- Can we prevent Childhood Asthma Before Birth?: Summary of the VDAART results so far. [JOURNAL ARTICLE]
- Expert Rev Respir Med 2016 Aug 26.
- DNA methylation profiling in human lung tissue identifies genes associated with COPD. [JOURNAL ARTICLE]
- Epigenetics 2016 Aug 26.:0.
Chronic obstructive pulmonary disease (COPD) is a smoking-related disease characterized by genetic and phenotypic heterogeneity. Although association studies have identified multiple genomic regions with replicated associations to COPD, genetic variation only partially explains the susceptibility to lung disease, and suggests the relevance of epigenetic investigations. We performed genome-wide DNA methylation profiling in homogenized lung tissue samples from 46 control subjects with normal lung function and 114 subjects with COPD, all former smokers. The differentially methylated loci were integrated with previous genome-wide association study results. The top 535 differentially methylated sites, filtered for a minimum mean methylation difference of 5% between cases and controls, were enriched for CpG shelves and shores. Pathway analysis revealed enrichment for transcription factors. The top differentially methylated sites from the intersection with previous GWAS were in CHRM1, GLT1D1, and C10orf11; sorted by GWAS P-value, the top sites included FRMD4A, THSD4, and C10orf11. Epigenetic association studies complement genetic association studies to identify genes potentially involved in COPD pathogenesis. Enrichment for genes implicated in asthma and lung function and for transcription factors suggests the potential pathogenic relevance of genes identified through differential methylation and the intersection with a broader range of GWAS associations.
- Cost-effectiveness and Budget Impact of Routine Use of Fractional Exhaled Nitric Oxide Monitoring for the Management of Adult Asthma Patients in Spain. [JOURNAL ARTICLE]
- J Investig Allergol Clin Immunol 2016 Aug 26; 27(2)
Fractional exhaled nitric oxide (FeNO) is a marker for Type-2 airway inflammation. The objective of this study was to evaluate cost-effectiveness and budget impact of FeNO monitoring for management of adult asthma in Spain.Cost-effectiveness model analysis was used to evaluate the economic outcomes when asthma management was assisted with FeNO monitoring. Over a one-year period, the model estimated the incremental cost per quality-adjusted life year (QALY) and incremental number of exacerbations avoided when FeNO monitoring was added to standard guideline-driven asthma care and compared to standard care alone. Univariate and multivariate sensitivity analyses explored uncertainty in the model. A budget impact model was used to examine the financial impact of FeNO assisted monitoring on the primary care settings across the Spanish health system.The results showed that adding FeNO to standard asthma care saved €62.53 per patient per year in the adult population, and improved QALYs by 0.026 per patient per year. The budget impact analysis demonstrated an estimated €129 million net yearly saving if FeNO assisted monitoring was used in primary care settings in Spain.The present economic model shows that adding FeNO to the treatment algorithm can save considerable economic resources and increase quality of life when used to manage asthma in combination with current treatment guidelines.
- Prevalence of sensitization to food allergens and challenge proven food allergy in patients visiting allergy centers in Rawalpindi and Islamabad, Pakistan. [Journal Article]
- Springerplus 2016; 5(1):1330.
In this study, we estimated the prevalence of food allergy in the adult allergic patients of Rawalpindi and Islamabad , Pakistan, based on self-report, skin prick test (SPT) and oral food challenge test (OFC). SPT was used for the estimation of sensitization to wheat, egg, milk, beef, chicken, mutton, fish, corn, lentils, rice, soya, peanut and banana. Among 689 patients, 39.19 % showed sensitivity to one or more foods, where, sensitization to wheat (156; 22.6 %) was highest, followed by egg (148; 21.48 %) and milk (138; 20.03 %). Sensitization to various proteins ranged between 15.53-15.97 %, while lentils, corn, rice, soya and peanut sensitization was 15.4, 16, 12.5, 12 and 11.5 % respectively. Only 7.1 % patients were SPT positive for banana allergen. SPT was performed in patients with self-reported food allergy (341/689) and also with no self-reported history of food allergy (348/689). SPT results were positive in 69.8 % of the self-report group, whereas, in the patients with no self-reported food allergy 9.2 % were found sensitized to one or more tested food allergens. 101 patients were recruited for OFC, 61 % of these were confirmed of food allergy. The prevalence of food allergy in the study population was 9 %. Food specific OFC results show that wheat allergy is affecting 1.6 % (95 % CI 0.9-2.84 %) of the total allergy patients, followed by egg allergy 1.31 % (95 % CI 0.70-2.47 %). Furthermore, corn allergy, rice allergy and peanut allergy were 1.02, 0.87 and 0.73 %, respectively. In conclusion, wheat allergy is the most prevalent, followed by egg, chicken, beef and fish allergy, respectively.
- Is spirometry essential in diagnosing asthma? No. [Journal Article]
- Br J Gen Pract 2016 Sep; 66(650):485.
- Is spirometry essential in diagnosing asthma? Yes. [Journal Article]
- Br J Gen Pract 2016 Sep; 66(650):484.
- Nociceptin reduces the inflammatory immune microenvironment in a conventional murine model of airway hyperresponsiveness. [JOURNAL ARTICLE]
- Clin Exp Allergy 2016 Aug 26.
Nociceptin/orphanin FQ (N/OFQ) and its receptor (NOP) are involved in airway hyperresponsiveness (AHR) and inflammation. However the role of nociceptin at modulating the inflammatory immune microenvironment in asthma is still unclear.To understand the role of N/OFQ in the regulation of a Th2-like environment we used a conventional murine model of AHR.Balb/c and CD1 mice were sensitized to ovalbumin (OVA) and treated with saline solution or N/OFQ, at days 0 and 7. A group of Balb/c mice were sacrificed at 7 and 14 days from the first sensitization for the inflammatory profile evaluation while a group of Balb/c and CD1 mice were aerosol-challenged from day 21 to 23 with OVA and sacrificed 24 hours later for functional evaluations.In OVA-sensitized mice, N/OFQ significantly reduced IL-4+CD4+T cells in lymph nodes (LN) and IL-13 in the lungs, while it induced IFN-γ increase in the lung. The efflux of dendritic cells (DCs) to the mediastinic LN and into the lung of OVA-sensitized mice were reduced in N/OFQ treated and sensitized mice. N/OFQ reduced the expression of CD80 on DCs, indicating its ability to modulate the activation of DCs. In a less prone Th2-like environment mice strain, such as CD1 mice, N/OFQ didn't modify lung resistances as observed in BALB/c mice. Finally, spectroscopic data showed the N/OFQ was able to interact onto the membrane of DCs obtained from Balb/c rather than CD1 mice, indicating its ability to modulate AHR in a Th2-like environment with a direct activity on DCs. This article is protected by copyright. All rights reserved.
- Drop-out rate among patients treated with omalizumab for severe asthma: Literature review and real-life experience. [JOURNAL ARTICLE]
- BMC Pulm Med 2016; 16(1):128.
In patients with asthma, particularly severe asthma, poor adherence to inhaled drugs negatively affects the achievement of disease control. A better adherence rate is expected in the case of injected drugs, such as omalizumab, as they are administered only in a hospital setting. However, adherence to omalizumab has never been systematically investigated. The aim of this study was to review the omalizumab drop-out rate in randomized controlled trials (RCTs) and real-life studies. A comparative analysis was performed between published data and the Italian North East Omalizumab Network (NEONet) database.In RCTs the drop-out rate ranged from 7.1 to 19.4 %. Although the reasons for withdrawal were only occasionally reported, patient decision and adverse events were the most frequently reported causes. In real-life studies the drop-out rate ranged from 0 to 45.5 %. In most cases lack of efficacy was responsible for treatment discontinuation. According to NEONet data, 32 % of treated patients dropped out, with an increasing number of drop outs observed over time. Patient decision and lack of efficacy accounted for most treatment withdrawals.Treatment adherence is particularly crucial in patients with severe asthma considering the clinical impact of the disease and the cost of non-adherence. The risk of treatment discontinuation has to be carefully considered both in the experimental and real-life settings. Increased knowledge regarding the main reasons for patient withdrawal is important to improve adherence in clinical practice.
- Subgroup Differences in the Associations between Dog Exposure during the First Year of Life and Early Life Allergic Outcomes. [JOURNAL ARTICLE]
- Clin Exp Allergy 2016 Aug 26.
The effect of dog exposure on the risk of children developing allergic disease remains controversial. Many analyses have not considered that associations may vary within population subgroups.Examine whether associations between living with a dog in the first year of life and allergic outcomes vary within subgroups selected a priori (race, gender and delivery mode).Black (n=496) and White (n=196) children enrolled in the WHEALS birth cohort study had a clinical examination at age 2 years to assess eczema and allergen-specific IgE (sIgE) and perform skin prick testing (SPT). Whether the child lived with an indoor dog in the first year of life was assessed through interview, as was doctor diagnosis of asthma at ages 3-6 years.Living with a dog was associated with decreased odds of having ≥1 positive SPT (OR=0.56, 95%CI 0.34, 0.91) and having eczema (OR=0.34, 95%CI 0.20, 0.60). The association with SPT was stronger in those children born via cesarian-section versus vaginally (OR=0.29, 95%CI 0.12, 0.74 versus OR=0.76, 95%CI 0.43, 1.37, respectively, interaction p=0.087) and in those who were firstborn versus not (OR=0.27, 95%CI 0.11, 0.67 versus OR=0.82, 95%CI 0.45, 1.47, respectively, interaction p=0.044). The association with eczema was stronger in children born vaginally compared with those born via cesarian-section (OR=0.17, 95%CI 0.06, 0.43 versus OR=0.65, 95%CI 0.31, 1.35, respectively, interaction p=0.025) and was stronger in Black versus White children (OR=0.30, 95%CI 0.15, 0.61 versus OR=0.78, 95%CI 0.29, 2.11, respectively, interaction p=0.12). Dog keeping was not significantly inversely associated with having ≥1 elevated sIgE and only approached statistical significance with asthma. This article is protected by copyright. All rights reserved.
- L-citrulline prevents Asymmetric Dimethylarginine-Mediated reductions in Nitric Oxide and Nitrosative Stress In Primary Human Airway Epithelial Cells. [JOURNAL ARTICLE]
- Clin Exp Allergy 2016 Aug 26.
Asthma is associated with reduced systemic levels of L-arginine and increased asymmetric dimethylarginine (ADMA). This imbalance leads to nitric oxide synthase (NOS) uncoupling with reduced nitric oxide (NO) formation and greater oxidative and nitrosative stress. Whether this imbalance also occurs in the bronchial epithelium of asthmatics is unknown.Subjects with asthma and healthy controls underwent bronchoscopy to obtain human bronchial epithelial cells (HBECs), which were cultured and stimulated with IL-13 and IFNγ (both 10ng/ml) to determine the effects of ADMA and varying concentrations of L-arginine, on NO- metabolites (nitrites + nitrates or NOx), hydrogen peroxide and nitrotyrosine levels. HBECs were also treated with L-citrulline to prevent ADMA-mediated effects in NO bioavailability and nitrosative stress.In HBECsIL-13 and IFNγ stimulated NOS2 and increased NOx levels. The addition of ADMA reduced NOx and increased H2 02 levels (p<0.001). Treatment with L-citrulline (800μM, 1600μM) rescued NOx when the L-arginine media concentration was 25 μM but failed to do so with higher concentrations (100μM). Under reduced L-arginine media conditions, HBECs treated with L-citrulline increased the levels of argininosuccinate, an enzyme that metabolizes L-citrulline to L-arginine. L-citrulline prevented the ADMA-mediated increase in nitrotyrosine in HBECs in cells from asthmatics and controls.Increasing ADMA reduces NO formation and increases oxidative and nitrosative stress in airway epithelial cells. L-citrulline supplementation restores NO formation, while preventing nitrosative stress. This article is protected by copyright. All rights reserved.