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Background: Whole-body plethysmography (WBP) with bronchial challenge testing to measure the (specific) airway resistance, (s)R(AW), is considered to be a more sensitive diagnostic procedure than spirometry, which can only measure the forced expiratory volume in one second (FEV1). The evidence for the added diagnostic value of WBP is not yet conclusive., Methods: In a prospective diagnostic study, we carried out WBP with bronchial challenge testing as well as a bronchodilation test in 400 patients with suspected asthma from June 2010 to October 2011. The bronchial provocation test was considered positive if the FEV1 fell by at least 20% and/or the airway resistance doubled, with an increase of the sR(AW) to at least 2.0 kPA × s and/or of the R(AW) to 0.5 kPA × s/L. Follow-up evaluation was performed one year later., Results: The prevalence of asthma in the 302 patients who completed follow-up was 27.5%. The sensitivity of WBP with sR(AW) measurement for asthma was 95.2% (95% confidence interval [CI] 88.3%-98.1%), and its specificity was 81.7% (95% CI 76.1%-86.3%). The sensitivity of FEV1 was 44.6% (95% CI 34.4%-55.3%), and its specificity was 91.3% (95% CI 86.6%-94.4%). The negative predictive value (NPV) of WBP with sR(AW) measurement was 97.8% (95% CI 94.5%-99.1%), while that of FEV1 was 81.3% (95% CI 76.0%-85.7%). The positive predictive value (PPV) of WBP with sR(AW) measurement was 66.4% (95% CI 57.5%-74.2%), while that of FEV1 was 66.1% (95% CI 53.0%-77.1%)., Conclusion: With sR(AW) measurement, asthma can be ruled out with high certainty. Improving the positive predictive value of testing for asthma remains a challenge, however, as sR(AW) measurement does not yield any increase in specificity.

Objectives: To compare the prognostic value of FENO with bronchoprovocation testing when the clinical course within the first year after assessment was taken into account; to compare the prognostic values with respect to eosinophilic versus non-eosinophilic inflammatory pattern., Methods: Cross-sectional diagnostic study with a delayed-type reference standard in 393 patients attending a private practice of pneumologists with complaints suspicious of obstructive airway disease., Index Test: FENO measurement. Reference standard: ratio FEV1/VC or airway resistance assessed by body plethysmography, with additional bronchoprovocation or bronchodilator testing, as well as spontaneous sputum (smear slides). This was combined with a follow-up evaluation by a structured interview after 12 months., Results: 302 (76.8%) patients were reached for follow-up. Regarding asthma diagnosis, the area under the curve (AUC) for FENO was 0.603 (95%CI 0.528-0.677) for the whole group. With eosinophilic asthma as target, AUC increased (0.819 (95%CI 0.703-0.934)) and exceeded that of bronchoprovocation (0.711 (95%CI 0.584-0.874)). FENO showed no diagnostic value in non-eosinophilic asthma. In patients reporting wheezing and allergic rhinitis at the initial assessment, its positive predictive value was 90.9% (95%CI 62.3%-98.4) at a cut-off of 45 ppb, and 100% (95%CI 56.6-100%) at 81 ppb., Conclusions: FENO bears limited information when measured non-specifically in primary care, but is useful for diagnosing eosinophilic asthma. If sputum is not available, information on wheezing and rhinitis can narrow down the range of patients in whom FENO is informative. Moreover, the evaluation of the clinical value of FENO benefits from taking into account follow-up data to confirm the diagnosis., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Objectives: To determine the diagnostic accuracy of fractional exhaled nitric oxide (FENO) measurement in pneumologists routine diagnostic work-up; and to determine the impact of the inflammatory pattern on diagnostic accuracy., Methods: Prospective diagnostic study in 393 patients attending a private practice of pneumologists with complaints suspicious of obstructive airway disease (OAD). Index test was FENO measurement. Reference standard was the Tiffeneau ratio (FEV(1)/VC) or airway resistance as assessed by whole body plethysmography, with additional bronchoprovocation or bronchodilator testing. Morning sputum was analysed with smear slides which were prepared and stained by Giemsa., Results: 154 patients were diagnosed as having asthma (145 diagnoses based on bronchial provocation, 9 based on bronchodilator results), 5 had COPD. For the whole group, asthma could be ruled in at FENO > 71 ppb (PPV 80%; 95% CI 63-90%) and ruled out at FENO ≤ 9 ppb (NPV 82%; 95% CI 67-91%) (area under the curve (AUC) = 0.656; 95% CI 0.600-0.712; p < 0.001). 128 patients delivered sputum. FENO was 44.3 ppb (sd 48.9) in patients with predominant eosinophilic inflammation, 18.5 ppb with neutrophilic inflammation, and 23.1 ppb in others (p = 0.003). Diagnostic accuracy of FENO increased when patients with neutrophilic inflammation were omitted from analysis (AUC = 0.745; 95% CI 0.651-0.838; p < 0.001). Then asthma could be ruled in at FENO > 31 ppb (PPV 82%; 95% CI 63-92%) and ruled out at FENO ≤ 12 ppb (NPV 81%; 95% CI 62-91%)., Conclusions: FENO measurement can be useful as an additional diagnostic tool in pneumologists' practice. The diagnostic value of FENO could be improved when inflammatory patterns are taken into account., (Copyright © 2012. Published by Elsevier Ltd.)

Objective: To determine the diagnostic accuracy and diagnostic patterns of clinical symptoms in patients suspected to suffer from obstructive airway diseases (OADs) within different health care sectors., Study Design and Setting: Ten general practices (219 patients), one practice of pneumologists (259 patients) and one specialist hospital (300 patients). Sensitivities, specificities, positive (LR+), and negative (LR-) likelihood ratios of clinical symptoms were compared with lung function testing., Results: Thirty-one percent had chronic obstructive pulmonary disease (COPD), 21% had asthma. Sensitivities increased and specificities decreased from outpatient to hospital setting. The multivariate model of adjusted likelihood ratios for COPD showed LR+=4.86 (95% confidence interval [CI]=2.09-11.29) and LR-=0.07 (95% CI=0.01-0.43) of the combination "wheezing," "dyspnea when going upstairs," "smoking" in general practice. In hospital, the combination "dyspnea when going upstairs," "dyspnea during minimal exercise," and "smoking" showed LR+=3.34 (95% CI=2.08-5.31) and LR-=0.02 (95% CI=0.01-0.12). The combination "no coughing," "dyspnea attacks," and "no smoking" showed LR+=4.08 (95% CI=1.67-10.4) and LR-=0.24 (95% CI=0.12-0.58) for asthma in general practice. The combination "dyspnea attacks" and "no dyspnea when walking" showed LR+=6.48 (95% CI=1.01-40.94) and LR-=0.28 (95% CI=0.11-0.75) for asthma in hospital., Conclusion: Clinical decision rules for OAD need to be derived from original studies in their respective settings or assessed on their transferability to other settings., (Copyright © 2012 Elsevier Inc. All rights reserved.)

The increasing panel of systemic therapies enables the individual management of cancer patients, even in advanced stages. However, diagnostic tools indicating early the efficacy of therapy are still needed. In prospectively collected sera of 161 patients with recurrent non-small cell lung cancer (NSCLC) receiving second-line chemotherapy, the courses of nucleosomes, cytokeratin-19 fragments (CYFRA 21-1), carcinoembryonic antigen (CEA), neuron-specific enolase (NSE), and progastrin-releasing peptide (ProGRP) were investigated and correlated with therapy response. At high specificity for detection of progressive disease, most sensitive biomarkers were identified and included in a combination model. High levels and insufficient decreases of nucleosomes and CYFRA 21-1 during the first cycle of therapy indicated poor outcome. Combination of nucleosome concentrations at day 8 and CYFRA 21-1 before start of the second cycle enabled the early detection of progressive disease with a sensitivity of 34.4% at 95% specificity (AUC 0.79) prior to imaging techniques. When cutoffs were fixed at the 90th percentile of responding patients, the combination model achieved sensitivities of 19% at 100% specificity and of 52% at 88% specificity. Thus, nucleosomes and CYFRA 21-1 showed to be valuable for the individual management of patients with recurrent NSCLC.

Purpose: Besides new therapeutic drugs, effective diagnostic tools indicating early the efficacy of therapy are required to improve the individual management of patients with nonoperable cancer diseases., Experimental Design: In prospectively collected sera of 128 patients with newly diagnosed small cell lung cancer receiving first-line chemotherapy, the courses of nucleosomes, progastrin-releasing peptide (ProGRP), neuron-specific enolase (NSE), cytokeratin-19 fragments (CYFRA 21-1), and carcinoembryonic antigen were investigated and correlated with therapy response objectified by computed tomography before start of the third treatment course., Results: In univariate analyses, high levels and insufficient decreases of nucleosomes, ProGRP, NSE, and CYFRA 21-1 during the first and second cycles of therapy correlated with poor outcome. Insufficient response to therapy was most efficiently indicated by the baseline values of nucleosomes, ProGRP, and CYFRA 21-1 before the second therapy cycle reaching areas under the curve (AUC) of 81.8%, 71.3%, and 74.9% in receiver operating characteristic curves, respectively. Combinations of nucleosomes with ProGRP (AUC 84.1%), CYFRA 21-1 (AUC 82.5%), and NSE (AUC 83.6%) further improved the diagnostic power in the high specificity range and yielded sensitivities of 47.1%, 35.3%, and 35.3% at 95% specificity, respectively. In multivariate analyses, including clinical and biochemical variables, only performance score and nucleosomes before cycle 2 were found to independently indicate therapy response., Conclusions: Biochemical markers specifically identified patients with insufficient therapy response at the early treatment phase and showed to be valuable for diseases management of small cell lung cancer.

Background and Aim: In patients with ventilatory pump disorder cardiac decompensation can occur after introduction of nasal intermittent positive pressure ventilation therapy (nasal IPPV). Therefore we carried out hemodynamic measurements in eight patients., Patients and Methods: Before starting non-invasive ventilation and 1 hour later we measured pulmonary artery pressures, central venous pressures, pulmonary capillary wedge pressures and cardiac output. Blood gas analysis of arterial and mixed venous blood were carried out. We calculated oxygen delivery and oxygen extraction rate., Results: After 1 hour of ventilation cardiac output was reduced from 5.9 l/min to 4.1 l/min, oxygen delivery was reduced from 1002 ml/min to 771 ml/min. These results were significant. Three patients were measured hourly during a prolonged period of ventilation. After 4 to 6 hours cardiac output almost reached again the level before ventilation., Conclusion: Similar to invasive ventilation or nCPAP-therapy non-invasive ventilation (nIPPV) causes a significant reduction of cardiac output 1 hour after starting ventilation. An adaptation of cardiac output could be reached after a couple of hours.