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There is no common response to all fungi&#44; and distinguishing clinical features have been identified&#58; low CD4 levels are associated with pathogens such as <span class="elsevierStyleItalic">Pneumocystis</span> and <span class="elsevierStyleItalic">Cryptococcus</span>&#44; while neutropenia can lead to <span class="elsevierStyleItalic">Aspergillus</span> and Mucoralean infections&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">Types of immunosuppression associated with these mycoses are listed in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#46; It is worth noting that many of the risk factors mentioned are associated with the chronic use of high-dose corticosteroids&#44; underlining the need for careful adjustment of immunosuppression and consideration of therapeutic alternatives&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0020" class="elsevierStylePara elsevierViewall">Clinical manifestations of pulmonary mycoses are not specific&#44; and while it is easy to suspect mycosis in the context of known immunosuppression&#44; the opposite approach must not be forgotten&#58; a diffuse&#44; slowly progressing pulmonary syndrome should alert to a possible fungal infection and lead to an investigation of any possible underlying immunosuppression&#46; Detailed history and examination may guide diagnosis&#58; involvement of paranasal sinuses may be suggestive of <span class="elsevierStyleItalic">Mucor</span>&#44; skin lesions in disseminated disease may be a good source for biopsy&#44; etc&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">With regard to diagnosis&#44; chest X-ray may be normal&#44; so computed tomography is the imaging test of choice&#46; Diffuse bilateral infiltrates with areas of ground glass and&#47;or multimodal patterns are common&#44; but not specific&#44;<a class="elsevierStyleCrossRef" href="#bib0410"><span class="elsevierStyleSup">1</span></a> and microbiological culture or the detection of fungal antigens may be positive in a colonization setting&#44; reducing their diagnostic value for invasive disease&#46; The yield of serological testing in immunocompromised patients is poor&#46; Biopsy has been conventionally considered as the unequivocal test for demonstrating invasive fungal proliferation&#44; but in many cases&#44; the clinical status of the patient prevents sampling&#46; Moreover&#44; the extreme seriousness of these diseases means that appropriate empirical treatment must be started as soon as possible&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">The European Organization of Research and Treatment of Cancer&#47;Mycoses Study Group &#40;EORTC&#47;MSG&#41; has defined invasive mycoses as&#58; proven &#40;consistent histological results or positive culture in sterile medium&#41;&#59; probable &#40;lower grade microbiological evidence in a patient with risk factors and consistent clinical syndrome&#41;&#59; and possible &#40;patients with clinical syndrome and risk factors&#44; despite absence of microbiological confirmation&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0415"><span class="elsevierStyleSup">2</span></a> These guidelines reflect the effort made in unifying criteria to assist the clinician in dealing with diagnostic uncertainty&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">It is important to point out that treatment does not depend exclusively on the administration of antifungals&#46; Immunosuppression must also be addressed and reduced or reversed to achieve a level of balance that remains poorly defined&#46; In a situation of irreversible immunosuppression&#44; there will be little response to antifungal treatment&#44; while recovery of the immune response may be associated with clinical worsening&#44; due to the inflammatory response&#46; This phenomenon is well established in HIV patients&#44; but has also been described in non-HIV patients&#46;<a class="elsevierStyleCrossRef" href="#bib0420"><span class="elsevierStyleSup">3</span></a></p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Aspergillosis</span><p id="par0040" class="elsevierStylePara elsevierViewall">Aspergillosis is the primary pulmonary mycosis among critically ill patients&#44;<a class="elsevierStyleCrossRef" href="#bib0425"><span class="elsevierStyleSup">4</span></a> the most common species being <span class="elsevierStyleItalic">A&#46; fumigatus</span>&#44; <span class="elsevierStyleItalic">A&#46; flavus</span>&#44; <span class="elsevierStyleItalic">A&#46; niger</span> and <span class="elsevierStyleItalic">A&#46; terreus</span>&#46; They are acquired by inhalation of conidia&#44; which in an immunocompetent individual are eradicated by alveolar macrophages and neutrophils&#46; Disease develops when this line of defense breaks down&#44; or&#44; more rarely&#44; in situations of excessive inhalation of conidia&#44; such as occurs during landslides or great catastrophes&#46;<a class="elsevierStyleCrossRef" href="#bib0430"><span class="elsevierStyleSup">5</span></a> Several clinical pulmonary forms have been described&#44; the most important of which are invasive pulmonary aspergillosis &#40;IPA&#41;&#44; chronic aspergillosis&#44; and aspergilloma&#46;<a class="elsevierStyleCrossRef" href="#bib0435"><span class="elsevierStyleSup">6</span></a> The type and severity of aspergillosis is determined by the characteristics of the patient &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46; Severe&#44; generalized immunosuppressive states&#44; such as prolonged neutropenia&#44; are associated with acute invasive disease&#44; while moderate&#44; localized immunosuppression&#44; such as preexisting cavities&#44; favors the development of forms such as aspergilloma&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Invasive Pulmonary Aspergillosis</span><p id="par0045" class="elsevierStylePara elsevierViewall">IPA is the most severe form of aspergillosis&#44; with a mortality of around 50&#37;&#46; It is caused by massive proliferation of <span class="elsevierStyleItalic">Aspergillus</span>&#44; with tissue invasion and high vascular tropism&#44; promoting ischemia and dissemination&#46;</p><p id="par0050" class="elsevierStylePara elsevierViewall">Serious risk factors include prolonged neutropenia in patients with hematological malignancies&#44; hematopoietic stem cell &#40;HSC&#41; and solid organ transplants&#44; particularly lung and heart&#46; Other factors thought to be intermediate include intensive care unit admission&#44; chronic obstructive lung disease &#40;COPD&#41; treated with inhaled or systemic corticosteroids&#44; chemotherapy and radiation therapy&#44; AIDS&#44; etc&#46;<a class="elsevierStyleCrossRefs" href="#bib0430"><span class="elsevierStyleSup">5&#44;7</span></a> Despite the varying importance of each risk factor&#44; IPA in critically ill patients mostly occurs in association with COPD and prolonged corticosteroid use&#44;<a class="elsevierStyleCrossRef" href="#bib0425"><span class="elsevierStyleSup">4</span></a> due to their higher prevalence&#46;</p><p id="par0055" class="elsevierStylePara elsevierViewall">IPA progresses with fever&#44; cough&#44; expectoration&#44; hemoptysis&#44; dyspnea&#44; and pleuritic pain&#46; Tracheobronchial involvement may be observed&#44; particularly in lung transplantation&#46;<a class="elsevierStyleCrossRef" href="#bib0445"><span class="elsevierStyleSup">8</span></a> If it disseminates&#44; the skin&#44; central nervous system &#40;CNS&#41;&#44; liver and kidneys may be affected&#46;<a class="elsevierStyleCrossRef" href="#bib0430"><span class="elsevierStyleSup">5</span></a></p><p id="par0060" class="elsevierStylePara elsevierViewall">CT reveals areas of ground glass opacities with multiple nodules and cavitated lesions&#46; Nodular lesions may be associated with perinodular hemorrhage&#44; producing the typical &#8220;halo&#8221; sign&#46; Subsequently&#44; as the disease progresses&#44; peripheral necrosis and cavitation with the air crescent sign&#44; or necrosis and central attenuation with the reversed halo sign may develop&#46; These radiological signs&#44; typically related with IPA&#44; may be imitated by other mycoses and even other non-fungal infections&#46; Moreover&#44; they are absent in many patients&#44; particularly those receiving corticosteroid treatment without neutropenia&#46;<a class="elsevierStyleCrossRefs" href="#bib0450"><span class="elsevierStyleSup">9&#44;10</span></a></p><p id="par0065" class="elsevierStylePara elsevierViewall">Sputum or bronchoalveolar lavage &#40;BAL&#41; cultures have certain limitations&#58; sensitivity is low &#40;cultures are negative in up to 50&#37; of IPAs&#41; and specificity is suboptimal&#44; as no distinction can be made between invasive infection and possible colonization&#46; Indeed&#44; 30&#37;&#8211;60&#37; of positive cultures from lung transplant patients are thought to be due to colonization&#46; Blood cultures are generally negative&#44; even in disseminated forms of the disease&#44; so yield is low&#46;<a class="elsevierStyleCrossRefs" href="#bib0425"><span class="elsevierStyleSup">4&#44;11</span></a></p><p id="par0070" class="elsevierStylePara elsevierViewall">Different diagnostic techniques have been proposed to improve sensitivity and to reduce wait time for cultures&#46; Detection of serum galactomannan&#44; a component of the <span class="elsevierStyleItalic">Aspergillus</span> cell wall&#44; in patients with hematological malignancies has a sensitivity of 71&#37; and a specificity of 89&#37;&#44;<a class="elsevierStyleCrossRef" href="#bib0465"><span class="elsevierStyleSup">12</span></a> but the yield is lower in transplant recipients and COPD patients&#46;<a class="elsevierStyleCrossRefs" href="#bib0470"><span class="elsevierStyleSup">13&#44;14</span></a> Galactomannan determination in BAL is more sensitive and specific than in blood in both hematological cancer patients and other groups&#46;<a class="elsevierStyleCrossRef" href="#bib0480"><span class="elsevierStyleSup">15</span></a> However&#44; false positives related with betalactam antibiotics&#44; <span class="elsevierStyleItalic">Bifidobacterium</span> colonization and presence of histoplasmosis&#44; blastomycosis or penicillinosis have been reported&#46;<a class="elsevierStyleCrossRefs" href="#bib0485"><span class="elsevierStyleSup">16&#44;17</span></a></p><p id="par0075" class="elsevierStylePara elsevierViewall">Another <span class="elsevierStyleItalic">Aspergillus</span> cell wall antigen is 1&#44;3-&#946;-<span class="elsevierStyleSmallCaps">d</span>-glucan&#44; and detection in serum yields similar results to galactomannan&#46; However&#44; it is present in the structure of most fungi&#44; including <span class="elsevierStyleItalic">Candida</span> and <span class="elsevierStyleItalic">Pneumocystis</span>&#44; so it is less specific and returns positive results for other invasive mycoses&#46;<a class="elsevierStyleCrossRef" href="#bib0490"><span class="elsevierStyleSup">17</span></a> Finally&#44; the use of polymerase chain reaction &#40;PCR&#41; techniques in BAL has been proposed&#44; resulting in sensitivity and specificity of 91&#37; and 92&#37;&#44; respectively&#46;<a class="elsevierStyleCrossRef" href="#bib0495"><span class="elsevierStyleSup">18</span></a> The definitive test is biopsy&#44; but in many cases sampling is not feasible&#44; due to the clinical instability of the patient&#46;</p><p id="par0080" class="elsevierStylePara elsevierViewall">Delay in treatment is associated with higher mortality&#46;<a class="elsevierStyleCrossRef" href="#bib0500"><span class="elsevierStyleSup">19</span></a> Accordingly&#44; if suspicion is well-grounded&#44; treatment should be initiated&#46; The antifungal agent of choice is voriconazole&#44; while liposomal amphotericin B is another alternative&#46; Second line options include posaconazole&#44; caspofungin or micafungin&#46; Treatment duration is at least 12 weeks&#44; and the regimen should be tailored according to resolution and prolonged stabilization of lesions&#46; Monitoring of galactomannan levels in blood may be useful&#46; Surgery is limited to debridement of areas of superficial necrosis and invasion of pericardium or great vessels due to contiguity&#46; Granulocyte stimulating factors are used in cases of neutropenia&#44; but there is no evidence of any reduction in mortality&#46;<a class="elsevierStyleCrossRefs" href="#bib0440"><span class="elsevierStyleSup">7&#44;10&#44;20&#44;21</span></a></p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Aspergilloma</span><p id="par0085" class="elsevierStylePara elsevierViewall">Aspergilloma is a fungus ball composed of hyphae&#44; fibrin&#44; mucus&#44; and cell detritus&#44; which develops within a preexisting lung cavity caused by tuberculosis&#44; cancer&#44; etc&#46; It is usually clinically asymptomatic&#44; or presents with local symptoms limited to cough and&#47;or hemoptysis that can be severe&#46; It can be seen on CT&#44; and is usually isolated and unchanging&#46; Culture of respiratory samples and <span class="elsevierStyleItalic">Aspergillus</span> antibody detection &#40;precipitins&#41; are often positive&#46; In the asymptomatic presentation&#44; monitoring is recommended&#44; while the treatment of choice for symptomatic forms is surgical resection&#46; Oral or intralesional antifungals have not shown long-term efficacy&#44; and their use is restricted to symptomatic cases that are not candidates for surgery&#46;<a class="elsevierStyleCrossRefs" href="#bib0430"><span class="elsevierStyleSup">5&#44;10&#44;22&#44;23</span></a></p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Chronic Pulmonary Aspergillosis</span><p id="par0090" class="elsevierStylePara elsevierViewall">Chronic pulmonary aspergillosis comprises a wide spectrum of clinical signs and symptoms due to chronic or subacute <span class="elsevierStyleItalic">Aspergillus</span> infection&#46; It is caused by local fungal growth&#44; predominantly in the lower lobes&#44; and dissemination is exceptional&#46; The main risk factor is chronic lung disease that generates some degree of local immunosuppression&#58; tuberculosis&#44; other mycobacterial infections&#44; asthma and COPD treated with corticosteroids&#44; lung cancer and bullae&#46; It is associated with mannose-binding lectin polymorphisms&#44; surfactant deficiency&#44; and low interferon production&#46;<a class="elsevierStyleCrossRefs" href="#bib0815"><span class="elsevierStyleSup">22&#44;23</span></a></p><p id="par0095" class="elsevierStylePara elsevierViewall">The most widely accepted classification subdivides chronic pulmonary aspergillosis into 3 forms&#58; cavitary&#44; necrotizing&#44; and fibrosing&#46;<a class="elsevierStyleCrossRef" href="#bib0525"><span class="elsevierStyleSup">24</span></a> The clinical subtype is determined by the characteristics of the patient and the efficiency of their immune system&#46;<ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005"><span class="elsevierStyleLabel">A&#46;</span><p id="par0100" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Chronic cavitary aspergillosis</span>&#58; this a progressive syndrome&#44; characterized by the development of multiple cavitated lung nodules&#46; The clinical course is chronic&#44; lasting months&#44; and the most important general symptoms are weight loss&#44; general malaise&#44; night sweats&#44; low-grade fever or fever&#46; Respiratory symptoms are few and non-specific&#58; productive chronic cough&#44; possible hemoptysis&#44; and dyspnea&#46; Multinodular involvement is observed on CT&#44; with progressive thick-walled cavities&#44; in which aspergillomas can form&#46;<a class="elsevierStyleCrossRefs" href="#bib0520"><span class="elsevierStyleSup">23&#44;25</span></a></p></li><li class="elsevierStyleListItem" id="lsti0010"><span class="elsevierStyleLabel">B&#46;</span><p id="par0105" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Chronic necrotizing aspergillosis</span>&#58; some authors consider this as a subacute form of IPA&#46; It occurs in more highly immunosuppressed patients&#44; and is characterized by more rapid and aggressive progression than the cavitary form&#44; with greater invasion and tissue damage&#46; In addition to general symptoms&#44; fever is more frequent and respiratory symptoms more florid&#46; CT shows patchy involvement with areas of necrosis&#59; cavity walls are usually thinner&#44; and the air crescent sign typical of IPA can be observed&#46;<a class="elsevierStyleCrossRefs" href="#bib0520"><span class="elsevierStyleSup">23&#44;25</span></a></p></li><li class="elsevierStyleListItem" id="lsti0015"><span class="elsevierStyleLabel">C&#46;</span><p id="par0110" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Chronic fibrosing aspergillosis</span>&#58; late development of the cavitary&#44; or more rarely&#44; the necrotizing form&#46; Imaging tests show progressive fibrosis&#44; impacting on lung function tests&#46;</p></li></ul></p><p id="par0115" class="elsevierStylePara elsevierViewall">Diagnostic suspicion is based on clinical and radiological findings&#46; Laboratory reports show elevated inflammatory reactants&#44; and precipitins are positive in most cases&#46; Anti-<span class="elsevierStyleItalic">Aspergillus</span> IgE can be detected in the absence of evidence of allergic bronchopulmonary aspergillosis&#46; Sputum culture is positive in around 40&#37;&#8211;50&#37; of cases&#44; but the yield of PCR or galactomannan detection in respiratory samples is higher&#46; Galactomannan may be elevated in blood &#40;although not as often as in IPA&#41;&#44; particularly in the necrotizing forms&#46;</p><p id="par0120" class="elsevierStylePara elsevierViewall">If clinical and radiological findings are consistent&#44; the presence of precipitins or positive cultures is very suggestive of this clinical entity&#46; However&#44; some patients have negative microbiological results&#59; moreover&#44; intercurrent or imitative processes &#40;mycobacterial infection&#44; in particular&#41; may be present&#44; so a bronchoscopy is often essential for obtaining samples with a better yield&#46; Definitive diagnosis is obtained from biopsy showing hyphae&#44; local necrosis and&#47;or granulomatous reaction&#46; Angioinvasion is generally absent&#44; and if it does occur&#44; it is more often in the necrotizing form&#46;<a class="elsevierStyleCrossRefs" href="#bib0815"><span class="elsevierStyleSup">22&#44;23&#44;25</span></a></p><p id="par0125" class="elsevierStylePara elsevierViewall">Chronic forms of aspergillosis are treated with oral azoles &#40;itraconazole or voriconazole&#41;&#44; administered long-term or even indefinitely&#44; due to the high risk of recurrence&#46; Alternatives include posaconazole or amphotericin B in severe cases&#46; Optimization of immunity is also recommended&#44; if possible&#46; Isolated cases of improvement with interferon have been reported in the literature&#46;<a class="elsevierStyleCrossRefs" href="#bib0520"><span class="elsevierStyleSup">23&#44;25</span></a> Treatment may be monitored with clinical and radiological surveillance and determination of precipitin titers&#46;<a class="elsevierStyleCrossRefs" href="#bib0455"><span class="elsevierStyleSup">10&#44;21</span></a> Despite treatment&#44; mid- to long-term control of the infection is often suboptimal&#46;</p><p id="par0130" class="elsevierStylePara elsevierViewall">The use of primary aspergillosis prophylaxis is under debate&#46; The main indications are listed in <a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#46;<a class="elsevierStyleCrossRefs" href="#bib0535"><span class="elsevierStyleSup">26&#8211;28</span></a> It is not recommended in patients with hematological malignancies and neutropenia expected to last less than 7 days&#44; or solid tumors receiving conventional chemotherapy&#46; The most widely recommended drug in the different guidelines is posaconazole&#44; as it has been most studied in clinical trials and has the advantage of being active against Mucorales fungi&#46; Voriconazole is a reasonable alternative&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0135" class="elsevierStylePara elsevierViewall">In lung transplant recipients&#44; evidence for the different recommendations for prophylaxis is low grade&#44; due to the lack of appropriate studies&#46;<a class="elsevierStyleCrossRefs" href="#bib0550"><span class="elsevierStyleSup">29&#44;30</span></a> In standard practice&#44; the tendency is to administer universal antifungal prophylaxis&#46;<a class="elsevierStyleCrossRef" href="#bib0560"><span class="elsevierStyleSup">31</span></a> Correct prophylactic dosing has not been well defined&#44; but azoles with anti-<span class="elsevierStyleItalic">Aspergillosis</span> activity &#40;itraconazole&#44; voriconazole or posaconazole&#41; and&#47;or inhaled amphotericin B are generally used&#46;</p></span></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Mucormycosis</span><p id="par0140" class="elsevierStylePara elsevierViewall">Mucormycosis is disease caused by Mucorales fungi&#44; the most commonly involved genera being <span class="elsevierStyleItalic">Rhizopus</span>&#44; <span class="elsevierStyleItalic">Mucor</span> and <span class="elsevierStyleItalic">Rhizomucor</span>&#46;</p><p id="par0145" class="elsevierStylePara elsevierViewall">They are acquired by inhalation or via damaged skin and mucous membranes&#46; They cause rapid vascular invasion&#44; thrombosis and secondary necrosis&#46;<a class="elsevierStyleCrossRef" href="#bib0565"><span class="elsevierStyleSup">32</span></a> The risk factors for mucormycosis are similar to those of aspergillosis&#44; but diabetes mellitus with poor metabolic control&#44; iron overload&#44; and the use of desferoxamine should also be taken into account&#46; Controversy persists on whether voriconazole prophylaxis can increase the risk of mucormycosis<a class="elsevierStyleCrossRefs" href="#bib0565"><span class="elsevierStyleSup">32&#8211;35</span></a>&#59; the reason for this association has not been clarified&#44; but it is posited that it may be due to <span class="elsevierStyleItalic">Aspergillosis</span> being displaced&#44; allowing the positive selection of Mucorales&#44; which are mostly resistant to voriconazole&#46; Paradoxically&#44; it is rare in HIV&#44; except in cases associated with the use of intravenous drugs and corticosteroid therapy&#46;<a class="elsevierStyleCrossRef" href="#bib0565"><span class="elsevierStyleSup">32</span></a></p><p id="par0150" class="elsevierStylePara elsevierViewall">The most common sites of infection are the paranasal sinuses&#44; the lungs and the skin&#46; Rhino-orbital mucormycosis is mostly seen in diabetics&#44; while in hematological patients the predominant forms are pulmonary&#46; Lung involvement behaves similarly to very severe and rapidly invasive micronodular interstitial pulmonary disease&#46; Mortality is around 70&#37;&#8211;75&#37;&#46;<a class="elsevierStyleCrossRefs" href="#bib0565"><span class="elsevierStyleSup">32&#44;36</span></a> Clinical symptoms include dyspnea&#44; cough&#44; chest pain&#44; and hemoptysis&#44; which on occasions can be massive&#46; It also has a high capacity for causing cavitation and progressive invasion&#44; which may affect the pericardium&#44; pleura&#44; mediastinum&#44; and chest wall&#46; Similarly to <span class="elsevierStyleItalic">Aspergillosis</span>&#44; endobronchial involvement and airway obstruction may also occur&#46;<a class="elsevierStyleCrossRef" href="#bib0505"><span class="elsevierStyleSup">20</span></a> Radiological findings are very varied and include infiltrates&#44; nodules&#44; cavities&#44; atelectasis&#44; pleural effusion&#44; and mediastinal lymphadenopathies&#46; Like <span class="elsevierStyleItalic">Aspergillus</span>&#44; it produces the halo sign&#44; and more characteristically&#44; the reverse halo sign&#46;<a class="elsevierStyleCrossRefs" href="#bib0565"><span class="elsevierStyleSup">32&#44;37</span></a></p><p id="par0155" class="elsevierStylePara elsevierViewall">The presentation&#44; then&#44; is similar to that of IPA&#44; but some factors guiding the diagnosis of mucormycosis are the following&#58; greater rhinosinusal&#44; palatine or facial involvement&#44; or the presence of thoracic subcutaneous tissue&#46;<a class="elsevierStyleCrossRef" href="#bib0595"><span class="elsevierStyleSup">38</span></a> Radiological findings of more than 10 nodules and pleural effusion are factors more often associated with mucormycosis than IPA&#46;<a class="elsevierStyleCrossRef" href="#bib0600"><span class="elsevierStyleSup">39</span></a> Moreover&#44; galactomannan and 1&#44;3-&#946;-<span class="elsevierStyleSmallCaps">d</span>-glucan are negative in this entity&#46; A history of voriconazole use and lack of response to this drug support the suspicion&#46; None of these findings is specific&#44; but are useful as guidance when waiting for microbiological results&#46;</p><p id="par0160" class="elsevierStylePara elsevierViewall">Diagnosis is made from respiratory cultures or biopsies&#46; Since its presence in respiratory samples is rare&#44; isolation in a consistent clinical context is considered diagnostic&#46; Blood cultures are negative&#44; even in invasive forms&#46;<a class="elsevierStyleCrossRefs" href="#bib0590"><span class="elsevierStyleSup">37&#44;38</span></a></p><p id="par0165" class="elsevierStylePara elsevierViewall">Treatment must be initiated promptly&#44;<a class="elsevierStyleCrossRefs" href="#bib0605"><span class="elsevierStyleSup">40&#44;41</span></a> with resolution of risk factors&#44; surgical debridement of accessible areas and administration of antifungal agents&#46;<a class="elsevierStyleCrossRef" href="#bib0565"><span class="elsevierStyleSup">32</span></a> Only amphotericin B and posaconazole are known to be effective&#46; Amphotericin B is the first line treatment&#44; while posaconazole is used in cases of renal dysfunction and in sequential oral treatment in the maintenance phase&#46; Duration of treatment has not been established and should be individualized according to clinical response and resolution of lesions&#46;<a class="elsevierStyleCrossRefs" href="#bib0505"><span class="elsevierStyleSup">20&#44;21&#44;38&#44;42&#44;43</span></a> Surgery plays a fundamental role in the resolution of local forms&#46; The effectiveness of granulocyte stimulating factors in neutropenic patients has been defined&#46;<a class="elsevierStyleCrossRefs" href="#bib0615"><span class="elsevierStyleSup">42&#44;44</span></a></p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Cryptococcosis</span><p id="par0170" class="elsevierStylePara elsevierViewall">The most important pathogens of the <span class="elsevierStyleItalic">Cryptococcus</span> genus are <span class="elsevierStyleItalic">Cryptococcus neoformans</span> &#40;<span class="elsevierStyleItalic">C&#46; neoformans</span>&#41; and the emerging <span class="elsevierStyleItalic">Cryptococcus gattii</span> &#40;<span class="elsevierStyleItalic">C&#46; gattii</span>&#41;&#46; They are ubiquitous and are isolated from soils&#44; particularly in areas frequented by birds and bats&#46;<a class="elsevierStyleCrossRef" href="#bib0630"><span class="elsevierStyleSup">45</span></a> While the distribution of <span class="elsevierStyleItalic">C&#46; neoformans</span> is universal&#44; <span class="elsevierStyleItalic">C&#46; gattii</span> is more common in subtropical regions&#44; and its presence has increased in recent years in some areas of the North Pacific&#46;<a class="elsevierStyleCrossRef" href="#bib0635"><span class="elsevierStyleSup">46</span></a></p><p id="par0175" class="elsevierStylePara elsevierViewall">The invasive capacity of <span class="elsevierStyleItalic">Cryptococcus</span> is due to its expression of a polysaccharide capsule with antiphagocytic properties&#46; It enters by the airways and causes 2 distinct clinical syndromes&#58; meningitis and meningoencephalitis&#46; Its pulmonary transit&#44; however&#44; can be blocked by a cell-mediated immune reaction and the development of granulomas&#59; in an immunocompromised host&#44; invasion can occur&#46;<a class="elsevierStyleCrossRefs" href="#bib0640"><span class="elsevierStyleSup">47&#8211;49</span></a></p><p id="par0180" class="elsevierStylePara elsevierViewall">The major risk factor is HIV infection&#44; particularly when CD4 counts are below 100<span class="elsevierStyleHsp" style=""></span>cells&#47;mm<span class="elsevierStyleSup">3</span>&#44; CNS involvement being the predominant clinical manifestation&#46;<a class="elsevierStyleCrossRef" href="#bib0655"><span class="elsevierStyleSup">50</span></a> In other immunosuppressive states&#44; such as chronic lung diseases&#44; patients on long-term corticosteroids&#44; or solid organ transplant recipients&#44; the resulting syndrome is predominantly respiratory&#46;<a class="elsevierStyleCrossRefs" href="#bib0510"><span class="elsevierStyleSup">21&#44;51</span></a><span class="elsevierStyleItalic">C&#46; gattii</span> affects the lungs&#44; even in immunocompetent patients&#46;<a class="elsevierStyleCrossRef" href="#bib0635"><span class="elsevierStyleSup">46</span></a></p><p id="par0185" class="elsevierStylePara elsevierViewall">Pulmonary cryptococcosis is characterized by fever&#44; with dyspnea&#44; dry cough&#44; night sweats&#44; and progressive&#44; occasionally fulminant&#44; respiratory failure&#46;<a class="elsevierStyleCrossRefs" href="#bib0640"><span class="elsevierStyleSup">47&#44;52&#44;53</span></a> Severe pulmonary presentations involve a risk of dissemination to the CNS and to other regions&#44; particularly the skin&#46;<a class="elsevierStyleCrossRef" href="#bib0675"><span class="elsevierStyleSup">54</span></a></p><p id="par0190" class="elsevierStylePara elsevierViewall">The most common radiological pattern is multiple nodular involvement&#46; Reticulonodular forms are more typical of invasive syndromes&#46; Involvement in the form of lobar or segmentary consolidation is also possible&#46; Thoracic lymphadenopathies may also occur&#46; Pleural effusion and cavitation are exceptional&#46;<a class="elsevierStyleCrossRef" href="#bib0680"><span class="elsevierStyleSup">55</span></a></p><p id="par0195" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Cryptococcus</span> in colonizations is unusual&#59; therefore&#44; isolation in a sputum or BAL culture consistent with clinical signs is sufficient for diagnosis&#46; <span class="elsevierStyleItalic">Cryptococcus</span> antigen determination in plasma is very useful&#44; but it can be negative in some limited pulmonary forms&#46;<a class="elsevierStyleCrossRefs" href="#bib0670"><span class="elsevierStyleSup">53&#44;56</span></a> Antigen detection in sputum or BAL is unreliable&#46;<a class="elsevierStyleCrossRef" href="#bib0640"><span class="elsevierStyleSup">47</span></a> Cerebrospinal fluid &#40;CSF&#41; can be studied by India ink staining&#44; antigen detection and&#47;or culture&#46; Routine lumbar puncture is not recommended for all pulmonary forms&#44; but rather in the presence of neurological symptoms&#44; severe immunosuppression&#44; signs of dissemination&#44; or high serum antigen levels&#46;<a class="elsevierStyleCrossRef" href="#bib0690"><span class="elsevierStyleSup">57</span></a></p><p id="par0200" class="elsevierStylePara elsevierViewall">The treatment of pulmonary forms has not been widely studied&#44; and the principal recommendations are based on the experience of treatment of HIV patients with CNS involvement&#46; For mild or moderate respiratory syndromes&#44; fluconazole for 6&#8211;12 months is recommended&#46;<a class="elsevierStyleCrossRefs" href="#bib0505"><span class="elsevierStyleSup">20&#44;21&#44;47&#44;58</span></a> In severe manifestations or CNS involvement&#44; at least 2 weeks combined treatment with amphotericin B and flucytosine is recommended&#46;<a class="elsevierStyleCrossRefs" href="#bib0510"><span class="elsevierStyleSup">21&#44;58&#44;59</span></a> This treatment should be followed sequentially by a 6&#8211;12 month course of fluconazole&#46; Treatment duration must be individualized on the basis of risk factors and recovery of immunosuppression status&#46; For example&#44; in HIV subjects&#44; maintenance treatment should continue until viral replication is controlled and a stable CD4 count<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>100<span class="elsevierStyleHsp" style=""></span>cells&#47;mm<span class="elsevierStyleSup">3</span> has been achieved&#46; Moreover&#44; initiation of antiretroviral treatment should be delayed for at least 4&#8211;8 weeks to avoid immune reconstitution inflammatory syndrome&#44; underlining once more the difficulties in achieving the immunological balance required in the management of opportunistic mycosis&#46;<a class="elsevierStyleCrossRefs" href="#bib0685"><span class="elsevierStyleSup">56&#44;60</span></a></p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Pneumocystosis</span><p id="par0205" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Pneumocystis jirovecii</span> is an atypical fungus&#44; acquired by the airborne route&#44; even in childhood&#46;<a class="elsevierStyleCrossRef" href="#bib0710"><span class="elsevierStyleSup">61</span></a> The main risk factor for developing this mycosis is HIV infection&#44; particularly when CD4 levels are below 200<span class="elsevierStyleHsp" style=""></span>cells&#47;mm<span class="elsevierStyleSup">3</span>&#46; It can&#44; however&#44; also occur in other cell-mediated immunosuppressive states common to other mycoses&#46;<a class="elsevierStyleCrossRefs" href="#bib0715"><span class="elsevierStyleSup">62&#44;63</span></a> It is important to note that the immunosuppressive agents most frequently cited are corticosteroids&#44; particularly in association with dose increases or reductions from previously high doses&#46;<a class="elsevierStyleCrossRefs" href="#bib0725"><span class="elsevierStyleSup">64&#44;65</span></a></p><p id="par0210" class="elsevierStylePara elsevierViewall">The clinical syndrome in patients with HIV infection is subacute&#44; with fever&#44; dry cough&#44; and progressive dyspnea&#44; and generalized asthenia and weight loss&#46; However&#44; in immunosuppressed patients without HIV infection&#44; the clinical picture is more acute&#44; prognosis is poorer and the rates of acute respiratory failure&#44; need for ventilatory support and mortality are higher&#46;<a class="elsevierStyleCrossRefs" href="#bib0725"><span class="elsevierStyleSup">64&#44;66&#8211;69</span></a> Some authors have associated this increased mortality in non-HIV patients with more severe immunosuppression status&#44; and with delay in diagnosis and treatment&#44; since the suspicion of pneumocystosis is not so strong&#46;<a class="elsevierStyleCrossRef" href="#bib0740"><span class="elsevierStyleSup">67</span></a></p><p id="par0215" class="elsevierStylePara elsevierViewall">Diffuse bilateral interstitial infiltrates may be seen on X-ray&#46; CT provides a more defined image of bilateral ground glass opacities&#44; possible pneumatoceles and pneumothorax due to local parenchymal damage&#46; It is rare to see lobar infiltrates&#44; nodules&#44; cavities&#44; or pleural effusion&#46; If the CT is normal&#44; the diagnosis should be questioned&#46;<a class="elsevierStyleCrossRef" href="#bib0755"><span class="elsevierStyleSup">70</span></a></p><p id="par0220" class="elsevierStylePara elsevierViewall">During pneumocystosis&#44; 1&#44;3-&#946;-<span class="elsevierStyleSmallCaps">d</span>-glucan levels are raised&#44; leading many authors to suggest that a positive finding in a high risk patient with consistent signs and symptoms may be sufficient to reach a diagnosis&#46; However&#44; in view of the association with pneumocystosis with other intercurrent processes&#44; the recommendation is to obtain a more specific diagnosis&#46;<a class="elsevierStyleCrossRefs" href="#bib0760"><span class="elsevierStyleSup">71&#44;72</span></a> Since it cannot be cultured&#44; visualization using immunofluorescence techniques is needed&#44; and yield is high&#46; Immunofluorescence can be used in induced sputum&#44; with sensitivity ranging between 55&#37; and 90&#37;&#44; or BAL with a sensitivity of around 90&#37;&#8211;100&#37;&#46; Biopsy is rarely necessary&#46; PCR values have yet to be defined&#46;<a class="elsevierStyleCrossRef" href="#bib0770"><span class="elsevierStyleSup">73</span></a></p><p id="par0225" class="elsevierStylePara elsevierViewall">If there is a clinical suspicion of pneumocystosis&#44; treatment must be initiated without waiting for sampling of respiratory specimens&#44; as eradication of pathogens from the respiratory secretions will take several weeks&#46;<a class="elsevierStyleCrossRefs" href="#bib0775"><span class="elsevierStyleSup">74&#44;75</span></a></p><p id="par0230" class="elsevierStylePara elsevierViewall">In HIV patients&#44; the treatment of choice is cotrimoxazole for 21 days&#46; Alternatives include pentamidine&#44; dapsone&#44; atovaquone&#44; or combined clindamycin and primaquine&#44; depending on severity&#46; Co-administration of corticosteroids is recommended in severe cases&#46;<a class="elsevierStyleCrossRef" href="#bib0785"><span class="elsevierStyleSup">76</span></a> Antiretroviral treatment must also be delayed for at least 2 weeks&#46;<a class="elsevierStyleCrossRefs" href="#bib0745"><span class="elsevierStyleSup">68&#44;76&#44;77</span></a></p><p id="par0235" class="elsevierStylePara elsevierViewall">Treatment of non-HIV patients is less widely studied&#44; and most of the recommendations for antimicrobials apply in these cases&#46; Corticosteroid treatment is more controversial in these patients&#46; Some small studies were not able to show clear efficacy in terms of mortality&#44; so corticosteroids should be continued in patients previously receiving this treatment&#44; and initiated in cases of severe lung inflammation&#46;<a class="elsevierStyleCrossRefs" href="#bib0510"><span class="elsevierStyleSup">21&#44;78&#44;79</span></a> Cotrimoxazole is the agent of choice for secondary prophylaxis and should be administered until immunological recovery&#46; Cotrimoxazole is also given for primary prophylaxis&#46; Alternatives include atovaquone&#44; dapsone&#44; or aerosolized pentamidine&#46; The main indications are listed in <a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>&#46;<a class="elsevierStyleCrossRefs" href="#bib0410"><span class="elsevierStyleSup">1&#44;27&#44;80&#44;81</span></a></p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Conflict of Interests</span><p id="par0240" class="elsevierStylePara elsevierViewall">The authors state that they have no conflict of interests&#46;</p></span></span>"
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          "titulo" => "Keywords"
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          "titulo" => "Resumen"
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          "identificador" => "xpalclavsec602854"
          "titulo" => "Palabras clave"
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          "identificador" => "sec0005"
          "titulo" => "Introduction"
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          "identificador" => "sec0010"
          "titulo" => "Aspergillosis"
          "secciones" => array:3 [
            0 => array:2 [
              "identificador" => "sec0015"
              "titulo" => "Invasive Pulmonary Aspergillosis"
            ]
            1 => array:2 [
              "identificador" => "sec0020"
              "titulo" => "Aspergilloma"
            ]
            2 => array:2 [
              "identificador" => "sec0025"
              "titulo" => "Chronic Pulmonary Aspergillosis"
            ]
          ]
        ]
        6 => array:2 [
          "identificador" => "sec0030"
          "titulo" => "Mucormycosis"
        ]
        7 => array:2 [
          "identificador" => "sec0035"
          "titulo" => "Cryptococcosis"
        ]
        8 => array:2 [
          "identificador" => "sec0040"
          "titulo" => "Pneumocystosis"
        ]
        9 => array:2 [
          "identificador" => "sec0045"
          "titulo" => "Conflict of Interests"
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        10 => array:1 [
          "titulo" => "References"
        ]
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    ]
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    "fechaRecibido" => "2014-10-22"
    "fechaAceptado" => "2015-02-20"
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          "clase" => "keyword"
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          "identificador" => "xpalclavsec602855"
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            0 => "Opportunistic pulmonary mycoses"
            1 => "<span class="elsevierStyleItalic">Aspergillus</span>"
            2 => "Invasive pulmonary aspergillosis"
            3 => "Mucormycosis"
            4 => "<span class="elsevierStyleItalic">Cryptococcus</span>"
            5 => "<span class="elsevierStyleItalic">Pneumocystis jirovecii</span>"
          ]
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          "clase" => "keyword"
          "titulo" => "Palabras clave"
          "identificador" => "xpalclavsec602854"
          "palabras" => array:6 [
            0 => "Micosis pulmonares oportunistas"
            1 => "<span class="elsevierStyleItalic">Aspergillus</span>"
            2 => "Aspergilosis pulmonar invasiva"
            3 => "Mucormicosis"
            4 => "<span class="elsevierStyleItalic">Cryptococcus</span>"
            5 => "<span class="elsevierStyleItalic">Pneumocystis jirovecii</span>"
          ]
        ]
      ]
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    "resumen" => array:2 [
      "en" => array:2 [
        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Mycoses are serious diseases with potentially fatal outcome&#46; The introduction of immunosuppressive treatments and life support techniques has led to a growing prevalence of different degrees of immunosuppression&#46; Compromised immune response is the primary risk factor for the development of opportunistic mycoses&#46; Early diagnosis and treatment are crucial for improving prognosis&#46; However&#44; isolation in cultures or identification using antigen detection techniques cannot distinguish between colonization and invasive infection&#44; and the clinical status of the patient often prevents biopsy sampling&#46; Clinicians thus find themselves in an uncertain position&#44; requiring them to quickly recognize clinical and radiological signs and interpret microbiological results in context&#46; The aim of this review is to provide a general overview of the profile of patients susceptible to these infections&#44; the role of the immune system and&#44; in more detail&#44; the major diagnostic developments that have gained most acceptance and recognition among the scientific community&#46;</p></span>"
      ]
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        "titulo" => "Resumen"
        "resumen" => "<span id="abst0010" class="elsevierStyleSection elsevierViewall"><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Las micosis son enfermedades graves y potencialmente letales&#46; Con el desarrollo de terapias inmunosupresoras y t&#233;cnicas de soporte vital&#44; la inmunosupresi&#243;n en sus diferentes grados es cada vez m&#225;s prevalente&#46; El deterioro de la respuesta inmune es el factor de riesgo principal para el desarrollo de las micosis oportunistas&#46; El diagn&#243;stico y tratamiento precoces son factores cruciales para mejorar el pron&#243;stico de estas enfermedades&#46; Sin embargo&#44; los aislamientos mediante cultivos o las t&#233;cnicas de detecci&#243;n antig&#233;nicas no son capaces de distinguir entre colonizaci&#243;n e infecci&#243;n invasiva&#44; y las biopsias rara vez se pueden realizar por la situaci&#243;n cl&#237;nica&#46; Ello sit&#250;a al m&#233;dico en una situaci&#243;n de incertidumbre en la que debe reconocer precozmente los signos cl&#237;nicos y radiol&#243;gicos e interpretar los resultados microbiol&#243;gicos en su contexto&#46; El objetivo de esta revisi&#243;n es aportar una visi&#243;n general del perfil de paciente que sufre estas infecciones&#44; el papel de su sistema inmune&#44; y de forma m&#225;s detallada&#44; los principales avances diagn&#243;sticos m&#225;s reconocidos y recomendados por la comunidad cient&#237;fica&#46;</p></span>"
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        "etiqueta" => "&#9734;"
        "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as&#58; Curbelo J&#44; Galv&#225;n JM&#44; Aspa J&#46; Actualizaci&#243;n sobre <span class="elsevierStyleItalic">Aspergillus</span>&#44; <span class="elsevierStyleItalic">Pneumocystis</span> y otras micosis pulmonares oportunistas&#46; Arch Bronconeumol&#46; 2015&#59;51&#58;647&#8211;653&#46;</p>"
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                  \t\t\t\t" class=""><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">&#8226; Disrupted natural barriers&#58; mucositis&#44; venous access lines&#44; surgical wounds&#44; intubation&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">&#8226; Prolonged neutropenia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">&#8226; Blood cancers&#44; whether associated or not associated with stem cell transplantation or graft-versus-host disease&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">&#8226; Disseminated malignant solid tumors&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">&#8226; Solid organ transplants&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">&#8226; HIV infection&#44; especially with CD4 counts<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>200<span class="elsevierStyleHsp" style=""></span>cells&#47;mm<span class="elsevierStyleSup">3</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">&#8226; Chronic lung diseases&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">&#8226; Connective tissue disease&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">&#8226; Immunosuppressive drugs&#44; primarily corticosteroids&#46; Other immunosuppressants associated with anti-TNF&#945; drugs and alemtuzumab&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Acute myeloid leukemia or intensively-treated myelodysplastic syndrome&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Allogenic stem cell transplantation with predicted prolonged neutropenia &#40;more than 2 weeks&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Graft-versus-host disease requiring high-dose corticosteroids&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Colonization before transplantation&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Induction with alemtuzumab or thymoglobulin&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Single-lung transplantation&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Colonization subsequent to cytomegalovirus infection&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Rejection and increased immunosuppression&nbsp;\t\t\t\t\t\t\n
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          "en" => "<p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Principal Indications for Primary Aspergillosis Prophylaxis&#46;</p>"
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                  \t\t\t\t" class=""><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">&#8226; HIV with CD4 count<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>200<span class="elsevierStyleHsp" style=""></span>cells&#47;mm<span class="elsevierStyleSup">3</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">&#8226; Prednisone treatment at doses<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>20<span class="elsevierStyleHsp" style=""></span>mg&#47;day for more than 1 month and presence of another cause of immunosuppression&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">&#8226; Alemtuzumab treatment&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">&#8226; Acute lymphoid leukemia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">&#8226; Blood cancer patient on intensive regimen containing purine analogs&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">&#8226; Stem cell transplant recipient&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">&#8226; Solid organ transplant recipient&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">&#8226; Rheumatic disease requiring induction immunosuppressive treatment &#40;e&#46;g&#46;&#44; corticosteroids and cyclophosphamide&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
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          "en" => "<p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Principal Indications for Primary Anti-<span class="elsevierStyleItalic">Pneumocystis jirovecii</span> Prophylaxis&#46;</p>"
        ]
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    "bibliografia" => array:2 [
      "titulo" => "References"
      "seccion" => array:1 [
        0 => array:2 [
          "identificador" => "bibs0005"
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              "etiqueta" => "1"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Imaging pneumonia in immunocompetent and immunocompromised individuals"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "J&#46;H&#46; Reynolds"
                            1 => "A&#46;K&#46; Banerjee"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
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Review
Updates on Aspergillus, Pneumocystis and Other Opportunistic Pulmonary Mycoses
Actualización sobre Aspergillus, Pneumocystis y otras micosis pulmonares oportunistas
José Curbeloa, José María Galvána, Javier Aspab,
Corresponding author
jaspa@separ.es

Corresponding author.
a Servicio de Medicina Interna, Instituto Princesa de Investigación IIS-IP, Madrid, Spain
b Servicio de Neumología, Instituto Princesa de Investigación IIS-IP, Madrid, Spain
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There is no common response to all fungi&#44; and distinguishing clinical features have been identified&#58; low CD4 levels are associated with pathogens such as <span class="elsevierStyleItalic">Pneumocystis</span> and <span class="elsevierStyleItalic">Cryptococcus</span>&#44; while neutropenia can lead to <span class="elsevierStyleItalic">Aspergillus</span> and Mucoralean infections&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">Types of immunosuppression associated with these mycoses are listed in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#46; It is worth noting that many of the risk factors mentioned are associated with the chronic use of high-dose corticosteroids&#44; underlining the need for careful adjustment of immunosuppression and consideration of therapeutic alternatives&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0020" class="elsevierStylePara elsevierViewall">Clinical manifestations of pulmonary mycoses are not specific&#44; and while it is easy to suspect mycosis in the context of known immunosuppression&#44; the opposite approach must not be forgotten&#58; a diffuse&#44; slowly progressing pulmonary syndrome should alert to a possible fungal infection and lead to an investigation of any possible underlying immunosuppression&#46; Detailed history and examination may guide diagnosis&#58; involvement of paranasal sinuses may be suggestive of <span class="elsevierStyleItalic">Mucor</span>&#44; skin lesions in disseminated disease may be a good source for biopsy&#44; etc&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">With regard to diagnosis&#44; chest X-ray may be normal&#44; so computed tomography is the imaging test of choice&#46; Diffuse bilateral infiltrates with areas of ground glass and&#47;or multimodal patterns are common&#44; but not specific&#44;<a class="elsevierStyleCrossRef" href="#bib0410"><span class="elsevierStyleSup">1</span></a> and microbiological culture or the detection of fungal antigens may be positive in a colonization setting&#44; reducing their diagnostic value for invasive disease&#46; The yield of serological testing in immunocompromised patients is poor&#46; Biopsy has been conventionally considered as the unequivocal test for demonstrating invasive fungal proliferation&#44; but in many cases&#44; the clinical status of the patient prevents sampling&#46; Moreover&#44; the extreme seriousness of these diseases means that appropriate empirical treatment must be started as soon as possible&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">The European Organization of Research and Treatment of Cancer&#47;Mycoses Study Group &#40;EORTC&#47;MSG&#41; has defined invasive mycoses as&#58; proven &#40;consistent histological results or positive culture in sterile medium&#41;&#59; probable &#40;lower grade microbiological evidence in a patient with risk factors and consistent clinical syndrome&#41;&#59; and possible &#40;patients with clinical syndrome and risk factors&#44; despite absence of microbiological confirmation&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0415"><span class="elsevierStyleSup">2</span></a> These guidelines reflect the effort made in unifying criteria to assist the clinician in dealing with diagnostic uncertainty&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">It is important to point out that treatment does not depend exclusively on the administration of antifungals&#46; Immunosuppression must also be addressed and reduced or reversed to achieve a level of balance that remains poorly defined&#46; In a situation of irreversible immunosuppression&#44; there will be little response to antifungal treatment&#44; while recovery of the immune response may be associated with clinical worsening&#44; due to the inflammatory response&#46; This phenomenon is well established in HIV patients&#44; but has also been described in non-HIV patients&#46;<a class="elsevierStyleCrossRef" href="#bib0420"><span class="elsevierStyleSup">3</span></a></p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Aspergillosis</span><p id="par0040" class="elsevierStylePara elsevierViewall">Aspergillosis is the primary pulmonary mycosis among critically ill patients&#44;<a class="elsevierStyleCrossRef" href="#bib0425"><span class="elsevierStyleSup">4</span></a> the most common species being <span class="elsevierStyleItalic">A&#46; fumigatus</span>&#44; <span class="elsevierStyleItalic">A&#46; flavus</span>&#44; <span class="elsevierStyleItalic">A&#46; niger</span> and <span class="elsevierStyleItalic">A&#46; terreus</span>&#46; They are acquired by inhalation of conidia&#44; which in an immunocompetent individual are eradicated by alveolar macrophages and neutrophils&#46; Disease develops when this line of defense breaks down&#44; or&#44; more rarely&#44; in situations of excessive inhalation of conidia&#44; such as occurs during landslides or great catastrophes&#46;<a class="elsevierStyleCrossRef" href="#bib0430"><span class="elsevierStyleSup">5</span></a> Several clinical pulmonary forms have been described&#44; the most important of which are invasive pulmonary aspergillosis &#40;IPA&#41;&#44; chronic aspergillosis&#44; and aspergilloma&#46;<a class="elsevierStyleCrossRef" href="#bib0435"><span class="elsevierStyleSup">6</span></a> The type and severity of aspergillosis is determined by the characteristics of the patient &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46; Severe&#44; generalized immunosuppressive states&#44; such as prolonged neutropenia&#44; are associated with acute invasive disease&#44; while moderate&#44; localized immunosuppression&#44; such as preexisting cavities&#44; favors the development of forms such as aspergilloma&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Invasive Pulmonary Aspergillosis</span><p id="par0045" class="elsevierStylePara elsevierViewall">IPA is the most severe form of aspergillosis&#44; with a mortality of around 50&#37;&#46; It is caused by massive proliferation of <span class="elsevierStyleItalic">Aspergillus</span>&#44; with tissue invasion and high vascular tropism&#44; promoting ischemia and dissemination&#46;</p><p id="par0050" class="elsevierStylePara elsevierViewall">Serious risk factors include prolonged neutropenia in patients with hematological malignancies&#44; hematopoietic stem cell &#40;HSC&#41; and solid organ transplants&#44; particularly lung and heart&#46; Other factors thought to be intermediate include intensive care unit admission&#44; chronic obstructive lung disease &#40;COPD&#41; treated with inhaled or systemic corticosteroids&#44; chemotherapy and radiation therapy&#44; AIDS&#44; etc&#46;<a class="elsevierStyleCrossRefs" href="#bib0430"><span class="elsevierStyleSup">5&#44;7</span></a> Despite the varying importance of each risk factor&#44; IPA in critically ill patients mostly occurs in association with COPD and prolonged corticosteroid use&#44;<a class="elsevierStyleCrossRef" href="#bib0425"><span class="elsevierStyleSup">4</span></a> due to their higher prevalence&#46;</p><p id="par0055" class="elsevierStylePara elsevierViewall">IPA progresses with fever&#44; cough&#44; expectoration&#44; hemoptysis&#44; dyspnea&#44; and pleuritic pain&#46; Tracheobronchial involvement may be observed&#44; particularly in lung transplantation&#46;<a class="elsevierStyleCrossRef" href="#bib0445"><span class="elsevierStyleSup">8</span></a> If it disseminates&#44; the skin&#44; central nervous system &#40;CNS&#41;&#44; liver and kidneys may be affected&#46;<a class="elsevierStyleCrossRef" href="#bib0430"><span class="elsevierStyleSup">5</span></a></p><p id="par0060" class="elsevierStylePara elsevierViewall">CT reveals areas of ground glass opacities with multiple nodules and cavitated lesions&#46; Nodular lesions may be associated with perinodular hemorrhage&#44; producing the typical &#8220;halo&#8221; sign&#46; Subsequently&#44; as the disease progresses&#44; peripheral necrosis and cavitation with the air crescent sign&#44; or necrosis and central attenuation with the reversed halo sign may develop&#46; These radiological signs&#44; typically related with IPA&#44; may be imitated by other mycoses and even other non-fungal infections&#46; Moreover&#44; they are absent in many patients&#44; particularly those receiving corticosteroid treatment without neutropenia&#46;<a class="elsevierStyleCrossRefs" href="#bib0450"><span class="elsevierStyleSup">9&#44;10</span></a></p><p id="par0065" class="elsevierStylePara elsevierViewall">Sputum or bronchoalveolar lavage &#40;BAL&#41; cultures have certain limitations&#58; sensitivity is low &#40;cultures are negative in up to 50&#37; of IPAs&#41; and specificity is suboptimal&#44; as no distinction can be made between invasive infection and possible colonization&#46; Indeed&#44; 30&#37;&#8211;60&#37; of positive cultures from lung transplant patients are thought to be due to colonization&#46; Blood cultures are generally negative&#44; even in disseminated forms of the disease&#44; so yield is low&#46;<a class="elsevierStyleCrossRefs" href="#bib0425"><span class="elsevierStyleSup">4&#44;11</span></a></p><p id="par0070" class="elsevierStylePara elsevierViewall">Different diagnostic techniques have been proposed to improve sensitivity and to reduce wait time for cultures&#46; Detection of serum galactomannan&#44; a component of the <span class="elsevierStyleItalic">Aspergillus</span> cell wall&#44; in patients with hematological malignancies has a sensitivity of 71&#37; and a specificity of 89&#37;&#44;<a class="elsevierStyleCrossRef" href="#bib0465"><span class="elsevierStyleSup">12</span></a> but the yield is lower in transplant recipients and COPD patients&#46;<a class="elsevierStyleCrossRefs" href="#bib0470"><span class="elsevierStyleSup">13&#44;14</span></a> Galactomannan determination in BAL is more sensitive and specific than in blood in both hematological cancer patients and other groups&#46;<a class="elsevierStyleCrossRef" href="#bib0480"><span class="elsevierStyleSup">15</span></a> However&#44; false positives related with betalactam antibiotics&#44; <span class="elsevierStyleItalic">Bifidobacterium</span> colonization and presence of histoplasmosis&#44; blastomycosis or penicillinosis have been reported&#46;<a class="elsevierStyleCrossRefs" href="#bib0485"><span class="elsevierStyleSup">16&#44;17</span></a></p><p id="par0075" class="elsevierStylePara elsevierViewall">Another <span class="elsevierStyleItalic">Aspergillus</span> cell wall antigen is 1&#44;3-&#946;-<span class="elsevierStyleSmallCaps">d</span>-glucan&#44; and detection in serum yields similar results to galactomannan&#46; However&#44; it is present in the structure of most fungi&#44; including <span class="elsevierStyleItalic">Candida</span> and <span class="elsevierStyleItalic">Pneumocystis</span>&#44; so it is less specific and returns positive results for other invasive mycoses&#46;<a class="elsevierStyleCrossRef" href="#bib0490"><span class="elsevierStyleSup">17</span></a> Finally&#44; the use of polymerase chain reaction &#40;PCR&#41; techniques in BAL has been proposed&#44; resulting in sensitivity and specificity of 91&#37; and 92&#37;&#44; respectively&#46;<a class="elsevierStyleCrossRef" href="#bib0495"><span class="elsevierStyleSup">18</span></a> The definitive test is biopsy&#44; but in many cases sampling is not feasible&#44; due to the clinical instability of the patient&#46;</p><p id="par0080" class="elsevierStylePara elsevierViewall">Delay in treatment is associated with higher mortality&#46;<a class="elsevierStyleCrossRef" href="#bib0500"><span class="elsevierStyleSup">19</span></a> Accordingly&#44; if suspicion is well-grounded&#44; treatment should be initiated&#46; The antifungal agent of choice is voriconazole&#44; while liposomal amphotericin B is another alternative&#46; Second line options include posaconazole&#44; caspofungin or micafungin&#46; Treatment duration is at least 12 weeks&#44; and the regimen should be tailored according to resolution and prolonged stabilization of lesions&#46; Monitoring of galactomannan levels in blood may be useful&#46; Surgery is limited to debridement of areas of superficial necrosis and invasion of pericardium or great vessels due to contiguity&#46; Granulocyte stimulating factors are used in cases of neutropenia&#44; but there is no evidence of any reduction in mortality&#46;<a class="elsevierStyleCrossRefs" href="#bib0440"><span class="elsevierStyleSup">7&#44;10&#44;20&#44;21</span></a></p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Aspergilloma</span><p id="par0085" class="elsevierStylePara elsevierViewall">Aspergilloma is a fungus ball composed of hyphae&#44; fibrin&#44; mucus&#44; and cell detritus&#44; which develops within a preexisting lung cavity caused by tuberculosis&#44; cancer&#44; etc&#46; It is usually clinically asymptomatic&#44; or presents with local symptoms limited to cough and&#47;or hemoptysis that can be severe&#46; It can be seen on CT&#44; and is usually isolated and unchanging&#46; Culture of respiratory samples and <span class="elsevierStyleItalic">Aspergillus</span> antibody detection &#40;precipitins&#41; are often positive&#46; In the asymptomatic presentation&#44; monitoring is recommended&#44; while the treatment of choice for symptomatic forms is surgical resection&#46; Oral or intralesional antifungals have not shown long-term efficacy&#44; and their use is restricted to symptomatic cases that are not candidates for surgery&#46;<a class="elsevierStyleCrossRefs" href="#bib0430"><span class="elsevierStyleSup">5&#44;10&#44;22&#44;23</span></a></p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Chronic Pulmonary Aspergillosis</span><p id="par0090" class="elsevierStylePara elsevierViewall">Chronic pulmonary aspergillosis comprises a wide spectrum of clinical signs and symptoms due to chronic or subacute <span class="elsevierStyleItalic">Aspergillus</span> infection&#46; It is caused by local fungal growth&#44; predominantly in the lower lobes&#44; and dissemination is exceptional&#46; The main risk factor is chronic lung disease that generates some degree of local immunosuppression&#58; tuberculosis&#44; other mycobacterial infections&#44; asthma and COPD treated with corticosteroids&#44; lung cancer and bullae&#46; It is associated with mannose-binding lectin polymorphisms&#44; surfactant deficiency&#44; and low interferon production&#46;<a class="elsevierStyleCrossRefs" href="#bib0815"><span class="elsevierStyleSup">22&#44;23</span></a></p><p id="par0095" class="elsevierStylePara elsevierViewall">The most widely accepted classification subdivides chronic pulmonary aspergillosis into 3 forms&#58; cavitary&#44; necrotizing&#44; and fibrosing&#46;<a class="elsevierStyleCrossRef" href="#bib0525"><span class="elsevierStyleSup">24</span></a> The clinical subtype is determined by the characteristics of the patient and the efficiency of their immune system&#46;<ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005"><span class="elsevierStyleLabel">A&#46;</span><p id="par0100" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Chronic cavitary aspergillosis</span>&#58; this a progressive syndrome&#44; characterized by the development of multiple cavitated lung nodules&#46; The clinical course is chronic&#44; lasting months&#44; and the most important general symptoms are weight loss&#44; general malaise&#44; night sweats&#44; low-grade fever or fever&#46; Respiratory symptoms are few and non-specific&#58; productive chronic cough&#44; possible hemoptysis&#44; and dyspnea&#46; Multinodular involvement is observed on CT&#44; with progressive thick-walled cavities&#44; in which aspergillomas can form&#46;<a class="elsevierStyleCrossRefs" href="#bib0520"><span class="elsevierStyleSup">23&#44;25</span></a></p></li><li class="elsevierStyleListItem" id="lsti0010"><span class="elsevierStyleLabel">B&#46;</span><p id="par0105" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Chronic necrotizing aspergillosis</span>&#58; some authors consider this as a subacute form of IPA&#46; It occurs in more highly immunosuppressed patients&#44; and is characterized by more rapid and aggressive progression than the cavitary form&#44; with greater invasion and tissue damage&#46; In addition to general symptoms&#44; fever is more frequent and respiratory symptoms more florid&#46; CT shows patchy involvement with areas of necrosis&#59; cavity walls are usually thinner&#44; and the air crescent sign typical of IPA can be observed&#46;<a class="elsevierStyleCrossRefs" href="#bib0520"><span class="elsevierStyleSup">23&#44;25</span></a></p></li><li class="elsevierStyleListItem" id="lsti0015"><span class="elsevierStyleLabel">C&#46;</span><p id="par0110" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Chronic fibrosing aspergillosis</span>&#58; late development of the cavitary&#44; or more rarely&#44; the necrotizing form&#46; Imaging tests show progressive fibrosis&#44; impacting on lung function tests&#46;</p></li></ul></p><p id="par0115" class="elsevierStylePara elsevierViewall">Diagnostic suspicion is based on clinical and radiological findings&#46; Laboratory reports show elevated inflammatory reactants&#44; and precipitins are positive in most cases&#46; Anti-<span class="elsevierStyleItalic">Aspergillus</span> IgE can be detected in the absence of evidence of allergic bronchopulmonary aspergillosis&#46; Sputum culture is positive in around 40&#37;&#8211;50&#37; of cases&#44; but the yield of PCR or galactomannan detection in respiratory samples is higher&#46; Galactomannan may be elevated in blood &#40;although not as often as in IPA&#41;&#44; particularly in the necrotizing forms&#46;</p><p id="par0120" class="elsevierStylePara elsevierViewall">If clinical and radiological findings are consistent&#44; the presence of precipitins or positive cultures is very suggestive of this clinical entity&#46; However&#44; some patients have negative microbiological results&#59; moreover&#44; intercurrent or imitative processes &#40;mycobacterial infection&#44; in particular&#41; may be present&#44; so a bronchoscopy is often essential for obtaining samples with a better yield&#46; Definitive diagnosis is obtained from biopsy showing hyphae&#44; local necrosis and&#47;or granulomatous reaction&#46; Angioinvasion is generally absent&#44; and if it does occur&#44; it is more often in the necrotizing form&#46;<a class="elsevierStyleCrossRefs" href="#bib0815"><span class="elsevierStyleSup">22&#44;23&#44;25</span></a></p><p id="par0125" class="elsevierStylePara elsevierViewall">Chronic forms of aspergillosis are treated with oral azoles &#40;itraconazole or voriconazole&#41;&#44; administered long-term or even indefinitely&#44; due to the high risk of recurrence&#46; Alternatives include posaconazole or amphotericin B in severe cases&#46; Optimization of immunity is also recommended&#44; if possible&#46; Isolated cases of improvement with interferon have been reported in the literature&#46;<a class="elsevierStyleCrossRefs" href="#bib0520"><span class="elsevierStyleSup">23&#44;25</span></a> Treatment may be monitored with clinical and radiological surveillance and determination of precipitin titers&#46;<a class="elsevierStyleCrossRefs" href="#bib0455"><span class="elsevierStyleSup">10&#44;21</span></a> Despite treatment&#44; mid- to long-term control of the infection is often suboptimal&#46;</p><p id="par0130" class="elsevierStylePara elsevierViewall">The use of primary aspergillosis prophylaxis is under debate&#46; The main indications are listed in <a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#46;<a class="elsevierStyleCrossRefs" href="#bib0535"><span class="elsevierStyleSup">26&#8211;28</span></a> It is not recommended in patients with hematological malignancies and neutropenia expected to last less than 7 days&#44; or solid tumors receiving conventional chemotherapy&#46; The most widely recommended drug in the different guidelines is posaconazole&#44; as it has been most studied in clinical trials and has the advantage of being active against Mucorales fungi&#46; Voriconazole is a reasonable alternative&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0135" class="elsevierStylePara elsevierViewall">In lung transplant recipients&#44; evidence for the different recommendations for prophylaxis is low grade&#44; due to the lack of appropriate studies&#46;<a class="elsevierStyleCrossRefs" href="#bib0550"><span class="elsevierStyleSup">29&#44;30</span></a> In standard practice&#44; the tendency is to administer universal antifungal prophylaxis&#46;<a class="elsevierStyleCrossRef" href="#bib0560"><span class="elsevierStyleSup">31</span></a> Correct prophylactic dosing has not been well defined&#44; but azoles with anti-<span class="elsevierStyleItalic">Aspergillosis</span> activity &#40;itraconazole&#44; voriconazole or posaconazole&#41; and&#47;or inhaled amphotericin B are generally used&#46;</p></span></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Mucormycosis</span><p id="par0140" class="elsevierStylePara elsevierViewall">Mucormycosis is disease caused by Mucorales fungi&#44; the most commonly involved genera being <span class="elsevierStyleItalic">Rhizopus</span>&#44; <span class="elsevierStyleItalic">Mucor</span> and <span class="elsevierStyleItalic">Rhizomucor</span>&#46;</p><p id="par0145" class="elsevierStylePara elsevierViewall">They are acquired by inhalation or via damaged skin and mucous membranes&#46; They cause rapid vascular invasion&#44; thrombosis and secondary necrosis&#46;<a class="elsevierStyleCrossRef" href="#bib0565"><span class="elsevierStyleSup">32</span></a> The risk factors for mucormycosis are similar to those of aspergillosis&#44; but diabetes mellitus with poor metabolic control&#44; iron overload&#44; and the use of desferoxamine should also be taken into account&#46; Controversy persists on whether voriconazole prophylaxis can increase the risk of mucormycosis<a class="elsevierStyleCrossRefs" href="#bib0565"><span class="elsevierStyleSup">32&#8211;35</span></a>&#59; the reason for this association has not been clarified&#44; but it is posited that it may be due to <span class="elsevierStyleItalic">Aspergillosis</span> being displaced&#44; allowing the positive selection of Mucorales&#44; which are mostly resistant to voriconazole&#46; Paradoxically&#44; it is rare in HIV&#44; except in cases associated with the use of intravenous drugs and corticosteroid therapy&#46;<a class="elsevierStyleCrossRef" href="#bib0565"><span class="elsevierStyleSup">32</span></a></p><p id="par0150" class="elsevierStylePara elsevierViewall">The most common sites of infection are the paranasal sinuses&#44; the lungs and the skin&#46; Rhino-orbital mucormycosis is mostly seen in diabetics&#44; while in hematological patients the predominant forms are pulmonary&#46; Lung involvement behaves similarly to very severe and rapidly invasive micronodular interstitial pulmonary disease&#46; Mortality is around 70&#37;&#8211;75&#37;&#46;<a class="elsevierStyleCrossRefs" href="#bib0565"><span class="elsevierStyleSup">32&#44;36</span></a> Clinical symptoms include dyspnea&#44; cough&#44; chest pain&#44; and hemoptysis&#44; which on occasions can be massive&#46; It also has a high capacity for causing cavitation and progressive invasion&#44; which may affect the pericardium&#44; pleura&#44; mediastinum&#44; and chest wall&#46; Similarly to <span class="elsevierStyleItalic">Aspergillosis</span>&#44; endobronchial involvement and airway obstruction may also occur&#46;<a class="elsevierStyleCrossRef" href="#bib0505"><span class="elsevierStyleSup">20</span></a> Radiological findings are very varied and include infiltrates&#44; nodules&#44; cavities&#44; atelectasis&#44; pleural effusion&#44; and mediastinal lymphadenopathies&#46; Like <span class="elsevierStyleItalic">Aspergillus</span>&#44; it produces the halo sign&#44; and more characteristically&#44; the reverse halo sign&#46;<a class="elsevierStyleCrossRefs" href="#bib0565"><span class="elsevierStyleSup">32&#44;37</span></a></p><p id="par0155" class="elsevierStylePara elsevierViewall">The presentation&#44; then&#44; is similar to that of IPA&#44; but some factors guiding the diagnosis of mucormycosis are the following&#58; greater rhinosinusal&#44; palatine or facial involvement&#44; or the presence of thoracic subcutaneous tissue&#46;<a class="elsevierStyleCrossRef" href="#bib0595"><span class="elsevierStyleSup">38</span></a> Radiological findings of more than 10 nodules and pleural effusion are factors more often associated with mucormycosis than IPA&#46;<a class="elsevierStyleCrossRef" href="#bib0600"><span class="elsevierStyleSup">39</span></a> Moreover&#44; galactomannan and 1&#44;3-&#946;-<span class="elsevierStyleSmallCaps">d</span>-glucan are negative in this entity&#46; A history of voriconazole use and lack of response to this drug support the suspicion&#46; None of these findings is specific&#44; but are useful as guidance when waiting for microbiological results&#46;</p><p id="par0160" class="elsevierStylePara elsevierViewall">Diagnosis is made from respiratory cultures or biopsies&#46; Since its presence in respiratory samples is rare&#44; isolation in a consistent clinical context is considered diagnostic&#46; Blood cultures are negative&#44; even in invasive forms&#46;<a class="elsevierStyleCrossRefs" href="#bib0590"><span class="elsevierStyleSup">37&#44;38</span></a></p><p id="par0165" class="elsevierStylePara elsevierViewall">Treatment must be initiated promptly&#44;<a class="elsevierStyleCrossRefs" href="#bib0605"><span class="elsevierStyleSup">40&#44;41</span></a> with resolution of risk factors&#44; surgical debridement of accessible areas and administration of antifungal agents&#46;<a class="elsevierStyleCrossRef" href="#bib0565"><span class="elsevierStyleSup">32</span></a> Only amphotericin B and posaconazole are known to be effective&#46; Amphotericin B is the first line treatment&#44; while posaconazole is used in cases of renal dysfunction and in sequential oral treatment in the maintenance phase&#46; Duration of treatment has not been established and should be individualized according to clinical response and resolution of lesions&#46;<a class="elsevierStyleCrossRefs" href="#bib0505"><span class="elsevierStyleSup">20&#44;21&#44;38&#44;42&#44;43</span></a> Surgery plays a fundamental role in the resolution of local forms&#46; The effectiveness of granulocyte stimulating factors in neutropenic patients has been defined&#46;<a class="elsevierStyleCrossRefs" href="#bib0615"><span class="elsevierStyleSup">42&#44;44</span></a></p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Cryptococcosis</span><p id="par0170" class="elsevierStylePara elsevierViewall">The most important pathogens of the <span class="elsevierStyleItalic">Cryptococcus</span> genus are <span class="elsevierStyleItalic">Cryptococcus neoformans</span> &#40;<span class="elsevierStyleItalic">C&#46; neoformans</span>&#41; and the emerging <span class="elsevierStyleItalic">Cryptococcus gattii</span> &#40;<span class="elsevierStyleItalic">C&#46; gattii</span>&#41;&#46; They are ubiquitous and are isolated from soils&#44; particularly in areas frequented by birds and bats&#46;<a class="elsevierStyleCrossRef" href="#bib0630"><span class="elsevierStyleSup">45</span></a> While the distribution of <span class="elsevierStyleItalic">C&#46; neoformans</span> is universal&#44; <span class="elsevierStyleItalic">C&#46; gattii</span> is more common in subtropical regions&#44; and its presence has increased in recent years in some areas of the North Pacific&#46;<a class="elsevierStyleCrossRef" href="#bib0635"><span class="elsevierStyleSup">46</span></a></p><p id="par0175" class="elsevierStylePara elsevierViewall">The invasive capacity of <span class="elsevierStyleItalic">Cryptococcus</span> is due to its expression of a polysaccharide capsule with antiphagocytic properties&#46; It enters by the airways and causes 2 distinct clinical syndromes&#58; meningitis and meningoencephalitis&#46; Its pulmonary transit&#44; however&#44; can be blocked by a cell-mediated immune reaction and the development of granulomas&#59; in an immunocompromised host&#44; invasion can occur&#46;<a class="elsevierStyleCrossRefs" href="#bib0640"><span class="elsevierStyleSup">47&#8211;49</span></a></p><p id="par0180" class="elsevierStylePara elsevierViewall">The major risk factor is HIV infection&#44; particularly when CD4 counts are below 100<span class="elsevierStyleHsp" style=""></span>cells&#47;mm<span class="elsevierStyleSup">3</span>&#44; CNS involvement being the predominant clinical manifestation&#46;<a class="elsevierStyleCrossRef" href="#bib0655"><span class="elsevierStyleSup">50</span></a> In other immunosuppressive states&#44; such as chronic lung diseases&#44; patients on long-term corticosteroids&#44; or solid organ transplant recipients&#44; the resulting syndrome is predominantly respiratory&#46;<a class="elsevierStyleCrossRefs" href="#bib0510"><span class="elsevierStyleSup">21&#44;51</span></a><span class="elsevierStyleItalic">C&#46; gattii</span> affects the lungs&#44; even in immunocompetent patients&#46;<a class="elsevierStyleCrossRef" href="#bib0635"><span class="elsevierStyleSup">46</span></a></p><p id="par0185" class="elsevierStylePara elsevierViewall">Pulmonary cryptococcosis is characterized by fever&#44; with dyspnea&#44; dry cough&#44; night sweats&#44; and progressive&#44; occasionally fulminant&#44; respiratory failure&#46;<a class="elsevierStyleCrossRefs" href="#bib0640"><span class="elsevierStyleSup">47&#44;52&#44;53</span></a> Severe pulmonary presentations involve a risk of dissemination to the CNS and to other regions&#44; particularly the skin&#46;<a class="elsevierStyleCrossRef" href="#bib0675"><span class="elsevierStyleSup">54</span></a></p><p id="par0190" class="elsevierStylePara elsevierViewall">The most common radiological pattern is multiple nodular involvement&#46; Reticulonodular forms are more typical of invasive syndromes&#46; Involvement in the form of lobar or segmentary consolidation is also possible&#46; Thoracic lymphadenopathies may also occur&#46; Pleural effusion and cavitation are exceptional&#46;<a class="elsevierStyleCrossRef" href="#bib0680"><span class="elsevierStyleSup">55</span></a></p><p id="par0195" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Cryptococcus</span> in colonizations is unusual&#59; therefore&#44; isolation in a sputum or BAL culture consistent with clinical signs is sufficient for diagnosis&#46; <span class="elsevierStyleItalic">Cryptococcus</span> antigen determination in plasma is very useful&#44; but it can be negative in some limited pulmonary forms&#46;<a class="elsevierStyleCrossRefs" href="#bib0670"><span class="elsevierStyleSup">53&#44;56</span></a> Antigen detection in sputum or BAL is unreliable&#46;<a class="elsevierStyleCrossRef" href="#bib0640"><span class="elsevierStyleSup">47</span></a> Cerebrospinal fluid &#40;CSF&#41; can be studied by India ink staining&#44; antigen detection and&#47;or culture&#46; Routine lumbar puncture is not recommended for all pulmonary forms&#44; but rather in the presence of neurological symptoms&#44; severe immunosuppression&#44; signs of dissemination&#44; or high serum antigen levels&#46;<a class="elsevierStyleCrossRef" href="#bib0690"><span class="elsevierStyleSup">57</span></a></p><p id="par0200" class="elsevierStylePara elsevierViewall">The treatment of pulmonary forms has not been widely studied&#44; and the principal recommendations are based on the experience of treatment of HIV patients with CNS involvement&#46; For mild or moderate respiratory syndromes&#44; fluconazole for 6&#8211;12 months is recommended&#46;<a class="elsevierStyleCrossRefs" href="#bib0505"><span class="elsevierStyleSup">20&#44;21&#44;47&#44;58</span></a> In severe manifestations or CNS involvement&#44; at least 2 weeks combined treatment with amphotericin B and flucytosine is recommended&#46;<a class="elsevierStyleCrossRefs" href="#bib0510"><span class="elsevierStyleSup">21&#44;58&#44;59</span></a> This treatment should be followed sequentially by a 6&#8211;12 month course of fluconazole&#46; Treatment duration must be individualized on the basis of risk factors and recovery of immunosuppression status&#46; For example&#44; in HIV subjects&#44; maintenance treatment should continue until viral replication is controlled and a stable CD4 count<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>100<span class="elsevierStyleHsp" style=""></span>cells&#47;mm<span class="elsevierStyleSup">3</span> has been achieved&#46; Moreover&#44; initiation of antiretroviral treatment should be delayed for at least 4&#8211;8 weeks to avoid immune reconstitution inflammatory syndrome&#44; underlining once more the difficulties in achieving the immunological balance required in the management of opportunistic mycosis&#46;<a class="elsevierStyleCrossRefs" href="#bib0685"><span class="elsevierStyleSup">56&#44;60</span></a></p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Pneumocystosis</span><p id="par0205" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Pneumocystis jirovecii</span> is an atypical fungus&#44; acquired by the airborne route&#44; even in childhood&#46;<a class="elsevierStyleCrossRef" href="#bib0710"><span class="elsevierStyleSup">61</span></a> The main risk factor for developing this mycosis is HIV infection&#44; particularly when CD4 levels are below 200<span class="elsevierStyleHsp" style=""></span>cells&#47;mm<span class="elsevierStyleSup">3</span>&#46; It can&#44; however&#44; also occur in other cell-mediated immunosuppressive states common to other mycoses&#46;<a class="elsevierStyleCrossRefs" href="#bib0715"><span class="elsevierStyleSup">62&#44;63</span></a> It is important to note that the immunosuppressive agents most frequently cited are corticosteroids&#44; particularly in association with dose increases or reductions from previously high doses&#46;<a class="elsevierStyleCrossRefs" href="#bib0725"><span class="elsevierStyleSup">64&#44;65</span></a></p><p id="par0210" class="elsevierStylePara elsevierViewall">The clinical syndrome in patients with HIV infection is subacute&#44; with fever&#44; dry cough&#44; and progressive dyspnea&#44; and generalized asthenia and weight loss&#46; However&#44; in immunosuppressed patients without HIV infection&#44; the clinical picture is more acute&#44; prognosis is poorer and the rates of acute respiratory failure&#44; need for ventilatory support and mortality are higher&#46;<a class="elsevierStyleCrossRefs" href="#bib0725"><span class="elsevierStyleSup">64&#44;66&#8211;69</span></a> Some authors have associated this increased mortality in non-HIV patients with more severe immunosuppression status&#44; and with delay in diagnosis and treatment&#44; since the suspicion of pneumocystosis is not so strong&#46;<a class="elsevierStyleCrossRef" href="#bib0740"><span class="elsevierStyleSup">67</span></a></p><p id="par0215" class="elsevierStylePara elsevierViewall">Diffuse bilateral interstitial infiltrates may be seen on X-ray&#46; CT provides a more defined image of bilateral ground glass opacities&#44; possible pneumatoceles and pneumothorax due to local parenchymal damage&#46; It is rare to see lobar infiltrates&#44; nodules&#44; cavities&#44; or pleural effusion&#46; If the CT is normal&#44; the diagnosis should be questioned&#46;<a class="elsevierStyleCrossRef" href="#bib0755"><span class="elsevierStyleSup">70</span></a></p><p id="par0220" class="elsevierStylePara elsevierViewall">During pneumocystosis&#44; 1&#44;3-&#946;-<span class="elsevierStyleSmallCaps">d</span>-glucan levels are raised&#44; leading many authors to suggest that a positive finding in a high risk patient with consistent signs and symptoms may be sufficient to reach a diagnosis&#46; However&#44; in view of the association with pneumocystosis with other intercurrent processes&#44; the recommendation is to obtain a more specific diagnosis&#46;<a class="elsevierStyleCrossRefs" href="#bib0760"><span class="elsevierStyleSup">71&#44;72</span></a> Since it cannot be cultured&#44; visualization using immunofluorescence techniques is needed&#44; and yield is high&#46; Immunofluorescence can be used in induced sputum&#44; with sensitivity ranging between 55&#37; and 90&#37;&#44; or BAL with a sensitivity of around 90&#37;&#8211;100&#37;&#46; Biopsy is rarely necessary&#46; PCR values have yet to be defined&#46;<a class="elsevierStyleCrossRef" href="#bib0770"><span class="elsevierStyleSup">73</span></a></p><p id="par0225" class="elsevierStylePara elsevierViewall">If there is a clinical suspicion of pneumocystosis&#44; treatment must be initiated without waiting for sampling of respiratory specimens&#44; as eradication of pathogens from the respiratory secretions will take several weeks&#46;<a class="elsevierStyleCrossRefs" href="#bib0775"><span class="elsevierStyleSup">74&#44;75</span></a></p><p id="par0230" class="elsevierStylePara elsevierViewall">In HIV patients&#44; the treatment of choice is cotrimoxazole for 21 days&#46; Alternatives include pentamidine&#44; dapsone&#44; atovaquone&#44; or combined clindamycin and primaquine&#44; depending on severity&#46; Co-administration of corticosteroids is recommended in severe cases&#46;<a class="elsevierStyleCrossRef" href="#bib0785"><span class="elsevierStyleSup">76</span></a> Antiretroviral treatment must also be delayed for at least 2 weeks&#46;<a class="elsevierStyleCrossRefs" href="#bib0745"><span class="elsevierStyleSup">68&#44;76&#44;77</span></a></p><p id="par0235" class="elsevierStylePara elsevierViewall">Treatment of non-HIV patients is less widely studied&#44; and most of the recommendations for antimicrobials apply in these cases&#46; Corticosteroid treatment is more controversial in these patients&#46; Some small studies were not able to show clear efficacy in terms of mortality&#44; so corticosteroids should be continued in patients previously receiving this treatment&#44; and initiated in cases of severe lung inflammation&#46;<a class="elsevierStyleCrossRefs" href="#bib0510"><span class="elsevierStyleSup">21&#44;78&#44;79</span></a> Cotrimoxazole is the agent of choice for secondary prophylaxis and should be administered until immunological recovery&#46; Cotrimoxazole is also given for primary prophylaxis&#46; Alternatives include atovaquone&#44; dapsone&#44; or aerosolized pentamidine&#46; The main indications are listed in <a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>&#46;<a class="elsevierStyleCrossRefs" href="#bib0410"><span class="elsevierStyleSup">1&#44;27&#44;80&#44;81</span></a></p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Conflict of Interests</span><p id="par0240" class="elsevierStylePara elsevierViewall">The authors state that they have no conflict of interests&#46;</p></span></span>"
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          "titulo" => "Introduction"
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          "identificador" => "sec0010"
          "titulo" => "Aspergillosis"
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              "identificador" => "sec0015"
              "titulo" => "Invasive Pulmonary Aspergillosis"
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              "titulo" => "Aspergilloma"
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              "titulo" => "Chronic Pulmonary Aspergillosis"
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          "titulo" => "Mucormycosis"
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          "titulo" => "Cryptococcosis"
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          "titulo" => "Pneumocystosis"
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          "titulo" => "Conflict of Interests"
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            0 => "Opportunistic pulmonary mycoses"
            1 => "<span class="elsevierStyleItalic">Aspergillus</span>"
            2 => "Invasive pulmonary aspergillosis"
            3 => "Mucormycosis"
            4 => "<span class="elsevierStyleItalic">Cryptococcus</span>"
            5 => "<span class="elsevierStyleItalic">Pneumocystis jirovecii</span>"
          ]
        ]
      ]
      "es" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Palabras clave"
          "identificador" => "xpalclavsec602854"
          "palabras" => array:6 [
            0 => "Micosis pulmonares oportunistas"
            1 => "<span class="elsevierStyleItalic">Aspergillus</span>"
            2 => "Aspergilosis pulmonar invasiva"
            3 => "Mucormicosis"
            4 => "<span class="elsevierStyleItalic">Cryptococcus</span>"
            5 => "<span class="elsevierStyleItalic">Pneumocystis jirovecii</span>"
          ]
        ]
      ]
    ]
    "tieneResumen" => true
    "resumen" => array:2 [
      "en" => array:2 [
        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Mycoses are serious diseases with potentially fatal outcome&#46; The introduction of immunosuppressive treatments and life support techniques has led to a growing prevalence of different degrees of immunosuppression&#46; Compromised immune response is the primary risk factor for the development of opportunistic mycoses&#46; Early diagnosis and treatment are crucial for improving prognosis&#46; However&#44; isolation in cultures or identification using antigen detection techniques cannot distinguish between colonization and invasive infection&#44; and the clinical status of the patient often prevents biopsy sampling&#46; Clinicians thus find themselves in an uncertain position&#44; requiring them to quickly recognize clinical and radiological signs and interpret microbiological results in context&#46; The aim of this review is to provide a general overview of the profile of patients susceptible to these infections&#44; the role of the immune system and&#44; in more detail&#44; the major diagnostic developments that have gained most acceptance and recognition among the scientific community&#46;</p></span>"
      ]
      "es" => array:2 [
        "titulo" => "Resumen"
        "resumen" => "<span id="abst0010" class="elsevierStyleSection elsevierViewall"><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Las micosis son enfermedades graves y potencialmente letales&#46; Con el desarrollo de terapias inmunosupresoras y t&#233;cnicas de soporte vital&#44; la inmunosupresi&#243;n en sus diferentes grados es cada vez m&#225;s prevalente&#46; El deterioro de la respuesta inmune es el factor de riesgo principal para el desarrollo de las micosis oportunistas&#46; El diagn&#243;stico y tratamiento precoces son factores cruciales para mejorar el pron&#243;stico de estas enfermedades&#46; Sin embargo&#44; los aislamientos mediante cultivos o las t&#233;cnicas de detecci&#243;n antig&#233;nicas no son capaces de distinguir entre colonizaci&#243;n e infecci&#243;n invasiva&#44; y las biopsias rara vez se pueden realizar por la situaci&#243;n cl&#237;nica&#46; Ello sit&#250;a al m&#233;dico en una situaci&#243;n de incertidumbre en la que debe reconocer precozmente los signos cl&#237;nicos y radiol&#243;gicos e interpretar los resultados microbiol&#243;gicos en su contexto&#46; El objetivo de esta revisi&#243;n es aportar una visi&#243;n general del perfil de paciente que sufre estas infecciones&#44; el papel de su sistema inmune&#44; y de forma m&#225;s detallada&#44; los principales avances diagn&#243;sticos m&#225;s reconocidos y recomendados por la comunidad cient&#237;fica&#46;</p></span>"
      ]
    ]
    "NotaPie" => array:1 [
      0 => array:2 [
        "etiqueta" => "&#9734;"
        "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as&#58; Curbelo J&#44; Galv&#225;n JM&#44; Aspa J&#46; Actualizaci&#243;n sobre <span class="elsevierStyleItalic">Aspergillus</span>&#44; <span class="elsevierStyleItalic">Pneumocystis</span> y otras micosis pulmonares oportunistas&#46; Arch Bronconeumol&#46; 2015&#59;51&#58;647&#8211;653&#46;</p>"
      ]
    ]
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          "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Association between degree of immunodeficiency and type of pulmonary aspergillosis&#46;</p>"
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                  \t\t\t\t" class=""><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">&#8226; Disrupted natural barriers&#58; mucositis&#44; venous access lines&#44; surgical wounds&#44; intubation&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">&#8226; Prolonged neutropenia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">&#8226; Blood cancers&#44; whether associated or not associated with stem cell transplantation or graft-versus-host disease&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">&#8226; Disseminated malignant solid tumors&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">&#8226; Solid organ transplants&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">&#8226; HIV infection&#44; especially with CD4 counts<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>200<span class="elsevierStyleHsp" style=""></span>cells&#47;mm<span class="elsevierStyleSup">3</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">&#8226; Chronic lung diseases&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">&#8226; Connective tissue disease&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">&#8226; Immunosuppressive drugs&#44; primarily corticosteroids&#46; Other immunosuppressants associated with anti-TNF&#945; drugs and alemtuzumab&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
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          "en" => "<p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Risks Factors for Opportunistic Mycosis&#46;</p>"
        ]
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                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Acute myeloid leukemia or intensively-treated myelodysplastic syndrome&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Allogenic stem cell transplantation with predicted prolonged neutropenia &#40;more than 2 weeks&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Graft-versus-host disease requiring high-dose corticosteroids&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleItalic">Lung transplantation</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Colonization before transplantation&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Colonization within 1 year pre-transplantation&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Presence of at least 2 of the following risk factors&#58;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Induction with alemtuzumab or thymoglobulin&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Single-lung transplantation&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Colonization subsequent to cytomegalovirus infection&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Rejection and increased immunosuppression&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Acquired hypogammaglobulinemia &#40;IgG less than 400<span class="elsevierStyleHsp" style=""></span>mg&#47;dl&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
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          "en" => "<p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Principal Indications for Primary Aspergillosis Prophylaxis&#46;</p>"
        ]
      ]
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        "etiqueta" => "Table 3"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
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                  <table border="0" frame="\n
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                  \t\t\t\t" class=""><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">&#8226; HIV with CD4 count<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>200<span class="elsevierStyleHsp" style=""></span>cells&#47;mm<span class="elsevierStyleSup">3</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">&#8226; Prednisone treatment at doses<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>20<span class="elsevierStyleHsp" style=""></span>mg&#47;day for more than 1 month and presence of another cause of immunosuppression&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">&#8226; Alemtuzumab treatment&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">&#8226; Acute lymphoid leukemia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">&#8226; Blood cancer patient on intensive regimen containing purine analogs&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">&#8226; Stem cell transplant recipient&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">&#8226; Solid organ transplant recipient&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">&#8226; Rheumatic disease requiring induction immunosuppressive treatment &#40;e&#46;g&#46;&#44; corticosteroids and cyclophosphamide&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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          "en" => "<p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Principal Indications for Primary Anti-<span class="elsevierStyleItalic">Pneumocystis jirovecii</span> Prophylaxis&#46;</p>"
        ]
      ]
    ]
    "bibliografia" => array:2 [
      "titulo" => "References"
      "seccion" => array:1 [
        0 => array:2 [
          "identificador" => "bibs0005"
          "bibliografiaReferencia" => array:81 [
            0 => array:3 [
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                      "autores" => array:1 [
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                          "etal" => false
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                            0 => "J&#46;H&#46; Reynolds"
                            1 => "A&#46;K&#46; Banerjee"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
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                      "Revista" => array:6 [
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                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22388581"
                            "web" => "Medline"
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                        ]
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            ]
            1 => array:3 [
              "identificador" => "bib0415"
              "etiqueta" => "2"
              "referencia" => array:1 [
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                  "contribucion" => array:1 [
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                      "titulo" => "Revised definitions of invasive fungal disease from the European Organization for Research and Treatment of Cancer&#47;Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group &#40;EORTC&#47;MSG&#41; Consensus Group"
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                        0 => array:2 [
                          "etal" => true
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                            0 => "B&#46; De Pauw"
                            1 => "T&#46;J&#46; Walsh"
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                            3 => "D&#46;A&#46; Stevens"
                            4 => "J&#46;E&#46; Edwards"
                            5 => "T&#46; Calandra"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
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                      "Revista" => array:6 [
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                        "fecha" => "2008"
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                            "web" => "Medline"
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                        ]
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            ]
            2 => array:3 [
              "identificador" => "bib0420"
              "etiqueta" => "3"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The impact of the host on fungal infections"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [
                            0 => "J&#46;R&#46; Perfect"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.amjmed.2011.10.010"
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                        "tituloSerie" => "Am J Med"
                        "fecha" => "2012"
                        "volumen" => "125"
                        "paginaInicial" => "S39"
                        "paginaFinal" => "S51"
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                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22196208"
                            "web" => "Medline"
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                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            3 => array:3 [
              "identificador" => "bib0425"
              "etiqueta" => "4"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Epidemiology&#44; diagnosis and treatment of fungal respiratory infections in the critically ill patient"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "J&#46; Garnacho-Montero"
                            1 => "P&#46; Olaechea"
                            2 => "F&#46; Alvarez-Lerma"
                            3 => "L&#46; Alvarez-Rocha"
                            4 => "J&#46; Blanquer"
                            5 => "B&#46; Galv&#225;n"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
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                        "fecha" => "2013"
                        "volumen" => "26"
                        "paginaInicial" => "173"
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                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23817660"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            4 => array:3 [
              "identificador" => "bib0430"
              "etiqueta" => "5"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Airway and parenchymal manifestations of pulmonary aspergillosis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "G&#46; Tunnicliffe"
                            1 => "L&#46; Schomberg"
                            2 => "S&#46; Walsh"
                            3 => "T&#46; Brendan"
                            4 => "T&#46; Harrison"
                            5 => "F&#46; Chua"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.rmed.2013.03.016"
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                            "web" => "Medline"
                          ]
                        ]
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            5 => array:3 [
              "identificador" => "bib0435"
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                0 => array:2 [
                  "contribucion" => array:1 [
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                      "titulo" => "Defining opportunistic invasive fungal infections in immunocompromised patients with cancer and hematopoietic stem cell transplants&#58; an international consensus"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "S&#46; Ascioglu"
                            1 => "J&#46;H&#46; Rex"
                            2 => "B&#46; de Pauw"
                            3 => "J&#46;E&#46; Bennett"
                            4 => "J&#46; Bille"
                            5 => "F&#46; Crokaert"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1086/323335"
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                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            6 => array:3 [
              "identificador" => "bib0440"
              "etiqueta" => "7"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Aspergilosis&#58; formas cl&#237;nicas y tratamiento"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "J&#46; Fort&#250;n"
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Article information
ISSN: 15792129
Original language: English
DOI:10.1016/j.arbr.2015.09.012
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