The prevalence of allergic airway diseases such as asthma and rhinitis has increased dramatically to epidemic proportions worldwide. Besides air pollution from industry derived emissions and motor vehicles, the rising trend can only be explained by gross changes in the environments where we live. The world economy has been transformed over the last 25 years with developing countries being at the core of these changes. Around the planet, in both developed and developing countries, environments are undergoing profound changes. Many of these changes are considered to have negative effects on respiratory health and to enhance the frequency and severity of respiratory diseases such as asthma in the general population. Increased concentrations of greenhouse gases, and especially carbon dioxide (CO₂), in the atmosphere have already warmed the planet substantially, causing more severe and prolonged heat waves, variability in temperature, increased air pollution, forest fires, droughts, and floods – all of which can put the respiratory health of the public at risk. These changes in climate and air quality have a measurable impact not only on the morbidity but also the mortality of patients with asthma and other respiratory diseases. The massive increase in emissions of air pollutants due to economic and industrial growth in the last century has made air quality an environmental problem of the first order in a large number of regions of the world. A body of evidence suggests that major changes to our world are occurring and involve the atmosphere and its associated climate. These changes, including global warming induced by human activity, have an impact on the biosphere, biodiversity, and the human environment. Mitigating this huge health impact and reversing the effects of these changes are major challenges. This statement of the World Allergy Organization (WAO) raises the importance of this health hazard and highlights the facts on climate-related health impacts, including: deaths and acute morbidity due to heat waves and extreme meteorological events; increased frequency of acute cardio-respiratory events due to higher concentrations of ground level ozone; changes in the frequency of respiratory diseases due to trans-boundary particle pollution; altered spatial and temporal distribution of allergens (pollens, molds, and mites); and some infectious disease vectors. According to this report, these impacts will not only affect those with current asthma but also increase the incidence and prevalence of allergic respiratory conditions and of asthma. The effects of climate change on respiratory allergy are still not well defined, and more studies addressing this topic are needed. Global warming is expected to affect the start, duration, and intensity of the pollen season on the one hand, and the rate of asthma exacerbations due to air pollution, respiratory infections, and/or cold air inhalation, and other conditions on the other hand.

Animal studies have reported that diesel exhaust particles (DEP), which constitute an important fraction of particulate air pollution, lead to inflammation and/or damage of the airways. To investigate the mechanisms underlying DEP-induced airway disease in humans, we have cultured human bronchial epithelial cells (HBEC) from surgically obtained bronchial explants and investigated the effects of purified DEP on the permeability and ciliary beat frequency (CBF) of HBEC, and on the release of inflammatory mediators from these cells. Exposure to 10–100 μg/ml DEP and a filtered solution of 50 μg/ml DEP significantly increased the electrical resistance of the cultures, reaching a maximum of 200% over baseline after 6 h incubation with 100 μg/ml DEP. In contrast, movement of 14C-labeled bovine serum albumin across cell cultures was not significantly altered by incubation of HBEC with DEP. Exposure to 50 μg/ml DEP, filtered DEP solution, and 100 μg/ml DEP significantly attenuated the CBF of these cells by 51%, 33%, and 73%, respectively, from baseline after 24 h incubation. Similarly, 50 μg/ml DEP, filtered DEP solution, and 100 μg/ml DEP significantly increased the release of interleukin-8 from 12.9 pg/μg cellular protein to 41.6, 114.9, and 44.3 pg/μg cellular protein, respectively, after 24 h incubation. The release of granulocyte-macrophage colony stimulating factor (GM-CSF) and soluble intercellular adhesion molecule-1 (sICAM-1) was also significantly increased after exposure for 24 h to 50 μg/ml DEP (GM-CSF from 0.033 pg/μg cellular protein to 0.056 pg/μg cellular protein and sICAM-1 from 7.2 pg/μg cellular protein to 12.5 pg/μg cellular protein). These results suggest that exposure of HBEC to DEP may lead to adverse functional changes and release of proinflammatory mediators from these cells, and that these effects may influence the development of airway disease.

Extravasation of monocytes into tissue and to the site of injury is a fundamental immunological process, which requires rapid responses via post translational modifications (PTM) of proteins. Protein arginine methyltransferase 7 (PRMT7) is an epigenetic factor that has the capacity to mono-methylate histones on arginine residues. Here we show that in chronic obstructive pulmonary disease (COPD) patients, PRMT7 expression is elevated in the lung tissue and localized to the macrophages. In mouse models of COPD, lung fibrosis and skin injury, reduced expression of PRMT7 associates with decreased recruitment of monocytes to the site of injury and hence less severe symptoms. Mechanistically, activation of NF-κB/RelA in monocytes induces PRMT7 transcription and consequential mono-methylation of histones at the regulatory elements of RAP1A, which leads to increased transcription of this gene that is responsible for adhesion and migration of monocytes. Persistent monocyte-derived macrophage accumulation leads to ALOX5 over-expression and accumulation of its metabolite LTB4, which triggers expression of ACSL4 a ferroptosis promoting gene in lung epithelial cells. Conclusively, inhibition of arginine mono-methylation might offer targeted intervention in monocyte-driven inflammatory conditions that lead to extensive tissue damage if left untreated.

Chronic obstructive pulmonary disease (COPD) is the third leading cause of death worldwide, and its global health burden is increasing. COPD is characterized by emphysema, mucus hypersecretion, and persistent lung inflammation, and clinically by chronic airflow obstruction and symptoms of dyspnea, cough, and fatigue in patients. A cluster of pathologies including chronic bronchitis, emphysema, asthma, and cardiovascular disease in the form of hypertension and atherosclerosis variably coexist in COPD patients. Underlying causes for COPD include primarily tobacco use but may also be driven by exposure to air pollutants, biomass burning, and workplace related fumes and chemicals. While no single animal model might mimic all features of human COPD, a wide variety of published models have collectively helped to improve our understanding of disease processes involved in the genesis and persistence of COPD. In this review, the pathogenesis and associated risk factors of COPD are examined in different mammalian models of the disease. Each animal model included in this review is exclusively created by tobacco smoke (TS) exposure. As animal models continue to aid in defining the pathobiological mechanisms of and possible novel therapeutic interventions for COPD, the advantages and disadvantages of each animal model are discussed.

Air pollution plays an important role in the mortality and morbidity of chronic airway diseases, such as asthma and chronic obstructive pulmonary disease (COPD). Particulate matter (PM) is a significant fraction of air pollutants, and studies have demonstrated that it can cause airway inflammation and injury. The airway epithelium forms the first barrier of defense against inhaled toxicants, such as PM. Airway epithelial cells clear airways from inhaled irritants and orchestrate the inflammatory response of airways to these irritants by secreting various lipid mediators, growth factors, chemokines, and cytokines. Studies suggest that PM plays an important role in the pathogenesis of chronic airway diseases by impairing mucociliary function, deteriorating epithelial barrier integrity, and inducing the production of inflammatory mediators while modulating the proliferation and death of airway epithelial cells. Furthermore, PM can modulate epithelial plasticity and airway remodeling, which play central roles in asthma and COPD. This review focuses on the effects of PM on airway injury and epithelial plasticity, and the underlying mechanisms involving mucociliary activity, epithelial barrier function, airway inflammation, epithelial-mesenchymal transition, mesenchymal-epithelial transition, and airway remodeling.