A cystic fibrosis child with lung function decline.

Respiratory infections are a major threat to cystic fibrosis patients. Besides bacteria, many fungi colonize the cystic fibrosis respiratory tract where an important fungal biota has been described. We report here the case of a 7-year-old cystic fibrosis child with pulmonary exacerbation and Arthrographis kalrae isolated from bronchoalveolar lavage fluid. To the best of our knowledge, this is the first reported case of lung infection due to Arhtrographis kalrae in a cystic fibrosis pediatric patient.

Inflammatory monocytes are detrimental to the host immune response during acute infection with Cryptococcus neoformans.

Cryptococcus neoformans is a leading cause of invasive fungal infections among immunocompromised patients. However, the cellular constituents of the innate immune response that promote clearance versus progression of infection upon respiratory acquisition of C. neoformans remain poorly defined. In this study, we found that during acute C. neoformans infection, CCR2+ Ly6Chi inflammatory monocytes (IM) rapidly infiltrate the lungs and mediate fungal trafficking to lung-draining lymph nodes. Interestingly, this influx of IM is detrimental to the host, since ablating IM or impairing their recruitment to the lungs improves murine survival and reduces fungal proliferation and dissemination. Using a novel conditional gene deletion strategy, we determined that MHC class II expression by IM did not mediate their deleterious impact on the host. Furthermore, although ablation of IM reduced the number of lymphocytes, innate lymphoid cells, and eosinophils in the lungs, the effects of IM were not dependent on these cells. We ascertained that IM in the lungs upregulated transcripts associated with alternatively activated (M2) macrophages in response to C. neoformans, consistent with the model that IM assume a cellular phenotype that is permissive for fungal growth. We also determined that conditional knockout of the prototypical M2 marker arginase 1 in IM and deletion of the M2-associated transcription factor STAT6 were not sufficient to reverse the harmful effects of IM. Overall, our findings indicate that C. neoformans can subvert the fungicidal potential of IM to enable the progression of infection through a mechanism that is not dependent on lymphocyte priming, eosinophil recruitment, or downstream M2 macrophage polarization pathways. These results give us new insight into the plasticity of IM function during fungal infections and the level of control that C. neoformans can exert on host immune responses.

Micosis pulmonares en niños: un enfoque diagnóstico / Pulmonary mycosis in children: a diagnostic approach

Pulmonary mycoses are invasive fungal infections that occur more and more frequently. The rising number of patients with immunodeficiencies, HIV infection, hematopoietic stem cell and solid organ transplant recipients, as well as the use of immunosuppressive therapies have increased the incidence of this disease. Diagnosis remains a challenge because the most accurate procedure is the isolation of the germ through culture of body fluids which have low sensitivity and a long development time (4-6 weeks). The diagnosis of pulmonary mycoses is based on the presence of risk factors, clinical and/or radiological symptoms suggestive of fungal infection and a positive microbiological test. Due to the fact that pulmonary mycoses are not usually considered in the differential diagnosis in the initial clinical evaluation of diseases and that the studies to establish the diagnosis are complex, they are diagnosed late when they have already become chronic with a high risk of morbidity and mortality

Las micosis pulmonares son infecciones invasivas que se presentan cada vez con mayor frecuencia en la población. El aumento del número de pacientes con inmunodeficiencias, infección por VIH, receptores de trasplante de células hematopoyéticas y órgano sólido, así como el uso de terapias inmunosupresoras ha incrementado la incidencia de esta enfermedad. El diagnóstico continúa siendo un reto debido a que el estándar de oro es el aislamiento del germen mediante cultivo de líquidos corporales los cuales tienen baja sensibilidad y un tiempo de desarrollo prolongado (4-6 semanas). El diagnóstico de las micosis pulmonares se basa en la presencia de factores de riesgo, cuadro clínico y/o radiológico sugestivo de infección fúngica y el estudio microbiológico positivo. Debido a que las micosis pulmonares habitualmente no se consideran dentro del diagnóstico diferencial en la evaluación clínica inicial de las enfermedades, asociado a la complejidad de estudios para establecer el diagnostico, las micosis pulmonares se diagnostican en forma tardía cuando ya existe enfermedad crónica, con alto riesgo de morbimortalidad

Fatal disseminated Rasamsonia infection in cystic fibrosis post-lung transplantation.

BACKGROUND: Disseminated fungal infections are a known serious complication in individuals with cystic fibrosis (CF) following orthotopic lung transplantation. Aspergillus fumigatus and Scedosporium species are among the more common causes of invasive fungal infection in this population. However, it is also important for clinicians to be aware of other emerging fungal species which may require markedly different antifungal therapies. CASE SUMMARY: We describe the first laboratory-documented case of a fatal disseminated fungal infection caused by Rasamsonia aegroticola in a 21-year-old female CF patient status post-bilateral lung transplantation, which was only identified post-mortem. Molecular analysis revealed the presence of the identical Rasamsonia strains in the patient's respiratory cultures preceding transplantation. DISCUSSION: We propose that the patient's disseminated fungal disease and death occurred as a result of recrudescence of Rasamsonia infection from her native respiratory system in the setting of profound immunosuppression post-operatively. Since Rasamsonia species have been increasingly recovered from the respiratory tract of CF patients, we further review the literature on these fungi and discuss their association with invasive fungal infections in the CF lung transplant host. CONCLUSION: Our report suggests Rasamsonia species may be important fungal pathogens that may have fatal consequences in immunosuppressed CF patients after solid organ transplantation.

Objective CT-based quantification of lung sequelae in treated patients with paracoccidioidomycosis.

This study presents methodology for objectively quantifying the pulmonary region affected by emphysemic and fibrotic sequelae in treated patients with paracoccidioidomycosis. This methodology may also be applied to any other disease that results in these sequelae in the lungs.Pulmonary high-resolution computed tomography examinations of 30 treated paracoccidioidomycosis patients were used in the study. The distribution of voxel attenuation coefficients was analyzed to determine the percentage of lung volume that consisted of emphysemic, fibrotic, and normal tissue. Algorithm outputs were compared with subjective evaluations by radiologists using a scale that is currently used for clinical diagnosis.Affected regions in the patient images were determined by computational analysis and compared with estimates by radiologists, revealing mean (± standard deviation) differences in the scores for fibrotic and emphysemic regions of 0.1% ±â€Š1.2% and -0.2% ±â€Š1.0%, respectively.The computational results showed a strong correlation with the radiologist estimates, but the computation results were more reproducible, objective, and reliable.

Clinical case of the month: a 22-year-old man with AIDS presenting with shortness of breath and an oral lesion.

Since the development of combination antiretroviral therapy (cART), the incidence and mortality associated with Kaposi sarcoma (KS) have been reduced, although not eliminated. Clinical presentations of KS range from simple skin involvement to disseminated disease, including involvement of the oral cavity and viscera, which portends a more ominous prognosis. Multiple case reports and data from clinical trials indicate that administration of systemic corticosteroids may aggravate KS. We present a case of disseminated KS following administration of prednisone for presumed immune reconstitution inflammatory syndrome (IRIS) associated with fungal pneumonia in an HIV-infected individual. The discussion that follows outlines the pathophysiology and clinical presentations associated with KS and existing data for the role of corticosteroids in promoting KS progression.

Endobronchial cryotherapy for a mycetoma.

Mycetoma is defined as a fungus ball that fills a preexisting lung cavity, most frequently being of tuberculous or sarcoid etiology. The most frequently isolated fungus is the species of Aspergillus, but other fungi such as Fusarium or Zygomycetes can also be present. Most patients lack symptoms. However, presentation may also be with hemoptysis, which can be massive and life-threatening. We describe the case of a 50-year-old man with a history of prior pulmonary tuberculosis, with recurrent episodes of cough and hemoptysis. He was diagnosed to have mycetoma in the left upper lobe cavity. The mycetoma was extracted through bronchoscopy under general anesthesia using a cryoprobe. Treatment was completed with amphotericin B instilled in the cavity and the patient was placed on oral itraconazole. This is the first case report to date in which cryotherapy was used to remove a mycetoma.

The mycoarray as an aid for the diagnosis of an imported case of histoplasmosis in an Italian traveler returning from Brazil.

We describe an imported case of histoplasmosis, whose serological profile was established by means of a protein-based microarray platform, the recently described mycoarray. Because of its peculiarities, such a novel tool greatly facilitates the rapid and multiparametric assessment of patients' serological status and lends itself to be employed as an aid in the diagnosis of primary mycoses, especially in nonendemic countries.

Reduced perfusion in pulmonary infiltrates of high-risk hematologic patients is a possible discriminator of pulmonary angioinvasive mycosis: a pilot volume perfusion computed tomography (VPCT) study.

RATIONALE AND OBJECTIVES: The aim of this study was to assess perfusion parameters in atypical pneumonia of heavily immunocompromised hematologic patients suspected of having invasive mycosis using volume perfusion computed tomography and establish their diagnostic role. MATERIALS AND METHODS: Volume perfusion computed tomographic data from 21 consecutive immunocompromised patients presenting with atypical parenchymal opacity of consolidation were analyzed with respect to the degree of perfusion of their pneumonias. All patients presented with clinical and laboratory signs of infection. Seventeen patients (10 men, seven women; mean age, 57 years; age range, 19-76 years) were found with proven (n = 9), probable (n = 2), or possible (n = 6) angioinvasive mycosis. One patient was diagnosed with bronchoinvasive aspergillosis. Four patients (all men; mean age, 71 years; age range, 67-79 years) were diagnosed with bacterial pneumonia. Volume perfusion computed tomography of the involved pulmonary areas was performed at 80 kV and 60 mAs, with 26 measurement points distributed over 65.9 seconds. Fifty milliliters of contrast material was injected at a rate of 5 mL/s, followed by a 50-mL saline chaser. Entire coverage of the pneumonic parenchymal consolidation was obtained in all patients, with the generation of parametric maps of blood flow (BF) using the maximal slope model and blood volume (BV) using Patlak analysis. The results of perfusion measurements were then analyzed and evaluated for all patients. RESULTS: Patients with proven, probable, or possible angioinvasive pulmonary fungal infection revealed very low levels of perfusion of their parenchymal consolidations, with BFs ranging from 0.01 to 23.86 mL/100 mL tissue/min and BVs ranging from 0.88 to 10.67 mL/100 mL tissue, lower than those of the adjacent thoracic musculature and of bacterial pneumonias. Bacterial pneumonias showed all increased perfusion parameters, with BFs ranging from 30.49 to 41.65 mL/100 mL tissue/min and BVs ranging from 10.07 to 49.90 mL/100 mL tissue. The cutoff BF value for differentiation was 23.89 mL/100 mL tissue/min, and the cutoff BV value was 9.6 mL/100 mL tissue. CONCLUSIONS: Patients with angioinvasive pulmonary mycosis showed lower perfusion parameters on volume perfusion computed tomography compared to those experiencing bacterial pneumonia.

Pulmonary paracoccidioidomycosis.

Paracoccidioidomycosis is a subacute or chronic systemic mycosis caused by Paracoccidioides brasiliensis, a soil saprophyte and thermally dimorphic fungus. The disease occurs mainly in rural workers in Latin America and is the most frequent endemic systemic mycosis in many countries of South America, where almost 10 million people are believed to be infected. Paracoccidioidomycosis should be regarded as a disease of travelers outside the endemic area. The primary pulmonary infection is subclinical in most cases, and individuals may remain infected throughout life without ever developing clinical signs. A small proportion of patients present with clinical disease. The lungs are frequently involved, and the pulmonary clinical manifestations must be differentiated from many other infectious and noninfectious conditions. Diagnosis should be based on epidemiological, clinical, and microbiological data. Effective treatment regimens are available to control the fungal infection, but most patients develop fibrotic sequelae that may severely hamper respiratory and adrenal function and the patient's well-being.

Clinician integrity and limits to patient autonomy.

A 28-year-old man with chronic granulomatous disease developed worsening respiratory status in the setting of chronic bacterial and fungal infections. The attending physician recommended transfer to the intensive care unit (ICU), but the patient declined. The patient understood that the nurses in the ICU have expertise in caring for patients with poor respiratory function. He also understood that he faced an increased risk of dying if he remained on the medical ward. At the same time, the patient was familiar with the nurses on the medical ward and felt comfortable there. Unsure of whether it was appropriate for clinicians to agree to provide less than optimal care for a critically ill patient, the clinicians on the medical ward requested a bioethics consultation. This article reviews the ethical issues that arise when patients ask clinicians to provide less than optimal care. Although it is well established that clinicians ought to respect patient autonomy, that obligation conflicted, in the present case, with the clinicians' sense of professional integrity. Future research on this vital but underexplored topic is needed to determine the extent to which clinicians' professional integrity places limits on the types of patient requests to which they should agree.

Aspergillus fumigatus colonization in cystic fibrosis: implications for lung function?

Aspergillus fumigatus is commonly found in the respiratory secretions of patients with cystic fibrosis (CF). Although allergic bronchopulmonary aspergillosis (ABPA) is associated with deterioration of lung function, the effects of A. fumigatus colonization on lung function in the absence of ABPA are not clear. This study was performed in 259 adults and children with CF, without ABPA. A. fumigatus colonization was defined as positivity of >50% of respiratory cultures in a given year. A cross-sectional analysis was performed to study clinical characteristics associated with A. fumigatus colonization. A retrospective cohort analysis was performed to study the effect of A. fumigatus colonization on lung function observed between 2002 and 2007. Longitudinal data were analysed with a linear mixed model. Sixty-one of 259 patients were at least intermittently colonized with A. fumigatus. An association was found between A. fumigatus colonization and increased age and use of inhaled antibiotics. In the longitudinal analysis, 163 patients were grouped according to duration of colonization. After adjustment for confounders, there was no significant difference in lung function between patients colonized for 0 or 1 year and patients with 2-3 or more than 3 years of colonization (p 0.40 and p 0.64) throughout the study. There was no significant difference in lung function decline between groups. Although colonization with A. fumigatus is more commonly found in patients with more severe lung disease and increased treatment burden, it is not independently associated with lower lung function or more severe lung function decline over a 5-year period.

Characteristics and consequences of airway colonization by filamentous fungi in 201 adult patients with cystic fibrosis in France.

A total of 657 sputum samples from 201 cystic fibrosis adult patients were collected during a 24-month period (2005-2006). We retrospectively analyzed the fungal colonization of the respiratory tract of these individuals by linking medical records and microbiological data. Filamentous fungi were isolated from specimens of 65.6% of the patients, with Aspergillus fumigatus being the predominant species recovered as it was found in specimens of 56.7% of the patients. We observed no difference for gender, pancreatic status and cirrhosis in patients with or without A. fumigatus colonization. We found a higher percentage of recovery of Pseudomonas aeruginosa, Stenotrophomonas maltophilia and nontuberculous mycobacteria in patients with A. fumigatus colonization. During the follow-up period of the study, 8.9% of the patients were diagnosed with allergic bronchopulmonary aspergillosis (ABPA). By a multivariate analysis we demonstrated that Scedosporium apiospermum was significantly associated with ABPA (Odds ratio = 13 [2-80]) as opposed to A. fumigatus (Odds ratio = 1.58 [0.49-5.05]).

Clinical associations and prevalence of Scedosporium spp. in Australian cystic fibrosis patients: identification of novel risk factors?

Risk factors for the association of Scedosporium in cases of cystic fibrosis (CF) and its clinical implications are poorly understood. Clinical, lung function and laboratory data of adult CF patients in Sydney (April 2008-March 2009) were prospectively analysed for such risk factors. Expectorated sputa were cultured for bacteria and examined for fungi using standard mycological and Scedosporium-selective media, and by an internal transcribed spacer region-targeted multiplex PCR assay. Scedosporium spp. (n = 4 each of Scedosporium prolificans, Scedosporium aurantiacum and Pseudallescheria boydii/ Scedosporium apiospermum complex [non-S. aurantiacum]) were recovered from 12 of 69 (17.4%) patients. Samples of 11 of the patients yielded isolates on Scedosporium- selective media (vs. 6 [8.7%] by non-selective culture) and one additional patient was noted by PCR. Of these patients, 83.3% were co-colonized with other moulds, most frequently Aspergillus fumigatus. Colonization was not associated with best FEV1/predicted, corticosteroid or antifungal therapies. By univariate analysis, patients with Scedosporium colonization were significantly less likely to be colonized with mucoid Pseudomonas aeruginosa (P = 0.025), while prior therapy with antistaphylococcal penicillins was a risk factor for colonization (P = 0.045). Bacterial colonization and antimicrobial exposure likely influence Scedosporium colonization, which is optimally detected with selective media. Studies are required to confirm independent risk factors for Scedosporium colonization and to determine its impact on lung disease.

A clinicopathological study of pulmonary mucormycosis in cancer patients: extensive angioinvasion but limited inflammatory response.

OBJECTIVES: Pulmonary mucormycosis (PMM) is an emerging, frequently lethal fungal infection in immunosuppressed cancer patients. We sought to characterize the histopathologic features of PMM in this population. METHODS: We identified patients with PMM who underwent autopsy or lung biopsy between 1990 and 2007. Histopathology slides were blindly reviewed by a pathologist and findings were scored on standardized forms. Pathologic findings were correlated with demographic and clinical data abstracted from patient's medical records. RESULTS: Twenty patients with PMM were included in this study. Nineteen patients (95%) had hematologic malignancies. High frequencies of angioinvasion (100%), hemorrhagic infarction (90%), coagulative necrosis (85%), and intra-alveolar hemorrhage (85%) were observed, whereas inflammatory infiltrates were uncommon (30%). Neutropenic patients had more extensive angioinvasion compared with non-neutropenic patients (77% versus 29%, P=0.06). Allogeneic hematopoietic stem cell transplantation (HSCT) recipients, all of whom had graft-versus-host disease, had more inflammatory cell infiltration but less intra-alveolar hemorrhage than non-HSCT patients (67% versus 14%, P=0.04; 50% versus 100%, P=0.02, respectively). CONCLUSIONS: PMM in immunocompromised cancer patients is characterized by extensive angioinvasion and coagulative necrosis. The different histopathologic features of PMM in neutropenic, non-neutropnic, and HSCT patients may reflect differences in the pathobiology of PMM in these populations.

Molecular diagnosis of disseminated adiaspiromycosis due to Emmonsia crescens.

Emmonsia crescens is a saprophytic fungus that is distributed worldwide, causing diseases mostly in rodents. It has also been described, though rarely, as an etiologic agent of pulmonary pathology in humans, potentially leading to death. A case of pulmonary adiaspiromycosis is reported in a 30-year-old immunocompetent man. The patient presented with a history of several weeks of weakness, cough, fever, and weight loss of 10 kg. Clinical and radiographic findings showed pulmonary lesions consistent with tuberculosis or histoplasmosis, but no pathogen was found with classical microbiological procedures. The diagnosis of adiaspiromycosis due to Emmonsia crescens was initially made using molecular biology techniques. Histological observations subsequently confirmed the presence of adiaspores in granulomas. To our knowledge, this is the first case of adiaspiromycosis diagnosed by PCR and sequencing. The patient was treated with itraconazole and was seen at 1 month with symptomatic improvement. Here we will discuss this rare fungal infection and its difficult treatment and diagnosis. As represented in this case, molecular biology is a powerful method to optimize diagnostic tests and therefore improve the care of the infected patient.

Fine needle aspiration of pulmonary adiaspiromycosis: a case report.

BACKGROUND: Pulmonary adiaspiromycosis is a common disease of many species of wild rodents and occasionally of humans, caused by the inhalation of spores of the fungus Chrysosporium parvum var crescens (Emmonsia crescens). CASE: A 74-year-old female with pulmonary adiaspiromycosis was diagnosed by radiologically guided lung fine needle aspiration (FNA). The specimen showed intracellular and extracellular 100-300 microm conidia with a distinct thick, trilaminar wall, which was positive for Gomori-methenamine silver and periodic acid-Schiff stain. The background consisted of a granulomatous process. CONCLUSION: FNA is an effective method of diagnosing pulmonary adiaspiromycosis, and pathologists need to be aware of the characteristic features of this unusual opportunistic fungal infection.