- Email: [email protected]
Pneumocystis jirovecii infection in patients with acute interstitial pneumonia
+Model
ARTICLE IN PRESS
Rev Clin Esp. 2018;xxx(xx):xxx---xxx
Revista Clínica Española www.elsevier.es/rce
BRIEF ORIGINAL
Pneumocystis jirovecii infection in patients with acute interstitial pneumonia M.T. Martínez-Rísquez a , V. Friaza b , C. de la Horra b , J. Martín-Juan c , E.J. Calderón b,d,e , F.J. Medrano b,d,e,∗ a
Departamento de Medicina Interna, Hospital San Juan de Dios del Aljarafe, Bormujos, Sevilla, Spain Instituto de Biomedicina de Sevilla, Hospital Universitario Virgen del Rocío/Consejo Superior de Investigaciones Científicas (CSIC)/Universidad de Sevilla, Sevilla, Spain c Departamento de Neumología, Hospital Universitario Virgen del Rocío, Sevilla, Spain d Departamento de Medicina Interna, Hospital Universitario Virgen del Rocío, Sevilla, Spain e Departamento de Medicina, Universidad de Sevilla, Sevilla, Spain b
Received 29 March 2018; accepted 14 April 2018
KEYWORDS Pneumocystis jirovecii; Acute interstitial pneumonia; Polymerase chain reaction
Abstract Objective: Acute interstitial pneumonia (AIP) is a severe disease of unknown etiology. Pneumocystis jirovecii is an atypical opportunistic fungus able to colonize patients with chronic pulmonary disease and inducing alveolar macrophage activation. The aim of this study was to evaluate the possible association between Pneumocystis jirovecii and AIP. Subjects and methods: The presence of P. jirovecii in bronchoalveolar lavage fluid in the four confirmed cases of AIP identified in a tertiary-care hospital over a period of 9 years was studied using a 2-step nested-PCR protocol assay. Results: P. jirovecii was identified in the four cases. None of them had HIV infection. Two of the patients were treated empirically with trimethoprim-sulfamethoxazole, the only survivor was being one of them. Conclusions: Our data suggest that Pneumocystis could trigger or favor the development of AIP. Further studies are needed to evaluate the role of the pathogen in the physiopathology of this disease. © 2018 Elsevier Espa˜ na, S.L.U. and Sociedad Espa˜ nola de Medicina Interna (SEMI). All rights reserved.
Please cite this article as: Martínez-Rísquez MT, Friaza V, de la Horra C, Martín-Juan J, Calderón EJ, Medrano FJ. Infección por Pneumocystis jirovecii en pacientes con neumonía intersticial aguda. Rev Clín Esp. 2018. https://doi.org/10.1016/j.rce.2018.04.016 ∗ Corresponding author. E-mail address: [email protected] (F.J. Medrano).
2254-8874/© 2018 Elsevier Espa˜ na, S.L.U. and Sociedad Espa˜ nola de Medicina Interna (SEMI). All rights reserved.
RCENG-1526; No. of Pages 4
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2
M.T. Martínez-Rísquez et al.
PALABRAS CLAVE Pneumocystis jirovecii; Neumonía intersticial aguda; Reacción en cadena de la polimerasa
Infección por Pneumocystis jirovecii en pacientes con neumonía intersticial aguda Resumen Objetivo: La neumonía intersticial aguda (NIA) es una enfermedad grave de etiología desconocida. Pneumocystis jirovecii es un hongo oportunista atípico capaz de colonizar pacientes con enfermedad pulmonar crónica e inducir la activación de los macrófagos alveolares. El objetivo de este trabajo fue valorar la posible asociación entre Pneumocystis jirovecii y la NIA. Sujetos y métodos: Se estudió la presencia de P. jirovecii mediante un método de PCR anidada de 2 pasos, en líquido de lavado broncoalveolar obtenido de los 4 casos confirmados de NIA identificados en un hospital terciario durante un período de 9 a˜ nos. Resultados: Se identificó P. jirovecii en los 4 casos. Ninguno de ellos estaba infectado por VIH. Se trató de forma empírica a 2 pacientes con trimetoprim-sulfametoxazol, siendo uno de ellos el único de los 4 casos que sobrevivió. Conclusiones: Nuestros datos sugieren que Pneumocystis podría desencadenar o favorecer el desarrollo de NIA. Es necesario realizar más estudios para evaluar el papel de este patógeno en la fisiopatología de dicha enfermedad. © 2018 Elsevier Espa˜ na, S.L.U. and Sociedad Espa˜ nola de Medicina Interna (SEMI). Todos los derechos reservados.
Background Idiopathic interstitial pneumonias (IIPs) are a heterogeneous group of acute and chronic lung diseases with progressive courses and unclear causes, characterized by expansion of the interstitial compartment of inflammatory cells and the potential of developing pulmonary fibrosis in many cases. The term idiopathic indicates an unknown cause, whereas interstitial refers to the involvement of the lung parenchyma by varying combinations of fibrosis and inflammation, in contrast to airspace disease typically seen in bacterial pneumonia. In 2002, the first international multidisciplinary consensus classification of IIPs, developed by the American Thoracic Society (ATS) and the European Respiratory Society (ERS), was published.1 In 2013, this classification was updated, and several changes were introduced. The major IIPs were grouped into the following types: chronic fibrosing (idiopathic pulmonary fibrosis and nonspecific interstitial pneumonia), smoking-related (respiratory bronchiolitis-associated interstitial lung disease and desquamative interstitial pneumonia) and acute/subacute (cryptogenic organizing pneumonia and acute interstitial pneumonia).2 Acute interstitial pneumonia (AIP) is clinically characterized as an interstitial lung disease causing rapid onset of respiratory failure, which is distinguishable from the other more chronic forms of interstitial pneumonia. AIP was described in 1935 and subsequently in 1944 by L. Hamman and A. Rich as a rapidly progressive lung disease with a process characterized by the presence of diffuse interstitial pneumonia and fibrosis, with a high mortality due to respiratory failure and right heart failure within 6 months of onset.3 The clinical and pathological features of this disorder were considered new and unusual, the histological features included diffuse alveolar damage, and its etiology is still unknown, although it has been proposed that infectious agents could trigger the process.4
In a fulminant case of AIP confirmed by biopsy at our hospital, Pneumocystis jirovecii was the only pathogen identified in the bronchoalveolar lavage (BAL) analysis. Pneumocystis jirovecii is an atypical opportunistic fungus with lung tropism and causes pneumonia in immunosuppressed individuals but rarely in nonimmunosuppressed patients.5 In the last few years, there has been a high prevalence of colonization by this pathogen in nonimmunosuppressed patients with different chronic pulmonary diseases such as idiopathic interstitial lung disease and chronic obstructive pulmonary disease (COPD).6,7 We can therefore hypothesize that Pneumocystis can be involved in the pathogenesis of AIP.
Patients and methods To evaluate the possible association between Pneumocystis jirovecii and AIP, we conducted a retrospective study that included all cases of biopsy-confirmed AIP with available BAL samples for microbiological analysis admitted to our hospital (a tertiary-care university hospital) from January 2001 to December 2009. Identification of P. jirovecii DNA was conducted by analyzing BAL samples using a 2-step protocol for a nested-polymerase chain reaction (PCR) assay that amplifies a portion of the gene encoding the mitochondrial large-subunit (mt LSU) ribosomal RNA (rRNA) with primers pAZ102-E and pAZ102-H in the first-round amplification, followed by pAZ102-X and pAZ102-Y in the second-round amplification.7 Pneumocystis DNA was extracted after samples were digested with proteinase K at 56 ◦ C by using a commercial kit (QIAGEN, Hilden, Germany). To prevent false positives from contamination, pipettes with filters were employed in all manipulations. DNA extraction, preparation of the reaction mixture, PCR amplification, and detection were performed in different areas under a
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Pneumocystis in patients with acute interstitial pneumonia
3
Table 1
Clinical and demographic characteristics of the 4 cases of acute interstitial pneumonia.
Case
Sex
Age, years
Smoking habit
Previous medical history
Use of steroids in the past 6 months
Treatment with TMP-SMX during the AIP episode
Clinical outcome
1
Male
75
No
Yes
No
Exitus
2
Male
48
No
No
Exitus
3 4
Female Male
55 51
Exsmoker Active Active
Sjögren’s syndrome CBS Breast cancer FSGS
No No
Yes Yes
Living Exitus
Abbreviations: AIP, acute interstitial pneumonia; CBS, chronic bronchial syndrome; FSGS, focal segmental glomerulonephritis; TMP-SMX: trimethoprim-sulfamethoxazole.
laminar flow hood. To detect any cross-contamination, all PCRs were performed with negative controls and sterile water. All samples that were positive according to the nested PCR were sequenced; polymorphisms at nucleotide positions 85 and 248 were detected by direct sequencing.
Results During the study period, 4 cases of AIP (1 woman and 3 men, 48---75 years of age) were identified. The patients’ most relevant characteristics are shown in Table 1. In 3 cases, the symptoms developed in less than a week. All patients experienced severe respiratory failure without hypercapnia and required admission to the intensive care unit and mechanical ventilation. One patient had a previous history of sicca syndrome and focal segmental glomerulonephritis and had been treated with oral corticosteroids. The female patient had been diagnosed with breast cancer 5 years before the study and had been treated with radiotherapy plus tamoxifen. The patient was in complete remission when the AIP occurred. None of the cases had human immunodeficiency virus infection. The microbiological stainings and conventional cultures for detecting bacteria, fungi and viruses in BAL samples were negative in all cases. The presence of Pneumocystis DNA was identified in all 4 cases. Two of the cases were typed as genotype 1, and 1 was typed as genotype 3. In the remaining case, the amplification was insufficient for sequencing. Two of the patients were treated empirically with a standard dose of trimethoprimsulfamethoxazole (20 mg of trimethoprim/kg per day), one of whom was the sole survivor of the AIP episodes.
inflammatory response caused by Pneumocystis colonization, which has already been described in a number of studies9,10 and which is similar to that observed during the development of pulmonary fibrosis,4 could be involved in the pathophysiology of AIP as in other IIPs. Moreover, the exudative phase of AIP is characterized by interstitial and intra-alveolar edema and hyperplasia of type II pneumocytes, findings commonly observed during the development of Pneumocystis pneumonia.8 The biological and histological changes that occur during Pneumocystis infection therefore resemble those of AIP. Based on these considerations and the fact that the only patient in our study with a successful outcome was treated with trimethoprim-sulfamethoxazole, we can suggest that Pneumocystis could trigger or favor the development of AIP. Further studies are needed to confirm the association between Pneumocystis colonization and AIP and to evaluate the possible role of the pathogen in the pathophysiology of this devastating disease, with its unknown etiology and high mortality.
Funding This study was funded by the Ministry of Health of the Government de Andalusia (project no. PI-0105-2012) and by The Iberian-American Program of Science and Technology for Development (Iberian-American Network for Pneumocystis: CYTED project no. 212RT0450).
References
Discussion Previous studies have shown a high prevalence of Pneumocystis jirovecii colonization in different pulmonary diseases such as IIP.6 However, our study is the first to describe the association between Pneumocystis infection and AIP. It is well known that Pneumocystis colonization significantly decreases pulmonary alveolar surfactant protein D (SP-D) levels,8 which appear to promote various lung aggressions, such as those produced by atmospheric pollutants, excess oxygen or lung inflammation, producing a further increase in oxidative stress, which is associated with the induction of pulmonary fibrosis. This finding raises the possibility that the activation of the local and systemic
1. American Thoracic Society, European Respiratory Society. American Thoracic Society/European Respiratory Society International Multidisciplinary Consensus Classification of the Idiopathic Interstitial Pneumonias. This joint statement of the American Thoracic Society (ATS), and the European Respiratory Society (ERS) was adopted by the ATS board of directors, June 2001 and by the ERS Executive Committee, June 2001. Am J Respir Crit Care Med. 2002;165:277---304. 2. Travis WD, Costabel U, Hansell DM, King TE Jr, Lynch DA, Nicholson AG, et al., ATS/ERS Committee on Idiopathic Interstitial Pneumonias. An official American Thoracic Society/European Respiratory Society statement: update of the international multidisciplinary classification of the idiopathic interstitial pneumonias. Am J Respir Crit Care Med. 2013;188:733---48.
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ARTICLE IN PRESS
4 3. Hamman L, Rich AR. Acute diffuse interstitial fibrosis of the lungs. Bull Johns Hopkins Hosp. 1944;74:177---212. 4. Bouros D, Nicholson AC, Polychronopoulos V, du Bois RM. Acute interstitial pneumonia. Eur Respir J. 2000;15: 412---8. 5. Cano S, Capote F, Pereira A, Calderon E, Castillo J. Pneumocystis carinii pneumonia in patients without predisposing illnesses. Acute episode and follow-up of five cases. Chest. 1993;104:376---81. 6. Vidal S, de la Horra C, Martín J, Montes-Cano MA, Rodríguez E, Respaldiza N, et al. Pneumocystis jirovecii colonisation in patients with interstitial lung disease. Clin Microbiol Infect. 2006;12:231---5. 7. Calderón EJ, Rivero L, Respaldiza N, Morilla R, Montes-Cano MA, Friaza V, et al. Systemic inflammation in patients with chronic
M.T. Martínez-Rísquez et al. obstructive pulmonary disease who are colonized with Pneumocystis jirovecii. Clin Infect Dis. 2007;45:e17---9. 8. Vassallo R, Standing JE, Limper AH. Isolated Pneumocystis carinii cell wall glucan provokes lower respiratory tract inflammatory responses. J Immunol. 2000;164:3755---63. 9. Fitzpatrick ME, Tedrow JR, Hillenbrand ME, Lucht L, Richards T, Norris KA, et al. Pneumocystis jirovecii colonization is associated with enhanced Th1 inflammatory gene expression in lungs of humans with chronic obstructive pulmonary disease. Microbiol Immunol. 2014;58:202---11. 10. Atochina N, Gow AJ, Beck JM, Haczku A, Inch A, Kadire H, et al. Delayed clearance of Pneumocystis carinii infection, increased inflammation, and altered nitric oxide metabolism in lungs of surfactant protein-D knockout mice. J Infect Dis. 2004;189:1528---39.
ARTICLE IN PRESS
Rev Clin Esp. 2018;xxx(xx):xxx---xxx
Revista Clínica Española www.elsevier.es/rce
BRIEF ORIGINAL
Pneumocystis jirovecii infection in patients with acute interstitial pneumonia M.T. Martínez-Rísquez a , V. Friaza b , C. de la Horra b , J. Martín-Juan c , E.J. Calderón b,d,e , F.J. Medrano b,d,e,∗ a
Departamento de Medicina Interna, Hospital San Juan de Dios del Aljarafe, Bormujos, Sevilla, Spain Instituto de Biomedicina de Sevilla, Hospital Universitario Virgen del Rocío/Consejo Superior de Investigaciones Científicas (CSIC)/Universidad de Sevilla, Sevilla, Spain c Departamento de Neumología, Hospital Universitario Virgen del Rocío, Sevilla, Spain d Departamento de Medicina Interna, Hospital Universitario Virgen del Rocío, Sevilla, Spain e Departamento de Medicina, Universidad de Sevilla, Sevilla, Spain b
Received 29 March 2018; accepted 14 April 2018
KEYWORDS Pneumocystis jirovecii; Acute interstitial pneumonia; Polymerase chain reaction
Abstract Objective: Acute interstitial pneumonia (AIP) is a severe disease of unknown etiology. Pneumocystis jirovecii is an atypical opportunistic fungus able to colonize patients with chronic pulmonary disease and inducing alveolar macrophage activation. The aim of this study was to evaluate the possible association between Pneumocystis jirovecii and AIP. Subjects and methods: The presence of P. jirovecii in bronchoalveolar lavage fluid in the four confirmed cases of AIP identified in a tertiary-care hospital over a period of 9 years was studied using a 2-step nested-PCR protocol assay. Results: P. jirovecii was identified in the four cases. None of them had HIV infection. Two of the patients were treated empirically with trimethoprim-sulfamethoxazole, the only survivor was being one of them. Conclusions: Our data suggest that Pneumocystis could trigger or favor the development of AIP. Further studies are needed to evaluate the role of the pathogen in the physiopathology of this disease. © 2018 Elsevier Espa˜ na, S.L.U. and Sociedad Espa˜ nola de Medicina Interna (SEMI). All rights reserved.
Please cite this article as: Martínez-Rísquez MT, Friaza V, de la Horra C, Martín-Juan J, Calderón EJ, Medrano FJ. Infección por Pneumocystis jirovecii en pacientes con neumonía intersticial aguda. Rev Clín Esp. 2018. https://doi.org/10.1016/j.rce.2018.04.016 ∗ Corresponding author. E-mail address: [email protected] (F.J. Medrano).
2254-8874/© 2018 Elsevier Espa˜ na, S.L.U. and Sociedad Espa˜ nola de Medicina Interna (SEMI). All rights reserved.
RCENG-1526; No. of Pages 4
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ARTICLE IN PRESS
2
M.T. Martínez-Rísquez et al.
PALABRAS CLAVE Pneumocystis jirovecii; Neumonía intersticial aguda; Reacción en cadena de la polimerasa
Infección por Pneumocystis jirovecii en pacientes con neumonía intersticial aguda Resumen Objetivo: La neumonía intersticial aguda (NIA) es una enfermedad grave de etiología desconocida. Pneumocystis jirovecii es un hongo oportunista atípico capaz de colonizar pacientes con enfermedad pulmonar crónica e inducir la activación de los macrófagos alveolares. El objetivo de este trabajo fue valorar la posible asociación entre Pneumocystis jirovecii y la NIA. Sujetos y métodos: Se estudió la presencia de P. jirovecii mediante un método de PCR anidada de 2 pasos, en líquido de lavado broncoalveolar obtenido de los 4 casos confirmados de NIA identificados en un hospital terciario durante un período de 9 a˜ nos. Resultados: Se identificó P. jirovecii en los 4 casos. Ninguno de ellos estaba infectado por VIH. Se trató de forma empírica a 2 pacientes con trimetoprim-sulfametoxazol, siendo uno de ellos el único de los 4 casos que sobrevivió. Conclusiones: Nuestros datos sugieren que Pneumocystis podría desencadenar o favorecer el desarrollo de NIA. Es necesario realizar más estudios para evaluar el papel de este patógeno en la fisiopatología de dicha enfermedad. © 2018 Elsevier Espa˜ na, S.L.U. and Sociedad Espa˜ nola de Medicina Interna (SEMI). Todos los derechos reservados.
Background Idiopathic interstitial pneumonias (IIPs) are a heterogeneous group of acute and chronic lung diseases with progressive courses and unclear causes, characterized by expansion of the interstitial compartment of inflammatory cells and the potential of developing pulmonary fibrosis in many cases. The term idiopathic indicates an unknown cause, whereas interstitial refers to the involvement of the lung parenchyma by varying combinations of fibrosis and inflammation, in contrast to airspace disease typically seen in bacterial pneumonia. In 2002, the first international multidisciplinary consensus classification of IIPs, developed by the American Thoracic Society (ATS) and the European Respiratory Society (ERS), was published.1 In 2013, this classification was updated, and several changes were introduced. The major IIPs were grouped into the following types: chronic fibrosing (idiopathic pulmonary fibrosis and nonspecific interstitial pneumonia), smoking-related (respiratory bronchiolitis-associated interstitial lung disease and desquamative interstitial pneumonia) and acute/subacute (cryptogenic organizing pneumonia and acute interstitial pneumonia).2 Acute interstitial pneumonia (AIP) is clinically characterized as an interstitial lung disease causing rapid onset of respiratory failure, which is distinguishable from the other more chronic forms of interstitial pneumonia. AIP was described in 1935 and subsequently in 1944 by L. Hamman and A. Rich as a rapidly progressive lung disease with a process characterized by the presence of diffuse interstitial pneumonia and fibrosis, with a high mortality due to respiratory failure and right heart failure within 6 months of onset.3 The clinical and pathological features of this disorder were considered new and unusual, the histological features included diffuse alveolar damage, and its etiology is still unknown, although it has been proposed that infectious agents could trigger the process.4
In a fulminant case of AIP confirmed by biopsy at our hospital, Pneumocystis jirovecii was the only pathogen identified in the bronchoalveolar lavage (BAL) analysis. Pneumocystis jirovecii is an atypical opportunistic fungus with lung tropism and causes pneumonia in immunosuppressed individuals but rarely in nonimmunosuppressed patients.5 In the last few years, there has been a high prevalence of colonization by this pathogen in nonimmunosuppressed patients with different chronic pulmonary diseases such as idiopathic interstitial lung disease and chronic obstructive pulmonary disease (COPD).6,7 We can therefore hypothesize that Pneumocystis can be involved in the pathogenesis of AIP.
Patients and methods To evaluate the possible association between Pneumocystis jirovecii and AIP, we conducted a retrospective study that included all cases of biopsy-confirmed AIP with available BAL samples for microbiological analysis admitted to our hospital (a tertiary-care university hospital) from January 2001 to December 2009. Identification of P. jirovecii DNA was conducted by analyzing BAL samples using a 2-step protocol for a nested-polymerase chain reaction (PCR) assay that amplifies a portion of the gene encoding the mitochondrial large-subunit (mt LSU) ribosomal RNA (rRNA) with primers pAZ102-E and pAZ102-H in the first-round amplification, followed by pAZ102-X and pAZ102-Y in the second-round amplification.7 Pneumocystis DNA was extracted after samples were digested with proteinase K at 56 ◦ C by using a commercial kit (QIAGEN, Hilden, Germany). To prevent false positives from contamination, pipettes with filters were employed in all manipulations. DNA extraction, preparation of the reaction mixture, PCR amplification, and detection were performed in different areas under a
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ARTICLE IN PRESS
Pneumocystis in patients with acute interstitial pneumonia
3
Table 1
Clinical and demographic characteristics of the 4 cases of acute interstitial pneumonia.
Case
Sex
Age, years
Smoking habit
Previous medical history
Use of steroids in the past 6 months
Treatment with TMP-SMX during the AIP episode
Clinical outcome
1
Male
75
No
Yes
No
Exitus
2
Male
48
No
No
Exitus
3 4
Female Male
55 51
Exsmoker Active Active
Sjögren’s syndrome CBS Breast cancer FSGS
No No
Yes Yes
Living Exitus
Abbreviations: AIP, acute interstitial pneumonia; CBS, chronic bronchial syndrome; FSGS, focal segmental glomerulonephritis; TMP-SMX: trimethoprim-sulfamethoxazole.
laminar flow hood. To detect any cross-contamination, all PCRs were performed with negative controls and sterile water. All samples that were positive according to the nested PCR were sequenced; polymorphisms at nucleotide positions 85 and 248 were detected by direct sequencing.
Results During the study period, 4 cases of AIP (1 woman and 3 men, 48---75 years of age) were identified. The patients’ most relevant characteristics are shown in Table 1. In 3 cases, the symptoms developed in less than a week. All patients experienced severe respiratory failure without hypercapnia and required admission to the intensive care unit and mechanical ventilation. One patient had a previous history of sicca syndrome and focal segmental glomerulonephritis and had been treated with oral corticosteroids. The female patient had been diagnosed with breast cancer 5 years before the study and had been treated with radiotherapy plus tamoxifen. The patient was in complete remission when the AIP occurred. None of the cases had human immunodeficiency virus infection. The microbiological stainings and conventional cultures for detecting bacteria, fungi and viruses in BAL samples were negative in all cases. The presence of Pneumocystis DNA was identified in all 4 cases. Two of the cases were typed as genotype 1, and 1 was typed as genotype 3. In the remaining case, the amplification was insufficient for sequencing. Two of the patients were treated empirically with a standard dose of trimethoprimsulfamethoxazole (20 mg of trimethoprim/kg per day), one of whom was the sole survivor of the AIP episodes.
inflammatory response caused by Pneumocystis colonization, which has already been described in a number of studies9,10 and which is similar to that observed during the development of pulmonary fibrosis,4 could be involved in the pathophysiology of AIP as in other IIPs. Moreover, the exudative phase of AIP is characterized by interstitial and intra-alveolar edema and hyperplasia of type II pneumocytes, findings commonly observed during the development of Pneumocystis pneumonia.8 The biological and histological changes that occur during Pneumocystis infection therefore resemble those of AIP. Based on these considerations and the fact that the only patient in our study with a successful outcome was treated with trimethoprim-sulfamethoxazole, we can suggest that Pneumocystis could trigger or favor the development of AIP. Further studies are needed to confirm the association between Pneumocystis colonization and AIP and to evaluate the possible role of the pathogen in the pathophysiology of this devastating disease, with its unknown etiology and high mortality.
Funding This study was funded by the Ministry of Health of the Government de Andalusia (project no. PI-0105-2012) and by The Iberian-American Program of Science and Technology for Development (Iberian-American Network for Pneumocystis: CYTED project no. 212RT0450).
References
Discussion Previous studies have shown a high prevalence of Pneumocystis jirovecii colonization in different pulmonary diseases such as IIP.6 However, our study is the first to describe the association between Pneumocystis infection and AIP. It is well known that Pneumocystis colonization significantly decreases pulmonary alveolar surfactant protein D (SP-D) levels,8 which appear to promote various lung aggressions, such as those produced by atmospheric pollutants, excess oxygen or lung inflammation, producing a further increase in oxidative stress, which is associated with the induction of pulmonary fibrosis. This finding raises the possibility that the activation of the local and systemic
1. American Thoracic Society, European Respiratory Society. American Thoracic Society/European Respiratory Society International Multidisciplinary Consensus Classification of the Idiopathic Interstitial Pneumonias. This joint statement of the American Thoracic Society (ATS), and the European Respiratory Society (ERS) was adopted by the ATS board of directors, June 2001 and by the ERS Executive Committee, June 2001. Am J Respir Crit Care Med. 2002;165:277---304. 2. Travis WD, Costabel U, Hansell DM, King TE Jr, Lynch DA, Nicholson AG, et al., ATS/ERS Committee on Idiopathic Interstitial Pneumonias. An official American Thoracic Society/European Respiratory Society statement: update of the international multidisciplinary classification of the idiopathic interstitial pneumonias. Am J Respir Crit Care Med. 2013;188:733---48.
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ARTICLE IN PRESS
4 3. Hamman L, Rich AR. Acute diffuse interstitial fibrosis of the lungs. Bull Johns Hopkins Hosp. 1944;74:177---212. 4. Bouros D, Nicholson AC, Polychronopoulos V, du Bois RM. Acute interstitial pneumonia. Eur Respir J. 2000;15: 412---8. 5. Cano S, Capote F, Pereira A, Calderon E, Castillo J. Pneumocystis carinii pneumonia in patients without predisposing illnesses. Acute episode and follow-up of five cases. Chest. 1993;104:376---81. 6. Vidal S, de la Horra C, Martín J, Montes-Cano MA, Rodríguez E, Respaldiza N, et al. Pneumocystis jirovecii colonisation in patients with interstitial lung disease. Clin Microbiol Infect. 2006;12:231---5. 7. Calderón EJ, Rivero L, Respaldiza N, Morilla R, Montes-Cano MA, Friaza V, et al. Systemic inflammation in patients with chronic
M.T. Martínez-Rísquez et al. obstructive pulmonary disease who are colonized with Pneumocystis jirovecii. Clin Infect Dis. 2007;45:e17---9. 8. Vassallo R, Standing JE, Limper AH. Isolated Pneumocystis carinii cell wall glucan provokes lower respiratory tract inflammatory responses. J Immunol. 2000;164:3755---63. 9. Fitzpatrick ME, Tedrow JR, Hillenbrand ME, Lucht L, Richards T, Norris KA, et al. Pneumocystis jirovecii colonization is associated with enhanced Th1 inflammatory gene expression in lungs of humans with chronic obstructive pulmonary disease. Microbiol Immunol. 2014;58:202---11. 10. Atochina N, Gow AJ, Beck JM, Haczku A, Inch A, Kadire H, et al. Delayed clearance of Pneumocystis carinii infection, increased inflammation, and altered nitric oxide metabolism in lungs of surfactant protein-D knockout mice. J Infect Dis. 2004;189:1528---39.