Sundeep Salvi

Different airway inflammatory responses in asthmatic and healthy humans exposed to diesel

Particulate matter (PM) pollution adversely affects the airways, with asthmatic subjects thought to be especially sensitive. The authors hypothesised that exposure to diesel exhaust (DE), a major source of PM, would induce airway neutrophilia in healthy subjects, and that either these responses would be exaggerated in subjects with mild allergic asthma, or DE would exacerbate pre-existent allergic airways. Healthy and mild asthmatic subjects were exposed for 2 h to ambient levels of DE (particles with a 50% cut-off aerodynamic diameter of 10 µm (PM10) 108 µg·m−3) and lung function and airway inflammation were assessed. Both groups showed an increase in airway resistance of similar magnitude after DE exposure. Healthy subjects developed airway inflammation 6 h after DE exposure, with airways neutrophilia and lymphocytosis together with an increase in interleukin‐8 (IL‐8) protein in lavage fluid, increased IL‐8 messenger ribonucleic acid expression in the bronchial mucosa and upregulation of the endothelial adhesion molecules. In asthmatic subjects, DE exposure did not induce a neutrophilic response or exacerbate their pre-existing eosinophilic airway inflammation. Epithelial staining for the cytokine IL‐10 was increased after DE in the asthmatic group. Differential effects on the airways of healthy subjects and asthmatics of particles with a 50% cut-off aerodynamic diameter of 10 µm at concentrations below current World Health Organisation air quality standards have been observed in this study. Further work is required to elucidate the significance of these differential responses.

Rhinovirus infection up‐regulates eotaxin and eotaxin‐2 expression in bronchial epithelial cells

Background Human rhinoviruses (RVs) are the most common precipitants of asthma exacerbations. RV infection of bronchial epithelium results in local airway inflammation inducing eosinophil recruitment and activation. Induction of eosinophil chemoattractants could represent a central mechanism, as well as a prime target for intervention.

Is Exposure to Biomass Smoke the Biggest Risk Factor for COPD Globally

A 1.5 million years ago, our ancestors Homo erectus learned to light fi re from wood to keep wild animals away. Over the years, the human race has used several biologic sources of fuel to produce fi re, not only for getting rid of enemies but also for cooking and heating. These sources have included wood, charcoal, dried twigs and grass, crop residues, and animal dung cakes, which collectively are called biomass fuels. Although the modern world has replaced these highly polluting fuel sources with cleaner sources, such as liquefi ed petroleum gas and electricity, it is estimated that 50% of all households worldwide and 90% of all rural households continue to use biomass fuel as their main domestic source of energy. 1 Even in some developed countries, such as Canada, Australia, and the western states of the United States, the persistent rise in cost of energy has prompted an increasing number of households to use wood or other biomass fuels for cooking and heating purposes. 2 For example, a recent study in New Mexico reported that 26% of the population was exposed to smoke from biomass fuel. 3 According to estimates, . 2 billion kg biomass are burned every day worldwide 4 in open fi res and ineffi cient stoves in poorly ventilated rooms, making biomass smoke one of the most important sources of indoor air pollution globally. Moreover, biomass burning also contributes significantly to outdoor air pollution, 5 thereby exposing many nonusers to biomass smoke components.

Could the airway epithelium play an important role in mucosal immunoglobulin A production

Immunoglobulin (Ig) A is the major immunoglobulin of the healthy respiratory tract and is thought to be the most important immunoglobulin for lung defence. The basis for the preferential generation of IgA‐secreting cells in the airway mucosa remains unclear. Given the half‐life of 5 days for the majority of IgA plasma cells, many IgA plasma cells must develop daily from B cells to guarantee a continuous supply of IgA antibodies in the airway mucosa. For this, the surrounding cells must provide a constant supply of cytokines necessary for B‐cell isotype switch, growth and differentiation into IgA‐secreting plasma cells. Studies with CD4+ T‐cell knockout mice, T‐cell receptor knockout mice and mice made transgenic for CTLA4‐Ig demonstrate normal mucosal IgA isotype switch, differentiation and IgA production, thereby suggesting that T cells are not critical for mucosal IgA production, and that other cell sources may be more important. Also, the bronchus‐associated lymphoid tissue (BALT), which is believed to be the major site where IgA isotype switch and differentiation of B cells into plasma cells occur with the help of cytokines released by T cells, is not a constitutive feature of the normal human lung. This indicates that other parts of the respiratory tract must carry out the BALT function. We have recently demonstrated that healthy human airway epithelial cells constitutively produce IL‐5, a major cytokine implicated in the growth and differentiation of post‐switch mIgA+ B cells to IgA‐producing plasma cells. Several studies have recently reported that the human airway epithelium also constitutively produces IL‐2, TGFβ, IL‐6 and IL‐10, factors which are essential for B‐cell clonal proliferation, IgA isotype switch and differentiation into IgA‐producing plasma cells. The close proximity of B cells to the airway epithelium probably ensures a constant supply of growth and differentiation factors necessary for mucosal IgA production. In addition, the epithelial cells produce a glycoprotein, called the secretory component, which not only confers increased stability to S‐IgA, but is also quantitatively the most important receptor of the mucosal immune system, since it is responsible for the external transport of locally produced polymeric IgA and IgM. Recent studies also suggest a possible role for epithelial cells in antigen presentation. Dendritic cells situated within the airway epithelium could directly present antigens to B cells and direct their isotype switch towards IgA1 and IgA2 with the help of cytokines produced by epithelial cells. Airway epithelial cells could therefore play a major role in the production of mucosal IgA antibodies which are essential for airway mucosal defence.

Exposure to biomass smoke as a cause for airway disease in women and children.

Purpose of reviewAn estimated 3 billion people (about half the worlds population) burn biomass fuel (wood, crop residues, animal dung and coal) for cooking and heating purposes exposing a large population, especially women and children, to high levels of indoor air pollution. Biomass smoke comprises gaseous air pollutants as well as particulate matter air pollutants, which have significant harmful effects. Recent findingsExposure to biomass smoke is a major contributor to morbidity and mortality. Children, women and the elderly are most affected. Apart from poor lung growth seen in growing children, the risk of developing respiratory tract infections (both upper as well as lower) is greatly increased in children living in homes using biomass. Women who spend many hours cooking food in poorly ventilated homes develop chronic obstructive lung disease (COPD), asthma, respiratory tract infections, including tuberculosis and lung cancer. It has been argued that exposure to biomass fuel smoke is a bigger risk factor for COPD than tobacco smoking. SummaryPhysicians need to be aware about the harmful effects of biomass smoke exposure and ensure early diagnosis and appropriate management to reduce the disease burden. More research needs to be done to study health effects due to biomass smoke exposure better. Reducing the exposure to biomass smoke through proper home ventilation, home design and, if possible, change of biomass to cleaner fuels is strongly recommended in order to reduce biomass smoke-induced mortality and morbidity.

Allergic susceptibility associated with diesel exhaust particle exposure: clear as mud

Abstract Exposure to elevated levels of particulate air pollution from motor vehicles is frequently associated with increased morbidity and mortality from cardiovascular conditions, lung cancer, and nonmalignant respiratory illnesses (e.g., asthma, bronchitis, respiratory tract infections). It appears, however, that less attention has been paid to the potential role of road traffic fumes in the induction of allergic conditions. Laboratory studies in humans and animals have shown that particulate toxic pollutants—particularly diesel exhaust particulates—can enhance allergic inflammation and can induce allergic immune responses. Most of these immune responses are mediated by the carbon core of diesel exhaust particulates. Polyaromatic hydrocarbons (e.g., anthracene, fluoranthene, pyrene, phenanthrene) are major chemical components of diesel exhaust particulates, and they have enhanced the production of immunoglobulin E. Although several large epidemiological studies have demonstrated a strong association between exposure to motor vehicle traffic emissions and allergic symptoms and reduced lung function, the evidence for the development of allergic sensitization from diesel exhaust particulates is less abundant than for the aforementioned associations. Recent comparisons of the prevalence of hay fever, as well as positive skin-prick tests, between citizens of former West and East Germany and between Hong Kong and China civilians, have demonstrated marked differences. Crucial variations in the level of particulate air pollution from motor vehicles in these countries may account for the observed increased prevalence of atopy. Although road-traffic pollution from automobile exhausts may be a risk factor for atopic sensitization, the evidence in support of this view remains conflictive. Some investigators have reported a clear association between the prevalence of allergy and road-traffic-related air pollution, whereas such a difference was not observed in other studies. Most discrepancies have been related to important variations in study design and methodology. In addition, inasmuch as exposure to ambient particles differs substantially in worldwide urban environments, perhaps qualitative—rather than quantitative—variations in particulate air pollution at different locations account for differences in the prevalence and/or severity of respiratory allergies.

Insights, attitudes and perceptions about asthma and its treatment: Findings from a multinational survey of patients from 8 Asia-Pacific countries and Hong Kong

The Asthma Insight and Management (AIM) survey was conducted in North America, Europe, the Asia‐Pacific region and Latin America to characterize patients’ insights, attitudes and perceptions about their asthma and its treatment. We report findings from the Asia‐Pacific survey.

Source of Biomass Cooking Fuel Determines Pulmonary Response to Household Air Pollution

Approximately 3 billion people-half the worldwide population-are exposed to extremely high concentrations of household air pollution due to the burning of biomass fuels on inefficient cookstoves, accounting for 4 million annual deaths globally. Yet, our understanding of the pulmonary responses to household air pollution exposure and the underlying molecular and cellular events is limited. The two most prevalent biomass fuels in India are wood and cow dung, and typical 24-hour mean particulate matter (PM) concentrations in homes that use these fuels are 300 to 5,000 μg/m(3). We dissected the mechanisms of pulmonary responses in mice after acute or subchronic exposure to wood or cow dung PM collected from rural Indian homes during biomass cooking. Acute exposures resulted in robust proinflammatory cytokine production, neutrophilic inflammation, airway resistance, and hyperresponsiveness, all of which were significantly higher in mice exposed to PM from cow dung. On the contrary, subchronic exposures induced eosinophilic inflammation, PM-specific antibody responses, and alveolar destruction that was highest in wood PM-exposed mice. To understand the molecular pathways that trigger biomass PM-induced inflammation, we exposed Toll-like receptor (TLR)2-, TLR3-, TLR4-, TLR5-, and IL-1R-deficient mice to PM and found that IL-1R, TLR4, and TLR2 are the predominant receptors that elicit inflammatory responses via MyD88 in mice exposed to wood or cow dung PM. In conclusion, this study demonstrates that subchronic exposure to PM collected from households burning biomass fuel elicits a persistent pulmonary inflammation largely through activation of TLR and IL-1R pathways, which could increase the risk for chronic respiratory diseases.

Insights, attitudes and perceptions about asthma and its treatment

The Asthma Insight and Management (AIM) survey was conducted in North America, Europe, the Asia‐Pacific region and Latin America to characterize patients’ insights, attitudes and perceptions about their asthma and its treatment. We report findings from the Asia‐Pacific survey.

Measuring lung function using sound waves: role of the forced oscillation technique and impulse oscillometry system.

Measuring lung function is an important component in the decision making process for patients with obstructive airways disease (OAD). Not only does it help in arriving at a specific diagnosis, but it also helps in evaluating severity so that appropriate pharmacotherapy can be instituted, it helps determine prognosis and it helps evaluate response to therapy. Spirometry is currently the most commonly performed lung function test in clinical practice and is considered to be the gold standard diagnostic test for asthma and COPD. However, spirometry is not an easy test to perform because the forceful expiratory and inspiratory manoeuvres require good patient co-operation. Children aged <5 years, elderly people and those with physical and cognitive limitations cannot perform spirometry easily.