<i>Pneumocystis jirovecii</i> colonization in patients with pulmonary alveolar proteinosis_Chinese Journal of Respiratory and Critical Care Medicine

Authors：

ZHAO Tingting ¹ , LI Yan ¹ , MA Miao ¹ , GAO Yujuan ¹ , SHI Shenyun ¹ , CAO Mengshu ¹ , XIN Xiaoyan ² , XIAO Yonglong ¹ ,  SU Xin ¹

1. Department of Respiratory and Critical Care Medicine, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu 210008, P. R. China;
2. Department of Radiology, Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu 210008, P. R. China;

Corresponding?author：

SU Xin, Email: suxinjs@163.com

Keywords：

Pulmonary alveolar proteinosis; Pneumocystis jirovecii; colonization; risk factors

DOI：

10.7507/1671-6205.202304082

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Objective To investigate the colonization, risk factors and prognosis of Pneumocystis jirovecii (P.jirovecii) colonization in patients with Pulmonary alveolar proteinosis (PAP). Methods The patients with Pulmonary alveolar proteinosis who were admitted to the Department of Respiratory and Critical Care Medicine, Nanjing Drum Tower Hospital from March 2019 to December 2022 were retrospectively analyzed. Polymerase chain reaction/next-generation metagenomic sequencing were used to detect the colonization of P. jirovecii in bronchoalveolar lavage fluid, and then to investigate the colonization rate, risk factors and outcome of P. jirovecii in PAP patients. Results A total of 25 patients were included in the study, of which 7 were colonized by P. jirovecii (28.0%). The rate of using antibiotics before admission in the colonizing group was significantly higher than that in the non-colonizing group (85.7% vs 33.3%, P=0.030). Total blood lymphocytes (1.4×10⁹/L vs. 1.8×10⁹/L, P=0.048), CD3⁺T cells (0.83×10⁹/L vs. 1.34×10⁹/L, P=0.010), CD4⁺T cells (0.48×10⁹/L vs. 0.85×10⁹/L, P=0.010) were significantly lower than those in the non-colonizing group, lactate dehydrogenase (469.9 U/L vs. 277.3 U/L, P=0.005) was significantly higher than those in the non-colonizing group. A higher proportion of colonizing group required combination therapy (57.1% vs. 11.1%, P=0.032); but there was no significant difference in the percentage of whole-lung ground-glass opacification, lung function, oxygen index and outcome. Lactate dehydrogenase was positively correlated with the percentage of whole-lung ground-glass opacification of PAP, but negatively correlated with oxygen index, percentage of predicted forced vital capacity and percentage of predicted diffusion capacity for carbon monoxide. Conclusions The colonization rate of P. jirovecii in PAP patients was high. Reduced lymphocyte count in peripheral blood of PAP patients and antibiotic use before diagnosing were risk factors for P. jirovecii colonization.

Citation： ZHAO Tingting, LI Yan, MA Miao, GAO Yujuan, SHI Shenyun, CAO Mengshu, XIN Xiaoyan, XIAO Yonglong, SU Xin. Pneumocystis jirovecii colonization in patients with pulmonary alveolar proteinosis. Chinese Journal of Respiratory and Critical Care Medicine, 2023, 22(8): 572-577. doi: 10.7507/1671-6205.202304082 Copy

1.	Jouneau S, Ménard C, Lederlin M. Pulmonary alveolar proteinosis. Respirology, 2020, 25(8): 816-826.
2.	Asai N, Motojima S, Ohkuni Y, et al. Pathophysiological mechanism of non-HIV Pneumocystis jirovecii pneumonia. Respir Investig, 2022, 60(4): 522-530.
3.	Ca?as-Arboleda A, Hernández-Flórez C, Garzón J, et al. Colonization by Pneumocystis jirovecii in patients with chronic obstructive pulmonary disease: association with exacerbations and lung function status. Braz J Infect Dis, 2019, 23(5): 352-357.
4.	Vera C, Rueda ZV. Transmission and colonization of Pneumocystis jirovecii. J Fungi, 2021, 7(11): 979.
5.	Xue T, Ma Z, Liu F, et al. Pneumocystis jirovecii colonization and its association with pulmonary diseases: a multicenter study based on a modified loop-mediated isothermal amplification assay. BMC Pulm Med, 2020, 20(1): 70.
6.	Gingerich AD, Norris KA, Mousa JJ. Pneumocystis pneumonia: immunity, vaccines, and treatments. Pathogens, 2021, 10(2): 236.
7.	Kumar A, Abdelmalak B, Inoue Y, et al. Pulmonary alveolar proteinosis in adults: pathophysiology and clinical approach. Lancet Respir Med, 2018, 6(7): 554-565.
8.	Wang YQ, Zhou XY, Saimi M, et al. Risk factors of mortality from Pneumocystis pneumonia in non-HIV patients: a meta-analysis. Front Public Health, 2021, 9: 680108.
9.	Olson G, Davis AM. Diagnosis and treatment of adults with community-acquired pneumonia. JAMA, 2020, 323(9): e45-e67.
10.	Ghembaza A, Vautier M, Cacoub P, et al. Risk factors and prevention of Pneumocystis jirovecii pneumonia in patients with autoimmune and inflammatory diseases. Chest, 2020, 158(6): 2323-2332.
11.	Shi SY, Zou RY, Chen LL, et al. Quantitative chest CT assessment of pulmonary alveolar proteinosis with deep learning: a real-world longitudinal study. Quant Imaging Med Surg, 2022, 12(12): 5394-5403.
12.	Riley L, Wang T, Ataya A. Pulmonary alveolar proteinosis (PAP). Am J Respir Crit Care Med, 2019, 200(8): 16-17.
13.	Zhang DM, Tian XL, Feng RE, et al. Secondary pulmonary alveolar proteinosis: a single-center retrospective study (a case series and literature review). BMC Pulm Med, 2018, 18(1): 15.
14.	Yan L, Wang Z, Zhao J, et al. Images: Secondary pulmonary alveolar proteinosis in brucellosis. Pulmonology, 2023, 29(4): 351-352.
15.	Vidal S, de la Horra C, Martín J, et al. Pneumocystis jirovecii colonisation in patients with interstitial lung disease. Clin Microbiol Infect, 2006, 12(3): 231-235.
16.	Whiteside SA, McGinniss JE, Collman RG. The lung microbiome: progress and promise. J Clin Invest, 2021, 131(15): e150473.
17.	Morris A, Norris KA. Colonization by Pneumocystis jirovecii and its role in disease. Clin Microbiol Rev, 2012, 25(2): 297-317.
18.	Seymour JF, Presneill JJ. Pulmonary alveolar proteinosis: progress in the first 44 years. Am J Respir Crit Care Med, 2002, 166(2): 215-235.
19.	Inoue Y, Trapnell BC, Tazawa R, et al. Characteristics of a large cohort of patients with autoimmune pulmonary alveolar proteinosis in Japan. Am J Respir Crit Care Med, 2008, 177(7): 752-762.
20.	Kho SS, Ganapaty S, Omar N, et al. Opportunistic actinomycosis in pulmonary alveolar proteinosis. Thorax, 2022, 77(8): 842-843.
21.	Le Gal S, Bonnet P, Huguenin A, et al. The shift from pulmonary colonization to Pneumocystis pneumonia. Med Mycol, 2020, 59(5): 510-513.
22.	Costabel U, Nakata K. Pulmonary alveolar proteinosis associated with dust inhalation: not secondary but autoimmune? Am J Respir Crit Care Med, 2010, 181(5): 427-428.
23.	Fishman JA, Gans H, the AST Infectious Diseases Community of Practice. Pneumocystis jiroveci in solid organ transplantation: Guidelines from the American Society of Transplantation Infectious Diseases Community of Practice. Clin Transplant, 2019, 33(9): e13587.
24.	Maskell NA, Waine DJ, Lindley A, et al. Asymptomatic carriage of Pneumocystis jiroveci in subjects undergoing bronchoscopy: a prospective study. Thorax, 2003, 58(7): 594-597.

1. Jouneau S, Ménard C, Lederlin M. Pulmonary alveolar proteinosis. Respirology, 2020, 25(8): 816-826.
2. Asai N, Motojima S, Ohkuni Y, et al. Pathophysiological mechanism of non-HIV Pneumocystis jirovecii pneumonia. Respir Investig, 2022, 60(4): 522-530.
3. Ca?as-Arboleda A, Hernández-Flórez C, Garzón J, et al. Colonization by Pneumocystis jirovecii in patients with chronic obstructive pulmonary disease: association with exacerbations and lung function status. Braz J Infect Dis, 2019, 23(5): 352-357.
4. Vera C, Rueda ZV. Transmission and colonization of Pneumocystis jirovecii. J Fungi, 2021, 7(11): 979.
5. Xue T, Ma Z, Liu F, et al. Pneumocystis jirovecii colonization and its association with pulmonary diseases: a multicenter study based on a modified loop-mediated isothermal amplification assay. BMC Pulm Med, 2020, 20(1): 70.
6. Gingerich AD, Norris KA, Mousa JJ. Pneumocystis pneumonia: immunity, vaccines, and treatments. Pathogens, 2021, 10(2): 236.
7. Kumar A, Abdelmalak B, Inoue Y, et al. Pulmonary alveolar proteinosis in adults: pathophysiology and clinical approach. Lancet Respir Med, 2018, 6(7): 554-565.
8. Wang YQ, Zhou XY, Saimi M, et al. Risk factors of mortality from Pneumocystis pneumonia in non-HIV patients: a meta-analysis. Front Public Health, 2021, 9: 680108.
9. Olson G, Davis AM. Diagnosis and treatment of adults with community-acquired pneumonia. JAMA, 2020, 323(9): e45-e67.
10. Ghembaza A, Vautier M, Cacoub P, et al. Risk factors and prevention of Pneumocystis jirovecii pneumonia in patients with autoimmune and inflammatory diseases. Chest, 2020, 158(6): 2323-2332.
11. Shi SY, Zou RY, Chen LL, et al. Quantitative chest CT assessment of pulmonary alveolar proteinosis with deep learning: a real-world longitudinal study. Quant Imaging Med Surg, 2022, 12(12): 5394-5403.
12. Riley L, Wang T, Ataya A. Pulmonary alveolar proteinosis (PAP). Am J Respir Crit Care Med, 2019, 200(8): 16-17.
13. Zhang DM, Tian XL, Feng RE, et al. Secondary pulmonary alveolar proteinosis: a single-center retrospective study (a case series and literature review). BMC Pulm Med, 2018, 18(1): 15.
14. Yan L, Wang Z, Zhao J, et al. Images: Secondary pulmonary alveolar proteinosis in brucellosis. Pulmonology, 2023, 29(4): 351-352.
15. Vidal S, de la Horra C, Martín J, et al. Pneumocystis jirovecii colonisation in patients with interstitial lung disease. Clin Microbiol Infect, 2006, 12(3): 231-235.
16. Whiteside SA, McGinniss JE, Collman RG. The lung microbiome: progress and promise. J Clin Invest, 2021, 131(15): e150473.
17. Morris A, Norris KA. Colonization by Pneumocystis jirovecii and its role in disease. Clin Microbiol Rev, 2012, 25(2): 297-317.
18. Seymour JF, Presneill JJ. Pulmonary alveolar proteinosis: progress in the first 44 years. Am J Respir Crit Care Med, 2002, 166(2): 215-235.
19. Inoue Y, Trapnell BC, Tazawa R, et al. Characteristics of a large cohort of patients with autoimmune pulmonary alveolar proteinosis in Japan. Am J Respir Crit Care Med, 2008, 177(7): 752-762.
20. Kho SS, Ganapaty S, Omar N, et al. Opportunistic actinomycosis in pulmonary alveolar proteinosis. Thorax, 2022, 77(8): 842-843.
21. Le Gal S, Bonnet P, Huguenin A, et al. The shift from pulmonary colonization to Pneumocystis pneumonia. Med Mycol, 2020, 59(5): 510-513.
22. Costabel U, Nakata K. Pulmonary alveolar proteinosis associated with dust inhalation: not secondary but autoimmune? Am J Respir Crit Care Med, 2010, 181(5): 427-428.
23. Fishman JA, Gans H, the AST Infectious Diseases Community of Practice. Pneumocystis jiroveci in solid organ transplantation: Guidelines from the American Society of Transplantation Infectious Diseases Community of Practice. Clin Transplant, 2019, 33(9): e13587.
24. Maskell NA, Waine DJ, Lindley A, et al. Asymptomatic carriage of Pneumocystis jiroveci in subjects undergoing bronchoscopy: a prospective study. Thorax, 2003, 58(7): 594-597.

Chinese Journal of Respiratory and Critical Care Medicine

Pneumocystis jirovecii colonization in patients with pulmonary alveolar proteinosis

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