Medical Resolution of a Tracheal Granuloma Caused by Bordetella Bronchiseptica Infection in an Adult Dog

Medical Resolution of a Tracheal Granuloma Caused by Bordetella Bronchiseptica Infection in an Adult Dog | 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 Case Report Medical Resolution of a Tracheal Granuloma Caused by Bordetella Bronchiseptica Infection in an Adult Dog Pablo Agüera-Espejo, Guadalupe Miró, José Luis Fontalba-Navas, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6636613/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract A 3-year-old male entire crossbreed dog was presented to the Internal Medicine Department with a one-week history of coughing. Pre-referral blood work revealed moderate leukocytosis, thrombocytopenia, and a mild increase in transaminase levels. Prior treatment with doxycycline and meloxicam did not result in clinical improvement. Thoracic computed tomography demonstrated marked bronchial wall thickening and moderate enlargement of the tracheobronchial lymph nodes, leading to compression of the trachea and right mainstem bronchus at the carina level. Tracheobronchoscopy identified narrowing of the distal trachea due to a mass effect originating from the tracheal muscle. Polymerase chain reaction (PCR) analysis of bronchoalveolar lavage fluid confirmed Bordetella bronchiseptica infection. Systemic antibiotic therapy failed to resolve clinical signs. However, complete clinical and radiological resolution was achieved following a one-month treatment course with inhaled gentamicin. At the time of writing, two years later, the dog is still alive and free of respiratory signs. Bordetella bronchiseptica bacterial diseases tracheal granuloma infection PCR inhaled gentamicin Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Background Bordetella bronchiseptica (B. bronchiseptica) is one of the most frequent bacteria isolated from the respiratory tract of both healthy and sick dogs (1) . It’s documented as one of the most common pathogens that cause canine respiratory infections. It acts as a primary agent or secondary when there are coinfections with other pathogens(Chambers et al. 2019 ; Canonne et al. 2020 ; Day et al. 2020 ; Fastrès et al. 2020 ; Reagan and Sykes 2020 ) (1–6) . Bordetella bronchiseptica infection most commonly presents as an acute-onset, often self-limiting, tracheobronchitis. Clinically, affected dogs may exhibit nasal discharge and coughing. However, a chronic refractory form has also been described, characterized by extension of the infection to the terminal bronchioles and alveoli, leading to a wide range of respiratory signs, from mild-to-severe pneumonia to fatal outcomes(Chambers et al. 2019 ; Canonne et al. 2020 ; Day et al. 2020 ; Fastrès et al. 2020 ; Reagan and Sykes 2020 ) (1–6) . The severity of the disease depends on multiple factors, including the virulence of the bacterial strain, bacterial load, immune status of the patient, and pre-existing respiratory tract disorders involving the larynx and trachea. Coinfection with other pathogens, such as Mycoplasma cynos, has been increasingly recognized as an exacerbating factor in B. bronchiseptica infection(Canonne et al. 2020 ) (6) . Cytology and bronchoalveolar lavage fluid (BALF) microbiological culture can be used for the diagnosis of B. bronchiseptica infectious respiratory disease. However, those tests may give a false negative result due to the absence of bacteria at the time of the test or because of poor collection technique. The risk of this can be reduced by using more sensitive diagnostic tests for B. bronchiseptica infection, such as BALF polymerase chain reaction (PCR) or the immunohistochemistry test(Canonne et al. 2016 ) (1,10) . Regarding the therapeutic management of B. bronchiseptica infection, eradication may be necessary in cases where it plays a role as the primary pathogen. For these clinical cases the efficacy of systemic antibiotics such as doxycycline or amoxicillin-clavulanic acid has been demonstrated(Lappin et al. 2017 ; Chambers et al. 2019 ; Fastrès et al. 2020 ; Reagan and Sykes 2020 ) (1–4,11) . However, in cases where treatment with systemic antibiotics is partial or failures, the efficacy of inhaled gentamicin as an alternative treatment has been recently documented(Lappin et al. 2017 ; Canonne et al. 2020 ; Fastrès et al. 2020 ) (3,6,11) . Additionally, depending on the severity of clinical signs, supportive therapy with anti-inflammatory drugs or even oxygen therapy may be required in more severe cases(Canonne et al. 2016 , 2020 ; Lappin et al. 2017 ; Chambers et al. 2019 ; Jaffey et al. 2019 ; Day et al. 2020 ; Fastrès et al. 2020 ; Reagan and Sykes 2020 ; Biénès et al. 2023 ) (1–11) . Case presentation A 3-year-old, intact male crossbreed dog was presented to the Internal Medicine department of our Veterinary Teaching Hospital with a one-week history of coughing. A five-day history of hyporexia, fever and vomiting were also reported. Routine vaccination and deworming were up to date. Blood work performed prior to referral showed moderate leucocytosis of 24.2 x 10 9 cells/L (reference range 6.0 x 10 9 to 17.0 x10 9 cells/L) moderate granulocytosis of 20.5 x10 9 cells/L (reference range 4.0 x10 9 to 12.6 x10 9 cells/L), moderate thrombocytopenia of 52 x10 9 (reference range 117 x10 9 – 460 x10 9 U/L) (Table 1), and a slight increase in alkaline phosphatase of 151 U/L (range 10 to 125 U/L) and alanine aminotransferase of 326 U/L (refence range 23 to 212 U/L). Treatment before referral included a 7-day course of 5 mg/kg doxycycline per os (po) BID (Ronaxan; Boehringer Ingelheim Animal Health Spain, S.A.U.) and 0.1 mg/kg meloxicam po SID (Metacam; Boehringer Ingelheim Animal Health Spain, S.A.) without clinical improvement. Upon presentation at the hospital, the owner reported the dog had always presented exhibited breathlessness, an increase of respiratory sounds and hacking cough during exercise. Physical examination revealed a slight enlargement of the submandibular lymph nodes, a temperature of 39.1ºC, a positive cough reflex and drooling. Cardiothoracic auscultation revealed a stridor, and an increase of breath sounds without heart murmurs or arrhythmias. It also exhibited a dorsal subconjunctival hemorrhage in the left eye. The rest of the physical examination was unremarkable. The patient was hospitalized for stabilization and monitoring before undergoing complementary tests. Initial treatments included amoxicilin-clavulanic acid at 20 mg/kg IV TID (Amoxicilina/Ácido clavulánico Normon; Laboratorios Normon, S.A.), 0.1 mg/kg meloxicam iv SID (Meloxidyl; Ceva Sante Animale), 1 mg/kg omeprazole iv BID (Omeprazol Normon; Laboratorios Normon, S.A.), 1.1 mg/kg mirtazapine po SID (Mirtazapina Alter; Laboratorios Alter, S.A.), nebulizations with sterile physiological saline solution (NaCl-0,9 FisioVet, B. Braun Vetcare, S.A.) and coupage. CBC was performed two days after admission to the hospital showing mild non-regenerative anemia 30.9% (range 37.3 to 61.7%), moderate leukocytosis of 26.78 x 10 3 cells/µL (range 5.05 to 16.76 x 10 3 cells/µL) with moderate neutrophilia of 21.63 x 10 3 cells/µL (range 2.95 to 11.64x 10 3 cells/µL) (Fig. 5 ), moderate monocytosis of 3.36 x 10 3 cells/µL(range 0.16 to 1.12 x 10 3 cells/µL), and moderate thrombocytopenia of 61 x 10 3 cells/µL (range 148 to 484 x 10 3 cells/µL) (Table 1). A blood smear showed a normal platelet count, moderate neutrophilia with a left shift, and mild monocytosis. A rapid test was carried out for the detection of Dirofilaria immitis antigen, antibodies to Anaplasma phagocytophilum, Anaplasma platys, Borrelia burgdorferi, Ehrlichia canis, and Ehrlichia ewingii obtaining negative results. Antibodies against Leishmania infantum were also negative and Angiostrongylus vasorum antigen test was negative. A preliminary cardiac ultrasound showed good cardiac contractility, normal size of the atria and ventricles, no pericardial or pleural effusion, and a moderate number of B-lines. Thoracic radiographs showed a diffuse broncho interstitial pattern and an area of radiopacity cranial to the carina (Fig. 1 ). Abdominal ultrasound revealed increased thickness of the stomach wall, with maintained stratigraphy. Mild generalized peritoneal reaction and mild reactive cranial and iliac mesenteric lymphadenopathy were also detected. Thoracic computed tomography (CT, 16x0.5 slice spiral CT-scanner, Toshiba Astelion TSX-032A, Toshiba Medical Systems, Ōtawara, Tochigi, Japan) was performed and showed a marked peribronchial alveolar-interstitial pattern in the ventral zone of the cranial and middle right lung lobes with a marked increase in the thickness of the bronchial walls in these lobes, these pulmonary changes were associated with a moderate enlargement of right and central tracheobronchial lymph nodes with heterogeneous contrast attenuation and enhancement, which caused compression of the right aspect of the trachea and the right mainstem bronchus at the level of the carina (Fig. 2 ). The left tracheobronchial lymph node was slightly enlarged without contrast enhancement or attenuation abnormalities. A tracheobronchoscopy was performed under general anaesthesia using a 3 mm flexible video endoscope (Flexible Video Ureteroscope, U41, Zhuhai Mindhao Medical Technology Co., Ltd., Tangjiawan Town, China) and a flexible video endoscope of 5 mm in diameter (Fujinon Corporation, 1-324 Uetake-Cho, Kita-Ku, Saitama-Shi, Saitama, Japan). It was observed that although the proximal trachea did not present macroscopic alterations, at the level of the distal trachea there was a loss of continuity of the tracheal cartilages. The distal trachea was narrowed by 50%. This narrowing was caused by a mass effect coming from the dorsal tracheal muscle (Fig. 3 ). This mass, or infiltrative process, extended towards the right cranial bronchus and right caudal bronchus, partially occluding the lumen of these two bronchi. In addition, marked accumulation of dense purulent-looking liquid was observed in the right cranial bronchus. The left main bronchi presented bronchomalacia. Brush cytology and biopsy samples of the tracheal mass were collected, and a BALF was performed and submitted for microbiological culture and RT-qPCR tests of B. bronchiseptica DNA and Mycoplasma cynos DNA (IDEXX Laboratories, Inc., Spain). The cytology of the mass showed a moderate number of neutrophils with characteristics of degeneration together with normal cells of the respiratory epithelium with intra and extracellular bacteria, consistent with a septic inflammatory process. The cytology of the BALF was consistent with an inflammatory non- septic process. Biopsy of the tracheal mass showed severe ulcerative and suppurative fibrinous tracheitis, with no evidence of neoplasia. Special histochemical stains did not detect fungal agents. No growth of bacteria or yeast was obtained from the BALF culture, however, the PCR was positive for B.bronchiseptica and negative to Mycoplasma cynos. After five days of hospitalization with the treatment prescribed since admission, the patient was stabilized, and it was discharged with 20 mg/kg amoxicillin-clavulanic acid po BID (Eupenclav, Laboratorios Normon, S.A.), 3 mg/kg marbofloxacin po SID (Marvovet, Fatro Ibérica, S.L.), 250 micrograms of inhaled fluticasone BID (Flixotide, GlaxoSmithKline, S.A.), and physiological saline solution nebulization (NaCl 0,9 FisioVet, B. Braun Vetcare, S.A.). Seven days after discharge from the hospital the patient was brighter but continued with cough and exercise intolerance persisted. Follow up thoracic radiographs showed a slight improvement in the broncho interstitial pattern and a decrease in size of the radiopacity located cranial to the carina. CBC results showed resolution of the anemia with a hematocrit of 39.3% (range 37.3 to 61.7%), but there was a mild leucocytosis of 18.76 x 10 3 cells/µL (range 5.05 to 16.76 x 10 3 cells/µL) with slight neutrophilia of 13.93 x 10 3 cells/µL (range 2.95 to 11.64 x 10 3 cells/µL) (Fig. 5 ), and moderate monocytosis of 3.32 (range 0.16–1.12 x 10 3 cells/µL) (Table 1). Inhaled gentamicine at 200 mg BID (Genta-gobens, Laboratorios Normon S.A.) and prednisolone at 0.5 mg/kg po SID (Prednicortone, Dechra Regulatory B.V.) were added to the treatment. Table 1: evolution of principal Complete Blood Count (CBC) parameters. CBC 2 days before referral CBC 2 days after referral CBC 9 days before referral CBC 37 days before referral Hematocrit (range 37.3–61.7%) 39.2% 30.9% 39.3% 39.6% Leucocytes (range 5.05 to 16.76 x 10 3 cells/µL) 24.20 x 10 3 cells/µL 26.78 x 10 3 cells/µL 18.76 x 10 3 cells/µL 11.70 x 10 3 cells/µL Neutrophils (range 2.95 to 11.64 x 10 3 cells/µL) 20.5 x 10 3 cells/µL 21.63 x 10 3 cells/µL 13.93 x 10 3 cells/µL 8.89 x 10 3 cells/µL The patient's respiratory signs markedly improved four days after the new treatment was started. Coughing episodes stopped, and exercise intolerance improved. Pulmonary auscultation was normal, the tracheal pinch was negative, and the dog was normothermic. Additionally, the subconjunctival haemorrhage had resolved. Follow-up thoracic radiographs were performed revealing a dramatic improvement in the lung pattern, with only a mild, generalized bronchial pattern remaining. The tracheal diameter was back to normality (Fig. 4 ). At this moment, oral antibiotics were withdrawn, having taken 16 days of 20 mg/kg amoxicillin-clavulanic acid po BID (Eupenclav, Laboratorios Normon, S.A.), and 11 days of 3 mg/kg marbofloxacin po SID (Marvovet, Fatro Ibérica S.L.). Inhaled gentamicin at 200 mg BID (Genta-gobens, Laboratorios Normon S.A.), and fluticasone, 250 micrograms BID (Flixotide, GlaxoSmithKline, S.A.), were maintained. Oral corticosteroids were gradually withdrawn as 0.5 mg/kg prednisolone po q 48 hours for 7 days and then treatment was stopped (Prednicortone, Dechra Regulatory B.V.). One month after starting treatment with inhaled gentamicin, 200 mg BID (Genta gobens, Laboratorios Normon S.A.), the patient showed complete clinical remission. CBC (Fig. 5 , Table 1) and thoracic radiographs had normalized, so the medical treatment was discontinued. A follow-up tracheobronchoscopy was suggested, but the owner declined it due to the resolution of clinical signs. Discussion Bordetella bronchiseptica infection, has been reported to induce clinical signs such as chronic cough or dyspnoea(Chambers et al. 2019 ; Canonne et al. 2020 ; Day et al. 2020 ; Fastrès et al. 2020 ; Reagan and Sykes 2020 ) (1,6) . Pulmonary changes such as fibrosis or bronchiolitis have been reported(Jaffey et al. 2019 ) (9) . In this case, although B. bronchiseptica is a common pathogen of the respiratory tract of dogs, no other pathogens were detected by histopathology, thoracic computed tomographymicrobiological culture or PCR that could explain the clinical signs. To the authors’ knowledge, this is the first case report of a tracheal granuloma secondary to B. bronchiseptica infection. The patient presented a subconjunctival hemorrhage not associated with ocular trauma or coagulopathies. A possible cause of this process is the rupture of vessels due to chronic coughing(Mimura et al. 2017 ; Parikh et al. 2022 ) (13,14) . In this case, the cytology of the BALF did not show intracellular microorganisms, but the brush cytology of the tracheal mass was consistent with a septic inflammatory process. This could be due to the fact that brushing procedures offer a greater number of ciliated cells from the tracheobronchial epithelium in contrast to samples collected by BALF(Canonne et al. 2016 ) (10) . The pathogen was not detected in the histopathological study of the tracheal lesion. This could be due to the presence of a low bacterial load at the time of sample collection, which may have been influenced by prior use of systemic antibiotics to which B bronchiseptica is sensitive(Lappin et al. 2017 ; Chambers et al. 2019 ; Fastrès et al. 2020 ; Reagan and Sykes 2020 ) (1–4,11) . According to a study published in ACVIM in 2016, the most sensitive test for B. bronchiseptica is the quantitative PCR of the BALF since numerous cases have been described in which this test was positive even on occasions in which the microbiological culture and the histopathological tests were negative(Canonne et al. 2016 ) (10) . In this case, the diagnosis was confirmed by positive quantitative PCR of B. bronchiseptica DNA in BALF. There are antimicrobials to which B. bronchiseptica colonies isolated in vitro are sensitive, and when administered systemically, they may not be as effective. This may be because these antibiotics do not reach effective therapeutic concentrations on the apical surfaces of the bronchial epithelium. B. bronchiseptica adherence to cilia induces ciliostasis, biofilm formation, and local immunosuppression in the tracheal and bronchial epithelium(Canonne et al. 2020 ) (6) . This fact would explain the lack of remission of clinical signs and radiographic findings in this dog. In the consulted literature there are three publications(Canonne et al. 2020 ; Biénès et al. 2023 ) (6–8) that have demonstrated the efficacy of inhaled gentamicin for the treatment of upper respiratory tract infections caused by aminoglycoside-sensible bacteria in dogs. In fact, two of them(Canonne et al. 2020 ) (6,8) had described the efficacy of inhaled gentamicin against B. bronchiseptica respiratory infection in dogs, which is why the treatment with inhaled gentamicin at 200 mg q 12 hours (Genta-gobens, Laboratorios Normon S.A.) was initiated. Complete remission of respiratory signs was achieved one month after starting this inhaled treatment. It would have been interesting to repeat the bronchoscopy and correlate it with the follow-up thoracic radiographs; however, given the excellent clinical progress, the owner declined. It must not forget that B. bronchiseptica can be the cause of acquired pneumonia in human immunocompromised patients(Baptista et al. 2020 ) (15) , likely due to close contact with infected animals. Though an early diagnosis of these cases may be necessary to establish an adequate treatment as soon as possible to avoid zoonotic transmission. To the authors’ knowledge this is the first documented case of a tracheal granuloma induced by B. bronchiseptica in a dog. What makes this case report even more interesting is that it achieved a complete resolution of clinical signs and granuloma by using inhaled gentamicin. Declarations Conflict of interest statement: The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported. Funding Statement: The authors received no specific funding for this work. Data availability statement: The data that support the findings of this study are not openly available and are available from the corresponding author upon reasonable request. Author Contribution Pablo Agüera-Espejo: writing, editing of manuscript.Guadalupe Miró: editing and review of manuscript.José Luis Fontalba-Navas: editing and review of manuscript.Sabela Atencia: case management, editing and final review of manuscript. Acknowledgement Acknowledgments to the diagnostic imaging department of AniCura Vetsia Veterinary Hospital forall their help during the writing of this case report. Ethics statements: The authors confirm that the ethical policies of the journal, as noted on the journal’s author guidelines page, have been adhered to. References Baptista RJIR, Costa JM de SS da, Badura RA (2020) Severe cavitary pneumonia caused by Bordetella bronchiseptica in an HIV-infected patient. Enfermedades Infecc y Microbiol Clínica 38:404–405. https://doi.org/10.1016/j.eimc.2020.02.014 Biénès T, Lyssens A, Machiels H, et al (2023) Intranasal and Serum Gentamicin Concentration: Comparison of Three Topical Administration Protocols in Dogs. Vet Sci 10:490. https://doi.org/10.3390/vetsci10080490 Canonne AM, Billen F, Tual C, et al (2016) Quantitative PCR and Cytology of Bronchoalveolar Lavage Fluid in Dogs with Bordetella bronchiseptica Infection. J Vet Intern Med 30:1204–1209. https://doi.org/10.1111/jvim.14366 Canonne AM, Roels E, Menard M, et al (2020) Clinical response to 2 protocols of aerosolized gentamicin in 46 dogs with Bordetella bronchiseptica infection (2012‐2018). J Vet Intern Med 34:2078–2085. https://doi.org/10.1111/jvim.15843 Chambers JK, Matsumoto I, Shibahara T, et al (2019) An Outbreak of Fatal Bordetella bronchiseptica Bronchopneumonia in Puppies. J Comp Pathol 167:41–45. https://doi.org/10.1016/j.jcpa.2018.12.002 Day MJ, Carey S, Clercx C, et al (2020) Aetiology of Canine Infectious Respiratory Disease Complex and Prevalence of its Pathogens in Europe. J Comp Pathol 176:86–108. https://doi.org/10.1016/j.jcpa.2020.02.005 Fastrès A, Canonne MA, Taminiau B, et al (2020) Analysis of the lung microbiota in dogs with Bordetella bronchiseptica infection and correlation with culture and quantitative polymerase chain reaction. Vet Res 51:46. https://doi.org/10.1186/s13567-020-00769-x Jaffey JA, Harmon M, Masseau I, et al (2019) Presumptive Development of Fibrotic Lung Disease From Bordetella bronchiseptica and Post-infectious Bronchiolitis Obliterans in a Dog. Front Vet Sci 6:352. https://doi.org/10.3389/fvets.2019.00352 Lappin MR, Blondeau J, Boothe D, et al (2017) Antimicrobial use Guidelines for Treatment of Respiratory Tract Disease in Dogs and Cats: Antimicrobial Guidelines Working Group of the International Society for Companion Animal Infectious Diseases. J Vet Intern Med 31:279–294. https://doi.org/10.1111/jvim.14627 Mimura T, Noma H, Yamagami S (2017) Letter to the Editor: Bilateral Subconjunctival Hemorrhage in a 3-Year-Old Girl with Mycoplasma Pneumonia. Open Ophthalmol J 11:322–325. https://doi.org/10.2174/1874364101711010322 Parikh AO, Christian CW, Forbes BJ, Binenbaum G (2022) Prevalence and Causes of Subconjunctival Hemorrhage in Children. Pediatr Emerg Care 38:e1428–e1432. https://doi.org/10.1097/pec.0000000000002795 Reagan KL, Sykes JE (2020) Canine Infectious Respiratory Disease. Vet Clin North Am: Small Anim Pr 50:405–418. https://doi.org/10.1016/j.cvsm.2019.10.009 Additional Declarations No competing interests reported. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-6636613","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Case Report","associatedPublications":[],"authors":[{"id":461536630,"identity":"f209bd2b-b11d-44f2-aca4-1bf8ed0aeaf5","order_by":0,"name":"Pablo Agüera-Espejo","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAr0lEQVRIiWNgGAWjYBADOdK1GJOuJbGBaKXm7MevSXzcY5e+4fjpBIYPf4jQYtmTUyY541ly7oYzuRsYZ7YRocXgQE6aNM8B5twNN3g3MPMS4zyD82/SpP8cqE83AGn5Q4zDDG6kH5NmOHA4AayFgY0ILZYz3jBb9hw4bjgT6JeDvcT4xZw//eGNHweq5fmOn9344AdRDmPgMYBzDhChAaSF/QFRCkfBKBgFo2AEAwDJ0Ts/VVz7eQAAAABJRU5ErkJggg==","orcid":"","institution":"AniCura Vetsia Veterinary Hospital","correspondingAuthor":true,"prefix":"","firstName":"Pablo","middleName":"","lastName":"Agüera-Espejo","suffix":""},{"id":461536631,"identity":"518b39a3-4533-457e-9de3-a807b2b45a7c","order_by":1,"name":"Guadalupe Miró","email":"","orcid":"","institution":"Complutense University of Madrid","correspondingAuthor":false,"prefix":"","firstName":"Guadalupe","middleName":"","lastName":"Miró","suffix":""},{"id":461536632,"identity":"1f40f646-8a43-456a-86c1-ea0d935d5cbd","order_by":2,"name":"José Luis Fontalba-Navas","email":"","orcid":"","institution":"AniCura Vetsia Veterinary Hospital","correspondingAuthor":false,"prefix":"","firstName":"José","middleName":"Luis","lastName":"Fontalba-Navas","suffix":""},{"id":461536633,"identity":"d40972f9-bf5f-4cbc-90bf-8eec61e16826","order_by":3,"name":"Sabela Atencia","email":"","orcid":"","institution":"AniCura Vetsia Veterinary Hospital","correspondingAuthor":false,"prefix":"","firstName":"Sabela","middleName":"","lastName":"Atencia","suffix":""}],"badges":[],"createdAt":"2025-05-10 20:08:05","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6636613/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6636613/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":83514467,"identity":"e5c35daa-c965-49f8-9de8-44d9837d81b4","added_by":"auto","created_at":"2025-05-27 17:53:27","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":36643,"visible":true,"origin":"","legend":"\u003cp\u003eRight lateral thoracic radiograph. There is a diffuse bronchointerstitial pattern and a localized increase in radiopacity in the cranial area near the carina. The tracheal diameter is decreased.\u003c/p\u003e","description":"","filename":"1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-6636613/v1/319dbb55322f927986a01f8c.jpg"},{"id":83514475,"identity":"fdea7a1f-cd3e-4f35-b73f-544fc7413844","added_by":"auto","created_at":"2025-05-27 17:53:29","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":32988,"visible":true,"origin":"","legend":"\u003cp\u003eThoracic computed tomography cross (A) and sagittal (B) section. There is a moderate enlargement of right and central tracheobronchial lymph nodes with heterogeneous contrast attenuation and enhancement (arrows) which causes compression to the right aspect of the trachea and the right mainstem bronchus at the level of the carina.\u003c/p\u003e","description":"","filename":"2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-6636613/v1/5a114aca3f7ee6ed639619a8.jpg"},{"id":83514468,"identity":"21533c9f-287e-40e5-ba26-95018b9be6e7","added_by":"auto","created_at":"2025-05-27 17:53:28","extension":"jpg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":28842,"visible":true,"origin":"","legend":"\u003cp\u003eTracheobronchoscopy. There is a mass effect originating from the dorsal tracheal muscle, causing a 50% narrowing of the tracheal diameter in the cranial region to the carina (A). This mass extends through the right cranial bronchus and presents with an ulcerative process and marked accumulation of dense, purulent fluid (B).\u003c/p\u003e","description":"","filename":"3.jpg","url":"https://assets-eu.researchsquare.com/files/rs-6636613/v1/45d1ad5a6a1d3310cdbe1c63.jpg"},{"id":83514472,"identity":"3c385c6f-0cbd-4794-8c35-eb2f60c4abdb","added_by":"auto","created_at":"2025-05-27 17:53:28","extension":"jpg","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":56204,"visible":true,"origin":"","legend":"\u003cp\u003eRight lateral thoracic radiograph. There is a slight diffuse bronchial pattern, with no masses or lymph nodes observed. The tracheal diameter is normal.\u003c/p\u003e","description":"","filename":"4.jpg","url":"https://assets-eu.researchsquare.com/files/rs-6636613/v1/da8f1ae4e6de2e0a896505e4.jpg"},{"id":83514863,"identity":"9592fbfe-1974-4699-8767-1623233cb41b","added_by":"auto","created_at":"2025-05-27 18:01:28","extension":"jpg","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":60005,"visible":true,"origin":"","legend":"\u003cp\u003eGraphical representation of antibiotic (pink area) and anti-inflammatory (blue area) treatment times before and after referral.\u003c/p\u003e","description":"","filename":"5.jpg","url":"https://assets-eu.researchsquare.com/files/rs-6636613/v1/dca938063cab9fee015eabd1.jpg"},{"id":90737928,"identity":"be55ac4f-7543-4cae-b9e3-3eeb84650f35","added_by":"auto","created_at":"2025-09-06 23:46:19","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":653642,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6636613/v1/ae580f0f-49ab-4d7e-99ff-a74d6210f319.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"\u003cp\u003eMedical Resolution of a Tracheal Granuloma Caused by Bordetella Bronchiseptica Infection in an Adult Dog\u003c/p\u003e","fulltext":[{"header":"Background","content":"\u003cp\u003eBordetella bronchiseptica (B. bronchiseptica) is one of the most frequent bacteria isolated from the respiratory tract of both healthy and sick dogs \u003csup\u003e(1)\u003c/sup\u003e. It’s documented as one of the most common pathogens that cause canine respiratory infections. It acts as a primary agent or secondary when there are coinfections with other pathogens(Chambers et al. \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e2019\u003c/span\u003e; Canonne et al. \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e2020\u003c/span\u003e; Day et al. \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e2020\u003c/span\u003e; Fastrès et al. \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e2020\u003c/span\u003e; Reagan and Sykes \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e2020\u003c/span\u003e) \u003csup\u003e(1–6)\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eBordetella bronchiseptica infection most commonly presents as an acute-onset, often self-limiting, tracheobronchitis. Clinically, affected dogs may exhibit nasal discharge and coughing. However, a chronic refractory form has also been described, characterized by extension of the infection to the terminal bronchioles and alveoli, leading to a wide range of respiratory signs, from mild-to-severe pneumonia to fatal outcomes(Chambers et al. \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e2019\u003c/span\u003e; Canonne et al. \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e2020\u003c/span\u003e; Day et al. \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e2020\u003c/span\u003e; Fastrès et al. \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e2020\u003c/span\u003e; Reagan and Sykes \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e2020\u003c/span\u003e) \u003csup\u003e(1–6)\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eThe severity of the disease depends on multiple factors, including the virulence of the bacterial strain, bacterial load, immune status of the patient, and pre-existing respiratory tract disorders involving the larynx and trachea. Coinfection with other pathogens, such as Mycoplasma cynos, has been increasingly recognized as an exacerbating factor in B. bronchiseptica infection(Canonne et al. \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e2020\u003c/span\u003e) \u003csup\u003e(6)\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eCytology and bronchoalveolar lavage fluid (BALF) microbiological culture can be used for the diagnosis of B. bronchiseptica infectious respiratory disease. However, those tests may give a false negative result due to the absence of bacteria at the time of the test or because of poor collection technique. The risk of this can be reduced by using more sensitive diagnostic tests for B. bronchiseptica infection, such as BALF polymerase chain reaction (PCR) or the immunohistochemistry test(Canonne et al. \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e2016\u003c/span\u003e) \u003csup\u003e(1,10)\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eRegarding the therapeutic management of B. bronchiseptica infection, eradication may be necessary in cases where it plays a role as the primary pathogen. For these clinical cases the efficacy of systemic antibiotics such as doxycycline or amoxicillin-clavulanic acid has been demonstrated(Lappin et al. \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e2017\u003c/span\u003e; Chambers et al. \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e2019\u003c/span\u003e; Fastrès et al. \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e2020\u003c/span\u003e; Reagan and Sykes \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e2020\u003c/span\u003e) \u003csup\u003e(1–4,11)\u003c/sup\u003e. However, in cases where treatment with systemic antibiotics is partial or failures, the efficacy of inhaled gentamicin as an alternative treatment has been recently documented(Lappin et al. \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e2017\u003c/span\u003e; Canonne et al. \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e2020\u003c/span\u003e; Fastrès et al. \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e2020\u003c/span\u003e) \u003csup\u003e(3,6,11)\u003c/sup\u003e. Additionally, depending on the severity of clinical signs, supportive therapy with anti-inflammatory drugs or even oxygen therapy may be required in more severe cases(Canonne et al. \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e2016\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e2020\u003c/span\u003e; Lappin et al. \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e2017\u003c/span\u003e; Chambers et al. \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e2019\u003c/span\u003e; Jaffey et al. \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e2019\u003c/span\u003e; Day et al. \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e2020\u003c/span\u003e; Fastrès et al. \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e2020\u003c/span\u003e; Reagan and Sykes \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e2020\u003c/span\u003e; Biénès et al. \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2023\u003c/span\u003e) \u003csup\u003e(1–11)\u003c/sup\u003e.\u003c/p\u003e"},{"header":"Case presentation","content":"\u003cp\u003eA 3-year-old, intact male crossbreed dog was presented to the Internal Medicine department of our Veterinary Teaching Hospital with a one-week history of coughing. A five-day history of hyporexia, fever and vomiting were also reported. Routine vaccination and deworming were up to date.\u003c/p\u003e\u003cp\u003eBlood work performed prior to referral showed moderate leucocytosis of 24.2 x 10\u003csup\u003e9\u003c/sup\u003e cells/L (reference range 6.0 x 10\u003csup\u003e9\u003c/sup\u003e to 17.0 x10\u003csup\u003e9\u003c/sup\u003e cells/L) moderate granulocytosis of 20.5 x10\u003csup\u003e9\u003c/sup\u003e cells/L (reference range 4.0 x10\u003csup\u003e9\u003c/sup\u003e to 12.6 x10\u003csup\u003e9\u003c/sup\u003e cells/L), moderate thrombocytopenia of 52 x10\u003csup\u003e9\u003c/sup\u003e (reference range 117 x10\u003csup\u003e9\u003c/sup\u003e – 460 x10\u003csup\u003e9\u003c/sup\u003e U/L) (Table\u0026nbsp;1), and a slight increase in alkaline phosphatase of 151 U/L (range 10 to 125 U/L) and alanine aminotransferase of 326 U/L (refence range 23 to 212 U/L). Treatment before referral included a 7-day course of 5 mg/kg doxycycline per os (po) BID (Ronaxan; Boehringer Ingelheim Animal Health Spain, S.A.U.) and 0.1 mg/kg meloxicam po SID (Metacam; Boehringer Ingelheim Animal Health Spain, S.A.) without clinical improvement. Upon presentation at the hospital, the owner reported the dog had always presented exhibited breathlessness, an increase of respiratory sounds and hacking cough during exercise.\u003c/p\u003e\u003cp\u003ePhysical examination revealed a slight enlargement of the submandibular lymph nodes, a temperature of 39.1ºC, a positive cough reflex and drooling. Cardiothoracic auscultation revealed a stridor, and an increase of breath sounds without heart murmurs or arrhythmias. It also exhibited a dorsal subconjunctival hemorrhage in the left eye. The rest of the physical examination was unremarkable.\u003c/p\u003e\u003cp\u003eThe patient was hospitalized for stabilization and monitoring before undergoing complementary tests. Initial treatments included amoxicilin-clavulanic acid at 20 mg/kg IV TID (Amoxicilina/Ácido clavulánico Normon; Laboratorios Normon, S.A.), 0.1 mg/kg meloxicam iv SID (Meloxidyl; Ceva Sante Animale), 1 mg/kg omeprazole iv BID (Omeprazol Normon; Laboratorios Normon, S.A.), 1.1 mg/kg mirtazapine po SID (Mirtazapina Alter; Laboratorios Alter, S.A.), nebulizations with sterile physiological saline solution (NaCl-0,9 FisioVet, B. Braun Vetcare, S.A.) and coupage. CBC was performed two days after admission to the hospital showing mild non-regenerative anemia 30.9% (range 37.3 to 61.7%), moderate leukocytosis of 26.78 x 10\u003csup\u003e3\u003c/sup\u003e cells/µL (range 5.05 to 16.76 x 10\u003csup\u003e3\u003c/sup\u003e cells/µL) with moderate neutrophilia of 21.63 x 10\u003csup\u003e3\u003c/sup\u003e cells/µL (range 2.95 to 11.64x 10\u003csup\u003e3\u003c/sup\u003e cells/µL) (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e5\u003c/span\u003e), moderate monocytosis of 3.36 x 10\u003csup\u003e3\u003c/sup\u003e cells/µL(range 0.16 to 1.12 x 10\u003csup\u003e3\u003c/sup\u003e cells/µL), and moderate thrombocytopenia of 61 x 10\u003csup\u003e3\u003c/sup\u003e cells/µL (range 148 to 484 x 10\u003csup\u003e3\u003c/sup\u003e cells/µL) (Table\u0026nbsp;1). A blood smear showed a normal platelet count, moderate neutrophilia with a left shift, and mild monocytosis. A rapid test was carried out for the detection of Dirofilaria immitis antigen, antibodies to Anaplasma phagocytophilum, Anaplasma platys, Borrelia burgdorferi, Ehrlichia canis, and Ehrlichia ewingii obtaining negative results. Antibodies against Leishmania infantum were also negative and Angiostrongylus vasorum antigen test was negative. A preliminary cardiac ultrasound showed good cardiac contractility, normal size of the atria and ventricles, no pericardial or pleural effusion, and a moderate number of B-lines.\u003c/p\u003e\u003cp\u003eThoracic radiographs showed a diffuse broncho interstitial pattern and an area of radiopacity cranial to the carina (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Abdominal ultrasound revealed increased thickness of the stomach wall, with maintained stratigraphy. Mild generalized peritoneal reaction and mild reactive cranial and iliac mesenteric lymphadenopathy were also detected.\u003c/p\u003e\u003cp\u003eThoracic computed tomography (CT, 16x0.5 slice spiral CT-scanner, Toshiba Astelion TSX-032A, Toshiba Medical Systems, Ōtawara, Tochigi, Japan) was performed and showed a marked peribronchial alveolar-interstitial pattern in the ventral zone of the cranial and middle right lung lobes with a marked increase in the thickness of the bronchial walls in these lobes, these pulmonary changes were associated with a moderate enlargement of right and central tracheobronchial lymph nodes with heterogeneous contrast attenuation and enhancement, which caused compression of the right aspect of the trachea and the right mainstem bronchus at the level of the carina (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e2\u003c/span\u003e). The left tracheobronchial lymph node was slightly enlarged without contrast enhancement or attenuation abnormalities.\u003c/p\u003e\u003cp\u003eA tracheobronchoscopy was performed under general anaesthesia using a 3 mm flexible video endoscope (Flexible Video Ureteroscope, U41, Zhuhai Mindhao Medical Technology Co., Ltd., Tangjiawan Town, China) and a flexible video endoscope of 5 mm in diameter (Fujinon Corporation, 1-324 Uetake-Cho, Kita-Ku, Saitama-Shi, Saitama, Japan). It was observed that although the proximal trachea did not present macroscopic alterations, at the level of the distal trachea there was a loss of continuity of the tracheal cartilages. The distal trachea was narrowed by 50%. This narrowing was caused by a mass effect coming from the dorsal tracheal muscle (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e3\u003c/span\u003e). This mass, or infiltrative process, extended towards the right cranial bronchus and right caudal bronchus, partially occluding the lumen of these two bronchi. In addition, marked accumulation of dense purulent-looking liquid was observed in the right cranial bronchus. The left main bronchi presented bronchomalacia. Brush cytology and biopsy samples of the tracheal mass were collected, and a BALF was performed and submitted for microbiological culture and RT-qPCR tests of B. bronchiseptica DNA and Mycoplasma cynos DNA (IDEXX Laboratories, Inc., Spain).\u003c/p\u003e\u003cp\u003eThe cytology of the mass showed a moderate number of neutrophils with characteristics of degeneration together with normal cells of the respiratory epithelium with intra and extracellular bacteria, consistent with a septic inflammatory process. The cytology of the BALF was consistent with an inflammatory non- septic process. Biopsy of the tracheal mass showed severe ulcerative and suppurative fibrinous tracheitis, with no evidence of neoplasia. Special histochemical stains did not detect fungal agents. No growth of bacteria or yeast was obtained from the BALF culture, however, the PCR was positive for B.bronchiseptica and negative to Mycoplasma cynos.\u003c/p\u003e\u003cp\u003eAfter five days of hospitalization with the treatment prescribed since admission, the patient was stabilized, and it was discharged with 20 mg/kg amoxicillin-clavulanic acid po BID (Eupenclav, Laboratorios Normon, S.A.), 3 mg/kg marbofloxacin po SID (Marvovet, Fatro Ibérica, S.L.), 250 micrograms of inhaled fluticasone BID (Flixotide, GlaxoSmithKline, S.A.), and physiological saline solution nebulization (NaCl 0,9 FisioVet, B. Braun Vetcare, S.A.). Seven days after discharge from the hospital the patient was brighter but continued with cough and exercise intolerance persisted. Follow up thoracic radiographs showed a slight improvement in the broncho interstitial pattern and a decrease in size of the radiopacity located cranial to the carina. CBC results showed resolution of the anemia with a hematocrit of 39.3% (range 37.3 to 61.7%), but there was a mild leucocytosis of 18.76 x 10\u003csup\u003e3\u003c/sup\u003e cells/µL (range 5.05 to 16.76 x 10\u003csup\u003e3\u003c/sup\u003e cells/µL) with slight neutrophilia of 13.93 x 10\u003csup\u003e3\u003c/sup\u003e cells/µL (range 2.95 to 11.64 x 10\u003csup\u003e3\u003c/sup\u003e cells/µL) (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e5\u003c/span\u003e), and moderate monocytosis of 3.32 (range 0.16–1.12 x 10\u003csup\u003e3\u003c/sup\u003e cells/µL) (Table\u0026nbsp;1). Inhaled gentamicine at 200 mg BID (Genta-gobens, Laboratorios Normon S.A.) and prednisolone at 0.5 mg/kg po SID (Prednicortone, Dechra Regulatory B.V.) were added to the treatment.\u003c/p\u003e\u003cp\u003eTable 1: evolution of principal Complete Blood Count (CBC) parameters.\u0026nbsp;\u003c/p\u003e\u003cdiv class=\"gridtable\"\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=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003ctable float=\"No\" id=\"Taba\" border=\"1\"\u003e\u003ccolgroup cols=\"5\"\u003e\u003c/colgroup\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCBC 2 days before referral\u003c/p\u003e \u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eCBC 2 days after referral\u003c/p\u003e \u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eCBC 9 days before referral\u003c/p\u003e \u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eCBC 37 days before referral\u003c/p\u003e \u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHematocrit (range 37.3–61.7%)\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e39.2%\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e30.9%\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e39.3%\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e39.6%\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLeucocytes (range 5.05 to 16.76 x 10\u003csup\u003e3\u003c/sup\u003e cells/µL)\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e24.20 x 10\u003csup\u003e3\u003c/sup\u003e cells/µL\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e26.78 x 10\u003csup\u003e3\u003c/sup\u003e cells/µL\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e18.76 x 10\u003csup\u003e3\u003c/sup\u003e cells/µL\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e11.70 x 10\u003csup\u003e3\u003c/sup\u003e cells/µL\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNeutrophils (range 2.95 to 11.64 x 10\u003csup\u003e3\u003c/sup\u003e cells/µL)\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e20.5 x 10\u003csup\u003e3\u003c/sup\u003e cells/µL\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e21.63 x 10\u003csup\u003e3\u003c/sup\u003e cells/µL\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e13.93 x 10\u003csup\u003e3\u003c/sup\u003e cells/µL\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e8.89 x 10\u003csup\u003e3\u003c/sup\u003e cells/µL\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/table\u003e\u003c/div\u003e\u003cp\u003eThe patient's respiratory signs markedly improved four days after the new treatment was started. Coughing episodes stopped, and exercise intolerance improved. Pulmonary auscultation was normal, the tracheal pinch was negative, and the dog was normothermic. Additionally, the subconjunctival haemorrhage had resolved.\u003c/p\u003e\u003cp\u003eFollow-up thoracic radiographs were performed revealing a dramatic improvement in the lung pattern, with only a mild, generalized bronchial pattern remaining. The tracheal diameter was back to normality (Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e4\u003c/span\u003e). At this moment, oral antibiotics were withdrawn, having taken 16 days of 20 mg/kg amoxicillin-clavulanic acid po BID (Eupenclav, Laboratorios Normon, S.A.), and 11 days of 3 mg/kg marbofloxacin po SID (Marvovet, Fatro Ibérica S.L.). Inhaled gentamicin at 200 mg BID (Genta-gobens, Laboratorios Normon S.A.), and fluticasone, 250 micrograms BID (Flixotide, GlaxoSmithKline, S.A.), were maintained. Oral corticosteroids were gradually withdrawn as 0.5 mg/kg prednisolone po q 48 hours for 7 days and then treatment was stopped (Prednicortone, Dechra Regulatory B.V.).\u003c/p\u003e\u003cp\u003eOne month after starting treatment with inhaled gentamicin, 200 mg BID (Genta gobens, Laboratorios Normon S.A.), the patient showed complete clinical remission. CBC (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e5\u003c/span\u003e, Table\u0026nbsp;1) and thoracic radiographs had normalized, so the medical treatment was discontinued. A follow-up tracheobronchoscopy was suggested, but the owner declined it due to the resolution of clinical signs.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eBordetella bronchiseptica infection, has been reported to induce clinical signs such as chronic cough or dyspnoea(Chambers et al. \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e2019\u003c/span\u003e; Canonne et al. \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e2020\u003c/span\u003e; Day et al. \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e2020\u003c/span\u003e; Fastr\u0026egrave;s et al. \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e2020\u003c/span\u003e; Reagan and Sykes \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e2020\u003c/span\u003e) \u003csup\u003e(1,6)\u003c/sup\u003e. Pulmonary changes such as fibrosis or bronchiolitis have been reported(Jaffey et al. \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e2019\u003c/span\u003e) \u003csup\u003e(9)\u003c/sup\u003e. In this case, although B. bronchiseptica is a common pathogen of the respiratory tract of dogs, no other pathogens were detected by histopathology, thoracic computed tomographymicrobiological culture or PCR that could explain the clinical signs. To the authors\u0026rsquo; knowledge, this is the first case report of a tracheal granuloma secondary to B. bronchiseptica infection.\u003c/p\u003e \u003cp\u003eThe patient presented a subconjunctival hemorrhage not associated with ocular trauma or coagulopathies. A possible cause of this process is the rupture of vessels due to chronic coughing(Mimura et al. \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e2017\u003c/span\u003e; Parikh et al. \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e2022\u003c/span\u003e) \u003csup\u003e(13,14)\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eIn this case, the cytology of the BALF did not show intracellular microorganisms, but the brush cytology of the tracheal mass was consistent with a septic inflammatory process. This could be due to the fact that brushing procedures offer a greater number of ciliated cells from the tracheobronchial epithelium in contrast to samples collected by BALF(Canonne et al. \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e2016\u003c/span\u003e) \u003csup\u003e(10)\u003c/sup\u003e. The pathogen was not detected in the histopathological study of the tracheal lesion. This could be due to the presence of a low bacterial load at the time of sample collection, which may have been influenced by prior use of systemic antibiotics to which B bronchiseptica is sensitive(Lappin et al. \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e2017\u003c/span\u003e; Chambers et al. \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e2019\u003c/span\u003e; Fastr\u0026egrave;s et al. \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e2020\u003c/span\u003e; Reagan and Sykes \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e2020\u003c/span\u003e) \u003csup\u003e(1\u0026ndash;4,11)\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eAccording to a study published in ACVIM in 2016, the most sensitive test for B. bronchiseptica is the quantitative PCR of the BALF since numerous cases have been described in which this test was positive even on occasions in which the microbiological culture and the histopathological tests were negative(Canonne et al. \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e2016\u003c/span\u003e) \u003csup\u003e(10)\u003c/sup\u003e. In this case, the diagnosis was confirmed by positive quantitative PCR of B. bronchiseptica DNA in BALF.\u003c/p\u003e \u003cp\u003eThere are antimicrobials to which B. bronchiseptica colonies isolated in vitro are sensitive, and when administered systemically, they may not be as effective. This may be because these antibiotics do not reach effective therapeutic concentrations on the apical surfaces of the bronchial epithelium. B. bronchiseptica adherence to cilia induces ciliostasis, biofilm formation, and local immunosuppression in the tracheal and bronchial epithelium(Canonne et al. \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e2020\u003c/span\u003e) \u003csup\u003e(6)\u003c/sup\u003e. This fact would explain the lack of remission of clinical signs and radiographic findings in this dog. In the consulted literature there are three publications(Canonne et al. \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e2020\u003c/span\u003e; Bi\u0026eacute;n\u0026egrave;s et al. \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2023\u003c/span\u003e) \u003csup\u003e(6\u0026ndash;8)\u003c/sup\u003e that have demonstrated the efficacy of inhaled gentamicin for the treatment of upper respiratory tract infections caused by aminoglycoside-sensible bacteria in dogs. In fact, two of them(Canonne et al. \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e2020\u003c/span\u003e) \u003csup\u003e(6,8)\u003c/sup\u003e had described the efficacy of inhaled gentamicin against B. bronchiseptica respiratory infection in dogs, which is why the treatment with inhaled gentamicin at 200 mg q 12 hours (Genta-gobens, Laboratorios Normon S.A.) was initiated. Complete remission of respiratory signs was achieved one month after starting this inhaled treatment.\u003c/p\u003e \u003cp\u003eIt would have been interesting to repeat the bronchoscopy and correlate it with the follow-up thoracic radiographs; however, given the excellent clinical progress, the owner declined.\u003c/p\u003e \u003cp\u003eIt must not forget that B. bronchiseptica can be the cause of acquired pneumonia in human immunocompromised patients(Baptista et al. \u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e2020\u003c/span\u003e) \u003csup\u003e(15)\u003c/sup\u003e, likely due to close contact with infected animals. Though an early diagnosis of these cases may be necessary to establish an adequate treatment as soon as possible to avoid zoonotic transmission.\u003c/p\u003e \u003cp\u003eTo the authors\u0026rsquo; knowledge this is the first documented case of a tracheal granuloma induced by B. bronchiseptica in a dog. What makes this case report even more interesting is that it achieved a complete resolution of clinical signs and granuloma by using inhaled gentamicin.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e \u003ch2\u003eConflict of interest statement:\u003c/h2\u003e \u003cp\u003eThe authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported.\u003c/p\u003e \u003c/p\u003e\u003ch2\u003eFunding Statement:\u003c/h2\u003e \u003cp\u003eThe authors received no specific funding for this work.\u003c/p\u003e \u003cp\u003eData availability statement: The data that support the findings of this study are not openly available and are available from the corresponding author upon reasonable request.\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003ePablo Ag\u0026uuml;era-Espejo: writing, editing of manuscript.Guadalupe Mir\u0026oacute;: editing and review of manuscript.Jos\u0026eacute; Luis Fontalba-Navas: editing and review of manuscript.Sabela Atencia: case management, editing and final review of manuscript.\u003c/p\u003e\u003ch2\u003eAcknowledgement\u003c/h2\u003e\u003cp\u003eAcknowledgments to the diagnostic imaging department of AniCura Vetsia Veterinary Hospital forall their help during the writing of this case report.\u003c/p\u003e\u003cp\u003eEthics statements:\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe authors confirm that the ethical policies of the journal, as noted on the journal\u0026rsquo;s author guidelines page, have been adhered to.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eBaptista RJIR, Costa JM de SS da, Badura RA (2020) Severe cavitary pneumonia caused by Bordetella bronchiseptica in an HIV-infected patient. Enfermedades Infecc y Microbiol Cl\u0026iacute;nica 38:404\u0026ndash;405. https://doi.org/10.1016/j.eimc.2020.02.014\u003c/li\u003e\n\u003cli\u003eBi\u0026eacute;n\u0026egrave;s T, Lyssens A, Machiels H, et al (2023) Intranasal and Serum Gentamicin Concentration: Comparison of Three Topical Administration Protocols in Dogs. Vet Sci 10:490. https://doi.org/10.3390/vetsci10080490\u003c/li\u003e\n\u003cli\u003eCanonne AM, Billen F, Tual C, et al (2016) Quantitative PCR and Cytology of Bronchoalveolar Lavage Fluid in Dogs with Bordetella bronchiseptica Infection. J Vet Intern Med 30:1204\u0026ndash;1209. https://doi.org/10.1111/jvim.14366\u003c/li\u003e\n\u003cli\u003eCanonne AM, Roels E, Menard M, et al (2020) Clinical response to 2 protocols of aerosolized gentamicin in 46 dogs with Bordetella bronchiseptica infection (2012‐2018). J Vet Intern Med 34:2078\u0026ndash;2085. https://doi.org/10.1111/jvim.15843\u003c/li\u003e\n\u003cli\u003eChambers JK, Matsumoto I, Shibahara T, et al (2019) An Outbreak of Fatal Bordetella bronchiseptica Bronchopneumonia in Puppies. J Comp Pathol 167:41\u0026ndash;45. https://doi.org/10.1016/j.jcpa.2018.12.002\u003c/li\u003e\n\u003cli\u003eDay MJ, Carey S, Clercx C, et al (2020) Aetiology of Canine Infectious Respiratory Disease Complex and Prevalence of its Pathogens in Europe. J Comp Pathol 176:86\u0026ndash;108. https://doi.org/10.1016/j.jcpa.2020.02.005\u003c/li\u003e\n\u003cli\u003eFastr\u0026egrave;s A, Canonne MA, Taminiau B, et al (2020) Analysis of the lung microbiota in dogs with Bordetella bronchiseptica infection and correlation with culture and quantitative polymerase chain reaction. Vet Res 51:46. https://doi.org/10.1186/s13567-020-00769-x\u003c/li\u003e\n\u003cli\u003eJaffey JA, Harmon M, Masseau I, et al (2019) Presumptive Development of Fibrotic Lung Disease From Bordetella bronchiseptica and Post-infectious Bronchiolitis Obliterans in a Dog. Front Vet Sci 6:352. https://doi.org/10.3389/fvets.2019.00352\u003c/li\u003e\n\u003cli\u003eLappin MR, Blondeau J, Boothe D, et al (2017) Antimicrobial use Guidelines for Treatment of Respiratory Tract Disease in Dogs and Cats: Antimicrobial Guidelines Working Group of the International Society for Companion Animal Infectious Diseases. J Vet Intern Med 31:279\u0026ndash;294. https://doi.org/10.1111/jvim.14627\u003c/li\u003e\n\u003cli\u003eMimura T, Noma H, Yamagami S (2017) Letter to the Editor: Bilateral Subconjunctival Hemorrhage in a 3-Year-Old Girl with Mycoplasma Pneumonia. Open Ophthalmol J 11:322\u0026ndash;325. https://doi.org/10.2174/1874364101711010322\u003c/li\u003e\n\u003cli\u003eParikh AO, Christian CW, Forbes BJ, Binenbaum G (2022) Prevalence and Causes of Subconjunctival Hemorrhage in Children. Pediatr Emerg Care 38:e1428\u0026ndash;e1432. https://doi.org/10.1097/pec.0000000000002795\u003c/li\u003e\n\u003cli\u003eReagan KL, Sykes JE (2020) Canine Infectious Respiratory Disease. Vet Clin North Am: Small Anim Pr 50:405\u0026ndash;418. https://doi.org/10.1016/j.cvsm.2019.10.009\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Bordetella bronchiseptica, bacterial diseases, tracheal granuloma, infection, PCR, inhaled gentamicin","lastPublishedDoi":"10.21203/rs.3.rs-6636613/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6636613/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eA 3-year-old male entire crossbreed dog was presented to the Internal Medicine Department with a one-week history of coughing. Pre-referral blood work revealed moderate leukocytosis, thrombocytopenia, and a mild increase in transaminase levels. Prior treatment with doxycycline and meloxicam did not result in clinical improvement.\u003c/p\u003e \u003cp\u003eThoracic computed tomography demonstrated marked bronchial wall thickening and moderate enlargement of the tracheobronchial lymph nodes, leading to compression of the trachea and right mainstem bronchus at the carina level. Tracheobronchoscopy identified narrowing of the distal trachea due to a mass effect originating from the tracheal muscle. Polymerase chain reaction (PCR) analysis of bronchoalveolar lavage fluid confirmed Bordetella bronchiseptica infection.\u003c/p\u003e \u003cp\u003eSystemic antibiotic therapy failed to resolve clinical signs. However, complete clinical and radiological resolution was achieved following a one-month treatment course with inhaled gentamicin.\u003c/p\u003e \u003cp\u003eAt the time of writing, two years later, the dog is still alive and free of respiratory signs.\u003c/p\u003e","manuscriptTitle":"Medical Resolution of a Tracheal Granuloma Caused by Bordetella Bronchiseptica Infection in an Adult Dog","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-05-27 17:53:15","doi":"10.21203/rs.3.rs-6636613/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"d057ca05-c951-4b75-8b2f-21af43e9494d","owner":[],"postedDate":"May 27th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-09-06T23:38:11+00:00","versionOfRecord":[],"versionCreatedAt":"2025-05-27 17:53:15","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-6636613","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6636613","identity":"rs-6636613","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}