Biologic Therapies for Severe Asthma

Biologic Therapies for Severe Asthma Patients with severe asthma are at increased risk for a decreased quality of life, fixed airway obstruction, hospitalization, and death. Biologics may be required to reduce the disease burden. This review discusses the mechanisms, efficacy, and safety of biologics for severe asthma

Predicting the course of asthma from childhood until early adulthood

PURPOSE OF REVIEW: To communicate recent insights about the natural history of childhood asthma, with a focus on prediction of persistence and remission of childhood asthma, up to early adulthood.RECENT FINDINGS: Lung function around the age of 8-9 years is the strongest predictor: obstructive lung function predicts asthma persistence up to early adulthood, whereas normal lung function predicts remission. The ability to predict asthma remission improves when lung function is combined with blood eosinophil levels and degree of bronchial hyperresponsiveness. Interventions, such as inhaled corticosteroids and immunotherapy do not appear to alter the course of asthma. Epigenetic studies have revealed potential novel biomarkers of asthma remission, such as micro-RNA patterns in blood. Specifically, lower serum levels of mi-R221-5p, which is associated with lower IL-6 release and eosinophilic inflammation, predict remission. Higher levels of blood DNA-methylation of a CpG site in Peroxisomal Biogenesis Factor 11 Beta were associated with asthma remission.SUMMARY: Lung function, allergic comorbidity and polysensitization in childhood predict the course of asthma. Recent epigenetic studies have provided a better understanding of underlying pathological processes in asthma remission, which may be used to improve prediction or develop novel treatments aimed at altering the course of asthma.</p

Ultrafine particles, particle components and lung function at age 16 years:The PIAMA birth cohort study

Background: Particulate matter (PM) air pollution exposure has been linked to lung function in adolescents, but little is known about the relevance of specific PM components and ultrafine particles (UFP). Objectives: To investigate the associations of long-term exposure to PM elemental composition and UFP with lung function at age 16 years. Methods: For 706 participants of a prospective Dutch birth cohort, we assessed associations of forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) at age 16 with average exposure to eight elemental components (copper, iron, potassium, nickel, sulfur, silicon, vanadium and zinc) in PM2.5 and PM10, as well as UFP during the preceding years (age 13–16 years) estimated by land-use regression models. After assessing associations for each pollutant individually using linear regression models with adjustment for potential confounders, independence of associations with different pollutants was assessed in two-pollutant models with PM mass and NO2, for which associations with lung function have been reported previously. Results: We observed that for most PM elemental components higher exposure was associated with lower FEV1, especially PM10 sulfur [e.g. adjusted difference −2.23% (95% confidence interval (CI) −3.70 to −0.74%) per interquartile range (IQR) increase in PM10 sulfur]. The association with PM10 sulfur remained after adjusting for PM10 mass. Negative associations of exposure to UFP with both FEV1 and FVC were observed [-1.06% (95% CI: −2.08 to −0.03%) and −0.65% (95% CI: −1.53 to 0.23%), respectively per IQR increase in UFP], but did not persist in two-pollutant models with NO2 or PM2.5. Conclusions: Long-term exposure to sulfur in PM10 may result in lower FEV1 at age 16. There is no evidence for an independent effect of UFP exposure

The genetics of asthma and the promise of genomics-guided drug target discovery

Asthma is an inflammatory airway disease that is estimated to affect 339 million people globally. The symptoms of about 5-10% of patients with asthma are not adequately controlled with current therapy, and little success has been achieved in developing drugs that target the underlying mechanisms of asthma rather than suppressing symptoms. Over the past 3 years, well powered genetic studies of asthma have increased the number of independent asthma-associated genetic loci to 128. In this Series paper, we describe the immense progress in asthma genetics over the past 13 years and link asthma genetic variants to possible drug targets. Further studies are needed to establish the functional significance of gene variants associated with asthma in subgroups of patients and to describe the biological networks within which they function. The genomics-guided discovery of plausible drug targets for asthma could pave the way for the repurposing of existing drugs for asthma and the development of new treatments