When Pneumonia is One-Sided: A Rare Unilateral Progressive Pneumocystis jirovecii Pneumonia Case

When Pneumonia is One-Sided: A Rare Unilateral Progressive Pneumocystis jirovecii Pneumonia Case | 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 When Pneumonia is One-Sided: A Rare Unilateral Progressive Pneumocystis jirovecii Pneumonia Case Mangsuer Nuermaimaiti, Bo Liu, Li Jiang This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8524345/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 Objective: To report a case of Pneumocystis jirovecii Pneumonia (PJP) characterized by predominant unilateral pulmonary infiltration, and to explore its pathogenic specificity and clinical management in combination with airway structural abnormalities.​ Methods: We retrospectively analyzed the clinical data of a post-renal transplantation patient with PJP admitted to Xuanwu Hospital, Capital Medical University, including medical history, imaging features, etiological results, treatment process and prognosis. A hypothesis regarding the pathogenic mechanism was proposed based on airway examination findings.​ Results: A 60-year-old male with a 1-year history of renal transplantation and long-term immunosuppressant use was admitted due to "cough and expectoration for 2 weeks". Admission CT showed severe exudation in the right lung and left lower lobe, which was confined to the right lung. Bronchoscopy revealed left airway stenosis, and next-generation sequencing (NGS) of bronchoalveolar lavage fluid (BALF) detected Pneumocystis jirovecii and two viruses. Despite immunosuppressant withdrawal and targeted anti-infective therapy, the patient developed type I respiratory failure. After ineffective treatment with prone position ventilation, tracheal intubation, mechanical ventilation and nitric oxide (NO) inhalation, venovenous extracorporeal membrane oxygenation (VV-ECMO) was initiated for 25 days. Multiple imaging examinations during treatment consistently showed that the lesion was mainly in the right lung, with slow progression of exudation in the left lung.​ Conclusion: This PJP case presented with rare unilateral infiltration progression. Left airway stenosis may interfere with the pathogenic process of pathogens through airway hydrodynamic changes, providing a new perspective for PJP pathogenesis research.​ Pneumocystis jirovecii Pneumonia Unilateral Pulmonary Infiltration Airway Stenosis Hydrodynamics Renal Transplantation Figures Figure 1 Figure 2 Figure 3 Introduction Pneumocystis jirovecii Pneumonia (PJP) is a common opportunistic infection in immunocompromised populations, particularly prevalent in patients with AIDS and organ transplant recipients 1-3 . The typical imaging manifestation of PJP is bilateral diffuse interstitial infiltration, presenting a "ground-glass" pattern spreading from the hilum to the periphery 1-2, 4 . Unilateral pulmonary involvement is extremely rare, with only a few cases reported in the literature. Herein, we report a case of PJP with predominant unilateral progression in a post-renal transplantation patient, and discuss the potential association between airway stenosis and unilateral lesion distribution, aiming to provide insights into the diagnosis and pathogenesis of atypical PJP 5 . Case Presentation Demographic and Clinical History A 60-year-old male patient with a history of renal transplantation for more than 1 year was admitted to Xuanwu Hospital, Capital Medical University on November 4, 2024, with the chief complaint of "cough and expectoration for 2 weeks". He had been taking oral immunosuppressants regularly since transplantation (specific drugs and doses were unavailable). During the course, he had no fever or chest pain, with normal mental state, appetite, bowel movements and urine output, and no significant weight change. Admission Examination Physical Examination: Temperature 36.5℃, pulse 88 beats/min, respiratory rate 20 breaths/min, blood pressure 130/80 mmHg, oxygen saturation 92% (room air). Coarse breath sounds were heard in both lungs, with moist rales in the right lung and slightly weakened breath sounds in the left lung. No obvious abnormalities were found in cardiac and abdominal examinations. Auxiliary Examinations: Chest CT ( Supplementary material-Video 1 ) showed severe exudation in the right lung and left lower lobe, which was confined to the right lung, suggesting pneumonia. Blood routine: White blood cell count 8.2×10⁹/L, neutrophil ratio 75%, lymphocyte ratio 18%, C-reactive protein 65 mg/L, procalcitonin 0.3 ng/mL.Liver and kidney function, electrolytes were basically normal. Clinical Course and Management On November 4, 2024, empirical anti-infective therapy (specific drugs unavailable) was initiated after admission. Bronchoscopy was performed on November 5, which revealed a large amount of white viscous secretions in the dorsal segment and basal segment of the right lower lobe. BALF was collected from the right upper lobe, right middle lobe and right lower lobe for culture, NGS, pathology and rapid on-site evaluation (ROSE). Meanwhile, left airway stenosis was found ( Pic 1 ), and previous biopsy had excluded tumor. On November 6, BALF NGS results showed Pneumocystis jirovecii (1250 sequences) and two types of viruses (specific virus types and sequence counts see Pic 2 ). Combined with the patient's immunosuppressive status and etiological results, the diagnosis of PJP complicated with viral infection was confirmed. Immunosuppressants were immediately discontinued, and targeted anti-infective therapy with trimethoprim-sulfamethoxazole (specific dose unavailable) was initiated. On November 7, the patient developed decreased oxygen saturation, dropping to 88% (nasal catheter oxygen inhalation 3 L/min). Arterial blood gas analysis indicated type I respiratory failure (pH 7.45, PaCO₂ 32 mmHg, PaO₂ 58 mmHg, FiO₂ 0.29). He was transferred to the intensive care unit (ICU) with a diagnosis of severe pneumonia and acute respiratory distress syndrome. Bed rest and awake prone position ventilation were given. Oxygenation improved more significantly when in right high position during prone ventilation, but the patient had poor activity tolerance, with dyspnea and SpO₂ dropping to 80% after activities such as eating. On November 9, the patient's oxygen saturation continued to decrease to 75% after activity, accompanied by cyanosis of the lips. Tracheal intubation and mechanical ventilation were performed (mode: PCV, PEEP 12 cmH₂O, FiO₂ 0.8), and prone position ventilation was continued. Twenty-four hours later, oxygenation improved insignificantly (P/F ratio only about 150 mmHg). NO inhalation (5 ppm) was added to improve V/Q ratio, but hypoxemia and hypercapnia still could not be corrected. Bedside chest X-ray (Pic 3 ) showed progression of right lung exudation. VV-ECMO support was initiated on the same day (mode: VV, blood flow 4.5 L/min, FiO₂ 0.7). On November 11, follow-up chest CT ( Supplementary material-Video 2 ) showed significant progression of exudation in the right lung and left lower lobe. Under ECMO support, lung-protective ventilation strategy was implemented (VT 6 ml/kg, PEEP 10 cmH₂O). Respiratory mechanics were measured daily to evaluate lung compliance. Prone position ventilation and bronchoscopic sputum drainage were performed daily, and BALF etiological testing was dynamically monitored to guide antibiotic adjustment. During treatment, the patient's lung compliance gradually improved. Repeated chest CT ( Supplementary material-Video 3 , the last scan before VV-ECMO withdrawal) showed reduced exudation in the right lung, no progression of exudation in the left lung, and the lesion remained mainly confined to the right lung. VV-ECMO was operated continuously for 25 days without adverse events such as bleeding, ECMO circuit or oxygenator coagulation failure. On December 5, 2024, a 24-hour spontaneous breathing trial (SBT) was performed and passed, followed by VV-ECMO withdrawal. Mechanical ventilation was continued, and respiratory mechanics measurement showed significant improvement in lung compliance. On December 10, 2024, follow-up chest CT ( Supplementary material-Video 4 ) showed significant improvement of right lung exudation, a small amount of exudation in the left lower lobe (improved compared with previous), and no obvious progression of exudation in the left lung. Discussion Pneumocystis jirovecii Pneumonia (PJP) remains a life-threatening opportunistic infection in immunocompromised populations, particularly among solid organ transplant recipients, where it contributes significantly to post-transplant morbidity and mortality 1-3 . Although the typical radiographic appearance of PJP is that of a bilateral alveolar-interstitial pattern, atypical radiographic presentations occur. These include unilateral disease, focal lesions and normal chest radiographic findings 6 . Atypical radiographic findings occur more commonly in patients with the acquired immunodeficiency syndrome and those with prior radiotherapy to the lungs 7 . The radiographic presentation of this patient was unique in a series of 186 cases of P carinii pneumonia in immunosuppressed pediatric oncology patients seen at this institution through 1986. Only two previous patients had unilateral disease, which rapidly evolved into bilateral radiographic findings 7 . The present case highlights the diagnostic and therapeutic challenges posed by atypical PJP, as it deviated markedly from the classic clinical and radiological phenotype. While bilateral diffuse interstitial infiltrates with a "ground-glass" pattern are the hallmark of PJP 8-9 , this patient exhibited persistently unilateral-predominant lung involvement—a highly atypical presentation with only sporadic cases documented in the literature 9-10 . Notably, from initial admission through disease progression and eventual recovery, lesions remained concentrated in the right lung and left lower lobe, with minimal progression in the left upper lobe—a distribution that correlated with structural airway abnormalities identified intraoperatively. Bronchoscopy revealed pre-existing stenosis of the left mainstem airway and relative narrowing of the left upper lobe ostium, with prior biopsy excluding malignant etiology. This anatomical finding prompted our investigation into its potential role in shaping lesion distribution 11 . To contextualize this observation, we draw an analogy between airway airflow and fluid dynamics in constricted channels: airflow is analogous to water flow, and P. jirovecii (and co-infecting viruses) to suspended particles (e.g., sand). Guided by the sedimentation principles outlined in Kenneth J et al.’s Physical Principles of Sedimentology (1989) 12-13 , regions of elevated flow velocity generate increased kinetic energy, preventing particle sedimentation. In constricted airways, abrupt luminal narrowing accelerates airflow, inducing turbulence and eddy currents that further hinder particle deposition 5 . Applying this framework to our patient, the stenotic left mainstem and left upper lobe airways likely created a high-velocity, turbulent airflow environment, limiting pathogen adhesion and colonization on the left lung mucosa. Conversely, the unobstructed right lung experienced relatively uniform, low-turbulence airflow, facilitating P. jirovecii (colonization), proliferation, and subsequent inflammatory exudation—consistent with the radiological predominance of right-sided lesions. This hydrodynamic hypothesis adds a novel dimension to our understanding of PJP pathogenesis, which is traditionally attributed to immune deficiency-driven unchecked pathogen replication 11 . However, we acknowledge critical limitations to this proposal: we did not perform computational fluid dynamics simulations to quantify airflow patterns in the stenotic airways, nor did we conduct site-specific pathogen quantification (e.g., quantitative PCR of BALF from left vs. right lobes) to directly link airflow dynamics to colonization density. Such experiments would be essential to validate the causal relationship between airway stenosis, hydrodynamic changes, and unilateral lesion distribution. Beyond pathogenesis, this case underscores the transformative role of advanced diagnostic and supportive care technologies in managing severe PJP. Metagenomic next-generation sequencing (mNGS) of bronchoalveolar lavage fluid (BALF) rapidly identified P. jirovecii (1250 sequences) and co-infecting viruses—an achievement that traditional staining or culture methods might have delayed 14 . This timely diagnosis was critical for discontinuing immunosuppressants and initiating targeted trimethoprim-sulfamethoxazole therapy 4 . For refractory hypoxemia due to acute respiratory distress syndrome (ARDS), venovenous extracorporeal membrane oxygenation (VV-ECMO) emerged as a life-saving intervention. After failing conventional measures (prone ventilation, nitric oxide inhalation), 25 days of VV-ECMO support—combined with lung-protective ventilation and daily bronchoscopic drainage—improved lung compliance and facilitated successful weaning, aligning with recent evidence that ECMO improves outcomes in severe PJP unresponsive to standard respiratory support 15 . Several limitations of this case report merit consideration. First, the etiology of left airway stenosis (congenital vs. acquired, e.g., post-inflammatory or iatrogenic) remains unclear due to the absence of pre-transplant imaging or longitudinal airway assessments. Second, the hydrodynamic hypothesis lacks direct experimental validation and is not yet supported by existing PJP literature, though analogous mechanisms have been described in other airway infections 5 . Third, incomplete documentation of immunosuppressant regimens (e.g., tacrolimus trough levels, steroid doses) and anti-infective drug dosing limits our ability to correlate pharmacotherapy with disease progression and response. Finally, we did not perform serial pathogen testing to assess how therapeutic interventions impacted P. jirovecii burden in relation to airway airflow dynamics. Conclusion This case reports a rare post-renal transplantation PJP with predominant unilateral pulmonary infiltration. Left airway stenosis may affect the pathogenic process of pathogens through airway hydrodynamic changes, providing a new perspective for PJP pathogenesis research. NGS is beneficial for early etiological diagnosis, and VV-ECMO combined with comprehensive treatment measures has important therapeutic value for severe patients. Abbreviations ARDS : Acute Respiratory Distress Syndrome BALF : Bronchoalveolar Lavage Fluid CT : Computed Tomography FiO₂ : Fraction of Inspired Oxygen ICU : Intensive Care Unit mNGS : Metagenomic Next-Generation Sequencing NGS : Next-Generation Sequencing NO : Nitric Oxide PaCO₂ : Partial Pressure of Carbon Dioxide PaO₂ : Partial Pressure of Oxygen PCV : Pressure Controlled Ventilation PEEP : Positive End-Expiratory Pressure PJP : Pneumocystis jirovecii Pneumonia P/F ratio : PaO₂/FiO₂ ratio SBT : Spontaneous Breathing Trial VV-ECMO : Venovenous Extracorporeal Membrane Oxygenation VT : Tidal Volume Declarations Conflicts of Interest Statement The authors declare that they have no known competing financial interests or personal relationships that could have influenced the work reported in this paper. This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. All authors confirm that there are no conflicts of interest regarding the publication of this manuscript, including but not limited to consulting fees, honoraria, stock ownership, research funding from pharmaceutical companies related to the medications or devices discussed in this case report. The authors have no affiliations with or involvement in any organization or entity with a financial interest in the subject matter or materials discussed in this manuscript. Funding Statement This work was supported by the Beijing Natural Science Foundation-Haidian Original Innovation Joint Fund project (No. L222019) and Training Fund for Open Projects at Clinical Institutes and Departments of Capital Medical University (No. CCMU2023ZKYXY012). Consent to Publish Written informed consent was obtained from the patient for the publication of this case report, including all clinical details, imaging studies, and associated medical information. The patient was informed that anonymized data would be publicly accessible and has provided explicit permission for its use in this publication. A copy of the written consent form is available for review by the Editor-in-Chief of the journal if required. All potentially identifying information (name, exact dates, medical record numbers) has been removed or anonymized to protect patient privacy. References Stringer JR BCMR. A new name for Pneumocystis carinii. Emerg Infect Dis 2002;8(9):891-896 Rogina P, Skvarc M. Diagnostic accuracy of (1-->3)-beta-D-glucan to predict Pneumocystis jirovecii pneumonia in non-HIV-infected patients. Radiol Oncol 2020;54(2):221-226.doi: 10.2478/raon-2020-0028.PubMed: 32463392 Walzer PD EJBJ. Pneumocystis carinii pneumonia. New Engl J Med 1973;288(17):869-878 Maertens J CADG. ECIL-8 guidelines for diagnosis, prevention, and treatment of Pneumocystis jirovecii pneumonia in haematology patients and stem cell transplant recipients. J Antimicrob Chemoth 2022;77(11):3059-3074 de Boer AS VDVD. Airway stenosis and microbial colonization: implications for pulmonary infection pathogenesis. Eur Respir Rev 2023;32(168) Friedman BA, Wenglin BD, Hyland RN, Rifkind D. Roentgenographically atypical Pneumocystis carinii pneumonia. Am Rev Respir Dis 1975;111(1):89-96.doi: 10.1164/arrd.1975.111.1.89.PubMed: 163066 Barrio JL, Suarez M, Rodriguez JL, Saldana MJ, Pitchenik AE. Pneumocystis carinii pneumonia presenting as cavitating and noncavitating solitary pulmonary nodules in patients with the acquired immunodeficiency syndrome. Am Rev Respir Dis 1986;134(5):1094-6.doi: 10.1164/arrd.1986.134.5.1094.PubMed: 3490810 Limper AH SSJS. Pneumocystis pneumonia. Lancet 2019;394(10212):2083-2092 Springsted E GBKV. Pneumocystis jirovecii pneumonia in newly diagnosed treatment-naïve chronic lymphocytic leukaemia. Bmj Case Rep 2021;14(6).doi: 10.1136/bcr-2021-2418888 Vieu Jean S MAHD. Pneumocystis jirovecii pneumonia in patients with inflammatory bowel disease–a case series. J Crohns Colitis 2023;17(4):472-479.doi: 10.1093/ecco-jcc/jjac153 Kovacs JA HGLA. Pneumocystis jirovecii: from bench to bedside. Nat Rev Microbiol 2018;16(12):747-762 Hsü KJ, Hsü KJ. Physics of sedimentology :textbook and reference 2nd ed. ed. Berlin: Springer; 2004. Hsü KJ. Physical principles of sedimentology :a readable textbook for beginners and experts. Berlin: Springer-Verlag; 1989. Li XF LZYJ. Diagnostic performance of metagenomic next-generation sequencing for Pneumocystis jirovecii pneumonia. Bmc Infect Dis 2022;22(1).doi: 10.1186/s12879-022-07065-x Rahman NM BRMA. Veno-venous ECMO for Pneumocystis jirovecii pneumonia: a systematic review and meta-analysis. Intens Care Med 2023;49(8):951-962 Additional Declarations No competing interests reported. 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09:55:49","extension":"pdf","order_by":5,"title":"","display":"","copyAsset":false,"role":"supplement","size":89041,"visible":true,"origin":"","legend":"","description":"","filename":"Pic2TranslationNotes.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8524345/v1/fbf6f3bd8ccbd4a71d217099.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"When Pneumonia is One-Sided: A Rare Unilateral Progressive Pneumocystis jirovecii Pneumonia Case","fulltext":[{"header":"Introduction","content":"\u003cp\u003ePneumocystis jirovecii Pneumonia (PJP) is a common opportunistic infection in immunocompromised populations, particularly prevalent in patients with AIDS and organ transplant recipients\u003csup\u003e1-3\u003c/sup\u003e. The typical imaging manifestation of PJP is bilateral diffuse interstitial infiltration, presenting a \u0026quot;ground-glass\u0026quot; pattern spreading from the hilum to the periphery\u003csup\u003e1-2, 4\u003c/sup\u003e. Unilateral pulmonary involvement is extremely rare, with only a few cases reported in the literature. Herein, we report a case of PJP with predominant unilateral progression in a post-renal transplantation patient, and discuss the potential association between airway stenosis and unilateral lesion distribution, aiming to provide insights into the diagnosis and pathogenesis of atypical PJP\u003csup\u003e5\u003c/sup\u003e.\u003c/p\u003e\n"},{"header":"Case Presentation","content":"\u003cp\u003e\u003cstrong\u003eDemographic and Clinical History\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eA 60-year-old male patient with a history of renal transplantation for more than 1 year was admitted to Xuanwu Hospital, Capital Medical University on November 4, 2024, with the chief complaint of \u0026quot;cough and expectoration for 2 weeks\u0026quot;. He had been taking oral immunosuppressants regularly since transplantation (specific drugs and doses were unavailable). During the course, he had no fever or chest pain, with normal mental state, appetite, bowel movements and urine output, and no significant weight change.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAdmission Examination\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003ePhysical Examination: Temperature 36.5℃, pulse 88 beats/min, respiratory rate 20 breaths/min, blood pressure 130/80 mmHg, oxygen saturation 92% (room air). Coarse breath sounds were heard in both lungs, with moist rales in the right lung and slightly weakened breath sounds in the left lung. No obvious abnormalities were found in cardiac and abdominal examinations.\u003c/p\u003e\n\u003cp\u003eAuxiliary Examinations: Chest CT (\u003cstrong\u003eSupplementary material-Video 1\u003c/strong\u003e) showed severe exudation in the right lung and left lower lobe, which was confined to the right lung, suggesting pneumonia. Blood routine: White blood cell count 8.2\u0026times;10⁹/L, neutrophil ratio 75%, lymphocyte ratio 18%, C-reactive protein 65 mg/L, procalcitonin 0.3 ng/mL.Liver and kidney function, electrolytes were basically normal.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eClinical Course and Management\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eOn November 4, 2024, empirical anti-infective therapy (specific drugs unavailable) was initiated after admission. Bronchoscopy was performed on November 5, which revealed a large amount of white viscous secretions in the dorsal segment and basal segment of the right lower lobe. BALF was collected from the right upper lobe, right middle lobe and right lower lobe for culture, NGS, pathology and rapid on-site evaluation (ROSE). Meanwhile, left airway stenosis was found (\u003cstrong\u003ePic 1\u003c/strong\u003e), and previous biopsy had excluded tumor.\u003c/p\u003e\n\u003cp\u003eOn November 6, BALF NGS results showed Pneumocystis jirovecii (1250 sequences) and two types of viruses (specific virus types and sequence counts see \u003cstrong\u003ePic 2\u003c/strong\u003e). Combined with the patient\u0026apos;s immunosuppressive status and etiological results, the diagnosis of PJP complicated with viral infection was confirmed. Immunosuppressants were immediately discontinued, and targeted anti-infective therapy with trimethoprim-sulfamethoxazole (specific dose unavailable) was initiated.\u003c/p\u003e\n\u003cp\u003eOn November 7, the patient developed decreased oxygen saturation, dropping to 88% (nasal catheter oxygen inhalation 3 L/min). Arterial blood gas analysis indicated type I respiratory failure (pH 7.45, PaCO₂ 32 mmHg, PaO₂ 58 mmHg, FiO₂ 0.29). He was transferred to the intensive care unit (ICU) with a diagnosis of severe pneumonia and acute respiratory distress syndrome. Bed rest and awake prone position ventilation were given. Oxygenation improved more significantly when in right high position during prone ventilation, but the patient had poor activity tolerance, with dyspnea and SpO₂ dropping to 80% after activities such as eating.\u003c/p\u003e\n\u003cp\u003eOn November 9, the patient\u0026apos;s oxygen saturation continued to decrease to 75% after activity, accompanied by cyanosis of the lips. Tracheal intubation and mechanical ventilation were performed (mode: PCV, PEEP 12 cmH₂O, FiO₂ 0.8), and prone position ventilation was continued. Twenty-four hours later, oxygenation improved insignificantly (P/F ratio only about 150 mmHg). NO inhalation (5 ppm) was added to improve V/Q ratio, but hypoxemia and hypercapnia still could not be corrected. Bedside chest X-ray \u003cstrong\u003e(Pic 3\u003c/strong\u003e) showed progression of right lung exudation. VV-ECMO support was initiated on the same day (mode: VV, blood flow 4.5 L/min, FiO₂ 0.7).\u003c/p\u003e\n\u003cp\u003eOn November 11, follow-up chest CT (\u003cstrong\u003eSupplementary material-Video 2\u003c/strong\u003e) showed significant progression of exudation in the right lung and left lower lobe. Under ECMO support, lung-protective ventilation strategy was implemented (VT 6 ml/kg, PEEP 10 cmH₂O). Respiratory mechanics were measured daily to evaluate lung compliance. Prone position ventilation and bronchoscopic sputum drainage were performed daily, and BALF etiological testing was dynamically monitored to guide antibiotic adjustment.\u003c/p\u003e\n\u003cp\u003eDuring treatment, the patient\u0026apos;s lung compliance gradually improved. Repeated chest CT (\u003cstrong\u003eSupplementary material-Video 3\u003c/strong\u003e, the last scan before VV-ECMO withdrawal) showed reduced exudation in the right lung, no progression of exudation in the left lung, and the lesion remained mainly confined to the right lung. VV-ECMO was operated continuously for 25 days without adverse events such as bleeding, ECMO circuit or oxygenator coagulation failure.\u003c/p\u003e\n\u003cp\u003eOn December 5, 2024, a 24-hour spontaneous breathing trial (SBT) was performed and passed, followed by VV-ECMO withdrawal. Mechanical ventilation was continued, and respiratory mechanics measurement showed significant improvement in lung compliance. On December 10, 2024, follow-up chest CT (\u003cstrong\u003eSupplementary material-Video 4\u003c/strong\u003e) showed significant improvement of right lung exudation, a small amount of exudation in the left lower lobe (improved compared with previous), and no obvious progression of exudation in the left lung.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003ePneumocystis jirovecii Pneumonia (PJP) remains a life-threatening opportunistic infection in immunocompromised populations, particularly among solid organ transplant recipients, where it contributes significantly to post-transplant morbidity and mortality\u003csup\u003e1-3\u003c/sup\u003e. Although the typical radiographic appearance of PJP is that of a bilateral alveolar-interstitial pattern, atypical radiographic presentations occur. These include unilateral disease, focal lesions and normal chest radiographic findings\u003csup\u003e6\u003c/sup\u003e.\u0026nbsp;Atypical radiographic findings occur more commonly in patients with the acquired immunodeficiency syndrome and those with prior radiotherapy to the lungs\u003csup\u003e7\u003c/sup\u003e.\u0026nbsp;The radiographic presentation of this patient was unique in a series of 186 cases of P carinii pneumonia in immunosuppressed pediatric oncology patients seen at this institution through 1986. Only two previous patients had unilateral disease, which rapidly evolved into bilateral radiographic findings\u003csup\u003e7\u003c/sup\u003e.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;The present case highlights the diagnostic and therapeutic challenges posed by atypical PJP, as it deviated markedly from the classic clinical and radiological phenotype. While bilateral diffuse interstitial infiltrates with a \u0026quot;ground-glass\u0026quot; pattern are the hallmark of PJP\u003csup\u003e8-9\u003c/sup\u003e, this patient exhibited persistently unilateral-predominant lung involvement\u0026mdash;a highly atypical presentation with only sporadic cases documented in the literature\u003csup\u003e9-10\u003c/sup\u003e. Notably, from initial admission through disease progression and eventual recovery, lesions remained concentrated in the right lung and left lower lobe, with minimal progression in the left upper lobe\u0026mdash;a distribution that correlated with structural airway abnormalities identified intraoperatively.\u003c/p\u003e\n\u003cp\u003eBronchoscopy revealed pre-existing stenosis of the left mainstem airway and relative narrowing of the left upper lobe ostium, with prior biopsy excluding malignant etiology. This anatomical finding prompted our investigation into its potential role in shaping lesion distribution\u003csup\u003e11\u003c/sup\u003e. To contextualize this observation, we draw an analogy between airway airflow and fluid dynamics in constricted channels: airflow is analogous to water flow, and P. jirovecii (and co-infecting viruses) to suspended particles (e.g., sand). Guided by the sedimentation principles outlined in Kenneth J et al.\u0026rsquo;s Physical Principles of Sedimentology (1989)\u003csup\u003e12-13\u003c/sup\u003e, regions of elevated flow velocity generate increased kinetic energy, preventing particle sedimentation. In constricted airways, abrupt luminal narrowing accelerates airflow, inducing turbulence and eddy currents that further hinder particle deposition\u003csup\u003e5\u003c/sup\u003e. Applying this framework to our patient, the stenotic left mainstem and left upper lobe airways likely created a high-velocity, turbulent airflow environment, limiting pathogen adhesion and colonization on the left lung mucosa. Conversely, the unobstructed right lung experienced relatively uniform, low-turbulence airflow, facilitating P. jirovecii (colonization), proliferation, and subsequent inflammatory exudation\u0026mdash;consistent with the radiological predominance of right-sided lesions.\u003c/p\u003e\n\u003cp\u003eThis hydrodynamic hypothesis adds a novel dimension to our understanding of PJP pathogenesis, which is traditionally attributed to immune deficiency-driven unchecked pathogen replication\u003csup\u003e11\u003c/sup\u003e. However, we acknowledge critical limitations to this proposal: we did not perform computational fluid dynamics simulations to quantify airflow patterns in the stenotic airways, nor did we conduct site-specific pathogen quantification (e.g., quantitative PCR of BALF from left vs. right lobes) to directly link airflow dynamics to colonization density. Such experiments would be essential to validate the causal relationship between airway stenosis, hydrodynamic changes, and unilateral lesion distribution.\u003c/p\u003e\n\u003cp\u003eBeyond pathogenesis, this case underscores the transformative role of advanced diagnostic and supportive care technologies in managing severe PJP. Metagenomic next-generation sequencing (mNGS) of bronchoalveolar lavage fluid (BALF) rapidly identified P. jirovecii (1250 sequences) and co-infecting viruses\u0026mdash;an achievement that traditional staining or culture methods might have delayed\u003csup\u003e14\u003c/sup\u003e. This timely diagnosis was critical for discontinuing immunosuppressants and initiating targeted trimethoprim-sulfamethoxazole therapy\u003csup\u003e4\u003c/sup\u003e. For refractory hypoxemia due to acute respiratory distress syndrome (ARDS), venovenous extracorporeal membrane oxygenation (VV-ECMO) emerged as a life-saving intervention. After failing conventional measures (prone ventilation, nitric oxide inhalation), 25 days of VV-ECMO support\u0026mdash;combined with lung-protective ventilation and daily bronchoscopic drainage\u0026mdash;improved lung compliance and facilitated successful weaning, aligning with recent evidence that ECMO improves outcomes in severe PJP unresponsive to standard respiratory support\u003csup\u003e15\u003c/sup\u003e.\u003c/p\u003e\n\u003cp\u003eSeveral limitations of this case report merit consideration. First, the etiology of left airway stenosis (congenital vs. acquired, e.g., post-inflammatory or iatrogenic) remains unclear due to the absence of pre-transplant imaging or longitudinal airway assessments. Second, the hydrodynamic hypothesis lacks direct experimental validation and is not yet supported by existing PJP literature, though analogous mechanisms have been described in other airway infections\u003csup\u003e5\u003c/sup\u003e. Third, incomplete documentation of immunosuppressant regimens (e.g., tacrolimus trough levels, steroid doses) and anti-infective drug dosing limits our ability to correlate pharmacotherapy with disease progression and response. Finally, we did not perform serial pathogen testing to assess how therapeutic interventions impacted P. jirovecii burden in relation to airway airflow dynamics.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eThis case reports a rare post-renal transplantation PJP with predominant unilateral pulmonary infiltration. Left airway stenosis may affect the pathogenic process of pathogens through airway hydrodynamic changes, providing a new perspective for PJP pathogenesis research. NGS is beneficial for early etiological diagnosis, and VV-ECMO combined with comprehensive treatment measures has important therapeutic value for severe patients.\u003c/p\u003e\n"},{"header":"Abbreviations","content":"\u003cp\u003e\u003cstrong\u003eARDS\u003c/strong\u003e: Acute Respiratory Distress Syndrome\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eBALF\u003c/strong\u003e: Bronchoalveolar Lavage Fluid\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCT\u003c/strong\u003e: Computed Tomography\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFiO₂\u003c/strong\u003e: Fraction of Inspired Oxygen\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eICU\u003c/strong\u003e: Intensive Care Unit\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003emNGS\u003c/strong\u003e: Metagenomic Next-Generation Sequencing\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eNGS\u003c/strong\u003e: Next-Generation Sequencing\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eNO\u003c/strong\u003e: Nitric Oxide\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePaCO₂\u003c/strong\u003e: Partial Pressure of Carbon Dioxide\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePaO₂\u003c/strong\u003e: Partial Pressure of Oxygen\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePCV\u003c/strong\u003e: Pressure Controlled Ventilation\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePEEP\u003c/strong\u003e: Positive End-Expiratory Pressure\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePJP\u003c/strong\u003e: Pneumocystis jirovecii Pneumonia\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eP/F ratio\u003c/strong\u003e: PaO₂/FiO₂ ratio\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSBT\u003c/strong\u003e: Spontaneous Breathing Trial\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eVV-ECMO\u003c/strong\u003e: Venovenous Extracorporeal Membrane Oxygenation\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eVT\u003c/strong\u003e: Tidal Volume\u003c/p\u003e\n"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eConflicts of Interest Statement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no known competing financial interests or personal relationships that could have influenced the work reported in this paper. This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. All authors confirm that there are no conflicts of interest regarding the publication of this manuscript, including but not limited to consulting fees, honoraria, stock ownership, research funding from pharmaceutical companies related to the medications or devices discussed in this case report. The authors have no affiliations with or involvement in any organization or entity with a financial interest in the subject matter or materials discussed in this manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding Statement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis work was supported by the Beijing Natural Science Foundation-Haidian Original Innovation Joint Fund project (No. L222019) and Training Fund for Open Projects at Clinical Institutes and Departments of Capital Medical University (No. CCMU2023ZKYXY012).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent to Publish\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWritten informed consent was obtained from the patient for the publication of this case report, including all clinical details, imaging studies, and associated medical information. The patient was informed that anonymized data would be publicly accessible and has provided explicit permission for its use in this publication. A copy of the written consent form is available for review by the Editor-in-Chief of the journal if required. All potentially identifying information (name, exact dates, medical record numbers) has been removed or anonymized to protect patient privacy.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eStringer JR BCMR. A new name for Pneumocystis carinii. \u003cem\u003eEmerg Infect Dis\u003c/em\u003e 2002;8(9):891-896\u003c/li\u003e\n\u003cli\u003eRogina P, Skvarc M. Diagnostic accuracy of (1--\u0026gt;3)-beta-D-glucan to predict Pneumocystis jirovecii pneumonia in non-HIV-infected patients. \u003cem\u003eRadiol Oncol\u003c/em\u003e 2020;54(2):221-226.doi: 10.2478/raon-2020-0028.PubMed: 32463392\u003c/li\u003e\n\u003cli\u003eWalzer PD EJBJ. Pneumocystis carinii pneumonia. \u003cem\u003eNew Engl J Med\u003c/em\u003e 1973;288(17):869-878\u003c/li\u003e\n\u003cli\u003eMaertens J CADG. 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Pneumocystis carinii pneumonia presenting as cavitating and noncavitating solitary pulmonary nodules in patients with the acquired immunodeficiency syndrome. \u003cem\u003eAm Rev Respir Dis\u003c/em\u003e 1986;134(5):1094-6.doi: 10.1164/arrd.1986.134.5.1094.PubMed: 3490810\u003c/li\u003e\n\u003cli\u003eLimper AH SSJS. Pneumocystis pneumonia. \u003cem\u003eLancet\u003c/em\u003e 2019;394(10212):2083-2092\u003c/li\u003e\n\u003cli\u003eSpringsted E GBKV. Pneumocystis jirovecii pneumonia in newly diagnosed treatment-na\u0026iuml;ve chronic lymphocytic leukaemia. \u003cem\u003eBmj Case Rep\u003c/em\u003e 2021;14(6).doi: 10.1136/bcr-2021-2418888\u003c/li\u003e\n\u003cli\u003eVieu Jean S MAHD. Pneumocystis jirovecii pneumonia in patients with inflammatory bowel disease\u0026ndash;a case series. \u003cem\u003eJ Crohns Colitis\u003c/em\u003e 2023;17(4):472-479.doi: 10.1093/ecco-jcc/jjac153\u003c/li\u003e\n\u003cli\u003eKovacs JA HGLA. Pneumocystis jirovecii: from bench to bedside. \u003cem\u003eNat Rev Microbiol\u003c/em\u003e 2018;16(12):747-762\u003c/li\u003e\n\u003cli\u003eHsü KJ, Hsü KJ. Physics of sedimentology :textbook and reference 2nd ed. ed. Berlin: Springer; 2004.\u003c/li\u003e\n\u003cli\u003eHsü KJ. Physical principles of sedimentology :a readable textbook for beginners and experts. Berlin: Springer-Verlag; 1989.\u003c/li\u003e\n\u003cli\u003eLi XF LZYJ. Diagnostic performance of metagenomic next-generation sequencing for Pneumocystis jirovecii pneumonia. \u003cem\u003eBmc Infect Dis\u003c/em\u003e 2022;22(1).doi: 10.1186/s12879-022-07065-x\u003c/li\u003e\n\u003cli\u003eRahman NM BRMA. Veno-venous ECMO for Pneumocystis jirovecii pneumonia: a systematic review and meta-analysis. \u003cem\u003eIntens Care Med\u003c/em\u003e 2023;49(8):951-962\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":"Pneumocystis jirovecii Pneumonia, Unilateral Pulmonary Infiltration, Airway Stenosis, Hydrodynamics, Renal Transplantation","lastPublishedDoi":"10.21203/rs.3.rs-8524345/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8524345/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eObjective:\u003c/strong\u003e To report a case of Pneumocystis jirovecii Pneumonia (PJP) characterized by predominant unilateral pulmonary infiltration, and to explore its pathogenic specificity and clinical management in combination with airway structural abnormalities.​\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods:\u003c/strong\u003e We retrospectively analyzed the clinical data of a post-renal transplantation patient with PJP admitted to Xuanwu Hospital, Capital Medical University, including medical history, imaging features, etiological results, treatment process and prognosis. A hypothesis regarding the pathogenic mechanism was proposed based on airway examination findings.​\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults:\u003c/strong\u003e A 60-year-old male with a 1-year history of renal transplantation and long-term immunosuppressant use was admitted due to \"cough and expectoration for 2 weeks\". Admission CT showed severe exudation in the right lung and left lower lobe, which was confined to the right lung. Bronchoscopy revealed left airway stenosis, and next-generation sequencing (NGS) of bronchoalveolar lavage fluid (BALF) detected Pneumocystis jirovecii and two viruses. Despite immunosuppressant withdrawal and targeted anti-infective therapy, the patient developed type I respiratory failure. After ineffective treatment with prone position ventilation, tracheal intubation, mechanical ventilation and nitric oxide (NO) inhalation, venovenous extracorporeal membrane oxygenation (VV-ECMO) was initiated for 25 days. Multiple imaging examinations during treatment consistently showed that the lesion was mainly in the right lung, with slow progression of exudation in the left lung.​\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion:\u003c/strong\u003e This PJP case presented with rare unilateral infiltration progression. Left airway stenosis may interfere with the pathogenic process of pathogens through airway hydrodynamic changes, providing a new perspective for PJP pathogenesis research.​\u003c/p\u003e","manuscriptTitle":"When Pneumonia is One-Sided: A Rare Unilateral Progressive Pneumocystis jirovecii Pneumonia Case","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-01-26 01:29:20","doi":"10.21203/rs.3.rs-8524345/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":"e608e4f7-4260-42c6-9dba-caf5dabaaddb","owner":[],"postedDate":"January 26th, 2026","published":true,"recentEditorialEvents":[{"type":"decision","content":"Rejected","date":"2026-05-04T13:16:16+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-05-02T01:33:25+00:00","index":64,"fulltext":""},{"type":"reviewerAgreed","content":"196269177574989595147077442636011728185","date":"2026-04-30T20:15:18+00:00","index":63,"fulltext":""}],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2026-05-04T13:25:55+00:00","versionOfRecord":[],"versionCreatedAt":"2026-01-26 01:29:20","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8524345","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8524345","identity":"rs-8524345","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}