Montelukast or salmeterol combined with an inhaled steroid in adult asthma: design and rationale of a randomized, double-blind comparative study (the IMPACT Investigation of Montelukast as a Partner Agent for Complementary Therapy-trial)

Asthma patients who continue to experience symptoms despite taking regular inhaled corticosteroids represent a management challenge. Leukotrienes play a key role in asthma pathophysiology, and since pro-inflammatory leukotrienes are poorly suppressed by corticosteroids it seems rational to add a leukotriene receptor antagonist (LTRA) when a low to moderate dose of inhaled corticosteroids does not provide sufficient disease control. Long acting beta2-agonist (LABA) treatment represents an alternative to LTRAs and both treatment modalities have been shown to provide additional disease control when added to corticosteroid treatment. To compare the relative clinical benefits of adding either a LTRA or a LABA to asthma patients inadequately controlled by inhaled corticosteroids, a randomized, double-blind, multi-centre, 48-week study will be initiated at approximately 120 centres throughout Europe, Latin America, Middle East, Africa and the Asia-Pacific region in early 2000. The study will compare the oral LTRA montelukast with the inhaled LABA salmeterol, each administered on a background of inhaled fluticasone, on asthma attacks, quality of life, lung function, eosinophil levels, healthcare utilization, and safety, in approximately 1200 adult asthmatic patients. The requirements for study enrollment include a history of asthma, FEV1 or PEFR values between 50% and 90% of the predicted value together with > or = 12% improvement in FEV1 after beta-agonist administration, a minimum pre-determined level of asthma symptoms and daily beta-agonist medication. The study will include a 4-week run-in period, during which patients previously taking inhaled corticosteroids are switched to open-label fluticasone (200 microg daily), followed by a 48-week double-blind, treatment period in which patients continuing to experience abnormal pulmonary function and daytime symptoms are randomized to receive montelukast (10 mg once daily) and salmeterol placebo, or inhaled salmeterol (100 microg daily) and montelukast placebo. All patients will continue with inhaled fluticasone (200 microg daily). During the study, asthma attacks, overnight asthma symptoms, and morning peak expiratory flow rate will be assessed using patient diary cards; quality of life will also be assessed using an asthma-specific quality-of life questionnaire. The results of this study are expected to provide physicians with important clinical evidence to help them make a rational and logical treatment choice for asthmatic patients experiencing breakthrough symptoms on inhaled corticosteroids.     

Short-term exposure to air pollution in a road tunnel enhances the asthmatic response to allergen.

The aim of this study was to assess whether air pollution in road tunnels would promote asthmatic reactions in persons with mild allergic asthma. Twenty volunteers with mild allergic asthma were exposed, inside a car, for 30 min in a Stockholm city road tunnel. As a control, the subjects were exposed to much lower pollution levels in a suburban area. Four hours after the exposure, the subjects inhaled a low dose of allergen. Asthmatic reaction during the early phase was measured as the increase in specific airway resistance 15 min after allergen inhalation and during the late phase as the decrease in lung function forced expiratory volume in one second 3-10 h after allergen inhalation. Asthma symptoms and drug use were monitored up to 18 h after allergen inhalation. The median nitrogen dioxide level during exposure was 313 microg x m-3 (range 203-462). The median levels of particles with 50% cut-off aerodynamic diameters of 10 (PM10) and 2.5 microm (PM2.5) were 170 (range 103-613) and 95 (range 61-218) micro x m-3, respectively. Subjective symptoms during tunnel exposure were not pronounced. However, subjects exposed to tunnel N02 levels of > or = 300 microg x m-3 had a significantly greater early reaction, following allergen exposure, as well as lower lung function and more asthma symptoms during the late phase, compared to control. Also, subjects with PM2.5 exposure > or = 100 microg x m-3 had a slightly increased early reaction compared to control. In conclusion, exposure to air pollution in road tunnels may significantly enhance asthmatic reactions to subsequently inhaled allergens.     

Effects of ambient particulate matter on peak expiratory flow rates and respiratory symptoms of asthmatics during Asian dust periods in Korea

OBJECTIVE: Dust generating events frequently produce ambient dust particles that are less than 10 microm in diameter, and these have been linked to adverse effects in the general population. However, the evidence linking these particles to adverse effects on the airways of asthmatic individuals is limited. The objective of this study was to investigate the possible adverse effects of Asian dust events on the respiratory functions and symptoms of subjects with bronchial asthma. METHODOLOGY: From March to June 2002, individuals were enrolled who had been diagnosed as having asthma by bronchial challenge or by their bronchodilator response. The patients were divided into three groups according to asthma severity: mild, moderate and severe. Patients with other major disease states were excluded. Patients completed twice-daily diaries monitoring PEF, respiratory symptoms, and daily activities. The daily and hourly mean levels of particulate matter <10 microm in diameter (PM(10)), as well as nitrogen dioxide (NO(2)), sulphur dioxide (SO(2)), ozone (O(3)) and carbon monoxide (CO) were measured at 10 monitoring sites in Incheon, Korea. RESULTS: Dust events occurred 14 times during the study period. On dusty days there were increased levels of PM(10), decreased levels of NO(2) and SO(2), and no change in the CO levels, compared to the levels on control days. An increase in PM(10) concentration was associated with increases in PEF variability of >20% (P<0.05), more night-time symptoms (P<0.05), and a decrease in the mean PEF (P<0.05), calculated by longitudinal data analysis. In contrast, there was no association between the PM(10) levels and bronchodilator inhaler use or daytime respiratory symptoms. Using a general additive Poisson regression model, a borderline association was noted between PM(10) and respiratory symptoms, with a relative risk of 1.05 (95% confidence interval (CI), 0.99--1.17). There was no association between the PM(10) concentrations and PEF measurements, with PEF variability of >20% between the morning and evening values and a relative risk of 1.05 (95% CI, 0.89--1.24) in all subjects. CONCLUSIONS: This study provides evidence that Asian dust events are impacting on the respiratory symptoms of subjects with bronchial asthma, and ambient air pollution, particularly elevated PM(10), might be one of the aggravating factors.     

Air pollution, bronchial asthma, and acute respiratory infections in minors, Habana City

OBJECTIVE: To identify the relationship between emergency visits for acute respiratory illnesses, acute bronchial asthma crisis (ABAC) and acute respiratory infections (ARI), in children less than 14 years of age, and the daily changes of air pollutant levels, in two central hospitals of Havana City, between October 1st 1996 and March 16 1998. MATERIAL AND METHODS: An ecological time series study was conducted. We assessed the relationship between the presence of acute respiratory illnesses, ABAC, and IRA, and exposure to levels of particles less than 10 microg/m3 (PM10), smoke, and sulfur dioxide (SO2); negative binomial regression models were used to assess latency periods of one to five days as well as the cumulative effect of seven days before the emergency visit. RESULTS: The levels of atmospheric pollutants were low, in general. The 24-hour mean values for PM10 levels, smoke, and SO2, were 59.2 microg/m3 (SD=29.2), 27.7 microg/m3 (SD=21.2), and 21.1 microg/m3 (SD=20.1), respectively. An increase of 20 microg/m3 in the daily average of black smoke was associated with a 2.2% increase (95% CI 0.9-3.6) in the number of emergency visits for ABAC. A 20 microg/m3 increase in the daily average of black smoke and SO was associated with an increase in ARI of 2.4% (95% CI 1.2-3.6), and 5% (95% CI 1.3-5.3), respectively, with a 5-day lag. We also observed a cumulative effect for all the contaminants studied. CONCLUSIONS: These results suggest that air pollution levels in Havana City affect children's respiratory health; therefore implementation of control measures is necessary, especially those aimed at decreasing motor vehicle exhaust fumes. The English version of this paper is available at: http://www.insp.mx/salud/index.html.     

Relationship between emergency consultations for respiratory diseases and air pollution in Juarez City, Chihuahua

OBJECTIVE: To assess the relationship of < or = 10 microns particles (PM10) and atmospheric ozone concentrations, with the daily number of emergency visits due to asthma and acute respiratory diseases, among children aged under 15, living in Ciudad Juarez, Chihuahua, Mexico. MATERIAL AND METHODS: Between 1998 and 1999, an ecologic study was conducted. Atmospheric data were obtained from the Environmental Protection Agency (EPA), from eight monitoring stations located in Ciudad Juarez, Chihuahua, and EI Paso, Texas. From July 1997 to December 1998, data from emergency room visits for respiratory illness were abstracted from existing medical records of two Mexican Institute of Social Security (IMSS) hospitals in Ciudad Juarez. Diagnoses were classified into two groups: a) asthma, and b) upper respiratory infections (URI), according to the International Classification of Diseases (ICD-9 and/or IDC-10). Statistical analysis was carried out using the Poisson regression time series method. RESULTS: During the study period, the mean 24-hour PM10 level was 34.46 micrograms/m3 (SD = 17.99) and the mean ozone level was 51.60 ppb (SD = 20.70). The model shows that an increase of 20 micrograms/m3 in the mean 24-hour exposure to PM10 was related to an increase of 4.97% (95% CI 0.97-9.13) in emergency visits for asthma, with a 5-day lag, as well as to an increase of 9% (95% CI 1.8-16.8) when a cumulative 5-day exposure was considered. URI increased 2.95% as a cause of emergency room visits, for each 20 micrograms/m3 increase in the mean 24-hour exposure to PM10. The impact of PM10 on emergency visits for asthma was greater on days with ozone ambient levels exceeded 49 ppb (median value). CONCLUSIONS: A positive association was found between environmental PM10 and ozone concentrations and the daily number of emergency room visits due to asthma and acute respiratory diseases, even with levels lower than the Mexican standard levels. Also, a synergic effect between PM10 and O3 was found.     

Acute effects of SO2 and particles from a power plant on respiratory symptoms of children, Thailand

Epidemiological studies to evaluate the acute effects of ambient SO2 on the respiratory health of children provide inconclusive results. A panel study to examine the association of short-term exposure to ambient SO2 and respiratory symptoms of 196 children for a period of 107 days was conducted in Thailand. Generalized Estimating Equations were used to examine the association of daily variation of air pollution with daily respiratory symptoms. During the study period, SO2 was not associated with respiratory symptoms in either asthmatics or non-asthmatics, whereas a 10 microg/m3 increase in PM10 was modestly associated with increases of lower respiratory symptom incidence (OR=1.03, 95%CI=0.98, 1.09) and cough (OR=1.04, 95% CI=1.00, 1.08) in asthmatics. At the low ambient air pollution concentrations observed, particulate matter rather than SO2 was associated on a microg/m3 basis with acute daily respiratory symptoms.     

Associations of particulate matter and daily mortality in Bangkok,Thailand

The association between airborne particles and daily mortality has been reported in many locations, but mainly in western countries. There is a need to investigate the association in locations where the emission sources, weather, and other environmental conditions differ from those in western countries. In this study, the acute effects of PM10 and visibility on daily mortality in Bangkok, Thailand, from 1992 to 1997, were examined. A Poisson regression model was developed to estimate the excess daily mortality associated with PM10 and visibility, while controlling for long-term trends, season, and variations in weather. It was found that increasing PM10 and decreasing visibility levels were independently associated with increasing daily mortality from all non-external causes, cardiovascular, respiratory, and other diseases. The observed associations were stronger for respiratory diseases than for cardiovascular and other diseases and were stronger for persons aged > or = 65 years than for those in the younger age group. The results of the PM10/mortality and visibility/mortality models were consistent, suggesting that visibility may be considered as a surrogate marker for the assessment of the adverse health effects of fine particulate matter when data from direct gravimetric measurements are not available.     

A study of twelve Southern California communities with differing levels and types of air pollution. II. Effects on pulmonary function

To study the possible chronic respiratory effects of air pollutants, we designed and initiated a 10-yr prospective study of Southern California public schoolchildren living in 12 communities with different levels and profiles of air pollution. The design of the study, exposure assessment methods, and survey methods and results related to respiratory symptoms and conditions are described in the accompanying paper. Pulmonary function tests were completed on 3,293 subjects. We evaluated cross-sectionally the effects of air pollution exposures based on data collected in 1986-1990 by existing monitoring stations and data collected by our study team in 1994. Expected relationships were seen between demographic, physical, and other environmental factors and pulmonary function values. When the data were stratified by sex, an association was seen between pollution levels and lower pulmonary function in female subjects, with the associations being stronger for the 1994 exposure data than the 1986-1990 data. After adjustment, PM10, PM2.5, and NO2 were each significantly associated with lower FVC, FEV1, and maximal midexpiratory flow (MMEF); acid vapor with lower FVC, FEV1, peak expiratory flow rate (PEFR), and MMEF; and O3 with lower PEFR and MMEF. Effects were generally larger in those girls spending more time outdoors. Stepwise regression of adjusted pulmonary function values for girls in the 12 communities showed that NO2 was most strongly associated with lower FVC (r = -0.74, p < 0.01), PM2.5 with FEV1 (r = -0.72, p < 0.01), O3 with PEFR (r = -0.75, p < 0.005), and PM2.5 with MMEF (r = -0.80, p < 0.005). There was a statistically significant association between ozone exposure and decreased FVC and FEV1 in girls with asthma. For boys, significant associations were seen between peak O3 exposures and lower FVC and FEV1, but only in those spending more time outdoors. These findings underline the importance of follow-up of this cohort.     

The effect of air pollution on inner-city children with asthma.

The effect of daily ambient air pollution was examined within a cohort of 846 asthmatic children residing in eight urban areas of the USA, using data from the National Cooperative Inner-City Asthma Study. Daily air pollution concentrations were extracted from the Aerometric Information Retrieval System database from the Environment Protection Agency in the USA. Mixed linear models and generalized estimating equation models were used to evaluate the effects of several air pollutants (ozone, sulphur dioxide (SO2), nitrogen dioxide (NO2) and particles with a 50% cut-off aerodynamic diameter of 10 microm (PM10) on peak expiratory flow rate (PEFR) and symptoms in 846 children with a history of asthma (ages 4-9 yrs). None of the pollutants were associated with evening PEFR or symptom reports. Only ozone was associated with declines in morning % PEFR (0.59% decline (95% confidence interval (CI) 0.13-1.05%) per interquartile range (IQR) increase in 5-day average ozone). In single pollutant models, each pollutant was associated with an increased incidence of morning symptoms: (odds ratio (OR)=1.16 (95% CI 1.02-1.30) per IQR increase in 4-day average ozone, OR=1.32 (95% CI 1.03-1.70) per IQR increase in 2-day average SO2, OR=1.48 (95% CI 1.02-2.16) per IQR increase in 6-day average NO2 and OR=1.26 (95% CI 1.0-1.59) per IQR increase in 2-day average PM10. This longitudinal analysis supports previous time-series findings that at levels below current USA air-quality standards, summer-air pollution is significantly related to symptoms and decreased pulmonary function among children with asthma.     

Daily respiratory mortality and PM10 pollution in Mexico City: importance of considering place of death.

Significant associations have been reported between particles with a 50% cut-off aerodynamic diameter of 10 mm (PM10) and ozone ambient concentrations, and daily number of deaths from respiratory causes. The aim of the present study was to assess such associations among elderly (> or =65 yrs) residents of Mexico City. Ambient air pollution data were provided by the Metropolitan Monitoring Network. During the study period, the average daily PM10 ranged 23.4-175.3 microg x m(-3), and ozone 1 h daily maximums ranged 39.4-216.7 ppb. Information was compiled on the primary and underlying causes of death. The analyses were conducted separately according to place of death (within or out of a hospital unit) using time-series methodology. The total number of deaths from all respiratory causes and mortality for chronic obstructive pulmonary diseases (COPD) were significantly related to PM10 over different lags: an increase of 10 microg x m(-3) was related to a 2.9% (95% (CI): 0.9-4.9%) increase and to a 4.1% (95% CI: 1.3%-6.9%) increase with a 3-day lag when death occurred out of medical units, respectively. For deaths occurring in medical units, a longer lag and smaller risk estimate was observed. An interactive effect between PM10 and ozone was detected. This study confirms that there is an important impact of PM10 on respiratory morbidity among elderly subjects. It also indicates that accounting for primary and underlying causes of death, and considering place of death may reduce misclassification and provide more accurate estimates of the adverse impact of PM10 on mortality.     

Association between plasma CC16 levels, the A38G polymorphism, and asthma

The effect of the A38G polymorphism on Clara cell secretory protein (CC16) gene expression and asthma was investigated by measuring plasma CC16 levels in 100 asthmatic and nonasthmatic children. Restriction digestion determined the A38G genotype and plasma CC16 levels were analyzed using a sensitive latex immunoassay. Asthmatics had lower mean plasma CC16 levels adjusted for age and gender (7.96 microg/L; 95% confidence interval [CI] = 6.79 to 9.31) than nonasthmatic subjects (9.98 microg/L; 95% CI = 8.83 to 11.26) (p = 0. 006). Similarly adjusted, mean plasma CC16 levels were also lower in 38A/38A (6.79 microg/L; 95% CI = 4.56 to 9.02) than 38G/38G subjects (10.01 microg/L; 95% CI = 7.90 to 12.12; p = 0.003). The odds ratio for asthma diagnosis of 38A/38A subjects was 4.78 (95% CI = 1.08 to 21.18; p = 0.04) compared with 38G/38G subjects. However, this was reduced when corrected from plasma CC16 level, suggesting that the odds of asthma was largely mediated through altered plasma CC16 levels. The 38A sequence was associated with reduced plasma CC16 levels and individuals with lower plasma CC16 levels were more likely to have asthma. This provides further evidence for a significant role of the CC16 gene, 38A allele in the development of asthma.     

Effects of atmospheric sulphur dioxide and particulate matter concentrations on emergency room admissions due to asthma in Ankara

Recent studies have associated short-term exposure to respirable particulate matter (PM(10)) and sulphur dioxide (SO(2)) with peak flow decrements, increased symptoms of respiratory irritation, increased use of asthma medications, and increased admission and hospitalization for asthma. To further delineate the association between SO(2), PM(10) exposure and asthmatic response, we compiled daily records of asthma emergency room visits from our hospital and data of meteorological conditions, SO(2) and PM(10) concentrations in Ankara area. Weekly averages of daily counts of emergency room visits for asthma were significantly associated with average weekly SO(2) and PM(10) exposure on previous week (r= 0.328, p= 0.017 and r= 0.355, p= 0.009 respectively). Admission to emergency room for asthma count was also negatively correlated with ambient temperature (r= -0.496, p= 0.0001) and strong wind existence (X(2)= 3.930, p= 0.047) on previous days. It was also positively correlated with ambient relative humidity (r= 0.531, p= 0.0001). We observed that numbers of emergency visits due to asthma were higher in winter months, April and September. In winter and early spring period there was concordance between asthma emergency admissions with air pollutants levels. During this period ambient temperatures were low as well. There were two discordance points in monthly variation of air pollution and asthma visits. We thought that first asthma visits peak was related to allergic pollens during April and second peak was due to opening of schools and increasing of respiratory infections for this reason during September. The general pattern of our results confirms that even low levels of air pollution encountered in Ankara are linked to short-term increases in the number of people visiting emergency department for asthma.     

Parental Smoking and the Risk of Respiratory Symptoms Among Schoolboys in Al-Khobar City, Saudi Arabia

The objective of this study was to measure the prevalence of parental smoking and its association with respiratory symptoms among 6- through 15-year-old schoolboys in Al-Khobar City, Saudi Arabia. This was a cross-sectional study. The methodology included the distribution of a self-administered questionnaire, which was completed by the parents of 1482 schoolboys who satisfied the selection criteria of the study. The overall rate of smoking among parents of this sample was 18.2% (32% among fathers and 4% among mothers). There was an increased risk associated with parental smoking and respiratory symptoms among asthmatic and nonasthmatic children. The magnitude of this risk was variable for different respiratory symptoms. The smoking rate among parents of asthmatic children was significantly higher than that of parents of normal children. The logistic regression model showed paternal smoking to be significantly associated with asthmatic children. The study concluded that there is an increased risk of respiratory symptoms among asthmatic and nonasthmatic children because of parental smoking. The smoking rate and trend among fathers and mothers were comparable to those reported earlier, indicating an ongoing problem. Schoolchildren with smoking parents may be better screened for bronchial asthma. Management of children presenting with respiratory symptoms should include an inquiry about exposure to passive smoking. Tobacco smoking should be considered a public health problem with serious implications, and the importation of tobacco should be banned.     

The presence of airway reactivity before the development of asthma

Exaggerated airway reactivity is an essential component of the current asthmatic. It is not clear, however, if airway reactivity is genetically determined or acquired. To examine the possibility that increased bronchial reactivity exists prior to the development of asthma, we report on 20 subjects who were studied before and after the onset of clinical asthma. Subjects were part of a larger on-going study of the Natural History of Asthma. Thirteen subjects indicated by their answers to the National Heart, Lung, and Blood Institute respiratory questionnaire that they were not asthmatic at their initial visit. Seven subjects had pulmonary symptoms on their initial visit, but had not been diagnosed as asthmatic. Bronchial reactivity was assessed using a standardized methacholine challenge. For the 20 subjects, there was a mean interval of 3.5 yr between the initial visit and the diagnosis of asthma. Ten of 13 nonasthmatic subjects had moderate or strongly positive responses (208 breath units or less) to methacholine prior to onset of asthma. These 13 subjects were compared to age- and sex-matched controls, from both asthmatic and nonasthmatic families, who had not become asthmatic. There was a difference in bronchial responses at the initial visit between the 13 study subjects and their control subjects from nonasthmatic families, but not between the subjects and their controls from asthmatic families. Five of 7 subjects with pulmonary symptoms had responses of 100 breath units or less. Overall, 19 of 20 subjects had strongly positive responses to methacholine after the diagnosis of asthma was established. The results show that enhanced airway reactivity usually precedes the development of asthma, which could support a genetic basis for it.     

Impact of smoking habits on the every day life of asthmatic adolescents

The impact of asthma on every day life is an important consideration in asthma management. Tobacco use often starts during adolescence, but little is known about its effect on the asthmatic process. The aim of this study is to describe the impact of smoking habits on the every day life of adolescents with asthma. A survey of respiratory symptoms in children aged 13-14 years was conducted in Bordeaux France as part of the International Study of Asthma and Allergies in Childhood (ISAAC). 494 out of the 3.302 adolescents surveyed had a diagnosis of asthma. They filled in a further questionnaire on smoking habits and on the impact asthma had on their every day life. Respiratory symptoms were more frequent among current smoking asthmatic adolescents than non-smoking asthmatic adolescents. The impact of asthma on daily life, with implications for performance at school, family life, psychological status and future job prospects were different for smokers and non-smokers, with problems more prevalent for active smoking asthmatic adolescents. In a multiple regression analysis with confounding factors adjustment, school absence was reported more often in active smokers. Active smoking has an important impact on the every day life of asthmatic adolescents.     

Asthma, Health Behaviors, Social Adjustment, and Psychosomatic Symptoms in Adolescence

The association of health behaviors, indicators of social adjustment, and psychosomatic symptoms with diagnosed asthma was assessed in a community-based sample of 4550 adolescents in South Western Sydney, Australia. The results of this survey found an asthma prevalence among 11-15-year-olds of 17.5%, being consistent with previous studies. Tobacco use and alcohol consumption were higher among asthmatic compared with nonasthmatic adolescents. Asthmatics reported feeling lonely more often, having a number of negative social perceptions and feelings, and having more frequent psychosomatic symptoms. The findings of the study suggest that adolescents with asthma represent an important vulnerable group of school children. Asthma education may need a greater life-style change focus, besides asthma self-management training.     

Acute health effects of PM10 pollution on symptomatic and asymptomatic children.

This study assessed the association between daily changes in respiratory health and respirable particulate pollution (PM10) in Utah Valley during the winter of 1990-1991. During the study period, 24-h PM10 concentrations ranged from 7 to 251 micrograms/m3. Participants included symptomatic and asymptomatic samples of fifth- and sixth-grade students. Relatively small but statistically significant (p less than 0.01) negative associations between peak expiratory flow (PEF) and PM10 were observed for both the symptomatic and asymptomatic samples. The association was strongest for the symptomatic children. Large associations between the incidence of respiratory symptoms, especially cough, and PM10 pollution were also observed for both samples. Again the association was strongest for the symptomatic sample. Immediate and delayed PM10 effects were observed. Respiratory symptoms and PEF changes were more closely associated with 5-day moving-average PM10 levels than with concurrent-day levels. These associations were also observed at PM10 levels below the 24-h standard of 150 micrograms/m3. This study indicates that both symptomatic and asymptomatic children may suffer acute health effects of respirable particulate pollution, with symptomatic children suffering the most.     

Asthma in the vicinity of power stations: II. Outdoor air quality and symptoms.

To assess longitudinally the effect of living in the vicinity of coal-fired power stations on children with asthma, 99 schoolchildren with a history of wheezing in the previous 12 months were studied for 1 year, using daily diaries and measurements of air quality. The children had been identified in a cross-sectional survey of two coastal areas: Lake Munmorah (LM), within 5 km of two power stations, and Nelson Bay (NB), free from major industry. Daily air quality [sulphur dioxide (SO2) and nitrogen oxides (NOx)], respiratory symptoms, and treatment for asthma were recorded throughout the year. Measurements of SO2 and NOx at LM were well within recommended guidelines although they were several times higher than at NB: maximum daily levels in SO2 (micrograms/m3) were 26 at LM, 11 at NB (standard, 365); yearly average SO2 was 2 at LM, 0.3 at NB (standard, 60); yearly average NOx (micrograms/m3) was 2 at LM, 0.4 at NB (standard, 94). Marked weekly fluctuations occurred in the prevalence of cough, wheezing, and breathlessness, without any substantial differences between LM and NB. Overall, the prevalence of symptoms was low (10% for wheezing, 20% for any symptom). Whether the daily SO2 and NOx levels affected the occurrence of respiratory symptoms was investigated in children at LM using a logistic regression (Korn and Whittemore technique). For these children as a group, air quality measurements were not associated with the occurrence of symptoms.     

Long-acting bronchodilators in premenstrual exacerbation of asthma

Premenstrual exacerbation (PME) of asthma occurs during the 5-10 days leading up to the menses and can be demonstrated in about 40% of asthmatic females. Peak expiratory flow rate (PEFR) and beta2-agonist consumption were recorded during three menstrual cycles in 67 females with mild-severe asthma. All were treated with inhaled glucocorticosteroids (IGC) and beta2-agonists, as required. Following, the patients with a premenstrual reduction in PEFR > 20%, received either salmeterol, 50 microg x 2 day(-1) or placebo, in the 10 days leading up to the menses, in a randomized, double-blind, cross-over design. Thirteen patients (19.4%) showed PME (mean +/- SEM decrease in PEFR 27 +/- 2.2%) in association with a significant increase in the mean daily beta2-agonist consumption. Following administration of salmeterol, there was a complete ablation of the PME in seven patients, a partial ablation in two patients and no effect in the remaining four patients. Only one patient showed a partial ablation of the PME following placebo. There was also a significant decrease in the beta2-agonists consumption in the responders. About 20% of the women with asthma, under chronic IGC treatment, had PME of asthma. In 54% of them, it could be prevented by the use of long-acting bronchodilators (LABD) during the 10 days leading up to the menses, and partially prevented in another 15%.     

Relationship between changes in diurnal variation of expiratory flows, lung volumes and respiratory symptoms after acute asthma

We looked at the comparative recovery of asthma symptoms and changes in airflow obstruction after an acute exacerbation of asthma in 26 asthmatics, aged 18-69 years (mean = 43). In the 4 weeks following the acute episode, they recorded their respiratory symptoms and twice-daily peak expiratory flow rates (PEFR). In 14 subjects, lung volumes were also measured on days 1, 7 and 30. Mean initial FVC and FEV1 [+/- SEM (% predicted)] were 2.30 +/- 0.16 (61%) and 1.18 +/- 0.08 (39%). The rate of improvement of airflow obstruction initially paralleled that of asthma symptoms in subjects with mild or with a recent onset of asthma. On the first study day, diurnal variation of PEFR was minimal, increased rapidly during the first week of treatment and stabilized thereafter. Mean daily delta PEFR was significantly higher in the first than at the fourth week (P = 0.005). Recovery of asthma symptoms was associated with an overall reduction in FRC and RV but there was no significant correlation between FRC or RV and dyspnea score or PEFR. Perception of airflow obstruction was generally lower, improvement of symptoms slower and of smaller amplitude in those with long-standing asthma. In conclusion, during recovery from acute asthma: (1) diurnal variation of PEFR is initially minimal, increases rapidly after beginning steroids and stabilize in the two following weeks; (2) in patients with more than mild or long-standing asthma, and magnitude and range of perception of asthma symptoms is reduced and correlates less with PEFR; and (3) no significant correlation could be found between FRC or RV and dyspnea score or PEFR.