Efficacy-based comparison between adults and children regarding using advanced counseling for asthma.

BACKGROUND: Asthma advanced counseling using smartphone applications has recently become one of the most effective and commonly used methods among adults and children with asthma. OBJECTIVES: We aimed to compare the advanced counseling effectiveness between adults and children with asthma. METHODS: A cohort prospective parallel study was performed on a group of adults and children nonsmoking patients with asthma, using a pressurized metered dose inhaler (pMDI). The patients were divided into two groups namely adults with asthma with ages ranging from 19 to 60 years and Children with asthma with ages ranging from 11 to 18 years, the two groups received a 2-month course of advanced counseling using "Asthma software" and "Asthma Dodge" smartphone applications, during which the two groups were monitored using the forced expiratory volume in the first second to the forced vital capacity (FEV1/FVC) ratio and asthma control test (ACT). The study has obtained ethical approval with the serial number REC-H-PhBSU-23002, adhering to the principles outlined in The Declaration of Helsinki, from the Ethical Approval Committee of Beni-Suef University Faculty of Pharmacy. RESULTS: With a total of 60 patients with asthma (N = 60), 31 adults (N = 31), and 29 children (N = 29), We found that starting from the first-month visit of counseling the children group showed superiority over the adult group in terms of the pulmonary function improvement p = .006. Also, regarding ACT scores the children group showed a superiority over the adult group this significance started from the first-month visit and continued to the second-month visit with p values = .032 and .011, respectively. CONCLUSION: The advanced counseling achieved better asthma control and pulmonary function improvement in children and adults; however, the improvement was much better in children with asthma than adults with asthma.

Association of serum vitamin C levels with Asthma in adults: results of NHANES 2003-2006 and mendelian randomization study.

BACKGROUND: The protective effect of vitamin C as an antioxidant against asthma in adults remains controversial. This study used an observational study and Mendelian randomization (MR) analysis to investigate the association between adult asthma and serum vitamin C levels. METHODS: Using information from the National Health and Nutrition Examination Survey (NHANES) 2003-2006, we carried out an observational study. A multivariate logistic regression model was employed to examine the connection between adult asthma and serum vitamin C levels. We used the inverse-variance weighted (IVW) method of MR analysis as the primary method to analyze the causal effect of serum vitamin C levels on asthma in adults. RESULTS: A total of 8,504 participants were included in the observational study, including 639 in the asthma group and 7,865 in the non-asthma group. Before sample weighting, serum vitamin C was associated with a reduced risk of asthma in adults (OR = 0.798, 95% CI: 0.673-0.945, P = 0.009). After sample weighting, serum vitamin C was not associated with adult asthma risk (OR = 0.829, 95% CI: 0.660 ~ 1.042, P = 0.104). MR analysis showed no causal relationship between serum vitamin C and adult asthma in either the UK Biobank (OR = 0.957, 95% CI: 0.871 ~ 1.053, P = 0.370) or FinnGen (OR = 0.973, 95% CI: 0.824 ~ 1.149, P = 0.750) cohorts. CONCLUSION: Our study did not support a causal association between serum vitamin C levels and adult asthma risk. The relationship between serum vitamin C and adult asthma requires further research.

Validation of the Asthma Severity Scoring System (ASSESS) in the ALLIANCE Cohort.

BACKGROUND: The Asthma Severity Scoring System (ASSESS) quantifies asthma severity in adolescents and adults. Scale performance in children younger than 12 years is unknown. OBJECTIVE: To validate the ASSESS score in the All Age Asthma Cohort and explore its use in children younger than 12 years. METHODS: Scale properties, responsiveness, and known-group validity were assessed in 247 children (median age, 11 years; interquartile range, 8-13 years) and 206 adults (median age, 52 years; interquartile range, 43-63 years). RESULTS: Overall, measures of internal test consistency and test-retest reliability were similar to the original data of the Severe Asthma Research Program. Cronbach α was 0.59 in children aged 12 to 18 years and 0.73 in adults, reflecting the inclusion of multiple and not-always congruent dimensions to the ASSESS score, especially in children. Analysis of known-group validity confirmed the discriminatory power, because the ASSESS score was significantly worse in patients with poor asthma control, exacerbations, and increased salbutamol use. In children aged 6 to 11 years, test-retest reliability was inferior compared with that in adults and adolescents (Cronbach α, 0.27) mostly because of a less lung function impairment in children with asthma of this age group. Known-group validity, however, confirmed good discriminative power regarding severity-associated variables similar to adolescents and adults. CONCLUSIONS: Test-retest reliability and validity of the ASSESS score was confirmed in the All Age Asthma Cohort. In children aged 6 to 11 years, internal consistency was inferior compared with that in older patients with asthma; however, test validity was good and thus encourages age-spanning usage of the ASSESS score in all patients 6 years or older.

Living in environmental justice areas worsens asthma severity and control: Differential interactions with disease duration, age at onset, and pollution.

BACKGROUND: Impoverished and historically marginalized communities often reside in areas with increased air pollution. OBJECTIVE: We evaluated the association between environmental justice (EJ) track and asthma severity and control as modified by traffic-related air pollution (TRAP). METHODS: We performed a retrospective study of 1526 adult asthma patients in Allegheny County, Pa, enrolled in an asthma registry during 2007-20. Asthma severity and control were determined using global guidelines. EJ tract designation was based on residency in census tracts with ≥30% non-White and/or ≥20% impoverished populations. TRAP exposures (NO2 and black carbon) for each census tract were normalized into pollution quartiles. Generalized linear model analyses determined the effect of EJ tract and TRAP on asthma. RESULTS: TRAP exposure in the highest quartile range was more frequent among patients living in an EJ tract (66.4% vs 20.8%, P < .05). Living in an EJ tract increased the odds of severe asthma in later onset asthma. The odds of uncontrolled asthma increased with disease duration in all patients living in EJ tracts (P < .05). Living in the highest quartile of NO2 also increased the odds of uncontrolled asthma in patients with severe disease (P < .05), while there was no effect of TRAP on uncontrolled asthma in patients with less severe disease (P > .05). CONCLUSIONS: Living in an EJ tract increased the odds of severe and uncontrolled asthma and was influenced by age at onset, disease duration, and potentially by TRAP exposure. This study underscores the need to better understand the complex environmental interactions that affect lung health in groups that have been economically and/or socially marginalized.

[THE EFFICACY OF BRONCHIAL THERMOPLASTY IN LONG-TERM MAINTENANCE OF ADULT PATIENTS WITH MODERATE TO SEVERE ASTHMA].

BACKGROUND AND AIMS: Bronchial thermoplasty (BT) is a bronchoscopic treatment for adult patients with moderate to severe asthma. A systematic review was conducted to examine the efficacy of this treatment. METHODS: Randomized controlled comparing BT to a control in adult patients with moderate to severe asthma were added to the previously conducted systematic review. Literature published prior to July 2022 was selected. RESULTS: Four trials were included in this study. BT resulted in significant improvement in quality of life. However, no significant difference in asthma control was observed. Moreover, the incidence of severe adverse events during the treatment period was increased by BT. Furthermore, BT did not improve lung function, increase withdrawal from oral corticosteroids, reduce frequency of rescue medication usage, or increase the number of symptom-free days. CONCLUSION: From a risk-benefit perspective, there is insufficient evidence to support a recommendation of BT in adult patients with moderate to severe asthma.

Factors associated with allergic rhinitis and combined allergic rhinitis and asthma syndrome (CARAS) in adults undergoing immunotherapy in a tropical country: Is ISAAC-III questionnaire useful in adult populations?

BACKGROUND: Allergic diseases affect about 10-30% of the population in low- or middle-income tropical countries. Few studies describe the factors associated with allergic diseases in adult patients undergoing immunotherapy in Latin American countries. OBJECTIVE: This study aimed to determine the factors associated with allergic rhinitis (AR) and AR in comorbidity with asthma (CARAS) in adults treated with immunotherapy in two allergy referral centers in Bogotá (Colombia). MATERIAL AND METHODS: Observational, cross-sectional study conducted between January 2018 and January 2019. ISAAC-III and sociodemographic questionnaires were applied to determine the factors associated with AR and CARAS in adults treated with immunotherapy who attended the allergy consult at the Fundación Santa Fe de Bogotá and Unimeq-Orl. RESULTS: Among 416 adults aged 18-68 years, 71.4% (n = 297) were women. Regarding the sensitization results obtained by skin prick test, the most frequent allergens were house dust mites (64.18%): 49.03% were positive for both Dermatophagoides pteronyssinus and Dermatophagoides farinae, while 28.61% were positive for Blomia tropicalis. Excluding house dust mites, the most frequent allergens were dog hair (31.01%), cat hair (15.1%), grasses (15.9%), and food (15.9%). The main factor associated with exclusive AR was regular acetaminophen use more than four times a year: Prevalence ratio (PR) = 1.77 (95% CI: 1.12-2.25). The main factor associated with CARAS was cesarean delivery PR: 1.44 (95% CI: 1.09-1.78). CONCLUSION: The main factor associated with AR was regular acetaminophen use, while that associated with CARAS was cesarean delivery. The ISAAC-III questionnaire can be a useful low-cost tool to assess the factors associated with allergic diseases in adults in tropical countries.

Environmental characteristics and disparities in adult asthma in north central Texas urban counties.

OBJECTIVES: Disparities in asthma prevalence present a persistent challenge to public health. The complex nature of the issue requires studies through a wide range of lenses. To date, little research has examined associations between asthma and multiple social and environmental factors simultaneously. This study aims to fill the gap with a focus on the impacts of multiple environmental characteristics and social determinants of health on asthma. STUDY DESIGN: This study uses secondary analysis with data from a variety of sources to analyze the effects of environmental and social factors on adult asthma occurrence in North Central Texas. METHOD: Hospital records and demographic and environmental data for four urban counties in North Central Texas (Collin, Dallas, Denton, and Tarrant) come from the Dallas/Fort Worth Hospital Council Foundation, the US census, the North Central Texas Council of Governments, and the Railroad Commission of Texas. The data were integrated using ArcGIS. A hotspot analysis was performed to inspect the spatial patterns of hospital visits for asthma exacerbations in 2014. The impacts of multiple environmental characteristics and social determinants of health were modeled using negative binomial regression. RESULTS: The results revealed spatial clusters of adult asthma prevalence and disparities by race, class, and education. The occurrence of asthma exacerbations was positively associated with exposure to traffic-related air pollution, energy-related drilling activities, and older housing stock and negatively linked to green space. CONCLUSIONS: Associations between built environmental characteristics and asthma prevalence have implications for urban planners, healthcare professionals, and policy makers. Empirical evidence for the role of social determinants of health supports continuing efforts in policies and practices to improve education and reduce socio-economic inequities.

A Study of the Relationship between Phthalate Exposure and the Occurrence of Adult Asthma in Taiwan.

Although phthalate esters contribute to airway remodeling by increasing bronchial cells' migration and proliferation, the relationship between human exposure to phthalates and asthma is not understood. We measured phthalate exposure in the human body and evaluated its effect on asthma. Asthma (n = 123) and asthma-free (n = 139) participants were, respectively, recruited from an asthma clinic and the community in Taiwan. The urine levels of six phthalate metabolites were determined by liquid chromatography tandem mass spectrometry. Compared with the controls, male asthma patients had higher means of mono-(2-ethylhexyl) phthalate (MEHP) (116.3 nmol/g), monobutyl phthalate (MBP) (850.3 nmol/g) and monoethyl phthalate (MEP) (965.8 nmol/g), and female patients had greater MBP (2902.4 nmol/g). Each 10-fold increase in the level of these phthalate metabolites was correspondingly associated with a 5.0-, 5.8-, 4.2- and 5.3-fold risk of contracting asthma. Male asthma patients were identified to have a higher proportion of MEHP exposure (32.5%) than the controls (25.3%). In asthma patients, an increase in urine MEHP levels and the total phthalate metabolite concentration were notably linked to increased risks of emergency room visits and being hospitalized. For the occurrence and acute clinical events of adult asthma, phthalate exposures and MEHP retention may contribute to higher risks of contracting this respiratory disorder.

Bioinformatic Analysis of Key Regulatory Genes in Adult Asthma and Prediction of Potential Drug Candidates.

Asthma is a common chronic disease that is characterized by respiratory symptoms including cough, wheeze, shortness of breath, and chest tightness. The underlying mechanisms of this disease are not fully elucidated, so more research is needed to identify better therapeutic compounds and biomarkers to improve disease outcomes. In this present study, we used bioinformatics to analyze the gene expression of adult asthma in publicly available microarray datasets to identify putative therapeutic molecules for this disease. We first compared gene expression in healthy volunteers and adult asthma patients to obtain differentially expressed genes (DEGs) for further analysis. A final gene expression signature of 49 genes, including 34 upregulated and 15 downregulated genes, was obtained. Protein-protein interaction and hub analyses showed that 10 genes, including POSTN, CPA3, CCL26, SERPINB2, CLCA1, TPSAB1, TPSB2, MUC5B, BPIFA1, and CST1, may be hub genes. Then, the L1000CDS2 search engine was used for drug repurposing studies. The top approved drug candidate predicted to reverse the asthma gene signature was lovastatin. Clustergram results showed that lovastatin may perturb MUC5B expression. Moreover, molecular docking, molecular dynamics simulation, and computational alanine scanning results supported the notion that lovastatin may interact with MUC5B via key residues such as Thr80, Thr91, Leu93, and Gln105. In summary, by analyzing gene expression signatures, hub genes, and therapeutic perturbation, we show that lovastatin is an approved drug candidate that may have potential for treating adult asthma.

[CQ IN THE LONG-TERM MANAGEMENT OF ADULT ASTHMATIC PATIENTS WHO ARE NOT ADEQUATELY CONTROLLED WITH INHALED CORTICOSTEROIDS MONOTHERAPY, WHICH IS MORE BENEFICIAL: ADDING A LONG ACTING BETA2 AGONIST OR A LONG ACTING MUSCARINIC ANTAGONIST?]

Long-acting beta2-agonists (LABA) are preferred add-on treatment for adult asthmatic patients whose symptoms cannot be controlled with inhaled corticosteroids (ICS) alone. However, over the last decade, long-acting muscarinic antagonists (LAMA) have gained approval for use in treating asthma, and their efficacy is anticipated. Therefore, we conducted a systematic review to investigate whether the addition of LABA or LAMA is more beneficial for the long-term management of adult asthmatic patients poorly controlled on ICS monotherapy. We extracted eight relevant randomized controlled trials (represented in 18 articles) conducted by June 2022 form the corresponding Cochrane review and additional searches through medical databases (CINAHL, Cochrane Library, EMBASE, MEDLINE, PsycINFO, and ICHUSHI (https://www.jamas.or.jp/)). While the LAMA add-on group showed a significantly better improvement in some respiratory function tests, the difference between groups did not exceed the minimum clinically important difference (MCID). On the other hand, the Asthma Quality of Life Questionnaire, a quality of life metric, was significantly higher in the LABA add-on group, but the difference also did not surpass the MCID. Because no outcomes exceeded the MCID, we could not determine whether adding LABA or LAMA on ICS is more beneficial in the long-term management of adult asthmatic patients. Given that no significant differences were found in the incidence of adverse events (including serious ones), when specific adverse events associated with one treatment occur, switching to the other treatment (from LABA to LAMA, or vice versa) can be considered as an option.

CC16 polymorphisms in asthma, asthma subtypes, and asthma control in adults from the Agricultural Lung Health Study.

BACKGROUND: The club cell secretory protein (CC16) has anti-inflammatory and antioxidant effects and is a potential early biomarker of lung damage. The CC16 single nucleotide polymorphism (SNP) rs3741240 risk allele (A) has been inconsistently linked to asthma; other tagging SNPs in the gene have not been explored. The aim was to determine whether CC16 tagging polymorphisms are associated with adult asthma, asthma subtypes or asthma control in the Agricultural Lung Health Study (ALHS). METHODS: The ALHS is an asthma case-control study nested in the Agricultural Health Study cohort. Asthma cases were individuals with current doctor diagnosed asthma, likely undiagnosed asthma, or asthma-COPD overlap defined by questionnaire. We also examined asthma subtypes and asthma control. Five CC16 tagging SNPs were imputed to 1000 Genomes Integrated phase 1 reference panel. Logistic regression was used to estimate associations between CC16 SNPs and asthma outcomes adjusted for covariates. RESULTS: The sample included 1120 asthma cases and 1926 controls of European ancestry, with a mean age of 63 years. The frequency of the risk genotype (AA) for rs3741240 was 12.5% (n = 382). CC16 rs3741240 was not associated with adult asthma outcomes. A tagging SNP in the CC16 gene, rs12270961 was associated with uncontrolled asthma (n = 208, ORadj= 1.4, 95% CI 1.0, 1.9; p = 0.03). CONCLUSION: This study, the largest study to investigate associations between CC16 tagging SNPs and asthma phenotypes in adults, did not confirm an association of rs3741240 with adult asthma. A tagging SNP in CC16 suggests a potential relationship with asthma control.

Alterations of serum and saliva oxidative markers in patients with bronchial asthma.

BACKGROUNDS: The development of asthma is highly affected by exposure to exogenous and endogenous oxidative molecules, but the impact of this exposure on the pathophysiology of asthma has received little attention. OBJECTIVES: Evaluating group of selective oxidative stress markers as a tool in the management of asthma disease. METHODS: In comparison with matched healthy controls, levels of the oxidant and antioxidant markers: lipid peroxidation malondialdehyde (MDA), Total glutathione (tGSH), Uric acid (UA), Glutathione peroxidase (GPx), Catalase (CAT) superoxide dismutase (SOD), and Total antioxidant capacity (TAC) were assessed in serum and saliva of different asthma groups. RESULTS: All oxidative markers in serum and saliva of asthma patients showed significant alterations from normal healthy controls (P < 0.05), except the salivary SOD (P = 0.441). Their levels in serum were significantly correlated with asthma severity (P < 0.05), and the distinguishing between childhood and adult asthma was significantly accomplished by GPx, SOD, TAC markers (P < 0.05). However, in patients with childhood asthma no significant differences were detected between the levels of GPx, CAT, UA, MDA in serum and saliva samples (P > 0.05). CONCLUSION: Determination of the oxidative markers GPx, CAT, UA in serum or saliva can distinguish asthma from healthy states. The serum levels of UA and TAC are highly effective in monitoring asthma severity, while the salivary GPx, CAT, UA, MDA are beneficial in the management of childhood asthma. Discrimination of the age factor between asthma groups can be achieved by testing GPx, SOD, TAC in serum.

Prevalence of asthma and its symptoms in Sri Lankan adults.

BACKGROUND: Data on adult asthma is scarce in Sri Lanka. The objective of this study was to estimate the prevalence of asthma and its symptoms in adult Sri Lankans.  METHODS: A cross-sectional study using a translated version of the European Community Respiratory Health Survey screening questionnaire on subjects ≥ 18 years from 7 provinces in Sri Lanka was conducted. The asthma was defined as "wheezing in the past 12 months (current wheeze)", self-reported asthma attack in the past 12 months or on current asthma medication use. RESULTS: Among 1872 subjects (45.1% males, 48.8% between 18-44 years of age), the prevalence of current wheeze was 23.9% (95%CI: 22.0%-25.9%), self-reported asthma was 11.8% (95%CI: 10.3%-13.2%) and current asthma medication use was 11.1% (95% CI: 9.6%-12.5%). The prevalences were higher in adults > 44 years, 31.4% positively responded to any of the above questions (95%CI: 29.3%-33.4%) and 60.9% of current wheezers did not report having asthma whilst 38.2% used asthma medication. Among current wheezers, 80.1% had at least one other symptom, cough being the commonest. Those with no current wheeze, self-reported asthma and on current asthma medication use, 30%, 35.9% and 36.6%, respectively, reported at least one other symptom. Smokers comprises 22% current wheezers, 20.6% of self-reported asthmatics and 18.7% of current asthma medication users. CONCLUSIONS: The prevalence of asthma in Sri Lankan adults is higher than the other South Asian countries and higher in the older age group. A significant percentage of symptomatic individuals did not report having asthma or being on medication.

Association between Temporary Housing Habitation after the 2011 Japan Earthquake and Mite Allergen Sensitization and Asthma Development.

INTRODUCTION: We previously reported an increased prevalence of asthma in adults who lived in temporary housing after the 2011 Great East Japan Earthquake. The goal of the current study was to investigate changes in asthma prevalence and mite-specific immunoglobulin E (IgE) titers in temporary housing residents during 2014-2019. METHODS: By using the Global Initiative for Asthma guidelines, we diagnosed asthma in Ishinomaki city temporary housing residents aged 15 years or older. We then analyzed serum antigen-specific IgE levels to Dermatophagoides farinae (Der f), Dermatophagoides pteronyssinus (Der p), and Aspergillus fumigatus. RESULTS: The prevalence of asthma exceeded 20% across all age-groups throughout the study period. The proportion of study participants with a "positive" antigen-specific IgE titer (i.e., ≥0.35 IUA/mL) was higher in asthmatics than in nonasthmatics for Der f and Der p but not for Aspergillus fumigatus. Among residents ≥50 years old who were diagnosed with asthma, the percentage with a Der f-specific IgE titer ≥0.10 IUA/mL was higher than the proportion with ≥0.35 IUA/mL. Among study participants, asthma onset occurred before the earthquake, during residence in shelters or temporary housing, and (starting in 2016) after moving out of temporary housing. The Der p-specific IgE level was positively correlated with the duration of temporary housing (p < 0.05, r = 0.41) and inversely correlated with the time elapsed since moving out of temporary housing (p < 0.05, r = -0.35). CONCLUSION: Mite allergen sensitization was found in both asthmatic and nonasthmatic temporary housing residents after the 2011 Japan earthquake and tsunami; asthma developed even after subjects moved out of temporary housing.

Mite avoidance decreased mite-specific IgE levels and ameliorated asthma symptoms in subjects who lived in temporary housing after natural disasters.

BACKGROUND: We previously reported an increased prevalence of asthma among patients who had lived in temporary housing after the 2011 Great East Japan Earthquake. We investigated the prognosis of asthma in former residents of temporary housing after allergen avoidance. METHODS: Asthma was diagnosed in adults ≥ 15 years from 2014 to 2019 who had lived in temporary housing in Ishinomaki City for at least 1 year. The disease prognosis after the intervention of allergen avoidance in cases that were followed for more than 3 years during the 6-year study period was analyzed. We measured the Dermatophagoides farinae -specific immunoglobulin E (IgE) levels in serum, and the amount of Dermatophagoides group 1 (Der 1) antigen on their futons or mattresses. We instructed residents in an allergen avoidance strategy that included 32 tasks, including using microfiber bedding covers. RESULTS: Of the 202 examinees who were followed for at least 3 years during the 6-year study period, 72(35.6%) were asthmatic during at least one examination. Of these 72 asthmatics, 55(76.4%) developed the disease after the earthquake, and more than half of the cases that we diagnosed at the examination were mild intermittent asthma. After the allergen-avoidance intervention, both the Der 1 level on the futons or mattresses of residents who were diagnosed with asthma but who were nonasthmatic at the final screening and their serum Der f-specific IgE levels significantly decreased (P < 0.01) at the final examination. CONCLUSION: Antigen avoidance ameliorated mild asthma that was prevalent among residents of temporary housing after the earthquake.

Overweight improves long-term survival in Japanese patients with asthma.

BACKGROUND: Obesity is a risk factor for severe and difficult-to-treat asthma. However, the impact of different physiques on long-term outcomes is poorly understood. We aimed to investigate the correlation between obesity and asthma-associated long-term mortality in Japanese adults. METHODS: From the data on 3146 individuals with air pollution-related respiratory diseases in the Omuta City Air Pollution-Related Health Damage Cohort Program, 697 adult patients with asthma were analyzed. Hazard ratios for long-term all-cause and respiratory disease -related mortality were compared in patients with different physiques using the Cox proportional hazard models. The classification of physiques was based on the WHO obesity criteria. RESULTS: Of the 697 patients, 439 died during the median observation period of 26.3 years. The number (% of total) of underweight, normal-weight, pre-obese, and obese class I-III individuals were 75 (10.8%), 459 (65.9%), 140 (20.1%), and 23 (3.3%), respectively. The Cox proportional hazard model (adjusted hazard ratio [95% confidence interval], P value) showed that pre-obese group had a significantly reduced risk for all-cause (0.65 [0.51 to 0.83], P < 0.05) and respiratory disease (0.55 [0.37 to 0.81], P < 0.05)-related mortality related to normal-weight group. CONCLUSIONS: Our cohort program demonstrated that being slightly overweight may reduce the risk of long-term mortality in patients with asthma. However, the influence of obesity on long-term outcomes remains unclear in asthma, because of the small number of obese patients included in our study. Our findings suggest that interventions, including nutrition and exercises, should be provided to Japanese patients with asthma.

The first year of treatment predicts the prognosis of asthma over 25 y-A prospective study.

BACKGROUND: An investigator-driven, real-life follow-up study of adult-onset steroid-naïve, newly diagnosed asthma (162 patients) to investigate the treatment results over the 25-year course of the disease and whether the first treatment year's forced expiratory volume in one second (FEV1 ) predicts the long-term prognosis. METHODS: Eighty-three per cent of the 133 living patients participated in the 25-year examinations. At this visit, basic asthma examinations including lung function, as well as questionnaires for health-related quality of life (HRQoL), GINA and the Asthma Control Test, were used for evaluation. The use of medication and remission was verified. RESULTS: There was no statistically significant change in mean FEV1 % predicted (FEV1 %) from baseline to the 25-year control. The changes in FEV1 % during the first year predicted the results at the end of follow-up. Normal FEV1 % at the end of the first year predicted normal FEV1 , and below-normal FEV1 % at 1 year predicted below-normal FEV1 % at 25 years. Twenty-nine patients (26.4%) had discontinued their medication, and six (5.5%) used ICS periodically. Clinical remission was reached by 16.4% of the patients, and 7.6% reached functional remission. The general HRQoL remained unchanged. CONCLUSION: In adult-onset asthma, the level of FEV1 reached during the first treatment year seems to predict the later lung function level. One quarter of the patients discontinued the asthma treatment, but their HRQoL was better than that of those continuing to use ICS. Clinical remission was reached by 16% of the patients, which is in concordance with other studies.

A cis-eQTL allele regulating reduced expression of CHI3L1 is associated with late-onset adult asthma in Japanese cohorts.

BACKGROUND: The chitinase-like protein YKL-40 plays a major role in inhibiting the inflammasome. Deregulation of inflammasome activation is emerging as a key modulator of pathologic airway inflammation in patients with asthma. We determined whether cis-expression quantitative trait loci (eQTLs) of the gene that encodes YKL-40, chitinase 3-like 1 (CHI3L1), are involved in the onset of asthma or in specific asthma phenotypes. METHODS: This case-control study, which was conducted at the University of Tsukuba, Japan, included a total of 2709 adults from the Tsukuba genome-wide association study (GWAS) cohort (734 healthy volunteers and 237 asthma patients), the Tsukuba replication cohort (375 healthy adult volunteers and 381 adult asthma patients), and the Hokkaido replication cohort (554 healthy adult volunteers and 428 adult asthma patients). Among 34 cis-eQTLs in CHI3L1 in the lung, rs946261 was associated with adult asthma in these Japanese cohorts. The genetic impact of rs946261 on asthma was also examined according to the age at onset and adult asthma clusters. RESULTS: In the Tsukuba GWAS cohort, the C allele at rs946261 was significantly associated with reduced expression of CHI3L1 mRNA in the lung and with development of asthma (odds ratio (OR) 1.27; P = 0.036). The association was also observed following analysis of the three Japanese cohorts (OR 1.16; P = 0.013). A stronger association was found with late-onset asthma that developed at 41 years of age or later (OR 1.24; 95% confidence interval (CI) 1.07-1.45; P = 0.0058) and with a specific asthma phenotype characterized by late onset, less atopy, and mild airflow obstruction (OR 1.29; 95% CI 1.03-1.61; P = 0.027). CONCLUSIONS: The genotype consisting of the cis-eQTL allele that reduces expression of CHI3L1 was specifically associated with late-onset adult asthma. Given the important role of YKL-40 in many pathophysiological processes, including cell growth, migration, chemotaxis, reorganization, and tissue remodeling, it may be involved in an important pathogenic role in the establishment of inflammation and remodeling in asthmatic airways. Our findings may indicate the presence of a specific endotype related to exaggerated activation of YKL-40 in the pathogenesis of late-onset adult asthma.

Association of plasma soluble CD14 level with asthma severity in adults: a case control study in China.

BACKGROUND: Soluble CD14 (sCD14) shedding from CD14 could regulate T lymphocyte activation and function, which has implicated in the pathogenesis of bronchial asthma. The level of sCD14 expression is obviously increased in asthmatic patients during acute asthma attacks. The objective of this study was to investigate the association between plasma sCD14 level and asthma severity in adults. METHODS: The plasma sCD14 level in asthma patients (n = 910) and healthy controls (n = 881) was quantified by commercially available enzyme-linked immunosorbent assay (ELISA) kits. The asthma cases were subdivided into intermittent asthma (n = 537), mild (n = 246), moderate (n = 96) and severe (n = 31) persistent asthma patients. Association between plasma sCD14 level and asthma severity, lung function parameters as well as asthma symptoms and signs in adults were performed using multivariate logistic regression models. RESULTS: We observed significant relationships of plasma sCD14 level with asthma severity, lung function parameters as well as asthma symptoms and signs in adults. After adjusting for multiple potential confounders, each one-unit increase in log sCD14 was significantly associated with 67, 82, 79 and 85% reduced ORs for intermittent asthma, mild, moderate and severe persistent asthma, respectively (all P < 0.0001). Compared with the participants of FEV1/FVC ≥75%, each one-unit increase in log sCD14 was significantly associated with a 37% decreased OR of FEV1/FVC < 75% (P < 0.0001). However, the adjusted odds ratios (ORs) of severe dyspnea, wheeze and cyanosis in asthma patients were 1.88, 1.46 and 2.20 for each one-unit increase in log sCD14, respectively. In addition, compared with health controls, the adjusted area under the curve (AUC) of sCD14 was 0.814 at a cut-off points of 0.53, and the sensitivity and specificity were 71.0 and 76.8% for predicting asthma in adults. And the adjusted AUC of sCD14 reached 0.786, 0.847, 0.887 and 0.917 in predicting intermittent asthma, mild, moderate and severe persistent asthma, respectively. CONCLUSIONS: Our results indicated that plasma sCD14 level is negatively associated with asthma severity, suggesting a protective role for sCD14 in the development of asthma in adults. And plasma sCD14 level might be a potential biomarker in prediction of asthma severity in adults.

High level of fluorescent oxidation products and worsening of asthma control over time.

High Fluorescent oxidation products level (FlOPs), a global oxidative stress biomarker, was associated cross-sectionally with poor asthma outcomes but its longitudinal association with asthma evolution has never been examined. We aimed to study the associations between FlOPs level at baseline and changes in current asthma, asthma attacks and asthma control status over 8 years. We used data from the second survey of the French EGEA cohort study as baseline and the third survey as follow-up. At baseline, the mean age of the 489 participants with ever asthma was 39 (± 16) years, 49% were women. Among participants with controlled asthma at baseline, high FlOPs level was significantly associated with worsening of asthma control at follow-up (odds-ratio adjusted for age, sex and smoking status (95% CI): 2.27 (1.32-3.90). No other significant associations were observed. In conclusion, results suggest FlOPs as a predictor of asthma evolution in adults and a good candidate marker in asthma management.