Subject(s)
Allergens/administration & dosage , Desensitization, Immunologic/methods , Milk Hypersensitivity/prevention & control , Milk , Allergens/adverse effects , Allergens/immunology , Animals , Child , Child, Preschool , Female , Hot Temperature , Humans , Male , Milk/adverse effects , Milk/immunologySubject(s)
Anti-Asthmatic Agents/therapeutic use , Asthma/drug therapy , Forkhead Transcription Factors/immunology , Omalizumab/therapeutic use , T-Lymphocytes, Regulatory/cytology , Asthma/immunology , CD4 Antigens , Child , Cross-Sectional Studies , Eosinophilia/drug therapy , Female , Flow Cytometry , Humans , Interleukin-2 Receptor alpha Subunit , Male , Prospective Studies , T-Lymphocytes, Regulatory/immunologyABSTRACT
'Phenotyping' asthma by multivariate analyses and more recently by unsupervised analysis has been performed in children cohorts. We describe the key findings that have emerged from these cohorts. It would appear that there are three wheeze phenotypes in children of preschool age: the mild episodic viral wheeze phenotype; the multitrigger atopic wheeze; and, less often encountered, the severe non-atopic wheeze. Early onset of allergy in asthma (more prevalent in boys) is associated with poor prognosis unlike the severe non-atopic wheeze phenotype which has a female predominance. The prognosis of the severe non-atopic wheeze depends on time of onset (early or late) of allergic expression. At school age, the risk of severe asthmatic exacerbations is associated with eosinophil predominant inflammation frequently related to allergic asthma, whereas neutrophil inflammation is associated with moderate-to-severe asthma with poorer lung function. Nevertheless, allergic asthma is also a heterogeneous disease with a severe allergic phenotype strongly associated with atopic dermatitis and very high eosinophil-driven inflammatory markers. Further studies are required to find non-invasive biological markers in very young children to better define wheezing phenotypes associated with an elevated risk of developing severe asthma with a view to personalizing treatment.
Subject(s)
Asthma/physiopathology , Phenotype , Child , Child, Preschool , Cohort Studies , Female , Humans , MaleABSTRACT
The relationship between asthma and obesity appears to be quite complex. The aim of this study was to assess the effect of excess weight on asthma control evolution in a cohort of asthmatics. A prospective database was set up, which enrolled adult asthmatics with persistent (mild, moderate or severe) asthma. The control of asthma was defined as a binary variable, acceptable or unacceptable. In order to evaluate the effect of body mass index (BMI; <25 or > or =25), data were analysed using a continuous time homogeneous Markov model in which the forces ruling the transition between the two health states were estimated. The following confounding covariates were also evaluated in the model: severity of asthma, current treatment with oral corticosteroids (OCS) and history of OCS over the year preceding inclusion. About 406 asthmatics were included who made a total of 1639 consultations; the median length of follow up was 182 days. Using a univariate model, overweight patients had a lower risk of transiting from the unacceptable to the acceptable health state (RR = 0.45; P < 0.01). The effect of weight remained significant (RR = 0.53; P < 0.01) in the multivariate model including the other covariates. Moreover, transition probabilities stabilized more rapidly for patients with BMI < 25 (200 vs 300 days). In this study, we thus demonstrated that there is an association between excess weight and transition from unacceptable to acceptable control. Because control of asthma clearly drives asthma management, this finding has consequences for defining original new strategies for managing asthma in overweight patients.
Subject(s)
Adrenal Cortex Hormones/therapeutic use , Anti-Asthmatic Agents/therapeutic use , Asthma/drug therapy , Asthma/epidemiology , Obesity/epidemiology , Adult , Asthma/diagnosis , Body Mass Index , Comorbidity , Female , Follow-Up Studies , Humans , Longitudinal Studies , Male , Markov Chains , Middle Aged , Obesity/diagnosis , Probability , Prospective Studies , Respiratory Function Tests , Risk Assessment , Severity of Illness Index , Treatment OutcomeABSTRACT
In studies of disease states and their relation to evolution, data on the state are usually obtained at in frequent time points during follow-up. Moreover in many applications, there are measured covariates on each individual under study and interest centres on the relationship between these covariates and the disease evolution. We developed a continuous-time Markov model with use of time-dependent covariates and a Markov model with piecewise constant intensities to model asthma evolution. Methods to estimate the effect of covariates on transition intensities, to test the assumption of time homogeneity and to assess goodness-of-fit are proposed. We apply these methods to asthma control. We consider a three-state model and we discuss in detail the analysis of asthma control evolution.
Subject(s)
Asthma/therapy , Markov Chains , Asthma/pathology , Asthma/prevention & control , Disease Progression , Follow-Up Studies , Humans , Likelihood Functions , Longitudinal StudiesABSTRACT
Control and severity of asthma are two different but complementary concepts. The severity of asthma could influence the control over time. The aim of this study was to demonstrate this relationship. A total 365 patients with persistent asthma (severity) were enrolled and followed-up prospectively. Data were analysed using a continuous time homogeneous Markov model of the natural history of asthma. Control of asthma was defined according to three health states which were qualified: optimal, suboptimal and unacceptable control (states 1, 2 and 3). Transition forces (denoted lambda(ij) from state i to state j) and transition probabilities between control states were assessed and the results stratified by asthma severity were compared. Models were validated by comparing expected and observed numbers of patients in the different states. Transition probabilities stabilised between 100-250 days and more rapidly in patients with mild-to-moderate asthma. Patients with mild-to-moderate asthma in suboptimal or unacceptable control had a high probability of transition directly to optimal control. Patients with severe asthma had a tendency to remain in unacceptable control. A Markov model is a useful tool to model the control of asthma over time. Severity modified clearly the health states. It could be used to compare the performance of different approaches to asthma management.
Subject(s)
Asthma/prevention & control , Asthma/physiopathology , Markov Chains , Severity of Illness Index , Adolescent , Adult , Aged , Child , Female , Follow-Up Studies , Health Status , Humans , Male , Middle Aged , Predictive Value of Tests , Prospective Studies , Reproducibility of Results , Time FactorsABSTRACT
In an unpredictable environment, the distributions of alleles from which polymorphism can be maintained forever belong to a certain set, the C-viability kernel. Such a set is calculated in the two-locus haploid model, as well as the corresponding fitnesses at any time which make this maintenance possible. The dependence of the C-viability kernel on the set U of admissible fitnesses and on the recombination rate r is studied. Notably, the C-viability kernel varies rapidly in the neighborhood of equal fitness of AB and ab; it becomes empty when ab has a fitness below a certain function, which is delineated, of the recombination rate. The properties of the two-locus model under constraints, out of equilibrium and with unpredictable selection are thus presented.
