Relevance of Pulmonary Alveolar Echinococcosis / Relevancia de equinococosis alveolar con afectación pulmonar

BACKGROUND: Pulmonary alveolar echinococcosis (PAE) is a chronic disease caused by Echinococcus multilocularis with very low incidence in developed countries. METHODS: This single-center, retrospective study included 34 patients who were diagnosed with PAE between January 2001 and February 2019 (15 males, 19 females, mean age: 52.4 ± 15.8 years, age range: 28-78 years) in Ataturk University Medical School, Erzurum, Turkey. RESULTS: The liver was the primary involved organ in all cases. Pulmonary involvement was detected in 13.0% (34/261) of all cases with hepatic alveolar echinococcosis (AE), and three patients (8.8%) had both pulmonary metastasis and brain metastasis. The route of spread to the lungs based on radiological data was hematogeneous in 25 patients (73.5%), transdiaphragmatic in three patients (8.8%) and both hematogeneous and transdiaphragmatic in six patients (17.7%). AE showed bilateral involvement in 19 patients (55.9%), whereas only the right lung was involved in 12 patients (35.3%) and the left lung in three patients (8.8%). Of the patients, five underwent surgery due to PAE and 29 patients received medical therapy with albendazole. A total of three patients died during the follow-up period (2, 5 and 10 years after the diagnosis of PAE), while 31 patients continued with follow-up and treatment for a mean duration of 5.4 ± 3.8 years (1-14 years). CONCLUSIONS: Patients with hepatic AE must, as a matter of course, be screened for possible lung involvement. Albendazole therapy may slow down disease progression in patients with widespread pulmonary involvement who are not eligible for surgery

INTRODUCCIÓN: La equinococosis alveolar con afectación pulmonar (PAE) es una enfermedad crónica causada por Echinococcus multilocularis, cuya incidencia es muy baja en los países desarrollados. MÉTODOS: Estudio unicéntrico, retrospectivo en el cual se diagnosticaron 34 pacientes con PAE entre enero de 2001 y febrero de 2019 (15 varones y 19 mujeres, edad media: 52,4 ± 15,8 años, rango de edad: 28-78 años) en la Escuela Médica Univesitaria de Ataturk, Erzurum, Turquía. RESULTADOS: En el total de los casos incluidos en el estudio el hígado fue el principal órgano afectado. La afectación pulmonar se detectó en el 13% (34/261) de los casos con equinococosis alveolar (AE), y 3 pacientes (8,8%) presentaron tanto metástasis pulmonar como cerebral. De acuerdo con los datos radiológicos, la propagación a los pulmones fue por vía hematógena en 25 pacientes (73,5%), transdiafragmática en 3 pacientes (8,8%) y tanto hematógena como transdiafragmática en 6 pacientes (17,7%). Diecinueve pacientes (55,9%) presentaron PAE con afectación pulmonar bilateral, mientras que 12 pacientes (35,3%) presentaron afectación solo del pulmón derecho y 3 (8,8%) solo del izquierdo. De todos los pacientes, 5 fueron sometidos a cirugía debido a la PAE y 29 recibieron tratamiento médico con albendazol. Tres pacientes fallecieron durante el período de seguimiento (2,5 y 10 años después del diagnóstico de PAE), mientras que 31 continuaron con el seguimiento y el tratamiento durante 5,4±3,8 años de media (1-14 años). CONCLUSIONES: Los pacientes con AE hepática se deben cribar de manera rutinaria para detectar una posible afectación pulmonar. El tratamiento con albendazol puede ralentizar la progresión de la enfermedad en pacientes con afectación pulmonar extendida que no son aptos para cirugía

COPD Pathogenesis: Finding the Common in the Complex.

Developing an effective treatment for COPD, and especially pulmonary emphysema, will require an understanding of how fundamental changes at the molecular level affect the macroscopic structure of the lung. Currently, there is no accepted model that encompasses the biochemical and mechanical processes responsible for pulmonary airspace enlargement. We propose that pulmonary emphysematous changes may be more accurately described as an emergent phenomenon, involving alterations at the molecular level that eventually reach a critical structural threshold where uneven mechanical forces produce alveolar wall rupture, accompanied by advanced clinical signs of COPD. The coupling of emergent morphologic changes with biomarkers to detect the process, and counteract it therapeutically, represents a practical approach to the disease.

Trefoil Factor 2 Promotes Type 2 Immunity and Lung Repair through Intrinsic Roles in Hematopoietic and Nonhematopoietic Cells.

Trefoil factors (TFFs) are small secreted proteins that regulate tissue integrity and repair at mucosal surfaces, particularly in the gastrointestinal tract. However, their relative contribution(s) to controlling baseline lung function or the extent of infection-induced lung injury are unknown issues. With the use of irradiation bone marrow chimeras, we found that TFF2 produced from both hematopoietic- and nonhematopoietic-derived cells is essential for host protection, proliferation of alveolar type 2 cells, and restoration of pulmonary gas exchange after infection with the hookworm parasite Nippostrongylus brasiliensis. In the absence of TFF2, lung epithelia were unable to proliferate and expressed reduced lung mRNA transcript levels for type 2 response-inducing IL-25 and IL-33 after infectious injury. Strikingly, even in the absence of infection or irradiation, TFF2 deficiency compromised lung structure and function, as characterized by distended alveoli and reduced blood oxygen levels relative to wild-type control mice. Taken together, we show a previously unappreciated role for TFF2, produced by either hematopoietic or nonhematopoietic sources, as a pro-proliferative factor for lung epithelial cells under steady-state and infectious injury conditions.

Featured Article: Immunomodulatory effect of hemozoin on pneumocyte apoptosis via CARD9 pathway, a possibly retarding pulmonary resolution.

Plasmodium falciparum, the most virulent malaria parasite species, causes severe symptoms especially acute lung injury (ALI), of which characterized by alveolar epithelium and endothelium destruction and accelerated to blood-gas-barrier breakdown. Parasitized erythrocytes, endothelial cells, monocytes, and cytokines are all involved in this mechanism, but hemozoin (HZ), the parasitic waste from heme detoxification, also mainly contributes. In addition, it is not clear why type II pneumocyte proliferation, alveolar restorative stage, is rare in malaria-associated ALI. To address this, in vitro culture of A549 cells with Plasmodium HZ or with interleukin (IL)-1ß triggered by HZ and monocytes (HZ-IL-1ß) was conducted to determine their alveolar apoptotic effect using ethidium bromide/acridine orange staining, annexin-V-FITC/propidium iodide staining, and electron mircroscopic study. Caspase recruitment domain-containing protein 9 ( CARD9), the apoptotic regulator gene, and IL-1ß were quantified by reverse-transcriptase PCR. Junctional cellular defects were characterized by immunohistochemical staining of E-cadherin. The results revealed that cellular apoptosis and CARD9 expression levels were extremely high 24 h after induction by HZ-IL-1ß when compared to the HZ- and non-treated groups. E-cadherin was markedly down-regulated by HZ-IL-1ß and HZ treatments. CARD9 expression was positively correlated with IL-1ß expression and the number of apoptotic cells. Interestingly, the localization of HZ in the vesicular surfactant of apoptotic pneumocyte was also identified and submitted to be a cause of alveolar resolution abnormality. Thus, HZ triggers monocytes to produce IL-1ß and induces pneumocyte type II apoptosis through CARD9 pathway in association with down-regulated E-cadherin, which probably impairs alveolar resolution in malaria-associated ALI. Impact statement The present work shows the physical and immunomodulatory properties of hemozoin on the induction of pneumocyte apoptosis in relation to IL-1ß production through the CARD9 pathway. This occurrence may be a possible pathway for the retardation of lung resolution leading to blood-gas-barrier breakdown. Our findings lead to the understanding of the host-parasite relationship focusing on the dysfunction in ALI induced by HZ, a possible pathway of the recovering lung epithelial retardation in malaria-associated ARDS.

A Fatal Strongyloides Stercoralis Hyperinfection Syndrome in a Patient With Chronic kidney Disease: A Case Report and Literature Review.

Strongyloides stercoralis hyperinfection syndrome is a rare but fatal disease, which occurs commonly in immunocompromised patients. Strongyloidiasis among patients with chronic kidney disease is rarely reported.A 55-year-old Chinese male presented to hospital with diarrhea and abdominal pain. He developed acute respiratory failure and progressed to diffuse alveolar hemorrhage owing to disseminated strongyloidiasis immediately. The bronchoalveolar lavage revealed filariform larvae of Strongyloides stercoralis.This patient was diagnosed with Strongyloides hyperinfection syndrome. Although albendazole, mechanical ventilator support, fluid resuscitation, vasopressor support, extracorporeal membrane oxygenation, hydrocortisone, and broadspectrum antimicrobials were actively used, the patient eventually died.Similar cases in patients with chronic kidney disease in the literature are also reviewed. Through literature review, we recommend that strongyloidiasis should be routinely investigated in patients with chronic kidney disease who will undergo immunosuppressive therapy.

Diffuse alveolar haemorrhage and severe hypoxemia from Strongyloides stercoralis hyperinfection syndrome.

Strongyloides stercoralis hyperinfection syndrome is a rare, yet highly fatal disorder. It occurs most commonly in immunocompromised patients. We report a case of a 36-year-old Ethiopian female who presented with abdominal pain and hypotension. Shortly thereafter, she developed acute respiratory failure and progressed to acute respiratory distress syndrome and septic shock. She was found to have diffuse alveolar hemorrhage due to disseminated strongyloidiasis. We discuss the clinical condition of Strongyloides hyperinfection syndrome presenting with severe hypoxemia and complicated by severe diffuse alveolar hemorrhage leading to death. Similar cases in the literature are also describe.

Infectious diseases causing diffuse alveolar hemorrhage in immunocompetent patients: a state-of-the-art review.

Diffuse alveolar hemorrhage (DAH) represents a syndrome that can complicate many clinical conditions and may be life-threatening, requiring prompt treatment. It is recognized by the signs of acute- or subacute-onset cough, hemoptysis, diffuse radiographic pulmonary infiltrates, anemia, and hypoxemic respiratory distress. DAH is characterized by the accumulation of intra-alveolar red blood cells originating most frequently from the alveolar capillaries. It must be distinguished from localized pulmonary hemorrhage, which is most commonly due to chronic bronchitis, bronchiectasis, tumor, or localized infection. Hemoptysis, the major sign of DAH, may develop suddenly or over a period of days to weeks; this sign may also be initially absent, in which case diagnostic suspicion is established after sequential bronchoalveolar lavage reveals worsening red blood cell counts. The causes of DAH can be divided into infectious and noninfectious, the latter of which may affect immunocompetent or immunodeficient patients. Pulmonary infections are rarely reported in association with DAH, but they should be considered in the diagnostic workup because of the obvious therapeutic implications. In immunocompromised patients, the main infectious diseases that cause DAH are cytomegalovirus, adenovirus, invasive aspergillosis, Mycoplasma, Legionella, and Strongyloides. In immunocompetent patients, the infectious diseases that most frequently cause DAH are influenza A (H1N1), dengue, leptospirosis, malaria, and Staphylococcus aureus infection. Based on a search of the PubMed and Scopus databases, we review the infectious diseases that may cause DAH in immunocompetent patients.

Reduced activity of the epithelial sodium channel in malaria-induced pulmonary oedema in mice.

Lung complications during malaria infection can range from coughs and impairments in gas transfer to the development of acute respiratory distress syndrome (ARDS). Infecting C57BL/6 mice with Plasmodium berghei K173 strain (PbK) resulted in pulmonary oedema, capillaries congested with leukocytes and infected red blood cells (iRBCs), and leukocyte infiltration into the lungs. This new model of malaria-associated lung pathology, without any accompanying cerebral complications, allows the investigation of mechanisms leading to the lung disease. The activity of the amiloride-sensitive epithelial sodium channel (ENaC) in alveolar epithelial cells is decreased by several respiratory tract pathogens and this is suggested to contribute to pulmonary oedema. We show that PbK, a pathogen that remains in the circulation, also decreased the activity and expression of ENaC, suggesting that infectious agents can have indirect effects on ENaC activity in lung epithelial cells. The reduced ENaC activity may contribute to the pulmonary oedema induced by PbK malaria.

An unusual presentation of alveolar hemorrhage.

We report the case of a female patient with an atypical case of alveolar haemorrhage secondary to disseminated strongyloidiasis. Although uncommon, clinicians should consider the diagnosis of pneumonia by disseminated strongyloidiasis in patients with endemic exposure to Strongyloides stercoralis who present with symptoms of cough, wheezing, and dyspnoea. Primary care physicians should strongly consider screening for strongyloidiasis in patients from endemic areas prior to considering the use of steroids or any other immunosuppressants. The best screening test would be serological testing.

Disseminated alveolar echinococcosis mimicking a metastatic malignancy.

Alveolar echinococcosis, which is caused by Echinococcus multilocularis, is a very aggressive and potentially fatal infestation which always affects the liver primarily and metastasizes to any part of the body. Imaging studies are usually highly suspicious of carcinoma or sarcoma, and biopsy may provide the first indication of infection. We report a case of disseminated alveolar echinococcosis with liver, lung, and bone involvement mimicking a metastatic malignancy.

Radiological findings of alveolar hydatid disease of the lung caused by Echinococcus multilocularis.

Alveolar hydatid disease is a highly malignant form of echinococcosis caused by the larvae of the cestode Echinococcus multilocularis. Alveolar hydatid disease always affects the liver and can metastasise to the lungs and brain. The case reports describe the radiological features of alveolar hydatid disease of the lung caused by E. multilocularis. Multiple nodules which varied in size and shape were seen on CXR, CT showed most nodules to be lobulated, well circumscribed and of varying shape. Multiple lobulated lesions located between two segments of the lung and of varying shape appear to be characteristic of pulmonary alveolar hydatid disease caused by E. multilocularis.

[Human pulmonary trichomonoses]. / Trichomonoses pulmonaires humaines.

Colonization of human lungs by various Trichomonas species is a frequent occurrence, but is unknown to most physicians. At this site of infection, the parasite develops into an amoeboid form that renders it unrecognizable. For this reason it has been overlooked until recently. Morphological identification is not feasible under these conditions and molecular tools provide the only means of identification. The species involved are not restricted to Trichomonas tenax, a saprophyte of the mouth that is usually cited in the rare cases of pleuropulmonary trichomoniasis reported in the literature. The recent discovery of species previously unknown in humans raises further questions, including the zoonotic potential of these microorganisms and the existence of species of animal origin that have adapted to humans. Anaerobiosis in poorly ventilated alveolar lumen, rather than immunodepression, seems to be the factor that promotes proliferation of this parasite. The diagnosis of trichomoniasis and its treatment by specific drugs will make it possible to evaluate the pathogenicity of these parasites.

Hepatopulmonary fistula caused by alveolar echinococcosis: report of a case.

Alveolar echinococcosis is a parasitosis endemic to red fox habitats in the northern hemisphere. The liver is the most commonly affected organ, followed by the lungs. We report the case of an elderly woman with hepatic alveolar echinococcosis (HAE) complicated by a hepatopulmonary fistula. We performed a one-stage operation for the hepatic and pulmonary lesions through the transdiaphragmatic route via a laparotomy. We report this case to emphasize that the first-line treatment for a hepatopulmonary fistula caused by HAE should be radical surgery, which results in relief of symptoms and a good outcome.

An unusual cause of alveolar hemorrhage post hematopoietic stem cell transplantation: a case report.

BACKGROUND: Hematopoietic stem cell transplantation is being increasingly used in cancer therapy. Diffuse alveolar hemorrhage, an early complication of stem cell transplant, results from bacterial, viral and fungal infections, coagulopathy, and engraftment syndrome, or can be idiopathic. Diffuse alveolar hemorrhage associated with Strongyloides stercoralis hyperinfection in stem cell transplant patients has been rarely reported. CASE PRESENTATION: We describe an unusual cause of alveolar hemorrhage post hematopoietic stem cell transplant due to Strongyloides hyperinfection. Therapy with parenteral ivermectin and thiabendazole was initiated but the patient deteriorated and died of respiratory failure and septic shock. CONCLUSION: Strongyloides stercoralis hyperinfection is an unusual cause of alveolar hemorrhage early after hematopoietic stem cell transplant with very high mortality.

Magnetic resonance imaging of alveolar echinococcosis experimentally induced in the rat lung.

Pulmonary alveolar echinococcosis (AE) caused by the metacestode of Echinococcus multilocularis is a lethal zoonosis and is a lesion secondarily induced by hematogenous dissemination from hepatic AE lesions. In the present study, a hematogenous pulmonary AE model was experimentally induced in rats by the injection of echinococcal larval tissue homogenate to the tail vein, and then the pathological and diagnostic aspects of pulmonary AE were examined by magnetic resonance imaging (MRI). Histological primary, mature and degenerated AE lesions were observed 5, 18 and 50 weeks after injection, respectively. These lesions were discriminated as signal-void, hypointense and hyperintense regions in T1-weighted MRI (T1WI), respectively. The change in signal intensity in T1WI might reflect the content of proteinaceous fluid as a result of AE cyst degeneration. Western blot analysis of sera with antibodies of two epitopes (Em18 and Em16) of E. multilocularis provided evidence for AE infection in the early stage. T1WI in combination with Western blot analysis could possibility become definitive and early signs of hematogenous pulmonary AE infection.

[Observation on the ultrastructure of Pneumocystis carinii].

OBJECTIVE: To study the life cycle and morphology of Pneumocystis carinii by ultrastructural observation. METHODS: Wistar rat model of P. carinii infection was established by subcutaneous injection with dexamethasone. Lung tissue of the infected rats was used for the transmission electron microscopical study. RESULTS: The organisms were mainly present in the lung alveolar cavity, and also in the alveolar septum, pulmonary macrophages and neutrophils. More trophozoites of P. carinii attached to the type I alveolar epithelial cells, and rarely to the type II alveolar epithelial cells. Most of these trophozoites showed pseudopodial evaginations on their pellicles. The nucleus-associated organelle and spindle microtubules were observed in some trophozoites. The precyst phase was in three forms: early, intermediate and late form. Synaptonemal complexes indicating meiotic nuclear divisions and a clump of mitochondria were also observed in the precyst. The pellicle of the cyst has a thickened portion with a pore. There were nucleus with nucleolus, mitochondrion, vesicles, endoplasmic reticulum and numerous ribosomes in the organisms, and tubular expansions on its surface. CONCLUSION: The life cycle of P. carinii consists of trophozoite, precyst and cyst stages. The presence of a single pore in the cyst wall reveals that pore formation may be a mode of excystation for intracystic bodies of P. carinii.

Secondary and primary murine alveolar echinococcosis: combined albendazole/nitazoxanide chemotherapy exhibits profound anti-parasitic activity.

In this study, the efficacies of chemotherapy employing nitazoxanide (NTZ), albendazole (ABZ), and a NTZ/ABZ-combination against alveolar echinococcosis (AE) were investigated in an experimental murine model. Following secondary infection, meaning i.p. injection of 20 Echinococcus multilocularis metacestodes, the drugs were administered by intragastric inoculation on a daily bases for a period of 5 weeks. Treatment was started either immediately on the day of infection, or at 2 months p.i., respectively. Application of the NTZ/ABZ-combination starting at 2 months p.i. was proven to be most effective in terms of reducing parasite weight (from 4.42+/-1.03 to 1+/-0.05 g; P=0.01). Inspection of treated parasites by transmission electron microscopy showed that ABZ- and NTZ-treated metacestode tissues, respectively, were heterogeneous in that both largely intact parasites as well as severely altered metacestodes could be observed. NTZ/ABZ-combination treatment induced the most severe ultrastructural alterations, including massive reduction in length and number of microtriches, severely damaged tegumental architecture, and progressive loss of viability of the germinal layer, associated with encapsulation by host connective tissue. A comparative pharmacokinetic study in mice revealed that the application of ABZ and NTZ in combination resulted in a two- to four-fold increase of albendazole sulfoxide serum levels for the period of 4-8 h following drug uptake compared to application of ABZ alone. In a third experiment, mice were orally infected with E. multilocularis eggs, and treated with NTZ starting at 2 months p.i. This resulted in a significantly lower lesion number in treated versus untreated mice (P=0.01). This investigation indicates the potential value for NTZ and/or a combined ABZ/NTZ chemotherapy against AE.

[Experimental rationale for the use of medapec as the drug of choice in treating echinococcosis]. / Eksperimental'noe obosnovanie prigodnosti medapeka v kachestve preparata vybora dlia lecheniia ékhinokokkozov.

The dosage form of medamine-medapec was found to have a high antiechinococcal activity in experiments on laboratory animals. Its efficacy was shown in treating larval alveolar echinococciasis in mice and cotton rats with different doses and courses as compared with medamine and albendazole. It was ascertained that for its high larvicidal activity, medapec should be given to animals regularly during a day. The daily dose of the drug should be gradually increased. In complying with these conditions, the duration of effective courses of therapy drastically reduces.

Structured treatment interruption in patients with alveolar echinococcosis.

In human alveolar echinococcosis (AE), benzimidazoles are given throughout life because they are only parasitostatic. It has been a longstanding goal to limit treatment, and recent reports suggest that, in selected cases, benzimidazoles may be parasitocidal. Previously, we showed that positron -emission tomography (PET) using [(18)F]fluoro-deoxyglucose discriminates active from inactive lesions in AE. We have now performed a 3-year prospective study in 23 patients and conducted a structured treatment interruption in those without signs of PET activity. Disease progression was further assessed by ultrasound, computerized tomography, laboratory parameters, and clinical examination. We found PET-negative lesions in 15 of 23 patients and benzimidazoles were discontinued in these patients. After 18 months, patients were reevaluated, and, of the 15 initially PET-negative patients, 8 showed either new activity on PET (n = 6) or signs of clinical progression (n = 2). Reinitiation of benzimidazoles halted parasite growth again. No further progression was detected after 36 months. PET had a sensitivity of 91% for the detection of active lesions. In conclusion, despite successful suppression of metabolic activity, in most cases benzimidazoles do not kill the parasite. PET is a reliable tool for assessing metabolic activity and for timely detection of relapses. Neither duration of treatment, kind of treatment, lesion size, calcifications, or regressive changes reliably indicate parasite death. We discourage the discontinuation of benzimidazoles in inoperable AE even after many years of treatment. However, patients with a poor compliance of benzimidazole intake or patients suffering from side effects to benzimidazoles might be assessed for PET negativity. If permanent discontinuation of benzimidazoles is attempted, the course of disease should be followed by PET.