RESUMEN
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.
Asunto(s)
Asma , Síndrome de Churg-Strauss , Reflujo Gastroesofágico , Granulomatosis con Poliangitis , Enfermedad Pulmonar Obstructiva Crónica , Humanos , Broncodilatadores/uso terapéutico , Volumen Espiratorio Forzado/fisiología , Asma/diagnóstico , Asma/tratamiento farmacológico , Asma/epidemiología , Enfermedad Pulmonar Obstructiva Crónica/tratamiento farmacológicoRESUMEN
In vitro studies have contributed substantially to the understanding of immunopathology of respiratory syncytial virus (RSV)-mediated disease. In the present study we compared the effect of RSV-infected dendritic cells on the time-course of the primary and memory/effector T cell response in vitro. Cultures with uninfected dendritic cells known to elicit T helper 2 (Th2) responses and with polyinosinic-polycytidylic acid (poly-IC)-stimulated dendritic cells known to elicit Th1 responses served as controls. At day 1 after stimulation there was a high proportion of interleukin (IL)-2 and tumour necrosis factor (TNF)-alpha-producing T cells with no difference in number of producing T cells as well as concentration of secreted cytokines between RSV-infected and control cultures. However, up to day 3 generation of IFN-gamma was reduced markedly. In addition, there was a reduced proliferation in RSV cultures. At day 7 the RSV-treated cultures showed a preponderance of IL-4 generation. At days 21-24, after three rounds of restimulation, memory/effector T cells matured under the influence of RSV were still not fully polarized but in contrast to the primary response displayed a predominance of Th1 cytokines. Contact with RSV-infected HEp-2 cells inhibited proliferation of T cells; memory effector T cells were less sensitive to contact inhibition than naive T cells. In addition, RSV inhibited the stimulated rearrangement of cortical actin more effectively in naive compared to memory T cells. In summary, we have shown that RSV infection of dendritic cells has a distinct modulatory effect on the primary response and a less pronounced effect on the memory response.
Asunto(s)
Células Dendríticas/inmunología , Células Dendríticas/virología , Infecciones por Virus Sincitial Respiratorio/inmunología , Subgrupos de Linfocitos T/inmunología , Presentación de Antígeno/inmunología , Proliferación Celular , Células Cultivadas , Citocinas/biosíntesis , Humanos , Tolerancia Inmunológica , Memoria Inmunológica , Inmunofenotipificación , Activación de Linfocitos/inmunologíaRESUMEN
BACKGROUND: Recent epidemiological studies have shown that growing up on a traditional farm provides protection from the development of allergic disorders such as hay fever and allergic asthma. We present experimental evidence that substances providing protection from the development of allergic diseases can be extracted from dust collected in stables of animal farms. METHODS: Stable dust was collected from 30 randomly selected farms located in rural regions of the Alps (Austria, Germany and Switzerland). The dust was homogenised with glass beads and extracted with physiological sodium chloride solution. This extract was used to modulate immune response in a well established mouse model of allergic asthma. RESULTS: Treatment of mice by inhalation of stable dust extract during sensitisation to ovalbumin inhibited the development of airway hyperresponsiveness and airway eosinophilia upon challenge, as well as the production of interleukin 5 by splenocytes and of antigen specific IgG(1) and IgE. Dust extract also suppressed the generation of human dendritic cells in vitro. The biological activity of the dust extract was not exclusively mediated by lipopolysaccharide. CONCLUSIONS: Stable dust from animal farms contains strong immune modulating substances. These substances can interfere with the development of both cellular and humoral immunity against allergens, thus suppressing allergen sensitisation, airway inflammation, and airway hyperresponsiveness in a murine model of allergic asthma.