Association between air pollution and asthma admission among children in Hong Kong

OBJECTIVE: To examine the association of air pollutants with hospital admission for childhood asthma in Hong Kong. METHODS: Data on hospital admissions for asthma, influenza and total hospital admissions in children aged < or =18 years at all Hospital Authority hospitals during 1997-2002 were obtained. Data on daily mean concentrations of particles with aerodynamic diameter <10 microm (i. e. PM10) and <2.5 microm (i. e. PM2.5), nitrogen dioxide (NO2), sulphur dioxide (SO2), and ozone (O3) and data on meteorological variables were associated with asthma hospital admissions using Poisson's regression with generalized additive models for correction of yearly trend, temperature, humidity, day-of-week effect, holiday, influenza admissions and total hospital admission. The possibility of a lag effect of each pollutant and the interaction of different pollutants were also examined. RESULTS: The association between asthma admission with change of NO2, PM10, PM2.5 and O3 levels remained significant after adjustment for multi-pollutants effect and confounding variables, with increase in asthma admission rate of 5.64% (3.21-8.14) at lag 3 for NO2, 3.67% (1.52-5.86) at lag 4 for PM10, 3.24% (0.93-5.60) at lag 4 for PM2.5 and 2.63% (0.64-4.67) at lag 2 for O3. Effect of SO2 was lost after adjustment. CONCLUSION: Ambient levels of PM10, PM2.5) NO2 and O3 are associated with childhood asthma hospital admission in Hong Kong.     

A comparison of serum haptoglobin levels between acute exacerbation and clinical remission in asthma

Background Bronchial asthma is characterized by airway inflammation, which underlies the phenomenon of bronchial hyperresponsiveness. The concentration of serum haploglobin (Hp), one of the acute phase reactant proteins, has been reported to correlate with bronchial hyperresponsiveness. The extent to which bronchoconstriction or airway inflammation contributes to airflow obstruction of exacerbation is presumed to determine the responsiveness to the initial bronchodilator therapy. Objective To see whether the Hp levels vary with the disease status of asthma, and also to test whether the Hp level at an acute exacerbation(AE) is correlated with the degree of response to initial bronchodilator therapy. Methods We measured serum Hp levels in 50 children with asthma at the times of an AE and a clinical remission(CR), and analysed the data according to the response to the initial bronchodilator therapy at AE. Results The serum concentration of Hp at AE (228.5 ± 80.8mg/dl, mean ± SD) was significantly (P < 0.01) higher than that at CR (152.3 ± 49.8mg/dl) in the total study population. The difference of Hp levels between AE and CR was more marked (101.7 ± 82.2 mg/dl) in the subjects (n= 19) who responded poorly (post-bronchodi-lator FEV₁ < 75% predicted) to the initial bronehodilator therapy at AE than that (61.0 ± 56.5mg/dl) of those (n= 31) who responded well (post-bronchodilator FEV₁± 75% predicted). The Hp level at AE eorrelated with the degree of response to initial bronchodilator therapy (r=?0.36, P < 0.05), whereas it had no relationship with the severity of exacerbation (r= 0.04. P= 0.79). Conclusion Our results showed that Hp levels may be increased al ihe time of exacerbation in a given asthma patient. The finding that the elevation of Hp level at AE is more marked in the cases with poor response to initial bronchodilaior therapy at AE suggests that the increased Hp level at AE in asthma might relied the degree of airway inflammation.     

Increased lymphoid MxA expression in acute asthma exacerbation in children

BACKGROUND: Although the association between acute asthma exacerbation and viral infection has been well documented, virus identification rates vary. It has recently been reported that the expression of MxA protein in lymphocytes, inducible by type I interferons, can serve as a sensitive marker for viral infection in the host. The objective was to determine the contribution of viral infection to precipitation of asthma attacks in children. METHODS: We studied 186 asthmatic children, aged 0-12 years, over a 1-year period to evaluate MxA protein levels in peripheral blood lymphocytes by using a flow cytometric analysis in whole blood. RESULTS: Of all the subjects, 80 (47%) exhibited significantly elevated levels of MxA expression in lymphocytes, presumably indicating the states of viral infection. The association of viral infections with acute asthma exacerbation seemed to be marked in younger children: enhanced MxA expression was seen in 73.3% of infants (aged 0-1 year), 49.5% of toddlers (aged 2-5 years), and 26% of schoolchildren (aged 6-12 years). Seasonal changes in the frequency of viral infection associated with deterioration were also observed. CONCLUSIONS: Flow cytometric assay of MxA protein expression in whole blood appears to be an easy and useful method to evaluate viral infections in acute asthma exacerbation.     

Persistence of rhinovirus RNA after asthma exacerbation in children

BACKGROUND: Rhinoviruses (RVs) are believed to cause most asthma exacerbations but their role in the severity of acute asthma and subsequent recovery of airway function is not defined. The importance of atopy in virus-host interactions is also not clear. OBJECTIVE: We postulated that RV infection and atopic skin prick responses influence the severity of asthma exacerbations as measured by peak expiratory flow (PEF). METHODS: Patients aged 4-12 years admitted with acute severe asthma to a hospital emergency room (ER) were recruited. PEF measurements were obtained and nasal aspirates (NA) were taken. Atopy was diagnosed by skin prick responses to allergen and the presence of RV RNA and respiratory syncytial virus (RSV) RNA in NAs was detected using validated PCR assays. Patients were restudied after 6 weeks and after 6 months. RESULTS: Fifty children with acute asthma (mean age+/-SD, 7.4+/-2.7) were enrolled; atopy was present in 37 (74%). RV RNA was detected in 41 (82%) and RSV RNA in six (12%) subjects. After 6 weeks 41 patients were restudied and RV RNA was again detected in 18 (44%). RV RNA was detected after 6 months in four of 16 patients restudied (25%; P=0.008 vs. ER) and in two of nine children from a control group with stable asthma (22%; P=0.009 vs. ER). Overall PEF measurements were reduced in asthmatics admitted to ER (% predicted, 63.4+/-16.4%) but did not differ between patients with RV RNA, RSV RNA or neither virus present. In subjects with RV RNA detectable in ER and after 6 weeks, measurements of PEF in ER were significantly lower than in patients in whom RV RNA was present in ER but absent after 6 weeks (P=0.009). Regression analysis linked persistence of RV RNA, but not skin prick responses to allergen, to severity of PEF reductions in ER. CONCLUSION: RV RNA was detectable in >40% of asthmatic children 6 weeks after an acute exacerbation. Asthma exacerbations were more severe in patients with persistence of RV RNA suggesting that the severity of acute asthma may be linked to prolonged and possibly more severe RV infections.     

Effects of air pollution on asthma hospitalization rates in different age groups in Hong Kong

AIMS: To assess the relationship between levels of ambient air pollutants and hospitalization rates for asthma in Hong Kong (HK). METHODS: This is a retrospective ecological study. Data of daily emergency hospital admissions to 15 major hospitals in HK for asthma and indices of air pollutants [sulphur dioxide (SO(2)), nitrogen dioxide (NO(2)), ozone (O(3)), particulates with an aerodynamic diameter of <10 microm particulate matter (PM(10)) and 2.5 microm (PM(2.5))] and meteorological variables from January 2000 to December 2005 were obtained from several government departments. Analysis was performed by the generalized additive models with Poisson distribution. The effects of time trend, season, other cyclical factors, temperature and humidity were adjusted. Autocorrelation and overdispersion were corrected. RESULTS: Altogether, 69 716 admissions were assessed. Significant associations were found between hospital admissions for asthma and levels of NO(2), O(3), PM(10) and PM(2.5). The relative risks (RR) for hospitalization for every 10 microg/m(3) increase in NO(2), O(3), PM(10) and PM(2.5) were 1.028, 1.034, 1.019 and 1.021, respectively, at a lag day that ranged from cumulative lag 0-4 to 0-5. In a multi-pollutant model, O(3) was significantly associated with increased admissions for asthma. The younger age group (0-14 years) tended to have a higher RR for each 10 microg/m(3) increase in pollutants than those aged 15-65 years. The elderly (aged >/=65 years) had a shorter 'best' lag time to develop asthma exacerbation following exposure to pollutants than those aged <65 years. CONCLUSION: Adverse effects of ambient concentrations of air pollutants on hospitalization rates for asthma are evident. Measures to improve air quality in HK are urgently needed.     

Decompensation of pollen-induced asthma in two towns with different pollution levels in La Mancha, Spain

BACKGROUND: Allergic diseases have increased in industrialized countries and this increase is associated not only with genetic factors but also with lifestyle and environmental factors such as air pollution. Our hypothesis was that asthma in pollen-allergic patients from two towns with very different pollution levels in La Mancha (Spain) could be affected to a very different degree. OBJECTIVE: Our objectives were to assess the risk factors associated with decompensation of pollen-induced asthma in the two towns and to perform a comparison between the patients from Puertollano (high pollution level) and Ciudad Real (low pollution level) with respect to daily symptoms, medication used and peak-flow measurements. METHODS: We designed a cohort study with 137 patients (66 from Puertollano and 71 from Ciudad Real), conducted over 3 years (1999-2001) and including two pollen seasons. The two populations presented similar demographic and clinical characteristics. The variables studied included: area of residence, sex, age, smoking status, asthma symptoms and positive prick tests. Clinical decompensation was monitored by symptoms recorded on diary cards, twice daily peak-flow measurements and the use of protocolized medication. RESULTS: There was a clinically relevant relationship between the place of residence and clinical decompensation. The risk of clinical decompensation in patients from Puertollano was up to three times higher than that of patients in Ciudad Real (P=0.034). Furthermore, patients from Puertollano and patients with moderate asthma presented more rapid decompensation compared with patients from Ciudad Real (P=0.020) and patients with mild asthma (P=0.049). CONCLUSION: In conclusion, pollen-allergic asthmatics in Puertollano present a poorer clinical course and become decompensated earlier than those from Ciudad Real and it could be due to air pollution.     

A randomized, double‐blind trial of the effect of glucocorticoid, antileukotriene and bβ‐agonist treatment on IL‐10 serum levels in children with asthma

BACKGROUND: Levels of an immunoregulatory and anti-inflammatory cytokine IL-10 are reduced in asthmatic airways, potentially contributing to more intense inflammation. Triamcinolone has anti-inflammatory properties and the anti-inflammatory effects of montelukast and formoterol have been discussed. OBJECTIVE: The purpose of this study was to define the effect of treatment with triamcinolone, montelukast and formoterol on the serum level of IL-10, eosinophil blood counts, eosinophil cationic response (ECP) and clinical parameters (symptom score, FEV1 and PC20H) in children with moderate asthma. METHODS: An 8-week, placebo-controlled and randomized, double-blind trial was carried out. The subjects were 91 children with moderate atopic asthma who were allergic to dust mite. Patients were randomly allocated to receive 400 microg triamcinolone (n = 19), 5 or 10 mg (according to age) montelukast (n = 18), 24 microg formoterol (n = 18) or placebo (n = 36). RESULTS: Seventy-nine children completed the study. After treatment with triamcinolone and montelukast the level of IL-10 in blood serum significantly increased, eosinophil blood counts and ECP levels significantly decreased and all clinical parameters improved; treatment with formoterol had no effect on IL-10 level, eosinophil blood counts in serum and bronchial hyper-reactivity; ECP level significantly decreased after treatment and asthma symptoms and FEV1 improved significantly. Mean IL-10 levels in serum before and after treatment with triamcinolone were 7.23 pg/mL with 95% CI, 6.74 -7.72% and 14.24 pg/mL with 95% CI, 11.6-16.88%, respectively (P < 0.001); with montelukast they were 6.59 pg/mL with 95% CI, 6.26-7.23% and 10.94 pg/mL with 95% CI, 8.24-12.65%, respectively (P < 0.002); with formoterol they were 7.06 pg/mL with 95% CI, 6.61-7.52% and 7.04 pg/mL with 95% CI, 6.15-7.93%. We found statistically significant correlations between serum level of IL-10 and serum level of ECP after treatment with triamcinolone and montelukast. CONCLUSION: This study demonstrates that one possible way by which triamcinolone and montelukast contribute to inhibition of inflammation is by increasing IL-10 levels.     

Do levels of airborne grass pollen influence asthma hospital admissions?

Background The effects of environmental factors and ambient concentrations of grass pollen on allergic asthma are yet to be established.
Objective We sought to estimate the independent effects of grass pollen concentrations in the air over Melbourne on asthma hospital admissions for the 1992–1993 pollen season.
Methods Daily grass pollen concentrations were monitored over a 24-h period at three stations in Melbourne. The outcome variable was defined as all-age asthma hospital admissions with ICD9-493 codes. The ambient air pollutants were average daily measures of ozone, nitrogen dioxide and sulphur dioxide, and the airborne particle index representing fine particulate pollution. Semi-parametric Poisson regression models were used to estimate these effects, adjusted for air temperature, humidity, wind speed, rainfall, day-of-the-week effects and seasonal variation.
Results Grass pollen was a strong independent non-linear predictor of asthma hospital admissions in a multi-pollutant model ( P =0.01). Our data suggest that grass pollen had an increasing effect on asthma hospital admissions up to a threshold of 30 grains/m³, and that the effect remains stable thereafter.
Conclusion Our findings suggest that grass pollen levels influence asthma hospital admissions. High grass pollen days, currently defined as more than 50 grains/m³, are days when most sensitive individuals will experience allergic symptoms. However, some asthmatic patients may be at a significant risk even when airborne grass pollen levels are below this level. Patients with pollen allergies and asthma would be advised to take additional preventive medication at lower ambient concentrations.     

Newly identified respiratory viruses in children with asthma exacerbation not requiring admission to hospital

There are few data describing the comprehensive identification in and influence of newly identified respiratory viruses on asthma exacerbations. Most studies focus on inpatients. In this preliminary study, the point prevalence and the associations of picornavirus species described recently and human bocavirus (HBoV) with the recovery from exacerbations in non‐hospitalized asthmatic children (median age 5.1 years) were examined. Human rhinoviruses (HRVs) were present in 52.6% of specimens, HBoV‐1 was in 7.7%. Viral co‐detections occurred in 25.6% of children and were associated (P = 0.04) with lower asthma quality of life scores upon presentation than were single viral detections. The undifferentiated presence or absence of virus did not influence the severity of asthma or recovery however when virus species were examined individually, specific clinical associations emerged. HRV species C (HRV‐Cs) were the viruses most frequently detected as single virus detections. Among 41 genotyped HRVs, more HRV‐Cs (n = 23) were identified than HRV‐As (n = 16) however HRV‐A detection was associated (P = 0.01) with worse asthma symptoms and cough for longer than was HRV‐C detection. Larger, PCR‐based studies are required to elucidate further the true impact of HRV species in childhood asthma exacerbations of both hospitalized and non‐hospitalized cohorts. J. Med. Virol. 82:1458–1461, 2010. © 2010 Wiley‐Liss, Inc.     

Evaluation of serum eosinophil cationic protein as a predictive marker for asthma exacerbation in patients with persistent disease

BACKGROUND: Eosinophilic inflammation is a feature of asthma. However, serological markers to indicate eosinophil activation in this process are not fully defined. OBJECTIVE: To evaluate the relationship of serum eosinophil cationic protein (ECP) to asthma worsening and a marker for treatment effectiveness, 26 adult patients with an asthma exacerbation were identified. METHODS: Identified asthma subjects were treated with oral corticosteroids (prednisone) for 14 days. The lung function variables, forced expiratory volume in one second (FEV1) and peak expiratory flow (PEF), were determined as percentage of predicted and the blood total eosinophil count and serum ECP levels were measured. Patients were re-evaluated after 14 days of corticosteroid treatment and then every 3 months thereafter during a 12-month period. RESULTS: Eighteen patients responded to prednisone treatment, whereas eight did not, assessed as improvement of their lung function parameters. Different serum ECP patterns could be seen in the responders compared with the non-responders. All 18 responders had considerably increased serum ECP at the time of exacerbation, whereas the non-responders had lower serum ECP levels. The serum ECP levels decreased to a greater extent in the responder patient group than in the non-responder patients following prednisone treatment. This difference in patterns was not seen with total blood eosinophil counts. CONCLUSION: Our findings suggest that serum ECP may be used to predict a response to corticosteroid therapy in adult patients with asthma.     

Ambient particulate matter induces an exacerbation of airway inflammation in experimental asthma: role of interleukin‐33

High levels of ambient environmental particulate matter (PM10 i.e. < 10 μm median aerodynamic diameter) have been linked to acute exacerbations of asthma. We examined the effects of delivering a single dose of Sydney PM10 by intranasal instillation to BALB/c mice that had been sensitized to ovalbumin and challenged repeatedly with a low (≈3 mg/m³) mass concentration of aerosolized ovalbumin for 4 weeks. Responses were compared to animals administered carbon black as a negative control, or a moderate (≈30 mg/m³) concentration of ovalbumin to simulate an allergen‐induced acute exacerbation of airway inflammation. Delivery of PM10 to mice, in which experimental mild chronic asthma had previously been established, elicited characteristic features of enhanced allergic inflammation of the airways, including eosinophil and neutrophil recruitment, similar to that in the allergen‐induced exacerbation. In parallel, there was increased expression of mRNA for interleukin (IL)‐33 in airway tissues and an increased concentration of IL‐33 in bronchoalveolar lavage fluid. Administration of a monoclonal neutralizing anti‐mouse IL‐33 antibody prior to delivery of particulates significantly suppressed the inflammatory response induced by Sydney PM10, as well as the levels of associated proinflammatory cytokines in lavage fluid. We conclude that IL‐33 plays a key role in driving airway inflammation in this novel experimental model of an acute exacerbation of chronic allergic asthma induced by exposure to PM10.     

CAPS评分对急性加重期慢性阻塞性肺疾病并无创通气患者远期预后评估

目的：探讨慢性阻塞性肺疾病和支气管哮喘生理评分(the COPD and asthma physiology score, CAPS)对慢性阻塞性肺疾病急性加重期(acute exacerbation of chronic obstructive pulmonary disease,AECOPD)并无创通气患者远期预后的评估效果。方法：以2014年6月至2015年10月在我院接受无创通气的AECOPD患者为观察对象,并根据其CAPS评分将其分为CAPS≥35组和CAPS<35组。比较不同CAPS评分患者出院时炎症细胞因子水平、肺功能和出院后1个月生活质量的差异。结果：CAPS≥35的患者出院时的CRP和IL-6等炎症细胞因子指标明显高于CAPS<35组患者,差异具有统计学意义(P<0.05);出院时CAPS<35的患者肺功能指标明显优于CAPS≥35组,差异具有统计学意义(P<0.05);治疗前,CAPS≥35组和CAPS<35组患者的生活质量各维度得分无明显差别,出院1个月时的调查结果显示：两组患者的生活质量均较治疗前增高,且CAPS<35组患者生活质量提高更明显(P<0.05)。结论：CAPS评分对AECOPD并无创通气患者的远期预后有较好的评估价值：CAPS评分高的患者病死率较高,预后较差。     

Serum eosinophil cationic protein levels measured during exacerbation of asthma: characteristics of patients with low titres

BACKGROUND: Serum eosinophil cationic protein (ECP) levels reflect ongoing eosinophilic airway inflammation and are used as a marker for asthma activity. ECP levels, however, may not be elevated in some asthmatic patients, even when they are symptomatic. OBJECTIVE: To clarify the characteristics of patients with 'low' ECP titres despite asthma exacerbation. METHODS: Serum ECP levels were measured in 113 asthmatic patients during exacerbation. Patients were divided into two groups according to ECP titre: a high ECP group (H; ECP > or = 16.0 microg/L) and a low ECP group (L; ECP <16.0 microg/L). Twenty-two patients who had recently received systemic steroids were excluded and the clinical features of the remaining patients in H (n = 54) and L (n = 37 were compared. RESULTS: Gender, atopic or smoking status, disease severity, inhaled steroid or theophylline usage, peak expiratory flow (% personal best) and forced expiratory volume in 1 s (FEV1) (% predicted) did not significantly differ between the two groups. Patients in L were significantly older and had longer disease duration and lower serum IgE levels than those in H. Multivariate analysis combining age, disease duration and IgE levels showed that age and disease duration were independently associated with ECP level. Airway wall thickness, assessed in a subset of patients using computed tomography, was significantly larger in L. CONCLUSION: Serum ECP levels in asthmatic patients may not be elevated during exacerbation and thus may not be a useful marker in patients who are older, have longer disease duration or possibly have thicker airway walls. Mechanisms other than eosinophilic inflammation, such as airway remodelling, may be involved in asthma exacerbation in these patients.     

Decreased expression of ectonucleotidase E‐NPP1 in leukocytes from subjects with severe asthma exacerbation

Several studies suggest that ATP and related nucleotides play a role in the pathophysiology of asthma. However, the functionality of ectonucleotidases in this disease has been scantly investigated. We studied total ectonucleotidase activity in leukocytes from patients suffering from asthma exacerbation and explored the expression of E‐NTPDase 1, 2, 3, and 8, and E‐NPP1, 2, and 3, in their polymorphonuclear cells by immunofluorescence and qPCR. Leukocytes from patients with mild or moderate asthma exacerbation had similar ectonucleotidase activity than leukocytes from healthy subjects, while in patients with severe asthma exacerbation, this activity was lower. Of the ectonucleotidases studied, only E‐NPP1 displayed diminished immunofluorescence and a significant decrease in its mRNA expression, both in patients with severe asthma exacerbation. This reduced E‐NPP1 expression could be responsible for increased amounts of ATP or other nucleotides, capable of worsening asthma exacerbation, and warranting further investigation.