Omalizumab for Severe Asthma: Beyond Allergic Asthma.

Different subsets of asthma patients may be recognized according to the exposure trigger and the frequency and severity of clinical signs and symptoms. Regarding the exposure trigger, generally asthma can be classified as allergic (or atopic) and nonallergic (or nonatopic). Allergic and nonallergic asthma are distinguished by the presence or absence of clinical allergic reaction and in vitro IgE response to specific aeroallergens. The mechanisms of allergic asthma have been extensively studied with major advances in the last two decades. Nonallergic asthma is characterized by its apparent independence from allergen exposure and sensitization and a higher degree of severity, but little is known regarding the underlying mechanisms. Clinically, allergic and nonallergic asthma are virtually indistinguishable in exacerbations, although exacerbation following allergen exposure is typical of allergic asthma. Although they both show several distinct clinical phenotypes and different biomarkers, there are no ideal biomarkers to stratify asthma phenotypes and guide therapy in clinical practice. Nevertheless, some biomarkers may be helpful to select subsets of atopic patients which might benefit from biologic agents, such as omalizumab. Patients with severe asthma, uncontrolled besides optimal treatment, notwithstanding nonatopic, may also benefit from omalizumab therapy, although currently there are no randomized double-blind placebo controlled clinical trials to support this suggestion. However, omalizumab discontinuation according to each patient's response to therapy and pharmacoeconomical analysis are questions that remain to be answered.

Urinary metabolomic profiling of asthmatics can be related to clinical characteristics.

Metabolomics has been increasingly explored to achieve an improved understanding of asthma. In the current observational and exploratory study, the first to have examined the relationship between oxidative stress extension, eosinophilic inflammation, and disease severity in asthmatic patients, metabolomics (using target aliphatic aldehydes and alkanes) was carried out using solid-phase microextraction (SPME) followed by a comprehensive two-dimensional gas chromatography coupled to mass spectrometry with a high-resolution time-of-flight analyzer (GC×GC-ToFMS). We were able to demonstrate that metabolomics can give valuable insights into asthma mechanisms once lipidic peroxidation assessed by urinary metabolomics is related to the clinical characteristics of nonobese asthmatics, such as disease severity, lung function, and eosinophilic inflammation. Nevertheless, considering our sample size, the obtained results require further validation using a much larger sample cohort.

Blurred lines. Eosinophilic COPD: ACOS or COPD phenotype?

Because asthma and COPD are both inflammatory chronic obstructive airway diseases, there are several clinical expressions which can cause confusion, such as: eosinophilic asthma with fixed obstruction, which is a risk factor and might progress to COPD; eosinophilic COPD; COPD with partial reversible obstruction with no asthmatic component and also eosinophilic asthma-COPD overlap syndrome (ACOS). While at the two extremes of these disorders the pathoimmunological processes are clearly different, in some patients there is overlap and the pathophysiological border between asthma and COPD is fused (or diffuse). The current guidelines are clearly insufficient for classification of the obstructive patients and, taking into account that binary separation between the two diseases is not completely clear, we should resist the temptation to label patients as ACOS and consider new airway disease taxonomy. Regardless of the condition concerned, eosinophils should be considered in the algorithm approach to obstructive patients: in COPD, as in asthma, they are related to the underlying pathological process; they have prognostic value and are related to therapeutic response. Therefore, eosinophils should be valued as useful biomarkers and included in a multidimensional diagnostic and therapeutic approach, bearing in mind the phenotypic, immunopathological and functional complexity of chronic obstructive airway disease.

Cluster analysis in phenotyping a Portuguese population.

BACKGROUND: Unbiased cluster analysis using clinical parameters has identified asthma phenotypes. Adding inflammatory biomarkers to this analysis provided a better insight into the disease mechanisms. This approach has not yet been applied to asthmatic Portuguese patients. AIM: To identify phenotypes of asthma using cluster analysis in a Portuguese asthmatic population treated in secondary medical care. METHODS: Consecutive patients with asthma were recruited from the outpatient clinic. Patients were optimally treated according to GINA guidelines and enrolled in the study. Procedures were performed according to a standard evaluation of asthma. Phenotypes were identified by cluster analysis using Ward's clustering method. RESULTS: Of the 72 patients enrolled, 57 had full data and were included for cluster analysis. Distribution was set in 5 clusters described as follows: cluster (C) 1, early onset mild allergic asthma; C2, moderate allergic asthma, with long evolution, female prevalence and mixed inflammation; C3, allergic brittle asthma in young females with early disease onset and no evidence of inflammation; C4, severe asthma in obese females with late disease onset, highly symptomatic despite low Th2 inflammation; C5, severe asthma with chronic airflow obstruction, late disease onset and eosinophilic inflammation. CONCLUSIONS: In our study population, the identified clusters were mainly coincident with other larger-scale cluster analysis. Variables such as age at disease onset, obesity, lung function, FeNO (Th2 biomarker) and disease severity were important for cluster distinction.

A ten-year experience and follow-up of three hundred patients fitted with the Biomet/Lorenz Microfixation TMJ replacement system.

The purpose of this paper is to present the postoperative results obtained after full temporomandibular joint (TMJ) reconstruction employing the Biomet/Lorenz Microfixation TMJ replacement system (Jacksonville, FL, USA) in 300 patients (201 unilateral, 99 bilateral). Objective data (maximum inter-incisal opening; MIO) and subjective data (function and speech, diet, and pain) were collected preoperatively and at postoperative evaluations performed over a 10-year period (mean 3.5, standard deviation 2.1 years). The MIO measures were obtained using a calliper rule. Subjective data were evaluated using a visual analogue scale with scores ranging from 0 to 5 for each variable. The results were analyzed with the paired t-test (two-sided, α=5%). Each patient showed significant improvements for all of the variables at evaluation on postoperative day 7. The results for MIO, function and speech, and diet, showed improvements at each postoperative evaluation over a maximum of 3 years, with stabilization of the results from the fourth year. Complaints of pain decreased considerably up to the 1-month postoperative evaluation, and no patient reported severe pain at 6 months after surgery. The results presented show that the reconstruction of the TMJ through the installation of the Biomet/Lorenz system prosthesis is a safe and effective option for proper reestablishment of the joint and stomatognathic system function; significant long-term improvements in mandibular range of motion are promoted and pain levels decrease.