Invasive pulmonary aspergillosis in heart transplant recipients: Two radiologic patterns with a different prognosis

doi:10.1016/j.healun.2014.05.003

The Journal of Heart and Lung Transplantation

Volume 33, Issue 10, October 2014, Pages 1034-1040

https://doi.org/10.1016/j.healun.2014.05.003 Get rights and content

Background

Computed tomography (CT) findings can be used to classify invasive pulmonary aspergillosis (IPA) in 2 patterns: airway-invasive (AIR) or angioinvasive (ANG).

Methods

AIR-IPA was considered when the CT revealed peribronchial consolidation or a tree-in-bud pattern and ANG-IPA when a nodule, cavity, halo sign, infarct-shaped, or mass-like consolidation was found. We evaluated the correlation among IPA patterns on CT and outcomes in heart transplant (HT) recipients.

Results

The study included 27 HT recipients with a CT scan performed at the time of IPA diagnosis. The study interval was from 1988 to 2011. Ten AIR-IPA patients (37.1%) were compared with 17 ANG-IPA patients (62.9%). During the post-transplantation period before IPA developed, AIR patients required hemodialysis more frequently (40% vs 5.9%, p = 0.04). AIR patients also had more intercurrent bacterial pneumonia (23.5% vs 70%, p < 0.001), and IPA was diagnosed later after onset of symptoms (2.7 vs 8.5 d, p = 0.09). After diagnosis, AIR-IPA patients required more mechanical ventilation (23.5% vs 90%, p < 0.01) and had a higher related mortality rate (23.5% vs 70%, p = 0.04).

Conclusions

Our study shows that the AIR pattern represents 37% of IPA episodes in HT recipients and is associated with a more protracted clinical presentation, later diagnosis, and higher mortality rate.

Section snippets

Methods

This study was performed at a 1,750-bed tertiary center in Spain serving a population that ranged between 650,000 and 715,000 inhabitants during the study period. The transplant database was reviewed to identify all IPA episodes diagnosed from August 1988 to August 2011. Patients with an initial lung CT scan, defined as the first CT scan available whenever IPA was suspected, were included in the analysis. The Local Ethics Committee approved this study and determined that specific informed

Results

The analysis during study period included 27 HT patients diagnosed with IPA with an initial chest CT scan. Median age was 54 years (range, 35–66 years), and 23 (85.8%) were men. Median time of IPA diagnosis after HT was 54 days (range, 29–91), and IPA occurred within the first 3 months (early IPA) in 20 patients.

As noted on chest CT findings, the ANG pattern was found in 17 patients (62.9%) and the AIR pattern in 10 (37.1%). Both populations had similar epidemiologic characteristics (Table 1),

Discussion

In our series, AIR-IPA radiologic presentation accounted for 37% of IPA cases in HT recipients and was related with a significantly poorer prognosis. Although AIR-IPA patients had fewer underlying conditions, they required more hemodialysis after transplantation and presented more clinically insidious disease that took longer to be diagnosed and led to more respiratory failure and more need of mechanical ventilation. Consistently with previous studies, the overall mortality rate was 41%,9, 19,

Disclosure statement

The authors thank all of their colleagues from the Cardiology, Heart Surgery, Radiology, Clinical Microbiology, and Infectious Diseases Departments for their help. They also thank the heart transplant recipients for their continuous support and friendship.

This study was partially financed by the PROMULGA Project, Instituto de Investigación Carlos III, PI1002868.

None of the authors has a financial relationship with a commercial entity that has an interest in the subject of the presented

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Cited by (29)

Selection of Aspergillus fumigatus isolates carrying the G448S substitution in CYP51A gene after long-term treatment with voriconazole in an immunocompromised patient
2022, Medical Mycology Case Reports
We present a case of a 55-year-old man with a heart transplant who acquired Invasive Aspergillosis by Aspergillus fumigatus with the focus in the kidney. During about two years of antifungal treatment, most of the time with voriconazole, it was possible to obtain nine isolates of A. fumigatus, with the same genotypic characteristics, but with an increase in MIC for several azoles. The two last isolates presented high MICs for Voriconazole (>8 μg/mL>). Sequencing of the CYP51A gene showed G448S amino acid substitution in the same two isolates. In long-term treatments with antifungals, it would be important to regularly evaluate the susceptibility of isolated strains, as resistance to azoles has been increasingly described around the world.
Invasive pulmonary aspergillosis in heart transplant recipients: Is mortality decreasing?
2021, Revista Portuguesa de Cardiologia
Citation Excerpt :
In this immunosuppressed population, Aspergillus species are opportunistic pathogens that can cause aggressive infections including sinusitis, tracheobronchitis, pneumonia, necrotizing cellulitis, brain abscess, and disseminated disease. In heart transplant (HT) recipients, Aspergillus spp. have been reported as the most common cause of invasive fungal infection and frequently causes pneumonia2 with a high attributable mortality, ranging from 53% to 78%.3–5 Although invasive pulmonary aspergillosis (IPA) is a serious disease in this population, little is known about its natural history.
Infection remains a major complication among heart transplant (HT) recipients, causing approximately 20% of deaths in the first year after transplantation. In this population, Aspergillus species can have various clinical presentations including invasive pulmonary aspergillosis (IPA), which has high mortality (53-78%).
To establish the characteristics of IPA infection in HT recipients and their outcomes in our setting.
Of 328 heart transplantations performed in our center between 1998 and 2016, five cases of IPA were identified. Patient medical records were examined and clinical variables were extracted.
All cases were male, with a mean age of 62 years. The most common indication for HT was nonischemic dilated cardiomyopathy. Productive cough was reported as the main symptom. The imaging assessment was based on chest radiography and chest computed tomography. The most commonly reported radiological abnormality was multiple nodular opacities in both techniques. Bronchoscopy was performed in all patients and A. fumigatus was isolated in four cases on BAL culture. Treatment included amphotericin in four patients, subsequently changed to voriconazole in three patients, and posaconazole in one patient, with total treatment lasting an average of 12 months. Neutropenia was found in only one patient, renal failure was observed in two patients, and concurrent cytomegalovirus infection occurred in three patients. All patients survived after a mean follow-up of 18 months.
IPA is a potentially lethal complication after HT. An early diagnosis and prompt initiation of aggressive treatment are the cornerstone for better survival.
A infeção continua a ser a principal complicação dos doentes submetidos a transplante cardíaco (TC), originando aproximadamente 20% de mortalidade no primeiro ano pós transplante. Nesta população, a infeção Aspergillus pode causar diferentes quadros clínicos, incluindo a aspergilose pulmonar invasiva (API), com elevada mortalidade (53 a 78%).
Estabelecer as características da infeção por API nos doentes de TC e apresentar os respetivos resultados do nosso centro.
De 328 transplantes cardíacos realizados no nosso centro entre 1998 e 2016, identificámos cinco casos de API. Os registos médicos dos doentes foram examinados e as variáveis clínicas foram analisadas
Todos os casos corresponderam a doentes do sexo masculino com a idade média de 62 anos. A indicação mais comum para TC foi a miocardiopatia dilatada não isquémica. A tosse produtiva foi registada como principal sintoma. A avaliação radiológica baseou-se na radiografia e na tomografia computorizada ao tórax. A alteração radiológica mais comum foi, em ambas as técnicas, o registo de densidades nodulares múltiplas. A broncoscopia foi realizada em todos os doentes e o aspergillus fumigatus foi isolado em quarto casos de cultura BAL. O tratamento incluiu anfotericina em quatro doentes com mudança subsequente para voriconazol em três doentes e posaconazol em um doente, duração média do tratamento total de 12 meses. A neutropenia foi observada apenas num doente, a insuficiência renal em dois doentes e a infeção por CMV concomitante ocorreu em três doentes. Todos os doentes sobreviveram após um seguimento médio até 18 meses.
A API representa uma complicação potencialmente letal após TC. O diagnóstico precoce e a instituição também precoce de tratamento agressivo constituem a pedra angular para uma melhor sobrevivência.
CT of invasive pulmonary aspergillosis (IPA) in cases with hematologic malignancy: Comparison of CT features in the group classified by the severity of neutropenia and underlying disease
2020, European Journal of Radiology
Citation Excerpt :
IPA has two phenotypes: the angio-invasive form and the airway-invasive form. The two forms show a different prognosis, with the prognosis of the airway-invasive form being worse than that of the angio-invasive form among patients who have undergone heart transplantation or HSCT [3,4]. In general, the incidence of the airway-invasive form (14–34%) is lower than that of the angio-invasive form [5].
To identify differences in the radiological findings of invasive pulmonary aspergillosis (IPA) among patients classified by severity of neutropenia, and differences in underlying disease.
We retrospectively reviewed computed tomography (CT) scans from the time of the diagnosis of IPA in 83 hematological malignancy patients with probable or proven IPA according to the EORTC-MSG criteria. We evaluated CT findings (radiological pattern, number of lesions, distribution, and presence of low attenuation area [LAA]), and compared the radiological findings of patients classified by degree of neutropenia with two different indicators (neutrophil count at the onset, and c-d-index) and underlying disease.
Neutropenia at the onset of IPA was associated with an increased frequency of LAA (p < 0.05), especially in FN (p < 0.01). Cases with a c-d-index of ≧5500 showed an increased incidence of the angio-invasive pattern. In contrast, cases with a c-d-index of 0 showed an increased incidence of the airway-invasive pattern (p < 0.05). The airway-invasive pattern was more frequent in cases with MM, while the angio-invasive pattern was more frequent in cases with AML (p < 0.01). Lower-predominant distribution was more frequent and random distribution was less frequent in cases with AML, random distribution was more frequent and lower-predominant distribution was less frequent in cases with ALL, and upper-predominant distribution was more frequent in cases with MDS (p < 0.05).
CT features of IPA vary according to the degree of neutropenia and underlying disease.
CT Halo sign: A systematic review
2020, European Journal of Radiology
Citation Excerpt :
When a study reported more than 50 % of the population as neutropenic, it was classified as a study on neutropenic patients, whereas when the population was <50 % it was classified as a mixed study with both neutropenic and non-neutropenic patients. Of the remaining 47 studies, 18 were on non-neutropenic patients, [10,11,27,51,53,62,69,70,100,105,123,124,153,162–165,172], 7 were on mixed group (neutropenic plus non neutropenic) [4,14,34,40,60,93,161] and in 22 studies the status of neutropenia was not specified.(7,17,26,36,38,43,50,76,88,107,122,126–128141,146,159,166–169171] There were 24 studies in immunocompetent individuals (175 patients) and 12 studies in mixed population (both IS + IC) with 597 patients.
The CT Halo sign or Halo sign (HS) refers to ground-glass opacity surrounding a nodule or mass in the lung parenchyma. We conducted a systematic review to find the etiological associations of HS. We also evaluated the diagnostic performances of HS for invasive fungal infections (IFI) in immunosuppressed patients.
The systematic review was conducted as per PRISMA guidelines. We searched the PubMed and EMBASE database till June 2018 without any restrictions. Only case reports, case series and original articles published in English language were included. A database created from the electronic searches was compiled and subsequent analysis was done. [PROSPERO registration: CRD42018094739]
168 studies were eligible, which included 51 case reports, 15 prospective studies, 102 retrospective studies. A total of 1977 patients (out of 6371) with HS were identified with age range between <1year-94years. The most common diagnosis in the immunosuppressed, mixed, immunocompetent and not specified groups were IFI (86.9 %, n = 1194), Cryptococcosis (51.6 %, n = 124), Cryptococcosis (40 %, n = 20) and lung neoplasms (81.8 %, n = 36) respectively. 14 studies (11 retrospective, 3 prospective) were included in quantitative analysis. The pooled sensitivity(sn), specificity(sp) and odd’s ratio (OR) of HS for diagnosing IFI were 50.4 %, 91 % and 6.61 respectively. Also, HS could not reliably differentiate IPA from mucormycosis in the pooled analysis.
HS can be seen in a large number of diverse conditions both in immunosuppressed and immunocompetent population. In immunosuppressed patients HS is specific for IFI but cannot rule it out. Additionally, it cannot reliably distinguish between IPA and mucormycosis.
Invasive pulmonary aspergillosis in heart transplant recipients: Is mortality decreasing?
2019, Revista Portuguesa de Cardiologia
Citation Excerpt :
In this immunosuppressed population, Aspergillus spp. – an opportunistic pathogen – can cause aggressive infections including sinusitis, tracheobronchitis, pneumonia, necrotizing cellulitis, brain abscess, or disseminated disease. In heart transplant (HT) recipients, Aspergillus spp. has been reported as the most common cause of invasive fungal infection and frequently causes pneumonia2 with a high attributable mortality, ranging from 53% to 78%.3–5 Although invasive pulmonary aspergillosis (IPA) is a serious disease in this population, little is known about its natural history.
Infection remains a major complication among heart transplant (HT) recipients, causing approximately 20% of deaths in the first year after transplantation. In this population, Aspergillus spp. can have various clinical presentations including invasive pulmonary aspergillosis (IPA), with high mortality (53-78%).
To establish the characteristics of IPA infection in HT recipients and their outcomes in our center.
Among 328 HTs performed in our center between 1998 and 2016, we identified five cases of IPA. Patient medical records were examined and clinical variables were extracted.
All cases were male, and mean age was 62 years. The most common indication for HT was non-ischemic dilated cardiomyopathy. Productive cough was reported as the main symptom. The radiological assessment was based on chest X-ray and chest computed tomography. The most commonly reported radiographic abnormality was multiple nodular opacities in both techniques. Bronchoscopy was performed in all patients and Aspergillus fumigatus was isolated in four cases on bronchoalveolar lavage culture. Treatment included amphotericin in four patients, subsequently changed to voriconazole in three, and posaconazole in one patient, with total treatment lasting an average of 12 months. Neutropenia was found in only one patient, renal failure was observed in two patients, and concurrent cytomegalovirus infection in three patients. All patients were alive after a mean follow-up of 18 months.
IPA is a potentially lethal complication after HT. Early diagnosis and prompt initiation of aggressive treatment are the cornerstone of better survival.
A infeção continua a ser uma complicação major nos recipientes para transplante cardíaco (TC), causando cerca de 20% de mortes no primeiro ano após o transplante. Nestes doentes, o Aspergillus species pode levar a várias apresentações clínicas incluindo a aspergilose pulmonar invasiva (API), com uma mortalidade elevada (53% a 78%).
Estabelecer as características da infeção por API nos recipientes para TC e os respetivos resultados no nosso serviço.
Dos 328 transplantes cardíacos realizados no nosso centro entre 1998 e 2016, identificámos cinco casos de API. Foram examinados os registos dos doentes e foram identificadas variáveis clínicas.
Em todos os casos os doentes eram do sexo masculino com idade média de 62 anos. A indicação mais comum para TC foi a miocardiopatia não isquémica dilatada. O principal sintoma foi tosse produtiva. A avaliação radiológica baseou-se na radiografia e na TAC torácicas. A alteração radiológica mais comum foi a densidade nodular múltipla em ambas as técnicas. A broncoscopia foi realizada em todos os doentes e o Aspergillus fumigatus foi isolado em quatro casos de cultura BAL. O tratamento incluiu anfotericina em quatro doentes com alteração subsequente para voriconazol em três doentes e posaconazol num doente, tendo o tratamento durado uma média de 12 meses. A neutropenia foi encontrada num doente apenas, a insuficiência renal foi observada em dois doentes e a infeção por CMV ocorreu em três doentes. Todos os doentes sobreviveram após seguimento de 18 meses.
A API representa uma complicação potencialmente mortal após o TC. Um diagnóstico precoce e a iniciação de um tratamento rapidamente agressivo constituem a pedra angular para uma melhor sobrevivência.
Approach to Peribronchovascular Disease on CT
2019, Seminars in Ultrasound, CT and MRI
Diseases that are predominantly peribronchovascular in distribution on computed tomography by definition involve the bronchi, adjacent vasculature, and associated lymphatics involving the central or axial lung interstitium. An understanding of diseases that can present with focal peribronchovascular findings is useful for establishing diagnoses and guiding patient management. This review will cover clinical and imaging features that may assist in differentiating amongst the various causes of primarily peribronchovascular disease.

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Original Clinical ScienceInvasive pulmonary aspergillosis in heart transplant recipients: Two radiologic patterns with a different prognosis

Background

Methods

Results

Conclusions

Section snippets

Methods

Results

Discussion

Disclosure statement

Blood

Am J Transplant

J Heart Lung Transplant

Clin Radiol

J Infect

Pneumonia after heart transplantation: a multi-institutional study. Spanish Transplantation Infection Study Group

Clin Infect Dis

Prevalence and outcome of invasive fungal infections in 1,963 thoracic organ transplant recipients: a multicenter retrospective study. Italian Study Group of Fungal Infections in Thoracic Organ Transplant Recipients

Transplantation

The isolation of Aspergillus fumigatus from respiratory tract specimens in heart transplant recipients is highly predictive of invasive aspergillosis

Transplantation

Evaluation of MycAssay Aspergillus for diagnosis of invasive pulmonary aspergillosis in patients without hematological cancer

PLoS One

Invasive aspergillosis in transplant recipients

Medicine (Baltimore)

Infectious complications in heart transplant recipients receiving cyclosporine and corticosteroids

Ann Intern Med

Fungal diagnosis: how do we do it and can we do better?

Curr Med Res Opin

Improved management of invasive pulmonary aspergillosis in neutropenic patients using early thoracic computed tomographic scan and surgery

J Clin Oncol

Imaging findings in acute invasive pulmonary aspergillosis: clinical significance of the halo sign

Clin Infect Dis

High-resolution computed tomography and pathologic findings in pulmonary aspergillosis: a pictorial essay

Can Assoc Radiol J

Glossary of terms for CT of the lungs: recommendations of the Nomenclature Committee of the Fleischner Society

Radiology

Invasive aspergillosis of the airways: radiographic, CT, and pathologic findings

Radiology

Clinical and radiological features of invasive pulmonary aspergillosis in transplant recipients and neutropenic patients

Transpl Infect Dis

Revised definitions of invasive fungal disease from the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) Consensus Group

Clin Infect Dis

Original Clinical Science
Invasive pulmonary aspergillosis in heart transplant recipients: Two radiologic patterns with a different prognosis