Multimorbidity in asthma, association with allergy, inflammatory markers and symptom burden, results from the Swedish GA2 LEN study.

BACKGROUND: Asthma is common worldwide and a large part of subjects with asthma have concomitant allergic multimorbidity in the form of rhinitis and/or eczema. OBJECTIVE: The aim of this study is to investigate whether the presence of allergic multimorbidity in asthma relates to allergic sensitization, allergic and respiratory symptoms, quality of life, inflammatory markers, lung function, use of medication and background factors. METHODS: A total of 437 asthmatics from the (GA2 LEN) cross-sectional survey in Sweden were grouped depending on the presence of rhinitis and/or eczema. The impact of allergic multimorbidity was assessed in terms of allergic sensitization, allergic and respiratory symptoms, quality of life, type-2 inflammatory markers (exhaled nitric oxide, eosinophil activation markers, periostin), lung function, use of medication and background factors. RESULTS: Subjects with asthma, rhinitis and eczema were more likely to be sensitized to seasonal allergens (67% vs 32%, P < .001), food allergens (54% vs 18%, P < .001) and to have a higher degree of sensitization than subjects with only asthma (23% vs 10%, P < .001). Subjects with allergic multimorbidity more often had allergic reactions to food (28% vs 10%, P = .002), more respiratory symptoms and anxiety/depression (40% vs, 14%, P < .001) than subjects with only asthma, despite having similar levels of type 2 inflammatory markers. Individuals with allergic multimorbidity were more likely to be diagnosed with asthma before the age of 12 (48% vs 27%, P = .016) and to have maternal heredity for allergy (53% vs 33%, P = .011) than subjects with only asthma. CONCLUSION AND CLINICAL RELEVANCE: Asthmatics with allergic multimorbidity are more likely to be sensitized to seasonal aeroallergens, food allergens and they have a higher degree of sensitization compared with those with only asthma. Allergic multimorbidity is associated with respiratory and allergy symptoms, anxiety and/or depression.

The dysphagia stress test for rapid assessment of swallowing difficulties in esophageal conditions.

BACKGROUND: Esophageal dysphagia is a common symptom in gastroenterology practice. Current rapid assessment tools are limited to oropharyngeal dysphagia and do not translate well to esophageal conditions. We aim to create a novel tool, the dysphagia stress test (DST), to evaluate swallowing in patients with esophageal disease characterized by dysphagia. METHODS: Adults with eosinophilic esophagitis (EoE), gastroesophageal reflux disease (GERD), achalasia, and dysphagia not otherwise specified (NOS) participated. Patient controls with non-esophageal diagnoses and healthy controls were also recruited. Participants completed the DST with five bolus challenges: water, applesauce, rice, bread, barium tablet and rated their swallowing difficulty and pain. A study clinician observed and documented water use and refusal of any challenges. Participants also completed measures of esophageal symptoms, hypersensitivity, and symptom anxiety to evaluate the DST validity. Collinearity of bolus challenges guided item reduction. KEY RESULTS: A total of 132 subjects participated. Both control groups and GERD patients had the best swallowing ability, while achalasia, EOE, and dysphagia NOS scored poorer. About 90% of patients were able to attempt or pass each of the bolus challenges, suggesting high acceptability. Construct validity of the DST is evidenced by modest negative correlations with symptom severity, hypersensitivity, and anxiety. The DST does not appear to be influenced by brain-gut processes. Applesauce, rice, and bread demonstrated collinearity; thus, the DST was reduced to three challenges. CONCLUSIONS & INFERENCES: The DST is the first rapid assessment tool designed for gastroenterology clinics with direct observation of swallowing ability across several conditions to mitigate issues related to patient self-report of esophageal symptoms.

Childhood wheezing, asthma, allergy, atopy, and lung function: different socioeconomic patterns for different phenotypes.

Identifying preventable exposures that lead to asthma and associated allergies has proved challenging, partly because of the difficulty in differentiating phenotypes that define homogeneous disease groups. Understanding the socioeconomic patterns of disease phenotypes can help distinguish which exposures are preventable. In the present study, we identified disease phenotypes that are susceptible to socioeconomic variation, and we determined which life-course exposures were associated with these inequalities in a contemporary birth cohort. Participants included children from the Avon Longitudinal Study of Parents and Children, a population-based birth cohort in England, who were born in 1991 and 1992 and attended the clinic at 7-8 years of age (n = 6,378). Disease phenotypes included asthma, atopy, wheezing, altered lung function, and bronchial reactivity phenotypes. Combining atopy with a diagnosis of asthma from a doctor captured the greatest socioeconomic variation, including opposing patterns between phenotype groups: Children with a low socioeconomic position (SEP) had more asthma alone (adjusted multinomial odds ratio = 1.50, 95% confidence interval: 1.21, 1.87) but less atopy alone (adjusted multinomial odds ratio = 0.80, 95% confidence interval: 0.66, 0.98) than did children with high SEP. Adjustment for maternal exposure to tobacco smoke during pregnancy and childhood exposure to tobacco smoke reduced the odds of asthma alone in children with a low SEP. Current inequalities among children who have asthma but not atopy can be prevented by eliminating exposure to tobacco smoke. Other disease phenotypes were not socially patterned or had SEP patterns that were not related to smoke exposure.

Image-Based Assessment of Allergic Inflammation under Conjunctival Provocation.

Conjunctival redness is an objective allergy symptom which can be analyzed using objective computer imaging methods. To evaluate allergic inflammation of the eyes, a robust and precise image-based method was developed and applied to analyze allergic hyperemia under the conjunctival provocation test (CPT). High-resolution digital photos were taken and analyzed via digital analysis software to obtain and document conjunctival redness. The evaluations made using this newly developed image-based method concurred with the study investigators' assessments: the therapeutic effects of the highest doses were superior to the lowest dose.

Longitudinal assessment of high versus low levels of fractional exhaled nitric oxide among children with asthma and atopy.

PURPOSE: Fractional exhaled nitric oxide (FeNO) has emerged as an important biomarker in asthma. Increasing evidence points to atopy as a confounding factor in the interpretation of elevated FeNO. We conducted a longitudinal study to understand the clinical significance of FeNO as an inflammatory biomarker. METHODS: We identified 19 children aged 13-15 years at baseline with a significant elevation in FeNO ≥ 80 parts per billion (ppb) and randomly selected a group of children of similar age with a moderate elevation (40-79 ppb) and normal-to-low FeNO (<40 ppb). Between November 2010 and July 2011, three additional study visits were conducted. RESULTS: Ninety-three children participated in the study. There were 16, 24, and 53 participants in the high, mid, and low FeNO groups. During 1.5 years of follow-up, mean FeNO levels were 82.6 ppb (standard deviation [SD] = 65.9) for atopic asthmatics, 50.6 ppb (SD = 42.6) for nonasthmatic atopics, 17.0 ppb (SD = 10.8) for nonatopic asthmatics, and 17.8 ppb (SD = 13.9) for nonatopic nonasthmatics (p < 0.001). FeNO levels remained stable: 63 % of the high FeNO group had a FeNO ≥ 80 across all 4 measurements and 87 % of the normal-to-low FeNO group had a FeNO of <40 across all 4 measurements. The high FeNO group also was found to have an elevation in IL-5 (p = 0.04), IL-6 (p = 0.003), IL-10 (p = 0.002), and total serum IgE (p < 0.001), after adjustment by age, sex, height, body mass index, and atopy and asthma status. CONCLUSIONS: An elevation of FeNO appears to indicate an atopic phenotype regardless of an asthma diagnosis, clinical symptoms, or corticosteroid use. An elevation of FeNO also is associated with a systemic elevation in inflammatory cytokines.

Effect of socio-economic status on quality of life in people affected with respiratory allergy.

In the present study we investigated the impact of respiratory allergy on quality of life in young people, and examined whether socio-economic status modifies the above dependence. The study was conducted in 458 female and 363 male university students, aged 18-25. Information on socio-economic status (SES) was collected using a questionnaire. The occurrence of allergy was determined on the basis of answers to the questions whether the allergy and specific allergens were medically diagnosed. Quality of life (QoL) was based on the Polish version of the SF-36 test. Respiratory allergy or respiratory and food allergy were declared by 19.2 % of women and 19.0 % of men. The prevalence of allergy was higher in students with high SES. The students suffering from allergy obtained lower scores in all domains of QoL, but the differences were statistically insignificant. However, the overall test result in allergic students was significantly lower than that in non-allergic students. Differences QoL were significantly associated with socio-economic variables. In persons with low SES, the differences in QoL between those suffering from allergy and those who did not have allergy were larger than in persons with high SES. The results indicate that the course of allergic diseases is highly dependent on socio-economic status. The prevalence of allergy among students of low status is lower than among those of high status. However, allergy to a greater extent impairs the quality of life of students with low than high SES.

Coexistence of allergic diseases: patterns and frequencies.

The atopic march hypothesis suggests that allergy diseases often progress from atopic dermatitis to allergic asthma, and allergic rhinitis. How often can the classic progression of allergic diseases be observed in the pediatric patient population? This study aimed to observe the pattern of allergic diseases progression, onset age, disease intervals, and frequency of the allergic march. Data from the National Health Insurance Research Database in the period 1996-2008 were used to obtain a cohort of children with allergic disease. Physician's diagnosis was used to confirm the allergic disease based on the international disease coding. The age of disease onset was compared. There were 10,729 children aged <5 years enrolled from the 200,000 individuals randomly sampled in 2000. Of these, 5866 (54.7%) had been diagnosed with at least one allergic disease. The rate of only one of three diseases diagnosed was 29.8% (3195 patients), whereas 18.8% had two allergic diseases and 6.1% had all three allergic diseases. Only 4.2% of cases matched the allergic march. Patients with more than one disease had earlier onset age than those who had only one disease (4.17 versus 2.79 and 2.32 years old; p < 0.05). The allergic march accounts for only 4.2% in this study. A patient with only one allergic disease after the age of 4.17 years will not have another allergic disease until the age of 12 years. However, a patient with an allergic disease before 2.79 years old will probably have another allergic disease in 1.96-2.5 years.

Assessment of antihistamines in the treatment of skin allergies.

PURPOSE OF REVIEW: Antihistamines, both old first-generation and new, are frequently prescribed to patients with allergic skin diseases. As the expected roles of antihistamines differ in each dermatosis, we should carefully consider the characteristics of each antihistamine prior to use. This review covers recent antihistamine topics, including novel pharmacological action, and enhancement of patient quality of life (QoL). RECENT FINDINGS: Nonsedative, second-generation antihistamines are recommended as first-line treatment for urticaria. For atopic dermatitis, most position papers doubt their efficacy of treatment due to insufficient evidence. However, recent articles revealed novel H1 receptor-independent properties for these agents, such as modulation of cytokine and chemokine production, tissue remodeling, and indicated its favorable effects on atopic dermatitis. Furthermore, several important benefits of second-generation antihistamines on the amelioration of atopic dermatitis symptoms, patient QoL and labor efficiency including loss of productivity and absenteeism from the workplace have been reported. In contrast, prescription of first-generation antihistamines for skin allergies should be avoided due to their bad risk/benefit ratio. Whereas they are not better in controlling itch, they also fail to improve patient labor efficiency unlike second-generation antihistamines. SUMMARY: Although antihistamine usefulness varies greatly, understanding the characteristics of each antihistamine will allow more personalized therapy for skin allergies.

Application of thermography for the assessment of allergen-induced skin reactions.

PURPOSE: The allergic response is commonly identified and assessed by skin testing. The usual method to quantify skin reactions is to mark wheal and erythema regions and assess the surfaces affected by the reactions; however, subjective interpretation of the outcome may cause errors. Skin thermography supplemented by a mathematical model based on the pathophysiology of heat generation was evaluated as a novel, objective, and sensitive indicator of the skin prick test result. METHODS: TH measurements were performed simultaneously with routine skin prick tests for 24 patients. Eight allergens and control (histamine) were examined. Thermographic images of both forearms were acquired every 70 s from 0 to 910 s after skin prick and analyzed with the use of dedicated software. The introduction of potential allergens and histamine at sites on the skin induces a complex sequence of events known as the local inflammatory response. The crucial steps of the process have been considered in the model. In the model, the authors assumed that the reaction takes place in the thin skin layer and that histamine is the principal mediator of the allergic reaction. Histamine penetrates the skin and binds to receptors of nearby capillaries and venules. The engorged vessels are, in turn, responsible for skin redness and an increase in skin temperature. RESULTS: The model parameters were determined by fitting the analytical solutions to the spatiotemporal distributions of the differences between measured and baseline temperatures. The model reproduces experimental data very well. The coefficient of determination ranged from 0.805 to 0.995. Seven model parameters were tested to find the optimal marker of the intensity and kinetics of the allergic reaction. The parameter which quantifies a release of histamine after allergen injection has appeared to be the best indicator of the allergen-induced response. The parameter correlates with the routine assessment based on wheal and erythema areas (correlation coefficient = 0.98). CONCLUSIONS: It was demonstrated that the thermographic measurements supplemented by the mathematical model offer a new approach to the quantification of allergen-induced skin reactions. Despite the applied simplifications, the proposed model reflected properly the mechanism of heat generation during skin prick test. Moreover, the continuous recording of the skin temperature represents an additional possibility to investigate the mechanism of the allergic reaction.

Allergies in Asia: differences in prevalence and management compared with western populations.

There is wide variability in the epidemiology and management of childhood asthma and related atopic diseases globally. Urbanized, affluent Western countries tend to have a higher prevalence of these diseases compared with Asian nations. However, recent studies have shown that the prevalence in Asia is increasing, although the rate of increase has slowed in the more developed Asian cities. Some possible causes for these differences are socioeconomic status, degree of urbanization, rates of infection, healthcare practices and genetic factors. Importantly, there are significant differences in the way asthma and allergic diseases are managed within Asia. This is of great concern because of the health implications, as these diseases are some of the most common chronic conditions that affect both adults and children. This review compares the differences in prevalence and management between Asia and the West, and discusses some of the possible reasons behind these variations.

Prevalence of rhinitis-related symptoms in Latin American children - results of the International Study of Asthma and Allergies in Childhood (ISAAC) phase three.

The aim of this study was to evaluate the prevalence of rhinitis-related symptoms among children living in different parts of Latin America (LA) considering all centers involved in ISAAC Phase Three (Ph3). 93,851 children (6-7 yr-old) from 35 centers in 14 LA countries and 165,917 adolescents (13-14 yr-old) from 56 centers in 17 LA countries were enrolled. The mean prevalence rate of current rhinoconjunctivitis was 12.7% and ranged from 5.5% in Rosario City (Argentina) to 21.2% in Caracas (Venezuela) for the schoolchildren. The mean prevalence rate of current rhinoconjunctivitis was 18.5% and ranged from 7.1% in Cuernavaca (México) to 45.1% in Asunción (Paraguay) for the adolescents. These indexes were among the higher observed during ISAAC Ph3. In general the prevalence of rhinitis-related symptoms was higher among the Spanish speaking centers. Environmental risk factors must be evaluated in order to explain the differences observed even in centers from the same country.

Epidemiology and current status of allergic rhinitis, asthma, and associated allergic diseases in Korea: ARIA Asia-Pacific workshop report.

The prevalence of allergic rhinitis and asthma has recently increased in Korea, and both conditions are recognized as major chronic respiratory diseases requiring active intervention. The prevalence of rhinitis among asthmatic patients is high, ranging from 60 to 80%, and could seriously affect asthma severity and outcome. We suggest that allergic rhinitis should be properly evaluated in asthmatic patients to achieve better asthma control.

iPAC: an initiative to fight the burden of allergies in children.

Allergies and asthma are common diseases in most parts of the world. Together, they represent a major burden on global health, as well as on health costs. However, efficient preventive measures are still lacking, and treatments are mostly symptomatic. The pathogenesis of the "allergic marathon'', the progression of the disease throughout childhood into adulthood is only partly understood. In addition, treatment protocols addressing the pathogenesis of the disease are not available to all patients, either due to economical reasons, or to insufficient efficacy or safety of the procedures. This editorial introduces a supplement dedicated to identify directions and means to fight the burden of allergies in childhood. This initiative is coordinated by iPAC (international Pediatric Allergy and Asthma Consortium).

Finnish Allergy Programme 2008-2018--time to act and change the course.

BACKGROUND: The prevalence of allergic diseases has grown in Finland, similarly to many other western countries. Although the origin of allergy remains unresolved, increasing body of evidence indicates that the modern man living in urban built environment is deprived from environmental protective factors (e.g. soil microorganisms) that are fundamental for normal tolerance development. The current dogma of allergen avoidance has not proved effective in halting the 'epidemic', and it is the Finnish consensus that restoring and strengthening tolerance should more be in focus. AIM: The national 10-year programme is aimed to reduce burden of allergies. The main goals are to (i) prevent the development of allergic symptoms; (ii) increase tolerance against allergens; (iii) improve the diagnostics; (iv) decrease work-related allergies; (v) allocate resources to manage and prevent exacerbations of severe allergies and (vi) decrease costs caused by allergic diseases. METHODS: For each goal, specific tasks, tools and evaluation methods are defined. Nationwide implementation acts through the network of local co-ordinators (primary care physicians, nurses, pharmacists). In addition, three nongovernmental organizations (NGOs) take care of the programme implementation. The 21 central hospital districts carry out a three step educational process: (i) healthcare personnel; (ii) representatives and educators of NGOs and (iii) patients and the general population. For outcome evaluation, repeated surveys are performed and healthcare registers employed at the beginning, at 5 years, and at the end of the programme. The process will be evaluated by an independent external body. CONCLUSION: The Finnish initiative is a comprehensive plan to reduce burden of allergies. The aim is to increase immunological tolerance and change attitudes to support health instead of medicalizing common and mild allergy symptoms. It is time to act, when allergic individuals are becoming a majority of western populations and their numbers are in rapid increase worldwide. The Programme is associated with the Global Alliance of Chronic Respiratory Diseases (GARD), WHO.

Anti-IgE and chemotherapy: a critical appraisal of treatment options for severe asthma.

In this narrative review the scientific rationale for the development of a therapeutic modality for asthma based on decreasing the circulating and cell-bound levels of immunoglobulin-E (IgE) is outlined. The one drug that has so far entered clinical practice to do this is a humanised monoclonal antibody to the Fc portion of the IgE molecule, omalizumab. It is highly effective in reducing IgE blood levels and its established mode of delivery is by subcutaneous injection. The clinical trial development of omalizumab is reviewed and the published data and claims for its efficacy and role in clinical practice is critically appraised. The target group of omalizumab has become focused on severe asthmatics who are still symptomatic after being administered with high-dose inhaled corticosteroids plus long-acting beta-agonists. The strongest evidence for effect is in those with frequent severe exacerbations.

Does unconventional medicine work through conventional modes of action?

It is often maintained that although conventional medicine works by means of pharmacotherapy with predominantly proved effects, unconventional therapies are more or less spiritual therapeutic approaches without a scientific basis. We hypothesize that both conventional and unconventional medicine might be effective because of similar modes of action. Certainly, this does not imply that every unconventional method has any effect. Conventional and effective unconventional medicine might both work by means of pharmacology (eg, substances in medical herbs), including pharmacologic interactions between the 2 treatment options (eg, herbs and drugs with coagulation effects). Both conventional and unconventional treatments involve a considerable risk of side effects, which are sometimes even severe. In general, the pattern of side effects of alternative treatments is similar to that observed with the use of conventional medicine. The placebo effect and suggestive aspects are also apparent in both treatments. Furthermore, mind-body medicine (eg, use of relaxation techniques) might be explained by pathophysiologic mechanisms. Overall, many aspects seem to contribute to the mosaic of joint modes of action involved in both conventional and unconventional medicine. This might demystify the aura of some of the complementary and alternative approaches and might help to bring both conventional and unconventional approaches together on a scientific basis.

Health-related quality of life in food hypersensitive schoolchildren and their families: parents' perceptions.

BACKGROUND: About 20% of schoolchildren and adolescents in Sweden suffer from perceived food hypersensitivity (e.g. allergy or intolerance). Our knowledge of how child food hypersensitivity affects parents HRQL and what aspects of the hypersensitivity condition relate to HRQL deterioration in the family is limited. Thus the aim of this study was to investigate the parent-reported HRQL in families with a schoolchild considered to be food hypersensitive. The allergy-associated parameters we operated with were number of offending food items, adverse food reactions, additional hypersensitivity, allergic diseases and additional family members with food hypersensitivity. These parameters, along with age and gender were assessed in relation to child, parent and family HRQL. METHODS: In May 2004, a postal questionnaire was distributed to parents of 220 schoolchildren with parent-reported food hypersensitivity (response rate 74%). Two questionnaires were used: CHQ-PF28 and a study-specific questionnaire including questions on allergy-associated parameters. In order to find factors that predict impact on HRQL, stepwise multiple linear regression analyses were carried out. RESULTS: An important predictor of low HRQL was allergic disease (i.e. asthma, eczema, rhino conjunctivitis) in addition to food hypersensitivity. The higher the number of allergic diseases, the lower the physical HRQL for the child, the lower the parental HRQL and the more disruption in family activities. Male gender predicted lower physical HRQL than female gender. If the child had sibling(s) with food hypersensitivity this predicted lower psychosocial HRQL for the child and lower parental HRQL. Food-induced gastro-intestinal symptoms predicted lower parental HRQL while food-induced breathing difficulties predicted higher psychosocial HRQL for the child and enhanced HRQL with regards to the family's ability to get along. CONCLUSION: The variance in the child's physical HRQL was to a considerable extent explained by the presence of allergic disease. However, food hypersensitivity by itself was associated with deterioration of child's psychosocial HRQL, regardless of additional allergic disease. The results suggest that it is rather the risk of food reactions and measures to avoid them that are associated with lower HRQL than the clinical reactivity induced by food intake. Therefore, food hypersensitivity must be considered to have a strong psychosocial impact.

Effect of phenytoin on mood and declarative memory during prescription corticosteroid therapy.

BACKGROUND: In humans and animals, corticosteroid excess is associated with impairment in declarative memory and changes in hippocampal structure. In animals, phenytoin pretreatment blocks the effects of stress on memory and hippocampal histology, although no studies have examined the use of phenytoin to prevent corticosteroid-associated memory changes in humans. Mood changes are also common with corticosteroids, but few treatment data are available. This report examines whether phenytoin can prevent mood or declarative memory changes secondary to bursts of prescription corticosteroids. METHODS: Thirty-nine patients with allergies or pulmonary or rheumatologic illnesses and given systemic corticosteroid therapy were randomized to receive either phenytoin (300 mg/day) or placebo concurrently with the corticosteroids. Mood was assessed with the Hamilton Rating Scale for Depression, Young Mania Rating Scale, and Activation (ACT) subscale of the Internal State Scale; declarative memory was assessed with the Rey Auditory Verbal Learning Test (RAVLT) at baseline and after approximately 7 days of corticosteroid plus phenytoin or placebo therapy. RESULTS: The two groups were similar in age, gender, education, and corticosteroid dose. The phenytoin-treated group showed significantly smaller increases on the ACT, a mania self-report scale, than the placebo-treated group. Groups did not differ significantly on RAVLT change scores. CONCLUSIONS: This is the first placebo-controlled study to examine whether a medication can prevent mood and memory changes secondary to corticosteroids. Phenytoin blocked the hypomanic effects of prescription corticosteroids; however, phenytoin did not block the declarative memory effects of corticosteroids.

Proposal for a risk assessment methodology for skin sensitization based on sensitization potency data.

In this paper, we propose a quantitative risk assessment methodology for skin sensitization aiming at the derivation of 'safe' exposure levels for sensitizing chemicals, used e.g., as ingredients in consumer products. Given the limited number of sensitizers tested in human sensitization tests, such as the human repeat-insult patch test (HRIPT) or the human maximization test (HMT), we used EC3 values from the local lymph node assay (LLNA) in mice because they provide the best quantitative measure of the skin sensitizing potency of a chemical. A comparison of LLNA EC3 values with HRIPT and HMT LOEL, and NOEL values was carried out and revealed that the EC3, expressed as area dose, can be used as a surrogate value for the human NOEL in risk assessment. The uncertainty/extrapolation factor approach was used to derive (a) an 'acceptable non-sensitizing area dose' (ANSAD) to protect non-allergic individuals against skin sensitization and (b) an 'acceptable non-eliciting area dose' (ANEAD) to protect allergic individuals against elicitation of allergic contact dermatitis. For ANSAD derivation, interspecies, intraspecies and time extrapolation factors are applied to the LLNA EC3. For ANEAD derivation, additional application of a variable sensitization-elicitation extrapolation factor is proposed. Values for extrapolation factors are derived and discussed, the proposed methodology is applied to the sensitizers methylchloroisothiazolinone/methylisothiazolinone, cinnamic aldehyde and nickel and results are compared to published risk assessments.