Fungal pneumonia, chronic respiratory diseases and glucocorticoids.

Invasive pulmonary aspergillosis (IPA) usually occurs in severely immunocompromised patients. The expanded use of glucocorticoids (GC) in clinical practice accounts for the increasing number of fungal infections reported in mildly or non-immunocompromised hosts. We report a series of 8 patients with fungal pneumonia in whom long term high dose GC treatment was the only risk factor for opportunistic infections. All patients except one had chronic underlying disorders (asthma, idiopathic fibrosis, chronic obstructive pulmonary disease, COPD). Seven patients were diagnosed with pulmonary aspergillosis. Etiological suspicion of fungal infection was obtained during lifetime in six cases and in one case was confirmed only in the post-mortem examination. In most cases bronchoscopic techniques allowed identification of the microorganism. However, delay in establishing the diagnosis (mean 20 days) precluded a prompt initiation of a specific treatment. The course of the fungal infection was ominous. All but one patient experienced progressive respiratory failure requiring ICU admission and mechanical ventilation support. Despite this, all of them died. The only survivor was a patient receiving early empirical antifungal treatment due to a high clinical suspicion of fungal infection. Based on the present and previous findings, antifungal treatment should be considered in chronic respiratory patients requiring high or repetitive doses of GC when there is clinical evidence of pneumonia and isolation of Aspergillus spp. from respiratory secretions.

Prognostic factors of non-HIV immunocompromised patients with pulmonary infiltrates.

STUDY OBJECTIVES: To assess the outcome and the prognostic factors in 200 non-HIV immunocompromised patients with pulmonary infiltrates (PIs). DESIGN: Prospective observational study. SETTING: An 800-bed university hospital. PATIENTS: Two hundred non-HIV immunocompromised patients (hematologic malignancies, 79 patients; hematopoietic stem cell transplants [HSCTs], 61 patients; and solid-organ transplants, 60 patients). METHODS: Investigation of prognostic factors related to mortality using a multiple logistic regression model. RESULTS: Specific diagnosis of the PI was obtained in 78% of the cases (infectious origin was determined in 74%). The overall mortality rate was 39% (78 of 200 patients). Patients with HSCT had the highest mortality rate (53%). A requirement for mechanical ventilation (odds ratio [OR], 28; 95% confidence interval [CI], 9 to 93), an APACHE (acute physiology and chronic health evaluation) II score of > 20 (OR, 5.5; 95% CI, 2 to 14.7), and a delay of > 5 days in establishing a specific diagnosis (OR, 3.4; 95% CI, 1.2 to 9.6) were the variables associated with mortality at the multivariate analysis. The subgroup analysis based on underlying disease confirmed the prognostic significance of these variables and the infectious etiology for the PI. CONCLUSIONS: Mortality in immunocompromised patients is high, particularly in patients undergoing HSCT. Achieving an earlier diagnosis potentially may improve the mortality rate of these patients.

Pulmonary infiltrates in patients receiving long-term glucocorticoid treatment: etiology, prognostic factors, and associated inflammatory response.

BACKGROUND: Glucocorticoid treatment alters immunoregulatory defense mechanisms and may therefore favor the development of different pulmonary infections. METHODS: The etiology, prognostic factors, and associated inflammatory response of pulmonary infiltrates in 33 patients receiving long-term glucocorticoid treatment (LTGCT) were prospectively evaluated. RESULTS: Aspergillus spp (n = 9, 31%) and Staphylococcus spp (n = 6, 21%) were the most common causative agents. Using different diagnostic techniques, we obtained a specific diagnosis in 28 of 33 episodes (85%) of pulmonary infiltrates. Bronchoscopic techniques provided the diagnosis in 64% of the cases. Crude mortality was 45%. Variables associated with mortality were as follows: age > 64 years, bilateral radiographic involvement, delay in diagnosis, inappropriate empirical treatment, Simplified Acute Physiology Score (SAPS) II > or = 25, and requirement for mechanical ventilation (MV). SAPS II > or = 25 (odds ratio [OR], 16; 95% confidence interval, 1 to 260) and MV requirement (OR, 50; 95% confidence interval, 2 to 360) were also significant on multivariate analysis. Pulmonary infections were associated with an increase in the concentration of relevant inflammatory cytokines such as tumor necrosis factor-alpha and interleukin-6 both in serum and BAL. This local and systemic inflammatory response was attenuated when compared with the response observed in patients with pulmonary infections but without glucocorticoid treatment or receiving glucocorticoids for a short period of time (< 9 days). CONCLUSIONS: Pulmonary infiltrates in patients receiving LTGCT are often caused by fungi and Gram-positive cocci, and are associated with attenuated local and systemic inflammatory response. Although in most cases, sputum cultures and bronchoscopic techniques are diagnostic, the associated mortality is high, particularly in those requiring MV.

Nosocomial pneumonia in immunosuppressed patients.

Nosocomial pneumonia represents a serious challenge for clinicians caring for IC patients. Although there have been advances in prophylactic, preemptive, and therapeutic measures, the implications of an inadequate empirical treatment for survival require a prompt and active attitude. A great diversity of diagnostic and laboratory procedures is currently available. In each case, the clinician must determine the tests that should be performed based on different variables. The proper use of noninvasive and bronchoscopic procedures substantially increases the diagnostic yield causing changes in the empirical treatment in most patients. The authors believe that fiberoptic bronchoscopy must be done early when the pulmonary infiltrates are identified if there is not a rapid (48 hours) and clear response to empiric treatment. This approach allows the establishment of a more specific treatment when the possibilities of full recovery are still high. The potential benefit of treatment modifications for survival in IC patients who require MV and undergo bronchoscopy is most probably minimal, because of the severity and irreversibility of the underlying pulmonary process. It is hoped that the application of molecular tools in diagnosis and the advances in preventive strategies and therapeutic agents will improve the survival of NP in a population of IC patients that is expected to grow over the next years.

Associated inflammatory response in pneumonia: role of adjunctive therapy with glucocorticoids.

PURPOSE OF REVIEW: This article reviews the potential use of glucocorticoids as adjunctive therapy in the management of patients with severe bacterial pneumonia or pulmonary infections of other etiologies. RECENT FINDINGS: The importance of an adequate assessment of the inflammatory process and the appearance of inflammatory markers that correlate with the severity of pneumonia is underlined. A recent randomized clinical trial indicates that adjunctive treatment of severe community-acquired pneumonia with glucocorticoids reduces complications and improves survival. The role of glucocorticoids in other lung infections is also reviewed. The design of new compounds with similar anti-inflammatory properties to classical glucocorticoids but with significantly fewer side effects constitutes a specific challenge for the near future. SUMMARY: Although adjunctive treatment with glucocorticoids in severe pneumonia is probably indicated, further randomized clinical trials are urgently needed to confirm the preliminary positive results. In this regard, a proper evaluation of the inflammatory response is likely to be essential for the accurate selection of the target population.

Pulmonary infections in non-HIV-immunocompromised patients.

PURPOSE OF REVIEW: Pulmonary infections are the most frequent complications in non-HIV-immunocompromised patients and portend a high mortality. This scenario represents a challenging task for clinicians and an important subject of clinical research from different perspectives. This review comments on the results of relevant original articles in this area published from 2003 to the present. RECENT FINDINGS: The present review addresses the etiology of the pulmonary infiltrates in immunocompromised patients, the use of new emerging diagnostic tools and medical devices in the clinical management of these infiltrates, and the greater understanding of the inflammatory immune response associated with infection in this setting. SUMMARY: Advances in diagnostic tests and therapeutic devices are facilitating the clinical management of pulmonary infections. New challenges are emerging, however, such as the growing evidence regarding the important role of respiratory viruses as a common cause of lower respiratory tract infections. Finally, new insights into the mechanisms of the inflammatory response associated with pulmonary complications can help understanding their pathogenesis, improve prevention and diagnosis, and anticipate future therapeutic modalities.

Pulmonary infiltrates in immunosuppressed patients: analysis of a diagnostic protocol.

A diagnostic protocol was started to study the etiology of pulmonary infiltrates in immunosuppressed patients. The diagnostic yields of the different techniques were analyzed, with special emphasis on the importance of the sample quality and the role of rapid techniques in the diagnostic strategy. In total, 241 patients with newly developed pulmonary infiltrates within a period of 19 months were included. Noninvasive or invasive evaluation was performed according to the characteristics of the infiltrates. Diagnosis was achieved in 202 patients (84%); 173 patients (72%) had pneumonia, and specific etiologic agents were found in 114 (66%). Bronchoaspirate and bronchoalveolar lavage showed the highest yields, either on global analysis (23 of 35 specimens [66%] and 70 of 134 specimens [52%], respectively) or on analysis of each type of pneumonia. A tendency toward better results with optimal-quality samples was observed, and a statistically significant difference was found in sputum bacterial culture. Rapid diagnostic tests yielded results in 71 of 114 (62.2%) diagnoses of etiological pneumonia.

Inflammatory responses in blood samples of human immunodeficiency virus-infected patients with pulmonary infections.

We analyzed the characteristics of the inflammatory response occurring in blood during pulmonary infections in human immunodeficiency virus (HIV)-infected patients. A prospective study of consecutive hospital admissions of HIV-infected patients with new-onset radiologic pulmonary infiltrates was carried out in a tertiary university hospital from April 1998 to May 2001. Plasma cyclic AMP receptor protein (CRP), interleukin 1beta (IL-1beta), IL-6, IL-8, IL-10, and tumor necrosis factor alpha (TNF-alpha) levels were determined at the time of admission and 4, 5, and 6 days later. Patients were included in a protocol addressed to study etiology and outcome of disease. A total of 249 episodes of infection were included, with the main diagnoses being bacterial pneumonia (BP) (118 episodes), Pneumocystis carinii pneumonia (PCP) (41 episodes), and mycobacteriosis (36 episodes). For these three patient groups, at the time of admission the median CRP and cytokine levels were as follows: CRP, 10.2, 3.8 and 5 mg/dl, respectively (P = 0.0001); IL-8, 19, 3, and 2.9 pg/ml (P = 0.045); and TNF-alpha, 46.4, 44, and 75 pg/ml, respectively (P = 0.029). There were no significant differences in levels of IL-1beta, IL-6, or IL-10 among the patient groups. A total of 23 patients died. At the time of admission, HIV-infected patients with BP had higher plasma CRP and IL-8 levels than did PCP and mycobacteriosis patients. TNF-alpha levels were higher in patients with mycobacteriosis. An elevated IL-8 level (>61 pg/ml) at the time of admission was an independent factor associated with higher mortality (odds ratio, 12; 95% confidence interval, 1.2 to 235.5).