Pulmonary audavoxx.complications ser estar the most audavoxx.common reason of morbidity and mortality in immunoaudavoxx.compromised patients, quem lack of a basic mechanisms of moving defense. Nevertheless of the cause of a immunodeficiency, the most typical audavoxx.complications ser estar infections (bacterial, viroses or fungal). Among the fungal infections, aspergillosis is a most audavoxx.common (incidence, 1-9%; mortality, 55-92%) audavoxx.complying with organ transplant. Although pulmonary authorized is the most audavoxx.common form of aspergillosis, central nervous sistema involvement e sinusitis are not unaudavoxx.common. Top top CT scans, a halo authorize represents an area of short attenuation around ns nodule, revealing edema or hemorrhage. A gold standard para the diagnosis is the culture identification of ns fungus in sputum, BAL fluid or biopsy samples. Failing this identification, the detection that galactomannan, i m sorry is 1 of ns fungal wall surface audavoxx.components, has presented sensitivity and specificity the 89% e 98%, respectively. Amphotericin B, liposomal amphotericin B, caspofungin and, especially, voriconazole ~ ~ effective against ns fungus. Return Pneumocystis jirovecii pneumonia have the right to be fatal, a incidence that this condition has lessened due to a prophylactic usar of trimethoprim-sulfamethoxazole. In immunoaudavoxx.compromised patients presenting audavoxx.com dyspnea and hypoxemia, screening para fungi is indicated. A 14- to 21-day food of trimethoprim-sulfamethoxazole in audavoxx.combination audavoxx.com corticosteroids is audavoxx.commonly efficacious. Another rare fungal infection is disseminated candidiasis, i m sorry is caused by Candida spp.

Keywords: Pneumonia; Immunosuppression; Lung diseases, fungal.

RESUMO

As audavoxx.complicações pulmonares se constituem na maior razão de morbidade e mortalidade no hospedeiro imunoaudavoxx.comprometido, devido à deficiência nos mecanismos básicos de defesa. Independência ao vivo da razão da imunodepressão, infecções bacterianas, virais e fúngicas são as acrescido frequentes. Entre as infecções fúngicas, der aspergilose denominações a adicionar audavoxx.comum (incidência de 1-9% e humanidade de 55-92%) nos muitos tipos de transplantados. Embora a forma pneumônica isso é a acrescido frequente, lesões são de sistema indignação central e sinusite algum são raras. O assina do aur em TC de tórax representar uma áreas de baixo atenuação em volta do nódulo, revelando edema alternativamente hemorragia. O padrão ouro para emprego diagnóstico denominada a identificação dá fungo pela cultura de escarro, amostras de LBA alternativamente biópsia. Na deficiência dessa identificação, a detecção de galactomanana, um dos audavoxx.componentes da parede celular de Aspergillus sp., sim mostrado sensibilidade e especificidade de 89% e 98%, respectivamente. Anfotericina B, anfotericina ns lipossomal, caspofungina e voriconazol têm efeito sobre emprego fungo, abranger destaque para esse último. Naquela pneumonia por Pneumocystis jirovecii, que pode ser fatal, teve seus incidência reduzida pelo uso extra de sulfametoxazol/trimetoprima. Dispneia e hipoxemia em pacientes imunodeprimidos expressar a cobrar da inspeção de fungos. Ministérios uso de sulfametoxazol/trimetoprima através dos 14-21 dia associado alcançar corticosteroides costuma ser eficaz. Naquela candidíase disseminada excluir outra rara enfermidade fúngica causada através Candida spp.

Palavras-chave: Pneumonia; Imunossupressão; Pneumopatias fúngicas.

IntroductionPulmonary audavoxx.complications ~ ~ the many audavoxx.common reason of morbidity and mortality in immunoaudavoxx.compromised patients. A multiple treatment options porque o patients audavoxx.com malignant diseases-especially a various chemotherapy regimens and the increasing usar of organ transplantation or hematopoietic cabinet transplantation-as fine as a increased survival of patients with autoimmune diseases, have significantly increased a number that immunoaudavoxx.compromised patients. This patients are characterized by susceptibility audavoxx.come infections resulted in by organisms whose virulence is low in habituais patients.Immunoaudavoxx.compromised patients are at a higher threat of emerging infection because they lack a basic mechanisms of cellular defense. Granulocytopenia, cabinet dysfunction (principally T lymphocyte dysfunction), congenital humor immunodeficiency, acquired pegue immunodeficiency, splenectomy e mechanical audavoxx.complications (especially early to the presence of catheters) are the principal factors the interfere with the defense of guts in immunoaudavoxx.compromised patients. This various types of defects ser estar more generally associated audavoxx.com certain microbe in the development the infections. The lack of pegue defense is most frequently associated with infection resulted in by Streptococcus pneumoniae; impaired cellular defense is most generally associated with infection brought about by mycobacteria; and granulocytopenia is most frequently associated with gram-negative bacteria and Staphylococcus aureus.(1)In children, immunological defects represent der major risk coeficiente for pulmonary involvement. Syndromes such together severe an unified immunodeficiency and the Wiskott-Aldrich syndrome cause high mortality in crianças who build pulmonary infection.Among adults, immunodeficiency is most frequently seen in patients audavoxx.com leukemia, lymphoma or AIDS, as well as in those it is registered to immunosuppressive therapy, associated or no to organ transplantation or bone marrow transplantation.In organ transplant recipients (principally liver transplant recipients e kidney transplant recipients), pneumonia occurs during uma of two phases. The o primeiro dia is a immediate phase, defined as the first month ~ transplantation, during which nosoaudavoxx.comial bacter pneumonia predominates. The second is a post-immediate phase, from the second to 6th months after ~ transplantation, i m sorry is identified by pulmonary infections led to by other agents, such as viruses, fungi, Pneumocystis jirovecii and mycobacteria.(1)The most audavoxx.common causal revendedor autorizado of fungal pneumonia are Aspergillus spp., which estão present in the localized e disseminated creates of a disease.The incidence that pneumocystosis among organ transplant recipients ranges from 2% audavoxx.come 4%, diminish after ns prophylactic use of the trimethoprim-sulfamethoxazole audavoxx.combination.In bone marrow transplant (BMT) recipients, porque o instance, pulmonary infection brought about by the various revendedor autorizado constitutes a most typical isolated audavoxx.complication.(2) Pulmonary infection is related to a immune condição of the recipient. Therefore, most species of bacterial e fungal pneumonia are diagnosed in the neutropenic period, before bone marrow engraftment. In addition to this major defect, troubles such as ns destruction of anatomical barriers (upper respiratory tract mucosa) and impairment of the cough reflex deserve to occur. One more serious problem is graft-versus-host disease (GVHD), which increases a risk that opportunistic infection with mechanisms that have yet to be audavoxx.completely defined.(1)Among ns GVHD-related causes of pneumonia, cytomegalovirus pneumonia e fungal epidemic (especially those caused by Aspergillus sp.) are the many noteworthy. This deserve to be attributed to impaired to move defense (mediated through T lymphocytes), and to deficiencies in ns number and function the macrophages.Although diagnostic resources are in consistent development and the accessibility of novo drugs (especially azole antifungal agents) is increasing, pulmonary infection continues to be as a most typical documented form of invasive epidemic in immunoaudavoxx.compromised patients.Aspergillosis is 1 of countless opportunistic fungal infections the principally affect a lungs. Ns incidence that aspergillosis in kidney transplant recipients, liver transplant recipients, BMT recipients e lung transplant recipients is, respectively, 1%, 2%, 7% and 9%. The mean mortality rate porque o this populace is 55-92%, which to represent 10-15% of ns deaths among all transplant recipients.(3)Regarding immune defense mechanisms, evidence shows that over there is innate immunity e immunity that creates through one evolutionary process during infection or disease. This last kind of immunity is recognized as adaptive immunity. For many years, cell-mediated immunity ser estar considered audavoxx.come be ns most effective, and humoral immunity was thought to it is in of secondary importance. However, that is currently accepted the cell-mediated immune is the gorjeta form the defense. Nevertheless, certain types of humor immune responses estão protective.In general, Th1-mediated immune is used porque o clearance of a fungal infection, conversely, Th2-mediated immunity habitually acts on ns susceptibility audavoxx.come infection.(4)A skilled cell-mediated defense requires an efficient contingent that lymphocytes: T-helper cells; T-suppressor cells; and effector lymphocytes.Many neoplastic diseases, particularly Hodgkin"s lymphomas, hairy cell leukemia and chronic lymphocytic leukemia, ~ ~ associated with the malfunctioning of a cell-mediated defense. Corticosteroid use, i m sorry is quite usual in these diseases, typically results in further impairment of moving immunity.In diagnostic terms, various aspects related to immunoaudavoxx.compromised patients in general, need to be taken right into consideration: first, an aggressive protocol the etiologic investigation is needed, since a delay in the diagnosis increases ns risk that death; second, if pulmonary infiltrate is determined early, fiberoptic bronchoscopy should be perform (fiberoptic bronchoscopy allows the identification or exclusion of an contagious etiology); and third, beforehand CT scans of the chest generally reveal lesions that are not checked out on routine chest X-rays.(5)Fungal pneumoniaDue audavoxx.come its incidence e morbidity, fungal pneumonia is 1 of a most severe infections in immunoaudavoxx.compromised patients, accounting for 30% of todos deaths among BMT recipients.(1)Pulmonary involvement habitually results a partir de systemic circulation of the fungus. Large-scale usar of antibiotics e prolonged periods of granulocytopenia, and corticosteroid therapy, ser estar extremely necessary factors para the event of fungal infection. Fungi of a genus Aspergillus ~ ~ the most usual causal agents. Other fungi, such together those of a genera Mucor, Fusarium, Rhizopus, Petriellidium, Cryptococcus, Histoplasma, Coccidioides and Candida, have also been identified as causal agents.Clinically, fungal pneumonia manifests as fever in patients who são de not respond to antibiotic therapy. However, the most significant finding is naquela focal lesion in a lung parenchyma, viewed on regimen chest X-rays and on CT scans of a chest.Blood culture, sputum culture and, particularly, BAL fluid society constitute the methods of identifying a fungi. Once these methods fail audavoxx.come detect ns etiologic agent, fine-needle aspiration is indicated. Fine-needle aspiration allows the characterization of the fungus in 50-67% of cases. The mean price of audavoxx.complications is 15%, e audavoxx.complications ~ ~ more typical in patient presenting with naquela platelet count of approximately 30,000/mm3.(6)AspergillosisInvasive aspergillosis is a most typical fungal infection amongst immunoaudavoxx.compromised neutropenic patients. In contrast to bacter infections, brought about by cytomegalovirus or by P. Jirovecii, in which prophylaxis has actually been displayed to reduce ns incidence of this diseases, ns number of cases of invasive aspergillosis has actually increased progressively. De acordo audavoxx.com to current studies, invasive aspergillosis affects 10-15% of BMT recipients. In most cases, aspergillosis affects somente the lungs. However, a significant part of patients build sinusitis e central nervous system infection. Ns most typical symptoms estão cough e dyspnea. However, pleuritic pain e hemoptysis can also occur.The lesions watched on regime chest X-rays incorporate single/multiple nodules, cavities e segmental/subsegmental consolidation. In a initial phase, ns most characteristic photo seen top top CT scans is the halo sign, an area of low attenuation that surrounds ns nodule and represents edema or hemorrhage (Figure 1). The halo sign ser estar described in an ext than 90% that neutropenic patients audavoxx.com invasive aspergillosis when HRCT scans to be taken in a initial step of the disease. At later stages, HRCT scans can concertos areas that necrosis and sequestration the lung tissue, which detaches itself from the neighboring parenchyma, resulting in the ar crescent sign.
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Unfortunately, a fungus is determined in no more than 30% of ns cases. Over there is a constant search para tests that might indicate the presence that Aspergillus sp. In immunoaudavoxx.compromised patients. One such example is detection with ELISA or galactomannan, der fungal cell wall surface audavoxx.component that is released during invasive aspergillosis. Prospective studies have shown der sensitivity of 89.7% and a specificity the 98.0%. Although more studies ser estar needed in order to definir its clinical usefulness, there have actually been reports stating that a positive serologic test result precedes a definitive diagnosis of aspergillosis by as countless as 17 days.(7)The usar of amphotericin b has been ns gold standard para the treatment of aspergillosis. However, a rate the therapeutic success remains low. Mortality rates are as high as 70-90%. It has been propose that, in ns presence of nephrotoxicity, liposomal amphotericin b should be used. An ext recently, ns triazole voriconazole has been presented to be much more effective and less toxic than amphotericin B.(8) ns use that caspofungin is yet another option. Caspofungin is one echinocandin and is to be used só in unique situations. The rate the success the prophylaxis porque o invasive aspergillosis is still low. Low doses of i.v. Amphotericin b or aerosol amphotericin B, and also azoles, have been used, return their use has no reduced the incidence or mortality rates.The most necessary determinant of survival, however, is ns resolution that neutropenia, bone marrow restore being quartel general to fighting the fungus and preventing the development of fatal audavoxx.complications.Pneumocystis jirovecii pneumonia
P. Jirovecii pneumonia accounted para as much as 10% of todos types of pneumonia that affected HIV-negative immunoaudavoxx.compromised patients. This incidence plunged after a trimethoprim-sulfamethoxazole mix began audavoxx.come be offered prophylactically. This type of pneumonia has occurred apenas um in patients who ~ ~ allergic audavoxx.come sulfa drugs, in patients who dá not adhere to the preventive therapy and, occasionally, in patients who beaudavoxx.come infected before prophylaxis.(9)Earlier researches (conducted in a pre-trimethoprim-sulfamethoxazole-prophylaxis era) showed the incidence the P. Jirovecii pneumonia to be 4% in kidney transplant recipients, 4% in heart transplant recipients, 11% in liver transplant recipients and 33% in heart-lung transplant recipients. In a post-prophylaxis era, a cleveland Clinic report of 1,299 solid body organ transplants confirmed that somente 25 instances occurred.(10) In BMT recipients, one incidence the 16% era reported ns pre-prophylaxis era. Currently, P. Jirovecii pneumonia occurs apenas um in patients who discontinue prophylaxis as result of intolerance or allergy phenomena.The clinical profile, a diagnostic investigation and the therapy of P. Jirovecii pneumonia estão no different em ~ those described para patients audavoxx.com HIV. Ns mean time em ~ BMT to ns onset of a disease is about 6 weeks. Large studies have actually reported that cough (generally dried cough), dyspnea and fever are the cardinal symptoms, followed by asthenia e weight loss. Interstitial/alveolar lesions and asymmetric infiltrates normally predominate in imaging check results. Cysts, pneumothorax e pleural effusion have additionally been reported. Hypoxemia is generally present, and the alveolar-arterial oxygen gradient increases significantly. Rise in lactate dehydrogenase is audavoxx.common however nonspecific. Ns reported sensitivity selection of trial and error induced sputum, BAL fluid and BAL fluid/biopsy samples porque o the detection the P. Jirovecii is 35-95%, 79-98% and 94-100%, respectively.(9)The treatment of choice porque o P. Jirovecii pneumonia is high doses of trimethoprim-sulfamethoxazole para 14-21 days. The alternative porque o patients audavoxx.com allergy or intolerance is a use that i.v. Pentamidine. The use that corticosteroids in the initial step of a disease in patients with hypoxemia, together reaudavoxx.commended for HIV patients, has actually been questioned for BMT recipients.Infections led to by Candida spp.The clinical manifestations of a fungal infections brought about by Candida spp. Range from localized mucosal epidemic to dissemination audavoxx.com multiple organ involvement. A immune solution is quartel general to the type of epidemic that this fungi will cause. Impaired cellular immunity is typically associated audavoxx.com infections that estão more severe, conversely, hematogenous dissemination can occur due to anatomical abnormalities (e.g., patients audavoxx.com heart valve prostheses).Neutropenic patients have the right to suffer hematogenous circulation of the fungus via the gastrointestinal tract, together occurs in GVHD.The following estão the significant risk factors porque o the invasive form: a) having naquela hematological malignancy; b) being a recipient of naquela solid organ transplant or hematopoietic stem cell transplant; e c) having undergone chemotherapy.Among younger, formerly healthy yet severely okay patients, such as crédito patients e patients audavoxx.com extensive burns, other risk factors estão associated audavoxx.com infection brought about by Candida spp.: use of centrais venous catheter; use of bruta parenteral nutrition; use of broad-spectrum antibiotics; high Acute Physiology e Chronic health and wellness Evaluation II score; hemodialysis; and abdominal surgery audavoxx.com gastrointestinal perforation.(11,12)The clinical presentation of a infections resulted in by Candida spp. Have the right to be together follows:a)Focal invasive infections, amongst which estão endophthalmitis, osteoarticular infection, meningitis, endocarditis, peritonitis, urinary street infection, pneumonia, empyema, mediastinitis e pericarditis.b)Candidemia and disseminated candidiasis, ns latter having actually been separated into 4 groups, as follows: catheter-related candidiasis; acute disseminated candidiasis; chronic disseminated candidiasis; e deep-organ candidiasis. The o primeiro dia two ser estar more closely associated with documented candidemia.The incidence that invasive candidiasis has der bimodal distribution, peaking in ~ both ends of the lei spectrum: 75:100,000 in children younger than 1 year the age; and 26:100,000 in adults older than 65 years of age.(12)The principal clinical manifestations include a following: fever that does not respond audavoxx.come broad-spectrum antibiotics, particularly in cases of prolonged catheter usar or other significant risk fator (or der audavoxx.combination of ns two); opportunity of associação with multiple organ infection; macronodular skin lesions or endophthalmitis resulted in by Candida spp.; and, occasionally, septic shock and multiple body organ dysfunction.The current treatment porque o patients presenting with disseminated candidemia e positive culture porque o Candida spp. Intends primarily in ~ removing a catheters e ruling lado de fora septic phlebitis, endocarditis e abscess. Ns prevalent types is C. Albicans. Steady patients have to be treated audavoxx.com fluconazole para another 14 mim after the disappearance of all signs e symptoms of ns infection. For unstable patient or patient in deteriorating wellness presenting, in one of two people case, audavoxx.com persistent candidemia for more 보다 5 days, ns audavoxx.combination that caspofungin audavoxx.com fluconazole or amphotericin b should it is in considered. Likewise, para patients infected audavoxx.com C. Glabrata, fluconazole (800 mg/day), caspofungin (50 mg/day) or amphotericin b (0.7-1.0 mg  kg−1  day−1) have the right to be used. Porque o patients infected audavoxx.com C. Krusei, ns initial dose of caspofungin should be boosted to 70 mg/day, adhered to by 50 mg/day or voriconazole (6 mg/kg every 12 h, audavoxx.complied with by 3 mg/kg every 12 h).(12-14)References1.Crawford SW, Meyers J.D. Respiratory diseases in bone marrow transplant patient In: Shelhamer J. Respiratory disease in a immunosuppressed host. Philadelphia: J.B. Lippincott; 1991. P. 595-623.2.Krowka MJ, Rosenow EC 3rd, Hoagland HC. Pulmonary symptom of bone marrow transplantation. Chest. 1985;87(2):237-46.3.Mayaud C, Cadranel J. A persistent challenge: ns diagnosis the respiratory disease in the non-AIDS immunoaudavoxx.compromised host. Thorax. 2000;55(6):511-7.4.Blanco JL, garcia ME. Immune an answer to fungal infections. Vet Immunol Immunopathol. 2008;125(1-2):47-70.5.Shorr AF, Susla GM, O"Grady NP. Pulmonary infiltrates in a non-HIV-infected immunoaudavoxx.compromised patient: etiologies, diagnostic strategies, and outaudavoxx.comes. Chest. 2004;125(1):260-71.6.Crawford SW, Hackman RC, clark JG. Biopsy diagnosis and clinical result of persistent focal distance pulmonary lesions after ~ marrow transplantation. Transplantation. 1989;48(2):266-71.7.Maertens J, Verhaegen J, Lagrou K, furgão Eldere J, Boogaerts M. Screening for circulating galactomannan as a noninvasive diagnostic tool para invasive aspergillosis in lengthy neutropenic patients and stem cabinet transplantation recipients: a prospective validation. Blood. 2001;97(6):1604-10.8.Herbrecht R, Denning DW, Patterson TF, Bennett JE, Greene RE, Oestmann JW, et al. Voriconazole versus amphotericin b for primary therapy the invasive aspergillosis. N Engl J Med. 2002;347(6):408-15.9.Tuan IZ, Dennison D, Weisdorf DJ. Pneumocystis carinii pneumonitis adhering to bone marrow transplantation. Bone Marrow Transplant. 1992;10(3):267-72.10.Gordon SM, LaRosa SP, Kalmadi S, Arroliga AC, Avery RK, Truesdell-LaRosa L, et al. Must prophylaxis porque o Pneumocystis carinii pneumonia in solid body organ transplant recipients ever before be discontinued? Clin epidemic Dis. 1999;28(2):240-6.11.Kirkpatrick CH. Chronic mucocutaneous candidiasis. Pediatr infect Dis J. 2001;20(2):197-206.12.Sobel JD, Vázquez JA. Modern diagnosis e management the fungal infections. Newtown, PA: Handbooks in health Care; 2003.13.Burke WA. Use of itraconazole in naquela patient with chronic mucocutaneous candidiasis. J to be Acad Dermatol. 1989;21(6):1309-10.14.Pappas PG, rex JH, Sobel JD, Filler SG, Dismukes WE, Walsh TJ, et al. Guidelines for treatment that candidiasis. Clin epidemic Dis. 2004;38(2):161-89.Study carried out at the audavoxx.comunidade University the Paraná, Curitiba, Brazil.Correspondence to: Rodney Frare e Silva.


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