Novel tests for diagnosis of invasive aspergillosis in patients with underlying respiratory diseases.

RATIONALE: Invasive pulmonary aspergillosis has been increasingly reported in nonneutropenic patients, including those with underlying respiratory diseases. OBJECTIVES: We compared the diagnostic performances of galactomannan, 1,3-ß-D-glucan, and Aspergillus-specific lateral-flow device tests with that of conventional culture by using bronchoalveolar lavage fluid samples from patients with underlying respiratory diseases. METHODS: We analyzed 268 bronchoalveolar lavage samples from 221 patients with underlying respiratory diseases (and without hematologic malignancy or previous solid organ transplantation) that were collected for routine microbiological workup between February 2012 and May 2014 at the University Hospital of Graz, Austria. Invasive pulmonary aspergillosis was defined according to European Organization of Research and Treatment of Cancer/Mycoses Study Group criteria modified for patients with respiratory diseases. MEASUREMENTS AND MAIN RESULTS: Thirty-one patients (14%) had probable or proven, 25 possible, and the remaining 165 patients no invasive pulmonary aspergillosis. Probable/proven aspergillosis was associated with a significantly higher (P = 0.034) 30-day mortality rate of 32%. Sensitivities, specificities, and diagnostic odd ratios differed markedly between galactomannan (cut-off 0.5: optical density index, 0.97, 0.81, 124.4; cut-off 1.0: 0.97, 0.93, 422.1; cut-off 3.0: 0.61, 0.99, 109.8), ß-D-glucan (cut-off 80 pg/ml: 0.90, 0.42, 6.57; cut-off 200 pg/ml: 0.70, 0.61, 3.7), lateral-flow device tests (0.77, 0.92, 41.8), and mycological culture (0.29, 0.97, 14). CONCLUSIONS: Probable or proven invasive pulmonary aspergillosis was diagnosed in 14% of our study population and associated with significantly higher 30-day mortality rates. Although the performance of ß-D-glucan was limited by low specificity and that of mycological culture by low sensitivity, the Aspergillus lateral-flow device seems to be a promising alternative to galactomannan testing, which remains the diagnostic gold standard for aspergillosis. Clinical trial registered with www.clinicaltrials.gov (NCT 02058316).

Diagnostic accuracy of the Aspergillus-specific bronchoalveolar lavage lateral-flow assay in haematological malignancy patients.

We evaluated the performance of the Aspergillus-specific lateral-flow device (LFD) test for diagnosing invasive pulmonary aspergillosis (IPA) in patients with underlying haematological malignancies. Participating centres were the two Austrian University Hospitals of Graz and Innsbruck. LFD performance was evaluated with 95 bronchoalveolar lavage fluid (BALF) samples from 72 patients collected prospectively in Graz, and with 24 BALF bio bank samples from 23 patients (21 samples with probable IPA) in Innsbruck. Invasive fungal infections were classified according to the revised European Organization of Research and Treatment of Cancer/Mycoses Study Group criteria. Overall, 27 patients (30 samples) had probable IPA, 32 (43 samples) possible and 36 (46 samples) did not fulfil IPA criteria. The vast majority of patients - in particular those with probable IPA - received mould-active treatment before bronchoscopy. Sensitivity, specificity, positive predictive value and negative-predictive-value for probable IPA diagnosis using the BALF-LFD test were 71%, 76%, 35% and 94% for the Graz cohort. Sensitivity of the BALF-LFD test for probable IPA was 57% in Innsbruck bio bank samples. Our results indicate that the BALF-LFD-test provides fast results with moderate sensitivities in patients with underlying haematological malignancies. Similar to other diagnostic tests and biomarkers sensitivity of the test may be influenced by ongoing systemic mould-active treatment.

Positional therapy in sleep apnoea - one fits all? What determines success in positional therapy in sleep apnoea syndrome.

INTRODUCTION: Positional therapy is a simple means of therapy in sleep apnoea syndrome, but due to controversial or lacking evidence, it is not widely accepted as appropriate treatment. In this study, we analysed data to positional therapy with regard to successful reduction of AHI and predictors of success. METHODS: All consecutive patients undergoing polysomnography between 2007 and 2011 were analysed. We used a strict definition of positional sleep apnoea syndrome (supine-exclusive sleep apnoea syndrome) and of therapy used. Patients underwent polysomnography initially and during follow-up. RESULTS: 1275 patients were evaluated, 112 of which had supine-exclusive sleep apnoea syndrome (AHI 5-66/h, median 13/h), 105 received positional therapy. With this treatment alone 75% (70/105) reached an AHI <5/h, in the follow-up 1 year later 37% (37/105) of these still had AHI<5/h, 46% (43/105) yielded an AHI between 5 and 10/h. Nine patient switched to APAP due to deterioration, 3 wanted to try APAP due to comfort reasons. At the last follow-up, 32% patients (34/105) were still on positional therapy with AHI <5/h. BMI was a predictor for successful reduction of AHI, but success was independent of sex, the presence of obstructive versus central sleep apnoea, severity of sleep apnoea syndrome or co-morbidities. CONCLUSION: Positional therapy may be a promising therapy option for patients with positional sleep apnoea. With appropriate adherence it yields a reasonable success rate in the clinical routine.

Sleep Related Breathing Disorders and Inflammation - The Missing Link? A Cohort Study Evaluating the Interaction of Inflammation and Sleep Related Breathing Disorders and Effects of Treatment.

INTRODUCTION: Sleep related breathing disorders (SRBD) are associated with both obesity and systemic inflammation. While the relationship between obesity and SRBD is established, the causality between inflammation and SRBD remains unclear. In this study we investigated the relation between SRBD and C-reactive protein (CRP) as a parameter of inflammation and the influence of SRBD treatment on CRP with additional regard to changes in metabolic and cardiovascular parameters. METHODS: Polysomnography (PSG) and laboratory data of patients diagnosed with SRBD over a period of 5 years were prospectively collected in a database and retrospectively analysed regarding the association of SRBD (according to apnoea-hypopnoea- index (AHI), duration of events and extent of desaturation) to CRP, blood pressure, cholesterol, fasting plasma glucose, HbA1c, quality of life measured via a visual analogue scale (VAS 0-100%), and the effects of SRBD therapy on these parameters. RESULTS: 716 patients were included in the study, 171 with mild SRBD (AHI ≥5 to <15/h), 209 with moderate SRBD (AHI 15 to <30/h), 336 with severe SRBD (AHI ≥30/h). Results according to severity of SRBD. Severe SRBD was significantly associated with elevated levels of CRP (3.7 [1.8-7.0] mg/l, vs. moderate (p = 0.001), and mild SRBD (p<0.001), and higher prevalence of hypertension as compared to moderate and mild SRBD (p<0.001, respectively). Results in highly successful treatment. If SRBD treatment was highly successful (AHI <5/h), CRP and quality of life improved significantly (p = 0.001 and p = 0.002), as did blood pressure (p<0.001 for systolic and diastolic values), although BMI increased (p<0.001). Results in partially successful treatment. If success was defined as reduction of AHI of ≥50%, CRP also decreased (p<0.001), as did blood pressure (p<0.001). Again, BMI increased (p<0.001). CONCLUSION: This is the first study to show an association of SRBD and CRP independently of BMI in a large cohort. The SRBD therapy-induced CRP decrease was not associated with BMI changes or metabolic changes but rather with the magnitude of AHI improvement.

Toxocarosis and putative DRESS syndrome in an oncological patient: a case report.

Toxocarosis is a parasitic infection caused by Toxocara canis or Toxocara cati. Their definite hosts are the domestic dog and cat, where their adult forms live within the lumen of the small intestine. In humans, infective larvae hatch after ingestion of eggs, but the juvenile stages fail to develop into mature adult worms. Instead, they migrate through the body with the potential to affect virtually every body site. DRESS syndrome (drug reaction with eosinophilia and systemic symptoms) is a serious cutaneous drug reaction, which also involves other organ systems. We report on a 45-year-old man who was admitted with fever up to 40 °C, skin rash and pruritus not responding to amoxicillin/clavulanic acid. Laboratory results showed a slightly elevated white blood cell count, with 62 % eosinophils. History revealed contact to roaming cats. Travel history was unremarkable. Extensive diagnostic workup was performed, and the patient was finally diagnosed with DRESS syndrome, responded to systemic corticosteroid therapy and was discharged. Serology for Toxocara came back positive a few days later. Stool was again sent for microscopy and was found positive for Giardia lamblia, which was treated with a 5-day course of metronidazole. The patient had again developed rash and eosinophilia (62 %). Total immunoglobulin (Ig)E was 1,689 U/l (normal limit: < 100 689 U/l). Follow-up serology showed a marked increase of Toxocara TES ELISA IgG (70 U, normal limit: < 20 U), confirming toxocarosis. Antiparasitic treatment with albendazole 400 mg bid for 5 days was initiated; eosinophilia resolved; and the patient had no further complaints. Although generalized exanthema due to Toxocara has not yet been described in literature, toxocarosis is known to cause a wide spectrum of cutaneous manifestations. Whether our patient had both, a drug reaction with eosinophilia and systemic symptoms and a parasitic infection, or whether a hypersensitivity reaction to Toxocara antigen was mimicking a DRESS syndrome remains unclear.