent. Thus, a total of 242 participants were enrolled in this study. Of these, 109 and 133 were included in the exploratory and control groups, respectively. Baseline clinical characteristics of the study population are shown in Table 1 . There were no statistically significant differences between the groups, except for the presence of malignant tumors other than lung cancer (p = 0.0228). Table 1 Baseline clinical characteristics of the study population Variable Irrigation group (n = 109) Control (N = 133) p value Age: median (range) 75 (44–89) 74 (21–89) 0.973 Men/Women (%) 63/46 (57.8/42.2) 76/57 (57.1/42.9) 1.000 PS 0 or 1 (%) 100 (91.7) 119 (89.5) 0.661 Past smoking history (%) 82 (75.2) 96 (72.2) 0.661 Pack-year: median (range) 33.5 (0–122) 32.1 (0–200) 0.594 inhaled medication (%) 18 (16.5) 17 (12.8) 0.465 EBUS-GS (%) 92 (84.4) 108 (81.2) 0.610 Diagnosed with LK before FB (%) 94 (86.2) 114 (85.7) 1.000 Diagnosed with LK by FB (%) 82 (75.2) 98 (73.7) 0.883 Past medical history COPD (%) 22 (20.2) 24 (18.0) 0.743 Bronchial asthma (%) 9 (8.3) 9 (6.8) 0.806 Interstitial pneumonia (%) 9 (8.2) 5 (3.8) 0.170 Malignant tumor complications other than lung cancer (%) 34 (31.2) 24 (18.0) 0.0228 Cerebrovascular disease (%) 9 (8.3) 16 (12.0) 0.399 Cardiovascular disease (%) 20 (18.3) 36 (27.1) 0.127 Diabetes mellitus (%) 24 (22.0) 30 (22.6) 1.000 Clinical background information. The exploratory group is compared with the control group. Past medical history includes COPD, bronchial asthma (BA), institutional pneumonia (IP), malignant tumor complications other than lung cancer, cerebrovascular disease, cardiovascular disease, and diabetes mellitus. FB, flexible bronchoscopy; PS, performance status. Reduction of bacterial colony formation To identify the efficacy of the irrigation procedure for the working channel, flushing samples were obtained at Points 1–4 during FB examinations from the first 14 patients in the exploratory group. The colony numbers of samples obtained at Point 3 (immediately after the irrigation procedure) were lower than those at Points 2 (after intubation and before irrigation) and 4 (after irrigation and endobronchial observation). The number of colonies obtained at Point 4 was significantly higher than that at Point 3 because of the suctioning of lower respiratory tract secretions, which contained considerable amounts of bacteria during FB-guided intubation (Figs. 2 and 3 ). Based on these results, the irrigation procedure was performed immediately prior to the intended procedures in the remaining patients in the exploratory group. Reduction of PBP with irrigation PBP developed in 3.8% (5/133) and 2.8% (3/109) of patients in the control and exploratory groups, respectively (p = 0.733). This result remains unchanged by using the definition of pneumonia in [ 11 ]. Forceps biopsy was undergone 92/109 in the irrigation group and 108/133 in the control group. Other examination includes BAL and bronchial brushing. Patients who were not diagnosed with lung cancer include chronic eosinophil pneumonia, cryptogenic organizing pneumonia. The frequency of PBP in the exploratory group was 26% lower than that in the control group, albeit statistically insignificant. No specific bacterial pathogens, other than components of the upper respiratory tract flora, were detected in the lower respiratory tract specimens obtained during FB examinations. While post-bronchoscopic fever (PBF) is also a common adverse event [ 19 , 20 ], patients who presented with fever (37.5°C or higher) within a day after FB were significantly fewer in the exploratory group than in the control group, 5.5% (6/109) vs. 14.3% (19/133), respectively (p = 0.0328) (Table 2 ). Interestingly, the number of prophylactic antibiotic prescriptions after FB examinations was lower in the exploratory group than in the control group (8.3% [9/109] vs. 17.3% [23/133]; p = 0.0553). Attending physician prescribed antibiotics when patients had symptoms or high risk of infection including PBF. Table 2 The frequency of PBP and PBF Variable Exploratory group (n = 109) Control group (N = 133) P value PBP (%) 3 (2.8) 5 (3.8) 0.733 Prescription of antibiotics after FB (%) 9 (8.3) 23 (17.3) 0.0553 PBF within a day after FB >=37.5°C (%) 6 (5.5) 19 (14.3) 0.0328 The frequency of post-bronchoscopy pneumonia (PBP) and post-bronchoscopy fever (PBF) after flexible bronchoscopy (FB). The exploratory group is compared with the control group. PBP was defined as the increase in white blood cells and/or C-reactive protein with newly appearing opacities on chest radiography or computed tomography within 14 d of the FB examination. The median time (range) to PBP is 7 d (4–12 d) in the exploratory group and 7 d (1–13 d) in the control group. The prescription of antibiotics after FB and the frequency of fever above 37.5℃ within 1 d after FB are also shown. FB, flexible bronchoscopy; PBP, post-bronchoscopy pneumonia; PBF, post-bronchoscopic fever. Discussion Key results In our study, we hypothesized that irrigation of the working channel before diagnostic procedures could reduce the frequency of PBP. We demonstrated that working channel irrigation with 100 mL of sterile saline significantly decreased the number of bacteria in the working channels. The number of PBP cases was three (2.8%) in the exploratory group and five (3.8%) in the control group. In these populations, irrigation contributed to a 26% reduction in PBP (p = 0.733). Since PBP occurs at a very low rate, typically under 5%, a large number of cases are needed to identify a significant difference. Even if the irrigation procedure reduces the frequency of PBP by 50%, a sample size approximately eight to ten times larger than that used in this study would be needed to show a statistically significant difference. Although the exact factors causing PBF are unclear, the inoculation of bacteria attached to instruments passing through the working channel may contribute to PBF. Our results show a reduction in the number of bacteria in the working channel after irrigation. Therefore, a significant reduction in PBF with irrigation was expected. Interestingly, the decrease in PBP and PBF in this study was achieved alongside a statistically significant reduction in antibiotic prescriptions compared with that in the control group, whereas prophylactic antibiotics for PBP generally lack efficacy. It is reasonable to ask whether we did not select a randomized design for this study. First of all, it is difficult to blind the irrigation. Since we started this study after confirming a reduction in the number of bacteria in the working channel after irrigation, randomization of patients might affect the prescription frequency of antibiotics, which can affect the frequency of PBP. As mentioned earlier, considering the number of cases required to achieve statistical significance, it was determined that conducting a randomized trial in a single center with a limited duration would be difficult. Regarding patient background, the proportion of patients with malignant diseases other than lung cancer was significantly higher in the exploratory group. Patients with malignant diseases have a higher risk of infectious complications owing to immunosuppression. This may explain why the suppressive effect of irrigation was not significant. Specimens obtained by FB have often been used to evaluate the pathogens of lower respiratory tract infections or the microbiome of the lower respiratory tract. Considering our results, conclusions must be carefully interpreted when obtaining specimens. It is necessary to confirm the procedures used to reduce contamination by microorganisms originating from the upper respiratory tract attached to the FB working channel. Without efforts to reduce the influence of upper respiratory tract microorganisms, these can be overestimated, especially in microbiome analyses using next-generation sequencing. In this situation, irrigation alone may be inadequate to reduce contamination. Irrigation prior to the diagnostic procedures evaluated in this study was simple. Suctioning 100 mL of sterile saline is an effortless and safe procedure, with minimal additional time and cost. The disadvantage of irrigation was that the maneuver required intubation or other procedures in which the FB was moved back and forth to the lower respiratory tract. Overall, the results of this study may be beneficial for reducing PBP, but the reduction was not statistically significant. A large number of cases must be accumulated to demonstrate its effectiveness in reducing the frequency of complications. Conclusions Irrigation by suctioning 100 mL of sterile saline significantly reduced the number of bacteria in the FB working channel. With irrigation before diagnostic procedures, the rates of major complications after FB, including PBP and PBF, also decreased. To confirm the practical significance of irrigation, further evaluation using additional cases from other institutions is required. Abbreviations FB, flexible bronchoscopy; PBF, post-bronchoscopic fever; PBP, post-bronchoscopy pneumonia. Declarations Other information Acknowledgements We are grateful to the microbiological laboratory of Yokohama City University Medical Center, Yokohama, Japan, especially to S. Okamatsu, Y. Ohnishi, A. Okawara, and Y. Takanami. Funding This study did not receive any specific grants from funding agencies in the public, commercial, or non-profit sectors. Author contributions MY was responsible for the organization and coordination of the trial and was the chief investigator. MY and SN were responsible for the data analysis. All authors contributed to the writing of the final manuscript. All members of the study team contributed to the management or administration of the trial. Conflict of interest The authors have no conflicts of interest. IRB information and informed consent The study was approved by the Institutional Review Board of the Yokohama City University School of Medicine under approved the study protocol (F230500045) and all participants gave written informed consent. Ethics approval and consent to participate Ethics, Consent to Participate, and Consent to Publish declarations: not applicable. Relevant meeting The 64th Annual Meeeting of the Japanese Respiratory Society (2024), April 6, 2024,Yokohama, Japan References Du Rand IA, Blaikley J, Booton R, Chaudhuri N, Gupta V, Khalid S, et al. British Thoracic Society guideline for diagnostic flexible bronchoscopy in adults: accredited by NICE. Thorax. 2013;68:i1-i44. Facciolongo N, Patelli M, Gasparini S, Lazzari Agli L, Salio M, Simonassi C, et al. Incidence of complications in bronchoscopy. 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Kobe J Med Sci. 2012;58:E110-E18. Takagi H, Nagaoka T, Ando K, Tsutsumi T, Ichikawa M, Koyama R, et al. Efficacy of antibiotic prophylaxis after endobronchial ultrasound-guided transbronchial needle aspiration: A preliminary prospective study. J Pulm Respir Med. 2017;07. Farrokhpour M, Kiani A, Mortaz E, Taghavi K, Farahbod AM, Fakharian A, et al. Procalcitonin and proinflammatory cytokines in early diagnosis of bacterial infections after bronchoscopy. Open Access Maced J Med Sci. 2019;7:913-19. Witte MC, Opal SM, Gilbert JG, Pluss JL, Thomas DA, Olsen JD, et al. Incidence of fever and bacteremia following transbronchial needle aspiration. Chest. 1986;89:85-87. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Published Journal Publication published 20 May, 2025 Read the published version in BMC Pulmonary Medicine → Version 1 posted Editorial decision: Revision requested 04 Mar, 2025 Editor assigned by journal 03 Mar, 2025 Submission checks completed at journal 03 Mar, 2025 First submitted to journal 24 Feb, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. 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Center","correspondingAuthor":false,"prefix":"","firstName":"Kenichi","middleName":"","lastName":"Seki","suffix":""},{"id":423818491,"identity":"28fb2f48-7d72-4b76-8176-e82662b61303","order_by":12,"name":"Shuhei Teranishi","email":"","orcid":"","institution":"Yokohama City University Medical Center","correspondingAuthor":false,"prefix":"","firstName":"Shuhei","middleName":"","lastName":"Teranishi","suffix":""},{"id":423818492,"identity":"e00acb10-6f14-469d-a276-dbd9be5ba082","order_by":13,"name":"Ken Tashiro","email":"","orcid":"","institution":"Yokohama City University Medical Center","correspondingAuthor":false,"prefix":"","firstName":"Ken","middleName":"","lastName":"Tashiro","suffix":""},{"id":423818493,"identity":"c6cece71-3a2f-4899-af6d-897369249e5d","order_by":14,"name":"Makoto Kudo","email":"","orcid":"","institution":"Yokohama City University Medical Center","correspondingAuthor":false,"prefix":"","firstName":"Makoto","middleName":"","lastName":"Kudo","suffix":""},{"id":423818494,"identity":"8ef26d56-32e6-47f4-88c5-d8124ff28460","order_by":15,"name":"Takeshi Kaneko","email":"","orcid":"","institution":"Yokohama City University Hospital","correspondingAuthor":false,"prefix":"","firstName":"Takeshi","middleName":"","lastName":"Kaneko","suffix":""}],"badges":[],"createdAt":"2025-02-25 01:38:25","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6100467/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6100467/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s12890-025-03726-6","type":"published","date":"2025-05-20T15:58:01+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":78248825,"identity":"e9685171-71e9-416f-9e9c-6a1cf2829673","added_by":"auto","created_at":"2025-03-11 09:40:28","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":34612,"visible":true,"origin":"","legend":"\u003cp\u003eThe number of consecutive patients examined by flexible bronchoscopy (FB) with irrigation is n=117. A total of 150 patients were retrospectively evaluated using FB without irrigation (control group). During the FB examination, 14 patients were administered antibiotics and were excluded from the study. One patient withdrew consent. The remaining patients comprised 109 in the exploratory group and 143 in the control group. Post-bronchoscopy pneumonia (PBP) developed in n=3 patients in the exploratory group and n = 5 in the control group.\u003c/p\u003e","description":"","filename":"Figure1.png","url":"https://assets-eu.researchsquare.com/files/rs-6100467/v1/c84d018c32b7154ac9de71d4.png"},{"id":78248824,"identity":"7458ff27-7b9b-4b08-86bb-b07122cf0358","added_by":"auto","created_at":"2025-03-11 09:40:28","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":50308,"visible":true,"origin":"","legend":"\u003cp\u003eColony counts after cultivation on blood and chocolate agar plates (N=14). All working channel flushing samples were obtained before FB examinations from the first 14 patients in the exploratory group. P values for the comparison between sampling point 3 v. s. sampling point 4 is p=0.008146 (blood agar), p=0.011413 (chocolate agar) and p=0.007162 (total).\u003c/p\u003e","description":"","filename":"Figure2.png","url":"https://assets-eu.researchsquare.com/files/rs-6100467/v1/d2f118f13ac27f1dd4b3d9e9.png"},{"id":78250969,"identity":"24d4af88-204c-45bf-8c58-f1bc114cd666","added_by":"auto","created_at":"2025-03-11 09:56:28","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":231683,"visible":true,"origin":"","legend":"\u003cp\u003eA representative image of culture plates. The plates correspond to Points one to four, starting from the far left. The far-left plate corresponds to samples taken before flexible bronchoscopy (FB). The next plate corresponds to samples taken after intubation but before irrigation. The following plate corresponds to samples taken after irrigation but before observation, and the far-right plate corresponds to samples taken after observation but before the procedure.\u003c/p\u003e","description":"","filename":"Figure3.png","url":"https://assets-eu.researchsquare.com/files/rs-6100467/v1/c288d7809312c84947e35060.png"},{"id":83460192,"identity":"b9784b22-e6ba-40b9-aabe-48679ed80846","added_by":"auto","created_at":"2025-05-26 16:11:50","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1012997,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6100467/v1/2f20478d-e570-4296-a538-d77ad24e32b9.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Reduction of post-bronchoscopy pneumonia by working channel irrigation with sterile saline before diagnostic procedures","fulltext":[{"header":"Key messages","content":"\u003cp\u003eAfter transbronchial biopsy with flexible bronchoscopy, pneumonia sometimes occurs as a complication. Although prophylactic antimicrobials may prevent post-bronchoscopy pneumonia in patients with tracheobronchial stenosis, the effect of irrigation of the working channel before diagnostic procedures was unknown. This study added that irrigation by suctioning 100 mL of sterile saline significantly reduced the number of bacteria in the flexible bronchoscopy working channel. This study might decrease the rates of post-bronchoscopy pneumonia.\u003c/p\u003e"},{"header":"Introduction","content":"\u003ch3\u003eBackgrounds\u003c/h3\u003e\n\u003cp\u003eFlexible bronchoscopy (FB) is the standard diagnostic procedure used to obtain specimens from the lower respiratory tract for various respiratory diseases, especially malignant conditions [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. Among complications that can occur after transbronchial biopsy with FB [\u003cspan additionalcitationids=\"CR3\" citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e–\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e], post-bronchoscopy pneumonia (PBP) [\u003cspan additionalcitationids=\"CR6 CR7 CR8 CR9 CR10\" citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e–\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e] sometimes leads to abscess formation [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e] within a tumor. Since long-term antimicrobial therapy is required for abscesses, evaluation and treatment of the malignant disease must be postponed, which may lead to disease progression or missed opportunities for definitive treatment. Therefore, prophylactic antibacterial administration has been examined but has generally failed to show effectiveness in the general population [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. Risk factors have been investigated [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e], and a retrospective, single-center, age- and sex-matched case-control study from Japan reported that tracheobronchial stenosis was an independent risk factor for PBP, according to multivariate analysis [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. Although prophylactic antimicrobials may prevent PBP in patients with tracheobronchial stenosis, no prospective study has yet demonstrated efficacy in these patients [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan additionalcitationids=\"CR17\" citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e–\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. Most importantly, prophylactic methods that do not involve antimicrobials are ideal, adhering to general principles of antimicrobial stewardship.\u003c/p\u003e \u003cp\u003eThe development of an infectious disease depends on both the virulence and the quantity of pathogens, as well as the host's immunological status. In some patients with chronic respiratory diseases, gram-negative organisms may be present as colonizers. However, in most cases of PBP, no particularly virulent bacteria are identified. Instead, bacteria from the oropharyngeal flora are typically found in lower respiratory tract samples collected during the procedure, which contribute to the development of PBP. Therefore, bacterial load, rather than virulence, is an essential factor in PBP development. Upper respiratory tract secretions can adhere to the FB working channel, leading to contamination of the lower respiratory tract. When biopsy forceps pass through the contaminated working channel and inoculate bacteria into the lesion, PBPs can develop. The increasing amount of tumor tissues required for genetic mutation testing and other purposes has led to a rise in the number of biopsy procedures, which may also be related.\u003c/p\u003e\n\u003ch3\u003eObjectives\u003c/h3\u003e\n\u003cp\u003eAccordingly, we hypothesized that irrigating the working channel before diagnostic procedures could reduce the frequency of PBP. First, we examined the efficacy of working channel irrigation with 100 mL of sterile saline suctioning and observed a significant reduction in bacterial colonies in channel-flush samples after irrigation. Subsequently, we compared the frequency of PBP after FB examinations with and without irrigation in clinical practice.\u003c/p\u003e "},{"header":"Patients and methods","content":"\u003ch2\u003eSetting\u003c/h2\u003e\u003cp\u003e Patients who underwent bronchoscopic examination at Yokohama City University Medical Center between June 2023 and March 2024 as participants in the exploratory group and between June 2022 and March 2023 as participants in the control group were enrolled. We utilized FB made in Olympus, product number BF-1TH1200, BF-1T260, BF-P290, BF-P260F and BF-F260. Bronchoscopes and radial EBUS probes (Olympus UM-S20-17S and UM-S20-20R-3) were reprocessed with an automated endoscope reprocessor (Olympus OER-2) and orthophthalaldehyde (DISOPA™ Solution 0.55%) according to the instruction manuals. To obtain specimens, disposable covered sheath, biopsy forceps and cytology brushes were used. There was no change in the reprocessing and disinfection methods during study periods.\u003c/p\u003e\n\u003ch3\u003eParticipants\u003c/h3\u003e\n\u003cp\u003ePatients were usually admitted to the hospital on the day of the bronchoscopic examination and discharged the next day if they had no complications. The procedures were conducted at an endoscopy unit. Patients were sedated with propofol and dexmedetomidine. They were intubated and breathed spontaneously with oxygen supplementation. Patients prescribed antibiotics during a bronchoscopic examination or received a bronchoscopic examination for the diagnosis of infectious diseases were excluded. Patients who underwent EBUS-TBNA were also excluded because the FBs were replaced from a standard FB to an FB for EBUS-TBNA after intubation and observation in our facility. The following items were collected from medical records: age, sex, ECOG (Eastern Cooperative Oncology Group) performance status, smoking history, inhaled medication, past medical history, diagnosis before and after FB, types of bronchoscopic examination, and use of prophylactic antibiotics after FB. The use of antibiotics after FB examinations was allowed and left to the discretion of the attending physicians.\u003c/p\u003e\n\u003ch3\u003eMicrobiological evaluation\u003c/h3\u003e\n\u003cp\u003eTo evaluate the efficacy of the working channel irrigation, working channel flushing samples were obtained at four points during FB examinations: 1) Before FB examinations; 2) After bronchoscopy-guided intubation, when the tip of the bronchoscope passes through the upper airway tract and reaches the lower respiratory tract, and before irrigation; 3) After working channel irrigation and before endotracheal observation; and 4) After endotracheal observation and before the intended procedure (observation with radial endobronchial ultrasound, bronchial brushing, forceps biopsy, or saline injection for BAL) to obtain specimens for clinical evaluation. Between points two and three, the working channel was irrigated with 100 mL of sterile saline via antegrade suction. Saline and air (5 mL) were flushed into the working channel and collected from the FB at each of the four steps. The sediments of collected samples were separated with a centrifuge at 420\u0026times;g for 5 min and resuspended in 50 \u0026micro;L of sterile saline. Ten microliters of the resuspended sediment were inoculated onto chocolate agar and blood agar plates. The number of colonies on each plate was counted after 48 h of incubation.\u003c/p\u003e\n\u003ch3\u003eEvaluation of PBP\u003c/h3\u003e\n\u003cp\u003eIn this study, PBP was defined as an increase in white blood cells and/or C-reactive protein with newly appearing opacities on chest radiography or computed tomography within 14 d of the FB examination. We monitored the frequency of PBP after FB examination in the exploratory group (with irrigation). This was retrospectively evaluated in the control group (without irrigation).\u003c/p\u003e\n\u003ch3\u003eStatistical methods\u003c/h3\u003e\n\u003cp\u003eGroups of categorical data were compared using Fisher\u0026rsquo;s exact test, and average values were compared using the Wilcoxon rank-sum test. Statistical analyses were performed using JMP Pro 17.2.0 (JMP Statistical Discovery LLC, CA, USA). Statistical significance was set at p\u0026thinsp;\u0026lt;\u0026thinsp;0.05.\u003c/p\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec9\" class=\"Section2\"\u003e \u003ch2\u003eParticipants\u003c/h2\u003e \u003cp\u003eA total of 267 patients underwent FB examinations (excluding EBUS-TBNA) between June 2022 and March 2023 and between June 2023 and March 2024 (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Fourteen patients were excluded because of antibiotic administration after the examinations (seven in the exploratory group and seven in the control group). Ten patients were excluded because they were diagnosed with infectious disease after FB from exploratory group. One patient from the exploratory group withdrew consent. Thus, a total of 242 participants were enrolled in this study. Of these, 109 and 133 were included in the exploratory and control groups, respectively. Baseline clinical characteristics of the study population are shown in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. There were no statistically significant differences between the groups, except for the presence of malignant tumors other than lung cancer (p\u0026thinsp;=\u0026thinsp;0.0228).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eBaseline clinical characteristics of the study population\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVariable\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eIrrigation group (n\u0026thinsp;=\u0026thinsp;109)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eControl (N\u0026thinsp;=\u0026thinsp;133)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003ep value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge: median (range)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e75 (44\u0026ndash;89)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e74 (21\u0026ndash;89)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.973\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMen/Women (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e63/46 (57.8/42.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e76/57 (57.1/42.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.000\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePS 0 or 1 (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e100 (91.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e119 (89.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.661\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePast smoking history (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e82 (75.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e96 (72.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.661\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePack-year: median (range)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e33.5 (0\u0026ndash;122)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e32.1 (0\u0026ndash;200)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.594\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003einhaled medication (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e18 (16.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e17 (12.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.465\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEBUS-GS (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e92 (84.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e108 (81.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.610\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDiagnosed with LK before FB (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e94 (86.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e114 (85.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.000\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDiagnosed with LK by FB (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e82 (75.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e98 (73.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.883\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePast medical history\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCOPD (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e22 (20.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e24 (18.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.743\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBronchial asthma (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9 (8.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9 (6.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.806\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eInterstitial pneumonia (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9 (8.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5 (3.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.170\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMalignant tumor complications other than lung cancer (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e34 (31.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e24 (18.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.0228\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCerebrovascular disease (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9 (8.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e16 (12.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.399\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCardiovascular disease (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e20 (18.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e36 (27.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.127\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDiabetes mellitus (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e24 (22.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e30 (22.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.000\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003eClinical background information. The exploratory group is compared with the control group. Past medical history includes COPD, bronchial asthma (BA), institutional pneumonia (IP), malignant tumor complications other than lung cancer, cerebrovascular disease, cardiovascular disease, and diabetes mellitus. FB, flexible bronchoscopy; PS, performance status.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eReduction of bacterial colony formation\u003c/h3\u003e\n\u003cp\u003e To identify the efficacy of the irrigation procedure for the working channel, flushing samples were obtained at Points 1\u0026ndash;4 during FB examinations from the first 14 patients in the exploratory group. The colony numbers of samples obtained at Point 3 (immediately after the irrigation procedure) were lower than those at Points 2 (after intubation and before irrigation) and 4 (after irrigation and endobronchial observation). The number of colonies obtained at Point 4 was significantly higher than that at Point 3 because of the suctioning of lower respiratory tract secretions, which contained considerable amounts of bacteria during FB-guided intubation (Figs.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e and \u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). Based on these results, the irrigation procedure was performed immediately prior to the intended procedures in the remaining patients in the exploratory group.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003eReduction of PBP with irrigation\u003c/h2\u003e \u003cp\u003ePBP developed in 3.8% (5/133) and 2.8% (3/109) of patients in the control and exploratory groups, respectively (p\u0026thinsp;=\u0026thinsp;0.733). This result remains unchanged by using the definition of pneumonia in [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. Forceps biopsy was undergone 92/109 in the irrigation group and 108/133 in the control group. Other examination includes BAL and bronchial brushing. Patients who were not diagnosed with lung cancer include chronic eosinophil pneumonia, cryptogenic organizing pneumonia. The frequency of PBP in the exploratory group was 26% lower than that in the control group, albeit statistically insignificant. No specific bacterial pathogens, other than components of the upper respiratory tract flora, were detected in the lower respiratory tract specimens obtained during FB examinations. While post-bronchoscopic fever (PBF) is also a common adverse event [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e], patients who presented with fever (37.5\u0026deg;C or higher) within a day after FB were significantly fewer in the exploratory group than in the control group, 5.5% (6/109) vs. 14.3% (19/133), respectively (p\u0026thinsp;=\u0026thinsp;0.0328) (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). Interestingly, the number of prophylactic antibiotic prescriptions after FB examinations was lower in the exploratory group than in the control group (8.3% [9/109] vs. 17.3% [23/133]; p\u0026thinsp;=\u0026thinsp;0.0553). Attending physician prescribed antibiotics when patients had symptoms or high risk of infection including PBF.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eThe frequency of PBP and PBF\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVariable\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eExploratory group (n\u0026thinsp;=\u0026thinsp;109)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eControl group\u003c/p\u003e \u003cp\u003e(N\u0026thinsp;=\u0026thinsp;133)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eP value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePBP (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e3 (2.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e5 (3.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.733\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePrescription of antibiotics after FB (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e9 (8.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e23 (17.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.0553\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePBF within a day after FB\u003c/p\u003e \u003cp\u003e\u0026gt;=37.5\u0026deg;C (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e6 (5.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e19 (14.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.0328\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003eThe frequency of post-bronchoscopy pneumonia (PBP) and post-bronchoscopy fever (PBF) after flexible bronchoscopy (FB). The exploratory group is compared with the control group. PBP was defined as the increase in white blood cells and/or C-reactive protein with newly appearing opacities on chest radiography or computed tomography within 14 d of the FB examination. The median time (range) to PBP is 7 d (4\u0026ndash;12 d) in the exploratory group and 7 d (1\u0026ndash;13 d) in the control group. The prescription of antibiotics after FB and the frequency of fever above 37.5℃ within 1 d after FB are also shown. FB, flexible bronchoscopy; PBP, post-bronchoscopy pneumonia; PBF, post-bronchoscopic fever.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e"},{"header":"Discussion","content":"\u003cdiv id=\"Sec13\" class=\"Section2\"\u003e \u003ch2\u003eKey results\u003c/h2\u003e \u003cp\u003eIn our study, we hypothesized that irrigation of the working channel before diagnostic procedures could reduce the frequency of PBP. We demonstrated that working channel irrigation with 100 mL of sterile saline significantly decreased the number of bacteria in the working channels. The number of PBP cases was three (2.8%) in the exploratory group and five (3.8%) in the control group. In these populations, irrigation contributed to a 26% reduction in PBP (p\u0026thinsp;=\u0026thinsp;0.733). Since PBP occurs at a very low rate, typically under 5%, a large number of cases are needed to identify a significant difference. Even if the irrigation procedure reduces the frequency of PBP by 50%, a sample size approximately eight to ten times larger than that used in this study would be needed to show a statistically significant difference. Although the exact factors causing PBF are unclear, the inoculation of bacteria attached to instruments passing through the working channel may contribute to PBF. Our results show a reduction in the number of bacteria in the working channel after irrigation. Therefore, a significant reduction in PBF with irrigation was expected. Interestingly, the decrease in PBP and PBF in this study was achieved alongside a statistically significant reduction in antibiotic prescriptions compared with that in the control group, whereas prophylactic antibiotics for PBP generally lack efficacy.\u003c/p\u003e \u003cp\u003eIt is reasonable to ask whether we did not select a randomized design for this study. First of all, it is difficult to blind the irrigation. Since we started this study after confirming a reduction in the number of bacteria in the working channel after irrigation, randomization of patients might affect the prescription frequency of antibiotics, which can affect the frequency of PBP. As mentioned earlier, considering the number of cases required to achieve statistical significance, it was determined that conducting a randomized trial in a single center with a limited duration would be difficult.\u003c/p\u003e \u003cp\u003eRegarding patient background, the proportion of patients with malignant diseases other than lung cancer was significantly higher in the exploratory group. Patients with malignant diseases have a higher risk of infectious complications owing to immunosuppression. This may explain why the suppressive effect of irrigation was not significant.\u003c/p\u003e \u003cp\u003eSpecimens obtained by FB have often been used to evaluate the pathogens of lower respiratory tract infections or the microbiome of the lower respiratory tract. Considering our results, conclusions must be carefully interpreted when obtaining specimens. It is necessary to confirm the procedures used to reduce contamination by microorganisms originating from the upper respiratory tract attached to the FB working channel. Without efforts to reduce the influence of upper respiratory tract microorganisms, these can be overestimated, especially in microbiome analyses using next-generation sequencing. In this situation, irrigation alone may be inadequate to reduce contamination.\u003c/p\u003e \u003cp\u003eIrrigation prior to the diagnostic procedures evaluated in this study was simple. Suctioning 100 mL of sterile saline is an effortless and safe procedure, with minimal additional time and cost. The disadvantage of irrigation was that the maneuver required intubation or other procedures in which the FB was moved back and forth to the lower respiratory tract.\u003c/p\u003e \u003cp\u003eOverall, the results of this study may be beneficial for reducing PBP, but the reduction was not statistically significant. A large number of cases must be accumulated to demonstrate its effectiveness in reducing the frequency of complications.\u003c/p\u003e \u003c/div\u003e"},{"header":"Conclusions","content":"\u003cp\u003eIrrigation by suctioning 100 mL of sterile saline significantly reduced the number of bacteria in the FB working channel. With irrigation before diagnostic procedures, the rates of major complications after FB, including PBP and PBF, also decreased. To confirm the practical significance of irrigation, further evaluation using additional cases from other institutions is required.\u003c/p\u003e "},{"header":"Abbreviations","content":"\u003cp\u003eFB,\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003eflexible bronchoscopy; PBF, post-bronchoscopic fever; PBP, post-bronchoscopy pneumonia.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003eOther information\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eAcknowledgements\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eWe are grateful to the microbiological laboratory of Yokohama City University Medical Center, Yokohama, Japan, especially to S. Okamatsu, Y. Ohnishi, A. Okawara, and Y. Takanami.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eFunding\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eThis study did not receive any specific grants from funding agencies in the public, commercial, or non-profit sectors.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eAuthor contributions\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eMY was responsible for the organization and coordination of the trial and was the chief investigator. MY and SN were responsible for the data analysis. All authors contributed to the writing of the final manuscript. All members of the study team contributed to the management or administration of the trial.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eConflict of interest\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eThe authors have no conflicts of interest.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eIRB information and informed consent\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eThe study was approved by the Institutional Review Board of the Yokohama City University School of Medicine under approved the study protocol (F230500045) and all participants gave written informed consent.\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eEthics approval and consent to participate\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eEthics, Consent to Participate, and Consent to Publish declarations: not applicable.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003cem\u003eRelevant meeting\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eThe 64th Annual Meeeting of the Japanese Respiratory Society (2024), April 6, 2024,Yokohama, Japan\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eDu Rand IA, Blaikley J, Booton R, Chaudhuri N, Gupta V, Khalid S, et al. British Thoracic Society guideline for diagnostic flexible bronchoscopy in adults: accredited by NICE. \u003cem\u003eThorax. \u003c/em\u003e2013;68:i1-i44.\u003c/li\u003e\n\u003cli\u003eFacciolongo N, Patelli M, Gasparini S, Lazzari Agli L, Salio M, Simonassi C, et al. Incidence of complications in bronchoscopy. Multicentre prospective study of 20,986 bronchoscopies. \u003cem\u003eMonaldi Arch Chest Dis. \u003c/em\u003e2009;71:8-14.\u003c/li\u003e\n\u003cli\u003eAsano F, Aoe M, Ohsaki Y, Okada Y, Sasada S, Sato S, et al. Deaths and complications associated with respiratory endoscopy: a survey by the Japan Society for Respiratory Endoscopy in 2010. \u003cem\u003eRespirology. \u003c/em\u003e2012;17:478-85.\u003c/li\u003e\n\u003cli\u003eStahl DL, Richard KM, Papadimos TJ. Complications of bronchoscopy: A concise synopsis. \u003cem\u003eInt J Crit Illn Inj Sci. \u003c/em\u003e2015;5:189-95.\u003c/li\u003e\n\u003cli\u003ePereira W, Kovnat DM, Khan MA, Iacovino JR, Spivack ML, Snider GL. 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Fibreoptic bronchoscopy and the use of antibiotic prophylaxis. \u003cem\u003eBr Med J (Clin Res Ed). \u003c/em\u003e1987;294(6581):1199.\u003c/li\u003e\n\u003cli\u003eYamamoto M, Nagano T, Okuno K, Nakata K, Takenaka K, Kobayashi K, et al. An open-label, prospective clinical study to evaluate the efficacy of prophylactic antibiotics after diagnostic bronchoscopy. \u003cem\u003eKobe J Med Sci. \u003c/em\u003e2012;58:E110-E18.\u003c/li\u003e\n\u003cli\u003eTakagi H, Nagaoka T, Ando K, Tsutsumi T, Ichikawa M, Koyama R, et al. Efficacy of antibiotic prophylaxis after endobronchial ultrasound-guided transbronchial needle aspiration: A preliminary prospective study. \u003cem\u003eJ Pulm Respir Med. \u003c/em\u003e2017;07.\u003c/li\u003e\n\u003cli\u003eFarrokhpour M, Kiani A, Mortaz E, Taghavi K, Farahbod AM, Fakharian A, et al. Procalcitonin and proinflammatory cytokines in early diagnosis of bacterial infections after bronchoscopy. \u003cem\u003eOpen Access Maced J Med Sci. \u003c/em\u003e2019;7:913-19.\u003c/li\u003e\n\u003cli\u003eWitte MC, Opal SM, Gilbert JG, Pluss JL, Thomas DA, Olsen JD, et al. Incidence of fever and bacteremia following transbronchial needle aspiration. \u003cem\u003eChest. \u003c/em\u003e1986;89:85-87.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-pulmonary-medicine","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"pulm","sideBox":"Learn more about [BMC Pulmonary Medicine](http://bmcpulmmed.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/pulm/default.aspx","title":"BMC Pulmonary Medicine","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Flexible bronchoscopy, post-bronchoscopy pneumonia","lastPublishedDoi":"10.21203/rs.3.rs-6100467/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6100467/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eBackground/Question\u003c/p\u003e\n\u003cp\u003eAfter transbronchial biopsy with flexible bronchoscopy, pneumonia sometimes occurs as a complication. The goal of our study was to determine whether irrigation of the working channel before diagnostic procedures can reduce the frequency of post-bronchoscopy pneumonia.\u003c/p\u003e\n\u003cp\u003eMethods\u003c/p\u003e\n\u003cp\u003eInitially, we examined the effect of working channel irrigation with 100 mL of sterile saline to reduce the number of bacteria attached to the working channel. Subsequently, we compared the frequency of post-bronchoscopy pneumonia in patients who underwent or did not undergo working channel irrigation before bronchoscopic biopsy or lavage fluid collection.\u003c/p\u003e\n\u003cp\u003eResults\u003c/p\u003e\n\u003cp\u003eA significant reduction in bacterial colonies was observed in the irrigated channel-flush samples. Of the 242 enrolled participants, 109 were in the exploratory group, whereas 133 were in the control group. The frequency of post-bronchoscopy pneumonia was 2.8% (n = 3) and 3.8% (n = 5) in the exploratory and control groups, respectively.\u003c/p\u003e\n\u003cp\u003eConclusions/Answer to the question\u003c/p\u003e\n\u003cp\u003eIrrigation by suctioning 100 mL of sterile saline significantly reduced the number of bacteria in the flexible bronchoscopy working channel. To confirm the practical significance of irrigation in reducing post-bronchoscopy pneumonia and post-bronchoscopy fever, further evaluation with additional cases from other institutions is required.\u003c/p\u003e","manuscriptTitle":"Reduction of post-bronchoscopy pneumonia by working channel irrigation with sterile saline before diagnostic procedures","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-03-11 09:40:23","doi":"10.21203/rs.3.rs-6100467/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-03-04T08:00:14+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-03-03T09:50:13+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-03-03T09:47:08+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Pulmonary Medicine","date":"2025-02-25T01:33:44+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-pulmonary-medicine","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"pulm","sideBox":"Learn more about [BMC Pulmonary Medicine](http://bmcpulmmed.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/pulm/default.aspx","title":"BMC Pulmonary Medicine","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"7badaa06-ae93-477e-9f1b-d45cb558ab99","owner":[],"postedDate":"March 11th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2025-05-26T16:06:49+00:00","versionOfRecord":{"articleIdentity":"rs-6100467","link":"https://doi.org/10.1186/s12890-025-03726-6","journal":{"identity":"bmc-pulmonary-medicine","isVorOnly":false,"title":"BMC Pulmonary Medicine"},"publishedOn":"2025-05-20 15:58:01","publishedOnDateReadable":"May 20th, 2025"},"versionCreatedAt":"2025-03-11 09:40:23","video":"","vorDoi":"10.1186/s12890-025-03726-6","vorDoiUrl":"https://doi.org/10.1186/s12890-025-03726-6","workflowStages":[]},"version":"v1","identity":"rs-6100467","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6100467","identity":"rs-6100467","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}