Biomarker guided antibiotic stewardship in community acquired pneumonia: A randomized controlled trial.

BACKGROUND: In community-acquired pneumonia (CAP), the role of biomarkers to shorten duration of antibiotic treatment has not been firmly established. We assessed the effectiveness of active feedback of treatment algorithms based on procalcitonin (PCT) and C-reactive protein (CRP), compared to standard care, on the duration of antibiotic treatment in patients hospitalized with community-acquired pneumonia (CAP) in non-ICU wards. METHODS AND FINDINGS: We performed a randomised, open label, parallel group, multi-centre trial in 3 Dutch teaching hospitals. Treatment was guided by a PCT algorithm, CRP algorithm or standard care. Participants were recruited by a member of the study team and randomised at day 2-3 of admission in a 1:1:1 ratio. Treatment was discontinued upon predefined thresholds of biomarkers that were assessed on admission, day 4 and days 5-7 if indicated. The primary outcome was total days on antibiotic treatment until day 30. In total 468 participants were included in this study. The median days on antibiotics (IQR) was 7 (IQR 7-10) in the control group, 4 (IQR 3-7) in the CRP group (rate ratio (RR) of 0.70, 95% CI 0.61-0.82 compared to standard care; p <0.001), and 5.5 (IQR 3-9) in the PCT group (RR of 0.78, 95% CI 0.68-0.89 compared to standard care; p <0.001). New antibiotics within the first 30 days were prescribed to 24, 23 and 35 patients in standard care, CRP and PCT groups, respectively. The hazard ratio for a new prescription in patients in the PCT group compared to standard care 1.63 (CI 0.97-2.75; p = 0.06). No difference in time to clinical stability or length of stay was found. CONCLUSIONS: A strategy of feedback of CRP-guided and PCT-guided treatment algorithms reduced the number of days on antibiotic in the first 30 days after hospital admission in non-ICU wards for CAP. The study was not powered to determine safety of shortening duration of antibiotic treatment. (NCT01964495).

[A man with yellow nails]. / Een man met gele nagels.

A 60-year-old man was referred to the outpatient clinic due to dyspnea of effort and productive coughing and rhinorrhea. Physical examination revealed swollen ankles and yellow, hyperkeratotic nails. HRCT showed bronchiectasis. This triad of symptoms indicates yellow nail syndrome. Vitamin E improved the yellow nails, while optimal expiration techniques alleviated respiratory symptoms.

Treatment with inhaled antibiotics in bronchiectasis, side effects, and evaluation of the tolerance test; analysis from the BATTLE randomized controlled trial.

INTRODUCTION: Tobramycin inhalation solution (TIS) is a treatment option for patients with frequent exacerbations of bronchiectasis. A possible side effect of TIS is the development of chronic cough and bronchospasm, whereby the guidelines suggest a (in hospital) tolerance test with the first dose of TIS. However, data on respiratory adverse events are not consistent. In the present analysis from the BATTLE study (NCT02657473), we evaluated the added value of the tolerance test and aimed to observe the development of inhaled treatment related bronchial hyperreactivity. METHODS: Fifty-seven patients from the BATTLE study were analyzed. Patients were randomized to receive TIS or placebo OD for 1 year. A tolerance test was performed with spirometry measurements before and after the first dose and with a bronchodilator in advance. Adverse events were strictly monitored. RESULTS: Fifty-seven patients (100%) passed the tolerance test with no decrease in spirometry measurements or development of local intolerability. During the study treatment, a total of five TIS-treated patients (17.8%) withdrew due to airway hyperresponsiveness after a mean of 9.2 (SD13.9) weeks and one placebo-treated patient (3.5%) after 2 weeks (TIS vs. placebo; p = 0.66). The other TIS-related adverse events were not clinically significant. CONCLUSION: The use of inhaled medication is well tolerated in the heterogenous bronchiectasis population, without signs of airway hyperresponsiveness after the first dose of inhaled medication. From this observation, it can be concluded that there is no additional value for this advised tolerance test. However, closely monitoring on adverse effects during the first weeks after starting TIS is recommended.

[A man with swollen eyelids]. / Een man met gezwollen oogleden.

A 74-old man developed severe periorbital emphysema after a video-assisted thoracoscopy for lung malignancy. Because of severe symptoms of pain and visual impairment, subcutaneous emphysema was evacuated by bilateral punctures and manual mobilisation of air through the puncture holes.

Procalcitonin-Guided Antibiotic Prescription in Patients With COVID-19: A Multicenter Observational Cohort Study.

BACKGROUND: Despite the low rate of bacterial coinfection, antibiotics are very commonly prescribed in hospitalized patients with COVID-19. RESEARCH QUESTION: Does the use of a procalcitonin (PCT)-guided antibiotic protocol safely reduce the use of antibiotics in patients with a COVID-19 infection? STUDY DESIGN AND METHODS: In this multicenter cohort, three groups of patients with COVID-19 were compared in terms of antibiotic consumption, namely one group treated based on a PCT-algorithm in one hospital (n = 216) and two control groups, consisting of patients from the same hospital (n = 57) and of patients from three similar hospitals (n = 486) without PCT measurements during the same period. The primary end point was antibiotic prescription in the first week of admission. RESULTS: Antibiotic prescription during the first 7 days was 26.8% in the PCT group, 43.9% in the non-PCT group in the same hospital, and 44.7% in the non-PCT group in other hospitals. Patients in the PCT group had lower odds of receiving antibiotics in the first 7 days of admission (OR, 0.33; 95% CI, 0.16-0.66 compared with the same hospital; OR, 0.42; 95% CI, 0.28-0.62 compared with the other hospitals). The proportion of patients receiving antibiotic prescription during the total admission was 35.2%, 43.9%, and 54.5%, respectively. The PCT group had lower odds of receiving antibiotics during the total admission only when compared with the other hospitals (OR, 0.23; 95% CI, 0.08-0.63). There were no significant differences in other secondary end points, except for readmission in the PCT group vs the other hospitals group. INTERPRETATION: PCT-guided antibiotic prescription reduces antibiotic prescription rates in hospitalized patients with COVID-19, without major safety concerns.

Effects of long-term tobramycin inhalation solution (TIS) once daily on exacerbation rate in patients with non-cystic fibrosis bronchiectasis.

BACKGROUND: Use of long-term tobramycin inhalation solution (TIS) has been shown beneficial in cystic fibrosis (CF) and earlier findings also suggest a benefit in non-CF bronchiectasis. We investigated the efficacy and safety of maintenance TIS once daily (OD) in frequent exacerbating bronchiectasis patients chronically infected by different pathogens sensitive for tobramycin. OBJECTIVE: The primary outcome was the frequency of exacerbations during the 12-month study period. Secondary outcomes were time to first exacerbation, change in lung function and quality of life (QoL), bacterial analysis and safety. MATERIALS/PATIENTS: IN THIS MULTICENTER RCT PATIENTS AGED ≥ 18-YEAR-OLD WERE INCLUDED WITH CONFIRMED BRONCHIECTASIS AND ≥ 2 EXACERBATIONS IN THE PRECEDING YEAR. PATIENTS WERE ASSIGNED (1:1) TO RECEIVE TIS OR PLACEBO OD FOR 1-YEAR.: RESULTS: 58 patients were included of which 52 were analyzed in the mITT analysis. TIS reduced exacerbation frequency with a RR of 0.74 (95% CI 0.49-1.14) (p = 0.15). Within the TIS population a decrease in number of exacerbations was found (2; p = 0.00), which was also seen in the placebo-treated patients (1.5; p = 0.00). In the TIS-treated patients the QoL improved (LRTI-VAS p = 0.02 Leicester Cough p = 0.02) without additional safety concerns. No differences were found for the other secondary outcomes. CONCLUSION: Long-term TIS OD is a safe treatment modality and showed a non-significant reduced exacerbation frequency of 0.74 as compared to placebo in bronchiectasis patients chronically infected by tobramycin sensitive pathogens. TIS OD may be a potential therapeutic strategy in selected patients with bronchiectasis suffering from a high burden of disease. TRAIL REGISTRATION NUMBER: The BATTLE study was registered at Clinical trials.gov number: NCT02657473 . Date: 13 august 2016.

The effect of maintenance azithromycin on radiological features in patients with bronchiectasis - Analysis from the BAT randomized controlled trial.

RATIONALE: Bronchiectasis (abnormal dilatation of bronchi) is usually diagnosed by high resolution computed tomography (HRCT) and radiological severity has been found to correspond with clinical outcome. A beneficial effect of macrolides maintenance treatment in frequent exacerbating bronchiectasis patients has been established in randomized trials. This study was undertaken to prospectively evaluate the effect of long-term azithromycin (AZM) on radiological features in patients with bronchiectasis. METHODS: The BAT randomized controlled trial (2008-2010) investigated the effect of 1 year of AZM (250 mg OD) in bronchiectasis with frequent exacerbations. Chest (HR)CT-scans at baseline and after one year of study treatment were obtained and scored by two radiologists according to the Brody - and the Bhalla scoring system. RESULTS: 77 (93%) patients conducted the BAT trial were evaluated in this post-hoc analysis. A significant improvement of the radiological features based on the Brody score was found after one year of AZM therapy as compared to placebo (p = 0.024), with a not significant improvement of the Bhalla score (p=0.071). Especially the consolidation (Bhalla) and parenchymal changes (Brody) sub scores significantly improved (both p=0.030), and even a radiological deterioration was seen on the Brody bronchiectasis sub score for the placebo treated patients (mean 14.5 (11.7) vs.15.7 (11.9)). CONCLUSIONS: The beneficial effect of long-term AZM treatment on radiological features was demonstrated in this randomized controlled trial. (HR)CT's can be used as an objective measure of treatment response in bronchiectasis. CLINICAL TRIAL REGISTRATION NUMBER: NCT00415350.

Heterogeneity of treatment response in bronchiectasis clinical trials.

BACKGROUND: Recent randomised clinical trials in bronchiectasis have failed to reach their primary end-points, suggesting a need to reassess how we measure treatment response. Exacerbations, quality of life (QoL) and lung function are the most common end-points evaluated in bronchiectasis clinical trials. We aimed to determine the relationship between responses in terms of reduced exacerbations, improved symptoms and lung function in bronchiectasis. METHODS: We evaluated treatment response in three randomised clinical trials that evaluated mucoactive therapy (inhaled mannitol), an oral anti-inflammatory/antibiotic (azithromycin) and an inhaled antibiotic (aztreonam). Treatment response was defined by an absence of exacerbations during follow-up, an improvement of QoL above the minimum clinically important difference and an improvement in forced expiratory volume in 1 s (FEV1) of ≥100 mL from baseline. RESULTS: Cumulatively the three trials included 984 patients. Changes in FEV1, QoL and exacerbations were heterogeneous in all trials analysed. Improvements in QoL were not correlated to changes in FEV1 in the azithromycin and aztreonam trials (r= -0.17, p=0.1 and r=0.04, p=0.4, respectively) and weakly correlated in the mannitol trial (r=0.22, p<0.0001). An important placebo effect was observed in all trials, especially regarding improvements in QoL. Clinical meaningful lung function improvements were rare across all trials evaluated, suggesting that FEV1 is not a responsive measure in bronchiectasis. CONCLUSIONS: Improvements in lung function, symptoms and exacerbation frequency are dissociated in bronchiectasis. FEV1 is poorly responsive and poorly correlated with other key outcome measures. Clinical parameters are poorly predictive of treatment response, suggesting the need to develop biomarkers to identify responders.

Criteria and definitions for the radiological and clinical diagnosis of bronchiectasis in adults for use in clinical trials: international consensus recommendations.

Bronchiectasis refers to both a clinical disease and a radiological appearance that has multiple causes and can be associated with a range of conditions. Disease heterogeneity and the absence of standardised definitions have hampered clinical trials of treatments for bronchiectasis and are important challenges in clinical practice. In view of the need for new therapies for non-cystic fibrosis bronchiectasis to reduce the disease burden, we established an international taskforce of experts to develop recommendations and definitions for clinically significant bronchiectasis in adults to facilitate the standardisation of terminology for clinical trials. Systematic reviews were used to inform discussions, and Delphi processes were used to achieve expert consensus. We prioritised criteria for the radiological diagnosis of bronchiectasis and suggest recommendations on the use and central reading of chest CT scans to confirm the presence of bronchiectasis for clinical trials. Furthermore, we developed a set of consensus statements concerning the definitions of clinical bronchiectasis and its specific signs and symptoms, as well as definitions for chronic bacterial infection and sustained culture conversion. The diagnosis of clinically significant bronchiectasis requires both clinical and radiological criteria, and these expert recommendations and proposals should help to optimise patient recruitment into clinical trials and allow reliable comparisons of treatment effects among different interventions for bronchiectasis. Our consensus proposals should also provide a framework for future research to further refine definitions and establish definitive guidance on the diagnosis of bronchiectasis.

Aetiology and disease severity are among the determinants of quality of life in bronchiectasis.

INTRODUCTION: Quality of life (QoL) is known to be impaired in patients with bronchiectasis, which is generally attributed to exacerbations and chronic pulmonary symptoms. The aim of this study was to determine if aetiology and disease severity are associated with QoL in bronchiectasis. METHODS: We conducted a retrospective analysis of clinical stable patients with bronchiectasis. Diagnostic workup into the aetiology of bronchiectasis was conducted according to the current guidelines. QoL was measured by QoL-B questionnaire (QoL-B), data on sputum microbiology, pulmonary function tests and the disease severity were obtained. RESULTS: The aetiology of bronchiectasis was investigated in the total of 200 patients. The most commonly identified aetiologies were post-infective (39.5%) and idiopathic (12.5%). Patients with chronic obstructive pulmonary disease (COPD)-related bronchiectasis showed a significant lower QoL (P < .05) as compared to the other aetiologies. In the total population, an increasing disease severity as measured by FACED, E-FACED and the bronchiectasis severity index was correlated with a lower QoL. CONCLUSIONS: Our results showed that QoL in bronchiectasis is related both to aetiology, with worse QoL in COPD-related bronchiectasis, and to disease severity, which suggests more attention in advance for these specific patient groups with bronchiectasis.

Plasma cytokine profile on admission related to aetiology in community-acquired pneumonia.

BACKGROUND: Potentially unnecessary antibiotic use for community-acquired pneumonia (CAP) contributes to selection of antibiotic-resistant pathogens. Cytokine expression at the time that treatment is started may assist in identifying patients not requiring antibiotics. We determined plasma cytokine patterns in patients retrospectively categorized as strict viral, pneumococcal or combined viral-bacterial CAP. OBJECTIVE: To investigate whether cytokine-based prediction models can be used to differentiate strict viral CAP from other aetiologies at admission. METHODS: From 344 hospitalized CAP patients, 104 patients were categorized as viral CAP (n = 17), pneumococcal CAP (n = 48) and combined bacterial-viral CAP (n = 39). IL-6, IL-10, IL-27, IFN-γ and C-reactive protein (CRP) were determined on admission in plasma. Prediction of strict viral aetiology was explored with two multivariate regression models and ROC curves. RESULTS: Viral pneumonia was predicted by logistic regression using multiple cytokine levels (IL-6, IL-27 and CRP) with an AUC of 0.911 (95% CI: 0.852-0.971, P < .001). For the same patients the AUC of CRP was 0.813 (95% CI: 0.728-0.898, P < .001). CONCLUSIONS: This study demonstrated differences in cytokine expression in selected CAP patients between viral and bacterial aetiology. Prospective validation studies are warranted.

Diagnosing ANCA-associated vasculitis in ANCA positive patients: A retrospective analysis on the role of clinical symptoms and the ANCA titre.

Currently no validated diagnostic system for antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is available. Therefore, diagnosing AAV is often challenging. We aimed to identify factors that lead to a clinical diagnosis AAV in ANCA positive patients in a teaching hospital in The Netherlands.In this study, all patients that tested positive for ANCA proteinase 3 (PR3) and/or myeloperoxidase (MPO) between 2005 and 2015 were analysed. Patients with a clinical diagnosis of AAV were compared with patients without a clinical diagnosis of AAV. Clinical symptoms and laboratory variables at presentation, including the ANCA titre, were collected for both patients with and without AAV. Clinical and laboratory variables related with AAV were investigated, using multivariable logistic regression.Two hundred thirty seven consecutive patients with a positive ANCA were included, of whom 119 were clinically diagnosed with AAV. Of the 118 ANCA positive patients without AAV, 87 patients had an alternative diagnosis, including inflammatory bowel disease (n = 24), other rheumatic diseases (n = 23), infection (n = 11), malignancy (n = 4), and other diagnoses (n = 25). In a multivariable regression model, a high ANCA titre (odds ratio [OR] 14.16, 95% confidence interval [CI] 6.93-28.94) and a high number of affected organ systems (OR 7.67, 95% CI 3.69-15.94) were associated with AAV.MPO and PR3 ANCA can be positive in a variety of diseases that mimic AAV. A higher ANCA titre and multiple affected organ systems may help to discriminate between AAV and other systemic illnesses in anti-PR3 and anti-MPO positive patients. A diagnostic scoring system incorporating these factors should be considered.

Validation of a visual analogue score (LRTI-VAS) in non-CF bronchiectasis.

BACKGROUND AND AIM: Quality of life in patients with non-cystic fibrosis (non-CF) bronchiectasis is largely defined by respiratory symptoms. To date, no disease-specific tool for symptom measurement in this patient group was available. We developed the lower respiratory tract infections - visual analogue scale (LRTI-VAS) in order to quickly and conveniently quantify symptoms in non-CF bronchiectasis. This study aimed to validate LRTI-VAS for use in non-CF bronchiectasis. METHODS: This study included outpatients with radiologically proven bronchiectasis and no evidence of CF. Results of LRTI-VAS were compared with other markers of disease activity {lung function parameters, oxygen saturation and three health-related quality of life questionnaires [Medical Outcomes Study Short-Form 36 Health Survey (SF-36), St Georges Respiratory Questionnaire (SGRQ) and Leicester Cough Questionnaire (LCQ)]} and validity, reliability and responsiveness were assessed. RESULTS: Thirty stable and 30 exacerbating participants completed the LRTI-VAS questionnaire. When testing for repeatability on two separate occasions, no statistically significant difference between total scores was found {1.4 [standard deviation (SD)] 5.3}, P = 0.16). Internal consistency was high across items (Cronbach's alpha 0.86). Correlation with SGRQ, SF-36 and LCQ total scores was high. Following antibiotic treatment, mean (SD) LRTI-VAS total score improved from 18.1 (SD 9.9) to 26.1 (SD 6.6) (P < 0.001). CONCLUSIONS: LRTI-VAS showed excellent validity, reliability and responsiveness to change and therefore appears a reliable tool for symptom measurement in non-CF bronchiectasis.

Aztreonam for inhalation solution in patients with non-cystic fibrosis bronchiectasis (AIR-BX1 and AIR-BX2): two randomised double-blind, placebo-controlled phase 3 trials.

BACKGROUND: The clinical benefit of inhaled antibiotics in non-cystic fibrosis bronchiectasis has not been established in randomised controlled trials. We aimed to assess safety and efficacy of aztreonam for inhalation solution (AZLI) in patients with non-cystic fibrosis bronchiectasis and Gram-negative bacterial colonisation. METHODS: AIR-BX1 and AIR-BX2 were two double-blind, multicentre, randomised, placebo-controlled phase 3 trials, which included patients aged 18 years or older who had bronchiectasis and history of positive sputum or bronchoscopic culture for target Gram-negative organisms. Patients were randomly assigned to receive either AZLI or placebo (1:1). Randomisation was done without stratification and the code was generated by a Gilead designee. In both studies, two 4-week courses of AZLI 75 mg or placebo (three-times daily; eFlow nebulizer) were each followed by a 4-week off-treatment period. Primary endpoint was change from baseline Quality of Life-Bronchiectasis Respiratory Symptoms scores (QOL-B-RSS) at 4 weeks. These trials are registered with ClinicalTrials.gov, numbers are NCT01313624 for AIR-BX1 and NCT01314716 for AIR-BX2. FINDINGS: We recruited participants from 47 ambulatory clinics for AIR-BX1 and 65 ambulatory clinics for AIR-BX2; studies were done between April 25, 2011, and July 1, 2013. In AIR-BX1, of the 348 patients screened, 134 were randomly assigned to receive AZLI and 132 to receive placebo. In AIR-BX2, of the 404 patients screened, 136 were randomly assigned to receive AZLI and 138 to receive placebo. The difference between AZLI and placebo for adjusted mean change from baseline QOL-B-RSS was not significant at 4 weeks (0.8 [95% CI -3.1 to 4.7], p=0.68) in AIR-BX1, but was significant (4.6 [1.1 to 8.2], p=0.011) in AIR-BX2. The 4.6 point difference in QOL-B-RSS after 4 weeks in AIR-BX2 was not deemed clinically significant. In both studies, treatment-related adverse events were more common in the AZLI group than in the placebo group, as were discontinuations from adverse events. The most commonly reported treatment-emergent adverse events were dyspnea, cough, and increased sputum. Each was more common for AZLI-treated than for placebo-treated patients, but the incidences were more balanced in AIR-BX2. INTERPRETATION: AZLI treatment did not provide significant clinical benefit in non-cystic fibrosis bronchiectasis, as measured by QOL-B-RSS, suggesting a continued need for placebo-controlled studies to establish the clinical benefit of inhaled antibiotics in patients with this disorder. FUNDING: Gilead Sciences.

Effect of azithromycin maintenance treatment on infectious exacerbations among patients with non-cystic fibrosis bronchiectasis: the BAT randomized controlled trial.

IMPORTANCE: Macrolide antibiotics have been shown beneficial in cystic fibrosis (CF) and diffuse panbronchiolitis, and earlier findings also suggest a benefit in non-CF bronchiectasis. OBJECTIVE: To determine the efficacy of macrolide maintenance treatment for adults with non-CF bronchiectasis. DESIGN, SETTING, AND PARTICIPANTS: The BAT (Bronchiectasis and Long-term Azithromycin Treatment) study, a randomized, double-blind, placebo-controlled trial conducted between April 2008 and September 2010 in 14 hospitals in The Netherlands among 83 outpatients with non-CF bronchiectasis and 3 or more lower respiratory tract infections in the preceding year. INTERVENTIONS: Azithromycin (250 mg daily) or placebo for 12 months. MAIN OUTCOME MEASURES: Number of infectious exacerbations during 12 months of treatment. Secondary end points included lung function, sputum bacteriology, inflammatory markers, adverse effects, symptom scores, and quality of life. RESULTS: Forty-three participants (52%) received azithromycin and 40 (48%) received placebo and were included in the modified intention-to-treat analysis. At end of study, the median number of exacerbations in the azithromycin group was 0 (interquartile range [IQR], 0-1), compared with 2 (IQR, 1-3) in the placebo group (P < .001). Thirty-two (80%) placebo-treated vs 20 (46%) azithromycin-treated individuals had at least 1 exacerbation (hazard ratio, 0.29 [95% CI, 0.16-0.51]). In a mixed-model analysis, change in forced expiratory volume in the first second of expiration (percent of predicted) over time differed between groups (F1,78.8 = 4.085, P = .047), with an increase of 1.03% per 3 months in the azithromycin group and a decrease of 0.10% per 3 months in the placebo group. Gastrointestinal adverse effects occurred in 40% of patients in the azithromycin group and in 5% in the placebo group (relative risk, 7.44 [95% CI, 0.97-56.88] for abdominal pain and 8.36 [95% CI, 1.10-63.15] for diarrhea) but without need for discontinuation of study treatment. A macrolide resistance rate of 88% was noted in azithromycin-treated individuals, compared with 26% in the placebo group. CONCLUSIONS AND RELEVANCE: Among adults with non-CF bronchiectasis, the daily use of azithromycin for 12 months compared with placebo resulted in a lower rate of infectious exacerbations. This could result in better quality of life and might influence survival, although effects on antibiotic resistance need to be considered. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00415350.

Treatment of haemothorax.

Haemothorax is a problem commonly encountered in medical practice and is most frequently related to open or closed chest trauma or to invasive procedures of the chest. Spontaneous haemothorax is less common and can have various causes, such as the use of anticoagulants, neoplasia, and rupture of pleural adhesions. Identification by radiography and thoracentesis is indicated and treatment of the underlying trauma should start immediately. After insertion of a large chest tube, antibiotic prophylaxis in trauma patients should be administered for 24 h. Further treatment depends on the haemodynamic stability of the patient, the volume of evacuated blood and the occurrence of persistent blood loss. Surgical exploration by VATS or thoracotomy is necessary if >1.500 ml of blood has accumulated and/or an ongoing production of >200 ml of blood per hour is observed. If the haemorrhage is less severe, careful investigation into the underlying cause must be performed and blood should be evacuated by tube thoracostomy. If clotted blood retained in spite of tube thoracostomy, intrapleural fibrinolytic therapy can be applied to breakdown clots and adhesions. If conservative treatment is insufficient, a surgical approach with VATS or thoracotomy is indicated to prevent subsequent complications.

A patient with endobronchial BALT lymphoma successfully treated with radiotherapy.

Low-grade bronchus-associated lymphoid tissue (BALT) lymphoma is a rare tumour originating from the marginal zone of lymphoid tissue. It is a subgroup of B-cell extranodal non-Hodgkin's lymphoma with an indolent course. We report a case of this tumour with characteristic histologic feature. The patient had non-specific respiratory complaints. The tumour occluded the right bronchus intermedius. He received radiation therapy alone, resulting in complete remission of the tumour and disappearance of symptoms.

Bronchoscopic diagnosis of pulmonary infiltrates in granulocytopenic patients with hematologic malignancies: BAL versus PSB and PBAL.

BACKGROUND: Treatment of patients with hematologic malignancies is often complicated by severe respiratory infections. Bronchoscopy is generally to be used as a diagnostic tool in order to find a causative pathogen. OBJECTIVES: In a prospective study the combination of protected specimen brush (PSB) and protected bronchoalveolar lavage (PBAL) was compared with bronchoalveolar lavage (BAL) for evaluated feasibility and diagnostic yield in granulocytopenic patients with hematologic malignancies and pulmonary infiltrates. METHODS: All specimens from 63 bronchoscopic procedures (35 BAL and 28 PSB-PBAL) were investigated by cytological examination and various microbiological tests. If clinically relevant and feasible, based on the clinical condition and/or the presence of thrombocytopenia, lung tissue samples were obtained. RESULTS: The majority of the 58 included patients were diagnosed as having acute myeloid leukaemia and developed a severe neutropenia (BAL-group: 27 days; PSB-PBAL group: 30 days). Microbiological and cytological examination of 63 bronchoscopic procedures (35 BAL and 28 PSB-PBAL) yielded causative pathogens in 9 (26%) patients of the BAL-group and 8 (29%) patients of the PSB-PBAL group (PSB and PBAL 4 each). Aspergillus fumigatus was the pathogen most frequently (13%) detected. Using all available examinations including the results of autopsy, a presumptive diagnosis was established in 43% of the patients in the BAL group and 57% of those in the PSB-PBAL group; in these cases microbial aetiology was correctly identified in 67% and 57%, respectively. The complication rate was of these procedures were low, and none of the patients experienced serious complications due to the invasive techniques. CONCLUSIONS: Our results showed that modern bronchoscopic techniques such as PSB and PBAL did not yield better diagnostic results compared to BAL in granulocytopenic patients with hematologic malignancies and pulmonary infiltrates. In approximately half of the cases a presumptive diagnosis was made by bronchoscopic procedures.

Legionnaires' disease at a Dutch flower show: prognostic factors and impact of therapy.

After a large outbreak of Legionnaires' disease in the Netherlands, we determined risk factors for intensive care unit (ICU) admission and death and the impact of adequate therapy on ICU-free survival among 141 hospitalized patients. Overall mortality rate was 13%, and ICU mortality rate was 36%. Smoking, temperature >38.5 degrees C, and bilateral infiltrates shown on chest x-ray were independent risk factors for ICU admission or death (all p<0.05). Starting adequate therapy within 24 hours after admission resulted in a higher ICU-free survival rate compared to therapy initiation after 24 hours: 78% versus 54%, respectively (p=0.005). However, delay in providing therapy to patients with urinary antigen tests with negative results did not influence outcome. These data suggest that by using the urinary antigen test on admission a more tailored approach to patients with community-acquired pneumonia may be applied.