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)

Incidence of tick-borne spotted fever group Rickettsia species in rodents in two regions in Kazakhstan.

Records on the distribution of Rickettsia spp. in their natural hosts in Central Asia are incomplete. Rodents and small mammals are potential natural reservoirs for Rickettsiae in their natural lifecycle. Studies about the maintenance of Rickettsia in wild animals are available for Western nations, but-to our knowledge-no studies and data are available in the Republic of Kazakhstan so far. The first case description of Rickettsioses in Kazakhstan was made in the 1950ies in the Almaty region and now Kyzylorda, East Kazakhstan, Pavlodar and North Kazakhstan are endemic areas. The existence of murine and endemic typhus was proven in arthropod vectors in the regions Kyzylorda and Almaty. Here we show for the first time investigations on tick-borne Rickettsia species detected by a pan-rickettsial citrate synthase gene (gltA) real-time PCR in ear lobes of small mammals (n = 624) in Kazakhstan. From all analysed small mammals 2.72% were positive for Rickettsia raoultii, R. slovaca or R. conorii. Sequencing of the rickettsial gene OmpAIV and the 23S-5S interspacer region revealed a similar heritage of identified Rickettsia species that was observed in ticks in previous studies from the region. In summary, this study proves that rodents in Kazakhstan serve as a natural reservoir of Rickettsia spp.

Canine scent detection in the diagnosis of lung cancer: revisiting a puzzling phenomenon.

Patient prognosis in lung cancer largely depends on early diagnosis. The exhaled breath of patients may represent the ideal specimen for future lung cancer screening. However, the clinical applicability of current diagnostic sensor technologies based on signal pattern analysis remains incalculable due to their inability to identify a clear target. To test the robustness of the presence of a so far unknown volatile organic compound in the breath of patients with lung cancer, sniffer dogs were applied. Exhalation samples of 220 volunteers (healthy individuals, confirmed lung cancer or chronic obstructive pulmonary disease (COPD)) were presented to sniffer dogs following a rigid scientific protocol. Patient history, drug administration and clinicopathological data were analysed to identify potential bias or confounders. Lung cancer was identified with an overall sensitivity of 71% and a specificity of 93%. Lung cancer detection was independent from COPD and the presence of tobacco smoke and food odours. Logistic regression identified two drugs as potential confounders. It must be assumed that a robust and specific volatile organic compound (or pattern) is present in the breath of patients with lung cancer. Additional research efforts are required to overcome the current technical limitations of electronic sensor technologies to engineer a clinically applicable screening tool.

Clinical and immunological effects of low-dose IFN-alpha treatment in patients with corticosteroid-resistant asthma.

BACKGROUND: Interferon (IFN)-alpha is a cytokine that possesses potent anti-viral and immunoregulatory activities. We aimed to assess clinical and immunological effects of low-dose IFN-alpha in patients with severe corticosteroid-resistant asthma with and without Churg-Strauss syndrome. There is currently no efficient pharmacological treatment available for this group of patients. METHODS: We studied 10 patients with corticosteroid-resistant asthma, in which 3x10(6) IU/day IFN-alpha were administrated in addition to the prednisone dose given already before introduction of the cytokine therapy. The prednisone dose was gradually reduced dependent on the clinical situation and used as a clinical readout to evaluate the efficacy of the cytokine therapy. To distinguish between IFN-alpha- and prednisone-mediated immunological changes, the corticosteroid dose was kept constant for at least 2 weeks upon introduction of the cytokine therapy in seven patients. The effects of treatment on clinical and immunological parameters were measured at 2-4 weeks and 5-10 months depending on the availability of the patient. RESULTS: Interferon-alpha treatment rapidly improved the clinical situation as assessed by lung function parameters and required prednisone dose. Important immunological changes included: decreased leukocyte numbers, increased relative numbers of CD4+ T cells, increased differentiation of T helper (Th)1 cells, and increased expression of interleukin (IL)-10 in peripheral blood mononuclear cells. CONCLUSION: Interferon-alpha treatment was associated with dramatic improvements in the condition of patients with corticosteroid-resistant asthma with and without Churg-Strauss syndrome. Potential mechanisms of action include the establishment of a correct Th1/Th2 balance and the induction of the anti-inflammatory IL-10 gene.

[Listeriosis during pregnancy (author's transl)]. / Listeriose in Graviditate.

Eight cases of materno-fetal listeriosis were discovered at the University Women's Hospital of Basel from May 1977 until June 1980. This represent an incidence of 0,15% of all births. This infectious disease has often a fatal course for the unborn child, therefore it is important to know the clinical manifestations occurring with it. Listeriosis during pregnancy has a typical-two-stage course: During the first phase we see commonly a flu-like illness abating rapidly, about two weeks later fever starts again and premature contractions ensue, but no therapy is successful in controlling the fever and the premature labour. The usual fate for the unborn child is stillbirth or premature delivery with subsequent neonatal death due to prematurity, RDS, sepsis and meningitis. The low fetal and neonatal survival rate can be improved by two relatively simple measures: 1) a high index of suspicion with early diagnosis, 2) an early treatment with ampicillin either in the antepartal or neonatal stage. We review the epidemiology, the bacteriology, the serology and the histo-pathology of this relatively rare but important disease during pregnancy.