Association Between the Cumulative Dose of Glucocorticoids Before the Development of Pneumonia and Death in Patients Receiving Long-term Glucocorticoids: a Secondary Analysis Based on a Chinese Cohort Study

Overview

Journal Front Med (Lausanne)

Specialty General Medicine

Date 2023 Aug 7

PMID 37547616

Authors

Hui-Jie Guo

Yi-Lu Ye

Rong Cao

Zhi-Hua Liu

Qun He

Affiliations

Soon will be listed here.

Abstract

Background: The present study aimed to evaluate the association between the cumulative dose of glucocorticoids (GCs) and case fatality in hospitalized patients who developed pneumonia while receiving glucocorticoid therapy.

Methods: This retrospective cohort study included 625 patients receiving long-term GC treatment who were hospitalized with pneumonia (322 male and 303 female). Data were obtained from the Dryad Digital Repository and were used to perform secondary analysis. Multivariable Cox proportional hazard regression model and restricted cubic splines (RCS) were used to evaluate the association between the cumulative dose of GCs and case fatality. Sensitivity analyses and subgroup analyses were performed.

Results: The 30-day and 90-day death rates were 22.9 and 26.2%, respectively. After adjusting for potential confounders, compared with those in the lowest quintile (≤ 1.5 g), the Cox proportional hazard regression model analysis showed that patients with different cumulative doses of GCs (1.5 to 2.95, 2.95 to 5, 5 to 11.5, and > 11.5 g) had lower risks for 30-day death, with respective hazard ratios of 0.86 (95% CI, 0.52 to 1.42), 0.81 (0.49 to 1.33), 0.29 (0.15 to 0.55), and 0.42 (0.22 to 0.79). The multivariable-adjusted RCS analysis suggested a statistically significant N-shaped association between the cumulative dose of GCs and 30-day death. A higher cumulative dose of GC tended to first lead to an increase in 30-day death within 1.8 g, then to a statistically significant decrease until around 8 g [HR for 1 g = 0.82 (0.69 to 0.97)], and again to an increase afterward. Similar results were found in the subgroup analyses and sensitivity analyses.

Conclusion: N-shaped association between the cumulative dose of GCs and case fatality was observed in patients receiving long-term GC treatment who were hospitalized with pneumonia. Our findings may help physicians manage these patients.

Citing Articles

What Harm Are We Doing to Our Patients with Asthma by Using High-Dose Inhaled Corticosteroids?.

Sin D, Busse W Am J Respir Crit Care Med. 2024; .

PMID: 39226124 PMC: 11755353. DOI: 10.1164/rccm.202407-1428ED.

References

Ajmal S, Mahmood M, Abu Saleh O, Larson J, Sohail M . Invasive fungal infections associated with prior respiratory viral infections in immunocompromised hosts. Infection. 2018; 46(4):555-558. DOI: 10.1007/s15010-018-1138-0. View

Rano A, Agusti C, Sibila O, Torres A . Pulmonary infections in non-HIV-immunocompromised patients. Curr Opin Pulm Med. 2005; 11(3):213-7. DOI: 10.1097/01.mcp.0000158728.14945.46. View

Maeda T, Babazono A, Nishi T, Matsuda S, Fushimi K, Fujimori K . Quantification of the effect of chemotherapy and steroids on risk of Pneumocystis jiroveci among hospitalized patients with adult T-cell leukaemia. Br J Haematol. 2014; 168(4):501-6. DOI: 10.1111/bjh.13154. View

Kim S, Lee J, Cho Y, Park Y, Lee C, Yoon H . Prognostic factors of Pneumocystis jirovecii pneumonia in patients without HIV infection. J Infect. 2014; 69(1):88-95. DOI: 10.1016/j.jinf.2014.02.015. View

Fardet L, Petersen I, Nazareth I . Prevalence of long-term oral glucocorticoid prescriptions in the UK over the past 20 years. Rheumatology (Oxford). 2011; 50(11):1982-90. DOI: 10.1093/rheumatology/ker017. View

Kim T, Moon S, Sung H, Kim M, Kim S, Choi S . Outcomes of non-HIV-infected patients with Pneumocystis pneumonia and concomitant pulmonary cytomegalovirus infection. Scand J Infect Dis. 2012; 44(9):670-7. DOI: 10.3109/00365548.2011.652665. View

Yang C, Yang A, Yang W, Lin C . Risk factors for Pneumocystis jiroveci pneumonia in glomerulonephritis patients receiving immunosuppressants. Intern Med. 2012; 51(20):2869-75. DOI: 10.2169/internalmedicine.51.6774. View

Alfakeekh K, Azar M, Sowailmi B, Alsulaiman S, Makdob S, Omair A . Immunosuppressive burden and risk factors of infection in primary childhood nephrotic syndrome. J Infect Public Health. 2018; 12(1):90-94. DOI: 10.1016/j.jiph.2018.09.006. View

Broder M, Sarsour K, Chang E, Collinson N, Tuckwell K, Napalkov P . Corticosteroid-related adverse events in patients with giant cell arteritis: A claims-based analysis. Semin Arthritis Rheum. 2016; 46(2):246-252. DOI: 10.1016/j.semarthrit.2016.05.009. View

10.

Yale S, Limper A . Pneumocystis carinii pneumonia in patients without acquired immunodeficiency syndrome: associated illness and prior corticosteroid therapy. Mayo Clin Proc. 1996; 71(1):5-13. DOI: 10.4065/71.1.5. View

11.

Waljee A, Rogers M, Lin P, Singal A, Stein J, Marks R . Short term use of oral corticosteroids and related harms among adults in the United States: population based cohort study. BMJ. 2017; 357:j1415. PMC: 6284230. DOI: 10.1136/bmj.j1415. View

12.

Park J, Curtis J, Kim M, Lee H, Song Y, Lee E . Pneumocystis pneumonia in patients with rheumatic diseases receiving prolonged, non-high-dose steroids-clinical implication of primary prophylaxis using trimethoprim-sulfamethoxazole. Arthritis Res Ther. 2019; 21(1):207. PMC: 6744623. DOI: 10.1186/s13075-019-1996-6. View

13.

Schacke H, Docke W, Asadullah K . Mechanisms involved in the side effects of glucocorticoids. Pharmacol Ther. 2002; 96(1):23-43. DOI: 10.1016/s0163-7258(02)00297-8. View

14.

Park J, Curtis J, Moon J, Song Y, Kim S, Lee E . Prophylactic effect of trimethoprim-sulfamethoxazole for pneumocystis pneumonia in patients with rheumatic diseases exposed to prolonged high-dose glucocorticoids. Ann Rheum Dis. 2017; 77(5):644-649. PMC: 5909751. DOI: 10.1136/annrheumdis-2017-211796. View

15.

Buttgereit F, Matteson E, Dejaco C, Dasgupta B . Prevention of glucocorticoid morbidity in giant cell arteritis. Rheumatology (Oxford). 2018; 57(suppl_2):ii11-ii21. DOI: 10.1093/rheumatology/kex459. View

16.

Agusti C, Rano A, Filella X, Gonzalez J, Moreno A, Xaubet A . Pulmonary infiltrates in patients receiving long-term glucocorticoid treatment: etiology, prognostic factors, and associated inflammatory response. Chest. 2003; 123(2):488-98. DOI: 10.1378/chest.123.2.488. View

17.

Li L, Hsu S, Gu X, Jiang S, Shang L, Sun G . Aetiology and prognostic risk factors of mortality in patients with pneumonia receiving glucocorticoids alone or glucocorticoids and other immunosuppressants: a retrospective cohort study. BMJ Open. 2020; 10(10):e037419. PMC: 7592294. DOI: 10.1136/bmjopen-2020-037419. View

18.

Minderhoud T, van Meer M, van Thiel R, den Hoed C, van Daele P, Schurink C . [Infections during glucocorticoid use]. Ned Tijdschr Geneeskd. 2018; 162. View

19.

Verhaert M, Blockmans D, De Langhe E, Henckaerts L . pneumonia in patients treated for systemic autoimmune disorders: a retrospective analysis of patient characteristics and outcome. Scand J Rheumatol. 2020; 49(5):345-352. DOI: 10.1080/03009742.2020.1762921. View

20.

Ewig S, Bauer T, Schneider C, Pickenhain A, Pizzulli L, Loos U . Clinical characteristics and outcome of Pneumocystis carinii pneumonia in HIV-infected and otherwise immunosuppressed patients. Eur Respir J. 1995; 8(9):1548-53. View