Bronchodilator Reversibility in the GAN Severe Asthma Cohort.

BACKGROUND AND OBJECTIVE: Positive bronchodilator reversibility (BDR) is a diagnostic criterion for asthma. However, patients with asthma may exhibit a negative BDR response. Aim: To describe the frequency of positive and Negative BDR response in patients with severe asthma and study associations with phenotypic characteristics. METHODS: A positive BDR response was defined as an increase in FEV1 >200 mL and >12% upon testing with a short-acting ß-agonist. RESULTS: BDR data were available for 793 of the 2013 patients included in the German Asthma Net (GAN) severe asthma registry. Of these, 250 (31.5%) had a positive BDR response and 543 (68.5%) a egative BDR response. Comorbidities significantly associated with a negative response were gastroesophageal reflux disease (GERD) (28.0% vs 40.0%, P<.01) and eosinophilic granulomatosis with polyangiitis (0.4% vs 3.0%; P<.05), while smoking history (active: 2.8% vs 2.2%; ex: 40.0% vs 41.7%) and comorbid chronic obstructive pulmonary disease (COPD) (5.2% vs 7.2%) were similar in both groups. Patients with a positive BDR response had worse asthma control (median Asthma Control Questionnaire 5 score, 3.4 vs 3.0, P<.05), more frequently reported dyspnea at rest (26.8% vs 16.4%, P<.001) and chest tightness (36.4% vs 26.2%, P<.001), and had more severe airway obstruction at baseline (FEV1% predicted, 56 vs 64, P<.001) and higher fractional exhaled nitric oxide (FeNO) levels (41 vs 33 ppb, P<0.05). There were no differences in diffusion capacity of the lung for carbon monoxide, single breath (% pred, 70% vs 71%). Multivariate linear regression analysis identified an association between positive BDR response and lower baseline FEV1% (P<.001) and chest tightness (P<.05) and a negative association between BDR and GERD (P<.05). CONCLUSION: In this real-life setting, most patients with severe asthma had a negative BDR response. Interestingly, this was not associated with smoking history or COPD, but with lower FeNO and presence of GERD.

Bronchodilator Reversibility in the GAN Severe Asthma Cohort

Background: Positive bronchodilator reversibility (BDR) is a diagnostic criterion for asthma. However, patients with asthma may exhibit a negative BDR response. Aim: To describe the frequency of positive and negative BDR response in patients with severe asthma and study associations with phenotypic characteristics. Methods: A positive BDR response was defined as an increase in FEV1 >200 mL and >12% upon testing with a short-acting ß-agonist. Results: BDR data were available for 793 of the 2013 patients included in the German Asthma Net (GAN) severe asthma registry. Of these, 250 (31.5%) had a positive BDR response and 543 (68.5%) a negative BDR response. Comorbidities significantly associated with a negative response were gastroesophageal reflux disease (GERD) (28.0% vs 40.0%, P<.01) and eosinophilic granulomatosis with polyangiitis (0.4% vs 3.0%; P<.05), while smoking history (active: 2.8% vs 2.2%; ex: 40.0% vs 41.7%) and comorbid chronic obstructive pulmonary disease (COPD) (5.2% vs 7.2%) were similar in both groups. Patients with a positive BDR response had worse asthma control (median Asthma Control Questionnaire 5 score, 3.4 vs 3.0, P<.05), more frequently reported dyspnea at rest (26.8% vs 16.4%, P<.001) and chest tightness (36.4% vs 26.2%, P<.001), and had more severe airway obstruction at baseline (FEV1% predicted, 56 vs 64, P<.001) and higher fractional exhaled nitric oxide (FeNO) levels (41 vs 33 ppb, P<0.05). There were no differences in diffusion capacity of the lung for carbon monoxide, single breath (% pred, 70% vs 71%). Multivariate linear regression analysis identified an association between positive BDR response and lower baseline FEV1% (P<.001) and chest tightness (P<.05) and a negative association between BDR and GERD (P<.05). Conclusion: In this real-life setting, most patients with severe asthma had a negative BDR response. Interestingly, this was not associated with smoking history or COPD, but with lower FeNO and presence of GERD. (AU)

Antecedentes: La reversibilidad broncodilatadora (RB) positiva es un criterio diagnóstico para el asma. Sin embargo, los pacientes con asma pueden presentar una prueba RB negativa. Objetivos: Describir la frecuencia de RB positivas y negativas en pacientes con asma grave y sus asociaciones con características fenotípicas. Métodos: La RB positiva se definió como un aumento del FEV1 > 200 ml y > 12% tras la inhalación de un agonista beta de acción corta (SABA). Resultados: De 2013 pacientes incluidos en el registro de asma grave del German Asthma Net (GAN), 793 tenían datos sobre RB. De estos, 250 (31,5%) tuvieron una prueba RB positiva y 543 (68,5%) negativa. Las comorbilidades significativamente asociadas con RB negativa fueron el reflujo gastroesofágico (ERGE) (28,0% frente a 40,0%, p<0,01) y EGPA (0,4% frente a 3,0%; p<0,05), mientras que el antecedente de tabaquismo (activo: 2,8% frente a 2,2%; exfumador: 40,0% vs. 41,7%) y la comorbilidad de la EPOC (5,2% vs. 7,2%) fueron similares en ambos grupos. Los pacientes con RB positiva tenían peor control del asma (mediana ACQ-5 3,4 vs. 3,0, p<0,05), más disnea en reposo (26,8% vs. 16,4%, p<0,001) y mayor opresión torácica (36,4% vs. 26,2%, p<0,001), además presentaban una obstrucción de las vías respiratorias más grave al inicio del estudio (FEV1% pred: 56 frente a 64, p<0,001) y niveles más altos de FeNO (41 frente a 33 ppb, p<0,05), mientras que la capacidad de difusión fue similar (DLCO-SB% pred. 70% vs. 71%). El análisis de regresión lineal multivariable identificó una asociación de FEV1% basal inferior (p<0,001) y opresión torácica (p<0,05) con RB positiva y ERGE (p<0,05) con RB negativa. Conclusión: En este entorno en vida real, la mayoría de los pacientes con asma grave tuvieron una RB negativa. Curiosamente, esto no se asoció con antecedentes de tabaquismo o EPOC, sino con FeNO más bajo y presencia de ERGE. (AU)

[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.

Priorities for future research into asthma diagnostic tools: A PAN-EU consensus exercise from the European asthma research innovation partnership (EARIP).

The diagnosis of asthma is currently based on clinical history, physical examination and lung function, and to date, there are no accurate objective tests either to confirm the diagnosis or to discriminate between different types of asthma. This consensus exercise reviews the state of the art in asthma diagnosis to identify opportunities for future investment based on the likelihood of their successful development, potential for widespread adoption and their perceived impact on asthma patients. Using a two-stage e-Delphi process and a summarizing workshop, a group of European asthma experts including health professionals, researchers, people with asthma and industry representatives ranked the potential impact of research investment in each technique or tool for asthma diagnosis and monitoring. After a systematic review of the literature, 21 statements were extracted and were subject of the two-stage Delphi process. Eleven statements were scored 3 or more and were further discussed and ranked in a face-to-face workshop. The three most important diagnostic/predictive tools ranked were as follows: "New biological markers of asthma (eg genomics, proteomics and metabolomics) as a tool for diagnosis and/or monitoring," "Prediction of future asthma in preschool children with reasonable accuracy" and "Tools to measure volatile organic compounds (VOCs) in exhaled breath."

[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.

[Standardization of spirometry: 2015 update. Published by German Atemwegsliga, German Respiratory Society and German Society of Occupational and Environmental Medicine]. / Leitlinie zur Spirometrie. Leitlinie der Deutschen Atemwegsliga, der Deutschen Gesellschaft für Pneumologie und Beatmungsmedizin und der Deutschen Gesellschaft für Arbeitsmedizin und Umweltmedizin zur Spirometrie.

Spirometry is a simple test and considered the gold standard in lung function. An obstructive ventilatory defect is a disproportionate reduction of maximal airflow from the lung in relation to the maximal volume that can be displaced from the lung. It implies airway narrowing and is defined by a reduced FEV1/FVC ratio below the 5th percentile of the predicted value (lower limit of normal, LLN). A restrictive disorder may be suspected when vital capacity (FVC) is reduced and FEV1/FVC is normal. It is definitely proven, however, only by a decrease in TLC below the 5th percentile of predicted value (LLN). The measurement of TLC by body plethysmography is necessary to confirm or exclude a restrictive defect or hyperinflation of the lung when FVC is below the LLN. 2012 a task force of the ERS published new reference values based on 74,187 records from healthy non-smoking males and females from 26 countries. The new reference equations for the 3-95 age range are now available that include appropriate age-dependent mean values and lower limits of normal (LLN). This presentation aims at providing the reader with recommendations dealing with standardization and interpretation of spirometry.

Predictive values of component-specific IgE for the outcome of peanut and hazelnut food challenges in children.

BACKGROUND: Oral challenges are the gold standard in food allergy diagnostic, but time-consuming. Aim of the study was to investigate the role of peanut- and hazelnut-component-specific IgE in the diagnostics of peanut and hazelnut allergy and to identify cutoff levels to make some challenges superfluous. METHODS: In a prospective and multicenter study, children with suspected peanut or hazelnut allergy underwent oral challenges. Specific IgE to peanut, hazelnut, and their components (Ara h 1, Ara h 2, Ara h 3, and Ara h 8, Cor a 1, Cor a 8, Cor a 9, and Cor a 14) were determined by ImmunoCAP-FEIA. RESULTS: A total of 210 children were challenged orally with peanut and 143 with hazelnut. 43% of the patients had a positive peanut and 31% a positive hazelnut challenge. With an area under the curve of 0.92 and 0.89, respectively, Ara h 2 and Cor a 14-specific IgE discriminated between allergic and tolerant children better than peanut- or hazelnut-specific IgE. For the first time, probability curves for peanut and hazelnut components have been calculated. A 90% probability for a positive peanut or hazelnut challenge was estimated for Ara h 2-specific IgE at 14.4 kU/l and for Cor a 14-specific IgE at 47.8 kU/l. A 95% probability could only be estimated for Ara h 2 at 42.2 kU/l. CONCLUSIONS: Ara h 2- and Cor a 14-specific IgE are useful to estimate the probability for a positive challenge outcome in the diagnostic work-up of peanut or hazelnut allergy making some food challenges superfluous.

[Omalizumab therapy in adolescents with severe allergic asthma - results of a post-marketing surveillance]. / Omalizumab-Therapie bei Jugendlichen mit schwerem allergischem Asthma - eine Anwendungsbeobachtung.

BACKGROUND: Omalizumab has been successfully established as add-on therapy to improve asthma control in adults and children aged 6 years and older with uncontrolled severe persistent allergic asthma (GINA 2009 step 5). PATIENTS AND METHODS: 15 patients between 12 and 20 years of age with severe allergic asthma, which was inadequately controlled despite intensive antiasthmatic therapy according to NVL step 4 /5, received treatment with omalizumab for 6 - 69 months. After 12 months of treatment the effect was evaluated by means of objective parameters. RESULTS: Significant improvements were found for the asthma-exacerbation rate and emergency treatment as well as for most of the lung function parameters. Systemic steroids could be discontinued in 10 of 11 patients. Asthma control has improved in all patients according to the ACT. Omalizumab was well tolerated by 13 patients. Adverse effects occurred in two patients in the first two and after 5 months, respectively. Only in one of them omalizumab had to be discontinued after 6 months due to the development of serum disease. CONCLUSIONS: Omalizumab can be considered a valuable add-on therapy in adolescent patients with severe allergic asthma that is inadequately controlled despite GINA step 5 treatment. A significant effect on clinical and functional parameters was shown over 12 months.

[New spirometric reference values for children and adolescents in Germany considering height and non-linear age effects: the LUNOKID-study]. / Neue spirometrische Referenzwerte für Kinder und Jugendliche in Deutschland unter Berücksichtigung der Größe und nichtlinearer Alterseffekte: Die LUNOKID-Studie.

BACKGROUND: Comparing children's lung function with reference values is important for diagnosing respiratory diseases. The values by Zapletal et al., commonly used nowadays, are not appropriate for the current stage of children's development. We have now developed new reference values and a lower limit of normal (LLN) for children in Germany, divided into small-range age and height categories. MATERIAL AND METHODS: We examined 4- to 18-year-old children in 3 German communities under field conditions. 1943 children were healthy and had a visually acceptable lung function which also fulfilled international quality criteria. We used the regression model LMS, which was introduced by Stanojevic and Quanjer in this context. RESULTS: There were significant differences between the measured lung function and the predicted values according to Zapletal et al. The lung function did not only depend on the child's height, but also in a non-linear way on the age. The variation coefficient did not depend on age. CONCLUSIONS: To avoid diagnostic errors, the currently often used reference values according to Zapletal et al. should no longer be used. The non-linear dependence on age corresponds to the recently published results by Stanojevic and Quanjer.

Definition, assessment and treatment of wheezing disorders in preschool children: an evidence-based approach.

There is poor agreement on definitions of different phenotypes of preschool wheezing disorders. The present Task Force proposes to use the terms episodic (viral) wheeze to describe children who wheeze intermittently and are well between episodes, and multiple-trigger wheeze for children who wheeze both during and outside discrete episodes. Investigations are only needed when in doubt about the diagnosis. Based on the limited evidence available, inhaled short-acting beta(2)-agonists by metered-dose inhaler/spacer combination are recommended for symptomatic relief. Educating parents regarding causative factors and treatment is useful. Exposure to tobacco smoke should be avoided; allergen avoidance may be considered when sensitisation has been established. Maintenance treatment with inhaled corticosteroids is recommended for multiple-trigger wheeze; benefits are often small. Montelukast is recommended for the treatment of episodic (viral) wheeze and can be started when symptoms of a viral cold develop. Given the large overlap in phenotypes, and the fact that patients can move from one phenotype to another, inhaled corticosteroids and montelukast may be considered on a trial basis in almost any preschool child with recurrent wheeze, but should be discontinued if there is no clear clinical benefit. Large well-designed randomised controlled trials with clear descriptions of patients are needed to improve the present recommendations on the treatment of these common syndromes.

A novel sidestream ultrasonic flow sensor for multiple breath washout in children.

OBJECTIVE: Inert gas multiple breath washout (MBW) for measuring Lung Clearance Index using mass spectrometry and 4% sulfur hexafluoride (SF(6)) as the tracer gas has been shown to be sensitive for detecting early Cystic Fibrosis (CF) lung disease. However, mass spectrometry requires bulky equipment and is expensive to buy and maintain. A novel sidestream ultrasonic device may overcome this problem. The aims of this study were to assess the feasibility and clinical validity of measuring lung volume (functional residual capacity, FRC) and the LCI using the sidestream ultrasonic flow sensor in children and adolescents with CF in relation to spirometry and plain chest radiographs. PATIENTS AND METHODS: MBW using the sidestream ultrasonic device and conventional spirometry were performed in 26 patients with CF and 22 healthy controls. RESULTS: In the controls (4.7-17.7 years) LCI was similar to that reported using mass spectrometry (mean (SD) 6.7 (0.5)). LCI was elevated in 77% of the CF children (6.8-18.9 years), whereas spirometry was abnormal in only 38.5%, 61.5%, and 26.9% for FEV(1), MEF(25), and FEV(1)/FVC, respectively. This was more marked in children <10 years. LCI correlated with the Crispin-Norman score, whereas FEV(1) did not. CONCLUSIONS: Sidestream ultrasonic MBW is a valid and simple alternative to mass spectrometry for assessing ventilation homogeneity in children.

Development of progressive pulmonary interstitial and intra-alveolar cholesterol granulomas (PICG) associated with therapy-resistant chronic systemic juvenile arthritis (CJA).

A girl aged 5 years with therapy-resistant chronic systemic juvenile arthritis (CJA) developed progressive fibrosing lung disease. Histology of an open lung biopsy revealed pulmonary interstitial and intra-alveolar cholesterol granulomas (PICG). Since treatment with steroids and immunosuppressive drugs did not prevent progression of lung fibrosis, an experimental treatment with a tumor necrosis factor alpha (TNF alpha) antagonist etanercept was started. Although development of chronic changes in the lung parenchyma could not be prevented, this treatment brought considerable relief and markedly improved the child's physical capacity. By ruling out other causes for development of PICG, we concluded that the primary disease had caused the development of cholesterol granulomata by macrophage activation. We suggest, therefore, that a trial with etanercept in children with otherwise therapy-resistant CJA should be considered, especially if pulmonary complications have developed.