The Clinical Respiratory Journal
ORIGINAL ARTICLE
Characteristics and outcomes of chronic pulmonary aspergillosis: a retrospective analysis of a tertiary hospital registry Boubou Camara1,2, Emilie Reymond2,6, Christel Saint-Raymond1,2, Hubert Roth1,2,7,8, Marie-Pierre Brenier-Pinchart2,3, Claudine Pinel2,3, Jacques Cadranel4,5, Gilbert Ferretti2,6, Hervé Pelloux2,3, Christophe Pison1,2,8 and Grenoble Aspergillus Committee* 1 Clinique Universitaire de Pneumologie, CHU Grenoble, Grenoble, France 2 Université Joseph Fourier, Grenoble, France 3 Laboratoire de Parasitologie-Mycologie, CHU Grenoble, Grenoble, France 4 Service de Pneumologie et Réanimation, Hôpital Tenon, Paris, France 5 Faculté de Médecine Pierre-et-Marie-Curie, Université Paris VI, Paris, France 6 Clinique d’Imagerie Médicale, CHU Grenoble, Grenoble, France 7 CRNH Rhône-Alpes, Pierre-Bénite, France 8 Inserm1055, Grenoble, France
Abstract Introduction: Our objective was to investigate characteristics risk factors and outcomes of patients with chronic pulmonary aspergillosis (CPA). Methods: The Aspergillosis Committee prospectively collected Aspergillus notifications from January 2000 to December 2011. A retrospective analysis of data was performed. Results: Among 1614 notifications registered, 44 cases of CPA in nonimmunocompromised patients were identified. The median age was 65 years (Q1–Q3: 54–75), the median body mass index (BMI) was 20 kg/m2 (Q1–Q3: 16–22) and 15 had chronic obstructive pulmonary disease. All patients had a positive specific serum precipitin antibody titer. Radiological presentations were: cavitations [single n = 31 (70%); multiple n = 12 (27%)] containing mycetomas [n = 18 (41%)], consolidations [n = 19 (43%)], emphysema [n = 15 (34%)] and sequelae of mycobacterial infection [n = 10 (23%)]. The median duration of follow-up was 30 months (Q1–Q3: 14–55). The median duration of antifungal treatment was 6 months (Q1–Q3: 3–12). Outcomes were unfavorable in 14 patients, and 12 (27%) died. Analysis by multivariate Cox regression model with bootstrapping showed that a higher BMI and a lower Charlson index score were predictive of favorable evolution, hazard ratio (95% confidence interval): BMI (+1) = 0.83 (0.71–0.97), Charlson (+1) = 1.37 (1.01–1.85). When analyses were restricted to chronic CPA and chronic necrotizing pulmonary aspergillosis, the multivariate Cox regression model showed that both BMI and Charlson index score were not statistically significant. Conclusion: Our results provide data on clinical characteristics and outcomes of CPA emphasizing the role of preexisting chronic respiratory conditions and protective effect of preserved BMI and lower Charlson index score. Please cite this paper as: Camara B, Reymond E, Saint-Raymond C, Roth H, Brenier-Pinchart M-P, Pinel C, Cadranel J, Ferretti G, Pelloux H, Pison C and Grenoble Aspergillus Committee. Characteristics and outcomes of chronic pulmonary aspergillosis: a retrospective analysis of a tertiary hospital registry. Clin Respir J 2015; 9: 65–73.
The Clinical Respiratory Journal (2015) • ISSN 1752-6981 © 2014 John Wiley & Sons Ltd
Key words Aspergillus – BMI – chronic pulmonary aspergillosis – COPD Correspondence Boubou Camara, MD, Clinique Universitaire de Pneumologie, Hôpital Albert Michallon, CHU de Grenoble, CS10217, 38043 Grenoble Cedex 9, France. Tel: +33 4 76 76 58 46 Fax: +33 4 76 76 87 32 email: [email protected] Received: 22 April 2013 Revision requested: 03 December 2013 Accepted: 04 January 2014 DOI:10.1111/crj.12105 *Aspergillus Commitee of Grenoble University Hospital: B. Camara, S. Quetant, B. Lebeau, A. Thiebaut-Bertrand, C. Saint-Raymond, D. Maubon, A. Bosseray, R. Hamidfar, C. Pinel, H. Pelloux, M. P. Brenier-Pinchart, M. R. Mallaret, D. Plantaz, S. Goutier, M. Cornet, O. Epaulard, E. Reymond and G. Ferretti. Authorship and contributorship Conception and design: B. Camara, H. Roth, J. Cadranel and C. Pison; data collection for the article: B. Camara, E. Reymond, C. Saint-Raymond, M. P. Brenier-Pinchart, C. Pinel, G. Ferretti, H. Pelloux and Grenoble Aspergillus Committee; literature search: B. Camara, H. Roth, M. P. Brenier-Pinchart and C. Pison; analysis and interpretation of data: B. Camara, E. Reymond, H. Roth, M. P. Brenier-Pinchart, G. Ferretti and C. Pison;
65
Chronic pulmonary aspergillosis in non-immunocompromised patients
statistical expertise: H. Roth; writing thearticle: B. Camara; critical revision of the article: H. Roth, M. P. Brenier-Pinchart, J. Cadranel, H. Pelloux and C. Pison; coordination: B. Camara; final approval of article: B. Camara, E. Reymond, C. Saint-Raymond, H. Roth, M. P. Brenier-Pinchart, C. Pinel, J. Cadranel, G. Ferretti, H. Pelloux and C. Pison.
non-interventional and retrospective analyses of medical records. Our study was conducted in accordance with legislation. The database was approved by the National Commission for Protection of Patients’ Rights and Electronic Data Recording (http://www.cnil.fr).
Ethics French law does not require approval of an Institutional Review Board or individual patient’s consent for such observational,
Abbreviations: AC Aspergillosis Committee BMI body mass index CCPA chronic cavitary pulmonary aspergillosis
Conflict of interest The authors report no conflicts of interest.
Introduction Chronic pulmonary aspergillosis (CPA) is a progressive pulmonary disorder that causes significant respiratory and systemic symptoms. In 2008, the Infectious Diseases Society of America (IDSA) distinguished three major subtypes of CPA (1): (i) chronic necrotizing pulmonary aspergillosis [CNPA, subacute invasive aspergillosis (IA), in mildly immunocompromised patients, with evidence implicating Aspergillus spp., occurring over 1–3 months, and marked radiological features]; (ii) chronic cavitary pulmonary aspergillosis (CCPA, pulmonary cavities which may or may not contain a fungal ball in a non-immunocompromised patient, with evidence implicating Aspergillus spp, presence of systemic or pulmonary symptoms and overt radiological progression); and (iii) simple aspergilloma (SA). CPA occurs in patients with underlying preexisting lung disease, with no severe immune impairment and characterized by pulmonary cavities with or without mycetoma, with Aspergillus antibody being positive (2, 3). A retrospective single-center study over an 11-year period was conducted in Grenoble University Hospital to investigate characteristics of patients with CPA. Our objectives were to describe the clinical and radiological characteristics, risk factors and outcomes related to antifungal treatment modalities.
Materials and methods Study design A working group composed of medical mycologists, infection control physicians and clinicians was created in 2000 in our hospital. The objective of the Aspergillosis Committee (AC) was management of IA and CPA (4, 5). The laboratory registers notifications of
66
Camara et al.
CI CNPA
confidence interval chronic necrotizing pulmonary aspergillosis COPD chronic obstructive pulmonary disease CPA chronic pulmonary aspergillosis CRP C-reactive protein CT computed tomography HR hazard ratio IA invasive aspergillosis ICS inhaled corticosteroids IDSA Infectious Diseases Society of America SA simple aspergilloma SD simple declarations WBC white blood cell
cases defined by microbiologic or serological signs of aspergillosis infections (presence of hyphae or Aspergillus positive culture, Aspergillus-positive antibody reaction or positive Aspergillus antigenemia). Clinicians reported cases with suspicion of IA or CPA. Data relating to host factors, demography, clinical microbiological and histological diagnoses resulted in a prospective registry of Aspergillus notifications. All suspected cases of IA and CPA were reviewed. Patients with cystic fibrosis were not included in this prospective registry.
Case definition of CPA and risk of CPA The criteria used for defining CPA were the diagnostic criteria published by Denning et al. (3, 6). All six following findings should be present for a diagnosis of CPA: (i) compatible chest imaging findings such as progressive pulmonary cavitation with associated cavity wall or pleural thickening on chest radiography or chest computed tomography (CT) scan; (ii) a stigma of aspergillosis infection in lung or pleural specimens (specific serum precipitin antibody titer, isolation or visualization of Aspergillus species); (iii) chronicity (at least 3 months) of pulmonary or constitutional symptoms; (iv) exclusion of a differential diagnoses that can mimic this disorder (e.g. Mycobacterial infection, pulmonary malignancy, Coccidioides immitis and Histoplasma capsulatum); (v) absence of significant systemic immunosuppression such as uncontrolled infection by human immunodeficiency infection, hematological malignancy, chronic granulomatous disease, progressive malignancy or systemic corticosteroid treatment (at daily dose >7.5 mg); and (vi) the presence of at least one marker of inflammation [raised white blood cell (WBC) count or abnormal value of C-reactive protein (CRP)]. Additional exclusion criteria were added to
The Clinical Respiratory Journal (2015) • ISSN 1752-6981 © 2014 John Wiley & Sons Ltd
Camara et al.
Chronic pulmonary aspergillosis in non-immunocompromised patients
1614 Aspergillus notifications from the Parasitology-Mycology Laboratory between 2000 and 2011
Simple declaration (n = 684; 42%)
Invasive aspergillosis (n = 588;36%) Proven: 14; Probable: 153 Possible: 85; Patients at risk: 336
Other alerts (n = 83; 5%)
Patients at high risk with notifications (n = 36) Unclassifiable (n = 47)
Chronic pulmonary aspergillosis notifications n = 259; 16%
Bronchial colonization (n = 142; 9%)
Aspergillus antibody (n = 51; 3%) Aspergillus antigenemia (n = 4; 0.2%) Excluded chronic pulmonary aspergillosis (n = 18; 1%)
Confirmed cases of chronic pulmonary aspergillosis (n = 44; 3%) Simple aspergilloma; n = 11 Chronic cavitary pulmonary aspergillosis; n = 11 Chronic necrotizing pulmonary aspergillosis; n = 22 Figure 1. Patient flowchart. From 2000 to 2011, 1614 notifications were prospectively recorded by the Mycology Laboratory: • Six hundred eighty-four notifications (42%) were simple declarations (SD) to the Aspergillus Committee (AC) [not at risk of chronic pulmonary aspergillosis (CPA) or invasive aspergillosis (IA)]. SD were the mycological notifications that corresponded to situations such as simple colonization, isolated Aspergillus positive antibody, simple sinus aspergilloma, otomycosis, Allergic bronchopulmomary aspergillosis and extrinsic allergic alveolitis. • IA defined according to references Ascioglu et al. (8), De Pauw et al. (9) and Stevens et al. (10) represented 588 cases (36%) [14 notifications of proven IA, 153 probable cases, 85 possible cases (8, 9) and 336 cases at risk (10)]. • Eighty-three other notifications (5%) were colonization or secondary infection in very fragile patients, but not immunocompromised (n = 36) or unclassifiable cases as IA or CPA (n = 47). • There were 259 cases (16%) of CPA, among them: ○
○ ○
One hundred ninety-seven patients at risk for CPA (142 patients had bronchial colonization by Aspergillus species, 51 patients had significant Aspergillus positive antibody and 4 patients had a positive Aspergillus antigenemia) Sixty-two patients had diagnostic criteria of a CPA, and 18 patients were excluded from the study Finally, from 1614 notifications, 44 cases of CPA (3%) in non-immunocompromised patients were identified: 11 cases were simple aspergilloma, 11 chronic cavitary pulmonary aspergillosis and 22 chronic necrotizing pulmonary aspergillosis.
those of CPA case definition described above: such as suspected cases of CPA with negative Aspergillus antibody titer. All cases suspected of CPA, with underlying conditions (7), were reviewed by the AC. This study included patients with the three major subtypes of CPA, namely CCPA, CNPA and SA (1) as described in the literature (3, 7).
The Clinical Respiratory Journal (2015) • ISSN 1752-6981 © 2014 John Wiley & Sons Ltd
Patients (Fig. 1) From 2000 to 2011, 1614 notifications were prospectively recorded by the Mycology Laboratory within our Registry (Fig. 1). Six hundred eighty-four (42%) were simple declarations to the AC. These mycological notifications corresponded to situations such as simple 67
Chronic pulmonary aspergillosis in non-immunocompromised patients
colonization, isolated Aspergillus positive antibody, simple sinus aspergilloma, otomycosis, allergic bronchopulmonary aspergillosis and extrinsic allergic alveolitis. Five hundred eighty-eight notifications (36%) were for IA: 14 notifications of proven IA, 153 probable cases, 85 possible cases (8, 9) and 336 cases in patients at risk for IA (10). Eighty-three other notifications (5%) were classified by the AC: as colonization or secondary infection in very fragile patients, but not immunocompromised (n = 36) and unclassifiable cases (n = 47). There were 259 notifications (16%) of suspected CPA: 142 patients had bronchial colonization by Aspergillus species, 51 patients had significant Aspergillus positive antibody detection, 4 patients had a positive Aspergillus antigenemia and 62 patients had diagnostic criteria of CPA. Among the patients who had a diagnostic criterion for CPA, 18 (1%) patients were excluded from the study. Of these three patients were duplicates, five patients had incomplete medical records, three patients presented an Aspergillus negative antibody reaction, five patients were incompatible after the second reading of imaging and two presented an IA (two lung transplant patients). Finally, from 1614 alerts, 44 cases of CPA (3%) in non-immunocompromised patients were identified: 11 SA, 11 CCPA and 22 CNPA (Fig. 1).
Data collection The clinical characteristics, biological data, treatment modalities for the underlying lung disease, chest CT and treatment outcome were recorded. A second reading of the chest CT was conducted by both senior radiologists E. R. and G. F. to evaluate radiological improvement or stabilization during treatment. Latest follow-up data were recorded in December 2011.
Camara et al.
period, continuing poor appetite, worsening cough severity, high sputum load, worsening persistent shortness of breath and symptoms not improving). Radiological improvement was considered with partial or complete disappearance of findings initially thought to be related to CPA (reduction of mycetoma – i.e. size and number, parenchymal consolidations, wall thickening cavity, pleural effusion, pleural thickening and nodules). No significant change of findings initially thought to be related to CPA was considered as radiological stability. Radiological deterioration was defined by increased findings of CPA initially present and/or appearance of new chest CT abnormalities (increased of pericavitary thickening, pleural thickening, size of fungal ball, fibrosis and chest volume loss, new cavitation or fungal ball). The definition of favorable evolution was clinical improvement with radiographic stability, or clinical stability with evidence of radiographic improvement, or both clinical and radiographic improvement or both clinical and radiographic stability. Unfavorable evolution was defined by clinical and/or radiological deterioration.
Statistical analysis Continuous data are expressed as median and first and third quartiles (Q1–Q3). Category variables are expressed as percentages. To study disease evolution and its potential predictive factors of all group and the subgroup of patient with CCPA and CNPA, we used Cox proportional hazards regression analysis with bootstrapping in univariate models, and then keeping variables significant at the P < 0.20 level in multivariate models with bootstrapping to test the internal validity (Stata 12, Stata Corp., College Station, TX, USA). A P value level
ORIGINAL ARTICLE
Characteristics and outcomes of chronic pulmonary aspergillosis: a retrospective analysis of a tertiary hospital registry Boubou Camara1,2, Emilie Reymond2,6, Christel Saint-Raymond1,2, Hubert Roth1,2,7,8, Marie-Pierre Brenier-Pinchart2,3, Claudine Pinel2,3, Jacques Cadranel4,5, Gilbert Ferretti2,6, Hervé Pelloux2,3, Christophe Pison1,2,8 and Grenoble Aspergillus Committee* 1 Clinique Universitaire de Pneumologie, CHU Grenoble, Grenoble, France 2 Université Joseph Fourier, Grenoble, France 3 Laboratoire de Parasitologie-Mycologie, CHU Grenoble, Grenoble, France 4 Service de Pneumologie et Réanimation, Hôpital Tenon, Paris, France 5 Faculté de Médecine Pierre-et-Marie-Curie, Université Paris VI, Paris, France 6 Clinique d’Imagerie Médicale, CHU Grenoble, Grenoble, France 7 CRNH Rhône-Alpes, Pierre-Bénite, France 8 Inserm1055, Grenoble, France
Abstract Introduction: Our objective was to investigate characteristics risk factors and outcomes of patients with chronic pulmonary aspergillosis (CPA). Methods: The Aspergillosis Committee prospectively collected Aspergillus notifications from January 2000 to December 2011. A retrospective analysis of data was performed. Results: Among 1614 notifications registered, 44 cases of CPA in nonimmunocompromised patients were identified. The median age was 65 years (Q1–Q3: 54–75), the median body mass index (BMI) was 20 kg/m2 (Q1–Q3: 16–22) and 15 had chronic obstructive pulmonary disease. All patients had a positive specific serum precipitin antibody titer. Radiological presentations were: cavitations [single n = 31 (70%); multiple n = 12 (27%)] containing mycetomas [n = 18 (41%)], consolidations [n = 19 (43%)], emphysema [n = 15 (34%)] and sequelae of mycobacterial infection [n = 10 (23%)]. The median duration of follow-up was 30 months (Q1–Q3: 14–55). The median duration of antifungal treatment was 6 months (Q1–Q3: 3–12). Outcomes were unfavorable in 14 patients, and 12 (27%) died. Analysis by multivariate Cox regression model with bootstrapping showed that a higher BMI and a lower Charlson index score were predictive of favorable evolution, hazard ratio (95% confidence interval): BMI (+1) = 0.83 (0.71–0.97), Charlson (+1) = 1.37 (1.01–1.85). When analyses were restricted to chronic CPA and chronic necrotizing pulmonary aspergillosis, the multivariate Cox regression model showed that both BMI and Charlson index score were not statistically significant. Conclusion: Our results provide data on clinical characteristics and outcomes of CPA emphasizing the role of preexisting chronic respiratory conditions and protective effect of preserved BMI and lower Charlson index score. Please cite this paper as: Camara B, Reymond E, Saint-Raymond C, Roth H, Brenier-Pinchart M-P, Pinel C, Cadranel J, Ferretti G, Pelloux H, Pison C and Grenoble Aspergillus Committee. Characteristics and outcomes of chronic pulmonary aspergillosis: a retrospective analysis of a tertiary hospital registry. Clin Respir J 2015; 9: 65–73.
The Clinical Respiratory Journal (2015) • ISSN 1752-6981 © 2014 John Wiley & Sons Ltd
Key words Aspergillus – BMI – chronic pulmonary aspergillosis – COPD Correspondence Boubou Camara, MD, Clinique Universitaire de Pneumologie, Hôpital Albert Michallon, CHU de Grenoble, CS10217, 38043 Grenoble Cedex 9, France. Tel: +33 4 76 76 58 46 Fax: +33 4 76 76 87 32 email: [email protected] Received: 22 April 2013 Revision requested: 03 December 2013 Accepted: 04 January 2014 DOI:10.1111/crj.12105 *Aspergillus Commitee of Grenoble University Hospital: B. Camara, S. Quetant, B. Lebeau, A. Thiebaut-Bertrand, C. Saint-Raymond, D. Maubon, A. Bosseray, R. Hamidfar, C. Pinel, H. Pelloux, M. P. Brenier-Pinchart, M. R. Mallaret, D. Plantaz, S. Goutier, M. Cornet, O. Epaulard, E. Reymond and G. Ferretti. Authorship and contributorship Conception and design: B. Camara, H. Roth, J. Cadranel and C. Pison; data collection for the article: B. Camara, E. Reymond, C. Saint-Raymond, M. P. Brenier-Pinchart, C. Pinel, G. Ferretti, H. Pelloux and Grenoble Aspergillus Committee; literature search: B. Camara, H. Roth, M. P. Brenier-Pinchart and C. Pison; analysis and interpretation of data: B. Camara, E. Reymond, H. Roth, M. P. Brenier-Pinchart, G. Ferretti and C. Pison;
65
Chronic pulmonary aspergillosis in non-immunocompromised patients
statistical expertise: H. Roth; writing thearticle: B. Camara; critical revision of the article: H. Roth, M. P. Brenier-Pinchart, J. Cadranel, H. Pelloux and C. Pison; coordination: B. Camara; final approval of article: B. Camara, E. Reymond, C. Saint-Raymond, H. Roth, M. P. Brenier-Pinchart, C. Pinel, J. Cadranel, G. Ferretti, H. Pelloux and C. Pison.
non-interventional and retrospective analyses of medical records. Our study was conducted in accordance with legislation. The database was approved by the National Commission for Protection of Patients’ Rights and Electronic Data Recording (http://www.cnil.fr).
Ethics French law does not require approval of an Institutional Review Board or individual patient’s consent for such observational,
Abbreviations: AC Aspergillosis Committee BMI body mass index CCPA chronic cavitary pulmonary aspergillosis
Conflict of interest The authors report no conflicts of interest.
Introduction Chronic pulmonary aspergillosis (CPA) is a progressive pulmonary disorder that causes significant respiratory and systemic symptoms. In 2008, the Infectious Diseases Society of America (IDSA) distinguished three major subtypes of CPA (1): (i) chronic necrotizing pulmonary aspergillosis [CNPA, subacute invasive aspergillosis (IA), in mildly immunocompromised patients, with evidence implicating Aspergillus spp., occurring over 1–3 months, and marked radiological features]; (ii) chronic cavitary pulmonary aspergillosis (CCPA, pulmonary cavities which may or may not contain a fungal ball in a non-immunocompromised patient, with evidence implicating Aspergillus spp, presence of systemic or pulmonary symptoms and overt radiological progression); and (iii) simple aspergilloma (SA). CPA occurs in patients with underlying preexisting lung disease, with no severe immune impairment and characterized by pulmonary cavities with or without mycetoma, with Aspergillus antibody being positive (2, 3). A retrospective single-center study over an 11-year period was conducted in Grenoble University Hospital to investigate characteristics of patients with CPA. Our objectives were to describe the clinical and radiological characteristics, risk factors and outcomes related to antifungal treatment modalities.
Materials and methods Study design A working group composed of medical mycologists, infection control physicians and clinicians was created in 2000 in our hospital. The objective of the Aspergillosis Committee (AC) was management of IA and CPA (4, 5). The laboratory registers notifications of
66
Camara et al.
CI CNPA
confidence interval chronic necrotizing pulmonary aspergillosis COPD chronic obstructive pulmonary disease CPA chronic pulmonary aspergillosis CRP C-reactive protein CT computed tomography HR hazard ratio IA invasive aspergillosis ICS inhaled corticosteroids IDSA Infectious Diseases Society of America SA simple aspergilloma SD simple declarations WBC white blood cell
cases defined by microbiologic or serological signs of aspergillosis infections (presence of hyphae or Aspergillus positive culture, Aspergillus-positive antibody reaction or positive Aspergillus antigenemia). Clinicians reported cases with suspicion of IA or CPA. Data relating to host factors, demography, clinical microbiological and histological diagnoses resulted in a prospective registry of Aspergillus notifications. All suspected cases of IA and CPA were reviewed. Patients with cystic fibrosis were not included in this prospective registry.
Case definition of CPA and risk of CPA The criteria used for defining CPA were the diagnostic criteria published by Denning et al. (3, 6). All six following findings should be present for a diagnosis of CPA: (i) compatible chest imaging findings such as progressive pulmonary cavitation with associated cavity wall or pleural thickening on chest radiography or chest computed tomography (CT) scan; (ii) a stigma of aspergillosis infection in lung or pleural specimens (specific serum precipitin antibody titer, isolation or visualization of Aspergillus species); (iii) chronicity (at least 3 months) of pulmonary or constitutional symptoms; (iv) exclusion of a differential diagnoses that can mimic this disorder (e.g. Mycobacterial infection, pulmonary malignancy, Coccidioides immitis and Histoplasma capsulatum); (v) absence of significant systemic immunosuppression such as uncontrolled infection by human immunodeficiency infection, hematological malignancy, chronic granulomatous disease, progressive malignancy or systemic corticosteroid treatment (at daily dose >7.5 mg); and (vi) the presence of at least one marker of inflammation [raised white blood cell (WBC) count or abnormal value of C-reactive protein (CRP)]. Additional exclusion criteria were added to
The Clinical Respiratory Journal (2015) • ISSN 1752-6981 © 2014 John Wiley & Sons Ltd
Camara et al.
Chronic pulmonary aspergillosis in non-immunocompromised patients
1614 Aspergillus notifications from the Parasitology-Mycology Laboratory between 2000 and 2011
Simple declaration (n = 684; 42%)
Invasive aspergillosis (n = 588;36%) Proven: 14; Probable: 153 Possible: 85; Patients at risk: 336
Other alerts (n = 83; 5%)
Patients at high risk with notifications (n = 36) Unclassifiable (n = 47)
Chronic pulmonary aspergillosis notifications n = 259; 16%
Bronchial colonization (n = 142; 9%)
Aspergillus antibody (n = 51; 3%) Aspergillus antigenemia (n = 4; 0.2%) Excluded chronic pulmonary aspergillosis (n = 18; 1%)
Confirmed cases of chronic pulmonary aspergillosis (n = 44; 3%) Simple aspergilloma; n = 11 Chronic cavitary pulmonary aspergillosis; n = 11 Chronic necrotizing pulmonary aspergillosis; n = 22 Figure 1. Patient flowchart. From 2000 to 2011, 1614 notifications were prospectively recorded by the Mycology Laboratory: • Six hundred eighty-four notifications (42%) were simple declarations (SD) to the Aspergillus Committee (AC) [not at risk of chronic pulmonary aspergillosis (CPA) or invasive aspergillosis (IA)]. SD were the mycological notifications that corresponded to situations such as simple colonization, isolated Aspergillus positive antibody, simple sinus aspergilloma, otomycosis, Allergic bronchopulmomary aspergillosis and extrinsic allergic alveolitis. • IA defined according to references Ascioglu et al. (8), De Pauw et al. (9) and Stevens et al. (10) represented 588 cases (36%) [14 notifications of proven IA, 153 probable cases, 85 possible cases (8, 9) and 336 cases at risk (10)]. • Eighty-three other notifications (5%) were colonization or secondary infection in very fragile patients, but not immunocompromised (n = 36) or unclassifiable cases as IA or CPA (n = 47). • There were 259 cases (16%) of CPA, among them: ○
○ ○
One hundred ninety-seven patients at risk for CPA (142 patients had bronchial colonization by Aspergillus species, 51 patients had significant Aspergillus positive antibody and 4 patients had a positive Aspergillus antigenemia) Sixty-two patients had diagnostic criteria of a CPA, and 18 patients were excluded from the study Finally, from 1614 notifications, 44 cases of CPA (3%) in non-immunocompromised patients were identified: 11 cases were simple aspergilloma, 11 chronic cavitary pulmonary aspergillosis and 22 chronic necrotizing pulmonary aspergillosis.
those of CPA case definition described above: such as suspected cases of CPA with negative Aspergillus antibody titer. All cases suspected of CPA, with underlying conditions (7), were reviewed by the AC. This study included patients with the three major subtypes of CPA, namely CCPA, CNPA and SA (1) as described in the literature (3, 7).
The Clinical Respiratory Journal (2015) • ISSN 1752-6981 © 2014 John Wiley & Sons Ltd
Patients (Fig. 1) From 2000 to 2011, 1614 notifications were prospectively recorded by the Mycology Laboratory within our Registry (Fig. 1). Six hundred eighty-four (42%) were simple declarations to the AC. These mycological notifications corresponded to situations such as simple 67
Chronic pulmonary aspergillosis in non-immunocompromised patients
colonization, isolated Aspergillus positive antibody, simple sinus aspergilloma, otomycosis, allergic bronchopulmonary aspergillosis and extrinsic allergic alveolitis. Five hundred eighty-eight notifications (36%) were for IA: 14 notifications of proven IA, 153 probable cases, 85 possible cases (8, 9) and 336 cases in patients at risk for IA (10). Eighty-three other notifications (5%) were classified by the AC: as colonization or secondary infection in very fragile patients, but not immunocompromised (n = 36) and unclassifiable cases (n = 47). There were 259 notifications (16%) of suspected CPA: 142 patients had bronchial colonization by Aspergillus species, 51 patients had significant Aspergillus positive antibody detection, 4 patients had a positive Aspergillus antigenemia and 62 patients had diagnostic criteria of CPA. Among the patients who had a diagnostic criterion for CPA, 18 (1%) patients were excluded from the study. Of these three patients were duplicates, five patients had incomplete medical records, three patients presented an Aspergillus negative antibody reaction, five patients were incompatible after the second reading of imaging and two presented an IA (two lung transplant patients). Finally, from 1614 alerts, 44 cases of CPA (3%) in non-immunocompromised patients were identified: 11 SA, 11 CCPA and 22 CNPA (Fig. 1).
Data collection The clinical characteristics, biological data, treatment modalities for the underlying lung disease, chest CT and treatment outcome were recorded. A second reading of the chest CT was conducted by both senior radiologists E. R. and G. F. to evaluate radiological improvement or stabilization during treatment. Latest follow-up data were recorded in December 2011.
Camara et al.
period, continuing poor appetite, worsening cough severity, high sputum load, worsening persistent shortness of breath and symptoms not improving). Radiological improvement was considered with partial or complete disappearance of findings initially thought to be related to CPA (reduction of mycetoma – i.e. size and number, parenchymal consolidations, wall thickening cavity, pleural effusion, pleural thickening and nodules). No significant change of findings initially thought to be related to CPA was considered as radiological stability. Radiological deterioration was defined by increased findings of CPA initially present and/or appearance of new chest CT abnormalities (increased of pericavitary thickening, pleural thickening, size of fungal ball, fibrosis and chest volume loss, new cavitation or fungal ball). The definition of favorable evolution was clinical improvement with radiographic stability, or clinical stability with evidence of radiographic improvement, or both clinical and radiographic improvement or both clinical and radiographic stability. Unfavorable evolution was defined by clinical and/or radiological deterioration.
Statistical analysis Continuous data are expressed as median and first and third quartiles (Q1–Q3). Category variables are expressed as percentages. To study disease evolution and its potential predictive factors of all group and the subgroup of patient with CCPA and CNPA, we used Cox proportional hazards regression analysis with bootstrapping in univariate models, and then keeping variables significant at the P < 0.20 level in multivariate models with bootstrapping to test the internal validity (Stata 12, Stata Corp., College Station, TX, USA). A P value level
