Exacerbation Of Respiratory Diseases Research Articles

Effects of hydrogen peroxide on mucociliary transport in human airway epithelial cells

The effects of environmental pollutants on airway clearance have not been well elucidated. This study examined mucociliary transport using different sized-fluorescent particles on polarized human airway epithelial cells which were maintained in an air–liquid interface (ALI) culture system. The effects of hydrogen peroxide (H2O2) exposure on mucociliary transport were also investigated. The movement of fluorescent particles with diameters of 10–14 and 2.5–4.5 µm was observed by fluorescent microscopy as an index of the mucociliary transport. The mixture of the particles with two different sizes was propelled concentrically on the apical surface by the interaction of ciliary activity and mucus in the control condition, whereas H2O2 exposure for 24 h significantly inhibited the movement of the particles. The particle sizes did not affect their movement after the control or H2O2 exposure. These results suggest that particle tracking on polarized human airway epithelial cells is a useful experimental tool for the evaluation of the effect of environmental pollutants on mucociliary transport. In addition, reactive oxygen species may impair mucociliary transport, leading to the airway damage and exacerbation of respiratory diseases.

Ozone Is Associated With an Increased Risk of Respiratory Exacerbations in Patients With Cystic Fibrosis

BackgroundTropospheric oxidant pollutants may injure the respiratory tract. Cystic fibrosis (CF) respiratory disease involves significant inflammation and excessive oxidative stress, and exposure to air pollutants can magnify the lung damage. The objective of this study was to investigate the association between the short-term variation in the concentration of air pollutants in metropolitan São Paulo, Brazil, and the occurrence of respiratory exacerbations in children and adolescents with CF.MethodsA longitudinal panel of repeated measurements was obtained from 103 patients attending the outpatient center of our institution from September 6, 2006 through September 4, 2007. Daily concentrations of inhaled particulate matter, sulfur dioxide, nitrogen dioxide, ozone (O3), carbon monoxide, and meteorologic variables, such as the minimum temperature and relative humidity, were evaluated. The generalized estimation equation model for binomial distribution was used to assess the impact of these measurements on the occurrence of acute respiratory exacerbations.ResultsIn total, 103 patients with CF (median age, 8.9 years) made 408 visits, with a mean ± SD of 4 ± 1.74 visits per patient (range, 2-9). A respiratory disease exacerbation was diagnosed on 142 visits (38.4%). An interquartile range increase in the O3 concentration (45.62 μg/m3) had a positive, delayed (2 days after exposure) effect on the risk of a respiratory exacerbation (relative risk = 1.86; 95% CI, 1.14-3.02).ConclusionsThis study demonstrates that exposure to short-term air pollution in a large urban center increases the risk of a pulmonary exacerbation in patients with CF.

Cooking fuels and prevalence of asthma: a global analysis of phase three of the International Study of Asthma and Allergies in Childhood (ISAAC)

Indoor air pollution from a range of household cooking fuels has been implicated in the development and exacerbation of respiratory diseases. In both rich and poor countries, the effects of cooking fuels on asthma and allergies in childhood are unclear. We investigated the association between asthma and the use of a range of cooking fuels around the world. For phase three of the International Study of Asthma and Allergies in Childhood (ISAAC), written questionnaires were self-completed at school by secondary school students aged 13-14 years, 244,734 (78%) of whom were then shown a video questionnaire on wheezing symptoms. Parents of children aged 6-7 years completed the written questionnaire at home. We investigated the association between types of cooking fuels and symptoms of asthma using logistic regression. Adjustments were made for sex, region of the world, language, gross national income, maternal education, parental smoking, and six other subject-specific covariates. The ISAAC study is now closed, but researchers can continue to use the instruments for further research. Data were collected between 1999 and 2004. 512,707 primary and secondary school children from 108 centres in 47 countries were included in the analysis. The use of an open fire for cooking was associated with an increased risk of symptoms of asthma and reported asthma in both children aged 6-7 years (odds ratio [OR] for wheeze in the past year, 1·78, 95% CI 1·51-2·10) and those aged 13-14 years (OR 1·20, 95% CI 1·06-1·37). In the final multivariate analyses, ORs for wheeze in the past year and the use of solely an open fire for cooking were 2·17 (95% CI 1·64-2·87) for children aged 6-7 years and 1·35 (1·11-1·64) for children aged 13-14 years. Odds ratios for wheeze in the past year and the use of open fire in combination with other fuels for cooking were 1·51 (1·25-1·81 for children aged 6-7 years and 1·35 (1·15-1·58) for those aged 13-14 years. In both age groups, we detected no evidence of an association between the use of gas as a cooking fuel and either asthma symptoms or asthma diagnosis. The use of open fires for cooking is associated with an increased risk of symptoms of asthma and of asthma diagnosis in children. Because a large percentage of the world population uses open fires for cooking, this method of cooking might be an important modifiable risk factor if the association is proven to be causal. BUPA Foundation, the Auckland Medical Research Foundation, the Health Research Council of New Zealand, the Asthma and Respiratory Foundation of New Zealand, the Child Health Research Foundation, the Hawke's Bay Medical Research Foundation, the Waikato Medical Research Foundation, Glaxo Wellcome New Zealand, the NZ Lottery Board, Astra Zeneca New Zealand, Hong Kong Research Grant Council, Glaxo Wellcome International Medical Affairs.

Associations Between Vitamin D and Self‐Reported Respiratory Disease in Older People from a Nationally Representative Population Survey

To investigate the association between serum 25-hydroxy vitamin D (25(OH)D) concentrations and respiratory diseases in older people. Cross-sectional, nationally representative sample. Community. Two thousand seventy noninstitutionalized adults aged 65 and older taking part in the Health Survey for England 2005. Serum 25(OH)D levels, self-reported long-term respiratory tract diseases, and covariates (age, sex, social class, season of examination, use of vitamin supplements, and physical health status). Participants with severe deficiency (25(OH)D < 35 nmol/L) had more than twice the risk of respiratory disease than those in the highest quartile of 25(OH)D status (>64 nmol/L), and those with moderate deficiency (second quartile: 25(OH)D 35-48.9 nmol/L) had 1.75 times greater odds of respiratory diseases, even after adjustment with covariates. Adjusted analysis showed that those in the third quartile (25(OH)D 49.0 to 63.9 nmol/L) also had a greater risk of respiratory disease (odds ratio = 1.63, 95% confidence interval = 1.04-2.57). Low serum 25(OH)D concentrations are associated with respiratory disease. Ensuring adequate 25(OH)D levels is of public health importance for older populations living in northern latitudes and may be an effective way to prevent concurrent respiratory infections and related complications in older people. Further studies are required to investigate whether vitamin D supplementation may reduce the incidence and exacerbations of respiratory disease.

Time series analysis of fine particulate matter and asthma reliever dispensations in populations affected by forest fires

BackgroundSeveral studies have evaluated the association between forest fire smoke and acute exacerbations of respiratory diseases, but few have examined effects on pharmaceutical dispensations. We examine the associations between daily fine particulate matter (PM2.5) and pharmaceutical dispensations for salbutamol in forest fire-affected and non-fire-affected populations in British Columbia (BC), Canada.MethodsWe estimated PM2.5 exposure for populations in administrative health areas using measurements from central monitors. Remote sensing data on fires were used to classify the populations as fire-affected or non-fire-affected, and to identify extreme fire days. Daily counts of salbutamol dispensations between 2003 and 2010 were extracted from the BC PharmaNet database. We estimated rate ratios (RR) and 95% confidence intervals (CIs) for each population during all fire seasons and on extreme fire days, adjusted for temperature, humidity, and temporal trends. Overall effects for fire-affected and non-fire-affected populations were estimated via meta-regression.ResultsFire season PM2.5 was positively associated with salbutamol dispensations in all fire-affected populations, with a meta-regression RR (95% CI) of 1.06 (1.04-1.07) for a 10 ug/m3 increase. Fire season PM2.5 was not significantly associated with salbutamol dispensations in non-fire-affected populations, with a meta-regression RR of 1.00 (0.98-1.01). On extreme fire days PM2.5 was positively associated with salbutamol dispensations in both population types, with a global meta-regression RR of 1.07 (1.04 - 1.09).ConclusionsSalbutamol dispensations were clearly associated with fire-related PM2.5. Significant associations were observed in smaller populations (range: 8,000 to 170,000 persons, median: 26,000) than those reported previously, suggesting that salbutamol dispensations may be a valuable outcome for public health surveillance during fire events.

Advances in pediatric asthma in 2012: Moving toward asthma prevention

Last year's "Advances in pediatric asthma: moving forward" concluded the following: "Now is also the time to utilize information recorded in electronic medical records to develop innovative disease management plans that will track asthma over time and enable timely decisions on interventions in order to maintain control that can lead to disease remission and prevention." This year's summary will focus on recent advances in pediatric asthma on modifying disease activity, preventing asthma exacerbations, managing severe asthma, and risk factors for predicting and managing early asthma, as indicated in Journal of Allergy and Clinical Immunology publications in 2012. Recent reports continue to shed light on methods to improve asthma management through steps to assess disease activity, tools to standardize outcome measures in asthma, genetic markers that predict risk for asthma and appropriate treatment, and interventions that alter the early presentation of asthma to prevent progression. We are well on our way to creating a pathway around wellness in asthma care and also to use new tools to predict the risk for asthma and take steps to not only prevent asthma exacerbations but also to prevent the early manifestations of the disease and thus prevent its evolution to severe asthma.

The air quality health index and asthma morbidity: a population-based study.

Background: Exposure to air pollution has been linked to the exacerbation of respiratory diseases. The Air Quality Health Index (AQHI), developed in Canada, is a new health risk scale for reporting air quality and advising risk reduction actions.Objective: We used the AQHI to estimate the impact of air quality on asthma morbidity, adjusting for potential confounders.Methods: Daily air pollutant measures were obtained from 14 regional monitoring stations in Ontario. Daily counts of asthma-attributed hospitalizations, emergency department (ED) visits, and outpatient visits were obtained from a provincial registry of 1.5 million patients with asthma. Poisson regression was used to estimate health services rate ratios (RRs) as a measure of association between the AQHI or individual pollutants and health services use. We adjusted for age, sex, season, year, and region of residence.Results: The AQHI values were significantly associated with increased use of asthma health services on the same day and on the 2 following days, depending on the specific outcome assessed. A 1-unit increase in the AQHI was associated with a 5.6% increase in asthma outpatient visits (RR = 1.056; 95% CI: 1.053, 1.058) and a 2.1% increase in the rate of hospitalization (RR = 1.021; 95% CI: 1.014, 1.028) on the same day and with a 1.3% increase in the rate of ED visits (RR = 1.013; 95% CI: 1.010, 1.017) after a 2-day lag.Conclusions: The AQHI values were significantly associated with the use of asthma-related health services. Timely AQHI health risk advisories with integrated risk reduction messages may reduce morbidity associated with air pollution in patients with asthma.

Use of an improved quantitative polymerase chain reaction assay to determine differences in human rhinovirus viral loads in different populations

Human rhinoviruses (HRV) frequently cause acute respiratory infections and chronic respiratory disease exacerbations. However, testing is not generally offered. We developed a modified HRV quantitative polymerase chain reaction (qPCR) assay to assess viral loads in the community and hospital patients. The assay had a lower limit of detection of 2 log10 viral copies/mL and displayed linearity over 5 log10 viral copies, with a lower limit of quantitation of 4 log10 viral copies/mL. Mean viral loads (95% confidence interval) for hospitalized children, university students, and institutionalized elderly, were 7.08 log10 viral copies/mL (6.7–7.5), 6.87 log10 viral copies/mL (6.5–7.2), and 7.09 log10 viral copies/mL (6.9–7.3), respectively (P = 0.67). Serial specimens of 14 university students showed a decrease of mean viral loads from 6.36 log10 viral copies/mL on day 1 to 2.32 log10 viral copies/mL 7 days past symptom onset (P < 0.001). Using an HRV qPCR, we showed that viral loads did not differ between the community and hospitalized populations and significantly decreased following symptoms onset in healthy individuals.

Wpływ zanieczyszczenia powietrza ozonem na układ oddechowy u dzieci

Ozone is an important component of air pollution. This review presents the negative impact of ozone air pollution on the respiratory system in children, including the induction and maintenance of inflammation in the airways and exacerbation of respiratory diseases. The relationship between the occurrence of exposure to elevated ozone concentrations and the prevalence of asthma in the context of selected genetic polymorphisms also are described. The possibilities of interventions to reduce exposure to ozone are discussed.

Acute Exacerbations of Respiratory Diseases

Steven Sahn: Acute Exacerbations of Respiratory Diseases. New Dehli: Jaypee Brothers Medical Publishers, 2012, 196pp., ISBN 978-9-3502-5267-3

P269 Feasibility and acceptability of non-invasive ventilation (NIV) as an aid to exercise in patients admitted with acute exacerbation of chronic respiratory disease

IntroductionPatients with acute exacerbations of chronic respiratory disease are often too breathless to exercise, leading to muscle deconditioning. Using NIV to assist exercise during an exacerbation might prevent this, but...

TRAFFIC-RELATED AIR POLLUTION INCREASES THE RISK OF EMERGENCY DEPARTMENT PRESENTATION WITH ASTHMA AMONG YOUNG CHILDREN IN WESTERN AUSTRALIA

Background and Aims: Previous studies have reported associations between air pollution and exacerbation of respiratory disease but very few have examined the influence on emergency department prese...

Susceptibility to Inhaled Flame-Generated Ultrafine Soot in Neonatal and Adult Rat Lungs

Over a quarter of the U.S. population is exposed to harmful levels of airborne particulate matter (PM) pollution, which has been linked to development and exacerbation of respiratory diseases leading to morbidity and mortality, especially in susceptible populations. Young children are especially susceptible to PM and can experience altered anatomic, physiologic, and biological responses. Current studies of ambient PM are confounded by the complex mixture of soot, metals, allergens, and organics present in the complex mixture as well as seasonal and temporal variance. We have developed a laboratory-based PM devoid of metals and allergens that can be replicated to study health effects of specific PM components in animal models. We exposed 7-day-old postnatal and adult rats to a single 6-h exposure of fuel-rich ultrafine premixed flame particles (PFPs) or filtered air. These particles are high in polycyclic aromatic hydrocarbons content. Pulmonary cytotoxicity, gene, and protein expression were evaluated at 2 and 24 h postexposure. Neonates were more susceptible to PFP, exhibiting increased lactate dehydrogenase activity in bronchoalveolar lavage fluid and ethidium homodimer-1 cellular staining in the lung in situ as an index of cytotoxicity. Basal gene expression between neonates and adults differed for a significant number of antioxidant, oxidative stress, and proliferation genes and was further altered by PFP exposure. PFP diminishes proliferation marker PCNA gene and protein expression in neonates but not adults. We conclude that neonates have an impaired ability to respond to environmental exposures that increases lung cytotoxicity and results in enhanced susceptibility to PFP, which may lead to abnormal airway growth.

Building-Related Illness

Abstract:Building-related illnesses represent a spectrum of disease. Important to their genesis are the unique features of the indoor air environment involving exposures to air pollution, mold spores, and various allergens. Specific building-related illnesses are primarily infectious, but also inclu

Case series demonstrating the presence of protozoa in the sputum of a proportion of respiratory patients

A Spanish study has demonstrated the presence of protozoa in the sputum of respiratory patients admitted to hospital with acute exacerbations of respiratory disease. These findings have not previously been replicated elsewhere in the world. Sputum was obtained from two case series of patients; firstly inpatients with an acute exacerbations of respiratory symptoms, and the other consisting mainly of chronic outpatients; both at Llandough Hospital, Cardiff, South Wales. Sputum, stained using the Papanicolaou method, was examined under a microscope using previously published criteria to determine the presence of protozoa. In the first series of ten inpatients, five patients (50%; 95% CI 24 – 76%) had protozoa in their sputum. In the second series of 17 generally less acute patients, one clearly had protozoa and two possibly had protozoa in their sputum. Protozoa may have an important pathogenic role in asthma which merits further examination.

Long-term activation of TLR3 by Poly(I:C) induces inflammation and impairs lung function in mice

BackgroundThe immune mechanisms associated with infection-induced disease exacerbations in asthma and COPD are not fully understood. Toll-like receptor (TLR) 3 has an important role in recognition of double-stranded viral RNA, which leads to the production of various inflammatory mediators. Thus, an understanding of TLR3 activation should provide insight into the mechanisms underlying virus-induced exacerbations of pulmonary diseases.MethodsTLR3 knock-out (KO) mice and C57B6 (WT) mice were intranasally administered repeated doses of the synthetic double stranded RNA analog poly(I:C).ResultsThere was a significant increase in total cells, especially neutrophils, in BALF samples from poly(I:C)-treated mice. In addition, IL-6, CXCL10, JE, KC, mGCSF, CCL3, CCL5, and TNFα were up regulated. Histological analyses of the lungs revealed a cellular infiltrate in the interstitium and epithelial cell hypertrophy in small bronchioles. Associated with the pro-inflammatory effects of poly(I:C), the mice exhibited significant impairment of lung function both at baseline and in response to methacholine challenge as measured by whole body plethysmography and an invasive measure of airway resistance. Importantly, TLR3 KO mice were protected from poly(I:C)-induced changes in lung function at baseline, which correlated with milder inflammation in the lung, and significantly reduced epithelial cell hypertrophy.ConclusionThese findings demonstrate that TLR3 activation by poly(I:C) modulates the local inflammatory response in the lung and suggest a critical role of TLR3 activation in driving lung function impairment. Thus, TLR3 activation may be one mechanism through which viral infections contribute toward exacerbation of respiratory disease.

The Effect of Particulate Matter 10 from Asian Dust on the Production of Reactive Oxygen Species, TGF-β, NF-κB, PDGF-α and Fibronectin in MRC-5 Fibroblast Cells

Background: Dust clouds blown by the wind from the arid deserts of Mongolia and Northeast China are known as Asian dust storms. Ambient particulate matter with a diameter <10 μm (PM10) is associated with the exacerbation of respiratory diseases and increased mortality of heart and lung disease patients. The fibrotic effects of PM10 of Asian dust to pulmonary fibroblast cells are unknown. This study examined the production of reactive oxygen species (ROS), TGF-β, NF-κB, PDGF-α and Fibronectin in fibroblasts exposed to Asian dust particles. Methods: Air samples were collected using a high volume air sampler (Sibata model HV500F) with an air flow of 500 L/min for at least 6 hours. The MRC-5 cells were exposed to 0, 50 and 100 μg/mL of PM10 for 24 hours. ROS was detected by measuring the level of oxidized DCF using FACS. TGF-β, NF-κB, PDGF-α and fibronectin were detected by western blotting. Results: There was no increase in the ROS, TGF-s and PDGF-α levels in the MRC-5 cells exposed to PM10. The NF-κ B level was higher in the MRC-5 cells exposed to 50 and 100 μg/mL of PM10 for 24 hours. The fibronectin level in the MRC-5 cells after 24 hours incubation with 50 μg/mL PM10 was significantly higher than the control group (PM10 50 μg/mL 113.27±8.65 of control, p=0.005). Conclusion: PM10 from Asian dust increases the activation of NF-κB and fibronectin expression in MRC-5 fibroblast cells.

Rhinovirus exposure impairs immune responses to bacterial products in human alveolar macrophages

Background:Rhinovirus infection is responsible for considerable morbidity and mortality as the major cause of exacerbations of asthma, and is also known to induce exacerbations of cystic fibrosis and chronic obstructive...

Air pollution as a determinant of asthma among schoolchildren in Mohammedia, Morocco

The objective of the study was to investigate whether air quality in western Morocco is truly a significant risk factor in the development and exacerbation of respiratory diseases and, in particular, asthma. The continuous measurement of the mean concentrations of sulfur dioxide (SO2) in the air and the density of Total Suspended Particulates (TSP) for a period of four years was determined. Information on individual characteristics and indoor environments from 1318 children with an average age of 12 years was evaluated by questionnaire, completed by parents (assisted by professional investigators) and symptoms/diseases were medically diagnosed and reported. We have used the Student's t-test, Chi-square tests & odds ratios (ORs) with 95% confidence intervals (CI 95%) for estimates of the risk of asthma. The prevalence of asthma varies in a significant way according to the zone (χ2 = 14.61, p < 0.05). Respiratory diseases (OR 6.27, 95% confidence interval [CI] 4.09 – 9.64, p < 0.0001), strongly polluted zone (OR 3.62, 95% CI 1.71 – 7.81, p ≤ 0.0001) and infectious diseases (OR 3.29, 95% CI 1.99 – 5.47, p < 0.0001) are high risk factors for asthma. Air pollution is a determinant factor but is not the only factor increasing the risk of asthma in children; other factors such as respiratory diseases, infectious diseases, genetic and passive smoking present a high-risk threat.

Filamentous Influenza A Virus Infection Predisposes Mice to Fatal Septicemia following Superinfection with Streptococcus pneumoniae Serotype 3

Previous studies have demonstrated that animals exposed to Streptococcus pneumoniae while recovering from influenza A virus infection exhibit exacerbated disease symptoms. However, many of the current animal models exploring dual viral and bacterial synergistic exacerbations of respiratory disease have utilized mouse-adapted influenza virus and strains of Streptococcus pneumoniae that in themselves are highly lethal to mice. Here we describe a mouse model of bacterial superinfection in which a mild, self-limiting influenza virus infection is followed by mild, self-limiting superinfection with S. pneumoniae serotype 3. S. pneumoniae superinfection results in rapid dissemination of the bacterium from the respiratory tract and systemic spread to all major organs of the mice, resulting in fatal septicemia. This phenomenon in mice was observed in superinfected animals undergoing an active viral infection as well as in mice that had completely cleared the virus 7 to 8 days prior to superinfection. Neutrophils were the predominant cellular inflammatory infiltrate in the lungs of superinfected mice compared to singly infected animals. Among other cytokines and chemokines, the neutrophil activator granulocyte colony-stimulating factor (G-CSF) was found to be significantly overexpressed in the spleens, lungs, and brains of superinfected animals. High G-CSF protein levels were observed in sera and lung lavage fluid from superinfected animals, suggesting that G-CSF is a major contributor to synergistic exacerbation of disease leading to fatal septicemia.