Incidence of orolingual angioedema after intravenous thrombolysis for stroke.

INTRODUCTION: Orolingual angioedema (OA) is a known adverse effect of intravenous (i.v.) alteplase. We analyzed all patients treated with i.v. alteplase for stroke at our hospital since approval of i.v. thrombolysis in Italy in 2004 to assess the incidence of this complication. PATIENTS AND RESULTS: Four hundred thirty-three patients received alteplase for stroke from April 2004 to May 2017. Two women developed OA (0.4%; 95% confidence interval 0.1 to 1.6%). Angioedema was mild in one case and severe in the other, with massive swelling of the lips, tongue, and oropharyngeal mucosa, and oropharyngeal bleeding, requiring intubation. Neither patient used ACE-inhibitors. DISCUSSION: The incidence of orolingual angioedema was very low in our series. Although OA is usually mild, anaphylactoid reactions may rarely occur, because of the variable degree of activation of the complement system and kinin cascade caused by alteplase. In such instances, admission to neurointensive care may be required. Specific bradykinin antagonists or drugs that target the kallikrein-kinin system are beginning to be used in the more severe cases. Thus, doctors and nurses caring for acute stroke patients need to be able to recognize and treat this complication.

Complications of non-invasive ventilation techniques: a comprehensive qualitative review of randomized trials.

Non-invasive ventilation (NIV) has become a common treatment for acute and chronic respiratory failure. In comparison with conventional invasive mechanical ventilation, NIV has the advantages of reducing patient discomfort, procedural complications, and mortality. However, NIV is associated with frequent uncomfortable or even life-threatening adverse effects, and patients should be thoroughly screened beforehand to reduce potential severe complications. We performed a detailed review of the relevant medical literature for NIV complications. All major NIV complications are potentially life-threatening and can occur in any patient, but are strongly correlated with the degree of pulmonary and cardiovascular involvement. Minor complications can be related to specific structural features of NIV interfaces or to variable airflow patterns. This extensive review of the literature shows that careful selection of patients and interfaces, proper setting of ventilator modalities, and close monitoring of patients from the start can greatly reduce NIV complications.

Effectiveness and predictors of success of noninvasive ventilation during H1N1 pandemics: a multicenter study.

BACKGROUND: The use of non-invasive ventilation (NIV) in acute hypoxemic respiratory failure (AHRF) due to H1N1 virus infection is controversial. In this multicenter study we aimed to assess the efficacy of NIV in avoiding endotracheal intubation (ETI) and to identify predictors of success or failure. METHODS: In this prospective multicenter study, 98 patients with new pulmonary infiltrate(s) sustained by H1N1 virus and a PaO(2)/FiO2<300 were eligible for study; 38/98 required immediate ETI, while the others received NIV as a first line therapy; 13/60 patients failed NIV and were intubated after 5.8+5.5 hours from enrolment. The remaining 47/60 patients were successfully ventilated with NIV. RESULTS: Hospital mortality was significantly higher in those patients who failed NIV vs. those who succeeded (53.8% vs. 2.1%; OR=0.52, P<0.001). ETI was associated with higher number of infectious complications, mainly sepsis and septic shock. The OR of having one of these events in the NIV failure group vs. NIV success was 16.7, P<0.001. According to logistic regression model, a SAPS II>29 and a PaO(2)/FIO(2)≤127 at admission and PaO2/FIO(2)≤149 after 1 hr of NIV were independently associated with the need for ETI. CONCLUSION: The early application of NIV, with the aim to avoid invasive ventilation, during the H1N1 pandemics was associated with an overall success rate of 47/98 (48%). Patients presenting at admission with an high SAPS II score and a low PaO(2)/FiO(2) ratio and/or unable to promptly correct gas exchange are at high risk of intubation and mortality.

Predicting mortality in hospitalized patients with 2009 H1N1 influenza pneumonia.

BACKGROUND: Community-acquired pneumonia (CAP) severity scores can identify patients at low risk for mortality who may be suitable for ambulatory care. Here, we follow the clinical course of hospitalized patients with CAP due to 2009 H1N1 influenza. OBJECTIVE: To evaluate the role of CAP severity scores as predictors of mortality. METHODS: This was a secondary data analysis of patients hospitalized with CAP due to 2009 H1N1 influenza confirmed by reverse transcriptase polymerase chain reaction enrolled in the CAPO (Community-Acquired Pneumonia Organization) international cohort study. CAP severity scores PSI (Pneumonia Severity Index), CURB-65 (confusion, urea, respiratory rate, blood pressure, age ≥ 65 years) and CRB-65 (confusion, respiratory rate, blood pressure, age ≥ 65 years) were calculated. Actual and predicted mortality rates were compared. A total of 37 predictor variables were evaluated to define those associated with mortality. RESULTS: Data from 250 patients with CAP due to 2009 H1N1 influenza were analyzed. Patients with low predicted mortality rates (0-1.5%) had actual mortality rates ranging from 2.6% to 17.5%. Obesity and wheezing were the only novel variables associated with mortality. CONCLUSIONS: The decision to hospitalize a patient with CAP due to 2009 H1N1 influenza should not be based on current CAP severity scores, as they underestimate mortality rates in a significant number of patients. Patients with obesity or wheezing should be considered at an increased risk for mortality.

Non-invasive continuous positive airway pressure in monolateral lung transplant patient with pneumonia and IPF.

Patients who undergo lung transplantation are prone to develop lower respiratory tract infections, leading to severe acute respiratory failure (ARF). Endotracheal intubation may not be indicated in these patients in light of a higher rate of mortality due to infections. The application of non-invasive ventilation could play a role in bridging these patients through the episode of ARF waiting for medical treatment to have effect. We report the evidence of morphological and physiological effects of the application of non-invasive continuous positive airway pressure during ARF sustained by pneumonia in a patient who underwent left lung transplantation because of idiopathic pulmonary fibrosis (IPF). We studied the effects of the application of positive end-expiratory pressure on both the right native lung affected by IPF and the transplanted lung affected by pneumonia.

Steps forward in LRTI and tuberculosis: update from the ERS Respiratory Infections Assembly.

Lower respiratory tract infections (LRTIs) and tuberculosis are among the leading reasons for seeking medical care. In the present report, the most recent advances in the fields of clinical research and basic science of LRTIs and tuberculosis are presented through analysis of some of the best abstracts presented at the 18th European Respiratory Society Annual Congress in Berlin. The role of viruses in chronic obstructive pulmonary disease exacerbations and the importance of new biomarkers in the diagnosis of bacterial infections in LRTI are discussed. New tools for the diagnosis of latent and active tuberculosis in special subgroups of patients (children, immunocompromised individuals, etc.), and the new epidemiological threat of multidrug-resistant and extensively drug-resistant tuberculosis cases is analysed.

The role of neutropenia on outcomes of cancer patients with community-acquired pneumonia.

Although the presence of neutropenia may predispose cancer patients to develop community-acquired pneumonia, the role of neutropenia on their outcomes has not been investigated. The purpose of the present study was to compare clinical outcomes of cancer community-acquired pneumonia patients with and without neutropenia. Patients with cancer, identified in the Community-Acquired Pneumonia Organization database, were divided into two groups according to the type of cancer and the presence of neutropenia: patients with solid cancer without neutropenia versus those with functional or absolute neutropenia. Among the 3,106 community-acquired pneumonia patients enrolled, 135 had cancer without neutropenia and 75 had cancer with neutropenia. No significant difference was found between patients with and without neutropenia regarding mean time to clinical stability (5.4+/-2.7 versus 4.9+/-2.7 days, respectively), mean length of hospital stay (9.2+/-7.7 versus 9.9+/-9.6 days) and in-hospital mortality (18 versus 15%, respectively). Using a multiple logistic regression model, neutropenia was not associated with mortality in cancer patients when adjusting for significant covariates (odds ratio 1.30). Lack of neutropenia, during the initial evaluation of a cancer community-acquired pneumonia patient, should not be considered an indicator of better clinical outcome.

Azithromycin and lower respiratory tract infections.

Azithromycin is a macrolide antibiotic that has been structurally modified from erythromycin with an expanded spectrum of activity and improved tissue pharmacokinetic characteristics relative to erythromycin. This allows once-daily administration for 3-5 days of treatment compared with traditional multi dosing 7-10-day treatment regimens. It has been successfully employed in lower respiratory tract infections. Recent data indicate that azithromycin may exert anti-inflammatory/immunomodulatory effects that may be of use in the treatment of both acute and chronic airway diseases. This review examines the role of azithromycin in lower respiratory tract infections analysing published data on exacerbations of chronic bronchitis, community-acquired pneumonia and cystic fibrosis both in adults and children. In addition, pharmacokinetic and pharmacodynamic properties of the drug are also considered.

Chlamydia pneumoniae and Mycoplasma pneumoniae.

Mycoplasma pneumoniae infection occurs worldwide and is the most common cause of community-acquired pneumonia (CAP) in 5- to 20-year-olds. The most reliable diagnostic test is the enzyme immunoassay, which allows immunoglobulin (Ig)G and IgM titration and presents 92% sensitivity and 95% specificity on paired samples. Potentially active drugs are tetracyclines, macrolides, ketolides, lincosamides, streptogamines, chloramphenicol, and fluoroquinolones. Chlamydia pneumoniae accounts for 6 to 20% of CAP cases, depending on several factors such as setting of the studied population, age group examined, and diagnostic methods used. The current gold standard for serological diagnosis of acute infection is microimmunofluorescence testing. Tetracyclines and erythromycin show good in vitro activity and so far have been the most commonly employed drugs in the treatment of C. pneumoniae infection. New macrolides, ketolides, and new fluoroquinolones are other potentially effective drugs.

Chlamydia pneumoniae and chronic bronchitis: association with severity and bacterial clearance following treatment.

BACKGROUND: A study was undertaken to evaluate Chlamydia pneumoniae chronic infection, other respiratory infections, and functional impairment in patients with chronic bronchitis (stage 1) and to examine chronic C pneumoniae infection, rate of acute exacerbations of chronic bronchitis, and rate of C pneumoniae eradication following antibiotic treatment (stage 2). METHODS: In the stage 1 study respiratory specimens from 42 patients with steady state chronic bronchitis were analysed for Gram staining, sputum culture, and C pneumoniae DNA detection by nested touchdown polymerase chain reaction (PCR). On the basis of the results of stage 1, a second population of 141 consecutive patients with steady state mild to moderate chronic bronchitis (FEV(1) >or=50% predicted) was studied. On admission, at regular intervals, and at exacerbation all patients underwent serological testing for C pneumoniae (microimmunofluorescence) and a nested touchdown PCR to detect C pneumoniae DNA was performed on peripheral blood mononuclear cells (PBMCs). Patients were assessed over a 12 month period. Information regarding the previous 12 months was taken from medical records. RESULTS: Chronic colonisation of the sputum with C pneumoniae was significantly associated with lower FEV(1) and greater airway bacterial colonisation. On admission to the stage 2 study, 80 patients were PCR negative and 61 were PCR positive. Over the 2 years a mean (SD) of 1.43 (1.32) acute exacerbations occurred in PCR negative patients and 2.03 (1.21) in PCR positive patients (p<0.01). During the 12 month follow up period 34 PCR positive patients had acute exacerbations and were treated with azithromycin for 6 weeks. Serological evidence of acute C pneumoniae reinfection/reactivation was found in two of the 34 patients. The rate of C pneumoniae DNA clearance from blood following treatment was 29% at follow up. CONCLUSION: Chronic colonisation with C pneumoniae is associated with a higher rate of exacerbations of chronic bronchitis. Long term treatment is required to obtain clearance of the organism from the blood.

Atypical pathogens and asthma: can they influence the natural history of the disease?

The association between respiratory infections and asthma exacerbations was first observed in the early '70s. In particular, the role of viral upper respiratory tract infections has been evaluated both in pediatric and adult populations. More recently, evidence of Mycoplasma and Chlamydia pneumoniae involvement in asthma attacks has been reported. These pathogens are also involved in chronic asthma, and both in vitro and animal model studies indicate that atypical agents may play a role in the pathogenesis of the disease. Further research is required to determine whether specific antibiotic treatment may alter the natural history of asthma.

Antibiotic treatment and baseline severity of disease in acute exacerbations of chronic bronchitis: a re-evaluation of previously published data of a placebo-controlled randomized study.

The study was designed to extend retrospectively the analysis of a previously reported study on chronic bronchitis patients with acute exacerbations treated with amoxicillin-clavulanic acid or matched placebo. We retrospectively re-clustered patients on the basis of severity of baseline lung function: Cluster 1 (104 patients) mean screening FEV(1)32.67+/-6.83 (SD); Cluster 2 (109 patients) mean screening FEV(1)54.12+/-5.56; Cluster 3 (122 patients) mean screening FEV(1)71.54+/-5.51. The success rate in the antibiotic group was significantly greater compared to the placebo group (P<0.001). When clinical improvement was analysed on the basis of patient re-clustering, 31.4% of Cluster 1 (severe COPD) patients treated with amoxicillin/clavulanate showed clinical improvement, whereas success was recorded in 58.8%. Conversely, 13.2% of Cluster 1 patients receiving placebo improved and 17% successfully recovered (P<0.001). Mild and moderate COPD patients (Clusters 2 and 3) were grouped together. In these two groups, 31.2% and 53.6% of patients receiving antibiotic treatment showed improvement or recovery, respectively, compared to 29.2% improvements and 30.2% successful recoveries among placebo-treated patients (P<0.001). In placebo-treated patients the improvement/success vs. failure rate was significantly different in Cluster 1 patients compared to Cluster 2+3 subjects (P<0.01, (2)test). The differences in final FEV(1)values in the treatment group and placebo group were significantly different (P<0.01) in favour of the active treatment group. Among more severe patients (Cluster 1), the comparison between screening and follow up FEV(1)values showed an improvement following antibiotic treatment and worsening after placebo (P<0.01). In Clusters 2 and 3 the difference between screening and follow up FEV(1)values was not significant for both treatment groups. Our patients with severe functional impairment and higher number of exacerbations per year are those who derive the greatest benefit from antibiotic treatment.

Community-acquired pneumonia: role of atypical organisms.

M. pneumoniae infection occurs world-wide and is the most common cause of community-acquired pneumonia (CAP) in the 5 to 20 year-old age group. The most reliable diagnostic test is enzyme immunoassay that allows immunoglobulin (Ig)G and IgM titration and presents 92% sensitivity and 95% specificity on paired samples. Potentially active drugs are tetracyclines, macrolides, ketolides, lincosamides, streptogamines, chloramphenicol, and fluoroquinolones. The incidence of Legionella infection, in spite of its world-wide diffusion, is highly variable in different studies, ranging from 1% to 27% of CAP. The most likely mode of transmission is direct inhalation from Legionella-contaminated water-supply systems. Extrapulmonary manifestations are relatively common but nonspecific. However, some signs and symptoms may raise the suspicion of Legionella infection: a sputum Gram stain with a high number of neutrophils without any organism, hyponatremia, and diarrhea in a critically ill patient. Urinary radioimmunoassay (RIA) antigen detection is the method of choice for L. pneumophila serogroup 1. The best treatment regimen is a full three-week treatment with a macrolide (erythromycin, clarithromycin, azithromycin). An alternative treatment regimen may be the association of second generation fluoroquinolones with tetracyclines. A notable improvement in most of the new fluoroquinolones is their activity against Legionella, so that their use as single agent may be hypothesised even if clinical data are still insufficient for a definitive indication. Chlamydia pneumoniae account for 6-20% of CAP depending on several factors such as setting of the studied population, age group examined, and diagnostic methods used. The current gold standard for serological diagnosis of acute infection is microimmunofluorescence testing. Tetracyclines and erythromycin show good in vitro activity and so far have been the most commonly employed drugs in the treatment of C. pneumoniae infection. New macrolides, ketolides, and new fluoroquinolones are other potentially effective drugs.

Temporal arteritis associated with Chlamydia pneumoniae DNA detected in an artery specimen.

Temporal arteritis is a clinical manifestation of giant cell arteritis. The etiology of this disease is still unknown. Sudden onset and wide variations of incidence are reported in different parts of the world. Acute onset is often associated with flu-like symptoms, indicating that infectious factors probably act as precipitating agents. We describe a 72-year-old man referred to our department in January 1999 for unremitting fever and temporal arteritis associated with Chlamydia pneumoniae infection.

Chlamydia pneumoniae DNA detection in peripheral blood mononuclear cells is predictive of vascular infection.

Abdominal aortic aneurysm tissue and peripheral blood mononuclear cells (PBMC) of 41 consecutive subjects undergoing abdominal aortic aneurysm surgery were analyzed by polymerase chain reaction (PCR) for the presence of Chlamydia pneumoniae, Mycoplasma pneumoniae, and Helicobacter pylori DNA. Twenty patients (49%) were positive for C. pneumoniae DNA-16 (39%) in both PBMC and aneurysm tissue, 3 (7.3%) in PBMC only, and 1 (2.4%) in the artery specimen only. Previous exposure to C. pneumoniae was confirmed in 19 (95%) of the 20 PCR positive subjects by C. pneumoniae-specific serology, using the microimmunofluorescence test. None was positive for H. pylori or M. pneumoniae DNA, either in the PBMC or in the artery specimens. In conclusion, carriage of C. pneumoniae DNA is common both in PBMC and in abdominal aortic tissue from patients undergoing abdominal aneurysm surgery. Blood PCR may be a useful tool for identifying subjects carrying C. pneumoniae in the vascular wall.

Demonstration of viable Chlamydia pneumoniae in atherosclerotic plaques of carotid arteries by reverse transcriptase polymerase chain reaction.

The presence of Chlamydia pneumoniae in atheromas has been demonstrated in several studies. Culture of the organism from arterial tissue has been difficult. We report the use of a reverse transcriptase polymerase chain reaction to detect viable Chlamydia pneumoniae in carotid atheromas. We analyzed 30 patients (14 females, mean age 69.6 +/- 8.8 years) who underwent surgery for the removal of atherosclerotic plaques from carotid arteries. During surgery, samples of lingual vein and superior thyroideal artery were also taken. We applied two molecular biology techniques to the carotid plaques on lingual vein or thyroideal artery samples: 1) polymerase chain reaction (PCR) and 2) reverse transcriptase-PCR (RT-PCR) for the detection of bacterial mRNA, employing PCR primers designed to detect a fragment of the 16S rRNA gene. Blood samples were obtained from the patients for determination of Chlamydia pneumoniae IgG, IgA, and IgM antibody titers by a microimmunofluorescence technique. The results of the present study confirmed the presence of viable Chlamydia pneumoniae in atheromas and support the hypothesis that the organism may be an active factor in the pathogenesis of atherosclerosis.

Treatment of Helicobacter pylori and Chlamydia pneumoniae infections decreases fibrinogen plasma level in patients with ischemic heart disease.

BACKGROUND: Chronic Chlamydia pneumoniae and Helicobacter pylori infections could be a risk factor for ischemic heart disease (IHD), possibly by increasing fibrinogen levels. The aim of our study was to evaluate changes in fibrinogen level in patients with IHD and H pylori and/or C pneumoniae positivity randomly assigned to antibiotic treatment. METHODS AND RESULTS: Eighty-four patients with chronic IHD, H pylori and/or C pneumoniae antibodies, and normal acute-phase reactants were randomly assigned to treatment or no treatment. Treatment consisted of omeprazole, clarithromycin, and tinidazole in H pylori-positive patients and clarithromycin alone in C pneumoniae-positive patients. The effect of treatment and other baseline variables on fibrinogen levels, determined at 6 months, was evaluated by multivariate analysis. Treatment significantly reduced fibrinogen level at 6 months in the overall study population and in the groups of patients divided according to H pylori or C pneumoniae positivity. In the 43 treated patients, mean (+/-SD) basal fibrinogen was 3.65+/-0.58 g/L, and mean final fibrinogen was 3. 09+/-0.52 g/dL (P<0.001), whereas in the 41 untreated patients, mean basal and final fibrinogen levels were 3.45+/-0.70 and 3.61+/-0.71 g/L, respectively. The largest decrease was observed in patients with both infections. Fibrinogen changes were also significantly and negatively correlated with age. CONCLUSIONS: Our data suggest that a short, safe, and effective course of antibiotic therapy might be suggested as a means of interacting with an "emerging" risk factor.

Incidence of Chlamydia pneumoniae infection in vertically HIV-1 infected children.

The rate of seroconversion for antibody to Chlamydia pneumoniae was analysed in blood samples of 26 vertically HIV-1 infected children and 14 seroreverter children (HIV-negative children born to HIV-positive mothers) during a 3-year study period. Seroconversion for Chlamydia pneumoniae was found in 13 of 26 HIV-1 infected children and in 1 of 14 in the seroreverter group (P=0.013). A lower mean CD4+ cell count and p24 antigen positivity at enrolment were significantly associated with seroconversion for Chlamydia pneumoniae. Signs and symptoms of acute respiratory infection were recorded in the 30 to 40 days preceding collection of the blood samples showing seroconversion for Chlamydia pneumoniae in 8 of 13 HIV-1 infected children and in the single seroreverter. This study confirms the potential role of Chlamydia pneumoniae in the pathogenesis of respiratory tract infections in HIV-1 infected subjects.