ABSTRACT
The article discusses the historical evolution of asthma treatment and highlights recent advancements in personalized medicine, specifically the use of biologics in severe asthma therapy and its potential combination with allergen immunotherapy (AIT). One of the major breakthroughs of biologics is their potential effect on airway remodeling, a crucial aspect of asthma chronicity. The article introduces the concept of disease-modifying antiasthmatic drugs, which aim to modify the course of asthma and possibly modulate or prevent airway remodeling. Furthermore, the critical importance of patient-centered outcome measures to evaluate the efficacy and effectiveness of asthma treatments is emphasized, with the innovative concept of asthma remission introduced as a potential outcome. Recent studies suggest that AIT can be used as an additional therapy to biologic agents for the treatment of allergic asthma. The combination of these treatments has been shown to induce improved clinical outcomes. However, AIT is actually not recommended for use in patients with severe asthma, but encouraging results from studies investigating the combined use of AIT and biologics indicate a novel approach to exploring these treatment modalities. In conclusion, the introduction of biologics and AIT has changed the scenario of respiratory allergy treatment, from a "one size fits all" approach to embracing "individual treatments."
ABSTRACT
Objective To study the effect of inhibiting the phosphorylation of signal transducer and activator of transcription-3 (STAT3) on Th2 cell-mediated airway inflammation and airway remodeling,and to explore the role of STAT3 in the pathophysiology of bronchial asthma.Methods Forty Balb/c mice were randomly divided into control group(n =10),asthma group(n =10),AG490 by intraperitoneal group (n =10),and AG490 by inhalation group (n =10).The mice were sensitized with ovalbumin to establish the asthmatic model.The histological changes were evaluated by means of HE staining,while total broalchial wall thickness(Wat) and smooth muscle thickness(Wam) were measured by using image analysis system.The percentages of collagen deposition were detected by way of Masson's trichrome staining; the bronchoalveolar lavage fluid (BALF) were collected,the total cell and the cell differentials were counted,the levels of IL-4,IL-5 in BALF were measured by enzyme-linked immunosorbent assay; the lung tissue extracts were analyzed for phosphorylation of STAT3 (p-STAT3) by Western blot.The SPSS 13.0 software was used to analyze the data.Results 1.The histological changes by HE staining showed that less inflammatory cells infiltration in airway and around the pulmonary vascular in AG490 administration groups compared with asthmatic group.Wat,Wam and the percentages of collagen deposition in AG490 administration groups was significantly lower than that in asthmatic group(F =49.5,41.7,58.2,all P ＜ 0.05).2.The level of p-STAT3 in the lung of AG490 administration groups were significantly lower than those in asthmatic group(F =34.17,P ＜ 0.05).3.The total cells and eosinophils amounts in BALF of AG490 administration groups were significantly lower than those in asthmatic group (F =42.5,64.7,all P ＜ 0.05).The levels of IL-4,IL-5 in BALF of AG490 administration groups were significantly lower than those in asthmatic group,respectively (F =39.2,75.1,all P ＜ 0.05).Conclusions STAT3 signaling pathway is pivotal in Th2 cell-mediated airway inflammation and airway remodeling in asthmatic models,and AG490 can ameliorate airway inflammation and airway remodeling efficiently by inhibiting the phosphorylation of STAT3,and targeting this signaling pathway may be a novel therapy for asthma.
ABSTRACT
A disfunção de vias aéreas em pacientes com Síndrome do Desconforto Respiratória Agudo (SDRA) é caracterizada por limitação do fluxo expiratório e hiperinsuflação dinâmica. As alterações morfológicas possivelmente associadas com tais alterações funcionais têm sido investigadas em modelos experimentais de lesão pulmonar aguda, que mostram necrose e descamação epitelial em vias aéreas distais. Entretanto, até o momento, essa avaliação não foi realizada em humanos. O objetivo deste estudo foi investigar as alterações estruturais e inflamatórias nas pequenas vias aéreas de pacientes com SDRA. Com este propósito, estudamos, retrospectivamente, o tecido pulmonar de 31 pacientes com SDRA (A: PaO2/FIO2<=200, 45±14anos, 16 homens) e 11 controles (C: 52±16anos, 7 homens) submetidos à autópsia. Por meio de análise de imagem, quantificamos a extensão das alterações epiteliais, a inflamação bronquiolar, a espessura da parede da via aérea e o conteúdo de proteínas da matriz extracelular (MEC) nas pequenas vias aéreas. As vias aéreas dos pacientes com SDRA apresentaram menor extensão de epitélio normal (A: 32,9±27.2%, C: 76,7±32.7%, p<0,001), maior extensão de descamação epitelial (A: 52,6±35.2%, C: 21,8±32.1%, p<0,01), maior índice de inflamação [A: 1(3), C: 0(1), p= 0,03], maior espessura da parede da via aérea (A: 138,7 ± 54,3 ?m, C: 86,4 ± 33,3 ?m, p< 0,01) e maior conteúdo de colágeno I, fibronectina, versicam e MMP-9 comparado aos controles (p<=0,03). Nos pacientes com SDRA, a extensão de epitélio normal apresentou correlação positiva com a PaO2/FiO2 (r=0,58; p=0,02) e correlação negativa com a pressão de platô utilizada (r=-0,52; p=0,04). A extensão de epitélio descamado apresentou correlação negativa com a PaO2/FiO2 (r=-0,52; p=0,04). Nossos dados mostram que as pequenas vias aéreas dos pacientes com SDRA apresentam alterações estruturais caracterizadas por descamação epitelial, inflamação e espessamento da parede com deposição de MEC. Estas alterações...
Airway dysfunction in patients with acute respiratory distress syndrome (ARDS) is evidenced by expiratory flow limitation and dynamic hyperinflation. The morphological alterations potentially associated with these functional changes have been investigated in experimental models of Acute Lung Injury, which show epithelial necrosis and denudation in distal airways. To date, however, no study has focused on the morphological airway changes in lungs from human subjects with ARDS. Objective: To evaluate structural and inflammatory changes in distal airways in ARDS patients. Methods and Results: We retrospectively studied autopsy lung tissue from 31 ARDS patients (A: PaO2/FIO2<=200, 45±14years, 16 males) and 11 controls (C: 52±16years, 7 males). Using image analysis, we quantified the extension of epithelial changes, bronchiolar inflammation, airway wall thickness, and extracellular matrix (ECM) protein content in distal airways. ARDS airways showed a shorter extension of normal epithelium (A:32.9±27.2%, C:76.7±32.7%, p<0.001), a larger extension of epithelium denudation (A:52.6±35.2%, C:21.8±32.1%, p<0.01), increased airway inflammation (p=0.03), higher airway wall thickness (A:138.7±54.3?m, C:86.4±33.3?m, p<0.01), and higher airway content of collagen I, fibronectin, versican and MMP-9 compared to controls (p<=0.03). The extension of normal epithelium showed a positive correlation with PaO2/FiO2 (r=0.58; p=0.02) and a negative correlation with plateau pressure (r=-0.52; p=0.04). The extension of denuded epithelium showed a negative correlation with PaO2/FiO2 (r=-0.52; p=0.04). Conclusion: Structural changes in small airways of patients with ARDS were characterized by epithelial denudation, inflammation and airway wall thickening with ECM remodeling. These changes are likely to contribute to functional airway changes in patients with ARDS.
