ResearchPad - asthma https://www.researchpad.co Default RSS Feed en-us © 2020 Newgen KnowledgeWorks <![CDATA[Associations of dog and cat ownership with wheezing and asthma in children: Pilot study of the Japan Environment and children's study]]> https://www.researchpad.co/article/elastic_article_14570 No previous study has used repeated measures data to examine the associations of dog/cat ownership with wheezing and asthma prevalence among children. This prospective study used repeated measurers analysis to determine whether dog/cat ownership in childhood is an independent risk factor for wheezing and asthma, after adjustment for gestational, socio-economical, and demographical confounders confounders, in Japan.MethodsWe conducted a multicenter pilot study of the Japan Environment and Children's Study (JECS) during 2009–2010. Among 440 newborn infants enrolled, 410 (52.8% males) were evaluated for dog/cat ownership in the home and history of wheezing and asthma in five follow-up questionnaire surveys (until age 6 years). Dog/cat ownership during follow-up period was categorized into four groups: 7.6% were long-term dog/cat owners, 5.9% were toddler-age owners, 5.9% were preschool-age owners, and 80.7% were never owners.ResultsThe prevalence of wheezing during follow-up period increased from 20.8% to 35.4% and the prevalence of asthma increased from 1.3% to 16.3%. A fitted logistic generalized estimating equation models including important confounders showed no significant associations of the interaction between dog and/or cat ownership and follow-up time with the risks of wheezing and asthma. However, the risks of wheezing and asthma were slightly lower for long-term and toddler-age dog/cat owners than for preschool-age and never owners.ConclusionsThe present findings suggest that dog and cat ownership from toddler-age does not increase the risks of wheezing and asthma compared with never owners among Japanese children. ]]> <![CDATA[A non-stationary Markov model for economic evaluation of grass pollen allergoid immunotherapy]]> https://www.researchpad.co/article/elastic_article_14555 Allergic rhino-conjunctivitis (ARC) is an IgE-mediated disease that occurs after exposure to indoor or outdoor allergens, or to non-specific triggers. Effective treatment options for seasonal ARC are available, but the economic aspects and burden of these therapies are not of secondary importance, also considered that the prevalence of ARC has been estimated at 23% in Europe. For these reasons, we propose a novel flexible cost-effectiveness analysis (CEA) model, intended to provide healthcare professionals and policymakers with useful information aimed at cost-effective interventions for grass-pollen induced allergic rhino-conjunctivitis (ARC).MethodsTreatments compared are: 1. no AIT, first-line symptomatic drug-therapy with no allergoid immunotherapy (AIT). 2. SCIT, subcutaneous immunotherapy. 3. SLIT, sublingual immunotherapy. The proposed model is a non-stationary Markovian model, that is flexible enough to reflect those treatment-related problems often encountered in real-life and clinical practice, but that cannot be adequately represented in randomized clinical trials (RCTs). At the same time, we described in detail all the structural elements of the model as well as its input parameters, in order to minimize any issue of transparency and facilitate the reproducibility and circulation of the results among researchers.ResultsUsing the no AIT strategy as a comparator, and the Incremental Cost Effectiveness Ratio (ICER) as a statistic to summarize the cost-effectiveness of a health care intervention, we could conclude that:SCIT systematically outperforms SLIT, except when a full societal perspective is considered. For example, for T = 9 and a pollen season of 60 days, we have ICER = €16,729 for SCIT vs. ICER = €15,116 for SLIT (in the full societal perspective).For longer pollen seasons or longer follow-up duration the ICER decreases, because each patient experiences a greater clinical benefit over a larger time span, and Quality-adjusted Life Year (QALYs) gained per cycle increase accordingly.Assuming that no clinical benefit is achieved after premature discontinuation, and that at least three years of immunotherapy are required to improve clinical manifestations and perceiving a better quality of life, ICERs become far greater than €30,000.If the immunotherapy is effective only at the peak of the pollen season, the relative ICERs rise sharply. For example, in the scenario where no clinical benefit is present after premature discontinuation of immunotherapy, we have ICER = €74,770 for SCIT vs. ICER = €152,110 for SLIT.The distance between SCIT and SLIT strongly depends on under which model the interventions are meta-analyzed.ConclusionsEven though there is a considerable evidence that SCIT outperforms SLIT, we could not state that both SCIT and SLIT (or only one of these two) can be considered cost-effective for ARC, as a reliable threshold value for cost-effectiveness set by national regulatory agencies for pharmaceutical products is missing. Moreover, the impact of model input parameters uncertainty on the reliability of our conclusions needs to be investigated further. ]]> <![CDATA[Possible risk factors for poor asthma control assessed in a cross-sectional population-based study from Telemark, Norway]]> https://www.researchpad.co/article/elastic_article_13801 This cross-sectional study of the general population of Telemark County, Norway, aimed to identify risk factors associated with poor asthma control as defined by the Asthma Control Test (ACT), and to determine the proportions of patients with poorly controlled asthma who had undergone spirometry, used asthma medication, or been examined by a pulmonary physician. In 2014–2015, the study recruited 326 subjects aged 16–50 years who had self-reported physician-diagnosed asthma and presence of respiratory symptoms during the previous 12 months. The clinical outcome measures were body mass index (BMI), forced vital capacity (FVC) and forced expiratory volume in one second (FEV1), fractional exhaled nitric oxide (FeNO), immunoglobulin E (IgE) in serum and serum C-reactive protein (CRP). An ACT score ≤ 19 was defined as poorly controlled asthma. Overall, 113 subjects (35%) reported poor asthma control. The odds ratios (ORs) and 95% confidence intervals (CIs) for factors associated with poorly controlled asthma were: self-reported occupational exposure to vapor, gas, dust, or fumes during the previous 12 months (OR 2.0; 95% CI 1.1–3.6), body mass index ≥ 30 kg/m2 (OR 2.2; 95% CI 1.2–4.1), female sex (OR 2.6; 95% CI 1.5–4.7), current smoking (OR 2.8; 95% CI 1.5–5.3), and past smoking (OR 2.3; 95% CI 1.3–4.0). Poor asthma control was also associated with reduced FEV1 after bronchodilation (β –3.6; 95% CI –7.0 to –0.2). Moreover, 13% of the participants with poor asthma control reported no use of asthma medication, 51% had not been assessed by a pulmonary physician, and 20% had never undergone spirometry. Because these data are cross-sectional, further studies assessing possible risk factors in general and objectively measured occupational exposure in particular are needed. However, our results suggest that there is room for improvement with regards to use of spirometry and pulmonary physician referrals when a patient’s asthma is inadequately controlled.

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<![CDATA[Likely questionnaire-diagnosed food allergy in 78, 890 adults from the northern Netherlands]]> https://www.researchpad.co/article/elastic_article_13854 It is challenging to define likely food allergy (FA) in large populations which limited the number of large studies regarding risk factors for FA.ObjectiveWe studied the prevalence and characteristics of self-reported FA (s-rFA) in the large, population-based Dutch Lifelines cohort and identified associated risk factors.MethodsLikely food allergic cases (LikelyFA) were classified based on questionnaire reported characteristics consistent with FA. Subjects with atypical characteristics were classified as Indeterminate. We investigated 13 potential risk factors for LikelyFA such as birth mode and living on a farm and addressed health-related quality of life (H-RQOL).ResultsOf the 78, 890 subjects, 12.1% had s-rFA of which 4.0% and 8.1% were classified as LikelyFA and Indeterminate, respectively. Younger age, female sex, asthma, eczema and nasal allergy increased the risk of LikelyFA (p-value range <1.00*10−250–1.29*10−7). Living in a small city/large village or suburb during childhood was associated with a higher risk of LikelyFA than living on a farm (p-value = 7.81*10−4 and p = 4.84*10−4, respectively). Subjects classified as Indeterminate more often reported depression and burn-out compared to those without FA (p-value = 1.46*10−4 and p = 8.39*10−13, respectively). No association was found with ethnicity, (duration of) breastfeeding, birth mode and reported eating disorder. Mental and physical component scores measuring H-RQOL were lower in both those classified as LikelyFA and Indeterminate compared to those without FA.ConclusionThe prevalence of s-rFA among adults is considerable and one-third reports characteristics consistent with LikelyFA. Living on a farm decreased the risk of LikelyFA. The association of poorer H-RQOL as well as depression and burn-out with questionable self-perceived FA is striking and a priority for future study. ]]> <![CDATA[Sputum microbiomic clustering in asthma and chronic obstructive pulmonary disease reveals a <i>Haemophilus</i>‐predominant subgroup]]> https://www.researchpad.co/article/elastic_article_6942 Sputum microbiomic cluster analysis and TDA demonstrates 2 subgroups of stable severe asthma and moderate‐to‐severe COPD differentiated according to dominance of Haemophilus. The Haemophilus‐high group had no defining clinical characteristics but had lower microbial diversity and increased levels of sputum TNFα and IL1β. γProteobacteria:Firmicutes (γP:F) differentiated the clusters and was the most predictive biomarker of the Haemophilus‐high group.

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<![CDATA[Subphenotypes of nonsteroidal antiinflammatory disease‐exacerbated respiratory disease identified by latent class analysis]]> https://www.researchpad.co/article/elastic_article_6890 Heterogeneity of NERD phenotype reflects differences in inflammatory response measured by airway cells and eicosanoids. Identifying subphenotypes provides a more insightful perception and suggests a need for more individualized approach. In aspect of logLTE4/logPGE2 ratio, latent class analysis assigned subject to different groups better than identification by disease severity or control emphasizing the heterogeneity in NERD subgroup. Abbreviations: LTE4, Leukotriene E4; NERD, NSAID‐exacerbated respiratory disease; PGE2, Prostaglandin E2

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<![CDATA[Matching‐adjusted comparison of oral corticosteroid reduction in asthma: Systematic review of biologics]]> https://www.researchpad.co/article/N821acc11-6eaa-4140-b07a-30e978fbc786 Oral corticosteroid (OCS) treatment for severe asthma is associated with substantial disease burden. Thus, OCS dosage reduction is desirable. Relative efficacy of biologics in reducing OCS treatment for severe, uncontrolled asthma is not fully characterized.ObjectiveWe performed a matching‐adjusted indirect comparison (MAIC) to assess the relative effects on OCS treatment reduction of three biologic asthma treatments.MethodsIn MAIC of benralizumab vs. mepolizumab and vs. dupilumab, patient‐level data from the Phase III benralizumab OCS‐sparing trial, ZONDA, were weighted to match treatment effect–modifying patient characteristics in comparator trials.ResultsAfter matching adjustment, mean difference between benralizumab and mepolizumab for OCS reduction was 6.08% (95% CI −22.22‐34.38; P = .67) by week 24, and odds ratio of OCS elimination was 2.32 (95% CI 0.48‐11.15; P = .29). A trend in annual asthma exacerbation rate reduction favouring benralizumab over mepolizumab was observed, although it was not statistically significant (rate ratio [RR] = 0.56 [95% CI 0.28‐1.13; P = .11]). Mean difference between benralizumab and dupilumab for OCS reduction was −0.71% (95% CI −20.56‐19.15; P = .94), and odds ratio of OCS elimination was 2.26 (95% CI 0.52‐9.84; P = .28). A non‐significant trend in annual asthma exacerbation rate reduction favouring benralizumab over dupilumab was observed (RR = 0.50 [95% CI 0.20‐1.28; P = .15]). Effective sample size was 49% (72 vs. 148) and 25% (36 vs. 142) of original sample size for MAIC of benralizumab vs. mepolizumab and benralizumab vs. dupilumab, respectively.Conclusions and Clinical RelevanceFollowing patient baseline characteristics matching across clinical trials, benralizumab demonstrated efficacy comparable to mepolizumab and dupilumab for OCS dosage reduction, OCS elimination, and annual exacerbation rate reduction. Comparatively low effective sample sizes indicated substantial differences for patient populations between ZONDA and mepolizumab and dupilumab trials. ]]> <![CDATA[Asthma control is associated with economic outcomes, work productivity and health-related quality of life in patients with asthma]]> https://www.researchpad.co/article/Nf27f906a-6a2b-4171-867d-25ee63f022e1

Background

The objective of this analysis was to examine the association between asthma control (based on Asthma Control Test (ACT) responses) and healthcare resource utilisation (HRU), work productivity and health-related quality of life (HRQoL) among a nationwide sample of US adults with a self-reported diagnosis of asthma and without comorbid chronic obstructive pulmonary disease.

Methods

Data were obtained from the 2015 and 2016 self-administered, internet-based National Health and Wellness Surveys. Patients were grouped by ACT score (≤15: poorly controlled; 16–19: partly controlled; 20–25: well-controlled asthma). Study outcomes included HRU (patient-reported healthcare provider visits, emergency department visits and hospitalisations during the previous 6 months); work productivity, measured using the Work Productivity and Activity Impairment-General Health Scale; HRU-associated costs and work productivity loss and HRQoL, measured using EuroQoL-5 Dimensions-5 Levels (EQ-5D-5L) and the Short Form Health Survey-36V.2 (SF-36V.2). Incremental differences in outcomes between groups were assessed using generalised linear models adjusted for covariates.

Results

Of 7820 eligible adults, 17.4% had poorly controlled, 20.1% partly controlled and 62.5% well-controlled asthma. Well-controlled asthma was associated with significantly lower HRU (p<0.001) and lower mean direct costs ($6012 vs $8554 and $15 262, respectively; p<0.001); well-controlled asthma was also associated with significantly lower mean scores for work absenteeism, work presenteeism, overall work impairment and activity impairment (all p<0.001), and lower mean indirect costs ($6353 vs $10 448 and $14 764, respectively; p<0.001). Clinically meaningful differences favouring well-controlled asthma were seen for all HRQoL measures, with statistically significantly higher adjusted mean EQ-5D-5L index and SF-6D Health Utilities Index scores (derived from SF-36V.2) for patients with well-controlled asthma compared with partly controlled or poorly controlled asthma (p<0.001).

Conclusions

The study demonstrates a clear relationship between asthma control and its impact on HRU, costs, work productivity and HRQoL. This will allow for better identification and management of patients with poorly controlled asthma.

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<![CDATA[Lifestyle, sick leave and work ability among Norwegian employees with asthma—A population-based cross-sectional survey conducted in Telemark County, Norway]]> https://www.researchpad.co/article/Ndae955f4-245c-442b-a4a6-579d96a7b9a3

Objective

To investigate whether physician-diagnosed asthma modifies the associations between multiple lifestyle factors, sick leave and work ability in a general working population.

Methods

A cross-sectional study was conducted in Telemark County, Norway, in 2013. A sample of 16 099 respondents completed a self-administered questionnaire. We obtained complete data on lifestyle, work ability and sick leave for 10 355 employed persons aged 18–50 years. We modelled sick leave and work ability using multiple logistic regression, and introduced interaction terms to investigate whether associations with lifestyle factors were modified by asthma status.

Results

Several lifestyle risk factors and a multiple lifestyle risk index were associated with sick leave and reduced work ability score among persons both with and without physician-diagnosed asthma. A stronger association between lifestyle and sick leave among persons with asthma was confirmed by including interaction terms in the analysis: moderate lifestyle risk score * asthma OR = 1.4 (95% CI 1.02–2.1); high lifestyle risk score * asthma OR = 1.6 (95% CI 1.1–2.3); very high lifestyle risk score * asthma OR = 1.6 (95% CI 0.97–2.7); obesity * asthma OR = 1.5 (95% CI 1.02–2.1); past smoking * asthma OR = 1.4 (95% CI 1.01–1.9); and current smoking * asthma OR = 1.4 (95% CI 1.03–2.0).

There was no significant difference in the association between lifestyle and work ability score among respondents with and without asthma.

Conclusions

In the present study, we found that physician-diagnosed asthma modified the association between lifestyle risk factors and sick leave. Asthma status did not significantly modify these associations with reduced work ability score. The results indicate that lifestyle changes could be of particular importance for employees with asthma.

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<![CDATA[Overuse of short-acting β2-agonists in asthma is associated with increased risk of exacerbation and mortality: a nationwide cohort study of the global SABINA programme]]> https://www.researchpad.co/article/Ndc8df19e-7134-45d3-84f4-56ddb249f47f

Background

Overuse of short-acting β2-agonists (SABA) may indicate poor asthma control and adverse health outcomes. Contemporary population-based data on use, risk factors and impact of SABA (over)use on asthma exacerbations and mortality are scarce, prompting initiation of the global SABINA (SABA use IN Asthma) programme.

Methods

By linking data from Swedish national registries, asthma patients aged 12–45 years with two or more collections of drugs for obstructive lung disease during 2006–2014 were included. SABA overuse was defined as collection of more than two SABA canisters in a 1-year baseline period following inclusion. SABA use was grouped into 3–5, 6–10 and ≥11 canisters per baseline-year. Cox regression was used to examine associations between SABA use and exacerbation (hospitalisations and/or oral corticosteroid claims) and mortality.

Results

The analysis included 365 324 asthma patients (mean age 27.6 years; 55% female); average follow-up was 85.4 months. 30% overused SABA, with 21% collecting 3–5 canisters per year, 7% collecting 6–10 canisters per year and 2% collecting ≥11 canisters per year. Increasing number of collected SABA canisters was associated with increased risk of exacerbation, as follows. 3–5 canisters: hazard ratio (HR) 1.26 (95% CI 1.24–1.28); 6–10 canisters: 1.44 (1.41–1.46); and ≥11 canisters: 1.77 (1.72–1.83), compared to two or fewer canisters per year. Higher SABA use was associated with incrementally increased mortality risk (2564 deaths observed), as follows. 3–5 canisters: HR 1.26 (95% CI 1.14–1.39); 6–10 canisters 1.67 (1.49–1.87); and ≥11 canisters: 2.35 (2.02–2.72) compared to two or fewer canisters per year.

Conclusion

One-third of asthma patients in Sweden collected three or more SABA canisters annually. SABA overuse was associated with increased risks of exacerbation and mortality. These findings emphasise that monitoring of SABA usage should be key in improving asthma management.

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<![CDATA[Aerosols for systemic treatment]]> https://www.researchpad.co/article/Ndab20c66-3a75-4923-afdb-568a2d23d72c

The development of a new group of drugs (polypeptides) have recently increased the interest of alternative administration to the enteral route because of its proteolytic activity and the catabolism of the “first-pass effect.” Aside from the “needle,” the administration in the respiratory tract via aerosol is the method with the best efficiency. But several problems prohibited its spreading: (1) the accuracy and the reproducibility of the inhaled dose (range ca. 1:4); (2) the small amount of inhaled drug in relation to the dose in the aerosol delivery system (range ca. 1%–10%); (3) the fear of allergic reactions of the respiratory system; (4) the variability of the drug transport into the systemic circulation. New approaches and data raise hopes in reducing the problems: (1) aerosol delivery systems with defined particle spectrum and storage systems; slow vital capacity inhaling maneuver; (2) delivery systems that nebulizes nearly the total amount of drug; (3) all studies with the inhalation application of insulin, heparin, ergotamin, ribavirin, aminoglycosides, and “cigarette smoke” do not reveal any relevant allergic reaction; (4) many studies were performed in the last 10 years on the influence of substances and especially of diseases on the transport of molecules through the respiratory tract. Only a few of them are relevant (exogen allergic alveolitis, active sarcoidosis, active smoking). Aerosols for systemic drug treatment seems to be a gained alternative to the “syringe.”

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<![CDATA[Virus, allergic sensitisation and cortisol in infant bronchiolitis and risk of early asthma]]> https://www.researchpad.co/article/N102443bc-2976-443a-9691-c22e24df5116

Background

Acute bronchiolitis during infancy and human rhinovirus (HRV) lower respiratory tract infections increases the risk of asthma in atopic children. We aimed to explore whether specific viruses, allergic sensitisation or cortisol levels during acute bronchiolitis in infancy increase the risk of early asthma, using recurrent wheeze as a proxy.

Methods

In 294 children with a mean (range) age of 4.2 (0–12) months enrolled during hospitalisation for acute infant bronchiolitis, we analysed virus in nasopharyngeal aspirates, serum specific immunoglobulin E against food and inhalant allergens, and salivary morning cortisol. These factors were assessed by regression analyses, adjusted for age, sex and parental atopy, for risk of recurrent wheeze, defined as a minimum of three parentally reported episodes of wheeze at the 2-year follow-up investigation.

Results

At 2 years, children with, compared to without, recurrent wheeze had similar rates of respiratory syncytial virus (RSV) (82.9% versus 81.8%) and HRV (34.9% versus 35.0%) at the acute bronchiolitis, respectively. During infancy, 6.9% of children with and 9.2% of children without recurrent wheeze at 2 years were sensitised to at least one allergen (p=0.5). Neither recurrent wheeze nor incidence rate ratios for the number of wheeze episodes at 2 years were significantly associated with specific viruses, high viral load of RSV or HRV, allergic sensitisation, or morning salivary cortisol level during acute bronchiolitis in infancy.

Conclusion

In children hospitalised with acute infant bronchiolitis, specific viruses, viral load, allergic sensitisation and salivary morning cortisol did not increase the risk of early asthma by 2 years of age.

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<![CDATA[Impact of socioeconomic status on participation and outcomes in the Salford Lung Studies]]> https://www.researchpad.co/article/N08e29f4e-ed62-4d7d-b20d-cba66c658398

COPD and asthma prevalence is associated with socioeconomic status (or “deprivation”), yet deprivation is rarely considered in typical large-scale efficacy randomised controlled trials that recruit highly selected patient populations. In this post hoc analysis of the Salford Lung Studies in COPD and asthma (two 12-month, open-label, effectiveness randomised controlled trials conducted in UK primary care), we evaluated the impact of patient deprivation on clinical outcomes with initiating fluticasone furoate/vilanterol versus continuing usual care.

Patients were categorised into deprivation quintiles based on postcode and a countrywide database of indices of deprivation, and trial outcomes by quintile were assessed.

52% of patients in the COPD study were included in the most deprived quintile, contrasting with 20% in the asthma study. Greater deprivation was associated with higher rates of primary/secondary healthcare contacts and costs. However, the treatment effect of fluticasone furoate/vilanterol versus usual care for primary (COPD: moderate/severe exacerbations; asthma: Asthma Control Test responders at week 24) and secondary/other (healthcare consumption, adherence, treatment modifications, study withdrawals, exacerbations, serious adverse events) outcomes was similar across deprivation quintiles.

Our findings support the recruitment of participants from all socioeconomic strata to allow assessment of data generalisability to routine clinical practice.

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<![CDATA[Novel measure of lung function for assessing disease activity in asthma]]> https://www.researchpad.co/article/Nc4aab9da-fb86-45d6-98bb-a63a72574a18

Introduction

In asthma, lung function measures are often discordant with clinical features such as disease activity or control.

Methods

We investigated a novel technique that provides a measure (σCL) of unevenness (inhomogeneity) in lung inflation/deflation. In particular, we compared σCL with FEV1% predicted (FEV1%pred) as measures of disease activity in the asthmatic lung.

Results

σCL correlated modestly with FEV1%pred. However, σCL is not simply a proxy for FEV1%pred as the effects of salbutamol on the two parameters were unrelated. Importantly, σCL reflected disease control better than FEV1.

Discussion

We conclude that σCL shows promise as an objective measure of disease activity in asthma.

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<![CDATA[Nickel allergy is associated with wheezing and asthma in a cohort of young German adults: results from the SOLAR study]]> https://www.researchpad.co/article/N901d91eb-b32f-4609-a581-c44ca3ca2f1b

Background

Nickel allergy is the most prevalent contact allergy. It belongs to a different hypersensitivity type to asthma and rhinoconjunctivitis. The aim of this analysis was to assess whether self-reported nickel allergy is associated with incident wheezing, asthma and rhinoconjunctivitis in young German adults, taking into account potential effect modification by sex.

Methods

In total, 2051 (70.6%) participants aged 19–24 years took part in the second phase of SOLAR (Study on Occupational Allergy Risks), a follow-up study of ISAAC II (the second phase of the International Study of Asthma and Allergies in Childhood) in Germany. Self-reported nickel allergy, as well as having pierced ears, and the three outcomes incident wheezing, asthma and rhinoconjunctivitis, were analysed stratified for sex. Logistic regression adjusted for potential confounders was performed.

Results

An association between self-reported nickel allergy and incident wheezing was observed for men and women, while only in males did pierced ears show a significant association with the outcome (adjusted OR 2.26, 95% CI 1.10–4.62). Also only in males, self-reported nickel allergy was associated with elevated odds for incident asthma (adjusted OR 4.34, 95% CI 1.22–15.41). Neither in men nor in women was a significant association observed for incident rhinoconjunctivitis.

Conclusion

Our results suggest that self-reported nickel allergy is associated with incident wheezing. Whether this association is due to environmental or genetic predisposition, or due to an overlap of the mechanisms of type I and type IV hypersensitivity, needs to be elucidated.

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<![CDATA[Intra-individual variation of particles in exhaled air and of the contents of Surfactant protein A and albumin]]> https://www.researchpad.co/article/N3daed577-6f93-4f19-9dc8-54ce3f8d7d6e

Introduction

Particles in exhaled air (PEx) provide samples of respiratory tract lining fluid from small airways containing, for example, Surfactant protein A (SP-A) and albumin, potential biomarkers of small airway disease. We hypothesized that there are differences between morning, noon, and afternoon measurements and that the variability of repeated measurements is larger between days than within days.

Methods

PEx was obtained in sixteen healthy non-smoking adults on 11 occasions, within one day and between days. SP-A and albumin were quantified by ELISA. The coefficient of repeatability (CR), intraclass correlation coefficient (ICC), and coefficient of variation (CV) were used to assess the variation of repeated measurements.

Results

SP-A and albumin increased significantly from morning towards the noon and afternoon by 13% and 25% on average, respectively, whereas PEx number concentration and particle mean mass did not differ significantly between the morning, noon and afternoon. Between-day CRs were not larger than within-day CRs.

Conclusions

Time of the day influences the contents of SP-A and albumin in exhaled particles. The variation of repeated measurements was rather high but was not influenced by the time intervals between measurements.

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<![CDATA[Validation of online Asthma Control Questionnaire and Asthma Quality of Life Questionnaire]]> https://www.researchpad.co/article/N555e23bc-a18a-4785-a339-5a85c1aa9519

Objective

Several newly developed eHealth applications use online questionnaires to monitor asthma control. The Asthma Control Questionnaire (ACQ) and Asthma Quality of Life Questionnaire (AQLQ) are two such commonly used questionnaires. These questionnaires are validated for use on paper. This study aims to validate them by assessing the agreement between online and paper versions of the ACQ and AQLQ.

Methods

Patients (aged 18 years and older) from the Self-Management in Asthma Supported by Hospitals, ICT, Nurses and General Practitioners (SMASHING)-trial and Davos@home study were included in this study. Patients completed both the paper and online Dutch versions of the ACQ and AQLQ in a random order within a 2-week interval. Agreement between the different versions was assessed with paired t-tests, intraclass correlation coefficients and Bland–Altman plots.

Results

In total 44 patients were eligible for analysis. The mean difference between the paper and online versions of the ACQ was 0.04 (p=0.40) and for the AQLQ it was 0.08 (p=0.06). The intraclass correlation coefficient scores were 0.94 for the ACQ and 0.95 for the AQLQ.

Conclusion

The online versions of the ACQ and AQLQ show high levels of agreement with the paper versions and can therefore be safely used in eHealth applications to respectively monitor asthma control and quality of life.

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<![CDATA[Dupilumab improves lung function in patients with uncontrolled, moderate-to-severe asthma]]> https://www.researchpad.co/article/N68cee356-d265-4362-aa06-480cda8ce61c

Background

Dupilumab, a fully human monoclonal antibody, blocks the shared receptor component for interleukin-4 and interleukin-13, key drivers of type 2 inflammation. In the phase 3 LIBERTY ASTHMA QUEST trial (NCT02414854) in patients with uncontrolled, moderate-to-severe asthma, add-on dupilumab 200 mg or 300 mg every 2 weeks reduced exacerbations and improved forced expiratory volume in 1 s (FEV1) and quality of life over 52 weeks. This analysis evaluates dupilimab's effect on lung function in the overall population, and subgroups with baseline elevated type 2 inflammatory biomarkers.

Methods

Patients were randomised to 52 weeks of subcutaneous dupilumab 200 mg every 2 weeks, 300 mg every 2 weeks, or matched-volume placebos. Lung function outcomes were analysed in the overall population, in patients with ≥150 eosinophils·µL−1, ≥300 eosinophils·µL−1, ≥25 ppb fractional exhaled nitric oxide (FeNO), and both ≥150 eosinophils·µL−1 and ≥25 ppb FeNO, at baseline.

Results

Dupilumab treatment (200 mg and 300 mg every 2 weeks) resulted in significant improvements versus placebo after 52 weeks in pre-bronchodilator FEV1 (0.20 and 0.13 L, respectively, versus placebo) and post-bronchodilator FEV1 (0.19 and 0.13 L, respectively), forced vital capacity (FVC) (0.20 and 0.14 L, respectively), forced expiratory flow (0.19 and 0.13 L·s−1, respectively) and pre-bronchodilator FEV1/FVC ratio (1.75% and 1.61%, respectively) in the overall population (p<0.001). Difference versus placebo in post-bronchodilator FEV1 slope of change (weeks 4–52) was significant (0.04 L·year−1; p<0.05). Greater improvements were achieved in patients with elevated baseline blood eosinophil and/or FeNO levels for most outcomes.

Conclusions

Dupilumab improves lung function outcomes, including large and small airway measurements and fixed airway obstruction, in patients with uncontrolled, moderate-to-severe asthma; particularly in patients with elevated biomarkers of type 2 inflammation.

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<![CDATA[The Projected Economic and Health Burden of Uncontrolled Asthma in the United States]]> https://www.researchpad.co/article/Naa4c1bb8-b54a-4842-8956-dee0f4f56266

Rationale: Despite effective treatments, a large proportion of patients with asthma do not achieve sustained asthma control. The “preventable” burden associated with lack of proper control is likely taking a high toll at the personal and population level.

Objectives: We predicted the future excess health and economic burden associated with uncontrolled asthma among American adolescents and adults for the next 20 years.

Methods: We built a probabilistic model that linked state-specific estimates of population growth, aging, asthma prevalence, and asthma control levels. We conducted several meta-analyses to estimate the adjusted differences in healthcare resource use, quality-adjusted life years (QALYs), and productivity loss across control levels. We projected, nationally and at the state level, total direct and indirect (due to productivity loss) costs (in 2018 dollars) and QALYs lost because of uncontrolled asthma from 2019 to 2038.

Measurements and Main Results: Total 20-year direct costs associated with uncontrolled asthma are estimated to be $300.6 billion (95% confidence interval [CI], $190.1 billion–411.1 billion). When indirect costs are added, total economic burden will be $963.5 billion (95% CI, $664.1 billion–1,262.9 billion). American adolescents and adults will lose an estimated 15.46 million (95% CI, 12.77 million–18.14 million) QALYs over this period because of uncontrolled asthma. Across states, the average 20-year per capita costs due to uncontrolled asthma ranged from $2,209 (Arkansas) to $6,132 (Connecticut).

Conclusions: The burden of uncontrolled asthma is substantial and will continue to grow. Given that a substantial fraction of this burden is preventable, better adherence to evidence-informed asthma management strategies by care providers and patients has the potential to substantially reduce costs and improve quality of life.

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<![CDATA[Real-life effectiveness of omalizumab in difficult-to-treat versus severe asthma: a national cohort study in Belgium]]> https://www.researchpad.co/article/Ne668a92b-3db0-47cf-b4a1-e6ac5a706ae7

Background

Guidelines recommend omalizumab in patients with uncontrolled severe allergic asthma. We investigated real-life use of omalizumab, the proportion of patients fulfilling eligibility criteria, its costs and its effectiveness.

Method

In a cohort of asthma patients initiating treatment with omalizumab in Belgium between 2010 and 2016, we investigated fulfilment of eligibility criteria (chronic use of high-dose inhaled corticosteroids (ICSs) plus long-acting β2-agonists (LABAs) and ≥2 severe asthma exacerbations in previous year), and compared hospitalisations and systemic corticosteroid consumption in the year before and after omalizumab initiation. We computed healthcare costs in the respective time periods and compared the cost per prevented hospitalisation in patients fulfilling eligibility criteria versus those who did not.

Results

Between 2010 and 2016, omalizumab treatment was initiated in 2068 patients with asthma; only 24% fulfilled the eligibility criteria, mainly due to nonadherence to high-dose ICSs + LABAs. The proportion of patients hospitalised for asthma decreased from 41% to 21% in eligible patients (absolute risk reduction, 20%), whereas the absolute risk reduction was 5% (from 19% to 14%) in noneligible patients. The cost per prevented hospitalisation was €44 238 versus €139 495, respectively. Chronic use of systemic corticosteroids was discontinued in 35% of eligible patients versus 15% of noneligible patients.

Conclusion

In Belgium, omalizumab is mostly initiated in uncontrolled asthma patients who are nonadherent to ICSs + LABAs. Omalizumab decreases hospitalisations and the use of systemic corticosteroids, but at a high cost. Careful management of patients with difficult-to-treat asthma should be a priority before prescribing omalizumab.

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