[Guideline for the Diagnosis and Treatment of Asthma - Addendum 2020 - Guideline of the German Respiratory Society and the German Atemwegsliga in Cooperation with the Paediatric Respiratory Society and the Austrian Society of Pneumology]. / S2k-Leitlinie zur Diagnostik und Therapie von Patienten mit Asthma ­ Addendum 2020.

The present addendum of the guideline for the diagnosis and treatment of asthma (2017) complements new insights into the diagnosis and management of asthma as well as for the newly approved drugs for the treatment of asthma. Current, evidence-based recommendations on diagnostic and therapeutic approaches are presented for children and adolescents as well as for adults with asthma.

Cryptochrome mediated magnetic sensitivity in Arabidopsis occurs independently of light-induced electron transfer to the flavin.

Cryptochromes are highly conserved blue light-absorbing flavoproteins which function as photoreceptors during plant development and in the entrainment of the circadian clock in animals. They have been linked to perception of electromagnetic fields in many organisms including plants, flies, and humans. The mechanism of magnetic field perception by cryptochromes is suggested to occur by the so-called radical pair mechanism, whereby the electron spins of radical pairs formed in the course of cryptochrome activation can be manipulated by external magnetic fields. However, the identity of the magnetosensitive step and of the magnetically sensitive radical pairs remains a matter of debate. Here we investigate the effect of a static magnetic field of 500 µT (10× earth's magnetic field) which was applied in the course of a series of iterated 5 min blue light/10 min dark pulses. Under the identical pulsed light conditions, cryptochrome responses were enhanced by a magnetic field even when exposure was provided exclusively in the 10 min dark intervals. However, when the magnetic stimulus was given exclusively during the 5 min light interval, no magnetic sensitivity could be detected. This result eliminates the possibility that magnetic field sensitivity could occur during forward electron transfer to the flavin in the course of the cryptochrome photocycle. By contrast, radical pair formation during cryptochrome flavin reoxidation would occur independently of light, and continue for minutes after the cessation of illumination. Our results therefore provide evidence that a magnetically sensitive reaction is entwined with dark-state processes following the cryptochrome photoreduction step.

Psychometric properties of an English short version of the Trier Inventory for chronic Stress.

BACKGROUND: Although a variety of instruments are available that capture stress experience, the assessment of chronic stress has been hindered by the lack of economical screening instruments. Recently, an English-language version of the Trier Inventory for Chronic Stress (TICS-EN) consisting of 57 items according to a systemic-requirement-resource model of health in nine subdomains of the chronic stress experience has been introduced. METHODS: We constructed a new 9-item short version of the TICS covering all nine subdomains and evaluated it in two samples (total N = 685). We then used confirmatory factor analysis to check factorial validity. RESULTS: This version showed a highly satisfactory model fit, was invariant across participant gender, demonstrated a very high correlation with the original TICS (r = .94), and showed a moderate correlation (r = .58) with a measure of perceived stress in the past month. CONCLUSIONS: Therefore, this theoretically driven instrument can be recommended as a short version of the TICS in English language.

[Staging of liver fibrosis in biliary atresia : Comparison of Chevallier and Ishak score as well as automated evaluation]. / Staging der Leberfibrose bei Gallengangatresie : Vergleich von Chevallier- und Ishak-Score sowie automatisierter Auswertung.

BACKGROUND: Biliary atresia (BA) is a rare disease of the newborn, resulting in liver cirrhosis due to obliterative cholangiopathy. Liver biopsies are commonly performed in order to confirm the diagnosis and in order to stage fibrosis. OBJECTIVES: The present study intended to analyze two established scores for evaluating liver fibrosis focusing on the interobserver variability as well as the prognostic reliability towards the time of liver transplantation. MATERIALS AND METHODS: Liver biopsies of BA patients between 2012 and 2015 were evaluated retrospectively by two pathologists at the Hannover Medical School (MHH) and the RWTH Aachen University Hospital. Fibrosis was measured using Ishak and Chevallier scores. Furthermore, a computerized automatically algorithm-based analyzation (ABAA) was performed. Results were evaluated towards the time point of liver transplantation and hepatoportoenterostomy (HPE). RESULTS: Overall, 34 liver biopsies were analyzed. The Ishak score showed a remarkable interobserver variability (ΚW = 0.68) while the Chevallier score was proven to have a poor interobserver variability (Fleiss' Κappa = -0.01). However, both scores were correlated positively, as was the ABAA (p < 0.001). Regarding prognostic reliability, ROC analyses of the Ishak score revealed the best validity towards an early liver transplantation within 12 months (AUC 0.813, p = 0.011). In addition, an increased Ishak score ≥4 reduced the survival time with the native liver (hazard ratio 6.6 [95% CI 1.9-23.3]). CONCLUSIONS: The Ishak score was revealed to have the best interobserver variability as well as prognostic validity towards an early liver transplantation in BA patients. Due to its easy applicability, the Ishak score was proven superior in comparison to the Chevallier score and ABAA. Therefore, use of the Ishak score is recommended in daily clinical routine for analyzing liver biopsies in BA patients.

Assessment of biological, psychological and adherence factors in the prediction of step-down treatment for patients with well-controlled asthma.

BACKGROUND AND OBJECTIVE: Inhaled corticosteroids (ICS) and inhaled corticosteroids combined with long-acting beta2-agonist (ICS/LABA) are standard treatments for asthma. However, factors that might help reduce medication in well-controlled asthma are unknown. We classified problems of asthma patients into biological, psychological and adherence factors, and investigated factors associated with the indication and failure of a medication step-down treatment. METHODS: Two hundred twenty two well-controlled asthma patients receiving ICS or ICS/LABA were assessed for physical and psychiatric problems and followed up for one year from adjustment of their treatment step. Factor B was defined as a presence of chronic upper airway complications. Factor P was defined as presence of psychiatric complications such as sleep disorder, depression, anxiety and somatoform disorders. Factor A was defined as poor adherence to ICS or ICS/LABA inhaler of 75% or less. Success in step-down treatment was defined as maintenance of well-controlled status for over one year after step-down. RESULTS: Factor B was the most important single negative predictive factor for indication for step-down treatment (Odds ratio; 0.19). Factor A increased the risk of failure to maintain step-down treatment most significantly by 23-fold, and factor B increased it by 11-fold. The combination of factors B and A increased failure by 24-fold, factors P and A by 21-fold, all three factors by 36-fold. Factor P only interacted with the other factors to reduce chances of stepping down, but did not constitute a problem factor when present alone. CONCLUSION AND CLINICAL RELEVANCE: The evaluation of biological, psychological and adherence problems may lead to a more proactive and targeted approach to step-down treatment for patients with well-controlled asthma.

[Guideline for the Diagnosis and Treatment of Asthma - Guideline of the German Respiratory Society and the German Atemwegsliga in Cooperation with the Paediatric Respiratory Society and the Austrian Society of Pneumology]. / S2k-Leitlinie zur Diagnostik und Therapie von Patienten mit Asthma.

The present guideline is a new version and an update of the guideline for the diagnosis and treatment of asthma, which replaces the previous version for german speaking countries from the year 2006. The wealth of new data on the pathophysiology and the phenotypes of asthma, and the expanded spectrum of diagnostic and therapeutic options necessitated a new version and an update. This guideline presents the current, evidence-based recommendations for the diagnosis and treatment of asthma, for children and adolescents as well as for adults with asthma.

Perceived triggers of asthma: key to symptom perception and management.

Adequate asthma management depends on an accurate identification of asthma triggers. A review of the literature on trigger perception in asthma shows that individuals vary in their perception of asthma triggers and that the correlation between self-reported asthma triggers and allergy tests is only modest. In this article, we provide an overview of psychological mechanisms involved in the process of asthma triggers identification. We identify sources of errors in trigger identification and targets for behavioural interventions that aim to improve the accuracy of asthma trigger identification and thereby enhance asthma control.

Omalizumab versus 'usual care': results from a naturalistic longitudinal study in routine care.

BACKGROUND: It is unclear how far the superior efficacy of omalizumab, established in randomized controlled clinical trials of patients with severe allergic asthma (SAA), translates into routine practice and when compared to matched controls. METHODS: New-onset omalizumab-treated (OT) patients with SAA (n = 53) were compared to a matched control group of usual-care (UC) patients (n = 53). Treatment and procedures were naturalistic. Subsequent to a baseline assessment, patients were followed up over at least 6 months with at least two follow-up assessments. Primary clinical outcomes were the number of asthma attacks, persistence of asthma symptoms and degree of control [asthma control test (ACT), Global Initiative for Asthma]. Secondary outcome criteria were quality of life (Euro-Qol 5D) and number of medications. For each outcome we compared within-group effects from baseline to 6-month follow-up as well as between-group effects. RESULTS: OT patients showed significant improvements in number [effect size (ES) = 0.03] and frequency (ES = 0.04) of asthma attacks as well as asthma control (ES = 0.09), whereas controls revealed no significant improvements in these measures. Further improvements in the OT group were found for 'perceived control always' (ACT, p = 0.006), no impairment (ACT, p = 0.02), reduction of sickness days (p = 0.002) and number of medications needed (p = 0.001). CONCLUSIONS: Substantial beneficial effects of omalizumab, similar to those observed in controlled trials and after marketing studies, were confirmed, particularly with regard to the reduction of asthma attacks, persistence of symptoms, asthma control and reduction of concomitant asthma medications. This study provides a tougher test and generalizable evidence for the effectiveness of omalizumab in routine care.

Effects of allergen and trigger factor avoidance advice in primary care on asthma control: a randomized-controlled trial.

BACKGROUND: Allergy contributes significantly to asthma exacerbation, yet avoidance of triggers, in particular allergens, is rarely addressed in detail in regular asthma review in primary care. OBJECTIVE: To determine whether structured, individually tailored allergen and trigger avoidance advice, given as part of a primary care asthma review, improves lung function and asthma control. METHODS: In a randomized-controlled trial 214 adults with asthma in six general practices were either offered usual care during a primary care asthma review or usual care with additional allergen and trigger identification (by skin prick testing and structured allergy assessment) and avoidance advice according to a standardized protocol by trained practice nurses. Main outcome measures were lung function, asthma control, asthma self-efficacy. RESULTS: Both intervention groups were equivalent in demographic and asthma-related variables at baseline. At 3-6-month follow-up, patients receiving the allergen and trigger avoidance review showed significant improvements in lung function (assessed by blinded research nurses) compared with those receiving usual care. Significantly more patients in the intervention group than in the control group showed improvements in forced expiratory volume in 1 s > or =15%. No significant differences were found in self-report measures of asthma control. Asthma-specific self-efficacy improved in both groups but did not differ between groups. CONCLUSIONS: Allergen and trigger identification and avoidance advice, given as part of a structured asthma review delivered in primary care by nurses results in clinically important improvements in lung function but not self-report of asthma control. TRIAL REGISTRATION: ISRCTN45684820.

On the use of magnets to disrupt the physiological compass of birds.

Behavioral researchers have attached magnets to birds during orientation experiments, assuming that such magnets will disrupt their ability to obtain magnetic information. Here, we investigate the effect of an attached magnet on the ability to derive directional information from a radical-pair based compass mechanism. We outline in some detail the geometrical symmetries that would allow a bird to identify magnetic directions in a radical-pair based compass. We show that the artificial field through an attached magnet will quickly disrupt the birds' ability to distinguish pole-ward from equator-ward headings, but that much stronger fields are necessary to disrupt their ability to detect the magnetic axis. Together with estimates of the functional limits of a radical-pair based compass, our calculations suggest that artificial fields of comparable size to the geomagnetic field are not generally sufficient to render a radical-pair based compass non-functional.

Efficient light harvesting through carotenoids.

We review the factors that control the efficiency of carotenoid-chlorophyll excitation transfer in photosynthetic light harvesting. For this we summarize first the recently developed theory that describes electronic couplings between carotenoids and chlorophylls and we outline in particular the influence of length of conjugated system and of symmetry breaking on the couplings. We focus hereby on the structurally solved lycopene-BChl system of LH 2 from Rhodospirillum molischianum and the peridinin-Chl a system of PCP from Amphidinium carterae. In addition, we review recent spectroscopic data for neurosporene, spheroidene and lycopene, three carotenoids with different lengths of conjugated systems. On the basis of the measured energies, emission lineshapes, solution and protein environment lifetimes for their 2A ( g ) (-) and 1B ( u ) (+) states as well as of the theoretically determined couplings, we conclude that the transfer efficiencies from the 2A ( g ) (-) state are controlled by the Car(2A ( g ) (-) )-BChl(Q(g)) electronic couplings and the 2A ( g ) (-) --> 1A ( g ) (-) internal conversion rates. We suggest that symmetry breaking and geometry rather than length of conjugated system dominate couplings involving the 2A ( g ) (-) state. Differences in transfer efficiencies from the 1B ( u ) (+) state in LH 2 and PCP are found to be dominated by the differences in spectral overlap. The role of the 1B ( u ) (+) state is likely to be influenced by a lower-lying (in longer polyenes), optically forbidden 1B ( u ) (-) state.

Increases in total respiratory resistance during forehead temperature stimulation.

We investigated the effects of forehead temperature stimulation on total respiratory resistance in healthy individuals. In two experiments involving a total of 38 participants we studied the time course and stability of the response at moderate temperature (20-23 degrees C). Small plastic bags filled with water were positioned on the forehead for a duration of 60 s. Oscillatory resistance (R(os)), heart period (HP), respiratory sinus arrhythmia (RSA), and ventilatory parameters were measured continuously. Experiment 1 showed similar phasic increases in R(os) during the first 20 s of stimulation with moderate (20-23 degrees C) as compared to cold (8-11 degrees C) temperature. Phasic increases by moderate temperature were replicated in Experiment 2 over five successive stimulation trials. Within-session stability of individual differences in response was only modest. Ventilatory adjustments did not facilitate the phasic R(os) increases. As increases were mainly due to the inspiratory component of R(os), a substantial contribution of upper airway artifacts was less likely. Increases in HP were the most pronounced responses to all stimulation conditions, while RSA did not increase significantly.

Respiratory resistance during emotional stimulation: evidence for a nonspecific effect of experienced arousal?

We investigated the effects of phasic emotional stimuli on total respiratory resistance (TRR) in 16 nonasthmatic students. Six series of happy, neutral, and depressing affective pictures and self-referent Velten statements were presented. Each stimulus was presented for 12 s and subsequently imagined for 12 s. TRR was measured by forced oscillations throughout the stimulus series, together with ventilation, cardiac activity (including respiratory sinus arrhythmia), and facial EMGs (corrugator supercilii, orbicularis oculi, and masseter). In addition, self-reports of mood, pleasure and arousal were obtained. TRR was increased during happy and depressing stimuli compared to neutral stimuli, with stronger effects for the inspiratory component of TRR. Ventilatory parameters did not explain the changes observed in TRR. Discrimination of affective categories by facial EMG was weak. Although EMG masseter activity did not account for this result, an influence of the respiration measurement procedure on facial EMG cannot be ruled out. The TRR results are in accordance with clinical reports of asthmatic symptom aggravation due to positive or negative emotional arousal.

Stability of total respiratory resistance under multiple baseline conditions, isometric arm exercise and voluntary deep breathing.

Little is known about total respiratory resistance (TRR) as a psychophysiological parameter in normal subjects. Therefore, we investigated TRR in 45 healthy students under multiple baseline conditions, isometric arm muscle tension and voluntary deep breathing (VDB). TRR was measured by the forced oscillation technique. In addition, heart rate (HR) as well as volume and time components of the respiratory cycle, respiratory timing and respiratory drive were monitored. Subjects repeated the protocol 14 days later. Coefficients of stability and dependability were calculated for 20 s measurement epochs within and between both sessions. Increases of HR and shortening of time components of the respiratory cycle were found during muscle tension, prolongation of time components and increases in volume were found for deep breathing. During both experimental tasks TRR increased significantly. Short-term as well as long-term stability of absolute TRR scores proved to be comparable or even better than reliability of other physiological parameters, however, difference scores from baseline revealed only low coefficients.

The structure of symptom report in asthma: a reevaluation.

OBJECTIVES: We studied the structure of symptom report in a sample of British asthma patients using the Asthma Symptom Checklist (ASC). METHODS: The ASC was administered to 193 patients, together with a questionnaire on demographics and asthma-related information and the Perceived Control of Asthma Questionnaire. RESULTS: Principal Component Analysis yielded evidence for a six-dimensional structure of the ASC, with positively correlated subscales for panic-fear, irritation, obstruction-dyspnea, obstruction-congestion, fatigue, and hyperventilation symptoms. Individual subscales showed good to excellent item characteristics and internal consistencies in individual subscales. Panic-fear and obstruction-congestion were related to self-reported duration of oral corticosteroid intake. Other ASC subscales were positively related to aspects of health care utilization, limitations in daily activity, and lower perceived control of asthma mainly in women. The dyspnea subscale of the ASC showed only little relationship with either of these variables. CONCLUSION: The ASC can reliably assess the multidimensional structure of asthma symptom report. Its subscales are associated with important aspects of asthma management behavior.

Relaxation therapy in adult asthma. Is there new evidence for its effectiveness?

Studies of relaxation training for adult asthma patients were reviewed for the period between 1980 and 2000. Six controlled and three uncontrolled studies were identified, employing a variety of methods, such as progressive relaxation, functional relaxation, autogenic training, or yoga. Most studies had low sample sizes and suffered from one or more methodological deficiencies, such as suboptimal data analysis, high dropout rates, problematic measurement procedures, or insufficient descriptions of methodology and results. Overall effects on parameters of lung function, symptoms, medication consumption, and health care use were generally negligible. Problems with the underlying rationale of relaxation therapy in asthma are discussed from a psychophysiological viewpoint. Examples are given of potential beneficial and detrimental effects of these techniques on lung function with respect to emotional processes, the musculoskeletal system, and ventilation as targets of a relaxation intervention. It remains to be demonstrated that relaxation training can significantly contribute to the standard treatment of asthma in adult patients.

Controlled and uncontrolled allergic asthma in routine respiratory specialist care - a clinical-epidemiological study in Germany.

BACKGROUND: Studies in the last decade showed high rates of poorly treated and poorly controlled asthma in the community. Extending these findings we describe the more recent situation in specialist respiratory care as the most frequent source of treatment provision using comprehensive clinical and patient assessments and exploring predictors for poor control. METHODS: This is a German cross-sectional, clinical epidemiological study in a nationally representative stratified treatment prevalence sample of N = 572 outpatients diagnosed with allergic asthma (AA; females 58.2%, aged 47.5 ± 16.3 (16-81 years). Treating physicians completed standardized clinical assessments (lung function, laboratory, clinical findings, severity, illness and treatment history, asthma control [GINA]), supplemented by patients' self-report measures (EQ5-D, AQLQ, ACT) and mental health module (CIDI-SF). RESULTS: A total of 65.4% of patients were rated (GINA) as controlled, 30.3% partially controlled, and 4.4% uncontrolled; the patient-rated ACT showed lower rates of control (19.9% controlled, 44.2% partial, 35.8% uncontrolled, kappa: 0.2). Consistent with findings of clinical measures, controlled asthma was highest among patients with pre-treatment stage I severity (83.6%) and decreased by pre-treatment severity (stage IV patients: 29.3%). Poorer control was associated with pre-treatment severity, nocturnal attacks, diminished adherence and comorbid anxiety/depression. Patients received complex multiple drug and non-drug interventions, largely consistent with guidelines. Degree of asthma control was associated with improved and even normalized quality of life findings. CONCLUSION: In this representative sample of longterm treated AA patients in specialist respiratory care we find better control rates and better adherence to guidelines as previous studies. Despite remarkable differences in clinician- vs patient-rated control ratings even the initially most severe stage IV patients (12.9% of patients) showed remarkable control rates and close to normal quality of life. Intensified treatment (e.g. omalizumab) was associated with improved control. Poorer control was associated with higher initial severity, diminished adherence, comorbid anxiety/depression and old age. LIMITATION: Findings apply to AA patients in respiratory specialist care sector which is likely to treat the more severely affected patients. Thus, findings cannot be generalized to the general population, other treatment settings or asthma types.

Emotion and pulmonary function in asthma: reactivity in the field and relationship with laboratory induction of emotion.

OBJECTIVE: We investigated the modulation of pulmonary function by mood states in the daily life of asthmatic patients and nonasthmatic control subjects and its relationship to the airway effects of laboratory induction of emotion using films. METHODS: Twenty asthmatic patients and 20 nonasthmatic control subjects participated in a laboratory session in which various emotions (ie, anxiety, anger, depression, happiness, elation, contentment, and neutrality) were induced by films. Respiratory resistance (Ros) was measured by forced oscillation. After this session, participants kept mood diaries, including regular spirometric self-assessments, for at least 3 weeks. Episodes of strong negative or positive mood were selected from these diaries and compared with conditions of relative affective neutrality. RESULTS: In asthmatic patients, negative mood states, and to a lesser degree positive mood states, were associated with a reduction in forced expiratory volume in the first second (FEV1) compared with neutral states. These effects were not observed in nonasthmatic control subjects. Self-reports of arousal varied in a reciprocal manner with FEV1, whereas physical activity did not vary systematically between mood episodes. A moderate negative relationship between changes in FEV1 during negative mood episodes and changes in Ros during viewing of the depressing film was also observed in asthmatic patients. CONCLUSION: Pulmonary function of asthmatic patients is negatively affected by strong mood states in daily life. Airway effects of negative emotion induction, particularly depression, can predict changes in pulmonary function in response to negative mood in the field.