Critical Points on the Use of Biologicals in Allergic Diseases and Asthma

Improved understanding of the contribution of immune-inflammatory mechanisms in allergic diseases and asthma has encouraged development of biologicals and small molecules specifically targeting the innate and adaptive immune response. There are several critical points impacting the efficacy of this stratified approach, from the complexity of disease endotypes to the effectiveness in real-world settings. We discuss here how these barriers can be overcome to facilitate the development of implementation science for allergic diseases and asthma.

Asthma Biomarkers: Do They Bring Precision Medicine Closer to the Clinic?

Measurement of biomarkers has been incorporated within clinical research of asthma to characterize the population and to associate the disease with environmental and therapeutic effects. Regrettably, at present, there are no specific biomarkers, none is validated or qualified, and endotype-driven choices overlap. Biomarkers have not yet reached clinical practice and are not included in current asthma guidelines. Last but not least, the choice of the outcome upholding the value of the biomarkers is extremely difficult, since it has to reflect the mechanistic intervention while being relevant to both the disease and the particular person. On the verge of a new age of asthma healthcare standard, we must embrace and adapt to the key drivers of change. Disease endotypes, biomarkers, and precision medicine represent an emerging model of patient care building on large-scale biologic databases, omics and diverse cellular assays, health information technology, and computational tools for analyzing sizable sets of data. A profound transformation of clinical and research pattern from population to individual risk and from investigator-imposed subjective disease clustering (hypothesis driven) to unbiased, data-driven models is facilitated by the endotype/biomarker-driven approach.

Antinuclear antibodies in asthma patients- a special asthma phenotype?

Several studies reported the appearance of asthma and autoimmune conditions in the same patient, but the clinical significance of this association was not yet assessed. One hundred asthmatic patients were observed for one year evolution with death, severe exacerbations, intake of > 1000 micrograms of beclometasone or equivalent [high ICS] and FEV1 decline >100 ml, in relation with ANA [ELISA], sputum and blood eosinophilia [EO], NSAID intolerance, BMI >25, chronic rhinosinusitis, smoking status and FEV1 <30% predicted [low FEV1]. After 1 year of observation, there were 5 deaths, 28 severe asthma exacerbations requiring hospitalisations, 24 cases requiring high inhaled corticosteroid intake, and 19 patients with fast FEV1 decline [>100 ml/year]. Multiple regression analysis pointed out several different independent risk factors for severe asthma evolution: for death presence of ANA [P=0.037], NSAID intolerance [P<0.001] and low FEV1 [P=0.021]; for evolution with severe exacerbations ANA [p=0.011], sputum EO [P<0.001], smoking [P=0.044] and NSAID intolerance [P=0.022]; for high ICS intake ANA [P=0.036], sputum EO [P=0.026] and low FEV1 [P=0.006]; for FEV1 decline >100 ml ANA [P=0.006], sputum EO [P=0.037], BMI>25 [P=0.046] and NSAID intolerance [P=0.017] The presence of ANA is an independent risk factor in asthma for evolution with death, severe exacerbations, high inhaled corticosteroid intake and FEV1 decline >100 ml