Asthma Publications (162550)
Significant negative correlations were found between FEV1%pred and RV%pred (r = -0.557, P < 0.001), TLC%pred (r = -0.387, P < 0.001), and RV/TLC (r = -0.485, P < 0.001) measured by BP, as well as difference in volumes between these two techniques (ΔRV%pred, ΔTLC%pred and ΔRV/TLC). In mild and moderate asthma, AUC of RV%pred detected by BP and ΔTLC%pred was 0.723 (95%CI 0.571-0.874, P = 0.005) and 0.739 (95%CI 0.607-0.872, P = 0.002) with sensitivity and specificity being 79.41% and 88.24%, and 65.22% and 56.52% at cut-off of 145.40% and 14.23%, respectively. In moderate and severe asthma, AUC of RV%pred detected by BP and ΔTLC%pred was 0.782 (95%CI 0.671-0.893, P < 0.001) and 0.788 (95%CI 0.681-0.894, P < 0.002) with sensitivity and specificity being 77.78% and 97.22%, and 73.53% and 52.94% at cut-off of 179.85% and 20.22%, respectively. In conclusion, lung volumes are reliable complement of FEV1 in identifying asthma severity levels.
The current state of the art management of AERD will be addressed including the ongoing central role for aspirin desensitization and high-dose aspirin therapy.
MEDLINE, Cochrane Library, EMBASE, and trial registries through January 28, 2016, with ongoing surveillance through November 11, 2016; references; experts.
English-language studies of folic acid supplementation in women. Excluded were poor-quality studies; studies of prepubertal girls, men, women without the potential for childbearing, and neural tube defect recurrence; and studies conducted in developing countries.
Two investigators independently reviewed abstracts, full-text articles, and risk of bias of included studies. One investigator extracted data and a second checked accuracy. Because of heterogeneity, data were not pooled.
Neural tube defects, harms of treatment (twinning, respiratory outcomes).
A total of 24 studies (N > 58 860) were included. In 1 randomized clinical trial from Hungary initiated in 1984, incidence of neural tube defects for folic acid supplementation compared with trace element supplementation was 0% vs 0.25% (Peto odds ratio [OR], 0.13 [95% CI, 0.03-0.65]; n = 4862). Odds ratios from cohort studies recruiting participants between 1984 and 1996 demonstrated beneficial associations and ranged from 0.11 to 0.27 (n = 19 982). Three of 4 case-control studies with data from 1976 through 1998 reported ORs ranging from 0.6 to 0.7 (n > 7121). Evidence of benefit led to food fortification in the United States beginning in 1998, after which no new prospective studies have been conducted. More recent case-control studies drawing from data collected after 1998 have not demonstrated a protective association consistently with folic acid supplementation, with ORs ranging from 0.93 to 1.4 and confidence intervals spanning the null (n > 13 990). Regarding harms, 1 trial (OR, 1.40 [95% CI, 0.89-2.21]; n = 4767) and 1 cohort study (OR, 1.04 [95% CI, 0.91-1.18]; n = 2620) found no statistically significant increased risk of twinning. Three systematic reviews found no consistent evidence of increased risk of asthma (OR, 1.06 [95% CI, 0.99-1.14]; n = 14 438), wheezing, or allergy.
In studies conducted before the initiation of food fortification in the United States in 1998, folic acid supplementation provided protection against neural tube defects. Newer postfortification studies have not demonstrated a protective association but have the potential for misclassification and recall bias, which can attenuate the measured association of folic acid supplementation with neural tube defects.
Compared with WT mice, the allergen-challenged MMVVδ mice displayed less airway hyperresponsiveness (AHR) and inflammation. These MMVVδ mice exhibited reduced levels of ROS and diminished recruitment of mast cells to the lungs. OVA-activated bone marrow-derived mast cells (BMMCs) from MMVVδ mice showed a significant inhibition of ROS and ox-CaMKII expression. ROS generation was dependent on intracellular Ca(2+) concentration in BMMCs. Importantly, OVA-activated MMVVδ BMMCs had suppressed degranulation, histamine release, leukotriene C4, and IL-13 expression. Adoptive transfer of WT, but not MMVVδ, BMMCs, reversed the alleviated AHR and inflammation in allergen-challenged MMVVδ mice. The CaMKII inhibitor KN-93 significantly suppressed IgE-mediated mast cell activation and asthma. These studies support a critical but previously unrecognized role of ox-CaMKII in mast cells that promotes asthma and suggest that therapies to reduce ox-CaMKII may be a novel approach for asthma.
We also assess the off-label use of omalizumab for other pathologies associated with IgE and report the latest findings concerning this drug and other new related drugs. To date, omalizumab has only been approved for severe allergic asthma and unresponsive chronic urticaria treatments. In allergic asthma, omalizumab has demonstrated its efficacy in reducing the dose of inhaled corticosteroids required by patients, decreasing the number of asthma exacerbations, and limiting the effect on airway remodeling. In CU, omalizumab treatment rapidly improves symptoms and in some cases achieves complete disease remission. In systemic mastocytosis, omalizumab also improves symptoms and its prophylactic use to prevent anaphylactic reactions has also been discussed. In other pathologies such as atopic dermatitis, food allergy, allergic rhinitis, nasal polyposis, and keratoconjunctivitis, omalizumab significantly improves clinical manifestations. Omalizumab acts in two ways: by sequestering free IgE and by accelerating the dissociation of the IgE-Fcε receptor I complex.
This study aimed to evaluate the effects of local delivery of SJT via inhalable microparticles in an asthma mouse model.
Microparticles containing SJT were produced by spray-drying with leucine as an excipient. SJT microparticles were evaluated with respect to their aerodynamic properties, in vitro cytotoxicity, in vivo toxicity, and therapeutic effects on ovalbumin (OVA)-induced asthma in comparison with orally-administered SJT.
SJT microparticles provided desirable aerodynamic properties (fine particle fraction of 48.9% ± 6.4% and mass median aerodynamic diameter of 3.7 ± 0.3 μm). SJT microparticles did not show any cytotoxicity against RAW 264.7 macrophages at concentrations of 0.01 - 3 mg/mL. Inhaled SJT microparticles decreased the levels of IL-4, IL-5, IL-13, IL-17A, eotaxin and OVA-IgE in bronchoalveolar lavage fluid (BALF) in mice with OVA-induced asthma. These effects were verified by histological evaluation of the levels of infiltration of inflammatory cells and collagen, destructions of alveoli and bronchioles, and hyperplasia of goblet cells in lung tissues. The effects of SJT microparticles in the asthma model were equivalent to those of orally-administered SJT extract.
This study suggests that SJT is a promising agent for inhalation therapy for patients with asthma.
Human bronchi were dissected and cultured for 48 h with 10 ng/mL TNF-α or IL-13. Guinea pig tracheas were maintained in organ culture for 72 h which was previously shown to trigger spontaneous AHR. All tissues were treated with increasing concentrations of MAG-DPA (0.1, 0.3, and 1 μmol/L). Pharmacomechanical reactivity, Ca(2+) sensitivity, and western blot analysis for specific phosphoproteins and transcription factors were performed to assess the effects of both cytokines, alone or in combination with MAG-DPA, on human and guinea pig airway preparations. Although 0.1 μmol/L MAG-DPA did not significantly reduce inflammatory biomarkers, the higher concentrations of MAG-DPA (0.3 and 1 μmol/L) blunted the activation of the TNF-α/NF κB pathway and abolished COX-2 expression in human and guinea pig tissues. Moreover, 0.3 and 1 μmol/L MAG-DPA consistently decreased the Ca(2+) sensitivity and pharmacological reactivity of cultured bronchial explants. Furthermore, in human bronchi, IL-13-stimulated phosphorylation of CPI-17 was reversed by 1 μmol/L MAG-DPA. This effect was further amplified in the presence of 100 μmol/L aspirin. MAG-DPA mediates antiphlogistic effects by increasing the resolution of inflammation, while resetting Ca(2+) sensitivity and contractile reactivity.
Several antioxidant tests including DPPH radical scavenging, hydrogen peroxide scavenging, reducing power determination, β-carotene-linoleic acid and total phenolic content tests were used for antioxidant activity evaluation. Antimicrobial and anticancer activities were also estimated using microbial strains, cancer cell lines and brine shrimp larva.
s: GC-Mass-FID analysis of volatile samples showed a total of 74 compounds of which palmitic acid (7.4-33.7%), linoleic acid (6.6-18.6%), heneicosane (1.3-9.6%) and myristic acid (1.4-6.0%) were detected as main volatile components. Moderate to good results were recorded for the plant in β-carotene-linoleic acid test. Total phenolic content of the extracts as gallic acid equivalents were estimated in the range of 15.7 to 79.6 μg/mg. Some microbial strains showed moderate sensitivities to plant extracts. Brine shrimp lethality test and cytotoxic cancer cell line assays showed mild cytotoxic activities for the plant.
Moderate to good antioxidant activities in β-carotene-linoleic acid test and presence of considerable amounts of unsaturated hydrocarbons may explain the plant traditional use in asthma and dyspnea. These findings also candidate it as a good choice for investigating its possible modern medical applications.
After the exclusion of 10 patients without diagnostic confirmation, 13 patients were included in the study. A diagnosis of CF was made with the CF gene study. CT findings were evaluated for the presence and distribution of parenchymal abnormalities including bronchiectasis, tree-in-bud (TIB) pattern, mucus plugging, consolidation, and mosaic attenuation.
Of the 13 patients, 7 (median age, 15 years) were confirmed as CF, 4 (median age, 19 years) had primary ciliary dyskinesia, 1 had bronchiectasis of unknown cause, and 1 had chronic asthma. CT of patients with CF showed bilateral bronchiectasis, TIB pattern, mosaic attenuation, and mucus plugging in all patients, with upper lung predominance (57%). In CT of the non-CF patients, bilateral bronchiectasis, TIB pattern, mosaic attenuation, and mucus plugging were also predominant features, with lower lung predominance (50%).
Korean patients with CF showed bilateral bronchiectasis, cellular bronchiolitis, mucus plugging, and mosaic attenuation, which overlapped with those of non-CF patients. CF gene study is recommended for the definitive diagnosis of CF in patients with these clinical and imaging features.
We found that Bcl6 is modestly associated with the BSs, and it had no significant effect on cytokine production in newly differentiated TH2 cells. Contrarily, in memory TH2 (mTH2) cells derived from adaptively transferred TH2 effectors, Bcl6 outcompeted STAT5 for binding to TH2 cytokine gene loci, particularly Interleukin4 (Il4) loci, and attenuated GATA binding protein 3 (GATA3) binding to highly conserved intron enhancer regions in mTH2 cells. Bcl6 suppressed cytokine production epigenetically in mTH2 cells to negatively tune histone acetylation at TH2 cytokine gene loci, including Il4 loci. In addition, IL-33, a pro-TH2 cytokine, diminished Bcl6's association with loci to which GATA3 recruitment was inversely augmented, resulting in altered IL-4, but not IL-5 and IL-13, production in mTH2 cells but no altered production in newly differentiated TH2 cells. Use of a murine asthma model that generates high levels of pro-TH2 cytokines, such as IL-33, suggested that the suppressive function of Bcl6 in mTH2 cells is abolished in severe asthma. These findings indicate a role of the interaction between TH2-promoting factors and Bcl6 in promoting appropriate IL-4 production in mTH2 cells and suggest that chronic allergic diseases involve the TH2-promoting factor-mediated functional breakdown of Bcl6, resulting in allergy exacerbation.