Kathleen Jahn

Galactomannan in Bronchoalveolar Lavage for Diagnosing Invasive Fungal Disease

RATIONALE Invasive fungal disease (IFD) is a significant cause of morbidity and mortality in immunocompromised patients. OBJECTIVES We hypothesize that galactomannan (GM), a component of fungal cell wall, as measured in bronchoalveolar lavage (BAL) might be a diagnostic adjunct in hematologic malignancies. METHODS A total of 568 hematologic cases undergoing diagnostic bronchoscopy because of respiratory symptoms and/or suspected IFD between 2009 and 2013 at a tertiary care center in Switzerland were included in this prospective, observational cohort study. We compared accuracy of the BAL GM ELISA determination in predicting IFD as classified by the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group (EORTC/MSG) definition. MEASUREMENTS AND MAIN RESULTS BAL GM was positive in 155 cases (29.2%). According to the EORTC/MSG criteria, IFD was classified as possible in 182 (34.3%), probable in 45 (8.5%), and proved in six (1.1%). BAL GM provided 50% sensitivity, 73.0% specificity, 16% positive predictive value, and 93% negative predictive value for diagnosing proven+probable IFD. Results were similar when antifungal treatment and radiologic suspicion of IFD were used as the gold standard. The area under the curve of the receiver operating characteristic curve for the diagnosis of proven+probable IFD was 0.716 (95% confidence interval, 0.638-0.794; P < 0.001). CONCLUSIONS GM in BAL had modest agreement with EORTC/MSG criteria for diagnosing IFD in immunocompromised patients with a high degree of antifungal exposure.

Propofol versus Midazolam in Medical Thoracoscopy: A Randomized, Noninferiority Trial

Background: Hypoxemia is a surrogate marker for periprocedural endoscopic complications. There are no data comparing the safety of propofol sedation with another sedative regimen in medical thoracoscopy. Objective: To evaluate whether sedation with propofol is as safe and effective as sedation with midazolam. Methods: Ninety consecutive patients undergoing medical thoracoscopy were randomly allocated to receive either intravenous propofol or midazolam. Predefined periprocedural complications included hypoxemia, hypotension, bleeding, need for airway insertion, mechanical ventilation, intensive care unit transfer and death. The primary endpoint was the mean lowest oxygen saturation during the procedure. Results: Randomized groups had similar demographics (64 ± 16 years, 57% male, 91% American Society of Anesthesiologists class III-IV) and a balanced distribution of procedures. The mean lowest oxygen saturation during the procedure was significantly lower in the propofol group as compared to the midazolam group (93 ± 6 vs. 96 ± 3%, p = 0.007). Patients randomized to propofol showed more episodes of hypoxemia (27 vs. 4%, p = 0.007) and hypotension (82 vs. 40%, p < 0.0001). No procedure had to be aborted. None of the patients required an artificial airway, mechanical ventilation or intensive care unit care, and none died. Conclusions: As assessed by the surrogate marker hypoxemia, propofol should not be considered the first choice for sedation in medical thoracoscopy.

Magnetic Resonance Imaging–Confirmed Pleuritis in Systemic Lupus Erythematosus–Associated Shrinking Lung Syndrome

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Treatment of COPD Exacerbation in Switzerland: Results and Recommendations of the European COPD Audit

Background: The European COPD Audit initiated by the European Respiratory Society (ERS) evaluated the management of hospital admissions due to exacerbation of chronic obstructive pulmonary disease (COPD) in several European countries. Data on the treatment of severe acute exacerbations of COPD (AECOPDs) in Switzerland are scarce. Objectives: In light of the GOLD 2010 guidelines, this work aims to examine the quality of care for AECOPD and to provide specific recommendations for the management of severe AECOPD in Switzerland. Methods: A total of 295 patients requiring hospital admission to 19 Swiss hospitals due to exacerbation of COPD during a predefined 60 days in 2011 were included in the study. We compared the Swiss data to the official GOLD 2010 recommendations and to the results of the other European countries. Results: Approximately 43% of the Swiss patients with severe AECOPD were current smokers at hospital admission, compared to 33% of the patients in other European countries (p < 0.001). In Switzerland and in Europe, spirometry data were not available for most patients at hospital admission (65 and 60%, respectively; p = 0.08). In comparison to other European countries, antibiotics were prescribed 14% less often in Switzerland (p < 0.001). Only 79% of the patients in the Swiss cohort received treatment with a short-acting bronchodilator at admission. Conclusions: Considering the overall high standard of health care in Switzerland, in light of the GOLD 2010 guidelines we are able to make 7 recommendations to improve and standardize the management of severe AECOPD for patients treated in Switzerland.

Flexible bronchoscopy with moderate sedation in COPD: a case–control study

Background Flexible bronchoscopy is increasingly used for diagnostic and therapeutic purposes. We aimed to examine the safety of flexible bronchoscopy with moderate sedation in patients with COPD. Methods This study is a prospective, longitudinal, case–control, single-center study including 1,400 consecutive patients. After clinical and lung function assessments, patients were dichotomized in COPD or non-COPD groups. The primary end point was the combined incidence of complications. Results The incidence of complications was similar in patients with and without COPD and independent of forced expiratory volume in the first second % predicted. Patients with COPD more frequently required insertion of a naso- or oropharyngeal airway; however, this difference was no longer significant after adjustment for age, gender, and duration of the procedure. Hypotension was significantly more common among patients with COPD. The number of episodes of hypoxemia ≤90% did not differ between the groups. However, patients with COPD had a lower mean and nadir transcutaneous oxygen saturation. Transcutaneous carbon dioxide tension (PtcCO2) change over the time course was similar in both groups, but both peak PtcCO2 and time on PtcCO2 >45 mmHg were higher in the COPD group. There were no differences in patient-reported outcomes. Conclusion The safety of flexible bronchoscopy is similar in patients with and without COPD. This finding confirms the suitability of the procedure for both clinical and research indications.

Molecular diagnostics for bacterial infections in bronchoalveolar lavage--a case-control, pilot study.

QUESTIONS UNDER STUDY The differentiation between infectious and noninfectious pulmonary complications is challenging. Rapid, accurate microbiological results may allow appropriate antibiotic therapy, withholding or adapting antibiotics, and thus reducing costs and risks of empirical antibiotic therapy. The objective of this proof-of-concept pilot study was to investigate the diagnostic yield of a new polymerase chain-reaction (PCR) and microarray-based rapid molecular diagnostic assay and compare the results to conventional microbiology cultures and clinical judgment. METHODS Bronchoalveolar lavage specimens were obtained from 35 patients undergoing bronchoscopy for diagnostic reasons. Cases (n = 22) consisted of patients with suspicion of pulmonary bacterial infection. Controls (n = 13) were identified among patients undergoing bronchoscopy for indications other than suspicion of infection. RESULTS Demographics were similar in cases and controls. The majority (73%) of patients with pulmonary infection were on empirical antibiotic therapy. Among the 22 cases, bacteria were identified by means of PCR in 77% (n = 17) as compared with 41% (n = 9) by culture (p = 0.030). In contrast, controls yielded a PCR positive result in 45% (n = 7), as compared with no positive cultures (p = 0.005). Compared with culture results, PCR had a sensitivity of 87.5% (95% confidence interval [CI] 47.4-97.9) and specificity of 28.6% (95% CI 8.6-58.1) to diagnose bacterial infection. Compared with clinical judgment, corresponding figures were 77.3% (95% CI 54.5-91.1) and 46.2% (95% CI 19.3-74.8), respectively. CONCLUSION The PCR- and microarray-based rapid molecular diagnostic assay offers an alternative to conventional cultures for detection of potentially pathogenic bacteria in bronchoalveolar lavage of patients with pneumonia. However, the clinical relevance is unclear as it may also detect colonisers in patients without a corresponding infection.

“Exercise induced asthma” is not always asthma

A 25 year old woman was referred to our center for further evaluation of an exercise-induced dyspnea. Moreover, the patient suffered from hoarseness and recurrent sinusitis and otitis. After initially finding nothing suspicious, a spiro-ergometry was performed. Interestingly, we saw a relevant limitation of the inspiratory flow-volume curve under maximal exercise load. Further evaluation (in particular the bronchoscopy and the resulting biopsies) led us to the final diagnosis of a granulomatosis with polyangiitis. After 4 weeks of an established therapy regime with prednisone and rituximab the prior detected subglottic stenosis and the inspiratory flow-volume curve limitation could no longer detected. We describe a rare differential diagnosis of an exercise-induced asthma and we underline the importance of a multimodal therapy concept. We highlight the critical nature of the flow-volume curve in spiro-ergometry under maximal exercise load. We recommend frequent follow-up control visits to monitor the subglottic stenosis.

Treatment of mycophenolate-resistant immune-related organizing pneumonia with infliximab

BackgroundThe development of pulmonary immune-related adverse events (irAEs) in patients undergoing PD-(L)1 targeted checkpoint inhibitors are rare, but may be life-threatening. While many published articles and guidelines are focusing on the presentation and upfront treatment of pulmonary irAEs, the strategy in patients with late-onset pneumonia that are resistant to commonly used immunosuppressive drugs remains unclear.Case presentationHere, we report the successful treatment of a mycophenolate-resistant organizing pneumonia (OP) with infliximab in a patient with metastatic melanoma after PD-1 blockade. The patient received two years of PD-1 targeted immunotherapy when he developed multiple nodular lung lesions mimicking a metastatic progression. However, wedge resection of these lesions showed defined areas of OP, which responded well to corticosteroids. Upon tapering, new foci of OP developed which were resistant to high-dose steroids and mycophenolate treatment. The TNFα antagonist infliximab led to a rapid and durable regression of the inflammatory lesions.ConclusionThis case describes a not well-studied situation, in which a mycophenolate-resistant PD-1 blocker-associated pneumonitis was successfully treated with a TNFα neutralizing antibody. The outcome of this case suggests that infliximab might be the preferable option compared to classical immunosuppressants in the case of steroid-resistant/−dependent late onset pulmonary irAEs.

Multiplex PCR on the Bronchoalveolar Lavage Fluid of Immunocompromised Patients

Characteristic Value Age, y 57.63 14.73 Male sex 306 (58.6) Hospitalization (IQR), d 11 (3; 25) Symptoms and signs Cough 300 (57.5) Dyspnea 124 (23.8) Sputum 118 (22.6) Fever 108 (20.7) Decrease in FEV1 % predicted 59 (11.3) Reasons for immunosuppression Allogenic HSCT 112 (21.5) Lung transplantation 83 (15.9) Other hematologic therapies 79 (15.1) Interstitial lung disease 59 (11.3) Connective tissue disease 52 (10.0) Chemotherapy 37 (7.1) Solid cancer 29 (5.6) HIV/AIDS 25 (4.8) Other conditions 20 (3.8) Renal transplantation 23 (4.4) Autologous HSCT 21 (4.0) Liver transplantation 5 (1.0) Treatment Systemic steroids 271 (51.9) Mycophenolate 154 (29.5) Tacrolimus 109 (20.9) Cyclosporine 75 (14.4) Chemotherapy 72 (13.8) Methotrexate 22 (4.2) Azathioprine 21 (4.0) Highly active antiretroviral agents 17 (3.3) (Continued) Pleural effusion 6 (1.1) Bronchiolitis 5 (0.96) Atelectasis 2 (0.38) Empyema and/or abscess 2 (0.38) Pleural plaques 1 (0.19) Cysts 1 (0.19) Macroscopic bronchoscopy findings No pathologic finding 193 (37.0) Erythema of the mucosa 167 (32.0) Purulent secretion 85 (16.3) Nonpurulent secretion 77 (14.8) Bloody secretion 40 (7.7) Endobronchial tumor 6 (1.1) Others 11 (2.1) Clinical final diagnosis Infection 320 (61.3) Nonpulmonary infection 122 (23.4) Progression of underlying disease 35 (6.7)

An unexpected cause of diffuse alveolar hemorrhage in a kidney transplant patient.

Diffuse alveolar hemorrhage (DAH) is a life-threatening condition requiring urgent treatment. There are many different treatment-relevant causes of DAH, making the diagnostic approach to these patients complex and necessitating a multidisciplinary team. We report the case of a kidney transplant recipient in whom all diagnostic efforts did not reveal the cause of DAH, and only autopsy was able to establish an unexpected diagnosis.