Variability in asthma: symptom perception, care, and outcomes

Asthma remains a global respiratory health concern. Substantial variations in asthma outcomes persist in Canada despite the dissemination of national management guidelines. Many factors and their interactions presumably contribute to variations in outcomes, including asthma prevalence, severity, symptom recognition, self-management behaviour, access to care, and management. This article reviews the physiology of symptom perception in asthma, specifically the role of dynamic lung hyperinflation (DH) on the perception of the intensity and quality of dyspnea in asthma, and the link between blunted perception and life-threatening asthma. Additionally, the magnitude and correlates of regional variation in emergency department visit rates and hospitalizations for asthma in Ontario are reviewed.     

One hundred years ago: How to be happy though a doctor

ObjectivesTo assess the growth of quality of life measures and to examine the availability of measures across specialties.DesignSystematic searches of electronic databases to identify developmental and evaluative work relating to health outcome measures assessed by patients.Results3921 reports that described the development and evaluation of patient assessed measures met the inclusion criteria. Of those that were classifiable, 1819 (46%) were disease or population specific, 865 (22%) were generic, 690 (18%) were dimension specific, 409 (10%) were utility, and 62 (1%) were individualised measures. During 1990-9 the number of new reports of development and evaluation rose from 144 to 650 per year. Reports of disease specific measures rose exponentially. Over 30% of evaluations were in cancer, rheumatology and musculoskeletal disorders, and older people''s health. The generic measures—SF-36, sickness impact profile, and Nottingham health profile—accounted for 612 (16%) reports.ConclusionsIn some specialties there are numerous measures of quality of life and little standardisation. Primary research through the concurrent evaluation of measures and secondary research through structured reviews of measures are prerequisites for standardisation. Recommendations for the selection of patient assessed measures of health outcome are needed.

What is already known on this topic

Quality of life measures are increasingly used for measuring health outcomes in evaluative researchThere is little standardisation in the use of such measures within clinical trials

What this study adds

There has been exponential growth in reports relating to the development and evaluation of quality of life measuresThe number of reports varies considerably according to the health problem     

Long term prognosis in preschool children with wheeze: longitudinal postal questionnaire study 1993-2004

Objectives To follow a population of preschool children with and without parent reported wheeze over a period of 6-11 years to determine prognosis and its important predictive factors.Design Longitudinal series of five postal surveys based on the international study of asthma and allergies in childhood questionnaire carried out between 1993 and 2004.Setting Two general practice populations, south Manchester.Participants 628 children aged less than 5 years at recruitment and those with at least six years’ follow-up data.Main outcome measures Parent completed questionnaire data for respiratory symptoms and associated features.Results Of 628 children included in the study, 201 (32%) had parent reported wheeze at the first observation (baseline), of whom 27% also reported the symptom on the second occasion (persistent asthma). The only important baseline predictors of persistent asthma were exercise induced wheeze (odds ratio 3.94, 95% confidence interval 1.72 to 9.00) and a history of atopic disorders (4.44, 1.94 to 10.13). The presence of both predictors indicated a likelihood of 53.2% of developing asthma; if only one feature was present this decreased to 17.2%, whereas if neither was present the likelihood was 10.9%. Family history of asthma was not predictive of persistent asthma among children with preschool wheeze.Conclusion Using two simple predictive factors (baseline parent reported exercise induced wheeze and a history of atopic disorders), it is possible to estimate the likelihood of future asthma in children presenting with preschool wheeze. The absence of baseline exercise induced wheeze and a history of atopic disorders reduces the likelihood of subsequent asthma by a factor of five.     

Interactive learning and action: realizing the promise of synthetic biology for global health

The emerging field of synthetic biology has the potential to improve global health. For example, synthetic biology could contribute to efforts at vaccine development in a context in which vaccines and immunization have been identified by the international community as being crucial to international development efforts and, in particular, the millennium development goals. However, past experience with innovations shows that realizing a technology’s potential can be difficult and complex. To achieve better societal embedding of synthetic biology and to make sure it reaches its potential, science and technology development should be made more inclusive and interactive. Responsible research and innovation is based on the premise that a broad range of stakeholders with different views, needs and ideas should have a voice in the technological development and deployment process. The interactive learning and action (ILA) approach has been developed as a methodology to bring societal stakeholders into a science and technology development process. This paper proposes an ILA in five phases for an international effort, with national case studies, to develop socially robust applications of synthetic biology for global health, based on the example of vaccine development. The design is based on results of a recently initiated ILA project on synthetic biology; results from other interactive initiatives described in the literature; and examples of possible applications of synthetic biology for global health that are currently being developed.     

Psychotic symptoms are associated with physical health problems independently of a mental disorder diagnosis: results from the WHO World Health Survey

This study explored whether physical health problems are related to psychotic symptoms independently of a mental disorder diagnosis. A total of 224,254 subjects recruited for the World Health Organization World Health Survey were subdivided into those with both a lifetime diagnosis of psychosis and at least one psychotic symptom in the 12 months prior to the evaluation, those with at least one psychotic symptom in the past 12 months but no lifetime diagnosis of psychosis, and those without psychotic symptoms in the past 12 months and without a lifetime diagnosis of psychosis. The three groups were compared for the presence of medical conditions, health problems, and access to health care. Medical conditions and health problems (angina, asthma, arthritis, tuberculosis, vision or hearing problems, mouth/teeth problems, alcohol consumption, smoking, and accidents), medication consumption, and hospital admissions (but not regular health care visits) were more frequent in individuals with psychotic symptoms but no psychosis diagnosis, compared to those with no symptoms and no diagnosis. The number of medical conditions increased with the number of psychotic symptoms. Given the sample analyzed, this trend seems to be independent from the socio‐economic development of the country or the specific health care system.     

The COMET Handbook: version 1.0

The selection of appropriate outcomes is crucial when designing clinical trials in order to compare the effects of different interventions directly. For the findings to influence policy and practice, the outcomes need to be relevant and important to key stakeholders including patients and the public, health care professionals and others making decisions about health care. It is now widely acknowledged that insufficient attention has been paid to the choice of outcomes measured in clinical trials. Researchers are increasingly addressing this issue through the development and use of a core outcome set, an agreed standardised collection of outcomes which should be measured and reported, as a minimum, in all trials for a specific clinical area.Accumulating work in this area has identified the need for guidance on the development, implementation, evaluation and updating of core outcome sets. This Handbook, developed by the COMET Initiative, brings together current thinking and methodological research regarding those issues. We recommend a four-step process to develop a core outcome set. The aim is to update the contents of the Handbook as further research is identified.     

Inupiat Health and Proposed Alaskan Oil Development: Results of the First Integrated Health Impact Assessment/Environmental Impact Statement for Proposed Oil Development on Alaska’s North Slope

We report on the first Health Impact Assessment (HIA) for proposed oil and gas development in Alaska’s North Slope region. Public health is not generally analyzed in the Environmental Impact Statement (EIS) process in the U.S. We conducted an HIA for proposed oil development within the National Petroleum Reserve - Alaska in response to growing concerns among North Slope Inupiat communities regarding the potential impacts of regional industrial expansion on their health and culture. We employed a qualitative HIA methodology, involving a combination of stakeholder input, literature review, and qualitative analysis, through which we identified potential health effects. The possible health outcomes identified include increases in diabetes and related metabolic conditions as a result of dietary change; rising rates of substance abuse, domestic violence, and suicide; increased injury rates; more frequent asthma exacerbations; and increased exposure to organic pollutant, including carcinogens and endocrine disruptors. There are also potential benefits, including funding for infrastructure and health care; increased employment and income; and continued funding of existing infrastructure. Based on these findings, we recommend a series of public health mitigation measures. This project represents the first formal effort to include a systematic assessment of public health within the U.S. EIS process. The inclusion of public health concerns within an EIS may offer an important and underutilized avenue through which to argue for environmental management strategies that focus on public health, and may offer communities a stronger voice in the EIS process. An erratum to this article can be found at     

Targets and outcomes of psychotherapies for mental disorders: an overview

It is not yet clear what mental disorders are and what are the causal pathways that lead to them. That makes it difficult to decide what the targets and outcomes of psychotherapies should be. In this paper, the main types of targets and outcomes of psychotherapies are described, and a brief overview is provided of some of the main results of research on these types. These include symptom reduction, personal targets and outcomes from the patient's perspective, improvement of quality of life, intermediate outcomes depending on the theoretical framework of the therapist, negative outcomes to be avoided, and economic outcomes. In line with the dominance of the DSM and ICD systems for diagnoses, most research has been focused on symptom reduction. This considerable body of research, with hundreds of randomized trials, has shown that for most mental disorders effective psychotherapies are available. There is also research showing that psychotherapies can result in improvement of quality of life in most mental disorders. However, relatively little research is available on patient‐defined outcomes, intermediate outcomes, negative outcomes and economic outcomes. Patients, relatives, therapists, employers, health care providers and society at large each have their own perspectives on targets and outcomes of psychotherapies. The perspective of patients should have more priority in research, and a standardization of outcome measures across trials is much needed.     

Vitamin D Supplementation for Childhood Asthma: A Systematic Review and Meta-Analysis

Importance

There is growing evidence that vitamin D plays a role in the pathogenesis of asthma but it is unclear whether supplementation during childhood may improve asthma outcomes.

Objectives

The objective of this systematic review and meta-analysis was to evaluate the efficacy and safety of vitamin D supplementation as a treatment or adjunct treatment for asthma.

Data Sources

We searched MEDLINE, Embase, CENTRAL, and CINAHL through July 2014.

Study Selection

We included RCTs that evaluated vitamin D supplementation in children versus active control or placebo for asthma.

Data Extraction and Synthesis

One reviewer extracted data and one reviewer verified data accuracy. We qualitatively summarized the main results of efficacy and safety and meta-analyzed data on comparable outcomes across studies. We used GRADE for strength of evidence.

Main Outcome Measures

Main planned outcomes measures were ED visits and hospitalizations. As secondary outcomes, we examined measures of asthma control, including frequency of asthma exacerbations, asthma symptom scores, measures of lung function, β₂-agonist use and daily steroid use, adverse events and 25-hydroxyvitamin D levels.

Results

Eight RCTs (one parallel, one crossover design) comprising 573 children aged 3 to 18 years were included. One study (moderate-quality, n = 100) reported significantly less ED visits for children treated with vitamin D. No other studies examined the primary outcome (ED visits and hospitalizations). There was a reduced risk of asthma exacerbations in children receiving vitamin D (low-quality; RR 0.41, 95% CI 0.27 to 0.63, 3 studies, n = 378). There was no significant effect for asthma symptom scores and lung function. The serum 25(OH)D level was higher in the vitamin D group at the end of the intervention (low-quality; MD 19.66 nmol/L, 95% CI 5.96 nmol/L to 33.37 nmol/L, 5 studies, n = 167).

Limitations

We identified a high degree of clinical diversity (interventions and outcomes) and methodological heterogeneity (sample size and risk of bias) in included trials.

Conclusions and Relevance

Randomized controlled trials provide some low-quality evidence to support vitamin D supplementation for the reduction of asthma exacerbations. Evidence on the benefits of vitamin D supplementation for other asthma-related outcomes in children is either limited or inconclusive. We recommend that future trials focus on patient-relevant outcomes that are comparable across studies, including standardized definitions of asthma exacerbations.     

Chemokines: structure,receptors and functions. A new target for inflammation and asthma therapy?

Five to 10% of the human population have a disorder of the respiratory tract called 'asthma'. It has been known as a potentially dangerous disease for over 2000 years, as it was already described by Hippocrates and recognized as a disease entity by Egyptian and Hebrew physicians. At the beginning of this decade, there has been a fundamental change in asthma management. The emphasis has shifted from symptom relief with bronchodilator therapies (e.g. beta(2)-agonists) to a much earlier introduction of anti-inflammatory treatment (e.g. corticosteroids). Asthma is now recognized to be a chronic inflammatory disease of the airways, involving various inflammatory cells and their mediators. Although asthma has been the subject of many investigations, the exact role of the different inflammatory cells has not been elucidated completely. Many suggestions have been made and several cells have been implicated in the pathogenesis of asthma, such as the eosinophils, the mast cells, the basophils and the lymphocytes. To date, however, the relative importance of these cells is not completely understood. The cell type predominantly found in the asthmatic lung is the eosinophil and the recruitment of these eosinophils can be seen as a characteristic of asthma. In recent years much attention is given to the role of the newly identified chemokines in asthma pathology. Chemokines are structurally and functionally related 8-10 kDa peptides that are the products of distinct genes clustered on human chromosomes 4 and 17 and can be found at sites of inflammation. They form a superfamily of proinflammatory mediators that promote the recruitment of various kinds of leukocytes and lymphocytes. The chemokine superfamily can be divided into three subgroups based on overall sequence homology. Although the chemokines have highly conserved amino acid sequences, each of the chemokines binds to and induces the chemotaxis of particular classes of white blood cells. Certain chemokines stimulate the recruitment of multiple cell types including monocytes, lymphocytes, basophils, and eosinophils, which are important cells in asthma. Intervention in this process, by the development of chemokine antagonists, might be the key to new therapy. In this review we present an overview of recent developments in the field of chemokines and their role in inflammations as reported in literature.     

Which population level environmental factors are associated with asthma,rhinoconjunctivitis and eczema? Review of the ecological analyses of ISAAC Phase One

The International Study of Asthma and Allergies in Childhood (ISAAC) Phase One showed large worldwide variations in the prevalence of symptoms of asthma, rhinoconjunctivitis and eczema, up to 10 to 20 fold between countries. Ecological analyses were undertaken with ISAAC Phase One data to explore factors that may have contributed to these variations, and are summarised and reviewed here.In ISAAC Phase One the prevalence of symptoms in the past 12 months of asthma, rhinoconjunctivitis and eczema were estimated from studies in 463,801 children aged 13 - 14 years in 155 centres in 56 countries, and in 257,800 children aged 6-7 years in 91 centres in 38 countries. Ecological analyses were undertaken between symptom prevalence and the following: Gross National Product per capita (GNP), food intake, immunisation rates, tuberculosis notifications, climatic factors, tobacco consumption, pollen, antibiotic sales, paracetamol sales, and outdoor air pollution.Symptom prevalence of all three conditions was positively associated with GNP, trans fatty acids, paracetamol, and women smoking, and inversely associated with food of plant origin, pollen, immunisations, tuberculosis notifications, air pollution, and men smoking. The magnitude of these associations was small, but consistent in direction between conditions. There were mixed associations of climate and antibiotic sales with symptom prevalence.The potential causality of these associations warrant further investigation. Factors which prevent the development of these conditions, or where there is an absence of a positive correlation at a population level may be as important from the policy viewpoint as a focus on the positive risk factors. Interventions based on small associations may have the potential for a large public health benefit.     

喘息的"度"与支气管哮喘阶梯治疗

目的:探讨掌握喘息"度"与支气管哮喘阶梯治疗的关系。方法:充分掌握支气管哮喘分级治疗方案和支气管哮喘病情,将喘息"度"细致化,与分级治疗用药"度"密切结合起来,对于完全理想的控制哮喘将会起到极大的指导作用,对于升阶梯和降阶梯治疗都会起到重要而细致的指导作用。必须将平喘治疗措施置于患者全身病情变化及总体治疗之下,会取得更加理想的哮喘控制效果。而强化支气管哮喘患者教育在支气管哮喘理想治疗中占据极为重要的地位,甚至直接关系到哮喘控制的持久性和稳定性。应得到高度重视。结果:喘息"度"与支气管哮喘的发作程度密切相关,准确把握并分级十分重要。结论:准确把握喘息"度"并与支气管哮喘分级治疗方法结合,将对稳定平息支气管哮喘起到意想不到的效果。     

The current conceptualization of negative symptoms in schizophrenia

Negative symptoms have long been conceptualized as a core aspect of schizophrenia. They play a key role in the functional outcome of the disorder, and their management represents a significant unmet need. Improvements in definition, characterization, assessment instruments and experimental models are needed in order to foster research aimed at developing effective interventions. A consensus has recently been reached on the following aspects: a) five constructs should be considered as negative symptoms, i.e. blunted affect, alogia, anhedonia, asociality and avolition; b) for each construct, symptoms due to identifiable factors, such as medication effects, psychotic symptoms or depression, should be distinguished from those regarded as primary; c) the five constructs cluster in two factors, one including blunted affect and alogia and the other consisting of anhedonia, avolition and asociality. In this paper, for each construct, we report the current definition; highlight differences among the main assessment instruments; illustrate quantitative measures, if available, and their relationship with the evaluations based on rating scales; and describe correlates as well as experimental models. We conclude that: a) the assessment of the negative symptom dimension has recently improved, but even current expert consensus‐based instruments diverge on several aspects; b) the use of objective measures might contribute to overcome uncertainties about the reliability of rating scales, but these measures require further investigation and validation; c) the boundaries with other illness components, in particular neurocognition and social cognition, are not well defined; and d) without further reducing the heterogeneity within the negative symptom dimension, attempts to develop successful interventions are likely to lead to great efforts paid back by small rewards.     

Structural brain changes related to disease duration in patients with asthma

Dyspnea is the impairing, cardinal symptom patients with asthma repeatedly experience over the course of the disease. However, its accurate perception is also crucial for timely initiation of treatment. Reduced perception of dyspnea is associated with negative treatment outcome, but the underlying brain mechanisms of perceived dyspnea in patients with asthma remain poorly understood. We examined whether increasing disease duration in fourteen patients with mild-to-moderate asthma is related to structural brain changes in the insular cortex and brainstem periaqueductal grey (PAG). In addition, the association between structural brain changes and perceived dyspnea were studied. By using magnetic resonance imaging in combination with voxel-based morphometry, gray matter volumes of the insular cortex and the PAG were analysed and correlated with asthma duration and perceived affective unpleasantness of resistive load induced dyspnea. Whereas no associations were observed for the insular cortex, longer duration of asthma was associated with increased gray matter volume in the PAG. Moreover, increased PAG gray matter volume was related to reduced ratings of dyspnea unpleasantness. Our results demonstrate that increasing disease duration is associated with increased gray matter volume in the brainstem PAG in patients with mild-to-moderate asthma. This structural brain change might contribute to the reduced perception of dyspnea in some patients with asthma and negatively impact the treatment outcome.     

Prevention of occupational asthma in Ontario

Occupational asthma continues to be one of the most common occupational lung diseases in industrialized areas. Primary and secondary preventive measures have been well described, but there are relatively few studies to support the effectiveness of such measures, although the benefits of tertiary measures such as early recognition and removal from further exposure to a causative sensitizing agent are well recognized. In Ontario, a combined approach of preventive measures has shown effectiveness in allergy and asthma from occupational exposure to natural rubber latex. In addition, a program to reduce exposure to diisocyanates and introduce medical surveillance was associated with earlier diagnosis and fewer cases in a compensation population. However there remain barriers to the early diagnosis of occupational asthma in Ontario, especially in workers of lower education and lower income. In addition, there is recognized need for further physician education to allow early suspicion and diagnosis of occupational asthma.     

Health Outcome after Major Trauma: What Are We Measuring?

Importance

Trauma is a global disease and is among the leading causes of disability in the world. The importance of outcome beyond trauma survival has been recognised over the last decade. Despite this there is no internationally agreed approach for assessment of health outcome and rehabilitation of trauma patients.

Objective

To systematically examine to what extent outcomes measures evaluate health outcomes in patients with major trauma.

Data Sources

MEDLINE, EMBASE, and CINAHL (from 2006–2012) were searched for studies evaluating health outcome after traumatic injuries.

Study selection and data extraction

Studies of adult patients with injuries involving at least two body areas or organ systems were included. Information on study design, outcome measures used, sample size and outcomes were extracted. The World Health Organisation International Classification of Function, Disability and Health (ICF) were used to evaluate to what extent outcome measures captured health impacts.

Results

34 studies from 755 studies were included in the review. 38 outcome measures were identified. 21 outcome measures were used only once and only five were used in three or more studies. Only 6% of all possible health impacts were captured. Concepts related to activity and participation were the most represented but still only captured 12% of all possible concepts in this domain. Measures performed very poorly in capturing concepts related to body function (5%), functional activities (11%) and environmental factors (2%).

Conclusion

Outcome measures used in major trauma capture only a small proportion of health impacts. There is no inclusive classification for measuring disability or health outcome following trauma. The ICF may provide a useful framework for the development of a comprehensive health outcome measure for trauma care.     

Development of spatiotemporal receptive fields of simple cells: II. Simulation and analysis

In part I of this article a correlation based model for the developmental process of spatiotemporal receptive fields has been introduced. In this model the development is described as an activity-dependent competition between four types of input from the lateral geniculate nucleus onto a cortical cell, viz. non-lagged ON and OFF and lagged ON and OFF inputs. In the present paper simulation results and a first analysis are presented for this model. We study the developmental process both before and after eye-opening and compare the results with experimental data from reverse correlation measurements. The outcome of the developmental process is determined mainly by the spatial and the temporal correlations between the different inputs. In particular, if the mean correlation between non-lagged and lagged inputs is weak, receptive fields with a widely varying degree of direction selectivity emerge. However, spatiotemporal receptive fields may show rotation of their preferred orientation as a function of response delay. Even if the mean correlation between two types of temporal input is not weak, direction-selective receptive fields may emerge because of an intracortical interaction between different cortical maps. In an environment of moving lines or gratings, direction-selective receptive fields develop only if the distribution of the directions of motion presented during development shows some anisotropy. In this case, a continuous map of preferred direction is also shown to develop. Received: 18 June 1997 / Accepted: 16 September 1997     

Can contracts drive clinical care?

The instrument through which a commissioner purchases health services from a provider is, as in other walks of life, a contract, so considerable importance has been attached by the NHS Executive to the contracting mechanism. A contract should in theory influence the quality of the service provided, but they are in many cases an inappropriate vehicle for driving clinical care. Much clinical activity is related to the management of chronic diseases and the effects of aging. The implicit contract here is based not on process and outcome measures but on mutual trust between doctors and patients that the doctors will provide the best care they can within budgetary constraints.     

Laboratory animal allergy: an update

Allergic reactions are among the most common conditions affecting the health of workers involved in the care and use of research animals. Between 11 and 44% of the individuals working with laboratory animals report work-related allergic symptoms. Of those who become symptomatic, 4 to 22% may eventually develop occupational asthma that can persist even after exposure ceases. Allergic symptoms consist of rashes where animals are in contact with the skin, nasal congestion and sneezing, itchy eyes, and asthma (cough, wheezing, and chest tightness). The generation of immunoglobulin E (IgE) antibodies is a prerequisite for the production of allergic symptoms. The mechanism by which IgE antibodies develop is becoming clearer. The propensity to produce IgE is genetically determined, and pre-existing allergy may be a risk factor for the development of laboratory animal allergy (LAA). However, exposure to animal allergens is the major risk factor for the development of LAA. Techniques to measure the airborne concentration of laboratory animal allergens have been developed. Research on animal allergens themselves indicates that many of the mouse and rat urinary proteins belong to a family of proteins called lipocalins, which share sequence homology with antigens of the parasitic agent that causes schistosomiasis. The fact that parasite infections also trigger IgE antibody responses may account for the development of LAA in persons who have never had any previous allergy. The prevention of LAA should be a major goal of an effective health and safety program in the animal research facility, and it can be accomplished by education and training of employees, reduction of exposure (including the use of personal protective gear), and changes in facility design. Medical surveillance programs can also play a role in improving health of individuals working with laboratory research animals. Early recognition of symptoms and evidence of sensitization can lead to interventions to reduce exposure and thereby avoid the long-term health consequences of LAA.     

Latent class regression on latent factors

In the research of public health, psychology, and social sciences, many research questions investigate the relationship between a categorical outcome variable and continuous predictor variables. The focus of this paper is to develop a model to build this relationship when both the categorical outcome and the predictor variables are latent (i.e. not observable directly). This model extends the latent class regression model so that it can include regression on latent predictors. Maximum likelihood estimation is used and two numerical methods for performing it are described: the Monte Carlo expectation and maximization algorithm and Gaussian quadrature followed by quasi-Newton algorithm. A simulation study is carried out to examine the behavior of the model under different scenarios. A data example involving adolescent health is used for demonstration where the latent classes of eating disorders risk are predicted by the latent factor body satisfaction.