Lower respiratory tract viral infections in hospitalized adult patients.

AIM: The epidemiology of lower respiratory tract (LRT) viral infections in adults is probably underestimated and the high frequency of multiple viral infections complicates the evaluation of the possible role of the single viruses. The aim of this study was to investigate the clinical epidemiology and impact of respiratory viral pathogens, in particular of those singularly detected, in bronchoalveolar lavage (BAL) specimens from hospitalized adult patients. METHODS: A panel for the detection of 16 respiratory viruses was used to prospectively evaluate 324 consecutive specimens obtained from 219 patients over a full-year period. RESULTS: Two-hundred-twenty-one specimens (68.2%) were positive for at least one virus, 119/324 (36.7%) to a single viral agent. The most commonly detected viruses were herpesviruses HHV-7 (26.2%), human cytomegalo-virus (HCMV, 22.2%), HHV-6 (19.8%), EBV (12.7%), enteroviruses and rhinoviruses (both 11.7%), parainfluenza viruses (4.9 %), and metapneumovirus (4.0%). Human cytomegalo-virus was significantly more prevalent as single viral pathogen with a viral load >105 copies/ml associated to pneumonia in solid organ transplant recipients. Other viral pathogens might account for some cases of pneumonia or respiratory insufficiency, although multiple infections were common. CONCLUSIONS: The use of a comprehensive diagnostic panel for respiratory viral infections may be useful to clarify the epidemiology and clinical impact of viral pathogens in hospitalized adult patients. The occurrence of multiple infections is a common finding and results should be interpreted taking into account the clinical context as well as viral load and the biological characteristics of each virus.

Combined cytomegalovirus prophylaxis in lung transplantation: effects on acute rejection, lymphocytic bronchitis/bronchiolitis, and herpesvirus infections.

Lung transplantation recipients are at high risk for herpesvirus infections. We evaluated the effect of combined cytomegalovirus (CMV) prophylaxis on CMV pneumonia, acute rejection episodes (ARE), lymphocytic bronchitis/bronchiolitis (LB), and obliterans bronchiolitis (OB) diagnosed in 180 transbronchial biopsies (TBB) of lung transplant recipients. At our center, 25 patients (control group; 1999-2002) received acyclovir for 12 months and 21 recipients (study group; 2003-2007) received combined CMV prophylaxis consisting of CMV-IG (Cytotect Biotest) for 12 months and ganciclovir or valganciclovir from postoperative day 21 for 3 weeks. Among the study group (since 2005), CMV shell vial viral culture and Epstein-Barr virus (EBV), human herpesvirus-6 (HHV-6), and HHV-7 DNA were determined on BAL specimens. In the study group, the number of LB was significantly lower than in the control group (2% vs 11%; P= .04). Similar results were obtained for ARE (6% vs 17%; P= .04). No difference was observed in OB (5% vs 5%; P= .53, NS). A reduction trend was found in CMV pneumonia (2% vs 7%; P= .23, NS). Logistic regression analysis showed a relationship between prophylaxis and a reduced prevalence of ARE (odds ratio [OR] 3.25, confidence interval [CI] 1.12-9.40; P= .03). Finally, in the study group, BAL EBV-DNA positivity and EBV-CMV coinfections were low (6% and 0%, respectively) compared with other herpesviruses and with the literature. Our data suggested the efficacy of combined CMV prophylaxis to prevent ARE and LB, 2 risk factors for chronic rejection, and a possible role to reduce the trend toward CMV pneumonia and EBV infections.

Rapid shell vial culture for the detection of respiratory viruses from bronchoalveolar lavage in immunocompromised patients.

AIM: Viral lower respiratory tract infections (LRTI) are an important cause of morbidity in immunocompromised patients. The aim of this study was to evaluate the clinical impact of rapid shell vial cultures from bronchoalveolar lavage (BAL). METHODS: Sixty-seven BAL samples from 46 patients have been retrospectively examined: 51 from 31 transplant recipients and 16 from 15 immunocompromised patients. BAL were inoculated on human embryonic lung fibroblasts and VERO cells to isolate the following viruses: cytomegalovirus (CMV), herpesviruses, varicella-zoster virus, respiratory syncytial virus, adenovirus, Influenza viruses A and B and Parainfluenza viruses. Clinical, microbiological, laboratory, and radiological data were collected. RESULTS: A LRTI was present in 56.7% of cases: viral 40.3%, bacterial and/or fungal 23.9%, and mixed 7.5%. CMV accounted for 92.6% of viral LRTI. The prevalence of viral infections did not differ between symptomatic and asymptomatic patients; only bacterial and/or fungal infections were significantly more prevalent in symptomatic patients. No clinical, radiological or laboratory feature was significantly associated with the presence of a viral LRTI. In lung transplant recipients the rate of CMV infection was 50%. The result of BAL suggested commencement of antiviral chemotherapy in 25/67 episodes. CONCLUSION: Rapid shell vial culture and immunofluorescence techniques from BAL could play an important role in the clinical management of immunocompromised subjects.

Usefulness of sequential Aspergillus galactomannan antigen detection combined with early radiologic evaluation for diagnosis of invasive pulmonary aspergillosis in patients undergoing allogeneic stem cell transplantation.

BACKGROUND: Early diagnosis of invasive pulmonary aspergillosis (IPA) is important as prompt treatment with antifungal drugs may increase patient survival. Our study investigated the efficiency of routine testing of the Aspergillus galactomannan antigen (AGA) test in combination with chest CT scans for IPA diagnosis. PATIENTS AND METHODS: From February 2002 to June 2004, 74 hemato-oncologic patients undergoing allogeneic stem cell transplantation were prospectively studied with serum AGA twice weekly from admission until death or discharge and weekly afterward when possible. Chest CT scans were performed when fever of unknown origin had lasted beyond 3 days of antibacterial therapy. RESULTS: Seven patients were classified with possible IPA and two patients, proven IPA. Fourteen patients showed positive results for AGA (OD index>or=1.0 on two subsequent sera). The sensitivity and specificity of the test were 100% and 93%, respectively; the positive and negative predictive values were 64% and 100%, respectively. All patients with possible/proven IPA showed abnormal CT signs; in four cases, imaging signs followed AGA positivity (median 5 days), whereas in five cases they preceded serologic positivity (median, 8 days). In the nine patients with IPA, antifungal therapy was promptly instituted, including lipid formulations of amphotericin B (n=5) or caspofungin (n=4). In only two of the nine patients (22%) with IPA, the primary cause of death was fungal infection. CONCLUSIONS: The combination of AGA detection and early chest CT scans might be considered useful tools to detect minimal changes of IPA. Based on these findings, aggressive antifungal therapy should be initiated.

Pulmonary Hypertension in Chronic Obstructive Pulmonary Disease and Pulmonary Fibrosis: Prevalence and Hemodynamic Differences in Lung Transplant Recipients at Transplant Center's Referral Time.

INTRODUCTION: Single or bilateral lung transplantation is a therapeutic procedure for end-stage lung diseases. In particular, in cases of chronic obstructive pulmonary disease (COPD) and pulmonary fibrosis, patients can be referred to the transplant center late and with important comorbilities. Pulmonary hypertension (PH) associated with lung diseases not only is an index of poor outcome but also is an indication for bilateral procedure. METHODS: We conducted a retrospective observational study. We analyzed right heart catheterization in a consecutive series of patients who underwent lung transplantation from 2006 to 2014 for end-stage COPD and pulmonary fibrosis. RESULTS: We included in the study 73 patients (35 with fibrosis and 38 with COPD); prevalence of PH was higher in the COPD group (84.3% vs 31.4%), and with worse hemodynamic parameters (mean pulmonary artery pressure [30.3 mm Hg vs 24.1 mm Hg]). The majority of COPD patients presented mild or moderate PH, and fibrosis patients showed normal pulmonary arterial pressures. CONCLUSIONS: COPD patients are referred to the Transplant Center with a higher prevalence of PH because of an echocardiographic screening or a late referral, but many patients survive on the waiting list and undergo the procedure. On the other hand, patients transplanted with interstitial diseases have a lower prevalence of PH; this can be explained by an earlier referral or a higher mortality on the waiting list and a more aggressive and rapidly progressing disease.

[Diagnostic contribution of the determination of CEA, pH, glucose and lactase dehydrogenase in the pleural fluid in patients with mesothelioma]. / Contributo diagnostico della determinazione del CEA, del pH, del glucosio e della lattico-deidrogenasi su liquido pleurico in pazienti affetti da mesotelioma.

The difficulty involved in the diagnosis of primary pleural neoplasms (mesotheliomas) in described. Personal experience with assays of certain chemicals is the pleural fluid is reported with evidence of the value of pH, glucose and CEA as indications of malignity.

[Usefulness of the determination of CEA and Ca 19-9 in the diagnosis and staging of bronchial carcinoma]. / Utilità della determinazione di CEA e Ca 19-9 nella diagnosi e stadiazione del carcinoma bronchiale.

The value of CEA and Ca 19-9 assays in the diagnosis and staging of lung cancer is examined. The particular sensitivity of CEA especially in extensive or metastasised tumours is demonstrated. The minimal sensitivity of Ca 19-9 is pointed out but also its absolute specificity in high risk control groups (smokers and BPCO). It is therefore concluded that Ca 19-9 might be used together with CEA in the diagnosis and staging of lung cancer.

[Collageno-vascular diseases and interstitial pulmonary fibrosis. An analysis of diagnostic tests]. / Malattie collageno-vascolari e fibrosi interstiziale polmonare. Una analisi dei tests diagnostici.

Collagenovascular diseases, particularly rheumatoid arthritis, LES and scleroderma frequently involve the lung. A group of 15 patients with collagen vasculopathies was analysed with a view to identifying the most suitable invasive and noninvasive tests for the diagnosis of the interstitial fibrosis of the lung that often accompanies such disorders. Among the noninvasive tests only the respiratory function tests (especially DLCO) are adequately sensitive, while chest X-rays, gallium scintigraphy of the lung and ACE are relatively unreliable. Bronchoalveolar lavage is often altered (though the intensity varies considerably) and transbronchial biopsy appears to be the ideal diagnostic examination.

[Respiratory function evaluation in esophageal surgery. Predictive value of tests]. / Valutazione funzionale respiratoria nella chirurgia esofagea. Valore predittivo dei tests.

In the context of major surgery the predictive significance of respiratory function tests in relation to postoperative pleuro-pulmonary complications is assessed. A statistical analysis is performed on a series of 85 oesophagectomy after thoracotomy and laparotomy. The most significant respiratory function indices are found to be those relating to volume restriction and the Mottley index.

Cardiac arrhythmias following lung resection in patients treated and untreated with digitalis prophylaxis.

Cardiac arrhythmias and failure following lung resection in patients treated and untreated with digitalis prophylaxis have been evaluated. In 82 patients without digitalis (1st group) 11% tachyarrhythmias and 5.7% cardiac failures were noted. In 100 patients treated with digitalis (2nd group) 7% arrhythmias and no cardiac failures were registered. Among cardiac complications only one death in the first group was observed. The mean period of incidence of arrhythmias appears dilated in the digitalis group (3rd vs. 5th postoperative day) and this could be attributed to the early suspension of the drug.

Tumor-associated trypsin inhibitor (TATI) in the diagnosis of lung cancer.

To evaluate the usefulness of tumor-associated trypsin inhibitor (TATI) as a marker for the diagnosis of lung cancer we determined serum levels of this peptide in 255 patients with lung cancer and in 74 patients with chronic obstructive lung disease. A reference population consisting of 151 healthy volunteers was also studied. TATI concentrations were measured by radioimmunoassay. As a cut-off point we used the 99th percentile of the TATI concentrations in a reference population, which was 32 micrograms/l. TATI does not appear to be a good tumor marker in lung cancer. Its sensitivity is poor in comparison with CEA and TPA. The correlation between TATI levels and stage of the disease and histological type was weak.

Tumor-associated trypsin inhibitor (TATI) in bone diseases.

The casual observation of high serum levels in (TATI) of tumor associated trypsin inhibitor in patients with osteosarcoma inspired us to evaluate the use of this peptide in the diagnosis of various bone diseases. We determined the serum concentrations of TATI in 35 patients with various bone diseases, i.e. degenerative diseases, bone metastasis and osteosarcomas. The cut off, determined as the 99th percentile of TATI serum levels in healthy volunteers was 32 micrograms/l. TATI has a better sensitivity in osteosarcomas (83%) than in metastatic bone diseases (33%). Its specificity in non-malignant bone diseases was not exceptional (82%). This is probably because TATI may also behave as on acute phase protein, the levels of which can rise in non-malignant diseases and also as a result of a tissue reaction in primary bone tumors.

Tailored cytomegalovirus management in lung transplant recipient: a single-center experience.

INTRODUCTION: Among solid organ recipients lung transplant recipients are at highest risk to be affected by cytomegalovirus infection (CMV) or to die from CMV disease. Two strategies are usually adopted in the clinical management of transplant recipients: antiviral prophylaxis and pre-emptive therapy. METHODS: In our center we adopted from 2007 a combined prophylaxis with anti-CMV immunoglobulins in the first post-transplant year and antiviral therapy (gancyclovir or valgancyclovir) from post-transplant day 15 for 3 weeks and in case of CMV bronchoalveolar lavage specimen positivity (polymerase chain reaction or shell vial). Moreover, we studied specific cellular immune response by an Elispot assay to define responder patients by the number of spot forming units (<5 nonresponders, 5-20 weeks, 20-100 good, >100 very good responders). RESULTS: We reduced acute rejections (from 17% to 6%, odds ratio 3.25), lymphocytic bronchitis bronchiolitis (from 11% to 2%), and first-year CMV pneumonia after the first post-transplant month (from 6.4% to 1%). We showed in nonresponders an earlier onset (68 vs 204 post-transplant days) and a longer duration (>14 days vs <14 days) of infection (P < .05 for all referred data). DISCUSSION: The morbility reduction has been obtained by antiviral therapy, increasing costs and risk of side effects. Our more recent studies show a population with a good immune response that probably doesn't need a pharmacological intervention but just a strict follow-up. CONCLUSION: Our proposed strategy is now tailoring the therapy on immune response clinical application, limiting to the specimen positivity in nonresponders.

Herpesviruses detection by quantitative real-time polymerase chain reaction in bronchoalveolar lavage and transbronchial biopsy in lung transplant: viral infections and histopathological correlation.

The monitoring of herpesvirus infection plays a central role in lung transplantation (LT). Herein we evaluated the prevalence of human cytomegalovirus (HCMV), human herpesvirus-6 (HHV-6), human herpesvirus-7 (HHV-7), and Epstein-Barr Virus (EBV) DNA in bronchoalveolar lavage (BAL) and transbronchial biopsy (TBB) specimens from LT patients. We associated the findings with the occurrence of interstitial pneumonia, acute rejection, or organizing pneumonia. Viral DNA was detected using real-time polymerase chain reaction (PCR) on 76 paired samples (BAL and TBB) from 27 patients who were receiving a universal combined prophylaxis (cytomegalovirus [CMV] immunoglobulin [Ig] + gancyclovir or valgancyclovir). Histopathological analysis was performed in accordance with the International Society for Heart and Lung Transplantation (ISHLT) criteria. Overall, HCMV results were positive in 25/76 (32.9%) specimens (BAL and/or TBB); HHV-6 in 16 (21.1%); HHV-7 in 40 (52.6%); and EBV in 13 (17.1%). Interstitial pneumonia was diagnosed in 6/76 (7.9%) cases: 5 (83.3%) were positive to HCMV (combined specimens; P < .0001); 5 (83.3%) to HHV-7; and 2 (33.3%) to EBV. An acute rejection episode was diagnosed in 19/76 (25%) cases: 7 (36.8%) were positive to HCMV; 5 (26.3%) to HHV-6; 10 (52.6%) to HHV-7, and 3 (15.8%) to EBV. No significant association was observed between virus detection or load and acute rejection. Organizing pneumonia was diagnosed in 4/76 (5.3%) cases: 1 (25%) positive to HCMV; 4 (100%) to HHV-6 (P < .05); 2 (50%) to HHV-7; and none to EBV. In conclusion, the prevalence of HCMV tended to be lower than that reported in the literature, confirming the importance of universal combined prophylaxis. HCMV was a relevant agent for interstitial pneumonia; although the small numbers limit the statistical analysis, our data did not support an association between herpesviruses and acute rejection episodes, whereas the role of HHV-6 in the pathogenesis of organizing pneumonia deserves further study. Viral detection on TBB could represent an adjunctive tool to complement that on BAL.

Prevalence and clinical impact of polyomaviruses KI and WU in lung transplant recipients.

The newly discovered polyomaviruses KI and WU (KIV and WUV) were isolated from secretions of patients with respiratory symptoms as well as in blood, spleen, lymphoid tissues, and stools, especially in immunocompromised conditions. The aim of this work was to evaluate the prevalence of KIV and WUV in bronchoalveolar lavage (BAL) from lung transplant recipients. We also examined potential correlations between these viruses and occurrences of pneumonia, acute respiratory insufficiency, or other acute respiratory conditions and acute rejection episodes. Discharge diagnosis was based on the International Classification of Diseases-Italian version 2002, based on the 9th-revision clinical modification. A rejection episode was diagnosed by transbronchial lung biopsy in accordance with the 2007 International Society for Heart and Lung Transplantation Working Formulation. Overall, we analyzed 53 BALs obtained from 24 transplant recipients. Positive polymerase chain reaction results were observed in 6 samples (11.3%) from 6 patients (25%), versus 7 samples (13.2%) from 7 patients (29.2%) for KIV and WUV, respectively. Regarding the diagnosis of pneumonia, the prevalence was 22.2% and 33.3% for KIV and WUV, respectively. In cases of acute respiratory insufficiency or other acute respiratory conditions, 2 out of 9 samples were positive for KIV (22.2%) and 4 out of 9 for WUV (44.4%). An Acute rejection episode (ARE) was diagnosed in 7 instances among 6 lung transplant patients: The corresponding BAL specimens showed positive results for KIV in 3 out of 7 (42.8%) cases with ARE vs 3 out of 46 (6.5%) without an ARE (P < .05), and for WUV in 3 out of 7 (42.8%) vs 4 out of 46 (8.7%) (P < .05), respectively. Although the small number of specimens limits the statistical analysis, our results showed a higher prevalence of WUV compared with KIV. The compromised pulmonary environment in the lung allograft may cause reactivation of these viruses. Their roles in this context need to be further evaluated.

Combined prophylaxis decreases incidence of CMV-associated pneumonia after lung transplantation.

Among solid-organ recipients, those with lung transplants are at highest risk of cytomegalovirus (CMV) infection or to die of CMV-associated disease. We evaluated the effect of combined CMV antiviral prophylaxis and CMV-immunoglobulin prophylaxis on CMV-associated pneumonia diagnosed in 303 follow-up transbronchial biopsy (TBB) specimens from lung transplant recipients. At our center, 24 recipients (control group; 1999-2002) received acyclovir for 24 months and 33 recipients (study group; 2003-2008) received combined CMV prophylaxis consisting of CMV immunoglobulin on days 1, 4, 8, 15, and 30 and monthly for 12 months plus gancyclovir or valgancyclovir from postoperative day 21 for 3 weeks followed by acyclovir for up to 24 months. The percentage of pneumonia-positive TBB specimens at 1-month follow-up was similar in the study and control groups: 9.1% (3 of 33 specimens) vs 8.3% (2 of 24) (P = .90). However, after the first month, the percentage of pneumonia-positive TBB specimens was significantly lower in the study group in the first year (months 3, 6, 9, and 12) of follow-up, at 1% (1 of 99) vs 6.4% (5 of 78) (P = .048), and in the first 2 years (months 3, 6, 9, 12, 18, and 24), at 0.8% (1 of 122) vs 6.5% (8 of 124) (P = .02). These data suggest the efficacy of combined prophylaxis to decrease the incidence of CMV-associated pneumonia after the first month in lung transplant recipients. The effect of combined prophylaxis after transplantation seems useful to prevent CMV-associated pneumonia not only in the first year after lung transplantation but also in the second year, which suggests a long-lasting immunologic role of prophylaxis.

Alpha-fetoprotein and mediastinal germ cell tumors.

The Authors discuss the utility of alpha-fetoprotein (AFP) determination in mediastinal dysembryomas. AFP should be determined in all cases of mediastinal lesion. High levels of up to 500 ng/ml are a sure sign of germ cell tumors. An extremely high level (greater than 1,000 ng/ml) is an indication that the lesion is a mesoblastoma. An increase in the AFP level in the follow-up of patients affected by germ cell tumors is a sure sign of the recurrence of the disease.