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1.
PLoS One ; 16(11): e0260274, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34807947

RESUMO

The clinical features by declining lung function remain uncharacterized in chronic pulmonary aspergillosis (CPA) patients. We investigated the clinical characteristics of CPA patients based on spirometric impairments (restrictive spirometric pattern [RSP] and obstructive spirometric pattern [OSP]) and their severity. We retrospectively analyzed medical records of CPA patients who underwent pulmonary function tests from March 2017 to February 2020. We used Global Lung Initiative 2012 equations with lower limit of normal. The clinical characteristics of patients with RSP were compared to those with OSP. Additionally, RSP patients' characteristics were analyzed according to forced vital capacity (FVC) tertile, and OSP patients' characteristics were analyzed according to forced expiratory volume in 1 second (FEV1) tertile. Among the 112 patients with CPA (52 [46%] with RSP and 60 [54%] with OSP), body mass index (BMI) was significantly lower in patients with RSP than in those with OSP (17.6 kg/m2 versus 20.3 kg/m2; P = 0.003), and non-tuberculous mycobacterial disease was more frequently observed in patients with RSP than in those with OSP (28.8% versus 11.7%; P = 0.004). Additionally, for patients with RSP, younger age and bilateral pulmonary lesions were more frequently observed in the first tertile group than in the other groups (P for trend: 0.025 and 0.001, respectively). For patients with OSP, low BMI, paracavitary infiltrates, and elevated WBC count were more frequently observed in the first tertile group than in the other groups (P for trend: < 0.001, 0.011, and 0.041, respectively). Differences in the clinical features of CPA patients were identified according to heterogeneous spirometric patterns and their severity. Further studies are needed to investigate the clinical significance of these findings.


Assuntos
Pulmão/fisiopatologia , Aspergilose Pulmonar/diagnóstico , Idoso , Aspergillus/isolamento & purificação , Doença Crônica , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Aspergilose Pulmonar/fisiopatologia , Espirometria , Capacidade Vital
2.
Respir Res ; 22(1): 263, 2021 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-34629055

RESUMO

BACKGROUND: Inhalation of fungal spores is a strong risk factor for severe asthma and experimentally leads to development of airway mycosis and asthma-like disease in mice. However, in addition to fungal spores, humans are simultaneously exposed to other inflammatory agents such as lipopolysaccharide (LPS), with uncertain relevance to disease expression. To determine how high dose inhalation of LPS influences the expression of allergic airway disease induced by the allergenic mold Aspergillus niger (A. niger). METHODS: C57BL/6J mice were intranasally challenged with the viable spores of A. niger with and without 1 µg of LPS over two weeks. Changes in airway hyperreactivity, airway and lung inflammatory cell recruitment, antigen-specific immunoglobulins, and histopathology were determined. RESULTS: In comparison to mice challenged only with A. niger, addition of LPS (1 µg) to A. niger abrogated airway hyperresponsiveness and strongly attenuated airway eosinophilia, PAS+ goblet cells and TH2 responses while enhancing TH1 and TH17 cell recruitment to lung. Addition of LPS resulted in more severe, diffuse lung inflammation with scattered, loosely-formed parenchymal granulomas, but failed to alter fungus-induced IgE and IgG antibodies. CONCLUSIONS: In contrast to the strongly allergic lung phenotype induced by fungal spores alone, addition of a relatively high dose of LPS abrogates asthma-like features, replacing them with a phenotype more consistent with acute hypersensitivity pneumonitis (HP). These findings extend the already established link between airway mycosis and asthma to HP and describe a robust model for further dissecting the pathophysiology of HP.


Assuntos
Alveolite Alérgica Extrínseca/microbiologia , Aspergillus niger/patogenicidade , Hiper-Reatividade Brônquica/microbiologia , Lipopolissacarídeos , Pulmão/microbiologia , Aspergilose Pulmonar/microbiologia , Esporos Fúngicos/patogenicidade , Alveolite Alérgica Extrínseca/induzido quimicamente , Alveolite Alérgica Extrínseca/imunologia , Alveolite Alérgica Extrínseca/fisiopatologia , Animais , Aspergillus niger/imunologia , Hiper-Reatividade Brônquica/induzido quimicamente , Hiper-Reatividade Brônquica/imunologia , Hiper-Reatividade Brônquica/fisiopatologia , Broncoconstrição , Modelos Animais de Doenças , Eosinófilos/imunologia , Exposição por Inalação , Pulmão/imunologia , Pulmão/fisiopatologia , Camundongos Endogâmicos C57BL , Aspergilose Pulmonar/imunologia , Aspergilose Pulmonar/fisiopatologia , Esporos Fúngicos/imunologia , Linfócitos T Auxiliares-Indutores/imunologia
4.
Med Mycol ; 58(7): 1000-1004, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-32343313

RESUMO

This study aimed to evaluate the impact of quantitative baseline Aspergillus-specific immunoglobulin G (IgG) serum levels on weight changes of patients with chronic pulmonary aspergillosis (CPA) under antifungal treatment. We retrospectively reviewed data of patients diagnosed with CPA between April 2015 and March 2018 at the National Aspergillosis Centre (Manchester, UK). All patients were on continued antifungal treatment for 12 months. Data on Aspergillus-specific IgG levels, St George's quality of life (SGQoL) variables and weight at baseline, 6 months and 12 months were extracted. We defined a high serum Aspergillus-specific IgG as ≥ 200 mg/l (Group A) and low level < 200 mg/l (Group B). Forty-nine patients (37 male; 12 female), median age 65 years (range: 29-86) were studied. Overall, 33% (n = 16) of the patients were in Group A. The baseline characteristics between the two groups were similar. The median Charlson comorbidity index was 4 (range: 0-5) and 3 (range: 0-9) for Group A and Group B, respectively (P = .543). There was a sustained decline in median Aspergillus IgG levels from baseline, through 6 month to 12 months of continues therapy from 170 (range: 20-1110) to 121 (range: 20-1126), and finally 107 (15-937) mg/l, respectively (P < .001). Group A patients gained more weight at 6 months (9/15 [60%] vs. 7/33 [21%], P = .012) and at 12 months of treatment (9/15 [60%] vs. 7/33 [22%]), and more patients in Group B lost weight ((13/33 [41%] vs. 1/15 [7%]), P = .015). However, there was no difference in QoL outcomes across groups at 6 (P = .3) and 12 (P = .7) months. A very high Aspergillus IgG may confer a higher likelihood of weight gain as a key, objective marker of clinical response, if patients can tolerate 12 months of antifungal therapy.


Assuntos
Anticorpos Antifúngicos/sangue , Antifúngicos/uso terapêutico , Aspergillus/imunologia , Imunoglobulina G/sangue , Aspergilose Pulmonar/tratamento farmacológico , Qualidade de Vida , Redução de Peso/efeitos dos fármacos , Adulto , Idoso , Idoso de 80 Anos ou mais , Doença Crônica , Feminino , Humanos , Itraconazol/uso terapêutico , Masculino , Pessoa de Meia-Idade , Aspergilose Pulmonar/fisiopatologia , Estudos Retrospectivos , Reino Unido , Voriconazol/uso terapêutico
5.
Clin Respir J ; 14(6): 571-577, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32077238

RESUMO

INTRODUCTION: Chronic pulmonary aspergillosis (CPA) is a fungal disease with high mortality and morbidity. Guidelines suggest treatment with azoles as first-line therapy. However, patients often develop treatment intolerance or increasingly azole resistance. OBJECTIVES: This retrospective review assesses outcomes in azole resistant or intolerant patients with CPA treated with cyclical echinocandin therapy. METHODS: We retrospectively examined records of 25 patients with CPA treated with cyclical caspofungin, 6 of whom were either azole-resistant or azole intolerant. Baseline characteristics, high-resolution computed tomography severity scores, forced expiratory volume after 1 minute (FEV1), forced vital capacity (FVC), body mass index and serology (Aspergillus fumigatus-specific IgG, Aspergillus fumigatus-specific IgE, total IgE and CRP) were assessed before and after caspofungin. RESULTS: Of the six patients, four (66%) started caspofungin due to intolerance and two (33%) due to pan-azole resistance. On treatment, there was stability in FEV1 with an overall mortality of 33% during the follow-up period with a median survival of 875.5 days (IQR 529-1024). No significant change in serology (A. fumigatus-specific IgG and CRP was seen. CONCLUSIONS: With pulsed echinocandin therapy, azole-intolerant or pan-resistant CPA patients have similar mortality rates to azole-naïve CPA patients. Pulsed echinocandin therapy may present a strategy to stabilize CPA in patients with pan resistance or intolerance to, azole therapy.


Assuntos
Antifúngicos/uso terapêutico , Azóis/normas , Equinocandinas/uso terapêutico , Aspergilose Pulmonar/tratamento farmacológico , Administração Intravenosa , Adulto , Idoso , Antifúngicos/administração & dosagem , Aspergillus fumigatus/imunologia , Azóis/uso terapêutico , Biomarcadores/sangue , Caspofungina/administração & dosagem , Caspofungina/uso terapêutico , Doença Crônica , Farmacorresistência Fúngica/fisiologia , Equinocandinas/administração & dosagem , Inibidores Enzimáticos/administração & dosagem , Inibidores Enzimáticos/uso terapêutico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde , Aspergilose Pulmonar/diagnóstico por imagem , Aspergilose Pulmonar/mortalidade , Aspergilose Pulmonar/fisiopatologia , Testes de Função Respiratória/métodos , Estudos Retrospectivos , Tomografia Computadorizada por Raios X/métodos , Reino Unido/epidemiologia
6.
Clin Microbiol Infect ; 25(9): 1157.e1-1157.e7, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30685498

RESUMO

OBJECTIVES: The treatment response in chronic pulmonary aspergillosis (CPA) is usually assessed based on the improvement in clinical and imaging findings. Herein, we evaluate serum Aspergillus fumigatus-specific IgG, serum galactomannan, weight change, and lung function for assessing treatment response in subjects with CPA. METHODS: We categorized treatment response as favourable (improved or stable clinical response with radiologically improved or stable disease) or unfavourable (worsening of symptoms or radiological progression) after 6 months of treatment with antifungal azoles. We measured A. fumigatus-specific IgG, serum galactomannan, weight, and lung function at baseline, 3 months, and 6 months in those with favourable and unfavourable treatment response. RESULTS: One hundred and twenty-six consecutive treatment-naïve subjects (53.2% (67/126) males; mean ± SD age, 42.3 ± 14.7 years) with CPA were included. One hundred and six and 20 were classified as having favourable and unfavourable response, respectively. After 6 months of treatment, the decline in serum A. fumigatus-specific IgG (n = 119) was similar in those with favourable or unfavourable response (mean ± SD, -26.3 ± 45.5 mgA/L vs. -3.4 ± 65.6 mgA/L; p 0.20). There was no significant change in the serum galactomannan (favourable vs. unfavourable: mean ± SD, -0.11 ± 2.8 vs. -0.62 ± 2; p 0.92) or FEV1 (favourable vs. unfavourable: mean ± SD, 24 ± 250 mL vs. -62 ± 154 mL; p 0.19) after 6 months of treatment. There was significant loss of weight (mean ± SD, -2.5 ± 4.5 kg) in subjects with unfavourable response. CONCLUSION: Serum A. fumigatus-specific IgG and serum galactomannan inconsistently decrease following treatment and may not be useful indicators for monitoring treatment response in CPA. Similarly, there is little change in pulmonary function following treatment. A gain in body weight is seen in those with favourable response.


Assuntos
Aspergilose Pulmonar/tratamento farmacológico , Adulto , Anticorpos Antifúngicos/sangue , Antifúngicos/uso terapêutico , Azóis/uso terapêutico , Peso Corporal , Doença Crônica , Feminino , Seguimentos , Galactose/análogos & derivados , Humanos , Imunoglobulina G/sangue , Pulmão/fisiologia , Masculino , Mananas/sangue , Pessoa de Meia-Idade , Estudos Prospectivos , Aspergilose Pulmonar/sangue , Aspergilose Pulmonar/imunologia , Aspergilose Pulmonar/fisiopatologia , Resultado do Tratamento
7.
Med Mycol ; 57(Supplement_2): S219-S227, 2019 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-30239804

RESUMO

Aspergillus colonization of the lower respiratory airways is common in normal people, and of little clinical significance. However, in some patients, colonization is associated with severe disease including poorly controlled asthma, allergic bronchopulmonary aspergillosis (ABPA) with sputum plugs, worse lung function in chronic obstructive pulmonary aspergillosis (COPD), invasive aspergillosis, and active infection in patients with chronic pulmonary aspergillosis (CPA). Therefore, understanding the pathophysiological mechanisms of fungal colonization in disease is essential to develop strategies to avert or minimise disease. Aspergillus cell components promoting fungal adherence to the host surface, extracellular matrix, or basal lamina are indispensable for pathogen persistence. However, our understanding of individual differences in clearance of A. fumigatus from the lung in susceptible patients is close to zero.


Assuntos
Aspergillus/crescimento & desenvolvimento , Interações Hospedeiro-Patógeno , Aspergilose Pulmonar/patologia , Aspergilose Pulmonar/fisiopatologia , Animais , Modelos Animais de Doenças , Humanos , Modelos Biológicos
8.
Intern Med ; 58(8): 1137-1140, 2019 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-30568135

RESUMO

A 64-year-old man who presented with repeated bouts of pneumothorax was admitted to our hospital because of gradually progressive dyspnea and repeated episodes of a fever. The physiological, radiological and pathological findings were consistent with pleuroparenchymal fibroelastosis (PPFE). In addition, the serum-specific precipitating antibody for Aspergillus was positive. After the administration of voriconazole, a marked improvement was observed in the imaging and physiological findings. Given this clinical course, we diagnosed the patient with PPFE secondary to aspergillosis. The present case suggests that a therapeutic approach based on the cause of secondary PPFE may improve the prognosis of PPFE.


Assuntos
Antifúngicos/uso terapêutico , Dispneia/tratamento farmacológico , Fibroelastose Endocárdica/tratamento farmacológico , Fibroelastose Endocárdica/microbiologia , Pneumotórax/tratamento farmacológico , Aspergilose Pulmonar/diagnóstico , Aspergilose Pulmonar/tratamento farmacológico , Doença Crônica/tratamento farmacológico , Dispneia/etiologia , Fibroelastose Endocárdica/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Pneumotórax/etiologia , Aspergilose Pulmonar/fisiopatologia , Resultado do Tratamento
9.
BMC Pulm Med ; 18(1): 185, 2018 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-30514257

RESUMO

BACKGROUND: Coexistence of aspergilloma and allergic bronchopulmonary aspergillosis (ABPA) has rarely been reported. Although the treatment for ABPA includes administration of corticosteroids and antifungal agents, little is known about the treatment for coexisting aspergilloma and ABPA. Furthermore, the impact of surgical resection for aspergilloma on ABPA is not fully understood. Here, we present an interesting case of recurrent ABPA with long-term follow-up after surgical resection of aspergilloma. CASE PRESENTATION: A 53-year-old man with a medical history of tuberculosis was referred to our hospital with cough and dyspnea. Imaging revealed multiple cavitary lesions in the right upper lobe of the lung, with a fungus ball and mucoid impaction. The eosinophil count, total serum immunoglobulin E (IgE), and Aspergillus-specific IgE levels were elevated. Specimens collected on bronchoscopy revealed fungal filaments compatible with Aspergillus species. Based on these findings, a diagnosis of ABPA with concomitant aspergilloma was made. Although treatment with corticosteroids and antifungal agents was administered, the patient's respiratory symptoms persisted. Therefore, he underwent lobectomy of the right upper lobe, which resulted in a stable condition without the need for medication. Twenty-three months after discontinuation of medical treatment, his respiratory symptoms gradually worsened with a recurrence of elevated eosinophil count and total serum IgE. Imaging revealed recurrent bronchiectasis and cavities with mucoid impaction in the right lower lobe, suggesting relapse of aspergilloma and ABPA. Corticosteroids and antifungal agents were re-administered; aspergilloma improved slightly over a 5-year period, and ABPA remained well controlled with low-dose prednisolone (5 mg/day). CONCLUSIONS: We describe the long-term follow-up outcomes of a patient with concomitant ABPA and aspergilloma, who underwent surgical resection for aspergilloma. Physicians should carefully monitor patients with coexisting ABPA and aspergilloma, as the condition may relapse after remission, even despite surgical resection for aspergilloma. Additionally, surgical resection for aspergilloma could result in resolution of ABPA.


Assuntos
Antifúngicos/administração & dosagem , Aspergilose Broncopulmonar Alérgica , Aspergillus , Eosinófilos , Glucocorticoides/administração & dosagem , Imunoglobulina E/sangue , Pulmão , Pneumonectomia , Complicações Pós-Operatórias , Aspergilose Broncopulmonar Alérgica/diagnóstico , Aspergilose Broncopulmonar Alérgica/etiologia , Aspergilose Broncopulmonar Alérgica/fisiopatologia , Aspergillus/efeitos dos fármacos , Aspergillus/isolamento & purificação , Broncoscopia/métodos , Humanos , Contagem de Leucócitos/métodos , Pulmão/diagnóstico por imagem , Pulmão/microbiologia , Masculino , Pessoa de Meia-Idade , Pneumonectomia/efeitos adversos , Pneumonectomia/métodos , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/fisiopatologia , Aspergilose Pulmonar/diagnóstico , Aspergilose Pulmonar/fisiopatologia , Aspergilose Pulmonar/cirurgia , Radiografia Torácica/métodos , Recidiva , Resultado do Tratamento
10.
Infect Immun ; 86(10)2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30104211

RESUMO

Humans are constantly exposed to the opportunistic mold Aspergillus fumigatus, and disease caused by this pathogen is often determined by the magnitude of local and systemic immune responses. We have previously shown a protective role for interleukin-22 (IL-22) after acute A. fumigatus exposure. Here, employing IL-22Cre R26ReYFP reporter mice, we identified iNKT cells, γδ T cells, and type 3 innate lymphoid cells (ILC3s) as lung cell sources of IL-22 in response to acute A. fumigatus exposure. As these cells often utilize common γ-chain cytokines for their development or maintenance, we determined the role of IL-7, IL-21, and IL-15 in lung IL-22 induction and A. fumigatus lung clearance. We observed that IL-7, IL-21, and IL-15 were essential for, partially required for, or negatively regulated the production of IL-22, respectively. Deficiency in IL-7 and IL-21, but not IL-15R, resulted in impaired fungal clearance. Surprisingly, however, the absence of IL-7, IL-21, or IL-15R signaling had no effect on neutrophil recruitment. The levels of IL-1α, an essential anti-A. fumigatus proinflammatory cytokine, were increased in the absence of IL-7 and IL-15R but decreased in the absence of IL-21. IL-7 was responsible for maintaining lung iNKT cells and γδ T cells, whereas IL-21 was responsible for maintaining lung iNKT cells and ILC3s. In contrast, IL-15R deficiency had no effect on the absolute numbers of any IL-22 cell source, rather resulting in enhanced per cell production of IL-22 by iNKT cells and γδ T cells. Collectively, these results provide insight into how the IL-22 response in the lung is shaped after acute A. fumigatus exposure.


Assuntos
Aspergillus fumigatus/efeitos dos fármacos , Citocinas/uso terapêutico , Interleucinas/uso terapêutico , Pulmão/fisiopatologia , Linfócitos/efeitos dos fármacos , Aspergilose Pulmonar/tratamento farmacológico , Aspergilose Pulmonar/fisiopatologia , Animais , Citocinas/imunologia , Humanos , Interleucinas/imunologia , Pulmão/microbiologia , Camundongos , Modelos Animais
11.
Respir Med ; 138: 1-6, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29724379

RESUMO

RATIONALE: Little is known about the role of Aspergillus precipitating antibody (APAb) in patients with Mycobacterium avium complex lung disease (MAC-LD). OBJECTIVES: We investigated the clinical characteristics of patients with MAC-LD positive for APAb. METHODS: We conducted a cross-sectional study targeting patients with MAC-LD. APAb was checked in all participants. Clinical variables included laboratory data, pulmonary function, high-resolution computed tomography findings, and health-related quality of life. RESULTS: We analyzed 109 consecutive patients. Their median age was 68 years, and the median duration of MAC-LD was 4.8 years. Twenty (18.3%) patients tested positive for APAb. APAb-positive patients had significantly longer duration of MAC-LD (9.4 vs. 4.0 years, P = 0.017), more severe bronchiectasis evaluated by modified Reiff score (6.5 vs. 4, P = 0.0049), and lower forced expiratory volume in 1 s (%FEV1) (75.1% vs. 86.2%, P = 0.013) than APAb-negative patients. Analysis of covariance adjusted for background factors and underlying pulmonary disease revealed that %FEV1 was also significantly lower in patients with APAb (P = 0.045). Ten patients were newly diagnosed with chronic pulmonary aspergillosis (N = 5) or allergic bronchopulmonary aspergillosis (N = 5). CONCLUSIONS: APAb is associated with lower pulmonary function, and observed especially in patients with longer duration of MAC-LD and severe bronchiectasis, even in the absence of cavitary lesions.


Assuntos
Anticorpos Antifúngicos/sangue , Aspergillus/imunologia , Infecção por Mycobacterium avium-intracellulare/complicações , Infecções Oportunistas/complicações , Aspergilose Pulmonar/complicações , Idoso , Biomarcadores/sangue , Bronquiectasia/microbiologia , Coinfecção/diagnóstico , Coinfecção/fisiopatologia , Estudos Transversais , Feminino , Volume Expiratório Forçado/fisiologia , Humanos , Pneumopatias/complicações , Pneumopatias/fisiopatologia , Masculino , Pessoa de Meia-Idade , Infecção por Mycobacterium avium-intracellulare/fisiopatologia , Infecções Oportunistas/diagnóstico , Infecções Oportunistas/fisiopatologia , Aspergilose Pulmonar/diagnóstico , Aspergilose Pulmonar/fisiopatologia , Qualidade de Vida , Testes de Função Respiratória , Tomografia Computadorizada por Raios X
12.
Infect Immun ; 86(7)2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29712727

RESUMO

The pulmonary mucus of cystic fibrosis (CF) patients displays elevated levels of the cathelicidin antimicrobial peptide LL-37, and the aim of this work was to assess the effect of LL-37 on the growth of Aspergillus fumigatus, a common pathogen of CF patients. Exposure of A. fumigatus to LL-37 and its derived fragment RK-31 (1.95 µg/ml) for 24 h had a positive effect on growth (199.94% ± 6.172% [P < 0.05] and 218.20% ± 4.63% [P < 0.05], respectively), whereas scrambled LL-37 peptide did not (85.12% ± 2.92%). Exposure of mycelium (preformed for 24 h) to 5 µg/ml intact LL-37 for 48 h increased hyphal wet weight (4.37 ± 0.23 g, P < 0.001) compared to the control (2.67 ± 0.05 g) and scrambled LL-37 (2.23 ± 0.09 g) treatments. Gliotoxin secretion from LL-37 exposed hyphae (169.1 ± 6.36 ng/mg hyphae, P < 0.05) was increased at 24 h compared to the results seen with the control treatment (102 ± 18.81 ng/mg hyphae) and the scrambled LL-37 treatment (96.09 ± 15.15 ng/mg hyphae). Shotgun proteomic analysis of 24-h LL-37-treated hyphae revealed an increase in the abundance of proteins associated with growth (eukaryotic translation initiation factor 5A [eIF-5A] [16.3-fold increased]), tissue degradation (aspartic endopeptidase [4.7-fold increased]), and allergic reactions (Asp F13 [10-fold increased]). By 48 h, there was an increase in protein levels indicative of cellular stress (glutathione peroxidase [9-fold increased]), growth (eIF-5A [6-fold increased]), and virulence (RNase mitogillin [3.7-fold increased]). These results indicate that LL-37 stimulates A. fumigatus growth and that this stimulation can result in increased fungal growth and secretion of toxins in the lungs of CF patients.


Assuntos
Peptídeos Catiônicos Antimicrobianos/metabolismo , Peptídeos Catiônicos Antimicrobianos/farmacocinética , Aspergillus fumigatus/crescimento & desenvolvimento , Aspergillus fumigatus/metabolismo , Fibrose Cística/fisiopatologia , Aspergilose Pulmonar/fisiopatologia , Aspergillus fumigatus/efeitos dos fármacos , Humanos , Catelicidinas
13.
Infect Immun ; 86(7)2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29712728

RESUMO

Chitin is a polysaccharide that provides structure and rigidity to the cell walls of fungi and insects. Mammals possess multiple chitinases, which function to degrade chitin, thereby supporting a role for chitinases in immune defense. However, chitin degradation has been implicated in the pathogenesis of asthma. Here, we determined the impact of acidic mammalian chitinase (AMCase) (Chia) deficiency on host defense during acute exposure to the fungal pathogen Aspergillus fumigatus as well as its contribution to A. fumigatus-associated allergic asthma. We demonstrate that chitin in the fungal cell wall was detected at low levels in A. fumigatus conidia, which emerged at the highest level during hyphal transition. In response to acute A. fumigatus challenge, Chia-/- mice unexpectedly demonstrated lower A. fumigatus lung burdens at 2 days postchallenge. The lower fungal burden correlated with decreased lung interleukin-33 (IL-33) levels yet increased IL-1ß and prostaglandin E2 (PGE2) production, a phenotype that we reported previously to promote the induction of IL-17A and IL-22. During chronic A. fumigatus exposure, AMCase deficiency resulted in lower dynamic and airway lung resistance than in wild-type mice. Improved lung physiology correlated with attenuated levels of the proallergic chemokines CCL17 and CCL22. Surprisingly, examination of inflammatory responses during chronic exposure revealed attenuated IL-17A and IL-22 responses, but not type 2 responses, in the absence of AMCase. Collectively, these data suggest that AMCase functions as a negative regulator of immune responses during acute fungal exposure and is a contributor to fungal asthma severity, putatively via the induction of proinflammatory responses.


Assuntos
Aspergillus fumigatus/imunologia , Quitinases/fisiologia , Aspergilose Pulmonar/imunologia , Animais , Asma/imunologia , Quimiocinas/análise , Quitina/análise , Feminino , Interleucina-33/análise , Pulmão/imunologia , Pulmão/microbiologia , Pulmão/fisiopatologia , Ativação de Macrófagos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Aspergilose Pulmonar/fisiopatologia
14.
BMJ Case Rep ; 20182018 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-29674397

RESUMO

A 68-year-old man, presented with 3 week history of infective symptoms and mild haemoptysis. Past medical history included severe emphysema and a chronic right upper lobe (RUL) cavity. He was discharged from follow-up a year ago in view of clinical and radiological stability; previous bronchoscopic examinations yielded no specific diagnosis. CT scan on admission confirmed complex cavitary consolidation of RUL. He developed massive haemoptysis requiring intubation and ventilation. CT pulmonary angiogram (CTPA) revealed 16 mm RUL pulmonary artery (PA) aneurysm which was successfully embolized. Sputum cultures, aspergillus antigen and rapidity of clinical progression suggested a diagnosis of subacute invasive aspergillosis (SAIA), prompting treatment with Voriconazole. Bronchoscopy showed blood ooze from RUL even after embolization. Unfortunately, patient continued to deteriorate and succumbed to profound septicaemia.


Assuntos
Aneurisma Infectado , Embolização Terapêutica/métodos , Hemoptise , Pneumonia , Aspergilose Pulmonar , Sepse , Voriconazol/administração & dosagem , Aneurisma Infectado/diagnóstico , Aneurisma Infectado/etiologia , Aneurisma Infectado/fisiopatologia , Aneurisma Infectado/terapia , Antifúngicos/administração & dosagem , Broncoscopia/métodos , Angiografia por Tomografia Computadorizada/métodos , Evolução Fatal , Hemoptise/diagnóstico , Hemoptise/etiologia , Hemoptise/terapia , Humanos , Masculino , Pessoa de Meia-Idade , Pneumonia/diagnóstico , Pneumonia/microbiologia , Pneumonia/fisiopatologia , Pneumonia/terapia , Aspergilose Pulmonar/complicações , Aspergilose Pulmonar/diagnóstico , Aspergilose Pulmonar/fisiopatologia , Aspergilose Pulmonar/terapia , Sepse/diagnóstico , Sepse/etiologia
15.
Eur Rev Med Pharmacol Sci ; 22(6): 1837-1842, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29630134

RESUMO

OBJECTIVE: To explore the clinical efficacy of sequential therapy with voriconazole on chronic obstructive pulmonary disease (COPD) patients in acute phase with pulmonary aspergillosis and its effects on cytokines and pulmonary functions. PATIENTS AND METHODS: A total of 110 COPD patients in acute phase with pulmonary aspergillosis who were admitted to the hospital between February 2015 and November 2016 were enrolled. We divided them randomly into two groups, i.e., the control group (n = 55) and the treatment group (n = 55). Patients in the control group took itraconazole capsules orally (200 mg/time, twice per day for three days followed by once per day). Patients in treatment group underwent sequential treatment with voriconazole through intravenous infusion at a dose of 5 mg/kg/time twice a day for 3 days followed by a dose of 4 mg/kg/time, twice a day for 8 days. Then, patients took voriconazole orally at a dose of 150 mL/time, twice a day for 6 days. Patients in two groups received the treatment for a total of 14 days. After treatment, we evaluated the levels of tumor necrosis factor α (TNF-α), interleukin 6 (IL-6), and IL-8. The total lung capacity (TLC), diffusing capacity of the lung for carbon monoxide (DLco), and arterial oxygen saturation (SaO2), were measured as well. RESULTS: The total effectiveness rates of the treatment group and the control group were 83.63% and 61.82%. The differences had statistical significance (p < 0.01). After treatment, the incidence of chest pain, cough, sputum-coughing, hemoptysis, cyanosis, and dyspnea in the treatment group was significantly fewer than that in the control group (p < 0.05). TCL, DLco, and SaO2 in the two groups were significantly ameliorated by treatment (p < 0.05). The amelioration in the treatment group was more prominent than that in the control group (p < 0.05). The levels of TNF-α, IL-8, and IL-6 in the two groups were decreased dramatically by the treatments. The decrease in the treatment group was significantly lower than those in the control group (p < 0.05). Occurrence of adverse reactions in treatment group and control group were 8.33% and 6.25%, respectively; (p > 0.05). CONCLUSIONS: Sequential therapy with voriconazole exhibits promising clinical efficacy in COPD patients in acute phase with pulmonary aspergillosis. The treatment ameliorated the clinical symptoms and vital signs of patients significantly. It also improved the pulmonary functions and inhibited the inflammatory responses of patients with evident clinical efficacy.


Assuntos
Antifúngicos/uso terapêutico , Citocinas/sangue , Aspergilose Pulmonar/tratamento farmacológico , Doença Pulmonar Obstrutiva Crônica/complicações , Voriconazol/uso terapêutico , Adulto , Idoso , Feminino , Humanos , Itraconazol/uso terapêutico , Pulmão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Aspergilose Pulmonar/imunologia , Aspergilose Pulmonar/fisiopatologia , Doença Pulmonar Obstrutiva Crônica/imunologia , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Resultado do Tratamento
16.
Mycopathologia ; 183(1): 45-59, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28516246

RESUMO

Bronchiectasis is a chronic irreversible airway abnormality associated with infectious agents that either cause or superinfect the airways. While the role of bacteria is well studied, much remains to be determined about fungi in both cystic fibrosis- and non-cystic fibrosis-related bronchiectasis. The airway is constantly exposed to inhaled ambient moulds of which Aspergillus represent the most ubiquitous. In a normal healthy host, this situation is of little consequence. The presence of anatomical or immunological abnormalities such as those in bronchiectasis leads to a range of fungal-related pathologies from asymptomatic airway colonization to fungal sensitization, allergic bronchopulmonary aspergillosis or chronic pulmonary aspergillosis. These entities are difficult to recognize, diagnose and treat due in part to a lack of validated biomarkers. Our true understanding of the complex relationships that regulate fungal-host interactions is still in its infancy and, several questions remain. This includes if fungal epidemiology in bronchiectasis is uniform across countries, and to what extent immunopathological mechanisms-related to fungal airway infections-occurs in different disease states. Specific triggers to allergic or infectious responses to Aspergillus require further exploration. How transition occurs between allergic and invasive phenotypes and their respective biomarkers is also important. Whether anti-fungal treatment is warranted in all cases and what the optimal management strategy is, particularly when treatment should commence and its expected duration remains unclear. Further research is clearly necessary and should be prioritized to better understand the clinical effects and impact of Aspergillus in the setting of bronchiectasis.


Assuntos
Aspergillus/classificação , Aspergillus/isolamento & purificação , Bronquiectasia/complicações , Interações Hospedeiro-Patógeno , Aspergilose Pulmonar/patologia , Aspergilose Pulmonar/fisiopatologia , Antifúngicos/uso terapêutico , Fibrose Cística/complicações , Humanos , Aspergilose Pulmonar/tratamento farmacológico
19.
Medicine (Baltimore) ; 96(42): e8315, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29049239

RESUMO

Chronic pulmonary aspergillosis (CPA) has recently been recognized as a significant global health burden. In China, the diagnosis of CPA is still unfamiliar to most doctors. The aim of this study was to demonstrate the clinical manifestations and diagnoses of CPA in China.A multidisciplinary team of doctors retrospectively screened 690 records of patients diagnosed with pulmonary aspergillosis from January 2000 to December 2016 at Peking Union Medical College Hospital, Beijing, China. Of these, 69 patients were diagnosed with CPA. The patients' clinical characteristics were then retrieved and analyzed. Demographic, laboratory, and radiological data for these patients were compared by CPA type.Of the 69 patients diagnosed with CPA, 10 patients were diagnosed with chronic cavitary pulmonary aspergillosis (CCPA), 15 patients with semi-invasive aspergillosis (SAIA), 41 patients with simple aspergilloma, and 3 patients with Aspergillus nodule. Further, 53.3% of the SAIA patients were obviously immunocompromised, and 60% of the CCPA patients, 26.7% of the SAIA patients, 7.3% of the simple aspergilloma cases were mildly immunocompromised. Previous underlying lung abnormalities were observed in 20% of CCPA patients, 53.3% of SAIA patients, and 80.5% of simple aspergilloma patients. The most common symptoms in the CPA patients were cough (92.8%), hemoptysis (63.8%), chronic sputum (23.2%), and fever (17.4%). The most common computerized tomography abnormalities were cavities (94.2%), nodule (84.1%), consolidation (4.3%), pleural thickening (2.9%), and infiltration (2.9%). CCPA, SAIA and simple aspergilloma patients were significantly different with respect to their course before diagnosis, constitutional symptoms, fever, hemoptysis, breathlessness, white blood cell count, erythrocyte sedimentation rate, high-sensitivity C-reactive protein count, presence of nodule, and presence of a solitary lesion (all P < .05). Furthermore, SAIA patients had a significantly shorter course before diagnosis and a significantly higher white blood cell count compared with CCPA patients (both P < .01).In China, underlying systemic immunocompromising conditions and lung diseases with mechanical impediments contribute to CPA. Simple aspergillosis was the most common diagnosis in CPA patients. The imaging characteristics of simple aspergillosis and Aspergillus nodules were quite discriminable, while CCPA, and SAIA were similar in their clinical and radiological features. Distinguishing between CCPA and SAIA depends mainly on the physician's clinical judgment.


Assuntos
Aspergilose Pulmonar/diagnóstico , Aspergilose Pulmonar/fisiopatologia , Adulto , Idoso , Proteína C-Reativa , China/epidemiologia , Tosse/fisiopatologia , Feminino , Hemoptise/fisiopatologia , Humanos , Hospedeiro Imunocomprometido , Pneumopatias/fisiopatologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto Jovem
20.
Chest ; 152(1): e11-e14, 2017 07.
Artigo em Inglês | MEDLINE | ID: mdl-28693782
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