Airway diseases such as pneumonia constitute a major health burden on a global scale; untreated pneumonia may develop to severe pneumonia and consequently lead to to fatal episodes of mortality and morbidity. The balance between inflammatory mediators is key for the outcome of the pulmonary infection; elimination of invading pathogen was marked by the release of cytokines and other inflammatory mediators from alveolar macrophages and glucocorticoid steroids (GCs) acting on the inflammatory component. Treatments of severe pneumonia with GCs have been developing for years with inconclusive results. In many cases GCs have been administered empirically without clinical evidence. Recent studies assess beneficial impact on treatment of severe pneumonia by suggesting specific dosage, period of administration, and tapered dosage. 1. Background Severe pneumonia patients represent a major concern for physicians because of the high mortality and morbidity rate attributed to these episodes [1]. During past decades, many strategies have been implemented with the aim of optimizing the outcome of patients with severe lung infections. State of immunocompromisation during severe pneumonia related to multiple drug-resistant infections which may contribute to severe hypoxemic respiratory failure triggering septic shock and fatal outcome associated with multiple organ dysfunction syndromes. Not only is colonizing of bacteria responsible as main coordinators but it is believed that excessive inflammatory cascade is also responsible in the core of immune reaction. Nowadays, antimicrobial therapy not completely enough to significantly reduce mortality number in severe pneumonia, additional therapy such GCs may constitute an important portion for better resolution of pneumonia. If not treated properly, severe pneumonia can eventually lead to several complications including acute respiratory distress syndrome (ARDS) and sepsis. They are characterized by persistent pulmonary inflammation and alveolar-capillary disruption and commonly affect critically ill patients, with an estimated mortality rate of more than 50% [2]. We reviewed recent reports to clarify whether systemic corticosteroids have an impact on the outcomes of patients with severe pneumonia. In addition, we explored possible explanations for the role mechanism of corticosteroid in severe pneumonia. 2. Role of Glucocorticosteroid in Sepsis and ARDS ARDS is common and frequently fatal; two pathological feature of lung derived from pulmonary fibrosis and sepsis, secondary to pneumonia, are the primary etiology of death
References
[1]
WHO, The Top 10 Causes of Death, 2013.
[2]
L. B. Ware and M. A. Matthay, “The acute respiratory distress syndrome,” The New England Journal of Medicine, vol. 342, no. 18, pp. 1334–1349, 2000.
[3]
J. A. Kellum, L. Kong, M. P. Fink et al., “Understanding the inflammatory cytokine response in pneumonia and sepsis: results of the genetic and inflammatory markers of sepsis (GenIMS) study,” Archives of Internal Medicine, vol. 167, no. 15, pp. 1655–1663, 2007.
[4]
R. P. Dellinger, “Steroid therapy of septic shock: the decision is in the eye of the beholder,” Critical Care Medicine, vol. 36, no. 6, pp. 1987–1989, 2008.
[5]
S. McGee and J. Hirschmann, “Use of corticosteroids in treating infectious diseases,” Archives of Internal Medicine, vol. 168, no. 10, pp. 1034–1046, 2008.
[6]
W. Schumer, “Steroids in the treatment of clinical septic shock,” Annals of Surgery, vol. 184, no. 3, pp. 333–341, 1976.
[7]
J. Carlet, “From mega to more reasonable doses of corticosteroids: a decade to recreate hope,” Critical Care Medicine, vol. 27, no. 4, pp. 672–674, 1999.
[8]
D. Annane, J. C. Raphael, P. Gajdos, and D. Cook, “Steroid replacement in sepsis: an unexplored side of a multifaceted drug class,” Critical Care Medicine, vol. 24, no. 5, pp. 899–900, 1996.
[9]
J. Briegel, W. Kellermann, H. Forst et al., “Low-dose hydrocortisone infusion attenuates the systemic inflammatory response syndrome,” Clinical Investigator, vol. 72, no. 10, pp. 782–787, 1994.
[10]
J. L. Moran, P. L. Graham, S. Rockliff, and A. D. Bersten, “Updating the evidence for the role of corticosteroids in severe sepsis and septic shock: a Bayesian meta-analytic perspective,” Critical Care, vol. 14, no. 4, article R134, 2010.
[11]
P. C. Minneci, K. J. Deans, S. M. Banks, P. Q. Eichacker, and C. Natanson, “Meta-analysis: the effect of steroids on survival and shock during sepsis depends on the dose,” Annals of Internal Medicine, vol. 141, no. 1, pp. 47–56, 2004.
[12]
D. Keh and C. L. Sprung, “Use of corticosteroid therapy in patients with sepsis and septic shock: an evidence-based review,” Critical Care Medicine, vol. 32, no. 11, pp. S527–S533, 2004.
[13]
H.-S. Lee, J. M. Lee, M. S. Kim, H. Y. Kim, B. Hwangbo, and J. I. Zo, “Low-dose steroid therapy at an early phase of postoperative acute respiratory distress syndrome,” Annals of Thoracic Surgery, vol. 79, no. 2, pp. 405–410, 2005.
[14]
G. U. Meduri, E. Golden, A. X. Freire et al., “Methylprednisolone infusion in early severe ards: results of a randomized controlled trial,” Chest, vol. 131, no. 4, pp. 954–963, 2007.
[15]
G. U. Meduri, A. J. Chinn, K. V. Leeper et al., “Corticosteroid rescue treatment of progressive fibroproliferation in late ARDS: patterns of response and predictors of outcome,” Chest, vol. 105, no. 5, pp. 1516–1527, 1994.
[16]
L. Cronin, D. J. Cook, J. Carlet et al., “Corticosteroid treatment for sepsis: a critical appraisal and meta- analysis of the literature,” Critical Care Medicine, vol. 23, no. 8, pp. 1430–1439, 1995.
[17]
R. P. Dellinger, M. Levy Mitchell, M. B. Andrew, et al., “Surviving sepsis campaign: international guidelines for management of severe sepsis and septic shock: 2012,” Critical Care Medicine, vol. 41, no. 2, pp. 580–637, 2013.
[18]
J. A. Kellum, L. Kong, M. P. Fink et al., “Understanding the inflammatory cytokine response in pneumonia and sepsis: results of the genetic and inflammatory markers of sepsis (GenIMS) study,” Archives of Internal Medicine, vol. 167, no. 15, pp. 1655–1663, 2007.
[19]
C. Montón, A. Torres, M. El-Ebiary, X. Filella, A. Xaubet, and J. P. de la Bellacasa, “Cytokine expression in severe pneumonia: a bronchoalveolar lavage study,” Critical Care Medicine, vol. 27, no. 9, pp. 1745–1753, 1999.
[20]
S. Hirao, H. Wada, K. Nakagaki et al., “Inflammation provoked by Mycoplasma pneumoniae extract: implications for combination treatment with clarithromycin and dexamethasone,” FEMS Immunology and Medical Microbiology, vol. 62, no. 2, pp. 182–189, 2011.
[21]
A. A. Alangari, “Genomic and non-genomic actions of glucocorticoids in asthma,” Annals of Thoracic Medicine, vol. 5, no. 3, pp. 133–139, 2010.
[22]
S. Vandevyver, L. Dejager, J. Tuckermann, and C. Libert, “New insights into the anti-inflammatory mechanisms of glucocorticoids: an emerging role for glucocorticoid-receptor-mediated transactivation,” Endocrinology, vol. 154, no. 3, pp. 993–1007, 2013.
[23]
T. Rhen and J. A. Cidlowski, “Antiinflammatory action of glucocorticoids—new mechanisms for old drugs,” The New England Journal of Medicine, vol. 353, no. 16, pp. 1711–1723, 2005.
[24]
A. Rano, A. Carlos, S. Oriol, and T. Antoni, “Associated inflammatory response in pneumonia: role of adjunctive therapy with glucocorticoids,” Current Opinion in Infectious Diseases, vol. 19, no. 2, pp. 179–184, 2006.
[25]
D. Snijders, J. M. A. Daniels, C. S. de Graaff, T. S. van der Werf, and W. G. Boersma, “Efficacy of corticosteroids in community-acquired pneumonia: a randomized double-blinded clinical trial,” American Journal of Respiratory and Critical Care Medicine, vol. 181, no. 9, pp. 975–982, 2010.
[26]
A. K. McDonough, J. R. Curtis, and K. G. Saag, “The epidemiology of glucocorticoid-associated adverse events,” Current Opinion in Rheumatology, vol. 20, no. 2, pp. 131–137, 2008.
[27]
M. Kolditz, M. Halank, B. Schulte-Hubbert, and G. H？ffken, “Adrenal function is related to prognosis in moderate community-acquired pneumonia,” European Respiratory Journal, vol. 36, no. 3, pp. 615–621, 2010.
[28]
S. Gotoh, N. Nishimura, O. Takahashi et al., “Adrenal function in patients with community-acquired pneumonia,” European Respiratory Journal, vol. 31, no. 6, pp. 1268–1273, 2008.
[29]
G. U. Meduri and C. R. Yates, “Systemic inflammation-associated glucocorticoid resistance and outcome of ARDS,” Annals of the New York Academy of Sciences, vol. 1024, pp. 24–53, 2004.
[30]
D. Mesotten, I. Vanhorebeek, and G. van den Berghe, “The altered adrenal axis and treatment with glucocorticoids during critical illness,” Nature Clinical Practice Endocrinology and Metabolism, vol. 4, no. 9, pp. 496–505, 2008.
[31]
D. Annane, E. Bellissant, P. E. Bollaert, J. Briegel, D. Keh, and Y. Kupfer, “Corticosteroids for severe sepsis and septic shock: a systematic review and meta-analysis,” British Medical Journal, vol. 329, no. 7464, pp. 480–484, 2004.
[32]
C. Alberti, C. Brun-Buisson, H. Burchardi et al., “Epidemiology of sepsis and infection in ICU patients from an international multicentre cohort study,” Intensive Care Medicine, vol. 28, no. 2, pp. 108–121, 2002.
[33]
S. Weitzman and S. Berger, “Clinical trial design in studies of corticosteroids for bacterial infections,” Annals of Internal Medicine, vol. 81, no. 1, pp. 36–42, 1974.
[34]
R. Lefering and E. A. M. Neugebauer, “Steroid controversy in sepsis and septic shock: a meta-analysis,” Critical Care Medicine, vol. 23, no. 7, pp. 1294–1303, 1995.
[35]
P. C. Minneci, K. J. Deans, S. M. Banks, P. Q. Eichacker, and C. Natanson, “Meta-analysis: the effect of steroids on survival and shock during sepsis depends on the dose,” Annals of Internal Medicine, vol. 141, no. 1, pp. 47–56, 2004.
[36]
P. Marik, P. Kraus, J. Sribante, I. Havlik, J. Lipman, and D. W. Johnson, “Hydrocortisone and tumor necrosis factor in severe community-acquired pneumonia: a randomized controlled study,” Chest, vol. 104, no. 2, pp. 389–392, 1993.
[37]
C. Montón, S. Ewig, A. Torres et al., “Role of glucocorticoids on inflammatory response in nonimmunosuppressed patients with pneumonia: a pilot study,” European Respiratory Journal, vol. 14, no. 1, pp. 218–220, 1999.
[38]
L. Amado-Rodriguez, G.-L. Adrián, L.-A. Inés, et al., “Anti-inflammatory effects of clarithromycin in ventilator-induced lung injury,” Respiratory Research, vol. 14, no. 1, p. 52, 2013.
[39]
O. Yildiz, M. Deganay, B. Aygen, M. Güven, F. Kele？timur, and A. Tutu？, “Physiological-dose steroid therapy in sepsis [ISRCTN36253388],” Critical Care, vol. 6, no. 3, pp. 251–258, 2002.
[40]
M. Confalonieri, R. Urbino, A. Potena et al., “Hydrocortisone infusion for severe community-acquired pneumonia: a preliminary randomized study,” American Journal of Respiratory and Critical Care Medicine, vol. 171, no. 3, pp. 242–248, 2005.
[41]
C. Garcia-Vidal, E. Calbo, V. Pascual, C. Ferrer, S. Quintana, and J. Garau, “Effects of systemic steroids in patients with severe community-acquired pneumonia,” European Respiratory Journal, vol. 30, no. 5, pp. 951–956, 2007.
[42]
S. C. A. Meijvis, H. Hardeman, H. H. F. Remmelts et al., “Dexamethasone and length of hospital stay in patients with community-acquired pneumonia: a randomised, double-blind, placebo-controlled trial,” The Lancet, vol. 377, no. 9782, pp. 2023–2030, 2011.
[43]
K. Mikami, M. Suzuki, H. Kitagawa et al., “Efficacy of corticosteroids in the treatment of community-acquired pneumonia requiring hospitalization,” Lung, vol. 185, no. 5, pp. 249–255, 2007.
[44]
S. Fernandez-Serrano, J. Dorca, C. Garcia-Vidal, et al., “Effect of corticosteroids on the clinical course of community-acquired pneumonia: a randomized controlled trial,” Crit Care, vol. 15, no. 2, article R96, 2011.
[45]
J. I. F. Salluh, P. Póvoa, M. Soares, H. C. Castro-Faria-Neto, F. A. Bozza, and P. T. Bozza, “The role of corticosteroids in severe community-acquired pneumonia: a systematic review,” Critical Care, vol. 12, no. 3, article R76, 2008.
[46]
D. Snijders, J. M. A. Daniels, C. S. de Graaff, T. S. van der Werf, and W. G. Boersma, “Efficacy of corticosteroids in community-acquired pneumonia: a randomized double-blinded clinical trial,” American Journal of Respiratory and Critical Care Medicine, vol. 181, no. 9, pp. 975–982, 2010.
[47]
M. S. Dehoux, A. Boutten, J. Ostinelli et al., “Compartmentalized cytokine production within the human lung in unilateral pneumonia,” American Journal of Respiratory and Critical Care Medicine, vol. 150, no. 3, pp. 710–716, 1994.
[48]
D. Annane, E. Bellissant, P.-E. Bollaert et al., “Corticosteroids in the treatment of severe sepsis and septic shock in adults: a systematic review,” Journal of the American Medical Association, vol. 301, no. 22, pp. 2362–2375, 2009.
[49]
D. Keh, T. Boehnke, S. Weber-Cartens et al., “Immunologic and hemodynamic effects of “low-dose” hydrocortisone in septic shock: a double-blind, randomized, placebo-controlled, crossover study,” American Journal of Respiratory and Critical Care Medicine, vol. 167, no. 4, pp. 512–520, 2003.
[50]
D. Annane, V. Sébille, C. Charpentier, et al., “Effect of treatment with low doses of hydrocortisone and fludrocortisone on mortality in patients with septic shock,” Journal of the American Medical Association, vol. 288, no. 7, pp. 862–871, 2002.
[51]
M. Oppert, S. Ralf, H. Claudia, et al., “Low-dose hydrocortisone improves shock reversal and reduces cytokine levels in early hyperdynamic septic shock,” Critical Care Medicine, vol. 33, no. 11, pp. 2457–2464, 2005.
[52]
P.-E. Bollaert, C. Charpentier, B. Levy, M. Debouverie, G. Audibert, and A. Larcan, “Reversal of late septic shock with supraphysiologic doses of hydrocortisone,” Critical Care Medicine, vol. 26, no. 4, pp. 645–650, 1998.
[53]
I. Kaufmann, J. Briegel, F. Schliephake et al., “Stress doses of hydrocortisone in septic shock: beneficial effects on opsonization-dependent neutrophil functions,” Intensive Care Medicine, vol. 34, no. 2, pp. 344–349, 2008.
[54]
D. Annane and J.-M. Cavaillon, “Corticosteroids in sepsis: from bench to bedside?” Shock, vol. 20, no. 3, pp. 197–207, 2003.
[55]
C. L. Sprung, D. Annane, D. Keh, et al., “Hydrocortisone therapy for patients with septic shock,” The New England Journal of Medicine, vol. 358, no. 2, pp. 111–124, 2008.
[56]
J. H. Beigel, J. Farrar, A. M. Han et al., “Avian influenza A (H5N1) infection in humans,” The New England Journal of Medicine, vol. 353, no. 13, pp. 1374–1385, 2005.
[57]
M. Confalonieri, R. Cifaldi, L. Dreas, M. Viviani, M. Biolo, and M. Gabrielli, “Methylprednisolone infusion for life-threatening H1N1-virus infection,” Therapeutic Advances in Respiratory Disease, vol. 4, no. 4, pp. 233–237, 2010.
[58]
J. M. Nicholls, L. L. M. Poon, K. C. Lee et al., “Lung pathology of fatal severe acute respiratory syndrome,” The Lancet, vol. 361, no. 9371, pp. 1773–1778, 2003.
[59]
C. K. Wong, C. W. K. Lam, A. K. L. Wu et al., “Plasma inflammatory cytokines and chemokines in severe acute respiratory syndrome,” Clinical and Experimental Immunology, vol. 136, no. 1, pp. 95–103, 2004.
[60]
M. J. Carter, “A rationale for using steroids in the treatment of severe cases of H5N1 avian influenza,” Journal of Medical Microbiology, vol. 56, no. 7, pp. 875–883, 2007.
[61]
I. N. Kandun, H. Wibisono, M. P. H. Endang, et al., “Three Indonesian clusters of H5N1 virus infection in 2005,” The New England Journal of Medicine, vol. 355, no. 21, pp. 2186–2194, 2006.
[62]
K. Chokephaibulkit, M. Uiprasertkul, P. Puthavathana et al., “A child with avian influenza A (H5N1) infection,” Pediatric Infectious Disease Journal, vol. 24, no. 2, pp. 162–166, 2005.
[63]
T. H. Tran, N. Thanh Liem, N. Thi Dung, et al., “Avian influenza A (H5N1) in 10 patients in Vietnam,” The New England Journal of Medicine, vol. 350, no. 12, pp. 1179–1188, 2004.
[64]
T. Xu, J. Qiao, L. Zhao et al., “Effect of dexamethasone on acute respiratory distress syndrome induced by the H5N1 virus in mice,” European Respiratory Journal, vol. 33, no. 4, pp. 852–860, 2009.
[65]
C. Brun-Buisson, J.-C. M. Richard, A. Mercat, A. C. M. Thiébaut, and L. Brochard, “Early corticosteroids in severe influenza A/H1N1 pneumonia and acute respiratory distress syndrome,” American Journal of Respiratory and Critical Care Medicine, vol. 183, no. 9, pp. 1200–1206, 2011.
[66]
A. M. Quispe-Laime, J. D. Bracco, P. A. Barberio et al., “H1N1 influenza A virus-associated acute lung injury: response to combination oseltamivir and prolonged corticosteroid treatment,” Intensive Care Medicine, vol. 36, no. 1, pp. 33–41, 2010.
[67]
K. Kudo, J. Takasaki, T. Manabe et al., “Systemic corticosteroids and early administration of antiviral agents for pneumonia with acute wheezing due to influenza a(H1N1)pdm09 in Japan,” PLoS ONE, vol. 7, no. 2, Article ID e32280, 2012.
[68]
C. Roberts, M. Nirmalan, and S. O'Shea, “Steroid-sensitive post-viral inflammatory pneumonitis (PVIP),” American Journal of Respiratory and Critical Care Medicine, vol. 182, no. 8, pp. 1089–1090, 2010.
[69]
H.-R. Kil, J.-H. Lee, K.-Y. Lee, J.-W. Rhim, Y.-S. Youn, and J.-H. Kang, “Early corticosteroid treatment for severe pneumonia caused by 2009 H1N1 influenza virus,” Critical Care, vol. 15, no. 2, article 413, 2011.
[70]
N. T. Liem, C. V. Tung, N. D. Hien et al., “Clinical features of human influenza a (H5N1) infection in Vietnam: 2004–2006,” Clinical Infectious Diseases, vol. 48, no. 12, pp. 1639–1646, 2009.
[71]
N. D. Hien, N. H. Ha, N. T. Van et al., “Human infection with highly pathogenic avian influenza virus (H5N1) in Northern Vietnam, 2004-2005,” Emerging Infectious Diseases, vol. 15, no. 1, pp. 19–23, 2009.
[72]
A. Mady, O. S. Ramadan, A. Yousef, Y. Mandourah, A. A. Amr, and M. Kherallah, “Clinical experience with severe 2009 H1N1 influenza in the intensive care unit at King Saud Medical City, Saudi Arabia,” Journal of Infection and Public Health, vol. 5, no. 1, pp. 52–56, 2012.
[73]
R. Perez-Padilla, D. de la Rosa-Zamboni, S. Ponce de Leon et al., “Pneumonia and respiratory failure from swine-origin influenza A (H1N1) in Mexico,” The New England Journal of Medicine, vol. 361, no. 7, pp. 680–689, 2009.
[74]
A.-N. Abdel-Ghafar, T. Chotpitayasunondh, Z. Gao et al., “Update on avian influenza A (H5N1) virus infection in humans,” The New England Journal of Medicine, vol. 358, no. 3, pp. 220–273, 2008.
[75]
N. Lee, D. Hui, A. Wu, et al., “A major outbreak of severe acute respiratory syndrome in Hong Kong,” The New England Journal of Medicine, vol. 348, no. 20, pp. 1986–1994, 2003.
[76]
S. M. Poutanen, M. P. H. Donald, B. Henry, et al., “Identification of severe acute respiratory syndrome in Canada,” The New England Journal of Medicine, vol. 348, no. 20, pp. 1995–2005, 2003.
[77]
J. C. Ho, G. C. Ooi, T. Y. Mok et al., “High-dose pulse versus nonpulse corticosteroid regimens in severe acute respiratory syndrome,” American Journal of Respiratory and Critical Care Medicine, vol. 168, no. 12, pp. 1449–1456, 2003.
[78]
W.-D. Jia, X.-L. Deng, X.-P. Tang et al., “Dose of glucocorticosteroids in the treatment of severe acute respiratory syndrome,” Nan Fang Yi Ke Da Xue Xue Bao, vol. 29, no. 11, pp. 2284–2287, 2009.
[79]
Y.-D. Xu, M. Jiang, R.-C. Chen, and J.-Q. Fang, “Evaluation of the efficacy and safety of corticosteroid in the treatment of severe SARS in Guangdong province with multi-factor regression analysis,” Chinese Critical Care Medicine, vol. 20, no. 2, pp. 84–87, 2008.
[80]
R.-C. Chen, X.-P. Tang, S.-Y. Tan et al., “Treatment of severe acute respiratory syndrome with glucosteroids: the Guangzhou experience,” Chest, vol. 129, no. 6, pp. 1441–1452, 2006.
[81]
L. J. Stockman, R. Bellamy, and P. Garner, “SARS: systematic review of treatment effects,” PLoS Medicine, vol. 3, no. 9, pp. 1525–1531, 2006.
[82]
M. Briel, R. Boscacci, H. Furrer, and H. C. Bucher, “Adjunctive corticosteroids for Pneumocystis jiroveci pneumonia in patients with HIV infection: a meta-analysis of randomised controlled trials,” BMC Infectious Diseases, vol. 5, article 101, 2005.
[83]
N. Patel and H. Koziel, “Pneumocystis jiroveci pneumonia in adult patients with AIDS: treatment strategies and emerging challenges to antimicrobial therapy,” Treatments in Respiratory Medicine, vol. 3, no. 6, pp. 381–397, 2004.
[84]
P. F. Volkow, P. Cornejo, J. W. Zinser, C. E. Ormsby, and G. Reyes-Terán, “Life-threatening exacerbation of Kaposi's sarcoma after prednisone treatment for immune reconstitution inflammatory syndrome,” AIDS, vol. 22, no. 5, pp. 663–665, 2008.
[85]
F. Fily, S. Lachkar, L. Thiberville, L. Favennec, and F. Caron, “Pneumocystis jirovecii colonization and infection among non HIV-infected patients,” Medecine et Maladies Infectieuses, vol. 41, no. 10, pp. 526–531, 2011.
[86]
F. Roblot, C. Godet, G. le Moal et al., “Analysis of underlying diseases and prognosis factors associated with Pneumocystis carinii pneumonia in immunocompromised HIV-negative patients,” European Journal of Clinical Microbiology and Infectious Diseases, vol. 21, no. 7, pp. 523–531, 2002.
[87]
S. H. Yale and A. H. Limper, “Pneumocystis carinii pneumonia in patients without acquired immunodeficiency syndrome: associated illnesses and prior corticosteroid therapy,” Mayo Clinic Proceedings, vol. 71, no. 1, pp. 5–13, 1996.
[88]
K. A. Sepkowitz, “Pneumocystis carinii pneumonia among patients with neoplastic disease,” Seminars in Respiratory Infections, vol. 7, no. 2, pp. 114–121, 1992.
[89]
D. Schiff, “Pneumocystis pneumonia in brain tumor patients: risk factors and clinical features,” Journal of Neuro-Oncology, vol. 27, no. 3, pp. 235–240, 1996.
[90]
B. Godeau, V. Coutant-Perronne, D. L. T. H. Du Le Thi Huong et al., “Pneumocystis carinii pneumonia in the course of connective tissue disease: report of 34 cases,” Journal of Rheumatology, vol. 21, no. 2, pp. 246–251, 1994.
[91]
J. G. Pareja, R. Garland, and H. Koziel, “Use of adjunctive corticosteroids in severe adult non-HIV Pneumocystis carinii pneumonia,” Chest, vol. 113, no. 5, pp. 1215–1224, 1998.
[92]
M. N. Vogel, M. Vatlach, P. Weissgerber, et al., “HRCT-features of Pneumocystis jiroveci pneumonia and their evolution before and after treatment in non-HIV immunocompromised patients,” European Journal of Radiology, vol. 81, no. 6, pp. 1315–1320, 2012.
