Qingling Zhang

Mechanistic impact of outdoor air pollution on asthma and allergic diseases

Over the past decades, asthma and allergic diseases, such as allergic rhinitis and eczema, have become increasingly common, but the reason for this increased prevalence is still unclear. It has become apparent that genetic variation alone is not sufficient to account for the observed changes; rather, the changing environment, together with alterations in lifestyle and eating habits, are likely to have driven the increase in prevalence, and in some cases, severity of disease. This is particularly highlighted by recent awareness of, and concern about, the exposure to ubiquitous environmental pollutants, including chemicals with oxidant-generating capacities, and their impact on the human respiratory and immune systems. Indeed, several epidemiological studies have identified a variety of risk factors, including ambient pollutant gases and airborne particles, for the prevalence and the exacerbation of allergic diseases. However, the responsible pollutants remain unclear and the causal relationship has not been established. Recent studies of cellular and animal models have suggested several plausible mechanisms, with the most consistent observation being the direct effects of particle components on the generation of reactive oxygen species (ROS) and the resultant oxidative stress and inflammatory responses. This review attempts to highlight the experimental findings, with particular emphasis on several major mechanistic events initiated by exposure to particulate matters (PMs) in the exposure-disease relationship.

Airway Microbiota in Severe Asthma and Relationship to Asthma Severity and Phenotypes.

Background The lower airways harbor a community of bacterial species which is altered in asthma. Objectives We examined whether the lower airway microbiota were related to measures of asthma severity. Methods We prospectively recruited 26 severe asthma, 18 non-severe asthma and 12 healthy subjects. DNA was extracted from induced sputum and PCR amplification of the V3-V5 region of bacterial 16S rRNA gene was performed. Results We obtained 138,218 high quality sequences which were rarefied at 133 sequences/sample. Twenty OTUs had sequences ≥1% of total. There were marked differences in the distribution of Phyla between groups (P = 2.8x10-118). Bacteroidetes and Fusobacteria were reduced in non-severe and severe asthmatic groups. Proteobacteria were more common in non-severe asthmatics compared to controls (OR = 2.26; 95% CI = 1.94–2.64) and Firmicutes were increased in severe asthmatics compared to controls (OR = 2.15; 95%CI = 1.89–2.45). Streptococcal OTUs amongst the Firmicutes were associated with recent onset asthma, rhinosinusitis and sputum eosinophilia. Conclusions Sputum microbiota in severe asthma differs from healthy controls and non-severe asthmatics, and is characterized by the presence of Streptococcus spp with eosinophilia. Whether these organisms are causative for the pathophysiology of asthma remains to be determined.

Impaired macrophage phagocytosis of bacteria in severe asthma

BackgroundBacteria are frequently cultured from sputum samples of severe asthma patients suggesting a defect in bacterial clearance from the airway. We measured the capacity of macrophages from patients with asthma to phagocytose bacteria.MethodsPhagocytosis of fluorescently-labelled polystyrene beads, Haemophilus influenzae or Staphylococcus aureus by broncholaveolar lavage alveolar macrophages (AM) and by monocyte-derived macrophages (MDM) from non-asthmatics, mild-moderate and severe asthmatic patients was assessed using fluorimetry.ResultsThere were no differences in phagocytosis of polystyrene beads by AMs or MDMs from any of the subject groups. There was reduced phagocytosis of Haemophilus influenzae and Staphylococcus aureus in MDMs from patients with severe asthma compared to non-severe asthma (p < 0.05 and p < 0.01, respectively) and healthy subjects (p < 0.01and p < 0.001, respectively). Phagocytosis of Haemophilus influenzae and Staphylococcus aureus by AM was also reduced in severe asthma compared to normal subjects (p < 0.05). Dexamethasone and formoterol did not suppress phagocytosis of bacteria by MDMs from any of the groups.ConclusionsPersistence of bacteria in the lower airways may result partly from a reduced phagocytic capacity of macrophages for bacteria. This may contribute to increased exacerbations, airway colonization and persistence of inflammation.

Does unrestrained single-chamber plethysmography provide a valid assessment of airway responsiveness in allergic BALB/c mice?

BackgroundUnrestrained plethysmography has been used to monitor bronchoconstriction because of its ease of use and ability to measure airway responsiveness in conscious animals. However, its reliability remains controversial.ObjectiveTo investigate if unrestrained plethysmography could provide a valid interpretation of airway responsiveness in allergic BALB/c mice.MethodsOvalbumin sensitized BALB/c mice were randomized to receive either a single-dose Ovalbumin challenge (OVA-1D group) or a three-dose Ovalbumin challenge (OVA-3D group). The OVA-1D group was further divided into OVA-1D-I (measured invasively, using lung resistance as the index of responsiveness) and OVA-1D-N group (measured non-invasively, using Penh as the index of responsiveness). Similarly the OVA-3D group was divided into OVA-3D-I and OVA-3D-N groups based on the above methods. The control groups were sensitized and challenged with normal saline. Bronchial alveolar lavage fluid was taken and airway histopathology was evaluated for airway inflammation. Nasal responsiveness was tested with histamine challenge.ResultsCompared with controls, a significant increase in airway responsiveness was shown in the OVA-1D-N group (P < 0.05) but not in the OVA-1D-I group. Both OVA-3D-I and OVA-3D-N groups showed higher responsiveness than their controls (P < 0.05). The nasal mucosa was infiltrated by eosinophic cells in all Ovalbumin immunized groups. Sneezing or nasal rubbing in allergic groups appeared more frequent than that in the control groups.ConclusionPenh can not be used as a surrogate for airway resistance. The invasive measurement is specific to lower airway. Penh measurement (done as a screening procedure), must be confirmed by a direct invasive measurement specific to lower airway in evaluating lower airway responsiveness.

Link between environmental air pollution and allergic asthma: East meets West.

With the levels of outdoor air pollution from industrial and motor vehicle emissions rising rapidly in the fastly-industrializing countries of South East Asia, the prevalence of asthma and allergic diseases has also been increasing to match those in the West. Epidemiological and experimental exposure studies indicate a harmful impact of outdoor air pollution from vehicles and factories both on the development of allergic diseases and asthma and the increase in asthma symptoms and exacerbations. The level of outdoor pollution in Asia is much higher and more diverse than those encountered in Western countries. This may increase the impact of outdoor pollution on health, particularly lung health in Asia. This review discusses the constituents of air pollution in Asia with a special focus on studies in mainland China and Taiwan where the levels of pollution have reached high levels and where such high levels particularly in winter can cause a thick haze that reduces visibility. The onus remains on regulatory and public health authorities to curb the sources of pollution so that the health effects on the population particularly those with lung and cardiovascular diseases and with increased susceptibility can be mitigated.

BAL Fluid 8-Isoprostane Concentrations in Eosinophilic Bronchitis and Asthma

Background. Oxidative stress has an important role in the pathophysiology of asthma. But oxidative stress of airway has not been assessed in patients with nonasthmatic eosinophilic bronchitis (EB). 8-epi-prostaglandin F2alpha (8-isoprostane) is a biomarker of oxidative stress. Objectives. We sought to determine whether oxidative stress (measured by 8-isoprostane) occurs in EB and whether 8-isoprostane is associated with airway function in EB and asthma. Methods. We measured 8-isoprostane concentrations in the bronchoalveolar lavage (BAL) fluid from 11 subjects with EB, 10 subjects with asthma, and 9 healthy control subjects. 8-isoprostane was measured by enzyme immunoassays. Results. We found that BAL fluid 8-isoprostane concentrations were raised both in EB and asthma. The median concentrations of 8-isoprostane in BAL fluid were significantly higher in subjects with asthma (12.78 pg/mL) when compared with EB (8.34 pg/mL) and healthy control subjects (5.07 pg/mL). Conclusions. Our study shows that oxidative stress is increased significantly in asthmatic subjects and the degree of oxidative stress in EB subjects is milder than that in asthma, as reflected by 8-isoprostane concentrations in the BAL fluid. The difference in airway function observed in subjects with EB and asthma could be associated with different elevation in 8-isoprostane concentration in the airways.

Cough and environmental air pollution in China.

With fast-paced urbanization and increased energy consumption in rapidly industrialized modern China, the level of outdoor and indoor air pollution resulting from industrial and motor vehicle emissions has been increasing at an accelerated rate. Thus, there is a significant increase in the prevalence of respiratory symptoms such as coughing, wheezing, and decreased pulmonary function. Experimental exposure research and epidemiological studies have indicated that exposure to particulate matter, ozone, nitrogen dioxide, and environmental tobacco smoke have a harmful influence on development of respiratory diseases and are significantly associated with cough and wheeze. This review mainly discusses the effect of air pollutants on respiratory health, particularly with respect to cough, the links between air pollutants and microorganisms, and air pollutant sources. Particular attention is paid to studies in urban areas of China where the levels of ambient and indoor air pollution are significantly higher than World Health Organization recommendations.

An Intratracheal Challenge Murine Model of Asthma: Can Bronchial Inflammation Affect the Nose?

Purpose Extensive data support the influence of the upper airway on lower airway inflammation and pathophysiology in allergic disease. However, few studies have focused on allergic inflammation in the nose after an isolated lower airway allergen challenge, a situation that can exist clinically when human subjects breathe primarily through the mouth, as occurs when nasally congested. This study used a mouse model to investigate whether upper airway inflammation and hyperresponsiveness were induced by an isolated lower airway allergen challenge. Methods BALB/c mice were sensitized by systemic intraperitoneal injection of ovalbumin/saline and challenged with intratracheal ovalbumin/saline. Inflammation in the nose and lungs was assessed by cytology and histology of nasal tissues and bronchoalveolar lavage fluid (BALF), while nasal airway resistance and response were measured over 3 days post-challenge. Results Intratracheal application of an allergen in anaesthetized mice resulted in exclusive deposition in the lower airway. Compared to control animals, ovalbumin-sensitized mice after challenge showed bronchial hyperreactivity and increased IL-5 in the serum BALF, as well as eosinophil infiltration in the lungs. However, nasal histology of the ovalbumin-sensitized mice showed no increase in eosinophil infiltration. The nasal lavage fluid revealed no increase in eosinophils or IL-5, and the nasal airway resistance did not increase after challenge either. Conclusions In a mouse allergy model, exclusive allergen challenge of the lower airway can elicit a pulmonary and systemic allergic response, but does not induce upper airway inflammatory or physiological responses.

Asthma Phenotypes Defined From Parameters Obtained During Recovery From a Hospital-Treated Exacerbation

BACKGROUND Asthma is a heterogeneous disease with diverse clinical manifestations and inflammatory pathologies that is punctuated by exacerbations. OBJECTIVE To describe the clinical and inflammatory characteristics of patients with asthma treated in hospital for an acute exacerbation. METHODS Data from 320 adult patients receiving treatment for an acute exacerbation of asthma were obtained. In 218 patients with complete data, we used the Ward hierarchical clustering to obtain clusters. Pulmonary function, blood cell counts, sputum cell counts, serum IgE levels, and fractional exhaled nitric oxide were measured on hospital admission. We selected 13 variables with which we performed the Ward minimum-variance hierarchical clustering. RESULTS Four clusters were defined. Clusters 1 (24.5%) and 3 (36.7%) were characterized by predominantly female patients with asthma with sputum neutrophilia, with cluster 1 associated with a small degree of airflow obstruction and early-onset asthma and cluster 3 with a moderate degree of reduction in FEV1. Clusters 2 (22.0%) and 4 (16.5%) were associated with high sputum eosinophilia and severe airflow obstruction. Cluster 4 was made exclusively of male smoking subjects, whereas cluster 2 was made up of predominantly female nonsmoking subjects with the worst FEV1, forced expiratory flow at 25% to 75% of forced vital capacity (% predicted), and partial pressure of oxygen in arterial blood on admission. There were no differences between clusters in terms of atopy, serum IgE, prevalence of nasal disease, dose of maintenance inhaled corticosteroids, or oral/systemic corticosteroid use and asthma exacerbations. CONCLUSIONS The clusters during recovery from an exacerbation of asthma were distinguished by airflow obstruction and a neutrophilic, eosinophilic, or mixed inflammation. Eosinophilic inflammation was found in smoking and nonsmoking patients with asthma during an exacerbation.

Bronchiectasis after bronchial thermoplasty

Bronchial thermoplasty (BT) is used in the treatment of severe refractory asthma. It has been found to be beneficial to long-term improvements in the rate of asthma exacerbation, quality of life questionnaire answers (AQLQ), hospitalization, and emergency room visits. Atelectasis and lung abscess as direct complication of BT, but not bronchiectasis, have been reported previously. In this study, we report bronchiectasis after BT in what we believe may be the first case, combined with optical coherence tomography (OCT) and a 3-year follow-up of chest computed tomography (CT), to evaluate a patient with severe persistent asthma. We describe a 49-year-old Chinese male who complained of recurrent wheezing lasting over 5 years. His chest CT scan was normal before BT, but one month thereafter, he presented with mild central bronchiectasis on high-resolution CT, which persisted for more than 4 years. It remains unclear why this patient developed bronchiectasis so early post-BT treatment. This case highlights the need for short-term and long-term safety data on BT.