Work-Related Asthma: Diagnosis and Prognosis of Immunological Occupational Asthma and Work-Exacerbated Asthma

Abstract The incidence and prevalence of asthma are increasing. One reason for this trend is the rise in adult-onset asthma, especially occupational asthma, which is 1 of the 2 forms of work-related asthma. Occupational asthma is defined as asthma caused by agents that are present exclusively in the workplace. The presence of pre-existing asthma does not rule out the possibility of developing occupational asthma. A distinction has traditionally been made between immunological occupational asthma (whether IgE-mediated or not) and nonimmunological occupational asthma caused by irritants, the most characteristic example of which is reactive airway dysfunction syndrome. The other form of work-related asthma is known as work-exacerbated asthma, which affects persons with pre-existing or concurrent asthma that is worsened by work-related factors. It is important to differentiate between the 2 entities because their treatment, prognosis, and medical and social repercussions can differ widely. In this review, we discuss diagnostic methods, treatment, and avoidance/nonavoidance of the antigen in immunological occupational asthma and work-exacerbated asthma. Key words: Specific inhalation challenge. Peak expiratory flow. Workplace. Irritants. Resumen La incidencia y prevalencia del asma van en aumento. El asma de inicio en la edad adulta y especialmente el asma ocupacional (AO) podrían ser una de las causas que influyeran en este incremento. El AO, una de las dos formas de asma relacionada con el trabajo (ART), se define como el asma causada por agentes que están presentes exclusivamente en el lugar de trabajo. Clásicamente, se ha realizado una distinción entre AO inmunológica (mediada o no por un mecanismo IgE) y AO no inmunológica causada por irritantes, cuyo ejemplo más característico es el síndrome reactivo de disfunción de la vía aérea. La presencia de asma previa no descarta la posibilidad de desarrollar AO. El asma exacerbada por el trabajo (AET) es la otra forma de ART y se define como aquel asma pre-existente o concurrente que empeora por factores relacionados con el trabajo. Diferenciar estas dos entidades es importante ya que su tratamiento, pronóstico y repercusiones médica y social, pueden diferir ampliamente. En esta revisión se discuten los diversos métodos diagnósticos, tratamientos y las diferentes estrategias de evitación / no evitación del antígeno tanto en el AO inmunológica como en el AET. Palabras clave: Prueba de provocación bronquial específica. Pico flujo espiratorio. Lugar de trabajo. Irritantes. X Muñoz, et al

Adaptations to Climate-Mediated Selective Pressures in Humans

Humans inhabit a remarkably diverse range of environments, and adaptation through natural selection has likely played a central role in the capacity to survive and thrive in extreme climates. Unlike numerous studies that used only population genetic data to search for evidence of selection, here we scan the human genome for selection signals by identifying the SNPs with the strongest correlations between allele frequencies and climate across 61 worldwide populations. We find a striking enrichment of genic and nonsynonymous SNPs relative to non-genic SNPs among those that are strongly correlated with these climate variables. Among the most extreme signals, several overlap with those from GWAS, including SNPs associated with pigmentation and autoimmune diseases. Further, we find an enrichment of strong signals in gene sets related to UV radiation, infection and immunity, and cancer. Our results imply that adaptations to climate shaped the spatial distribution of variation in humans

The Role of Geography in Human Adaptation

Various observations argue for a role of adaptation in recent human evolution, including results from genome-wide studies and analyses of selection signals at candidate genes. Here, we use genome-wide SNP data from the HapMap and CEPH-Human Genome Diversity Panel samples to study the geographic distributions of putatively selected alleles at a range of geographic scales. We find that the average allele frequency divergence is highly predictive of the most extreme FST values across the whole genome. On a broad scale, the geographic distribution of putatively selected alleles almost invariably conforms to population clusters identified using randomly chosen genetic markers. Given this structure, there are surprisingly few fixed or nearly fixed differences between human populations. Among the nearly fixed differences that do exist, nearly all are due to fixation events that occurred outside of Africa, and most appear in East Asia. These patterns suggest that selection is often weak enough that neutral processes—especially population history, migration, and drift—exert powerful influences over the fate and geographic distribution of selected alleles

Host Genetics and HIV-1: The Final Phase?

This is a crucial transition time for human genetics in general, and for HIV host genetics in particular. After years of equivocal results from candidate gene analyses, several genome-wide association studies have been published that looked at plasma viral load or disease progression. Results from other studies that used various large-scale approaches (siRNA screens, transcriptome or proteome analysis, comparative genomics) have also shed new light on retroviral pathogenesis. However, most of the inter-individual variability in response to HIV-1 infection remains to be explained: genome resequencing and systems biology approaches are now required to progress toward a better understanding of the complex interactions between HIV-1 and its human host

Diesel exhausts particles: Their role in increasing the incidence of asthma. Reviewing the evidence of a causal link

Exposure to air pollutants has been correlated with an increase in the severity of asthma and in the exacerbation of pre-existing asthma. However, whether or not environmental pollution can cause asthma remains a controversial issue. The present review analyzes the current scientific evidence of the possible causal link between diesel exhaust particles (DEP), the solid fraction of the complex mixture of diesel exhaust, and asthma. The mechanisms that influence the expression and development of asthma are complex. In children prolonged exposure to pollutants such as DEPs may increase asthma prevalence. In adults, this causal relation is less clear, probably because of the heterogeneity of the studies carried out. There is also evidence of physiological mechanisms by which DEPs can cause asthma. The most frequently described interactions between cellular responses and DEP are the induction of pulmonary oxidative stress and inflammation and the activation of receptors of the bronchial epithelium such as toll-like receptors or increases in Th2 and Th17 cytokines, which generally orchestrate the asthmatic response. Others support indirect mechanisms through epigenetic changes, pulmonary microbiome modifications, or the interaction of DEP with environmental antigens to enhance their activity. However, in spite of this evidence, more studies are needed to assess the harmful effects of pollution – not only in the short term in the form of increases in the rate of exacerbations, but in the medium and long term as well, as a possible trigger of the disease.MJC is a researcher supported by the Miguel Servet programme from Instituto de Salud Carlos III (CP12/03101). This Project was supported by FIS PI15/01900 and Fondo Europeo de Desarrollo Regional (FEDER).Peer reviewe

A genome-wide association study of pulmonary tuberculosis in Morocco

Although epidemiological evidence suggests a human genetic basis of pulmonary tuberculosis (PTB) susceptibility, the identification of specific genes and alleles influencing PTB risk has proven to be difficult. Previous genome-wide association (GWA) studies have identified only three novel loci with modest effect sizes in sub-Saharan African and Russian populations. We performed a GWA study of 550,352 autosomal SNPs in a family-based discovery Moroccan sample (on the full population and on the subset with PTB diagnosis at <25 years), which identified 143 SNPs with p < 1 × 10(−4). The replication study in an independent case/control sample identified four SNPs displaying a p < 0.01 implicating the same risk allele. In the combined sample including 556 PTB subjects and 650 controls these four SNPs showed suggestive association (2 × 10(−6) < p < 4 × 10(−5)): rs358793 and rs17590261 were intergenic, while rs6786408 and rs916943 were located in introns of FOXP1 and AGMO, respectively. Both genes are involved in the function of macrophages, which are the site of latency and reactivation of Mycobacterium tuberculosis. The most significant finding (p = 2 × 10(−6)) was obtained for the AGMO SNP in an early (<25 years) age-at-onset subset, confirming the importance of considering age-at-onset to decipher the genetic basis of PTB. Although only suggestive, these findings highlight several avenues for future research in the human genetics of PTB