Development of a diagnostic score using FeNO and symptoms to predict asthma.

BACKGROUND: Fractional exhaled nitric oxide (FeNO) is known as effective for ruling-in asthma. The diagnostic value might be increased in combination with clinical signs and symptoms (CSS). The aim was to develop a new model for ruling-in and ruling-out asthma. METHODS: Diagnostic multi-centre study in three practices of pneumologists in Germany. Whole-body plethysmography was combined with bronchodilation tests or bronchial provocation as diagnostic reference standard. Follow-up was performed after 3 months. An expert committee evaluated test results, symptoms, and course of disease for the final diagnosis. Relevant CSS known from guidelines were used to enable combinatorial development of decision rules. Outcomes of multiple logistic regression modeling were translated into a diagnostic score and internally validated by ten-fold cross validation. RESULTS: 308 patients with complete follow-up were included. 186 (60.4%) were female, average age was 44.7 years and 161 (52.5%) had asthma. The average area under the receiver operating curve (AUC) of the diagnostic score was 0.755 (interquartile range 0.721-0.814). Allergic rhinitis, wheezing, dyspnea on exertion, coughing attacks at night, and awakening by shortness of breath were leading symptoms for ruling-in asthma. Frequent coughing and frequent respiratory infections were leading symptoms for ruling-out. The combination of FeNO and CSS allowed ruling-in asthma with a probability of up to 99%, and ruling-out with a post-test probability down to 9%. CONCLUSION: The diagnostic scoring model increased the diagnostic value of FeNO in combination with CSS. The new decision rule allowed to rule-in asthma with high certainty, and also to rule-out with acceptable certainty.

Diagnostic accuracy of FeNO in asthma and predictive value for inhaled corticosteroid responsiveness: A prospective, multicentre study.

Background: Fractional exhaled nitric oxide (FeNO) is promising for diagnosing asthma and could replace bronchial provocation (BP). To date, cut-off values have been derived by post hoc analysis only. The aim was to validate the diagnostic accuracy for predefined FeNO cut-off values and the predictive value for responsiveness to inhaled corticosteroids (ICS). Methods: We conducted a prospective, diagnostic, multicentre study with patients attending three private practices of pneumologists in Upper Bavaria, Germany, from July 3, 2020 to Jan 21, 2022. Index test was FENO measurement. Reference standard was Tiffeneau ratio (FEV1/VC) or airway resistance as assessed by whole body plethysmography, with additional BP or bronchodilation test. Follow-up was performed after 12 weeks. Analyses of Receiver Operating Characteristics curves were conducted to determine the diagnostic accuracy and predictive value of FeNO. Findings: 308 patients with complete follow-up were recruited, 186 (60·4%) were female, average age was 44·7 years, 161 (52·3%) had asthma. Regarding diagnostic accuracy, the area under the curve (AUC) was 0·718 (95% CI 0·661-0·775; p < 0·001). Sensitivity at FeNO >50 ppb was 0·24 (95% CI 0·18-0·32), specificity 0·99 (0·95-1·0), positive predictive value (PPV) 0·95 (0·84-0·99), negative predictive value (NPV) 0·54 (0·48-0·60). In 66 patients with ´wheezing´ and ´allergic rhinitis´, the sensitivity at FeNO >33 ppb was 0·49 (0·34-0·64), specificity 0·88 (0·64-0·99), PPV 0·92 (0·75-0·99), NPV 0·38 (0·23-0·54). In 68 patients with ICS medication, responsiveness was predicted at the cut-off >43 ppb, with a sensitivity of 0·55 (95%CI 0·36-0·74), specificity 0·82 (0·66-0·92), PPV 0·70 (0·47-0·87), NPV 0·71 (0·56-0·84). Interpretation: FeNO measurement allows a valid ruling-in of an asthma diagnosis, whereas ruling-out of asthma is not possible. Enhanced probability of ICS responsiveness is also given with increased FeNO values. Funding: Circassia Germany gave 25% discount on the purchase of three NIOX VERO devices.

Evaluation of the diagnostic accuracy of fractional exhaled nitric oxide (FeNO) in patients with suspected asthma: study protocol for a prospective diagnostic study.

INTRODUCTION: The measurement of fractional exhaled nitric oxide (FeNO) is promising for diagnosing asthma and might substitute for bronchial provocation (BP) tests. To evaluate the diagnostic accuracy of FeNO within a confirmatory study, the following hypotheses will be tested: (1) A FeNO cut-off >50 ppb (parts per billion) is suitable for diagnosing asthma (sensitivity 35%, specificity 95%); (2) If the clinical symptoms 'allergic rhinitis' and 'wheezing' are present, asthma can be diagnosed at FeNO >33 ppb with a positive predictive value (PPV) >70% and (3) A FeNO >33 ppb can predict responsiveness to inhaled corticosteroid (ICS) with a PPV >70%. METHODS AND ANALYSIS: A prospective diagnostic study will be conducted in three practices of pneumologists in Germany. 300 patients suspected of suffering from asthma will be included. As an index test, patients perform FeNO measurement with the device NIOX VERO. As reference a test, patients are examined with whole bodyplethysmography and BP, if necessary. After 3 months, patients with an asthma diagnosis will be examined again to verify the diagnosis and evaluate ICS responsiveness. Patients who did not receive an asthma diagnosis at the initial examination will be phoned after 3 months and asked about persistent respiratory symptoms to exclude false negative findings. As a primary target, sensitivity and specificity of FeNO >50 ppb will be determined. As a secondary target the PPV for asthma at FeNO >33 ppb, when the symptoms 'allergic rhinitis' and 'wheezing' are present, will be calculated. Regarding ICS responsiveness, the PPV of FeNO >33 ppb will be determined. ETHICS AND DISSEMINATION: The study was approved by the Ethical Committee of the Technical University of Munich (Reference number 122/20 S). The major results will be published in peer-reviewed academic journals and disseminated through conferences. TRIAL REGISTRATION NUMBER: DRKS00021125.

Double plating in Vancouver type B1 periprosthetic proximal femur fractures: A biomechanical study.

Periprosthetic hip fractures are an increasing problem in modern orthopedic and trauma surgery. Many options for the operative treatment are available to the surgeon ranging from modern variable angular systems to standard plates, screws, and cerclages. However, there is no gold standard and therefore, the aim of this study, was to investigate the biomechanical characteristics of double plating versus a lateral standard plate in a Vancouver B1 fracture model. Ten 4th generation composite femora were used to implant cementless total hip prosthesis and create Vancouver B1 periprosthetic fractures. Afterwards, the osteotomies were fixed using the locking compression plate in combination with the locking attachment plate (LCP, LAP, DePuy Synthes, Solothurn, Switzerland)-group I. Group II additionally achieved a 5-hole 4.5/5.0 mm LCP anteriorly. Each construct was cyclically loaded to failure in axial compression. Axial construct stiffness was 50.87 N/mm (SD 1.61) for group I compared to 738.68 N/mm (SD 94.8) for group II, this difference was statistically significant (p = 0.016). The number of cycles to failure was also significant higher for group II (2,375 vs. 13,000 cycles; p = 0.016). Double plating can significantly increase construct stiffness and stability, and thus, is an option in the treatment of complex periprosthetic fractures, in revision surgery and for patients with the inability to partial weight bear. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:234-239, 2017.

Volatile isoflurane sedation in cerebrovascular intensive care patients using AnaConDa(®): effects on cerebral oxygenation, circulation, and pressure.

PURPOSE: The anesthetic-conserving device AnaConDa(®), a miniature vaporizer, allows volatile sedation in the intensive care unit (ICU). We investigated the effects of isoflurane sedation on cerebral and systemic physiology parameters in neuromonitored ICU stroke patients. METHODS: Included in the study were 19 consecutive ventilated patients with intracerebral hemorrhage (12), subarachnoid hemorrhage (4), and ischemic stroke (3) who were switched from intravenous propofol or midazolam to inhalative isoflurane sedation for an average of 3.5 days. During the sedation transition, the following parameters were assessed: mean arterial pressure (MAP), intracranial pressure (ICP), cerebral perfusion pressure (CPP), middle cerebral artery mean flow velocity (MFV) and cerebral fractional tissue oxygen extraction (FTOE), as well as systemic cardiopulmonary parameters and administered drugs. RESULTS: After the first hour, mean ICP showed an increase of 2.1 mmHg that was not clinically relevant. Likewise, MFV did not change. MAP and CPP, however, decreased by 6.5 and 6.3 mmHg, respectively. FTOE was reduced slightly from 0.24 to 0.21 (p = 0.03). Over an observation period of 12 h, ICP remained stable, while MAP and thus CPP showed distinct decreases (CPP: -10 mmHg at 6 h, p < 0.001; -7.5 mmHg at 12 h, p = 0.005, when compared to preswitch levels) despite a 1.5-fold increase in vasopressor administration. CONCLUSIONS: We suggest that that it is possible to reach sufficient sedation levels in cerebrovascular ICU patients by applying volatile isoflurane long-term without a relevant increase in ICP, if baseline ICP values are low or only moderately elevated. However, caution should be exercised in view of isoflurane's decreasing effect on MAP and CPP. Multimodal neuromonitoring is strongly recommended when applying this off-label sedation method.